|
|
☒
|
QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
|
☐
|
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
|
|
|
Delaware
|
26-0662915
|
(State or Other Jurisdiction of
Incorporation or Organization)
|
(I.R.S. Employer
Identification No.)
|
|
|
88 Sidney Street, Cambridge, Massachusetts
|
02139
|
(Address of Principal Executive Offices)
|
(Zip Code)
|
|
Large accelerated filer
|
☒
|
Accelerated filer
|
☐
|
Non-accelerated filer
|
☐ (Do not check if a smaller reporting company)
|
Smaller reporting company
|
☐
|
|
|
Emerging growth company
|
☐
|
|
|
Page
No.
|
|
||
Item 1.
|
|
|
|
||
|
||
|
||
|
||
|
||
Item 2.
|
||
Item 3.
|
||
Item 4.
|
||
|
||
Item 1A.
|
||
Item 6.
|
||
|
|
September 30,
2017 |
|
December 31,
2016 |
||||
Assets
|
|
|
|
||||
Current assets:
|
|
|
|
||||
Cash and cash equivalents
|
$
|
132,741
|
|
|
$
|
160,754
|
|
Marketable securities
|
375,187
|
|
|
380,560
|
|
||
Collaboration receivable – related party
|
3,489
|
|
|
4,886
|
|
||
Royalty receivable – related party
|
715
|
|
|
—
|
|
||
Tenant improvement and other receivables
|
859
|
|
|
3,428
|
|
||
Prepaid expenses and other current assets
|
15,316
|
|
|
10,264
|
|
||
Total current assets
|
528,307
|
|
|
559,892
|
|
||
Marketable securities
|
133,804
|
|
|
32,250
|
|
||
Property and equipment, net
|
24,019
|
|
|
25,337
|
|
||
Other non-current assets
|
1,070
|
|
|
1,615
|
|
||
Total assets
|
$
|
687,200
|
|
|
$
|
619,094
|
|
Liabilities and stockholders’ equity
|
|
|
|
||||
Current liabilities:
|
|
|
|
||||
Accounts payable
|
$
|
17,899
|
|
|
$
|
17,106
|
|
Accrued expenses
|
30,760
|
|
|
32,002
|
|
||
Deferred revenue – related party
|
35,867
|
|
|
35,913
|
|
||
Deferred rent
|
3,586
|
|
|
3,412
|
|
||
Total current liabilities
|
88,112
|
|
|
88,433
|
|
||
Deferred revenue, net of current portion – related party
|
134,202
|
|
|
154,297
|
|
||
Deferred rent, net of current portion
|
15,080
|
|
|
17,773
|
|
||
Total liabilities
|
237,394
|
|
|
260,503
|
|
||
Stockholders’ equity:
|
|
|
|
||||
Preferred stock, $0.001 par value; 25,000,000 shares authorized; no shares issued or outstanding at September 30, 2017 and December 31, 2016
|
—
|
|
|
—
|
|
||
Common stock, $0.001 par value; 125,000,000 shares authorized; 48,617,989 and 42,220,444 shares issued and outstanding at September 30, 2017 and December 31, 2016, respectively
|
49
|
|
|
42
|
|
||
Additional paid-in capital
|
1,160,048
|
|
|
842,013
|
|
||
Accumulated other comprehensive loss
|
(515
|
)
|
|
(313
|
)
|
||
Accumulated deficit
|
(709,776
|
)
|
|
(483,151
|
)
|
||
Total stockholders’ equity
|
449,806
|
|
|
358,591
|
|
||
Total liabilities and stockholders’ equity
|
$
|
687,200
|
|
|
$
|
619,094
|
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
|
2017
|
|
2016
|
|
2017
|
|
2016
|
||||||||
Collaboration revenue – related party
|
$
|
10,643
|
|
|
$
|
8,985
|
|
|
$
|
32,497
|
|
|
$
|
47,244
|
|
Royalty revenue – related party
|
715
|
|
|
—
|
|
|
715
|
|
|
—
|
|
||||
Total revenue
|
11,358
|
|
|
8,985
|
|
|
33,212
|
|
|
47,244
|
|
||||
Operating expenses:
|
|
|
|
|
|
|
|
||||||||
Research and development (net of $1,078 and $4,038 of cost reimbursement from related party for the three months ended September 30, 2017 and 2016, respectively, and $6,343 and $18,754 of cost reimbursement from related party for the nine months ended September 30, 2017 and 2016, respectively)
|
72,917
|
|
|
60,643
|
|
|
215,465
|
|
|
155,485
|
|
||||
General and administrative
|
17,458
|
|
|
11,854
|
|
|
48,411
|
|
|
35,335
|
|
||||
Total operating expenses
|
90,375
|
|
|
72,497
|
|
|
263,876
|
|
|
190,820
|
|
||||
Loss from operations
|
(79,017
|
)
|
|
(63,512
|
)
|
|
(230,664
|
)
|
|
(143,576
|
)
|
||||
Interest income
|
1,880
|
|
|
678
|
|
|
4,279
|
|
|
1,591
|
|
||||
Net loss
|
$
|
(77,137
|
)
|
|
$
|
(62,834
|
)
|
|
$
|
(226,385
|
)
|
|
$
|
(141,985
|
)
|
Net loss per share – basic and diluted
|
$
|
(1.59
|
)
|
|
$
|
(1.63
|
)
|
|
$
|
(4.94
|
)
|
|
$
|
(3.72
|
)
|
Weighted-average number of common shares used in computing net loss per share – basic and diluted
|
48,459,424
|
|
|
38,548,153
|
|
|
45,851,203
|
|
|
38,124,425
|
|
|
Three Months Ended
September 30, |
|
Nine Months Ended
September 30, |
||||||||||||
|
2017
|
|
2016
|
|
2017
|
|
2016
|
||||||||
Net loss
|
$
|
(77,137
|
)
|
|
$
|
(62,834
|
)
|
|
$
|
(226,385
|
)
|
|
$
|
(141,985
|
)
|
Other comprehensive income (loss)
|
|
|
|
|
|
|
|
||||||||
Unrealized gain (loss) on available-for-sale securities
|
135
|
|
|
(268
|
)
|
|
(202
|
)
|
|
347
|
|
||||
Comprehensive loss
|
$
|
(77,002
|
)
|
|
$
|
(63,102
|
)
|
|
$
|
(226,587
|
)
|
|
$
|
(141,638
|
)
|
|
Nine Months Ended
September 30, |
||||||
|
2017
|
|
2016
|
||||
Operating activities
|
|
|
|
||||
Net loss
|
$
|
(226,385
|
)
|
|
$
|
(141,985
|
)
|
Adjustments to reconcile net loss cash (used in) provided by operating activities:
|
|
|
|
||||
Depreciation
|
4,778
|
|
|
3,986
|
|
||
Stock-based compensation expense
|
35,128
|
|
|
32,246
|
|
||
Net amortization of premium and discounts on investments
|
25
|
|
|
534
|
|
||
Loss on disposal of property and equipment
|
40
|
|
|
—
|
|
||
Changes in operating assets and liabilities:
|
|
|
|
||||
Collaboration receivable – related party
|
1,397
|
|
|
43
|
|
||
Royalty receivable – related party
|
(715
|
)
|
|
—
|
|
||
