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8-K - ASTERIAS BIOTHERAPEUTICS, INC 8-K 6-3-2015 - Asterias Biotherapeutics, Inc. | form8k.htm |
EX-99.1 - EXHIBIT 99.1 - Asterias Biotherapeutics, Inc. | ex99_1.htm |
Exhibit 99.2
ASCO May 30, 2015 1 Long-term Follow-up of Patients with Acute Myelogenous Leukemia Receiving an Autologous Telomerase-based Dendritic Cell VaccineH. Jean Khoury, MD, FACP, Robert H. Collins Jr., MD, William Blum, MD, Patrick Stiff, MD, Jane S Lebkowski, PhD, Edward Wirth III, MD PhD, Kevin Nishimoto PhD and John F. DiPersio, MD, PhD
AST-VAC1: Autologous Dendritic Cells Pulsed with hTERT mRNA 2 Dendritic Cells: Potent Antigen Presenting Cells Telomerase: “Universal” Tumor Antigen Objective: Stimulate Anti-Tumor Immune Responses in Patients with AML AST-VAC1 is an immunotherapeutic product that comprises mature DC transfected with mRNA encoding hTERT and the lysosomal targeting signal, LAMP (4,5) - enhances immunostimulatory capacity
AST-VAC1 Production 3 Leukapheresis Harvest Immature Dendritic Cells Differentiation LAMP hTERT mRNA ImmatureDendritic Cells DC Maturation MatureDendritic Cells Monocyte Enriched PBMCs CryopreservedAutologous DC Vaccine Product Release Based on: Demonstration of positive hTERT transfection Mature Dendritic Cells by immunophenotype Product Sterility1x107 viable cells/dose post-thaw
18 years or older AML with intermediate or high risk cytogenetics in CR1 within 6 months from induction chemotherapy and may or may not have received consolidation including autologous stem cell transplantationAML in CR2 with a CR1 of > 6 months durationExclusion: AML with t(15;17), t(8;-21), inv(16), or t(16:16)], leptomeningeal disease, candidates for allogeneic stem cell transplant within 6 months of screening, documented allergy to penicillin or beta-lactam antibiotics, active or ongoing autoimmune disorder, active second malignancy or history of another malignancy within the last 2 years Leukapheresis Primary Vaccination Rest Boost Vaccination 6-weeks 4-weeks 12-weeks Consolidation BM biopsy BM biopsy BM biopsy AML in CR Product Manufacture Extended Boost monthly until depletion of vaccine or relapse Long-term Follow-up DiPersio et al, ASH 2009 4 AML Clinical Trial Design and Study Schema: Patient Enrollment 2007-2010 8 weeks median Multicenter, open-label study.Primary Objectives:Feasibility of manufactureSafety and tolerability of vaccineSecondary objectives: hTERT immunologic responseRelapse-free survival Eligibility Criteria
Patient Demographics and Disease Status 5 Total Patients: N=33 Age (years) Median 61.2 Mean (SD) 58.3 (11.79) Min, Max 30.5, 75.4 Sex Male 17 (51.5%) Female 16 (48.5%) Race American Indian or Alaska Native 0 Asian 0 Black or African American 5 (15.2%) Native Hawaiian or Other Pacific Islander 0 White 28 (84.8%) Duration from AML Diagnosis to Leukapheresis (months) Median 7.1 Mean (SD) 8.9 (7.23) Min, Max 2.5, 39.3 In First CR at Screening? Yes 29 (87.9%) No 4 (12.1%) Median Follow-up 52 (13-59) mos.
AST-VAC1: Manufacturing Review and Disposition to Patients 6 24 Patients Had Successful AST-VAC1 Production Campaigns 24 Patients Reassessed for Eligibility 3 Patients Florid Relapse Prior to Vaccination 2 Patients in Early Relapse at Time of Vaccination 21 Patients Received at Least 3 Vaccinations Median Time to Product Release 8 weeksProduction of AST-VAC1 success in 24 or 33 (73%) AML patients2 Required a Second Manufacturing CampaignMost common production failures.Low leukapheresis cell numbersPoor DC maturationNo telomerase expression5 of 23 (22%) patients relapsed before vaccination of product. 33 Patients Enrolled in Phase 2 Clinical Trial 19 Patients in CR Vaccinated Mean # Doses Delivered 17.2 (9.7)# Patients Receiving All 12 Intended Doses: 13 (14th pt withdrew consent before last dose) AST-VAC1 Successfully Produced for 73% of Patients
AST-VAC1 in AML: Excellent Safety Profile 7 21 Total Patients Received AST-VAC116 CR1 3 CR2 2 Early Relapse Safety and TolerabilityDuring Leukapheresis:No Grade 3-4 Adverse EventsDuring Vaccination Period:Serious Adverse Events Grade 3-4 (2)Possibly Related: Idiopathic thrombocytopenic purpura (1 day 73)Unrelated: Appendicitis with perforation/obstruction, hypokalemia (1)Grade 3-4 Adverse Events: 4 patientsUnrelated: (4)Cytopenias associated with impending relapse (2)Hypertension (1)Grade 1-2 Adverse Events: 14 patientsHeadache (5)Fatigue (3)Rash (3)Sinus Congestion (3)URI (3)Diarrhea (2)Erythema (2)Hemorrhoids (2) Database Through 2010 All “Possibly Related” Adverse Events Occurred within One Year Post-Vaccination: Majority within 100 days
AST-VAC1 in AML: DTH and hTERT Specific T Cell Responses 8 19 Total Patients in CR At Time of AST-VAC1 Administration16 CR1 3 CR2 11 of the 19 AML patients in CR developed cell immune responses to telomerase DTH responses hTERT specificT cell responses 11 of the 19 AML patients in CR developed DTH responses g-IFN Elispot used with 90 hTERT overlapping peptides spanning the entire hTERT protein** In one case , hTERT mRNA transfected autologous dendritic cells were used to detect hTERT specific T cell responses. Patients self-recorded the presence and size of induration at the vaccination site. A patient was considered a DTH responder if induration of at least 5 mm (0.2 inches) in diameter at the injection site was recorded 24 to 72 hours after the third or subsequent vaccinations.
