þ
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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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27-3948465
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(State or other jurisdiction of
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(I.R.S. Employer
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incorporation or organization)
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Identification No.)
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Large accelerated filer
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¨
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Accelerated filer
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¨
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Non-accelerated filer
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þ
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Smaller reporting company
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þ
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Emerging growth company
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þ
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(Unaudited)
September 30, 2018 |
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December 31, 2017
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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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8,111,682
|
|
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$
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355,563
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Prepaid expenses
|
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525,582
|
|
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161,844
|
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||
Deferred offering costs
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—
|
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159,795
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Due from related party
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—
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75,000
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||
Total current assets
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8,637,264
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752,202
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Property and equipment, net
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40,233
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40,707
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Other assets
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5,580
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5,580
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Total assets
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$
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8,683,077
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$
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798,489
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Liabilities and Stockholders’ Equity (Deficit)
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Current Liabilities:
|
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Accounts payable
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$
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2,882,876
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$
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2,658,637
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Accrued expenses
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229,401
|
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1,180,225
|
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||
Note payable
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5,190,000
|
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—
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Convertible promissory notes, net
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—
|
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8,329,045
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Convertible promissory notes, related party, net
|
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—
|
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244,816
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||
Accrued interest
|
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—
|
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560,380
|
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Total current liabilities
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8,302,277
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12,973,103
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Commitments and contingencies (Note 8)
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Stockholders’ equity (deficit):
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Common stock* - $0.0001 par value, 350,000,000 and 250,000,000 shares authorized; 25,983,538 and 11,888,240 shares issued and outstanding as of September 30, 2018 and December 31, 2017, respectively
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2,598
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11,888
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Additional paid-in-capital
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40,879,119
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7,167,189
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Accumulated deficit
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(40,500,917
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)
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(19,353,691
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)
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Total stockholders’ equity (deficit)
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380,800
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(12,174,614
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)
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Total liabilities and stockholders’ equity (deficit)
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$
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8,683,077
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$
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798,489
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Three Months Ended
September 30, |
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Nine Months Ended
September 30, |
||||||||||||
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2018
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2017
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2018
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2017
|
||||||||
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(Unaudited)
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(Unaudited)
|
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(Unaudited)
|
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(Unaudited)
|
||||||||
Operating expenses (income):
|
|
|
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|
|
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||||||
Research and development
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$
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(1,785,645
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)
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$
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367,551
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$
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5,815,580
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$
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2,832,787
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General and administrative
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1,565,992
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1,973,256
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9,865,455
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6,115,088
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||||
Total operating expenses (income)
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(219,653
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)
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2,340,807
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15,681,035
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8,947,875
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||||
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Income (loss) from operations
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219,653
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(2,340,807
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)
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(15,681,035
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)
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(8,947,875
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)
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Other income (expense):
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Interest income
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42,431
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—
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127,560
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|
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—
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||||
Interest expense
|
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(1,038,014
|
)
|
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(110,508
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)
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(5,593,751
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)
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(281,638
|
)
|
||||
Total other expense, net
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(995,583
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)
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(110,508
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)
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(5,466,191
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)
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(281,638
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)
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||||
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Loss before income taxes
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(775,930
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)
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(2,451,315
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)
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(21,147,226
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)
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(9,229,513
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)
|
||||
Benefit from (provision for) income taxes
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—
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—
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—
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—
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||||
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Net loss
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$
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(775,930
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)
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$
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(2,451,315
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)
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$
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(21,147,226
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)
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$
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(9,229,513
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)
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|
|
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||||||||
Net loss per common share, basic and diluted*
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$
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(0.03
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)
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$
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(0.08
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)
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$
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(0.87
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)
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$
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(0.29
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)
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Weighted-average common shares, basic and diluted*
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25,818,495
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31,545,000
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24,269,266
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31,545,000
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Common Stock*
|
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Shares
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Amount
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Additional Paid-in-Capital
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Accumulated Deficit
|
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Stock Subscription Receivable
|
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Total
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|||||||||||
Balance as of December 31, 2016
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11,888,240
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$
|
11,888
|
|
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$
|
1,148,457
|
|
|
$
|
(7,747,874
|
)
|
|
$
|
(25
|
)
|
|
$
|
(6,587,554
|
)
|
|
|
|
|
|
|
|
|
|
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|||||||||||
Payment of stock subscription receivable
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
25
|
|
|
25
|
|
|||||
Share-based compensation
|
|
—
|
|
|
—
|
|
|
6,018,732
|
|
|
—
|
|
|
—
|
|
|
6,018,732
|
|
|||||
Net loss
|
|
—
|
|
|
—
|
|
|
—
|
|
|
(11,605,817
|
)
|
|
—
|
|
|
(11,605,817
|
)
|
|||||
Balance as of December 31, 2017
|
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11,888,240
|
|
|
11,888
|
|
|
7,167,189
|
|
|
(19,353,691
|
)
|
|
—
|
|
|
(12,174,614
|
)
|
|||||
|
|
|
|
|
|
|
|
|
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|
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|||||||||||
Change in par value from $0.001 to $0.0001
|
|
—
|
|
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(10,699
|
)
|
|
10,699
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|||||
Issuance of shares as a result of reverse recapitalization
|
|
1,864,808
|
|
|
186
|
|
|
(978,860
|
)
|
|
—
|
|
|
—
|
|
|
(978,674
|
)
|
|||||
Issuance of common stock
|
|
7,111,631
|
|
|
711
|
|
|
16,136,950
|
|
|
—
|
|
|
—
|
|
|
16,137,661
|
|
|||||
Warrants issued with common stock
|
|
—
|
|
|
—
|
|
|
1,995,000
|
|
|
—
|
|
|
—
|
|
|
1,995,000
|
|
|||||
Warrants issued to placement agents
|
|
—
|
|
|
—
|
|
|
913,000
|
|
|
—
|
|
|
—
|
|
|
913,000
|
|
|||||
Stock issuance costs
|
|
—
|
|
|
—
|
|
|
(2,568,079
|
)
|
|
—
|
|
|
—
|
|
|
(2,568,079
|
)
|
|||||
Conversion of convertible debt and accrued interest
|
|
4,827,001
|
|
|
483
|
|
|
9,229,336
|
|
|
—
|
|
|
—
|
|
|
9,229,819
|
|
|||||
Beneficial conversion feature
|
|
—
|
|
|
—
|
|
|
3,077,887
|
|
|
—
|
|
|
—
|
|
|
3,077,887
|
|
|||||
Share-based compensation
|
|
—
|
|
|
—
|
|
|
5,055,000
|
|
|
—
|
|
|
—
|
|
|
5,055,000
|
|
|||||
Exercise of warrants, net of commissions
|
|
291,858
|
|
|
29
|
|
|
840,997
|
|
|
—
|
|
|
|
|
841,026
|
|
||||||
Net loss
|
|
—
|
|
|
—
|
|
|
—
|
|
|
(21,147,226
|
)
|
|
—
|
|
|
(21,147,226
|
)
|
|||||
Balance as of September 30, 2018 (unaudited)
|
|
25,983,538
|
|
|
$
|
2,598
|
|
|
$
|
40,879,119
|
|
|
$
|
(40,500,917
|
)
|
|
$
|
—
|
|
|
$
|
380,800
|
|
|
|
Nine Months Ended
September 30, |
||||||
|
|
2018
|
|
2017
|
||||
|
|
(Unaudited)
|
|
(Unaudited)
|
||||
Cash flows from operating activities
|
|
|
|
|
|
|
||
Net loss
|
|
$
|
(21,147,226
|
)
|
|
$
|
(9,229,513
|
)
|
Adjustments to reconcile net loss to net cash used in operating activities:
|
|
|
|
|
||||
Share-based compensation
|
|
5,055,000
|
|
|
4,749,834
|
|
||
Accrued interest on note payable
|
|
150,000
|
|
|
—
|
|
||
Accrued interest on convertible promissory notes
|
|
25,578
|
|
|
252,464
|
|
||
Amortization of debt discount
|
|
2,060,000
|
|
|
29,174
|
|
||
Depreciation
|
|
14,417
|
|
|
2,522
|
|
||
Beneficial conversion feature
|
|
3,077,887
|
|
|
—
|
|
||
Changes in operating assets and liabilities:
|
|
|
|
|
||||
Prepaid expenses and other assets
|
|
(363,738
|
)
|
|
(40,443
|
)
|
||
Accounts payable
|
|
(754,435
|
)
|
|
1,067,247
|
|
||
Accrued expenses
|
|
(878,181
|
)
|
|
3,311
|
|
||
Net cash used in operating activities
|
|
(12,760,698
|
)
|
|
(3,165,404
|
)
|
||
|
|
|
|
|
||||
Cash flows from investing activities
|
|
|
|
|
||||
Purchase of property and equipment
|
|
(13,943
|
)
|
|
(1,600
|
)
|
||
Loan payments from related party
|
|
75,000
|
|
|
—
|
|
||
Net cash provided by (used in) investing activities
|
|
61,057
|
|
|
(1,600
|
)
|
||
|
|
|
|
|
||||
Cash flows from financing activities
|
|
|
|
|
||||
Borrowings from note payable
|
|
3,000,000
|
|
|
—
|
|
||
Payments of note payable issuance costs
|
|
(20,000
|
)
|
|
—
|
|
||
Borrowings from convertible promissory notes
|
|
345,000
|
|
|
4,284,999
|
|
||
Principal payments of convertible promissory notes
|
|
(275,000
|
)
|
|
—
|
|
||
Proceeds from issuance of common stock and warrants
|
|
18,132,661
|
|
|
—
|
|
||
Payment of stock issuance costs
|
|
(1,495,284
|
)
|
|
—
|
|
||
Payment of deferred offering costs
|
|
(159,795
|
)
|
|
—
|
|
||
Proceeds from exercise of warrants
|
|
928,178
|
|
|
—
|
|
||
Payment of stock subscription receivable
|
|
—
|
|
|
25
|
|
||
Net cash provided by financing activities
|
|
20,455,760
|
|
|
4,285,024
|
|
||
|
|
|
|
|
||||
Net increase in cash and cash equivalents
|
|
7,756,119
|
|
|
1,118,020
|
|
||
|
|
|
|
|
||||
Cash and cash equivalents as of beginning of period
|
|
355,563
|
|
|
360,811
|
|
||
|
|
|
|
|
||||
Cash and cash equivalents as of end of period
|
|
$
|
8,111,682
|
|
|
$
|
1,478,831
|
|
|
|
|
|
|
||||
Supplemental disclosure of cash flow information
|
|
|
|
|
|
|||
Cash paid during the period for interest
|
|
$
|
280,287
|
|
|
$
|
—
|
|
|
|
|
|
|
||||
Supplemental disclosure of noncash financing activities
|
|
|
|
|
|
|||
Conversion of convertible notes and accrued interest to common stock
|
|
$
|
9,229,819
|
|
|
$
|
—
|
|
Assumption of liabilities from reverse recapitalization transaction
|
|
$
|
978,674
|
|
|
$
|
—
|
|
Warrants issued to placement agents
|
|
$
|
913,000
|
|
|
$
|
—
|
|
Commissions owed and accrued for exercise of warrants
|
|
$
|
87,152
|
|
|
$
|
—
|
|
|
|
September 30, 2018
|
|
December 31, 2017
|
||||
Compensation and benefits
|
|
$
|
—
|
|
|
$
|
1,065,225
|
|
Clinical costs
|
|
138,000
|
|
|
—
|
|
||
Other
|
|
91,401
|
|
|
115,000
|
|
||
Total
|
|
$
|
229,401
|
|
|
$
|
1,180,225
|
|
|
|
Three Months Ended
September 30, |
|
Nine Months Ended
September 30, |
||||||||
|
|
2018
|
|
2017
|
|
2018
|
|
2017
|
||||
Options outstanding under the Private Innovate Plan
|
|
6,428,577
|
|
|
6,509,824
|
|
|
6,428,577
|
|
|
6,509,824
|
|
Options and warrants outstanding under the Amended Omnibus Plan (subject to stockholder approval)
|
|
1,202,843
|
|
|
—
|
|
|
1,202,843
|
|
|
—
|
|
Warrants issued at an exercise price of $2.54
|
|
349,555
|
|
|
—
|
|
|
349,555
|
|
|
—
|
|
Warrants issued at an exercise price of $3.18
|
|
1,410,309
|
|
|
—
|
|
|
1,410,309
|
|
|
—
|
|
Total
|
|
9,391,284
|
|
|
6,509,824
|
|
|
9,391,284
|
|
|
6,509,824
|
|
|
September 30, 2018
|
||
Original principal
|
$
|
4,800,000
|
|
Additional premium
|
240,000
|
|
|
Accrued interest
|
150,000
|
|
|
Note payable
|
$
|
5,190,000
|
|
•
|
Expected dividend yield.
