Attached files
Exhibit 10.62
Confidential Materials Omitted and Filed Separately with the Securities and Exchange Commission Pursuant to a Request for Confidential Treatment under Rule 24b-2 under the Exchange Act of 1934, as amended. Confidential Portions are marked: [***]
AMENDMENT TO NOTICE OF GRANT AWARD – RFA 13-03A - CIRM Strategic Partnership III
Track A Awards
California Institute for Regenerative Medicine
Track A Awards
California Institute for Regenerative Medicine
Amendment Number: 1
Amendment Date: 11/26/14
Amendment Date: 11/26/14
|
Grant Number:
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SP3A-07552
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Total Award Amount:
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$14,323,318
|
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Grantee Name:
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Asterias Biotherapeutics
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Project Period Start Date:
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10/1/2014
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Grantee ID:
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PR-Y0035A-SF
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Project Period End Date:
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9/30/2018
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Principal Investigator:
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Jane Stephanie Lebkowki
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||
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Project Title:
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A Phase I/IIa Dose Escalation Safety Study of AST-OPC1 in Patients with Cervical Sensorimotor Complete Spinal Cord Injury
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||
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Authorized Organization Official and Address:
Katharine E. Spink Chief Operating Officer 230 Constitution Dr. Menlo Park, CA 94025 |
Official and Address to Receive Payments:
Katharine E. Spink, Ph.D. 230 Constitution Drive Menlo Park, CA 94025 |
||
This Amendment is CIRM-initiated in response to condition F of the original Notice of Grant Award. The terms and conditions of the original NGA and any prior Amendments to the NGA continue in full force and effect as specified below. The following changes are effective immediately:
| A. | Change in Milestones and Release of Funds for Process Development activities |
This Amendment provides final, negotiated Milestones for Process Development activities and releases funding for these activities. This Amendment also revises previously, negotiated Clinical Milestones. The complete, final set of negotiated Milestones is attached in Appendix A to this Amendment.
| B. | Rebudgeting & Payments |
Based on negotiated Milestones, the budget has been revised as follows:
|
Revised
Year 1 |
Revised
Year 2 |
Revised
Year 3 |
Revised
Year 4
|
|
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Personnel Costs
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$[***]
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$[***]
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$[***]
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$[***]
|
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Travel
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$[***]
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$[***]
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$[***]
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$[***]
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Supplies
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$[***]
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$[***]
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$[***]
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$[***]
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Equipment
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$[***]
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$[***]
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$[***]
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$[***]
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Consultants/Subcontracts
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$[***]
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$[***]
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$[***]
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$[***]
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Total Direct Project Costs
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$[***]
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$[***]
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$[***]
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$[***]
|
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Facilities Costs
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$[***]
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$[***]
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$[***]
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$[***]
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Indirect Costs
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$[***]
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$[***]
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$[***]
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$[***]
|
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TOTAL COSTS
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$5,310,115
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$4,975,178
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$3,221,962
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$815,989
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Payment Schedule
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Payment
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Budget Year
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Date
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Amount
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Status
|
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1/17
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1
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10/23/14
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$916,554
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Paid
|
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2/17
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1
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12/15/14
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$1,207,492
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Scheduled
|
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3/17
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1
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1/1/15
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$1,062,023
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Scheduled
|
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4/17
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1
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4/1/15
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$1,062,023
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Scheduled
|
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5/17
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1
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7/1/15
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$1,062,023
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Scheduled
|
1
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6/17
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2
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10/1/15
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$1,243,794
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Scheduled
|
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7/17
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2
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1/1/16
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$1,243,795
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Scheduled
|
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8/17
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2
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4/1/16
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$1,243,794
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Scheduled
|
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9/17
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2
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7/1/16
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$1,243,795
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Scheduled
|
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10/17
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3
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10/1/16
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$805,490
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Scheduled
|
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11/17
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3
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1/1/17
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$805,491
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Scheduled
|
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12/17
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3
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4/1/17
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$805,490
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Scheduled
|
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13/17
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3
|
7/1/17
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$805,491
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Scheduled
|
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14/17
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4
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10/1/17
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$203,997
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Scheduled
|
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15/17
|
4
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1/1/18
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$203,997
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Scheduled
|
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16/17
|
4
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4/1/18
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$203,997
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Scheduled
|
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17/17
|
4
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7/1/18
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$203,998
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Scheduled
|
By continuing to accept and use CIRM funds provided under this award, Grantee and Principal Investigator accept the modified terms reflected in this Amendment.