Tenant improvement and other receivables
|
2,558
|
|
|
271
|
|
||
Prepaid expenses and other current and non-current assets
|
(4,444
|
)
|
|
(2,464
|
)
|
||
Accounts payable
|
742
|
|
|
1,668
|
|
||
Accrued expenses
|
(1,242
|
)
|
|
7,328
|
|
||
Deferred revenue – related party
|
(20,141
|
)
|
|
185,992
|
|
||
Deferred rent
|
(2,519
|
)
|
|
2,166
|
|
||
Net cash (used in) provided by operating activities
|
(210,778
|
)
|
|
89,785
|
|
||
Investing activities
|
|
|
|
||||
Purchases of marketable securities
|
(604,525
|
)
|
|
(367,587
|
)
|
||
Proceeds from maturities and sales of marketable securities
|
508,116
|
|
|
334,448
|
|
||
Purchases of property and equipment
|
(3,347
|
)
|
|
(8,693
|
)
|
||
Net cash used in investing activities
|
(99,756
|
)
|
|
(41,832
|
)
|
||
Financing activities
|
|
|
|
||||
Payment of public offering costs, net of reimbursements
|
(89
|
)
|
|
(124
|
)
|
||
Proceeds from public offering of common stock, net of commissions
|
270,250
|
|
|
162,150
|
|
||
Net proceeds from stock option exercises and employee stock purchase plan
|
12,360
|
|
|
3,759
|
|
||
Net cash provided by financing activities
|
282,521
|
|
|
165,785
|
|
||
Net change in cash and cash equivalents
|
(28,013
|
)
|
|
213,738
|
|
||
Cash and cash equivalents at beginning of the period
|
160,754
|
|
|
71,764
|
|
||
Cash and cash equivalents at end of the period
|
$
|
132,741
|
|
|
$
|
285,502
|
|
Supplemental disclosure of non-cash investing and financing transactions
|
|
|
|
||||
Additions to property and equipment in accounts payable and accrued expenses
|
$
|
226
|
|
|
$
|
497
|
|
Proceeds from stock option exercises in other receivables
|
$
|
95
|
|
|
$
|
—
|
|
Public offering costs in other receivables, net of amounts in accounts payable and accrued expenses
|
$
|
318
|
|
|
$
|
124
|
|
|
Level 1
|
|
Level 2
|
|
Level 3
|
|
Total
|
||||||||
Cash equivalents
|
$
|
88,556
|
|
|
$
|
19,993
|
|
|
$
|
—
|
|
|
$
|
108,549
|
|
Marketable securities:
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
—
|
|
|
11,185
|
|
|
—
|
|
|
11,185
|
|
||||
U.S. Treasuries
|
151,814
|
|
|
—
|
|
|
—
|
|
|
151,814
|
|
||||
Government securities
|
53,131
|
|
|
13,701
|
|
|
—
|
|
|
66,832
|
|
||||
Corporate debt securities
|
—
|
|
|
279,160
|
|
|
—
|
|
|
279,160
|
|
||||
Total cash equivalents and marketable securities
|
$
|
293,501
|
|
|
$
|
324,039
|
|
|
$
|
—
|
|
|
$
|
617,540
|
|
|
Amortized
Cost |
|
Unrealized
Gains |
|
Unrealized
Losses |
|
Fair
Value |
||||||||
Current:
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
$
|
10,240
|
|
|
$
|
1
|
|
|
$
|
(10
|
)
|
|
$
|
10,231
|
|
U.S Treasuries
|
113,824
|
|
|
4
|
|
|
(45
|
)
|
|
113,783
|
|
||||
Government securities
|
42,443
|
|
|
—
|
|
|
(32
|
)
|
|
42,411
|
|
||||
Corporate debt securities
|
208,850
|
|
|
3
|
|
|
(91
|
)
|
|
208,762
|
|
||||
Non-current:
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
960
|
|
|
—
|
|
|
(6
|
)
|
|
954
|
|
||||
U.S Treasuries
|
38,162
|
|
|
—
|
|
|
(131
|
)
|
|
38,031
|
|
||||
Government securities
|
24,492
|
|
|
—
|
|
|
(71
|
)
|
|
24,421
|
|
||||
Corporate debt securities
|
70,535
|
|
|
2
|
|
|
(139
|
)
|
|
70,398
|
|
||||
|
$
|
509,506
|
|
|
$
|
10
|
|
|
$
|
(525
|
)
|
|
$
|
508,991
|
|
|
Amortized
Cost |
|
Unrealized
Gains |
|
Unrealized
Losses |
|
Fair
Value |
||||||||
Current:
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
$
|
11,280
|
|
|
$
|
2
|
|
|
$
|
(3
|
)
|
|
$
|
11,279
|
|
U.S. Treasuries
|
141,678
|
|
|
2
|
|
|
(62
|
)
|
|
141,618
|
|
||||
Government securities
|
19,533
|
|
|
—
|
|
|
(23
|
)
|
|
19,510
|
|
||||
Corporate debt securities
|
208,285
|
|
|
3
|
|
|
(135
|
)
|
|
208,153
|
|
||||
Non-current:
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
7,600
|
|
|
6
|
|
|
(13
|
)
|
|
7,593
|
|
||||
Government securities
|
4,499
|
|
|
—
|
|
|
(21
|
)
|
|
4,478
|
|
||||
Corporate debt securities
|
20,248
|
|
|
—
|
|
|
(69
|
)
|
|
20,179
|
|
||||
|
$
|
413,123
|
|
|
$
|
13
|
|
|
$
|
(326
|
)
|
|
$
|
412,810
|
|
Program
|
Milestone
|
Amount
|
||
65/35 program in IO field
|
Specified clinical development event
|
|
$25.0
|
million
|
65/35 program in IO field
|
Specified regulatory milestone events
|
Up to $183.8
|
million
|
|
50/50 program in IO field
|
Specified clinical development event
|
|
$20.0
|
million
|
50/50 program in IO field
|
Specified regulatory milestone events
|
Up to $148.8
|
million
|
|
I&I field
|
Specified clinical development event
|
|
$25.0
|
million
|
I&I field
|
Specified regulatory milestone events
|
Up to $236.3
|
million
|
|
I&I field
|
Specified commercial milestone events
|
Up to $125.0
|
million
|
Undelivered Element
|
BESP
|
Unit(s) of Accounting
|
Principal/Agent
|
Recognition Method
|
||
April 2015 modification
|
||||||
AG-881 program licenses (1)
|
|
$33.2
|
million
|
2
|
Principal
|
Upon delivery of the licenses to Celgene, which occurred immediately upon the execution of the AG-881 Agreements
|
On-going development services (2) (3)
|
|
$12.7
|
million
|
4
|
Principal
|
Proportionally as services are delivered over the performance period, expected to be through September 2017
|
On-going development services (2) (3)
|
|
$97.3
|
million
|
4
|
Agent
|
Proportionally as services are delivered over the performance period, expected to be through December 2017
|
On-going research and development (2)
|
|