The expected dividend is assumed to be zero as the Company has never paid dividends and has no current plans to pay any dividends on the Company’s common stock.
|
•
|
Expected stock-price volatility.
As the Company’s common stock has a limited trading history as a public company, the expected volatility is derived from the average historical volatilities of publicly traded companies within the Company’s industry that the Company considers to be comparable to the Company’s business over a period approximately equal to the expected term.
|
•
|
Risk-free interest rate.
The risk-free interest rate is based on the U.S. Treasury yield in effect at the time of grant for zero coupon U.S. Treasury notes with maturities approximately equal to the expected term.
|
•
|
Expected term.
The expected term represents the period that the stock-based awards are expected to be outstanding. The Company’s historical share option exercise experience does not provide a reasonable basis upon which to estimate an expected term for employees because of a lack of sufficient data. Therefore, the Company estimates the expected term by using the simplified method provided by the Securities and Exchange Commission. The simplified method calculates the expected term as the average of the time-to-vesting and the contractual life of the options. The expected term for non-employees is the contractual life of the option.
|
|
|
Three Months Ended
September 30, |
|
Nine Months Ended
September 30, |
|||
|
|
2018
|
2017
|
|
2018
|
|
2017
|
Expected dividend yield
|
|
0%
|
0%
|
|
0%
|
|
0%
|
Expected stock-price volatility
|
|
66% – 68%
|
62%
|
|
66% – 72%
|
|
73%
|
Risk-free interest rate
|
|
2.8% – 3.0%
|
1.6%
|
|
2.7% – 3.0%
|
|
2.2%
|
Expected term of options
|
|
8.5 – 9.1
|
6.5
|
|
8.5 – 9.5
|
|
8.7
|
|
|
Number of
Shares
|
|
Weighted-Average
Exercise Price
|
|
Aggregate
Intrinsic
Value
|
|
Weighted-Average
Remaining
Contractual Life
(in years)
|
||||||
Outstanding at December 31, 2017
|
|
6,843,296
|
|
|
$
|
1.56
|
|
|
$
|
6,617,433
|
|
|
9.04
|
|
Options granted
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
||
Options forfeited
|
|
(414,719
|
)
|
|
2.08
|
|
|
—
|
|
|
—
|
|
||
Options exercised
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
||
Outstanding at September 30, 2018
|
|
6,428,577
|
|
|
1.53
|
|
|
34,080,300
|
|
|
7.99
|
|
||
Exercisable at September 30, 2018
|
|
5,534,191
|
|
|
1.44
|
|
|
29,819,823
|
|
|
7.90
|
|
||
Vested and expected to vest at September 30, 2018
|
|
6,378,011
|
|
|
$
|
1.52
|
|
|
$
|
33,841,611
|
|
|
7.98
|
|
|
|
Three Months Ended
September 30, |
|
Nine Months Ended
September 30, |
|
|
|
2018
|
|
2018
|
|
Expected dividend yield
|
|
0%
|
|
0%
|
|
Expected stock-price volatility
|
|
65% – 73%
|
|
65% – 73%
|
|
Risk-free interest rate
|
|
2.8% – 3.1%
|
|
2.8% – 3.1%
|
|
Expected term of options
|
|
5.0 – 10.0
|
|
5.0 – 10.0
|
|
|
|
Number of
Shares
|
|
Weighted-Average
Exercise Price
|
|
Aggregate
Intrinsic
Value
|
|
Weighted-Average
Remaining
Contractual Life
(in years)
|
||||||
Outstanding at December 31, 2017
|
|
1,683
|
|
|
$
|
45.00
|
|
|
$
|
—
|
|
|
9.04
|
|
Options granted
|
|
1,202,843
|
|
|
6.12
|
|
|
—
|
|
|
9.82
|
|
||
Options forfeited
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
||
Options exercised
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
||
Outstanding at September 30, 2018
|
|
1,204,526
|
|
|
6.17
|
|
|
869,003
|
|
|
9.82
|
|
||
Exercisable at September 30, 2018
|
|
270,676
|
|
|
6.43
|
|
|
175,359
|
|
|
9.40
|
|
||
Vested and expected to vest at September 30, 2018
|
|
1,126,051
|
|
|
$
|
6.18
|
|
|
$
|
809,494
|
|
|
9.82
|
|
|
|
Three Months Ended
September 30, |
|
Nine Months Ended
September 30, |
||||||||||||
|
|
2018
|
|
2017
|
|
2018
|
|
2017
|
||||||||
Research and development
|
|
$
|
(2,950,000
|
)
|
|
$
|
314,206
|
|
|
$
|
2,467,000
|
|
|
$
|
1,627,606
|
|
General and administrative
|
|
(181,000
|
)
|
|
962,728
|
|
|
2,588,000
|
|
|
3,122,228
|
|
||||
Total share-based compensation
|
|
$
|
(3,131,000
|
)
|
|
$
|
1,276,934
|
|
|
$
|
5,055,000
|
|
|
$
|
4,749,834
|
|
|
|
|
|
|
|
|
|
|
•
|
continuation of pre-clinical work in NASH by studying larazotide in both ex-vivo and animal models;
|
•
|
continued collaboration with Dr. Anthony Blikslager of North Carolina State University to explore life-cycle extension of our lead molecule larazotide acetate; and
|
•
|
initiation of a collaboration with Dr. James Nataro of the University of Virginia, Charlottesville to study larazotide’s effect on Environmental Enteric Dysfunction.
|
|
|
Three Months Ended September 30,
|
|
|
|
|
|||||||||
|
|
2018
|
|
2017
|
|
$ Change
|
|
% Change
|
|||||||
Operating expenses (income):
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
Research and development
|
|
$
|
(1,785,645
|
)
|
|
$
|
367,551
|
|
|
$
|
(2,153,196
|
)
|
|
(586
|
)%
|
General and administrative
|
|
1,565,992
|
|
|
1,973,256
|
|
|
(407,264
|
)
|
|
(21
|
)%
|
|||
Total operating expenses (income)
|
|
(219,653
|
)
|
|
2,340,807
|
|
|
(2,560,460
|
)
|
|
(109
|
)%
|
|||
|
|
|
|
|
|
|
|
|
|||||||
Income (loss) from operations
|
|
219,653
|
|
|
(2,340,807
|
)
|
|
(2,560,460
|
)
|
|
(109
|
)%
|
|||
Other expense, net
|
|
(995,583
|
)
|
|
(110,508
|
)
|
|
885,075
|
|
|
801
|
%
|
|||
|
|
|
|
|
|
|
|
|
|||||||
Net loss
|
|
$
|
(775,930
|
)
|
|
$
|
(2,451,315
|
)
|
|
$
|
(1,675,385
|
)
|
|
(68
|
)%
|
|
|
Nine Months Ended September 30,
|
|
|
|
|
|||||||||
|
|
2018
|
|
2017
|
|
$ Change
|
|
% Change
|
|||||||
|
|
|
|
|
|
|
|
|
|||||||
Operating expenses:
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
Research and development
|
|
$
|
5,815,580
|
|
|
$
|
2,832,787
|
|
|
$
|
2,982,793
|
|
|
105
|
%
|
General and administrative
|
|
9,865,455
|
|
|
6,115,088
|
|
|
3,750,367
|
|
|
61
|
%
|
|||
Total operating expenses
|
|
15,681,035
|
|
|
8,947,875
|
|
|
6,733,160
|
|
|
75
|
%
|
|||
|
|
|
|
|
|
|
|
|
|||||||
Loss from operations
|
|
(15,681,035
|
)
|
|
(8,947,875
|
)
|
|
6,733,160
|
|
|
75
|
%
|
|||
Other income (expense), net
|
|
(5,466,191
|
)
|
|
(281,638
|
)
|
|
5,184,553
|
|
|
1,841
|
%
|
|||
|
|
|
|
|
|
|
|
|
|||||||
Net loss
|
|
$
|
(21,147,226
|
)
|
|
$
|
(9,229,513
|
)
|
|
$
|
11,917,713
|
|
|
129
|
%
|
|
|
Nine Months Ended September 30,
|
||||||
|
|
2018
|
|
2017
|
||||
Net cash (used in) provided by:
|
|
|
|
|
|
|
||
Operating activities
|
|
$
|
(12,760,698
|
)
|
|
$
|
(3,165,404
|
)
|
Investing activities
|
|
61,057
|
|
|
(1,600
|
)
|
||
Financing activities
|
|
20,455,760
|
|
|
4,285,024
|
|
||
Net increase (decrease) in cash and cash equivalents
|
|
$
|
7,756,119
|
|
|
$
|
1,118,020
|
|
•
|
the number, size, complexity, results and timing of our drug development programs;
|
•
|
the number of nonclinical and clinical studies necessary to demonstrate acceptable evidence of the safety and efficacy of our product candidates;
|
•
|
the terms of any collaborative or other strategic arrangement that we may establish;
|
•
|
changes in standards of care which could increase the size and complexity of clinical studies;
|
•
|
the ability to locate patients to participate in a study given the limited number of patients available for orphan or ultra-orphan indications;
|
•
|
the number of patients who participate, the rate of enrollment, and the ratio of randomized to evaluable patients in each clinical study;
|
•
|
the number and location of sites and the rate of site initiation in each study;
|
•
|
the duration of patient treatment and follow-up;
|
•
|
the potential for additional safety monitoring or other post-marketing studies that may be requested by regulatory agencies;
|
•
|
the time and cost to manufacture clinical trial material and commercial product, including process development and scale-up activities, and to conduct stability studies, which can last several years;
|
•
|
the degree of difficulty and cost involved in securing alternate manufacturers or suppliers of drug product, components or delivery devices, as necessary to meet FDA requirements and/or commercial demand;
|
•
|
the costs, requirements, timing of, and the ability to, secure regulatory approvals;
|
•
|
the extent to which we increase our workforce and the costs involved in recruiting, training and incentivizing new employees;
|
•
|
the costs related to developing, acquiring and/or contracting for sales, marketing and distribution capabilities, supply chain management capabilities, and regulatory compliance capabilities, if we obtain regulatory approval for a product candidate and commercialize it without a partner;
|
•
|
the costs involved in evaluating competing technologies and market developments or the loss in sales in case of such competition; and
|
•
|
the costs involved in establishing, enforcing or defending patent claims and other proprietary rights.
|
•
|
inability to enroll enough patients in the clinical trials;
|
•
|
slow implementation, enrollment and completion of the clinical trials;
|
•
|
low patient compliance and adherence to dosing and reporting requirements, such as incomplete reporting of patient reported outcomes in the clinical trials or missed doses;
|
•
|
lack of safety and efficacy in the clinical trials;
|
•
|
delays in the manufacture of supplies for drug components due to delays in formulation, process development, or manufacturing activities;
|
•
|
requirements for additional nonclinical or clinical studies based on changes to formulation and/or changes to regulatory requirements; and
|
•
|
requirements for additional clinical studies based on inconclusive clinical results or changes in market, standard of care, and/or regulatory requirements.
|
•
|
delays during regulatory review and/or requirements for additional chemistry, manufacturing and controls, or nonclinical or clinical studies, resulting in increased costs and/or delays in marketing approval and subsequent commercialization of our product candidates in the United States and other markets;
|
•
|
inability to consistently manufacture commercial supplies of drug and delivery devices resulting in slowed market development and lower revenue;
|
•
|
inability to enforce our intellectual property rights in and to our product candidates;
|
•
|
reduction in the safety profile of our product candidates following approval; and
|
◦
|
the ability of our future sales organization or our potential commercialization partners to effectively sell our product candidates;
|
◦
|
lack of success in educating physicians and patients about the benefits, administration, and use of our product candidates;
|
◦
|
low patient demand for our product candidates;
|
◦
|
the availability, perceived advantages, relative cost, relative safety and relative efficacy of other products or treatments for the targeted indications of our product candidates; and
|
◦
|
poor prescription coverage and inadequate reimbursement for our product candidates.
