UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 10-Q
|
☒ |
QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 |
For the quarterly period ended June 30, 2021
or
|
☐ |
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 |
For the transition period from to
Commission File Number: 000-29089
Agenus Inc.
(exact name of registrant as specified in its charter)
|
Delaware |
|
06-1562417 |
|
(State or other jurisdiction of incorporation or organization) |
|
(I.R.S. Employer Identification No.) |
3 Forbes Road, Lexington, Massachusetts 02421
(Address of principal executive offices, including zip code)
Registrant’s telephone number, including area code:
(781) 674-4400
Securities registered or to be registered pursuant to Section 12(b) of the Act.
|
Title of each class |
Trading symbol(s) |
Name of each exchange on which registered |
|
Common stock, par value $0.01 |
AGEN |
The Nasdaq Capital Market |
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
|
Large accelerated filer |
|
☐ |
|
Accelerated filer |
|
☒ |
|
Non-accelerated filer |
|
☐ |
|
Smaller reporting company |
|
☐ |
|
|
|
|
|
Emerging growth company |
|
☐ |
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
Number of shares outstanding of the issuer’s Common Stock as of August 4, 2021: 233,114,645 shares
Agenus Inc.
Six Months Ended June 30, 2021
Table of Contents
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Page |
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PART I |
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ITEM 1. |
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2 |
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Condensed Consolidated Balance Sheets as of June 30, 2021 (Unaudited) and December 31, 2020 |
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2 |
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3 |
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4 |
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6 |
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Notes to Unaudited Condensed Consolidated Financial Statements |
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7 |
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ITEM 2. |
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Management's Discussion and Analysis of Financial Condition and Results of Operations |
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18 |
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ITEM 3. |
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23 |
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ITEM 4. |
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24 |
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PART II |
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ITEM 1. |
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25 |
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ITEM 1A. |
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25 |
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ITEM 6. |
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80 |
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81 |
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PART I - FINANCIAL INFORMATION
|
Item 1. |
Financial Statements |
AGENUS INC. AND SUBSIDIARIES
CONDENSED CONSOLIDATED BALANCE SHEETS
(Amounts in thousands, except share and per share amounts)
|
|
|
June 30, 2021 (unaudited) |
|
|
December 31, 2020 |
|
||
|
ASSETS |
|
|
|
|
|
|
|
|
|
Cash and cash equivalents |
|
$ |
73,543 |
|
|
$ |
99,871 |
|
|
Accounts receivable |
|
|
1,436 |
|
|
|
1,157 |
|
|
Prepaid expenses |
|
|
13,628 |
|
|
|
10,746 |
|
|
Other current assets |
|
|
4,247 |
|
|
|
2,009 |
|
|
Total current assets |
|
|
92,854 |
|
|
|
113,783 |
|
|
Property, plant and equipment, net of accumulated amortization and depreciation of $49,528 and $47,201 at June 30, 2021 and December 31, 2020, respectively |
|
|
28,710 |
|
|
|
26,790 |
|
|
Operating lease right-of-use assets |
|
|
32,282 |
|
|
|
33,480 |
|
|
Goodwill |
|
|
24,706 |
|
|
|
25,452 |
|
|
Acquired intangible assets, net of accumulated amortization of $12,813 and $11,841 at June 30, 2021 and December 31, 2020, respectively |
|
|
9,594 |
|
|
|
10,886 |
|
|
Other long-term assets |
|
|
4,153 |
|
|
|
4,123 |
|
|
Total assets |
|
$ |
192,299 |
|
|
$ |
214,514 |
|
|
LIABILITIES, CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS’ DEFICIT |
|
|
|
|
|
|
|
|
|
Current portion, long-term debt |
|
$ |
838 |
|
|
$ |
833 |
|
|
Current portion, liability related to sale of future royalties and milestones |
|
|
62,682 |
|
|
|
57,362 |
|
|
Current portion, deferred revenue |
|
|
28,153 |
|
|
|
17,186 |
|
|
Current portion, operating lease liabilities |
|
|
2,258 |
|
|
|
1,950 |
|
|
Accounts payable |
|
|
19,164 |
|
|
|
17,015 |
|
|
Accrued liabilities |
|
|
30,203 |
|
|
|
29,057 |
|
|
Other current liabilities |
|
|
25,456 |
|
|
|
6,481 |
|
|
Total current liabilities |
|
|
168,754 |
|
|
|
129,884 |
|
|
Long-term debt, net of current portion |
|
|
18,947 |
|
|
|
18,879 |
|
|
Liability related to sale of future royalties and milestones, net of current portion |
|
|
186,562 |
|
|
|
176,263 |
|
|
Deferred revenue, net of current portion |
|
|
14,828 |
|
|
|
28,282 |
|
|
Operating lease liabilities, net of current portion |
|
|
34,808 |
|
|
|
34,065 |
|
|
Contingent purchase price considerations |
|
|
4,127 |
|
|
|
10,208 |
|
|
Other long-term liabilities |
|
|
1,750 |
|
|
|
1,514 |
|
|
Commitments and contingencies |
|
|
|
|
|
|
|
|
|
CONVERTIBLE PREFERRED STOCK |
|
|
|
|
|
|
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|
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Preferred stock, par value $0.01 per share; 5,000,000 shares authorized: |
|
|
|
|
|
|
|
|
|
Series C-1 convertible preferred stock; 8,459 and 12,459 shares designated, issued, and outstanding at June 30, 2021 and December 31, 2020, respectively |
|
|
18,275 |
|
|
|
26,917 |
|
|
STOCKHOLDERS’ DEFICIT |
|
|
|
|
|
|
|
|
|
Series A-1 convertible preferred stock; 31,620 shares designated, issued, and outstanding at June 30, 2021 and December 31, 2020; liquidation value of $33,355 at June 30, 2021 |
|
|
0 |
|
|
|
0 |
|
|
Common stock, par value $0.01 per share; 400,000,000 shares authorized; 225,262,889 and 196,090,980 shares issued at June 30, 2021 and December 31, 2020, respectively |
|
|
2,253 |
|
|
|
1,961 |
|
|
Additional paid-in capital |
|
|
1,353,243 |
|
|
|
1,257,502 |
|
|
Accumulated other comprehensive income (loss) |
|
|
260 |
|
|
|
2,772 |
|
|
Accumulated deficit |
|
|
(1,602,874 |
) |
|
|
(1,465,907 |
) |
|
Total stockholders’ deficit attributable to Agenus Inc. |
|
|
(247,118 |
) |
|
|
(203,672 |
) |
|
Non-controlling interest |
|
|
(8,634 |
) |
|
|
(7,826 |
) |
|
Total stockholders’ deficit |
|
|
(255,752 |
) |
|
|
(211,498 |
) |
|
Total liabilities, convertible preferred stock and stockholders’ deficit |
|
$ |
192,299 |
|
|
$ |
214,514 |
|
See accompanying notes to unaudited condensed consolidated financial statements.
2
AGENUS INC. AND SUBSIDIARIES
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(Unaudited)
(Amounts in thousands, except per share amounts)
|
|
|
Three Months Ended June 30, |
|
|
Six Months Ended June 30, |
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||||||||||
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2021 |
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2020 |
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2021 |
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2020 |
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||||
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Revenue: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development |
|
$ |
1,708 |
|
|
$ |
18,068 |
|
|
$ |
3,279 |
|
|
$ |
19,996 |
|
|
Service revenue |
|
|
1,196 |
|
|
|
1,023 |
|
|
|
2,825 |
|
|
|
1,023 |
|
|
Other revenue |
|
|
— |
|
|
|
8 |
|
|
|
35 |
|
|
|
52 |
|
|
Non-cash royalty revenue related to the sale of future royalties |
|
|
7,826 |
|
|
|
7,846 |
|
|
|
16,310 |
|
|
|
21,002 |
|
|
Total revenues |
|
|
10,730 |
|
|
|
26,945 |
|
|
|
22,449 |
|
|
|
42,073 |
|
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cost of service revenue |
|
|
(667 |
) |
|
|
(634 |
) |
|
|
(1,772 |
) |
|
|
(634 |
) |
|
Research and development |
|
|
(45,508 |
) |
|
|
(38,550 |
) |
|
|
(82,184 |
) |
|
|
(74,913 |
) |
|
General and administrative |
|
|
(16,650 |
) |
|
|
(14,195 |
) |
|
|
(33,003 |
) |
|
|
(24,809 |
) |
|
Contingent purchase price consideration fair value adjustment |
|
|
(14,300 |
) |
|
|
(6,840 |
) |
|
|
(13,256 |
) |
|
|
(2,456 |
) |
|
Operating loss |
|
|
(66,395 |
) |
|
|
(33,274 |
) |
|
|
(107,766 |
) |
|
|
(60,739 |
) |
|
Other income (expense): |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Loss on modification of debt |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
(2,720 |
) |
|
Non-operating income (expense) |
|
|
(920 |
) |
|
|
(340 |
) |
|
|
1,938 |
|
|
|
(1,392 |
) |
|
Interest expense, net |
|
|
(16,676 |
) |
|
|
(14,630 |
) |
|
|
(32,566 |
) |
|
|
(28,664 |
) |
|
Net loss |
|
|
(83,991 |
) |
|
|
(48,244 |
) |
|
|
(138,394 |
) |
|
|
(93,515 |
) |
|
Dividends on Series A-1 convertible preferred stock |
|
|
(53 |
) |
|
|
(52 |
) |
|
|
(105 |
) |
|
|
(105 |
) |
|
Less: net loss attributable to non-controlling interest |
|
|
(701 |
) |
|
|
(764 |
) |
|
|
(1,427 |
) |
|
|
(1,361 |
) |
|
Net loss attributable to Agenus Inc. common stockholders |
|
$ |
(83,343 |
) |
|
$ |
(47,532 |
) |
|
$ |
(137,072 |
) |
|
$ |
(92,259 |
) |
|
Per common share data: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic and diluted net loss attributable to Agenus Inc. common stockholders |
|
$ |
(0.37 |
) |
|
$ |
(0.28 |
) |
|
$ |
(0.65 |
) |
|
$ |
(0.59 |
) |
|
Weighted average number of Agenus Inc. common shares outstanding: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic and diluted |
|
|
222,906 |
|
|
|
169,130 |
|
|
|
211,681 |
|
|
|
157,096 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Other comprehensive income (loss): |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Foreign currency translation gain (loss) |
|
|
1,262 |
|
|
$ |
466 |
|
|
$ |
(2,512 |
) |
|
$ |
1,693 |
|
|
Other comprehensive income (loss) |
|
|
1,262 |
|
|
|
466 |
|
|
|
(2,512 |
) |
|
|
1,693 |
|
|
Comprehensive loss |
|
$ |
(82,081 |
) |
|
$ |
(47,066 |
) |
|
$ |
(139,584 |
) |
|
$ |
(90,566 |
) |
See accompanying notes to unaudited condensed consolidated financial statements.
3
AGENUS INC. AND SUBSIDIARIES
CONDENSED CONSOLIDATED STATEMENTS OF CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS’ DEFICIT
(Unaudited)
(Amounts in thousands)
|
|
|
Series C-1 |
|
|
|
Series A-1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||
|
|
|
Convertible |
|
|
|
Convertible |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||
|
|
|
Preferred Stock |
|
|
|
Preferred Stock |
|
|
Common Stock |
|
|
|
|
|
|
Treasury Stock |
|
|
|
|
|
|
|
|
|
|
|
|
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|
||||||||||||||||||||
|
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|
Number of Shares |
|
|
Amount |
|
|
|
Number of Shares |
|
|
Par Value |
|
|
Number of Shares |
|
|
Par Value |
|
|
Additional Paid-In Capital |
|
|
Number of Shares |
|
|
Amount |
|
|
Accumulated Other Comprehensive Income (Loss) |
|
|
Non-controlling Interest |
|
|
Accumulated Deficit |
|
|
Total |
|
|||||||||||||
|
Balance at December 31, 2020 |
|
|
12 |
|
|
$ |
26,917 |
|
|
|
|
32 |
|
|
$ |
0 |
|
|
|
196,093 |
|
|
$ |
1,961 |
|
|
$ |
1,257,502 |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
2,772 |
|
|
$ |
(7,826 |
) |
|
$ |
(1,465,907 |
) |
|
$ |
(211,498 |
) |
|
Net loss |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
(726 |
) |
|
|
(53,677 |
) |
|
|
(54,403 |
) |
|
Other comprehensive income |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
(3,774 |
) |
|
|
— |
|
|
|
— |
|
|
|
(3,774 |
) |
|
Share-based compensation |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
3,669 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
263 |
|
|
|
— |
|
|
|
3,932 |
|
|
Shares sold at the market |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
18,950 |
|
|
|
190 |
|
|
|
60,669 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
60,859 |
|
|
Payment of CEO payroll in shares |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
19 |
|
|
|
— |
|
|
|
68 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
68 |
|
|
Issuance of shares for services |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
5 |
|
|
|
— |
|
|
|
20 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
20 |
|
|
Conversion of series C-1 convertible preferred stock |
|
|
(2 |
) |
|
|
(4,321 |
) |
|
|
|
— |
|
|
|
— |
|
|
|
2,000 |
|
|
|
20 |
|
|
|
4,301 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
4,321 |
|
|
Exercise of stock options and employee share purchases |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
796 |
|
|
|
8 |
|
|
|
2,518 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
2,526 |
|
|
Balance at March 31, 2021 |
|
|
10 |
|
|
$ |
22,596 |
|
|
|
|
32 |
|
|
$ |
0 |
|
|
|
217,863 |
|
|
$ |
2,179 |
|
|
$ |
1,328,747 |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
(1,002 |
) |
|
$ |
(8,289 |
) |
|
$ |
(1,519,584 |
) |
|
$ |
(197,949 |
) |
|
Net loss |
|
|
— |
|
|
$ |
— |
|
|
|
|
— |
|
|
$ |
— |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
— |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
— |
|
|
$ |
(701 |
) |
|
$ |
(83,290 |
) |
|
|
(83,991 |
) |
|
Other comprehensive income |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
1,262 |
|
|
|
— |
|
|
|
— |
|
|
|
1,262 |
|
|
Share-based compensation |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
5,075 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
356 |
|
|
|
— |
|
|
|
5,431 |
|
|
Shares sold at the market |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
3,392 |
|
|
|
34 |
|
|
|
9,113 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
9,147 |
|
|
Issuance of warrants |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
70 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
70 |
|
|
Payment of CEO payroll in shares |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
24 |
|
|
|
— |
|
|
|
87 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
87 |
|
|
Issuance of shares for services |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
9 |
|
|
|
— |
|
|
|
31 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
31 |
|
|
Conversion of series C-1 convertible preferred stock |
|
|
(2 |
) |
|
|
(4,321 |
) |
|
|
|
— |
|
|
|
— |
|
|
|
2,000 |
|
|
|
20 |
|
|
|
4,301 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
4,321 |
|
|
Exercise of stock options |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
1,012 |
|
|
|
10 |
|
|
|
3,062 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
3,072 |
|
|
Issuance of shares for 2020 employee bonus |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
1,486 |
|
|
|
15 |
|
|
|
2,757 |
|
|
|
(521 |
) |
|
|
(1,497 |
) |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
1,275 |
|
|
Retirement of treasury shares |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
(521 |
) |
|
|
(5 |
) |
|
|
— |
|
|
|
521 |
|
|
|
1,497 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
1,492 |
|
|
Balance at June 30, 2021 |
|
|
8 |
|
|
$ |
18,275 |
|
|
|
|
32 |
|
|
$ |
0 |
|
|
|
225,265 |
|
|
$ |
2,253 |
|
|
$ |
1,353,243 |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
260 |
|
|
$ |
(8,634 |
) |
|
$ |
(1,602,874 |
) |
|
$ |
(255,752 |
) |
See accompanying notes to unaudited condensed consolidated financial statements.
4
AGENUS INC. AND SUBSIDIARIES
CONDENSED CONSOLIDATED STATEMENTS OF CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS’ DEFICIT
(Unaudited)
(Amounts in thousands)
|
|
|
Series C-1 |
|
|
|
Series A-1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||
|
|
|
Convertible |
|
|
|
Convertible |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||
|
|
|
Preferred Stock |
|
|
|
Preferred Stock |
|
|
Common Stock |
|
|
|
|
|
|
Treasury Stock |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||||||||||||
|
|
|
Number of Shares |
|
|
Amount |
|
|
|
Number of Shares |
|
|
Par Value |
|
|
Number of Shares |
|
|
Par Value |
|
|
Additional Paid-In Capital |
|
|
Number of Shares |
|
|
Amount |
|
|
Accumulated Other Comprehensive Income (Loss) |
|
|
Non-controlling Interest |
|
|
Accumulated Deficit |
|
|
Total |
|
|||||||||||||
|
Balance at December 31, 2019 |
|
|
12 |
|
|
$ |
26,917 |
|
|
|
|
32 |
|
|
$ |
0 |
|
|
|
137,819 |
|
|
$ |
1,378 |
|
|
$ |
1,059,583 |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
(1,324 |
) |
|
$ |
(5,981 |
) |
|
$ |
(1,284,993 |
) |
|
$ |
(231,337 |
) |
|
Net loss |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
(597 |
) |
|
|
(44,674 |
) |
|
|
(45,271 |
) |
|
Other comprehensive income |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
1,227 |
|
|
|
— |
|
|
|
— |
|
|
|
1,227 |
|
|
Share-based compensation |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
2,397 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
2,397 |
|
|
Shares sold at the market |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
24,716 |
|
|
|
247 |
|
|
|
64,876 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
65,123 |
|
|
Amendment of 2015 warrants and issuance of 2020 warrants |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
3,145 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
3,145 |
|
|
Payment of consultant in shares |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
4 |
|
|
|
0 |
|
|
|
12 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
12 |
|
|
Exercise of stock options and employee share purchases |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
765 |
|
|
|
8 |
|
|
|
2,196 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
2,204 |
|
|
Balance at March 31, 2020 |
|
|
12 |
|
|
$ |
26,917 |
|
|
|
|
32 |
|
|
$ |
0 |
|
|
|
163,304 |
|
|
$ |
1,633 |
|
|
$ |
1,132,209 |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
(97 |
) |
|
$ |
(6,578 |
) |
|
$ |
(1,329,667 |
) |
|
$ |
(202,500 |
) |
|
Net loss |
|
|
— |
|
|
$ |
— |
|
|
|
|
— |
|
|
$ |
— |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
— |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
— |
|
|
|
(764 |
) |
|
|
(47,480 |
) |
|
|
(48,244 |
) |
|
Other comprehensive income |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
466 |
|
|
|
— |
|
|
|
— |
|
|
|
466 |
|
|
Share-based compensation |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
2,464 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
2,464 |
|
|
Shares sold at the market |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
7,290 |
|
|
|
73 |
|
|
|
19,834 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
19,907 |
|
|
Issuance of shares for business acquisition |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
405 |
|
|
|
4 |
|
|
|
896 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
900 |
|
|
Payment of CEO payroll in shares |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
31 |
|
|
|
— |
|
|
|
88 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
88 |
|
|
Payment of consultant in shares |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
10 |
|
|
|
— |
|
|
|
31 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
31 |
|
|
Exercise of stock options |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
290 |
|
|
|
3 |
|
|
|
921 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
924 |
|
|
Vesting of nonvested shares |
|
|
— |
|
|
|
— |
|
|
|
|
— |
|
|
|
— |
|
|
|
88 |
|
|
|
1 |
|
|
|
(1 |
) |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
Balance at June 30, 2020 |
|
|
12 |
|
|
$ |
26,917 |
|
|
|
|
32 |
|
|
$ |
0 |
|
|
|
171,418 |
|
|
$ |
1,714 |
|
|
$ |
1,156,442 |
|
|
|
— |
|
|
$ |
— |
|
|
$ |
369 |
|
|
$ |
(7,342 |
) |
|
$ |
(1,377,147 |
) |
|
$ |
(225,964 |
) |
See accompanying notes to unaudited condensed consolidated financial statements.
5
AGENUS INC. AND SUBSIDIARIES
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(Unaudited)
(Amounts in thousands, except per share amounts)
|
|
|
Six Months Ended June 30, |
|
|||||
|
|
|
2021 |
|
|
2020 |
|
||
|
Cash flows from operating activities: |
|
|
|
|
|
|
|
|
|
Net loss |
|
$ |
(138,394 |
) |
|
$ |
(93,515 |
) |
|
Adjustments to reconcile net loss to net cash used in operating activities: |
|
|
|
|
|
|
|
|
|
Depreciation and amortization |
|
|
3,452 |
|
|
|
3,491 |
|
|
Share-based compensation |
|
|
9,589 |
|
|
|
4,950 |
|
|
Non-cash royalty revenue |
|
|
(16,310 |
) |
|
|
(21,002 |
) |
|
Non-cash interest expense |
|
|
31,997 |
|
|
|
28,191 |
|
|
Change in fair value of contingent obligations |
|
|
13,256 |
|
|
|
2,456 |
|
|
Loss on modification of debt |
|
|
— |
|
|
|
2,720 |
|
|
Changes in operating assets and liabilities: |
|
|
|
|
|
|
|
|
|
Accounts receivable |
|
|
(263 |
) |
|
|
766 |
|
|
Prepaid expenses |
|
|
(2,895 |
) |
|
|
(266 |
) |
|
Accounts payable |
|
|
1,896 |
|
|
|
6,106 |
|
|
Deferred revenue |
|
|
(2,488 |
) |
|
|
(4,599 |
) |
|
Accrued liabilities and other current liabilities |
|
|
3,495 |
|
|
|
(3,532 |
) |
|
Other operating assets and liabilities |
|
|
(1,636 |
) |
|
|
2,354 |
|
|
Net cash used in operating activities |
|
|
(98,301 |
) |
|
|
(71,880 |
) |
|
Cash flows from investing activities: |
|
|
|
|
|
|
|
|
|
Purchases of plant and equipment |
|
|
(2,466 |
) |
|
|
(1,762 |
) |
|
Cash paid for business acquisition, net |
|
|
— |
|
|
|
(972 |
) |
|
Net cash used in investing activities |
|
|
(2,466 |
) |
|
|
(2,734 |
) |
|
Cash flows from financing activities: |
|
|
|
|
|
|
|
|
|
Net proceeds from sale of equity |
|
|
70,005 |
|
|
|
85,030 |
|
|
Proceeds from employee stock purchases and option exercises |
|
|
5,598 |
|
|
|
3,128 |
|
|
Proceeds from issuance of long-term debt |
|
|
— |
|
|
|
6,197 |
|
|
Repayments of debt |
|
|
(462 |
) |
|
|
(1,000 |
) |
|
Payment of finance lease obligation |
|
|
(387 |
) |
|
|
(1,430 |
) |
|
Net cash provided by financing activities |
|
|
74,754 |
|
|
|
91,925 |
|
|
Effect of exchange rate changes on cash |
|
|
(280 |
) |
|
|
52 |
|
|
Net increase (decrease) in cash, cash equivalents and restricted cash |
|
|
(26,293 |
) |
|
|
17,363 |
|
|
Cash, cash equivalents and restricted cash, beginning of period |
|
|
102,505 |
|
|
|
61,808 |
|
|
Cash, cash equivalents and restricted cash, end of period |
|
$ |
76,212 |
|
|
$ |
79,171 |
|
|
Supplemental cash flow information: |
|
|
|
|
|
|
|
|
|
Cash paid for interest |
|
$ |
577 |
|
|
$ |
590 |
|
|
Supplemental disclosures - non-cash activities: |
|
|
|
|
|
|
|
|
|
Purchases of plant and equipment in accounts payable and accrued liabilities |
|
|
1,159 |
|
|
|
662 |
|
|
Issuance of common stock, $0.01 par value, in connection with payment for services |
|
|
51 |
|
|
|
31 |
|
|
Conversion of series C-1 convertible preferred stock to common stock, $0.01 par value |
|
|
8,642 |
|
|
|
— |
|
|
Insurance financing agreement |
|
|
987 |
|
|
|
— |
|
|
Issuance of common stock, $0.01 par value, for payment of 2020 employee bonus |
|
|
2,767 |
|
|
|
— |
|
|
Issuance of common stock, $0.01 par value, in connection with business acquisition |
|
|
— |
|
|
|
900 |
|
|
Contingent purchase price consideration in connection with business acquisition |
|
|
— |
|
|
|
144 |
|
|
Lease right-of-use assets obtained in exchange for new operating lease liabilities |
|
|
854 |
|
|
|
8,600 |
|
|
Lease right-of-use assets obtained in exchange for new finance lease liabilities |
|
|
156 |
|
|
|
2,434 |
|
See accompanying notes to unaudited condensed consolidated financial statements.
6
AGENUS INC. AND SUBSIDIARIES
NOTES TO UNAUDITED CONDENSED CONSOLIDATED FINANCIAL STATEMENTS
June 30, 2021
Note A - Business, Liquidity and Basis of Presentation
Agenus Inc. (including its subsidiaries, collectively referred to as “Agenus,” the “Company,” “we,” “us,” and “our”) is a clinical-stage immuno-oncology (“I-O”) company advancing an extensive pipeline of immune checkpoint antibodies, adoptive cell therapies and neoantigen vaccines, to fight cancer and infections. Our business is designed to drive success in I-O through speed, innovation and effective combination therapies. We believe that combination therapies and a deep understanding of each patient’s cancer will drive substantial expansion of the patient population benefiting from current I-O therapies. In addition to a diverse pipeline, we have assembled fully integrated end-to-end capabilities including novel target discovery, antibody generation, cell line development and current good manufacturing practice manufacturing. We believe that these fully integrated capabilities enable us to produce novel candidates on timelines that are shorter than the industry standard. Leveraging our science and capabilities, we have forged important partnerships to advance our innovation.
We are developing a comprehensive I-O portfolio driven by the following platforms and programs, which we intend to utilize individually and in combination:
|
|
• |
our multiple antibody discovery platforms, including our proprietary display technologies, designed to drive the discovery of future CPM antibody candidates; |
|
|
• |
our antibody candidate programs, including our CPM programs; |
|
|
• |
our vaccine programs, including Prophage™, AutoSynVax™ and PhosPhoSynVax ™; |
|
|
• |
our saponin-based vaccine adjuvants, principally our QS-21 Stimulon™ adjuvant, or QS-21 Stimulon; and |
|
|
• |
our cell therapy subsidiary, MiNK Therapeutics, Inc. (formerly AgenTus Therapeutics, Inc.), which is designed to drive the advancement of a novel allogeneic invariant natural killer T cell (“iNKT”) therapy in immune diseases. |
Our business activities include product research and development, intellectual property prosecution, manufacturing, regulatory and clinical affairs, corporate finance and development activities, and support of our collaborations. Our product candidates require clinical trials and approvals from regulatory agencies, as well as acceptance in the marketplace. Part of our strategy is to develop and commercialize some of our product candidates by continuing our existing arrangements with academic and corporate collaborators and licensees and by entering into new collaborations.
Our cash and cash equivalents at June 30, 2021 were $73.5 million, a decrease of $26.3 million from December 31, 2020.
We have incurred losses since our inception. As of June 30, 2021, we had an accumulated deficit of $1.6 billion.
During the past five years, we have successfully financed our operations through income and revenues generated from corporate partnerships, advance royalty sales and issuance of equity. Based on our current plans and projections, we believe our quarter end cash resources of $73.5 million at June 30, 2021, plus the $200.0 million fee received subsequently in connection with our transaction with Bristol Myers Squibb Company (see Subsequent Events Note), will be sufficient to satisfy our liquidity requirements for more than one year from when these financial statements were issued. We are presently in partnership, and out licensing discussions and contemplating additional financial transactions which, if consummated, could extend our cash resources substantially beyond 2022.
Management continues to address the Company’s liquidity position and has the flexibility to adjust spending as needed in order to preserve liquidity. In March 2020, in response to the COVID-19 pandemic, we streamlined our organization, which included a headcount reduction, and our CEO, Dr. Garo Armen, elected to receive his base salary in stock rather than cash for the remainder of 2020 and through the first half of 2021. We continuously evaluate the likelihood of success of our programs. As such, our decisions to continue to fund or eliminate funding of each of our programs are predicated on these determinations, on an ongoing basis. We are prepared to discontinue funding of any activities that do not impact our core priorities if they do not prove to be feasible, and to restrict capital expenditures and/or reduce the scale of our operations. We expect our potential sources of funding to include: (1) collaborations, out-licensing and/or partnering opportunities for our portfolio programs and product candidates with multiple parties (2) milestone payments from our existing partnerships (3) consummating additional third-party agreements, (4) selling assets, (5) securing project financing and/or (6) selling equity securities.
The accompanying unaudited interim condensed consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles (“U.S. GAAP”) for interim financial information and with the instructions to Article 10 of Regulation S-X. Accordingly, they do not include all of the information and footnotes required by U.S. GAAP for complete annual consolidated financial statements. In the opinion of our management, the condensed consolidated financial statements include all
7
normal and recurring adjustments considered necessary for a fair presentation of our financial position and operating results. All significant intercompany transactions and accounts have been eliminated in consolidation. Operating results for the six months ended June 30, 2021, are not necessarily indicative of the results that may be expected for the year ending December 31, 2021. For further information, refer to our consolidated financial statements and footnotes thereto included in our Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission (“SEC”) on March 16, 2021.
The preparation of consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosures of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenues and expenses during the reporting period. Management bases its estimates on historical experience and on various assumptions that are believed to be reasonable under the circumstances. Actual results could differ materially from those estimates.
For our foreign subsidiaries, the local currency is the functional currency. Assets and liabilities of our foreign subsidiaries are translated into U.S. dollars using rates in effect at the balance sheet date while revenues and expenses are translated into U.S. dollars using average exchange rates during the period. The cumulative translation adjustment resulting from changes in exchange rates are included in the consolidated balance sheets as a component of accumulated other comprehensive loss in total stockholders’ deficit.
Note B - Net Loss Per Share
Basic net loss per common share is calculated by dividing the net loss attributable to common stockholders by the weighted average number of common shares outstanding (including common shares issuable under our Amended and Restated Directors’ Deferred Compensation Plan, or “DDCP”). Diluted loss per common share is calculated by dividing loss attributable to common stockholders by the weighted average number of common shares outstanding (including common shares issuable under our DDCP) plus the dilutive effect of outstanding instruments such as warrants, stock options, non-vested shares and convertible preferred stock. Because we reported a net loss attributable to common stockholders for all periods presented, diluted loss per common share is the same as basic loss per common share, as the effect of utilizing the fully diluted share count would have reduced the net loss per common share. The following securities (listed on an as-if-converted-to-Common-Stock basis) have been excluded from the computation of diluted weighted average shares outstanding as of June 30, 2021 and 2020, as they would be anti-dilutive (in thousands):
|
|
|
Three and Six Months Ended June 30, |
|
|||||
|
|
|
2021 |
|
|
2020 |
|
||
|
Warrants |
|
|
1,980 |
|
|
|
1,950 |
|
|
Stock options |
|
|
33,789 |
|
|
|
26,079 |
|
|
Non-vested shares |
|
|
1,215 |
|
|
|
873 |
|
|
Series A-1 convertible preferred stock |
|
|
333 |
|
|
|
333 |
|
|
Series C-1 convertible preferred stock |
|
|
8,459 |
|
|
|
12,459 |
|
Note C - Investments
Cash equivalents consisted of the following as of June 30, 2021 and December 31, 2020 (in thousands):
|
|
|
June 30, 2021 |
|
|
December 31, 2020 |
|
||||||||||
|
|
|
Cost |
|
|
Estimated Fair Value |
|
|
Cost |
|
|
Estimated Fair Value |
|
||||
|
Institutional money market funds |
|
$ |
54,068 |
|
|
$ |
54,068 |
|
|
$ |
64,256 |
|
|
$ |
64,256 |
|
|
U.S. Treasury Bills |
|
|
5,000 |
|
|
|
5,000 |
|
|
|
20,000 |
|
|
|
20,000 |
|
|
Total |
|
$ |
59,068 |
|
|
$ |
59,068 |
|
|
$ |
84,256 |
|
|
$ |
84,256 |
|
As a result of the short-term nature of our investments, there were minimal unrealized holding gains or losses for the three and six months ended June 30, 2021 and 2020.
8
Note D - Goodwill and Acquired Intangible Assets
The following table sets forth the changes in the carrying amount of goodwill for the six months ended June 30, 2021 (in thousands):
|
Balance, December 31, 2020 |
|
$ |
25,452 |
|
|
Foreign currency translation adjustment |
|
|
(746 |
) |
|
Balance, June 30, 2021 |
|
$ |
24,706 |
|
Acquired intangible assets consisted of the following as of June 30, 2021 and December 31, 2020 (in thousands):
|
|
|
As of June 30, 2021 |
|
|||||||||||
|
|
|
Amortization period (years) |
|
Gross carrying amount |
|
|
Accumulated amortization |
|
|
Net carrying amount |
|
|||
|
Intellectual property |
|
7-15 years |
|
$ |
16,796 |
|
|
$ |
(10,956 |
) |
|
$ |
5,840 |
|
|
Trademarks |
|
4-4.5 years |
|
|
1,277 |
|
|
|
(991 |
) |
|
|
286 |
|
|
Other |
|
2-7 years |
|
|
2,296 |
|
|
|
(866 |
) |
|
|
1,430 |
|
|
In-process research and development |
|
Indefinite |
|
|
2,038 |
|
|
|
— |
|
|
|
2,038 |
|
|
Total |
|
|
|
$ |
22,407 |
|
|
$ |
(12,813 |
) |
|
$ |
9,594 |
|
|
|
|
As of December 31, 2020 |
|
|||||||||||
|
|
|
Amortization period (years) |
|
Gross carrying amount |
|
|
Accumulated amortization |
|
|
Net carrying amount |
|
|||
|
Intellectual property |
|
7-15 years |
|
$ |
17,013 |
|
|
$ |
(10,112 |
) |
|
$ |
6,901 |
|
|
Trademarks |
|
4-4.5 years |
|
|
1,310 |
|
|
|
(980 |
) |
|
|
330 |
|
|
Other |
|
2-6 years |
|
|
2,272 |
|
|
|
(749 |
) |
|
|
1,523 |
|
|
In-process research and development |
|
Indefinite |
|
|
2,132 |
|
|
|
— |
|
|
|
2,132 |
|
|
Total |
|
|
|
$ |
22,727 |
|
|
$ |
(11,841 |
) |
|
$ |
10,886 |
|
The weighted average amortization period of our finite-lived intangible assets is 9 years. Amortization expense related to acquired intangibles is estimated at $1.1 million for the remainder of 2021, $2.2 million for the year ending December 31, 2022, $1.7 million for the year ending December 31, 2023 and $0.6 million for the each of the years ending December 31, 2024 and 2025.
Note E - Debt
Debt obligations consisted of the following as of June 30, 2021 and December 31, 2020 (in thousands):
|
Debt instrument |
|
Balance at June 30, 2021 |
|
|
|
Current Portion: |
|
|
|
|
|
Debentures |
|
$ |
146 |
|
|
Other |
|
|
692 |
|
|
Long-term Portion: |
|
|
|
|
|
2015 Subordinated Notes |
|
|
12,750 |
|
|
Other |
|
|
6,197 |
|
|
Total |
|
$ |
19,785 |
|
9
|
Debt instrument |
|
Balance at December 31, 2020 |
|
|
|
Current Portion: |
|
|
|
|
|
Debentures |
|
$ |
146 |
|
|
Other |
|
|
687 |
|
|
Long-term Portion: |
|
|
|
|
|
2015 Subordinated Notes |
|
|
12,682 |
|
|
Other |
|
|
6,197 |
|
|
Total |
|
$ |
19,712 |
|
As of both June 30, 2021 and December 31, 2020, the principal amount of our outstanding debt balance was $20.0 million.
Payroll Protection Program
In May 2020, we entered into promissory notes with Bank of America, NA for aggregate loan proceeds of approximately $6.2 million (collectively, the “Loan”) under the Small Business Administration (the “SBA”) Paycheck Protection Program of the Coronavirus Aid, Relief and Economic Security Act of 2020 (the “CARES Act”). We believe we used at least 60% of the Loan proceeds for covered payroll costs and no more than 40% of the Loan proceeds for rent and utilities in accordance with the relevant terms and conditions of the CARES Act, as amended by the Paycheck Protection Program Flexibility Act. Each Loan has a two-year term and bears interest at a rate of 1.00% per annum.
The Loan may be forgiven partially or fully if the Loan proceeds are used for covered payroll costs, rent and utilities, provided that such amounts are incurred during the twenty-four week period commencing on receipt of the Loan proceeds, and at least 60% of any forgiven amount has been used for covered payroll costs. Any forgiveness of the Loan will be subject to approval by the SBA.
Though we have submitted our forgiveness application, it has not yet been approved. As such, we cannot yet determine if the Loan will be partially or fully forgiven. Therefore, we have classified the Loan proceeds as debt in our condensed consolidated balance sheet.
Note F – Liability Related to the Sale of Future Royalties and Milestones
The following table shows the activity within the liability account in the six months ended June 30, 2021 (in thousands):
|
|
|
Period from December 31, 2020 to June 30, 2021 |
|
|
|
Liability related to sale of future royalties and milestones - beginning balance |
|
$ |
234,041 |
|
|
Non-cash royalty revenue |
|
|
(16,310 |
) |
|
Non-cash interest expense recognized |
|
|
31,899 |
|
|
Liability related to sale of future royalties and milestones - ending balance |
|
|
249,630 |
|
|
Less: unamortized transaction costs |
|
|
(386 |
) |
|
Liability related to sale of future royalties and milestones, net |
|
$ |
249,244 |
|
Healthcare Royalty Partners
In January 2018, we, through our wholly-owned subsidiary Antigenics, LLC (“Antigenics”), entered into a Royalty Purchase Agreement (the “HCR Royalty Purchase Agreement”) with Healthcare Royalty Partners III, L.P. and certain of its affiliates (collectively, “HCR”). Pursuant to the terms of the HCR Royalty Purchase Agreement, we sold to HCR 100% of Antigenics’ worldwide rights to receive royalties from GlaxoSmithKline (“GSK”) on sales of GSK’s vaccines containing our QS-21 Stimulon adjuvant. At closing, we received gross proceeds of $190.0 million from HCR. Although we sold all of our rights to receive royalties on sales of GSK’s vaccines containing QS-21, as a result of our obligation to HCR, we are required to account for these royalties as revenue when earned, and we recorded the $190.0 million in proceeds from this transaction as a liability on our condensed consolidated balance sheet that will be amortized using the interest method over the estimated life of the HCR Royalty Purchase
10
Agreement. The liability is classified between the current and non-current portion of liability related to sale of future royalties and milestones in the condensed consolidated balance sheets based on the estimated recognition of the royalty payments to be received by HCR in the next 12 months from the financial statement reporting date.
In June 2021, we entered into an amendment to the HCR Royalty Purchase Agreement in which HCR was granted the option to directly pay us the final $25.3 million milestone, if achieved. Under the terms of the original agreement, the milestone, if achieved, was to be paid through royalties received from GSK.
During the six months ended June 30, 2021, we recognized $16.3 million of non-cash royalty revenue, and we recorded $31.9 million of related non-cash interest expense related to the HCR Royalty Purchase Agreement.
As royalties are remitted to HCR from GSK, the balance of the recorded liability will be effectively repaid over the life of the HCR Royalty Purchase Agreement. To determine the amortization of the recorded liability, we are required to estimate the total amount of future royalty payments to be received by HCR. The sum of these amounts less the $190.0 million proceeds we received will be recorded as interest expense over the life of the HCR Royalty Purchase Agreement. Periodically, we assess the estimated royalty payments to be paid to HCR from GSK, and to the extent the amount or timing of the payments is materially different from our original estimates, we will prospectively adjust the amortization of the liability. During the six months ended June 30, 2021, our estimate of the effective annual interest rate over the life of the agreement increased to 28.5%, which results in a retrospective interest rate of 23.7%.
Note G - Accrued and Other Current Liabilities
Accrued liabilities consisted of the following as of June 30, 2021 and December 31, 2020 (in thousands):
|
|
|
June 30, 2021 |
|
|
December 31, 2020 |
|
||
|
Payroll |
|
$ |
6,682 |
|
|
$ |
7,643 |
|
|
Professional fees |
|
|
6,180 |
|
|
|
4,457 |
|
|
Contract manufacturing costs |
|
|
5,617 |
|
|
|
6,274 |
|
|
Research services |
|
|
6,369 |
|
|
|
4,649 |
|
|
Other |
|
|
5,355 |
|
|
|
6,034 |
|
|
Total |
|
$ |
30,203 |
|
|
$ |
29,057 |
|
Other current liabilities consisted of the following as of June 30, 2021 and December 31, 2020 (in thousands):
|
|
|
June 30, 2021 |
|
|
December 31, 2020 |
|
||
|
Consideration associated with achieved contingent milestones |
|
$ |
19,337 |
|
|
$ |
- |
|
|
Other |
|
|
6,119 |
|
|
|
6,481 |
|
|
Total |
|
$ |
25,456 |
|
|
$ |
6,481 |
|
Note H - Fair Value Measurements
We measure our contingent purchase price considerations at fair value.
The fair values of our contingent purchase price considerations, $4.1 million, are based on significant inputs not observable in the market, which require them to be reported as Level 3 liabilities within the fair value hierarchy. The valuation of these liabilities use assumptions we believe would be made by a market participant and are mainly based on estimates from a Monte Carlo simulation of our market capitalization and share price, as well as other factors impacting the probability of triggering the milestone payments. Market capitalization and share price were evolved using a geometric Brownian motion, calculated daily for the life of the contingent purchase price considerations.
The significant unobservable inputs include the anticipated timelines to achieve the contingent purchase milestones and our estimated credit spread, the weighted average values of which (weighted based on the value of each contingent liability), are shown in the table below.
|
|
|
June 30, 2021 |
|
|
December 31, 2020 |
|
||
|
Period of time to achieve milestones (in years) |
|
|
1.0 |
|
|
|
1.3 |
|
|
Credit spread |
|
|
5.0 |
% |
|
|
5.5 |
% |
11
Liabilities measured at fair value are summarized below (in thousands):
|
Description |
|
June 30, 2021 |
|
|
Quoted Prices in Active Markets for Identical Assets (Level 1) |
|
|
Significant Other Observable Inputs (Level 2) |
|
|
Significant Unobservable Inputs (Level 3) |
|
||||
|
Liabilities: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Contingent purchase price considerations |
|
$ |
4,127 |
|
|
$ |
— |
|
|
$ |
— |
|
|
$ |
4,127 |
|
|
Total |
|
$ |
4,127 |
|
|
$ |
— |
|
|
$ |
— |
|
|
$ |
4,127 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Description |
|
December 31, 2020 |
|
|
Quoted Prices in Active Markets for Identical Assets (Level 1) |
|
|
Significant Other Observable Inputs (Level 2) |
|
|
Significant Unobservable Inputs (Level 3) |
|
||||
|
Liabilities: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Contingent purchase price consideration |
|
$ |
10,208 |
|
|
$ |
— |
|
|
$ |
— |
|
|
$ |
10,208 |
|
|
Total |
|
$ |
10,208 |
|
|
$ |
— |
|
|
$ |
— |
|
|
$ |
10,208 |
|
The following table presents our liabilities measured at fair value using significant unobservable inputs (Level 3), as of June 30, 2021 (in thousands):
|
Balance, December 31, 2020 |
|
$ |
10,208 |
|
|
Change in fair value of contingent purchase price considerations during the period |
|
|
13,256 |
|
|
Transfer to current liabilities |
|
|
(19,337 |
) |
|
Balance, June 30, 2021 |
|
$ |
4,127 |
|
In June 2021, the second contingent milestone was achieved pursuant to the terms of the Share Exchange Agreement dated January 10, 2014, by and among us, 4-AB, the former shareholders of 4-AB and Vischer AG, as Representative (the "Share Exchange Agreement"), triggering a $10.0 million payment, which was paid in July 2021. In July 2021, the third contingent milestone was achieved pursuant to the terms of the Share Exchange Agreement, triggering an additional $10.0 million payment. As such, as of June 30, 2021, the $19.3 million liability associated with both aforementioned milestones is recorded in “Other current liabilities” in our condensed consolidated balance sheet.
The fair value of our outstanding debt balance at both June 30, 2021 and December 31, 2020 was $19.9 million, based on the Level 2 valuation hierarchy of the fair value measurements standard using a present value methodology that was derived by evaluating the nature and terms of each note and considering the prevailing economic and market conditions at the balance sheet date. The principal amount of our outstanding debt balance at both June 30, 2021 and December 31, 2020 was $20.0 million.
Note I - Revenue from Contracts with Customers
Gilead Collaboration Agreement
On December 20, 2018, we entered into a series of agreements with Gilead Sciences, Inc. (“Gilead”) focused on the development and commercialization of up to five novel immuno-oncology therapies. Pursuant to the terms of the license agreement, the option and license agreements and the stock purchase agreement we entered into with Gilead (collectively, the “Gilead Collaboration Agreements”), at the closing of the transaction on January 23, 2019, we received an upfront cash payment from Gilead of $120.0 million and Gilead made a $30.0 million equity investment in Agenus. On November 6, 2020, we received notice from Gilead that it was returning AGEN1423 to us and voluntarily terminating the applicable license agreement. The termination was effective as of February 4, 2021. The option and license agreements and the stock purchase agreement remain in full force and effect. We remain eligible to receive up to $1.1 billion in aggregate potential milestones.
Collaboration Revenue
12
For the three months ended June 30, 2021 and 2020, we recognized approximately $1.4 million and $4.0 million, respectively, of research and development revenue related to the Gilead Collaboration Agreements based on the partial satisfaction of the over time performance obligations as of quarter end.
For the six months ended June 30, 2021 and 2020, we recognized approximately $2.4 million and $5.8 million, respectively, of research and development revenue related to the Gilead Collaboration Agreements based on the partial satisfaction of the over time performance obligations as of period end.
We expect to recognize deferred research and development revenue of $14.5 million and $27.1 million for the remainder of 2021 and 2022, respectively, related to performance obligations that are unsatisfied or partially unsatisfied as of June 30, 2021.
Incyte Collaboration Agreement
For both the three months ended June 30, 2021 and 2020, we recognized approximately $0.2 million of research and development revenue for research and development services provided.
For the six months ended June 30, 2021 and 2020, we recognized approximately $0.7 million and $0.3 million, respectively, of research and development revenue for research and development services provided.
Disaggregation of Revenue
The following tables present revenue (in thousands) for the three and six months ended June 30, 2021 and 2020, disaggregated by geographic region and revenue type. Revenue by geographic region is allocated based on the domicile of our respective business operations.
|
|
|
Three months ended June 30, 2021 |
|
|||||||||
|
|
|
United States |
|
|
Rest of World |
|
|
Total |
|
|||
|
Revenue Type |
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development services |
|
$ |
318 |
|
|
$ |
— |
|
|
$ |
318 |
|
|
Other services |
|
|
— |
|
|
|
1,196 |
|
|
|
1,196 |
|
|
Recognition of deferred revenue |
|
|
1,390 |
|
|
|
— |
|
|
|
1,390 |
|
|
Non-cash royalty revenue |
|
|
7,826 |
|
|
|
— |
|
|
|
7,826 |
|
|
|
|
$ |
9,534 |
|
|
$ |
1,196 |
|
|
$ |
10,730 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three months ended June 30, 2020 |
|
|||||||||
|
Revenue Type |
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development services |
|
$ |
237 |
|
|
$ |
— |
|
|
$ |
237 |
|
|
License fee revenue |
|
|
13,857 |
|
|
|
— |
|
|
|
13,857 |
|
|
Other services |
|
|
— |
|
|
|
1,023 |
|
|
|
1,023 |
|
|
Recognition of deferred revenue |
|
|
3,974 |
|
|
|
— |
|
|
|
3,974 |
|
|
Recognition of deferred grant revenue |
|
|
8 |
|
|
|
— |
|
|
|
8 |
|
|
Non-cash royalty revenue |
|
|
7,846 |
|
|
|
— |
|
|
|
7,846 |
|
|
|
|
$ |
25,922 |
|
|
$ |
1,023 |
|
|
$ |
26,945 |
|
13
|
|
|
Six months ended June 30, 2021 |
|
|||||||||
|
|
|
United States |
|
|
Rest of World |
|
|
Total |
|
|||
|
Revenue Type |
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development services |
|
$ |
855 |
|
|
$ |
— |
|
|
$ |
855 |
|
|
Other services |
|
|
— |
|
|
|
2,825 |
|
|
|
2,825 |
|
|
Recognition of deferred revenue |
|
|
2,424 |
|
|
|
— |
|
|
|
2,424 |
|
|
Recognition of deferred grant revenue |
|
|
35 |
|
|
|
— |
|
|
|
35 |
|
|
Non-cash royalty revenue |
|
|
16,310 |
|
|
|
— |
|
|
|
16,310 |
|
|
|
|
$ |
19,624 |
|
|
$ |
2,825 |
|
|
$ |
22,449 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Six months ended June 30, 2020 |
|
|||||||||
|
Revenue Type |
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development services |
|
$ |
334 |
|
|
$ |
— |
|
|
$ |
334 |
|
|
License fee revenue |
|
|
13,857 |
|
|
|
— |
|
|
|
13,857 |
|
|
Other services |
|
|
— |
|
|
|
1,023 |
|
|
|
1,023 |
|
|
Recognition of deferred revenue |
|
|
5,805 |
|
|
|
— |
|
|
|
5,805 |
|
|
Recognition of deferred grant revenue |
|
|
8 |
|
|
|
44 |
|
|
|
52 |
|
|
Non-cash royalty revenue |
|
|
21,002 |
|
|
|
— |
|
|
|
21,002 |
|
|
|
|
$ |
41,006 |
|
|
$ |
1,067 |
|
|
$ |
42,073 |
|
Contract Balances
Contract assets primarily relate to our rights to consideration for work completed in relation to our research and development services performed but not billed at the reporting date. The contract assets are transferred to receivables when the rights become unconditional. Currently, we do not have any contract assets which have not transferred to a receivable. We had no asset impairment charges related to contract assets in the period. Contract liabilities primarily relate to contracts where we received payments but have not yet satisfied the related performance obligations. The advance consideration received from customers for research and development services or licenses bundled with other promises is a contract liability until the underlying performance obligations are transferred to the customer.
The following table provides information about contract liabilities from contracts with customers (in thousands):
|
Six months ended June 30, 2021 |
|
Balance at beginning of period |
|
|
Additions |
|
|
Deductions |
|
|
Balance at end of period |
|
||||
|
Contract liabilities: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Deferred revenue |
|
$ |
45,284 |
|
|
$ |
- |
|
|
$ |
(2,453 |
) |
|
$ |
42,831 |
|
The change in contract liabilities is primarily related to the recognition of $2.4 million of revenue related to the Gilead Collaboration Agreements during the six months ended June 30, 2021. Deferred revenue related to the Gilead Collaboration Agreements of $41.7 million as of June 30, 2021, which was comprised of the $142.5 million initial transaction price, less $100.8 million of license and collaboration revenue recognized from the effective date of the contract, will be recognized as the combined performance obligation is satisfied.
We also recorded a $1.4 million receivable as of June 30, 2021, for research and development and other services provided.
During the six months ended June 30, 2021, we did not recognize any revenue from amounts included in the contract asset or the contract liability balances from performance obligations satisfied in previous periods. None of the costs to obtain or fulfill a contract were capitalized.
14
Note J - Share-based Compensation Plans
We primarily use the Black-Scholes option pricing model to value stock options granted to employees and non-employees, including stock options granted to members of our Board of Directors. However, the fair value of stock option market-based awards is calculated based on a Monte Carlo simulation as of the date of issuance. All stock options have 10-year terms and generally vest ratably over a 3 or 4-year period.
A summary of option activity for the six months ended June 30, 2021 is presented below:
|
|
|
Options |
|
|
Weighted Average Exercise Price |
|
|
Weighted Average Remaining Contractual Term (in years) |
|
|
Aggregate Intrinsic Value |
|
||||
|
Outstanding at December 31, 2020 |
|
|
28,966,901 |
|
|
$ |
3.70 |
|
|
|
|
|
|
|
|
|
|
Granted |
|
|
7,965,208 |
|
|
|
3.38 |
|
|
|
|
|
|
|
|
|
|
Exercised |
|
|
(1,703,924 |
) |
|
|
3.14 |
|
|
|
|
|
|
|
|
|
|
Forfeited |
|
|
(908,023 |
) |
|
|
3.15 |
|
|
|
|
|
|
|
|
|
|
Expired |
|
|
(530,919 |
) |
|
|
5.71 |
|
|
|
|
|
|
|
|
|
|
Outstanding at June 30, 2021 |
|
|
33,789,243 |
|
|
$ |
3.64 |
|
|
|
7.60 |
|
|
$ |
63,679,505 |
|
|
Vested or expected to vest at June 30, 2021 |
|
|
33,789,243 |
|
|
$ |
3.64 |
|
|
|
7.60 |
|
|
$ |
63,679,505 |
|
|
Exercisable at June 30, 2021 |
|
|
14,730,962 |
|
|
$ |
3.97 |
|
|
|
5.98 |
|
|
$ |
23,402,449 |
|
The weighted average grant-date fair values of stock options granted during the six months ended June 30, 2021 and 2020 were $1.99 and $1.46, respectively.
As of June 30, 2021, there was approximately $38.7 million of total unrecognized share-based compensation expense related to these stock options and stock options granted under a subsidiary plan which, if all milestones are achieved, will be recognized over a weighted average period of 2.7 years.
Certain employees and consultants have been granted non-vested stock. The fair value of non-vested market-based awards is calculated based on a Monte Carlo simulation as of the date of issuance. The fair value of other non-vested stock is calculated based on the closing sale price of our common stock on the date of issuance.
A summary of non-vested stock activity for the six months ended June 30, 2021 is presented below:
|
|
|
Non-vested Shares |
|
|
Weighted Average Grant Date Fair Value |
|
||
|
Outstanding at December 31, 2020 |
|
|
886,816 |
|
|
$ |
2.14 |
|
|
Granted |
|
|
1,813,651 |
|
|
|
3.05 |
|
|
Vested |
|
|
(1,485,651 |
) |
|
|
2.87 |
|
|
Forfeited |
|
|
— |
|
|
|
— |
|
|
Outstanding at June 30, 2021 |
|
|
1,214,816 |
|
|
$ |
2.69 |
|
As of June 30, 2021, there was approximately $1.3 million of unrecognized share-based compensation expense related to these non-vested shares which will be recognized over a period of 1.6 years.
During the six months ended June 30, 2021, 104,372 shares were issued under the 2019 Employee Stock Purchase Plan and 1,703,924 shares were issued as a result of stock option exercises. Additionally, 1,485,651 shares were issued as payment for a portion of the 2020 employee bonus, with 521,442 of those shares being withheld to cover taxes, resulting in a net share issuance of 964,209.
15
The impact on our results of operations from share-based compensation for the three and six months ended June 30, 2021 and 2020, was as follows (in thousands):
|
|
|
Three Months Ended June 30, |
|
|
Six Months Ended June 30, |
|
||||||||||
|
|
|
2021 |
|
|
2020 |
|
|
2021 |
|
|
2020 |
|
||||
|
Research and development |
|
$ |
1,296 |
|
|
$ |
839 |
|
|
$ |
2,164 |
|
|
$ |
2,042 |
|
|
General and administrative |
|
|
4,135 |
|
|
|
1,625 |
|
|
|
7,199 |
|
|
|
2,819 |
|
|
Total share-based compensation expense |
|
$ |
5,431 |
|
|
$ |
2,464 |
|
|
$ |
9,363 |
|
|
$ |
4,861 |
|
Note K – Restricted Cash
As of June 30, 2021, and December 31, 2020, we maintained non-current restricted cash of $2.7 million and $2.6 million, respectively. This amount is included within “Other long-term assets” in our condensed consolidated balance sheets, and as of June 30, 2021, is comprised of letters of credit required under two of our facility leases.
