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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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