$30.5
|
million
|
1
|
Principal
|
Ratably over the performance period, expected to be through April 2016
|
Committee participations (4)
|
|
$0.8
|
million
|
1
|
Principal
|
Ratably over the performance period, expected to be through December 2016
|
May 2016 modification (supplants undelivered elements of April 2015 modification)
|
||||||
On-going development services (2) (3)
|
|
$67.8
|
million
|
3
|
Principal
|
Proportionally as services are delivered over the performance period, expected to be through December 2019
|
On-going development services (2) (3)
|
|
$22.4
|
million
|
3
|
Agent
|
Proportionally as services are delivered over the performance period, expected to be through December 2019
|
On-going research and development (2)
|
|
$207.0
|
million
|
1
|
Principal
|
Ratably over the performance period, expected to be through May 2022
|
Committee participations (4)
|
|
$1.5
|
million
|
1
|
Principal
|
Ratably over the performance period, expected to be through December 2022
|
Additional development services
|
|
$48.7
|
million
|
1
|
Principal
|
Proportionally as services are delivered over the performance period, expected to begin in September 2020
|
(1)
|
The BESP was developed by probability weighting multiple cash flow scenarios using the income approach. Our management estimates within the models include the expected, probability-weighted net profits from estimated future sales, an estimate of the direct cost incurred to generate future cash flows, a discount rate and other business forecast factors. There are significant judgments and estimates inherent in the determination of the BESP of these units of accounting. These judgments and estimates include assumptions regarding future operating performance, the timelines of the clinical trials and regulatory approvals, and other factors. If different reasonable assumptions are utilized, the BESP and revenue recognized would vary.
|
(2)
|
The BESP was developed using our management’s best estimate of the cost of obtaining these services at arm’s length from a third-party provider.
|
(3)
|
The BESP was developed using internal full time equivalent costs to support the development services.
|
(4)
|
The BESP was developed using our management’s best estimate of the anticipated participation hours and the market rate for comparable participants.
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
Undelivered Element
|
2017
|
|
2016
|
|
2017
|
|
2016
|
||||||||
April 2015 modification
|
|
|
|
|
|
|
|
||||||||
AG-881 program licenses
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
1,356
|
|
On-going development services (principal)
|
—
|
|
|
—
|
|
|
—
|
|
|
1,656
|
|
||||
On-going research and development
|
—
|
|
|
—
|
|
|
—
|
|
|
4,584
|
|
||||
Committee participations
|
—
|
|
|
—
|
|
|
—
|
|
|
89
|
|
||||
May 2016 modification
|
|
|
|
|
|
|
|
||||||||
On-going development services (principal)
|
3,283
|
|
|
3,134
|
|
|
10,895
|
|
|
4,797
|
|
||||
On-going research and development
|
6,425
|
|
|
5,814
|
|
|
19,479
|
|
|
8,516
|
|
||||
Committee participations
|
41
|
|
|
37
|
|
|
124
|
|
|
54
|
|
||||
Total collaboration revenue - related party
|
$
|
9,749
|
|
|
$
|
8,985
|
|
|
$
|
30,498
|
|
|
$
|
21,052
|
|
|
Modification
Period |
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
Undelivered Element
|
2017
|
|
2016
|
|
2017
|
|
2016
|
|||||||||
On-going development services (agent)
|
April 2015
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
7,456
|
|
On-going development services (agent)
|
May 2016
|
1,078
|
|
|
3,453
|
|
|
6,329
|
|
|
4,780
|
|
||||
Total reduction of research and development expenses
|
|
$
|
1,078
|
|
|
$
|
3,453
|
|
|
$
|
6,329
|
|
|
$
|
12,236
|
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
|
2017
|
|
2016
|
|
2017
|
|
2016
|
||||||||
Collaboration revenue - related party
|
|
|
|
|
|
|
|
||||||||
Development activities
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
1,192
|
|
Commercialization activities
|
$
|
894
|
|
|
$
|
—
|
|
|
$
|
1,999
|
|
|
$
|
—
|
|
Reduction of research and development expenses
|
|
|
|
|
|
|
|
||||||||
Development activities
|
$
|
—
|
|
|
$
|
585
|
|
|
$
|
14
|
|
|
$
|
6,518
|
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
|
2017
|
|
2016
|
|
2017
|
|
2016
|
||||||||
Collaboration revenue - related party
|
$
|
10,643
|
|
|
$
|
8,985
|
|
|
$
|
32,497
|
|
|
$
|
22,244
|
|
Reduction of research and development expenses
|
$
|
1,078
|
|
|
$
|
4,038
|
|
|
$
|
6,343
|
|
|
$
|
18,754
|
|
|
September 30,
2017 |
|
December 31,
2016 |
||||
Accrued compensation
|
$
|
11,273
|
|
|
$
|
11,092
|
|
Accrued research and development costs
|
16,043
|
|
|
20,266
|
|
||
Accrued professional fees
|
3,089
|
|
|
476
|
|
||
Accrued other
|
355
|
|
|
168
|
|
||
Total accrued expenses
|
$
|
30,760
|
|
|
$
|
32,002
|
|
|
Number of
Stock Options
|
|
Weighted-
Average
Exercise
Price
|
|||
Outstanding at December 31, 2016
|
5,218,880
|
|
|
$
|
46.79
|
|
Granted
|
1,494,252
|
|
|
50.61
|
|
|
Exercised
|
(529,618
|
)
|
|
19.31
|
|
|
Forfeited/expired
|
(362,903
|
)
|
|
72.43
|
|
|
Outstanding at September 30, 2017
|
5,820,611
|
|
|
$
|
48.68
|
|
Exercisable at September 30, 2017
|
2,969,761
|
|
|
$
|
41.87
|
|
Vested and expected to vest at September 30, 2017
|
5,820,611
|
|
|
$
|
48.68
|
|
|
Number of
