Slide 1: Interim Analysis Results RESTORE-CLI
Interim Analysis Results RESTORE-CLI November 18, 2010 Richard J. Powell MD, on behalf of the RESTORE-CLI Investigators "This presentation includes the individual comments and opinions of Richard Powell MD, chief of vascular surgery at Dartmouth-Hitchcock Medical Center in Lebanon, NH. None of Dr. P
Slide 2: Outline
Outline Overview: Aastrom's Expanded Autologous Cellular Therapy Description: Critical Limb Ischemia Brief Overview: Study Design & Efficacy/Safety Data of Interest 2nd Interim Analysis Population Description: Patients enrolled, randomized, and treated in time for 6 month follow-up 2nd Interim Analy
Slide 3: Aastrom's Approach
™@® Aastrom’s Approach ‘Asmall quantity (approx. 50m) Over a period of about 12 days. Ina single inpatient procedure, ‘of bone marrow is taken from Aastrom’s proprietary system the expanded mixed-cel therapy the patient’s hip in a 15-minute expands the naturaly occuring produced from this process is
Slide 4: Aastrom's Therapy
Aastrom's Therapy Bone Marrow Expanded Autologous Cells Leveraging the body's regenerative systems and pathways Removes damaged tissue Reduces Inflammation Grows new blood vessels (Angiogenesis)
Slide 5: Aastrom's Technology
Monocytes Mesenchymal Stem cells Macrophages Aastrom's Technology Relative Size Density Relative Size Endothelial Precursors Starting Bone Marrow Density Aastrom's technology dramatically expands the tissue regenerative cell populations Aastrom's Technology Monocytes Granulocytes Lymphocytes
Slide 6: Key Cellular Components
M@® Key Cellular Components: MONOCYTES / MACROPHAGES: cota Removes Damaged Tissue Remodels Matrix ENDOTHELIAL p31 Proliferation Growth Factors Cytokines | Grow New Vessels-Angiogonesis Increases Blood Flow Helps Stabilize Tissues aastron™
Slide 7: Critical Limb Ischemia (CLI) Limited Therapeutic Options
Critical Limb Ischemia (CLI) Limited Therapeutic Options No CLI therapy approved for no- option patients Amputation - only option Within one year of diagnosis... 25% will require amputation 25% will die4 Post-amputation mortality at 4 years as high as 76%3 Our Focus: 400,000 "No-Option" Patients4 CL
Slide 8: Brief Overview: Study Design
Brief Overview: Study Design Original Protocol: Up to 150 patients in a prospective, controlled, randomized, double-blind study Based on positive 1st interim (February 2010), stopped enrollment at 86 randomized patients 72 Patients enrolled, randomized, and eligible for treatment were analyzed Enrol
Slide 9: 2nd Interim, November '10: Efficacy and Safety Data Evaluated
2nd Interim, November'10: Efficacy and Safety Data Evaluated Patients: All enrolled, randomized, treated and completing 6-month follow-up Evaluations: Time to first occurrence of treatment failure (TTF) Major amputation of treated leg All-cause mortality Doubling of wound size from baseline De novo
Slide 10: Results Interim Analysis November 2010
Results Interim Analysis November 2010 6-month evaluation
Slide 11: Patient Demographics - ITT population
11 Patient Demographics - ITT population Parameter TRC N = 48 Control N = 24 % Male 71 58 Age (mean, range) 69 (34-90) 67 (40-85) % Current, % Past smokers 17, 67 38, 46 % Current, % Past alcohol 44, 23 29, 33 BMI (mean, range) 26.9 (14-38) 28.1 (18-40) Creatinine mg/dL (mean, range) 1.2 (0.5-2.8) 1
Slide 12: Disposition of Treated Patients at Interim
Disposition of Treated Patients at 6 month Interim * All 3 patients had a major amputation TRC N = 48 Control N =24 Completed 34 (71) 18 (75) Died 3 (6) 1 (4) Withdrew 6 (13) 0 (0) -w/endpoint* 3 (6) 0 (0) -w/o endpoint 3 (6) 0 (0) Continuing 5 (10) 5 (21)
Slide 13: Time to First Occurrence of Treatment Failure: ITT Population, 2nd Interim
Time to First Occurrence of Treatment Failure: ITT Population, 2nd Interim 56% risk reduction: HR 0.44 (0.22-0.86)
Slide 14: Aastrom's Therapy Prolongs Time to the First CLI Event
Aastrom's Therapy Prolongs Time to the First CLI Event
Slide 15: Time to Treatment Failure: Comparison of Interim Analyses
Time to Treatment Failure: Comparison of Interim Analyses Similar shape, p value as 2nd IA Interim 2 Interim 1