The following table provides a reconciliation of cash, cash equivalents and restricted cash that sums to the total of the same such amounts shown in the condensed consolidated statements of cash flows (in thousands):
|
|
|
Six Months Ended June 30, 2021 |
|
|
Six Months Ended June 30, 2020 |
|
||||||||||
|
|
|
Beginning of Period |
|
|
End of Period |
|
|
Beginning of Period |
|
|
End of Period |
|
||||
|
Cash and cash equivalents |
|
$ |
99,871 |
|
|
$ |
73,543 |
|
|
$ |
61,808 |
|
|
$ |
79,171 |
|
|
Restricted cash |
|
|
2,634 |
|
|
|
2,669 |
|
|
|
— |
|
|
|
— |
|
|
Cash, cash equivalents and restricted cash |
|
$ |
102,505 |
|
|
$ |
76,212 |
|
|
$ |
61,808 |
|
|
$ |
79,171 |
|
Note L – Equity
At the Market Offerings
During the three and six months ended June 30, 2021, we received net proceeds of approximately $9.1 million and $70.0 million from the sale of approximately 3.4 million and 22.3 million shares of our common stock at an average price per share of approximately $2.78 and $3.23, respectively, in at-the-market offerings under our At Market Issuance Sales Agreement (the “Sales Agreement”) with B. Riley FBR, Inc. (“B. Riley”) dated July 22, 2020.
Series C-1 Preferred Stock Conversion
During the three and six months ended June 30, 2021, holders of shares of Series C-1 Preferred Stock converted a portion of such shares into 2.0 million and 4.0 million shares, respectively, of our common stock. As of June 30, 2021, 8,459 shares of Series C-1 Convertible Preferred Stock remained outstanding.
Note M - Recent Accounting Pronouncements
Recently Issued and Adopted
In December 2019, the Financial Accounting Standards Board (“FASB”) issued ASU No. 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes (“ASU 2019-12”). ASU 2019-12 enhances and simplifies multiple aspects of the income tax accounting guidance in ASC 740. We adopted the standard on January 1, 2021. The adoption did not have a material impact on our consolidated financial statements.
Recently Issued, Not Yet Adopted
In January 2017, the FASB issued ASU 2017-04, Intangibles – Goodwill and Other (Topic 350) that will eliminate the requirement to calculate the implied fair value of goodwill to measure a goodwill impairment charge. Instead, an impairment charge will be based on the excess of a reporting unit’s carrying amount over its fair value. The guidance is effective for the Company in the first quarter of fiscal 2023. Early adoption is permitted. We do not anticipate the adoption of this guidance to have a material impact on our consolidated financial statements, absent any goodwill impairment.
16
No other new accounting pronouncement issued or effective during the six months ended June 30, 2021 had or is expected to have a material impact on our consolidated financial statements or disclosures.
Note M – Subsequent Events
License Agreement
On May 17, 2021, we entered into a License, Development and Commercialization Agreement (“License Agreement”) with Bristol Myers Squibb Company (“BMS”) to collaborate on the development and commercialization of our pre-clinical proprietary anti-TIGIT bispecific antibody program AGEN1777. Pursuant to the License Agreement, we received an upfront cash payment of $200.0 million and are eligible to receive up to $1.36 billion in aggregate development, regulatory and commercial milestone payments plus the tiered royalties described below. In July 2021, the License Agreement closed, and we received the $200.0 million upfront payment.
Under the License Agreement, we granted BMS an exclusive worldwide license under certain of our intellectual property rights to develop, manufacture and commercialize AGEN1777 and its derivatives in all fields; provided, we retained an option to access the licensed antibodies for use in clinical studies in combination with certain of our other pipeline assets subject to certain restrictions. In exchange, BMS is responsible for all of the development, regulatory approval, manufacturing and commercialization costs with respect to products containing AGEN1777. In addition to the upfront and potential milestone payments described above, we will receive tiered double-digit royalties on worldwide net sales of products containing AGEN1777 ranging from the low double-digit to mid-teens percent. Additionally, we have the option, but not the obligation, to co-fund a minority of the global development costs of products containing AGEN1777 or its derivatives, in exchange for increased tiered royalties on U.S. net sales of co-funded products ranging from the mid-teens to low twenties percent and ex-U.S. net sales of co-funded products ranging from the low double digits to mid-teens percent. All royalties are subject to certain reductions under certain circumstances as described in the License Agreement. Finally, we also have the option to co-promote AGEN1777 in the U.S.
The royalty term shall terminate on a product-by-product and country-by-country basis on the latest of (i) 10 year anniversary of the first commercial sale of such product in such country, (ii) the expiration of any regulatory exclusivity period that covers such product in such country, and (iii) the expiration of the last-to-expire licensed patent that covers such product in such country.
The License Agreement includes customary representations and warranties, covenants, indemnification obligations for a transaction of this nature. Under the terms of the License Agreement, we and BMS each have the right to terminate the agreement for material breach by, or insolvency of, the other party following notice, and if applicable, a cure period. BMS may also terminate the License Agreement in its entirety, or on a product-by-product or country-by-country basis, for convenience upon 180 days’ notice.
Legal Proceedings
In July 2021, an Agenus stockholder filed a derivative complaint against members of our board of directors and certain senior management in the Delaware Court of Chancery with Agenus as a nominal defendant. The complaint challenges equity awards made in December 2020 on the ground that they were improperly granted. The complaint asserts claims for breach of fiduciary duty, waste, and unjust enrichment. The plaintiff seeks an award of damages to Agenus, an order rescinding the challenged awards, granting other equitable relief, such as disgorgement, and an award of attorneys’ fees. The defendants intend to pursue dismissal of the complaint in its entirety. The financial impact of the plaintiff's claims are not estimable.
17
|
Item 2. |
Management’s Discussion and Analysis of Financial Condition and Results of Operations |
Forward Looking Statements
This Quarterly Report on Form 10-Q and other written and oral statements we make from time to time contain certain “forward-looking” statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 (the “Exchange Act”). You can identify these forward-looking statements by the fact they use words such as “could,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe,” “will,” “potential,” “opportunity,” “future” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. You can also identify forward-looking statements by the fact that they do not relate strictly to historical or current facts. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes to differ materially from current expectations. These statements relate to, among other things, our business strategy, our research and development, our product development efforts, our ability to commercialize our product candidates, the activities of our licensees, our prospects for initiating partnerships or collaborations, the timing of the introduction of products, the effect of new accounting pronouncements, uncertainty regarding our future operating results and our profitability, anticipated sources of funds as well as our plans, objectives, expectations, and intentions.
We have included more detailed descriptions of these risks and uncertainties and other risks and uncertainties applicable to our business that we believe could cause actual results to differ materially from any forward-looking statements in Part II-Item 1A “Risk Factors” of this Quarterly Report on Form 10-Q. We encourage you to read those descriptions carefully. Although we believe we have been prudent in our plans and assumptions, no assurance can be given that any goal or plan set forth in forward-looking statements can be achieved. We caution investors not to place significant reliance on forward-looking statements contained in this document; such statements need to be evaluated in light of all the information contained in this document. Furthermore, the statements speak only as of the date of this document, and we undertake no obligation to update or revise these statements.
ASV™, Agenus™, AutoSynVax™, MiNK™, PSV™, PhosPhoSynVax™, Prophage™, Retrocyte Display™ and Stimulon™ are trademarks of Agenus Inc. and its subsidiaries. All rights reserved.
Overview
We are a clinical-stage immuno-oncology (“I-O”) company advancing an extensive pipeline of immune checkpoint antibodies, adoptive cell therapies and neoantigen vaccines, to fight cancer and infections. Our business is designed to drive success in I-O through speed, innovation and effective combination therapies. We believe that combination therapies and a deep understanding of each patient’s cancer will drive substantial expansion of the patient population benefiting from current I-O therapies. In addition to a diverse pipeline, we have assembled fully integrated end-to-end capabilities including novel target discovery, antibody generation, cell line development and current good manufacturing practice manufacturing. We believe that these fully integrated capabilities enable us to produce novel candidates on timelines that are shorter than the industry standard. Leveraging our science and capabilities, we have forged important partnerships to advance our innovation.
We are developing a comprehensive I-O portfolio driven by the following platforms and programs, which we intend to utilize individually and in combination:
|
|
• |
our multiple antibody discovery platforms, including our proprietary display technologies, designed to drive the discovery of future CPM antibody candidates; |
|
|
• |
our antibody candidate programs, including our CPM programs; |
|
|
• |
our vaccine programs, including Prophage™, AutoSynVax™ and PhosPhoSynVax™; |
|
|
• |
our saponin-based vaccine adjuvants, principally our QS-21 Stimulon™ adjuvant, or QS-21 Stimulon; and |
|
|
• |
our cell therapy subsidiary, MiNK Therapeutics, Inc. (“MiNK Therapeutics”), which is designed to drive the advancement of a novel allogeneic invariant natural killer T cell (“iNKT”) therapy in immune diseases. |
We assess development, commercialization and partnering strategies for each of our product candidates periodically based on several factors, including pre-clinical and clinical trial results, competitive positioning and funding requirements and resources. Our anti-CTLA-4 and anti-PD-1 programs (zalifrelimab and balstilimab, respectively) are in late phase clinical trials designed to support BLA filings under the U.S. Food and Drug Administration (“FDA”) accelerated approval pathway. We announced interim data from these trials in February, March and September 2020. We initiated the rolling submission of our BLA for balstilimab monotherapy to treat 2nd line cervical cancer in September 2020. We completed this BLA filing in April 2021 and the FDA accepted this application in June 2021, granting it priority review with a Prescription Drug User Fee Act (“PDUFA”) target action date of December 16, 2021. We expect to solidify our strategy for the balstilimab/zalifrelimab combination filing, pending further discussion with the FDA.
18
We have formed collaborations with companies such as Bristol Myers Squibb Company (“BMS”), Betta Pharmaceuticals Co., Ltd. (“Betta”), Gilead Sciences, Inc. (“Gilead”), Incyte Corporation (“Incyte”), Merck Sharpe & Dohme (“Merck”) and Recepta Biopharma SA (“Recepta”). Through these alliances, as well as our own internal programs, we currently have more than a dozen antibody programs in pre-clinical or clinical development.
Pursuant to our collaboration agreement with Incyte, we have exclusively licensed to Incyte monospecific antibodies targeting GITR, OX40, TIM-3 and LAG-3, which Incyte is currently advancing in various clinical trials, as well as an additional undisclosed target that Incyte is advancing in preclinical studies. Under the terms of our agreement, Incyte is responsible for all future development expenses, and we are eligible to receive up to an additional $500.0 million in potential milestone payments plus royalties on any future sales. Pursuant to our collaboration and license agreement with Merck, we exclusively licensed to Merck a monospecific antibody targeting ILT4, which Merck is advancing in a Phase 2 clinical trial. Under the terms of our agreement, Merck is responsible for all future development expenses, and we are eligible to receive up to an additional $85.0 million in potential milestone payments plus royalties on any future sales. In September 2018, we, through our wholly-owned subsidiary, Agenus Royalty Fund, LLC, entered into a royalty purchase agreement (the “XOMA Royalty Purchase Agreement”) with XOMA (US) LLC (“XOMA”). Pursuant to the terms of the XOMA Royalty Purchase Agreement, XOMA purchased 33% of all future royalties and 10% of all future milestone payments that we are entitled to receive from Incyte and Merck, net of certain of our obligations to a third party. After taking into account our obligations under the XOMA Royalty Purchase Agreement, as of June 30, 2021, we remain eligible to receive up to $450.0 million and $76.5 million in potential development, regulatory and commercial milestones from Incyte and Merck, respectively.
In December 2018, we entered into a series of agreements with Gilead to collaborate on the development and commercialization of up to five novel I-O therapies (the “Gilead Collaboration Agreements”). Pursuant to the Gilead Collaboration Agreements, Gilead received worldwide exclusive rights to our bispecific antibody, AGEN1423, as well as the exclusive option to exclusively license AGEN1223, a bispecific antibody, and AGEN2373, a monospecific antibody. All three assets have entered clinical development. In November 2020, Gilead elected to return AGEN1423 to us and to voluntarily terminate the license agreement effective as of February 4, 2021. The option agreements remain in place, and we are responsible for developing each program up to the option decision points, at which time Gilead may acquire exclusive rights to the programs on option exercise. For either, but not both, of the option programs, we have the right to opt-in to share Gilead’s development and commercialization costs in the United States in exchange for a profit (loss) share on a 50:50 basis and revised milestone payments. Pursuant to the terms of the Gilead option agreements, we remain eligible to receive up to $100.0 million in option exercise fees and, if exercised, up to an additional $1.0 billion in aggregate milestone payments, as well as royalties on any future sales.
In June 2020, we entered into a license and collaboration agreement (the “Betta License Agreement”) with Betta, pursuant to which we granted Betta an exclusive license to develop, manufacture and commercialize balstilimab and zalifrelimab in Greater China. Under the terms of the Betta License Agreement, we received $15.0 million upfront and are eligible to receive up to $100.0 million in milestone payments plus royalties on any future sales in Greater China.
In May 2021, we entered into a License, Development and Commercialization Agreement (“BMS License Agreement”) with BMS to collaborate on the development and commercialization of our pre-clinical proprietary anti-TIGIT bispecific antibody program AGEN1777. Under the BMS License Agreement, we granted BMS an exclusive worldwide license under certain of our intellectual property rights to develop, manufacture and commercialize AGEN1777 and its derivatives in all fields; provided, we retained an option to access the licensed antibodies for use in clinical studies in combination with certain of our other pipeline assets subject to certain restrictions. Pursuant to the BMS License Agreement, we received an upfront cash payment of $200.0 million in July 2021 and are eligible to receive up to $1.36 billion in aggregate development, regulatory and commercial milestone payments plus tiered royalties. In exchange, BMS is responsible for all of the development, regulatory approval, manufacturing and commercialization costs with respect to products containing AGEN1777. We have the option, but not the obligation, to co-fund a minority of the global development costs of products containing AGEN1777 or its derivatives, in exchange for increased tiered royalties. Finally, we also have the option to co-promote AGEN1777 in the U.S.
Our QS-21 Stimulon adjuvant is partnered with GlaxoSmithKline (“GSK”) and is a key component in multiple GSK vaccine programs. These programs are in various stages, with the most advanced being GSK’s shingles vaccine, Shingrix. In October 2017, GSK’s shingles vaccine was approved in the United States by the FDA. In January 2018, we entered into a Royalty Purchase Agreement with Healthcare Royalty Partners III, L.P. and certain of its affiliates (together, “HCR”), pursuant to which HCR purchased 100% of our worldwide rights to receive royalties from GSK on GSK’s sales of vaccines containing our QS-21 Stimulon adjuvant. We do not incur clinical development costs for products partnered with GSK. We were also entitled to receive up to $40.35 million in milestone payments from HCR based on sales of GSK’s vaccines as follows: (i) $15.1 million upon reaching $2.0 billion last-twelve-months net sales any time prior to 2024 (the “First HCR Milestone”) and (ii) $25.25 million upon reaching $2.75 billion last-twelve-months net sales any time prior to 2026 (the “Second HCR Milestone”). We received the First HCR Milestone after GSK’s net sales of Shingrix for the twelve months ended December 31, 2019 exceeded $2.0 billion, and we remain eligible to receive the Second HCR Milestone.
19
Our business activities include product research and development, intellectual property prosecution, manufacturing, regulatory and clinical affairs, corporate finance and development activities, and support of our collaborations. Our product candidates require clinical trials and approvals from regulatory agencies, as well as acceptance in the marketplace. Part of our strategy is to develop and commercialize some of our product candidates by continuing our existing arrangements with academic and corporate collaborators and licensees and by entering into new collaborations.
Our subsidiary MiNK Therapeutics (formerly AgenTus Therapeutics, Inc.) is focused on the development of unmodified iNKT cell therapies for the treatment of cancer and other life-threatening illnesses. In May 2020 and June 2020, the FDA cleared Investigational New Drug applications for AGENT-797, an allogeneic iNKT therapy, for the treatment of patients with hematological malignancies, including multiple myeloma and B cell lymphoma, and COVID-19-realted pneumonia, respectively. In November 2020, MiNK Therapeutics dosed its first COVID-19 patient with AGENT-797, and trials for hematological malignancies commenced in April 2021. In July 2021 MiNK Therapeutics announced that it had confidentially submitted a draft registration statement on Form S-1 with the Securities and Exchange Commission (the "SEC") relating to the proposed initial public offering of its common stock. The number of shares to be offered and the price range for the proposed offering have not yet been determined. The initial public offering is expected to take place after the SEC completes its review process, subject to market and other conditions. MiNK Therapeutics licenses intellectual property assets from Agenus and has its own governance.
Historical Results of Operations
Three months ended June 30, 2021 compared to the three months ended June 30, 2020
Research and development revenue
We recognized research and development revenue of approximately $1.7 million and $18.1 million during the three months ended June 30, 2021 and 2020, respectively. Research and development revenues in the second quarter of 2021 primarily consisted of $1.4 million related to the recognition of deferred revenue earned under our Gilead Collaboration Agreements and $0.2 million of research service revenue earned under our Incyte Collaboration Agreement. Research and development revenues in the second quarter of 2020 primarily consisted of $4.0 million related to the recognition of deferred revenue earned under our Gilead Collaboration Agreements and $13.9 million related to the recognition of an upfront fee under our Betta License Agreement.
Non-cash royalty revenue related to the sale of future royalties
In January 2018, we sold 100% of our worldwide rights to receive royalties from GSK on sales of GSK’s vaccines containing our QS-21 Stimulon adjuvant to HCR. As described in Note F to our Condensed Consolidated Financial Statements, this transaction has been recorded as a liability that amortizes over the estimated life of our Royalty Purchase Agreement with HCR. As a result of this liability accounting, even though the royalties are remitted directly to HCR, we record these royalties from GSK as revenue. During both the three months ended June 30, 2021 and 2020, we recognized approximately $7.8 million, in non-cash royalty revenue related to our agreement with GSK.
Research and development expense
Research and development expense includes the costs associated with our internal research and development activities, including compensation and benefits, occupancy costs, manufacturing costs, costs of consultants, and administrative costs. Research and development expense increased 18% to $45.5 million for the three months ended June 30, 2021 from $38.6 million for the three months ended June 30, 2020. Increased expenses in the three months ended June 30, 2021 primarily relate to a $5.7 million increase in third-party services and other related expenses related to the advancement of our antibody programs, a $0.3 million increase in personnel related expenses, a $0.6 million increase in expenses attributable to the activities of our subsidiaries and a $0.3 million increase in other research and development expenses.
General and administrative expense
General and administrative expense consists primarily of personnel costs, facility expenses, and professional fees. General and administrative expenses increased 17% to $16.7 million for the three months ended June 30, 2021 from $14.2 million for the three months ended June 30, 2020. Increased expenses in the three months ended June 30, 2021 primarily relate to a $2.0 million increase in personnel related expenses, primarily due to increased share-based compensation expense, a $0.4 million increase in professional fees, primarily due to increased expenses related to commercial readiness activities and a $0.2 million increase in expenses attributable to the activities of our subsidiaries.
Contingent purchase price consideration fair value adjustment
Contingent purchase price consideration fair value adjustment represents the change in the fair value of our purchase price considerations, which mainly resulted from changes in our market capitalization and share price and changes in the credit spread since each reporting period end. The fair value of our contingent purchase price considerations is mainly based on estimates from a Monte Carlo simulation of our market capitalization and share price.
20
Non-operating income (expense)
Non-operating income (expense) includes our foreign currency translation adjustment and other income or expense. Non-operating expense increased $0.6 million for the three months ended June 30, 2021, from expense of $0.3 million for the three months ended June 30, 2020 to expense of $0.9 million for the three months ended June 30, 2021, primarily due to increased foreign currency exchange losses in the second quarter of 2021 compared to the second quarter of 2020.
Interest expense, net
Interest expense, net increased to approximately $16.7 million for the three months ended June 30, 2021 from $14.6 million for the three months ended June 30, 2020, due to increased non-cash interest recorded in connection with our Royalty Purchase Agreement with HCR.
Six months ended June 30, 2021 compared to the six months ended June 30, 2020
Research and development revenue
We recognized research and development revenue of approximately $3.3 million and $20.0 million during the six months ended June 30, 2021 and 2020, respectively. Research and development revenues in the first half of 2021 primarily consisted of $2.4 million related to the recognition of deferred revenue earned under our Gilead Collaboration Agreements and $0.7 million of research service revenue earned under our Incyte Collaboration Agreement. Research and development revenues in the first half of 2020 primarily consisted of $5.8 million related to the recognition of deferred revenue earned under our Gilead Collaboration Agreements and $13.9 million related to the recognition of an upfront fee under our Betta License Agreement.
Non-cash royalty revenue related to the sale of future royalties
In January 2018, we sold 100% of our worldwide rights to receive royalties from GSK on sales of GSK’s vaccines containing our QS-21 Stimulon adjuvant to HCR. As described in Note F to our Condensed Consolidated Financial Statements, this transaction has been recorded as a liability that amortizes over the estimated life of our Royalty Purchase Agreement with HCR. As a result of this liability accounting, even though the royalties are remitted directly to HCR, we will record these royalties from GSK as revenue. During the six months ended June 30, 2021 and 2020, we recognized approximately $16.3 million and $21.0 million, respectively, in non-cash royalty revenue related to our agreement with GSK.
Research and development expense
Research and development expense includes the costs associated with our internal research and development activities, including compensation and benefits, occupancy costs, manufacturing costs, costs of consultants, and administrative costs. Research and development expense increased 10% to $82.2 million for the six months ended June 30, 2021 from $74.9 million for the six months ended June 30, 2020. Increased expenses in the six months ended June 30, 2021 primarily relate to a $5.6 million increase in third-party services and other related expenses related to the advancement of our antibody programs, a $1.3 million increase in expenses attributable to the activities of our subsidiaries and a $0.4 million increase in other research and development expenses.
General and administrative expense
General and administrative expense consists primarily of personnel costs, facility expenses, and professional fees. General and administrative expenses increased 33% to $33.0 million for the six months ended June 30, 2021 from $24.8 million for the six months ended June 30, 2020. Increased expenses in the six months ended June 30, 2021 primarily relate to a $1.4 million increase in professional fees, primarily due to increased expenses related to commercial readiness activities, a $4.7 million increase in personnel related expenses, primarily due to both increased share-based compensation expense and increased headcount, a $1.4 million increase in expenses attributable to the activities of our subsidiaries and a $0.7 million increase in other general and administrative expenses.
Contingent purchase price consideration fair value adjustment
Contingent purchase price consideration fair value adjustment represents the change in the fair value of our purchase price considerations, which mainly resulted from changes in our market capitalization and share price and changes in the credit spread since each reporting period end. The fair value of our contingent purchase price considerations is mainly based on estimates from a Monte Carlo simulation of our market capitalization and share price.
Non-operating income (expense)
Non-operating income (expense) includes our foreign currency translation adjustment and other income or expense. Non-operating income increased $3.3 million for the six months ended June 30, 2021, from expense of $1.4 million for the six months ended June 30, 2020 to income of $1.9 million for the six months ended June 30, 2021, primarily due to our increased foreign currency exchange gains in the first half of 2021 compared to the first half of 2020.
Interest expense, net:
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Interest expense, net increased to approximately $32.6 million for the six months ended June 30, 2021 from $28.7 million for the six months ended June 30, 2020, due to increased non-cash interest recorded in connection with our Royalty Purchase Agreement with HCR.
Research and Development Programs
For the six months ended June 30, 2021, our research and development programs consisted largely of our antibody programs as indicated in the following table (in thousands).
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Six Months Ended June 30, |
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Year Ended December 31, |
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||||||||||
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Research and Development Program |
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Product |
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2021 |
|
|
2020 |
|
|
2019 |
|
|
2018 |
|
|
Prior to 2018 |
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|
Total |
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||||||
|
Antibody programs* |
|
Various |
|
$ |
68,191 |
|
|
$ |
118,200 |
|
|
$ |
126,400 |
|
|
$ |
97,011 |
|
|
$ |
256,288 |
|
|
$ |
666,090 |
|
|
Heat shock proteins for cancer |
|
Prophage and ASV |
|
|
495 |
|
|
|
1,076 |
|
|
|
13,235 |
|
|
|
13,235 |
|
|
|
335,890 |
|
|
|
363,931 |
|
|
Vaccine adjuvant |
|
QS-21 Stimulon |
|
|
1,331 |
|
|
|
304 |
|
|
|
872 |
|
|
|
211 |
|
|
|
14,098 |
|
|
|
16,816 |
|
|
Cell therapies and other research and development programs |
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Various |
|
|
12,167 |
|
|
|
23,037 |
|
|
|
27,832 |
|
|
|
14,143 |
|
|
|
78,342 |
|
|
|
155,521 |
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|
Total research and development expenses |
|
|
|
$ |
82,184 |
|
|
$ |
142,617 |
|
|
$ |
168,339 |
|
|
$ |
124,600 |
|
|
$ |
684,618 |
|
|
$ |
1,202,358 |
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* |
Prior to 2014, costs were incurred by 4-AB, which we acquired in February 2014. |
Research and development program costs include compensation and other direct costs plus an allocation of indirect costs, based on certain assumptions and our review of the status of each program. Our product candidates are in various stages of development and significant additional expenditures will be required if we start new clinical trials, encounter delays in our programs, apply for regulatory approvals, continue development of our technologies, expand our operations, and/or bring our product candidates to market. The total cost of any particular clinical trial is dependent on a number of factors such as trial design, length of the trial, number of clinical sites, number of patients, and trial sponsorship. The process of obtaining and maintaining regulatory approvals for new therapeutic products is lengthy, expensive, and uncertain. Because of the current stage of our product candidates, among other factors, we are unable to reliably estimate the cost of completing our research and development programs or the timing for bringing such programs to various markets or substantial partnering or out-licensing arrangements, and, therefore, when, if ever, material cash inflows are likely to commence. Active programs involving QS-21 Stimulon depend on our licensee successfully completing clinical trials, successfully manufacturing QS-21 Stimulon to meet demand, obtaining regulatory approvals and successfully commercializing product candidates containing QS-21 Stimulon.
Liquidity and Capital Resources
We have incurred annual operating losses since inception, and we had an accumulated deficit of $1.6 billion as of June 30, 2021. We expect to incur significant losses over the next several years as we continue development of our technologies and product candidates, manage our regulatory processes, initiate and continue clinical trials, and prepare for potential commercialization of products. To date, we have financed our operations primarily through corporate partnerships, advance royalty sales and the issuance of equity. From our inception through June 30, 2021, we have raised aggregate net proceeds of approximately $1.5 billion through the sale of common and preferred stock, the exercise of stock options and warrants, proceeds from our Employee Stock Purchase Plan, royalty monetization transactions, and the issuance of convertible and other notes.
We maintain an effective registration statement (the “Registration Statement”), covering an unlimited amount of common stock, preferred stock, warrants, debt securities and units. The Registration Statement includes prospectuses covering the offer, issuance and sale of up to 100 million shares of our common stock from time to time in “at-the-market offerings” pursuant to an At Market Issuance Sales Agreement (the “Sales Agreement”) with B. Riley FBR, Inc. as our sales agent. We sold approximately 22.3 million shares of our common stock pursuant to the Sales Agreement during the six months ended June 30, 2021, and received aggregate net proceeds totaling $70.0 million. As of June 30, 2021, we had approximately 60.0 million shares that remained available for sale under the Sales Agreement.
As of June 30, 2021, we had debt outstanding of $20.0 million in principal. In February 2015, we issued senior subordinated promissory notes in the aggregate principal amount of $14.0 million with annual interest at 8% (the “2015 Subordinated Notes”). In February 2020, we amended $13.5 million of the 2015 Subordinated Notes, extending the due date by three years to February 2023.
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The remaining $0.5 million of the 2015 Subordinated Notes were repaid in February 2020. In April 2020, we repaid an additional $0.5 million of the 2015 Subordinated Notes, leaving $13.0 million outstanding. In May 2020, we received $6.2 million under the Paycheck Protection Program of the Coronavirus Aid, Relief and Economic Security Act of 2020 (the “CARES Act”) which is classified as debt in our condensed consolidated balance sheet as we cannot yet determine if the amount will be partially or fully forgiven.
Our cash and cash equivalents at June 30, 2021 were $73.5 million, a decrease of $26.3 million from December 31, 2020.
During the past five years, we have successfully financed our operations through income and revenues generated from corporate partnerships, advance royalty sales and issuance of equity. Based on our current plans and projections, we believe our quarter end cash resources of $73.5 million as of June 30, 2021, plus the $200.0 million fee received subsequently in connection with our transaction with BMS, will be sufficient to satisfy our liquidity requirements for more than one year from when these financial statements were issued. We are presently in partnership, and out licensing discussions and contemplating additional financial transactions which, if consummated, could extend our cash resources substantially beyond 2022.
Management continues to address the Company’s liquidity position and has the flexibility to adjust spending as needed in order to preserve liquidity. In March 2020, in response to the COVID-19 pandemic, we streamlined our organization, which included a headcount reduction, and our CEO, Dr. Garo Armen, elected to receive his base salary in stock rather than cash for the remainder of 2020 and through the first half of 2021. We continuously evaluate the likelihood of success of our programs. As such, our decisions to continue to fund or eliminate funding of each of our programs are predicated on these determinations, on an ongoing basis. We are prepared to discontinue funding of any activities that do not impact our core priorities if they do not prove to be feasible, and to restrict capital expenditures and/or reduce the scale of our operations. We expect our potential sources of funding to include: (1) collaborations, out-licensing and/or partnering opportunities for our portfolio programs and product candidates with multiple parties (2) milestone payments from our existing partnerships (3) consummating additional third-party agreements, (4) selling assets, (5) securing project financing and/or (6) selling equity securities.
Our future cash requirements include, but are not limited to, supporting clinical trial and regulatory efforts and continuing our other research and development programs. Since inception, we have entered into various agreements with contract manufacturers, institutions, and clinical research organizations (collectively “third party providers”) to perform pre-clinical activities and to conduct and monitor our clinical studies and trials. Under these agreements, subject to the enrollment of patients and performance by the applicable third-party provider, we have estimated our total payments to be $476.8 million over the term of the related activities. Through June 30, 2021, we have expensed $351.8 million as research and development expenses and $342.9 million has been paid under these agreements. The timing of expense recognition and future payments related to these agreements is subject to the enrollment of patients and performance by the applicable third-party provider. We plan to enter into additional agreements with third party providers and we anticipate significant additional expenditures will be required to initiate and advance our various programs.
Part of our strategy is to develop and commercialize some of our product candidates by continuing our existing collaboration arrangements with academic and collaboration partners and licensees and by entering into new collaborations. As a result of our collaboration agreements, we will not completely control the efforts to attempt to bring those product candidates to market. For example, our collaboration with Incyte for the development, manufacture and commercialization of CPM antibodies against certain targets is managed by a joint steering committee, which is controlled by Incyte.
Net cash used in operating activities for the six months ended June 30, 2021 and 2020 was $98.3 million and $71.9 million, respectively. Our future ability to generate cash from operations will depend on achieving regulatory approval and market acceptance of our product candidates, achieving benchmarks as defined in existing collaboration agreements, and our ability to enter into new collaborations. See “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Forward Looking Statements” in Part I, Item 2, and the risks highlighted under Part II, Item 1A. “Risk Factors”, of this Quarterly Report on Form 10-Q.
Off-Balance Sheet Arrangements
We did not have any off-balance sheet arrangements as of June 30, 2021.
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Item 3. |
Quantitative and Qualitative Disclosures About Market Risk |
Our primary market risk exposure is foreign currency exchange rate risk. International revenues and expenses are generally transacted by our foreign subsidiaries and are denominated in local currency. Less than 0.1%, and approximately 0.3% of our cash used in operations for the six months ended June 30, 2021 and the year ended December 31, 2020, respectively, was from our foreign subsidiaries. We are also exposed to foreign currency exchange rate fluctuation risk related to our transactions denominated in foreign currencies. We do not currently employ specific strategies, such as the use of derivative instruments or hedging, to manage these
23
exposures. Our currency exposures vary but are primarily concentrated in the Euro, Swiss Franc and British Pound, in large part due to our subsidiaries, AgenTus Therapeutics SA, a company formerly with operations in Belgium, Agenus Switzerland a company formerly with operations in Switzerland and Agenus UK Limited, with operations in England. There has been no material change to our interest rate exposure and our approach toward interest rate and foreign currency exchange rate exposures, as described in our Annual Report on Form 10-K for the year ended December 31, 2020.
We had cash and cash equivalents at June 30, 2021 of $73.5 million, which are exposed to the impact of interest rate changes, and our interest income fluctuates as interest rates change. Additionally, in the normal course of business, we are exposed to fluctuations in interest rates as we seek debt financing and invest excess cash. Due to the short-term nature of our investments in money market funds and U.S. Treasury Bills, our carrying value approximates the fair value of these investments at June 30, 2021.
We invest our cash and cash equivalents in accordance with our investment policy. The primary objectives of our investment policy are to preserve principal, maintain proper liquidity to meet operating needs, and maximize yields. We review our investment policy annually and amend it as deemed necessary. Currently, the investment policy prohibits investing in any structured investment vehicles and asset-backed commercial paper. Although our investments are subject to credit risk, our investment policy specifies credit quality standards for our investments and limits the amount of credit exposure from any single issue, issuer, or type of investment. We do not invest in derivative financial instruments. Accordingly, we do not believe that there is currently any material market risk exposure with respect to derivatives or other financial instruments that would require disclosure under this item.
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Item 4. |
Controls and Procedures |
Evaluation of Disclosure Controls and Procedures
Under the supervision and with the participation of our management, including our Principal Executive Officer and Principal Financial Officer, we conducted an evaluation of the effectiveness of our disclosure controls and procedures, as such term is defined under Rule 13a-15(e) and Rule 15d-15(e) promulgated under the Exchange Act. Based on this evaluation, our Principal Executive Officer and our Principal Financial Officer concluded that, as of the end of the period covered by this Quarterly Report on Form 10-Q, our disclosure controls and procedures were effective and were designed to ensure that information we are required to disclose in the reports that we file or submit under the Exchange Act is accumulated and communicated to management, including our Principal Executive Officer and Principal Financial Officer, as appropriate, to allow timely decisions regarding required disclosure, and is recorded, processed, summarized and reported within the time periods specified in the Securities and Exchange Commission’s rules and forms. It should be noted that any system of controls is designed to provide reasonable, but not absolute, assurances that the system will achieve its stated goals under all reasonably foreseeable circumstances. Our Principal Executive Officer and Principal Financial Officer have each concluded that our disclosure controls and procedures as of the end of the period covered by this report are effective at a level that provides such reasonable assurances.
Changes in Internal Control Over Financial Reporting
There was no change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) that occurred during the three months ended June 30, 2021 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
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PART II - OTHER INFORMATION
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Item 1. |
Legal Proceedings |
In July 2021, an Agenus stockholder filed a derivative complaint against members of our board of directors and certain senior management in the Delaware Court of Chancery with Agenus as a nominal defendant. The complaint challenges equity awards made in December 2020 on the ground that they were improperly granted. The complaint asserts claims for breach of fiduciary duty, waste, and unjust enrichment. The plaintiff seeks an award of damages to Agenus, an order rescinding the challenged awards, granting other equitable relief, such as disgorgement, and an award of attorneys’ fees. The defendants intend to move to pursue dismissal of the complaint in its entirety. The financial impact of the plaintiff's claims are not estimable.
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Item 1A. |
Risk Factors |
Summary of Risk Factors
Our business is subject to a number of risks and uncertainties. The following is a summary of the principal risk factors described in this section:
Risks Related to our Financial Position and Need for Additional Capital
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• |
We have historically incurred net losses and anticipate that we will continue to incur net losses in the future. |
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• |
If we fail to obtain additional financing, we will not be able to complete development and commercialization of our product candidates. |
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• |
Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates. |
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• |
Our independent registered public accounting firm has included an explanatory paragraph relating to our ability to continue as a going concern in its report on our audited financial statements. |
Risks Related to the Development of Our Product Candidates
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• |
Our business is highly dependent on the success of our balstilimab and zalifrelimab programs. |
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• |
Preliminary or interim data that we report on our clinical trials could change materially by the time the data is finalized. |
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• |
Our clinical trials or those of our current and future collaborators may reveal significant adverse events. |
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• |
If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected. |
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• |
We have limited resources, and the number of product candidates that we are attempting to simultaneously advance creates a significant strain on these resources and could prevent us from successfully advancing any candidates. |
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• |
We may not be able to advance clinical development or commercialize our cancer vaccine candidates or realize any benefits from these programs. |
Risks Related to the Commercialization of Our Product Candidates
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• |
We may not be able to commercialize, or may be delayed in commercializing, our product candidates. |
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• |
We expect the novel nature of our product candidates to create challenges in obtaining regulatory approval. |
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• |
Our product candidates may cause undesirable side effects. |
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• |
Our competitors may have superior products, manufacturing capability, expertise and/or resources. |
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• |
Even if our product candidates receive marketing approval, such products may not achieve market acceptance or coverage, or may become subject to unfavorable pricing regulations or third-party reimbursement practices. |
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• |
The market opportunities for our product candidates may small, and our estimates of the prevalence of our target patient populations may be inaccurate. |
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• |
We have no experience in marketing, selling and distributing products or performing commercial compliance. |
Risks Related to Manufacturing and Supply
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• |
Manufacturing challenges could result in having insufficient quantities of our drug candidates or drugs or such quantities at an acceptable cost. |
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• |
We own and operate our own clinical scale manufacturing infrastructure, which is costly and time-consuming. |
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• |
We are building our own commercial scale manufacturing facticity, which is costly and time-consuming. |
25
Risks Related to Our Reliance on Third Parties
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• |
We are dependent upon third parties to further develop and commercialize certain of our antibody programs. |
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• |
Failure to enter into and/or maintain licensing, distribution and/or collaboration agreements may adversely effect our business. |
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• |
If third parties do not carry out their contractual duties, we may not be able to obtain regulatory approval of or commercialize any potential product candidates. |
Risks Related to Government Regulation
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The regulatory approval process for our product candidates is uncertain and will be lengthy. |
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• |
We may fail to obtain regulatory approval of our product candidates. |
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Our relationships with third parties are subject to extensive healthcare laws and regulations. |
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If we receive regulatory approval of any product candidates or therapies, we will be subject to ongoing regulatory obligations and continued regulatory review. |
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Healthcare regulatory reform measures may have an adverse effect on our business. |
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Laws and regulations governing any international operations may preclude us from developing, manufacturing and selling certain products outside of the United States and require us to develop and implement costly compliance programs |
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Risks associated with doing business internationally could negatively affect our business. |
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Our ability to use net operating losses and tax credits to offset future income may be subject to limitations. |
Risks Related to Our Intellectual Property
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We may be unable to obtain and enforce patent protection for our product candidates and related technology. |
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If we fail to comply with our intellectual property licenses, we could lose important license rights. |
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We may not be able to protect our intellectual property rights throughout the world. |
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Changes in U.S. patent law could diminish the value of patents. |
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We may be unable to protect the confidentiality of our proprietary information. |
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Our employees, consultants or independent contractors could wrongfully use or disclose confidential information. |
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We may infringe the patents and other proprietary rights of third parties. |
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We may become involved in lawsuits to protect or enforce our patents. |
Risks Related to Business Operations, Employee Matters and Managing Growth
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We may encounter difficulties in managing our recent growth and/or corporate consolidation efforts. |
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Legal claims against us may reduce demand for our products and/or result in substantial damages. |
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Information technology security breaches could result in a material disruption in our business and subject us to sanctions and penalties. |
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We may be unsuccessful at advancing our cell therapy business through MiNK Therapeutics with separate funding. |
Risks Related to Our Common Stock
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Our stock’s trading volume and public trading price has been volatile. |
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We do not intend to pay cash dividends on our common stock. |
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Anti-takeover provisions under our charter documents and Delaware law could delay or prevent a change of control. |
Our future operating results could differ materially from the results described in this Quarterly Report on Form 10-Q due to the risks and uncertainties described below. You should consider carefully the following information about risks below in evaluating our business. If any of the following risks actually occur, our business, financial conditions, results of operations and future growth prospects would likely be materially and adversely affected. In these circumstances, the market price of our common stock would likely decline.
We cannot assure investors that our assumptions and expectations will prove to be correct. Important factors could cause our actual results to differ materially from those indicated or implied by forward-looking statements. See “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Forward Looking Statements” in this Quarterly Report on Form 10-Q. Factors that could cause or contribute to such differences include those factors discussed below.
Risks Related to Our Financial Position and Need for Additional Capital
26
We have incurred net losses in every year since our inception and anticipate that we will continue to incur net losses in the future.
Investment in I-O product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate effect or an acceptable safety profile, gain regulatory approval and become commercially viable. We have no products approved for commercial sale and have not generated any revenue from product sales to date, and we continue to incur significant research and development and other expenses related to our ongoing operations. As a result, we are not profitable and have incurred losses in each period since our inception. Our net losses for the years ended December 31, 2020, 2019, and 2018, were $182.9 million, $111.6 million and $162.0 million, respectively. During the six months ended June 30, 2021, we generated a net loss of $138.4 million. We expect to incur significant losses for the foreseeable future as we continue our research and development efforts, seek regulatory approvals, and begin commercial readiness efforts for our product candidates. We anticipate that our expenses will increase substantially if, and as, we:
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conduct clinical trials for our pipeline of product candidates; |
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further develop our antibody programs and platforms, our vaccine programs, and our saponin-based vaccine adjuvants; |
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continue to discover and develop additional product candidates; |
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maintain, expand and protect our intellectual property portfolio; |
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hire additional clinical, scientific manufacturing and commercial personnel; |
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expand in-house manufacturing capabilities; |
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establish a commercial manufacturing source and secure supply chain capacity sufficient to provide commercial quantities of any product candidates for which we may obtain regulatory approval; |
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acquire or in-license other product candidates and technologies; |
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seek regulatory approvals for any product candidates that successfully complete clinical trials; |
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establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain regulatory approval; and |
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add operational, regulatory, financial and management information systems and personnel, including personnel to support our product development and planned commercialization efforts. |
To become profitable, we or any current or potential future licensees and collaboration partners must develop and eventually commercialize products with significant market potential at an adequate profit margin after cost of goods sold and other expenses. This will require us to be successful in a range of challenging activities, including completing clinical trials, obtaining marketing approval for product candidates, obtaining adequate reimbursement for product candidates, manufacturing, marketing and selling products for which we may obtain marketing approval and satisfying any post-marketing requirements. We may never succeed in any or all of these activities and, even if we do, we may never generate revenue that is significant or large enough to achieve profitability. If we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would decrease the value of our company and could impair our ability to raise capital, maintain our research and development efforts, expand our business or continue our operations. A decline in the value of our company also could cause our stockholders to lose all or part of their investment.
Even if we succeed in commercializing one or more of our product candidates, we will continue to incur substantial research and development and other expenditures to develop and market additional product candidates in our pipeline. We may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenue. Our prior losses and expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital.
Furthermore, our ability to generate cash from operations is dependent on the success of our licensees and collaboration partners, as well as the likelihood and timing of new strategic licensing and partnering relationships and/or successful development and commercialization of product candidates, including through our antibody programs and platforms, our vaccine programs, and our saponin-based vaccine adjuvants.
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We will require additional capital to fund our operations, and if we fail to obtain necessary financing, we will not be able to complete the development and commercialization of our product candidates.
Our operations have consumed substantial amounts of cash since inception. We expect to continue to spend substantial amounts to conduct further research and development and preclinical or nonclinical testing and studies and clinical trials of our current and future programs, to build a supply chain, to seek regulatory approvals for our product candidates and to launch and commercialize any products for which we receive regulatory approval, including building our own commercial organization. To date, we have financed our operations primarily through the sale of equity, assets, notes, corporate partnerships and interest income. In order to finance future operations, we will be required to raise additional funds in the capital markets, through arrangements with collaboration partners or from other sources.
As of June 30, 2021, we had $73.5 million of cash and cash equivalents. Based on our current plans and projections, we believe that our cash resources as of June 30, 2021, plus the $200.0 million fee received subsequently in connection with our transaction with BMS, will be sufficient to satisfy our liquidity requirements for more than one year from when these financial statements were issued. We are presently in partnership, and out licensing discussions and contemplating additional financial transactions which, if consummated, could extend our cash resources substantially beyond 2022. However, our future capital requirements and the period for which our existing resources will support our operations may vary significantly from what we expect, and we will in any event require additional capital in order to complete clinical development of our current programs. Our monthly spending levels will vary based on new and ongoing development and corporate activities. Because the length of time and activities associated with development of our product candidates is highly uncertain, we are unable to estimate the actual funds we will require for development and any approved marketing and commercialization activities. Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to:
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the initiation, progress, timing, costs and results of preclinical or nonclinical testing and studies and clinical trials for our product candidates; |
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the clinical development plans we establish for our product candidates; |
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the number and characteristics of future product candidates that we develop or may in-license; |
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our ability to establish and maintain strategic partnerships, licensing or other arrangements and the financial terms of such arrangements; |
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the timing, receipt and amount of sales of, or royalties on, our future products and those of our partners, if any; |
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the outcome, timing and cost of meeting regulatory requirements established by the FDA, the European Medicines Agency (the “EMA”) and other comparable foreign regulatory authorities; |
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the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights; |
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the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates; |
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the effect of competing technological and market developments; |
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the costs of establishing and maintaining a clinical and commercial supply chain for the development and manufacture of our product candidates; |
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the cost and timing of establishing, expanding and scaling manufacturing capabilities; and |
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the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own. |
We do not have any committed external source of funds or other support for our development efforts and we cannot be certain that additional funding will be available on acceptable terms, or at all. Until we can generate sufficient product or royalty revenue to finance our cash requirements, which we may never do, we expect to finance our future cash needs through a combination of public or private equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements and other marketing or distribution arrangements. If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the development or commercialization of one or more of our products or product candidates or one or more of our other research and development initiatives. Any of the above events could significantly harm our business, prospects, financial condition and results of operations and cause the price of our common stock to decline and we may become insolvent.
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From time to time we have issued, and in the future expect to issue, projections regarding our future cash position. Such projections include the expectation that we will be able to raise additional funds from the aforementioned sources and our ability to do so is subject to the risks described herein.
General economic conditions in the United States and abroad, whether as a result of a public health crisis, such as COVID-19, the policies of the Biden Administration or otherwise, may have a material adverse effect on our liquidity and financial condition, particularly if our ability to raise additional funds is impaired.
Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
We may seek additional capital through a combination of public and private equity offerings, debt financings, strategic partnerships and alliances and licensing arrangements. To the extent that we raise additional capital through the sale of equity or convertible debt securities, our stockholders’ ownership interest will be diluted, and the terms may include liquidation or other preferences that adversely affect their rights as a stockholder. The incurrence of indebtedness would result in increased fixed payment obligations and could involve certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business. If we raise additional funds through strategic partnerships and alliances and licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies or product candidates or grant licenses on terms unfavorable to us. We also could be required to seek collaborators for one or more of our current or future product candidates at an earlier stage than otherwise would be desirable or relinquish our rights to product candidates or technologies that we otherwise would seek to develop or commercialize ourselves.
The nature and length of our operating history may make it difficult to evaluate our technology and product development capabilities and predict our future performance.
We have no products approved for commercial sale and have not generated any revenue from product sales. Our ability to generate product revenue or profits, which we do not expect will occur until 2022, if ever, will depend on the successful development and eventual commercialization of our product candidates, which may never occur. We may never be able to develop or commercialize a marketable product.
All of our programs require additional pre-clinical or clinical research and development, manufacturing supply, capacity and/or expertise, building of a commercial organization, substantial investment and/or significant marketing efforts before we generate any revenue from potential product sales. Other programs of ours require additional discovery research and then preclinical development. In addition, our product candidates must be approved for marketing by the FDA or certain other health regulatory agencies, including the EMA, before we may commercialize any product.
Our operating history, particularly in light of the rapidly evolving I-O field, may make it difficult to evaluate our technology and industry and predict our future performance. We will encounter risks and difficulties frequently experienced by clinical stage companies in rapidly evolving fields. If we do not address these risks successfully, our business will suffer. Similarly, we expect that our financial condition and operating results will fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond our control. As a result, our stockholders should not rely upon the results of any quarterly or annual period as an indicator of future operating performance.
In addition, as a clinical stage company, we have encountered unforeseen expenses, difficulties, complications, delays and other known and unknown circumstances. As we advance our product candidates, we will need to transition from a company with a research and clinical focus to a company capable of supporting commercial activities. We may not be successful in such a transition.
Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and stock price.
Global credit and financial markets have experienced extreme volatility and disruptions in the past several years, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability, and the volatility of such market and economic conditions have increased as a result of the COVID-19 pandemic. The scope, duration and long-term impact of the COVID-19 pandemic are unknown at this time, so there can be no assurance how significant any deterioration in credit and financial markets and confidence in economic conditions will be and how long it may continue. Our general business strategy may be adversely affected by any such economic downturn, volatile business environment or continued unpredictable and unstable market conditions. If the current equity and credit markets deteriorate, or do not improve, it may make any necessary debt or equity financing more difficult, more costly, and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on
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our growth strategy, financial performance and stock price and could require us to delay or abandon clinical development plans for some or all of our pipeline candidates. In addition, there is a risk that one or more of our current service providers, manufacturers and other partners may not survive these difficult economic times, which could directly affect our ability to attain our operating goals on schedule and on budget.
As of June 30, 2021, we had cash and cash equivalents of $73.5 million. While we are not aware of any downgrades, material losses, or other significant deterioration in the fair value of our cash equivalents and investments since June 30, 2021, no assurance can be given that deterioration of the global credit and financial markets would not negatively impact our current portfolio of cash equivalents or our ability to meet our financing objectives. Furthermore, our stock price may decline due in part to the volatility of the stock market and any general economic downturn.
Our independent registered public accounting firm has included an explanatory paragraph relating to our ability to continue as a going concern in its report on our audited financial statements, and it is possible that such report on our financial statements may include such an explanation again in the future.
We believe we have sufficient capital, including funds received from BMS in July 2021, to fund our operations for more than one year from when these financial statements were issued. Going forward, if we are unable to obtain sufficient funding to support our operations, we could be forced to delay, reduce or eliminate all of our research and development programs, product portfolio expansion or commercialization efforts, our financial condition and results of operations will be materially and adversely affected, and we may be unable to continue as a going concern. In the future, reports from our independent registered public accounting firm may also contain statements expressing substantial doubt about our ability to continue as a going concern. If we seek additional financing to fund our business activities in the future and there remains substantial doubt about our ability to continue as a going concern, investors or other financing sources may be unwilling to provide additional funding to us on commercially reasonable terms, if at all.
Our obligations to the holders of our promissory notes could materially and adversely affect our liquidity.
In February 2015, we issued the 2015 Subordinated Notes in the aggregate principal amount of $14.0 million, of which $13.0 million remains outstanding, with annual interest of 8%. The 2015 Subordinated Notes were previously due February 20, 2020, and in February 2020, we amended the 2015 Subordinated Notes to extend the maturity date to February 20, 2023. The 2015 Subordinated Notes include default provisions that allow for the acceleration of the principal payment of the 2015 Subordinated Notes in the event we become involved in certain bankruptcy proceedings, become insolvent, fail to make a payment of principal or (after a grace period) interest on the 2015 Subordinated Notes, default on other indebtedness with an aggregate principal balance of $13.0 million or more if such default has the effect of accelerating the maturity of such indebtedness, or become subject to a legal judgment or similar order for the payment of money in an amount greater than $13.0 million if such amount will not be covered by third-party insurance. If we default on the 2015 Subordinated Notes and the repayment of such indebtedness is accelerated, our liquidity could be materially and adversely affected.
In May 2020, we issued promissory notes in the aggregate principal amount of approximately $6.2 million pursuant to the CARES Act (the “PPP Loan”). Under the current terms of the CARES Act, our PPP Loan is eligible for forgiveness if the proceeds are used for covered payroll costs, rent and utilities during the 8 to 24-week period immediately following receipt of the proceeds. Though our forgiveness submission has not yet been accepted, we believe we used the proceeds of the PPP Loan in accordance with the relevant terms and conditions of the CARES Act. However, the CARES Act regulations have been revised multiple times since they were initially published in March 2020. Our PPP Loan may not qualify for forgiveness under the final regulations of the CARES Act, and we may be required to repay the PPP Loan in full, with interest.
If we do not have sufficient cash on hand to service or repay our 2015 Subordinated Notes or PPP Loan, we may be required to raise additional capital which entails the risks described herein.
Risks Related to the Development of Our Product Candidates
Our business is highly dependent on the success of our balstilimab and zalifrelimab programs initially targeting second-line cervical cancer, which still require significant additional clinical development.
Our business and future success depends in large part on our ability to obtain regulatory approval of, and then successfully launch and commercialize, our initial product candidates targeting second line cervical cancer.
Our anti-PD-1 and anti-CTLA-4 programs (balstilimab and zalifrelimab, respectively) are in Phase 2 expansion trials with both balstilimab monotherapy and balstilimab/zalifrelimab combination trials for patients with second-line cervical cancer that are designed to support BLA filings under the FDA’s accelerated approval pathway. In June 2021, the FDA accepted our first BLA, for
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balstilimab monotherapy and set a target action date of December 16, 2021. A global, randomized, Phase 3 confirmatory clinical trial designed to support global registration of our balstilimab monotherapy is planned. We expect to solidify our strategy for the balstilimab/zalifrelimab combination filing, pending further discussion with the FDA. These timelines are aggressive and subject to various factors outside of our control, including regulatory review and approval. In order to file a BLA and seek accelerated approval, we must launch a confirmatory trial which will need to be well underway at the time of BLA approval. We have initiated, but not yet completed the trial intended to satisfy this requirement, and there is no guarantee that the trial will be considered substantially underway at the time of BLA approval or that it will ultimately demonstrate the predicted clinical benefit of balstilimab. Furthermore, the COVID-19 pandemic could prevent us from initiating a confirmatory trial on our planned timeline. There is no guarantee that our BLA submissions will be approved, or, even if approved, that any accelerated approval will not be withdrawn or that we will be able to successfully commercialize these assets. If our anti-PD-1 and anti-CTLA-4 programs encounter safety, efficacy, supply or manufacturing problems, developmental delays, regulatory or commercialization issues or other problems, our development plans and business would be significantly harmed.
Even though we have observed positive results to date, they may not necessarily be predictive of the final results of the trials or future clinical trials or otherwise be sufficient to support an accelerated approval. Many companies in the pharmaceutical, biopharmaceutical and biotechnology industries have suffered significant setbacks in clinical trials after achieving positive results, and we cannot be certain that we will not face similar setbacks.
All of our other product candidates are in earlier stages of development and will require additional nonclinical and/or clinical development, regulatory review and approval in multiple jurisdictions, substantial investment, access to sufficient commercial manufacturing capacity and significant marketing efforts before we can generate any revenue from product sales.
The successful development of immune modulating antibodies, including our balstilimab and zalifrelimab programs, is highly uncertain.
