|
|
x
|
QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
|
o
|
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15 (d) OF THE SECURITIES EXCHANGE ACT OF 1934
|
|
|
Delaware
|
|
2836
|
|
20-1450200
|
(State or other jurisdiction of
incorporation or organization)
|
|
(Primary Standard Industrial
Classification Code Number)
|
|
(I.R.S. Employer
Identification Number)
|
|
Large accelerated filer
|
o
|
|
|
Accelerated filer
|
x
|
|
|
|
|
|
|
Non-accelerated filer
|
o
|
(Do not check if a smaller reporting company)
|
|
Smaller reporting company
|
o
|
|
|
|
Page
|
|
|
|
|
|
|||
|
|||
|
|||
|
|||
|
|
|
|
|
|
|
|
|
|
|
|
|
September 30, 2016
|
|
December 31, 2015
|
||||
|
(Unaudited)
|
|
|
||||
ASSETS
|
|
|
|
||||
Current assets:
|
|
|
|
||||
Cash and cash equivalents
|
$
|
48,694
|
|
|
$
|
70,241
|
|
Investment securities, available for sale - short-term
|
56,613
|
|
|
23,820
|
|
||
Accounts receivable, interest and other receivables
|
305
|
|
|
440
|
|
||
Prepaid expenses and other current assets
|
1,975
|
|
|
2,389
|
|
||
Total current assets
|
107,587
|
|
|
96,890
|
|
||
Investment securities, available for sale - long-term
|
23,791
|
|
|
56,304
|
|
||
Property and equipment, net
|
11,064
|
|
|
6,882
|
|
||
Other assets
|
262
|
|
|
330
|
|
||
TOTAL ASSETS
|
$
|
142,704
|
|
|
$
|
160,406
|
|
LIABILITIES AND STOCKHOLDERS’ EQUITY
|
|
|
|
||||
Current liabilities:
|
|
|
|
||||
Accounts payable
|
$
|
1,618
|
|
|
$
|
2,106
|
|
Accrued expenses and other current liabilities
|
6,796
|
|
|
5,080
|
|
||
Current portion of capital lease obligation
|
19
|
|
|
13
|
|
||
Current portion of deferred rent
|
246
|
|
|
246
|
|
||
Total current liabilities
|
8,679
|
|
|
7,445
|
|
||
Long-term liabilities:
|
|
|
|
||||
Long-term debt
|
20,076
|
|
|
—
|
|
||
Capital lease obligation
|
136
|
|
|
118
|
|
||
Deferred rent and other liabilities
|
726
|
|
|
826
|
|
||
TOTAL LIABILITIES
|
29,617
|
|
|
8,389
|
|
||
Commitments and contingencies: (Note: 9)
|
|
|
|
||||
Stockholders’ equity:
|
|
|
|
||||
Preferred stock: $0.01 par value; 10,000,000 shares authorized: no shares issued and outstanding
|
—
|
|
|
—
|
|
||
Common stock, $0.01 par value; 200,000,000 shares authorized at September 30, 2016 and December 31, 2015, 27,774,415 shares issued and 27,096,952 shares outstanding at September 30, 2016; 27,609,344 shares issued and 26,931,881 shares outstanding at December 31, 2015
|
278
|
|
|
276
|
|
||
Treasury stock: 677,463 shares held at September 30, 2016 and December 31, 2015
|
(5,056
|
)
|
|
(5,056
|
)
|
||
Additional paid-in capital
|
328,582
|
|
|
318,591
|
|
||
Accumulated other comprehensive income (loss)
|
78
|
|
|
(302
|
)
|
||
Accumulated deficit
|
(210,795
|
)
|
|
(161,492
|
)
|
||
Total stockholders’ equity
|
113,087
|
|
|
152,017
|
|
||
Total liabilities and stockholders’ equity
|
$
|
142,704
|
|
|
$
|
160,406
|
|
|
|||||||||||||||
|
Three months ended September 30,
|
|
Nine months ended September 30,
|
||||||||||||
|
2016
|
|
2015
|
|
2016
|
|
2015
|
||||||||
REVENUES
|
|
|
|
|
|
|
|
||||||||
Grants
|
$
|
114
|
|
|
$
|
57
|
|
|
$
|
307
|
|
|
$
|
248
|
|
Total revenues
|
114
|
|
|
57
|
|
|
307
|
|
|
248
|
|
||||
OPERATING EXPENSES
|
|
|
|
|
|
|
|
||||||||
Research and development
|
13,290
|
|
|
9,792
|
|
|
36,459
|
|
|
23,522
|
|
||||
General and administrative
|
4,252
|
|
|
3,882
|
|
|
12,715
|
|
|
8,856
|
|
||||
Total operating expenses
|
17,542
|
|
|
13,674
|
|
|
49,174
|
|
|
32,378
|
|
||||
Loss from operations
|
(17,428
|
)
|
|
(13,617
|
)
|
|
(48,867
|
)
|
|
(32,130
|
)
|
||||
OTHER INCOME (EXPENSE):
|
|
|
|
|
|
|
|
||||||||
Interest income
|
224
|
|
|
211
|
|
|
687
|
|
|
432
|
|
||||
Interest expense
|
(515
|
)
|
|
—
|
|
|
(1,123
|
)
|
|
—
|
|
||||
Other expense
|
—
|
|
|
(2
|
)
|
|
—
|
|
|
(2
|
)
|
||||
Total other income (expense)
|
(291
|
)
|
|
209
|
|
|
(436
|
)
|
|
430
|
|
||||
NET LOSS
|
$
|
(17,719
|
)
|
|
$
|
(13,408
|
)
|
|
$
|
(49,303
|
)
|
|
$
|
(31,700
|
)
|
|
|
|
|
|
|
|
|
||||||||
Net loss per common share attributable to common shareholders, basic and diluted
|
$
|
(0.66
|
)
|
|
$
|
(0.51
|
)
|
|
$
|
(1.83
|
)
|
|
$
|
(1.21
|
)
|
