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ý
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QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
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¨
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TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
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Delaware
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33-0903395
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(State or Other Jurisdiction of Incorporation or Organization)
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(I.R.S. Employer Identification No.)
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2505 Meridian Parkway, Suite 100
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Durham, North Carolina
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27713
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(Address of Principal Executive Offices)
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(Zip Code)
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Large accelerated filer
o
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Accelerated filer
x
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Non-accelerated filer
o
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Smaller reporting company
o
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(Do not check if a smaller reporting company)
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Page
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September 30, 2015
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December 31, 2014
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||||
ASSETS
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Current assets:
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Cash and cash equivalents
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$
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44,720
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$
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128,462
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Short-term investments, available-for-sale
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176,080
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106,114
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Accounts receivable
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525
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106
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Prepaid expenses and other current assets
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8,183
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2,775
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Total current assets
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229,508
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237,457
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Long-term investments
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159,486
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52,973
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Property and equipment, net of accumulated depreciation
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2,439
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1,310
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Other long-term assets
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75
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138
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Total assets
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$
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391,508
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$
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291,878
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LIABILITIES AND STOCKHOLDERS' EQUITY
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Current liabilities:
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Accounts payable
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$
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12,919
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$
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5,938
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Accrued liabilities
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7,782
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6,833
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Loan payable, net
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375
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4,296
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Total current liabilities
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21,076
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17,067
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Long-term liabilities
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221
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175
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Total liabilities
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21,297
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17,242
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Commitments and contingencies
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—
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—
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Stockholders’ equity:
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Preferred stock, $0.001 par value, 10,000,000 shares authorized at September 30, 2015 and December 31, 2014; no shares issued and outstanding as of September 30, 2015 and December 31, 2014
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—
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—
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Common stock, $0.001 par value, 200,000,000 shares authorized at September 30, 2015 and December 31, 2014; 46,142,340 and 41,031,770 shares issued and outstanding as of September 30, 2015 and December 31, 2014, respectively
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46
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41
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Additional paid-in capital
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671,380
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496,602
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Accumulated other comprehensive gain, net
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356
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35
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Accumulated deficit
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(301,571
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)
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(222,042
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)
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Total stockholders’ equity
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370,211
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274,636
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Total liabilities and stockholders’ equity
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$
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391,508
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$
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291,878
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Three Months Ended September 30,
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Nine Months Ended September 30,
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||||||||||||
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2015
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2014
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2015
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2014
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Revenues:
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Contract revenue
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$
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2,271
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$
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1,185
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$
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6,104
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$
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2,884
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Collaboration and licensing revenue
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—
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—
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1,548
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—
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Total revenues
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2,271
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1,185
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7,652
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2,884
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Operating expenses:
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Research and development
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26,406
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13,328
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65,611
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29,712
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General and administrative
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8,613
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4,717
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22,068
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11,812
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Total operating expenses
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35,019
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18,045
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87,679
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41,524
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Loss from operations
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(32,748
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)
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(16,860
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)
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(80,027
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)
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(38,640
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)
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Other income (expense):
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Interest income (expense), net
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299
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(91
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)
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498
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(425
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)
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Net loss
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(32,449
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)
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(16,951
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)
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(79,529
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)
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(39,065
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)
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Other comprehensive loss:
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Unrealized (loss) gain on investments, net
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(1,448
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)
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(43
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)
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321
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(63
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)
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Comprehensive loss
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$
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(33,897
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)
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$
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(16,994
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)
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$
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(79,208
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)
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$
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(39,128
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)
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Per share information:
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Net loss, basic and diluted
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$
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(0.70
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)
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$
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(0.47
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)
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$
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(1.84
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)
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$
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(1.26
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)
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Weighted-average shares outstanding, basic and diluted
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46,059,112
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35,845,792
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43,112,314
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30,939,752
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Nine Months Ended September 30,
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2015
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2014
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Cash flows from operating activities:
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Net loss
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$
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(79,529
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)
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$
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(39,065
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)
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Adjustments to reconcile net loss to net cash used in operating activities:
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Depreciation of property and equipment
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444
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183
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Amortization of debt costs
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64
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118
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Amortization of premium/discount on investments
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1,186
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734
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Share-based compensation
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8,882
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2,777
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Amortization of deferred lease obligation
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4
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—
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Changes in operating assets and liabilities:
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Accounts receivable
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(419
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)
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(654
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)
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Prepaid expenses and other assets
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(5,354
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)
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(780
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)
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Accounts payable and accrued liabilities
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7,931
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6,483
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Net cash used in operating activities
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(66,791
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)
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(30,204
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)
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Cash flows from investing activities:
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Purchase of property and equipment
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(1,574
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)
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(703
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)
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Purchase of short-term investments
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(56,294
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)
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(138,058
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)
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Purchase of long-term investments
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(212,766
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)
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—
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Sales of short-term investments
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1,003
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2,499
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Maturities of short-term investments
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90,822
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20,690
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Net cash used in investing activities
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(178,809
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)
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(115,572
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)
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Cash flows from financing activities:
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Proceeds from exercise of stock options
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1,967
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2,148
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Proceeds from employee stock purchase plan stock purchases
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1,054
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426
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|
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Proceeds from exercise of warrants
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1,000
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6
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|
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Proceeds from public offering, net of offering costs
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161,880
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111,845
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Repayment of debt
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(3,975
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)
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(4,275
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)
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Payments for deferred financing costs
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(68
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)
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—
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Net cash provided by financing activities
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161,858
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110,150
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Net decrease in cash and cash equivalents
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(83,742
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)
|
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(35,626
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)
|
||
Cash and cash equivalents:
|
|
|
|
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||||
Beginning of period
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128,462
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|
|
109,976
|
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End of period
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$
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44,720
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|
|
$
|
74,350
|
|
|
|
|
|
|
||||
Supplemental disclosure cash flow information:
|
|
|
|
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Cash paid for interest
|
|
$
|
156
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|
|
$
|
552
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•
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Level 1
— Valuations based on unadjusted quoted prices in active markets for identical assets or liabilities that the Company has the ability to access.
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•
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Level 2
— Valuations based on quoted prices for similar assets or liabilities in active markets, quoted prices for identical or similar assets or liabilities in markets that are not active, and models for which all significant inputs are observable, either directly or indirectly.
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•
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Level 3
— Valuations based on inputs that are unobservable and significant to the overall fair value measurement.
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Fair Value Measurements
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||||||||||||||
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September 30, 2015
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||||||||||||||
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Total
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Quoted Prices in
Active Markets for Identical Assets (Level 1) |
|
Significant Other
Observable Inputs (Level 2) |
|
Significant
Unobservable Inputs (Level 3) |
||||||||
Cash equivalents
|
|
|
|||||||||||||
Money market funds
|
$
|
17,847
|
|
|
$
|
17,847
|
|
|
$
|
—
|
|
|
$
|
—
|
|
Commercial paper
|
24,996
|
|
|
—
|
|
|
24,996
|
|
|
—
|
|
||||
Total cash equivalents
|
42,843
|
|
|
17,847
|
|
|
24,996
|
|
|
—
|
|
||||
Short-term investments
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
22,093
|
|
|
—
|
|
|
22,093
|
|
|
—
|
|
||||
Corporate bonds
|
3,001
|
|
|
—
|
|
|
3,001
|
|
|
—
|
|
||||
U.S. Treasury securities
|
149,144
|
|
|
149,144
|
|
|
—
|
|
|
—
|
|
||||
Preferred stock of U.S. corporation
|
1,842
|
|
|
—
|
|
|
|
|
|
1,842
|
|
||||
Total short-term investments
|
176,080
|
|
|
149,144
|
|
|
25,094
|
|
|
1,842
|
|
||||
Long-term investments
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
16,816
|
|
|
—
|
|
|
16,816
|
|
|
—
|
|
||||
U.S. Treasury securities
|
142,670
|
|
|
142,670
|
|
|
—
|
|
|
—
|
|
||||
Total long-term investments
|
159,486
|
|
|
142,670
|
|
|
16,816
|
|
|
—
|
|
||||
Total assets
|
$
|
378,409
|
|
|
$
|
309,661
|
|
|
$
|
66,906
|
|
|
$
|
1,842
|
|
|
|
|
|
|
|
|
|
||||||||
|
Fair Value Measurements
|
||||||||||||||
|
December 31, 2014
|
||||||||||||||
|
Total
|
|
Quoted Prices in
Active Markets for Identical Assets (Level 1) |
|
Significant Other
Observable Inputs (Level 2) |
|
Significant
Unobservable Inputs (Level 3) |
||||||||
Cash equivalents
|
|
|
|
|
|
|
|
||||||||
Money market funds
|
$
|
125,606
|
|
|
$
|
125,606
|
|
|
$
|
—
|
|
|
$
|
—
|
|
Certificates of deposit
|
480
|
|
|
—
|
|
|
480
|
|
|
—
|
|
||||
Total cash equivalents
|
126,086
|
|
|
125,606
|
|
|
480
|
|
|
—
|
|
||||
Short-term investments
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
16,981
|
|
|
—
|
|
|
16,981
|
|
|
—
|
|
||||
Corporate bonds
|
69,892
|
|
|
—
|
|
|
69,892
|
|
|
—
|
|
||||
Commercial paper
|
11,240
|
|
|
—
|
|
|
11,240
|
|
|
—
|
|
||||
U.S. Treasury securities
|
8,000
|
|
|
8,000
|
|
|
—
|
|
|
—
|
|
||||
Total short-term investments
|
106,114
|
|
|
8,000
|
|
|
98,114
|
|
|
—
|
|
||||
Long-term investments
|
|
|
|
|
|
|
|
||||||||
Certificates of deposit
|
10,996
|
|
|
—
|
|
|
10,996
|
|
|
—
|
|
||||
U.S. Treasury securities
|
40,197
|
|
|
40,197
|
|
|
—
|
|
|
—
|
|
||||
Preferred stock of U.S. corporation
|
1,781
|
|
|
—
|
|
|
—
|
|
|
1,781
|
|
||||
Total long-term investments
|
52,973
|
|
|
40,197
|
|
|
10,996
|
|
|
1,781
|
|
||||
Total assets
|
$
|
285,173
|
|
|
$
|
173,803
|
|
|
$
|
109,590
|
|
|
$
|
1,781
|
|
|
Fair Value Measurements
(Level 3) |
||
Preferred stock of U.S. corporation:
|
|
||
Fair value at December 31, 2014
|
$
|
1,781
|
|
Fair value increase recorded in other comprehensive gain
|
61
|
|
|
Fair value at September 30, 2015
|
$
|
1,842
|
|
|
September 30, 2015
|
|
December 31, 2014
|
||||
Accrued compensation
|
$
|
3,080
|
|
|
$
|
3,057
|
|
Accrued research and development expenses
|
2,604
|
|
|
1,116
|
|
||
Deferred revenue
|
—
|
|
|
1,545
|
|
||
Other accrued liabilities
|
2,098
|
|
|
1,115
|
|
||
Total accrued liabilities
|
$
|
7,782
|
|
|
$
|
6,833
|
|
|
|
September 30, 2015
|
||||||||||||||
|
|
Amortized Cost
|
|
Gross Unrealized Gains
|
|
Gross Unrealized Losses
|
|
Estimated Fair Value
|
||||||||
Corporate bonds
|
|
$
|
3,001
|
|
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
3,001
|
|
Certificates of deposit
|
|
38,884
|
|
|
32
|
|
|
(7
|
)
|
|
38,909
|
|
||||
U.S. Treasury securities
|
|
291,672
|
|
|
147
|
|
|
(5
|
)
|
|
291,814
|
|
||||
Preferred stock of U.S. corporation
|
|
1,545
|
|
|
297
|
|
|
—
|
|
|
1,842
|
|
||||
Total investments
|
|
$
|
335,102
|
|
|
$
|
476
|
|
|
$
|
(12
|
)
|
|
$
|
335,566
|
|
|
|
|
|
|
|
|
|
|
||||||||
|
|
December 31, 2014
|
||||||||||||||
|
|
Amortized Cost
|
|
Gross Unrealized Gains
|
|
Gross Unrealized Losses
|
|
Estimated Fair Value
|
||||||||
Corporate bonds
|
|
$
|
69,947
|
|
|
$
|
—
|
|
|
$
|
(56
|
)
|
|
$
|
69,891
|
|
Certificates of deposit
|
|
28,039
|
|
|
1
|
|
|
(62
|
)
|
|
27,978
|
|
||||
U.S. Treasury securities
|
|
48,279
|
|
|
—
|
|
|
(82
|
)
|
|
48,197
|
|
||||
Commercial paper
|
|
11,242
|
|
|
—
|
|
|
(2
|
)
|
|
11,240
|
|
||||
Preferred stock of U.S. corporation
|
|
1,545
|
|
|
236
|
|
|
—
|
|
|
1,781
|
|
||||
Total investments
|
|
$
|
159,052
|
|
|
$
|
237
|
|
|
$
|
(202
|
)
|
|
$
|
159,087
|
|
Maturing in one year or less
|
$
|
174,238
|
|
Maturing after one year through two years
|
159,486
|
|
|
Total debt investments
|
333,724
|
|
|
Preferred stock of U.S. corporation
|
1,842
|
|
|
Total investments
|
$
|
335,566
|
|
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
|
|
2015
|
|
2014
|
|
2015
|
|
2014
|
||||||||
Research and development expense
|
|
$
|
1,594
|
|
|
$
|
524
|
|
|
$
|
3,820
|
|
|
$
|
428
|
|
General and administrative expense
|
|
2,085
|
|
|
838
|
|
|
5,062
|
|
|
2,349
|
|
||||
Total share-based compensation expense
|
|
$
|
3,679
|
|
|
$
|
1,362
|
|
|
$
|
8,882
|
|
|
$
|
2,777
|
|
•
|
fees paid to consultants and contract research organizations (CROs), including in connection with our preclinical and clinical trials, and other related clinical trial fees, such as for investigator grants, patient screening, laboratory work, clinical trial database management, clinical trial material management and statistical compilation and analysis;
|
•
|
salaries and related overhead expenses, which include stock option and employee stock purchase program compensation and benefits, for personnel in research and development functions;
|
•
|
payments to third-party manufacturers, which produce, test and package our drug substance and drug product (including continued testing of process validation and stability);
|
•
|
costs related to legal and compliance with regulatory requirements; and
|
•
|
license fees for and milestone payments related to licensed products and technologies.