Successful development of immune modulating antibodies, such as our balstilimab and zalifrelimab programs, is highly uncertain and is dependent on numerous factors, many of which are beyond our control. Immune modulating antibodies that appear promising in the early phases of development may fail to reach, or remain in, the market for several reasons, including:
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clinical trial results may show our candidates to be less effective than expected (e.g., a clinical trial could fail to meet its primary endpoint(s)) or to have unacceptable side effects, toxicities or other negative consequences; |
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failure to receive the necessary regulatory approvals or a delay in receiving such approvals. Among other things, such delays may be caused by slow enrollment in clinical trials, patients dropping out of trials, length of time to achieve trial endpoints, additional time requirements for data analysis, or BLA preparation, discussions with the FDA, an FDA request for a diagnostic or additional nonclinical or clinical data, or unexpected safety or manufacturing issues; |
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manufacturing costs, formulation issues, pricing or reimbursement issues, or other factors that make the candidates uneconomical; |
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proprietary rights of others and their competing products and technologies that may prevent our candidates from being commercialized; and |
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failure to initiate or successfully complete confirmation trials for candidates that receive accelerated approval. |
The length of time necessary to complete clinical trials and to submit an application for marketing approval for a final decision by a regulatory authority may be difficult to predict for immune modulating antibodies, including for the balstilimab/zalifrelimab combination.
Even if we are successful in obtaining marketing approval, commercial success of any approved products will also depend in large part on the availability of insurance coverage and adequate reimbursement from third-party payors, including government payors, such as the Medicare and Medicaid programs, and managed care organizations, which may be affected by existing and future healthcare reform measures designed to reduce the cost of healthcare. Third-party payors may limit the definition of the target treatment population to one smaller than that implied in the label granted by regulatory authorities, and could require us to conduct additional studies, including post-marketing studies related to the cost-effectiveness of a product, to qualify for reimbursement, which could be costly and divert our resources. If government and other healthcare payors were not to provide adequate insurance coverage and reimbursement levels for any one of our products once approved, market acceptance and commercial success would be reduced.
In addition, if any of our products are approved for marketing, we will be subject to significant regulatory obligations regarding the submission of safety and other post-marketing information and reports and registration, and will need to continue to comply (or ensure that our third-party providers comply) with current good manufacturing practices (“cGMPs”) and good clinical
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practices (“GCPs”), for any clinical trials that we conduct post-approval. In addition, there is always the risk that we or a regulatory authority might identify previously unknown problems with a product post-approval, such as adverse events of unanticipated severity or frequency. Compliance with these requirements is costly and any failure to comply or other issues with our product candidates’ post-approval could have a material adverse effect on our business, financial condition and results of operations.
Interim top-line and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.
From time to time, we may publish interim top-line or preliminary data from our clinical trials. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available and mature over time. Preliminary or top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, interim and preliminary data should be viewed with caution until the final data are available. Multiple times last year, and most recently in June 2021, we reported positive interim data from our lead trials of balstilimab and zalifrelimab. In April 2021, we also reported new clinical responses from a Phase 1/2 trial of AGEN1181, and in June 2021, we reported Phase 1 clinical responses for AGEN2373. Each of these results may not be indicative of the final results from the relevant study, and the final results may not support a marketing approval for any of these candidates. There is no guarantee that either balstilimab monotherapy or balstilimab/zalifrelimab combination therapy (or any of our earlier stage programs) will receive marketing approval in any jurisdiction, and failure to achieve marketing approval for either of these programs could have a material adverse impact on our business. Any adverse differences between preliminary or interim data and final data could significantly harm our business prospects.
Preclinical development is uncertain. Some of our antibody programs are in early stage development that may experience delays or may never advance to clinical trials, which would adversely affect our ability to obtain regulatory approvals or commercialize these programs on a timely basis or at all, and which would have an adverse effect on our business.
Several of our proprietary antibody programs are currently in early stage development, and many of our antibody programs are pre-clinical. We cannot be certain of the timely completion or outcome of our preclinical testing and studies and cannot predict if the FDA or other regulatory authorities will accept our proposed clinical programs or if the outcome of our preclinical testing and studies will ultimately support the further development of our programs. As a result, we cannot be sure that we will be able to submit Investigational New Drug applications (“INDs”) or similar applications for our preclinical programs on the timelines we expect, if at all, and we cannot be sure that submission of INDs or similar applications will result in the FDA or other regulatory authorities allowing clinical trials to begin.
Our clinical trials or those of our current and future collaborators may reveal significant adverse events not seen in our preclinical or nonclinical studies and may result in a safety profile that could inhibit regulatory approval or market acceptance of any of our product candidates.
Before obtaining regulatory approvals for the commercial sale of any products, we must demonstrate through potentially lengthy, complex and expensive preclinical studies and clinical trials that our product candidates are both safe and effective for use in each target indication. Failure can occur at any time during the clinical trial process.
Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy profile despite having progressed through nonclinical studies and initial clinical trials. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or unacceptable safety issues, notwithstanding promising results in earlier trials. Most product candidates that commence clinical trials are never approved as products and there can be no assurance that any of our current or future clinical trials will ultimately be successful or support further clinical development of any of our product candidates.
We intend to develop our existing antibody candidates, and may develop future product candidates, alone and in combination with one or more additional cancer therapies. The uncertainty resulting from the use of our product candidates in combination with other cancer therapies may make it difficult to accurately predict side effects in future clinical trials.
If significant adverse events or other side effects are observed in any of our current or future clinical trials, we may have difficulty recruiting patients to our clinical trials, patients may drop out of our trials, or we may be required to abandon the trials or our development efforts of one or more product candidates altogether. We, the FDA or other applicable regulatory authorities, or an institutional review board may suspend clinical trials of a product candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to unacceptable health risks or adverse side effects. Some potential therapeutics developed in the biotechnology industry that initially showed therapeutic promise in early-stage trials have later been found to cause side effects
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that prevented their further development. Even if the side effects do not preclude the drug from obtaining or maintaining marketing approval, undesirable side effects may inhibit market acceptance of any approved product due to its tolerability versus other therapies. Any of these developments could materially harm our business, financial condition and prospects.
Positive results from preclinical and clinical studies of our product candidates are not necessarily predictive of the results of later preclinical studies and any future clinical trials of our product candidates. If we cannot replicate the positive results from our earlier studies of our product candidates in our later studies and future clinical trials, we may be unable to successfully develop, obtain regulatory for and commercialize our product candidates.
Any positive results from our preclinical studies of our product candidates may not necessarily be predictive of the results from required later preclinical studies and clinical trials. Similarly, even if we are able to complete our planned preclinical studies or any future clinical trials of our product candidates according to our current development timeline, the positive results from such preclinical studies and clinical trials of our product candidates may not be replicated in subsequent preclinical studies or clinical trial results. Moreover, positive results observed in interim data may not necessarily be predictive of the results from final, more mature data.
For example, in 2018 we presented early data on our balstilimab and zalifrelimab programs at major oncology conferences that demonstrated a clinical benefit (i.e., complete response, partial response or disease stabilization) in more than 60% of patients treated with balstilimab and zalifrelimab at that time. In September 2020, we reported interim data from our registrational trials of these same programs that showed overall response rates of approximately 14% with balstilimab monotherapy and approximately 22% with balstilimab/zalifrelimab combination therapy. Similarly, in April 2021, we provided updated data from our registrational trial of balstilimab as a monotherapy in our BLA submission, which showed an overall response rate of 15%. We may not be able to replicate these positive results in future clinical trials for these programs and, in the case of interim results, the final data readouts may not show similar positive results. The final data readouts on these programs may not show similar positive results.
Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stage clinical trials after achieving positive results in early-stage development and we cannot be certain that we will not face similar setbacks. These setbacks have been caused by, among other things, preclinical and other nonclinical findings made while clinical trials were underway, or safety or efficacy observations made in preclinical studies and clinical trials, including previously unreported adverse events. Moreover, preclinical, nonclinical and clinical data are often susceptible to varying interpretations and analyses and many companies that believed their product candidates performed satisfactorily in preclinical studies and clinical trials nonetheless failed to obtain FDA or EMA approval.
If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected.
We may experience difficulties in patient enrollment in our clinical trials for a variety of reasons. The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the study until its conclusion. The enrollment of patients depends on many factors, including:
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the severity of the disease under investigation; |
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the patient eligibility and exclusion criteria defined in the protocol; |
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the size of the patient population required for analysis of the trial’s primary endpoints; |
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the proximity of patients to trial sites; |
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the design of the trial; |
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our ability to recruit clinical trial investigators with the appropriate competencies and experience; |
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clinicians’ and patients’ perceptions as to the potential advantages and risks of the product candidate being studied in relation to other available therapies, including any new drugs that may be in clinical development or approved for the indications we are investigating; |
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the efforts to facilitate timely enrollment in clinical trials; |
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the patient referral practices of physicians; |
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the ability to monitor patients adequately during and after treatment; |
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our ability to obtain and maintain patient consents; and |
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the risk that patients enrolled in clinical trials will drop out of the trials before completion. |
In addition, our clinical trials will compete with other clinical trials for product candidates that are in the same therapeutic areas as our product candidates, and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our trials may instead opt to enroll in a trial being conducted by one of our competitors. Since the number of qualified clinical investigators is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patients who are available for our clinical trials in such clinical trial site. Moreover, because our product candidates represent a departure from more commonly used methods for our targeted therapeutic areas, potential patients and their doctors may be inclined to use conventional or newly launched competitive therapies, rather than enroll patients in any future clinical trial.
Delays in patient enrollment may result in increased costs or may affect the timing or outcome of the planned clinical trials, which could prevent completion of these trials and adversely affect our ability to advance the development of our product candidates. The COVID-19 pandemic may cause delays in the patient enrollment in our clinical trials and could prevent the completion and/or timely completion of such trials.
The number of product candidates that we are attempting to simultaneously advance creates a significant strain on our resources and may prevent us from successfully advancing any product candidates. If, due to our limited resources and access to capital, we prioritize development of certain product candidates, such decisions may prove to be wrong and may adversely affect our business.
We are currently advancing multiple immune modulating antibodies, vaccines, vaccine adjuvants and adoptive cell therapies (MiNK Therapeutics subsidiary). Simultaneously advancing so many product candidates creates a significant strain on our limited human and financial resources. As a result, we may not be able to provide sufficient resources to any single product candidate to permit the successful development and commercialization of such product candidate, causing material harm to our business.
If, due to our limited resources and access to capital, we prioritize development of certain product candidates that ultimately prove to be unsuccessful, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential or a greater likelihood of success. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities.
Risks Related to the Commercialization of Our Product Candidates
If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals for our product candidates, we will not be able to commercialize, or will be delayed in commercializing, our product candidates, and our ability to generate revenue will be materially impaired.
Our product candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, import and export are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by comparable
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authorities in other countries. Before we can commercialize any of our product candidates, we must obtain marketing approval. Except for Prophage in Russia, we have not received approval to market any of our product candidates from regulatory authorities in any jurisdiction and it is possible that none of our product candidates or any product candidates we may seek to develop in the future will ever obtain regulatory approval. We, as a company, have limited experience in filing and supporting the applications necessary to gain regulatory approvals and rely in part on third-party contract research organizations (“CROs”) and/or regulatory consultants to assist us in this process. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing regulatory approval also requires the submission of information about the drug manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority. Our product candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use.
The process of obtaining regulatory approvals, both in the United States and abroad, is expensive, may take many years if additional clinical trials are required, if approval is obtained at all, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted IND, Premarket Approval, BLA or equivalent application types, may cause delays in the approval or rejection of an application. The FDA and comparable authorities in other countries have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies. Our product candidates could be delayed in receiving, or fail to receive, regulatory approval for many reasons, including the following:
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the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; |
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we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a product candidate is safe and effective for its proposed indication or a related companion diagnostic is suitable to identify appropriate patient populations; |
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the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval; |
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we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; |
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the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; |
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the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an BLA or other submission or to obtain regulatory approval in the United States or elsewhere; |
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the FDA or comparable foreign regulatory authorities may fail to approve our manufacturing processes or facilities or those of our third-party manufacturers with which we contract for clinical and commercial supplies; and |
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the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval. |
Of the large number of drugs in development, only a small percentage successfully complete the FDA or foreign regulatory approval processes and are commercialized. The lengthy approval process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval to market our product candidates, which would significantly harm our business, results of operations and prospects.
We expect the novel nature of our product candidates to create further challenges in obtaining regulatory approval. As a result, our ability to develop product candidates and obtain regulatory approval may be significantly impacted.
The general approach for FDA approval of a new biologic or drug is for sponsors to seek licensure or approval based on dispositive data from well-controlled, Phase 3 clinical trials of the relevant product candidate in the relevant patient population. Phase 3 clinical trials typically involve hundreds of patients, have significant costs and take years to complete. We are utilizing and, in the future, intend to utilize FDA’s accelerated approval program for our product candidates given the limited alternatives for treatments for certain rare diseases, cancer and autoimmune diseases, but the FDA may not agree with our plans. Moreover, even if we do receive accelerated approval from the FDA for one or more of our product candidates, there is no guarantee that we will be able to successfully complete one or more confirmatory trials needed to obtain full approval.
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The FDA may also require a panel of experts, referred to as an Advisory Committee, to deliberate on the adequacy of the safety and efficacy data to support approval. The opinion of the Advisory Committee, although not binding, may have a significant impact on our ability to obtain approval of any product candidates that we develop based on the completed clinical trials.
Moreover, approval of genetic or biomarker diagnostic tests may be necessary in order to advance some of our product candidates to clinical trials or potential commercialization. In the future, regulatory agencies may require the development and approval of such tests. Accordingly, the regulatory approval pathway for such product candidates may be uncertain, complex, expensive and lengthy, and approval may not be obtained.
In addition, even if we were to obtain approval, regulatory authorities may approve any of our product candidates for fewer or more limited indications than we request, for instance, regulatory authorities may only approve the balstilimab monotherapy to individuals with PD-L1 positive tumors, may not approve the price we intend to charge for our products, may grant approval contingent on the performance of costly post-marketing clinical trials, or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could reduce the size of the potential market for our product candidates and materially harm the commercial prospects for our product candidates.
If we experience delays in obtaining approval or if we fail to obtain approval of our product candidates, the commercial prospects for our product candidates may be harmed and our ability to generate revenues will be materially impaired.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of our product candidates in other jurisdictions.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, while a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others. For example, even if the FDA grants marketing approval of a product candidate, comparable regulatory authorities in foreign jurisdictions must also approve the manufacturing, marketing and promotion of the product candidate in those countries. Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from, and greater than, those in the United States, including additional nonclinical studies or clinical trials as clinical trials conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions. In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we intend to charge for our products is also subject to approval.
We may also submit marketing applications in other countries. Regulatory authorities in jurisdictions outside of the United States have requirements for approval of product candidates with which we must comply prior to marketing in those jurisdictions. Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our products in certain countries. If we fail to comply with the regulatory requirements in international markets and/or receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of our product candidates will be harmed.
Our product candidates may cause undesirable side effects that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.
Undesirable side effects caused by our product candidates could cause us to interrupt, delay or halt preclinical studies or could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other regulatory authorities. As is the case with many treatments for cancer and autoimmune diseases, it is likely that there may be side effects associated with their use. Results of our trials could reveal a high and unacceptable severity and prevalence of these or other side effects. In such an event, our trials could be suspended or terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our product candidates for any or all targeted indications. The treatment-related side effects could affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may harm our business, financial condition and prospects significantly.
Further, clinical trials by their nature utilize a sample of the potential patient population. With a limited number of patients and limited duration of exposure, rare and severe side effects of our product candidates may only be uncovered with a significantly larger number of patients exposed to the product candidate. If our product candidates receive marketing approval and we or others identify undesirable side effects caused by such product candidates (or any other similar drugs) after such approval, a number of potentially significant negative consequences could result, including:
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regulatory authorities may withdraw or limit their approval of such product candidates; |
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regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication; |
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we may be required to create a medication guide outlining the risks of such side effects for distribution to patients; |
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we may be required to change the way such product candidates are distributed or administered, conduct additional clinical trials or change the labeling of the product candidates; |
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regulatory authorities may require a Risk Evaluation and Mitigation Strategy(“REMS”), plan to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools; |
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we may be subject to regulatory investigations and government enforcement actions; |
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we may decide to remove such product candidates from the marketplace; |
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we could be sued and held liable for injury caused to individuals exposed to or taking our product candidates; and |
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our reputation may suffer. |
We believe that any of these events could prevent us from achieving or maintaining market acceptance of the affected product candidates and could substantially increase the costs of commercializing our product candidates, if approved, and significantly impact our ability to successfully commercialize our product candidates and generate revenues.
Our competitors may have superior products, manufacturing capability, selling and marketing expertise and/or financial and other resources.
Our product candidates and the product candidates in development by our collaboration partners may fail because of competition from major pharmaceutical companies and specialized biotechnology companies that market products, or that are engaged in the development of product candidates and for the treatment cancer. Many of our competitors, including large pharmaceutical companies, have substantially greater financial, technical and other resources than we do, such as larger research and development staff, experienced marketing and manufacturing organizations and well-established sales forces. Our competitors may:
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develop safer or more effective therapeutic drugs or therapeutic vaccines and other products; |
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establish superior intellectual property positions; |
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discover technologies that may result in medical insights or breakthroughs, which render our drugs or vaccines obsolete, possibly before they generate any revenue, if ever; |
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adversely affect our ability to recruit patients for our clinical trials; |
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solidify partnerships or strategic acquisitions that may increase the competitive landscape; |
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develop or commercialize their product candidates sooner than we commercialize our own, if ever; or |
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implement more effective approaches to sales, marketing and patient assistance programs and capture some of our potential market share. |
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies. Established pharmaceutical companies may also invest heavily to accelerate discovery and development of novel therapeutics or to in-license novel therapeutics that could make the product candidates that we develop obsolete. Mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated in our competitors. Competition may increase further as a result of advances in the commercial applicability of technologies and greater availability of capital for investment in these industries.
There is no guarantee that our product candidates will be able to compete with potential future products being developed by our competitors.
The CPM drug landscape is crowded with several competitors developing assets against a number of targets. Our development plans are spread out across various indications and lines of therapy, either alone or in combination with other assets. Our competitors range from small cap to large cap companies, with assets in pre-clinical or clinical stages of development. Therefore, the landscape is dynamic and constantly evolving. We and our partners have CPM antibody programs, currently in clinical stage development targeting various pathways (as mono- or multi-specifics) including PD-1, CTLA-4, GITR, OX40, TIM-3, LAG-3, CD73, TGFb and
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CD137. We are aware of many companies that have antibody-based products on the market or in clinical development that are directed to the same biological targets as these programs, including, without limitation, the following: (1) BMS markets ipilimumab, an anti-CTLA-4 antibody, and nivolumab, an anti-PD-1 antibody, and is developing agents targeting LAG-3, TIM-3, OX40 and TGFb. BMS also has next generation anti-CTLA-4 antibodies in the clinic, which may be competitive to our next generation anti-CTLA-4 program, (2) Merck has an approved anti-PD-1 antibody, as well as anti-CTLA-4 and LAG-3 antagonists recruiting in clinical trials, (3) Regeneron has an approved anti-PD-1 antibody as well as antibodies targeting LAG-3 and GITR in the clinic, (4) Roche/Genentech has an approved anti-PD-L1 antibody as well as bispecific antibodies targeting CD137, TIM-3 and LAG-3 in clinical development, (5) AstraZeneca has an approved anti PD-L1 antibody, as well as antibodies targeting CTLA-4 and CD73 in the clinic, (6) Pfizer has an approved anti-PD-L1 (with Merck KgaA) as well as agents targeting PD-1, TGFbR1 and CD137 in clinical development and (7) GSK has an approved anti PD-1 antibody as well as antibodies targeting TIM-3 and LAG-3 in the clinic. Besides these PD-1 and PD-L1 antibodies that were approved in the U.S., we are also aware of competitors with approved PD-1 agents in ex-U.S. geographies such as China. These include Innovent Biologics (Eli Lilly has ex-China rights), Shanghai Junshi Biosciences (Coherus BioSciences has rights to co-develop in U.S. and Canada), Shanghai HengRui Pharmaceuticals and Beigene (Novartis has ex-China rights).
We are also aware of other competitors with clinical-stage PD-1/PD-L1 agents including but not limited to AbbVie, Amgen, Arcus Biosciences, Akeso Bio, Biocad Ltd., Boehringer Ingelheim, Checkpoint Therapeutics, CStone Pharmaceuticals (EQRx has ex-China rights), CSPC ZhongQi Pharmaceutical Technology, GSK, Gilead Sciences, Genor Biopharma/ Apollomics, Genrix (Shanghai) Biopharmaceutical, Incyte, ImmuneOncia Therapeutics Inc., Jounce Therapeutics, Janssen Pharmaceuticals, Lee’s Pharmaceuticals, Mabspace Biosciences, Maxinovel Pharmaceuticals, Novartis, 3D Medicines, Shanghai Henlius Biotech Co Ltd, Sinocelltech, Shandong New Time Pharmaceutical Co Ltd, and Taizhou Houdeaoke Technology. In addition, we are also aware of anti-PD-(L)1 monospecific agents that are preclinical in stage. We are also aware of competitors developing bispecifics targeting PD-1 or PD-L1.
We are aware of companies developing “next-generation” anti-CTLA-4 approaches, which may be competitive to our next-generation anti-CTLA-4 program (AGEN1181). For example, BMS has 3 next-generation CTLA-4 programs in the clinic: a non-fucosylated anti CTLA-4 antibody, a peptide-masked version of ipilimumab and a peptide masked version of the non-fucosylated anti CTLA-4 antibody; the peptide masked versions are designed to localize activity to the tumor and minimize systemic toxicity associated with parent drug. We are also aware of companies advancing clinical stage, CTLA-4 targeting multispecifics as a next-generation approach, including, but not limited to, Macrogenics, Xencor, AstraZeneca, Akeso Biopharma, Alphamab, Alpine Immune Sciences, and Sichuan Baili Pharmaceuticals. We are also aware of next-generation assets targeting CTLA-4 preclinically.
We are also aware of competitors with clinical stage monospecific drug candidates against CTLA-4, GITR, OX40, LAG-3, TIM-3, CD73, TGFb, and CD137, in addition to those named earlier in this section. As outlined above, some of these include, but are not limited to AbbVie, Adagene, Arcus Biosciences, Alligator Biosciences, Beigene, Compass Therapeutics, Corvus Pharmaceuticals, CStone Therapeutics, Innovent Biologics, Inhibrx, Lyvgen Biopharma, MedPacto, Novartis, Astellas, Servier, Scholar Rock, and Sanofi. We are also aware of preclinical stage competitors developing monospecific agents against these targets. Further, we are also aware of competitors developing bispecifics targeting these pathways.
Additionally, the FDA has cleared an IND filing for AGEN1777, our TIGIT bispecific program licensed to BMS; we are aware of clinical stage anti-TIGIT antibodies that could compete with this program. These include, but are not limited to, Arcus Biosciences, Beigene, Compugen, iTeos Therapeutics (partnered with GSK), Merck, Mereo Biopharma, Roche, Innovent Biologics, Merck KGaA and Seagen Inc. Additionally, some competitors are also developing TIGIT bispecifics; for example, Innovent has a clinical stage bispecific co-targeting PD-1 and TIGIT. We are also aware of competitor programs, in monospecific and bispecific formats, that are in preclinical development against this target. There is no guarantee that our antibody product candidates will be able to successfully compete with our competitors’ antibody products and product candidates.
We are conducting both monotherapy and combination trials in second line cervical cancer. We are aware that Merck’s PD-1 antagonist, Keytruda, has been approved in advanced cervical cancer. Additionally, we are aware that Seagen Inc. and Genmab A/S have submitted a BLA for tisotumab vedotin, a drug co-developed by these companies, for use in recurrent/metastatic cervical cancer patients, including in the second line setting. We are also aware that another PD-1 antagonist, Libtayo, being developed by Regeneron and Sanofi in second line cervical cancer, has demonstrated overall survival benefit and that a BLA is expected to be submitted to regulators in 2021. Beyond these developments, we are also aware of industry sponsored clinical trials, including exploratory studies, that are underway in this setting. Clinical stage competitors include, but are not limited to, BMS (anti-PD-1 alone or in combination with CTLA-4), Iovance Biotherapeutics (autologous TILs), Merck KgaA (anti-PD-L1/TGFb), Roche (anti-PD-L1 alone or in combination with anti-TIGIT), Vaccibody (HPV vaccine in combination with anti-PD-L1), Biocad (anti-PD-1), Genor Biopharma (anti-PD-1), Gloria Biosciences (Anti-PD-1), Shanghai Henlius Biotech (anti-PD-1 in combination with albumin bound paclitaxel), Akeso Bio (anti-PD-1/CTLA-4 bispecific), Lee Pharmaceuticals (anti-PD-L1) and Innovent Biologics (anti-PD-1 alone or in combination with anti-CTLA-4).
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We have autologous vaccine programs in clinical development including our Prophage vaccine in clinical development for GBM. We are aware of other therapeutic options in GBM that could compete with our vaccine, including but not limited to the following: Merck markets temozolomide for treatment of patients with newly diagnosed glioblastoma (“ndGBM”) and refractory astrocytoma. Other companies are developing vaccines for the treatment of patients with ndGBM, including, but not limited to, Mimivax Inc. (SurVaxM). Other companies may begin development programs as well. We are advancing our neoantigen vaccine, AutoSynVax, in solid tumors. There are companies advancing neoantigen vaccines that compete with our HSP based vaccines including, but not limited to: Gritstone Oncology, BioNTech, Moderna/Merck, Genocea Biosciences, ISA Pharmaceuticals, Nouscom, and Vaccibody.
In addition, and prior to regulatory approval, if ever, our vaccines and our other product candidates may compete for access to patients with other products in clinical development, with products approved for use in the indications we are studying, or with off-label use of products in the indications we are studying. We anticipate that we will face increased competition in the future as new companies enter markets we seek to address and scientific developments surrounding immunotherapy and other traditional cancer therapies continue to accelerate.
Our subsidiary company, MiNK Therapeutics, is advancing invariant natural killer T cell (iNKT) therapy. We are aware of competitors advancing NKT therapies, including but not limited to, Kuur Therapeutics, Suda Pharmaceuticals, Appia Bio and BrightPath Biotherapeutics.
Several other vaccine adjuvants are in development or in use and could compete with QS-21 Stimulon for inclusion in vaccines. These adjuvants may include but are not limited to: (1) oligonucleotides, under development by Pfizer, Idera, and Dynavax, (2) MF59, under development by Novartis, (3) IC31, under development by Intercell (now part of Valneva), (4) MPL, under development by GSK, (5) Matrix-MTM, under development by Novavax, (6) AS03, under development by GSK, and (7) TQL 1055, under development by Adjuvance Technologies. In the past, we have provided QS-21 Stimulon to other entities under materials transfer arrangements. In at least one instance, it is possible that this material was used without our permission to develop synthetic formulations and/or derivatives of QS-21. In addition, other companies and academic institutions are developing saponin adjuvants, including derivatives and synthetic formulations. These sources may be competitive to our ability to execute future partnering and licensing arrangements involving QS-21 Stimulon. The existence of products developed by these and other competitors, or other products of which we are not aware, or which other companies may develop in the future, may adversely affect the marketability of products developed or sold using QS-21 Stimulon.
We are also aware of a third party that manufactures pre-clinical material purporting to be comparable to QS-21 Stimulon. The claims being made by this third party may create marketplace confusion and have an adverse effect on the goodwill generated by us and our partners with respect to QS-21 Stimulon. We are also aware of other manufacturers of QS-21. Any diminution of this goodwill may have an adverse effect on our ability to commercialize future products, if any, incorporating this technology, either alone or with a third party.
Even if we obtain regulatory approval to market our product candidates, the availability and price of our competitors’ products could limit the demand and the price we are able to charge for our product candidates. We may not be able to implement our business plan if the acceptance of our product candidates is inhibited by price competition or the reluctance of physicians to switch from existing methods of treatment to our product candidates, or if physicians switch to other new drug or biologic products or choose to reserve our product candidates for use in limited circumstances.
Even if our product candidates receive marketing approval, we, or others, may subsequently discover that such product is less effective than previously believed or causes undesirable side effects that were not previously identified and our ability to market such product will be compromised.
Clinical trials of our product candidates are conducted in carefully defined subsets of patients who have agreed to enter into such clinical trials. Consequently, it is possible that our clinical trials may indicate an apparent positive effect of a product candidate that is greater than the actual positive effect, if any, or alternatively fail to identify undesirable side effects. If one or more of our product candidates receives regulatory approval, and we, or others, later discover that they are less effective than previously believed, or cause undesirable side effects, a number of potentially significant negative consequences could result, including:
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withdrawal or limitation by regulatory authorities of approvals of such product; |
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seizure of the product by regulatory authorities; |
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recall of the product; |
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restrictions on the marketing of the product or the manufacturing process for any component thereof; |
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requirement by regulatory authorities of additional warnings on the label, such as a “black box” warning or contraindication; |
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requirement that we implement a risk evaluation and mitigation strategy or create a medication guide outlining the risks of such side effects for distribution to patients; |
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commitment to expensive additional safety studies prior to approval or post-marketing studies required by regulatory authorities of such product; |
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the product may become less competitive; |
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initiation of regulatory investigations and government enforcement actions; |
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initiation of legal action against us to hold us liable for harm caused to patients; and |
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harm to our reputation and resulting harm to physician or patient acceptance of our products. |
Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, financial condition and results of operations.
Even if our product candidates receive marketing approval, such products may fail to achieve the degree of market acceptance by physicians, patients, third- party payors and others in the medical community necessary for commercial success.
If balstilimab and zalifrelimab or any other future product candidates receive marketing approval, whether as single agents or in combination with other therapies, they may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. For example, current approved immunotherapies, and other cancer treatments like chemotherapy and radiation therapy, are well established in the medical community, and doctors could continue to rely on these therapies. If balstilimab and zalifrelimab or any other future product candidates do not achieve an adequate level of acceptance, we may not generate significant product revenues and we may not become profitable. The degree of market acceptance of balstilimab and zalifrelimab or any future products, if approved for commercial sale, will depend on a number of factors, including:
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efficacy and potential advantages compared to alternative treatments; |
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the ability to offer our products, if approved, for sale at competitive prices; |
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convenience and ease of administration compared to alternative treatments; |
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the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; |
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the strength of marketing and distribution support; |
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sufficient third-party coverage or reimbursement, including of combination therapies; |
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adoption of a companion diagnostic and/or complementary diagnostic; and |
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the prevalence and severity of any side effects. |
Even if we are able to commercialize any product candidates, such products may not receive coverage or may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, all of which would harm our business.
The legislation and regulations that govern marketing approvals, pricing and reimbursement for new drug products vary widely from country to country. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or drug licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. In the United States, approval and reimbursement decisions are not linked directly, but there is increasing scrutiny from the Congress and regulatory authorities of the pricing of pharmaceutical products. As a result, we might obtain marketing approval for a product candidate in a particular country, but then be subject to price regulations that delay our commercial launch of the product candidate, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product candidate in that
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country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval.
Significant uncertainty exists as to the coverage and reimbursement status of our product candidates for which we seek regulatory approval. Our ability to commercialize any drugs successfully will depend, in part, on the extent to which reimbursement for these drugs and related treatments will be available from government health administration authorities, private health insurers and other organizations. Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. Obtaining and maintaining adequate reimbursement for our product candidates, if approved, may be difficult. Moreover, the process for determining whether a third-party payor will provide coverage for a product may be separate from the process for setting the price of a product or for establishing the reimbursement rate that such a payor will pay for the product. Further, one payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage and reimbursement for our products, if they are approved, by third-party payors.
A primary trend in the healthcare industry in the United States and elsewhere is cost containment. Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. Third-party payors may also seek, with respect to an approved product, additional clinical evidence that goes beyond the data required to obtain marketing approval. They may require such evidence to demonstrate clinical benefits and value in specific patient populations or they may call for costly pharmaceutical studies to justify coverage and reimbursement or the level of reimbursement relative to other therapies before covering our products. Third party payors may manage utilization by implementing a drug formulary, establishing different copays for different drugs or requiring a prescriber to obtain prior authorization from the relevant third-party payor before a drug will be covered for a particular patient. We expect to experience pricing pressures in connection with the sale of our product candidates due to the trend toward managed health care and additional legislative, administrative, or regulatory changes. The downward pressure on healthcare costs in general, particularly prescription drugs, has become intense and new products face increasing challenges in entering the market successfully. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs in exchange for coverage or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold. Our ability to commercialize our product candidates successfully may be adversely affected by discounts or rebates that we are required to provide in order to ensure coverage of our products and compete in the marketplace. Accordingly, we cannot be sure that reimbursement will be available for any drug that we commercialize and, if reimbursement is available, we cannot be sure as to the level of reimbursement and whether it will be adequate. Coverage and reimbursement may impact the demand for, or the price of, any product candidate for which we obtain marketing approval. If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketing approval.
There may be significant delays in obtaining reimbursement for newly-approved drugs, and coverage may be more limited than the indications for which the drug is approved by the FDA or comparable regulatory authorities outside of the United States. Moreover, eligibility for reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our inability to promptly obtain coverage and profitable payment rates from both government-funded and private payors for any approved drugs that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize drugs and our overall financial condition.
The market opportunities for our product candidates may be limited to those patients who are ineligible for or have failed prior treatments and may be small, and our estimates of the prevalence of our target patient populations may be inaccurate.
Cancer and autoimmune therapies are sometimes characterized as first-line, second-line, third-line and even fourth-line, and the FDA often approves new therapies initially only for last-line use. Initial approvals for new cancer and autoimmune therapies are often restricted to later lines of therapy, and in the case of cancer specifically, for patients with advanced or metastatic disease. Indeed, the BLA that the FDA has accepted the submission of, and the BLA that we intend to file in the future, for balstilimab and zalifrelimab target second-line cervical cancer. This will limit the number of cervical cancer patients who may be eligible to use balstilimab and zalifrelimab, if approved.
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Our projections of both the number of people who have the diseases we are targeting, as well as the subset of people with these diseases in a position to receive our therapies, if approved, are based on our beliefs and estimates. These estimates have been derived from a variety of sources, including scientific literature, input from key opinion leaders, patient foundations, or secondary market research databases, and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of these diseases. The number of patients may turn out to be lower than expected. Additionally, the potentially addressable patient population for our product candidates may be limited or may not be amenable to treatment with our product candidates. For instance, we expect our product candidates targeting cervical cancer to target the smaller patient populations that suffer from the respective diseases we seek to treat. Furthermore, regulators and payors may further narrow the therapy-accessible treatment population. Even if we obtain significant market share for our product candidates, because certain of the potential target populations are small, we may never achieve profitability without obtaining regulatory approval for additional indications.
We are currently building marketing, sales and commercial compliance functions, and as a company, we have no experience in marketing, selling and distributing products or performing commercial compliance. If we are unable to establish such capabilities or enter into agreements with third parties to perform such functions, we may not be able to generate product revenue.
We currently have a small number of employees that are tasked with building our marketing, sales and commercial compliance functions, and we currently have limited sales, marketing, distribution or commercial compliance capabilities and have no experience as a company performing such tasks. Developing an in-house marketing team, sales force and commercial compliance function will require significant capital expenditures, management resources and time and may ultimately prove to be unsuccessful. In the event we develop and deploy these capabilities, we will have to compete with other pharmaceutical and biotechnology companies to recruit, hire, train and retain personnel qualified to perform these tasks. If we fail to market and sell our approved products in compliance with applicable laws and regulations, we may be subject to fines or other penalties.
In addition to establishing internal sales, marketing and distribution capabilities, we may pursue collaborative arrangements regarding the sales and marketing of our products, however, there can be no assurance that we will be able to establish or maintain such collaborative arrangements, or if we are able to do so, that they will have effective sales forces. Any revenue we receive will depend upon the efforts of such third parties, which may not be successful. We may have little or no control over the marketing and sales efforts of such third parties and our revenue from product sales may be lower than if we had commercialized our product candidates ourselves. We also face competition in our search for third parties to assist us with the sales and marketing efforts of our product candidates.
There can be no assurance that we will be able to develop in-house sales and distribution capabilities or establish or maintain relationships with third-party collaborators to commercialize any product in the United States or overseas.
Risks Related to Manufacturing and Supply
Our product candidates are uniquely manufactured. If we or any of our third-party manufacturers encounter difficulties in manufacturing our product candidates, our ability to provide supply of our product candidates for clinical trials or our products for patients, if approved, could be delayed or stopped, or we may be unable to maintain a commercially viable cost structure.
The manufacturing process used to produce certain of our product candidates is complex and novel and has not yet been validated for commercial production. As a result of these complexities, the cost to manufacture certain of our product candidates is potentially higher than traditional antibodies and the manufacturing process is less reliable and is more difficult to reproduce. Furthermore, our manufacturing process for certain of our product candidates has not been scaled up to commercial production. The actual cost to manufacture and process certain of our product candidates could be greater than we expect and could materially and adversely affect the commercial viability of such product candidates.
Our manufacturing process may be susceptible to logistical issues associated with the collection of materials sourced from various suppliers as well as shipment of the final product to clinical centers, manufacturing issues associated with interruptions in the manufacturing process, contamination, equipment or reagent failure, improper installation or operation of equipment, vendor or operator error, inconsistency in production batches, and variability in product characteristics. Even minor deviations from normal manufacturing processes could result in reduced production yields, lot failures, product defects, product recalls, product liability claims and other supply disruptions. If microbial, viral, or other contaminations are discovered in our product candidates or in our manufacturing facilities in which our product candidates are made, production at such manufacturing facilities may be interrupted for an extended period of time to investigate and remedy the contamination. Further, as we transition from late-stage clinical trials toward approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods, are altered along the way in an effort to optimize processes and results. Such changes carry the risk that they will not achieve these intended objectives, and any of these changes could cause our product candidates to perform differently and affect the results of planned clinical trials or other future clinical trials.
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Although we continue to optimize our manufacturing process for our antibody product candidates, doing so is a difficult and uncertain task, and there are risks associated with scaling to the level required for commercialization, including, among others, cost overruns, potential problems with process scale-up, process reproducibility, stability issues, lot consistency, and timely availability of reagents and/or raw materials. We ultimately may not be successful in transferring our in-house clinical scale production system to any commercial scale manufacturing facilities that we establish ourselves or establish at a contract manufacturing organization (“CMO”). If we are unable to adequately validate or scale-up the manufacturing process for our product candidates with our contracted CMO, we will need to transfer to another manufacturer and complete the manufacturing validation process, which can be lengthy. If we are able to adequately validate and scale-up the manufacturing process for our product candidates with a contract manufacturer, we will still need to negotiate with such contract manufacturer an agreement for commercial supply and it is not certain we will be able to come to agreement on terms acceptable to us for all product candidates. As a result, we may ultimately be unable to reduce the cost of goods for our product candidates to levels that will allow for an attractive return on investment if and when those product candidates are commercialized.
In November 2020, we announced a new long-term lease in Emeryville, CA for cGMP manufacturing space, which we intend to use for certain of our own commercial manufacturing requirements and are in the process of building out. We have never built, owned or operated a commercial manufacturing building, and there is no guarantee that we will be successful doing so.
The manufacturing process for any products that we may develop is subject to the FDA and foreign regulatory authority approval process. If we or our CMOs are unable to reliably produce products to specifications acceptable to the FDA or other regulatory authorities, we may not obtain or maintain the approvals we need to commercialize such products. Even if we obtain regulatory approval for any of our product candidates, there is no assurance that either we or our CMOs will be able to manufacture the approved product to specifications acceptable to the FDA or other regulatory authorities, to produce it in sufficient quantities to meet the requirements for the potential launch of the product, or to meet potential future demand. Any of these challenges could delay completion of clinical trials, require bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of our product candidates, impair commercialization efforts, increase our cost of goods, and have an adverse effect on our business, financial condition, results of operations and growth prospects. Our future success depends on our ability to manufacture our products on a timely basis with acceptable manufacturing costs, while at the same time maintaining good quality control and complying with applicable regulatory requirements, and an inability to do so could have a material adverse effect on our business, financial condition, and results of operations. In addition, we could incur higher manufacturing costs if manufacturing processes or standards change, and we could need to replace, modify, design, or build and install equipment, all of which would require additional capital expenditures. Specifically, because our product candidates may have a higher cost of goods than conventional therapies, the risk that coverage and reimbursement rates may be inadequate for us to achieve profitability may be greater.
We own and operate our own clinical scale manufacturing facility and infrastructure in addition to or in lieu of relying on CMOs for the manufacture of clinical supplies of our product candidates. This is costly and time-consuming.
We own and operate the manufacturing pilot plant that supplies our antibody drug substance requirements for clinical proof-of-concept studies. Any performance failure on the part of our existing facility could delay clinical development or marketing approval of our antibody programs.
We own and operate the cGMP manufacturing pilot plant originally used to manufacture our autologous and allogeneic vaccines in Lexington, MA. Manufacturing of autologous or allogeneic vaccines is complex, and various factors could cause delays or an inability to supply the vaccine.
We have given our corporate QS-21 Stimulon licensee, GSK, manufacturing rights for QS-21 Stimulon for use in their product programs. We have retained the right to manufacture QS-21 for ourselves and third parties, although no other such programs are anticipated to bring us substantial revenues in the near future, if ever. Although we have the right to secure certain quantities of QS-21 from GSK and we have some internal supply in-house, we currently do not have an alternative long-term supply partner for this adjuvant. In January 2019, we announced that the Bill & Melinda Gates Foundation awarded us a grant to develop an alternative, plant cell culture-based manufacturing process with the goal of ensuring the continuous future supply of QS-21 Stimulon adjuvant. While we are pursuing this in partnership with Phyton Biotech, there is no guarantee that we will be successful in these development efforts.
We also may encounter problems hiring and retaining the experienced scientific, quality-control and manufacturing personnel needed to operate our manufacturing processes, which could result in delays in production or difficulties in maintaining compliance with applicable regulatory requirements.
Any problems in our manufacturing process or facilities, or that of our licensees and suppliers, could make us a less attractive
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collaborator for potential partners, including larger pharmaceutical companies and academic research institutions, which could limit our access to additional attractive development programs.
The FDA, the EMA and other foreign regulatory authorities may require us to submit samples of any lot of any approved product together with the protocols showing the results of applicable tests at any time. Under some circumstances, the FDA, the EMA or other foreign regulatory authorities may require that we not distribute a lot until the relevant agency authorizes its release. Slight deviations in the manufacturing process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls. Lot failures or product recalls could cause us to delay product launches or clinical trials, which could be costly to us and otherwise harm our business, financial condition, results of operations and prospects. Problems in our manufacturing process could restrict our ability to meet market demand for our products.
We are dependent on suppliers for some of our components and materials used to manufacture our product candidates.
We currently depend on suppliers for some of the components necessary for our product candidates. We cannot be sure that these suppliers will remain in business, that they will be able to meet our supply needs, or that they will not be purchased by one of our competitors or another company that is not interested in continuing to produce these materials for our intended purpose. There are, in general, relatively few alternative sources of supply for these components. These suppliers may be unable or unwilling to meet our future demands for our clinical trials or commercial sale. Establishing additional or replacement suppliers for these components could take a substantial amount of time and it may be difficult to establish replacement suppliers who meet regulatory requirements. Any disruption in supply from a supplier or manufacturing location could lead to supply delays or interruptions which would damage our business, financial condition, results of operations and prospects. If we are able to find a replacement supplier, the replacement supplier would need to be qualified and may require additional regulatory authority approval, which could result in further delay. While we seek to maintain adequate inventory of the materials used to manufacture our products, any interruption or delay in the supply of materials, or our inability to obtain materials from alternate sources at acceptable prices in a timely manner, could impair our ability to meet the demand of our customers and cause them to cancel orders. In addition, as part of the FDA’s approval of our product candidates, we will also require FDA approval of the individual components of our process, which include the manufacturing processes and facilities of our suppliers. Our reliance on these suppliers subjects us to a number of risks that could harm our business, and financial condition, including, among other things: interruption of product candidate or commercial supply resulting from modifications to or discontinuation of a supplier’s operations; delays in product shipments resulting from uncorrected defects, reliability issues, or a supplier’s variation in a component; a lack of long-term supply arrangements for key components with our suppliers; inability to obtain adequate supply in a timely manner, or to obtain adequate supply on commercially reasonable terms; difficulty and cost associated with locating and qualifying alternative suppliers for our components and precursor cells in a timely manner; production delays related to the evaluation and testing of products from alternative suppliers, and corresponding regulatory qualifications; delay in delivery due to our suppliers prioritizing other customer orders over ours; and fluctuation in delivery by our suppliers due to changes in demand from us or their other customers. If any of these risks materialize, our manufacturing costs could significantly increase and our ability to meet clinical and commercial demand for our products could be impacted.
We rely on third parties for the manufacture of clinical supplies of certain of our product candidates and expect to rely on third parties for commercial supplies of any approved product candidates. This reliance on third parties increases the risk that we will not have sufficient quantities of our drug candidates or drugs or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.
We expect to rely on third-party manufacturers for the manufacture of commercial supplies of our drug candidates. At present, we do not have long-term supply agreements with all of the vendors needed to produce our product candidates for commercial sale and we may be unable to establish such agreements with third-party manufacturers or do so on acceptable terms.
The agreements that we do have in place with our third-party manufacturers obligate us to make significant non-refundable deposits to reserve manufacturing slots prior to the receipt of marketing approval for our product candidates. Additionally, if our product candidates are approved, we will be required to make minimum purchases and will have limited ability to purchase product in excess of our forecasted needs. As a result, if product sales fall below our minimum purchase obligations, we will be obligated to purchase more product than we can successfully sell, and if product demand exceeds the amount that we can purchase from our manufacturers, we will have to forgo some product sales. Either of these events may materially harm our financial prospects. Finally, reliance on third-party manufacturers entails additional risks, including:
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reliance on the third party for regulatory compliance and quality assurance; |
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the possible breach of the manufacturing agreement by the third party; |
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the possible failure of the third party to manufacture our drug candidate according to our schedule, or at all, including if the third-party manufacturer gives greater priority to the supply of other drugs over our drug candidates, or otherwise does not satisfactorily perform according to the terms of the manufacturing agreement; |
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equipment malfunctions, power outages, natural or man-made calamities or other general disruptions experienced by our third-party manufacturers to their respective operations and other general problems with a multi-step manufacturing process; |
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the possible misappropriation or disclosure by the third party or others of our proprietary information, including our trade secrets and know-how; and |
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the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us. |
The agreements that we have in place with our third-party suppliers and manufacturers significantly limit the liability of such suppliers and manufacturers for failing to supply or manufacture, as applicable, our product candidates pursuant to the terms of our agreements, or as required by applicable regulation or law. As a result, if we suffer losses due to our suppliers or manufacturers failure to perform, we will have limited remedies available against such suppliers and manufacturers and are unlikely to be able to recover such losses from them.
Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside of the United States. Facilities used by our third-party manufacturers must be inspected by the FDA before potential approval of the drug candidate. Similar regulations apply to manufacturers of our drug candidates for use or sale in foreign countries. We will not control the manufacturing process and will be completely dependent on our third-party manufacturers for compliance with the applicable regulatory requirements for the manufacture of our drug candidates. If our manufacturers cannot successfully manufacture material that conforms to the strict regulatory requirements of the FDA and any applicable foreign regulatory authority, they will not be able to secure the applicable approval for their manufacturing facilities. If these facilities are not approved for commercial manufacture, we may need to find alternative manufacturing facilities, which could result in delays in obtaining approval for the applicable drug candidate as alternative qualified manufacturing facilities may not be available on a timely basis or at all. In addition, our manufacturers are subject to ongoing periodic unannounced inspections by the FDA and corresponding state and foreign agencies for compliance with cGMPs and similar regulatory requirements. Failure by any of our manufacturers to comply with applicable cGMPs or other regulatory requirements could result in sanctions being imposed on us or the contract manufacturer, including fines, injunctions, civil penalties, delays, suspensions or withdrawals of approvals, operating restrictions, interruptions in supply and criminal prosecutions, any of which could significantly and adversely affect supplies of our drug candidates and have a material adverse impact on our business, financial condition and results of operations. Any drugs that we may develop may compete with other drug candidates and drugs for access to manufacturing facilities. There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing for us.
Our anticipated future dependence upon others for the commercial manufacture of our drug candidates or drugs may adversely affect our future profit margins and our ability to commercialize any drugs that receive marketing approval on a timely and competitive basis.
Risks Related to Our Reliance on Third Parties
We are dependent upon our collaborations with BMS, Gilead, Incyte and Betta Pharmaceuticals Co., Ltd. (“Betta Pharmaceuticals”) to further develop and commercialize certain of our antibody programs. If we or BMS, Gilead, Incyte or Betta Pharmaceuticals fail to perform as expected, the potential for us to generate future revenues under such collaborations could be significantly reduced, the development and/or commercialization of these antibodies may be terminated or substantially delayed, and our business could be adversely affected.
In May 2021, we entered into a License, Development and Commercialization Agreement with BMS to collaborate on the development and commercialization of our anti-TIGIT bispecific antibody program AGEN1777. Pursuant to the license agreement, we received an upfront cash payment of $200.0 million and are eligible to receive up to $1.36 billion in aggregate development, regulatory and commercial milestone payments plus the tiered royalties. Additionally, we hold the option to co-fund a minority of the global development costs of products containing AGEN1777 or its derivatives, in exchange for increased tiered royalties on U.S. net sales of co-funded products. There can be no assurance that any of the development, regulatory or sales milestones will be achieved,
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or that we will receive any future milestone or royalty payments under the license agreement. BMS’s activities will be influenced by, among other things, the efforts and allocation of resources by BMS, which we cannot control. If BMS does not perform in the manner we expect or fulfill its responsibilities in a timely manner, or at all, the clinical development, manufacturing, regulatory approval, and commercialization efforts related to the licensed antibodies could be delayed or terminated.
In addition, our license with BMS may be unsuccessful due to other factors, including, without limitation, the following:
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BMS may terminate the agreement or any individual program for convenience upon 180 days’ notice; |
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BMS may change the focus of its development and commercialization efforts or prioritize other programs more highly and, accordingly, reduce the efforts and resources allocated to our licensed antibodies; and |
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BMS may choose not to develop and commercialize antibody products, if any, in all relevant markets or for one or more indications, if at all. |
In December 2018, we entered into a series of agreements with Gilead to collaborate on the development and commercialization of up to five novel I-O therapies. Pursuant to the collaboration agreements, Gilead received (i) worldwide exclusive rights to AGEN1423, a bispecific antibody, (ii) the exclusive option to license exclusively AGEN1223, a bispecific antibody, and AGEN2373, a monospecific antibody, and (iii) the right of first negotiation for two additional, undisclosed programs. Gilead had the exclusive right to develop and commercialize AGEN1423, and we were eligible to receive potential development and commercial milestones of up to $552.5 million in the aggregate. In November 2020, Gilead elected to return AGEN1423 to us and voluntarily terminated the license agreement effective as of February 4, 2021. The option agreements remain in place, and we are responsible for developing each program up to the option decision point, at which time Gilead may acquire exclusive rights to each program on option exercise. During the option period, we are eligible to receive milestones of up to $30.0 million in the aggregate. If Gilead exercises an option, it would be required to pay an upfront option exercise fee of $50.0 million for each option that is exercised. Following any option exercise, we would be eligible to receive additional development and commercial milestones of up to $520.0 million in the aggregate for each such option program, as well as tiered royalty payments on aggregate net sales ranging from the high single digit to mid-teen percent, subject to certain reductions under certain circumstances. For either, but not both, of the option programs, we will have the right to opt-in to share Gilead’s development and commercialization costs in the United States for such option program in exchange for a profit (loss) share on a 50:50 basis and revised milestone payments. There is no guarantee that we will be able to successfully advance the option programs to the option decision point, and, even if we do, there is no guarantee that Gilead will exercise its option for either program. If Gilead does not exercise its option for either of the option programs, there is no guarantee that we will be able to advance any such program ourselves or with another partner.
In February 2017, we amended the terms of our collaboration agreement with Incyte to, among other things, convert the GITR and OX40 programs from profit-share programs, where we and Incyte shared all costs and profits on a 50:50 basis, to royalty-bearing programs, where Incyte funds 100% of the costs and we are eligible for potential milestones and royalties. In addition, the profit-share programs relating to TIGIT and one undisclosed target were removed from the collaboration, with TIGIT reverting to Agenus and the undisclosed target reverting to Incyte, each with a potential 15% royalty to the other party on any global net sales. The remaining three royalty-bearing programs in the collaboration targeting TIM-3, LAG-3 and one undisclosed target remain unchanged, and there are no more profit-share programs under the collaboration. For each program in the collaboration, Incyte has exclusive rights and all decision-making authority for manufacturing, clinical development and commercialization. Accordingly, the timely and successful completion by Incyte of clinical development and commercialization activities will significantly affect the timing and amount of any royalties or milestones we may receive under the collaboration agreement. In addition, in March 2017 we transferred manufacturing responsibilities to Incyte for antibodies under that collaboration. Any delays or weaknesses in the ability of Incyte to successfully manufacture could have an adverse impact on those programs. Incyte’s activities will be influenced by, among other things, the efforts and allocation of resources by Incyte, which we cannot control. If Incyte does not perform in the manner we expect or fulfill its responsibilities in a timely manner, or at all, the clinical development, manufacturing, regulatory approval, and commercialization efforts related to antibodies under the collaboration could be delayed or terminated. There can be no assurance that any of the development, regulatory or sales milestones will be achieved, or that we will receive any future milestone or royalty payments under the collaboration agreement. In September 2018, we sold to XOMA a portion of the royalties and milestones we are entitled to receive from Incyte.
In addition, our collaboration with Incyte may be unsuccessful due to other factors, including, without limitation, the following:
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Incyte may terminate the agreement or any individual program for convenience upon 12 months’ notice; |
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Incyte has control over the development of assets in the collaboration; |
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Incyte may change the focus of its development and commercialization efforts or prioritize other programs more highly and, accordingly, reduce the efforts and resources allocated to our collaboration; |
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Incyte may choose not to develop and commercialize antibody products, if any, in all relevant markets or for one or more indications, if at all; and |
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If Incyte is acquired during the term of our collaboration, the acquirer may have competing programs or different strategic priorities that could cause it to reduce its commitment to our collaboration. |
If Incyte terminates our collaboration agreement, we may need to raise additional capital and may need to identify and come to agreement with another collaboration partner to advance certain of our antibody programs. Even if we are able to find another partner, this effort could cause delays in our timelines and/or additional expenses, which could adversely affect our business prospects and the future of our antibody product candidates under the collaboration.
In June 2020, we entered into a license and collaboration agreement with Betta Pharmaceuticals to collaborate on the development and commercialization of balstilimab and zalifrelimab in greater China. Pursuant to the license and collaboration agreement, Betta Pharmaceuticals received an exclusive license to develop, manufacture and commercialize zalifrelimab and balstilimab in all fields (other than intravesical delivery) in greater China. Under the agreement, Betta Pharmaceuticals is responsible for all of the development, regulatory approval, manufacturing and commercialization costs in greater China. As part of the collaboration, Betta Pharma made an upfront cash payment of $15.0 million and agreed to make up to $100.0 million in aggregate milestone payments plus tiered royalties on net sales of zalifrelimab and balstilimab. Royalties range from mid-single digit to low-twenties percent, subject to certain reductions under certain circumstances. Accordingly, the timely and successful completion by Betta Pharmaceuticals of development, regulatory approval, manufacturing and commercialization activities will significantly affect the timing and amount of any milestones or royalties we may receive from Betta Pharmaceuticals. Betta Pharmaceuticals’ activities will be influenced by, among other things, the efforts and allocation of resources by Betta Pharmaceuticals, which we cannot control.