|
•
|
regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication;
|
•
|
we may be required to change the way the product is administered, conduct additional clinical studies or change the labeling of the product;
|
•
|
inability to raise sufficient funding to initiate or to continue a clinical study;
|
•
|
delays in obtaining regulatory approval to commence a clinical study;
|
•
|
delays in identifying and reaching agreement on acceptable terms with prospective CROs and clinical study sites and investigators, which agreements can be subject to extensive negotiation and may vary significantly among study sites;
|
•
|
delays in obtaining regulatory approval in a prospective country;
|
•
|
delays in obtaining ethics committee approval to conduct a clinical study at a prospective site;
|
•
|
delays in reaching agreements on acceptable terms with prospective CMOs or other vendors for the production and supply of clinical trial material and, if necessary, drug administration devices, which agreements can be subject to extensive negotiation;
|
•
|
delays in the production or delivery of sufficient quantities of clinical trial material from our CMOs and other vendors to initiate or continue a clinical study;
|
•
|
delays due to product candidate recalls as a result of stability failure, excessive product complaints or other failures of the product candidate during its use or testing;
|
•
|
invalidation of clinical data caused by premature unblinding or integrity issues;
|
•
|
invalidation of clinical data caused by mixing up of the active drug and placebo through randomization or manufacturing errors;
|
•
|
delays on the part of our CROs, CMOs and other third-party contractors in developing procedures and protocols or otherwise conducting activities in accordance with applicable policies and procedures and in accordance with agreed upon timelines;
|
•
|
delays in identifying and hiring or engaging, as applicable, additional employees or consultants to assist in managing clinical study-related activities;
|
•
|
delays in recruiting and enrolling individuals to participate in a clinical study, which historically can be challenging in orphan diseases;
|
•
|
delays caused by patients dropping out of a clinical study due to side effects, concurrent disorders, difficulties in adhering to the study protocol, unknown issues related to different patient profiles than in previous studies, or otherwise;
|
•
|
delays in having patients complete participation in a clinical study, including returning for post-treatment follow-up;
|
•
|
delays resulting from study sites dropping out of a trial, providing inadequate staff support for the study, problems with shipment of study supplies to clinical sites, or focusing our staff’s efforts on enrolling studies that compete for the same patient population;
|
•
|
suspension of enrollment at a study site or the imposition of a clinical hold by the FDA or other regulatory authority following an inspection of clinical study operations at study sites or finding of a drug-related serious adverse event; and
|
•
|
delays in quality control/quality assurance procedures necessary for study database lock and analysis of unblinded data.
|
•
|
the size of the target patient population;
|
•
|
other ongoing studies competing for the same patient population;
|
•
|
the eligibility criteria for the clinical trial;
|
•
|
the design of the clinical study;
|
•
|
the perceived risks and benefits of the product candidate under study;
|
•
|
the efforts to facilitate timely enrollment in clinical trials;
|
•
|
the proximity and availability of clinical trial sites for prospective patients; and
|
•
|
the ability to monitor patients adequately during and after treatment.
|
•
|
lack of adequate funding to continue the study;
|
•
|
failure to conduct the study in accordance with regulatory requirements or the study’s protocol;
|
•
|
inspection of clinical study operations or sites by the FDA or other regulatory authorities resulting in the imposition of a clinical hold;
|
•
|
unforeseen safety issues, including adverse side effects; or
|
•
|
changes in governmental regulations or administrative actions.
|
•
|
issue warning letters or untitled letters;
|
•
|
impose civil or criminal penalties;
|
•
|
suspend or terminate any ongoing clinical studies;
|
•
|
close the facilities of a CMO;
|
•
|
refuse to approve pending applications or supplements to approved applications;
|
•
|
suspend or withdraw regulatory approval;
|
•
|
exclude our product from reimbursement under government healthcare programs, including Medicaid or Medicare;
|
•
|
impose restrictions or affirmative obligations on our or our CMOs’ operations, including costly new manufacturing requirements; or
|
•
|
seize or detain products or require a product recall.
|
•
|
the safety and efficacy of our product as demonstrated in clinical studies;
|
•
|
acceptance in the medical and patient communities of our product as a safe and effective treatment;
|
•
|
the perceived advantages of our product over alternative treatments, including with respect to the incidence and severity of any adverse side effects and the cost of treatment;
|
•
|
the indications for which our product is approved;
|
•
|
claims or other information (including limitations or warnings) in our product’s approved labeling;
|
•
|
reimbursement and coverage policies of government and other third-party payers;
|
•
|
smaller than expected market size due to lack of disease awareness of a rare disease, or the patient population with a specific rare disease being smaller than anticipated;
|
•
|
availability of alternative treatments;
|
•
|
pricing and cost-effectiveness of our product relative to alternative treatments;
|
•
|
inappropriate diagnostic efforts due to limited knowledge and/or resources among clinicians;
|
•
|
the prevalence of off-label substitution of chemically equivalent products or alternative treatments; and
|
•
|
the resources we devote to marketing our product and restrictions on promotional claims we can make with respect to the product.
|
•
|
obtain and maintain patents and other exclusivity with respect to our products;
|
•
|
prevent third parties from infringing upon our proprietary rights;
|
•
|
maintain proprietary know-how and trade secrets;
|
•
|
operate without infringing upon the patents and proprietary rights of others; and
|
•
|
obtain and maintain appropriate licenses to patents or proprietary rights held by third parties if infringement would otherwise occur or if necessary to secure exclusive rights to them, both in the United States and in foreign countries.
|
•
|
infringement and other intellectual property claims which, with or without merit, may be expensive and time consuming to litigate and may divert management’s time and attention from our core business;
|
•
|
substantial damages for infringement, including the potential for treble damages and attorneys’ fees, which we may have to pay if it is determined that the product and/or its use at issue infringes or violates the third party’s rights;
|
•
|
a court prohibiting us from selling or licensing the product unless the third-party licenses its intellectual property rights to us, which it may not be required to do;
|
•
|
if a license is available from the third party, we may have to pay substantial royalties, fees and/or grant cross-licenses to the third party; and
|
•
|
redesigning our products or processes so they do not infringe, which may not be possible or may require substantial expense and time.
|
•
|
our ability to set an appropriate price for our products;
|
•
|
the rate and scope of adoption of our products by healthcare providers;
|
•
|
our ability to generate revenue or achieve or maintain profitability;
|
•
|
the future revenue and profitability of our potential customers, suppliers and collaborators; and
|
•
|
our access to additional capital.
|
•
|
significant costs of related litigation;
|
•
|
decreased demand for our products and loss of revenue;
|
•
|
impairment of our business reputation;
|
•
|
a “clinical hold,” suspension or termination of a clinical study or amendments to a study design;
|
•
|
delays in enrolling patients to participate in our clinical studies;
|
•
|
withdrawal of clinical study participants;
|
•
|
substantial monetary awards to patients or other claimants; and
|
•
|
the inability to commercialize our products and product candidates.
|
•
|
the federal healthcare program anti-kickback statute prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering, or arranging for or recommending the purchase, lease, or order of any good, facility, service or item for which payment is made, in whole or in part, under a federal healthcare program;
|
•
|
the federal civil and criminal false claims laws and civil monetary penalties laws, including civil whistleblower or qui tam actions, 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 making a false statement to improperly avoid, decrease or conceal an obligation to pay money to the federal government;
|
•
|
the federal Health Insurance Portability and Accountability Act of 1996 (“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, 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 omnibus rule, such as health plans, clearinghouses and healthcare providers, and their associates;
|
•
|
HIPAA, imposes criminal liability for, among other things, 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 payor (e.g., public or private) and knowingly or willfully falsifying, concealing, or covering up by any trick, scheme 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;
|
•
|
the federal transparency law, enacted as part of the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the “ACA”), and its implementing regulations, require 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;
|
•
|
analogous state laws and regulations, including but not limited to: 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 payors, 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; and
|
•
|
European Union (“EU”), data protection regulations, which may require member states of the EU to impose minimum restrictions on the collection and use of personal data that, in many respects, are more stringent, and impose more significant burdens on subject businesses, than current privacy standards in the United States.
|
•
|
regulatory or legal developments in the United States and foreign countries;
|
•
|
results from or delays in clinical trials of our product candidates;
|
•
|
announcements of regulatory approval or disapproval of, or delays in clinical trials for, INN-202 (for celiac disease), INN-217 (for NASH), INN-289 (for Crohn’s disease), INN-108 (for ulcerative colitis), and INN-329 (for magnetic resonance cholangiopancreatography or MRCP) or any future product candidates;
|
•
|
commercialization of our product candidates;
|
•
|
FDA or other U.S. or foreign regulatory actions affecting us or our industry;
|
•
|
introductions and announcements of new products by us, any commercialization partners or our competitors, and the timing of these introductions and announcements;
|
•
|
variations in our financial results or those of companies that are perceived to be similar to us;
|
•
|
changes in the structure of healthcare payment systems;
|
•
|
announcements by us or our competitors of significant acquisitions, licenses, strategic partnerships, joint ventures or capital commitments;
|
•
|
market conditions in the pharmaceutical and biopharmaceutical sectors and issuance of securities analysts’ reports or recommendations;
|
•
|
actual or anticipated quarterly variations in our results of operations or those of our competitors;
|
•
|
changes in financial estimates or guidance, including our ability to meet our future revenue and operating profit or loss estimates or guidance;
|
•
|
our liquidity position;
|
•
|
sales of substantial amounts of our stock by insiders and other stockholders, or the expectation that such sales might occur;
|
•
|
general economic, industry and market conditions;
|
•
|
additions or departures of key personnel;
|
•
|
intellectual property, product liability or other litigation against us;
|
•
|
expiration or termination of our potential relationships with strategic partners; and
|
•
|
the other factors described in this section entitled “Risk Factors.”
|
•
|
provide that vacancies on the Board may be filled only by a majority of directors then in office, even though less than a quorum;
|
•
|
authorize the Board to issue shares of preferred stock and determine the price and other terms of those shares, including preferences and voting rights, without stockholder approval;
|
•
|
require that stockholders give advance notice to nominate directors or submit proposals for consideration at stockholder meetings; and
|
•
|
being permitted to provide only two years of audited financial statements, in addition to any required unaudited interim financial statements, with correspondingly reduced “management’s discussion and analysis of financial condition and results of operations” disclosure;
|
•
|
not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting;
|
•
|
not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements;
|
•
|
reduced disclosure obligations regarding executive compensation; and
|
•
|
exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments not previously approved.
|
|
|
|
|
FILED
|
|
INCORPORATED BY REFERENCE
|
||||||
EXHIBIT NO.
|
|
DESCRIPTION
|
|
HEREWITH
|
|
FORM
|
|
FILE NO.
|
|
EXHIBIT
|
|
FILING DATE
|
10.1
|
†
|
|
X
|
|
|
|
|
|
|
|
|
|
10.2
|
|
|
X
|
|
|
|
|
|
|
|
|
|
31.1
|
|
|
X
|
|
|
|
|
|
|
|
|
|
31.2
|
|
|
X
|
|
|
|
|
|
|
|
|
|
32.1
|
|
|
X
|
|
|
|
|
|
|
|
|
|
32.2
|
|
|
X
|
|
|
|
|
|
|
|
|
|
101.INS
|
|
XBRL Instance Document
|
|
X
|
|
|
|
|
|
|
|
|
101.SCH
|
|
XBRL Taxonomy Extension Schema Document
|
|
X
|
|
|
|
|
|
|
|
|
101.CAL
|
|
XBRL Taxonomy Extension Calculation Linkbase Document
|
|
X
|
|
|
|
|
|
|
|
|
101.DEF
|
|
XBRL Taxonomy Extension Definition Document
|
|
X
|
|
|
|
|
|
|
|
|
101.LAB
|
|
XBRL Taxonomy Extension Label Linkbase Document
|
|
X
|
|
|
|
|
|
|
|
|
101.PRE
|
|
XBRL Taxonomy Extension Presentation Linkbase Document
|
|
X
|
|
|
|
|
|
|
|
|
†
|
Portions of this exhibit (indicated by asterisks) have been omitted pursuant to a request for confidential treatment pursuant to Rule 24b-2 under the Securities Exchange Act of 1934.
|
|
|
INNOVATE BIOPHARMACEUTICALS, INC.
|
|
|
|
a Delaware corporation
|
|
|
|
|
|
Date:
|
November 13, 2018
|
By:
|
/s/ Jay P. Madan
|
|
|
|
Jay P. Madan
|
|
|
|
President, Chief Business Officer and Interim Principal Financial Officer
|
1.01
|
During the Term, Amarex agrees to provide services as described in project orders (as amended by any subsequent Amendments (defined below), each a “Project Work Order”) which will be requested of Amarex by Innovate, the form of which is set forth as Exhibit 1. Such services shall be performed in accordance with applicable laws and regulations and the terms and conditions of this Agreement. Amarex agrees to grant Innovate access to Amarex’s electronic data capture system.
|
1.02
|
After receipt of a Project Work Order request, Amarex shall provide Innovate with a Project Work Order describing the services to be performed and a fee for performing the services. The Project Work Order will be negotiated and mutually agreed to and approved in writing before any work is performed by Amarex and, once executed, will be incorporated by reference into this Agreement.
|
1.03
|
Innovate or Amarex may request changes in any Project Work Order (a “Change Proposal”) by providing written notification of such changes to the other party, whereupon Innovate and Amarex shall review such request and negotiate in good faith the changes to be implemented. If the parties reach agreement regarding the Change Proposal, Amarex shall submit to Innovate a Project Work Order Amendment (“Amendment”) which will detail all changes and associated cost estimates, and any other proposed revision to the services under the relevant Project Work Order. If the parties execute and deliver such Amendment, it will then be incorporated as part of this Agreement. In the event of a conflict between the terms
|
2.01
|
This Agreement shall be effective from the Effective Date and shall thereafter remain in full force and effect for a period of three (3) years, unless earlier terminated as provided herein (“Initial Term”).