|
•
|
develop brincidofovir for the prevention of CMV infection in HCT recipients;
|
•
|
develop brincidofovir for the treatment of AdV infections, for the prevention of CMV in kidney transplant recipients, and for other indications;
|
•
|
advance the development of our other product candidates, subject to the availability of additional funding; and
|
•
|
expand operations in Europe.
|
|
|
Three Months Ended September 30,
|
|
Nine Months Ended September 30,
|
||||||||||||
|
|
2015
|
|
2014
|
|
2015
|
|
2014
|
||||||||
Direct research and development expenses
|
|
$
|
18,937
|
|
|
$
|
9,571
|
|
|
$
|
45,819
|
|
|
$
|
20,303
|
|
Research and development personnel costs
|
|
6,348
|
|
|
3,062
|
|
|
16,519
|
|
|
7,506
|
|
||||
Indirect research and development expenses
|
|
1,121
|
|
|
695
|
|
|
3,273
|
|
|
1,903
|
|
||||
Total research and development expenses
|
|
$
|
26,406
|
|
|
$
|
13,328
|
|
|
$
|
65,611
|
|
|
$
|
29,712
|
|
•
|
manufacturing to produce, test and package our drug substance and drug product for brincidofovir;
|
•
|
initiation, enrollment, and conduct of SUPPRESS;
|
•
|
initiation, enrollment, and conduct of AdVise; and
|
•
|
initiation, enrollment and conduct of SUSTAIN and SURPASS.
|
|
|
Three Months Ended September 30,
|
|
Dollar Change
|
|
% Change
|
|||||||||
|
|
2015
|
|
2014
|
|
Increase/(Decrease)
|
|||||||||
Revenues:
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
Contract revenue
|
|
$
|
2,271
|
|
|
$
|
1,185
|
|
|
$
|
1,086
|
|
|
91.6
|
%
|
Collaboration and licensing revenue
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|||
Total revenues
|
|
2,271
|
|
|
1,185
|
|
|
1,086
|
|
|
91.6
|
%
|
|||
Operating expenses:
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
Research and development
|
|
26,406
|
|
|
13,328
|
|
|
13,078
|
|
|
98.1
|
%
|
|||
General and administrative
|
|
8,613
|
|
|
4,717
|
|
|
3,896
|
|
|
82.6
|
%
|
|||
Total operating expenses
|
|
35,019
|
|
|
18,045
|
|
|
16,974
|
|
|
94.1
|
%
|
|||
Loss from operations
|
|
(32,748
|
)
|
|
(16,860
|
)
|
|
(15,888
|
)
|
|
94.2
|
%
|
|||
Other income (expense):
|
|
|
|
|
|
|
|
|
|||||||
Interest income (expense), net
|
|
299
|
|
|
(91
|
)
|
|
390
|
|
|
NM
|
|
|||
Net loss
|
|
$
|
(32,449
|
)
|
|
$
|
(16,951
|
)
|
|
$
|
(15,498
|
)
|
|
91.4
|
%
|
•
|
an increase in clinical trial expenses of $9.4 million related to our ongoing Phase 3 SUPPRESS study and our AdVise study, as well as the costs of our Phase 3 SUSTAIN and SURPASS studies;
|
•
|
an increase in compensation and other employee related costs of $3.3 million, consisting of $2.2 million of compensation and benefits expense related to the addition of new employees as we continue to grow our clinical, regulatory, development and manufacturing departments and $1.1 million of share-based compensation; and
|
•
|
an increase of $1.0 million in legal and consulting expenses mainly related to the preparation of regulatory filings.
|
•
|
an increase in compensation and other employee related costs of $2.5 million, consisting of an increase of $1.3 million of share-based compensation, and $1.2 million of compensation and benefit expense related to the addition of new employees to support commercialization and overall growth of the company;
|
•
|
an increase of $0.5 million in legal, accounting and consulting costs; and
|
•
|
an increase in other costs of $0.4 million as we expand our commercialization preparations to launch brincidofovir.
|
|
|
Nine Months Ended September 30,
|
|
Dollar Change
|
|
% Change
|
|||||||||
|
|
2015
|
|
2014
|
|
Increase/(Decrease)
|
|||||||||
Revenues:
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
Contract revenue
|
|
$
|
6,104
|
|
|
$
|
2,884
|
|
|
$
|
3,220
|
|
|
111.7
|
%
|
Collaboration and licensing revenue
|
|
1,548
|
|
|
—
|
|
|
1,548
|
|
|
—
|
|
|||
Total revenues
|
|
7,652
|
|
|
2,884
|
|
|
4,768
|
|
|
165.3
|
%
|
|||
Operating expenses:
|
|
|
|
|
|
|
|
|
|
|
|||||
Research and development
|
|
65,611
|
|
|
29,712
|
|
|
35,899
|
|
|
120.8
|
%
|
|||
General and administrative
|
|
22,068
|
|
|
11,812
|
|
|
10,256
|
|
|
86.8
|
%
|
|||
Total operating expenses
|
|
87,679
|
|
|
41,524
|
|
|
46,155
|
|
|
111.2
|
%
|
|||
Loss from operations
|
|
(80,027
|
)
|
|
(38,640
|
)
|
|
(41,387
|
)
|
|
107.1
|
%
|
|||
Other income (expense):
|
|
|
|
|
|
|
|
|
|||||||
Interest income (expense), net
|
|
498
|
|
|
(425
|
)
|
|
923
|
|
|
NM
|
|
|||
Net loss
|
|
$
|
(79,529
|
)
|
|
$
|
(39,065
|
)
|
|
$
|
(40,464
|
)
|
|
103.6
|
%
|
•
|
an increase in clinical trial expenses of $19.7 million related to our ongoing Phase 3 SUPPRESS study and our AdVise study, as well as the costs of our Phase 3 SUSTAIN and SURPASS studies;
|
•
|
an increase in compensation and other employee related costs of $9.0 million, consisting of $5.6 million of compensation and benefit expense related to the addition of new employees as we continue to grow our clinical, regulatory, development and manufacturing departments and $3.4 million of share-based compensation;
|
•
|
an increase of $4.1 million in drug manufacturing costs for raw materials as we began primary and secondary brincidofovir manufacturing campaigns; and
|
•
|
an increase of $2.1 million in legal and consulting expenses mainly related to the preparation of regulatory filings.
|
•
|
an increase in compensation and other employee related costs of $4.6 million, consisting of an increase of $2.7 million of share-based compensation and $1.9 million of compensation and benefits related to the addition of new employees to support commercialization and overall growth of the company;
|
•
|
an increase in other costs of $3.4 million as we expand our commercialization preparations to launch brincidofovir; and
|
•
|
an increase of $1.2 million in legal, accounting and consulting costs.
|
|
|
Nine Months Ended September 30,
|
||||||
|
|
2015
|
|
2014
|
||||
Net cash (used in) provided by:
|
|
|
|
|
|
|
||
Operating activities
|
|
$
|
(66,791
|
)
|
|
$
|
(30,204
|
)
|
Investing activities
|
|
(178,809
|
)
|
|
(115,572
|
)
|
||
Financing activities
|
|
161,858
|
|
|
110,150
|
|
||
Net decrease in cash and cash equivalents
|
|
$
|
(83,742
|
)
|
|
$
|
(35,626
|
)
|
•
|
continue the development of our lead product candidate, brincidofovir, for the prevention of cytomegalovirus (CMV) infection in hematopoietic cell transplant (HCT) recipients and solid organ transplant recipients;
|
•
|
continue the development of brincidofovir for the treatment of adenovirus (AdV) infection;
|
•
|
seek to obtain regulatory approvals for brincidofovir;
|
•
|
prepare for the potential commercialization of brincidofovir;
|
•
|
scale-up manufacturing capabilities to commercialize brincidofovir for any indications for which we receive regulatory approval;
|
•
|
begin outsourcing of the commercial manufacturing of brincidofovir for any indications for which we receive regulatory approval;
|
•
|
establish an infrastructure for the sales, marketing and distribution of brincidofovir for any indications for which we receive regulatory approval;
|
•
|
expand our research and development activities and advance our clinical programs;
|
•
|
maintain, expand and protect our intellectual property portfolio;
|
•
|
continue our research and development efforts and seek to discover additional product candidates; and
|
•
|
add operational, financial and management information systems and personnel, including personnel to support our product development and commercialization efforts and operations as a public company.
|
•
|
obtaining favorable results for and advancing the development of brincidofovir, initially for the prevention of CMV in HCT recipients, including successfully completing Phase 3 clinical development;
|
•
|
obtaining United States and foreign regulatory approval for brincidofovir, initially for the prevention of CMV infection in HCT recipients;
|
•
|
obtaining U.S. and foreign regulatory approvals for brincidofovir for the treatment of AdV infection;
|
•
|
launching and commercializing brincidofovir, including establishing a sales force and collaborating with third parties;
|
•
|
achieving broad market acceptance of brincidofovir in the medical community and with third-party payers;
|
•
|
obtaining traditional approval in the U. S. for brincidofovir for CMV prevention; and
|
•
|
generating, in licensing or otherwise acquiring a pipeline of product candidates which progress to clinical development.