In addition, our collaboration with Betta Pharmaceuticals may be unsuccessful due to other factors, including, without limitation, that Betta Pharmaceuticals:
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may terminate any of the license and collaboration agreement for convenience upon 90 days’ notice; |
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has control over the development, regulatory approval, manufacturing and commercialization of balstilimab and zalifrelimab in greater China; |
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may change the focus of its business efforts or prioritize other programs more highly and, accordingly, reduce the efforts and resources allocated to balstilimab and zalifrelimab; and |
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may choose not to develop and commercialize balstilimab and zalifrelimab in all markets within greater China or for one or more indications, if at all. |
Additionally, the US-China relationship has deteriorated in recent years and, further deterioration may impact the ability of Agenus and Betta Pharmaceuticals to successfully collaborate.
Failure to enter into and/or maintain additional significant licensing, distribution and/or collaboration agreements in a timely manner and on favorable terms to us may hinder or cause us to cease our efforts to develop and commercialize our product candidates, increase our development timelines, and/or increase our need to rely on partnering or financing mechanisms, such as sales of debt or equity securities, to fund our operations and continue our current and anticipated programs. Even if we enter into and maintain such agreements, they may not prove successful, and/or we may not receive significant payments from agreements.
Part of our strategy is to develop and commercialize many of our product candidates by continuing or entering into arrangements with academic, government, or corporate collaborators and licensees. Our success depends on our ability to negotiate such agreements on favorable terms and on the success of the other parties in performing research, pre-clinical and clinical testing, completing regulatory applications, and commercializing product candidates. Our research, development, and commercialization efforts with respect to antibody candidates from our technology platforms are, in part, contingent upon the participation of institutional and corporate collaborators. For example, in February 2015, we began a broad collaboration with Incyte to pursue the discovery and development of antibodies, in December 2018 we entered into a partnership with Gilead relating to five of our antibody programs and in May 2021 we entered into a license agreement with BMS relating to our anti-TIGIT bispecific antibody program. Furthermore, we have a collaboration arrangement with Recepta for balstilimab and zalifrelimab, giving Recepta rights to certain South American countries and requiring us to agree upon development plans for these product candidates. Disagreements or the failure of either party to perform satisfactorily could have an adverse impact on these programs.
The Brain Tumor Trials Collaborative, through the NCI, is sponsoring a Phase 2 clinical trial of our Prophage vaccine candidate in combination with Merck’s pembrolizumab in patients with glioma. When our licensees or third-party collaborators sponsor clinical
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trials using our product candidates, we cannot control the timing of enrollment, data readout, or quality of such trials or related activities.
Our ability to advance our antibody programs depends in part on such collaborations. In addition, from time to time we engage in efforts to enter into licensing, distribution and/or collaboration agreements with one or more pharmaceutical or biotechnology companies to assist us with development and/or commercialization of our other product candidates. Any licensing, distribution and/or collaborations agreements, we enter into, including those with BMS, Gilead and Incyte, may pose a number of risks, including the following:
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collaborators have significant discretion in determining the efforts and resources that they will apply; |
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collaborators may not perform their obligations as expected; |
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collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs or license arrangements based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as a strategic transaction that may divert resources or create competing priorities; |
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collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; |
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collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products and product candidates if the collaborators believe that the competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; |
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product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; |
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collaborators may fail to comply with applicable regulatory requirements regarding the development, manufacture, distribution or marketing of a product candidate or product; |
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collaborators with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; |
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disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or terminations of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive; |
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collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation; |
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collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; |
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if a collaborator of ours is involved in a business combination, the collaborator might deemphasize or terminate the development or commercialization of any product candidate licensed to it by us; and |
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collaborations may be terminated by the collaborator, and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates. |
If our current or future collaborations do not result in the successful discovery, development and commercialization of products or if one of our collaborators terminates its agreement with us, we may not receive any future research funding or milestone or royalty payments under the collaboration. If we do not receive the funding we expect under these agreements, our development of our technology and product candidates could be delayed and we may need additional resources to develop product candidates and our technology. All of the risks relating to product development, regulatory approval and commercialization described herein also apply to the activities of our therapeutic collaborators.
Additionally, if one of our collaborators, such as BMS, Incyte or Recepta, terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception in the business and financial communities could be adversely affected.
Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators. We face significant competition in seeking appropriate collaborators. Our ability to reach a definitive agreement for a
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collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors.
If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may have to curtail the development of a product candidate, reduce or delay its development program or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms, or at all. If we fail to enter into collaborations or do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we may not be able to further develop our product candidates, bring them to market and generate revenue from sales of drugs or continue to develop our technology, and our business may be materially and adversely affected.
We rely on third parties to conduct our clinical trials. If these third parties do not successfully carry out their contractual duties or meet expected deadlines or comply with regulatory requirements, we may not be able to obtain regulatory approval of or commercialize any potential product candidates.
We depend upon third parties, including independent investigators, to conduct our clinical trials under agreements with universities, medical institutions, CROs, strategic partners and others. Such reliance obligates us to negotiate budgets and contracts with CROs and trial sites, which may result in delays to our development timelines and increased costs.
We rely heavily on third parties over the course of our clinical trials, and, as a result, have limited control over the clinical investigators and limited visibility into their day-to-day activities, including with respect to their compliance with the approved clinical protocol. Nevertheless, we are responsible for ensuring that each of our trials is conducted in accordance with the applicable protocol, legal and regulatory requirements and scientific standards, and our reliance on third parties does not relieve us of our regulatory responsibilities. We and these third parties are required to comply with GCP requirements, which are regulations and guidelines enforced by the FDA and comparable foreign regulatory authorities for product candidates in clinical development. Regulatory authorities enforce these GCP requirements through periodic inspections of trial sponsors, clinical investigators and trial sites. If we or any of these third parties fail to comply with applicable GCP requirements, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to suspend or terminate these trials or perform additional nonclinical studies or clinical trials before approving our marketing applications. We cannot be certain that, upon inspection, such regulatory authorities will determine that any of our clinical trials comply with the GCP requirements. In addition, our clinical trials must be conducted with biologic product produced under cGMP requirements and may require a large number of patients.
Our failure or any failure by these third parties to comply with these regulations or to recruit a sufficient number of patients may require us to repeat clinical trials, which would delay the regulatory approval process. Moreover, our business may be implicated if any of these third parties violates federal or state fraud and abuse or false claims laws and regulations or healthcare privacy and security laws.
The persons engaged by third parties conducting our clinical trials are not our employees and, except for remedies that may be available to us under our agreements with such third parties, we cannot control whether or not such persons devote sufficient time and resources to our ongoing pre-clinical and clinical programs. These third parties may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other product development activities, which could affect their performance on our behalf. If these third parties do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to complete development of, obtain regulatory approval of or successfully commercialize our product candidates. As a result, our financial results and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenue could be delayed.
If any of our relationships with these third-party CROs or others terminate, we may not be able to enter into arrangements with alternative CROs or other third parties or to do so on commercially reasonable terms. Switching or adding additional CROs involves additional cost and requires management time and focus. In addition, there is a natural transition period when a new CRO begins work. As a result, delays may occur, which can materially impact our ability to meet our desired clinical development timelines. Though we carefully manage our relationships with our CROs, there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.
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Risks Related to Government Regulations
The regulatory approval process for our product candidates in the United States, European Union and other jurisdictions is currently uncertain and will be lengthy, time-consuming and inherently unpredictable and we may experience significant delays in the clinical development and regulatory approval, if any, of our product candidates.
The research, testing, manufacturing, labeling, approval, selling, import, export, marketing and distribution of drug products, including biologics, are subject to extensive regulation by the FDA in the United States and regulatory authorities in states and other countries. We are not permitted to market any biological product in the United States for commercial use until we receive a biologics license from the FDA. In June 2021, the FDA accepted submission of our first BLA, for balstilimab monotherapy. Even after submission of our BLA, we expect the novel nature of our product candidates to create further challenges in obtaining regulatory approval. Accordingly, the regulatory approval pathway for our product candidates may be uncertain, complex, expensive and lengthy, and we may never obtain regulatory approval for our product candidates.
The FDA may also require a panel of experts, referred to as an Advisory Committee, to deliberate on the adequacy of the safety and efficacy data to support approval. The opinion of the Advisory Committee, although not binding, may have a significant impact on our ability to obtain approval of any product candidates that we develop based on the completed clinical trials.
The FDA may disagree with our regulatory plan and we may fail to obtain regulatory approval of our product candidates.
Although the regulatory framework for approving immunotherapy products is evolving, the general approach for FDA approval of a new biologic or drug has historically been to provide dispositive data from two well-controlled, Phase 3 clinical trials of the relevant biologic or drug in the relevant patient population. Phase 3 clinical trials typically involve hundreds of patients, have significant costs and take years to complete. We intend to utilize an accelerated approval approach for our product candidates given the limited alternatives for cancer treatments, but the FDA may not agree with our plans.
In addition, our clinical trial results may also not support approval of our product candidates. Our product candidates could fail to receive regulatory approval for many reasons, including the following:
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the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; |
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we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that our product candidates are safe and effective for any of their proposed indications; |
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the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval; |
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we may be unable to demonstrate that our product candidates’ clinical and other benefits outweigh their safety risks; |
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the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from nonclinical studies or clinical trials; |
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the data collected from clinical trials of our product candidates may be deemed by the FDA or comparable foreign regulatory authorities to be insufficient to support the submission of a BLA or other comparable submission in foreign jurisdictions or to obtain regulatory approval in the United States or elsewhere; |
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the FDA or comparable foreign regulatory authorities may fail to approve or find deficiencies with the manufacturing processes and controls or facilities of third-party manufacturers with which we contract for clinical and commercial supplies or any facilities that we may own in the future; and |
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the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner that could render our clinical data insufficient for approval. |
The FDA, the EMA and other regulatory authorities may implement additional regulations or restrictions on the development and commercialization of our product candidates, which may be difficult to predict.
The FDA, the EMA and regulatory authorities in other countries have each expressed interest in further regulating biotechnology products, such as antibodies, vaccines, adjuvants and adoptive cell therapies. Agencies at both the federal and state level in the United States, as well as the U.S. Congressional committees and other governments or governing agencies, have also expressed interest in further regulating the biotechnology industry. Such action may delay or prevent commercialization of some or all of our product candidates. Adverse developments in clinical trials of antibodies, vaccines, adjuvants or adoptive cell therapies products conducted by others may cause the FDA or other oversight bodies to change the requirements for approval of any of our
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product candidates. Similarly, the EMA governs the development of antibodies, vaccines, adjuvants and adoptive cell therapies in the European Union and may issue new guidelines concerning the development and marketing authorization for such products and require that we comply with these new guidelines. These regulatory review agencies and committees and the new requirements or guidelines they promulgate may lengthen the regulatory review process, require us to perform additional studies or trials, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval limitations or restrictions. As we advance our product candidates, we will be required to consult with these regulatory agencies and comply with applicable requirements and guidelines. If we fail to do so, we may be required to delay or discontinue development of such product candidates. These additional processes may result in a review and approval process that is longer than we otherwise would have expected. Delays as a result of an increased or lengthier regulatory approval process or further restrictions on the development of our product candidates can be costly and could negatively impact our ability to complete clinical trials and commercialize our current and future product candidates in a timely manner, if at all.
Breakthrough Therapy Designation, Fast Track Designation or Regenerative Medicine Advanced Therapy Designation by the FDA, even if granted for any of our product candidates, may not lead to a faster development, regulatory review or approval process, and it does not increase the likelihood that any of our product candidates will receive marketing approval in the United States.
We may seek a Breakthrough Therapy Designation for some of our product candidates. A breakthrough therapy is defined as a therapy that is intended, alone or in combination with one or more other therapies, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the therapy may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For therapies that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Therapies designated as breakthrough therapies by the FDA may also be eligible for priority review and accelerated approval. Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. In any event, the receipt of a Breakthrough Therapy Designation for a product candidate may not result in a faster development process, review or approval compared to therapies considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that such product candidates no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.
We have received Fast Track Designation for investigation of balstilimab in combination with zalifrelimab for the treatment of patients with relapsed or refractory metastatic cervical cancer and balstilimab alone for the treatment of cervical cancer, and we intend to apply for such designation for our other product candidates in the future. If a therapy is intended for the treatment of a serious or life-threatening condition and the therapy demonstrates the potential to address unmet medical needs for this condition, the therapy sponsor may apply for Fast Track Designation. The FDA has broad discretion whether or not to grant this designation, so even if we believe a particular product candidate is eligible for this designation; we cannot assure our stockholders that the FDA would decide to grant it. We may not experience a faster development process, review or approval compared to conventional FDA procedures for the product candidate for which we have received, or may receive in the future, Fast Track Designation. The FDA may withdraw Fast Track Designation if it believes that the designation is no longer supported by data from our clinical development program. Fast Track Designation alone does not guarantee qualification for the FDA’s priority review procedures.
We may seek Regenerative Medicine Advanced Therapy (“RMAT”) designation for some of our product candidates including our allogeneic cell therapies. In 2017, the FDA established the RMAT designation as part of its implementation of the 21st Century Cures Act to expedite review of any drug that meets the following criteria: it qualifies as a RMAT, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, with limited exceptions; it is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such a disease or condition. Like Breakthrough Therapy Designation, RMAT designation provides potential benefits that include more frequent meetings with FDA to discuss the development plan for the product candidate, and eligibility for rolling review and priority review. Products granted RMAT designation may also be eligible for accelerated approval on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of sites, including through expansion to additional sites. RMAT-designated products that receive accelerated approval may, as appropriate, fulfill their post-approval requirements through the submission of clinical evidence, clinical trials, patient registries, or other sources of real world evidence, such as electronic health records; through the collection of larger confirmatory data sets; or via post-approval monitoring of all patients treated with such therapy prior to approval of the therapy. There is no assurance that we will be able to obtain RMAT designation for any of our product candidates. RMAT designation does not change the FDA’s standards for product approval, and there is no assurance that such designation will result in expedited review or approval or that the approved indication will not be
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narrower than the indication covered by the designation. Additionally, RMAT designation can be revoked if the criteria for eligibility cease to be met as clinical data emerges.
We may seek priority review designation for one or more of our other product candidates, but we might not receive such designation, and even if we do, such designation may not lead to a faster development or regulatory review or approval process.
If the FDA determines that a product candidate offers a treatment for a serious condition and, if approved, the product would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A priority review designation means that the goal for the FDA to review an application is six months, rather than the standard review period of ten months. We may request priority review for our product candidates. The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a priority review designation does not necessarily result in expedited development or regulatory review or approval process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures. Receiving priority review from the FDA does not guarantee approval within the six-month review cycle or at all.
We may not be able to obtain or maintain orphan drug designations from the FDA for our current and future product candidates, as applicable.
Our strategy includes filing for orphan drug designation where available for our product candidates, but thus far, our applications for orphan drug designation with respect to balstilimab and zalifrelimab have been rejected.
Under the Orphan Drug Act, the FDA may grant orphan drug designation to a drug or biologic intended to treat a rare disease or condition, which is defined as one occurring in a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug or biologic will be recovered from sales in the United States. In the United States, orphan drug designation entitles a party to financial incentives, such as opportunities for grant funding toward clinical trial costs, tax advantages and user-fee waivers. In addition, if a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full new drug application, or NDA, or BLA, to market the same drug or biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or where the original manufacturer is unable to assure sufficient product quantity.
In addition, exclusive marketing rights in the United States may be limited if we seek approval for an indication broader than the orphan-designated indication or may be lost if the FDA later determines that the request for designation was materially defective or if we are unable to assure sufficient quantities of the product to meet the needs of patients with the orphan- designated disease or condition. Further, even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs with different active moieties may receive and be approved for the same condition, and only the first applicant to receive approval will receive the benefits of marketing exclusivity. Even after an orphan-designated product is approved, the FDA can subsequently approve a later drug with the same active moiety for the same condition if the FDA concludes that the later drug is clinically superior if it is shown to be safer, more effective or makes a major contribution to patient care. Orphan drug designation neither shortens the development time or regulatory review time of a drug, nor gives the drug any advantage in the regulatory review or approval process. In addition, while we may again seek orphan drug designation for our product candidates, we may never receive such designations.
Our relationships with healthcare providers and physicians and third-party payors will be subject to applicable anti- kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.
Healthcare providers, physicians and third-party payors in the United States and elsewhere play a primary role in the recommendation and prescription of pharmaceutical products. Arrangements with third-party payors and customers can expose pharmaceutical manufactures to broadly applicable fraud and abuse and other healthcare laws and regulations, including, without limitation, the federal Anti-Kickback Statute and the federal False Claims Act (the “FCA”), which may constrain the business or financial arrangements and relationships through which such companies sell, market and distribute pharmaceutical products. In particular, the promotion, sales and marketing of healthcare items and services, as well as certain business arrangements in the healthcare industry, are subject to extensive laws designed to prevent fraud, kickbacks, self- dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements generally. Activities subject to these laws also involve the improper use of information obtained in the course of patient recruitment for clinical trials. The applicable federal, state and foreign healthcare laws and regulations laws that may affect our ability to operate include, but are not limited to:
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the federal Anti-Kickback Statute, which prohibits, among other things, knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation of any good, facility, item or service for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs. A person or entity can be found guilty of violating the statute without actual knowledge of the statute or specific intent to violate it. In addition, a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA. The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers, and formulary managers on the other. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution; |
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federal civil and criminal false claims laws and civil monetary penalty laws, including the FCA, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, false or fraudulent claims for payment to, or approval by, Medicare, Medicaid, or other federal healthcare programs, knowingly making, using or causing to be made or used a false record or statement material to a false or fraudulent claim or an obligation to pay or transmit money to the federal government, or knowingly concealing or knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the federal government. Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery; |
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the federal anti-inducement law, prohibits, among other things, the offering or giving of remuneration, which includes, without limitation, any transfer of items or services for free or for less than fair market value (with limited exceptions), to a Medicare or Medicaid beneficiary that the person knows or should know is likely to influence the beneficiary’s selection of a particular supplier of items or services reimbursable by a federal or state governmental program; |
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federal laws, including the Medicaid Drug Rebate Program, that require pharmaceutical manufacturers to report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs; |
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the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty of violating HIPAA without actual knowledge of the statute or specific intent to violate it; |
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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their respective implementing regulations, which impose, among other things, requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates that perform services for them that involve the use or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information without appropriate authorization. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions; |
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the federal Physician Payment Sunshine Act, created under the Patient Protection and Affordable Care Act, and its implementing regulations, which require manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the United States Department of Health and Human Services (“HHS”), information related to payments or other “transfers of value” made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, and other categories of healthcare providers beginning in reports submitted in 2022, as well as ownership and investment interests held by physicians and their immediate family members; |
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the U.S. Federal Food, Drug, and Cosmetic Act, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; |
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federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; and |
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analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, and may be broader in scope than their federal equivalents; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts. |
The distribution of pharmaceutical products is subject to additional requirements and regulations, including extensive record-keeping, licensing, storage and security requirements intended to prevent the unauthorized sale of pharmaceutical products.
The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations. Federal and state enforcement bodies have recently increased their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry. Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time- and resource-consuming and can divert a company’s financial resources and management’s attention away from the business.
On January 31, 2019, the HHS and HHS Office of Inspector General proposed an amendment to one of the existing Anti- Kickback Statute safe harbors (42 C.F.R. 1001.952(h)) which would prohibit certain pharmaceutical manufacturers from offering rebates to pharmacy benefit managers (“PBMs”), in the Medicare Part D and Medicaid managed care programs. The proposed amendment would remove protection for “discounts” from Anti-Kickback enforcement action and would include criminal and civil penalties for knowingly and willfully offering, paying, soliciting, or receiving remuneration to induce or reward the referral of business reimbursable under federal health care programs. At the same time, HHS also proposed to create a new safe harbor to protect point-of-sale discounts that drug manufacturers provide directly to patients and adds another safe harbor to protect certain administrative fees paid by manufacturers to PBMs. The revisions to the federal Anti-Kickback regulations referenced above were initially scheduled to take effect in 2022 but have now been delayed to 2023 under the Biden Administration.
The failure to comply with any of these laws or regulatory requirements subjects entities to possible legal or regulatory action. Depending on the circumstances, failure to meet applicable regulatory requirements can result in civil, criminal and administrative penalties, damages, fines, disgorgement, individual imprisonment, possible exclusion from participation in federal and state funded healthcare programs, contractual damages and the curtailment or restricting of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws. Any action for violation of these laws, even if successfully defended, could cause a pharmaceutical manufacturer to incur significant legal expenses and divert management’s attention from the operation of the business. Prohibitions or restrictions on sales or withdrawal of future marketed products could materially affect business in an adverse way.
We have adopted a code of business conduct and ethics, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent inappropriate conduct may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. Efforts to ensure that our business arrangements will comply with applicable healthcare laws may involve substantial costs. It is possible that governmental and enforcement authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of civil, criminal and administrative penalties, damages, disgorgement, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could adversely affect our ability to operate our business and our results of operations. In addition, the approval and commercialization of any of our product candidates outside the United States will also likely subject us to foreign equivalents of the healthcare laws mentioned above, among other foreign laws.
Even if we receive regulatory approval of any product candidates or therapies, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our product candidates.
If any of our product candidates are approved, they will be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping, export, import, conduct of post-marketing studies and submission of safety, efficacy and other post-market information, including both federal and state requirements in the United States
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and requirements of comparable foreign regulatory authorities. In addition, we will be subject to continued compliance with cGMP and GCP requirements for any clinical trials that we conduct post- approval.
Manufacturers and manufacturers’ facilities are required to comply with extensive FDA, and comparable foreign regulatory authority requirements, including ensuring that quality control and manufacturing procedures conform to cGMP regulations. As such, we and our contract manufacturers will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any BLA, other marketing application, and previous responses to inspection observations. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production and quality control.
Any regulatory approvals that we receive for our product candidates may be subject to limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials and surveillance to monitor the safety and efficacy of the product candidate. The FDA may also require a risk evaluation and mitigation strategies, or REMS, program as a condition of approval of our product candidates, which could entail requirements for long-term patient follow-up, a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. In addition, if the FDA or a comparable foreign regulatory authority approves our product candidates, we will have to comply with requirements including submissions of safety and other post-marketing information and reports and registration.
The FDA may impose consent decrees or withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with our product candidates, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:
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restrictions on the marketing or manufacturing of our products, withdrawal of the product from the market or voluntary or mandatory product recalls; |
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fines, warning letters or holds on clinical trials; |
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refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of license approvals; |
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product seizure or detention or refusal to permit the import or export of our product candidates; and |
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injunctions or the imposition of civil or criminal penalties. |
The FDA strictly regulates marketing, labeling, advertising, and promotion of products that are placed on the market. Products may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses and a company that is found to have improperly promoted off-label uses may be subject to significant liability. The policies of the FDA and of other regulatory authorities may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained which would adversely affect our business, prospects and ability to achieve or sustain profitability.
We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, either in the United States or abroad. For example, policy changes by the new presidential administration may impact our business and industry. The previous administration took several executive actions imposing burdens on, or otherwise materially delaying, the FDA’s ability to engage in routine regulatory and oversight activities, such as implementing statutes through rulemaking, issuance of guidance and review and approval of marketing applications. While the new administration has revoked a number of the executive orders imposing these burdens or delays, it is difficult to predict what executive actions the new administration may implement, and the extent to which such action may impact the FDA’s ability to exercise its regulatory authority. If any executive actions impose constraints on FDA’s ability to engage in oversight and implementation activities in the normal course, our business may be negatively impacted.
Healthcare insurance coverage and reimbursement may be limited or unavailable in certain market segments for our product candidates, if approved, which could make it difficult for us to sell any product candidates or therapies profitably.
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The success of our product candidates, if approved, depends on the availability of adequate coverage and reimbursement from third-party payors. In addition, because our product candidates represent new approaches to the treatment of the diseases they target, we cannot be sure that coverage and reimbursement will be available for, or accurately estimate the potential revenue from, our product candidates or assure that coverage and reimbursement will be available for any product that we may develop.
Patients who are provided medical treatment for their conditions generally rely on third-party payors to reimburse all or part of the costs associated with their treatment. Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid, and commercial payors are critical to new product acceptance.
Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which drugs and treatments they will cover and the amount of reimbursement. Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a product is:
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a covered benefit under its health plan; |
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safe, effective and medically necessary; |
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appropriate for the specific patient; |
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cost-effective; and |
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neither experimental nor investigational. |
In the United States, no uniform policy of coverage and reimbursement for products exists among third-party payors. As a result, obtaining coverage and reimbursement approval of a product from a government or other third-party payor is a time- consuming and costly process that could require us to provide to each payor supporting scientific, clinical and cost- effectiveness data for the use of our products on a payor-by-payor basis, with no assurance that coverage and adequate reimbursement will be obtained. Even if we obtain coverage for a given product, the resulting reimbursement payment rates might not be adequate for us to achieve or sustain profitability or may require co-payments that patients find unacceptably high. Further, even if one payor provides coverage for a given product, other payors may not provide coverage for that product. Additionally, third-party payors may not cover, or provide adequate reimbursement for, long-term follow-up evaluations required following the use of product candidates. Patients are unlikely to use our product candidates unless coverage is provided, and reimbursement is adequate to cover a significant portion of the cost of our product candidates. Because our product candidates may have a higher cost of goods than conventional therapies, and may require long-term follow-up evaluations, the risk that coverage and reimbursement rates may be inadequate for us to achieve profitability may be greater. There is significant uncertainty related to insurance coverage and reimbursement of newly approved products. It is difficult to predict at this time what third-party payors will decide with respect to the coverage and reimbursement for our product candidates.
If we obtain appropriate approval in the future to market any of our current product candidates in the United States, we may be required to provide discounts or rebates under government healthcare programs or to certain government and private purchasers in order to obtain coverage under federal healthcare programs such as Medicaid. Participation in such programs may require us to track and report certain drug prices. We may be subject to fines and other penalties if we fail to report such prices accurately.
Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to cap or reduce healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for newly approved products and, as a result, they may not cover or provide adequate payment for our product candidates. There has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries and proposed federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient support programs, and reform government program reimbursement methodologies for drugs. For example, in October 2017, California became the first state to pass legislation requiring pharmaceutical manufacturers to announce planned drug price increases. While this legislation does not directly affect drug prices, it puts further pressure on pharmaceutical manufacturers in setting prices. Oregon has passed a similar law, requiring pharmaceutical manufacturers to disclose cost components, and other states are likely to follow. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. We expect to experience pricing pressures in connection with the sale of any of our product candidates due to the trend toward managed healthcare, the increasing influence of health maintenance organizations, cost containment initiatives and additional legislative changes.
Ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations.
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Changes in regulations, statutes or the interpretation of existing regulations could impact our business in the future by requiring, for example: (i) changes to our manufacturing arrangements; (ii) additions or modifications to product labeling; (iii) the recall or discontinuation of our products; or (iv) additional record-keeping requirements. If any such changes were to be imposed, they could adversely affect the operation of our business.
In the United States, there have been and continue to be a number of legislative initiatives to contain healthcare costs. For example, in March 2010, the Patient Protection and Affordable Care Act (“ACA”), was passed, which substantially changes the way healthcare is financed by both governmental and private insurers, and significantly impacts the U.S. pharmaceutical industry. The ACA, among other things, subjects biological products to potential competition by lower-cost biosimilars, addresses a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increases the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extends the rebate program to individuals enrolled in Medicaid managed care organizations, establishes annual fees and taxes on manufacturers of certain branded prescription drugs, and creates a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% (increased to 70% pursuant to the Bipartisan Budget Act of 2018, effective as of 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D.
Since its enactment, there have been numerous executive, administrative, judicial, and legislative challenges to certain aspects of the ACA. Under the Trump administration, there were ongoing efforts to modify or repeal all or certain provisions of the Healthcare Reform Act. For example, tax reform legislation was enacted at the end of 2017 that eliminated the tax penalty established under ACA for individuals who do not maintain the mandated health insurance coverage beginning in 2019. The ACA has also been subject to judicial challenge. The case Texas v. Azar, which challenges the constitutionality of the ACA, including provisions that are unrelated to healthcare reform but were enacted as part of the ACA, was argued before the Supreme Court in November 2020. Pending resolution of the litigation, all of the ACA but the individual mandate to buy health insurance remains in effect.
Beyond the ACA, there have been ongoing health care reform efforts, including a number of recent actions. Some recent healthcare reform efforts have sought to address certain issues related to the COVID-19 pandemic, including an expansion of telehealth coverage under Medicare, accelerated or advanced Medicare payments to healthcare providers and payments to providers for COVID-19-related expenses and lost revenues. Other reform efforts affect pricing or payment for drug products, which was a focus of the Trump Administration. For example, in May of 2018, President Trump and the Secretary of the Department of Health and Human Services released a “blueprint” for lowering prescription drug prices and out-of-pocket costs, which contained proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price of their products and reduce the out of pocket costs of product candidates paid by consumers. Subsequent to the ACA, the Medicaid Drug Rebate Program was subject to statutory and regulatory changes and the discount that manufacturers of Medicare Part D brand name drugs must provide to Medicare Part D beneficiaries during the coverage gap increased from 50% to 70%. A number of regulations were issued in late 2020 and early 2021, some of which have been and may continue to be subject to scrutiny and legal challenge. For example, courts temporarily enjoined a new “most favored nation” payment model for select drugs covered under Medicare Part B that was to take effect on January 1, 2021 and would limit payment based on international drug price and CMS subsequently indicated that the rule would not be implemented without further rulemaking.
The nature and scope of health care reform in the wake of the transition from the Trump administration to the Biden administration remains uncertain but early actions suggest additional changes as well as challenges to actions taken under the Trump administration. The Department of Justice under the Biden administration informed the Supreme Court in connection with case Texas v. Azar, that the government no longer takes the position that the individual mandate is unconstitutional and cannot be severed from the rest of the ACA. President Biden temporarily halted implementation of new rules issued immediately prior to the transition that had not yet taken effect (which included a number of health care reforms) to allow for review by the new administration. By Executive Order, President Biden directed federal agencies to reconsider rules and other policies that limit Americans’ access to health care, and consider actions that will protect and strengthen that access. With respect to prescription drugs specifically, President Biden supported reforms to lower drug prices during his campaign for the presidency. The American Rescue Plan Act of 2021, comprehensive COVID-19 relief legislation recently enacted under the Biden administration, includes a number of healthcare-related provisions, such as support to rural health care providers, increased tax subsidies for health insurance purchased through insurance exchange marketplaces, financial incentives to states to expand Medicaid programs and elimination of the Medicaid drug rebate cap effective in 2024.
Moreover, on May 30, 2018, the Right to Try Act, was signed into law. The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase I clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program. There is no obligation for a drug manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act, but the manufacturer must develop an internal policy and respond to patient requests according to that policy. We expect that additional foreign, federal and state
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healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in limited coverage and reimbursement and reduced demand for our products, once approved, or additional pricing pressures.
These laws, and future state and federal healthcare reform measures may be adopted in the future, any of which may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.
European Union drug marketing and reimbursement regulations may materially affect our ability to market and receive coverage for our products in the European member states.
We intend to seek approval to market our product candidates in both the United States and in selected foreign jurisdictions. If we obtain approval in one or more foreign jurisdictions for our product candidates, we will be subject to rules and regulations in those jurisdictions. In some foreign countries, particularly those in the European Union, the pricing of pharmaceutical products is subject to governmental control and other market regulations which could put pressure on the pricing and usage of our product candidates. In these countries, pricing negotiations with governmental authorities can take considerable time after obtaining marketing approval of a product candidate. In addition, market acceptance and sales of our product candidates will depend significantly on the availability of adequate coverage and reimbursement from third-party payors for our product candidates and may be affected by existing and future healthcare reform measures.
Much like the Anti-Kickback Statute prohibition in the United States, the provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is also prohibited in the European Union. The provision of benefits or advantages to physicians is governed by the national anti-bribery laws of European Union Member States. Infringement of these laws could result in substantial fines and imprisonment.
Payments made to physicians in certain European Union Member States must be publicly disclosed. Moreover, agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her competent professional organization and/or the regulatory authorities of the individual European Union Member States. These requirements are provided in the national laws, industry codes or professional codes of conduct, applicable in the European Union Member States. Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.
In addition, in most foreign countries, including the European Economic Area, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing and reimbursement vary widely from country to country. For example, the European Union provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. Reference pricing used by various European Union member states and parallel distribution, or arbitrage between low-priced and high-priced member states, can further reduce prices. A member state may approve a specific price for the medicinal product, or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market. In some countries, we may be required to conduct a clinical trial or other studies that compare the cost-effectiveness of any of our product candidates to other available therapies in order to obtain or maintain reimbursement or pricing approval. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. Historically, products launched in the European Union do not follow price structures of the United States and generally prices tend to be significantly lower. Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries. If pricing is set at unsatisfactory levels or if reimbursement of our products is unavailable or limited in scope or amount, our revenues from sales by us or our strategic partners and the potential profitability of any of our product candidates in those countries would be negatively affected.
European data collection is governed by restrictive regulations governing the use, processing, and cross-border transfer of personal information.
The collection and use of personal health data in the European Union (“EU”), was previously governed by the provisions of the Data Protection Directive, which has been replaced by the General Data Protection Regulation 2016/679 (“GDPR”) as of May 2018.
The GDPR imposes a broad range of strict requirements on companies subject to the GDPR, such as us, including requirements relating to having legal bases for processing personal information relating to identifiable individuals and transferring such information outside the European Economic Area, (“EEA”), including to the United States, providing details to those individuals
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regarding the processing of their personal information, keeping personal information secure, having data processing agreements with third parties who process personal information, responding to individuals’ requests to exercise their rights in respect of their personal information, reporting security breaches involving personal data to the competent national data protection authority and affected individuals, appointing data protection officers, conducting data protection impact assessments, and record-keeping. The GDPR substantially increases the penalties to which we could be subject in the event of any non-compliance, including fines of up to 10 million Euros or up to 2% of our total worldwide annual turnover for certain comparatively minor offenses, or up to 20 million Euros or up to 4% of our total worldwide annual turnover for more serious offenses. Given the new law, we face uncertainty as to the exact interpretation of the new requirements, and we may be unsuccessful in implementing all measures required by data protection authorities or courts in interpretation of the new law.
In particular, national laws of member states of the EU are in the process of being adapted to the requirements under the GDPR, thereby implementing national laws which may partially deviate from the GDPR and impose different obligations from country to country, so that we do not expect to operate in a uniform legal landscape in the EU. Also, in the field of handling genetic data, the GDPR specifically allows national laws to impose additional and more specific requirements or restrictions, and European laws have historically differed quite substantially in this field, leading to additional uncertainty.
With respect to our clinical trials in the EEA, we must also ensure that we maintain adequate safeguards to enable the transfer of personal data outside of the EEA, in particular to the United States in compliance with European data protection laws including the GDPR. We expect that we will continue to face uncertainty as to whether our efforts to comply with our obligations under European privacy laws will be sufficient. If we are investigated by a European data protection authority, we may face fines and other penalties. Any such investigation or charges by European data protection authorities could have a negative effect on our existing business and on our ability to attract and retain new clients or pharmaceutical partners. We may also experience hesitancy, reluctance, or refusal by European or multi-national clients or pharmaceutical partners to continue to use our products and solutions due to the potential risk exposure as a result of the current (and, in particular, future) data protection obligations imposed on them by certain data protection authorities in interpretation of current law, including the GDPR. Such clients or pharmaceutical partners may also view any alternative approaches to compliance as being too costly, too burdensome, too legally uncertain, or otherwise objectionable and therefore decide not to do business with us. Any of the foregoing could materially harm our business, prospects, financial condition and results of operations.
Laws and regulations governing any international operations may preclude us from developing, manufacturing and selling certain products outside of the United States and require us to develop and implement costly compliance programs.
Because we have operations outside of the United States, we must dedicate additional resources to comply with numerous laws and regulations in each jurisdiction in which we plan to operate. The Foreign Corrupt Practices Act (“FCPA”) prohibits any U.S. individual or business from paying, offering, authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem. We, directly or through our CROs, are conducting clinical trials in countries that Transparency International has identified as “perceived as more corrupt”, including, Brazil, Chile, Georgia, Russia and Ukraine. In addition, the FCPA presents particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.
Various laws, regulations and executive orders also restrict the use and dissemination outside of the United States, or the sharing with certain non-U.S. nationals, of information classified for national security purposes, as well as certain products and technical data relating to those products. If we expand our presence outside of the United States, it will require us to dedicate additional resources to comply with these laws, and these laws may preclude us from developing, manufacturing, or selling certain products and product candidates outside of the United States, which could limit our growth potential and increase our development costs.
The failure to comply with laws governing international business practices may result in substantial civil and criminal penalties and suspension or debarment from government contracting. The SEC also may suspend or bar issuers from trading securities on U.S. exchanges for violations of the FCPA’s accounting provisions.
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We are subject to certain U.S. and foreign anti-corruption, anti-money laundering, export control, sanctions, and other trade laws and regulations. We can face serious consequences for violations.
Among other matters, U.S. and foreign anti-corruption, anti-money laundering, export control, sanctions, and other trade laws and regulations, which are collectively referred to as Trade Laws, prohibit companies and their employees, agents, clinical research organizations, legal counsel, accountants, consultants, contractors, and other partners from authorizing, promising, offering, providing, soliciting, or receiving directly or indirectly, corrupt or improper payments or anything else of value to or from recipients in the public or private sector. Violations of Trade Laws can result in substantial criminal fines and civil penalties, imprisonment, the loss of trade privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm, and other consequences. We have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations. We also expect our non-U.S. activities to increase in time. We plan to engage third parties for clinical trials and/or to obtain necessary permits, licenses, patent registrations, and other regulatory approvals and we can be held liable for the corrupt or other illegal activities of our personnel, agents, or partners, even if we do not explicitly authorize or have prior knowledge of such activities.
Inadequate funding for the FDA and other government agencies could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, statutory, regulatory, and policy changes and the impact of crises that hinder its operations, such as COVID-19. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.
Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, over the last several years, including most recently from December 22, 2018 to January 25, 2019, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA and other government employees and stop critical activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
If we do not comply with environmental laws and regulations, we may incur significant costs and potential disruption to our business.
We use or may use hazardous, infectious, and radioactive materials, and recombinant DNA in our operations, which have the potential of being harmful to human health and safety or the environment. We store these hazardous (flammable, corrosive, toxic), infectious, and radioactive materials, and various wastes resulting from their use, at our facilities pending use and ultimate disposal. We are subject to a variety of federal, state, and local laws and regulations governing use, generation, storage, handling, and disposal of these materials. We may incur significant costs complying with both current and future environmental health and safety laws and regulations. In particular, we are subject to regulation by the Occupational Safety and Health Administration, the Environmental Protection Agency, the Drug Enforcement Agency, the Department of Transportation, the Centers for Disease Control and Prevention, the National Institutes of Health, the International Air Transportation Association, and various state and local agencies. At any time, one or more of the aforementioned agencies could adopt regulations that may affect our operations. We are also subject to regulation under the Toxic Substances Control Act and the Resource Conservation Development programs.
Although we believe that our current procedures and programs for handling, storage, and disposal of these materials comply with federal, state, and local laws and regulations, we cannot eliminate the risk of accidents involving contamination from these materials. Although we have a workers’ compensation liability policy, we could be held liable for resulting damages in the event of an accident or accidental release, and such damages could be substantially in excess of any available insurance coverage and could substantially disrupt our business.
If we or our employees, independent contractors, consultants, commercial partners and vendors fail to comply with laws or regulations, it could adversely impact our reputation, business and stock price.
We are exposed to the risk of employee fraud or other misconduct our employees, independent contractors, consultants, commercial partners and vendors. Misconduct by employees could include intentional and/or negligent failures to comply with FDA regulations, to provide accurate information to the FDA, to comply with manufacturing standards we have established, to comply with federal and state health care fraud and abuse, transparency, and/or data privacy laws and regulations (including the California
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Consumer Privacy Act) and security laws and regulations, to report financial information or data accurately or to disclose unauthorized activities to us. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices; to promote transparency; and to protect the privacy and security of patient data. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. If we obtain FDA approval of any of our product candidates and begin commercializing those products in the United States, our potential exposure under such laws will increase significantly, and our costs associated with compliance with such laws are also likely to increase. These laws may impact, among other things, our current activities with principal investigators and research patients, as well as proposed and future sales, marketing and education programs.
While we have adopted a corporate compliance program, we may not be able to protect against all potential issues of noncompliance. Efforts to ensure that our business complies with all applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations, or case law involving applicable laws and regulations.
Employee misconduct could also involve the improper use or disclosure of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. In addition, during the course of our operations, our directors, executives and employees may have access to material, nonpublic information regarding our business, our results of operations or potential transactions we are considering. We may not be able to prevent a director, executive or employee from trading in our common stock on the basis of, or while having access to, material, nonpublic information. If a director, executive or employee was to be investigated, or an action was to be brought against a director, executive or employee for insider trading, it could have a negative impact on our reputation and our stock price. Such a claim, with or without merit, could also result in substantial expenditures of time and money, and divert the attention of our management team.
Risks associated with doing business internationally could negatively affect our business.
We currently have research and development operations in the United Kingdom (“UK”) and clinical operations in eastern Europe, and we expect to pursue pathways to develop and commercialize our product candidates in both U.S. and ex-U.S. jurisdictions. Various risks associated with foreign operations may impact our success. Possible risks of foreign operations include fluctuations in the value of foreign and domestic currencies, requirements to comply with various jurisdictional requirements such as data privacy regulations, disruptions in the import, export, and transportation of patient tumors and our products or product candidates, the product and service needs of foreign customers, difficulties in building and managing foreign relationships, the performance of our licensees or collaborators, geopolitical instability, unexpected regulatory, economic, or political changes in foreign and domestic markets, including without limitation any resulting from the UK’s withdrawal from the EU or our current political regime, and limitations on the flexibility of our operations and costs imposed by local labor laws.
The exit of the UK from the European Union may materially affect the regulatory regime that governs our handling of EU personal data and expose us to legal and business risks under European data privacy and protection law.
As a result of the UK exiting the EU, commonly known as Brexit, since January 1, 2021, any transfers of personal data to the UK are subject to the requirements of Chapter V of the GDPR and of the Law Enforcement Directive and absent an adequacy finding under GDPR, transfers of personal data from the EU to the UK, including to our facility in Cambridge, UK, would be illegal without adequate safeguards provided for under EC-approved mechanisms, such as current standard contractual clauses or, if approved in the future, an EU-UK privacy shield similar to the current framework in place between the EU and the United States. The extensive authority of UK intelligence and law enforcement agencies, including to conduct surveillance on personal data flows, could reduce the likelihood that the EC would give the UK an adequacy finding and reduce the likelihood that the EC would approve an EU-UK privacy shield. Accordingly, we may be exposed to legal risk for any of our EU-UK personal data transfers, including those that involve sensitive data such as patient and genetic data. Given the uncertainties surrounding the UK’s departure from the EU, it is difficult to precisely identify or quantify the risks described above.
Additionally, it is possible that, over time, the UK Data Protection Act could become less aligned with the GDPR, which could require us to implement different compliance measures for the UK and the European Union and result in potentially enhanced compliance obligations for EU personal data.
As a result, Brexit adds legal risk, uncertainty, complexity and cost to our handling of EU personal information and our privacy and data security compliance programs. If we do not successfully manage such risk, our prospects may be materially harmed.
Our ability to use net operating losses and research and development credits to offset future taxable income may be subject to certain limitations.
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As of December 31, 2020, we had U.S. federal and state net operating loss, or Net Operating Losses (“NOLs”), carryforwards of $733.1 million and $237.0 million, respectively, which may be available to offset future taxable income. The federal NOLs include $596.4 million which expire at various dates through 2038 and $136.7 million which carryforward indefinitely. The state NOLs expire at various dates through 2038. As of December 31, 2020, we also had U.S. federal and state research and development tax credit carryforwards of $8.7 million and $6.7 million, respectively, which may be available to offset future tax liabilities and begin to expire in 2021. In addition, in general, under Sections 382 and 383 of the Code and corresponding provisions of state law, a corporation that undergoes an “ownership change” is subject to limitations on its ability to utilize its pre-change net operating loss carryforwards or tax credits, or NOLs or credits, to offset future taxable income or taxes. For these purposes, an ownership change generally occurs where the aggregate stock ownership of one or more stockholders or groups of stockholders who owns at least 5% of a corporation’s stock increases its ownership by more than 50 percentage points over its lowest ownership percentage within a specified testing period. Our existing NOLs or credits may be subject to limitations arising from previous ownership changes, including in connection with our recent private placements, IPO and other transactions. In addition, future changes in our stock ownership, many of which are outside of our control, could result in an ownership change under Sections 382 and 383 of the Code and our ability to utilize NOLs or credits may be impaired. Our NOLs or credits may also be impaired under state law. Accordingly, we may not be able to utilize a material portion of our NOLs or credits. Furthermore, our ability to utilize our NOLs or credits is conditioned upon our attaining profitability and generating U. S. federal and state taxable income. As described above under “Risk factors—Risks Related to Our Financial Position and Need for Additional Capital,” we have incurred significant net losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future; and therefore, we do not know whether or when we will generate the U.S. federal or state taxable income necessary to utilize our NOLs or credits that are subject to limitation by Sections 382 and 383 of the Code. The reduction of the corporate tax rate under the TCJA caused a reduction in the economic benefit of our net operating loss carryforwards and other deferred tax assets available to us. Under the TCJA, net operating loss carryforwards generated after December 31, 2017 will not be subject to expiration.
Risks Related to Our Intellectual Property
If we are unable to obtain and enforce patent protection for our product candidates and related technology, our business could be materially harmed.
We rely upon a combination of patents, trade secret protection and confidentiality agreements to protect the intellectual property related to our product candidates and technology. Any disclosure to or misappropriation by third parties of our confidential proprietary information could enable competitors to duplicate or surpass our technological achievements, eroding our competitive position in the market. Our patent applications may not result in issued patents, and, even if issued, the patents may be challenged and invalidated. Moreover, our patents and patent applications may not be sufficiently broad to prevent others from practicing our technologies or developing competing products. We also face the risk that others may independently develop similar or alternative technologies or may design around our proprietary property.
Issued patents may be challenged, narrowed, invalidated or circumvented. In addition, court decisions may introduce uncertainty in the enforceability or scope of patents owned by biotechnology companies. The legal systems of certain countries do not favor the aggressive enforcement of patents, and the laws of foreign countries may not allow us to protect our inventions with patents to the same extent as the laws of the United States. Because patent applications in the United States and many foreign jurisdictions are typically not published until 18 months after filing, or in some cases not at all, and because publications of discoveries in scientific literature lag behind actual discoveries, we cannot be certain that we were the first to make the inventions claimed in our issued patents or pending patent applications, or that we were the first to file for protection of the inventions set forth in our patents or patent applications. As a result, we may not be able to obtain or maintain protection for certain inventions. Therefore, the enforceability and scope of our patents in the United States and in foreign countries cannot be predicted with certainty and, as a result, any patents that we own, or license may not provide sufficient protection against competitors. We may not be able to obtain or maintain patent protection from our pending patent applications, from those we may file in the future, or from those we may license from third parties. Moreover, even if we are able to obtain patent protection, such patent protection may be of insufficient scope to achieve our business objectives.
Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time. Patents have a limited lifespan. In the United States, the natural expiration of a patent is generally 20 years after its effective filing date. Various extensions may be available; however, the life of a patent, and the protection it affords, is limited. Without patent protection for our product candidates, we may be open to competition from biosimilar or generic versions of our product candidates. Furthermore, the product development timeline for biotechnology products is lengthy and it is possible that our issued patents covering our product candidates in the United States and other jurisdictions may expire prior to commercial launch. For example, if we encounter delays in our development efforts, including our clinical trials, the period of time during which we could market our product candidates under patent protection could be reduced.
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Our strategy depends on our ability to identify and seek patent protection for our discoveries. This process is expensive and time consuming, and we and our current or future licensors or licensees may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner or in all jurisdictions where protection may be commercially advantageous. It is also possible that we or our current licensors or licensees, or any future licensors or licensees, may not identify patentable aspects of inventions made in the course of development and commercialization activities in time to obtain patent protection on them. Therefore, these and any of our patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business. Defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the future, for example with respect to proper priority claims, inventorship, etc. If we or our current licensors or licensees, or any future licensors or licensees, fail to establish, maintain or protect such patents and other intellectual property rights, such rights may be reduced or eliminated. If our current licensors or licensees, or any future licensors or licensees, are not fully cooperative or disagree with us as to the prosecution, maintenance or enforcement of any patent rights, such patent rights could be compromised. If there are material defects in the form or preparation of our patents or patent applications, such patents or applications may be invalid and unenforceable. Despite our efforts to protect our proprietary rights, unauthorized parties may be able to obtain and use information that we regard as proprietary. The issuance of a patent does not ensure that it is valid or enforceable, so even if we obtain patents, they may not be valid or enforceable against third parties. In addition, the issuance of a patent does not give us the right to practice the patented invention. Third parties may have blocking patents that could prevent us from marketing our own patented product and practicing our own patented technology. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
The patent landscapes in the fields of antibody, vaccine, adjuvant and adoptive cell therapy development, manufacture and commercialization are crowded. For example, we are aware of third-party patents directed to methods for identifying and producing therapeutic products such as antibodies, vaccines, adjuvants and adoptive cell therapies. We are also aware of third-party patents directed to products targeting numerous antigens for which we also seek to identify, develop, and commercialize products. For example, some patents claim products based on competitive binding with existing products, some claim products based on specifying sequence or other structural information, and some claim various methods of discovery, production, or use of such products.
These or other third-party patents could impact our freedom to operate in relation to our technology platforms, as well as in relation to development and commercialization of products identified by us as therapeutic candidates. As we discover and develop our candidates, we will continue to conduct analyses of these third-party patents to determine whether we believe we might infringe them, and if so, whether they would be likely to be deemed valid and enforceable if challenged. If we determine that a license for a given patent or family of patents is necessary or desirable, there can be no guarantee that a license would be available on favorable terms, or at all. Inability to obtain a license on favorable terms, should such a license be determined to be necessary or desirable, could, without limitation, result in increased costs to design around the third-party patents, delay product launch, or result in cancellation of the affected program or cessation of use of the affected technology.
Third parties may also seek to market biosimilar versions of any approved products. Alternatively, third parties may seek approval to market their own products similar to or otherwise competitive with our products. In these circumstances, we may need to defend and/or assert our patents, including by filing lawsuits alleging patent infringement. In any of these types of proceedings, a court or agency with jurisdiction may find our patents invalid and/or unenforceable. Even if we have valid and enforceable patents, these patents still may not provide protection against competing products or processes sufficient to achieve our business objectives.
Through our acquisitions of 4-AB, PhosImmune and certain assets of Celexion, we own, co-own, or have exclusive rights to a number of patents and patent applications directed to various methods and compositions, including methods for identifying therapeutic antibodies and product candidates arising out of such entities’ technology platforms. In particular, we own patents and patent applications relating to our Retrocyte DisplayTM technology platform, a high throughput antibody expression platform for the identification of fully-human and humanized monoclonal antibodies. This patent family is projected to expire between 2029 and 2031. Through our acquisition of PhosImmune, we own, co-own, or have exclusive rights to patents and patent applications directed to various methods and compositions, including a patent directed to methods for identifying phosphorylated proteins using mass spectrometry. This patent is projected to expire in 2023. In addition, as we advance our research and development efforts with our institutional and corporate collaborators, we are seeking patent protection for newly identified therapeutic antibodies and product candidates. We can provide no assurance that any of our patents, including the patents that we acquired or in-licensed in connection with our acquisitions of 4-AB, PhosImmune and certain assets of Celexion, will have commercial value, or that any of our existing or future patent applications, including the patent applications that we acquired or in-licensed in connection with our acquisitions of 4-AB, PhosImmune and certain assets of Celexion, will result in the issuance of valid and enforceable patents.
Our issued patents covering Prophage vaccine and methods of use thereof, alone or in combination with other agents, expired or will expire at various dates between 2015 and 2024. In particular, our issued U.S. patents covering Prophage composition of matter expired in 2015. In addition, our issued patents covering QS-21 Stimulon composition of matter expired in 2008. We continue to explore means of extending the life cycle of our patent portfolio.
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The patent position of biopharmaceutical, pharmaceutical or biotechnology companies, including ours, is generally uncertain and involves complex legal and factual considerations. The standards which the USPTO and its foreign counterparts use to grant patents are not always applied predictably or uniformly and can change. There is also no uniform, worldwide policy regarding the subject matter and scope of claims granted or allowable in biopharmaceutical, pharmaceutical or biotechnology patents. The laws of some foreign countries do not protect proprietary information to the same extent as the laws of the United States, and many companies have encountered significant problems and costs in protecting their proprietary information in these foreign countries. Outside the United States, patent protection must be sought in individual jurisdictions, further adding to the cost and uncertainty of obtaining adequate patent protection outside of the United States. Accordingly, we cannot predict whether additional patents protecting our technology will issue in the United States or in foreign jurisdictions, or whether any patents that do issue will have claims of adequate scope to provide competitive advantage. Moreover, we cannot predict whether third parties will be able to successfully obtain claims or the breadth of such claims. The allowance of broader claims may increase the incidence and cost of patent interference proceedings, opposition proceedings, post-grant review, inter partes review, and/or reexamination proceedings, the risk of infringement litigation, and the vulnerability of the claims to challenge. On the other hand, the allowance of narrower claims does not eliminate the potential for adversarial proceedings and may fail to provide a competitive advantage. Our issued patents may not contain claims sufficiently broad to protect us against third parties with similar technologies or products or provide us with any competitive advantage.
If any of our owned or in-licensed patent applications do not issue as patents in any jurisdiction, we may not be able to compete effectively.
Changes in either the patent laws or their interpretation in the United States and other countries may diminish our ability to protect our inventions, obtain, maintain, and enforce our intellectual property rights and, more generally, could affect the value of our intellectual property or narrow the scope of our owned and licensed patents. With respect to our patent portfolio, as of the date of this filing, we own, co-own or have exclusive rights to approximately 40 issued United States patents and approximately 35 issued foreign patents. We also own, co-own or have exclusive rights to approximately 40 pending United States patent applications and approximately 350 pending foreign patent applications. Our patent positions, and those of other biopharmaceutical, pharmaceutical and biotechnology companies, are generally uncertain and involve complex legal, scientific, and factual questions. The standards which the United States Patent and Trademark Office (“USPTO”) uses to grant patents, and the standards which courts use to interpret patents, are not always applied predictably or uniformly and can change, particularly as new technologies develop. Consequently, the level of protection, if any, that will be provided by our patents if we attempt to enforce them and they are challenged, is uncertain. In addition, the type and extent of patent claims that will be issued to us in the future is uncertain. Any patents that are issued may not contain claims that permit us to stop competitors from using similar technology. With respect to both in- licensed and owned intellectual property, we cannot predict whether the patent applications we and our licensors are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors or other third parties.
The patent prosecution process is expensive, time-consuming, and complex, and we may not be able to file, prosecute, maintain, enforce, or license all necessary or desirable patents and patent applications at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output in time to obtain patent protection. Although we enter into non-disclosure and confidentiality agreements with parties who have access to confidential or patentable aspects of our research and development output, such as our employees, corporate collaborators, outside scientific collaborators, contract research organizations, contract manufacturers, consultants, advisors and other third parties, any of these parties may breach such agreements and disclose such output before a patent application is filed, thereby jeopardizing our ability to seek patent protection. In addition, our ability to obtain and maintain valid and enforceable patents depends on whether the differences between our inventions and the prior art allow our inventions to be patentable over the prior art. Furthermore, publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot be certain that we or our licensors were the first to make the inventions claimed in any of our owned or licensed patents or pending patent applications, or that we or our licensors were the first to file for patent protection of such inventions.