Patricia Olson, Ph.D.
Executive Director of Scientific Activities, CIRM
Executive Director of Scientific Activities, CIRM
2
APPENDIX A – Confidential SP3A-07552
AMENDMENT TO NOTICE OF GRANT AWARD – RFA 13-03A - Strategic Partnership III – Part A
Awards
California Institute for Regenerative Medicine
Awards
California Institute for Regenerative Medicine
|
Grant Number:
|
SP3A-07552
|
Total Award Amount:
|
$14,323,318
|
|
Grantee Name:
|
Asterias Biotherapeutics, Inc.
|
Project Period Start Date:
|
10/1/2014
|
|
Grantee ID:
|
PR-Y0035A-SF
|
Project Period End Date:
|
9/30/2018
|
|
Principal Investigator:
|
Jane Stephanie Lebkowki
|
||
|
Project Title:
|
A Phase I/IIa Dose Escalation Safety Study of AST-OPC1 in Patients with Cervical Sensorimotor Complete Spinal Cord Injury
|
||
Milestone achievement is an important indicator of progress and is a major factor in review of progress reports. Insufficient progress through Milestones may result in loss of further funding. The Milestones summarized below replace the Milestones proposed in the original Application. These Milestones will be used as a basis for review in the progress reports and progress Evaluation Meetings unless further modified with Prior Approval from CIRM.
Clinical Trial Milestones: Year 1
(Q4 2014-Q3 2015)
(Q4 2014-Q3 2015)
|
Milestone
|
Target
completion
date
|
Progress or
Go/ No Go |
Comments
|
|
|
Clinical/
Regulatory |
1. Execute contracts with [***] and all other contractors necessary to open all eight clinical sites.
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Q4 2014
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Progress
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Applies to contracts with vendors and service providers. Does not apply to contracts with all eight clinical sites, which will likely extend into Q2-3 2015 for completion.
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CMC
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2. Complete final release of sufficient cGMP‑grade material to supply proposed clinical plan
Success criteria: At least [***] differentiated cells meeting specified release criteria
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Q4 2014
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Progress
|
|
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Clinical/
Regulatory |
3. Open first site
Success criteria: First site open for enrollment, including site initiation, site agreement signed and IRB approval and imaging CRO contract signed
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Q1 2015
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Progress
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Based on previous experience, it will likely take 5-6 months to complete IRB review and site training after obtaining FDA clearance for the trial.
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3
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Clinical/
Regulatory |
4. Enroll first subject
Success criteria: First subject enrolled in first cohort
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Q1 2015
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Progress
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Enrollment will likely be slow at first, but is expected to accelerate as more sites open and outreach efforts reach referral centers
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|
Clinical/
Regulatory |
5. Execute contracts with all clinical sites
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Q3 2015
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Progress
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Agreements signed with, and IRB approvals obtained at, all eight clinical sites.
|
|
Clinical/
Regulatory |
6. Complete site initiation for remaining seven clinical sites
Success criteria: Eight clinical sites open for enrollment
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Q3 2015
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Progress
|
Currently anticipated first four sites are Shepherd
[***]; however, this is subject to change based on results of final site qualification visits and other considerations. Sites 5-8 are being determined, with identification/site qualification visits anticipated in Q1 2015.
|
|
Clinical/
Regulatory |
7. Complete enrollment, DMC review of 30 day safety data from first cohort
Success criteria: Enrollment of 3 subjects within 6 months; DMC approves escalation to second dose cohort
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Q3 2015
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Go/no go
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If safety concerns deemed by DMC serious enough to pose an undue risk to patients are observed in the first dose cohort, a no go decision will be made.