|
•
|
significantly delay, scale back or discontinue the development or commercialization of our product candidates, including brincidofovir;
|
•
|
seek corporate partners for brincidofovir or any of our other product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available; or
|
•
|
relinquish or license on unfavorable terms, our rights to technologies or product candidates that we otherwise would seek to develop or commercialize ourselves.
|
•
|
successful completion of nonclinical studies and successful enrollment and completion of clinical trials;
|
•
|
receipt of marketing approvals from the FDA and corresponding regulatory authorities outside the United States for our product candidates;
|
•
|
establishing commercial manufacturing capabilities;
|
•
|
launching commercial sales of the product, whether alone or in collaboration with others;
|
•
|
acceptance of the product by patients, the medical community and third-party payers;
|
•
|
effectively competing with other therapies;
|
•
|
a continued acceptable safety profile of the product following approval; and
|
•
|
obtaining, maintaining, enforcing and defending intellectual property rights and claims.
|
•
|
regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;
|
•
|
clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs;
|
•
|
we might be required to change one of our clinical research organizations (CROs) during ongoing clinical programs;
|
•
|
the number of subjects required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be insufficient or slower than we anticipate or subjects may drop out of these clinical trials at a higher rate than we anticipate;
|
•
|
our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
|
•
|
we might have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the subjects are being exposed to unacceptable health risks;
|
•
|
regulators or institutional review boards may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements;
|
•
|
the cost of clinical trials of our product candidates may be greater than we anticipate;
|
•
|
agency or judicial enforcement actions which impact our clinical trials;
|
•
|
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 or our investigators to suspend or terminate the trials.
|
•
|
inability to raise funding necessary to initiate or continue a trial;
|
•
|
delays in obtaining regulatory approval to commence a trial;
|
•
|
delays in reaching agreement with the FDA and foreign health authorities on final trial design;
|
•
|
imposition of a clinical hold following an inspection of our clinical trial operations or trial sites by the FDA or other regulatory authorities;
|
•
|
delays caused by disagreements with existing CROs and/or clinical trial sites;
|
•
|
delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites;
|
•
|
delays in obtaining required institutional review board approval at each site;
|
•
|
delays in recruiting suitable patients to participate in a trial;
|
•
|
delays in having subjects complete participation in a trial or return for post-treatment follow-up;
|
•
|
delays caused by subjects dropping out of a trial due to side effects or otherwise;
|
•
|
clinical sites dropping out of a trial to the detriment of enrollment;
|
•
|
agency or judicial enforcement actions against us;
|
•
|
time required to add new clinical sites; and
|
•
|
delays by our contract manufacturers to produce and deliver sufficient supply of clinical trial materials.
|
•
|
regulatory authorities may withdraw their approval of the product or impose restrictions on its distribution in a form of a modified risk evaluation and mitigation strategy (REMS);
|
•
|
regulatory authorities may require the addition of labeling statements, such as warnings or contraindications;
|
•
|
we may be required to change the way the product is administered or to conduct additional clinical studies;
|
•
|
we could be sued and held liable for harm caused to patients; and
|
•
|
our reputation may suffer.
|
•
|
issue an untitled or warning letter asserting that we are in violation of the law;
|
•
|
seek an injunction or impose civil or criminal penalties or monetary fines;
|
•
|
suspend or withdraw regulatory approval;
|
•
|
suspend any ongoing clinical trials;
|
•
|
refuse to approve a pending application or supplements to an application submitted by us;
|
•
|
recall and/or seize product; or
|
•
|
refuse to allow us to enter into supply contracts, including government contracts.
|
•
|
the federal healthcare anti-kickback statute which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or paying remuneration (including any kickback, bribe or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, under federal healthcare programs such as Medicare and Medicaid;
|
•
|
the federal civil and criminal false claims laws and civil monetary penalties, including civil whistleblower or
qui tam
actions, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, to the federal government, claims for payment or approval that are false or fraudulent or from knowingly
|
•
|
the federal Health Insurance Portability and Accountability Act of 1996 (HIPAA) which, among other things, imposes criminal liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or to obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payer (e.g., public or private) and knowingly or willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statement in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters;
|
•
|
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH) and its implementing regulations, and as amended again by the final HIPAA omnibus rule, Modifications to the HIPAA Privacy, Security, Enforcement, and Breach Notification Rules Under HITECH and the Genetic Information Nondiscrimination Act; Other Modifications to HIPAA, published in January 2013, which imposes certain obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information without appropriate authorization by entities subject to the rule, such as health plans, clearinghouses and healthcare providers;
|
•
|
the federal Food, Drug and Cosmetic Act (FDCA) which prohibits, among other things, the adulteration or misbranding of drugs and devices;
|
•
|
the federal transparency law, enacted as part of the Patient Protection and Affordable Care Act and Health Care and Education Reconciliation Act of 2010 (collectively, the Health Care Reform Law), and its implementing regulations, which requires manufacturers of drugs, devices, biologicals and medical supplies to report to the U.S. Department of Health and Human Services information related to payments and other transfers of value made to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; and
|
•
|
analogous state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by state governmental and non-governmental third-party payers, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; and state laws and regulations that require manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities.
|
•
|
inability to meet our product specifications and quality requirements consistently;
|
•
|
delay or inability to procure or expand sufficient manufacturing capacity;
|
•
|
manufacturing and product quality issues related to scale-up of manufacturing;
|
•
|
costs and validation of new equipment and facilities required for scale-up;
|
•
|
failure to comply with cGMP and similar foreign standards;
|
•
|
inability to negotiate manufacturing agreements with third parties under commercially reasonable terms;
|
•
|
termination or nonrenewal of manufacturing agreements with third parties in a manner or at a time that is costly or damaging to us;
|
•
|
reliance on a limited number of sources, and in some cases, single sources for product components, such that if we are unable to secure a sufficient supply of these product components, we will be unable to manufacture and sell our product candidates in a timely fashion, in sufficient quantities or under acceptable terms;
|
•
|
lack of qualified backup suppliers for those components that are currently purchased from a sole or single source supplier;
|
•
|
operations of our third-party manufacturers or suppliers could be disrupted by conditions unrelated to our business or operations, including the bankruptcy of the manufacturer or supplier;
|
•
|
carrier disruptions or increased costs that are beyond our control; and
|
•
|
failure to deliver our products under specified storage conditions and in a timely manner.
|
•
|
lacks or does not devote sufficient time and resources to the development and commercialization of CMX157;
|
•
|
lacks or does not devote sufficient capital to fund the development and commercialization of CMX157;
|
•
|
develops, either alone or with others, products that compete with CMX157;
|
•
|
fails to gain the requisite regulatory approvals for CMX157;
|
•
|
does not successfully commercialize CMX157;
|
•
|
does not conduct its activities in a timely manner;
|
•
|
terminates its license with us;
|
•
|
does not effectively pursue and enforce intellectual property rights relating to CMX157; or
|
•
|
merges with a third-party that wants to terminate the collaboration.
|
•
|
demonstration of clinical safety and efficacy in our clinical trials;
|
•
|
relative convenience, ease of administration and acceptance by physicians, patients, pharmacists and health care payers;
|
•
|
prevalence and severity of any AEs;
|
•
|
limitations or warnings contained in the FDA-approved label for the relevant product candidate;
|
•
|
availability of alternative treatments;
|
•
|
pricing and cost-effectiveness;
|
•
|
effectiveness of our or any future collaborators’ sales and marketing strategies;
|
•
|
ability to obtain hospital formulary approval;
|
•
|
ability to ensure availability for product through appropriate channels;
|
•
|
ability to maintain adequate inventory; and
|
•
|
ability to obtain and maintain sufficient third-party coverage or reimbursement, which may vary from country to country.
|
•
|
recruiting and retaining talented people;
|
•
|
training employees that we recruit;
|
•
|
establishing compliance standards;
|
•
|
setting the appropriate system of incentives;
|
•
|
managing additional headcount;
|
•
|
ensuring that appropriate support functions are in place to support sales force organizational needs; and
|
•
|
integrating a new business unit into an existing corporate architecture.
|
•
|
different regulatory requirements for drug approvals in foreign countries;
|
•
|
reduced protection for intellectual property rights;
|
•
|
unexpected changes in tariffs, trade barriers and regulatory and labor requirements;
|
•
|
economic weakness, including inflation, or political instability in particular foreign economies and markets;
|
•
|
compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;
|
•
|
foreign taxes, including withholding of payroll taxes;
|
•
|
foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country;
|
•
|
workforce uncertainty in countries where labor unrest is more common than in the United States;
|
•
|
production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and
|
•
|
business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.
|
•
|
discover and develop medicines that are superior to other products in the market;
|
•
|
demonstrate through our clinical trials that our product candidates, including brincidofovir, are differentiated from existing and future therapies;
|
•
|
evaluate new potential indications across the lifecycle of brincidofovir;
|
•
|
attract qualified scientific, product development and commercial personnel;
|
•
|
obtain and successfully defend and enforce patent and/or other proprietary protection for our medicines and technologies;
|
•
|
obtain required regulatory approvals;
|
•
|
successfully collaborate with pharmaceutical companies in the discovery, development and commercialization of new medicines; and
|
•
|
negotiate competitive pricing and reimbursement with third-party payers.
|
•
|
our research methodology or that of our collaboration partners may be unsuccessful in identifying potential product candidates;
|
•
|
our potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval; and
|
•
|
our collaboration partners may change their development profiles for potential product candidates or abandon a therapeutic area.
|
•
|
audit and object to any BARDA contract-related costs and fees on grounds that they are not allowable under the FAR, and require us to reimburse all such costs and fees;
|
•
|
suspend or prevent us for a set period of time from receiving new contracts or extending our existing contract based on violations or suspected violations of laws or regulations;
|
•
|
claim nonexclusive, nontransferable rights to product manufactured and intellectual property developed under the BARDA contract and may, under certain circumstances, such as circumstances involving public health and safety, license such inventions to third parties without our consent;
|
•
|
cancel, terminate or suspend our BARDA contract based on violations or suspected violations of laws or regulations;
|
•
|
terminate our BARDA contract in whole or in part for the convenience of the government for any reason or no reason, including if funds become unavailable to the applicable governmental agency;
|
•
|
reduce the scope and value of our BARDA contract;
|
•
|
decline to exercise an option to continue the BARDA contract;
|
•
|
direct the course of a development program in a manner not chosen by the government contractor;
|
•
|
require us to perform the option segments even if doing so may cause us to forego or delay the pursuit of other opportunities with greater commercial potential;
|
•
|
take actions that result in a longer development timeline than expected; and
|
•
|
change certain terms and conditions in our BARDA contract.
|
•
|
FAR, and agency-specific regulations supplements to the FAR, which comprehensively regulate the procurement, formation, administration and performance of government contracts and implement federal procurement policy in numerous areas, such as employment practices, protection of the environment, accuracy and retention periods of records, recording and charging of costs, treatment of laboratory animals and human subject research;
|
•
|
business ethics and public integrity obligations, which govern conflicts of interest and the hiring of former government employees, restrict the granting of gratuities and funding of lobbying activities and incorporate other requirements such as the Anti-Kickback Act and the Foreign Corrupt Practices Act;
|
•
|
export and import control laws and regulations; and
|
•
|
laws, regulations and executive orders restricting the use and dissemination of information classified for national security purposes and the exportation of certain products and technical data.
|
•
|
termination of contracts;
|
•
|
forfeiture of profits;
|
•
|
suspension of payments;
|
•
|
fines; and
|
•
|
suspension or prohibition from conducting business with the U.S. government.