Weighted-average shares outstanding, basic and diluted
|
26,966,630
|
|
|
26,376,456
|
|
|
26,919,984
|
|
|
26,301,914
|
|
||||
|
|
|
|
|
|
|
|
||||||||
Net loss
|
$
|
(17,719
|
)
|
|
$
|
(13,408
|
)
|
|
$
|
(49,303
|
)
|
|
$
|
(31,700
|
)
|
Other comprehensive income (loss):
|
|
|
|
|
|
|
|
||||||||
Unrealized gain (loss) on investment securities
|
(18
|
)
|
|
—
|
|
|
380
|
|
|
(204
|
)
|
||||
Comprehensive loss
|
$
|
(17,737
|
)
|
|
$
|
(13,408
|
)
|
|
$
|
(48,923
|
)
|
|
$
|
(31,904
|
)
|
|
|||||||
|
Nine months ended September 30,
|
||||||
|
2016
|
|
2015
|
||||
CASH FLOWS FROM OPERATING ACTIVITIES
|
|
|
|
||||
Net loss
|
$
|
(49,303
|
)
|
|
$
|
(31,700
|
)
|
Adjustments to reconcile net loss to net cash used in operating activities:
|
|
|
|
||||
Share-based compensation
|
9,243
|
|
|
5,938
|
|
||
Depreciation expense
|
1,619
|
|
|
769
|
|
||
Amortization of premium on investment securities, net
|
449
|
|
|
377
|
|
||
Amortization of lease liability
|
(100
|
)
|
|
(54
|
)
|
||
Amortization of deferred financing costs
|
275
|
|
|
—
|
|
||
Loss on disposition of investment securities
|
—
|
|
|
14
|
|
||
Loss on disposition of fixed assets
|
20
|
|
|
2
|
|
||
Changes in operating assets and liabilities:
|
|
|
|
||||
Receivables
|
135
|
|
|
(90
|
)
|
||
Prepaid expenses and other assets
|
482
|
|
|
(681
|
)
|
||
Accounts payable
|
(488
|
)
|
|
325
|
|
||
Accrued liabilities and other
|
1,716
|
|
|
1,510
|
|
||
NET CASH USED IN OPERATING ACTIVITIES
|
(35,952
|
)
|
|
(23,590
|
)
|
||
CASH FLOWS FROM INVESTING ACTIVITIES
|
|
|
|
||||
Purchase of investment securities
|
(26,116
|
)
|
|
(79,100
|
)
|
||
Proceeds from sale of investment securities
|
25,767
|
|
|
7,743
|
|
||
Purchases of property and equipment
|
(5,787
|
)
|
|
(4,597
|
)
|
||
CASH USED IN INVESTING ACTIVITIES
|
(6,136
|
)
|
|
(75,954
|
)
|
||
CASH FLOWS FROM FINANCING ACTIVITIES
|
|
|
|
||||
Proceeds from notes payable
|
20,000
|
|
|
—
|
|
||
Payment of debt issuance costs
|
(199
|
)
|
|
—
|
|
||
Proceeds from exercise of stock options
|
562
|
|
|
—
|
|
||
Proceeds from issuance of common stock - ESPP
|
188
|
|
|
442
|
|
||
Payment of issuance costs on common stock
|
—
|
|
|
(8
|
)
|
||
Payment on capital lease obligation
|
(10
|
)
|
|
(5
|
)
|
||
NET CASH PROVIDED BY FINANCING ACTIVITIES
|
20,541
|
|
|
429
|
|
||
NET CHANGE IN CASH AND CASH EQUIVALENTS
|
(21,547
|
)
|
|
(99,115
|
)
|
||
CASH AND CASH EQUIVALENTS AT BEGINNING OF PERIOD
|
70,241
|
|
|
191,602
|
|
||
CASH AND CASH EQUIVALENTS AT END OF PERIOD
|
$
|
48,694
|
|
|
$
|
92,487
|
|
SUPPLEMENTAL CASH FLOW INFORMATION:
|
|
|
|
||||
Interest paid
|
$
|
710
|
|
|
$
|
—
|
|
NON-CASH INVESTING AND FINANCING ACTIVITIES:
|
|
|
|
||||
Accrued issuance costs for long-term debt
|
$
|
1,390
|
|
|
$
|
—
|
|
Purchases of property and equipment in accounts payables and accrued liabilities
|
$
|
1,066
|
|
|
$
|
—
|
|
Capital lease obligation incurred for property and equipment
|
$
|
34
|
|
|
$
|
65
|
|
|
As of September 30,
|
||||
|
2016
|
|
2015
|
||
Common Stock Equivalents:
|
Number of shares
|
||||
Warrants to purchase common stock
|
—
|
|
|
355,392
|
|
Unvested shares of restricted stock
|
88,236
|
|
|
117,647
|
|
Options to purchase common stock
|
4,501,561
|
|
|
3,547,949
|
|
|
4,589,797
|
|
|
4,020,988
|
|
Office furniture
|
|
5 years
|
Laboratory equipment
|
|
5 years
|
Computer equipment and software
|
|
3 to 5 years
|
Equipment under capital lease
|
|
5 years
|
Leasehold improvements
|
|
Shorter of asset’s useful life or remaining term of lease
|
|
|
|
Fair Value Measurements at Reporting Date
|
||||||||||||
|
Balance at
September 30, 2016 |
|
Quoted prices in active
markets for identical
assets (Level 1)
|
|
Significant other
observable inputs
(Level 2)
|
|
Significant unobservable
inputs (Level 3)
|
||||||||
|
(in thousands)
|
||||||||||||||
Cash Equivalents:
|
|
|
|
|
|
|
|
||||||||
Money market funds
|
$
|
40,440
|
|
|
$
|
40,440
|
|
|
$
|
—
|
|
|
$
|
—
|
|
Total Cash Equivalents
|
$
|
40,440
|
|
|
$
|
40,440
|
|
|
$
|
—
|
|
|
$
|
—
|
|
|
|
|
|
|
|
|
|
||||||||
Investment Securities:
|
|
|
|
|
|
|
|
||||||||
U.S. government agency-backed securities
|
$
|
30,781
|
|
|