Thereafter, this Agreement may be renewed upon Innovate’s written request for up to two (2) additional one (1) year terms (“each a Renewal Term,” and together with the Initial Term, the “Term”).
|
3.01
|
As compensation for Amarex’s services hereunder, Innovate shall pay Amarex the undisputed amounts of each invoice prepared by Amarex relevant to services performed under each Project Work Order or any portion thereof. All payments by Innovate for undisputed amounts shall be made within [***] days of the date of Innovate’s receipt of a written invoice from Amarex. Innovate shall notify Amarex of any disputed amounts within [***] days of Innovate’s receipt of the disputed invoice. The parties shall negotiate in good faith to resolve any disputed amounts in accordance with
Section 13.04
. Unless otherwise expressly provided herein, each party shall be responsible for its own expenses relating to its performance of this Agreement and shall not incur expenses for the other party’s account unless expressly authorized in writing to do so by the other party. Further, Innovate will reimburse Amarex for all pre-approved, reasonable out-of-pocket expenses (without markup) incurred by Amarex in connection with the services; provided, however, that any travel and lodging (if requested by Innovate) expenses must be consistent with Amarex’s company travel policy and any all out-of-pocket expenses that individually or cumulatively exceed [***] Dollars ($[***]) must be approved by Innovate in advance; such pre-approval may be accomplished via e-mail communication. For clarity, reasonable out-of-pocket expenses described or set forth in, and not in excess of, a Project Work Order budget are deemed pre-approved by Innovate. Upon Innovate’s request, Amarex shall provide reasonable documentation to substantiate any out-of-pocket expense. All such out-of-pocket expenses shall be included on the appropriate invoice described in this
Section 3.01
.
|
3.02
|
All invoices and/or other requests for payment shall be billable and payable in U.S. Dollars unless otherwise agreed upon in writing by both parties.
|
3.03
|
All invoices and/or other requests for payment shall be itemized with a reasonable degree of specificity to ensure accuracy in accounting for services and/or goods provided and billed for. All invoices and/or other requests for payment shall be sent to:
|
3.04
|
Payments to Amarex will be made out to Amarex Clinical Research, LLC (Tax ID: [***]).
|
3.05
|
A [***]% annual interest rate will be charged to any and all undisputed amounts that remain unpaid past their applicable due dates.
|
3.06
|
During the Term and for a period of [***] months after its expiration or termination, upon fourteen (14) days’ prior written notice, at its expense once annually and at reasonable times during normal business hours, Innovate shall have the right to audit and examine all records which are necessary to verify performance by Amarex of the services in accordance with any Project Work Order. Innovate will not be entitled to audit (i) data or information of other customers or clients of Amarex; (ii) any cost information unless such is the basis of an out-of-pocket expense; (iii) Amarex’s quality assurance reviews and contract management reports; or (iv) any other confidential Information of Amarex that is not directly relevant for the authorized purposes of the audit. Any notice shall contain detailed information regarding the records and time periods being audited. The auditors and other representatives of Innovate will execute and deliver such confidentiality and non-disclosure agreements and comply with such reasonable security and confidentiality requirements as Amarex may require in connection with such audits. If errors or deficiencies are identified as a result of an audit, Amarex shall take prompt action to correct any such error or deficiency mutually agreed upon by the parties in accordance with the dispute mechanism set forth herein, including refunding any overpayments by Innovate to Amarex within thirty (30) days of being notified of such overpayment.
|
4.01
|
With respect to any and all information indicated in writing or reasonably understood from the context as being of a confidential nature, including but not limited to, protocols, data forms, and study results acquired by Amarex from Innovate as a result of this Agreement or from performance of the services to be rendered hereunder, Amarex agrees that it will not use said information other than for the purposes of this Agreement, and it will not disclose any of said information to any third party; provided, however, that Amarex may disclose such information (i) on a need-to-know basis to its agents, employees and consultants who are under a written obligation to maintain the confidentiality of said information, (ii) in
|
1)
|
which can be shown by written documentation to have been known to Amarex prior to its receipt from Innovate;
|
2)
|
which is or lawfully becomes generally available to the public through no fault of Amarex;
|
3)
|
which is lawfully acquired from third parties who have a right to disclose such information; or
|
4)
|
which by mutual agreement is released from a confidential status.
|
4.02
|
Innovate will treat Amarex confidential information, including but not limited to, business information, pricing, proprietary software and programs, in accordance with the same terms as Amarex’s treatment of Innovate information, as detailed in
Section 4.01
above.
|
4.03
|
The terms of this
Section 4
,
Section 6
,
Section 9
, and the parties’ obligations hereunder, shall survive for three (3) years after termination or expiration of this Agreement and the completion of all Project Work Orders duly made a part hereof. Further, the provisions of this Agreement that would by their nature survive the expiration or termination of this Agreement, shall survive any expiration or termination of this Agreement for three (3) years.
|
5.01
|
This Agreement or any Project Work Order may be terminated by Innovate at any time by giving a 30-day prior written notice to Amarex. During the 30-day period between the notice of termination and the effectiveness of such termination, Amarex shall use all reasonable efforts to terminate its work under any Project Work Order being terminated as early as practicable and to reduce or eliminate further costs, and to cancel, if permitted under the terms of applicable agreements, any third party obligations. Within thirty (30) days after the completion of wind-up of the applicable Project Work Order (which wind-up includes receipt by Innovate of any statistical analyses and other deliverables prepared by Amarex, if any, prior to the date of termination), Amarex shall provide Innovate with a written itemized statement of all services already performed by Amarex under the Project Work Order being terminated. In the event of termination of a Project Work Order pursuant to this
Section 5.01
, Amarex shall be entitled to a payment based on the pro rate amount of services provided by it under such Project Work Order through the later date of termination or winding up period plus pass-through related costs incurred through such date. If the amount already paid by Innovate to Amarex exceeds such pro rate amount, Amarex shall refund such excess to Innovate and if such pro rate amount is greater than the amounts already paid by Innovate
|
5.02
|
This Agreement may also be terminated by either party (a) upon material default in performance of the other party, provided that any defaulting party shall be given not less than thirty (30) days’ prior written notice of default and the opportunity to cure the default during such period or (b) immediately upon the other party becoming insolvent or bankrupt or making an assignment for the benefit of its creditors, upon appointment of a trustee or receiver for the other party of all or substantially all of its property, or upon the filing of a involuntary petition (unless the case is dismissed by midnight at the end of the sixtieth (60
th
) day after commencement) or voluntary petition by or against the other party under any bankruptcy or insolvency law, the reorganization or rearrangement provisions of the United States Bankruptcy Code, or any similar law. If this Agreement is terminated pursuant to this
Section 5.02
, Amarex shall retain such sums as may have been paid to it by Innovate under the terms of this Agreement to compensate Amarex for services already performed. If the amount previously paid by Innovate exceeds the sum earned by Amarex for services already performed in accordance with the Project Work Order, the excess shall be refunded to Innovate. Innovate shall pay Amarex any additional undisputed amounts owed but not yet paid for services already performed.
|
5.03
|
If payments for undisputed amounts in any invoice are not received within [***] days of receipt of the applicable invoice, and after fifteen (15) days’ written notice to Innovate, Amarex shall have the right to cease all work and to terminate this Agreement and the applicable Project Work Order if the past due balance is in excess of $[***]. Should any part of the invoice be in dispute, Innovate shall pay the remainder of the undisputed amount according to the terms and conditions described herein while said dispute is being resolved, and the parties will work in good faith to resolve the disputed portion of the invoice within a forty-five (45) day period beginning from the time that Amarex received notification of the disputed portion of the invoice. In addition, Innovate shall provide Amarex with written notice setting forth (in detail) the basis of the dispute and the parties agree to use best efforts to resolve such dispute in an expeditious manner.
|
5.04
|
Any payments due under this
Section 5
shall be made within [***] days after termination.
|
6.01
|
Innovate agrees to indemnify, defend and hold harmless Amarex and its officers, directors, employees, agents, advisors, representatives, successors and permitted assigns from and against any loss, damage, cost and expense (including, without limitation, reasonable attorneys’ fees and expenses) incurred in connection with any third-party claims, proceedings or investigations to the extent arising out of or in connection with actual or alleged gross negligence or willful misconduct of Innovate or its employees.
|
6.02
|
Amarex agrees to indemnify, defend and hold harmless Innovate and its respective officers, directors, employees, agents, advisors, representatives, successors and permitted assigns from and against any loss, damage, cost and expense (including, without limitation, reasonable attorneys’ fees and expenses) incurred in connection with any third-party claims, proceedings or investigations to the extent arising out of or in connection with actual or alleged gross negligence, willful misconduct of Amarex or its employees or permitted contractors.
|
6.03
|
Each party shall indemnify, defend, protect and hold harmless the other party and its respective officers, directors, employees, agents, advisors, representatives, successors and permitted assigns from and against any loss, damage, cost and expense (including, without limitation, reasonable attorneys’ fees and expenses) incurred in connection with any third-party claims, proceedings or investigations to the extent arising out of or in connection with: (i) any breach by such first party or its agents, employees or contractors of any covenant, representation, warranty or other obligation contained in this Agreement; or (ii) any injury to any person, including death, illness or bodily injury, or damage to real or tangible personal property, based on the negligence, gross negligence, willful misconduct of such first party or its employees or permitted contractors.
|
6.04
|
Any party seeking indemnification pursuant to this
Section 6
(the “Indemnitee”) shall give notice within a reasonable amount of time to the party from whom indemnification is sought (the “Indemnitor”) of any claim, proceeding or investigation. The Indemnitee shall cooperate in the defense of such claim, proceeding or investigation, subject to reimbursement by the Indemnitor for all reasonable out-of-pocket expenses. The Indemnitor shall, at its option, assume control of the defense of any such claim, proceeding or investigation. The indemnities set forth in
Sections 6.01 and 6.02
shall include amounts paid in settlement, provided, however, that no such settlement shall be entered into without the Indemnitor’s consent, which consent shall not be unreasonably withheld. In no event shall the Indemnitor compromise or settle any claim, proceeding or investigation in a manner that admits fault or negligence on the part of the Indemnitee, or does not fully release the Indemnitee from all claims and all future claims arising out of the subject, or that would otherwise adversely affect any rights of the Indemnitee, without the prior written consent of the Indemnitee. The Indemnitee shall have the right to retain separate legal counsel at its own expense to participate in the defense of any such claim, proceeding or investigation.
|
7.01
|
Neither party shall disclose the existence of this Agreement, except as required by law, or as required to fulfill regulatory obligations as the sponsor of an IND, NDA, BLA, 510K, IDE, or PMA, nor use or publish the other party’s name in promotion, advertising or for any other purpose, without prior written approval of the other party. This Agreement does not entitle either party to the use of the trademarks, copyrights or other intellectual property of the other party.
|
8.01
|
Amarex shall perform services under this Agreement only as an independent contractor and nothing contained herein shall be construed to be inconsistent with that relationship or status. Amarex and its consultants and subcontractors shall not be considered employees or agents of Innovate. This Agreement shall not constitute, create or in any way be interpreted as a joint venture, partnership or business organization of any kind.
|
8.02
|
Neither party shall, during the term of this Agreement, and for a period of twelve (12) months following expiration or termination thereof, without the prior written consent of the other party, for itself or on behalf of or through any third party, directly or indirectly, solicit to employ or engage as an independent contractor, any employee or consultant of the other party who was in any way involved in rendering or receiving services under this Agreement or any Project Work Order. Notwithstanding the above, the following shall not be prohibited: (a) any solicitation if, at the time of such solicitation, the individual is no longer employed by the other party as an employee or independent contractor for reasons not associated with pursuing a future business or employment relationship with the soliciting party; (b) solicitations initiated through general print advertisements and other general circulation materials, including web-based postings, not directly targeted at such individuals; and (c) solicitations of such individuals who have first contacted either party on their own initiative, directly or through third party recruiters, regarding employment or engagement as an independent contractor.