|
•
|
impairment of our business reputation and significant negative media attention;
|
•
|
withdrawal of participants from our clinical studies;
|
•
|
significant costs to defend the related litigation and related litigation;
|
•
|
distraction of management’s attention from our primary business;
|
•
|
substantial monetary awards to patients or other claimants;
|
•
|
inability to commercialize our product candidates, including brincidofovir; and
|
•
|
decreased demand for our product candidates, if approved for commercial sale.
|
•
|
multiple, conflicting and changing laws and regulations such as tax laws, privacy regulations, export and import restrictions, employment, immigration and labor laws, regulatory requirements, and other governmental approvals, permits and licenses;
|
•
|
difficulties in staffing and managing foreign operations;
|
•
|
risks associated with obtaining and maintaining, or the failure to obtain or maintain, regulatory approvals for the sale or use of our products in various countries;
|
•
|
complexities associated with managing government payor systems, multiple payor-reimbursement regimes or patient self-pay systems;
|
•
|
financial risks, such as longer payment cycles, difficulty enforcing contracts and collecting accounts receivable and exposure to foreign currency exchange rate fluctuations;
|
•
|
general political and economic conditions in the countries in operate, including terrorism and political unrest, curtailment of trade and other business restrictions;
|
•
|
regulatory and compliance risks that relate to maintaining accurate information and control over activities that may fall within the purview of the U.S. Foreign Corrupt Practices Act, its books and records provisions or its anti-bribery provisions, or similar anti-bribery or anti-corruption laws and regulations.
|
•
|
results of clinical trials of our product candidates or those of our competitors;
|
•
|
any delay in filing an application for any of our product candidates and any adverse development or perceived adverse development with respect to regulatory review of that application;
|
•
|
failure to successfully develop and commercialize our product candidates, including brincidofovir;
|
•
|
termination of any of our license or collaboration agreements;
|
•
|
any agency or judicial enforcement actions against us;
|
•
|
inability to obtain additional funding;
|
•
|
regulatory or legal developments in the United States and other countries applicable to our product candidates;
|
•
|
adverse regulatory decisions;
|
•
|
changes in the structure of healthcare payment systems;
|
•
|
inability to obtain adequate product supply for our product candidates, or the inability to do so at acceptable prices;
|
•
|
introduction of new products, services or technologies by our competitors;
|
•
|
failure to meet or exceed financial projections we provide to the public;
|
•
|
failure to meet or exceed the estimates and projections of the investment community;
|
•
|
changes in the market valuations of similar companies;
|
•
|
market conditions in the pharmaceutical and biotechnology sectors, and the issuance of new or changed securities analysts’ reports or recommendations;
|
•
|
announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors;
|
•
|
significant lawsuits (including patent or stockholder litigation), and disputes or other developments relating to proprietary rights (including patents, litigation matters and our ability to obtain patent protection for our technologies);
|
•
|
additions or departures of key scientific or management personnel;
|
•
|
sales of our common stock by us or our stockholders in the future;
|
•
|
trading volume of our common stock;
|
•
|
general economic, industry and market conditions; and
|
•
|
the other factors described in this “Risk Factors” section.
|
•
|
authorizing the issuance of “blank check” preferred stock, the terms of which may be established and shares of which may be issued without stockholder approval which could be used to institute a “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;
|
•
|
allowing the authorized number of our directors to be changed only by resolution of our board of directors;
|
•
|
limiting the removal of directors;
|
•
|
creating a staggered board of directors;
|
•
|
requiring that stockholder actions must be effected at a duly called stockholder meeting and prohibiting stockholder actions by written consent;
|
•
|
eliminating the ability of stockholders to call a special meeting of stockholders; and
|
•
|
establishing advance notice requirements for nominations for election to the board of directors or for proposing matters that can be acted upon at duly called stockholder meetings.
|
Number
|
|
Description
|
3.1(1)
|
|
Amended and Restated Certificate of Incorporation of the Registrant.
|
|
|
|
3.2(1)
|
|
Amended and Restated Bylaws of the Registrant.
|
|
|
|
4.1(2)
|
|
Form of Common Stock Certificate of the Registrant.
|
|
|
|
4.2(2)
|
|
Form of Warrant to Purchase Stock issued to participants in the Registrant's Series F Preferred Stock financing dated February 7, 2011.
|
|
|
|
4.3(2)
|
|
Amended and Restated Investor Rights Agreement dated February 7, 2011 by and among the Registrant and certain of its stockholders.
|
|
|
|
4.4(3)
|
|
Amendment to Amended and Restated Investor Rights Agreement dated October 29, 2014 by and among the Registrant and certain of its stockholders.
|
|
|
|
10.1(4)
|
|
Contract modification No. 27, dated July 14, 2015, to the contract by and between the Registrant and the Biomedical Advanced Research and Development Authority of the United States Department of Health and Human Services dated February 16, 2011, as amended.
|
|
|
|
10.2*
|
|
Contract modification No. 28, dated September 1, 2015, to the contract by and between the Registrant and the Biomedical Advanced Research and Development Authority of the United States Department of Health and Human Services dated February 16, 2011, as amended.
|
|
|
|
10.3*
|
|
Contract modification No. 29, dated September 11, 2015, to the contract by and between the Registrant and the Biomedical Advanced Research and Development Authority of the United States Department of Health and Human Services dated February 16, 2011, as amended.
|
|
|
|
31.1
|
|
Certification of Principal Executive Officer pursuant to Rule 13a-14(a) or Rule 15d-14(a) of the Securities Exchange Act of 1934, as amended.
|
|
|
|
31.2
|
|
Certification of Principal Financial Officer pursuant to Rule 13a-14(a) or Rule 15d-14(a) of the Securities Exchange Act of 1934, as amended.
|
|
|
|
32.1
|
|
Certification of Principal Executive Officer pursuant to Rule 13a-14(b) of the Securities Exchange Act of 1934, as amended, and 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
|
|
|
|
32.2
|
|
Certification of Principal Financial Officer pursuant to Rule 13a-14(b) of the Securities Exchange Act of 1934, as amended, and 18 U.S.C. Section 1350, as adopted pursuant Section 906 of the Sarbanes-Oxley Act of 2002.
|
|
|
|
101.INS
|
|
XBRL Instance Document.
|
|
|
|
101.SCH
|
|
XBRL Taxonomy Extension Schema Document.
|
|
|
|
101.CAL
|
|
XBRL Taxonomy Extension Calculation Linkbase Document.
|
|
|
|
101.DEF
|
|
XBRL Taxonomy Extension Definition Linkbase Document.
|
|
|
|
101.LAB
|
|
XBRL Taxonomy Extension Label Linkbase Document.
|
|
|
|
101.PRE
|
|
XBRL Taxonomy Extension Presentation Linkbase Document.
|
(1)
|
Incorporated by reference to Chimerix, Inc.’s Current Report on Form 8-K (No. 001-35867), filed with the SEC on April 16, 2013.
|
(2)
|
Incorporated by reference to Chimerix, Inc.’s Registration Statement on Form S-1 (No. 333-187145), as amended.
|
(3)
|
Incorporated by reference to Chimerix, Inc.'s Current Report on Form 8-K (No. 001-35867) filed with the SEC on October 29, 2014.
|
(4)
|
Incorporated by reference to Chimerix, Inc.'s Quarterly Report on Form 10-Q (No. 001-35867) filed with the SEC on August 6, 2015.
|
|
CHIMERIX, INC.
|
|
|
|
|
November 5, 2015
|
By:
|
/s/ M. Michelle Berrey
|
|
|
M. Michelle Berrey, MD, MPH
|
|
|
President and Chief Executive Officer
|
|
|
|
November 5, 2015
|
By:
|
/s/ Timothy W. Trost
|
|
|
Timothy W. Trost
|
|
|
Senior Vice President, Chief Financial Officer and Corporate Secretary
|
CONTINUATION SHEET
|
REFERENCE NO. OF DOCUMENT BEING CONTINUED
HHSO100201100013C/0028
|
PAGE OF
|
||||||
2
|
23
|
|||||||
NAME OF OFFEROR OR CONTACTOR
CHIMERIX, INC. 1377270
|
||||||||
ITEM NO.
(A)
|
SUPPLIES/SERVICES
(B)
|
QUANTITY
(C)
|
UNIT
(D)
|
UNIT PRICE
(E)
|
AMOUNT
(F)
|
|||
|
efforts within Option 2/CLIN 0003 that involve […***…] and […***…] cannot be performed until the receipt and approval of all required Protocols by BARDA inclusive of all IRB, OHRP approvals and any required Ethics Approvals for any clinical trials/studies and any required approved OLAW Assurances and IIA approvals from OLAW for any non clinical animal studies.
2. The incorporation of the attached Statement of Work (SOW) changes in the paragraph above also result in the incorporation of the attached changes into the contract into WBS Milestones/Deliverables and Technical Deliverables and Contract Milestones and Go/No Go Decision Gates dated 20 August 20l5 under Article F.2. Deliverables.
3. The total amount, scope and period of performance of Option 2/CLIN 0003 remains unchanged. The total amount, scope and period of performance of all other CLINs that are currently being performed under the contract remain unchanged. This modification does not exercise any unexercised Option CLINs under the contract and does not authorize any performance of efforts under any unexercised Option CLINs under the contract. In addition, the total amount, scope and period of performance of all unexercised Option CLINs under the contract remain unchanged.
B. This is a no cost bilateral modification. All other terms and conditions of the contract remain unchanged.
Period of Performance: 02/16/2011 to 06/30/2016
|
|
|
|
|
1.
|
PREAMBLE
|
I.
|
[…***…]
|
II.
|
[…***…]
|
III.
|
[…***…]
|
IV.
|
[…***…]
|
2.
|
PHASE I: [
…***…
]
|
2.1
|
Program Management
|
2.1.1
|
The overall management, integration and coordination of all contract activities, including a technical and administrative infrastructure to ensure the efficient planning, initiation, implementation, and direction of all contract activities;
|
2.1.2
|
A Principal Investigator (PI) responsible for project management, communication, tracking, monitoring and reporting on status and progress, and modification to the project requirements and timelines, including projects undertaken by subcontractors; The contract deliverables list (reference), identifies all contract deliverables and reporting requirements for this contract.
|
2.1.3
|
Project Manager(s) with responsibility for monitoring and tracking day-to-day progress and timelines, coordinating communication and project activities; costs incurred; and program management; The contract deliverables list (reference), identifies all contract deliverables and reporting requirements for this contract.
|
2.1.4
|
A BARDA Liaison with responsibility for effective communication with the Project Officer and Contracting Officer.
|
2.1.5
|
Administrative and legal staff to provide development of compliant subcontracts, consulting, and other legal agreements, and ensure timely acquisition of all proprietary rights, including IP rights, and reporting all inventions made in the performance of the project.
|
2.1.6
|
Administrative staff with responsibility for financial management and reporting on all activities conducted by the Contractor and any subcontractors.
|
2.1.8
|
Contract Review Meetings.
|
2.1.8.1
|
The Contractor shall participate in regular meetings to coordinate and oversee the contract effort as directed by the Contracting and Project Officers. Such meetings may include, but are not limited to, meeting of the Contractors and subcontractors to discuss clinical manufacturing progress, product development, product assay development, scale up manufacturing development, clinical sample assays development, preclinical/clinical study designs and regulatory issues; meetings with individual contractors and other HHS officials to discuss the technical, regulatory, and ethical aspects of the program; and meeting with technical consultants to discuss technical data provided by the Contractor.
|
2.1.8.2
|
The Contractor shall participate in teleconferences every two weeks between the Contractor and subcontractors and BARDA to review technical progress. Teleconferences or additional face-to-face meetings shall be more frequent at the request of BARDA.
