UNITED STATES
SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (date of earliest event reported): October 2, 2017

Asterias Biotherapeutics, Inc.

(Exact name of registrant as specified in its charter)
 
Delaware
001-36646
46-1047971
     
(State or other jurisdiction of incorporation)
(Commission File Number)
(IRS Employer Identification No.)

6300 Dumbarton Circle
Fremont, CA 94555
(Address of principal executive offices)

(510) 456-3800
(Registrant's telephone number, including area code)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
 
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
 
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
 
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
 
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
 
Emerging growth company ☒
 
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
 


Item 7.01
Regulation FD Disclosure
 
On October 2, 2017, Asterias Biotherapeutics, Inc. (the “Company”)  announced new 12-month efficacy and safety data from the first efficacy cohort (Cohort 2) in the Company’s ongoing Phase 1/2a SCiStar study. The 12-month data showed 67% of Cohort 2 subjects have recovered two or more motor levels on at least one side through 12 months, which is more than double the rates of recovery seen in both matched historical controls and published data in a similar population.  The Company also announced that the FDA granted the Company’s request for AST-OPC1 to be designated a Regenerative Medicine Advanced Therapy (RMAT) under the 21st Century Cures Act.  A copy of the Company's press release relating to this announcement is furnished herewith as Exhibit 99.1, which text of which is incorporated by reference into this Item 7.01.
 
On October 2, 2017, Asterias Biotherapeutics, Inc. posted a PowerPoint presentation on its website. The presentation is furnished herewith as Exhibit 99.2.
 
The information in this Item 7.01 and related exhibits filed as Exhibits 99.1 and  99.2 are being furnished and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall such exhibits be deemed incorporated by reference in any filing made by the Company under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 9.01
Financial Statements and Exhibits

(d)
Exhibits .

Exhibit No.
 
Description
99.1
 
Press Release, dated October 2, 2017
99.2
 
PowerPoint Presentation, October 2017

SIGNATURES
 
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 
ASTERIAS BIOTHERAPEUTICS, INC.
   
Date: October 2, 2017
By:
/s/ Ryan D. Chavez
   
Chief Financial Officer and General Counsel
 
 


Exhibit 99.1
 
Asterias Announces Two Significant Developments for Spinal Cord Injury Program

67% of Cohort 2 subjects have recovered two or more motor levels on at least one side through 12 months

AST-OPC1 receives Regenerative Medicine Advanced Therapy (RMAT) designation from FDA

FREMONT, Calif. October 2, 2017 – Asterias Biotherapeutics, Inc. (NYSE American: AST), a biotechnology company pioneering the field of regenerative medicine, today announced new 12-month data from the first efficacy cohort in the company’s ongoing Phase 1/2a SCiStar study designated to evaluate safety and efficacy of AST-OPC1.   The 12-month data showed 67% (4/6) of Cohort 2 (AIS-A injuries administered 10 million AST-OPC1 cells) subjects have recovered 2 or more motor levels on at least one side through 12 months, which is more than double the rates of recovery seen in both matched historical controls and published data in a similar population.  Also, the FDA granted the company’s request for AST-OPC1 to be designated a Regenerative Medicine Advanced Therapy (RMAT) under the 21st Century Cures Act.


“The 12-month results suggest that many of the Cohort 2 subjects are seeing a durable clinical benefit above and beyond what you would expect to see from spontaneous recovery following a severe spinal cord injury,” stated Dr. Edward Wirth III, Chief Medical Officer. “Our target for the entire SCiStar study since its commencement was that at 12 months 45-50% of study subjects would recover at least 2 motor levels on at least one side, and it is exciting that Cohort 2 has exceeded this target recovery rate.”

“We are very encouraged by these early results and look forward to continuing to pursue this important program,” stated Mike Mulroy, President and Chief Executive Officer.  “We are also excited about the RMAT designation and I’d like to commend our clinical operations team on these developments and our entire employee base on several other recent positive developments at Asterias:

·
Full enrollment of Cohort 3 (AIS-A; 20 million AST-OPC1 cells), securing the final $1.5 million payment under our $14.3 million grant from the California Institute for Regenerative Medicine;
·
Full enrollment of Cohort 4 (AIS-B; 10 million AST-OPC1 cells), our first cohort with some sensory function below the injury site; and
·
Receipt of United Kingdom regulatory approval to initiate the clinical trial of our cancer immunotherapy product AST-VAC2 in subjects with early and late stage non-small cell lung cancer.”