|
9.01
|
All information, materials, documents and raw data supplied to Amarex or developed by Amarex as a result of performing the services hereunder are owned by Innovate. All such information shall be disclosed to Innovate. Innovate shall have the right to make any use of such information. Following completion of the services outlined in a Project Work Order, Amarex will ensure return to Innovate of client data or other materials furnished to Amarex, at Innovate’s cost. All Intellectual Property Rights subsisting in or relating to any calculations, data, methods, specifications, papers, documents, and any other items, material or information generated in any form or media in the performance of the services by Amarex under this Agreement are vested in and are the sole and exclusive property of Innovate, except that Amarex shall have the rights to any innovative methodology developed which has generic applications and is not specific to any particular Innovate Project. Accordingly, without additional consideration, Amarex hereby assigns to Innovate its entire right, title and interest in and to such Intellectual Property Rights and other work product that Innovate is to own under this
Section 9.01
, waives all moral rights thereto, and shall cause its employees, agents, contractors, subsidiaries and their respective employees, agents and contractors to do the same. “Intellectual Property Rights” means, without limitation, and
|
10.01
|
Communications regarding routine operational matters may be carried out using e-mail. All other administrative communications provided for in this Agreement shall be sent via first class mail (subject to
Section 10.02
below), postage prepaid, addressed to the respective parties as follows:
|
President and CEO
|
Chief Operating Officer and Chief Medical Officer
|
10.02
|
Other than routine correspondence described in
Section 10.01
, any communication required under this Agreement shall be sent by certified mail and addressed to the respective parties at the addresses set forth in
Section 10.01
above. All legal notices shall be in writing and sent by certified mail, return receipt requested, to such addresses, to the attention of the relevant contact person specified above. Such notices shall be effective upon mailing.
|
11.01
|
Neither party shall have the right to assign (including by operation of law) this Agreement or any of the rights or obligations hereunder without the prior written consent of the other party, except that either party may assign without such consent this Agreement or any of its rights or obligations hereunder to any of affiliated companies or subsidiaries or to a successor to substantially all of the business of such party to which this Agreement relates, whether in a merger, sale of stock, sale of assets or other transaction. Any assignment or attempted assignment by either party in violation of the terms of this
Section 11.01
shall be null and void and of no legal effect.
|
12.01
|
Amarex provides services to its customers on a contractual fee-for-service basis. Amarex represents and provides its sole warranty that it will perform the services in a timely, workmanlike manner by qualified (and, where appropriate, licensed) personnel with due care and diligence in accordance with generally prevailing industry standards, Innovate instructions (provided that Amarex will not have any liability for following Innovate instructions that run counter to industry standards, applicable regulations, or Amarex SOPs), and applicable government regulations, laws and rules, as well as the objectives of this Agreement. Amarex represents that all staff assigned to provide the contracted services will undergo standard and ongoing training such that Amarex’s staff will have the facilities, equipment and requisite training, expertise, qualification, experience and skill to render the services in the manner required by this paragraph above.
|
12.02
|
Amarex represents that: (i) it will handle all information containing personal data in accordance with all applicable laws governing patient privacy; (ii) all individuals and subcontractors performing services hereunder are and shall be subject to binding written obligations to assign all of their right, title and interest in and to any Inventions and related intellectual property rights (including enforcement rights) to Amarex or Innovate and to abide by the obligations of confidentiality set forth (and in the absence of such binding written obligations by and between Amarex and one (1) or more individuals and/or subcontractors that Amarex intends will perform services hereunder, Amarex shall notify Innovate and take all commercially reasonable actions requested by Innovate to achieve the foregoing); and (iii) it is not a debarred or disqualified person or entity under the authority of the Generic Drug Enforcement Act of 1992, as amended, or any other law or regulation
|
12.03
|
Innovate shall be entitled, with a minimum prior notice of [***] business days and during the term of the related Project Work Order, to inspect the conduct of services and to validate compliance with the requirements of this Agreement and applicable laws by Amarex relating to a Project Work Order under this Agreement. Innovate will not be responsible for payment to Amarex for time spent on audits that are no more frequent than once per year, and last no more than [***] per audit. Innovate may perform additional audits where an audit by a regulatory authority has revealed a deficiency that affects a project with Innovate. Furthermore, Amarex agrees to respond to all audit findings from Innovate within forty-five (45) days of receipt of the audit report and respond to any subsequent follow-up discussions as deemed necessary by Innovate including possible discussions with regulatory authorities. In the case of a disagreement, Amarex and Innovate will attempt to resolve the dispute in good faith within fifteen (15) days. In the event that the parties cannot come to an agreement then without limiting any other remedies Innovate may have under this Agreement or otherwise, Innovate may terminate this Agreement or any Project Work Order for convenience in accordance with
Section 5
. Except with respect to audit findings that are the subject of a
bona fide
dispute, Amarex will at its expense promptly come into compliance with the requirements of this Agreement as a result of any audit findings that apply to the integrity and proper conduct of the services under a Project Work Order.
|
13.01
|
This Agreement constitutes the entire agreement between the parties on the subject matter to be described and defined in future Project Work Orders and supersedes all prior contracts, agreements and understandings relating to the same subject between the parties. The parties intend this Agreement to be a complete statement of the terms of their agreement and no change or modification of any of the provisions of this Agreement shall be effective unless it is in writing and signed by a duly authorized officer of Amarex and Innovate. The parties agree that no “click-through,” “shrink-wrap,” “browse-wrap” or similar terms that have not been specifically negotiated by the parties, whether before, on, or after the date of this Agreement, will be effective to add to or modify the terms of this Agreement, regardless of any party's and/or its representative’s “acceptance” of those terms by electronic means.
|
13.02
|
This Agreement may be signed in any number of counterparts, which, when taken together, will constitute one and the same Agreement. Delivery of an executed counterpart by facsimile or by email transmission in portable document format, or similar format, is as effective as executing and delivering this Agreement in the presence of the other party to this Agreement.
|
13.03
|
This Agreement shall be governed by the laws of the State of Delaware, U.S.A.
|
13.04
|
In the event of a dispute between the parties regarding this Agreement, the parties shall first attempt to resolve their dispute within fifteen (15) days’ after such dispute is raised through amicable discussion between designated executives of each party with requisite authority to resolve such dispute(s). If at the end of such fifteen (15) day period the dispute remains unresolved, the parties may seek relief for such dispute using any appropriate judicial mechanism which may be available, subject to Section 13.03 (governing law). The provisions of this Section 13.04 will not restrict in any way the parties’ rights to seek preliminary injunctive or other equitable relief from any court having jurisdiction.
|
13.05
|
No party shall be deemed in breach of its obligations, for failure or delay in fulfilling or performing any term of this Agreement or any Project Work Order if such failure or delay results from an act or event that is beyond the reasonable control of and not the fault of the nonperforming party, and if the nonperforming party has been unable to avoid or overcome the act or event by the exercise of customary due diligence.
|
13.06
|
The invalidity or unenforceability of any term or provision of this Agreement shall not affect the validity or enforceability of any other term or provision of this Agreement.
|
13.07
|
Termination of this Agreement shall be without prejudice to any rights that shall have accrued to the benefit of either party prior to such termination, and shall not relieve either party of any obligations that have accrued to the other party prior to such termination or that survive such termination. In addition, upon expiration or termination of this Agreement, each party promptly will return or destroy all Confidential Information of the other party hereunder (except that each party may retain one (1) copy of the Confidential Information of the other party received hereunder, solely for record purposes).
|
13.08
|
Amarex will maintain or cause to be maintained, with financially sound and reputable insurers, such insurance coverages with respect to liabilities, losses or damage in respect of the assets, properties and businesses of Amarex as may customarily be carried or maintained under similar circumstances by companies of established reputation engaged in similar businesses, in each case in such amounts (giving effect to self-insurance), with such deductibles, covering such risks and otherwise on such terms and conditions as shall be customary for companies similarly situated in the industry.
|
For and on behalf of Innovate Biopharmaceuticals, Inc.:
|
For and on behalf of Amarex Clinical Research, LLC:
|
|||
Print Name:
|
Jay Madan
|
Print Name:
|
Kazem Kazempour
|
|
Signature:
|
/s/ Jay Madan
|
Signature:
|
/s/ Kazem Kazempour
|
|
Title:
|
President
|
Title:
|
President and CEO (Member)
|
|
Date:
|
Aug. 17, 2018
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Date:
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20 Aug 18
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•
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An experienced CRO
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•
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Data management
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•
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Biostatistics
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•
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Safety tracking, monitoring, and reporting
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•
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Previous multi-CRO integration
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•
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Strong sponsor-oriented focus from CRO
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Amarex’s experience in global clinical research studies enables rapid study start up, expedited regulatory approval, and efficient trial conduct.
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Amarex has over 19 years of experience which includes managing all aspects of clinical development, all trial phases, and a wide range of therapeutic areas. We have extensive experience in the conduct of gastrointestinal (GI) trials – this experience results in rapid study start up, expedited regulatory approval, accurate protocol execution, and efficient trial conduct.
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Amarex can perform this study with either electronic CRFs (EDC) or paper CRFs.
Using either paper or EDC, we employ true parallel processing that provides views of accumulating data throughout the trial helping you to make better decisions.
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Amarex has significant experience offering data management services with either paper-based or EDC solutions. Amarex’s preference is to use EDC options for data management. This allows for much better insight into data collection and faster data lock at the end of the study. We can use either a client preferred system or our own in-house system. We are able to integrate our clinical trial management system (CTMS) system with either approach. Additionally, our Parallel Processing approach enables us to accelerate study start up and shorten the period of post-data lock at study closeout. Data integrity is maintained through the use of in-house, access-control servers, regular data back-ups with off-site storage, and extensive electronic checks. At study completion, Innovate will receive a complete set of electronic images of those same CRFs.
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We offer excellence in SAP writing through final analysis reporting.
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Amarex provides full, in-house biostatistical support with a staff of biostatisticians who have extensive experience with ICH E9 (Statistical Principles for Clinical Trials) guidelines as well as analysis and reporting of clinical trial data. Amarex’s biostatisticians will, design all required tables, listings, and graphs, and provide final output of all clinical trial data and final analyses. They also provide insight into the need for expanded analyses in order to clarify a trial’s outcome with respect to all endpoints evaluated. All analyses are performed with SAS.
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Amarex can provide full safety reporting services for the Innovate project.
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Amarex can provide safety reporting services for the Innovate project. The Safety Associates would set up and periodically reconcile the safety tracking system; receive, process, evaluate and prepare the narrative for all SAEs; prepare CIOMS reports; and then distribute the reports to the study sites, and regulatory personnel.
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We have extensive experience working alongside other CROs and understand the challenges of multi-CRO integration.
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Amarex has previously worked on clinical trials requiring the integration of work from several CROs by providing project management, data management, site management, monitoring, and safety services. We have extensive experience working alongside other CROs and understand the challenges that sometimes arise with multi-CRO integration.
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Customer satisfaction is very important to us, and we work hard to make sure our staff is prepared to meet your needs through constant communication and tracking.
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Amarex is a Sponsor-oriented CRO, and as such our project teams are responsive to your requests. In addition to regular status reporting, Amarex has developed many innovative ways to communicate with Sponsors, including providing access to the most up-to-date study information through WebView
SM
. Innovate’s satisfaction is critical to the Amarex team, and our service delivery is based on this concept.
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Amarex has the experience to help Innovate meet its goals.
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Amarex offers Innovate performance, reliability, demonstrated therapeutic experience, and responsive customer service that lead to high-quality results. Amarex has the resources and the right approach to deliver the results that will make this project a success.