|
2.1.9
|
Integrated Master Schedule
|
2.1.9.1
|
Within 30 calendar days of the effective date of the contract, the Contractor shall submit a first draft of an updated Integrated Master Schedule in a format agreed upon by BARDA to the Project Officer and the Contracting Officer for review and comment. The Integrated Master Schedule shall be incorporated into the contract, and will be used to monitor performance of the contract. Contractor shall include the key milestones and Go/No Go decision gates. The IMS for the period of performance will be mutually agreed upon at the PMBR
|
2.1.10
|
Integrated Master Plan
|
2.1.10.1
|
Work Breakdown Structure: The Contractor shall utilize a WBS template agreed upon by BARDA for reporting on the contact. The Contractor shall expand and delineate the Contract Work Breakdown Structure (CWBS) to a level agreed upon by BARDA as part of their Integrated Master Plan for contract reporting. The CWBS shall be discernable and consistent. BARDA may require Contractor to furnish WBS data at the work package level or at a lower level if there is significant complexity and risk associated with the task.
|
2.1.10.2
|
GO/NO-GO Decision Gates: The Integrated Master Plan outlines key milestones with “Go/No Go” decision criteria (entrance and exit criteria for each phase of the project). The project plan should include, but not be limited to, milestones in manufacturing, non-clinical and clinical studies, and regulatory submissions.
|
2.1.10.3
|
Earned Value Management System Plan: Subject to the requirements under HHSAR Clause 352.234-4, the Contractor shall use principles of Earned Value Management System (EVMS) in the management of this contract. The Seven Principles are:
|
I.
|
Plan all work scope for the program to completion.
|
II.
|
Break down the program work scope into finite pieces that can be assigned to a responsible person or organization for control of technical, schedule, and cost objectives.
|
III.
|
Integrate program work scope, schedule, and cost objectives into a performance measurement baseline plan against which accomplishments may be measured. Control Changes to the baseline.
|
IV.
|
Use actual cost incurred and recorded in accomplishing the work performed.
|
V.
|
Objectively assess accomplishments at the work performance level.
|
VI.
|
Analyze significant variances from the plan, forecast impacts, and prepare an estimate at completion based on performance to date and work to be performed.
|
VII.
|
Use earned value information in the company’s management processes.
|
2.1.11
|
Decision Gate Reporting: On completion of a stage of the product development, as defined in the agreed upon Integrated Master Schedule and Integrated Master Plan, the Contractor shall prepare and submit to the Project Officer and the Contracting Officer a Decision Gate Report that contains (i) sufficient detail, documentation and analysis to support successful completion of the stage according to the predetermined qualitative and quantitative criteria that were established for Go/No Go decision making; and (ii) a description of the next stage of product development to be initiated and a request for approval to proceed to the next stage of product development.
|
2.1.12
|
Risk Management Plan: The Contractor shall develop a risk management plan within 90 days of contract award highlighting potential problems and/or issues that may arise during the life of the contract, their impact on cost, schedule and performance, and appropriate remediation plans. This plan should reference relevant WBS elements where appropriate. Updates to this plan shall be included every three months (quarterly) in the monthly Project Status Report.
|
2.1.13
|
Performance Measurement Baseline Review (PMBR): The Contractor shall submit a plan for a PMBR to occur within 90 days of contract award. At the PMBR, the Contractor and BARDA shall mutually agree upon the budget, schedule and technical plan baselines (Performance Measurement Baseline). These baselines shall be the basis for monitoring and reporting progress throughout the life of the contract. The PMBR is conducted to achieve confidence that the baselines accurately capture the entire technical scope of work, are consistent with contract schedule requirements, are reasonably and logically planned, and have adequate resources assigned. The goals of the PMBR are as
FOLLOWS
:
|
I.
|
Jointly assess areas such as the Contractor’s planning for complete coverage of the SOW, logical scheduling of the work activities, adequate resources, and identification of inherent risks
|
II.
|
Confirm the integrity of the Performance Measurement Baseline (PMB)
|
III.
|
Foster the use of EVM as a means of communication
|
IV.
|
Provide confidence in the validity of Contractor reporting
|
V.
|
Identify risks associated with the PMB
|
VI.
|
Present any revised PMBs for mutual agreement
|
VII.
|
Present an Integrated Master Schedule: The Contractor shall deliver an initial program level Integrated Master Schedule (IMS) that rolls up all time-phased WBS elements down to the activity level. This IMS shall include the dependencies that exist between tasks. This IMS will be agreed to and finalized at the PMBR. DI-MGMT-81650 may be referenced as guidance in creation of the IMS (see http://www.acq.osd.mil/pm/).
|
VIII.
|
Present the Risk Management Plan
|
2.1.14
|
Deviation Request: During the course of contract performance, in response to a need to change IMS activities as baselined at the PMBR, the Contractor shall submit a Deviation Report. This report shall request a change in the agreed-upon IMS and timelines. This report shall include: (i) discussion of the justification/rationale for the proposed change; (ii) options for addressing the needed changes from the agreed upon timelines, including a cost-benefit analysis of each option; and (iii) recommendations for the preferred option that includes a full analysis and discussion of the effect of the change on the entire product development program, timelines, and budget.
|
2.1.15
|
Monthly and Annual Reports: The Contractor shall deliver Project Status Reports on a monthly basis. The reports shall address the items below cross referenced to the WBS, SOW, IMS, and EVM:
|
I.
|
Executive summary highlighting the progress, issues, and relevant activities in manufacturing, non-clinical, clinical, and regulatory;
|
II.
|
Progress in meeting contract milestones, detailing the planned progress and actual progress during the reporting period, explaining any differences between the two and corrective steps;
|
III.
|
Updated IMS;
|
IV.
|
Updated EVM;
|
V.
|
Updated Risk Management Plan (Every 3 months);
|
VI.
|
Three month rolling forecast of planned activities;
|
VII.
|
Progress of regulatory submissions;
|
VIII.
|
Estimated and actual expenses;
|
2.1.16
|
Data Management: The Contractor shall develop and implement data management and quality control systems/procedures, including transmission, storage, confidentiality, and retrieval of all contract data;
|
2.1.16.1
|
Provide for the statistical design and analysis of data resulting from the research;
|
2.1.16.2
|
Provide raw data or specific analyses of data generated with contract funding to the Project Officer, upon request.
|
2.2
|
Non-Clinical Toxicology
|
2.2.1
|
N/A (no scope)
|
2.3
|
Non-Clinical
|
2.3.1
|
Develop and validate […***…] to lower […***…].
|
2.3.2
|
[…***…]: Conduct […***…] studies including […***…] studies, […***…], and […***…] studies in […***…].
|
2.3.3
|
[…***…]
|
2.3.3.1
|
Conduct […***…] study in […***…].
|
2.3.3.2
|
Conduct […***…] studies including […***…] studies, […***…] studies including […***…] for CMX-001 and […***…] in […***…].
|
2.3.4
|
Use of […***…] as a CMX-001 Surrogate in […***…] Studies.
|
2.3.4.1
|
Dose […***…] with […***…] to identify the concentration of the […***…] in […***…] associated with […***…] of […***…].
|
2.3.5
|
Scaling of […***…] to […***…] by conducting studies with […***…] to determine […***…] in […***…].
|
2.3.6
|
[…***…] determination of CMX001, […***…] and […***…] in the […***…].
|
2.3.7
|
Conduct […***…] experiments to demonstrate […***…] following effective […***…] prior to […***…].
|
2.3.8
|
Conduct studies to optimize […***…] in […***…].
|
2.3.9
|
Conduct CMX001 […***…] study in […***…] at a dose of CMX001 equivalent or less than […***…] with treatment beginning at the […***…]
|
2.4
|
Clinical
|
2.4.1
|
Measurement of […***…] levels in […***…] and correlate the […***…] levels to studies conducted in […***…].
|
2.4.2
|
Conduct expanded access protocol ([…***…]).
|
2.4.3
|
Analyze data and provide a Final Report for […***…] evaluation of CMX001 in patients […***…]
|
2.5
|
Regulatory
|
2.5.1
|
Engaging the FDA on a path to support the treatment of smallpox indication with CMX-001
|
2.5.2
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including meetings to review EUA and/or all other data packages;
|
2.5.3
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA; (ii) final minutes of any informal meeting with the FDA;
|
2.5.4
|
Obtain FDA concurrence on the feasibility of the proposed […***…] with CMX001/[…***…]/[…***…] in the […***…], including FDA feedback on […***…] and review of data for the first […***…] enrolled in the […***…] sub-study
|
2.5.5
|
Develop and submit a revised […***…] for CMX001 for Treatment of Smallpox, including […***…] for FDA review and comment, and revise the […***…] as requested by FDA
|
2.6
|
CMC
|
2.6.1
|
Validation of the […***…] process: Validation of the process to demonstrate the […***…] of a […***…] of acceptable quality will be performed.
|
2.6.2
|
Validation of the […***…] process to produce […***…]: Validation of the process to demonstrate the […***…] of a […***…] of acceptable quality will be performed.
|
3.
|
PHASE II: [
…***…
]
|
3.1
|
Program Management (consistent with section 2.1)
|
3.1.2
|
Program management scope in BASE year is consistent with program management scope in each option year.
|
3.2
|
Non-Clinical toxicology
|
3.2.11
|
N/A (no scope)
|
3.3
|
Non-Clinical
|
3.3.4
|
Quantify […***…] concentrations in […***…] from […***…].
|
3.3.5
|
Determine […***…] for CMX001 in […***…] in […***…].
|
3.3.6
|
Scaling of […***…] to […***…] - Review with BARDA and FDA the […***…] generated to support scaling between […***…] and […***…] using […***…] as well as comparisons of […***…] in the […***…].
|
3.3.7
|
Determine […***…] for CMX001 in […***…] in […***…].
|
3.3.8
|
Conduct […***…].
|
3.3.9
|
Conduct […***…] and […***…]
|
3.3.10
|
Chimerix will provide […***…] for the […***…] and […***…] conducted under […***…]
|
3.4
|
Clinical
|
3.4.6
|
N/A (No scope)
|
3.5
|
Regulatory
|
3.5.3
|
Engaging the FDA on a path to support the treatment of smallpox indication with CMX001
|
3.5.4
|
Generating all necessary documentation for […***…]. […***…]
|
3.5.5
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including meetings to review EUA (if needed) and/or all other data packages;
|
3.5.6
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA relating to the smallpox program; (ii) final draft minutes of any informal meeting with the FDA relating to the smallpox program.
|
3.6
|
CMC
|
3.6.1
|
N/A (No scope)
|
4.
|
PHASE III: [
…***…
]
|
4.1
|
Program Management
(Consistent with section 2.1)
|
4.1.12
|
Program management scope in BASE year is consistent with program management scope in each option year.
|
4.2
|
Non-Clinical toxicology
|
4.2.11
|
N/A (no scope)
|
4.3
|
Non-Clinical
|
4.3.7
|
[…***…] studies: A […***…] study will be conducted with the […***…] of CMX001 selected based on the results of the […***…] and […***…] studies. […***…] will be […***…] to receive […***…] beginning at the […***…] or the FDA agreed upon trigger for treatment. The first […***…] study will be a […***…] study of CMX001 in the […***…] model. A study will be conducted with an […***…] of CMX001 to determine the […***…] after observation of the FDA agreed upon trigger for treatment. These studies will include […***…] and […***…]. The primary endpoint will be […***…].
|
4.3.8
|
A […***…] study of CMX001 in the […***…]: The delayed treatment study will evaluate the […***…] of CMX001 at […***…]. The study will include […***…] and […***…] agreed upon with the FDA. The primary endpoint will be […***…]. A […***…] study to measure […***…] in the selected […***…] will be conducted to confirm the […***…]. A […***…] study will be conducted prior to […***…] studies in the […***…] to 1) determine […***…] and […***…] of […***…] and 2) to confirm presence of […***…] at fixed intervals […***…].