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Clinical Trial Milestones: Year 2
(Q4 2014-Q3 2016)
(Q4 2014-Q3 2016)
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Milestone
|
Target
completion
date
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Progress or
Go/ No Go |
Comments
|
|
|
Clinical/
Regulatory |
8. Enroll first subject in second dose cohort
Success criteria: Enrollment of first subject in second cohort
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Q4 2015
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Progress
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Assumes acceptable safety in cohort 1. Target is to enroll first subject within one month of DMC approval of dose escalation.
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4
|
Clinical/
Regulatory |
9. Complete enrollment, DMC review of safety data from second dose cohort
Success criteria: Enrollment of 5 subjects in second cohort; DMC approves escalation to third dose cohort
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Q1 2016
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Go/no go
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Enrollment should be more rapid in second dose cohort as more sites open, outreach completed. It is expected to take 4-6 months to enroll 5 patient cohort.
If safety concerns deemed by DMC serious enough to pose an undue risk to patients are observed in the second dose cohort, a no go decision will be made.
|
|
Clinical/
Regulatory |
10. Enroll first subject in third dose cohort
Success criteria:
Enrollment of first subject in the third cohort
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Q2 2016
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Progress
|
Assumes acceptable safety in cohort 2. Target is to enroll first subject within 1‑2 months of DMC approval of dose escalation.
|
|
Clinical/
Regulatory |
11. Initial (6 month) activity readout from second dose cohort
Success criteria: Continued demonstration of safety. If ≥ 2 of 5 subjects show ≥ 2 neurological levels improvement in motor function, this could be a possible early sign of efficacy
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Q3 2016
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Progress
|
Based on historical controls, anticipated spontaneous frequency of ≥ 2 neurological level improvement in motor function is 1 of 5 subjects (21%) at 6 months. However, given early timepoint, small number of subjects, and dose at low end of likely efficacious range, data will not be used as a go/no go decision point.
|
|
Clinical/
Regulatory |
12. Complete enrollment of Phase 1/2a dose escalation study
Success criteria: Enrollment of 5 subjects in third dose cohort
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Q3 2016
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Progress
|
Target is to enroll 5 subjects in third dose cohort within 4‑6 months.
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Clinical Trial Milestones: Year 3
(Q4 2015-Q3 2017)
(Q4 2015-Q3 2017)
|
Milestone
|
Target
completion
date
|
Progress
or Go/ No Go |
Comments
|
|
|
Clinical/
Regulatory |
13. Initial (6 month) activity readout from third dose cohort
Success criteria: Continued demonstration of safety. If ≥ 2 of 5 subjects show ≥ 2 neurological levels improvement in motor function, this could be a possible early sign of efficacy.
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Q1 2017
|
Progress
|
Based on historical controls, anticipated spontaneous frequency of ≥ 2 neurological level improvement in mot function is 1 of 5 subjects (21 %) at 6 months. If the data show a higher frequency of improvement this could be a promising early sign of efficacy. However, subjects will also be followed to 1 year as improvements may take longer than 6 months to manifest.
|
|
Clinical/
Regulatory |
14. Complete one year follow-up of Phase 1/2a dose escalation study
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Q3 2017
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Progress
|
5
Clinical Trial Milestones: Year 4
(Q4 2016-Q3 2018)
(Q4 2016-Q3 2018)
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Milestone
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Target
completion
date
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Progress or
Go/ No Go |
Comments
|
|
|
Clinical/
Regulatory |
15. Complete study report
Success criteria: No major safety concerns identified; ≥ 2 of 5 subjects show two neurological levels of improvement in at least one dose cohort
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Q4 2017
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Go/no go
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Go/no go decision point for subsequent clinical trials, primarily from a safety perspective. Will also be looking for evidence that are meeting TPP of >40% of patients achieving 2 neurological levels of improvement as preliminary efficacy readout for justification of investment in subsequent trials.