Cohort 2 (AIS-A 10 million cell): 12-Month Efficacy and Safety Results

Improvements in upper extremity motor function are being measured using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scale, widely used to quantify functional status of patients with spinal cord injuries. Both subjects and physicians consistently report that improvements in upper extremity motor function are the most desirable functional improvement target in the quadriplegic population, since even relatively modest changes can potentially have a significant impact on functional independence, quality of life and cost of care. The SCiStar study is monitoring two separate ISNCSCI measurements of upper extremity motor function. The upper extremity motor score (UEMS), is a linear scale used to quantify motor function at each of five upper extremity muscle groups driving arm and hand function; these scores are also used to determine "motor levels", which define the level within the cord above which a subject has normal function.  As suggested by existing research, patients with severe spinal cord injuries that show two motor levels of improvement on at least one side may regain the ability to perform daily activities such as feeding, dressing and bathing, which significantly reduces the overall level of daily assistance needed for the patient and associated healthcare costs.

A total of six subjects were enrolled and dosed in Cohort 2, with all six subjects completing a 12-month follow-up visit. The results include the following highlights:

·
Motor Level Improvement – Additional motor level improvement was seen in Cohort 2 at 12 months.
o
Four of six subjects (67%) achieved at least two motor levels of improvement over baseline on at least one side as of their latest follow-up visit through 12 months, which compares favorably to the rates of recovery at 9 months (50%) and at 3 months and 6 months (33%). Furthermore, the rate of recovery at 12 months is more than double the rates of recovery seen at 12 months in both matched historical controls (29%) and published data in a similar patient population (26%).
o
All six subjects (100%) achieved at least one motor level of improvement on both sides as of their latest follow-up through 12 months.  This compares favorably to the matched historical controls, in which 74% of the subjects saw at least one motor level of improvement on at least one side of the body and thereby 26% of subjects saw no motor level improvement or got worse after their injury.
o
In addition, one patient (18%) achieved three motor levels of improvement on one side as of his 12-month follow-up visit.  In the matched historical controls, 8% of subjects achieved three or more motor levels of improvement on at least one side at 12 months.
 

·
Upper Extremity Motor Score – Additional improvement in the average UEMS score for Cohort 2 was observed at 12 months.  The average UEMS improvement for Cohort 2 at 12 months was 12.3 points, 57% greater than the average UEMS improvement at 12 months in the matched historical controls (7.8 points).

·
Magnetic Resonance Imaging (MRI) Data - All six subjects in Cohort 2 (100%) had serial MRI scans at 12 months that indicated no sign of lesion cavities in any patient. This is in contrast to published data suggesting that 50% of all spinal cord injuries and up to 80% of those meeting the inclusion criteria for the SCiStar trial develop a lesion cavity by 6 months post injury.  The MRI results are consistent with formation of a tissue matrix at the injury site, which is supportive evidence showing that AST-OPC1 cells have durably engrafted to help prevent cavitation at the injury site.

·
Safety - The trial results to date continue to suggest a positive safety profile for AST-OPC1. On September 18, 2017, an independent Data Monitoring Committee (DMC) recommended the SCiStar study continue as planned after it completed a regularly scheduled review of the accumulated safety data to date from the study.

RMAT Designation

The RMAT designation is intended to facilitate expedited development, review and approval for important new regenerative medicine therapies for which preliminary clinical evidence indicates the potential to address a serious or life-threatening disease or condition. In addition to providing an avenue for increased and earlier interactions with the FDA, RMAT-designated products may be eligible for priority review and accelerated approval.

“We are honored by the FDA’s interest in the therapeutic potential of AST-OPC1 and greatly appreciate their decision to provide support to accelerate its regulatory review and potential approval. We look forward to continuing to work closely and constructively with the FDA to advance the development of AST-OPC1 for the thousands of patients each year in the United States alone that suffer a severe cervical spinal cord injury and currently do not have access to any approved therapies to help treat their debilitating condition,” said Jane Lebkowski, Chief Scientific Officer.

Enrollment and Cohort 3 and 4 Update

Asterias has completed enrollment and dosing in four of the five planned SCiStar study cohorts and has enrolled twenty-four subjects in the SCiStar study.   Three subjects have now been enrolled in the fifth and final cohort, Cohort 5 (AIS-B 20 million-cell cohort).  The company expects to complete enrollment for Cohort 5 this year.

Asterias intends to report 6-month data from Cohort 3 (AIS-A 20 million-cell cohort) and Cohort 4 (AIS-B 10 million-cell cohort) in early 2018 after the 6-month results are collected for the two cohorts.
 

About the SCiStar Trial

The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 subjects with subacute motor complete (AIS-A or AIS-B) cervical (C-4 to C-7) SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A subjects have lost all motor and sensory function below their injury site, while AIS-B subjects have lost all motor function but may have retained some minimal sensory function below their injury site. AST-OPC1 is administered 21 to 42 days post-injury. Subjects will be followed by neurological exams and imaging procedures to assess the safety and activity of the product.
 