If the scope of any patent protection we obtain is not sufficiently broad, or if we lose any of our patent protection, our ability to prevent our competitors from commercializing similar or identical technology and product candidates would be adversely affected.
The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions, and has been the subject of much litigation in recent years. As a result, the issuance, scope, validity, enforceability, and commercial value of our patent rights are highly uncertain. Our approximately 40 pending United States patent applications and approximately 350 pending foreign patent applications may not result in patents being issued which protect our product candidates or patents which effectively prevent others from commercializing competitive technologies and product candidates.
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No consistent policy regarding the scope of claims allowable in patents in the biotechnology field has emerged in the United States. The patent situation outside of the United States is even more uncertain. Changes in either the patent laws or their interpretation in the United States and other countries may diminish our ability to protect our inventions and enforce our intellectual property rights, and more generally could affect the value of our intellectual property. In particular, our ability to stop third parties from making, using, selling, offering to sell, or importing products that infringe our intellectual property will depend in part on our success in obtaining and enforcing patent claims that cover our technology, inventions and improvements. With respect to both licensed and company-owned intellectual property, we cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our products and the methods used to manufacture those products. Moreover, even our issued patents do not guarantee us the right to practice our technology in relation to the commercialization of our products. The area of patent and other intellectual property rights in biotechnology is an evolving one with many risks and uncertainties, and third parties may have blocking patents that could be used to prevent us from commercializing our patented product candidates and practicing our proprietary technology. Our issued patent and those that may issue in the future may be challenged, invalidated, or circumvented, which could limit our ability to stop competitors from marketing related products or limit the length of the term of patent protection that we may have for our product candidates. In addition, the rights granted under any issued patents may not provide us with protection or competitive advantages against competitors with similar technology. Furthermore, our competitors may independently develop similar technologies. For these reasons, we may have competition for our product candidates. Moreover, because of the extensive time required for development, testing and regulatory review of a potential product, it is possible that, before any particular product candidate can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any advantage of the patent.
Moreover, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance. Even if patent applications we own or license issue as patents, they may not issue in a form that will provide us with any meaningful protection, prevent competitors or other third parties from competing with us, or otherwise provide us with any competitive advantage. Any patents that we own or in-license may be challenged, narrowed, circumvented, or invalidated by third parties. Consequently, we do not know whether our product candidates will be protectable or remain protected by valid and enforceable patents. Our competitors or other third parties may be able to circumvent our patents by developing similar or alternative technologies or products in a non-infringing manner which could materially adversely affect our business, financial condition, results of operations and prospects.
The issuance of a patent is not conclusive as to its inventorship, scope, validity, or enforceability, and patents that we own or license may be challenged in the courts or patent offices in the United States and abroad. We or our licensors may be subject to a third party preissuance submission of prior art to the USPTO or to foreign patent authorities or become involved in opposition, derivation, revocation, reexamination, post-grant and inter partes review, or interference proceedings or other similar proceedings challenging our owned or licensed patent rights. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate or render unenforceable, our owned or in-licensed patent rights, allow third parties to commercialize our product candidates, and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize products without infringing third-party patent rights. Moreover, we, or one of our licensors, may have to participate in interference proceedings declared by the USPTO to determine priority of invention or in post-grant challenge proceedings, such as oppositions in a foreign patent office, that challenge our or our licensor’s priority of invention or other features of patentability with respect to our owned or in-licensed patents and patent applications. Such challenges may result in loss of patent rights, loss of exclusivity, or in patent claims being narrowed, invalidated, or held unenforceable, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our product candidates. Such proceedings also may result in substantial cost and require significant time from our scientists and management, even if the eventual outcome is favorable to us.
In addition, given the amount of time required for the development, testing, and regulatory review of new product candidates, patents protecting such product candidates might expire before or shortly after such product candidates are commercialized. As a result, our intellectual property may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.
We may in the future co-own patent rights relating to future product candidates with third parties. Some of our in-licensed patent rights are, and may in the future be, co-owned with third parties. In addition, our licensors may co-own the patent rights we in-license with other third parties with whom we do not have a direct relationship. Our exclusive rights to certain of these patent rights are dependent, in part, on inter-institutional or other operating agreements between the joint owners of such patent rights, who are not parties to our license agreements. If our licensors do not have exclusive control of the grant of licenses under any such third-party co-owners’ interest in such patent rights or we are otherwise unable to secure such exclusive rights, such co-owners may be able to license their rights to other third parties, including our competitors, and our competitors could market competing products and technology. In addition, we may need the cooperation of any such co- owners of our patent rights in order to enforce such patent rights
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against third parties, and such cooperation may not be provided to us. Any of the foregoing could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects.
If we fail to comply with our obligations under our intellectual property licenses with third parties, we could lose license rights that are important to our business.
We are currently party to various intellectual property license agreements. These license agreements impose, and we expect that future license agreements may impose, various diligence, milestone payment, royalty, insurance, prosecution, enforcement and other obligations on us. These licenses typically include an obligation to pay an upfront payment, yearly maintenance payments and royalties on sales. If we fail to comply with our obligations under the licenses, the licensors or licensees may have the right to terminate their respective license agreements, in which event we might not be able to market or obtain royalties or other revenue from any product that is covered by the agreements. Termination of the license agreements or reduction or elimination of our licensed rights may result in our having to negotiate new or reinstated licenses with less favorable terms, which could adversely affect our competitive business position and harm our business. In addition, court decisions may introduce uncertainty with respect to terms of a license agreement such as the impact of a challenge to the validity of a licensed patent on the payment obligations or termination rights of the license.
We may not be able to protect our intellectual property rights throughout the world.
Filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive. The requirements for patentability may differ in certain countries, particularly developing countries. For example, China has a heightened requirement for patentability, and specifically requires a detailed description of medical uses of a claimed drug. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as laws in the United States. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and, further, may export otherwise infringing products to territories where we have patent protection, but enforcement on infringing activities is inadequate. These products may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biopharmaceuticals, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. In addition, certain countries in Europe and certain developing countries, including India and China, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In those countries, we may have limited remedies if our patents are infringed or if we are compelled to grant a license to our patents to a third party, which could materially diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we own or license. Finally, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in foreign intellectual property laws.
Obtaining and maintaining our patent protection depends on compliance with various procedural, documentary, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
Periodic maintenance fees, renewal fees, annuity fees and various other governmental fees on patents and/or applications will be due to the USPTO and various foreign patent offices at various points over the lifetime of our patents and/or applications. We have systems in place to remind us to pay these fees, and we rely on our outside counsel or service providers to pay these fees when due. Additionally, the USPTO and various foreign patent offices require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. We employ reputable law firms and other professionals to help us comply, and in many cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with rules applicable to the particular jurisdiction. However, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. If such an event were to occur, it could have a material adverse effect on our business. In addition, we are responsible for the payment of patent fees for patent rights that we have licensed from other parties.
If any licensor of these patents does not itself elect to make these payments, and we fail to do so, we may be liable to the licensor for any costs and consequences of any resulting loss of patent rights.
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Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
Obtaining and enforcing patents in the biopharmaceutical industry involves both technological and legal complexity, and therefore, is costly, time-consuming and inherently uncertain. In addition, the United States has enacted and implemented wide-ranging patent reform legislation. Further, recent U.S. Supreme Court rulings have either narrowed the scope of patent protection available in certain circumstances or weakened the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained.
For our U.S. patent applications containing a claim not entitled to priority before March 16, 2013, there is a greater level of uncertainty in the patent law. In September 2011, the Leahy-Smith America Invents Act, or the American Invents Act (“AIA”) was signed into law. The AIA includes a number of significant changes to U.S. patent law, including provisions that affect the way patent applications are prosecuted and also affect patent litigation. The USPTO has developed regulations and procedures to govern administration of the AIA, and many of the substantive changes to patent law associated with the AIA. It is not clear what other, if any, impact the AIA will have on the operation of our business. Moreover, the AIA and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business and financial condition.
An important change introduced by the AIA is that, as of March 16, 2013, the United States transitioned to a “first-inventor-to- file” system for deciding which party should be granted a patent when two or more patent applications are filed by different parties claiming the same invention. A third party that files a patent application in the USPTO after that date but before us could therefore be awarded a patent covering an invention of ours even if we had made the invention before it was made by the third party. This requires us to be cognizant going forward of the time from invention to filing of a patent application. Furthermore, our ability to obtain and maintain valid and enforceable patents depends on whether the differences between our technology and the prior art allow our technology to be patentable over the prior art. Since patent applications in the United States and most other countries are confidential for a period of time after filing, we cannot be certain that we were the first to either (i) file any patent application related to our product candidates or (ii) invent any of the inventions claimed in our patents or patent applications.
Among some of the other changes introduced by the AIA are changes that limit where a patentee may file a patent infringement suit and providing opportunities for third parties to challenge any issued patent in the USPTO. This applies to all of our U.S. patents, even those issued before March 16, 2013. Because of a lower evidentiary standard in USPTO proceedings compared to the evidentiary standard in United States federal court necessary to invalidate a patent claim, a third party could potentially provide evidence in a USPTO proceeding sufficient for the USPTO to hold a claim invalid even though the same evidence would be insufficient to invalidate the claim if first presented in a district court action. Accordingly, a third party may attempt to use the USPTO procedures to invalidate our patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action.
If we are unable to protect the confidentiality of our proprietary information, the value of our technology and products could be adversely affected.
In addition to patent protection, we also rely on other proprietary rights, including protection of trade secrets, and other proprietary information. To maintain the confidentiality of trade secrets and proprietary information, we enter into confidentiality agreements with our employees, consultants, collaborators and others upon the commencement of their relationships with us. These agreements require that all confidential information developed by the individual or made known to the individual by us during the course of the individual’s relationship with us be kept confidential and not disclosed to third parties. Our agreements with employees and our personnel policies also provide that any inventions conceived by the individual in the course of rendering services to us shall be our exclusive property. However, we may not obtain these agreements in all circumstances, and individuals with whom we have these agreements may not comply with their terms. Thus, despite such agreement, such inventions may become assigned to third parties. In the event of unauthorized use or disclosure of our trade secrets or proprietary information, these agreements, even if obtained, may not provide meaningful protection, particularly for our trade secrets or other confidential information. To the extent that our employees, consultants or contractors use technology or know-how owned by third parties in their work for us, disputes may arise between us and those third parties as to the rights in related inventions. To the extent that an individual who is not obligated to assign rights in intellectual property to us is rightfully an inventor of intellectual property, we may need to obtain an assignment or a license to that intellectual property from that individual, or a third party or from that individual’s assignee. Such assignment or license may not be available on commercially reasonable terms or at all.
Adequate remedies may not exist in the event of unauthorized use or disclosure of our proprietary information. The disclosure of our trade secrets would impair our competitive position and may materially harm our business, financial condition and results of operations. Costly and time-consuming litigation could be necessary to enforce and determine the scope of our proprietary rights, and failure to maintain trade secret protection could adversely affect our competitive business position. In addition, others may
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independently discover or develop our trade secrets and proprietary information, and the existence of our own trade secrets affords no protection against such independent discovery.
Depending upon the nature of the product and the specifics of the related FDA marketing approval, data exclusivity under the Biologics Price Competition and Innovation Act (“BPCIA”) or related laws in the U.S. or certain foreign countries and territories may be available for our products. The BPCIA provides that FDA shall not approve certain biosimilars from the date of first licensure of a reference product for 12 years, subject to certain restrictions. However, we may not obtain or be eligible for data exclusivity because of, for example, the nature of the product with respect to other products on the market, our relationships with our partners (including our licensors and licensees), failing to claim the exclusivity at the appropriate time or otherwise failing to satisfy applicable requirements. If we are unable to obtain data exclusivity, our competitors may obtain earlier approval of competing products, and our business, financial condition, results of operations and prospects could be materially harmed.
We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties.
We may have received confidential and proprietary information from third parties. In addition, we employ individuals who were previously employed at other biopharmaceutical, biotechnology or pharmaceutical companies. We may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise improperly used or disclosed confidential information of these third parties or our employees’ former employers. Further, we may be subject to ownership disputes in the future arising, for example, from conflicting obligations of consultants or others who are involved in developing our product candidates. We may also be subject to claims that former employees, consultants, independent contractors, collaborators or other third parties have an ownership interest in our patents or other intellectual property. Litigation may be necessary to defend against these and other claims challenging our right to and use of confidential and proprietary information. If we fail in defending any such claims, in addition to paying monetary damages, we may lose our rights therein. Such an outcome could have a material adverse effect on our business. Even if we are successful in defending against these claims, litigation could result in substantial cost and be a distraction to our management and employees.
Our commercial success depends significantly on our ability to operate without infringing the patents and other proprietary rights of third parties.
Our success will depend in part on our ability to operate without infringing the proprietary rights of third parties. Other entities may have or obtain patents or proprietary rights that could limit our ability to make, use, sell, offer for sale or import our future approved products or impair our competitive position. In particular, the patent landscapes around the discovery, development, manufacture and commercial use of our product candidates are crowded.
Third parties may have or obtain valid and enforceable patents or proprietary rights that could block us from developing product candidates using our technology. Our failure to obtain a license to any technology that we require may materially harm our business, financial condition and results of operations. Moreover, our failure to maintain a license to any technology that we require may also materially harm our business, financial condition, and results of operations. Furthermore, we would be exposed to a threat of litigation.
In the biopharmaceutical industry, significant litigation and other proceedings regarding patents, patent applications, trademarks and other intellectual property rights have become commonplace. The types of situations in which we may become a party to such litigation or proceedings include:
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we or our collaborators may initiate litigation or other proceedings against third parties seeking to invalidate the patents held by those third parties or to obtain a judgment that our products or processes do not infringe those third parties’ patents; |
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if our competitors file patent applications that claim technology also claimed by us or our licensors or licensees, we or our licensors or licensees may be required to participate in interference, derivation or other proceedings to determine the priority of invention, which could jeopardize our patent rights and potentially provide a third party with a dominant patent position; |
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if third parties initiate litigation claiming that our processes or products infringe their patent or other intellectual property rights, we and our collaborators will need to defend against such proceedings; and |
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if a license to necessary technology is terminated, the licensor may initiate litigation claiming that our processes or products infringe or misappropriate their patent or other intellectual property rights and/or that we breached our obligations under the license agreement, and we and our collaborators would need to defend against such proceedings. |
These lawsuits would be costly and could affect our results of operations and divert the attention of our management and scientific personnel. There is a risk that a court would decide that we or our collaborators are infringing the third party’s patents and
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would order us or our collaborators to stop the activities covered by the patents. In that event, we or our collaborators may not have a viable alternative to the technology protected by the patent and may need to halt work on the affected product candidate or cease commercialization of an approved product. In addition, there is a risk that a court will order us or our collaborators to pay the other party damages. An adverse outcome in any litigation or other proceeding could subject us to significant liabilities to third parties and require us to cease using the technology that is at issue or to license the technology from third parties. We may not be able to obtain any required licenses on commercially acceptable terms or at all. Any of these outcomes could have a material adverse effect on our business.
The biopharmaceutical industry has produced a significant number of patents, and it may not always be clear to industry participants, including us, which patents cover various types of products or methods of use. The coverage of patents is subject to interpretation by the courts, and the interpretation is not always uniform or predictable. If we are sued for patent infringement, we would need to demonstrate that our products or methods either do not infringe the patent claims of the relevant patent or that the patent claims are invalid, and we may not be able to do this. Proving invalidity is difficult. For example, in the United States, proving invalidity requires a showing of clear and convincing evidence to overcome the presumption of validity enjoyed by issued patents. Even if we are successful in these proceedings, we may incur substantial costs and divert management’s time and attention in pursuing these proceedings, which could have a material adverse effect on us. If we are unable to avoid infringing the patent rights of others, we may be required to seek a license, defend an infringement action or challenge the validity of the patents in court. Patent litigation is costly and time consuming. We may not have sufficient resources to bring these actions to a successful conclusion. In addition, if we do not obtain a license, develop or obtain non-infringing technology, fail to defend an infringement action successfully or have infringed patents declared invalid, we may incur substantial monetary damages, encounter significant delays in bringing our product candidates to market and be precluded from manufacturing or selling our product candidates.
The cost of any patent litigation or other proceeding, even if resolved in our favor, could be substantial. Some of our competitors may be able to sustain the cost of such litigation and proceedings more effectively than we can because of their substantially greater resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace. Patent litigation and other proceedings may also absorb significant management time.
We may not identify relevant third-party patents or may incorrectly interpret the relevance, scope or expiration of a third-party patent which might adversely affect our ability to develop and market our product candidates.
We cannot guarantee that any of our or our licensors’ patent searches or analyses, including the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete or thorough, nor can we be certain that we have identified each and every third-party patent and pending patent application in the United States and abroad that is relevant to or necessary for the commercialization of our product candidates in any jurisdiction. For example, U.S. patent applications filed before November 29, 2000 and certain U.S. patent applications filed after that date that will not be filed outside the United States remain confidential until patents issue. Patent applications in the United States and elsewhere are published approximately 18 months after the earliest filing for which priority is claimed, with such earliest filing date being commonly referred to as the priority date. Therefore, patent applications covering our product candidates could have been filed by third parties without our knowledge. Additionally, pending patent applications that have been published can, subject to certain limitations, be later amended in a manner that could cover our product candidates or the use of our product candidates. The scope of a patent claim is determined by an interpretation of the law, the written disclosure in a patent and the patent’s prosecution history. Our interpretation of the relevance or the scope of a patent or a pending application may be incorrect, which may negatively impact our ability to market our product candidates. We may incorrectly determine that our product candidates are not covered by a third-party patent or may incorrectly predict whether a third party’s pending application will issue with claims of relevant scope. Our determination of the expiration date of any patent in the United States or abroad that we consider relevant may be incorrect, which may negatively impact our ability to develop and market our product candidates. Our failure to identify and correctly interpret relevant patents may negatively impact our ability to develop and market our product candidates.
If we fail to identify and correctly interpret relevant patents, we may be subject to infringement claims. We cannot guarantee that we will be able to successfully settle or otherwise resolve such infringement claims. If we fail in any such dispute, in addition to being forced to pay damages, which may be significant, we may be temporarily or permanently prohibited from commercializing any of our product candidates that are held to be infringing. We might, if possible, also be forced to redesign product candidates so that we no longer infringe the third-party intellectual property rights. Any of these events, even if we were ultimately to prevail, could require us to divert substantial financial and management resources that we would otherwise be able to devote to our business and could adversely affect our business, financial condition, results of operations and prospects.
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We may become involved in lawsuits to protect or enforce our patents, which could be expensive, time consuming and unsuccessful.
Third parties may infringe or misappropriate our intellectual property, including our existing patents, patents that may issue to us in the future, or the patents of our licensors or licensees to which we have a license. As a result, we may be required to file infringement claims to stop third-party infringement or unauthorized use. Further, we may not be able to prevent, alone or with our licensors or licensees, misappropriation of our intellectual property rights, particularly in countries where the laws may not protect those rights as fully as in the United States.
If we or one of our licensors or licensees were to initiate legal proceedings against a third party to enforce a patent covering our product candidates, the defendant could counterclaim that the patent covering our product candidates is invalid and/or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace, and there are numerous grounds upon which a third party can assert invalidity or unenforceability of a patent.
In addition, within and outside of the United States, there has been a substantial amount of litigation and administrative proceedings, including interference and reexamination proceedings before the USPTO or oppositions and other comparable proceedings in various foreign jurisdictions, regarding patent and other intellectual property rights in the biopharmaceutical industry. Notably, the AIA, introduced new procedures, including inter partes review and post grant review. These procedures may be used by competitors to challenge the scope and/or validity of our patents, including those patents perceived by our competitors as blocking entry into the market for their products, and the outcome of such challenges.
Even after they have been issued, our patents and any patents which we license may be challenged, narrowed, invalidated or circumvented. If our patents are invalidated or otherwise limited or will expire prior to the commercialization of our product candidates, other companies may be better able to develop products that compete with ours, which could adversely affect our competitive business position, business prospects and financial condition.
The following are non-exclusive examples of litigation and other adversarial proceedings or disputes that we could become a party to involving our patents or patents licensed to us:
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we or our collaborators may initiate litigation or other proceedings against third parties to enforce our patent rights; |
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third parties may initiate litigation or other proceedings seeking to invalidate patents owned by or licensed to us or to obtain a declaratory judgment that their product or technology does not infringe our patents or patents licensed to us; |
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third parties may initiate opposition proceedings, post-grant review, inter partes review, or reexamination proceedings challenging the validity or scope of our patent rights, requiring us or our collaborators and/or licensors or licensees to participate in such proceedings to defend the validity and scope of our patents; |
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there may be a challenge or dispute regarding inventorship or ownership of patents currently identified as being owned by or licensed to us; |
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the USPTO may initiate an interference or derivation proceeding between patents or patent applications owned by or licensed to us and those of our competitors, requiring us or our collaborators and/or licensors or licensees to participate in an interference or derivation proceeding to determine the priority of invention, which could jeopardize our patent rights; or |
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third parties may seek approval to market biosimilar versions of our future approved products prior to expiration of relevant patents owned by or licensed to us, requiring us to defend our patents, including by filing lawsuits alleging patent infringement. |
These lawsuits and proceedings would be costly and could affect our results of operations and divert the attention of our managerial and scientific personnel. There is a risk that a court or administrative body could decide that our patents are invalid or not infringed by a third party’s activities, or that the scope of certain issued claims must be further limited. An adverse outcome in a litigation or proceeding involving our own patents could limit our ability to assert our patents against these or other competitors, affect our ability to receive royalties or other licensing consideration from our licensees, and may curtail or preclude our ability to exclude third parties from making, using and selling similar or competitive products. An adverse outcome may also put our pending patent applications at risk of not issuing, or issuing with limited and potentially inadequate scope to cover our product candidates. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution. Additionally, it is also possible that prior art of which we are aware, but which we do not believe affects the validity or enforceability of a claim, may, nonetheless, ultimately be found by a court of law or an administrative panel to affect the validity or enforceability of a claim, for example, if a priority claim is found to be improper. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we could lose at least part, and perhaps all, of the patent protection on our relevant product
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candidates. Such a loss of patent protection could have a material adverse impact on our business.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation or administrative proceedings, there is a risk that some of our confidential information could be compromised by disclosure. In addition, during the course of litigation or administrative proceedings, there could be public announcements of the results of hearings, motions or other interim proceedings or developments or public access to related documents. If investors perceive these results to be negative, the market price for our common stock could be significantly harmed. Any of these occurrences could adversely affect our competitive business position, business prospects, and financial condition.
Intellectual property rights do not necessarily address all potential threats to our competitive advantage. The degree of future protection for our proprietary rights is uncertain because legal means afford only limited protection and may not adequately protect our rights or permit us to gain or keep our competitive advantage. For example:
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others may be able to develop a platform that is similar to, or better than, ours in a way that is not covered by the claims of our patents; |
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others may be able to make compounds that are similar to our product candidates but that are not covered by the claims of our patents; |
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we might not have been the first to make the inventions covered by patents or pending patent applications; |
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we might not have been the first to file patent applications for these inventions; |
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any patents that we obtain may not provide us with any competitive advantages or may ultimately be found invalid or unenforceable; or |
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we may not develop additional proprietary technologies that are patentable. |
If we do not obtain patent term extension and/or data exclusivity for any product candidates we may develop, our business may be materially harmed.
Depending upon the timing, duration and specifics of any FDA marketing approval of any product candidates we may develop, one or more of our owned or in-licensed U.S. patents may be eligible for limited patent term extension under the Hatch-Waxman Act. The Hatch-Waxman Act permits a patent term extension of up to five years as compensation for patent term lost during the FDA regulatory review process. A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended. Similar extensions as compensation for patent term lost during regulatory review processes are also available in certain foreign countries and territories, such as in Europe under a Supplementary Patent Certificate. However, we may not be granted an extension in the United States and/or foreign countries and territories because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents, or otherwise failing to satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. If we are unable to obtain patent term extension or the term of any such extension is shorter than what we request, our competitors may obtain approval of competing products following our patent expiration, and our business, financial condition, results of operations and prospects could be materially harmed.
We may be subject to claims challenging the inventorship of our patents and other intellectual property.
We or our licensors may be subject to claims that former employees, collaborators or other third parties have an interest in our owned or in-licensed patent rights, trade secrets, or other intellectual property as an inventor or co-inventor. For example, we or our licensors may have inventorship disputes arise from conflicting obligations of employees, consultants or others who are involved in developing our product candidates. Litigation may be necessary to defend against these and other claims challenging inventorship or our licensors’ ownership of our owned or in-licensed patent rights, trade secrets or other intellectual property. If we or our licensors fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, intellectual property that is important to our product candidates. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects.
If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.
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Our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. We may not be able to protect our rights to these trademarks and trade names, which we need to build name recognition among potential partners or customers in our markets of interest. At times, competitors or other third parties may adopt trade names or trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion. We also have partners who may market or refer to our trademarks or trade names and may use the trademarks or trade names is ways that impair our branding strategy. Recepta and Betta Pharmaceuticals have rights to balstilimab and zalifrelimab in certain South American countries and greater China, respectively, and each may adopt a marketing strategy, including use or registration of trademarks and tradenames, that could impair our brand identity or strategy and possibly cause market confusion. If we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable, or that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In this case, we could ultimately be forced to cease use of such trademarks. In addition, there could be potential trade name or trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks or trade names. Over the long term, if we are unable to establish name recognition based on our trademarks and trade names, then we may not be able to compete effectively and our business may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could adversely affect our business, financial condition, results of operations and prospects.
Intellectual property rights do not necessarily address all potential threats.
The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations and may not adequately protect our business or permit us to maintain our competitive advantage. For example:
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others may be able to make products that are similar to our product candidates or utilize similar technology but that are not covered by the claims of the patents that we license or may own; |
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we, or our current or future licensors or collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or own now or in the future; |
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we, or our current or future licensors or collaborators, might not have been the first to file patent applications covering certain of our or their inventions; |
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others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; |
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it is possible that our current or future pending owned or licensed patent applications will not lead to issued patents; |
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issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors or other third parties; |
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our competitors or other third parties might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; |
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we may not develop additional proprietary technologies that are patentable; |
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the patents of others may harm our business; and |
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we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property. |
Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations and prospects.
Risks Related to Business Operations, Employee Matters and Managing Growth
We have undergone significant growth across multiple locations over the past few years, and are focusing on further enhancing core areas and capabilities as we move toward commercialization. In addition, we have consolidated certain sites while expanding others to focus on our core priorities and future needs. We may encounter difficulties in managing these growth and/or consolidation efforts, either of which could disrupt our operations.
Over the past few years, we have more than tripled our headcount, in part through various acquisitions and the expansion of our research and development activities both nationally and internationally. While we have restructured our organization over the past few
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years, we expect to continue increasing our headcount in certain core areas as we continue to build our development, manufacturing and commercialization capabilities and integrate our acquired technology platforms. To manage these organizational changes, we must continue to implement and improve our managerial, operational and financial systems and continue to recruit, train and retain qualified personnel. If our management is unable to effectively manage our growth, our expenses may increase more than expected, our timelines may be delayed, our ability to generate revenue could be reduced, and we may not be able to implement our business strategy.
As part of our efforts to optimize efficiency across our organization, we previously closed offices in Germany and Switzerland and consolidated these operations in the UK. In January 2020, our subsidiary MiNK closed its Waterloo, Belgium office and consolidated those operations in our Lexington, MA facility. In March 2020, as a result of the COVID-19 pandemic, we completed a company-wide reduction in force. If these transition efforts prove to be unsuccessful, or if we identify management or operational gaps in connection with our changes, it could cause delays in discovery timelines and increased costs for certain of our internal and partnered programs, which also could have an adverse effect on our business, financial condition and results of operations. We are still in the process of liquidating 4-AB and transferring intellectual property rights from Switzerland to the United States or elsewhere. There could be adverse tax consequences resulting from this migration of intellectual property rights, which could have an adverse effect on our business and operations.
Product liability and other claims against us may reduce demand for our products and/or result in substantial damages.
We face an inherent risk of product liability exposure related to testing our product candidates in human clinical trials and manufacturing antibodies in our Berkeley, CA facility and may face even greater risks if we ever sell products commercially. An individual may bring a product liability claim against us if one of our product candidates causes, or merely appears to have caused, an injury. Product liability claims may result in:
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regulatory investigations; |
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injury to our reputation; |
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withdrawal of clinical trial volunteers; |
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costs of related litigation; |
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substantial monetary awards to plaintiffs; and |
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decreased demand for any future products. |
We manufacture the Prophage vaccines from a patient’s cancer cells, and medical professionals must inject the vaccines into the same patient from which they were manufactured. A patient may sue us if a hospital, a shipping company, or we fail to receive the removed cancer tissue or deliver that patient’s vaccine. We do not have any other insurance that covers loss of or damage to the Prophage vaccines or tumor material, and we do not know whether such insurance will be available to us at a reasonable price or at all. We have limited product liability coverage for use of our product candidates. Our product liability policy provides $10.0 million aggregate coverage and $10.0 million per occurrence coverage. This limited insurance coverage may be insufficient to fully cover us for future claims.
We are also subject to laws generally applicable to businesses, including but not limited to, federal, state and local wage and hour, employee classification, mandatory healthcare benefits, unlawful workplace discrimination and whistle-blowing. Any actual or alleged failure to comply with any regulation applicable to our business or any whistle-blowing claim, even if without merit, could result in costly litigation, regulatory action or otherwise harm our business, results of operations, financial condition, cash flow and future prospects.
We are highly reliant on certain members of our management team. In addition, we have limited internal resources and if we fail to recruit and/or retain the services of key employees and external consultants as needed, we may not be able to achieve our strategic and operational objectives.
Both Garo H. Armen, Ph.D., the Chairman of our Board of Directors and our Chief Executive Officer who co-founded the Company in 1994, and Jennifer Buell, Ph.D., our President and Chief Operating Officer, are integral to building our company and developing our technology. If either Dr. Armen or Dr. Buell is unable or unwilling to continue his or her relationship with Agenus, our business may be adversely impacted. We have employment agreements with Dr. Armen and Dr. Buell. They both play an important role in our day-to-day activities, and we do not carry key employee insurance policies for Dr. Armen, Dr. Buell or any other employee. The loss of the services of Dr. Armen or Dr. Buell, other key employees, and other scientific and medical advisors, and our inability to find suitable replacements could result in delays in product development and harm our business.
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The bulk of our operations are conducted at our facilities in Cambridge, UK, Lexington, MA and Berkeley, CA. The Cambridge, New England and Northern California regions are headquarters to many other biopharmaceutical companies and many academic and research institutions. Competition for skilled personnel in our market is intense and may limit our ability to hire and retain highly qualified personnel on acceptable terms or at all.
Our future growth success depends to a significant extent on the skills, experience and efforts of our executive officers and key members of our clinical and scientific staff. We face intense competition for qualified individuals from other pharmaceutical, biopharmaceutical and biotechnology companies, as well as academic and other research institutions. To attract and retain employees at our company, in addition to salary and cash incentives, we have provided stock options that vest over time. The value to employees of stock options that vest over time may be significantly affected by movements in our stock price that are beyond our control, and may at any time be insufficient to counteract more lucrative offers from other companies. Despite our efforts to retain valuable employees, members of our management, scientific and development teams may terminate their employment with us on short notice. Employment of our key employees is at-will, which means that any of our employees could leave our employment at any time, with or without notice. We may be unable to retain our current personnel or attract or assimilate other highly qualified management and clinical personnel in the future on acceptable terms. The loss of any or all of these individuals could harm our business and could impair our ability to support our collaboration partners or our growth generally.
Our internal computer systems, or those of our third-party CROs, CMOs, licensees, collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption in our business and operations or could subject us to sanctions and penalties that could have a material adverse effect on our reputation or financial condition.
Despite the implementation of security measures, our internal computer systems and those of our current and future CROs, CMOs, licensees, collaborators and other contractors and consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. Potential vulnerabilities can also be exploited from inadvertent or intentional actions of our employees, third-party vendors, business partners, or by malicious third parties. Attacks of this nature are increasing in their frequency, levels of persistence, sophistication and intensity, and are being conducted by sophisticated and organized groups and individuals with a wide range of motives (including, but not limited to, industrial espionage) and expertise, including organized criminal groups, “hacktivists,” nation states and others. In July 2020, the United States Government charged a pair of Chinese hackers working on behalf of China’s intelligence service in relation to the hacking of U.S. based biotechnology companies researching COVID-19 vaccines. In addition to the extraction of sensitive information, such attacks could include the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering and other means to affect service reliability and threaten the confidentiality, integrity and availability of information. In addition, the prevalent use of mobile devices increases the risk of data security incidents. While we are not aware of any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations. For example, the loss of clinical trial data from completed, on-going or future clinical trials could result in delays in our regulatory approval efforts and significant costs to recover or reproduce the data. Likewise, we rely on third parties to manufacture certain of our drug candidates and conduct clinical trials, and similar events relating to their computer systems could also have a material adverse effect on our business. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liabilities and the further development and commercialization of our product candidates could be delayed. We do not maintain cyber liability insurance, and would therefore have no coverage for any losses resulting from any data security incident.
We use and store customer, vendor, employee and business partner and, in certain instances patient, personally identifiable information in the ordinary course of our business. We are subject to various domestic and international privacy and security regulations, including but not limited to the HIPAA, which mandates, among other things, the adoption of uniform standards for the electronic exchange of information in common healthcare transactions, as well as standards relating to the privacy and security of individually identifiable health information, which require the adoption of administrative, physical and technical safeguards to protect such information. In addition, many states have enacted comparable laws addressing the privacy and security of health information, some of which are more stringent than HIPAA. Failure to comply with these standards, or a computer security breach or cyber-attack that affects our systems or results in the unauthorized release of proprietary or personally identifiable information, could subject us to criminal penalties and civil sanctions, and our reputation could be materially damaged, and our operations could be impaired. We may also be exposed to a risk of loss or litigation and potential liability, which could have a material adverse effect on our business, results of operations and financial condition.
Natural or man-made calamities, or public health crises, could disrupt our business and materially adversely affect our operations and those of our strategic partners.
Our operations, and those of our CROs, CMOs, and other contractors and consultants together with regulatory agencies such as the FDA or EMA, could be subject to earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes,
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typhoons, fires, extreme weather conditions, medical epidemics and other natural or man-made disasters or business interruptions. The occurrence of any of these business disruptions could prevent us, or our collaborators and business partners or regulators, from using all or a significant portion of our, or their, facilities or disrupt our supply chain, and, it may be difficult or, in certain cases, impossible for us to continue certain activities, such as for example our manufacturing capabilities, for a substantial period of time. The disaster recovery and business continuity plans we have in place currently are limited and are unlikely to prove adequate in the event of a serious disaster or similar event. We may incur substantial expenses and delays as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business. We rely in part on third-party manufacturers to produce and process some of our product candidates. Our ability to obtain some of our clinical supplies of our product candidates could be disrupted if the operations of these suppliers are affected by a man-made or natural disaster or other business interruption.
We own an antibody pilot plant manufacturing facility and lease additional office space in Berkeley, CA. This location is in an area of seismic activity near active earthquake faults and active wildfire activity. In October 2019, Pacific Gas and Electric Company (“PG&E”), the utility supplier for our Berkeley, CA facility provided notice to all residents and businesses in Almeda County (where Berkeley, CA is located) that it would shut off power to the county for a multiday period due to the risk of wildfires. The emergency backup generators located at our Berkeley, CA facility are not able to power the entire facility and only have enough fuel capacity to provide emergency power for a few hours. We have plans in place to maintain the fuel supply of our generators in the event of an extended power interruption, but there is no guarantee that such plans will be adequate to maintain emergency power at our Berkeley, CA facility. In addition, many of our employees reside in Alameda County and may be unable to leave home for the duration of any power shut off. While PG&E did not shut off power to our facility in October 2019, PG&E may do so in the future on short notice. We do not maintain earthquake insurance coverage for our owned and leased properties in Berkeley, CA.
In March 2020, we put in place a number of protective measures in response to the COVID-19 pandemic. These measures include cancelling all commercial business travel, requesting employees to limit non-essential personal travel, asking some employees to self-quarantine at home, adjusting our facilities janitorial and sanitary policies, encouraging employees to work from home to the extent their job function enables them to do so, staggering the working hours of employees that are unable to perform their duties remotely and reconfiguring our facilities for physical distancing. We are revisiting these measures on a regular basis as the pandemic evolves, and we are likely to take additional action as we learn more and as instruction is provided by national, state and local governmental agencies. These measures have resulted, and any future actions are likely to result, in a disruption to our business. Our employees are also impacted by the closures of their children’s schools for lengthy periods of time. For instance, in both California and Massachusetts, all public and private elementary and secondary schools were closed for the duration of the 2019-2020 academic year, leaving many of our employees with no choice but to work from home while also caring for their children, which caused a loss in employee productivity. We expect this state of affairs to continue for the duration of the pandemic. In addition, in March 2020, the United States government announced that it would suspend air travel between the United States and parts of Europe for a 30-day period and subsequently revised this suspension to include the UK, where we have an office and employees. Starting in July 2020, the European Union banned entry by travelers from the US. In the event the governments in Massachusetts, California or the UK further extend their shelter in place orders, travel bans, or otherwise prohibit employees from going to work for a longer period of time, our business will be disrupted and our programs and timelines are likely to be delayed, depending on the ultimate length and severity of the mandate. Not all of our employees are able to perform their duties or function remotely.
The operations of our strategic partners could also be impacted by calamities or public health crises, which could materially and adversely affect our cash resources and operations. For instance, at the beginning of 2020, we projected receipt of approximately $60.0 million of cash milestone payments from existing partners in 2020. Although we did receive $25.1 million of this in 2020, as a result of the impact of COVID-19 on our partner’s programs and trials, the remaining $35.0 million was delayed and not received in 2020, which impacts our cash runway and ability to fund our operations. Additional delays resulting from COVID-19 or other crises are likely to materially adversely affect our business.
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Failure to realize the anticipated benefits of our strategic acquisitions and licensing transactions could adversely affect our business, operations and financial condition.
An important part of our business strategy has been to identify and advance a pipeline of product candidates by acquiring and in-licensing product candidates, technologies and businesses that we believe are a strategic fit with our existing business. Since we acquired 4-AB in 2014, we have completed numerous additional strategic acquisitions and licensing transactions. The ultimate success of these strategic transactions entails numerous operational and financial risks, including:
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higher than expected development and integration costs; |
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difficulty in combining the technologies, operations and personnel of acquired businesses with our technologies, operations and personnel; |
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exposure to unknown liabilities; |
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difficulty or inability to form a unified corporate culture across multiple office sites both nationally and internationally; |
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inability to retain key employees of acquired businesses; |
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disruption of our business and diversion of our management’s time and attention; and |
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difficulty or inability to secure financing to fund development activities for such acquired or in-licensed product candidates, technologies or businesses. |
We have limited resources to integrate acquired and in-licensed product candidates, technologies and businesses into our current infrastructure, and we may fail to realize the anticipated benefits of our strategic transactions. Any such failure could have an adverse effect on our business, operations and financial condition.
We intend to advance our cell therapy business through our subsidiary, MiNK Therapeutics, eventually with separate funding. Moving intellectual property assets into MiNK Therapeutics in foreign jurisdictions could have adverse tax consequences, and there is no guarantee that we will be able to attract external funding. Moreover, even if the business is funded, there is no guarantee that it will be successful.
We are currently in the process of pursuing external funding and partnership opportunities to advance MiNK Therapeutics, but Agenus is currently funding such operations. There is no guarantee that external funding will be available. If funding is available, there is no guarantee that it will be on attractive or acceptable terms, or that it will be adequate to advance the business to an inflection point for additional funding, including any potential initial public offering. Similarly, there is no guarantee that partnership opportunities will be available on attractive terms, if at all. If external funding is not available, we may be forced to either retire these programs or continue to use internal resources to advance them. In addition, our cell therapy assets are early stage and just recently entered the clinic. Even if adequate funding and partnership opportunities are available, there is no guarantee that we or MiNK Therapeutics will be successful in advancing one or more product candidates through clinical development. In addition, most of the efforts being made on behalf of MiNK Therapeutics are utilizing several members of Agenus’ management team and Agenus’ internal general and administrative resources. The current structure could distract management and divert Agenus resources from Agenus’ own core pipeline and programs.
The cell therapy assets necessary to enable MiNK Therapeutics are currently owned or controlled by Agenus in the United States and Switzerland. In connection with capitalizing MiNK Therapeutics, these assets will be transferred or licensed to new legal entities within the United States and Europe and potentially others. Transferring these assets or licensing them on an exclusive basis would require that taxes be paid based on the fair market value of the assets. We may not have adequate net operating losses to offset any tax liabilities in the relevant jurisdictions. Moreover, we have previously disclosed our interest in potentially issuing a tax-free dividend to Agenus’ stockholders in the form of stock of MiNK Therapeutics. There is no guarantee that any such dividend will be tax-free or that it will be issued at all, or the timing thereof. If we issue a dividend in the form of stock, there could be adverse tax consequences for certain of our stockholders.
Risks Related to our Common Stock
The trading volume and public trading price of our common stock has been volatile.
During the period from our initial public offering on February 4, 2000 to June 30, 2021, and the six-months ended June 30, 2021, the closing price of our common stock has fluctuated between $1.59 (or $0.27 pre-reverse stock split) and $315.78 (or $52.63 pre-reverse stock split) per share and $2.56 and $5.49 per share, respectively. The average daily trading volume for the six-months ended June 30, 2021 was approximately 4,447,602 shares, while the average daily trading volume for the year ended December 31, 2020 was approximately 2,557,223 shares. The market may experience significant price and volume fluctuations that are often
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unrelated to the operating performance of individual companies. In addition to general market volatility, many factors may have a significant adverse effect on the market price of our stock, including:
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continuing operating losses, which we expect over the next several years if we are able to transition to a commercial organization; |
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announcements of decisions made by public officials or delays in any such announcements; |
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results of our pre-clinical studies and clinical trials or delays in anticipated timing; |
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delays in our regulatory filings or those of our partners; |
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announcements of new collaboration agreements with strategic partners or developments by our existing collaboration partners; |
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announcements of acquisitions; |
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announcements of technological innovations, new commercial products, failures of products, or progress toward commercialization by our competitors or peers; |
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failure to realize the anticipated benefits of acquisitions; |
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developments concerning proprietary rights, including patent and litigation matters; |
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publicity regarding actual or potential results with respect to product candidates under development; |
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quarterly fluctuations in our financial results, including our average monthly cash used in operating activities; |
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variations in the level of expenses related to any of our product candidates or clinical development programs; |
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additions or departures of key management or scientific personnel; |
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conditions or trends in the biopharmaceutical, biotechnology and pharmaceutical industries generally; |
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other events or factors, including those resulting from war, incidents of terrorism, natural disasters or responses to these events; |
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changes in accounting principles; |
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general economic and market conditions and other factors that may be unrelated to our operating performance or the operating performance of our competitors, including changes in market valuations of similar companies; and |
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sales of common stock by us or our stockholders in the future, as well as the overall trading volume of our common stock. |
In the past, securities class action litigation has often been brought against a company following a significant decline in the market price of its securities. This risk is especially relevant for us because many biopharmaceutical, biotechnology and pharmaceutical companies experience significant stock price volatility.
The trading market for our common stock will depend in part on the research and reports that securities or industry analysts publish about us or our business. If one or more of the analysts who covers us downgrades our stock, or publishes inaccurate or unfavorable research about our business, our stock price would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, demand for our stock could decrease, which could cause our stock price and trading volume to decline.
We do not intend to pay cash dividends on our common stock and, consequently your ability to obtain a return on your investment will depend on appreciation in the price of our common stock.
We have never declared or paid any cash dividend on our common stock and do not intend to do so in the foreseeable future. We currently anticipate that we will retain future earnings for the development, operation and expansion of our business. Therefore, the success of an investment in shares of our common stock will depend upon any future appreciation in their value. There is no guarantee that shares of our common stock will appreciate in value or maintain their current value.
Failure to maintain effective internal controls in accordance with Section 404 of the Sarbanes-Oxley Act of 2002 and to comply with changing regulation of corporate governance and public disclosure could have a material adverse effect on our operating results and the price of our common stock.
The Sarbanes-Oxley Act of 2002 and rules adopted by the SEC and Nasdaq have resulted in significant costs to us. In particular, our efforts to comply with Section 404 of the Sarbanes-Oxley Act of 2002 and related regulations regarding the required assessment of
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our internal control over financial reporting, and our independent registered public accounting firm’s audit of internal control over financial reporting, have required commitments of significant management time. We expect these commitments to continue.
Our internal control over financial reporting (as defined in Rules 13a-15 of the Exchange Act) is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of our consolidated financial statements for external purposes in accordance with U.S. GAAP. Because of its inherent limitations, internal control over financial reporting may not prevent or detect all deficiencies or weaknesses in our financial reporting. While our management has concluded that there were no material weaknesses in our internal control over financial reporting as of December 31, 2020, our procedures are subject to the risk that our controls may become inadequate because of changes in conditions or as a result of a deterioration in compliance with such procedures. No assurance is given that our procedures and processes for detecting weaknesses in our internal control over financial reporting will be effective.
Changing laws, regulations and standards relating to corporate governance and public disclosure, are creating uncertainty for companies. Laws, regulations and standards are subject to varying interpretations in some cases due to their lack of specificity, and as a result, their application in practice may evolve over time as new guidance is provided, which could result in continuing uncertainty regarding compliance matters and higher costs caused by ongoing revisions to disclosure and governance practices. If we fail to comply with these laws, regulations and standards, our reputation may be harmed, and we might be subject to sanctions or investigation by regulatory authorities, such as the SEC. Any such action could adversely affect our operating results and the market price of our common stock.
The sale of a significant number of shares could cause the market price of our stock to decline.
The sale by us or the resale by stockholders of a significant number of shares of our common stock could cause the market price of our common stock to decline. As of August 4, 2021, we had 233,114,645 shares of common stock outstanding. Except for the 4,962,779 shares of common stock issued to Betta Pharmaceuticals in July 2020, substantially all of these shares are eligible for sale on Nasdaq, although certain of the shares are subject to sales volume and other limitations. We have filed registration statements to permit the sale of approximately 36,000,000 shares of common stock under our equity incentive plans, and to permit the sale of 1,500,000 shares of common stock under our 2015 Inducement Equity Plan. We have also filed registration statements to permit the sale of approximately 667,000 shares of common stock under our Employee Stock Purchase Plan, to permit the sale of 425,000 shares of common stock under our Directors’ Deferred Compensation Plan, to permit the sale of approximately 31,100,319 shares of common stock pursuant to various private placement agreements and to permit the sale of up to 100,000,000 shares of our common stock pursuant to our At Market Issuance Sales Agreement. As of August 4, 2021, an aggregate of approximately 94,381,626 of these shares remained available for sale. In October 2018, we completed a private placement of 18,459 shares of Series C-1 convertible preferred stock, convertible into 18,459,000 shares of common stock. The resale of all 18,459,000 shares of common stock underlying the 18,459 shares of Series C-1 convertible preferred stock was registered with the SEC pursuant to a Registration Statement on Form S-3 filed with the SEC on November 8, 2018 and declared effective on December 10, 2018. As part of our collaboration with Betta Pharmaceuticals, we completed a private placement of 4,962,779 shares of common stock in July 2020, the resale of which must be registered with the SEC by October 2021. As part of our collaboration with Gilead, we completed a private placement of 11,111,111 shares of common stock in January 2019, and on October 25, 2019, we filed a Registration Statement on Form S-3 to register the resale of these shares by Gilead, as required under our agreement. In connection with our acquisition of PhosImmune in December 2015, we issued 1,631,521 shares of our common stock to the shareholders of PhosImmune and other third parties having a fair market value of approximately $7.4 million at closing. In addition, we may be obligated in the future to pay certain contingent milestones payments, payable at our election in cash or shares of our common stock of up to $30.0 million in the aggregate. If we elect to pay any of these contingent milestones in shares, we are obligated to file registration statements covering any such shares. The market price of our common stock may decrease based on the expectation of such sales.
As of June 30, 2021, warrants to purchase approximately 1,980,000 shares of our common stock with a weighted average exercise price per share of $4.89 were outstanding.
As of June 30, 2021, options to purchase 33,789,243 shares of our common stock with a weighted average exercise price per share of $3.64 were outstanding. These options are subject to vesting that occurs over a period of up to four years following the date of grant. As of June 30, 2021, we had 14,730,962 vested options and 1,214,816 non-vested shares outstanding.
As of June 30, 2021, our outstanding shares of Series A-1 Convertible Preferred Stock were convertible into 333,333 shares of our common stock.
As of June 30, 2021, our outstanding shares of Series C-1 Convertible Preferred Stock were convertible into 8,459,000 shares of our common stock.
We may issue additional common stock, preferred stock, restricted stock units, or securities convertible into or exchangeable for our common stock. Furthermore, substantially all shares of common stock for which our outstanding stock options or warrants are exercisable are, once they have been purchased, eligible for immediate sale in the public market. The issuance of additional common
78
stock, preferred stock, restricted stock units, or securities convertible into or exchangeable for our common stock or the exercise of stock options or warrants would dilute existing investors and could adversely affect the price of our securities. In addition, such securities may have rights senior to the rights of securities held by existing investors.
Anti-takeover provisions under our charter documents and Delaware law could delay or prevent a change of control which could limit the market price of our common stock and may prevent or frustrate attempts by our stockholders to replace or remove our current management.
Our certificate of incorporation and bylaws contain provisions that could make it more difficult for a third party to acquire us without the consent of our Board of Directors. Our certificate of incorporation provides for a staggered board and removal of directors only for cause. Accordingly, stockholders may elect only a minority of our Board at any annual meeting, which may have the effect of delaying or preventing changes in management. In addition, under our certificate of incorporation, our Board of Directors may issue additional shares of preferred stock and determine the terms of those shares of stock without any further action by our stockholders. Our issuance of additional preferred stock could make it more difficult for a third party to acquire a majority of our outstanding voting stock and thereby effect a change in the composition of our Board of Directors. Our certificate of incorporation also provides that our stockholders may not take action by written consent. Our bylaws require advance notice of stockholder proposals and director nominations and permit only our president or a majority of the Board of Directors to call a special stockholder meeting. These provisions may have the effect of preventing or hindering attempts by our stockholders to replace our current management. In addition, Delaware law prohibits a corporation from engaging in a business combination with any holder of 15% or more of its capital stock until the holder has held the stock for three years unless, among other possibilities, the board of directors approves the transaction. Our Board of Directors may use this provision to prevent changes in our management. Also, under applicable Delaware law, our Board of Directors may adopt additional anti-takeover measures in the future.
These anti-takeover provisions and other provisions in our certificate of incorporation and bylaws could make it more difficult for stockholders or potential acquirers to obtain control of our board of directors or initiate actions that are opposed by the then-current board of directors and could also delay or impede a merger, tender offer or proxy contest involving our company. These provisions could also discourage proxy contests and make it more difficult for our stockholders and other stockholders to elect directors of their choosing or cause us to take other corporate actions they desire. Any delay or prevention of a change of control transaction or changes in our board of directors could cause the market price of our common stock to decline.
We have broad discretion in the use of our existing cash, cash equivalents and investments and may not use them effectively.
Our management has broad discretion in the application of our cash, cash equivalents and investments. Because of the number and variability of factors that will determine our use of our cash, cash equivalents and investments, their ultimate use may vary substantially from their currently intended use. Our management might not apply our cash, cash equivalents and investments in ways that ultimately increase the value of our stockholders investment. The failure by our management to apply these funds effectively could harm our business. Pending their use, we may invest our cash in short-term, investment- grade, interest-bearing securities. These investments may not yield a favorable return to our stockholders. If we do not use our resources in ways that enhance stockholder value, we may fail to achieve expected financial results, which could cause our stock price to decline.
If securities or industry analysts do not continue to publish research or publish inaccurate or unfavorable research about our business, our stock price and trading volume could decline.
The trading market for our common stock depends in part on the research and reports that securities or industry analysts publish about us or our business. If one or more of the analysts who covers us downgrades our stock or publishes inaccurate or unfavorable research about our business, our stock price may decline. If one or more of these analysts ceases coverage of our company or fails to publish reports on us regularly, demand for our stock could decrease, which might cause our stock price and trading volume to decline.
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Item 6. |
Exhibits |
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Exhibit No. |
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Description |
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10.1 |
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10.2 |
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31.1 |
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31.2 |
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32.1 |
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101.INS |
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XBRL Instance Document (the instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document) |
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101.SCH |
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Inline XBRL Taxonomy Extension Schema Document |
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101.CAL |
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Inline XBRL Taxonomy Extension Calculation Linkbase Document |
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101.DEF |
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Inline XBRL Taxonomy Extension Definition Linkbase Document |
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101.LAB |
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Inline XBRL Taxonomy Extension Label Linkbase Document |
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101.PRE |
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Inline XBRL Taxonomy Extension Presentation Linkbase Document |
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104 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document and included in Exhibit 101)
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80
AGENUS INC.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
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Date: |
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August 9, 2021 |
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AGENUS INC. |
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/s/ CHRISTINE M. KLASKIN |
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Christine M. Klaskin VP, Finance, Principal Financial Officer, Principal Accounting Officer |
81
Exhibit 10.1
Execution Version
LICENSE, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT
DATED AS OF MAY 17, 2021
BY AND BETWEEN
AGENUS INC.
AND
BRISTOL-MYERS SQUIBB COMPANY
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Table of Contents
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ARTICLE 1 DEFINITIONS |
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ARTICLE 2 LICENSES |
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2.4 |
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ARTICLE 3 GOVERNANCE |
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ARTICLE 4 DEVELOPMENT |
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ARTICLE 5 REGULATORY |
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ARTICLE 6 COMMERCIALIZATION |
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ARTICLE 7 MANUFACTURING |
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
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7.1 |
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ARTICLE 8 PAYMENTS |
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8.6 |
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8.7 |
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8.8 |
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8.9 |
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8.15 |
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8.16 |
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ARTICLE 9 INTELLECTUAL PROPERTY MATTERS |
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9.1 |
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9.3 |
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9.6 |
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ARTICLE 10 REPRESENTATIONS, WARRANTIES AND COVENANTS; COMPLIANCE |
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ARTICLE 11 INDEMNIFICATION |
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ii
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
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11.4 |
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ARTICLE 12 CONFIDENTIALITY |
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12.2 |
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12.4 |
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12.5 |
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ARTICLE 13 TERM AND TERMINATION |
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13.1 |
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13.6 |
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ARTICLE 14 EFFECTS OF EXPIRATION OR TERMINATION |
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14.2 |
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14.3 |
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14.7 |
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14.8 |
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ARTICLE 15 DISPUTE RESOLUTION |
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15.1 |
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15.2 |
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15.3 |
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ARTICLE 16 MISCELLANEOUS |
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16.2 |
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16.3 |
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16.4 |
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16.5 |
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16.6 |
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16.7 |
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iii
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
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16.10 |
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16.11 |
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16.13 |
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iv
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
LICENSE, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT
This License, Development and Commercialization Agreement (this “Agreement”), dated as of May 17, 2021 (the “Execution Date”), is made by and between Agenus Inc., a Delaware corporation with offices at 3 Forbes Road, Lexington, Massachusetts 02421 (“Agenus”), and Bristol-Myers Squibb Company, a Delaware corporation headquartered at 345 Park Avenue, New York, New York 10154 (“Licensee”). Agenus and Licensee are sometimes referred to herein individually as a “Party” and collectively as the “Parties.”