$
|
—
|
|
|
$
|
30,781
|
|
|
$
|
—
|
|
Corporate debt securities
|
46,624
|
|
|
—
|
|
|
46,624
|
|
|
—
|
|
||||
Municipal bonds
|
2,999
|
|
|
—
|
|
|
2,999
|
|
|
—
|
|
||||
Total Investment Securities
|
$
|
80,404
|
|
|
$
|
—
|
|
|
$
|
80,404
|
|
|
$
|
—
|
|
|
|
|
Fair Value Measurements at Reporting Date
|
||||||||||||
|
Balance at
December 31, 2015 |
|
Quoted prices in active
markets for identical
assets (Level 1)
|
|
Significant other
observable inputs
(Level 2)
|
|
Significant unobservable
inputs (Level 3)
|
||||||||
|
(in thousands)
|
||||||||||||||
Cash Equivalents:
|
|
|
|
|
|
|
|
||||||||
Money market funds
|
$
|
52,714
|
|
|
$
|
52,714
|
|
|
$
|
—
|
|
|
$
|
—
|
|
U.S. government agency-backed securities
|
9,500
|
|
|
—
|
|
|
9,500
|
|
|
—
|
|
||||
Total Cash Equivalents
|
$
|
62,214
|
|
|
$
|
52,714
|
|
|
$
|
9,500
|
|
|
$
|
—
|
|
|
|
|
|
|
|
|
|
||||||||
Investment Securities:
|
|
|
|
|
|
|
|
||||||||
U.S. government agency-backed securities
|
$
|
22,388
|
|
|
$
|
—
|
|
|
$
|
22,388
|
|
|
$
|
—
|
|
Corporate debt securities
|
51,547
|
|
|
—
|
|
|
51,547
|
|
|
—
|
|
||||
Municipal bonds
|
6,189
|
|
|
—
|
|
|
6,189
|
|
|
—
|
|
||||
Total Investment Securities
|
$
|
80,124
|
|
|
$
|
—
|
|
|
$
|
80,124
|
|
|
$
|
—
|
|
|
Amortized Cost
|
|
Gross Unrealized Gains
|
|
Gross Unrealized Losses
|
|
Aggregate Estimated Fair Value
|
||||||||
|
(in thousands)
|
||||||||||||||
Investment Securities:
|
|
||||||||||||||
U.S. government agency-backed securities
|
$
|
30,755
|
|
|
$
|
27
|
|
|
$
|
(1
|
)
|
|
$
|
30,781
|
|
Corporate debt securities
|
46,572
|
|
|
81
|
|
|
(29
|
)
|
|
46,624
|
|
||||
Municipal bonds
|
2,999
|
|
|
1
|
|
|
(1
|
)
|
|
2,999
|
|
||||
Total Investment Securities
|
$
|
80,326
|
|
|
$
|
109
|
|
|
$
|
(31
|
)
|
|
$
|
80,404
|
|
|
September 30, 2016
|
|
December 31, 2015
|
||||
|
(in thousands)
|
||||||
Accrued manufacturing costs
|
$
|
1,965
|
|
|
$
|
2,412
|
|
Accrued payroll
|
1,338
|
|
|
1,332
|
|
||
Accrued property and equipment purchases
|
1,034
|
|
|
139
|
|
||
Accrued patient treatment costs
|
628
|
|
|
333
|
|
||
Accrued preclinical study costs
|
521
|
|
|
—
|
|
||
Accrued medical facility fees
|
159
|
|
|
282
|
|
||
Accrued other
|
1,151
|
|
|
582
|
|
||
Total accrued expenses and other current liabilities
|
$
|
6,796
|
|
|
$
|
5,080
|
|
A summary of activity within the ESPP follows:
|
Nine months ended September 30,
|
||||||
|
2016
|
|
2015
|
||||
|
(amounts in thousands)
|
||||||
Deductions from employees
|
$
|
290
|
|
|
$
|
296
|
|
Share-based compensation expense recognized
|
$
|
208
|
|
|
$
|
166
|
|
Remaining share-based compensation expense
|
$
|
58
|
|
|
$
|
300
|
|
Proceeds received by the Company for ESPP
|
$
|
188
|
|
|
$
|
159
|
|
Number of shares purchased by employees under ESPP
|
17,115
|
|
9,829
|
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
|
|
2016
|
|
2015
|
|
2016
|
|
2015
|
||||||||
|
|
(in thousands)
|
||||||||||||||
General and administrative
|
|
$
|
1,640
|
|
|
$
|
1,336
|
|
|
$
|
5,063
|
|
|
$
|
3,412
|
|
Research and development
|
|
1,421
|
|
|
966
|
|
|
4,180
|
|
|
2,526
|
|
||||
Total
|
|
$
|
3,061
|
|
|
$
|
2,302
|
|
|
$
|
9,243
|
|
|
$
|
5,938
|
|
|
Options
|
|
Weighted-
Average Exercise Price Per Share |
|
(in years)
Weighted-
Average Contractual Life |
|
(in thousands)
Aggregate
Intrinsic
Value
(1)
|
|||||
Outstanding at December 31, 2015
|
3,628,973
|
|
|
$
|
10.32
|
|
|
8.03
|
|
$
|
39,021
|
|
Granted
|
1,086,457
|
|
|
$
|
17.40
|
|
|
|
|
|
||
Exercised
|
(147,956
|
)
|
|
$
|
3.79
|
|
|
|
|
|
||
Canceled or forfeited
|
(65,913
|
)
|
|
$
|
12.34
|
|
|
|
|
|
||
Outstanding at September 30, 2016
|
4,501,561
|
|
|
$
|
12.22
|
|
|
7.79
|
|
$
|
37,844
|
|
Exercisable at September 30, 2016
|
2,157,935
|
|
|
$
|
7.62
|
|
|
6.71
|
|
$
|
27,779
|
|
•
|
CaspaCIDe is our safety switch, incorporated into our HSCT, and in certain of our TCR, product candidates, where it is inactive unless the patient experiences a serious side effect. In that event, rimiducid is administered to fully or partially eliminate the cells, with the goal of terminating or attenuating the therapy and resolving the serious side effect.
