Exhibit 10.27


 


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


Amendment Number:  1

Amendment Date:  11/26/14


	
Grant Number:

	
SP3A-07552

	
Total Award Amount:

	
$14,323,318


	
Grantee Name:

	
Asterias Biotherapeutics

	
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


	 	 
	
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


	
Personnel Costs

	
$[***]

	
$[***]

	
$[***]

	
$[***]


	
Travel

	
$[***]

	
$[***]

	
$[***]

	
$[***]


	
Supplies

	
$[***]

	
$[***]

	
$[***]

	
$[***]


	
Equipment

	
$[***]

	
$[***]

	
$[***]

	
$[***]


	
Consultants/Subcontracts

	
$[***]

	
$[***]

	
$[***]

	
$[***]


	
Total Direct Project Costs

	
$[***]

	
$[***]

	
$[***]

	
$[***]


	
Facilities Costs

	
$[***]

	
$[***]

	
$[***]

	
$[***]


	
Indirect Costs

	
$[***]

	
$[***]

	
$[***]

	
$[***]


	
TOTAL COSTS

	
$5,310,115

	
$4,975,178

	
$3,221,962

	
$815,989





 


Payment Schedule


	
Payment

	
Budget Year

	
Date

	
Amount

	
Status


	
1/17

	
1

	
10/23/14

	
$916,554

	
Paid


	
2/17

	
1

	
12/15/14

	
$1,207,492

	
Scheduled


	
3/17

	
1

	
1/1/15

	
$1,062,023

	
Scheduled


	
4/17

	
1

	
4/1/15

	
$1,062,023

	
Scheduled


	
5/17

	
1

	
7/1/15

	
$1,062,023

	
Scheduled





 



1







	
6/17

	
2

	
10/1/15

	
$1,243,794

	
Scheduled


	
7/17

	
2

	
1/1/16

	
$1,243,795

	
Scheduled


	
8/17

	
2

	
4/1/16

	
$1,243,794

	
Scheduled


	
9/17

	
2

	
7/1/16

	
$1,243,795

	
Scheduled


	
10/17

	
3

	
10/1/16

	
$805,490

	
Scheduled


	
11/17

	
3

	
1/1/17

	
$805,491

	
Scheduled


	
12/17

	
3

	
4/1/17

	
$805,490

	
Scheduled


	
13/17

	
3

	
7/1/17

	
$805,491

	
Scheduled


	
14/17

	
4

	
10/1/17

	
$203,997

	
Scheduled


	
15/17

	
4

	
1/1/18

	
$203,997

	
Scheduled


	
16/17

	
4

	
4/1/18

	
$203,997

	
Scheduled


	
17/17

	
4

	
7/1/18

	
$203,998

	
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



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


 


	
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)


 


	 	
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.

	
Q4 2014

	
Progress

	
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.


	
 


CMC

	
2.      Complete final release of sufficient cGMP‐grade material to supply proposed clinical plan


 


Success criteria:  At least [***] differentiated cells meeting specified release criteria

	
 


Q4 2014

	
 


Progress

	 
	
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

	
Q1 2015

	
Progress

	
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.





 



3







	
Clinical/

 Regulatory

	
4.      Enroll first subject


 


Success criteria:  First subject enrolled in first cohort

	
 


Q1 2015

	
 


Progress

	
Enrollment will likely be slow at first, but is expected to accelerate as more sites open and outreach efforts reach referral centers


	
Clinical/

 Regulatory

	
5.      Execute contracts with all clinical sites

	
Q3 2015

	
Progress

	
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


 

	
 


 


Q3 2015

	
 


 


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

	
 


Q3 2015

	
 


Go/no go

	
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.










Clinical Trial Milestones:  Year 2

 (Q4 2014-Q3 2016)


 


	 	
Milestone

	
Target 


completion 


date

	
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


 

	
 


Q4 2015

	
 


Progress

	
Assumes acceptable safety in cohort 1.  Target is to enroll first subject within one month of DMC approval of dose escalation.





 



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

	
 


Q1 2016

	
 


Go/no go

	
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

	
 


Q2 2016

	
 


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


 

	
 


Q3 2016

	
 


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

	
 


Q3 2016

	
 


Progress

	
Target is to enroll 5 subjects in third dose cohort within 4‐6 months.










Clinical Trial Milestones:  Year 3

 (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.

	
 


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

	
Q3 2017

	
Progress

	 



 



5







Clinical Trial Milestones:  Year 4

 (Q4 2016-Q3 2018)


 


	 	
Milestone

	
Target 


completion d


ate

	
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

	
 


 


 


Q4 2017

	
 


 


 


Go/no go

	
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)


 


	 	
Milestone

	
Target 


completion


 date

	
Progress or

Go/

 No Go

	
Comments


	
Regulatory

	
14.            Obtain guidance from FDA regarding


 


 


[***]


 


 


 


 

	
Q2 2015

	
Progress

	 



 



6







	
CMC

	
15.      Select [***] for AST-OPC1 commercial production


 


Success criteria:  Selection of [***] CIRM Clinical Advisory Panel will be consulted [***].

	
Q3 2015

	
Progress

	
[***] for commercial-scale production of AST‐OPC1.  [***]. Performance will be compared.





 


Product Development Milestones:  Year 2

 (Q4 2015-Q3 2016)


 


	 	
Milestone

	
Target 


completion 


date

	
Progress or

Go/

 No Go

	
Comments


	
CMC

	
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

	
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

	
17.      Establish OPC1 production process suitable to support cGMP Production for advanced clinical trials

  


 


 


 


 


 


 


 


Success criteria: [***]

	
Q3 2016

	
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







	
Pharm/Tox

	
18.      Initiate [***] comparability testing of AST-OPC1 made with the final process.


 


Success criteria:  Study initiated

	
Q3 2016

	
Progress

	
 


[***]


	
CMC

	
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)


 


	 	
Milestone

	
Target 


completion 


date

	
Progress or

Go/

 No Go

	
Comments


	
CMC

	
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

	
21.      Implement new assays for OPC1 characterization


 


Success criteria:  [***].


 

	
Q1 2017

	
Progress

	
[***]


	
CMC

	
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)


 


	 	
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