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STUDY PARAMETERS
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Number of sites
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[***]
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Number of countries participating in study
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[***]
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Number of subjects screened
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[***]
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Number of subjects randomized/enrolled
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[***]
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Number of subjects completed
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[***]
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MEDICAL MONITORING
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Estimated number of SAEs
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[***]
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Estimated number of reportable events
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[***]
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DATA MANAGEMENT
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Estimated Number of Adverse Events and Concomitant Medications to code
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[***]
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Number of unique pages in eCRF book
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[***]
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Number of central labs and outside data vendors
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[***]
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Number interim database locks
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[***]
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BIOSTATISTICS
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Number of stat. tables for interim analysis (uniques/replicate)
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[***]
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Number of stat. listings for interim analysis (uniques/replicate)
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[***]
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Number of stat. tables for final analysis (uniques/replicates)
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[***]
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Number of listings for final analysis (uniques/replicates)
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[***]
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Number of graphs for final analysis (uniques/replicates)
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[***]
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CLINICAL STUDY REPORT WRITING
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Write interim clinical trial report
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[***]
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Write final clinical trial report
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[***]
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PROJECT MANAGEMENT
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Number of months for project setup
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[***]
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Number of months for enrollment
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[***]
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Number of months for follow-up (treatment period)
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[***]
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Number of months of active study phase for monitoring
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[***]
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Number of months for close out
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[***]
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Number of months of project management (including set up and close out)
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[***]
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Service
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Not Required
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Amarex
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Innovate or Other
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PROTOCOL AND INFORMED CONSENT DEVELOPMENT
X
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PROJECT MANAGEMENT
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Meetings, Training, and Study Start Up
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Prepare for and participate in Kick-off Meeting (Telecon) & Study Start-Up
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X
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X
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Plan or Assist with Planning of Investigator's Meeting
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X
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Prepare for and Attend Investigator's Meeting
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X
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Attend Project Meetings at Sponsor Office (if requested)
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X
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X
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Communication and Tracking
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Coordinate Amarex's Internal Project Team
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X
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Communicate with Sponsor
(includes standard teleconferences with activities reports, emails, faxes) |
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X
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X
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Collaborate with vendors associated with study:
•
central laboratory ([***]);
•
clinical monitoring ([***]);
•
ePRO ([***]);
•
drug depot ([***].
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X
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X
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Tracking Systems Setup
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X
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REGULATORY SERVICES
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X
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PRODUCT MANAGEMENT
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Set up of WebView product supply tracking and email alert system. Track drug shipments to sites, drug supply depots, auto-email requests for resupply based on randomization. Require acknowledgement email from drug depot.
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X
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Maintenance for WebView Resupply and Tracking
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X
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Develop Pharmacy Manual (includes up to 1 round of edits)
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X
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X
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DATA MANAGEMENT SERVICES
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Data Management
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Develop Data Management Plan
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X
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Standard Data Cleaning (Run edit checks; generate, process, and track data queries)
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X
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Data Operations
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Develop Edit Specifications
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X
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Program Edit Checks
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X
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Set Up SAS Data Transfer from [***]
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X
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Receive, Load, and Reconcile Clean SAS Data from [***]
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X
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Set Up Transfer of Final SAS Data to Sponsor
(in Amarex's format) |
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X
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Set Up of Coding System to Code AEs and Medications
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X
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Code Adverse Events and Medications
(Using MedDRA and WHO Drug ATC Level) |
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X
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Perform Data Transfer to Sponsor
(Including export of final SAS Analysis Datasets) |
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X
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EDC
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Development of CRF Screen Shots
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X
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X
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EDC Programming
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X
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EDC Maintenance
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X
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Conduct Electronic Data Capture Site Training by WebEx
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X
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Prepare EDC Manual and Completion Instructions (includes up to 1 round of edits)
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X
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Conduct QC of EDC Database
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X
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Provide Electronic Data Capture Help Desk
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X
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CLINICAL SITE SERVICES
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X
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SAFETY
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SAE Start Up
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X
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Prepare and Implement Safety Management Plan (includes draft Safety Exchange Agreement and information on safety table/listing output frequency)
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X
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Set Up EDC SAE Reporting Module
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X
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Receive, Process, Evaluate, Prepare Narrative, and Report SAEs (CIOMS)
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X
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Prepare and Distribute SUSAR Letters to Sites
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X
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Follow up with Sites to Collect Additional SAE Information
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X
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Submit Expedited Safety Reports to Regulatory Authorities
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X
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Prepare Standard Aggregate Safety Tables and Listings for Quarterly Review by Sponsor, and for Inclusion in the Annual Report/DSUR
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X
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Prepare and Submit Full Annual Report/DSUR to Regulatory Authorities
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X
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Append Historical SAEs to Safety System
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X
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Prepare Subject Narratives for CSR
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X
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DATA SAFETY MONITORING BOARD (DSMB) for Interim Analysis – for sample size re-assessment
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Establish and Manage 3-Member DSMB
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X
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Develop DSMB Charter (includes up to 1 round of edits)
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X
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Organize, Conduct and Participate in DSMB Meetings
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X
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ENROLLMENT, RANDOMIZATION AND STRATIFICATION
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Develop WebView Enrollment/Randomization/Stratification Module [***]
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X
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Generate WebView Randomization/Stratification Code and Plan
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X
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Conduct WebView Enrollment/Randomization/Stratification Maintenance (including ongoing cross-checking randomization/ stratification on a monthly basis)
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X
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BIOSTATISTICS
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Prepare Statistical Analysis Plan (1 draft and 1 final, mock templates for TLGs, and data set conventions)
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NA
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Program Tables, Listings and Graphs for Interim Analysis
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X
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X
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Program Tables, Listings and Graphs for Final Analysis
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X
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X
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Conduct QC Audit of Stats
|
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X
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Production and Review of Tables, Listings, and Graphs for Interim Analysis
|
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X
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Production and Review of Tables, Listings, and Graphs for Final Analysis
|
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X
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Prepare Statistical Report (includes up to 1 round of edits)
|
|
X
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Convert Data to CDISC
|
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X
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|
Effective project management is the cornerstone of any trial; and Amarex’s well established processes and SOPs will make sure your study is completed on time, within budget, and with the quality data you expect.
|
Besides defensible study design, reliable data, and correct analyses methods, user friendly SOPs are an additional component necessary for successful clinical product development. We have developed a set of FDA/ICH-based clinical, data management, biostatistics, safety compliance and coding, regulatory, and medical writing SOPs that help to protect the quality and integrity of all clinical trial data that is managed, monitored, analyzed, and reported by Amarex. These SOPs provide for a systematic, standard, and documented monitoring, management, analyses, and presentation of the clinical trial data.
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The ability to initiate solutions to study-related issues before they become problems maintains timelines, increases efficiency, and helps to eliminate clinical trial problems.
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Our thorough preparatory work, including written plans for the major components of a project, combined with Parallel Processing, enables a process we call “Prospective Issues Resolution” – the anticipation and identification of potential trial conduct and analysis issues, along with the presentation of several potential resolutions to the Sponsor. The ability to initiate solutions to study-related challenges before they become problems maintains timelines, increases efficiency, and helps to eliminate problems routinely faced during the conduct of a clinical trial.
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A Project Plan will be jointly developed to ensure project success.
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Shortly after the project has been awarded, Innovate and Amarex’s project team will meet to discuss and finalize a detailed Project Plan. This plan may include, but will not be limited to, the following:
|
•
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Description of individual roles and responsibilities
|
•
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Timeline schedule and monitoring of key milestones
|
•
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Organizational design plan with strategies and resources required to achieve milestones
|
•
|
General policy guide for decision making and individual actions
|
•
|
Communication plan for the Amarex’s project team, Innovate, and Investigators
|
•
|
A project reporting plan
|
Effective and efficient communication between Amarex and Innovate will ensure smooth study conduct.
|
Amarex believes that effective project communication with Innovate is the single most important factor in ensuring that a cohesive partnership exists. We make every effort to ensure that the lines of communication are open and encourage candid feedback from all participants.
To facilitate optimal communication throughout the study, the following activities will take place:
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The Amarex project team will meet regularly to review project status.
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Coordination of Amarex’s internal project team comprises all activities required to facilitate smooth and efficient conduct of the study. The Amarex project team will meet regularly to review all aspects of the project including timeline adherence and status of project deliverables.
|
The Project Manager will lead teleconferences to review project status, discuss milestones, and identify and resolve study issues.
|
Amarex’s Project Manager will schedule, coordinate, and conduct teleconferences with Innovate and other study vendors on a regular basis throughout the study. The purpose of the teleconferences will be to review the status of the project, discuss key upcoming milestones, identify project issues, and develop an action plan for issue resolution. We want to be sure that you are fully aware of your study’s status in a timely manner.
|
While a core team of individuals will participate on each call, other subject-matter experts may also be included in order to facilitate expedient issue identification and resolution.
|
The Project Manager will prepare and distribute an agenda for each teleconference to facilitate efficient use of call time. While a core team of individuals will participate on each call, other subject-matter experts may also be included in order to facilitate expedient issue identification and resolution. After each teleconference, action items and resolutions will be issued. The action items discussed during the teleconferences will always be a part of the agenda for the following teleconference.
|
WebView
SM
product resupply provides effective, timely, and efficient distribution over the course of your study – ensuring that sites have product when they need it.
|
Amarex will use WebView
SM
as an inventory system to keep track of product supply for each site. With the WebView
SM
resupply system, every time a subject is randomized, an accounting of that site’s supplies is evaluated. If the site’s supplies are below a predefined limit, emails will be sent to pre-selected individuals and a request for more product to the site will be initiated and sent to the distribution depot. Follow up emails to the site will be sent until resupply receipt has been confirmed.
|
A well-organized project kickoff meeting will set the stage for the project. Early agreement on all aspects of study conduct will guarantee smooth execution.
|
At the beginning of the project, the Project Manager, Clinical Data Manager, Medical Monitor (if used), and Biostatistician will meet with Innovate and other applicable vendors to review the timelines, activities, tracking outputs, and expectations for the study. Amarex will assist in preparing a meeting agenda to facilitate the discussion of all tasks associated with the conduct of the study and prepare meeting minutes to summarize discussions and agreements reached at the meeting. This kickoff meeting will require about 4 hours and is included in the budget as a one-time event that will occur via teleconference.
|
|
Amarex will send a data manager and statistician to meet in person with the Innovate team in North Carolina on a periodic basis. The initial meeting will be to provide training on the EDC system, and later on to discuss data lock and final analysis. These are anticipated to be 8 hour meetings.
|
Amarex will provide an experienced and thoroughly trained data management team for your project.
|
At the beginning of the project, Amarex will assemble an experienced data management team consisting of a Clinical Data Manager, Clinical Data Coordinator, SAS Programmer, Database Programmer, and Biostatistician.
|
•
|
Coordinate and attend all data management team meetings
|
•
|
Ensure on time and accurate completion of all data management activities
|
•
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Determine the data management services required for your project and prepare timelines that will be reviewed and mutually agreed upon by Amarex and Innovate.
|
•
|
Maintain frequent communications with the Amarex Project Manager, Innovate and other study vendor representatives to report on the status of data management activities.
|
Amarex has comprehensive data and computer systems that are 21CFR Part 11 Compliant.
|
The Amarex Data System allows us to process data (either electronically or on paper), conduct data editing checks, generate data queries, tabulate, and document data with extreme efficiency. The Amarex Data System offers an audit trail of WHO made each data change, WHEN the change was made, and WHAT was changed. All Amarex computer systems are Part 11 Compliant.
|
Using EDC, we employ true parallel processing that provides views of accumulating data throughout the trial helping you to make better decisions.
|
Amarex provides the latest in EDC technology for trial data management.
|
Reliability
The EDC platform is a Microsoft product, and at Amarex clinical researchers (not IT programmers) provide complete support for your EDC system. |
|
Ease of Use - Minimal Training
The EDC platform has an intuitive web based interface, modeled on the most commonly used internet programs, which makes Amarex’s EDC software solution as easy as can be for site staff to quickly master secure trial data entry.
Amarex’s EDC provides an intuitive navigation interface with a hierarchical study tree that gives you the ability to drill down from study, to site, to patient, to visit, to eCRF page. Clicking on different levels of the tree provides summaries and details about each study component.
Flexible task-based workflow in the Administrator’s module provides trial managers with screens to easily define and manage study sites, users, user roles, imports and exports.
Amarex’s EDC provides a robust interface for easily managing the permissions for each user role within the trial. Easily configurable, out-of-the-box task lists for study coordinators, investigators and monitors provide pre-defined lists for each role within the clinical trial process for identifying incomplete CRFs, completed CRFs awaiting signatures, signed CRFs awaiting monitoring, CRFs with action queries, and CRFs with open queries.
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Data Capture and Monitoring
Sophisticated trial management features include dynamic visit schedule allocation based upon subject status e.g., Screened, Enrolled, Randomized, etc.). It’s easy to add unplanned eCRFs and Visits by site users. Functionalities such as radio buttons, check boxes, dropdown lists and calendar controls minimize data entry time, and the Date and Time fields even support the use of “Today” and “Now” buttons for data entry efficiency. |
|
Amarex’s EDC can allow data calculations to be performed immediately, while data is entered into the fields required for calculation, even before the data is saved. This immediate feedback helps to prevent data entry and transcription errors prior to saving. Amarex’s EDC will also automatically trigger dual data validation at the time of entry and at the time of posting to the server.