|
•
|
Our “Go” switch incorporated into our GoCAR-T product candidates is designed to allow control of the activation and proliferation of the T cells through the scheduled administration of a course of rimiducid infusions that may continue until the desired patient outcome is achieved. In the event of emergence of side effects, the level of activation of the GoCAR-T cells is designed to be attenuated by extending the interval between rimiducid doses, reducing the dosage per infusion, or suspending further rimiducid administration.
|
•
|
BPX-501
We are developing a CaspaCIDe product candidate, BPX-501, as an adjunct T cell therapy administered after allogeneic HSCT. BPX-501 is designed to improve transplant outcomes by enhancing the recovery of the immune system following an HSCT procedure. BPX-501 addresses the risk of infusing donor T cells by enabling the elimination of donor T cells through the activation of the CaspaCIDe safety switch if there is an emergence of uncontrolled GvHD.
|
•
|
BPX-701
is a CaspaCIDe-enabled natural high affinity T cell receptor, or TCR, product candidate designed to target malignant cells expressing the preferentially-expressed antigen in melanoma, or PRAME. Initial planned indications for BPX-701 development are Refractory or Relapsed Acute Myeloid Leukemia, or AML, and Myelodysplastic Syndromes, or MDS, with an additional study planned for metastatic uveal melanoma. Each of these is an orphan indication where PRAME is highly expressed and for which current treatment options are limited.
|
•
|
BPX-601
is a GoCAR-T product candidate containing our proprietary iMC, inducible MyD88/CD40, activation switch, designed to treat solid tumors expressing prostate stem cell antigen, or PSCA. Preclinical data shows enhanced T cell proliferation, persistence and
in vivo
anti-tumor activity compared to traditional CAR T therapies. The initial planned indication for BPX-601 development is non-resectable pancreatic cancer.
|
•
|
per patient clinical trial costs;
|
•
|
the number of patients that participate in the clinical trials;
|
•
|
the number of sites included in the clinical trials;
|
•
|
the process of collection, differentiation, selection and expansion of immune cells for our cellular immuno-therapies;
|
•
|
the countries in which the clinical trials are conducted;
|
•
|
the outcomes of our clinical trials;
|
•
|
the length of time required to enroll eligible patients;
|
•
|
the number of doses that patients receive;
|
•
|
the drop-out or discontinuation rates of patients;
|
•
|
potential additional safety monitoring or other studies requested by regulatory agencies;
|
•
|
the duration of patient follow-up; and
|
•
|
the efficacy and safety profile of the product candidates.
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||||||||||
|
2016
|
|
2015
|
|
Change
|
|
2016
|
|
2015
|
|
Change
|
||||||||||||
|
(in thousands)
|
|
(in thousands)
|
||||||||||||||||||||
Grant revenues
|
$
|
114
|
|
|
$
|
57
|
|
|
$
|
57
|
|
|
$
|
307
|
|
|
$
|
248
|
|
|
$
|
59
|
|
Operating expenses:
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||||
Research and development
|
13,290
|
|
|
9,792
|
|
|
3,498
|
|
|
36,459
|
|
|
23,522
|
|
|
12,937
|
|
||||||
General and administrative
|
4,252
|
|
|
3,882
|
|
|
370
|
|
|
12,715
|
|
|
8,856
|
|
|
3,859
|
|
||||||
Total operating expenses
|
17,542
|
|
|
13,674
|
|
|
3,868
|
|
|
49,174
|
|
|
32,378
|
|
|
16,796
|
|
||||||
Loss from operations
|
(17,428
|
)
|
|
(13,617
|
)
|
|
(3,811
|
)
|
|
(48,867
|
)
|
|
(32,130
|
)
|
|
(16,737
|
)
|
||||||
Other income (expense):
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||||
Interest income
|
224
|
|
|
211
|
|
|
13
|
|
|
687
|
|
|
432
|
|
|
255
|
|
||||||
Interest expense
|
(515
|
)
|
|
—
|
|
|
(515
|
)
|
|
(1,123
|
)
|
|
—
|
|
|
(1,123
|
)
|
||||||
Other expense
|
—
|
|
|
(2
|
)
|
|
2
|
|
|
—
|
|
|
(2
|
)
|
|
2
|
|
||||||
Total other income (expense)
|
(291
|
)
|
|
209
|
|
|
(500
|
)
|
|
(436
|
)
|
|
430
|
|
|
(866
|
)
|
||||||
Net loss
|
$
|
(17,719
|
)
|
|
$
|
(13,408
|
)
|
|
$
|
(4,311
|
)
|
|
$
|
(49,303
|
)
|
|
$
|
(31,700
|
)
|
|
$
|
(17,603
|
)
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||||||||||
Product Candidates
|
2016
|
|
2015
|
|
Change
|
|
2016
|
|
2015
|
|
Change
|
||||||||||||
|
(in thousands)
|
|
(in thousands)
|
||||||||||||||||||||
BPX-501
|
$
|
6,706
|
|
|
$
|
4,294
|
|
|
$
|
2,412
|
|
|
$
|
19,211
|
|
|
$
|
9,891
|
|
|
$
|
9,320
|
|
BPX-601
|
702
|
|
|
333
|
|
|
369
|
|
|
2,601
|
|
|
525
|
|
|
2,076
|
|
||||||
BPX-701
|
678
|
|
|
648
|
|
|
30
|
|
|
958
|
|
|
1,006
|
|
|
(48
|
)
|
||||||
General
|
5,204
|
|
|
4,517
|
|
|
687
|
|
|
13,689
|
|
|
12,100
|
|
|
1,589
|
|
||||||
Total
|
$
|
13,290
|
|
|
$
|
9,792
|
|
|
$
|
3,498
|
|
|
$
|
36,459
|
|
|
$
|
23,522
|
|
|
$
|
12,937
|
|
|
Nine Months Ended September 30,
|
||||||||||
|
2016
|
|
2015
|
|
Change
|
||||||
|
(in thousands)
|
||||||||||
Net cash used in operating activities
|
$
|
(35,952
|
)
|
|
$
|
(23,590
|
)
|
|
$
|
(12,362
|
)
|
Net cash used in investing activities
|
(6,136
|
)
|
|
(75,954
|
)
|
|
69,818
|
|
|||
Net cash provided by financing activities
|
20,541
|
|
|
429
|
|
|
20,112
|
|
|||
Net change in cash and cash equivalents
|
$
|
(21,547
|
)
|
|
$
|
(99,115
|
)
|
|
$
|
77,568
|
|
•
|
successful enrollment in, and successful completion of, clinical trials;
|
•
|
receipt of marketing approvals from applicable regulatory authorities;
|
•
|
making arrangements with third-party manufacturers;
|
•
|
obtaining and maintaining patent and trade secret protection and regulatory exclusivity;
|
•
|
launching commercial sales of our products, if and when approved, whether alone or in collaboration with others; and
|
•
|
market acceptance of our products, if and when approved.