|
4.3.9
|
Conduct additional studies in […***…] to determine […***…] and […***…] for CMX001 at […***…].
|
4.3.10
|
Conduct […***…] of […***…].
|
4.3.11
|
Conduct additional studies for […***…] of […***…] to be used in […***…].
|
4.4
|
Clinical
|
4.4.7
|
Clinical […***…] studies to evaluate […***…] used in previous clinical studies and […***…] used in previous clinical studies and […***…]. This study will […***…] to […***…] to determine if […***…] are comparable.
|
4.5
|
Regulatory
|
4.5.2
|
Generating all necessary data and preparing documentation for an […***…] meeting submissions to regulatory agencies;
|
4.5.3
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including the […***…] Meeting, meetings to review […***…], EUA (if needed) and/or all other data packages;
|
4.5.4
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA relating to this Contract; (ii) final draft minutes of any informal meeting with the FDA;
|
4.5.5
|
Preparing an […***…] submission […***…].
|
4.6
|
CMC
|
4.6.1
|
[…***…] in order to generate […***…] for registration and clinical trial supplies.
|
4.6.2
|
[…***…]. Validation of the process to demonstrate the […***…] of a […***…] of acceptable quality will be performed.
|
5.
|
PHASE IV: [
…***…
]
|
5.1
|
Program Management
(Consistent with section 2.1)
|
5.1.12
|
Program management scope in BASE year is consistent with program management scope in each option year.
|
5.2
|
Non-Clinical toxicology
|
5.2.12
|
N/A (no scope)
|
5.3
|
Non-Clinical
|
5.3.8
|
[…***…] studies. ). […***…] will be randomized to receive […***…] beginning at the […***…]. These studies will include […***…] and […***…] as well as […***…] including […***…]. The primary endpoint will be […***…].
|
5.3.1
|
[…***…] Studies. This study will determine the […***…] at the […***…]. […***…] and […***…] at the […***…]. The primary endpoint will be […***…]. If FDA requires a […***…] in the […***…] studies, the […***…] study may not be needed.
|
5.3.2
|
Conduct […***…] Studies. This study will determine the […***…] at the […***…]. […***…] and […***…] at the […***…].
|
5.4
|
Clinical
|
5.4.1
|
Phase 3 development including […***…] study, […***…] study, phases II […***…] study. A […***…] study will be conducted to compare the […***…] of CMX001 in […***…] to […***…]. A […***…] study will be conducted to compare the […***…] of CMX001 when […***…]. A […***…] study will be conducted to […***…] to support an NDA.
|
5.4.2
|
Measurement of […***…] in […***…] and correlate the […***…] to studies conducted in […***…] (if required)
|
5.4.3
|
Compile […***…] for NDA submission. A […***…] collected from all CMX001 studies, irrespective of indication, will be populated and analyzed in order to support an NDA for smallpox.
|
5.5
|
Regulatory
|
5.5.1
|
Generating all necessary data and preparing documentation for NDA submissions to regulatory agencies;
|
5.5.2
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including meetings to review IND, NDA and/or all other data packages;
|
5.5.3
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA; (ii) final draft minutes of any informal meeting with the FDA
|
5.6
|
CMC
|
5.6.1
|
[…***…]. […***…] of the process to demonstrate the […***…] of a […***…] will be performed.
|
6.
|
PHASE V: [
…***…
]
|
6.1
|
Program Management
(Consistent with section 2.1)
|
6.1.1
|
Program management scope in BASE year is consistent with program management scope in each option year.
|
6.2
|
Non-Clinical toxicology
|
6.2.3
|
N/A (no scope)
|
6.3
|
Non-Clinical
|
6.3.4
|
[…***…] Studies. This study replicates […***…] if a larger sample size is necessary to achieve a […***…] result.
|
6.4
|
Clinical
|
6.4.4
|
Compile […***…]. A database of […***…] data collected from all CMX001 clinical studies, irrespective of […***…], will be populated and analyzed in order to support an NDA for smallpox.
|
6.5
|
Regulatory
|
6.5.2
|
Generating all necessary data and preparing documentation for NDA submissions to regulatory agencies;
|
6.5.3
|
Submitting NDA documentation to the FDA in a timely manner, consistent with timelines set out in the contract and by the FDA.
|
6.5.4
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including meetings to review IND, EUA and/or all other data packages;
|
6.5.5
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA; (ii) final draft minutes of any informal meeting with the FDA;
|
6.6
|
CMC
|
6.6.1
|
[…***…]. […***…] of the process to demonstrate the […***…] of a […***…] will be performed.
|
7.
|
Other Items
|
7.1
|
Facilities, Equipment and Other Resources. (Contract: Section J)
|
7.1.4
|
The […***…] and use of […***…];
|
7.1.5
|
The acquisition, handling, storage and shipment of […***…], including […***…] required for working with the […***…];
|
7.1.6
|
The […***…] of […***…] under cGMP;
|
7.1.6.1
|
The design and conduct of […***…]; and
|
7.1.6.2
|
The conduct of […***…] studies to determine […***…] of […***…]
|
7.1.7
|
Design and conduct of […***…] under GCP.
|
REVISED MILESTONES ARTICLE F.2 DELIVERABLES
|
|||||||
Current
Milestone # |
Milestone Definition
|
Go Criteria
|
No-Go Criteria
|
Deliverable
|
WBS/SOW #
|
Segment
|
|
•
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
2.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
3.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
4.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
5.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
|
|
|
[…***…]
|
|
|
|
|
6.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
7.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
8.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
|
|
[…***…]
|
[…***…]
|
|
|
|
|
9.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
|
10.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
|
11.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
12.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
|
13.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
|
14.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
15.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
|
|
|
[…***…]
|
|
|
|
|
16.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
17.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
|
18.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
19.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
|
|
[…***…]
|
|
|
|
|
20.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
21.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
22.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
23.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
24.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
|
|
[…***…]
|
|
|
|
|
|
25.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
26.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
BCA MILESTONE
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
NEW OPTION 1 MILESTONE TO BE ADDED TO ARTICLE F.2 DELIVERABLES OF THE CONTRACT
|
|||||||
1.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
|
|
|
|
|
|
[…***…]
|
|
2.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
|
3.
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
[…***…]
|
CONTINUATION SHEET
|
REFERENCE NO. OF DOCUMENT BEING CONTINUED
HHSO100201100013C/0029
|
PAGE OF
|
||||||
2
|
23
|
|||||||
NAME OF OFFEROR OR CONTACTOR
CHIMERIX, INC. 1377270
|
||||||||
ITEM NO.
(A)
|
SUPPLIES/SERVICES
(B)
|
QUANTITY
(C)
|
UNIT
(D)
|
UNIT PRICE
(E)
|
AMOUNT
(F)
|
|||
|
follows:
CLI
N 0004:
Total Estimated Cost: $[...***...]
Total Fixed Fee: $[...***...]
Total Estimated Cost Plus Fixed Fee: $12,918,174.00
The total period of performance of CLIN 0004 under the contract is from 11 September 2015 through 31 October 2016.
2. This modification also results in an increase in the total amount of the
contract from $53,213,599.00 by $12,918,174.00 to $66,131,773.00 as well as the
following:
Total Estimated Cost of the Contract: From $[...***...] By $[...***...] To
$[...***...].
Total Fixed Fee of the Contract: From $[...***...] By $[...***...] To $[...***...].
Total Estimated Cost Plus Fixed Fee of the Contract: From $53,213,599.00 By
$12,918,174.00 To $66,131,773.00.
3. In Block 14 of the SF 26, the following CAN Number is added: Appropriation Year:
2015, Object Class: 25103, CAN# 1992015 $12,918,174.00
4. In Block 15G of the SF 26, the amount of $53,213,599.00 is hereby changed to
$66,131,773.00.
5. The Government and the Contractor bilaterally modify Attachment 1, Statement of
Work dated 20 August 2015, under PART III, LIST OF DOCUMENTS, EXHIBITS AND OTHER
ATTACHMENTS, SECTION J - LIST OF ATTACHMENTS for the purposes of incorporating
within scope Non-Clinical Pivotal Studies and within scope Process Validation
efforts per recent FDA guidance under CLIN 0004 and to delete Clinical Studies that
are not needed at this time per recent FDA guidance under CLIN 0004. As such,
Attachment 1, Statement of Work dated 20 August 2015, under PART III, LIST OF
DOCUMENTS, EXHIBITS AND OTHER ATTACHMENTS, SECTION J - LIST OF ATTACHMENTS is hereby deleted and replaced with the attached Statement of Work dated 11 September 2015 (14 Pages attached herein). The efforts within CLIN 0004 that involve [...***...] and [...***...] cannot be performed until the receipt and approval of all required Protocols by BARDA inclusive of all IRB, OHRP approvals and any required Ethics Approvals for any clinical trials/studies and any required approved OLAW Assurances and IIA approvals from OLAW for any non clinical animal studies.
6. The incorporation of the attached Statement of Work (SOW) in the paragraph above
also results in the incorporation of the attached changes (6 Pages attached herein)
into the contract into WBS Milestones/Deliverables and Technical Deliverables and
Technical Deliverables and Contract Milestones and Go/No Go Decision Gates dated 11
Continued ...
|
CONTINUATION SHEET
|
REFERENCE NO. OF DOCUMENT BEING CONTINUED
HHSO100201100013C/0029
|
PAGE OF
|
||||||
3
|
23
|
|||||||
NAME OF OFFEROR OR CONTACTOR
CHIMERIX, INC. 1377270
|
||||||||
ITEM NO.
(A)
|
SUPPLIES/SERVICES
(B)
|
QUANTITY
(C)
|
UNIT
(D)
|
UNIT PRICE
(E)
|
AMOUNT
(F)
|
|||
|
September 2015 under Article F.2. Deliverables.
7. Total expenses for all domestic and foreign travel (transportation, lodging,
subsistence and incidental expenses) incurred in direct performance of this contract shall not exceed $[...***...] during the base segment/CLIN 0001, $[...***...] during Option Period 1/CLIN 0002, $[...***...] during Option Period 2/CLIN 0003 and $[...***...] for CLIN 0004.
8. The first and second sentences in Article G.7. INDIRECT COST RATES of the
contract are replaced with the following:
The following rates will be utilized for billing purposes during both the base period/CLIN 0001, Option 1/CLIN 0002, Option 2/CLIN 0003 and CLIN 0004 ONLY.
FY 11 (Retroactive Adjustment base period/CLIN 0001 ONLY) - Fringe Benefits at [...***...]% and Indirect at [...***...]%.
FY 12 and 13 (Retroactive Adjustment and Billing, base period/CLIN 0001 ONLY and Billing, Option 1/CLIN 0002, Option 2/CLIN 0003 and CLIN 0004 ONLY) - Fringe Benefits at [...***...]% and Indirect at [...***...]%.
9. The total amount, scope and period of performance of all other CLIN(s) that are currently being performed under the contract remain unchanged. This modification does not exercise any unexercised Option CLINs under the contract and does not authorize any performance of efforts under any unexercised Option CLINs under the contract. In addition, the total amount, scope and period of performance of all unexercised Option CLINs under the contract remain unchanged.
B. This is a bilateral modification. All other terms and conditions of the contract remain unchanged.
Delivery: 10/31/2016
Delivery Location Code: HHS
HHS
200 Independence Avenue, SW
Washington DC 20201 US
Appr. Yr.: 2015 CAN: 1992015 Object Class: 25103
FOB: Destination
Period of Performance: 02/16/2011 to 10/31/2016
Change Item 4 to read as follows(amount shown is the obligated amount):
Pivotal Studies and Validation Studies.
12,918,174.00
Reports and Other Data Deliverables.
September 2015 under Article F.2. Deliverables.