The study is being conducted at nine centers in the U.S. Clinical sites involved in the study include the Medical College of Wisconsin in Milwaukee, Shepherd Medical Center in Atlanta, University of Southern California (USC) jointly with Rancho Los Amigos National Rehabilitation Center in Los Angeles, Indiana University, Rush University Medical Center in Chicago, Santa Clara Valley Medical Center in San Jose jointly with Stanford University, Thomas Jefferson University Hospital in partnership with Magee Rehabilitation Hospital in Philadelphia, UC San Diego Health in San Diego, California, and Washington University School of Medicine in partnership with Barnes-Jewish Hospital in St. Louis, MO.

Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.

Additional information on the Phase 1/2a trial, including trial sites, can be found at www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com).

About AST-OPC1

AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells originally isolated in 1998, has been shown in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site.

In a previous Phase 1 clinical trial, five subjects with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. Based on the results of this study, Asterias received clearance from FDA to progress testing of AST-OPC1 to subjects with cervical spine injuries in the current SCiStar study, which represents the first targeted population for registration trials. Asterias has completed enrollment in the first four cohorts of this study. Results to date have continued to support the safety of AST-OPC1. Additionally, Asterias has recently reported results suggesting reduced cavitation and improved motor function in subjects administered AST-OPC1 in the SCiStar trial.  In September 2017, the FDA granted the company’s request for AST-OPC1 to be designated a Regenerative Medicine Advanced Therapy (RMAT) under the 21st Century Cures Act, based on a subset of the Cohort 2 data and other data from the SCiStar study, that were available as of the date of Asterias’ RMAT application.
 

About Asterias Biotherapeutics

Asterias Biotherapeutics, Inc. is a biotechnology company pioneering the field of regenerative medicine. The company's proprietary cell therapy programs are based on its pluripotent stem cell and immunotherapy platform technologies. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is undergoing continuing development by Asterias based on promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML), with current efforts focused on streamlining and modernizing the manufacturing process. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin a first-in-human (FIH) clinical trial of AST-VAC2 in non-small cell lung cancer in 2017. Additional information about Asterias can be found at www.asteriasbiotherapeutics.com.
 
FORWARD-LOOKING STATEMENTS

Statements pertaining to future financial and/or operating and/or clinical research results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias' filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.

Contacts:
Investor Relations
(510) 456-3892
InvestorRelations@asteriasbio.com
or
EVC Group, Inc.
Michael Polyviou/Greg Gin
(646) 445-4800
mpolyviou@evcgroup.com

Media
Thomas D. Gibson
GIBSON Communications, LLC
(201) 476-0322 – Main
(201) 264-3646 – Mobile
tom@tomgibsoncommunications.com

 


Exhibit 99.2
 
 Clinical-Stage Cell Therapy Programs Addressing Significant Unmet Medical Needs in Neurology and Oncology   Asterias Biotherapeutics NYSE American: ASTOctober 2017  14219863Text  04698Text  230237246Text 
 

 Statements pertaining to future financial and/or operating results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as “will,” “believes,” “plans,” “anticipates,” “expects,” “estimates”) should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias’ filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.  Forward-Looking Statements 
 

 Disclaimers on Patient Stories  AST-OPC1 is a cell-based therapy still under development and the Food and Drug Administration (“FDA”) has not evaluated or approved AST-OPC1 for commercial sale for any use. The company is in the early stages of testing AST-OPC1 in a Phase 1/2a clinical research study for patients with severe cervical spinal cord injuries. The clinical trial process is complex, expensive, and takes time. Approval by FDA of AST-OPC1 for commercial use may take years, require additional studies, and may not occur at all.While the initial results of the patients described in this presentation have been encouraging, results for patients treated with AST-OPC1 will vary by patient. Also, the long-term safety and efficacy results for patients treated with AST-OPC1, including those patients described in this presentation, are still unknown. Future studies are likely necessary to distinguish efficacy due to a patient receiving AST-OPC1 cells from any natural recovery which may occur in the patient over time following the patient’s traumatic injury.Not all patients with spinal cord injuries are eligible to participate in the current study as criteria such as type and timing of injury apply. Additional information on the existing trial, including trial sites and eligibility criteria, can be found at www.clinicaltrials.gov or at www.scistar-study.com. 
 

 A cell therapy company with lead programs in: Neurology: Spinal cord injuryImmunotherapy: Lung cancer, AMLFunding Partners:California Institute of Regenerative MedicineCancer Research UK  Background Information 
 

 Investment Highlights  14219863Text  04698Text  230237246Text    Strong Leadership TeamTechnology Platforms with Broad ApplicationSpinal Cord Injury Program Generating Exciting DataCancer Immunotherapy Programs Provide Multiple Shots-on-GoalMultiple Near-Term Data Readouts and other Events Provide Future Potential CatalystsNon-Dilutive Funding Opportunities for ProgramsNear-Term Partnering Opportunities 
 