|
•
|
initiate or continue clinical trials of BPX-501, BPX-701 and BPX-601 and any other product candidates;
|
•
|
continue the research and development of our product candidates; seek to discover additional product candidates; seek regulatory approvals for our product candidates if they successfully complete clinical trials;
|
•
|
establish a sales, marketing and distribution infrastructure and scale-up manufacturing capabilities to commercialize any products that may receive regulatory approval; enhance operational, financial and information management systems and hire additional personnel, including personnel to support development of our product candidates and, if a product candidate is approved, our commercialization efforts; and
|
•
|
incur additional costs associated with being a public company.
|
|
|
Commitment
|
|
Less Than 1 Year
|
|
1 to 3 Years
|
|
3 to 5 Years
|
|
More Than 5 Years
|
||||||||||
|
|
(in thousands)
|
||||||||||||||||||
License agreements (1)
|
|
$
|
143,324
|
|
|
$
|
1,422
|
|
|
$
|
6,112
|
|
|
$
|
8,345
|
|
|
$
|
127,445
|
|
Long-term debt obligations (2)
|
|
20,000
|
|
|
—
|
|
|
15,619
|
|
|
4,381
|
|
|
—
|
|
|||||
Operating lease agreements (3)
|
|
14,206
|
|
|
1,968
|
|
|
4,092
|
|
|
2,427
|
|
|
5,719
|
|
|||||
Manufacturing build-out obligation (4)
|
|
10,341
|
|
|
10,341
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|||||
Manufacturing arrangements (5)
|
|
3,499
|
|
|
2,671
|
|
|
828
|
|
|
—
|
|
|
—
|
|
|||||
Sponsored research agreements (6)
|
|
2,762
|
|
|
1,080
|
|
|
1,682
|
|
|
—
|
|
|
—
|
|
|||||
Preclinical studies (7)
|
|
645
|
|
|
645
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|||||
Capital lease agreements (8)
|
|
265
|
|
|
54
|
|
|
109
|
|
|
102
|
|
|
—
|
|
|||||
Other
|
|
344
|
|
|
272
|
|
|
72
|
|
|
—
|
|
|
—
|
|
|||||
Total contractual obligations
|
|
$
|
195,386
|
|
|
$
|
18,453
|
|
|
$
|
28,514
|
|
|
$
|
15,255
|
|
|
$
|
133,164
|
|
(1)
|
License agreements
- We have entered into several license agreements under which we obtained rights to certain intellectual property. Under the agreements, we could be obligated for payments upon successful completion of clinical and regulatory milestones regarding the products covered by the licenses. The obligations listed in the table above represent estimates of when the milestones will be achieved. The milestones may not be completed when estimated or at all. See Note 12 to the audited financial statements included in our Annual Report.
|
(2)
|
Long-term debt obligations
- Obligations under our credit facility. See Note 5 to the unaudited financial statements included herein and Note 15 to the audited financial statements included in our Annual Report.
|
(3)
|
Operating lease agreements
- The amounts above are comprised of one five-year lease agreement and one 11-year lease agreement. The first lease expires on January 31, 2020 and the second lease expires on August 31, 2026. See Note 6 to the unaudited financial statements included herein and Note 12 to the audited financial statements included in our Annual Report.
|
(4)
|
Manufacturing build-out obligation
- We entered into a construction contract to build-out our manufacturing facilities. The obligation listed in the table above represents the remaining agreed upon costs.
|
(5)
|
Manufacturing arrangements
- We have entered into a number of manufacturing service arrangements with various terms. The obligations listed in the table above represent estimates of when certain services will be performed.
|
(6)
|
Sponsored research agreements
- We have entered into a number of separate sponsored research agreements to undertake research which is of mutual interest to all parties. The various commitments range from 14 months to three years.
|
(7)
|
Preclinical studies
- We have entered into a number of preclinical studies with various terms. The obligations listed in the table above represent estimates of when certain services will be performed.
|
(8)
|
Capital lease agreements
- We have entered into a number of office equipment lease agreements with various terms. The commitments include equipment, maintenance and supplies. See Note 12 to the audited financial statements included in our Annual Report.
|
|
Bellicum Pharmaceuticals, Inc.