7. Total expenses for all domestic and foreign travel (transportation, lodging,
subsistence and incidental expenses) incurred in direct performance of this contract shall not exceed $[...***...] during the base segment/CLIN 0001, $[...***...] during Option Period 1/CLIN 0002, $[...***...] during Option Period 2/CLIN 0003 and $[...***...] for CLIN 0004.
8. The first and second sentences in Article G.7. INDIRECT COST RATES of the
contract are replaced with the following:
The following rates will be utilized for billing purposes during both the base period/CLIN 0001, Option 1/CLIN 0002, Option 2/CLIN 0003 and CLIN 0004 ONLY.
FY 11 (Retroactive Adjustment base period/CLIN 0001 ONLY) - Fringe Benefits at [...***...]% and Indirect at [...***...]%.
FY 12 and 13 (Retroactive Adjustment and Billing, base period/CLIN 0001 ONLY and Billing, Option 1/CLIN 0002, Option 2/CLIN 0003 and CLIN 0004 ONLY) - Fringe Benefits at [...***...]% and Indirect at [...***...]%.
9. The total amount, scope and period of performance of all other CLIN(s) that are
currently being performed under the contract remain unchanged. This modification
does not exercise any unexercised Option CLINs under the contract and does not
authorize any performance of efforts under any unexercised Option CLINs under the
contract. In addition, the total amount, scope and period of performance of all
unexercised Option CLINs under the contract remain unchanged.
B. This is a bilateral modification. All other terms and conditions of the
contract remain unchanged.
Delivery: 10/31/2016
Delivery Location Code: HHS
HHS
200 Independence Avenue, SW
Washington DC 20201 US
Appr. Yr.: 2015 CAN: 1992015 Object Class: 25103
FOB: Destination
Period of Performance: 02/16/2011 to 10/31/2016
Change Item 4 to read as follows(amount shown is the obligated amount):
Pivotal Studies and Validation Studies.
12,918,174.00
Reports and Other Data Deliverables.
|
1.
|
PREAMBLE
|
I.
|
[...***...]
|
II.
|
[...***...]
|
III.
|
[...***...]
|
IV.
|
[...***...]
|
V.
|
[...***...]
|
2.
|
PHASE I: [...***...]
|
2.1
|
Program Management
|
2.1.1
|
The overall management, integration and coordination of all contract activities, including a technical and administrative infrastructure to ensure the efficient planning, initiation, implementation, and direction of all contract activities;
|
2.1.2
|
A Principal Investigator (PI) responsible for project management, communication, tracking, monitoring and reporting on status and progress, and modification to the project requirements and timelines, including projects undertaken by subcontractors; The contract deliverables list (reference), identifies all contract deliverables and reporting requirements for this contract.
|
2.1.3
|
Project Manager(s) with responsibility for monitoring and tracking day-to-day progress and timelines, coordinating communication and project activities; costs incurred; and program management; The contract deliverables list (reference), identifies all contract deliverables and reporting requirements for this contract.
|
2.1.4
|
A BARDA Liaison with responsibility for effective communication with the Project Officer and Contracting Officer.
|
2.1.5
|
Administrative and legal staff to provide development of compliant subcontracts, consulting, and other legal agreements, and ensure timely acquisition of all proprietary rights, including IP rights, and reporting all inventions made in the performance of the project.
|
2.1.6
|
Administrative staff with responsibility for financial management and reporting on all activities conducted by the Contractor and any subcontractors.
|
2.1.7
|
Contract Review Meetings.
|
2.1.7.1
|
The Contractor shall participate in regular meetings to coordinate and oversee the contract effort as directed by the Contracting and Project Officers. Such meetings may include, but are not limited to, meeting of the Contractors and subcontractors to discuss clinical manufacturing progress, product development, product assay development, scale up manufacturing development, clinical sample assays development, preclinical/clinical study designs and regulatory issues; meetings with individual contractors and other HHS officials to discuss the technical, regulatory, and ethical aspects of the program; and meeting with technical consultants to discuss technical data provided by the Contractor.
|
2.1.7.2
|
The Contractor shall participate in teleconferences every two weeks between the Contractor and subcontractors and BARDA to review technical progress. Teleconferences or additional face-to-face meetings shall be more frequent at the request of BARDA.
|
2.1.8
|
Integrated Master Schedule
|
2.1.8.1
|
Within 30 calendar days of the effective date of the contract, the Contractor shall submit a first draft of an updated Integrated Master Schedule in a format agreed upon by BARDA to the Project Officer and the Contracting Officer for review and comment. The Integrated Master Schedule shall be incorporated into the contract, and will be used to monitor performance of the contract. Contractor shall include the key milestones and Go/No Go decision gates. The IMS for the period of performance will be mutually agreed upon at the PMBR
|
2.1.9
|
Integrated Master Plan
|
2.1.9.1
|
Work Breakdown Structure: The Contractor shall utilize a WBS template agreed upon by BARDA for reporting on the contact. The Contractor shall expand and delineate the Contract Work Breakdown Structure (CWBS) to a level agreed upon by BARDA as part of their Integrated Master Plan for contract reporting. The CWBS shall be discernable and consistent. BARDA may require Contractor to furnish WBS data at the work package level or at a lower level if there is significant complexity and risk associated with the task.
|
2.1.9.2
|
GO/NO-GO Decision Gates: The Integrated Master Plan outlines key milestones with “Go/No Go” decision criteria (entrance and exit criteria for each phase of the project). The project plan should include, but not be limited to, milestones in manufacturing, non-clinical and clinical studies, and regulatory submissions.
|
2.1.9.3
|
Earned Value Management System Plan: Subject to the requirements under HHSAR Clause 352.234-4, the Contractor shall use principles of Earned Value Management System (EVMS) in the management of this contract. The Seven Principles are:
|
I.
|
Plan all work scope for the program to completion.
|
II.
|
Break down the program work scope into finite pieces that can be assigned to a responsible person or organization for control of technical, schedule, and cost objectives.
|
III.
|
Integrate program work scope, schedule, and cost objectives into a performance measurement baseline plan against which accomplishments may be measured. Control Changes to the baseline.
|
IV.
|
Use actual cost incurred and recorded in accomplishing the work performed.
|
V.
|
Objectively assess accomplishments at the work performance level.
|
VI.
|
Analyze significant variances from the plan, forecast impacts, and prepare an estimate at completion based on performance to date and work to be performed.
|
VII.
|
Use earned value information in the company’s management processes.
|
2.1.10
|
Decision Gate Reporting: On completion of a stage of the product development, as defined in the agreed upon Integrated Master Schedule and Integrated Master Plan, the Contractor shall prepare and submit to the Project Officer and the Contracting Officer a Decision Gate Report that contains (i) sufficient detail, documentation and analysis to support successful completion of the stage according to the predetermined qualitative and quantitative criteria that were established for Go/No Go decision making; and (ii) a description of the next stage of product development to be initiated and a request for approval to proceed to the next stage of product development.
|
2.1.11
|
Risk Management Plan: The Contractor shall develop a risk management plan within 90 days of contract award highlighting potential problems and/or issues that may arise during the life of the contract, their impact on cost, schedule and performance, and appropriate remediation plans. This plan should reference relevant WBS elements where appropriate. Updates to this plan shall be included every three months (quarterly) in the monthly Project Status Report.
|
2.1.12
|
Performance Measurement Baseline Review (PMBR): The Contractor shall submit a plan for a PMBR to occur within 90 days of contract award. At the PMBR, the Contractor and BARDA shall mutually agree upon the budget, schedule and technical plan baselines (Performance Measurement Baseline). These baselines shall be the basis for monitoring and reporting progress throughout the life of the contract. The PMBR is conducted to achieve confidence that the baselines accurately capture the entire technical scope of work, are consistent with contract schedule requirements, are reasonably and logically planned, and have adequate resources assigned. The goals of the PMBR are as
FOLLOWS
:
|
I.
|
Jointly assess areas such as the Contractor’s planning for complete coverage of the SOW, logical scheduling of the work activities, adequate resources, and identification of inherent risks
|
II.
|
Confirm the integrity of the Performance Measurement Baseline (PMB)
|
III.
|
Foster the use of EVM as a means of communication
|
IV.
|
Provide confidence in the validity of Contractor reporting
|
V.
|
Identify risks associated with the PMB
|
VI.
|
Present any revised PMBs for mutual agreement
|
VII.
|
Present an Integrated Master Schedule: The Contractor shall deliver an initial program level Integrated Master Schedule (IMS) that rolls up all time-phased WBS elements down to the activity level. This IMS shall include the dependencies that exist between tasks. This IMS will be agreed to and finalized at the PMBR. DI-MGMT-81650 may be referenced as guidance in creation of the IMS (see http://www.acq.osd.mil/pm/).
|
VIII.
|
Present the Risk Management Plan
|
2.1.13
|
Deviation Request: During the course of contract performance, in response to a need to change IMS activities as baselined at the PMBR, the Contractor shall submit a Deviation Report. This report shall request a change in the agreed-upon IMS and timelines. This report shall include: (i) discussion of the justification/rationale for the proposed change; (ii) options for addressing the needed changes from the agreed upon timelines, including a cost-benefit analysis of each option; and (iii) recommendations for the preferred option that includes a full analysis and discussion of the effect of the change on the entire product development program, timelines, and budget.
|
2.1.14
|
Monthly and Annual Reports: The Contractor shall deliver Project Status Reports on a monthly basis. The reports shall address the items below cross referenced to the WBS, SOW, IMS, and EVM:
|
I.
|
Executive summary highlighting the progress, issues, and relevant activities in manufacturing, non-clinical, clinical, and regulatory;
|
II.
|
Progress in meeting contract milestones, detailing the planned progress and actual progress during the reporting period, explaining any differences between the two and corrective steps
|
III.
|
Updated IMS;
|
IV.
|
Updated EVM;
|
V.
|
Updated Risk Management Plan (Every 3 months);
|
VI.
|
Three month rolling forecast of planned activities;
|
VII.
|
Progress of regulatory submissions;
|
VIII.
|
Estimated and actual expenses;
|
2.1.15
|
Data Management: The Contractor shall develop and implement data management and quality control systems/procedures, including transmission, storage, confidentiality, and retrieval of all contract data;
|
2.1.15.1
|
Provide for the statistical design and analysis of data resulting from the research;
|
2.1.15.2
|
Provide raw data or specific analyses of data generated with contract funding to the Project Officer, upon request.
|
2.2
|
Non-Clinical Toxicology
|
2.2.1
|
N/A (no scope)
|
2.3
|
Non-Clinical
|
2.3.1
|
Develop and validate [...***...] to lower [...***...].
|
2.3.2
|
[...***...]: Conduct [...***...] studies including [...***...] studies, [...***...], and [...***...] studies in [...***...].
|
2.3.3
|
[...***...]
|
2.3.3.1
|
Conduct [...***...] study in [...***...].
|
2.3.3.2
|
Conduct [...***...] studies including [...***...] studies, [...***...] studies including [...***...] for CMX-001 and [...***...] in [...***...].
|
2.3.4
|
Use of [...***...] as a CMX-001 Surrogate in [...***...] Studies.
|
2.3.4.1
|
Dose [...***...] with [...***...] to identify the concentration of the [...***...] in [...***...] associated with [...***...] of [...***...].
|
2.3.5
|
Scaling of [...***...] to [...***...] by conducting studies with [...***...] to determine [...***...] in [...***...].
|
2.3.6
|
[...***...] determination of CMX001, [...***...] and [...***...] in the [...***...].
|
2.3.7
|
Conduct [...***...] experiments to demonstrate [...***...] following effective [...***...] prior to [...***...].
|
2.3.8
|
Conduct studies to optimize [...***...] in [...***...].