Whereas, Agenus has discovered and developed AGEN1777 and [**] (each, as defined below);
Whereas, Licensee has experience in the development, manufacture and commercialization of pharmaceutical and biologic products in the Field in the Territory; and
Whereas, Agenus wishes to grant a license to Licensee under certain intellectual property rights related to the Licensed Antibodies to further develop, manufacture, and commercialize Licensed Products in the Territory, and Licensee wishes to take such license, in each case, in accordance with the terms and conditions set forth below.
Now Therefore, in consideration of the foregoing premises and the mutual promises, covenants and conditions contained in this Agreement and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows:
As used in this Agreement, the following initially capitalized terms will have the meanings set forth in this Article 1 (Definitions) or as otherwise defined elsewhere in this Agreement:
1.1[**]
1.2[**]
1.3[**]
1.4“Affiliate” means any entity directly or indirectly controlled by, controlling, or under common control with, a Person, at any time but only for so long as such control exists. For purposes of this definition, “control” (including, with correlative meanings, “controlled by,” “controlling” and “under common control with”) means (a) possession, direct or indirect, of the power to direct or cause direction of the management or policies of an entity (whether through ownership of securities or other ownership interests, by contract or otherwise), or (b) beneficial ownership of more than fifty percent (50%) (or the maximum ownership interest permitted by Applicable Law) of the voting securities or other ownership or general partnership interest
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
(whether directly or pursuant to any option, warrant or other similar arrangement) or other comparable equity interests of an entity.
1.5“AGEN1777” means that certain Agenus proprietary TIGIT[**] Bispecific Antibody referred to as AGEN1777[**].
1.6“AGEN1777 Licensed Product” means a Licensed Product that contains AGEN1777.
1.7“Agenus FC Platform” means the [**] disclosed or claimed in any Agenus FC Platform Patent.
1.8“Agenus FC Platform Patent” means those Patents listed in Schedule 1.8 (Agenus FC Platform Patents) [**].
1.9“Agenus GDP Trial Know-How” means the Arising Know-How developed, created, conceived, or reduced to practice during the Term by or on behalf of Agenus or any of its Affiliates in the performance of any Agenus GDP Trial.
1.10“Agenus Know-How” means all Know-How Controlled by Agenus or its Affiliates as of the Execution Date or during the Term that is [**] to Exploit any Licensed Antibody or Licensed Product in the Field in the Territory (other than any Joint Arising Know-How), including all biological, chemical, pharmacological, toxicological, clinical, assay and other methods of screening, related structure activity relationship Know-How, and trade secrets.
1.11“Agenus Ongoing Studies” means any ongoing IND-enabling studies or CMC activities for any Licensed Antibody being conducted by Agenus as of the Execution Date as set forth on Schedule 1.11 (Agenus Ongoing Studies).
1.12“Agenus Other Component” means any (a) pharmaceutically active compound, substance, or therapeutic agent that is not a Licensed Antibody, or (b) product that does not contain a Licensed Antibody, in each case ((a) and (b)), that is owned or controlled by Agenus or any of its Affiliates as of the Execution Date or during the Term.
1.13“Agenus Patent” means any Patent that is Controlled by Agenus or its Affiliates as of the Execution Date or during the Term (other than any Joint Arising Patent) that is [**] to Exploit any Licensed Antibody or Licensed Product in the Field in the Territory, including any Patent set forth on Schedule 1.13 (Agenus Patents).
1.14“Agenus Technology” means Agenus Know-How and Agenus Patents.
1.15“Analytical Release Testing and Characterization” means all activities associated with carrying out the analytical testing and release of any Licensed Product in the Field in the Territory. Such activities will include: transferring test methods, developing and validating new analytical tests required in the Territory, amending the release specifications to be in compliance with local Applicable Law, conducting the release testing of such Licensed Product in
2
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
the Field in the Territory and final release of such Licensed Product in the Field, including raw materials, intermediates, drug substance, and drug product.
1.16“Applicable Law” means any applicable United States federal, state, local, foreign, or multinational law (including data protection and privacy laws), statute, standard, ordinance, code, rule, regulation, resolution, or promulgation, or any order, writ, judgment, injunction, decree, stipulation, ruling, determination, or award entered by or with any Governmental Authority, or any license, franchise, permit, or similar right granted under any of the foregoing, or any similar provision having the force or effect of law. For clarity, any specific references to any Applicable Law or any portion thereof, will be deemed to include all then-current amendments thereto or any replacement or successor law, statute, standard, ordinance, code, rule, regulation, resolution, order, writ, judgment, injunction, decree, stipulation, ruling, or determination thereto.
1.17“Audited Party” means the Party being audited by the Auditing Party pursuant to Section 8.16 (Records; Audits).
1.18“Auditing Party” means the Party conducting an Audit pursuant to Section 8.16 (Records; Audits).
1.19“Biosimilar Application” means an application submitted to the FDA under subsection (k) of Section 351 of the PHSA naming a Licensed Product as a reference product and seeking approval of a product as biosimilar or interchangeable to such Licensed Product, an application submitted under Article 10(4) of Directive 2001/83/EC (as amended, including by EU Directive 2004/27/EC) in the European Economic Area or any member state thereof or any foreign equivalents thereof.
1.20“Biosimilar Product” means, with respect to a Licensed Product, (a) a biopharmaceutical product that (i) [**] or (ii) [**] or (b) [**].
1.21“Bispecific Antibody” means a molecule, or a covalently linked plurality of molecules, which comprise(s) two (2) [**], wherein the first [**] to TIGIT and the second [**] to [**]. For purposes of this definition, (a) [**]; and (b) [**].
1.22“Business Day” means a day other than a Saturday, Sunday, or bank or other public holiday in New York, New York, United States.
1.23“Calendar Quarter” means each three (3) month period commencing January 1, April 1, July 1, or October 1 of any year; provided, however, that (a) the first Calendar Quarter of the Term will extend from the Effective Date to the end of the first full Calendar Quarter thereafter, and (b) the last Calendar Quarter of the Term will commence on the last-to-occur of any of the foregoing dates during the Term and end upon the expiration or termination of this Agreement.
1.24“Calendar Year” means the period beginning on the 1st of January and ending on the 31st of December of the same year; provided, however, that (a) the first Calendar Year of the Term will commence on the Effective Date and end on December 31 of the same year, and (b) the last Calendar Year of the Term will commence on January 1 of the Calendar Year in which this
3
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Agreement terminates or expires and end on the date of termination or expiration of this Agreement.
1.25“Change of Control” means, with respect to a Person, that: (a) any Person or group (as defined in Section 13(g) of the Securities and Exchange Act of 1934, as amended) acquires (in one or more transactions) directly or indirectly the beneficial ownership of any voting security of the subject Person, or if the percentage ownership of such acquiring Person or group in the voting securities of the subject Person is increased or decreased (in one or more transactions) through stock redemption, cancellation, or other recapitalization, and immediately after such acquisition or increase or decrease such acquiring Person or group is, directly or indirectly, the beneficial owner of voting securities representing fifty percent (50%) or more of the total voting power of all of the then outstanding voting securities of the subject Person; (b) a merger, consolidation, recapitalization, or reorganization or other transaction(s) involving the subject Person is consummated that would result in (i) shareholders or equity holders of the subject Person immediately prior to such transaction(s), owning less than fifty percent (50%) of the outstanding voting securities of the surviving entity (or its parent entity) immediately following such transaction, (ii) any Person or group holding, directly or indirectly, the beneficial ownership of voting securities representing fifty percent (50%) or more of the total voting power of all of the then outstanding voting securities of the subject Person or (iii) the members of the board of directors or similar governing body of the subject Person immediately prior to such transaction(s) constituting less than a majority of the members of the board of directors or similar governing body of the surviving entity immediately following such transaction(s); or (c) there is a sale, transfer or other disposition to a Third Party of all or substantially all of the subject Person’s consolidated assets taken as a whole, through one or more transactions.
1.26“Clinical Trial” means a Phase I Clinical Trial, Phase I/II Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IIIb or Phase IV Clinical Trial, or Registrational Trial, as the case may be.
1.27“CMC” means chemistry, manufacturing, and controls.
1.28“Combination Product” means any product or treatment regimen that comprises, or is a combination of, (a) any Licensed Antibody and (b) any Other Component, where (a) and (b) are sold for a single price.
1.29“Commercialize” means, with respect to a product, to promote, market, distribute, sell (and offer for sale or contract to sell), import, export, or otherwise commercially exploit, or provide product support for such product and to conduct activities, other than Development or Manufacturing, in preparation for conducting the foregoing activities, including activities to produce commercialization support data and to secure and maintain market access and reimbursement. “Commercializing” and “Commercialization” will have correlative meanings. For clarity, Commercialization does not include Development and Manufacturing.
1.30“Competing Product” means [**].
4
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
1.31“Control” and “Controlled by” means, with respect to any Know-How, Patent, data, other intellectual property right, Regulatory Approval, Pricing Approval, Regulatory Data, Bispecific Antibody or Multispecific Antibody, possession by a Party or any of its Affiliates (whether by ownership, license grant, or other means) of the legal right to grant the right to access, reference or use, or to grant a license or a sublicense to, such Know-How, Patent, data, other intellectual property right, Regulatory Approval, Pricing Approval, or Regulatory Data or any of the foregoing with respect to such Bispecific Antibody or Multispecific Antibody, as applicable, as provided for herein without [**], except under any (a) [**], (b) [**] or (c) [**]. [**].
1.32“Country-Specific Clinical Trial” means any Clinical Trial for [**] that (a) [**], and (b) [**].
1.33“Designated Officer” means [**].
1.34“Develop” means to research, develop, develop biomarkers, analyze, test, and conduct pre-clinical trials, Clinical Trials (for clarity, Phase IIIb or Phase IV Clinical Trials and any pre-clinical/clinical/CMC commitments following the receipt of Regulatory Approval) and all other regulatory trials (which conduct may include funding clinical grants or providing supplies, including comparators), for any compound or product, as well as any and all activities pertaining to manufacturing development, formulation development, and the development of manufacturing processes, medical affairs, and lifecycle management (including the conduct of Phase IIIb or Phase IV Clinical Trial not explicitly for registrational purposes and non-interventional studies), including new Indications, new formulations, and all other activities (including regulatory activities) related to supporting, securing, and maintaining Regulatory Approval for any compound or product. Develop will include Manufacturing Development Activities and Analytical Release Testing and Characterization for Licensed Products for use in Clinical Trials. “Developed” and “Development” will have correlative meanings.
1.35“Development Activities” means those Development activities undertaken by or on behalf of: (a) Licensee or its Affiliates with respect to a Licensed Antibody or Licensed Product in the Field in the Territory; or (b) Agenus or its Affiliates with respect to any Agenus GDP Trials or any Agenus Ongoing Studies.
1.36“Diligent Efforts” means [**].
1.37“Dollar” or “$” means the legal tender of the United States of America.
1.38“Effective Date” means the Business Day following the date on which HSR Clearance occurs, or, if the Parties together determine that no HSR Filing is required for the activities and licenses contemplated under this Agreement, the Execution Date.
1.39“Effective Date Disclosure Schedules” means the disclosure schedules provided by Agenus to Licensee after the Execution Date and prior to the Effective Date.
1.40“EMA” means the European Medicines Agency or any successor Regulatory Authority having substantially the same function and authority over drugs in the European Union.
5
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
1.41“E.U.” means the European Union.
1.42“Execution Date Disclosure Schedules” means the disclosure schedules provided by Agenus to Licensee prior to the Execution Date.
1.43“Exploit” means to Develop, Manufacture or Commercialize, including to research, make, have made, distribute, sell, offer for sale, import, and export. “Exploiting” and “Exploitation” will have correlative meanings.
1.44“FD&C Act” means the U.S. Federal Food, Drug and Cosmetic Act, as amended, and the regulations promulgated thereunder.
1.45“FDA” means the United States Food and Drug Administration or any successor Regulatory Authority having substantially the same function and authority over drugs in the U.S.
1.46[**]
1.47“Field” means all uses, including the prevention, treatment or control of any disease, disorder or condition.
1.48“First Commercial Sale” means, with respect to a Licensed Product in any country in the Territory, the first sale of such Licensed Product in the Field to a Third Party in such country intended for use by an end-user customer of such Licensed Product in such country following Regulatory Approval of such Licensed Product in such country, [**].
1.49[**]
1.50“Force Majeure” means any circumstances whatsoever that are not within the reasonable control of the Party affected thereby, potentially including an act of God, war, act of terrorism, insurrection, riot, strike or labor dispute, pandemic or epidemic, shortage of materials, fire, explosion, flood, government requisition or allocation, breakdown of or damage to plant, equipment or facilities, interruption or delay in transportation, fuel supplies or electrical power, embargo, boycott, order, or act of civil or military authority.
1.51“FTE” means the equivalent of the work of one (1) duly qualified individual of either Party full time for one (1) year (consisting of a total of [**] hours per year) carrying out Development, Manufacturing, or Commercialization activities, or other scientific or technical work under this Agreement. Overtime and work on weekends, holidays, and the like, in each case, will not be counted with any multiplier (e.g., time-and-a-half or double time) toward the number of hours that are used to calculate the FTE contribution. The portion of an FTE billable for one (1) individual during a given accounting period will be determined by dividing the number of hours worked directly by such individual on the work to be conducted under this Agreement during such accounting period and the number of FTE hours applicable for such accounting period based on [**] working hours per Calendar Year.
1.52“Global [**] Development Costs” means [**]. Notwithstanding the foregoing, and for clarity, Global [**] Development Costs do not include any payments made by Licensee or
6
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
its Affiliates (i) to Agenus under this Agreement, including any Upfront License Fee, Development Milestone Payments, Sales Milestone Payments, or Royalty Payments, other than the Agenus GDP Trial Costs, or (ii) to any Third Party under any Third Party license agreement.
1.53 “Good Clinical Practice” or “GCP” means all applicable Good Clinical Practice standards for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of Clinical Trials, including, as applicable, (a) as set forth in the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (“ICH”) Harmonised Tripartite Guideline for Good Clinical Practice (CPMP/ICH/135/95), as amended, and any other guidelines for good clinical practice for trials on medicinal products in the Territory, (b) U.S. Code of Federal Regulations Title 21, Parts 50 (Protection of Human Subjects), 54 (Financial Disclosure by Clinical Investigators), 56 (Institutional Review Boards), and 312 (Investigational New Drug Application), as may be amended from time to time, and (c) the equivalent Applicable Law in any relevant country, each as may be amended and applicable from time to time and, in each case, that provide for, among other things, assurance that the clinical data and reported results are credible and accurate and protect the rights, integrity, and confidentiality of trial subjects.
1.54“Good Laboratory Practice” or “GLP” means all applicable Good Laboratory Practice standards, including, as applicable, (a) as set forth in the Good Laboratory Practice standards promulgated or endorsed by the FDA as defined in 21 C.F.R. Part 58 for the conduct of nonclinical laboratory studies, and (b) the equivalent Applicable Law in any relevant country, each as may be amended and applicable from time to time.
1.55“Good Manufacturing Practice” or “GMP” means all applicable current Good Manufacturing Practice including, as applicable, (a) the principles detailed in the U.S. Current Good Manufacturing Practice regulations, 21 C.F.R. Sections 210, 211, 600, and 610, (b) the principles detailed in the ICH Q7 guidelines, and (c) the equivalent Applicable Law in any relevant country, each as may be amended and applicable from time to time.
1.56“Government Official” means: (a) any officer or employee of: (i) a government, or any department or agency thereof; (ii) a government-owned or controlled company, institution, or other entity, including a government-owned hospital or university; or (iii) a public international organization (such as the United Nations, the International Monetary Fund, the International Committee of the Red Cross, and the World Health Organization), or any department or agency thereof; (b) any political party or party official or candidate for public or political party office; or (c) any person acting in an official capacity on behalf of any of the foregoing.
1.57“Governmental Authority” means any multi-national, federal, state, local, provincial, prefectural, municipal (or other political subdivision) or governmental authority of any nature (including any governmental division, subdivision, department, agency, bureau, branch, office, commission, council, court, tribunal or other entity), in each case, entitled to exercise any administrative, executive, judicial, legislative, police, regulatory, or taxing authority or power, any court or tribunal (or any department, bureau, or division thereof), or any governmental arbitrator or arbitral body. For clarity, any Regulatory Authority will be a Governmental Authority.
7
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
1.58“HSR Act” means the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as codified at 15 U.S.C. § 18a, as may be amended from time to time, and the rules and regulations promulgated thereunder, or foreign equivalent thereof under Applicable Law (including all additions, supplements, extensions and modifications thereto).
1.59“HSR Clearance” means the expiration or termination of all applicable waiting periods and requests for information (and any extensions thereof) under the HSR Act with respect to this Agreement.
1.60“HSR Filing” means (a) filings by Agenus and Licensee with the United States Federal Trade Commission (the “FTC”) and the Antitrust Division of the United States Department of Justice (the “DOJ”) of a Notification and Report Form for Certain Mergers and Acquisitions (as that term is defined in the HSR Act) with respect to this Agreement, together with all required documentary attachments thereto, or (b) equivalent filings, if any, with applicable governmental authorities where such filings are required.
1.62“IND” means an investigational new drug application, clinical trial authorization, or similar application, submission, or a clinical trial exemption to the applicable Regulatory Authority, in each case, the filing of which is necessary to commence or conduct any Clinical Trial of a pharmaceutical or biological product in humans in such jurisdiction.
1.63“Indication” means [**].
1.64“Invention” means any discovery or invention, whether or not patentable, conceived or otherwise made by either Party, or by both Parties, under this Agreement.
1.65“Know-How” means all technical, scientific, regulatory, and other information, results, knowledge, techniques and data, in whatever form and whether or not confidential, patented or patentable, including Inventions, invention disclosures, discoveries, plans, processes, practices, methods, knowledge, trade secrets, know-how, instructions, skill, experience, ideas, concepts, data (including biological, chemical, pharmacological, toxicological, pharmaceutical, physical and analytical, safety, quality control, and pre-clinical and clinical data), formulae, formulations, compositions, specifications, marketing, pricing, distribution, cost, sales and manufacturing data or descriptions, and all chemical or biological materials and other tangible materials. Know-How does not include any Patent claiming any of the foregoing.
1.66“Licensed Antibody” means (a) AGEN1777 and (b) [**], and, in each case ((a) and (b)), [**]. For the avoidance of doubt, [**].
1.67“Licensed Product” means any [**] Licensed Antibody [**].
1.68“Licensee Arising Reversion Know-How” means, with respect to any Terminated Territory, any Licensee Arising Know-How Controlled by Licensee that is [**] to Exploit any Reversion Product [**], excluding any Know-How related to any Other Component.
8
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
1.69“Licensee Arising Reversion Patent” means, with respect to any Terminated Territory, any Licensee Arising Patent Controlled by Licensee that is [**] to Exploit any Reversion Product [**], excluding any Patent that claims any Other Component.
1.70“Licensee Background Reversion Know-How” means, with respect to any Terminated Territory, subject to Section 14.2.4, any and all Know-How, excluding any Licensee Arising Know-How or Joint Arising Know-How, whether or not patentable, Controlled by Licensee or its Affiliates as of the effective date of termination for such Terminated Territory that is [**] to Exploit any Reversion Product [**], excluding any Know-How related to any Other Component.
1.71“Licensee Background Reversion Patent” means, with respect to any Terminated Territory, subject to Section 14.2.4, any Patent, excluding any Licensee Arising Patent or Joint Arising Patent, Controlled by Licensee or its Affiliates as of the effective date of termination for such Terminated Territory that is [**] the Exploitation of a Reversion Product [**].
1.72“Licensee Reversion Technology” means Licensee Arising Reversion Know-How, Licensee Background Reversion Know-How, Licensee Arising Reversion Patents and Licensee Background Reversion Patents.
1.73“Licensee Technology” means any Know-How or Patent Controlled by Licensee or any of its Affiliates as of the Execution Date or during the Term that is [**] for [**]. For clarity, Licensee Technology includes any Licensee Arising Know-How and Licensee Arising Patent that is [**] for [**].
1.74[**]
1.75“Manufacture” or “Manufacturing” or “Manufactured” means, with respect to a compound or product, the receipt, handling and storage of active pharmaceutical ingredients, drug substance or drug product, medical devices and other materials, the manufacturing, processing, packaging and labeling, holding (including storage), quality assurance and quality control testing (including release) of such compound or product (other than quality assurance and quality control related to the development of manufacturing processes and manufacturing development and formulation development, all of which activities will be considered Development Activities) and shipping of such compound or product.
1.76“Manufacturing Development Activities” means development of test methods, stability testing, formulation development, process development, quality assurance activities, quality control activities, qualification and validation activities, analytic process development, manufacturing process validation, scale-up, and all other activities, including CMC-related activities, necessary for or related to the Manufacture of any Licensed Antibody or Licensed Product for use in the Field in the Territory.
1.77“Marketing Authorization Application” or “MAA” means an application to the appropriate Regulatory Authority for approval to sell any product [**] in any particular country or regulatory jurisdiction, including any (a) Biologics License Application submitted under Section
9
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
351(a) of the PHSA, (b) New Drug Application submitted under Section 505 of the FD&C Act, or (c) substantially similar application or submission filed with a Regulatory Authority in a country or group of countries within the Territory to obtain Product Approval to Commercialize such product in that country or in that group of countries.
1.78“Monospecific Antibody” means, (a) a molecule which comprises of only one (1) [**], wherein such [**] to TIGIT or [**] and no other antigen, or (b) a molecule which comprises of two (2) [**], wherein such [**] both [**] to TIGIT or both [**] to [**], in either case, and no other antigen. For purposes of this definition, (i) [**]; and (ii) [**].
1.79“Multispecific Antibody” means a molecule, or a covalently linked plurality of molecules, which comprise(s) three (3) or more [**], wherein the first [**] TIGIT, the second [**] to [**], and the remaining [**] to any antigen(s) (for clarity, including TIGIT and [**]). For purposes of this definition, (a) [**]; and (b) [**].
1.81“Other Components” means any (a) [**], or (b) [**]. “Other Components” do not include [**].
1.82“Patent Challenge” means: (a) initiation or request of an interference, nullity actions, inter-partes reexaminations, inter-partes review, post-grant review, derivation proceeding or opposition proceeding (or any equivalent proceeding in any country outside of the United States with respect to any of the foregoing) with respect to, (b) making, filing or maintaining any claim, demand, lawsuit or cause of action to challenge the validity or enforceability of, or (c) opposing any extension of, or the grant of a supplementary protection certificate with respect to, in each case ((a) through (c)), any Agenus Patent.
1.83“Patents” means any and all (a) issued patents, (b) pending patent applications, including all provisional and priority patent applications, substitutions, continuations, continuations-in-part, provisional, converted provisionals, divisionals, renewals and all patents granted thereon, (c) patents-of-addition, supplementary protection certificates, international applications and utility models, reissues, reexaminations, and extensions or restorations by existing or future extension or restoration mechanisms, including patent term adjustments, patent term extensions, supplementary protection certificates, or the equivalent thereof, (d) inventor’s certificates, (e) other forms of government-issued rights substantially similar to any of the foregoing, and (f) United States and foreign counterparts of any of the foregoing.
1.84“Person” means any individual, firm, corporation, partnership, limited liability company, trust, business trust, joint venture, Governmental Authority, association, or other entity.
1.85“Phase I Clinical Trial” means [**].
1.86“Phase I/II Clinical Trial” means [**].
1.87“Phase II Clinical Trial” means [**].
10
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
1.88“Phase III Clinical Trial” means [**].
1.89“Phase IIIb or Phase IV Clinical Trial” means [**].
1.90“PHSA” means the U.S. Public Health Service Act, 42 U.S.C. §§ 201 et seq., as amended from time to time.
1.91“PMDA” means the Pharmaceuticals and Medical Devices Agency, or any successor Regulatory Authority having substantially the same function and authority over drugs in Japan.
1.92“PRC” means the People’s Republic of China, which for purposes of this Agreement, will exclude Hong Kong Special Administrative Region, Macau Special Administrative Region and Taiwan.
1.93“Pre-Marketing” means all sales and marketing activities undertaken prior to and in preparation for the launch of Licensed Products in the Territory. Pre-Marketing will include market research, key opinion leader development, advisory boards, medical education, disease-related public relations, health care economic studies, sales force training, and other pre-launch activities prior to the First Commercial Sale of a Licensed Product in a given country or other regulatory jurisdiction in the Territory.
1.94“Pricing Approval” means, with respect to any country where a Governmental Authority authorizes reimbursement or access, or approves or determines pricing, for pharmaceutical or biologic products, receipt (or, if required to make such authorization, approval of determination effective publication) of such reimbursement or access authorization or pricing approval or determination (as the case may be).
1.95“Product Approval” means all approvals from a Governmental Authority necessary for the marketing and sale of a product in a given country or regulatory jurisdiction, which may include the approval of an MAA [**].
1.96“Product-Specific Know-How” means Agenus Know-How that is not related to the Agenus FC Platform.
1.97“Product-Specific Licensed Patents” means the Agenus Patents, excluding the Agenus FC Platform Patents.
1.98“Product Specifications” means, with respect to a Licensed Product, the Manufacturing, performance, quality-control, and Packaging and Labeling specifications for such Licensed Product in the Territory, as such specifications may be amended by Licensee from time to time.
1.99“Promotional Materials” means all written, printed, video, or graphic advertising, promotional, educational, and communication materials (other than any Licensed Product labels and package inserts) for marketing, advertising, and promoting any Licensed Product in the Field
11
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
in the Territory, in each case, for use (a) by a sales representative, (b) in advertisements, web sites, or direct mail pieces, or (c) otherwise in promotion of any Licensed Product.
1.100“Prosecution” or “Prosecute” means, with respect to a particular Patent, all activities associated with the prosecution and maintenance of such Patent (and patent application(s) derived from such Patent), as well as re-examinations, reissues, applications for patent term adjustments and extensions, supplementary protection certificates and the like with respect to that Patent, together with the conduct of interference, opposition, invalidation, reexamination, reissue proceeding, post-grant review, inter partes review, derivation proceeding or other similar administrative proceeding or administrative appeal thereof, with respect to that Patent.
1.101“Registrational Trial” means [**].
1.102“Regulatory Approval” means [**].
1.103“Regulatory Authority” means, in a particular country or regulatory jurisdiction, any applicable Governmental Authority involved in granting Regulatory Approval or Pricing Approval of a product in such country or regulatory jurisdiction.
1.104“Regulatory Data” means any and all research data, pharmacology data, CMC data, pre-clinical data, clinical data, and all other documentation submitted, or required to be submitted, to Regulatory Authorities in association with regulatory filings for a Licensed Product (including information in any applicable Drug Master Files (“DMFs”), or similar documentation).
1.105“Regulatory Exclusivity” means any [**] conferred by any Governmental Authority with respect to a Licensed Product, other than any rights conferred by a Patent.
1.106“Regulatory Materials” means regulatory applications, submissions, notifications, communications, correspondence, registrations, Regulatory Approvals, Pricing Approvals, or other filings made to, received from or otherwise conducted with a Regulatory Authority in order to Develop, Manufacture, obtain marketing authorization, market, sell, or otherwise Commercialize a Licensed Product in a particular country or regulatory jurisdiction. Regulatory Materials include INDs, MAAs, import drug licenses, presentations, responses, and applications for other Regulatory Approvals or Pricing Approvals.
1.107“Reversion Product” means, with respect to a Terminated Territory, any Licensed Product that is being Exploited by Licensee or any of its Related Parties [**].
1.108“Related Parties” means (a) with respect to Licensee, Licensee’s Affiliates and Sublicensees of the rights granted to Licensee hereunder (excluding distributors, even if they are granted a sublicense under the rights granted to Licensee under Section 2.1 (Grant to Licensee)), and (b) with respect to Agenus, Agenus’ Affiliates.
1.109“Royalty Rate” means any royalty rate set forth in Table 8.5.1 in Section 8.5.1 (Royalty Rates) or Table 8.5.2 in Section 8.5.2 ([**]).
12
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
1.110“Royalty Payment” means any royalty payment pursuant to Section 8.5 (Royalty Payments).
1.111“Royalty Term” means, with respect to each Licensed Product on a country-by-country basis in the Territory, the period of time beginning on the First Commercial Sale of such Licensed Product in such country and ending the later of (a) ten (10) years from the First Commercial Sale of such Licensed Product in such country, (b) the expiration of the last to expire Valid Claim within the Agenus Patents in such country claiming or covering such Licensed Antibody or Licensed Product [**], or (c) the expiration of the Regulatory Exclusivity period for such Licensed Product in such country.
1.112[**]
1.113[**]
1.114“Special Resolution Mechanisms Schedule” means Schedule 1.114 (Special Resolution Mechanisms Schedule).
1.115 [**].
1.116“Terminated Territory” means any [**]with respect to which this Agreement has been terminated. For clarity, if this Agreement is terminated in its entirety, the Terminated Territory shall be worldwide.
1.117“Territory” means worldwide, excluding any Terminated Territory.
1.118“Third Party” means any Person other than Agenus, Licensee, or their respective Affiliates.
1.119“Third Party License Agreement” means any agreement under which Agenus or any of its Affiliates Controls (a) any Agenus Technology owned by a Third Party as of the Execution Date or (b) [**].
1.120“United States” or “U.S.” means the United States of America and its possessions and territories.
1.121“Valid Claim” means (a) a claim of an issued and unexpired patent that has not been held permanently revoked, unenforceable or invalid by a decision of a court or other Governmental Authority of competent jurisdiction, unappealable or unappealed within the time allowed for appeal and that is not admitted to be invalid or unenforceable through reissue, disclaimer or otherwise (i.e., only to the extent the subject matter is disclaimed or is sought to be deleted or amended through reissue), or (b) a claim of a pending patent application that has not been abandoned, finally rejected or expired without the possibility of appeal or refiling; provided, however, that [**].
1.122[**]
13
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
1.123[**]
1.124Additional Definitions. The following terms have the meanings set forth in the corresponding Sections of this Agreement:
|
Section |
|
|
“AAA” |
15.3.1 |
|
[**] |
2.4.3 |
|
“Agenus” |
Preamble |
|
“Agenus Arising Patents” |
9.1.2(a) |
|
“Agenus Arising Know-How” |
9.1.2(a) |
|
“Agenus Arising Technology” |
9.1.2(a) |
|
“Agenus Co-Funding Share” |
4.6.2(a) |
|
“Agenus GDP Trial” |
4.4.2 |
|
“Agenus GDP Trial Costs” |
4.4.3(b) |
|
“Agenus GDP Trial Plan and Budget” |
4.4.3(b) |
|
“Agenus Indemnitees” |
11.2 |
|
[**] |
2.3.3 |
|
“Agenus Pipeline Combination Trial” |
4.4.2 |
|
“Agenus Pipeline Combination Trial Plan” |
4.4.2 |
|
“Agenus Pipeline Combination Trial Agreement” |
4.4.2 |
|
Section |
|
|
Preamble |
|
|
“Alliance Manager” |
3.4 |
|
“Anticipated [**] Approval Notice” |
6.3.1 |
|
“Arising Know-How” |
9.1.2(a) |
|
“Arising Patent” |
9.1.2(a) |
|
“Arising Technology” |
9.1.2(a) |
|
“Audit” |
8.16 |
|
“Bankrupt Party” |
14.9 |
|
“Breaching Party” |
13.2 |
|
“Chairperson” |
3.1.1 |
|
“Claim” |
11.1 |
|
“Competitive Activities” |
2.4.1 |
|
“Co-Funding Option” |
4.6.1 |
|
“Co-Funding Option Exercise Date” |
4.6.1 |
|
“Co-Funding Option Period” |
4.6.1 |
|
“Co-Promote Option” |
6.3.1 |
|
“Co-Promote Opt-in Deadline” |
6.3.1 |
|
“Co-Promotion Agreement” |
6.3.2 |
|
“Confidential Information” |
12.1.1 |
|
Section |
|
|
13.2.1 |
|
|
“Deferred Co-Funding Development Costs” |
4.6.2(b) |
|
“Development Costs” |
4.5 |
|
“Development Milestone” |
8.2 |
|
“Development Milestone Notification Notice” |
8.2 |
|
“Development Milestone Payment” |
8.2 |
|
“Dispute” |
15.1 |
|
“DMFs” |
1.104 |
|
“DOJ” |
1.60 |
|
“Execution Date” |
Preamble |
|
[**] |
1.61 |
|
“FTC” |
1.60 |
|
“GAAP” |
1.80 |
|
“[**]” |
8.12.2 |
|
“Global Development Plan” |
4.3.1 |
|
“HSR Proceeding” |
16.2.2 |
|
“ICH” |
1.52 |
|
“Indemnified Party” |
11.3.1 |
|
“Indemnifying Party” |
11.3.1 |
|
“Joint Arising Know-How” |
9.1.2(a) |
14
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
9.1.2(a)
“Joint Arising Technology”
9.1.2(a)
“Joint Development Committee” or “JDC”
3.1.1
“Licensee”
Preamble
“Licensed Antibody Pre-Clinical Studies”
4.4.6
“Licensee Arising Know-How”
9.1.2(a)
“Licensee Arising Patent”
9.1.2(a)
“Licensee Arising Technology”
9.1.2(a)
“Licensee Indemnitees”
11.1
“Licensee Reversion Know-How”
14.5
“Losses”
11.1
“Manufacturing Technology Transfer”
2.6.2
|
Section |
|
|
2.6.2 |
|
|
“Manufacturing Technology Transfer Notice” |
2.6.2 |
|
“Material Breach Notice” |
13.2.1 |
|
“[**] Trial” |
4.4.3(e) |
|
“[**]” |
8.11.2 |
|
“[**]” |
8.11.2 |
|
“Packaging and Labeling” |
7.2 |
|
“Party” or “Parties” |
Preamble |
|
“Product Marks” |
9.6.5(a) |
|
“[**]” |
2.5 |
|
“[**] Royalty Rate” |
8.5.1 |
|
“[**] Notice” |
4.6.1 |
|
“Research Tool Pre-Clinical Studies” |
4.4.6 |
|
“Retained Rights” |
2.2.3 |
|
“Reversion License” |
14.2.1 |
2.1Grant to Licensee. Subject to the terms and conditions of this Agreement, including the Retained Rights, Agenus hereby grants to Licensee during the Term an exclusive (even as to Agenus and its Affiliates), worldwide, sublicensable (in accordance with Section 2.3.2 (Sublicensees)), royalty-bearing (in accordance with Section 8.5 (Royalty Payments)) license, under the Agenus Technology and Agenus’ interest in and to the Joint Arising Technology, in each case, to Exploit the Licensed Antibodies and Licensed Products in the Field in the Territory.
15
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
2.2Additional Licensing Provisions.
2.2.1Negative Covenant. Licensee covenants that it will not use or practice any of the Agenus Technology, except for the purposes expressly permitted in Section 2.1 (Grant to Licensee) or Article 12 (Confidentiality), or otherwise under this Agreement, provided that, nothing in this Section 2.2.1 (Negative Covenant) shall limit Licensee’s use or practice of any Agenus Know-How that is in or becomes part of the public domain other than as a result of Licensee’s breach of its obligations under Section 12.1.1 (Confidentiality).
2.2.2Limitations. Except as expressly set forth in this Article 2 (Licenses) or other terms of this Agreement, nothing in this Agreement will be deemed to grant to Licensee any ownership or other rights in or to any products or technologies owned or controlled or developed or otherwise obtained by or on behalf of Agenus as of the Effective Date or thereafter, nor to any intellectual property or other proprietary rights therein, all of which will remain solely and exclusively owned or controlled (as applicable) by Agenus. For clarity, unless otherwise agreed between the Parties in writing, Licensee is not granted a license under the Agenus Technology or any other intellectual property rights owned or controlled by Agenus in and to any Agenus Other Component to Exploit such Agenus Other Component, including as one component of a Combination Product.
2.2.3Agenus Retained Rights. Agenus retains all rights to the Agenus Technology except those expressly granted to Licensee under the terms of this Agreement. Without limiting the foregoing, and notwithstanding anything to the contrary in this Agreement, Agenus hereby retains the right under the Agenus Technology to (a) [**]; (b) [**]; and (c) [**] (collectively (a) through (c), the “Retained Rights”).
2.2.4License Grant to Agenus. Subject to the terms and conditions of this Agreement, Licensee hereby grants to Agenus, for [**], a [**], royalty-free license, under any Licensee Technology to [**].
2.3Performance by Affiliates, Sublicensees and Subcontractors.
2.3.1Performance by Affiliates. Agenus recognizes that Licensee may perform some or all of its obligations under this Agreement through Affiliates; provided, however, that Licensee will remain responsible for the performance by its Affiliates and will cause its Affiliates to comply with the provisions of this Agreement in connection with such performance. Licensee hereby expressly waives any requirement that Agenus exhaust any right, power, or remedy, or proceed against an Affiliate for any obligation or performance hereunder prior to proceeding directly against Licensee. Wherever in this Agreement Licensee delegates responsibility to Affiliates, Licensee agrees that such entities may not make decisions inconsistent with this Agreement, amend the terms of this Agreement, or act contrary to its terms in any way.
2.3.2Sublicensees. Licensee will have the right (but not the obligation) to sublicense, through multiple tiers, those rights granted to it under Section 2.1 (Grant to Licensee) to one or more of its Affiliates or Third Parties (each such Third Party, but excluding any subcontractors, a “Sublicensee”); provided that [**]. Licensee shall provide Agenus a copy of any such sublicense agreement between Licensee and the applicable Sublicensee (which copy may be reasonably redacted for any information that is not required for Agenus to assess Licensee’s compliance with this Agreement, including any financial terms) within [**] after execution of such sublicense agreement. For clarity, any information and terms of the sublicense agreement disclosed to Agenus shall constitute the Confidential Information of Licensee. Except as otherwise agreed by the Parties in connection with sublicenses granted pursuant to the above proviso, Licensee will remain responsible for the performance by any of its Sublicensees and will cause its Sublicensees to comply with the applicable provisions of this Agreement in connection with such performance, including the non-compete, negative covenant, reporting, audit, inspection and confidentiality provisions. For clarity, Licensee will remain directly responsible for all amounts owed to Agenus under this Agreement. Except as otherwise agreed by the Parties in connection with sublicenses granted pursuant to the above proviso, Licensee hereby expressly waives any requirement that Agenus exhaust any right, power, or remedy, or proceed against a Sublicensee, for any obligation or performance hereunder prior to proceeding directly against Licensee.
16
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
2.3.3Subcontractors. Agenus may freely subcontract its obligations under this Agreement to its Affiliates or any Third Party without the prior consent of Licensee, except that [**]. In the case of any subcontracting of any Development activities by Agenus under this Agreement to a Third Party, such Third Party must have entered into a written agreement with Agenus that includes terms and conditions that are consistent with the applicable terms and conditions in this Agreement, including terms and conditions protecting and limiting use and disclosure of Confidential Information at least to the same extent as under Article 12 (Confidentiality) of this Agreement. For clarity, Licensee may subcontract any of its obligations under this Agreement to any Third Party. Each Party is responsible for compliance by its subcontractors performing its obligations under this Agreement with the applicable terms and conditions of this Agreement in the same way and to the same extent as such Party.
2.4.1Exclusivity Covenant. Except in the exercise of a Party’s rights or as provided under this Agreement, including in the case of Agenus, the conduct of [**] in accordance with this Agreement: (a) Agenus hereby covenants and agrees that [**] it will not, and will cause its Related Parties not to, [**]; and (b) Licensee hereby covenants and agrees that [**] it will not, and will cause its Related Parties not to, [**] (each of (a) and (b), “Competitive Activities”); provided that the foregoing restriction shall not apply to [**].
2.4.2[**]
2.4.3[**]
2.5Materials Transfer. Within [**] after the Effective Date (or as soon as reasonably practical thereafter), Agenus will transfer to Licensee, at [**] cost and expense, the amounts of [**] set forth in Schedule 2.5 (Materials Transfer), which schedule shall also indicate [**]. Title to such amounts of [**] will transfer to Licensee upon [**]. Prior to the date of the first shipment of [**].
17
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
2.6.1Agenus Know-How Transfer. Within [**] after the Effective Date, Agenus will, at its cost, provide documents and other information and materials in their existing form containing Agenus Know-How. Thereafter during the Term, without limiting Section 9.1.2(b), Agenus will, at its cost, use Diligent Efforts to provide to Licensee documents and other information and materials in their existing form containing Agenus Know-How to the extent not previously provided to Licensee under this Section 2.6.1 (Agenus Know-How Transfer), promptly upon Licensee’s request not more than once per [**]. Notwithstanding the foregoing, Agenus’ obligations under this Section 2.6.1 (Agenus Know-How Transfer) do not include provision of Manufacturing-related Agenus Know-How, which will be provided in accordance with Section 2.6.2 (Manufacturing Technology Transfer) and Section 2.6.3 (Agenus Assistance) to Licensee which, subject to Section 2.6.3 (Agenus Assistance), will be at no additional cost to Licensee.
2.6.2Manufacturing Technology Transfer. Agenus will use Diligent Efforts to assist Licensee with respect to the one-time transfer of Manufacturing capabilities with respect to the Licensed Antibodies to Licensee (or its designee), including: [**] (the “Manufacturing Technology Transfer”) as provided in this Section 2.6 (Technology Transfer). Subject to its compliance with Applicable Laws and this Agreement, Licensee will commence the Manufacturing Technology Transfer by written notice to Agenus (the “Manufacturing Technology Transfer Notice”) no later than [**] from the Effective Date. Within [**] following the provision of such written notice, Agenus will use Diligent Efforts to commence and Agenus will, thereafter, use Diligent Efforts to perform the Manufacturing Technology Transfer to Licensee or its designee in accordance with the Manufacturing Technology Transfer Agreement, if any, agreed to by the Parties, which, subject to Section 2.6.3 (Agenus Assistance), will be at [**] sole cost and expense. Without limiting Agenus’ obligation to perform the Manufacturing Technology Transfer, after Licensee provides the Manufacturing Technology Transfer Notice, the Parties will use good faith efforts to negotiate a manufacturing technology transfer agreement (the “Manufacturing Technology Transfer Agreement”) detailing a plan for the Manufacturing Technology Transfer, which agreement shall be consistent with this Section 2.6.2 (Manufacturing Technology Transfer) and Section 2.6.3 (Agenus Assistance).
2.6.3Agenus Assistance. Agenus will use Diligent Efforts to make available to Licensee, at [**] cost and expense, up to a total of [**] FTE hours of assistance provided by experienced Agenus CMC employees to perform its obligations under Section 2.6.2 (Manufacturing Technology Transfer); provided that [**]. Such transfers will occur in an orderly fashion and in a manner such that the value, usefulness, and confidentiality of the transferred Agenus Know-How, Regulatory Materials, Regulatory Data, and other regulatory documentation are preserved in all material respects. Notwithstanding the foregoing, Agenus will not be required to provide any assistance under Section 2.6.2 (Manufacturing Technology Transfer) to the extent Agenus determines it would unreasonably interfere with Agenus’ own business [**].
3.1Joint Development Committee.
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
3.1.1Formation; Composition. No later than [**] after the Effective Date, the Parties will establish a joint development committee (the “Joint Development Committee” or “JDC”) comprised of up to [**] representatives from each Party with sufficient seniority within the applicable Party to make decisions arising within the scope of the JDC’s responsibilities. Each Party may replace its JDC representatives at any time upon written notice to the other Party. Either Party’s representatives at the JDC may invite non-members to participate in the discussions and meetings of the JDC, provided that such participants will have no voting authority at the JDC and are bound by confidentiality and non-use obligations similar to those set out in Article 12 (Confidentiality) and such participation has been approved by the other Party prior to such discussion or meeting, such approval not to be unreasonably conditioned, withheld or delayed. The JDC will be chaired by [**] (“Chairperson”). The role of the Chairperson will be to convene and preside at meetings of the JDC. The Chairperson will have no additional powers or rights beyond those held by the other JDC representatives. The Alliance Managers will work with the Chairperson to prepare and circulate agendas and to ensure the preparation of minutes.
3.1.2Specific Responsibilities. The JDC will:
(a)facilitate the flow of information between the Parties with respect to the Development of the Licensed Antibodies and Licensed Products, including sharing a summary of material Development data and results, and review and discuss any Development reports and updates;
(b)review and discuss the Global Development Plan, and any update or amendment thereto;
(c)review and approve any proposed [**];
(d)as needed, form subcommittees or working groups (in each case, that have no decision-making powers) that are responsible for the oversight and information sharing with respect to any specific aspect of activities under this Agreement; and
(e)perform such other functions as appropriate, to further the purposes of this Agreement, in each case, as agreed in writing by the Parties.
3.1.3Meetings. During the Term, the JDC will meet on a [**] basis, unless otherwise agreed to by the JDC. No later than [**] prior to any meeting of the JDC, the Alliance Managers will jointly prepare and circulate an agenda for such meeting; provided, however, that either Party may propose additional topics to be included on such agenda, prior to such meeting so long as the other Party consents to such later addition of such agenda items (which consent shall not be unreasonably conditioned, withheld or delayed). The JDC may meet in person, by videoconference or by teleconference; provided that, unless otherwise agreed by the Parties, at least [**] meeting per Calendar Year will be held in person. The location of the in-person JDC meetings will alternate between a location selected by Licensee and a location selected by Agenus, with Licensee selecting the location of the first in-person JDC meeting. Each Party will bear the expense of its respective JDC members’ participation in JDC meetings. Meetings of the JDC will be effective only if at least [**] JDC members from each Party (which members do not include
19
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
such Party’s Alliance Manager) are present or participating (including by videoconference or teleconference) in such meeting. The Alliance Managers will be responsible for preparing reasonably detailed written minutes of all JDC meetings that reflect material decisions made and action items identified at such meetings. The Alliance Managers will send draft meeting minutes to each member of the JDC for review and approval within [**] after each JDC meeting. Such minutes will be deemed approved unless one or more members of the JDC objects to the accuracy of such minutes within [**] of receipt.
3.1.4Decision-Making. The representatives from each Party on the JDC will have, collectively, one (1) vote on behalf of that Party, and all decision making will be by consensus. Disputes at the JDC will be handled in accordance with Section 3.2 (Resolution of JDC Disputes).
3.2Resolution of JDC Disputes.
3.2.1Within the JDC. All decisions within the JDC will be made by consensus; provided that if the JDC is unable to reach consensus on any issue for which it is responsible within [**] after a Party affirmatively states that a decision needs to be made, then [**] will have final decision-making authority with respect to such matter.
3.2.2Limitations on Decision-Making. Without [**] prior written consent, [**] may not unilaterally make a decision (in exercise of its final decision-making authority on any such matters) that (a) [**], (b) [**], (c) [**], or (d) [**]. In addition, no exercise by [**] of its decision-making authority can amend or waive compliance with any terms of this Agreement.
3.3Discontinuation of JDC. The JDC will continue to exist until the earliest of: (a) [**], (b) [**] or (c) the Parties agreeing to disband the JDC; provided that, if in the case of clause (b) [**], then the JDC will continue to exist for so long as [**]. Once the JDC is disbanded, the JDC will have no further obligations under this Agreement and, thereafter, the Alliance Managers will be the points of contact for the exchange of information between the Parties under this Agreement and any references in this Agreement to decisions of the JDC will automatically become references to decisions by and between the Parties in writing, subject to the other terms of this Agreement and consistent with the terms of Section 3.2 (Resolution of JDC Disputes).
3.4Alliance Manager. Within [**] of the Effective Date, each Party will appoint an individual (from the Party or from any Affiliate of such Party) who possesses a general understanding of Development, Manufacturing, and Commercialization issues regarding pharmaceutical and biologic products to act as the facilitator of the meetings of the JDC and the first point of contact between the Parties with regard to questions relating to this Agreement or the overall business relationship and related matters between the Parties (each, an “Alliance Manager”). Each Party may replace its Alliance Manager at any time upon written notice to the other Party.
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
4.1Overview of Development. Except for the Agenus Ongoing Studies and subject to Agenus’ right and obligation (if applicable) to conduct Agenus GDP Trials, Agenus Pipeline Combination Trials, Licensed Antibody Pre-Clinical Studies, and the Co-Funding Option, Licensee will be solely responsible, directly or through its Affiliates, Sublicensees and subcontractors, for the Development of Licensed Products for use in the Field and in the Territory.
4.2Objectives under the Global Development Plan.
4.2.1Development Diligence Obligations. Licensee will use [**] to Develop [**] Licensed Product, and obtain Regulatory Approval (and Pricing Approval, if applicable) for [**] Licensed Product in the Field in each of the [**].
4.2.2Compliance. Each Party will conduct the Development Activities for which it is responsible under this Agreement in accordance with the Global Development Plan and sound and ethical business and scientific practices, and in compliance with all Applicable Law, including GCPs and GLPs, and also including all applicable pharmacovigilance, data privacy, and data protection laws in the Territory, in all material respects. In addition, each Party will not use in any capacity, in connection with its Development, Manufacturing, or Commercialization (as applicable) of the Licensed Antibodies or Licensed Products hereunder, any Person who has been debarred pursuant to Section 306 of the FD&C Act (or similar Applicable Law outside of the U.S.), or who is the subject of a conviction described in such section. Each Party will inform the other Party in writing immediately if it or any Person who is performing services for such Party hereunder is debarred or is the subject of a conviction described in Section 306 (or similar Applicable Law outside of the U.S.), or if any action, suit, claim, investigation, or legal administrative proceeding is pending or, to such Party’s knowledge, is threatened, relating to the debarment of such Party or any Person used in any capacity by Licensee in connection with its Development (or Commercialization) of the Licensed Antibodies or the Licensed Products hereunder.
4.3.1General. Licensee will detail the Development Activities in a global Development plan (the “Global Development Plan”), which Licensee will prepare, review, and update as set forth in this Section 4.3 (Global Development Plan). The Global Development Plan will set forth, among other things, the following: (a) [**]; (b) [**]; (c) [**]; (d) [**]; (e) [**]; and (f) [**].
4.3.2Initial Global Development Plan and Updates and Amendments. The initial Global Development Plan for the Licensed Products is attached hereto as Schedule 4.3.2 (Initial Global Development Plan). Licensee will review, update, and amend as appropriate, the then-current Global Development Plan not less often than [**] (during the [**]) to reflect any material changes, reprioritizations of, or additions to the Global Development Plan; provided that (a) if the JDC is disbanded pursuant to Section 3.3 (Discontinuation of JDC), Licensee will provide such updates or amendments no less often than [**] (during the [**] of each) and (b) Licensee shall not establish or amend any Agenus GDP Trial Plan and Budget without Agenus’ prior written consent not to be unreasonably conditioned, withheld or delayed.
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
4.3.3Estimate of Global [**] Development Costs. During [**], upon Agenus’ request (no more than [**] per Calendar Year), Licensee shall provide Agenus a [**] budget for the Global [**] Development Costs [**].
4.4.1Agenus Ongoing Studies. Agenus will be responsible for completing, and will use [**] to complete, at [**] cost and expense, all of the Agenus Ongoing Studies. Without limiting the foregoing, Schedule 1.11 (Agenus Ongoing Studies) includes Agenus’ good faith estimate of [**] for each Agenus Ongoing Study as of the Effective Date.
4.4.2Agenus Co-Development. Subject to the terms of this Agreement, Agenus will have the right to perform any Clinical Trial of Licensed Products that is: (i) set forth in the Global Development Plan and mutually agreed by the Parties to be performed by Agenus (such Clinical Trial, an “Agenus GDP Trial”); or (ii) for Development in combination with one or more Agenus Other Components conducted prior to the Regulatory Approval of the subject Licensed Product in the country in which such Clinical Trial is being conducted (such Clinical Trial, an “Agenus Pipeline Combination Trial”); provided that with respect to each Agenus Pipeline Combination Trial: (A) [**] (1) [**] and (2) [**]; (B) such Agenus Pipeline Combination Trial [**]; and (C) such Agenus Pipeline Combination Trial is conducted pursuant to an Agenus Pipeline Combination Trial Agreement. Notwithstanding the foregoing, [**]. Notwithstanding anything to the contrary contained in this Agreement, nothing in this Agreement shall restrict or limit Agenus from conducting a Clinical Trial of any Licensed Product for Development in combination with one or more Agenus Other Components after the Regulatory Approval of such Licensed Product in the country where such Clinical Trial is being conducted using such Licensed Product [**].
4.4.3Agenus GDP Trials.
(a)Diligence. Agenus will be responsible for the completion of, and will use [**] to complete, each Agenus GDP Trial in accordance with the applicable Agenus GDP Trial Plan and Budget and this Agreement. Agenus will conduct each Agenus GDP Trial under an IND held by [**].
(b)Agenus GDP Trial Plan and Budget. With respect to each Agenus GDP Trial, the Parties shall agree in writing on a detailed plan for such Agenus GDP Trial and a budget of the estimated internal and external Development costs and expenses to be incurred by or on behalf of Agenus in the performance of such Agenus GDP Trial, and any proposed change or amendment thereto (such costs and expenses, the “Agenus GDP Trial Costs”, and such plan and budget, the “Agenus GDP Trial Plan and Budget”). Agenus shall not, and shall cause its Affiliates not to, commence any activities and may not incur any costs and expenses in relation to any Agenus GDP Trial unless and until the applicable Agenus GDP Trial Plan and Budget has been agreed between the Parties in writing. [**]
(c)Supply of Licensed Antibodies and Licensed Products. With respect to each Agenus GDP Trial other than the [**] Trial, Licensee shall [**] Manufacture and supply to Agenus Licensed Antibodies and Licensed Products [**] for the purpose of Agenus
22
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
performing its obligations under the Global Development Plan with respect to such Agenus GDP Trial, in the quantity specified in the Global Development Plan to be supplied by Licensee to Agenus.
(d)Pharmacovigilance Agreement. Promptly upon the Parties’ mutual agreement to include in the Global Development Plan any Agenus GDP Trial, the Parties will negotiate in good faith a pharmacovigilance agreement on customary terms with respect to the exchange of safety data arising from any and all Agenus GDP Trial(s). Agenus will not initiate any Agenus GDP Trial until such pharmacovigilance agreement has been executed by the Parties.
4.4.4Agenus Pipeline Combination Trials. Agenus may exercise its right to conduct an Agenus Pipeline Combination Trial by providing Licensee with written notice of its intent with respect thereto, which notice shall include a data package that contains the following: [**]. Following such notice and provided that the conditions in subclauses (i) and (ii) of Section 4.4.2 (Agenus Co-Development) are satisfied, the Parties will discuss and use good faith efforts to agree within [**] of such notice a separate agreement for the conduct of such Agenus Pipeline Combination Trial (an “Agenus Pipeline Combination Trial Agreement”). The Agenus Pipeline Combination Trial Agreement will (A)[**], (B) [**] (C) [**] (D) [**] (E) [**], and (F) be otherwise consistent with the terms of this Agreement. The Agenus Pipeline Combination Trial will be conducted in accordance with the applicable Agenus Pipeline Combination Trial Plan, and any updates or amendments to any Agenus Pipeline Combination Trial Plan will not be effective unless and until mutually agreed by the Parties. For the avoidance of doubt, Agenus shall not, and shall cause its Affiliates not to, perform any activities with respect to any Agenus Pipeline Combination Trial unless and until the Parties have executed an Agenus Pipeline Combination Trial Agreement with respect to such Agenus Pipeline Combination Trial.