Stock Units
|
|
Weighted-Average
Grant Date Fair Value
|
|||
Unvested shares at December 31, 2016
|
77,050
|
|
|
$
|
49.60
|
|
Granted
|
60,750
|
|
|
51.04
|
|
|
Vested
|
(7,500
|
)
|
|
122.22
|
|
|
Forfeited/expired
|
(10,300
|
)
|
|
39.76
|
|
|
Unvested shares at September 30, 2017
|
120,000
|
|
|
$
|
46.63
|
|
|
Number of
Stock Units
|
|
Weighted-Average
Grant Date Fair Value
|
|||
Unvested shares at December 31, 2016
|
200,613
|
|
|
$
|
53.36
|
|
Granted
|
16,391
|
|
|
50.83
|
|
|
Vested
|
—
|
|
|
—
|
|
|
Forfeited/expired
|
(25,630
|
)
|
|
51.00
|
|
|
Unvested shares at September 30, 2017
|
191,374
|
|
|
$
|
53.46
|
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
|
2017
|
|
2016
|
|
2017
|
|
2016
|
||||||||
Stock options
|
$
|
11,330
|
|
|
$
|
11,425
|
|
|
$
|
32,315
|
|
|
$
|
30,288
|
|
Restricted stock units
|
634
|
|
|
510
|
|
|
2,104
|
|
|
1,367
|
|
||||
Performance-based stock options
|
—
|
|
|
—
|
|
|
—
|
|
|
46
|
|
||||
Employee Stock Purchase Plan
|
243
|
|
|
208
|
|
|
709
|
|
|
545
|
|
||||
Total stock-based compensation expense
|
$
|
12,207
|
|
|
$
|
12,143
|
|
|
$
|
35,128
|
|
|
$
|
32,246
|
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
|
2017
|
|
2016
|
|
2017
|
|
2016
|
||||||||
Research and development expense
|
$
|
7,620
|
|
|
$
|
7,903
|
|
|
$
|
22,835
|
|
|
$
|
19,992
|
|
General and administrative expense
|
4,587
|
|
|
4,240
|
|
|
12,293
|
|
|
12,254
|
|
||||
Total stock-based compensation expense
|
$
|
12,207
|
|
|
$
|
12,143
|
|
|
$
|
35,128
|
|
|
$
|
32,246
|
|
|
Three and Nine Months Ended September 30,
|
||||
|
2017
|
|
2016
|
||
Stock options
|
5,820,611
|
|
|
5,431,068
|
|
Restricted stock units
|
120,000
|
|
|
66,300
|
|
Employee Stock Purchase Plan options
|
5,348
|
|
|
5,977
|
|
Total common stock equivalents
|
5,945,959
|
|
|
5,503,345
|
|
•
|
establishing an appropriate safety profile with investigational new drug application, or IND, and/or new drug application, or NDA, enabling toxicology and clinical studies;
|
•
|
the successful enrollment in, and completion of, clinical trials;
|
•
|
the receipt of marketing approvals from applicable regulatory authorities;
|
•
|
establishing compliant commercial manufacturing capabilities or making arrangements with third-party manufacturers;
|
•
|
obtaining and maintaining patent and trade secret protection, and regulatory exclusivity for our product candidates;
|
•
|
launching commercial sales of the products, if and when approved, whether alone or in collaboration with others; and
|
•
|
maintaining an acceptable safety profile of the products following approval.
|
•
|
employee-related expenses, including salaries, benefits and stock-based compensation expense;
|
•
|
expenses incurred under agreements with third parties, including contract research organizations, or CROs, that conduct research and development and both preclinical and clinical activities on our behalf, and the cost of consultants;
|
•
|
the cost of lab supplies and acquiring, developing and manufacturing preclinical and clinical study materials; and
|
•
|
facilities, depreciation, and other expenses, which include direct and allocated expenses for rent and the maintenance of facilities, insurance and other operating costs.
|
|
Three Months Ended September 30,
|
|
|
|
|
|||||||||
|
2017
|
|
2016
|
|
$ Change
|
|
% Change
|
|||||||
Collaboration revenue – related party
|
$
|
10,643
|
|
|
$
|
8,985
|
|
|
$
|
1,658
|
|
|
18
|
%
|
Royalty revenue – related party
|
715
|
|
|
—
|
|
|
715
|
|
|
100
|
%
|
|||
Total revenue
|
11,358
|
|
|
8,985
|
|
|
2,373
|
|
|
26
|
%
|
|||
Operating expenses:
|
|
|
|
|
|
|
|
|||||||
Research and development (net of $1,078 and $4,038 of cost reimbursement from related party for the three months ended September 30, 2017 and 2016, respectively)
|
72,917
|
|
|
60,643
|
|
|
12,274
|
|
|
20
|
%
|
|||
General and administrative
|
17,458
|
|
|
11,854
|
|
|
5,604
|
|
|
47
|
%
|
|||
Loss from operations
|
(79,017
|
)
|
|
(63,512
|
)
|
|
(15,505
|
)
|
|
24
|
%
|
|||
Interest income
|
1,880
|
|
|
678
|
|
|
1,202
|
|
|
177
|
%
|
|||
Net loss
|
$
|
(77,137
|
)
|
|
$
|
(62,834
|
)
|
|
$
|
(14,303
|
)
|
|
23
|
%
|
|
Three Months Ended September 30,
|
|
|
|
|
|||||||||
|
2017
|
|
2016
|
|
$ Change
|
|
% Change
|
|||||||
IDH2 inhibitor (IDHIFA
®
)
|
$
|
1,558
|
|
|
$
|
3,744
|
|
|
$
|
(2,186
|
)
|
|
(58
|
)%
|
IDHIFA
®
reduction of R&D expenses
|
—
|
|
|
(585
|
)
|
|
585
|
|
|
(100
|
)%
|
|||
IDH1 inhibitor (ivosidenib)
|
34,496
|
|
|
26,222
|
|
|
8,274
|
|
|
32
|
%
|
|||
Pan-IDH inhibitor (AG-881)
|
3,309
|
|
|
5,713
|
|
|
(2,404
|
)
|
|
(42
|
)%
|
|||
AG-881 reduction of R&D expenses
|
(1,078
|
)
|
|
(3,453
|
)
|
|
2,375
|
|
|
(69
|
)%
|
|||
PKR activator (AG-348)
|
10,882
|
|
|
4,442
|
|
|
6,440
|
|
|
145
|
%
|
|||
MTAP-deleted cancers program (AG-270)
|
5,748
|
|
|
4,275
|
|
|
1,473
|
|
|
34
|
%
|
|||
Discontinued backup PKR activator (AG-519)
|
58
|
|
|
9,112
|
|
|
(9,054
|
)
|
|
(99
|
)%
|
|||
Other research and platform programs
|
17,944
|
|
|
11,173
|
|
|
6,771
|
|
|
61
|
%
|
|||
Total research and development expenses, net
|
$
|
72,917
|
|
|
$
|
60,643
|
|
|
$
|
12,274
|
|
|
20
|
%
|
•
|
IDHIFA® costs decreased as a result of less internal and external expenses related to ongoing translational work on clinical and preclinical biomarkers.