 Strong Leadership Team with Proven Track Record  Name  Experience  Don BaileyChairman  Former CEO of Questcor Pharmaceuticals, led Questcor’s corporate turnaround  Mike MulroyPresident and CEO  Former EVP of Strategic Affairs, CFO and GC of Questcor PharmaceuticalsKey executive during Questcor’s growth and eventual salePrior investment banking experience at Citigroup and Merrill Lynch  Ryan ChavezCFO & GC  Former General Counsel for Mallinckrodt ARD divisionPart of corporate team at Questcor; held financial positions at GE  Katy Spink, Ph.D.EVP, COO  Former SVP, Cell Therapy Program Operations at GeronPrior to Geron, Dr. Spink was a management consultant at McKinsey  Ed Wirth, M.D., Ph.D.CMO  Former CSO of InVivo Therapeutics25 years experience translational research at the University of Chicago, Geron and InVivo  Jane Lebkowski, Ph.D.CSO  Former CSO of GeronOver 30 years experience in R&D of cell and gene therapies at Geron, Applied Immune Sciences, and Rhône Poulenc Rorer  14219863Text  04698Text  230237246Text 
 

 Technology Platforms  Pluripotent Stem CellsPluripotentCan derive any cell type for each indicationIP and Know-HowImmortal SourceConsistency: Can support entire product life cycle from one cell sourceScalable Manufacturing: One cell source can support entire life cycle of a product  Cancer ImmunotherapyTrains patient’s immune system to attack cancer cells by targeting cells that express telomeraseIP and Know-HowTelomerase plays critical role in cancer cells but is not expressed on non-cancer cells; implicated in >85% of cancers      OPC1Program  VAC2Program  VAC1Program 
 

 PROGRAM  PRECLIN  PHASE 1  PHASE 2  PHASE 3  Partners/Funding  AST-OPC1Spinal Cord Injury (subacute)             AST-VAC1Leukemia (AML) Autologous            AST-VAC2Lung Cancer Allogeneic                        Phase 1/2a in progress; positive early efficacy data  Positive phase 2 dataProcess development in progress  Phase 1 to be initiated in October 2017  Clinical Programs – Development Pipeline  14219863Text  04698Text  230237246Text 
 

 Spinal Cord Injury Program  14219863Text  04698Text  230237246Text 
 

 Significant unmet medical need for patients with severe spinal cord injuries (“SCI”) Asterias is conducting a Phase 1/2a study (“the SCiStar study”) in severe cervical SCIMore than 25 patients have been administered AST-OPC1; strong safety profile to dateThe therapeutic goal for AST-OPC1 is to help restore arm, hand and finger function in SCI patients thereby increasing their independence and quality of lifeAST-OPC1 is a cellular therapy utilizing oligodendrocyte progenitor cells (OPCs)OPCs are found in the human body and are precursors to oligodendrocyte cells which have multiple MOAs, including electrical insulation for nerve axons in the form of a myelin sheathAST-OPC1 administers OPCs into the body to supplement the body’s own internal supply of OPCs with a non-patient specific supply of cells AST-OPC1 is made from a well-established, pluripotent embryonic stem cell line originally isolated in the 1990sPrior efficacy updates from the SCiStar study have shown promising initial results; a key open issue for the program has been showing benefit through 12 mos.  AST-OPC1 Overview  14219863Text  04698Text  230237246Text 
 

 SCiStar Study in Cervical Spinal Cord Injury      Dosing complete    Currently enrolling  Cohort 1 – AIS-A 2 million3 subjects  Cohort 2 – AIS-A 10 million6 subjects  Cohort 3 – AIS-A 20 million6 subjects  Cohort 4 – AIS-B 10 million6 subjects  Cohort 5 – AIS-B 20 million5-6 subjects  Enrollment Progress  Recent Operational AchievementsCompleted enrollment and dosing of Cohorts 3 and 4Initiated enrollment of Cohort 5 Obtained FDA concurrence to expand the eligibility criteria to C-4 subjects and extend the dosing windowOpened three additional clinical sites for the SCiStar study, bringing the total number of participating sites to nineRMAT designation  4 cohorts enrolled to dateMore than 20 subjects enrolled to dateStudy enrollment to be completed later this year  Upcoming Data Readouts  12 mos. – Q417  6 mos. – Q11812 mos. –Q318  6 mos. – Q11812 mos. –Q318  6 mos. – 1H1812 mos. –2H18 
 

 FDA has granted the Regenerative Medicine Advanced Therapy (RMAT) designation for AST-OPC1 The RMAT designation is granted to regenerative medicine therapies for which “preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs” for a “serious or life-threatening condition”1Upon RMAT designation, sponsors are eligible for increased and earlier interactions with FDA to help facilitate an efficient development program, including discussion of which approval pathways would be appropriate and the size of clinical trialsThe RMAT designation will help Asterias facilitate the expedited review of AST-OPC1 and its developmentAsterias will use the RMAT Designation to initiate formal discussions with FDA on the next study for AST-OPC1  RMAT Designation  1 21st Century Cures Act, Section 3033; 2 FDA Submission to Congress re 21st Century Cures Act, June 6 20172 This may not be an exhaustive list of companies with therapies receiving RMAT designation  Companies with therapies receiving RMAT designation (2) 
 