Regardless of whether edit checks involve a single field, multiple fields, multiple forms, or visits, validation messages can be triggered and alert the user immediately upon its detection. There’s no need to save the form first or to run any batch job to detect even the most complex validation checks.
The built-in messaging and notification subsystem easily triggers internal and external (via any email address) notifications of over 30 key study-related activities such as Enrollment of a Subject, Dropped Subjects, Completion of an AE Form, Opening or Responding to a Query, or Data Export Available.
The data review and signatures feature in Amarex’s EDC includes an out of the box task list for eCRFs awaiting signatures. The system supports a signature password that is different than the login password, and signatures are supported at different levels (single form or group of forms). Permissions for signing eCRFs can be set at the CRF category level. Examples of common configurations include; Signing of any eCRFs restricted to Investigator only and signing of any eCRFs shared between Investigator and Coordinator roles.
Data Monitoring & Cleaning in the platform is fast and efficient. The system supports read-only access for CRAs and Monitors with the ability to monitor and query data. Using the out of the box Task List for Monitoring and Query Management, Data Managers and CRAs can open, respond to, and close a query.
Amarex will work with [***] to prepare specific reports to support [***] in risk-based monitoring. The types of data assessed could be missing data, primary endpoint data, ePRO data, etc. These reports will be programmed and then produced on a monthly basis.
The system provides the ability to easily perform monitoring (source document verification) at the field, page, visit, patient, site, and the study level. Monitors can lock and unlock data from the page level up to the study level and perform monitoring activities across multiple studies and sites through a single sign-on.
|
|
Reports Package
Amarex’s EDC contains a robust Standard Reporting Module. A sample of the extensive list of easy to access reports includes: Summary Reports, Project Status Reports, Subject Enrollment Reports, Subject Status Reports, eCRF Status Reports, Open Query Reports, Comments and Queries by eCRF, Security Permissions by Role, Visit Reports, Data Group Specifications and Code List Reports. The system also renders custom standard reports that include AE Reports, Concomitant Medication Reports, Drug Inventory Reports, SAE Reports and MedWatch Forms. |
|
Programming Process
Amarex starts the programming process by preparing mock eCRF screen shots for review by the Sponsor. Once the basic screen shots are approved, Amarex begins the process of programming the EDC platform to support the eCRF. The first round of User Acceptance Testing (UAT) includes review of the programmed eCRF. Following UAT 1, edits are programmed and reviewed in UAT 2. After modifications from UAT 2 are made, a final UAT 3 is conducted to fine tune the system. After UAT 3 the EDC system is ready for production and to go live for use in the trial. |
|
EDC Data Output
Exports are available on demand as SAS Transport Files, CSVs, Tab Delimited and XML. In addition, the latest version of the platform has an SDTM custom output module that allows the study design to create SDTM compliant outputs at the beginning of the study so that getting SDTM during the course of a study is just a push of a button. Other custom outputs are available. Beyond data exports, a set of standard reports is available and a wizard-driven Ad Hoc reporting tool. Setting up custom reports - even for non-technical users - is a very straightforward process. |
Amarex will establish procedures and timelines for data transfer from all Central Labs to ensure accurate collection.
|
Before study start, it will be important for Amarex to discuss formats of any electronic data to be transmitted by vendors (e.g., central lab data) and to have at least one test transfer of “dummy” data of each type. This will allow us to validate the electronic transmission process and ensure data integrity for subsequent analyses.
|
•
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Check that all eCRFs have been completed, monitored and signed.
|
•
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Conduct final programmed edit checks for data logic and consistency. All remaining queries resolved.
|
•
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Conduct final manual edit checks for logic and consistency. All remaining queries resolved.
|
•
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Final verification and client approval of all AE coding.
|
•
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Final verification and client approval of all medication coding.
|
•
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Final SAE reconciliation between the clinical and safety database.
|
•
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Final database QC.
|
•
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Final update of draft data listings provided to client for review and approval.
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All Amarex systems are in compliance with 21CFR 11 and preserve integrity of electronic records.
|
All systems are setup and tested in compliance to 21 Code of Federal Regulations (CFR), Section 11 and FDA’s 1999 and 2004 Guidance for Computerized Systems Used in Clinical Trials (CSUCT). Amarex’s computer server room is climate controlled with anti-static flooring and secured with a keypad and combination door lock. Access to the room is limited to Amarex’s IT staff. Equipment includes high-density filing systems located in a fire-protected document storage room that is secured by a keypad combination door. All original study-related documents and Case Report Forms will be stored here.
|
Production of validated graphs render a reader-friendly report, resulting in “understandability” and fewer FDA questions during review.
|
As soon as the SAP is approved, Amarex will begin designing the templates for data summary tables, data listings, and graphs to be used in interim analyses, the final report and/or for safety monitoring committees. All data summary tables, data listings, and graphs will be programmed in SAS and validated by a second statistician/programmer before finalization.
|
•
|
Interim Analysis – Amarex estimates that the following will be prepared for the interim analysis:
|
•
|
[***] unique and [***] replicate tables
|
•
|
[***] unique and [***] replicate listings
|
•
|
Analysis Datasets – Amarex will create SAS datasets using SAS programs, and the data conversion process will be validated. These SAS validated datasets will be sent to Innovate after the study is completed.
|
•
|
Final Analysis – Amarex estimates that the following will be prepared for the final analysis:
|
•
|
[***] unique and [***] replicate tables
|
•
|
[***] unique and [***] replicate listings
|
•
|
[***] unique and [***] replicate graphs
|
Once the database has been locked, the final statistical analysis will be completed for inclusion in the CSR.
|
Following database lock for the interim and final analyses, tables and listings, including all statistical analyses, will be generated. Statistical conclusions and the statistical sections for the Clinical Study Report will be provided to the Medical Writer for inclusion in the Clinical Study Reports.
|
Amarex’s WebView
SM
provides superior enrollment/ randomization usability over conventional IVRS systems.
|
In order to facilitate enrollment, we suggest that the use of WebView
SM
for online randomization/stratification. The use of the WebView
SM
central randomization system provides many advantages over telephone-based Interactive Voice Recognition Systems (IVRS) or envelope/fax-based systems. These advantages include:
|
•
|
A computerized enrollment/randomization/stratification procedure that is fully validated and 21 CFR, Part 11 compliant.
|
•
|
24-hour, rapid, and secure access to enrollment/ randomization/stratification data.
|
•
|
User-friendly screens for entry of enrollment and/or randomization/stratification data. Entry of these data is much like ordering products on-line through the Web, which negates the need for tedious, often frustrating, and time-consuming verbal confirmation and verification prompts that are standard to telephone-based randomization systems.
|
•
|
Ability to instantly review (revise if needed) and print the enrollment/randomization/stratification confirmation.
|
•
|
Availability of real-time notification and real-time access to site-specific subject accrual numbers, as well as preliminary demographics of the subject population (or any other subject- or site-specific data desired by Innovate) through WebView
SM
Status Reports.
|
Amarex will set up a tracking system and adhere to standard policies and procedures to handle SAEs.
|
Amarex will begin the pharmacovigilance for each study by reviewing current SOPs in order to ensure compliance to current regulatory standards and protocol requirements. Amarex will set up a secure Serious Adverse Event (SAE) tracking system for this study in OpenClinica. [***] will be the main contact for site discussions on all SAEs. All SAEs will be followed to resolution or stabilization. A Safety Management plan will be prepared that will have two main objectives: 1) provide information on SAE Reporting, and 2) describe the frequency and types of safety table and listing outputs that will be provided. Safety tables and listings for aggregate safety will be prepared on a quarterly basis for review by Amarex, Innovate, and [***]. Amarex will also run a set for inclusion in the annual report/DSUR.
|
SAEs and non-serious adverse events are reported immediately to Amarex.
|
Amarex will design a SAE reporting form and prepare a protocol-specific SAE Reporting Plan (part of the Safety Management Plan). Each Principal Investigator and his/her staff will be instructed to immediately report any SAEs or any non-serious adverse event that requires withdrawal from the study through OpenClinica. Sites will report all SAEs with supportive documents according to the SAE plan. Sites will be provided with an [***] toll-free telephone number for access to the Medical Monitor. Amarex will work through [***] and EDC queries to collect relevant necessary safety information not already provided by the site in the initial reporting, and will setup a safety exchange agreement with [***] for this purpose. [***] will be responsible for interfacing with the sites.
|
The Safety Monitor will ensure that each event is recorded properly and reported.
|
We will review each SAE and forward its findings to Innovate to determine the appropriate interval of reporting. Amarex will notify Innovate of all SAEs within 1 day of receiving an initial report from a study site.
|
Amarex will use MedDRA and WHO Drug coding dictionaries unless otherwise directed by Innovate.
|
Amarex generally codes adverse events using the MedDRA version specified by the Sponsor (other adverse event coding dictionaries are also available). Coding will be performed to all MedDRA levels. Auto-encoding will be reviewed by the Amarex Medical Monitor for consistency according to the Data Management Plan, and coding reports will be forwarded to Innovate for approval. Coding for concomitant medications is usually done according to WHO Drug ATC levels. However, Amarex can code concomitant medications using a client-specified dictionary and auto-encoder. Processing and review of medication coding follows the same procedure as for AE coding review. Innovate is responsible for their licensing obligations with MedDRA and WHO Drug.
|
Amarex will organize and assemble the DSMB for the Innovate study.
|
Amarex will organize and assemble the DSMB for the Innovate study and will be responsible for the drafting and development of the written DSMB Charter (which will provide guidance to the DSMB), meeting organization, written data report to the DSMB, meeting agenda, and meeting minutes. The DSMB chairman of the committee, prior to the first meeting, will approve the DSMB Charter. Amarex will work with Innovate to identify three voting members to participate in the meetings. One will be the chair, one will be a medical person, and the third will be a blinded statistician.
|
•
|
The committee will review all safety information (in blinded fashion, if appropriate to the study, and unblinded only as deemed necessary by the DSMB chairman).
|
•
|
Amarex will record minutes of the meeting and prepare appropriate follow up documentation, according to the approved DSMB Charter.
|
•
|
Amarex will assist the DSMB chairman in the distribution of committee recommendations, according to the approved Charter.
|
AMAREX DIRECT SERVICES FEES
|
|
|
|
|
|
|
Bid ID
|
Service
|
Unit Description
|
Unit Cost $
|
No.
Units
|
Total
Cost $
|
Category
Total $
|
B
|
PROJECT MANAGEMENT
|
|
|
|
|
|
|
Meetings, Training, and Study Start Up
|
|
|
|
|
|
10
|
Prepare for and Participate in Kick-off Meeting (Telecon) & Study Start-Up
|
per protocol
|
[***]
|
[***]
|
[***]
|
|
|
Communication and Tracking
|
|
|
|
|
|
16
|
Coordinate Amarex's Internal Project Team
|
per month
|
[***]
|
[***]
|
[***]
|
|
17
|
Communicate with Sponsor
(includes standard teleconferences with activities reports, emails, faxes)
|
per month
|
[***]
|
[***]
|
[***]
|
|
19
|
Tracking Systems Setup
|
fixed fee
|
[***]
|
[***]
|
[***]
|
[***]
|
D
|
PRODUCT MANAGEMENT
|
|
|
|
|
|
50
|
Set up of WebView product supply tracking and email alert system. Track drug shipments to sites, supply depots, auto-email requests for resupply based on randomization. Require acknowledgement email from supply depot.