|
2.3.9
|
Conduct CMX001 [...***...] study in [...***...] at a dose of CMX001 equivalent or less than [...***...] with treatment beginning at the [...***...]
|
2.4
|
Clinical
|
2.4.1
|
Measurement of [...***...] levels in [...***...] and correlate the [...***...] levels to studies conducted in [...***...].
|
2.4.2
|
Conduct expanded access protocol ([...***...]).
|
2.4.3
|
Analyze data and provide a Final Report for [...***...] evaluation of CMX001 in patients [...***...]
|
2.5
|
Regulatory
|
2.5.1
|
Engaging the FDA on a path to support the treatment of smallpox indication with CMX-001
|
2.5.2
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including meetings to review EUA and/or all other data packages;
|
2.5.3
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA; (ii) final minutes of any informal meeting with the FDA;
|
2.5.4
|
Obtain FDA concurrence on the feasibility of the proposed [...***...] [...***...] with CMX001/[...***...]/[...***...] in the [...***...], including FDA feedback on [...***...] and review of data for the first [...***...] enrolled in the [...***...] sub-study
|
2.5.5
|
Develop and submit a revised [...***...] for CMX001 for Treatment of Smallpox, including [...***...] for FDA review and comment, and revise the [...***...] as requested by FDA
|
2.6
|
CMC
|
2.6.1
|
Validation of the [...***...] process: Validation of the process to demonstrate the [...***...] of a [...***...] of acceptable quality will be performed.
|
2.6.2
|
Validation of the [...***...] process to produce [...***...]: Validation of the process to demonstrate the [...***...] of a [...***...] of acceptable quality will be performed.
|
3.
|
PHASE II: [...***...]
|
3.1
|
Program Management (consistent with section 2.1)
|
3.1.2
|
Program management scope in BASE year is consistent with program management scope in each option year.
|
3.2
|
Non-Clinical toxicology
|
3.2.11
|
N/A (no scope)
|
3.3
|
Non-Clinical
|
3.3.4
|
Quantify [...***...] concentrations in [...***...] from [...***...].
|
3.3.5
|
Determine [...***...] for CMX001 in [...***...] in [...***...].
|
3.3.6
|
Scaling of [...***...] to [...***...] - Review with BARDA and FDA the [...***...] generated to support scaling between [...***...] and [...***...] using [...***...] as well as comparisons of [...***...] in the [...***...].
|
3.3.7
|
Determine [...***...] for CMX001 in [...***...] in [...***...].
|
3.3.8
|
Conduct [...***...].
|
3.3.9
|
Conduct [...***...] and [...***...]
|
3.3.10
|
Chimerix will provide [...***...] for the [...***...] and [...***...] conducted under [...***...]
|
3.4
|
Clinical
|
3.4.6
|
N/A (No scope)
|
3.5
|
Regulatory
|
3.5.3
|
Engaging the FDA on a path to support the treatment of smallpox indication with CMX001
|
3.5.4
|
Generating all necessary documentation for [...***...]. [...***...]
|
3.5.5
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including meetings to review EUA (if needed) and/or all other data packages;
|
3.5.6
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA relating to the smallpox program; (ii) final draft minutes of any informal meeting with the FDA relating to the smallpox program.
|
3.6
|
CMC
|
3.6.1
|
N/A (No scope)
|
4.
|
PHASE III: [...***...]
|
4.1
|
Program Management
(Consistent with section 2.1)
|
4.1.12
|
Program management scope in BASE year is consistent with program management scope in each option year.
|
4.2
|
Non-Clinical toxicology
|
4.2.11
|
N/A (no scope)
|
4.3
|
Non-Clinical
|
4.3.7
|
[...***...] studies: A [...***...] study will be conducted with the [...***...] of CMX001 selected based on the results of the [...***...] and [...***...] studies. [...***...] will be [...***...] to receive [...***...] beginning at the [...***...] or the FDA agreed upon trigger for treatment. The first [...***...] study will be a [...***...] study of CMX001 in the [...***...] model. A study will be conducted with an [...***...] of CMX001 to determine the [...***...] after observation of the FDA agreed upon trigger for treatment. These studies will include [...***...] and [...***...]. The primary endpoint will be [...***...].
|
4.3.8
|
A [...***...] study of CMX001 in the [...***...]: The delayed treatment study will evaluate the [...***...] of CMX001 at [...***...]. The study will include [...***...] and [...***...] agreed upon with the FDA. The primary endpoint will be [...***...]. A [...***...] study to measure [...***...] in the selected [...***...] will be conducted to confirm the [...***...]. A [...***...] study will be conducted prior to [...***...] studies in the [...***...] to 1) determine [...***...] and [...***...] of [...***...] and 2) to confirm presence of [...***...] at fixed intervals [...***...].
|
4.3.9
|
Conduct additional studies in [...***...] to determine [...***...] and [...***...] for CMX001 at [...***...].
|
4.3.10
|
Conduct [...***...] of [...***...].
|
4.3.11
|
Conduct additional studies for [...***...] of [...***...] to be used in [...***...].
|
4.4
|
Clinical
|
4.4.7
|
Clinical [...***...] studies to evaluate [...***...] used in previous clinical studies and [...***...] used in previous clinical studies and [...***...]. This study will [...***...] to [...***...] to determine if [...***...] are comparable.
|
4.5
|
Regulatory
|
4.5.2
|
Generating all necessary data and preparing documentation for an [...***...] meeting submissions to regulatory agencies;
|
4.5.3
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including the [...***...] Meeting, meetings to review [...***...], EUA (if needed) and/or all other data packages;
|
4.5.4
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA relating to this Contract; (ii) final draft minutes of any informal meeting with the FDA;
|
4.5.5
|
Preparing an [...***...] submission [...***...].
|
4.6
|
CMC
|
4.6.1
|
[...***...] in order to generate [...***...] for registration and clinical trial supplies.
|
4.6.2
|
[...***...]. Validation of the process to demonstrate the [...***...] of a [...***...] of acceptable quality will be performed.
|
5.
|
PHASE IV: [...***...]
|
5.1
|
Program Management
(Consistent with section 2.1)
|
5.1.12
|
Program management scope in BASE year is consistent with program management scope in each option year.
|
5.2
|
Non-Clinical toxicology
|
5.2.12
|
N/A (no scope)
|
5.3
|
Non-Clinical
|
5.3.8
|
[...***...] study. A [...***...] study will be conducted with dose and study design subject to FDA feedback received at the [...***...] Meeting. [...***...] will be randomized to receive [...***...] beginning at the [...***...] or the FDA agreed upon trigger for treatment. These studies will include [...***...] and appropriate [...***...] assessments. The primary endpoint will be [...***...].
|
5.3.9
|
[...***...] study. A [...***...] study in the [...***...] will be conducted with dose and study design subject to FDA feedback received at the [...***...] Meeting. The study design proposed may be a [...***...] study of CMX001 in the [...***...]. The [...***...] study will evaluate the [...***...] of CMX001 at various fixed intervals after [...***...]. The study will include [...***...] and appropriate [...***...] agreed upon with the FDA. The primary endpoint will be [...***...]. Additional [...***...] studies per FDA feedback may be conducted as lead-in studies.
|
5.4
|
Clinical
|
5.4.6
|
N/A (No scope)
|
5.5
|
Regulatory
|
5.5.3
|
Generating all necessary data and preparing documentation for NDA submissions to regulatory agencies;
|
5.5.4
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including meetings to review IND, NDA and/or all other data packages relating to this Contract;
|
5.5.5
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA; (ii) final draft minutes of any informal meeting with the FDA relating to this Contract
|
5.6
|
CMC
|
5.6.1
|
[...***...]. [...***...] of the process to demonstrate the [...***...] of the final [...***...] process of [...***...] will be performed at new manufacturing site either at commercial scale or larger scale. May include a campaign of [...***...] and [...***...], the production of [...***...] to support the [...***...] of required necessary reference standards to support [...***...].
|
6.
|
PHASE V: [...***...]
|
6.1
|
Program Management
(Consistent with section 2.1)
|
6.1.13
|
Program management scope in BASE year is consistent with program management scope in each option year.
|
6.2
|
Non-Clinical toxicology
|
6.2.10
|
N/A (no scope)
|
6.3
|
Non-Clinical
|
6.3.7
|
[...***...] Studies. This study replicates [...***...] if a larger sample size is necessary to achieve a [...***...] result.
|
6.4
|
Clinical
|
6.4.6
|
Compile [...***...]. A database of [...***...] data collected from all CMX001 clinical studies, irrespective of [...***...], will be populated and analyzed in order to support an NDA for smallpox.
|
6.5
|
Regulatory
|
6.5.2
|
Generating all necessary data and preparing documentation for NDA submissions to regulatory agencies;
|
6.5.3
|
Submitting NDA documentation to the FDA in a timely manner, consistent with timelines set out in the contract and by the FDA.
|
6.5.4
|
Preparing materials for and requesting, scheduling and participating in all meetings with the FDA, including meetings to review IND, EUA and/or all other data packages;
|
6.5.5
|
Providing BARDA with (i) the initial draft minutes and final draft minutes of any formal meeting with the FDA; (ii) final draft minutes of any informal meeting with the FDA;
|
6.6
|
CMC
|
6.6.1
|
[...***...]. [...***...] of the process to demonstrate the [...***...] of a [...***...] will be performed.
|
7.
|
Other Items
|
7.1
|
Facilities, Equipment and Other Resources. (Contract: Section J)
|
7.1.11
|
The [...***...] and use of [...***...];
|
7.1.12
|
The acquisition, handling, storage and shipment of [...***...], including [...***...] required for working with the [...***...];
|
7.1.13
|
The [...***...] of [...***...] under cGMP;
|
7.1.13.1
|
The design and conduct of [...***...]; and
|
7.1.13.2
|
The conduct of [...***...] studies to determine [...***...] of [...***...]
|
7.1.14
|
Design and conduct of [...***...] under GCP.
|
REVISED MILESTONES ARTICLE F.2 DELIVERABLES
|
||||||
Current
Milestone # |
Milestone Definition
|
Go Criteria
|
No-Go Criteria
|
Deliverable
|
WBS/SOW #
|
Segment
|
1.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
2.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
3.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
4.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
5.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
6.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
|
|
|
[...***...]
|
|
|
|
7.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
8.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
9.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
10.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
11.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
|
|
[...***...]
|
[...***...]
|
|
|
[...***...]
|
12.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
13.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
14.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
15.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
16.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
17.
|
No longer in development plan.
|
|
|
|
N/A
|
N/A
|
18.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
|
|
|
[...***...]
|
|
|
|
19.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
20.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
21.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
22.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
|
|
[...***...]
|
|
|
|
|
23.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
BCA MILESTONE
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
NEW OPTION MILESTONES TO BE ADDED TO ARTICLE F.2 DELIVERABLES OF THE CONTRACT
|
||||||
25.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
26.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
27.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
28.
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
[...***...]
|
Date:
|
November 5, 2015
|
/s/ M. Michelle Berrey
|
|
|
M. Michelle Berrey, M.D., MPH
|
|
|
President and Chief Executive Officer
|
Date:
|
November 5, 2015
|
/s/ Timothy W. Trost
|
|
|
Timothy W. Trost
|
|
|
Senior Vice President, Chief Financial Officer and Corporate Secretary
|
By:
|
/s/ M. Michelle Berrey
|
|
|
Name:
|
M. Michelle Berrey, M.D., MPH
|
|
Title:
|
President and Chief Executive Officer
|
|
|
|
Date:
|
November 5, 2015
|
By:
|
/s/ Timothy W. Trost
|
|
|
Name:
|
Timothy W. Trost
|
|
Title:
|
Senior Vice President, Chief Financial Officer
and Corporate Secretary
|
|
||
Date:
|
November 5, 2015
|