 SCiStar Study Measuring Motor Function Improvement  Devastating impact on quality and duration of life with no treatment optionsIn cervical cord repair/regeneration of axons only required over a short distance to reinnervate motor neurons for arms & hands    UEMS Upper Extremity Motor Score: Sum of All Motor Function Measured at all Levels of the Upper Extremities C5-T1; 50 Points Maximum for Both Sides (25 per Side)    Motor Level: Level at Which All Motor Function Above it is Normal  Two Methods to Measure Improvement in Motor Function using an internationally recognized exam   Rationale 
 

 Potential to Have Clinically Meaningful Benefit    Capability            C1-C3  C4  C5  C6  C7-C8  Bowel            Bladder            Bed Mobility            Transfers            Pressure Relief            Eating            Dressing            Grooming            Bathing            Wheelchair            Car Transport            Daily Home Care  24 hr Attendant  18-24 hr Attendant  6-12 hr Assistance  4 hr Housework  1 hr Housework  Total Assist  Partial Assist  Independent    Steeves et al., Top Spinal Cord Inj Rehabil 2012; 18(1): 1-14   14219863Text  04698Text  230237246Text  Significant lifetime direct healthcare costs; can reach $5 millionVery high unemployment rate; 63% of cervical injury patients are unemployed 8 years post-injuryMotor level improvements translate into clinically significant improvements in ability to self-care and significant reductions in cost of careRecovery of two motor levels can save significant healthcare costs associated with paid attendant care   
 

 Our target since commencement of the SCiStar study is that at 12 months 45-50% of study subjects will recover at least 2 motor levels on at least one sideMatched historical control group showed at 12 months 29% of patients spontaneously recovered 2 or more motor levels on at least one side of the body Published article showed at 12 months 26% of patients spontaneously recovered 2 or more motor levels on at least one side of the bodyAt 9 months, 50% of Cohort 2 subjects had recovered 2 or more motor levels on at least one side of the body  12 Month Target for SCiStar Study 
 

 Cohort 2 12 Month Summary Results  Observation at 12 months  Cohort 2  Matched Controls  2 or more motor levels on at least one side  67%(4/6)  29%(18/62)  At least 1 motor level on both sides  100%(6/6)  50%(31/62)  3 or more motor levels on at least one side  18%(1/6)  8%(5/62)  Mean Increase in UEMS  12.3 pts  7.8 pts 
 

   Cohort 2 Two Motor Level Recovery at 12 Months   Cohort 2 (AIS-A 10 million cells) motor level recovery vs. comparators      Cohort 2 – 10 million (n=6)  Matched historical control      Steeves, 2012    26%  29%  67%  50%  33%  18%      Initial 12 mo. Target  45% - 50%  *  *One subject does not have 9 month follow-up data 
 

   Cohort 2 UEMS Improvement at 12 Months  *One subject does not have 9 month follow-up data  Matched historical control  Cohort 2 – 10 million (n=6)  Error bars at 1 Standard Error    *  12.3 points  7.8 points  Cohort 2 (AIS-A 10 million cells) mean UEMS improvement vs. matched historical control 
 

 12 Month MRI Results Continue to Support Durable Engraftment of AST-OPC1 Cells  Cavitation is estimated to occur in ~80% of spinal cord injury patients meeting SCiStar study inclusion criteria100% (6/6) of Cohort 2 subjects had serial MRI scans at 12 months that indicated no sign of lesion cavities in any subjectThe MRI results are consistent with formation of a tissue matrix at injury site, which is supportive evidence showing that AST-OPC1 cells have durably engrafted to help prevent cavitation at the injury site(1)  (1) Wirth et al, Exp Neurology 1995  Cohort 2 subject365 Day T2 –weighted sagittal MRI    Green arrow shows the AST-OPC1 injection site in the sagittal planeSlightly bright signal is consistent with the presence of an AST-OPC1 graftThis result is consistent with results observed in all six Cohort 2 subjects 
 

 Personal Stories  Lucas threw the first pitch at a MLB game on August 13thLucas can now write with a pen, type e-mails at 40 words per minute, use his phone, and feed himself.  Kris can now use his hands and fingers to feed himself, drink, text, send e-mails, sign his name and even play video games. 
 