Slide 16: Time to Treatment Failure: Comparison of Interim Analyses
Time to Treatment Failure: Comparison of Interim Analyses Similar treatment event rate for both interim analyses Control event rate differs slightly
Slide 17: Treatment Failure: Rates for 1st and 2nd Interim Analyses
Treatment Failure: Rates for 1st and 2nd Interim Analyses Similar Treatment Event Rate for Both Interim Analyses Control Event Rate Differs Slightly
Slide 18: Composite Event Rates - 1st & 2nd Interims
Composite Event Rates - 1st & 2nd Interims TRC TRC TRC Control Control Control N (%) with Event 1st Interim * N = 32 2nd Interim N = 16 Total N = 48 1st Interim * N = 14 2nd Interim N = 10 Total N = 24 Amputation 8 (25) 2 (13) 10 (21) 6 (43) 0 (0) 6 (25) De novo Gangrene 5 (16) 1 (6) 6 (13) 2 (14) 3
Slide 19: Amputation-Free Survival: ITT population, 2nd Interim
19 Amputation-Free Survival: ITT population, 2nd Interim 24% risk reduction: HR 0.76 (0.30-1.92)
Slide 20: Amputation Free Survival: Comparison of Interim Analyses 1 and 2
20 Amputation Free Survival: Comparison of Interim Analyses 1 and 2 Dissimilar shape, p value IA 1 vs IA 2 Interim 2 Interim 1
Slide 21: Amputation Free Survival: Comparison of Interim Analyses
Amputation Free Survival: Comparison of Interim Analyses Similar Treatment Event Rate for Both Interim Analyses Control Event Rate Markedly Different
Slide 22: Amputation Free Survival - Rates for 1st and 2nd Interim Analyses
Amputation Free Survival - Rates for 1st and 2nd Interim Analyses Similar Treatment Event Rate for Both Interim Analyses Control Event Rate Differs Markedly
Slide 23: Typical Event Rates in No-Option CLI Trials
Typical Event Rates in No-Option CLI Trials: Author N AFS Event Rate Time Period Horie et al. (2010) G-CSF mobilized PBMNC 140 43% 1 year Nikol et al. (2008) Talisman 201 Placebo 56 51.8% 1 year Brass et al. (2006) Circulase Placebo 177 17.5% 6 months Onodera et al. (2010) BM-MNC or M-PBMNC 185 27-3
Slide 24: Differences in Baseline Characteristics: 1st and 2nd IA
Differences in Baseline Characteristics: IA 1 and IA 2 TRC TRC Control Control Parameter 1st Interim N (%) 2nd Interim N (%) 1st Interim N (%) 2nd Interim N (%) Treated Patients 32 16 14 10 Male 25 (78) 9 (56) 8 (57) 6 (60) Female 7 (22) 7 (44) 6 (43) 4 (40) Baseline Physical Examination Previous Am
Slide 25: Safety Evaluation
™@® Safety Evaluation: aastron™
Slide 26: Safety Overview: All Aspirated Patients
26 Safety Overview: All Aspirated Patients Safety Parameter TRC N = 53 Control N = 24 N (%) with Adverse Events 46 (87) 22 (92) N (%) Serious Adverse Event 23 (43) 12 (50) N (%) withdrawal due to AE 1 (2) 0 (0) N (%) Deaths * 3 (6) 1 (4) * An additional TRC treated patient died after the study compl
Slide 27: Safety Overview: AEs in >10% of Patients
27 Safety Overview: All Aspirated Patients; AEs in > 10% of Patients Preferred Term N (%) TRC N = 53 Control N = 24 Pain in extremity 17 (32) 4 (17) Gangrene 6 (11) 6 (25) Cellulitis 5 (9) 6 (25) Skin Ulcer 7 (13) 4 (17) Localized infection 5 (9) 3 (13) Nausea 5 (9) 3 (13)
Slide 28: Summary: RESTORE-CLI 6-Month Interim Analysis
Summary: RESTORE-CLI 6-Month Interim Analysis Continued evidence of an excellent safety profile Time to treatment failure continues to be statistically significant (p = 0.0132) > All events of this composite (amputation, death, doubling in wound size and de novo gangrene) are delayed in comparison t
Slide 29: Impact on Phase 3 Plans
Impact on Phase 3 Plans Improved Phase 3 sample size understanding Phase 3 Interim Analysis planned to reassess sample size estimates Improved understanding of key design issues Continuing the work to support the Phase 3 program launch in the 1st half of 2011
Slide 30: Next Steps
Next Steps: Awaiting FDA Feedback from SPA (submitted 10/18/2010) Finalize the protocols based on their response Ensure FDA agreement with production of Aastrom's expanded autologous cell therapy (CMC amendment) Launch Phase 3 studies
Slide 31: Acknowledgements
"Aastrom would like to thank all of the patients, clinical coordinators, and investigators for contributing to and participating in the Aastrom Phase 2b, RESTORE-CLI trial."