|
•
|
Ivosidenib costs increased as a result of: (i) start-up costs for the AGILE clinical trial; (ii) initiation of the ClarIDHy clinical trial; (iii) the ongoing enrollment in the expansion portion of the phase 1 clinical trial evaluating single agent ivosidenib in patients with IDH1 mutant-positive advanced hematologic malignancies; and (iv) other research and development activities, including manufacturing-related activities, needed to prepare for a potential NDA submission in 2017.
|
•
|
AG-881 costs decreased as our phase 1 trial in patients with advanced IDH1 or IDH2 mutant-positive hematologic malignancies and our phase 1 trial in IDH1 or IDH2 mutant-positive advanced solid tumors, including glioma, both completed their dose escalation portions. However, we continue to incur costs related to patients still on both studies and planning for future development.
|
•
|
AG-348 costs increased as a result of the selection of AG-348 instead of AG-519, which occurred in the fourth quarter of 2016.
|
•
|
AG-270 costs increased as we prepare for a potential IND filing in 2017.
|
•
|
AG-519 costs decreased as a result of the selection of AG-348 instead of AG-519, which occurred in the fourth quarter of 2016.
|
•
|
The increase in the costs of other research and platform programs include activities related to exploratory efforts, target validation and lead optimization for our discovery and follow-on programs, and our proprietary metabolomics platform.
|
|
Nine Months Ended September 30,
|
|
|
|
|
|||||||||
|
2017
|
|
2016
|
|
$ Change
|
|
% Change
|
|||||||
Collaboration revenue – related party
|
$
|
32,497
|
|
|
$
|
47,244
|
|
|
$
|
(14,747
|
)
|
|
(31
|
)%
|
Royalty revenue – related party
|
715
|
|
|
—
|
|
|
715
|
|
|
100
|
%
|
|||
Total revenue
|
33,212
|
|
|
47,244
|
|
|
(14,032
|
)
|
|
(30
|
)%
|
|||
Operating expenses:
|
|
|
|
|
|
|
|
|||||||
Research and development (net of $6,343 and $18,754 of cost reimbursement from related party for the nine months ended September 30, 2017 and 2016, respectively)
|
215,465
|
|
|
155,485
|
|
|
59,980
|
|
|
39
|
%
|
|||
General and administrative
|
48,411
|
|
|
35,335
|
|
|
13,076
|
|
|
37
|
%
|
|||
Loss from operations
|
(230,664
|
)
|
|
(143,576
|
)
|
|
(87,088
|
)
|
|
61
|
%
|
|||
Interest income
|
4,279
|
|
|
1,591
|
|
|
2,688
|
|
|
169
|
%
|
|||
Net loss
|
$
|
(226,385
|
)
|
|
$
|
(141,985
|
)
|
|
$
|
(84,400
|
)
|
|
59
|
%
|
|
Nine Months Ended September 30,
|
|
|
|
|
|||||||||
|
2017
|
|
2016
|
|
$ Change
|
|
% Change
|
|||||||
IDH2 inhibitor (IDHIFA
®
)
|
$
|
5,023
|
|
|
$
|
9,260
|
|
|
$
|
(4,237
|
)
|
|
(46
|
)%
|
IDHIFA
®
reduction of R&D expenses
|
(14
|
)
|
|
(1,824
|
)
|
|
1,810
|
|
|
(99
|
)%
|
|||
IDH1 inhibitor (ivosidenib)
|
104,157
|
|
|
69,794
|
|
|
34,363
|
|
|
49
|
%
|
|||
Ivosidenib reduction of R&D expenses (1)
|
—
|
|
|
(9,873
|
)
|
|
9,873
|
|
|
(100
|
)%
|
|||
Pan-IDH inhibitor (AG-881)
|
14,517
|
|
|
15,448
|
|
|
(931
|
)
|
|
(6
|
)%
|
|||
AG-881 reduction of R&D expenses
|
(6,329
|
)
|
|
(7,057
|
)
|
|
728
|
|
|
(10
|
)%
|
|||
PKR activator (AG-348)
|
29,172
|
|
|
14,633
|
|
|
14,539
|
|
|
99
|
%
|
|||
MTAP-deleted cancers program (AG-270)
|
15,381
|
|
|
12,336
|
|
|
3,045
|
|
|
25
|
%
|
|||
Discontinued backup PKR activator (AG-519)
|
3,600
|
|
|
18,654
|
|
|
(15,054
|
)
|
|
(81
|
)%
|
|||
Other research and platform programs
|
49,958
|
|
|
34,114
|
|
|
15,844
|
|
|
46
|
%
|
|||
Total research and development expenses, net
|
$
|
215,465
|
|
|
$
|
155,485
|
|
|
$
|
59,980
|
|
|
39
|
%
|
(1)
|
Celgene and we agreed to terminate the 2010 Agreement, effective as of August 15, 2016, as to the program directed to the IDH1 target, for which ivosidenib is the lead development candidate. As a result of the termination, we obtained global development and commercial rights to ivosidenib and the IDH1 program and expect to fund all the future development and commercialization costs related to the program. For the
nine months ended September 30, 2016
,
we recognized a reduction in R&D expenses of
$9.9 million
for ivosidenib related to the 2010 Agreement. As a result of the termination of the 2010 Agreement, we did not recognize a reduction in R&D expenses for the
nine months ended September 30, 2017
and do not expect to recognize reductions in the future.
|
•
|
IDHIFA® costs decreased as a result of less internal and external expenses related to ongoing translational work on clinical and preclinical biomarkers.