 Summary and Next Steps  Cohorts 1 and 2 data support:A strong safety profile for AST-OPC1 Encouraging evidence of efficacy amongst the most severely impaired SCI patientsEvidence of dose dependence of efficacyProlonged effects sustained at least a year after administration  SCiStar study data and RMAT designation will be used to:Design a randomized, controlled trialSelect dose, key endpoints, and inclusion criteria Evaluate expansion into less severely impaired SCI patients where recovery of lower extremity function may be possible 
 

 What’s Next for AST-OPC1  14219863Text  04698Text  230237246Text  1H’18  2H’18  Cohort 3 - 6 month data updateCohort 4 - 6 month data updateSCiStar study 6 month update, including Cohort 5  Cohort 3 - 12 month updateCohort 4 - 12 month updateSCiStar study 12 month update, including Cohort 5  Data Updates  Other 2018 Potential Catalysts  Regulatory clearance for randomized controlled trial for AST-OPC1Non-dilutive funding to partially offset costs for next trialJapanese partnership 
 

 Cancer Immunotherapy  14219863Text  04698Text  230237246Text 
 

 AST-VAC is a Cell Immuno-Oncology Platform with the Ability to Universally Attack Cancer Cells  Telomerase antigenUniversal cancer antigen, conferring proliferative abilityNormal adult cells do not express telomerase, ensuring safety  Dendritic cell immunotherapyStimulates diverse immune responses to extend remission  LAMP proteinLAMP enhances antigen presentation by dendritic cells to increase immune responseLicensed from Immunomic Therapeutics  Two programs:AST-VAC1 (autologous)AST-VAC2 (allogeneic) 
 

 VAC Platform Likely Synergistic with Other Promising Immunotherapies    Immune Checkpoint InhibitorsAntibodies/BiologicsEnhance Immunogenicity and Immune-mediated Attack on TumorsMany Received Accelerated Approval for Specific Second Line IndicationsEfficacious only in a small subset of tumors    Car-T CellsHighly Engineered T Cells to Target and Kill Tumor Cells with Specific TargetsEffective – targeting inductionRelapses common (antigen escape)Toxicities – not a good option for maintenance    VAC1 and VAC2Stimulate T cell Responses to Tumor by engineering mature dendritic cellsPOC data in AML supporting technologyLow level of toxicities – potential positioning as maintenance therapy after patients enter remission with Car-T or other approachPotential to expand efficacy of ICIs by stimulating new T cell responses    Tumor Cell            Synergy    Induction/Remission 
 

 AST-VAC Platform is Designed to Overcome Limitations of First Generation Dendritic Cell Therapies  Design characteristic  Provenge  VAC1  VAC2  Scientific rationale  APC-based product  X  X  X  Increase T-cell stimulationMinimize toxicity  Mature dendritic cells    X  X  Maximize T-cell stimulation  mRNA loading by transfection    X  X  Broadened antigen presentation  Telomerase antigen    X  X  Plays critical role in tumor immortality, making antigen escape challengingDemonstrated ability to overcome tolerance  LAMP sequence transfected    X  X  Enhances Stimulation of CD4+ cells and Diversifies the Type of T cell immune responses targeting tumor  Intradermal delivery    X  X  Access lymph nodesOne of the most immunogenic sites  Cryopreserved product    X  X  Preserves product integrityAvailable “on Demand”Straightforward supply chain logistics  Manufacturing scalability      X  Product consistencyLower Cost  Provenge is an approved therapy, with up to $300M in annual sales and sold for over $800M, but AST-VAC programs have improved design characteristics: 
 

 AST-VAC1 Has Shown Clinical Success in Early Stage Trials and Provides Proof of Concept for AST-VAC2 Program  57%  10-20%  >60 years oldN = 7  20-40%  58%  All patientsN = 19  Relapse Free Survival at 52 Months(% of patients)      Historical(2)  AST-VAC1(1)  VAC1 Phase 2 results published: Cancer (2017) 123:3061.Mayer NEJM 1994; Rollig, J Clin Onc 2011ITP is commonly observed in AML patients and may not be linked to treatment with AST-VAC1 or any other therapies.  Program HighlightsPhase 2 Multicenter, open-label trialTreated 19 patients with AML in complete remission (CR)Intermediate and high risk patients, evaluated by cytogeneticsN=7 in very high risk >60 year age groupRobust safety in 40 patients treatedClear anti-telomerase immune responseProcess Development Underway to Improve TATPotential Partnering Opportunity 
 

 AST-VAC2 Builds on AST-VAC1 POC With An Allogeneic Dendritic Cell Product  Product to be supplied from a single master cell bank, allowing scalability/consistencyThousands of patient treatments can be manufactured in a single batch  14219863Text  04698Text  230237246Text                                  Culture  ElectroporateRNA  Culture  Leukapheresis  Cryopreserve  Thaw  Injections                                  Thaw  Inject  VAC1 Process:  VAC2 Process:                                                 
 