|
per project
|
[***]
|
[***]
|
[***]
|
|
51
|
Maintenance for WebView Product Resupply and Tracking
|
per month
|
[***]
|
[***]
|
[***]
|
[***]
|
E
|
DATA MANAGEMENT SERVICES
|
|
|
|
|
|
|
Data Management
|
|
|
|
|
|
56
|
Develop Data Management Plan
|
per project
|
[***]
|
[***]
|
[***]
|
|
64
|
Standard Data Cleaning (Run edit checks; generate, process, and track data queries)
|
per query
|
[***]
|
[***]
|
[***]
|
|
|
Data Operations
|
|
|
|
|
|
76
|
Develop Edit Specifications
|
per project
|
[***]
|
[***]
|
[***]
|
|
77
|
Program Edit Checks
|
per edit check
|
[***]
|
[***]
|
[***]
|
|
79
|
Set Up SAS Data Transfer [***]
|
fixed cost/per lab-vendor
|
[***]
|
[***]
|
[***]
|
|
80
|
Receive, Load, and Reconcile Clean SAS Data [***]
|
per transfer/per lab-vendor
|
[***]
|
[***]
|
[***]
|
|
81
|
Set Up Transfer of Final SAS Data to Sponsor
(in Amarex's format)
|
per dataset
|
[***]
|
[***]
|
[***]
|
|
82
|
Perform Data Transfer to Sponsor
(Including export of final SAS Analysis Datasets)
|
per transfer
|
[***]
|
[***]
|
[***]
|
|
139
|
Set Up of Coding System to Code AEs and Medications and Prepare Medical Coding Plan
|
fixed cost
|
[***]
|
[***]
|
[***]
|
|
140
|
Code Adverse Events and Medications
(Using MedDRA and WHO Drug ATC Level)
|
per term
|
[***]
|
[***]
|
[***]
|
|
|
EDC Support
|
|
|
|
|
|
85
|
Conduct Electronic Data Capture Site Training by WebEx
|
per training
|
[***]
|
[***]
|
[***]
|
|
86
|
Prepare EDC Manual and Completion Instructions (includes up to 1 round of edits)
|
per manual
|
[***]
|
[***]
|
[***]
|
|
87
|
Prepare User Acceptance Testing (UAT) Management Plan
|
per document
|
[***]
|
[***]
|
[***]
|
|
88
|
Conduct QC of EDC Database
|
per subject enrolled
|
[***]
|
[***]
|
[***]
|
|
89
|
Provide Electronic Data Capture Help Desk
|
per month
|
[***]
|
[***]
|
[***]
|
[***]
|
|
EDC PROGRAMMING
|
|
|
|
|
|
91
|
Development of CRF Screen Shots
|
per unique page
|
[***]
|
[***]
|
[***]
|
|
92
|
EDC Programming (Initiation)
|
per study
|
[***]
|
[***]
|
[***]
|
|
93
|
EDC Programming (UAT 1)
|
per study
|
[***]
|
[***]
|
[***]
|
|
94
|
EDC Programming (System Activation)
|
per study
|
[***]
|
[***]
|
[***]
|
|
95
|
EDC Maintenance
|
per month
|
[***]
|
[***]
|
[***]
|
[***]
|
G
|
SAFETY
|
|
|
|
|
|
126
|
SAE Start Up
|
fixed fee
|
[***]
|
[***]
|
[***]
|
|
127
|
Prepare and Implement Safety Management Plan [***]
|
per plan
|
[***]
|
[***]
|
[***]
|
|
128
|
Set Up EDC SAE Reporting Module
|
per project
|
[***]
|
[***]
|
[***]
|
|
129
|
Quarterly and Annual Aggregate Safety Tables and Listings
|
per project
|
[***]
|
[***]
|
[***]
|
|
130
|
Receive, Process, Evaluate, Prepare Narrative, and Report SAEs (CIOMS)
|
per event
|
[***]
|
[***]
|
[***]
|
|
134
|
Prepare and Distribute SUSAR Letters to Sites
|
per reportable event
|
[***]
|
[***]
|
[***]
|
|
135
|
Append Historical SAEs to Safety System
|
per SAE
|
[***]
|
[***]
|
[***]
|
|
189
|
Prepare Subject Narratives for CSR
|
per narrative
|
[***]
|
[***]
|
[***]
|
[***]
|
AMAREX DIRECT SERVICES FEES
|
|
|
|
|
|
|||
Bid ID
|
Service
|
Unit Description
|
Unit Cost $
|
No.
Units
|
Total
Cost $
|
Category
Total $
|
||
H
|
DATA SAFETY MONITORING BOARD (DSMB)
|
|
|
|
|
|
||
142
|
Establish and Manage 3-Member DSMB
|
fixed cost
|
[***]
|
[***]
|
[***]
|
|
|
|
143
|
Develop DSMB Charter (includes up to 1 round of edits)
|
per project
|
[***]
|
[***]
|
[***]
|
|
|
|
144
|
Organize, Conduct and Participate in DSMB Meetings
|
per meeting
|
[***]
|
[***]
|
[***]
|
|
[***]
|
|
I
|
RANDOMIZATION AND ENROLLMENT
|
|
|
|
|
|
||
155
|
Develop WebView Enrollment/Randomization/Stratification Module [***]
|
per project
|
[***]
|
[***]
|
[***]
|
|
|
|
156
|
Generate WebView Randomization/Stratification Code and Plan
|
per project
|
[***]
|
[***]
|
[***]
|
|
|
|
157
|
Conduct WebView Enrollment/Randomization/Stratification Maintenance (including ongoing cross-checking randomization/ stratification on a monthly basis)
|
per month
|
[***]
|
[***]
|
[***]
|
|
[***]
|
|
J
|
BIOSTATISTICS
|
|
|
|
|
|
||
162
|
Program Tables [***]
|
per unique table
|
[***]
|
[***]
|
[***]
|
|
|
|
163
|
Program Tables [***]
|
per replicate table
|
[***]
|
[***]
|
[***]
|
|
|
|
164
|
Program Listings [***]
|
per unique listing
|
[***]
|
[***]
|
[***]
|
|
|
|
165
|
Program Listings [***]
|
per replicate listing
|
[***]
|
[***]
|
[***]
|
|
|
|
168
|
Program Tables for Final Analysis (unique tables)
|
per unique table
|
[***]
|
[***]
|
[***]
|
|
|
|
169
|
Program Tables for Final Analysis (replicate tables)
|
per replicate table
|
[***]
|
[***]
|
[***]
|
|
|
|
170
|
Program Listings for Final Analysis (unique listings)
|
per unique listing
|
[***]
|
[***]
|
[***]
|
|
|
|
171
|
Program Listings for Final Analysis (replicate listings)
|
per replicate listing
|
[***]
|
[***]
|
[***]
|
|
|
|
172
|
Program Graphs for Final Analysis (unique graph)
|
per unique graph
|
[***]
|
[***]
|
[***]
|
|
|
|
173
|
Program Graphs for Final Analysis (replicate graph)
|
per replicate graph
|
[***]
|
[***]
|
[***]
|
|
|
|
174
|
Conduct QC Audit of Stats
|
per lock
|
[***]
|
[***]
|
[***]
|
|
|
|
175
|
Production and Review of Tables, Listings, and Graphs [***](per unique display)
|
per unique display
|
[***]
|
[***]
|
[***]
|
|
|
|
176
|
Production and Review of Tables, Listings, and Graphs [***] (per replicate display)
|
per replicate display
|
[***]
|
[***]
|
[***]
|
|
|
|
177
|
Production and Review of Tables, Listings, and Graphs for Final Analysis (per unique display)
|
per unique display
|
[***]
|
[***]
|
[***]
|
|
|
|
178
|
Production and Review of Tables, Listings, and Graphs for Final Analysis (per replicate display)
|
per replicate display
|
[***]
|
[***]
|
[***]
|
|
|
|
179
|
Prepare Statistical Report (includes up to 1 round of edits and Report for DSMB)
First report for DSMB, Second for Final CSR
|
per report
|
[***]
|
[***]
|
[***]
|
|
|
|
|
Other
|
|
|
|
|
|
||
181
|
Convert Trial Data to CDISC (ADaM or SDTM)
|
per type
|
[***]
|
[***]
|
[***]
|
|
|
|
182
|
QA CDISC Data Conversion
|
per type
|
[***]
|
[***]
|
[***]
|
|
|
|
184
|
Prepare Program for Risk-Based Monitoring
|
per data type
|
[***]
|
[***]
|
[***]
|
|
|
|
185
|
Run Risk-Based Programs
|
per program per month
|
[***]
|
[***]
|
[***]
|
|
[***]
|
|
|
|
|
|
|
|
|
||
|
TOTAL OF ACTIVITY-BASED COSTING
|
|
|
|
[***]
|
|
|
|
|
|
|
|
|
|
|
||
|
EXECUTIVE DISCOUNT ( [***]%)
|
|
|
|
[***]
|
|
|
|
|
|
|
|
|
|
|
||
|
TOTAL WITH DISCOUNT
|
|
|
|
$
|
1,067,819.48
|
|
|
OPTIONAL SERVICES
|
|
|
|
|
|
|
Bid ID
|
Service
|
Unit Description
|
Unit
Cost $
|
No.
Units
|
Total
Cost $
|
Category
Total $
|
13
|
Attend Project Meetings at Sponsor Office Upon Request
(includes travel time)
|
per person / per day
|
[***]
|
[***]
|
[***]
|
[***]
|
ESTIMATED PASS THROUGH COSTS
|
|
|
|
|
|
|
Bid ID
|
Service
|
Unit Description
|
Unit
Cost $
|
No.
Units
|
Total
Cost $
|
Category
Total $
|
A
|
TRAVEL AND MEETINGS
|
|
|
|
|
|
|
Meetings-Amarex's Personnel
|
|
|
|
|
|
6
|
Travel Expenses for Meetings at Sponsor Office, if requested by Sponsor
|
per person
|
[***]
|
[***]
|
[***]
|
[***]
|
F
|
PRINTING & ASSEMBLY OF STUDY MATERIALS
|
|
|
|
|
|
36
|
Miscellaneous Printing/Copying
|
per month
|
[***]
|
[***]
|
[***]
|
[***]
|
G
|
SHIPPING COSTS (CRFs, Study Binders, etc.)
|
|
|
|
|
|
39
|
Overnight delivery (UPS/FedEx)
|
per month
|
[***]
|
[***]
|
[***]
|
[***]
|
I
|
MISCELLANEOUS
|
|
|
|
|
|
48
|
DSMB Honorarium
|
per person per meeting
|
[***]
|
[***]
|
[***]
|
|
51
|
Ad Hoc Electronic Data Transfers Over 12MB, if requested by Sponsor
|
per transfer
|
[***]
|
[***]
|
[***]
|
|
52
|
WebEx Host Line Fee, if requested by Sponsor
|
per usage
|
[***]
|
[***]
|
[***]
|
[***]
|
|
|
|
|
|
|
|
|
TOTAL OF ESTIMATED PASS THROUGHS
|
|
|
|
[***]
|
|
Payment Description
|
Percentage Due
|
Amount
|
Execution of Project Work Order
|
[***]
%
|
$
[***]
|
Monthly Unit-Based Billing
|
Balance Due
|
$
[***]
|
TOTAL
|
|
$1,067,819.48
|
•
|
Payments are due 30 days after delivery of an invoice.
|
•
|
Late payment fee: 1% per month interest on all past due, unpaid balances.
|
•
|
Payments will be made out to: Amarex Clinical Research, LLC
|
•
|
Tax ID: [***]
|
•
|
Payments will be sent to:
|
•
|
Payments will be wire transferred to the Amarex Clinical Research, LLC bank account at:
|
For and on behalf of Innovate Biopharmaceuticals, Inc.:
|
For and on behalf of Amarex Clinical Research, LLC:
|
||
Print Name:
|
Christopher Prior
|
Print Name:
|
Kazem Kazempour
|
Signature:
|
/s/ Christopher Prior
|
Signature:
|
/s/ Kazem Kazempour
|
Title:
|
Chief Executive Officer
|
Title:
|
President and CEO (Member)
|
Date:
|
August 15, 2018
|
Date:
|
20 Aug 18
|
1.
|
I have reviewed this quarterly report on Form 10-Q of Innovate Biopharmaceuticals, Inc. (the “registrant”);
|
2.
|
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
|
3.
|
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
|
4.
|
The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
|
(a)
|
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;
|
(b)
|
Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;
|
(c)
|
Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
|
(d)
|
Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
|
5.
|
The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):
|
(a)
|
All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and
|
(b)
|
Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.
|
|
|
By:
|
/s/ Christopher Prior
|
Date:
|
November 13, 2018
|
|
Christopher Prior
|
|
|
|
Chief Executive Officer
|
|
|
|
(Principal Executive Officer)
|
1.
|
I have reviewed this quarterly report on Form 10-Q of Innovate Biopharmaceuticals, Inc. (the “registrant”);
|
2.
|
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
|
3.
|
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
|
4.
|
The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
|
(a)
|
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;
|
(b)
|
Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;
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(c)
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Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
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(d)
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Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
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5.
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The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):
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(a)
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All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and
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(b)
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Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.
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|
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By:
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/s/ Jay Madan
|
Date:
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November 13, 2018
|
|
Jay Madan
|
|
|
|
President, Chief Business Officer and Interim Principal Financial Officer
|
|
|
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(Principal Financial Officer)
|
|
|
By:
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/s/ Christopher Prior
|
Date:
|
November 13, 2018
|
|
Christopher Prior
|
|
|
|
Chief Executive Officer
|
|
|
|
(Principal Executive Officer)
|
|
|
By:
|
/s/ Jay Madan
|
Date:
|
November 13, 2018
|
|
Jay Madan
|
|
|
|
President, Chief Business Officer and Interim Principal Financial Officer
|
|
|
|
(Principal Financial Officer)
|