4.4.5[**]
4.4.6Pre-Clinical Studies. Subject to the terms of this Agreement, Agenus retains the right to conduct internal, pre-clinical studies of the Licensed Antibodies and Licensed Products (“Licensed Antibody Pre-Clinical Studies”). [**] Subject to the terms of this Agreement, Agenus also retains the right to conduct pre-clinical studies involving the use of Bispecific Antibodies or Multispecific Antibodies that are not proprietary to Licensee or its Related Parties and that are solely used as research tools (for the avoidance of doubt, excluding Licensed Antibodies and provided that such Bispecific Antibodies or Multispecific Antibodies are not intended for use in the treatment of or other administration in humans) (“Research Tool Pre-Clinical Studies”) [**]. For the avoidance of doubt, any publication of the results of any Licensed Antibody Pre-Clinical Studies or Research Tool Pre-Clinical Studies under this Section 4.4.6 (Pre-Clinical Studies) will be subject to the publication and disclosure provisions in Article 12 (Confidentiality).
4.5Development Costs. Subject to Agenus’ exercise of the Co-Funding Option and accordingly its responsibility for the Agenus Co-Funding Share in accordance with Section 4.6.2 (Exercise of Agenus Co-Funding Option), Licensee will be solely responsible for one hundred
23
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
percent (100%) of all internal and external Development costs and expenses incurred by Licensee or its Affiliates with respect to its Development Activities (the “Development Costs”). For the avoidance of doubt, Agenus shall be solely responsible for all costs and expenses incurred in connection with any [**], Licensed Antibody Pre-Clinical Study and Research Tool Pre-Clinical Study.
4.6.1Grant of Option. Licensee hereby grants to Agenus the option (the “Co-Funding Option”) to co-fund the Shared [**] Development Costs. Licensee will keep Agenus reasonably informed of the Development of [**], and, no later than [**], provide Agenus with written notice thereof along with an [**] and [**] (the “[**] Notice”). Agenus may exercise the Co-Funding Option by providing written notice to Licensee at any time beginning upon Agenus’ receipt of the [**]Notice and ending [**] thereafter (the “Co-Funding Option Period” and the date Agenus provides such notice, the “Co-Funding Option Exercise Date”). If Agenus does not exercise the Co-Funding Option during the Co-Funding Option Period, then the Co-Funding Option will expire. For clarity, the Co-Funding Option does not apply to any Licensed Products [**], or to any Development Costs that are not Shared [**] Development Costs.
4.6.2Exercise of Agenus Co-Funding Option.
(a)Agenus Co-Funding Share. If Agenus exercises the Co-Funding Option during the Co-Funding Option Period, (i) Agenus will be responsible for [**] of: (A) [**]; and (B) [**] (collectively, [**] the “Shared [**] Development Costs” and Agenus’ share of the Shared [**] Development Costs, the “Agenus Co-Funding Share”); and (ii) Agenus will be entitled to receive the increased Royalty Rates on Net Sales of AGEN1777 Licensed Products as set forth in Section 8.5.2 (Royalty Rates for AGEN1777 Licensed Products upon Exercise of Co-Funding Option). For purposes of determining the Agenus Co-Funding Share, Shared [**] Development Costs will (1) [**], (2) [**], and (3) [**].
(b)Changes to Global Development Plan Budget. Notwithstanding the foregoing, if, at any time following the Co-Funding Option Exercise Date, Licensee (after review and discussion with the JDC) increases the aggregate budgeted Shared AGEN1777 Development Costs set forth in the Global Development Plan to more than [**] of the aggregate budgeted Shared AGEN1777 Development Costs in the Global Development Plan effective on the Co-Funding Option Exercise Date, Agenus may elect, by written notice to Licensee, to defer payment responsibility for the Agenus Co-Funding Share that exceeds [**] of the aggregate budgeted Shared AGEN1777 Development Costs in the Global Development Plan effective on the Co-Funding Option Exercise Date (such excess Shared AGEN1777 Development Costs, the “Deferred Co-Funding Development Costs”), and instead have such amounts deducted from up to [**] of each future Development Milestone Payments, Sales Milestone Payments, or Royalty Payments that become payable by Licensee under this Agreement (i.e., Licensee’s next-to-occur payment obligation for such Development Milestone Payments, Sales Milestone Payments or Royalty Payments shall be reduced by a corresponding amount, provided that such reduction shall not exceed [**] of such payment that would otherwise be payable by Licensee under Article 8 (Payments) after taking into account any reductions or deductions thereunder, provided that, with
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
respect to Royalty Payments, subject to the royalty floor in accordance with Section 8.9 (Royalty Floor), and any such amount to the extent not deducted against any such payment obligation shall be rolled-over and shall be deducted against any subsequent payment obligation(s) for Development Milestone Payments, Sales Milestone Payments or Royalty Payments until such amount is fully deducted, always subject to such [**] cap with respect to such subsequent payment obligation and without being subject to Section 8.15 (Late Payments), provided that, with respect to Royalty Payments, always subject to the royalty floor in accordance with Section 8.9 (Royalty Floor)).
(c)Invoices and Payments.
(i)Within [**] of the Co-Funding Option Exercise Date, Licensee will provide to Agenus an invoice for the Agenus Co-Funding Share with respect to Shared [**] Development Costs incurred prior to the Co-Funding Option Exercise Date, such invoice shall also set forth in reasonable detail all such Shared [**] Development Costs. Notwithstanding Section 8.14 (General Payment Procedures), Agenus will remit such payment to Licensee within [**] of Agenus’ receipt of such invoice.
(ii)Upon and after Agenus’ exercise of the Co-Funding Option, within [**] of the end of each [**], Licensee will provide to Agenus an invoice setting forth the Agenus Co-Funding Share for the preceding [**], including reasonable detail of all Shared [**] Development Costs incurred by Licensee and its Affiliates for the preceding [**]. Agenus will remit such payment to Licensee in accordance with the terms of Section 8.14 (General Payment Procedures).
4.6.3Termination of Agenus Co-Funding. Agenus may, at any time upon at least [**] prior written notice to Licensee (or at least [**] prior written notice following consummation of a Change of Control of Licensee), elect to cease funding the Agenus Co-Funding Share. If Agenus provides such notice to Licensee, Agenus’ funding obligations with respect to the Agenus Co-Funding Share shall cease on the date that is [**] (or [**], in the event of a notice following a Change of Control of Licensee) following the date Agenus provides such notice. In such an event, (a) beginning with the first Calendar Quarter after the effective date of cessation of such funding obligations of Agenus, (i) Agenus will no longer be required to fund any portion of Development Costs and (ii) [**]; and (b) with respect to the Calendar Quarter during which such effective date of cessation of such funding obligations of Agenus occurs, Agenus shall pay for the Agenus Co-Funding Share of the applicable proportion of the Shared [**] Development Costs during such Calendar Quarter, and [**].
4.7Records, Reports, and Information.
4.7.1General. Each Party will, and will cause each of its Related Parties to, maintain current and accurate records of all Development Activities, and with respect Agenus, Licensed Antibody Pre-Clinical Studies, conducted by it and them under this Agreement and all data and other information resulting from such activities (which records will include, as applicable, books, records, reports, research notes, charts, graphs, comments, computations, analyses, recordings, photographs, computer programs, and documentation thereof (e.g., samples of
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
materials and other graphic or written data generated in connection with such Development Activities, and with respect Agenus, Licensed Antibody Pre-Clinical Studies)). Such records will properly reflect all work done and results achieved in the performance of such Development Activities, and with respect Agenus, Licensed Antibody Pre-Clinical Studies, in sufficient detail and in good scientific manner appropriate for regulatory and patent purposes. Each Party will document all of its Development Activities, and with respect Agenus, Licensed Antibody Pre-Clinical Studies, to be conducted pursuant to this Agreement in formal written study reports according to applicable national and international guidelines (e.g., ICH, GCP and GLP).
4.7.2Licensee Status Updates in the Territory. At least [**], during the [**] and [**], Licensee will provide Agenus with reports summarizing, since the previous such report, (a) [**], (b) [**], and (c) [**]; provided that if the JDC is disbanded pursuant to Section 3.3 (Discontinuation of JDC), Licensee will provide such reports at least [**]during the [**] of each Calendar Year. Without limiting the foregoing, upon reasonable request by Agenus: (a) Licensee will promptly, but in any event within [**] after receipt of Agenus’ request, provide to Agenus copies of [**] related to such Development Activities under the Global Development Plan for the Licensed Products in the Field in [**], including [**]; and (b) Licensee will promptly provide to Agenus [**] generated in connection with Licensee’s Development Activities, including [**].
4.8Agenus Status Updates in the Territory.
4.8.1Agenus Ongoing Studies and Agenus GDP Trials. At least [**], during the [**], Agenus will provide Licensee with reports summarizing, since the previous such report, the Development Activities [**] performed by Agenus [**]. In addition, Agenus will provide Licensee with other information [**]. Without limiting the foregoing, Agenus will promptly after Licensee’s reasonable request, provide to Licensee copies of [**] generated in connection with Agenus’ Development Activities with respect to any Agenus Ongoing Studies and Agenus GDP Trial(s).
4.8.2Licensed Antibody Pre-Clinical Studies. With respect to each Licensed Antibody Pre-Clinical Study, promptly after completion of such Licensed Antibody Pre-Clinical Study, Agenus shall provide to Licensee a copy of [**] generated in connection with such Licensed Antibody Pre-Clinical Study.
4.9Research Tool Pre-Clinical Studies. Except as required under [**], Agenus will have no obligation to disclose or provide any reports or updates in respect of any Research Tool Pre-Clinical Studies.
5.1Regulatory Data and Regulatory Materials. At Licensee’s election by written notice, Agenus will either (a) within [**] after the Effective Date, deliver to Licensee all Regulatory Materials and Regulatory Data for AGEN1777, or (b) continue to hold all such Regulatory Materials and Regulatory Data and complete the filing of the first IND for AGEN1777. In either scenario (a) or (b) in the preceding sentence, Agenus will make available to Licensee all
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Regulatory Materials and Regulatory Data [**] after the Effective Date. Subject to the foregoing and Section 5.2.2 (Initial IND for AGEN1777), Agenus will and hereby does assign to Licensee all of its rights, title, and interest in and to such Regulatory Materials and Regulatory Data. Licensee may only use the Regulatory Materials and Regulatory Data provided by Agenus to Exploit the Licensed Antibodies and Licensed Products in the Field in the Territory.
5.2Regulatory Filings, Regulatory Approvals and Pricing Approvals.
5.2.1General Responsibilities; Ownership of Regulatory Approvals and Pricing Approvals. Subject to Section 5.2.2 (Initial IND for AGEN1777), Licensee will be responsible for the preparation of all Regulatory Materials for obtaining and maintaining the Regulatory Approvals and Pricing Approvals for the Licensed Products in the Field in the Territory (including in connection with patient information leaflets, product inserts, and labeling and packaging for the Licensed Products in the Field in the Territory), and Licensee will submit such Regulatory Materials, as applicable, to the applicable Governmental Authorities in the Territory. To the extent allowed by Applicable Law, all Regulatory Approvals and Pricing Approvals for the Licensed Products in the Field in the Territory will be held and owned by Licensee (or its Affiliate or designee) in its name.
5.2.2Initial IND for AGEN1777.
(a)If Agenus has filed the first IND for AGEN1777 prior to the Effective Date, then Agenus shall promptly (and in any event, within [**] of Licensee’s request) transfer such IND to Licensee upon Licensee’s request.
(b)If Agenus has not filed the first IND for AGEN1777 prior to the Effective Date and Licensee provides notice to Agenus to continue to hold the applicable Regulatory Materials and Regulatory Data and file the first IND for AGEN1777 pursuant to Section 5.1 (Regulatory Data and Regulatory Materials), then Agenus shall [**]. Following Agenus’ receipt of the first IND for AGEN1777, at Licensee’s request, Agenus will promptly (and in any event, within [**] of Licensee’s request) transfer and assign the first IND for AGEN1777 to Licensee pursuant to Section 5.1 (Regulatory Data and Regulatory Materials).
(c)If Agenus has not filed the first IND for AGEN1777 prior to the Effective Date, and Licensee elects, upon written notice to Agenus, to file the first IND for AGEN1777, Licensee shall have the right to file the first IND for AGEN1777, and [**].
(d)[**]
5.2.3Agenus GDP Trials. In addition, the Parties shall perform their respective regulatory and other obligations as set out in Schedule 5.2.3 (Agenus Study Conduct Responsibilities) with regard to each Agenus GDP Trial.
5.2.4Cost of Regulatory Activities. All regulatory costs incurred by Licensee and its Affiliates in connection with the preparation of Regulatory Materials for, and obtaining of Product Approvals of, the Licensed Products in the Field in the Territory will be borne solely by Licensee. Except as otherwise provided in this Agreement, Licensee will be responsible for all
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
regulatory costs involved in the maintenance of all Regulatory Approvals for the Licensed Products in the Field in the Territory. [**].
5.2.5Regulatory Reporting. As part of the [**]updates provided in Section 4.7.1 (Records, Reports, and Information; General), Licensee will keep Agenus reasonably informed in connection with the preparation of all [**] Regulatory Materials, Regulatory Authority review of Regulatory Materials, Regulatory Approvals, and Pricing Approvals, in each case, with respect to the Licensed Products for sale in the Field in the [**].
5.3No Other Regulatory Filings. Except as otherwise expressly set forth in this Article 5 (Regulatory) or otherwise agreed by the Parties or any of their Affiliates, Licensee (and its Affiliates) will not file any Regulatory Materials, Regulatory Approvals, or Pricing Approvals for any other products that are claimed or covered by any Agenus Technology.
5.4Rights of Reference; Further Assurances.
5.4.1Rights Granted to Licensee. Subject to the rules of the relevant Regulatory Authority and the terms and conditions of this Agreement, Agenus hereby grants to Licensee and its Related Parties a right of reference (without any further action required on the part of Agenus or its Related Parties, whose authorization to file this right of reference with any Regulatory Authority is hereby granted) to any Regulatory Approval, IND and Pricing Approval Controlled by Agenus or any of its Affiliates during the Term relating to any Licensed Antibody (but not any other pharmaceutically active compounds, substances, or therapeutic agents), including the right to rely upon, access, inspect, copy, and otherwise use all information and data included in or used to support any such Regulatory Approval, IND or Pricing Approval (as applicable), solely for Licensee’s or its Related Parties’ use in the Development or Commercialization of the Licensed Products in the Field in the Territory during the Term in accordance with this Agreement.
5.4.2Rights Granted to Agenus. Upon transfer and assignment of the Regulatory Materials and Regulatory Data to Licensee in accordance with Section 5.1 (Regulatory Data and Regulatory Materials), Licensee will grant and hereby grants to Agenus and its designees a right of reference (without any further action required on the part of Licensee or its Related Parties, whose authorization to file this right of reference with any Regulatory Authority is hereby granted) to: (a) [**]; and (b) [**].
5.4.3Further Assurances. The Party granting rights to the other Party under Section 5.4.1 (Rights Granted to Licensee) and Section 5.4.2 (Rights Granted to Agenus) will take such actions as may be reasonably requested by the other Party to give effect to the intent of such Sections and to give the other Party the benefit of the granting Party’s Regulatory Approvals and Pricing Approvals as provided in this Section 5.4.3 (Further Assurances). Such actions may include providing a signed statement that the other Party may rely on, and that the Regulatory Authority may access, in support of the other Party’s application for Regulatory Approval and Pricing Approval in the Field or providing any underlying raw data or information submitted by such Party to the Regulatory Authority with respect to any Regulatory Materials, Regulatory Approvals, or Pricing Approvals Controlled by such Party or its Affiliates that relates to the Licensed Products.
28
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
6.1Commercialization in the Field in the Territory. Subject to the Co-Promote Option, Licensee will be solely responsible for Commercializing the Licensed Products in the Territory for use in the Field, which Commercialization will be in accordance with this Agreement, and will be responsible for [**] of the costs and expenses (including Pre-Marketing and other Commercialization costs and expenses) incurred in connection with the Commercialization of the Licensed Products in the Territory for use in the Field.
6.2.1Commercialization Diligence Obligations. Licensee will use [**] to Commercialize [**] Licensed Product for use in the Field in [**].
6.2.2Specific Commercialization Obligations. Without limiting the generality of Section 6.1 (Commercialization in the Field in the Territory) or Section 6.2.1 (Commercialization Diligence Obligations), in connection with the Commercialization of the Licensed Products in the Field in the Territory, Licensee will comply with all Applicable Law in all material respects.
6.3.1Grant of Option. Licensee hereby grants to Agenus the option to co-promote AGEN1777 Licensed Products in the U.S. (the “Co-Promote Option”). Licensee will keep Agenus reasonably informed of the planned Commercialization of [**] in the Field in the Territory, and, no later than [**] prior to the date that is reasonably expected for the first Regulatory Approval for the first Indication for an [**], provide Agenus with written notice thereof (the “Anticipated [**] Approval Notice”). Agenus may exercise the Co-Promote Option, by providing written notice to Licensee at any time until [**] following Agenus’ receipt of the Anticipated [**] Approval Notice (the “Co-Promote Opt-in Deadline”). If Agenus does not exercise the Co-Promote Option prior to the Co-Promote Opt-in Deadline, [**] the Co-Promote Option will expire, and Agenus shall have no further rights with respect to the Co-Promote Option. For clarity, the Co-Promote Option does not apply to any Licensed Products [**].
6.3.2Option Exercise. If Agenus exercises the Co-Promote Option for [**], Agenus and Licensee will promptly negotiate in good faith an agreement (the “Co-Promotion Agreement”), which will contain the terms set forth on Schedule 6.3.2 (Co-Promotion Agreement Terms) and other reasonable and customary terms for similar arrangements. Agenus shall not perform any promotional activities or otherwise Commercialize [**] until the Parties have executed such Co-Promotion Agreement.
7.1Manufacturing. Upon Agenus’ completion of the CMC activities included as part of the Agenus Ongoing Studies, Agenus will transfer to Licensee all Licensed Products
29
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Manufactured in connection with such activities, except as [**] for Agenus to complete the Agenus Ongoing Studies and future Licensed Antibody Pre-Clinical Studies as agreed between the Parties in writing and set forth on Schedule 2.5 (Materials Transfer). Except for the CMC activities that are included in the Agenus Ongoing Studies, following the completion of the Manufacturing Technology Transfer under Section 2.6.3 (Agenus Assistance), Licensee will be solely responsible for, and will bear all costs and expenses of, Manufacturing, and supplying all of its requirements of Licensed Product for its use in the Development and Commercialization of the Licensed Products in the Field within the Territory. Notwithstanding the foregoing or anything else herein, at the election of Licensee at its sole discretion, exercisable by written notice to Agenus within [**] of the Effective Date, and subject to any manufacturing capacity constraints that Agenus may have at the time of such request, the Parties shall conduct good faith discussions regarding the terms of a supply agreement (and a corresponding quality agreement with customary terms and conditions) pursuant to which Agenus would supply the Licensed Products to Licensee for its Clinical Trials. The price at which Licensee will purchase such Licensed Products under such supply agreement will be consistent with the price at which similar biopharmaceutical products are supplied under similar circumstances. In addition, such supply agreement (and the corresponding quality agreement) shall otherwise include mutually agreed terms as are customary for agreements of such type.
7.2Packaging and Labeling; Certain Other Manufacturing Activities. Notwithstanding anything to the contrary contained herein, Licensee or its designated Third Party will be responsible (at its sole cost and expense) for all final product labeling and packaging (whether in commercial or clinical packaging presentation), including insertion of materials such as patient inserts, patient medication guides, professional inserts and any other written, printed or graphic materials accompanying the Licensed Products for use in the Field in the Territory and considered to be part of such finished Licensed Product packaging and labeling, and handling, storage, quality control, quality assurance, and the testing and release aspects of Analytical Release Testing and Characterization and related activities, of the Licensed Products for use in the Field in the Territory in connection with the foregoing (collectively, “Packaging and Labeling”). Licensee or its designated Third Party will ensure that all such Packaging and Labeling complies with Applicable Law, GMPs, and the Regulatory Approvals for the Licensed Products in the Field in the Territory, including the Product Specifications, in all material respects. Licensee or its designated Third Party will also be responsible for performing the testing and release aspects of Analytical Release Testing and Characterization of the Licensed Products. To the extent that a Third Party is involved in Packaging and Labeling or other activities described in this Section 7.2 (Packaging and Labeling; Certain Other Manufacturing Activities), Licensee will be wholly responsible for, and bear one hundred percent (100%) of the costs related to, qualifying such Third Party to perform such activities.
8.1Upfront License Fee. [**] Licensee will make a payment to Agenus of two hundred million Dollars ($200,000,000) (“Upfront License Fee”). Licensee will pay the Upfront License Fee by wire or electronic transfer of immediately available funds into an account designated by Agenus and will be paid by a U.S. entity from a bank account domiciled in the U.S.
30
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
and made in Dollars. The Upfront License Fee will be nonrefundable and noncreditable against any other payments due hereunder.
8.2Development Milestone Payments. Subject to [**], Licensee will pay to Agenus the milestone payments described in this Section 8.2 (Development Milestone Payments) and set forth in Table 8.2 (Development Milestones) below following the first achievement by Licensee (or its Related Parties) of the corresponding milestone events for the first Licensed Product to achieve such milestone event in the Field in the Territory (each such Development milestone event, a “Development Milestone” and its corresponding milestone payment, a “Development Milestone Payment”). Licensee will promptly notify Agenus in writing of, but in no event later than [**] after, the achievement of each Development Milestone (each, a “Development Milestone Notification Notice”). Licensee will pay the applicable Development Milestone Payment set forth in Table 8.2 (Development Milestones) by electronic transfer of immediately available funds into an account designated by Agenus within [**] after the achievement (first occurrence) of the applicable Development Milestone; provided, however, that [**]. As used in this Section 8.2 (Development Milestone Payments), (a) [**], and (b) [**]. Except as provided under [**], each Development Milestone Payment is non-refundable and non-creditable against any other payments due hereunder. For clarity, [**].
8.3Sales Milestone Payments. Subject to [**], within [**] following the end of the Calendar Year in which each of the sales milestone events described in Table 8.3 below is first
31
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
achieved for [**], whether by Licensee or any Related Party, Licensee will pay, or cause to be paid, Agenus the corresponding payment set forth in Table 8.3, which, except as provided under Section 4.6.2(b) (Changes to Global Development Plan Budget) and [**], will be non-refundable and non-creditable (each such sales milestone event, a “Sales Milestone” and its corresponding milestone payment, a “Sales Milestone Payment”). Such Sales Milestone Payment will be paid by electronic transfer of immediately available funds into an account designated by Agenus.
|
Table 8.3 – Sales Milestones |
|
|
Sales Milestone [**] |
Sales Milestone Payment |
|
[**] |
[**] |
|
[**] |
[**] |
|
[**] |
[**] |
|
Maximum Sales Milestone Payments |
[**] |
For clarity, if two (2) or more Sales Milestones are first achieved in the same Calendar Year, then payment of the corresponding Sales Milestone Payments will be concurrently due for all such achieved Sales Milestones. By way of example, if Licensee achieves [**] in Net Sales in a Calendar Year but has not achieved [**] in any prior Calendar Year, then the Sales Milestone Payments of [**] and [**] will be due simultaneously.
8.4Additional Milestone Payment Terms.
8.4.1Milestone Payments for Licensed Products. All milestone payments described in Section 8.2 (Development Milestone Payments) and Section 8.3 (Sales Milestone Payments) will be paid [**].
8.4.2[**]
8.5.1Royalty Rates. As further consideration for the rights granted to Licensee under this Agreement, subject to [**], during each applicable Royalty Term, Licensee will pay to Agenus, [**], a tiered royalty on [**] worldwide Net Sales of the Licensed Products, on a [**] basis, based on the Royalty Rates as set forth in Table 8.5.1.
32
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
|
Table 8.5.1 – Royalties |
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Net Sales Thresholds [**] worldwide Net Sales for each Licensed Product: |
Royalty Rates for [**] |
Royalty Rates for [**] (the “[**] Royalty Rate”) |
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[**] |
||
For clarity, the foregoing [**] Royalty Rates will apply for any Licensed Products [**] regardless of whether Agenus has exercised the [**].
8.5.2Royalty Rates for [**]. If Agenus exercises its Co-Funding Option pursuant to Section 4.6.2(a) (Agenus Co-Funding Share) and has not terminated its obligation under [**] and [**], during each applicable Royalty Term, in lieu of the Royalty Rates on Net Sales of [**] set forth in Section 8.5.1 (Royalty Rates), subject to [**], Licensee will pay to Agenus, [**], a tiered royalty on [**] Net Sales of any [**], on an [**]-by-[**] basis, based on the Royalty Rate as set forth in Table 8.5.2:
For clarity, with respect to each Licensed Product and a country in the Territory, no Royalty Payments shall be due or payable on any future sales of such Licensed Product in such country held in inventory (determined in accordance with GAAP) as of the date of expiration of the Royalty Term for such Licensed Product in such country to the extent such future sales do not result in a Net Sale prior to the date of expiration of the Royalty Term in accordance with GAAP. [**]
33
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
8.10Royalty Payments and Reports. Licensee will calculate all Royalty Payments payable to Agenus pursuant to Section 8.5 (Royalty Payments) with respect to [**]of each Licensed Product at the end of each [**], which amounts will be converted to Dollars at such time in accordance with Section 8.13 (Currency Conversion). Licensee will provide to Agenus within [**] after the end of a given [**] a statement of the amount of Net Sales of each Licensed Product, (a) [**] and (b) [**], in each case, during such [**] (including such amounts expressed in local currency and as converted to Dollars), and will pay to Agenus the Royalty Payments due for Net Sales during such [**] within [**] after the end of such [**]. Without limiting the generality of the foregoing, Licensee will require its Related Parties to account for its Net Sales and to provide such reports with respect thereto as if such sales were made by Licensee.
8.11Third Party License Agreements.
8.11.1[**]
8.11.2[**]
8.11.5[**]
8.12.1VAT. The Parties agree to cooperate with one another and use reasonable efforts to ensure that value added tax or similar payment (“VAT”) in respect of any payments made by Licensee to Agenus under this Agreement does not represent an unnecessary cost in respect of payments made under this Agreement. For purposes of clarity, all sums payable under this Agreement will be exclusive of VAT. In the event that any VAT is owing in any jurisdiction in respect of any such payment, Licensee will pay such VAT, and such payment will be made after deduction of such VAT. In the event that any deducted VAT is later recovered by Licensee or an Affiliate, Licensee will reimburse Agenus within [**] of recovery for the deducted amount. In the event that any VAT is owed in any jurisdiction in respect of any such payment, Agenus will provide to Licensee tax invoices showing the correct amount of VAT in respect of such payments hereunder.
8.12.2Withholding Tax Matters. If Licensee is required to make a payment to Agenus subject to a deduction of tax or withholding tax, then the sum payable by Licensee (in respect of which such deduction or withholding is required to be made) will be made to Agenus [**] deduction of the amount required to be so deducted or withheld, which deducted or withheld amount will be paid to the applicable Governmental Authority in accordance with Applicable Law. [**].
34
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
8.12.3[**]
8.12.4Tax Cooperation. To the extent Licensee is required to deduct and withhold taxes on any payments to Agenus, Licensee will pay the amounts of such taxes to the proper Governmental Authority in a timely manner and promptly transmit to Agenus an official tax certificate or other evidence of such withholding sufficient to enable Agenus to claim such payments of taxes. Licensee agrees to cooperate with Agenus in claiming refunds or exemptions from, or reductions in, such deductions or withholdings under any Applicable Law or treaty to ensure that any amounts required to be withheld pursuant to this Section 8.12 (Taxes and Withholding) are reduced to the fullest extent permitted by Applicable Law or treaty. In addition, the Parties shall cooperate to minimize indirect taxes (such as value added tax, sales tax, consumption tax and other similar taxes) in connection with this Agreement, as applicable.
8.13Currency Conversion. All payments hereunder will be made in Dollars. For the purpose of calculating any sums due under, or otherwise reimbursable pursuant to, this Agreement (including the calculation of Net Sales expressed in currencies other than Dollars), any amount expressed in a foreign currency will be converted into Dollars in a manner consistent with such Party’s normal practices used to prepare its audited financial statements for external reporting purposes, in accordance with GAAP, consistently applied, or by using a reputable source such as the Wall Street Journal or Reuters, at the paying Party’s discretion.
8.14General Payment Procedures. Unless otherwise expressly payable in certain time frames as provided in this Agreement, the receiving Party will invoice the paying Party for all amounts due to such receiving Party under this Agreement, and such payments will be made [**] following the receipt by the paying Party of an invoice from the receiving Party specifying the amount due. All milestone payments under this Agreement will be paid by a U.S. entity from a bank account domiciled in the U.S. and made in Dollars.
8.15Late Payments. Any amount required to be paid by a Party hereunder that is not paid on the date due will accrue interest at an annual rate of [**] above the prime rate as published by Citibank, N.A., New York, New York, or any successor thereto, at 12:01 a.m. on the first day of each [**] in which such payments are overdue, (or the maximum legal interest rate allowed by Applicable Law, if less) from and after such date calculated on the number of days such payment is late and the late Party will be responsible for reasonable legal fees and expenses incurred by the other Party in connection with the collection thereof.
8.16Records; Audits. Each Party and its Related Parties will keep full, true, and accurate records and books of account containing all particulars that may be necessary for the purpose of confirming the accuracy of, and calculating, as applicable: (a) in the case of Agenus as the Auditing Party, [**]; and (b) in the case of Licensee as the Auditing Party, [**], in each case ((a) and (b)), and any other records reasonably required to be maintained with respect to the Audited Party’s obligations under this Agreement, during the Term and for [**] thereafter or such longer period as required by Applicable Law. Each Party will have a right to request an audit of the other Party in order to confirm the accuracy of the foregoing as provided in this Section 8.16 (Records; Audits) (an “Audit”); provided, however, that each Party will only have the right to request such Audit [**] during any given Calendar Year and [**], and may only Audit the records
35
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
or books during the [**] period immediately prior to the date of such Audit. Upon the written request by a Party to Audit the other Party, the Auditing Party will engage an independent, internationally recognized accounting firm reasonably acceptable to the Audited Party to perform a review as is reasonably necessary to enable such accounting firm to calculate or otherwise confirm the accuracy of: (i) in the case of Agenus as the Auditing Party, [**]; and (ii) in the case of Licensee as the Auditing Party, [**], in each case ((i) and (ii)), for the Calendar Year(s) requested by the Auditing Party; provided that (1) such accounting firm will be given access to, and will be permitted to examine and copy such books and records of the Audited Party upon [**] prior written notice to the Audited Party, and at all reasonable times on Business Days, (2) prior to any such examination taking place, such accounting firm will enter into a confidentiality agreement with the Audited Party reasonably acceptable to the Audited Party in order to keep all information and data contained in such books and records strictly confidential and only use the same for the purpose of the reviews, preparation of any audit reports or findings, or calculations that they need to perform in order to determine any amounts being reviewed, and (3) such accounting firm will use reasonable efforts to minimize any disruption to the Audited Party’s business. The Audited Party will make personnel reasonably available during regular business hours to answer queries on all such books and records to the extent required for the purpose of the Audit. The accounting firm will deliver a copy of their findings to each of the Parties within [**] of the completion of the review, and, unless the Audited Party invokes the dispute resolution mechanism set forth in Section 15.1 (Disputes) within [**] of the Audited Party’s receipt of such finding, the findings of such accounting firm will be final and binding on each of the Parties. Any undisputed underpayments by the Audited Party will be paid to the Auditing Party within [**] of notification of the results of such Audit. Any undisputed overpayments made by the Audited Party will be refunded by the Auditing Party within [**] of notification of the results of such Audit. The cost of the accounting firm will be the responsibility of the Auditing Party unless the accounting firm’s calculation shows that the actual Royalty Payments payable, Net Sales, Agenus Co-Funding Share, Agenus GDP Trial Costs or any other applicable amount audited hereunder (as applicable) to be different, by more than [**], than the amounts as paid or reported by Audited Party for the period subject to the Audit, in which case, the Audited Party will reimburse the Auditing Party for the cost of the Audit.
ARTICLE 9
INTELLECTUAL PROPERTY MATTERS
9.1.1Background Technology. As between the Parties, and except with respect to any Arising Technology, which is addressed in Section 9.1.2 (Arising Technology): (a) Agenus will retain all rights, title, and interest in and to any Patent, Know-How, and other intellectual property right owned or controlled by Agenus or any of its Related Parties as of the Effective Date or generated or obtained by or on behalf of Agenus or any of its Related Parties during the Term outside of the scope of performance of activities under this Agreement, and (b) Licensee will retain all rights, title, and interest in and to any Patent, Know-How, and other intellectual property right owned or controlled by Licensee or any of its Related Parties as of the Effective Date or generated or obtained by or on behalf of Licensee or any of its Related Parties during the Term outside of the scope of performance of activities under this Agreement.
36
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
(a)“Arising Know-How” means any and all Know-How (including, for clarity, all Inventions and data) developed, created, conceived, or reduced to practice during the Term solely by or on behalf of a Party or any of its Affiliates or jointly by or on behalf of Agenus or any of its Related Parties and Licensee or any of its Related Parties in the performance of activities under this Agreement. “Arising Patent” means any Patent claiming any such Arising Know-How. “Arising Technology” means the Arising Know-How and Arising Patents, with inventorship being determined in accordance with United States patent laws (regardless of where the applicable activities occurred). Arising Know-How invented solely by or on behalf of Agenus or any of its Affiliates, excluding any [**] (collectively, the “Agenus Arising Know-How”), and all Arising Patents claiming any such Agenus Arising Know-How (the “Agenus Arising Patents”) will be solely owned by Agenus or any of its Affiliates (the Agenus Arising Know-How and Agenus Arising Patents collectively, “Agenus Arising Technology”). Arising Know-How invented solely by or on behalf of Licensee or any of its Affiliates and [**] (collectively, the “Licensee Arising Know-How”), and all Arising Patents claiming any Licensee Arising Know-How (the “Licensee Arising Patents”) will be solely owned by Licensee or any of its Related Parties (the Licensee Arising Know-How and Licensee Arising Patents collectively, the “Licensee Arising Technology”). Arising Technology invented jointly by or on behalf of Agenus or any of its Related Parties and Licensee or any of its Related Parties (“Joint Arising Know-How”), and all Arising Patents claiming any such Joint Arising Know-How (the “Joint Arising Patents”) will be jointly owned by both Parties (Joint Arising Know-How and the Joint Arising Patents are together, the “Joint Arising Technology”).
(b)Agenus will disclose to Licensee any Agenus Arising Technology that is Agenus Technology promptly upon Licensee’s request (but not more than once per [**]) to the extent it has not been previously disclosed to Licensee under this Section 9.1.2(b). Licensee will disclose to Agenus any Licensee Arising Technology that is Licensee Technology, to the extent it has not been previously disclosed to Agenus and to the extent it is necessary for Licensee to conduct any Agenus GDP Trial. Each Party will require its Affiliates, and all of its or its Affiliates’ employees, subcontractors, consultants or agents involved in the Exploitation of Licensed Antibodies or Licensed Products to assign all of its or their right, title and interest in or to any Arising Technology to it or such Affiliates; provided that the foregoing obligation does not extend to [**]; provided further that, each Party shall ensure that [**]. Each Party will, and will cause its Affiliates and all of its or its Affiliates’ employees, licensees, sublicensees, independent contractors and agents involved in the Exploitation of the Licensed Antibodies or Licensed Products to cooperate and take all additional actions and to execute such agreements, instruments and documents as may be reasonably required to perfect the other Party’s right, title and interest in and to Arising Technology.
(c)Each Party will have an undivided one-half (1/2) interest in and to the Joint Arising Technology. Each Party will exercise its ownership rights in and to such Joint Arising Technology, including the right to license and sublicense or otherwise to exploit, transfer, or encumber its ownership interest, without [**], but subject to [**]. At the reasonable written request of a Party, the other Party will in writing grant such consents and confirm that no such [**] is required to effect the foregoing regarding Joint Arising Technology. Each Party, for itself and
37
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
on behalf of any of its Related Parties, and employees, subcontractors, consultants, and agents of any of the foregoing, hereby assigns (and to the extent such assignment can only be made in the future hereby agrees to assign), to the other Party a joint and undivided interest in and to all Joint Arising Technology, to the extent required to give effect to the other Party’s joint ownership rights in such Joint Arising Technology in accordance with the first sentence of this Section 9.1.2(c). [**].
9.2Prosecution and Maintenance.
9.2.1Product-Specific Licensed Patents.
(a)[**] First Right. [**] will have the first right, responsibility, and discretion to Prosecute all Product-Specific Licensed Patents at its sole cost and expense.
(b)Abandonment. [**] may in its sole discretion elect to discontinue Prosecution of a Product-Specific Licensed Patent in any country, on a Patent-by-Patent basis. [**] will give [**] prompt notice at least [**] prior to the deadline for the next filing, office action, or payment with the relevant patent office, if [**] elects to discontinue Prosecution of any Product-Specific Licensed Patent or any other action with respect to any Product-Specific Licensed Patent, or declines to pay costs for the Prosecution of a Product-Specific Licensed Patent in any country. [**] will have the option, but not the obligation, to assume control of such Prosecution at its own expense. In the event [**] assumes control of the Prosecution of any Product-Specific Licensed Patent, then [**] will (i) provide [**] with copies of any relevant communications, filings, drafts, and documents, as well as written notice of any pending deadlines or communications applicable thereto, (ii) execute and deliver any legal papers reasonably requested by [**] to effectuate transfer of control of the Prosecution of such Product-Specific Licensed Patents, and (iii) notwithstanding Section 9.2.1(c) (Cooperation), [**] will (A) regularly and promptly provide [**] with copies of all Product-Specific Licensed Patents and other material submissions and correspondence with Governmental Authorities concerning such Product-Specific Licensed Patents in sufficient time to allow for review and comment by [**]; and (B) provide [**] and its patent counsel with an opportunity to consult with [**] and its patent counsel regarding the filing and contents of any such application, amendment, submission, or response, and the advice and suggestions of [**] and its patent counsel will be considered by [**] in good faith, and [**] shall have the final decision making authority with respect to the filing and contents of any such application, amendment, submission or response.
(c)Cooperation. [**] will determine the overall strategy for the Prosecution of the Product-Specific Licensed Patents, provided that [**] shall consult with [**] regarding such overall strategy and consider [**] comments with respect thereto in good faith. [**] will keep [**] informed of the status of all material actions taken with respect to the Prosecution of the Product-Specific Licensed Patents, and in particular, will (i) regularly and promptly provide [**] with copies of all Product-Specific Licensed Patents and other material submissions and correspondence with Governmental Authorities concerning such Product-Specific Licensed Patents in sufficient time to allow for review and comment by [**]; and (ii) provide [**] and its patent counsel with an opportunity to consult with [**] and its patent counsel regarding the filing and contents of any such application, amendment, submission, or response, and the advice and
38
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
suggestions of [**] and its patent counsel will be considered by [**] in good faith, and [**] shall have the final decision making authority with respect to the filing and contents of such application, amendment, submission or response.
9.2.2Agenus FC Platform Patents. [**] will have the sole right and discretion to Prosecute all Agenus FC Platform Patents at its sole cost and expense. [**] will keep [**] informed of the status of all material actions taken with respect to the Agenus FC Platform Patents, and in particular, will (a) regularly and promptly provide [**] with copies of all Agenus FC Platform Patents and other material submissions and correspondence with Governmental Authorities concerning such Agenus FC Platform Patents in sufficient time to allow for review and comment by [**], and (b) provide [**] and its patent counsel with an opportunity to consult with [**] and its patent counsel regarding the filing and contents of any such application, amendment, submission, or response, and the advice and suggestions of [**] and its patent counsel will be considered by [**] in good faith, and [**] shall have the final decision making authority with respect to the filing and contents of such application, amendment, submission or response.
9.3Notice. Each Party will promptly provide written notice to the other Party reasonably detailing any known or alleged infringement of any Agenus Patent or if it receives notice of a Patent Challenge with respect to any Agenus Patent.
9.4Enforcement of Intellectual Property Rights.
(a)[**] or any of its Related Parties will have the first right to: (i) institute and direct legal proceedings against any Third Party believed to be infringing, misappropriating, or otherwise violating any Product-Specific Licensed Patent or Product-Specific Know-How; and (ii) defend the Product-Specific Licensed Patents from any claim of, invalidity or unenforceability in connection therewith.
(b)If [**] or any of its Related Parties does not undertake efforts to abate such violation of intellectual property rights or respond to such claim of invalidity or unenforceability, including commencement of a lawsuit against the accused person if necessary, within [**] after receiving notice of such infringement of such Product-Specific Licensed Patent or misappropriation or violation of such Product-Specific Know-How, then, upon [**] prior written consent with respect to any Product-Specific Licensed Patent, not to be unreasonably conditioned, withheld or delayed, [**] will be entitled (but will not be obligated) to take all actions reasonably necessary to abate such violation or respond to such claim, including commencement of a lawsuit against the accused person if necessary. [**] will keep [**] informed of the status of all material actions taken with respect to such proceedings, including providing [**] copies of material correspondence, submissions and other documents with respect to such proceedings, and shall consider in good faith the comments of [**] and its patent counsel with respect to such actions, and [**] shall have the final decision making authority with respect to the conduct of such proceedings.
39
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
9.4.2[**] Sole Right. Except as otherwise provided in this Section 9.4.2 ([**] Sole Right), [**] will have the sole right and discretion to institute and direct legal proceedings against any Third Party believed to be infringing, misappropriating, or otherwise violating any Agenus FC Platform Patent or Agenus Know-How that is not Product-Specific Know-How, and to defend the Agenus FC Platform Patents from any claim of, invalidity or unenforceability in connection therewith. [**] will keep [**] informed of the status of all material actions taken with respect to such proceedings, including providing [**] copies of material correspondence, submissions and other documents with respect to such proceedings, and shall consider in good faith the comments of [**] and its patent counsel with respect to such actions, and [**] shall have the final decision making authority with respect to the conduct of such proceedings. In addition, and notwithstanding the foregoing or anything else herein, in the event that a Third Party is believed to be infringing any Agenus FC Platform Patent in a country in the Territory, and [**], then [**] may notify [**] in writing, and [**]. [**] will consider [**] concerns with respect to such potential Third Party infringement in good faith, and [**] will consider [**] concerns with enforcing such Agenus FC Platform Patent against such Third Party in good faith. If the Agenus FC Platform Patents are [**], then [**].
9.4.3Proceeds. All amounts recovered from enforcement of any such rights by an enforcing Party relating to such intellectual property licensed under this Agreement will be first used to reimburse each Party’s reasonable out-of-pocket costs and expenses incurred in connection with such action, and any remainder of such recovery will be [**]. The Parties will keep each other informed of the status of, and of their respective activities regarding, any enforcement action pursuant to this Section 9.4 (Enforcement of Intellectual Property Rights).
9.5Cooperation in Enforcement Proceedings. For any action by a Party pursuant to Section 9.4 (Enforcement of Intellectual Property Rights), in the event that such Party is unable to initiate or prosecute such action solely in its own name, the other Party or its Affiliates, as applicable, will join such action voluntarily and will execute all documents necessary for such Party to initiate, prosecute, and maintain such action; provided that such Party shall reimburse the other Party or its Affiliates all reasonable costs and expenses, including any adverse awards of costs against the other Party, incurred as a result of the joining of such action. If either Party initiates an enforcement action pursuant to Section 9.4 (Enforcement of Intellectual Property Rights), then, at such Party’s request, the other Party will cooperate to the extent reasonably necessary and at the first Party’s sole expense for reasonable, out-of-pocket costs (except for the expenses of the non-controlling Party’s counsel, if any). Upon the reasonable request of the Party instituting any such action, such other Party will join the suit and may be represented in any such legal proceedings using counsel of its own choice at its own expense. Each Party will, if possible, assert and not waive the joint defense privilege with respect to all communications between the Parties reasonably the subject thereof with respect to any such action.
9.6.1Notice of Allegations. Each Party will notify the other Party in writing of any allegations it receives from a Third Party alleging that the Manufacture, production, use, Development, Commercialization, sale, or distribution of a Licensed Product or any technology or intellectual property licensed under this Agreement infringes, misappropriates, or otherwise
40
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
violates the intellectual property rights of such Third Party. The applicable Party will provide such notice to the other Party promptly, but in no event after more than [**] following receipt of such allegations.
9.6.2Litigation. In the event that a Party receives notice that it or any of its Affiliates or Sublicensees have been individually named as a defendant in a legal proceeding by a Third Party alleging infringement, misappropriation, or other violation of a Third Party’s Patents or other intellectual property right as a result of the Manufacture, production, use, Development, Commercialization, sale, or distribution of a Licensed Product or any technology or intellectual property licensed under this Agreement, such Party will immediately notify the other Party in writing within [**] after the receipt of such notice. Such written notice will include a copy of any summons or complaint (or the equivalent thereof) received regarding the foregoing. Each Party will, if possible, assert and not waive the joint defense privilege with respect to all communications between the Parties with respect to such legal proceeding. In such event, the Parties will use reasonable efforts to agree how best to mitigate or control the defense of any such legal proceeding; provided, however, [**] or any of its Related Parties will have the right, but not the obligation, to assume the primary responsibility for the conduct of the defense of any such claim at its expense. [**] will have the right, but not the obligation, to participate and be separately represented in any such suit at its sole option and at its own expense. [**] will reasonably cooperate with [**] or any of its Related Parties. If a Party or any of its Affiliates have been individually named as a defendant in a legal proceeding relating to the alleged infringement, misappropriation, or other violation of a Third Party’s Patents or other intellectual property right as a result of the Manufacture, production, use, Development, sale, or distribution of a Licensed Product, the other Party will be allowed to join in such action, at its own expense.
9.6.3Information Exchange. The Parties will keep each other informed of the status of and of their respective activities regarding any infringement litigation initiated by a Third Party concerning the Manufacture, production, use, Development, Commercialization, sale, or distribution of a Licensed Product or settlement thereof.
9.6.4Actions for Infringement; Injunction. Notwithstanding anything to the contrary in Section 9.4 (Enforcement of Intellectual Property Rights), [**] will have the right to bring an action for infringement of the Agenus Patents (other than the Agenus FC Platform Patents, except [**]) under Section 351(l)(6) of the PHSA following the agreement on a list of Patents for litigation under Section 351(l)(4) or exchange of patent lists pursuant to Section 351(l)(5)(B) of such act, or as required following any equivalent or similar certification or notice in any other country. The Parties’ rights and obligations with respect to the foregoing legal actions, as well as any patent litigation that will proceed outside of Section 351(l)(6) of the PHSA, will be as set forth in Section 9.4 (Enforcement of Intellectual Property Rights) through Section 9.6 (Defense); provided that within [**] of reaching agreement on a list of Patents for litigation under Section 351(l)(4) or exchange of patent lists pursuant to Section 351(l)(5)(B), [**] will notify [**] as to whether or not it elects to prosecute such infringement. Without limiting the foregoing, each Party will, within [**], notify the other Party in writing if it becomes aware of the submission by a Third Party to a Regulatory Authority of a Biosimilar Application, including if such Party receives a copy of the Biosimilar Application or notice of commercial marketing provided by such Third Party applicant for such Biosimilar Application pursuant to Section 351(l)(8)(A) of the PHSA, or
41
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
any equivalent or similar certification or notice in any other country. Each Party that is permitted under Applicable Law to obtain a copy of the Biosimilar Application and related confidential information (including in accordance with Section 351(l)(1)(B)(iii) of the PHSA) shall seek and obtain such information and to the extent permissible under Applicable Law provide copies of such Biosimilar Application and related confidential information to the other Party at [**] cost. As permitted by Applicable Law, [**] shall provide information regarding any Product-Specific Licensed Patent or any other patent that should be listed pursuant to Section 351(l)(1)(3)(A) or Section 351(l)(7) of the PHSA. Upon [**] request, and at [**] cost, [**] shall assist in seeking an injunction against any commercial marketing by the filer of a Biosimilar Application as permitted pursuant to Section 351(l)(8)(B) of the PHSA or in filing an action for infringement or declaratory judgment under Section 351(l)(9) of the PHSA against the filer of such Biosimilar Application. The Parties recognize that procedures other than those set forth above may apply with respect to applications for Biosimilar Products. In the event that the Parties determine that certain provisions of Applicable Law in any relevant country apply to actions taken by the Parties with respect to applications for Biosimilar Products in such country, the Parties shall, at [**] cost, comply with any such Applicable Law in such country (and any relevant and reasonable procedures established by the Parties) in exercising their rights and obligations with respect to applications for Biosimilar Products under this Section 9.6.4 (Actions for Infringement; Injunction), and shall notify each other of any actions taken to comply with any such Applicable Law in such country. The Party that does not control the actions contemplated by this Section 9.6.4 (Actions for Infringement; Injunction) shall cooperate with the controlling Party in implementing any decisions that the controlling Party elects to take pursuant to this Section 9.6.4 (Actions for Infringement; Injunction). In addition, and notwithstanding the foregoing or anything else herein, in the event that following agreement on a list of Patents for litigation under Section 351(l)(4) the PHSA or exchange of patent lists pursuant to Section 351(1)(5)(B) of such act, [**], then [**] may notify [**] in writing, and the Parties will discuss whether and how [**] will [**], [**] will consider [**] concerns with respect to such infringement action in good faith. If [**], then [**].
(a)Licensed Product Trademarks. [**] shall be solely responsible for the selection (including the creation, searching and clearing), registration, maintenance, policing and enforcement of all trademarks, trade dress, advertising taglines or slogans developed for use in connection with the marketing, sale or distribution of Licensed Antibodies and Licensed Products in the Field in the Territory (the “Product Marks”). As between the Parties, [**] shall own all Product Marks, and all trademark registrations for said marks and all goodwill with respect thereto.
(b)Use of Name. Neither Party shall, without the other Party’s prior written consent, use any trademarks or other marks of the other Party (including the other Party’s corporate name), trademarks, advertising taglines or slogans confusingly similar thereto, in connection with such Party’s marketing or promotion of Licensed Antibodies or Licensed Products under this Agreement or for any other purpose, except as may be expressly authorized in writing in connection with activities under this Agreement and except to the extent required to comply with Applicable Law; provided that [**] shall be permitted to use [**] name, trademark, and logo in [**] corporate presentation materials and on its website, solely for the purpose of [**] and
42
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
provided that such use is in accordance with [**] trademark use guidelines as provided by [**] to [**] in writing from time to time.
(c)Further Actions. Each Party shall, at [**] cost, upon the reasonable request of the other Party, provide such assistance and execute such documents as are reasonably necessary for such Party to exercise its rights or perform its obligations pursuant to this Section 9.6.5 (Trademarks); provided, however, that neither Party shall be required to take any action pursuant to this Section 9.6.5 (Trademarks) that such Party reasonably determines in its sole judgment and discretion conflicts with or violates any applicable court or government order or decree or Applicable Law.
9.7Patent Challenge. Agenus will be permitted to terminate this Agreement upon [**] written notice to Licensee, if Licensee or any of its Related Parties, directly or indirectly, initiates, files, maintains, or otherwise makes any Patent Challenge with respect to any Agenus Patent, unless (a) [**], (b) [**], or (c) [**].
ARTICLE 10
REPRESENTATIONS, WARRANTIES AND COVENANTS; COMPLIANCE
10.1Mutual Representations and Warranties. Each Party hereby represents and warrants to the other Party as follows, as of the Execution Date and the Effective Date:
10.1.1Corporate Existence and Power. It is a company or corporation duly organized, validly existing, and in good standing under the laws of the jurisdiction in which it is incorporated, and has full corporate power and authority and the legal right to own and operate its property and assets and to carry on its business as it is now being conducted and as contemplated in this Agreement, including the right to grant the licenses granted by it hereunder.
10.1.2Authority and Binding Agreement. (a) It has the corporate power and authority and the legal right to enter into this Agreement and perform its obligations hereunder, (b) it has taken all necessary corporate action on its part required to authorize the execution and delivery of this Agreement and the performance of its obligations hereunder, and (c) this Agreement has been duly executed and delivered on behalf of such Party, and constitutes a legal, valid, and binding obligation of such Party that is enforceable against it in accordance with its terms, except as enforcement may be affected by bankruptcy, insolvency, or other similar laws and by general principles of equity.
10.1.3No Conflicts. The execution, delivery, and performance of this Agreement by it does not (a) conflict with any agreement, instrument, or understanding, oral or written, to which it is a party and by which it may be bound or (b) violate any Applicable Law.
10.1.4All Consents and Approvals Obtained. Except with respect to Regulatory Approvals and Pricing Approvals for the Development, Manufacturing or Commercialization of the Licensed Products or as otherwise described in this Agreement, (a) all necessary consents, approvals and authorizations of, and (b) all notices to, and filings by such Party with, in either case ((a) or (b)), all Governmental Authorities and other Persons required to be obtained or provided
43
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
by such Party as of the Execution Date or the Effective Date, as applicable, in connection with the execution, delivery, and performance of this Agreement have been obtained and provided, except for those approvals, if any, not required as of the Execution Date or the Effective Date, as applicable.
10.1.5No Litigation. There is no action or proceeding pending or, to the knowledge of such Party, threatened, that could reasonably be expected to impair or delay the ability of such Party to perform its obligations under this Agreement.
10.1.6Debarment. Neither such Party, nor any Affiliate of such Party, has been debarred by any Regulatory Authority, including under Section 306 of the FD&C Act (or similar Applicable Law outside of the U.S.), is under investigation for debarment action by any Regulatory Authority, has been disqualified as an investigator pursuant to Section 306 of the FD&C Act (or similar Applicable Law outside of the U.S.), has a disqualification hearing pending, or is currently employing or using any Person that has been so debarred or disqualified by any Regulatory Authority to perform any of such Party’s obligations under this Agreement.
10.2Additional Representations, Warranties and Covenants of Agenus. Agenus hereby represents and warrants to Licensee as of the Execution Date except as set forth in the Execution Date Disclosure Schedules and as of the Effective Date except as set forth in the Effective Date Disclosure Schedules and covenants to Licensee during the Term the following additional representations, warranties and covenants as set forth below. No disclosure made by Agenus in the Effective Date Disclosure Schedules shall be deemed to amend or supplement the Execution Date Disclosure Schedules for any purpose under hereunder, including for purposes of this Section 10.2 (Additional Representations, Warranties and Covenants of Agenus) or the indemnification provisions in Section 11.1 (Indemnification by Agenus). For the avoidance of doubt, a disclosure made by Agenus in the Effective Date Disclosure Schedules may not cure a deficiency in the Execution Date Disclosure Schedules. Agenus acknowledges and agrees that any disclosure made in the Effective Date Disclosure Schedules cannot cure a breach of any covenant or obligation of Agenus hereunder this Agreement, and no such disclosure that relates to or reflects any such breach by Agenus shall be deemed to qualify under any representation or warranty hereunder.
10.2.1Title to Agenus Patents and Agenus Know-How. Agenus is the [**] owner of, or has all licenses and rights necessary to, the Agenus Patents and Agenus Know-How to [**], free and clear of any [**] that do not adversely affect or diminish Agenus’ ability to [**]. Neither Agenus nor any of its Affiliates has [**] with respect to, or otherwise [**] in or to (a) any [**], in each case, [**] or (b) any [**] that would be an [**], as applicable, but for [**]. Without limiting the foregoing, Agenus and its Affiliates have obtained from [**] [**] assignments that vest in Agenus or its applicable Affiliate [**], either [**]. Neither Agenus nor any of its Affiliates has received written notice of [**].
10.2.2Scheduled Agenus Patents. Schedule 1.13 (Agenus Patents) sets forth a [**] list of all Agenus Patents, as they exist as of the Execution Date. [**].
10.2.3[**].
44
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
10.2.4[**]
10.2.5[**]
10.2.6Proceedings. Neither Agenus nor any of its Affiliates, nor, to the knowledge of Agenus, its subcontractors, has received written notice of any proceedings pending before or threatened by any Regulatory Authority with respect to [**].