   Cancer Research UK Partnership to Execute AST-VAC2 Clinical Trial in NSCLC  Asterias Performed Scale-up and Transfer of AST-VAC2 Manufacturing ProcessCRUK Will:Execute cGMP Manufacture of AST-VAC2 for Clinical TrialPrepare and File of Regulatory DossierExecute 24 patient Phase 1 trial in Patients with Advanced and Resected Non-small Cell Lung Cancer (NSCLC)    Advantages of CRUK PartnershipExternal validationAdvancement of AST-VAC2 Program at minimal cost to Asterias shareholdersEstimated saving of >$20M+Combine CRUK expertise in oncology drug development with Asterias expertise in cell therapyAccess to network of CRUK investigatorsStatusReceived regulatory approval to initiate trialDP manufactured for useEnrollment underway 
 

 AST-VAC2: First Clinical Trial Underway      Patient PopulationPatients with NSCLC  Treatment ARMHLA-A2+ Patients with Advanced Disease12 PatientsDose 1x107 AST-VAC26 Doses id.  HLA A2 Typing        2 Year Follow-up for Responses/ Relapse  Control ARMHLA-A2- Patients with Advanced Disease12 Patients No Vaccine  Treatment ARMHLA-A2+ Patients with Resected Disease12 PatientsDose 1x107 AST-VAC26 Doses id.  Control ARMHLA-A2- Patients with Resected Disease12 PatientsNo Vaccine    ARM A  ARM B  ARM C  ARM D  SafetyReview  LTFU    Establish safety of AST-VAC2 in resected and advanced cancerAssess the generation of anti-hTERT and anti-VAC2 Immune Responses Periodically Over 1 Year Investigate Initial Measures of Clinical Activity as Progression Over 2 Years    TrialObjectives  Study will provide POC data for AST-VAC2 to Enable Broad Development 
 

 POC Data from Phase 1 Study of AST-VAC2 in NSCLC Enables Broad Development of hESC-DC Platform  Demonstration of safety and immune responses in NSCLC study  Demonstration of safety and immune responses in NSCLC study  Phase 2b/pivotal trials in NSCLC  Expansion of AST-VAC2 into additional cancer indications  Investigation of combination with checkpoint / other immune pathway inhibition  Amenability of platform to other neo-antigens  Enables:  Rationale:  Safety data generated in adjuvant and advanced settings  Telomerase expressed in >85% of all cancersPlays a critical role in cancer cell survival and proliferation  Multiple preclinical studies suggest combining checkpoint inhibitors with immune activators will improve clinical responses  DC platform can be used to present any antigen / multiple antigens 
 

 Next Steps  14219863Text  04698Text  230237246Text        Program  Next Steps      VAC1  Identify alternatives to move forward with phase 2/3 study in AML      VAC2  2017Sites openedFPI dosed in NSCLC trialFirst safety data generated  2018Further data on safety and immune response Use data to evaluate best approach to broaden platform  2019Data on clinical activity in NSCLCSecond trial/added trial arm as monotherapy or in combination with other therapy 
 

 Company Milestones  14219863Text  04698Text  230237246Text  6 month data Cohort 29 month data Cohort 2  Complete enrollment in Cohort 3Complete enrollment Cohort 412 month data Cohort 2Complete trial enrollment  6 month data Cohort 36 month data Cohort 46 month data Cohort 5  12 month data Cohort 312 month data Cohort 412 month data Cohort 5Topline efficacy data, all cohorts  OPC1  VAC  MHRA clearance for VAC2 trialFPI in VAC2 trial  VAC2 interim data  VAC2 interim data 
 

 Appendix  14219863Text  04698Text  230237246Text 
 

       AST-OPC1 Potential Mechanisms of Action  Secretes neurotrophic factors  Promote increased neurite outgrowth  Myelination of axons  Rag2-/- γc-/- /shi mouse + AST-OPC1    Control Media  AST-OPC1 CM    shiverer mouse  shi mouse + AST-OPC1    TubIII  Prevents Cavitation  Control  AST-OPC1   
 

 AST-OPC1 Reduces SCI Cavity Formation and Induces Persistent Myelination  Brown: antibody to human nuclear antigen labels AST-OPC1; Blue: Eriochrome Cyanine stains myelin  9 months post-transplant with AST-OPC1        hNucEC  1 mm  100 µm  50 µm    AST-OPC1 in SCI Lesion; Significantly Reduced Cavity Formation  Robust AST-OPC1 survival (brown)  Myelinated Fibers (blue)  Rat Thoracic Spinal Cord Injury Model  9 months vehicle        hNucEC  1 mm  100 µm  50 µm  Cavity forms in untreated SCI lesion  Myelinated axons do not extend across cavity 
 

 Models of Spinal Cord Injury Used to Evaluate Safety/Activity of AST-OPC1  MidlineContusion Injury at T10   Unilateral ContusionInjury at C5/C6  Thoracic Injury   Cervical Injury     Transplant AST-OPC1 7 days post- injury at injury site  EvaluateEfficacy & ActivityHistological EffectsCell SurvivalCell PhenotypeCell MigrationToxicity       T10  C5   
 