AST-VAC1 in AML: Kinetics of Development of Detectable hTERT Specific T Cell Responses 9 ID Age Status at Start of Vaccination Detection of Positive hTERT Specific T cell Responses Timepoints Post Vaccination Any Timepoint Primary Vaccinations Rest Boost Vaccinations 1641 33 CR1 + + - + 2141 37 CR1 + - - + 2411 41 CR1 - - - - 1541*# 43 CR1 + - + - 2021 48 CR1 - - - - 1911* 50 CR1 - - - - 3432 52 CR2 + + - - 2741 54 CR1 - - - - 3051 54 CR1 + + - + 1711 54 CR2 - - - - 0221* 55 CR1 - - - - 2221 57 CR1 - - - - 3531 61 CR1 + - - + 0321 61 CR1 - - - - 3951* 63 CR1 + - + + 2531 65 CR1 + + + + 2831 66 CR1 + + - + 0421 72 CR2 + + - - 1012* 75 CR1 + + - - *: terminated during vaccination stage #DC based ELISpot Used. hTERT Specific T Cells Responses Were First Detected in the Primary Vaccination, Rest, or Boost Phases
Long-term Relapse Status: Greater Than 50% Of Patients Relapse-free (median 52 +/- 17 months) 10 Long-term Follow-up (2013-2014) % Patients Relapse-free*** Median (Range) Follow-up(mos) Relapse-free Patients with hTERT specific T cell responses All Patients in CR 11/19*(58%) 52 (13-59) 7/11(64%) Patients in CR2 3/3**(100%) 50 (24-59) 2/3(67%) Patients >60 years old 4#/7(57%) 54 (52-59) 4/4(100%) *five patients lost to long-term follow-up or date of relapse unavailable**One patient lost to long-term follow-up at 24 months# One patient Received nilotinib during vaccination period for a secondary Philadelphia chromosome positive abnormality observed in first relapse which was not observed in the vaccination period Favorable Outcome Compared to Historical Data Especially in Patients Over 60 years old where 5 year relapse-free survival <10% 0 20 40 60 80 0 50 100 Relapse-free Survival Time to Relapse (Months) P e r c e n t R e l a p s e d All Patients in CR All Patients > 60yo
Relapse Free-Survival and hTERT-Immune Response 11 Relapse Post-Hoc Analysis Shows Potential Trend that hTERT-specific T Cell Responses Associated with Longer Relapse-free SurvivalRequires Confirmation in Additional Trials
Summary 12 AST-VAC1 Produced for 73% of Patients Enrolled in TrialMean 17.2 Doses AST-VAC1 Delivered per Patient11/19 developed hTERT Specific T cell Responses58% Relapse-free median 52 mos follow-up.4/7 patients >60 years old relapse–free median 54 mos follow-upFavorable Survival Compared to Historical AnalysesOutcome Requires Confirmation in Additional Clinical Trials
Acknowledgements 13 Clinical Investigators and Staff: • Emory University: Martha Arellano, Edumund Waller, Mersiha Torlak, Susan Sunay, Ellie Hamilton • Washington University: Camille Abboud, Elizabeth Procknow, Jeremy Gabriel, Mary Kay Belota • Ohio State University: Anders Lindquist, Lynn O’Donnell • UT Southwestern Medical Center at Dallas: Madhuri Vusirikala, Simrit Parmar, Tracee Rainey, Candice Penn, Carter Blood Center • Loyola University Medical Center: Sandra Zakrzewski, Mala Parthasarathy Vaccine Product Manufacture: Lonza Inc: Eric Neidinger, David Smith and Philip Vanek Project Team: • David Rhodes, Neeru Batra, Glenn Dawes, Deena Gruver, Sean Cullen, Jerrod Denham, Heidi Christ-Schmidt“The Patients and their Families”