10.2.7[**]
10.2.8[**]
10.2.9[**]
10.2.10No Conflicting Grants. Neither Agenus nor any of its Affiliates has granted, and Agenus will not grant and will cause its Affiliates not to grant, any Affiliate (with respect to Agenus) or Third Party [**] rights [**] that would [**]. Agenus and its Affiliates are not a party to any [**] agreements or arrangements with Third Parties (a) relating to [**] that would (i) [**], or (ii) [**] or (b) [**], any [**], with respect to any [**], is [**] to [**] any [**] in [**].
10.2.11Related Agreements. Schedule 10.2.11 (Related Agreements) sets forth a [**] list of all Third Party License Agreements and any other [**], entered into by Agenus or any of its Affiliates that relate to [**] of any [**], excluding [**]. Agenus has provided Licensee [**] copies of all such agreements; provided that such copies may have been redacted with respect to financial and other sensitive terms that are not applicable to Agenus’ obligations or Licensee’s rights hereunder.
10.2.12Third Party License Agreements. (a) The licenses granted to Agenus or its Affiliates in the Third Party License Agreements are [**] and, by their terms, are [**], (b) Agenus or its Affiliate, if applicable, [**] under any of the Third Party License Agreements that would [**], nor, [**], is any counterparty thereto [**], (c) neither Agenus nor any of its Affiliates has received [**], (d) [**], no facts or circumstances exist that would reasonably be expected to give rise to [**] and (e) the [**] of [**] does not [**].
10.2.13[**]
10.2.14[**]
10.2.15Disclosure of [**]. Agenus has made available to Licensee for review [**] included in [**] for Licensee to assess [**] or [**], and all such [**] is [**].
10.2.16[**]
10.2.17[**]
10.2.18[**]
45
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
10.2.19[**]
10.2.20[**]
10.2.21Execution Date Covenant. During the period from the Execution Date until the Effective Date, neither Agenus nor [**], shall commit any act or permit the occurrence of any omission that, if such act had been committed or such omission had occurred prior to the Execution Date, would have caused [**] as of the Execution Date.
10.3Additional Representations, Warranties and Covenants of Licensee. Licensee hereby represents and warrants to Agenus as of the Effective Date and covenants to Agenus during the Term that:
10.3.1Compliance. In the performance of this Agreement, or the exercise of any rights obtained hereunder, Licensee will comply with and will cause its Related Parties to materially comply with, all Applicable Laws now or hereafter in effect.
10.4.1Compliance with Anti-Corruption Laws. In connection with this Agreement, each Party has complied and will comply with all Applicable Law and industry codes dealing with government procurement, conflicts of interest, corruption or bribery, including, if applicable, the U.S. Foreign Corrupt Practices Act of 1977, as amended, the UK Bribery Act 2010 and any laws enacted to implement the Organization of Economic Cooperation and Development Convention on Combating Bribery of Foreign Officials in International Business Transactions.
10.4.2Prohibited Conduct. In connection with this Agreement, neither Party has made, offered, given, promised to give, or authorized, and during the Term neither Party will make, offer, give, promise to give, or authorize, any bribe, kickback, donation [**], payment or transfer of anything of value, directly or indirectly, to any person (including healthcare professionals, hospitals, hospital services or departments or healthcare organizations) or to any Government Official for the purpose of: (a) improperly influencing any act or decision of the person or Government Official; (b) inducing the person or Government Official to do or omit to do an act in violation of a lawful or otherwise required duty; (c) corruptly obtaining or retaining business; (d) securing any improper advantage; (e) inducing the person or Government Official to improperly influence the act or decision of any organization, including any government or government instrumentality to assist Licensee or Agenus in obtaining or retaining business; or (f) engaging in any act that might cause a reasonable person to infer that Licensee or Agenus is making improper payments to any person or Government Official.
10.4.3Notifications and Requests for Information. Each Party will notify the other Party of any violations of this Section 10.4 (Covenants by the Parties) by any of the Party’s employees, subcontractors, consultants, and agents as soon as reasonably practicable (in any event, within [**]) after discovering and reasonably confirming any incident or violation being reported to or identified by the applicable Party. Each Party will to comply with requests for disclosure of information, including answering questionnaires and narrowly tailored audit inquiries, to enable
46
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
the other Party to ensure compliance with all Applicable Law, including anti-corruption laws, related to the subject matter of this Agreement.
10.4.4Cooperation in Investigation. Each Party agrees to cooperate in good faith to investigate the extent of any potential violations of Applicable Law in connection with this Agreement.
10.4.5Nondisparagement. Each Party shall not, and shall not permit its employees, officers, or directors to, intentionally disparage, defame or discredit the other Party to Third Parties.
10.5No Other Representations or Warranties. EXCEPT AS EXPRESSLY STATED IN THIS AGREEMENT, NO REPRESENTATIONS OR WARRANTIES WHATSOEVER, WHETHER EXPRESS OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT, OR NON-MISAPPROPRIATION OF THIRD PARTY INTELLECTUAL PROPERTY RIGHTS, ARE MADE OR GIVEN BY OR ON BEHALF OF A PARTY. EXCEPT AS EXPRESSLY STATED IN THIS AGREEMENT, ALL IMPLIED REPRESENTATIONS AND WARRANTIES, WHETHER ARISING BY OPERATION OF LAW OR OTHERWISE, ARE HEREBY EXPRESSLY EXCLUDED.
11.1Indemnification by Agenus. Agenus shall indemnify, defend, and hold Licensee, its Affiliates, and its and their respective directors, officers, agents, and employees (collectively, the “Licensee Indemnitees”) harmless from and against any and all losses, damages, liabilities, costs and expenses (including reasonable attorneys’ fees and expenses) (collectively, “Losses”) arising in connection with any and all charges, complaints, actions, suits, proceedings, hearings, investigations, claims, demands, judgments, orders, decrees, stipulations, or injunctions by a Third Party (each a “Claim”) to the extent resulting or otherwise arising from (a) [**], (b) [**], (c) [**]; or (d) [**] (i) [**] or (ii) [**] (A) in each case ((a) through (d)), [**] or (B) [**].
11.2Indemnification by Licensee. Licensee shall indemnify, defend and hold Agenus, its Affiliates, its and their respective directors, agents and employees (collectively, the “Agenus Indemnitees”) harmless from and against any and all Losses arising in connection with any and all Claims to the extent resulting or otherwise arising from (a) [**], (b) [**], or (c) [**] (A) in each case ((a) through (c)), [**] or (B) [**].
11.3Indemnification Procedures.
11.3.1General. A Party believing that it or any other Agenus Indemnitee or Licensee Indemnitee, as applicable, is entitled to indemnification under, as applicable, Section 11.1 (Indemnification by Agenus) or Section 11.2 (Indemnification by Licensee) (an “Indemnified Party”) will give prompt written notification to the other Party (the “Indemnifying Party”) of the commencement of any Claim for which indemnification may be sought or, if earlier,
47
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
upon the assertion of any such Claim by a Third Party (it being understood and agreed, however, that the failure by an Indemnified Party to give notice of a Claim as provided in this Section 11.3.1 (Indemnification Procedures; General) will not relieve the Indemnifying Party of its indemnification obligation under this Agreement, except and only to the extent that, such Indemnifying Party is actually materially prejudiced as a result of such failure to give notice). Within [**] after delivery of such notification, the Indemnifying Party may, upon written notice thereof to the Indemnified Party, assume control of the defense of such Claim with counsel reasonably satisfactory to the Indemnified Party; provided that if a Party believes that a Claim presented to it for indemnification is one as to which the Party seeking indemnification is not entitled to indemnification under, as applicable, Section 11.1 (Indemnification by Agenus) or Section 11.2 (Indemnification by Licensee), then it will so notify the Party seeking indemnification and shall not be so entitled to assume the defense of such Claim. Nothing in this Section 11.3.1 (Indemnification Procedures; General) shall override [**].
11.3.2Defense. If the Indemnifying Party elects to assume the defense of such Claim, the Indemnified Party and any other Agenus Indemnitee or Licensee Indemnitee, as applicable, may participate in such defense at its own expense; provided that if the Indemnified Party reasonably concludes, based on advice from counsel, that the Indemnifying Party and the Indemnified Party or any other Agenus Indemnitee or Licensee Indemnitee, as applicable, have conflicting interests with respect to such Claim under Applicable Law or ethical rules, then the Indemnifying Party will be responsible for the reasonable fees and expenses of counsel to the Indemnified Party or any other Agenus Indemnitee or Licensee Indemnitee, as applicable, solely in connection therewith.
11.3.3Cooperation. The Indemnifying Party will keep the Indemnified Party advised of the status of such Claim and the defense thereof and will consider recommendations made by the Indemnified Party with respect thereto. The Indemnified Party shall, and shall cause or any other Agenus Indemnitee or Licensee Indemnitee, as applicable, to, reasonably cooperate with the Indemnifying Party in its defense of any claim for which the Indemnifying Party has assumed the defense.
11.3.4Settlement. The Indemnified Party will not, and will cause any other Agenus Indemnitee or Licensee Indemnitee, as applicable, not to, agree to any settlement of such Claim without the prior written consent of the Indemnifying Party, which consent will not be unreasonably conditioned, withheld or delayed. The Indemnifying Party will not agree to any settlement of such Claim or consent to any judgment in respect thereof that does not include a complete and unconditional release of the Indemnified Party and any other Agenus Indemnitee or Licensee Indemnitee, as applicable, from all liability with respect thereto or that imposes any liability or obligation on the Indemnified Party or any other Agenus Indemnitee or Licensee Indemnitee, as applicable, or adversely affects the Indemnified Party or any other Agenus Indemnitee or Licensee Indemnitee, as applicable, in each case, without the prior written consent of the Indemnified Party, which consent will not be unreasonably conditioned, withheld or delayed.
48
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
11.4.1[**] shall maintain a program of self-insurance sufficient to satisfy its obligations hereunder.
11.4.2[**] shall procure and maintain commercially reasonable levels of insurance or other adequate or commercially reasonable forms of protection to satisfy its obligations under this Agreement (including its indemnification obligations and any obligations with respect to Development of Licensed Antibodies or Licensed Products under this Agreement). [**] will provide [**] with written evidence of such insurance prior to commencement of this Agreement and upon expiration of any one coverage. [**] will provide [**] with written notice at least [**] prior to the cancellation, nonrenewal, or material change in such insurance that materially adversely affects the rights of [**] hereunder.
11.4.3It is understood that such insurance or other protection will not be construed to create a limit of either Party’s liability with respect to its indemnification obligations under this Article 11 (Indemnification) or other obligations under this Agreement.
12.1.1During the Term and for a period of [**] thereafter, each Party receiving Confidential Information of the other Party will (a) maintain in confidence such Confidential Information at least to the same extent such Party maintains its own proprietary information of similar kind and value (which shall be no less than a reasonable standard), (b) not disclose such Confidential Information to any Third Party without the prior written consent of the other Party, except as otherwise expressly permitted below, and (c) not use such Confidential Information for any purpose except those permitted by this Agreement. As used herein, “Confidential Information” means all Know-How and other information and materials received by either Party from or on behalf of the other Party or its Affiliates pursuant to this Agreement; provided that, notwithstanding the foregoing, (x) (i) the Licensee Arising Know-How and [**] and (ii) all Regulatory Materials and Regulatory Data, which are owned or Controlled by Licensee or any of its Affiliates, related to any Licensed Product in the Field, in each case ((i) and (ii)), will be the Confidential Information of Licensee, and Licensee shall constitute the disclosing Party and Agenus the receiving Party with respect thereto, (y) (1) the Agenus Know-How, (2) Agenus Arising Know-How and (3) all Regulatory Materials and Regulatory Data, which are owned or Controlled by Agenus or any of its Affiliates, related to any Licensed Product in the Field, in each case ((1) through (3)) will be the Confidential Information of Agenus, and Agenus shall constitute the disclosing Party and Licensee the receiving Party with respect thereto, and (z) the Joint Arising Know-How and the terms of this Agreement will be the Confidential Information of each Party, and each Party shall be deemed the disclosing Party and the receiving Party with respect thereto. The foregoing obligations and the other obligations set forth in this Section 12.1 (Confidential Information) will not apply with respect to any portion of such Confidential Information that, that the receiving Party can demonstrate by contemporaneous tangible records or other competent proof:
49
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
(a)is publicly disclosed by the disclosing Party, either before or after it becomes known to the receiving Party;
(b)was known to the receiving Party or any or its Affiliates, without any obligation to keep it confidential, prior to when it was received from the disclosing Party;
(c)is subsequently disclosed to the receiving Party or any of its Affiliates by a Third Party that is lawfully in possession thereof without obligation to keep it confidential;
(d)has been published by a Third Party or otherwise enters the public domain through no fault of the receiving Party or any of its Affiliates in breach of this Agreement; or
(e)has been independently developed or acquired by the receiving Party or any of its Affiliates without the aid, application, or use of the disclosing Party’s Confidential Information;
provided that the exceptions in subclauses (b) and (c) above shall not apply with respect to the Joint Arising Know-How.
12.1.2Use of Confidential Information. Except as set forth above, each Party agrees that it will provide or permit access to Confidential Information of the other Party only to (a) the receiving Party’s attorneys, independent accountants, and financial advisors for the sole purpose of enabling such attorneys, independent accountants, and financial advisors to provide advice to the receiving Party, and (b) the receiving Party’s Affiliates, directors, officers, employees, consultants, advisors, and actual and bona fide potential collaborators, subcontractors, sublicensees, subdistributors and investors providing royalty financing or similar monetization of payments under this Agreement, and to the directors, officers, employees, consultants, advisors, and actual and bona fide potential collaborators, subcontractors, sublicensees, subdistributors, ethics committees and institutional review board, and investors of such Affiliates, in each case, who have a need to know such Confidential Information to assist the receiving Party with the activities contemplated or required of it by this Agreement; provided that in each case, the Person to whom Confidential Information is being disclosed is subject to obligations of confidentiality and non-use with respect to such Confidential Information substantially similar to the obligations of confidentiality and non-use of the receiving Party pursuant to this Section 12.1 (Confidential Information), provided further that the foregoing obligation shall be deemed satisfied if the duration of such confidentiality and non-use obligations is at least [**] and such obligations of confidentiality and non-use are otherwise substantially similar to those contained in this Section 12.1 (Confidential Information). In addition, each Party will remain responsible for any failure by its attorneys, independent accountants, and financial advisors, Affiliates, and its and its Affiliates’ respective directors, officers, employees, consultants, advisors and actual and bona fide potential collaborators, subcontractors, sublicensees, and subdistributors, to treat such Confidential Information as required under this Section 12.1 (Confidential Information). In addition, each Party may disclose the other Party’s Confidential Information to the extent such disclosure is reasonably
50
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
necessary for: (i) filing or prosecuting Patents in a manner consistent with this Agreement; or (ii) filing and submitting any Regulatory Materials in a manner consistent with this Agreement.
12.1.3Equitable Remedies. Each Party acknowledges that a Party in breach of any of its obligations under this Section 12.1 (Confidential Information) will cause the non-breaching Party irreparable harm, for which monetary damages will be an inadequate remedy. Therefore, notwithstanding anything to the contrary in this Agreement, in the event of any such breach, the non-breaching Party will be entitled, in addition to any other remedy available to it under this Agreement, at law or in equity, to seek equitable relief as provided in Section 15.3.2 (Equitable Remedies).
12.2Publicity. The Parties agree to publish the joint press release in the form set out in Schedule 12.2 (Publicity) within [**] of the Execution Date. Any other press releases or other public statements or disclosures regarding the subject matter of this Agreement to be made by [**]or its Affiliates will be subject to the express prior written consent of [**]; provided that a disclosure will be permitted without [**] consent to the extent that it does not contain information beyond that included in a prior disclosure approved in writing by [**] and that such previously published information remains true and correct at the time of such subsequent disclosure. [**], provided that [**]. [**].
12.3Permitted Disclosures. The receiving Party will have the right to disclose any Confidential Information provided by the other Party hereunder if such disclosure is [**]; and no such disclosure will cause any such information to cease to be Confidential Information hereunder, except to the extent such disclosure results in a public disclosure of such information. If reasonably possible, [**]. For clarity, either Party may disclose without any limitation [**]. Notwithstanding the foregoing, if a Party is [**], such Party shall be entitled to [**], provided that [**]. In the event of any such filing, each Party will provide the other Party with a copy of this Agreement [**] prior to such filing ([**]), and shall reasonably consider the [**].
12.4Publications. Except for disclosures permitted under this Agreement, either Party, its Affiliates, or their respective employee(s) or consultant(s) wishing to make a publication related to any Licensed Antibody or Licensed Product or that otherwise may reasonably contain Know-How, or other intellectual property, of the other Party or its Affiliates will use reasonable efforts, to the extent practicable, to deliver to such other Party a copy of the proposed written publication or an outline of an oral disclosure at least [**] prior to submission for publication or presentation. [**].
12.5Use of Names. Except as otherwise set forth in this Agreement, neither Party will use the name of the other Party in relation to this transaction in any public announcement, press release or other public document without the written consent of such other Party, which consent will not be unreasonably conditioned, withheld or delayed; provided, however, that subject to Section 12.4 (Publications), either Party may use the name of the other Party in any document filed with any Regulatory Authority or Governmental Authority, including the Securities and Exchange Commission.
51
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
12.6Effects of Termination. Except in the case of Agenus for any Confidential Information of Licensee that is Licensee Reversion Technology, within [**] after the effective date of any termination of this Agreement, each Party shall destroy (and cause its Affiliates to destroy) all tangible items comprising, bearing or containing any Confidential Information of the other Party that are in its or its Affiliates’ possession or Control; provided that such Party may retain one copy of such Confidential Information for its legal archives, and provided further that such Party shall not be required to destroy electronic files containing Confidential Information that are made in the ordinary course of its business information back-up procedures pursuant to its electronic record retention and destruction practices that apply to its own general electronic files and information.
ARTICLE 13
TERM AND TERMINATION
13.1Term. This Agreement shall take effect automatically without further action of either Party on the Effective Date; provided, however, that the provisions of Section 10.2.21 (Execution Date Covenant), Article 12 (Confidentiality) and Article 16 (Miscellaneous) shall become binding and effective as of the Execution Date. Unless earlier terminated pursuant to this Article 13 (Term and Termination), this Agreement will remain in effect until the expiration of the last Royalty Term in the Territory (the “Term”). Following the expiration of the Royalty Term for a Licensed Product in a country or jurisdiction, the license granted to Licensee pursuant to Section 2.1 (Grant to Licensee) will become irrevocable, perpetual, royalty-free, and fully-paid.
13.2.1Either Party may, without prejudice to any other remedies available to it at law or in equity, terminate this Agreement upon written notice to the other Party in the event that the other Party (the “Breaching Party”) materially breaches this Agreement. The Breaching Party will have [**] (or [**] for non-payment) after written notice thereof (a “Material Breach Notice”) was provided to the Breaching Party by the non-Breaching Party to remedy such breach; provided that with respect to any alleged breach by a Party of [**].
13.3Termination as a Result of Bankruptcy. Each Party may terminate this Agreement upon written notice to the other Party if such other Party (or any controlling Affiliate of such other Party) (a) makes an assignment of a substantial portion of its assets for the benefit of creditors, (b) appoints or suffers appointment of a receiver or trustee over all or substantially all of its property that is not dismissed or discharged within [**] after such appointment, (c) proposes a written agreement of composition or extension of its debts, (d) proposes or is a party to any dissolution or liquidation, (e) files a petition under any bankruptcy or insolvency law or is the subject of any such petition that is not dismissed within [**] of the filing thereof or (f) admits in writing its inability to meet its obligations as they generally become due, then the other Party may terminate this Agreement.
52
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
13.4Termination for Convenience by Licensee. Licensee may terminate this Agreement in its entirety or on a country-by-country basis, in each case, at will, in its sole discretion, by providing not less than [**] prior written notice to Agenus. [**].
13.5Termination by Licensee for [**]. Licensee may terminate this Agreement in its entirety or on a country-by-country basis upon written notice to Agenus based on [**]. Upon such termination for [**] shall be responsible, at its cost and expense, for the wind-down of any Development of the Licensed Products (including any Clinical Trials for the Licensed Products being conducted by or on behalf of Licensee) and any Commercialization activities for the Licensed Products, in each case, in the applicable terminated country(ies). Such termination shall become effective upon [**]. Following any such notice of termination under this Section 13.5 (Termination by Licensee for [**]), [**]; provided that, for clarity, [**].
13.6.1[**]
13.6.2[**]
13.6.3[**]
ARTICLE 14
EFFECTS OF EXPIRATION OR TERMINATION
14.1Termination of Licenses. Upon the termination of this Agreement with respect to each Terminated Territory, all rights and licenses granted to Licensee hereunder with respect to such Terminated Territory will immediately terminate and be of no further force and effect; provided that (a) if the Agreement is terminated by [**], then Licensee and its Affiliates will be entitled, during the period beginning on the effective date of such termination and ending on the last day of the [**] following such date, to sell or dispose in such Terminated Territory any inventory of Licensed Product that remains on hand as of the effective date of such termination (the “Sell-Off Right”), so long as Licensee pays to Agenus the Royalty Payments applicable to said subsequent sales of the Licensed Products in the Field in such Terminated Territory, as applicable, in accordance with the terms and conditions set forth in this Agreement, and otherwise complies with the terms set forth in this Agreement and Licensee shall retain a non-exclusive license hereunder to sell or dispose the Licensed Products in the Field in such Terminated Territory during such period and (b) if such Terminated Territory is not worldwide, then [**]. For clarity, [**].
14.2.1With respect to each Terminated Territory, Licensee will grant, and effective as of the applicable effective date of termination hereby grants, to Agenus and its Affiliates (a) (i) [**] and (ii) [**], in each case ((i) and (ii)), to [**]; (b) [**]; and (c) [**] (such license grants, the “Reversion License”), which Reversion License shall be [**].
53
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
14.2.3[**]
14.2.4[**]
14.3Assignments. Upon the termination of this Agreement for any reason with respect to any Terminated Territory, Licensee will promptly, in each case, within [**] thereafter, and at [**], except where such termination is by [**], in which case, at the cost of [**] ([**]):
14.3.1assign to Agenus, at Agenus’ sole discretion and direction, all of Licensee’s rights, title, and interests in and to any (a) Promotional Materials used by Licensee, its Affiliates or Sublicensees [**], including any copyrights with respect thereto and (b) Product Marks, including any goodwill associated therewith, and any technology, applications, Internet domain name registrations for such Product Marks [**] and in the event Agenus exercises such right to have assigned such Promotional Materials, Licensee will grant, and hereby does grant effective as of the later of the effective date of the applicable termination and Agenus’ request for such assignment, a royalty-free right and license to any housemarks, trademarks, names, and logos of Licensee contained therein for a transitional period of [**];
14.3.2to the extent permitted by Applicable Law, assign to Agenus, at Agenus’ sole discretion, election, and direction, the management and continued performance of any Clinical Trials for any Reversion Product for such Terminated Territory ongoing hereunder as of the effective date of the applicable termination that Agenus elects to assume the performance thereof in respect of which Agenus will assume full financial responsibility from and after the effective date of such termination and, with respect to any other Clinical Trial for any Licensed Product for such Terminated Territory ongoing hereunder as of the effective date of the applicable termination, Licensee shall orderly wind-down such Clinical Trial in compliance with Applicable Laws and accepted pharmaceutical industry norms and ethical practices, such wind-down activities shall be at [**] cost unless this Agreement is terminated by Licensee under [**], in which case [**] shall be responsible for the cost of such wind-down activities and shall reimburse such costs in accordance with the terms of Section 8.14 (General Payment Procedures);
14.3.3at Agenus’ written request [**], assign, and will cause its Affiliates to assign, to Agenus or its designee, all of Licensee’s and its Affiliates’ rights under Third Party contracts to the extent [**] relating to the Development, Manufacture or Commercialization of the Licensed Antibodies or the Reversion Products, to the extent that [**], and Agenus will assume Licensee’s or such Affiliate’s obligations under such assigned contracts, except to the extent such obligations relate to the period of performance prior to assignment or to any breach of such agreements by Licensee or such Affiliates;
14.3.4to the extent permitted by Applicable Law, transfer to Agenus, at Agenus’ sole discretion and direction, all of Licensee’s rights, title, and interests in and to any and all regulatory filings, Regulatory Approvals, Pricing Approvals, and other Regulatory Materials for any Reversion Product in such Terminated Territory; and provide a copy of (a) the material tangible embodiments of the foregoing and (b) any other material books, records, files, and documents in the possession and Control of Licensee to the extent solely related to any Reversion Product, which embodiments and documents may be redacted to exclude Confidential Information
54
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
of Licensee or its Related Parties; provided, however, that to the extent that any Regulatory Materials or other asset described in this Section 14.3 (Assignments) is not assignable by Licensee, then such agreement or other asset will not be assigned, and upon the request of Agenus, the Parties will reasonably cooperate to take such steps as may be reasonably necessary to allow Agenus to obtain and to enjoy the benefits of such agreement or other asset to the extent applicable to the rights to be assigned to Agenus (and Agenus shall bear any corresponding burden). For purposes of clarity, (A) Agenus will have the right to request that Licensee take any or all of the foregoing actions in whole or in part, or with respect to all or any portion of the assets set forth in the foregoing provisions, and (B) to the extent Agenus requests Licensee to transfer its rights, title, and interests in the items set forth in this Section 14.3 (Assignments) to Agenus, Licensee will also cause its Affiliates to transfer and assign to Agenus all of such Affiliates’ rights, title, and interests in and to the foregoing items set forth in this Section 14.3 (Assignments).
14.4Effect on Sublicenses. In the event of any termination of this Agreement for any reason for any Terminated Territory, any Sublicensee for such Terminated Territory, from the effective date of the applicable termination, will [**]; provided that (a) [**] and (b) [**].
14.5Disclosure and Delivery. Upon the termination of this Agreement for any reason with respect to any Terminated Territory, upon Agenus’ request, Licensee will (a) subject to the Sell-Off Right, remove or destroy any materials that contain any Licensed Antibody or Licensed Product and (b) provide documents and other information and materials in their existing form containing any Know-How within the Licensee Reversion Technology (such Know-How, the “Licensee Reversion Know-How”) to Agenus, to the extent not previously provided to Agenus, which documents and materials may be redacted to remove any Know-How other than Licensee Reversion Know-How; provided that [**]. [**] will be responsible for [**] costs and expenses incurred in performance of the foregoing, except, where such termination is by [**].
14.6Disposition of Commercialization Related Materials. Upon the termination of this Agreement for any reason with respect to a Terminated Territory, Licensee will promptly deliver to Agenus (a) a list identifying any wholesalers and other distributors involved in the Commercialization of any Reversion Product in such Terminated Territory as well as any customer lists (e.g., purchasers) related to the Commercialization of any Reversion Product in such Terminated Territory (if any) in electronic, sortable form, and (b) except and solely to the extent necessary for Licensee to exercise the Sell-Off Right, all Promotional Materials used by Licensee, its Affiliates or Sublicensees solely to Commercialize any Reversion Product in such Terminated Territory as of the effective date of termination that are in Licensee’s or its Affiliates’ possession.
14.7Accrued Rights. Expiration or termination this Agreement for any reason will be without prejudice to any rights that will have accrued to the benefit of a Party prior to the effective date of such expiration or termination. Such expiration or termination will not relieve a Party from obligations that are expressly indicated to survive the expiration or termination of this Agreement.
14.8Survival. Notwithstanding anything to the contrary contained herein, the following provisions will survive any expiration or termination of this Agreement: [**]. Except as set forth in this Article 14 (Effects of Expiration or Termination) or otherwise expressly set forth herein,
55
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
upon expiration or termination of this Agreement all other rights and obligations of the Parties will cease.
14.9Rights in Bankruptcy. All rights and licenses granted under or pursuant to this Agreement by Agenus and Licensee are, and will otherwise be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of right to “intellectual property” as defined under Section 101 of the U.S. Bankruptcy Code. The Parties agree that each Party, as licensee of certain rights under this Agreement, will retain and may fully exercise all of its rights and elections under the U.S. Bankruptcy Code. The Parties further agree that, in the event of the commencement of a bankruptcy proceeding by or against a Party (such Party, the “Bankrupt Party”) under the U.S. Bankruptcy Code, (a) the other Party will be entitled to a complete duplicate of (or complete access to, as appropriate) any intellectual property licensed to such other Party and all embodiments of such intellectual property, which, if not already in such other Party’s possession, will be promptly delivered to it (i) upon any such commencement of a bankruptcy proceeding upon such other Party’s written request therefore, unless the Bankrupt Party elects to continue to perform all of its obligations under this Agreement or (ii) if not delivered under clause (i), following the rejection of this Agreement by the Bankrupt Party upon written request therefore by the other Party, and (b) the Bankrupt Party will not unreasonably interfere with the other Party’s rights to intellectual property and all embodiments of intellectual property, and will assist and not unreasonably interfere with the other Party in obtaining intellectual property and all embodiments of intellectual property from another entity. The “embodiments” of intellectual property includes all tangible, intangible, electronic, or other embodiments of rights and licenses hereunder, including all compounds and products embodying intellectual property, Licensed Products, filings with Regulatory Authorities and related rights and Agenus Know-How in the case that Agenus is the Bankrupt Party and Licensee Know-How in the case Licensee is the Bankrupt Party.
15.1Disputes. The Parties recognize that, from time to time, disputes, controversies, or claims may arise that stem from or are related to a Party’s respective rights or obligations under this Agreement or a Party’s actual or alleged breach of this Agreement (a “Dispute”). It is the desire of the Parties to establish procedures to facilitate the resolution of Disputes arising under this Agreement in an expedient manner by mutual cooperation and without resort to litigation. To accomplish this objective, the Parties agree to follow the procedures set forth in this Article 15 (Dispute Resolution) if and when a Dispute arises under this Agreement. If the Parties are unable to resolve any Dispute within [**] after such Dispute is submitted for resolution, then either Party may, by written notice to the other Party, have such dispute referred to Designated Officers of each Party for attempted resolution. If the Designated Officers cannot reach resolution of the Dispute within [**] after such referral, the Dispute will be referred to the Parties’ designated executive officers or their delegates for attempted resolution. In the event the designated executive officers or their delegates are not able to resolve such Dispute within such [**] period after receipt of written notice, then either Party may submit such Dispute, or the unresolved portion thereof, for resolution by arbitration in accordance with Section 15.3 (Arbitration).
56
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
15.2Choice of Law. This Agreement will be governed by and construed in accordance with the laws of the State of New York and the patent laws of the United States without reference to any rules of conflict of laws that might otherwise make this Agreement subject to the substantive law of another jurisdiction. The United Nations Convention on Contracts for the International Sale of Goods does not apply to this Agreement and is expressly and entirely excluded.
15.3.1General. If the Parties fail to resolve any Dispute through escalation to the Designated Officers or escalation to the designated executive officers under Section 15.1 (Disputes), and a Party desires to pursue resolution of such Dispute, except as set forth in [**], [**] or [**], such Party will provide the other Party with a demand for arbitration, and the Dispute will be submitted by either Party for final resolution by arbitration administered by the American Arbitration Association (the “AAA”) in accordance with its Commercial Arbitration Rules (or the AAA International Arbitration Rules, if recommended under the AAA guidelines), as such rules may be modified by this Section 15.3 (Arbitration) or otherwise by subsequent written agreement of the Parties. Any disputes concerning the propriety of the commencement of the arbitration or the scope or applicability of this agreement to arbitrate will be finally settled by the arbitral tribunal. The arbitration will be conducted by a tribunal of [**] arbitrators, each of which will be independent, conflict-free and having at least [**]. An arbitrator will be deemed to meet this qualification unless a Party objects within [**] after the arbitrator is nominated. Within [**] after initiation of arbitration, each Party will nominate one (1) arbitrator and the two (2) Party-nominated arbitrators will nominate a third arbitrator, who will serve as the chairperson of the tribunal, within [**] of the second arbitrator’s appointment. The seat of arbitration will be New York City, New York and the language of the proceedings, including all communications, will be English. The Parties agree that any award or decision made by the arbitral tribunal will be final and binding upon them and may be enforced in the same manner as a judgment or order of a court of competent jurisdiction, and the Parties undertake to carry out any award without delay. The arbitral tribunal will render its final award or decision within [**] from the date on which the request for arbitration by one of the Parties wishing to have recourse to arbitration is received by the AAA. The arbitral tribunal will resolve the Dispute by applying the provisions of this Agreement and the governing law set forth in Section 15.2 (Choice of Law). The arbitration agreement described in this Section 15.3 (Arbitration) shall be governed by the laws of New York.
15.3.2Equitable Remedies. Notwithstanding anything to the contrary herein, the Parties do not intend to deprive any court of its jurisdiction to issue, at the request of a Party, a pre-arbitral injunction, pre-arbitral attachment or other order to avoid irreparable harm, maintain the status quo, preserve the subject matter of the Dispute, or aid the arbitration proceedings and the enforcement of any award. Without prejudice to such provisional or interim remedies in aid of arbitration as may be available under the jurisdiction of a competent court, the arbitral tribunal will have full authority to grant provisional or interim remedies and to award damages for the failure of any Party to the dispute to respect the arbitral tribunal’s order to that effect.
15.3.3Waiver of Jury Trial. EACH PARTY WAIVES: (A) ITS RIGHT TO TRIAL OF ANY ISSUE BY JURY, AND (B) ANY CLAIM FOR ATTORNEY FEES, COSTS AND PREJUDGMENT INTEREST.
57
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
15.3.4Awards. The arbitral tribunal will be authorized to award compensatory damages, but will not be authorized to (a) [**], (b) [**], or (c) [**]; provided, however, that [**]. Each Party will bear its own attorney’s fees, costs, and disbursements arising out of the arbitration, and will pay an equal share of the fees and costs of the administrator and the arbitral tribunal; provided, however, that the arbitral tribunal will be authorized to determine whether a Party is the prevailing Party, and if so, to award to that prevailing party reimbursement for any or all of its reasonable attorneys’ fees, costs and disbursements (including, for example, expert witness fees and expenses, photocopy charges, travel expenses, etc.), or the fees and costs of the administrator and the arbitral tribunal.
15.3.5Exceptions. Notwithstanding anything in this Section 15.3 (Arbitration), in the event of a Dispute with respect to (a) [**], (b) [**], or (c) [**], such Dispute will not be submitted to an arbitration proceeding in accordance with this Section 15.3 (Arbitration), unless otherwise agreed by the Parties in writing or specified in (a), and instead, either Party may initiate litigation in a court of competent jurisdiction in any country in which such rights apply.
15.3.6Confidentiality. All proceedings and decisions of the arbitrator(s) in connection with an arbitral proceeding pursuant to this Section 15.3 (Arbitration) will be deemed Confidential Information of each of the Parties and will be subject to Article 12 (Confidentiality).
16.1Entire Agreement; Amendment. This Agreement, together with the Schedules and Exhibits hereto, contains the entire understanding of the Parties with respect to the subject matter hereof. Any other express or implied agreements and understandings, negotiations, writings and commitments, either oral or written, in respect to the subject matter hereof are superseded by the terms of this Agreement, including the Mutual Confidential Disclosure Agreement, dated July 10, 2020, by and between Licensee and Agenus. The Schedules and Exhibits to this Agreement are incorporated herein by reference and will be deemed a part of this Agreement. This Agreement may be amended, or any term hereof modified, only by a written instrument duly executed by authorized representatives of each of the Parties.
16.2.1HSR Filing. Each of Licensee and Agenus shall make an HSR Filing within [**] after the Execution Date, unless the Parties together determine that no HSR Filing is required for the activities and licenses contemplated under the Agreement. The Parties shall cooperate with one another to the extent necessary in the preparation of any such filings. Each Party shall be responsible for its own costs and expenses associated with any such filings.
16.2.2HSR Clearance. In connection with obtaining HSR Clearance, Licensee and Agenus shall [**] to resolve as promptly as practicable any objections that may be asserted by the FTC or the DOJ with respect to the transactions notified in the HSR Filing. The term “[**]” as used in this Section 16.2.2 (HSR Clearance) shall not require Licensee or any of its Affiliates to (a) [**], or (b) [**] (such litigation or judicial or administrative proceeding, an “HSR
58
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Proceeding”). Neither Party may seek early termination (or early determination) of HSR Clearance without the other Party’s prior written consent.
16.2.3Cooperation. In connection with obtaining HSR Clearance, each of Licensee and Agenus shall (a) cooperate with each other in connection with any investigation or other inquiry relating to an HSR Filing and the transactions contemplated by this Agreement; (b) keep the other Party or its counsel informed of any communication received from or given to the FTC or DOJ relating to the HSR Filing and the transactions contemplated by this Agreement (and provide a copy to the other Party if such communication is in writing); (c) reasonably consult with each other in advance of any meeting or conference with the FTC or DOJ, and, to the extent permitted by the FTC or DOJ, give the other Party or its counsel the opportunity to attend and participate in such meetings and conferences; and (d) permit the other Party or its counsel to review in advance, and in good faith consider the views of the other Party or its counsel concerning, any submission, filing or communication (and documents submitted therewith) intended to be given to the FTC or DOJ. Without limiting the foregoing, Agenus shall cooperate fully in any HSR Proceeding initiated by Licensee; provided that Agenus shall not agree to or effectuate any remedy without the prior written consent of Licensee.
16.2.4Termination for Failure or Delay to Obtain HSR Clearance. This Agreement shall terminate upon notice given by Licensee to Agenus if the Effective Date has not occurred within [**] after the date on which the HSR Filing is made.
16.3Force Majeure. Neither Party will be liable for any failure to perform, or be considered in breach of, its obligations under this Agreement (other than obligations to make payments of money) to the extent such performance has been delayed, interfered with, or prevented by an event of Force Majeure, and the obligations of such Party under this Agreement (other than obligations to make payments of money) whose performance is affected by Force Majeure will be suspended during, but not longer than, the continuance of the event of Force Majeure. The Parties agree the effects of [**]. If a Party experiences an event of Force Majeure, it will provide prompt notice of such event to the other Party, including an estimate of the likely period of time during which its performance will be affected, and will use reasonable efforts to remove the condition constituting Force Majeure. In the event of a prolonged condition of Force Majeure that makes it unreasonable to continue to perform other activities then being performed by the Parties and their Affiliates pursuant to this Agreement, the Parties will consult with each other and may appropriately scale back their respective activities in order to avoid waste or inappropriate usage of resources under the circumstances, and neither Party will be liable for any such reasonable scale back, or be considered in breach of its obligations under this Agreement (other than obligations to make payments of money to the other Party), in each case, as a result of such reasonable scale back.
16.4Notices. Any notice required or permitted to be given under this Agreement will be in writing, will specifically refer to this Agreement and will be deemed to have been sufficiently given for all purposes: (a) if mailed by first class certified or registered mail, postage prepaid (which notice will be effective [**] after such mailing); (b) express delivery service (which notice will be effective on the first (1st) Business Day after delivery to such service); (c) personally delivered to the appropriate addresses (which notice will be effective upon delivery to such
59
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
addresses) set forth below or to such other addresses for a Party as such Party may inform the other Party in writing; or (d) sent by electronic mail to a Party’s electronic mail address set forth below or to such other electronic mail address for a Party as such Party may inform the other Party in writing, provided that such notice delivered by electronic mail must be followed by notice delivered in accordance with any of the methods set forth in subclause (a), (b) or (c), and such notice will be effective on the notice effective date set forth in subclause (a), (b) or (c) respectively:
|
If to Agenus: |
Agenus Inc. |
3 Forbes Road
Lexington, Massachusetts 02421-7305, USA
Attention: Chief Executive Officer
Copy to: Legal Department
E-mail address: [**]
|
With copies to: |
Ropes & Gray LLP |
Prudential Tower
800 Boylston Street
Boston, Massachusetts 02199-3600, USA
Attention: [**]
E-mail address: [**]
|
If to Licensee: |
Bristol-Myers Squibb Company |
[**]
[**]
Attention: [**]
|
With copies to: |
Bristol-Myers Squibb Company |
[**]
[**]
Attention: [**]
16.5Assignment. Neither Party may assign or transfer this Agreement or any rights or obligations hereunder without the prior written consent of the other Party, except that a Party may make such an assignment or transfer without the other Party’s written consent to [**]. In addition and notwithstanding anything to the contrary set forth in this Agreement, either Party may, without the other Party’s written consent, assign its rights and obligations under this Agreement to any Third Party in connection with (a) [**] or (b) [**] (i) [**] or (ii) [**]. Any assignment under (a) or (b) will be deemed a Change of Control of the assigning Party. Any permitted successor or assignee of rights or obligations hereunder will, in a writing delivered to the other Party, expressly assume the performance of such rights or obligations. In the event of an assignment or transfer as permitted above in this Section 16.5 (Assignment), if this Agreement is assigned or transferred to[**], the assigning or transferring Party will remain responsible (jointly and severally) with such [**] for the performance of such assigned or transferred obligations. Any assignment or transfer, or attempted assignment or transfer, by either Party in violation of the terms of this Section 16.5 (Assignment) will be null and void and of no legal effect. This Agreement will be binding on, and inure to the benefit of, each Party, its successors, and permitted assigns.
60
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
16.6[**]
16.7Severability. If any one or more of the provisions of this Agreement is held to be invalid or unenforceable by any court of competent jurisdiction from which no appeal can be or is taken, such provision will be considered severed from this Agreement and will not serve to invalidate any remaining provisions hereof. The Parties will make a good faith effort to replace any invalid or unenforceable provision with a valid and enforceable one such that the objectives contemplated by the Parties when entering this Agreement may be realized.
16.8Cumulative Remedies. No remedy referred to in this Agreement is intended to be exclusive, but each will be cumulative and in addition to any other remedy referred to in this Agreement or otherwise available under Applicable Law.
16.9Ambiguities; No Presumption. Each of the Parties acknowledges and agrees that this Agreement has been diligently reviewed by and negotiated by and between them, that in such negotiations each of them has been represented by competent counsel and that the final agreement contained herein, including the language whereby it has been expressed, represents the joint efforts of the Parties and their counsel. Accordingly, in interpreting this Agreement or any provision hereof, no presumption will apply against either Party as being responsible for the wording or drafting of this Agreement or any such provision, and ambiguities, if any, in this Agreement will not be construed against either Party, irrespective of which Party may be deemed to have authored the ambiguous provision.
16.10Headings. The headings for each Article and Section in this Agreement have been inserted for convenience of reference only and are not intended to limit or expand on the meaning of the language contained in the particular article or section.
16.11Interpretation. Except where the context expressly requires otherwise, (a) the use of any gender herein will be deemed to encompass references to either or both genders, and the use of the singular will be deemed to include the plural (and vice versa), (b) the words “include,” “includes,” and “including” will be deemed to be followed by the phrase “without limitation,” (c) the word “will,” when used to indicate a duty or obligation, will be construed to have the same meaning and effect as the word “shall,” (d) any definition of or reference to any agreement, instrument or other document herein will be construed as referring to such agreement, instrument or other document as from time to time amended, supplemented or otherwise modified (subject to any restrictions on such amendments, supplements or modifications set forth herein), (e) any reference herein to any Person will be construed to include such Person’s successors and assigns, (f) the words “herein,” “hereof,” and “hereunder,” and words of similar import, will be construed to refer to this Agreement in its entirety and not to any particular provision hereof, (g) all references herein to Articles, Sections, Exhibits, or Schedules will be construed to refer to Articles, Sections, Exhibits, or Schedules of this Agreement, and references to this Agreement include all Exhibits and Schedules hereto, (h) the word “notice” means notice in writing (whether or not specifically stated) and will include notices, consents, approvals and other written communications contemplated under this Agreement, (i) provisions that require that a Party or the Parties “agree,” “consent” or “approve” or the like will require that such agreement, consent, or approval be specific and in writing, whether by written agreement, letter, or otherwise (but excluding instant
61
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
messaging), (j) references to any specific law, rule, or regulation, or article, section or other division thereof, will be deemed to include the then-current amendments thereto or any replacement or successor law, rule, or regulation thereof, (k) the term “or” will be interpreted in the inclusive sense commonly associated with the term “and/or,” and (l) references to “days” will mean calendar days, unless otherwise specified.
16.12No Consequential or Punitive Damages. NEITHER PARTY WILL BE LIABLE TO THE OTHER PARTY FOR INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL DAMAGES, EXEMPLARY, PUNITIVE, OR MULTIPLE DAMAGES ARISING OUT OF THIS AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, OR, FOR LOST PROFITS ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT REGARDLESS OF ANY NOTICE OF SUCH DAMAGES. NOTHING IN THIS SECTION 16.12 (NO CONSEQUENTIAL OR PUNITIVE DAMAGES) IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY WITH RESPECT TO RECOVERY OF DAMAGES AWARDED TO THIRD PARTY CLAIMANTS (OTHER THAN AN INDEMNITEE) IN [**], OR DAMAGES AVAILABLE FOR [**].
16.13No Waiver. Any delay in enforcing a Party’s rights under this Agreement or any waiver as to a particular default or other matter will not constitute a waiver of such Party’s rights to the future enforcement of its rights under this Agreement, except with respect to an express written and signed waiver relating to a particular matter for a particular period of time.
16.14No Third Party Beneficiaries. No Person other than Licensee, Agenus, and their respective Affiliates, successors and permitted assignees hereunder, will be deemed an intended beneficiary hereunder or have any right to enforce any obligation of this Agreement.
16.15Independent Contractors. It is expressly agreed that Licensee and Agenus will be independent contractors and that the relationship between Licensee and Agenus will not constitute a partnership, joint venture, or agency. Neither Licensee nor Agenus will have the authority to make any statements, representations, or commitments of any kind, or to take any action, that would be binding on the other Party, without the prior written consent of such other Party.
16.16Counterparts; Facsimile Signatures. This Agreement may be executed in two (2) or more counterparts, each of which will be deemed an original, but all of which together will constitute one and the same instrument. This Agreement may be executed by delivery of electronically scanned copies of original signatures delivered by facsimile; electronic PDF file, or electronic mail, and such signatures will be deemed to bind each Party as if they were original signatures.
[No Further Text on This Page]
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[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
In Witness Whereof, the Parties have executed this Agreement by their duly authorized representatives as of the Execution Date.
Bristol-Myers Squibb CompanyAgenus Inc.
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By: /s/ Elizabeth A. Mily |
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By: /s/ Garo Armen |
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Printed: Elizabeth A. Mily |
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Printed: Garo Armen |
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Title: EVP, Strategy and Business Development |
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Title: Chairman and CEO |
[Signature Page to License, Development and Commercialization Agreement]
Exhibit 10.1
Schedule 1.5
AGEN1777 Antibody Structure
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Schedule 1.8
Agenus FC Platform Patents
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Agenus Ongoing Studies
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Agenus Patents
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Schedule 1.114
Special Resolution Mechanisms Schedule
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Schedule 2.5
Materials Transfer
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
AGEN1777 Initial Global Development Plan
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Report Information for Agenus GDP Trials
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Agenus Study Conduct Responsibilities
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Co-Promotion Agreement Terms
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Related Agreements
[**]
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.1
Joint Press Release
1
[**] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed separately with the Commission.
Exhibit 10.2
AMENDMENT NO. 1 TO ROYALTY Purchase AGREEMENT
This Amendment No. 1 to Royalty Purchase Agreement (this “Amendment”) is made and entered into as of June 22, 2021 by and among Antigenics LLC, a Delaware limited liability company (the “Seller”) and the entities set forth on Schedule 1 to the (as defined below) Agreement in the proportions set forth thereon (collectively, the “Buyer”). Capitalized terms used herein but not defined shall have the meanings ascribed to such terms in the Agreement (as defined below).
WHEREAS, Seller and Buyer are parties to that certain Royalty Purchase Agreement, dated as of January 6, 2018 (the “Agreement”);
WHEREAS, pursuant to Section 8.12(a) of the Agreement, the Agreement may not be amended, changed or modified except with the written consent of the Parties; and
WHEREAS, the Parties desire to enter into this Amendment to amend certain provisions of the Agreement in order to remove the obligation that Seller be required to maintain a reserve of freely available cash during the Payment Term as set forth herein.
NOW, THEREFORE, in consideration of the foregoing recitals and the agreements contained herein, and for other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the Parties agree as follows:
1.Amendment. Section 2.02(b) of the Agreement is hereby deleted in its entirety and replace with the following:
“2.02(b)Notwithstanding anything to the contrary in this Section 2.02, upon and after the occurrence of either (or both) of the following sales milestones, in the Purchaser’s sole discretion, either (x) Purchaser shall promptly make one or more cash payments of either (or both) of the Sales Milestone Payments ((as defined below), net of any amounts due to Purchaser hereunder from Seller), in which case the Purchaser shall retain all Royalties from the Joint Escrow Account; or (y) all subsequent Royalties from and after the occurrence of such sales milestones shall be paid from the Joint Escrow Account (net of any amounts due to Purchaser hereunder from Seller) to the Seller, by distribution to the Seller Account until the aggregate amount of Sales Milestone Payments equals the applicable amount, or amounts, as the case may be, set forth below, after which payment of all Royalties from the Joint Escrow Account shall revert to the Purchaser in accordance with the terms of Section 2.02(a):
i. if Net Sales of Products equal or exceed an aggregate of $2,000,000,000 during any period of twelve consecutive months prior to January 1, 2024, Seller shall be entitled to receive a Sales Milestone Payment in an amount equal to $15,100,000 (the “2024 Sales Milestone Payment”); and
ii. if Net Sales of Products equal or exceed an aggregate of $2,750,000,000 during any period of twelve consecutive months prior to January 1, 2026, Seller shall be entitled to receive a Sales Milestone Payment in an amount equal to $25,250,000 (together with the 2024 Sales Milestone Payment, the “Sales Milestone Payments”).
1
Exhibit 10.2
For the avoidance of doubt, the sales milestones set forth above can be achieved during concurrent time periods (e.g., if Net Sales of the Products for any twelve consecutive months ending prior to January 1, 2024 exceed $2,750,000,000, then Purchaser shall owe Seller Sales Milestone Payments in an amount equal to $40,350,000).”
2.Miscellaneous.
2.1No Other Amendments. Except as set forth herein, this Amendment shall not be deemed to amend, waive or alter any other provisions of the Agreement, and the Agreement shall continue in full force and effect in accordance with its terms, as amended hereby.
2.2Entire Agreement. This Amendment, together with the Agreement, contains the entire agreement of the Parties with respect to the subject matter hereof and supersedes all prior agreements, understandings and negotiations, both written and oral, between the Parties with respect to the subject matter of this Amendment. All references in the Agreement to the Agreement shall be deemed to be references to the Agreement as amended by this Amendment.
2.3Amendments. This Amendment or any term or provision hereof may not be amended, changed or modified except with the written consent of the Parties.
2.4Binding. The provisions of this Amendment shall be binding upon and inure to the benefit of the Parties and their respective successors and permitted assigns.
2.5Counterparts; Effectiveness. This Amendment may be executed in two or more counterparts, each of which shall be an original, but all of which together shall constitute one and the same instrument. This Amendment shall become effective when each Party shall have received a counterpart hereof signed by the other Party. Any counterpart may be executed by facsimile or .pdf signature and such facsimile or .pdf signature shall be deemed an original.
2.6Governing Law. This Amendment shall be governed by, and construed, interpreted and enforced in accordance with, the laws of the State of New York without giving effect to the principles of conflicts of law thereof that would apply any other law.
[Signature page follows.]
2
Exhibit 10.2
IN WITNESS WHEREOF, the Parties have caused this Amendment to be duly executed as of the date first above written.
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SELLER:
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Antigenics LLC By: /s/ Garo H. Armen
Name: Garo H. Armen
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BUYER: |
HealthCare Royalty Partners III, L.P. By: HealthCare Royalty GP III, LLC, its general partner
By: /s/ Clarke B. Futch
Name: Clarke B. Futch
HCRP Overflow Fund, L.P. By: HCRP Overflow GP, LLC, its general partner
By: /s/ Clarke B. Futch
Name: Clarke B. Futch
HCR Molag Fund, L.P. By: HCR Molag Fund GP, LLC, its general partner
By: /s/ Clarke B. Futch
Name: Clarke B. Futch
HCR Stafford Fund, L.P. By: HCR Stafford Fund GP, LLC, its general partner
By: /s/ Clarke B. Futch
Name: Clarke B. Futch
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[Signature Page to Amendment No. 1 to Royalty Interest Acquisition Agreement]
Certification Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended
I, Garo H. Armen, certify that:
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I have reviewed this Quarterly Report on Form 10-Q of Agenus Inc.; |
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2. |
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; |
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3. |
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the Registrant as of, and for, the periods presented in this report; |
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4. |
The Registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the Registrant and have: |
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designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the Registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared; |
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designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with U.S. generally accepted accounting principles; |
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evaluated the effectiveness of the Registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and |
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disclosed in this report any change in the Registrant’s internal control over financial reporting that occurred during the Registrant’s most recent fiscal quarter (the Registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the Registrant’s internal control over financial reporting; and |
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5. |
The Registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the Registrant’s auditors and the audit committee of the Registrant’s board of directors (or persons performing the equivalent function): |
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a. |
all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the Registrant’s ability to record, process, summarize and report financial information; and |
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b. |
any fraud, whether or not material, that involves management or other employees who have a significant role in the Registrant’s internal control over financial reporting. |
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Date: August 9, 2021 |
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/s/ GARO H. ARMEN, PH.D. |
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Garo H. Armen, Ph.D. |
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Chief Executive Officer and Principal Executive Officer |
Certification Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended
I, Christine M. Klaskin, certify that:
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I have reviewed this Quarterly Report on Form 10-Q of Agenus Inc.; |
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2. |
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; |
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3. |
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the Registrant as of, and for, the periods presented in this report; |
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4. |
The Registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the Registrant and have: |
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a. |
designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the Registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared; |
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designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with U.S. generally accepted accounting principles; |
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evaluated the effectiveness of the Registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and |
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disclosed in this report any change in the Registrant’s internal control over financial reporting that occurred during the Registrant’s most recent fiscal quarter (the Registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the Registrant’s internal control over financial reporting; and |
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5. |
The Registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the Registrant’s auditors and the audit committee of the Registrant’s board of directors (or persons performing the equivalent function): |
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a. |
all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the Registrant’s ability to record, process, summarize and report financial information; and |
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b. |
any fraud, whether or not material, that involves management or other employees who have a significant role in the Registrant’s internal control over financial reporting. |
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Date: August 9, 2021 |
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/s/ CHRISTINE M. KLASKIN |
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Christine M. Klaskin |
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VP, Finance and Principal Financial Officer |
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Certification
Pursuant to 18 U.S.C. Section 1350,
As Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002
In connection with the Quarterly Report on Form 10-Q of Agenus Inc. (the “Company”) for the quarterly period ended June 30, 2021 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), each of the undersigned to his/her knowledge hereby certifies, pursuant to 18 U.S.C. Section 1350, that:
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(i) |
The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and |
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(ii) |
The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company. |
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/s/ GARO H. ARMEN, PH.D. |
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Garo H. Armen, Ph.D. |
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Chief Executive Officer and Principal Executive Officer |
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/s/ CHRISTINE M. KLASKIN |
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Christine M. Klaskin |
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VP, Finance and Principal Financial Officer |
Date: August 9, 2021
A signed original of this written statement required by Section 906 has been provided to the Company and will be retained by the Company and furnished to the Securities and Exchange Commission or its staff upon request.
The foregoing certification is being furnished to the Securities and Exchange Commission as an exhibit to the Report and should not be considered filed as part of the Report.