    Activity/ Efficacy Biodistribution Dosing/Delivery Toxicity Tumorigenicity Ectopic Tissue Immune Rejection    Survives in the Spinal CordPredominantly Neural Cell TypesGreatest Activity in Subacute InjuryImproves Locomotor ActivityReduces Parenchymal CavitationActive Doses EstablishedMigrates Up 5cm in Spinal CordNo Distribution Outside CNSDoes Not Increase MortalityDoes Not Induce AllodyniaDoes Not Induce Systemic ToxicityDoes Not Produce TeratomasProduces Low Frequency (1-2%) Small Ectopic Tissue at Injury Site Not Highly Susceptible to Direct Immune Responses  28 Animal Studies >3000 Rodents and Pigs    Safety/Efficacy Profile of AST-OPC1 in Nonclinical Studies  
 

 Cohort 2 subject-by-subject data  All Cohort 2 subjects have seen motor level and UEMS improvement (on both sides)In matched historical controls, 26% of patients saw no motor level improvement or got worse after SCI 
 

 AST-VAC Cancer Immunotherapy Technology  Dendritic Cells (DCs) are professional antigen presenting cells. They present antigens to T cells and activate them.AST-VAC2 starts with a stem cell-derived mature DC.The DCs are transfected with an mRNA encoding the tumor antigen hTERT fused to LAMP.The resulting protein is processed by the DCs and displayed on their surface by MHC proteins.                                                                                                                                                                              hTERT  LAMP                                                                                                                                            MHC Class II + PeptideLysosomeMHC Class I + PeptideEndoplasmic ReticulumhTERT-LAMP ProteinhTERT-LAMP mRNAhTERT-LAMP DNA     
 

 LAMP is a key component of our technology  Normally, cytoplasmic antigens (like our transfected hTert) are processed through the Endoplasmic Reticulum and presented on MHC Class I receptorsLAMP (Lysosome-Associated Membrane Protein) transports a portion of the hTert antigen to the MIIC complex where it is processed, combined with MHC Class II receptors, and displayed on the cell surface.This allows VAC2 to target not only CD8 T cells (stimulated through MHC Class I) but also CD4 T cells (which are stimulated through MHCI Class I)                                                                                                                                                                                MIIC  EndoplasmicReticulum  Trans-Golgi  MHCII + Peptide  LAMP   
 

 Prostate Cancer Trial Demonstrated Utility of LAMP Signal Sequence for Improving Antigen Presentation  Su et al, J Immunol 2005  20 Patients Treated  11 hTERT only  9 LAMP-hTERT  Patients treated with LAMP hTERT showed:Similar numbers of hTERT specific CD8+ (cytotoxic) T cells (p = 0.87)Significantly increased hTERT specific CD4+ (helper) T cells (p = 0.004)Increased cytolytic activity against hTERT-positive cell linesIncreased expression of markers of central memory T-cell function (CD62L, CCR7, IL-2)  15-hTERT  18- LAMP-hTERT 
 

 Activation of Helper and Cytotoxic T Cells Amplifies Attack on Tumor Cells   hTERT Specific CD8 and CD4+ Cells Can Directly Kill Tumor CellshTERT Specific CD4+ Cells Provide Cytokines that Can Accentuate and Lengthen the Duration of Activity of CD4+Cells. CD4+ Positive Cells Can Potentiate the Formation of Long-Lived “Memory” T Cells which Can Lead to Long-Term Protective Immunity.  AST-VAC1 and AST-VAC2  MHC Class II  MHC Class I  Dendritic Cell  hTERT-LAMP mRNA  This Branch Enabled by LAMP Fusion                    Memory T cells     
 

 AST-VAC2 Stimulates Antigen-specific T cells With a Single HLA Match  Interferon gamma detected through ELISpot assay shows strong T cell response(1)  Single HLA match (A*0201)    Nishimoto et al, Regen Med. 2011                                                                                                                                                                                                      VAC2T CellsTumor Cellor Peptides                IFNg   
 

   AST-VAC Technology Could be Used in Combination with Immune Checkpoint Inhibitors  Checkpoint inhibitors make tumors more susceptible to immune function, potentially boosting the impact of dendritic cell immunotherapy by reducing cancer cell resistanceRecent preclinical studies have shown that PD-1 blockade in combination with DC therapy in treating glioblastoma results in increased survival rates than with either treatment alone(1)Proof of concept for the DC therapy combination approach has been demonstrated in humans for treating myeloma(2)    PD-1 blockade rescues the survival benefit after DC vaccination in mice with established tumor burden  Antonios et al. JCI Insight 2016Rosenblatt et al. ASH 2015 Poster