|
•
|
Ivosidenib costs increased as a result of: (i) start-up costs for the AGILE clinical trial; (ii) initiation of the ClarIDHy clinical trial; (iii) the ongoing enrollment in the expansion portion of the phase 1 clinical trial evaluating single agent ivosidenib in patients with IDH1 mutant-positive advanced hematologic malignancies; and (iv) research and development activities, including manufacturing-related activities, needed to prepare for a potential NDA submission in 2017.
|
•
|
AG-881 costs decreased as our phase 1 trial in patients with advanced IDH1 or IDH2 mutant-positive hematologic malignancies and our phase 1 trial in IDH1 or IDH2 mutant-positive advanced solid tumors, including glioma, both completed their dose escalation portions. However, we continue to incur costs related to patients still on both studies and planning for future development.
|
•
|
AG-348 costs increased as a result of the selection of AG-348 instead of AG-519, which occurred in the fourth quarter of 2016.
|
•
|
AG-270 costs increased as we prepare for a potential IND filing in 2017.
|
•
|
AG-519 costs decreased as a result of the selection of AG-348 instead of AG-519, which occurred in the fourth quarter of 2016.
|
•
|
The increase in the costs of other research and platform programs include activities related to exploratory efforts, target validation and lead optimization for our discovery and follow-on programs, and our proprietary metabolomics platform.
|
|
Nine Months Ended September 30,
|
||||||
|
2017
|
|
2016
|
||||
Net cash (used in) provided by operating activities
|
$
|
(210,778
|
)
|
|
$
|
89,785
|
|
Net cash used in investing activities
|
(99,756
|
)
|
|
(41,832
|
)
|
||
Net cash provided by financing activities
|
282,521
|
|
|
165,785
|
|
||
Net change in cash and cash equivalents
|
$
|
(28,013
|
)
|
|
$
|
213,738
|
|
•
|
the scope, progress, results and costs of drug discovery, preclinical development, laboratory testing and clinical trials for our product candidates;
|
•
|
the success of our collaborations;
|
•
|
the extent to which we acquire or in-license other medicines and technologies;
|
•
|
the costs, timing and outcome of regulatory review of our product candidates;
|
•
|
the costs associated with preparation for the potential commercial launch of one or more of our product candidates;
|
•
|
the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; and
|
•
|
our ability to establish and maintain additional collaborations on favorable terms, if at all.
|
•
|
initiate and continue clinical trials for our product candidates, including: ivosidenib, AG-881 and AG-348;
|
•
|
continue our research and preclinical development of our product candidates;
|
•
|
seek to identify additional product candidates;
|
•
|
seek marketing approvals for our product candidates that successfully complete clinical trials;
|
•
|
establish a sales, marketing and distribution infrastructure to commercialize any medicines for which we may obtain marketing approval;
|
•
|
require the manufacture of larger quantities of product candidates for clinical development and, potentially, commercialization;
|
•
|
maintain, expand and protect our intellectual property portfolio;
|
•
|
hire additional clinical, quality control and scientific personnel;
|
•
|
add additional personnel to support our product development and planned future commercialization efforts and our operations;
|
•
|
add equipment and physical infrastructure to support our research and development; and
|
•
|
acquire or in-license other medicines and technologies.
|
•
|
the scope, progress, results and costs of drug discovery, preclinical development, laboratory testing and clinical trials for our product candidates;
|
•
|
the success of, and developments regarding, our collaborations;
|
•
|
the costs, timing and outcome of regulatory review of our product candidates;
|
•
|
the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims;
|
•
|
our ability to establish and maintain additional collaborations on favorable terms, if at all; and
|
•
|
the extent to which we acquire or in-license other medicines and technologies.
|
•
|
the research methodology used may not be successful in identifying appropriate biomarkers or potential product candidates; or
|
•
|
potential product candidates may, on further study, be shown to have harmful side effects or other characteristics that indicate that they are unlikely to be medicines that will receive marketing approval and achieve market acceptance.
|
•
|
successful enrollment in, and completion of, clinical trials;
|
•
|
safety, tolerability and efficacy profiles that are satisfactory to the U.S. Food and Drug Administration, or FDA, or any comparable foreign regulatory authority for marketing approval;
|
•
|
timely receipt of marketing approvals from applicable regulatory authorities;
|
•
|
establishing both clinical and commercial manufacturing capabilities or making arrangements with third-party manufacturers;
|
•
|
the performance of our collaborators;
|
•
|
obtaining and maintaining patent and trade secret protection and non-patent exclusivity for our medicines;
|
•
|
launching commercial sales of the medicines, if and when approved, whether alone or in collaboration with others;
|
•
|
acceptance of the medicines, if and when approved, by patients, the medical community and third-party payors;
|
•
|
effectively competing with other therapies;
|
•
|
continuing acceptable safety profile for the medicines following approval;
|
•
|
enforcing and defending intellectual property rights and claims; and
|
•
|
achieving desirable medicinal properties for the intended indications.
|
•
|
be delayed in obtaining marketing approval for our product candidates;
|
•
|
not obtain marketing approval at all;
|
•
|
obtain approval for indications or patient populations that are not as broad as intended or desired;
|
•
|
obtain approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings;
|
•
|
be subject to additional post-marketing testing requirements; or
|
•
|
have the medicine removed from the market after obtaining marketing approval.
|
•
|
regulators or institutional review boards may not authorize us, our collaborators or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;
|
•
|
we or our collaborators may have delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;
|
•
|
clinical trials of our product candidates may produce negative or inconclusive results, and we or our collaborators may decide, or regulators may require us, to conduct additional clinical trials, including testing in more subjects, or abandon product development programs;
|
•
|
the number of patients required for clinical trials of our product candidates may be larger than we anticipate; enrollment in these clinical trials, which may be particularly challenging for some of the orphan diseases we target in our RGD programs, may be slower than we anticipate; or participants may drop out of these clinical trials at a higher rate than we anticipate;
|
•
|
third-party contractors used by us or our collaborators may fail to comply with regulatory requirements or meet their contractual obligations in a timely manner, or at all;
|
•
|
we or our collaborators might have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks;
|
•
|
regulators, institutional review boards, or the data safety monitoring board for such trials may require that we, our collaborators or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;
|
•
|
the cost of clinical trials of our product candidates may be greater than anticipated;
|
•
|
the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; and
|
•
|
our product candidates may have undesirable side effects or other unexpected characteristics, causing us, our collaborators or our investigators, regulators or institutional review boards to suspend or terminate the trials.