|
|
|
|
|
Date: November 9, 2016
|
By:
|
/s/ Thomas J. Farrell
|
|
|
Thomas J. Farrell
|
|
|
President and Chief Executive Officer
|
|
|
|
Date: November 9, 2016
|
By:
|
/s/ Alan A. Musso
|
|
|
Alan A. Musso
|
|
|
Chief Financial Officer and Treasurer
Principal Financial and Accounting Officer
|
Time Period
|
Annual Base Rent Rate Per
Square Foot of Net Rentable Area
|
Payment
|
12/17/12 - 12/31/12
|
$28.25
|
$12,087.15 total
|
1/1/13 - 11/30/13
|
$28.25
|
$24,980.06 per month
|
12/1/13 - 12/16/13
|
$28.25
|
$12,892.96 total
|
12/17/13 - 12/31/13
|
$28.75
|
$12,301.05 total
|
1/1/14 - 11/30/14
|
$28.75
|
$25,422.19 per month
|
12/1/14 - 12/16/14
|
$28.75
|
$13,121.12 total
|
12/17/14 - 12/31/14
|
$29.25
|
$12,514.95 total
|
1/1/15 - 1/31/15
|
$29.25
|
$25,864.31 per month
|
Time Period
|
Annual Base Rent Rate Per
Square Foot of Net Rentable Area
|
Payment
|
11/22/13 - 11/30/13
|
$28.25
|
$2,573.55 total
|
12/1/13 - 12/16/13
|
$28.25
|
$4,427.65 total
|
12/17/13 - 12/31/13
|
$28.75
|
$4,224.40 total
|
1/1/14 - 11/30/14
|
$28.75
|
$8,730.42 per month
|
12/1/14 - 12/16/14
|
$28.75
|
$4,506.02 total
|
12/17/14 - 12/31/14
|
$29.25
|
$4,297.86 total
|
1/1/15 - 1/31/15
|
$29.25
|
$8,882.25 per month
|
Time Period
|
Annual Base Rent Rate Per
Square Foot of Net Rentable Area
|
Payment
|
2/1/15 - 11/30/15
|
$29.25
|
$85,924.31 per month
|
12/1/15 - 12/16/15
|
$29.25
|
$44,348.00 total
|
12/17/15 - 12/31/15
|
$29.75
|
$42,286.95 total
|
1/1/16 - 11/30/16
|
$29.75
|
$87,393.10 per month
|
12/1/16 - 12/16/16
|
$29.75
|
$45,106.08 total
|
12/17/16 - 12/31/16
|
$30.25
|
$43,297.65 total
|
1/1/17 - 11/30/17
|
$30.25
|
$88,861.90 per month
|
12/1/17 - 12/16/17
|
$30.25
|
$46,184.16 total
|
12/17/17 - 12/31/17
|
$30.75
|
$43,708.35 total
|
1/1/18 - 11/30/18
|
$30.75
|
$90,330.69 per month
|
12/1/18 - 12/16/18
|
$30.75
|
$46,622.24 total
|
12/17/18 - 12/31/18
|
$31.25
|
$44,419.05 total
|
1/1/19 - 10/31/19
|
$31.25
|
$91,799.48 per month
|
11/1/19 - 1/31/20
|
$31.75
|
$93,268.27 per month
|
(a)
|
Amendment to Lease
. The parties acknowledge and agree that the Lease has not been amended or modified in any respect, other than by this Fifth Amendment, and there are no other agreements of any kind currently in force and effect between the parties.
|
(b)
|
Counterparts
. For the convenience of the parties any number of counterparts hereof may be executed, and each such executed counterpart shall be deemed an original, and all such counterparts together shall constitute one and the same instrument. Facsimile or .PDF transmission of an executed counterpart of this Fifth Amendment shall be deemed to constitute due and sufficient delivery of such counterpart, and such facsimile or .PDF signatures shall be deemed original signatures for purposes of enforcement and construction of this Fifth Amendment.
|
(c)
|
Entire Agreement
. The Lease, as amended by this Fifth Amendment, sets forth all covenants, agreements and understandings among the parties with respect to the subject matter hereof and there are no other covenants, conditions or understandings, either written or oral, between the parties hereto except as set forth in the Lease and this Fifth Amendment.
|
(d)
|
Full Force and Effect
. Except as expressly amended hereby, all other items and provisions of the Lease remain unchanged and continue to be in full force and effect.
|
(e)
|
Conflicts
. The terms of this Fifth Amendment shall control over any conflicts between the terms of the Lease and the terms of this Fifth Amendment.
|
(f)
|
Authority of Tenant
. Tenant warrants and represents unto Landlord that (i) Tenant has full right and authority to execute, deliver and perform this Fifth Amendment; and (ii) the person executing this Fifth Amendment was authorized to do so.
|
(g)
|
Capitalized Terms
. Capitalized terms not defined herein shall have the same meanings attached to such terms under the Lease.
|
(h)
|
Successors and Assigns
. This Fifth Amendment shall be binding upon and inure to the benefit of the parties hereto and their respective successors and assigns.
|
(i)
|
Governing Law
. This Fifth Amendment shall be governed by, and construed in accordance with, the laws of the State of Texas, with venue in connection with any legal action thereunder being in Harris County, Texas.