|
Process Development Milestones: Year 1
(Q4 2014-Q3 2015)
(Q4 2014-Q3 2015)
|
Milestone
|
Target
completion
date
|
Progress or
Go/ No Go |
Comments
|
|
|
Regulatory
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14. Obtain guidance from FDA regarding
[***]
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Q2 2015
|
Progress
|
6
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CMC
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15. Select [***] for AST-OPC1 commercial production
Success criteria: Selection of [***] CIRM Clinical Advisory Panel will be consulted [***].
|
Q3 2015
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Progress
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[***] for commercial-scale production of AST‑OPC1. [***]. Performance will be compared.
|
Product Development Milestones: Year 2
(Q4 2015-Q3 2016)
(Q4 2015-Q3 2016)
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Milestone
|
Target
completion
date
|
Progress or
Go/ No Go |
Comments
|
|
|
CMC
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16. Produce cGMP [***] for commercial production
Success Criteria:
[***]
capable of supporting the production of [***] lots of AST-OPC1 per year over a [***] year product life cycle.
|
Q3 2016
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Go/no go
|
Vial number requirements are based on conservative estimates of the number of manufacturing runs required for the commercial life of the product. This can be easily achieved by [***].
|
|
CMC
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17. Establish OPC1 production process suitable to support cGMP Production for advanced clinical trials
Success criteria: [***]
|
Q3 2016
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Go/no go
|
Success criteria are established by minimum criteria to enable production ofAST-OPC1 for pivotal study using the new cell bank and manufacturing process.
It is anticipated that the pivotal trial will enroll 100‑150 patients requiring between 1E7 and 2E7 cells per patient thus requiring a maximum of 3E9 cells for the pivotal study. [***].
[***]
|
7
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Pharm/Tox
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18. Initiate [***] comparability testing of AST-OPC1 made with the final process.
Success criteria: Study initiated
|
Q3 2016
|
Progress
|
[***]
|
|
CMC
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19. Transfer for development and prequalification [***]
Success criteria: Assays accepted for full development
|
Q3 2016
|
Progress
|
Product Development Milestones: Year 3
(Q4 2016-Q3 2017)
(Q4 2016-Q3 2017)
|
Milestone
|
Target
completion
date
|
Progress or
Go/ No Go |
Comments
|
|
|
CMC
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20. Complete process lockdown for tech transfer of improved manufacturing process
Success criteria:
[***]
|
Q4 2016
|
Go/No Go
|
Potential timeline risk as no precedent exists for development of registration- ready hESC‑based manufacturing process. Impact of any delay will be on initiation of pivotal trial, not on proposed CIRM project scope.
|
8
|
CMC
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21. Implement new assays for OPC1 characterization
Success criteria: [***].
|
Q1 2017
|
Progress
|
[***]
|
|
CMC
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22. Lock down manufacturing process. Complete draft batch record. Produce material for [***].
Success criteria: [***].
|
Q3 2017
|
Progress
|
|
|
CMC
|
23. Complete the [***] of AST-OPC1 made with the final process.
Success criteria: [***].
|
Q2 2017
|
Progress
|
[***]
|
|
Regulatory
|
24. Obtain FDA feedback on [***]
Success criteria: Concurrence with FDA regarding [***].
|
Q2 2017
|
Progress
|
|
|
Pharm/tox
|
25. Initiate [***] to demonstrate equivalence of improved manufacturing process
Success criteria: [***].
|
Q3 2017
|
Progress
|
[***]
|
9
Product Development Milestones: Year 4
(Q4 2017-Q3 2018)
(Q4 2017-Q3 2018)
|
Milestone
|
Target
completion
date
|
Progress or
Go/ No Go |
Comments
|
|
|
CMC
|
26. Successfully complete [***], enabling cGMP manufacture of registration-enabling manufacturing process
Success criteria: [***].
|
Q4 2017
|
Progress
|
[***]
|
|
Pharm/tox
|
27. Complete [***] for manufacturing process improvements
Success criteria: [***].
|
Q3 2018
|
Go/No go
|
[***]
|
10