|
•
|
severity of the disease under investigation;
|
•
|
availability and efficacy of approved medications for the disease under investigation;
|
•
|
eligibility criteria for the study in question;
|
•
|
perceived risks and benefits of the product candidate under study;
|
•
|
efforts to facilitate timely enrollment in clinical trials;
|
•
|
patient referral practices of physicians;
|
•
|
the ability to monitor patients adequately during and after treatment; and
|
•
|
proximity and availability of clinical trial sites for prospective patients.
|
•
|
the development of our therapeutic product candidates may be adversely affected if we are unable to appropriately select patients for enrollment in our clinical trials;
|
•
|
our therapeutic product candidates may not receive marketing approval if safe and effective use of a therapeutic product candidate depends on an in vitro diagnostic; and
|
•
|
we may not realize the full commercial potential of any therapeutics that receive marketing approval if, among other reasons, we are unable to appropriately select patients who are likely to benefit from therapy with our medicines.
|
•
|
regulatory authorities may withdraw their approval of the product or seize the product;
|
•
|
we, or any future collaborators, may be required to recall the product, change the way the product is administered or conduct additional clinical trials;
|
•
|
additional restrictions may be imposed on the marketing of, or the manufacturing processes for, the particular product;
|
•
|
we may be subject to fines, injunctions or the imposition of civil or criminal penalties;
|
•
|
regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication, including, for example, the black box warning for differentiation syndrome on the label for IDHIFA®;
|
•
|
we, or any future collaborators, may be required to create a Medication Guide outlining the risks of the previously unidentified side effects for distribution to patients;
|
•
|
we, or any future collaborators, could be sued and held liable for harm caused to patients;
|
•
|
the product may become less competitive; and
|
•
|
our reputation may suffer.
|
•
|
efficacy and potential advantages compared to alternative treatments;
|
•
|
the approval, availability, market acceptance and reimbursement for the companion diagnostic;
|
•
|
the ability to offer our medicines for sale at competitive prices;
|
•
|
convenience and ease of administration compared to alternative treatments;
|
•
|
the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
|
•
|
ensuring uninterrupted product supply;
|
•
|
the strength of marketing and distribution support;
|
•
|
sufficient third-party coverage or reimbursement; and
|
•
|
the prevalence and severity of any side effects.
|
•
|
our inability to recruit and retain adequate numbers of effective sales and marketing personnel;
|
•
|
the inability of sales personnel to obtain access to physicians or persuade adequate numbers of physicians to prescribe any future medicines;
|
•
|
the lack of complementary medicines to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and
|
•
|
unforeseen costs and expenses associated with creating an independent sales and marketing organization.
|
•
|
decreased demand for any product candidates or medicines that we may develop;
|
•
|
injury to our reputation and significant negative media attention;
|
•
|
withdrawal of clinical trial participants;
|
•
|
significant costs to defend the related litigation;
|
•
|
substantial monetary awards to trial participants or patients;
|
•
|
loss of revenue;
|
•
|
reduced resources of our management to pursue our business strategy; and
|
•
|
the inability to commercialize any medicines that we may develop.
|
•
|
Collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations. Under the 2010 Agreement, the AG-881 Agreements and programs under a co-development and co-commercialization agreement pursuant to the 2016 Agreement, development and commercialization plans and strategies for licensed programs, such as IDHIFA®, will be conducted in accordance with a plan and budget approved by a joint committee comprised of equal numbers of representatives from each of us and Celgene, as to which Celgene may have final decision-making authority. For example, Celgene has elected not to participate in our planned perioperative study of ivosidenib and AG-881 in patients with low grade glioma and, pursuant to the AG-881 Agreements, we will fund the trial ourselves.
|
•
|
Collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities. For example, under the 2016 Agreement, it is possible for Celgene to elect not to progress into preclinical development a product candidate that we have nominated and the joint research committee confirmed, without triggering a termination of the collaboration arrangement.
|
•
|
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, which may result in a need for additional capital to pursue further development or commercialization of the applicable product candidate. For example, under the 2010 Agreement and the 2016 Agreement, it is possible for Celgene to terminate the agreement, upon 90 days prior written notice, with respect to any product candidate at any point in the research, development and clinical trial process, without triggering a termination of the remainder of the collaboration arrangement.
|
•
|
Collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our medicines or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours.
|
•
|
Collaborators with marketing and distribution rights to one or more medicines may not commit sufficient resources to the marketing and distribution of such medicine or medicines.
|
•
|
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 proprietary information or expose us to potential litigation. For example, under specified circumstances Celgene has the first right to maintain or defend our intellectual property rights with respect to IDHIFA® under the 2010 Agreement and, although we may have the right to assume the maintenance and defense of
|
•
|
Disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our medicines or product candidates or that result in costly litigation or arbitration that diverts management attention and resources.
|
•
|
We may lose certain valuable rights under circumstances identified in our collaborations, including, in the case of our agreements with Celgene, if we undergo a change of control.
|
•
|
Collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates. For example, Celgene can terminate its agreements with us, in their entirety or with respect to IDHIFA® under the 2010 Agreement or any program under the 2016 Agreement, upon 90 days’ notice and can terminate each entire agreement with us in connection with a material breach of the agreement by us that remains uncured for a period ranging from 60 to 90 days.
|
•
|
Collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner or at all.
|
•
|
If a present or future collaborators of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under such collaboration could be delayed, diminished or terminated.
|
•
|
reliance on the third party for regulatory compliance and quality assurance;
|
•
|
the possible breach of the manufacturing agreement by the third party;
|
•
|
the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us; and
|
•
|
reliance on the third party for regulatory compliance, quality assurance, environmental and safety and pharmacovigilance reporting.
|
•
|
restrictions on such medicine, manufacturers or manufacturing processes;
|
•
|
restrictions on the labeling or marketing of a medicine;
|
•
|
restrictions on distribution or use of a medicine;
|
•
|
requirements to conduct post-marketing studies or clinical trials;
|
•
|
warning letters or untitled letters;
|
•
|
withdrawal of the medicine from the market;
|
•
|
refusal to approve pending applications or supplements to approved applications that we submit;
|
•
|
recall of medicines;
|
•
|
damage to relationships with any potential collaborators;
|
•
|
unfavorable press coverage and damage to our reputation;
|
•
|
fines, restitution or disgorgement of profits or revenue;
|
•
|
suspension or withdrawal of marketing approvals;
|
•
|
refusal to permit the import or export of our medicines;
|
•
|
product seizure;
|
•
|
injunctions or the imposition of civil or criminal penalties; and
|
•
|
litigation involving patients using our medicines.