|
Months following the Commencement Date
|
Annual Rate/SF
|
Annual Base Rent
|
Monthly Installments
|
61 - 72
|
$36.50
|
$923,596.00
|
$79,966.33
|
73 - 84
|
$37.80
|
$956,491.20
|
$79,707.60
|
85 - 96
|
$39.10
|
$989,386.40
|
$82,448.87
|
97 - 108
|
$40.50
|
$1,024,812.00
|
$85,401.00
|
109 - 120
|
$41.90
|
$1,060,237.60
|
$88,353.13
|
121 - 132
|
$43.35
|
$1,096,888.00
|
$91,407.33
|
Months following the Commencement Date
|
Annual Rate/SF
|
Annual Base Rent
|
Monthly Installments
|
61 - 72
|
$26.50
|
$18,682.50
|
$1,556.88
|
73 - 84
|
$27.80
|
$19,599.00
|
$1,633.25
|
85 - 96
|
$29.10
|
$20,515.50
|
$1,709.63
|
97 – 108
|
$30.50
|
$21,502.50
|
$1,791.88
|
109 - 120
|
$31.90
|
$22,489.50
|
$1,874.13
|
121 - 132
|
$33.35
|
$23,512.00
|
$1,959.33
|
Months following the Commencement Date
|
Annual Rate/SF
|
Annual Base Rent
|
Monthly Installments
|
61 - 120
|
$8.00
|
$6,464.50
|
$538.67
|
121 - 132
|
$9.00
|
$7,272.00
|
$606.00
|
Period
|
Annual Rate/SF
|
Annual Base Rent
|
Monthly Installments
|
Expansion Date – August 31, 2016
|
$20.75
|
$69,056.00
|
$5,754.67
|
September 1, 2016 – August 31, 2017
|
$21.80
|
$72,550.00
|
$6,045.83
|
September 1, 2017 – August 31, 2018
|
$22.95
|
$76,378.00
|
$6,364.83
|
September 1, 2018 – August 31, 2019
|
$24.10
|
$80,205.00
|
$6,683.75
|
September 1, 2019 – August 31, 2020
|
$25.30
|
$84,198.00
|
$7,016.50
|
September 1, 2020 – August 31, 2021
|
$26.50
|
$88,192.00
|
$7,349.33
|
September 1, 2021 – August 31, 2022
|
$27.80
|
$92,518.00
|
$7,709.83
|
September 1, 2022 – August 31, 2023
|
$29.10
|
$96,845.00
|
$8,070.42
|
September 1, 2023 – August 31, 2024
|
$30.50
|
$101,504.00
|
$8,458.67
|
September 1, 2024 – August 31, 2025
|
$31.90
|
$106,163.00
|
$8,846.92
|
September 1, 2025 – August 31, 2026
|
$33.35
|
$110,989.00
|
$9,249.08
|
Months following the commencement of the Extended Term
|
Annual Rate/SF
|
Annual Base Rent
|
Monthly Installments
|
1 - 12
|
$34.65
|
$24,427.00
|
$2,035.58
|
13 - 24
|
$35.99
|
$25,372.00
|
$2,114.33
|
25 - 36
|
$37.37
|
$26,344.00
|
$2,195.33
|
37 - 48
|
$38.79
|
$27,346.00
|
$2,278.83
|
49 - 60
|
$40.25
|
$28,378.00
|
$2,364.83
|
Months following the commencement of the Extended Term
|
Annual Rate/SF
|
Annual Base Rent
|
Monthly Installments
|
1 - 60
|
$9.00
|
$7,272.00
|
$606.00
|
1.
|
Acceptance of Appointment by Escrow Agent
. The Escrow Agent hereby agrees to act as the escrow agent under this Escrow Agreement and acknowledges receipt of the Escrow Amount and agrees to hold and disburse the Escrow Amount pursuant to
Section 7
of
Exhibit G
to the Original Lease.
|
2.
|
Compensation of Escrow Agent
. The Escrow Agent acknowledges receipt of a fee from Tenant of $________ in consideration for its agreement to act as Escrow Agent under this Escrow Agreement.
|
3.
|
Investment of Escrow Amount
. The Escrow Agent shall deposit the Escrow Amount in a federally insured interest bearing account(s) (Escrow Account) reasonably acceptable to Landlord, Tenant, and Escrow Agent. All interest on the Escrow Amount shall be deposited in the Escrow Account and constitute a part of the Escrow Amount. The Escrow Amount (including any interest thereon) shall be owned by Tenant until disbursed in accordance with this Escrow Agreement.
|
4.
|
Term
. The term of this Escrow Agreement shall commence on the date the Escrow Amount is received by Escrow Agent and shall continue in full force and effect until all of the Escrow Amounts have been fully disbursed as provided herein.
|
5.
|
Supplement of Escrow Amount
. Landlord and Tenant agree and acknowledge that
Section 7
of
Exhibit G
to the Original Lease obligates Tenant to deposit additional amounts with Landlord if the reasonable estimate of the Excess Cost at any given time is greater than originally anticipated (whether due to a change order or otherwise), and in the event the projected Excess Cost exceeds the Escrow Amount, then Tenant agrees to promptly deposit such additional amounts as required under
Section 7
of
Exhibit G
to the Original Lease, and such additional amounts shall be deemed a part of the Escrow Amount.
|
6.
|
Disbursement of Escrow Amount
. Escrow Agent shall make disbursements of the Escrow Amount pursuant to the Agreement, and shall pay Landlord (or DPR, upon Landlord’s request) from the Escrow Amount as and when the same would be required of Tenant under the Agreement, except as otherwise expressly set forth in this Escrow Agreement. Only Landlord shall be authorized to submit a draw request to Escrow Agent, a copy of which shall be delivered simultaneously by Landlord to Tenant. Landlord shall make draw requests only in accordance with the terms of the Agreement. A disbursement shall be made by Escrow Agent to Landlord (or DPR, upon Landlord’s request) within two (2) business days (such period, the “Objection Period”) after receipt of the applicable draw request; provided, however, that Tenant shall have the right to contest any such draw request by providing notice thereof to Landlord and Escrow Agent prior to the expiration of the Objection Period, in which event any amounts objected to shall be held by Escrow Agent. Landlord and Tenant shall then in good faith discuss Tenant’s objection, and attempt to reach a resolution within fourteen (14) days (“Negotiation Period”). If Landlord and Tenant reach a resolution within the Negotiation Period, then Landlord and Tenant shall jointly agree in writing upon the agreed disbursement amount and instruct Escrow Agent to immediately disburse the same; if, however, Landlord and Tenant are unable to resolve Tenant’s objection within the Negotiation Period, Landlord may make a second written request to Escrow Agent to release the amount objected to by Tenant and such amount shall be immediately disbursed to Landlord for payment
|
7.
|
Final Draw Request
. Landlord shall notify Tenant and Escrow Agent in writing of the occurrence of the Leasehold Improvements Completion Date (as defined in the Agreement) and shall promptly submit a draw request in accordance with Section 6 above for any outstanding invoices payable to the contractor (the “Final Draw Request”). In the event that any portion of the Escrow Amount remains unused following payment of the Final Draw Request by Escrow Agent to Landlord, such amounts shall be refunded to Tenant by Escrow Agent one hundred forty (140) days following the Final Draw Request, whereupon this Escrow Agreement shall terminate and be of no further force or effect, except for those provisions that expressly survive such termination.
|
8.
|
Reimbursement of Landlord’s Costs
. Tenant acknowledges that Landlord has accommodated Tenant’s request to use Escrow Agent, and Tenant agrees to directly pay Landlord, within ten (10) days following receipt of an invoice from Landlord, for Landlord’s reasonable, out-of-pocket costs (including reasonable attorneys’ fees) related to establishing the Escrow Account and this Escrow Agreement.
|
9.
|
Rights, Privileges, Immunities and Liabilities of Escrow Agent
. The following shall govern the rights, privileges, immunities and liabilities of the Escrow Agent:
|
10.
|
Notices
. Except as otherwise provided herein, all notices, demands, requests, and other communications required or permitted hereunder shall be given in writing and sent by (i) personal delivery, (ii) national courier service with proof of delivery, or (iii) United States mail, postage prepaid, registered or certified mail, return receipt requested, addressed to the addressee at such party's address set forth herein, or to such other address as such party may specify by written notice, sent in accordance with this paragraph at least thirty (30) days prior to the date of the giving of such notice. Any such notice or communication shall be deemed to have been given and received either at the time of personal delivery, or in the case of mail, as of the date of deposit in an official depository of the United States mail, or in the case of delivery service, upon receipt. To the extent actual receipt is required, rejection or other refusal to accept or the inability to deliver because of changed address of which no notice was received shall be deemed to be receipt of the notice, demand, request or other communication sent.
|
11.
|
Binding Effect of Agreement and Assignment
. This Escrow Agreement shall be binding on, inure to the benefit of and be enforceable by Landlord, Tenant, and Escrow Agent.
|
12.
|
No Third Party Beneficiary
. This Escrow Agreement is for the sole benefit of the parties hereto and is not for the benefit of any third party.
|
13.
|
Choice of Law
. This Escrow Agreement shall be governed by and construed and enforced in accordance with the laws of the State of Texas, and venue in any action arising under this Agreement shall be in a Court of competent jurisdiction in Harris County, Texas.
|
14.
|
Multiple Counterparts
. This Escrow Agreement may be executed in multiple counterparts each of which shall be deemed an original but all of which together shall constitute one and the same instrument.
|
15.
|
Amendment
. This Escrow Agreement may be amended only by a written instrument executed by all three parties hereto.
|
16.
|
Time of Essence
. Time is of the essence of this Escrow Agreement. However, if the final date of any period which is set out in any provision or if this Agreement falls on a Saturday, Sunday or legal holiday under the law of the United States or the State of Texas in such event, the time of such period shall be extended to the next day which is not a Saturday, Sunday or legal holiday.
|
17.
|
Invalid Provision
. If any provision of this Agreement is held to be legal, invalid or unenforceable under present or future all laws, such provision shall be fully severable and this Escrow Agreement shall be construed and enforced as such illegal, invalid or unenforceable provision had never comprised a part of this Escrow Agreement. The remaining provisions of this Escrow Agreement shall remain in full force and effect and shall not be effected by such illegal, invalid, or unenforceable provisions or by its severance from this Agreement.
|
18.
|
Entire Agreement
. This Escrow Agreement sets forth the entire agreement between Landlord, Tenant, and Escrow Agent relating to the matters recited herein, and may not be contradicted by evidence of prior, contemporaneous, or subject to oral agreements of the parties.
|
19.
|
Number and Gender
. Whenever the context so requires, references herein to the singular number shall include the plural, and likewise the plural shall include the singular; words noting gender shall be construed to include the masculine, feminine and neuter, where appropriate. If any party to this Escrow Agreement consists of more than one person or entity, the obligations of each person or entity constituting a party hereunder shall be joint and several.
|
Period
|
Annual Rate/SF
|
Annual Base Rent
|
Monthly Installments
|
Effective Date – August 31, 2017
|
$21.80
|
$4,621.60
|
$385.13
|
September 1, 2017 – August 31, 2018
|
$22.95
|
$4,865.40
|
$405.45
|
September 1, 2018 – August 31, 2019
|
$24.10
|
$5,109.20
|
$425.77
|
September 1, 2019 – August 31, 2020
|
$25.30
|
$5,363.60
|
$446.97
|
September 1, 2020 – August 31, 2021
|
$26.50
|
$5,618.00
|
$468.17
|
September 1, 2021 – August 31, 2022
|
$27.80
|
$5,893.60
|
$491.13
|
September 1, 2022 – August 31, 2023
|
$29.10
|
$6,169.20
|
$514.10
|
September 1, 2023 – August 31, 2024
|
$30.50
|
$6,466.00
|
$538.83
|
September 1, 2024 – August 31, 2025
|
$31.90
|
$6,762.80
|
$563.57
|
September 1, 2025 – August 31, 2026
|
$33.35
|
$7,070.20
|
$589.18
|
|
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;
|
|
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
|
|
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.
|
Date: November 9, 2016
|
By:
|
/s/ Thomas J. Farrell
|
|
|
Thomas J. Farrell
|
|
|
President and Chief Executive Officer
|
|
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;
|
|
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
|
|
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.
|
Date: November 9, 2016
|
By:
|
/s/ Alan A. Musso
|
|
|
Alan A. Musso
|
|
|
Chief Financial Officer and Treasurer
(Principal Financial and Accounting Officer)
|
|
/s/ Thomas J. Farrell
|
|
|
Thomas J. Farrell
|
|
|
President and Chief Executive Officer
|
|
|
(Principal Executive Officer)
|
|
|
November 9, 2016
|
|
|
|
|
|
|
|
|
/s/ Alan A. Musso
|
|
|
Alan A. Musso
|
|
|
Chief Financial Officer and Treasurer
|
|
|
(Principal Financial and Accounting Officer)
|
|
|
November 9, 2016
|