|
•
|
the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or arranging of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid;
|
•
|
the federal False Claims Act imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties, currently set at $10,781.40 to $21,562.80 per false claim;
|
•
|
the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
|
•
|
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;
|
•
|
the federal Physician Payments Sunshine Act requires applicable manufacturers of covered drugs to report payments and other transfers of value to physicians and teaching hospitals; and
|
•
|
analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws and transparency statutes, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers.
|
•
|
an annual, non-deductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents;
|
•
|
an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program;
|
•
|
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;
|
•
|
expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal Anti-Kickback Statute, new government investigative powers and enhanced penalties for noncompliance;
|
•
|
a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% 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;
|
•
|
extension of manufacturers’ Medicaid rebate liability to individuals enrolled in Medicaid managed care organizations;
|
•
|
expansion of eligibility criteria for Medicaid programs;
|
•
|
expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;
|
•
|
new requirements to report certain financial arrangements with physicians and teaching hospitals;
|
•
|
a new requirement to annually report drug samples that manufacturers and distributors provide to physicians;
|
•
|
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research;
|
•
|
a new Independent Payment Advisory Board, or IPAB, which has authority to recommend certain changes to the Medicare program to reduce expenditures by the program that could result in reduced payments for prescription drugs; and
|
•
|
a Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models.
|
•
|
establish a classified board of directors such that not all members of the board are elected at one time;
|
•
|
allow the authorized number of our directors to be changed only by resolution of our board of directors;
|
•
|
limit the manner in which stockholders can remove directors from the board;
|
•
|
establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to our board of directors;
|
•
|
require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by written consent;
|
•
|
limit who may call stockholder meetings;
|
•
|
authorize our board of directors to issue preferred stock without stockholder approval, which could be used to institute a shareholder rights plan, or so-called “poison pill,” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our board of directors; and
|
•
|
require the approval of the holders of at least 75% of the votes that all our stockholders would be entitled to cast to amend or repeal certain provisions of our charter or bylaws.
|
•
|
regulatory actions with respect to our product candidates or our competitors’ products and product candidates;
|
•
|
announcements by us or our competitors of significant acquisitions, strategic partnerships, joint ventures, collaborations or capital commitments;
|
•
|
the timing and results of clinical trials of product candidates;
|
•
|
commencement or termination of collaborations for our development programs;
|
•
|
failure or discontinuation of any of our development programs;
|
•
|
results of clinical trials of product candidates of our competitors;
|
•
|
regulatory or legal developments in the United States and other countries;
|
•
|
developments or disputes concerning patent applications, issued patents or other proprietary rights;
|
•
|
the recruitment or departure of key personnel;
|
•
|
the level of expenses related to any of our product candidates or clinical development programs;
|
•
|
the results of our efforts to develop additional product candidates or products;
|
•
|
actual or anticipated changes in estimates as to financial results or development timelines;
|
•
|
announcement or expectation of additional financing efforts;
|
•
|
sales of our common stock by us, our insiders or other stockholders;
|
•
|
variations in our financial results, including levels of royalties on sales of IDHIFA®, or results of companies that are perceived to be similar to us;
|
•
|
changes in estimates or recommendations by securities analysts, if any, that cover our stock;
|
•
|
changes in the structure of healthcare payment systems;
|
•
|
market conditions in the pharmaceutical and biotechnology sectors;
|
•
|
general economic, industry and market conditions; and
|
•
|
the other factors described in this “Risk Factors” section.
|
|
|
|
Incorporated by Reference
|
|||||||||
Exhibit
Number
|
Description of Exhibit
|
|
Form
|
|
File Number
|
|
Date of Filing
|
|
Exhibit
Number
|
|
Filed
Herewith
|
|
3.1
|
|
8-K
|
|
001-36014
|
|
July 29, 2013
|
|
3.1
|
|
|
|
|
3.2
|
|
8-K
|
|
001-36014
|
|
July 29, 2013
|
|
3.2
|
|
|
|
|
31.1
|
|
|
|
|
|
|
|
|
|
X
|
||
31.2
|
|
|
|
|
|
|
|
|
|
X
|
||
32.1
|
|
|
|
|
|
|
|
|
|
X
|
||
32.2
|
|
|
|
|
|
|
|
|
|
X
|
||
101.INS
|
XBRL Instance Document
|
|
|
|
|
|
|
|
|
|
X
|
|
101.SCH
|
XBRL Taxonomy Extension Schema Document
|
|
|
|
|
|
|
|
|
|
X
|
|
101.CAL
|
XBRL Taxonomy Calculation Linkbase Document
|
|
|
|
|
|
|
|
|
|
X
|
|
101.DEF
|
XBRL Taxonomy Extension Definition Linkbase Document
|
|
|
|
|
|
|
|
|
|
X
|
|
101.LAB
|
XBRL Taxonomy Label Linkbase Document
|
|
|
|
|
|
|
|
|
|
X
|
|
101.PRE
|
XBRL Taxonomy Presentation Linkbase Document
|
|
|
|
|
|
|
|
|
|
X
|
|
AGIOS PHARMACEUTICALS, INC.
|
||
|
|
|
|
Date: November 1, 2017
|
By:
|
|
/s/ David P. Schenkein
|
|
|
|
David P. Schenkein
President and Chief Executive Officer
(principal executive officer)
|
|
|
|
|
Date: November 1, 2017
|
By:
|
|
/s/ Andrew Hirsch
|
|
|
|
Andrew Hirsch
Chief Financial Officer
(principal financial officer)
|
1.
|
I have reviewed this Quarterly Report on Form 10-Q of Agios Pharmaceuticals, Inc.;
|
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;
|
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;
|
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:
|
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;
|
b.
|
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 generally accepted accounting principles;
|
c.
|
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
|
d.
|
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
|
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 functions):
|
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
|
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.
|
|
/s/ David P. Schenkein
|
|
David P. Schenkein
|
|
President and Chief Executive Officer
|
|
(principal executive officer)
|
1.
|
I have reviewed this Quarterly Report on Form 10-Q of Agios Pharmaceuticals, Inc.;
|
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;
|
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;
|
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:
|
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;
|
b.
|
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 generally accepted accounting principles;
|
c.
|
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
|
d.
|
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
|
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 functions):
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a.
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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.
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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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/s/ Andrew Hirsch
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Andrew Hirsch
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Chief Financial Officer
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(principal financial officer)
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(1)
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The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
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(2)
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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/ David P. Schenkein
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David P. Schenkein
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President and Chief Executive Officer
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(principal executive officer)
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(1)
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The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
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(2)
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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/ Andrew Hirsch
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Andrew Hirsch
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Chief Financial Officer
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(principal financial officer)
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