Vericel Corporation · NASDAQ:VCEL
Vericel — Aastrom Biosciences — American Heart Association Scientific Sessions 2011
24 slides from Vericel's conference presentation, Nov 14, 2011
Slide 1: Ixmyelocel-T Safe and Improves Time to Treatment Failure in Critical Limb Ischemia
Patient-Specific Cellular Therapy (Ixmyelocel-T) is Safe and Improves Time to Treatment Failure in Patients with Critical Limb Ischemia and No Revascularization Options American Heart Assoc Scientific Sessions 2011 William Marston MD For the RESTORE-CLI Clinical Investigators Orlando, FL November 14
Slide 2: RESTORE-CLI Investigators
RESTORE-CLI Investigators Scott Berceli W Todd Bohannon Anthony Comerota Carlo Dall’Olmo Raul Guzman Brian Halloran Peter Henke Timothy Henry Colleen Johnson William Marston Jeff Martinez Farrell Mendelsohn Richard Powell Jorge Saucedo Patrick Stiff Edith Tzeng Omaida Velazquez
Slide 3: Disclosures
Disclosures William Marston, MD TITLE: Chief, Division of Vascular Surgery Professor, Department of Surgery University of North Carolina FINANCIAL DISCLOSURE: Aastrom (Consultant/Advisory Board)
Slide 4: Ixmyelocel-T: Description
Ixmyelocel-T: Description Autologous (patient-specific), expanded multicellular therapy Target population: CLI patients with no options for revascularization Cell source: Bone marrow Cell delivery: Twenty intramuscular injections in lower extremity
Slide 5: Ixmyelocel-T Production
Ixmyelocel-T Production 5 Bone marrow (approx. 50ml / 3 tablespoons) is taken from patient’s hip 15 minute outpatient procedure automated system expands key beneficial cell types Expanded multicellular therapy is administered to the same patient 20 minute in-office procedure for CLI patients Day 1 D
Slide 6: Ixmyelocel-T Cell Expansion
Ixmyelocel-T Cell Expansion 6 Starting Bone Marrow Red Blood Cells Lymphocytes T + B Granulocytes Monocytes Mesenchymal Stem Cells CD45 Aastrom Proprietary Expansion Process ixmyelocel-T Therapeutic Effect RBC extraction < 0.1% remaining Cell Reduction Cell Amplification -5X -5X +200X +50X ~300 mill
Slide 7: Ixmyelocel-T Has Multiple Biological Activities
Ixmyelocel-T Has Multiple Biological Activities Remodeling of tissues Secretion of MMPs Phagocytosis and efferocytosis Contraction of ECM Promotion of angiogenesis Secretion of angiogenic cytokines Activation of eNOS Resolution of inflammation Secretion of anti-inflammatory cytokines Alternatively a
Slide 8: Phase 2b RESTORE-CLI Study Design
Phase 2b RESTORE-CLI Study Design Randomized, placebo controlled Double-blind Powered as Phase 2 safety study 150 patients 18 active centers No-option CLI patients who had rest pain with or without baseline wounds 7
Slide 9: Key Inclusion Criteria
Key Inclusion Criteria Age 18-90 Diagnosed CLI Ischemic rest pain > 2 weeks duration Ulceration or gangrene of toe or foot Toe systolic pressure < 50 mmHg Ankle systolic pressure < 70 mmHg Infrainguinal occlusive arterial disease judged not amenable to revascularization 8
Slide 10: Key Exclusion Criteria
Key Exclusion Criteria Previous amputation at talus or above Failed ipsilateral revascularization within 2 weeks of randomization Active infection of target extremity HbA1C > 10% Untreated aorto-iliac occlusive disease Exposed tendon or bone in wound 9
Slide 11: Study Protocol
Study Protocol 2:1 randomization ixmyelocel-T placebo injection (acellular vehicle) One-time set of 20 intramuscular injections 0.5 ml each Lower thigh Calf Foot 12 month follow-up 10
Slide 12: Defined Study Outcomes
Defined Study Outcomes Safety population: all pts randomized and aspirated Efficacy population: all pts randomized, aspirated and treated Primary (safety): All adverse events Primary efficacy: Time to first occurrence of treatment failure (TTF) Major amputation of treated leg All-cause mortality Dou
Slide 13: RESTORE-CLI Results: Patient Flow
RESTORE-CLI Results: Patient Flow Based on interim analysis, randomization stopped at 86 patients 9 withdrew prior to aspiration 77 aspirated 72 received treatment injections 48 ixmyelocel-T 24 placebo control 12
Slide 14: Patient Disposition – All Treated Patients
13 * All 3 patients had a major amputation prior to withdrawing from the study. Ixmyelocel-T N = 48 Control N =24 Completed 39 (81) 21 (88) Died 3 (6) 2 (8) Withdrew 6 (13) 1 (4) -w/endpoint* 3 (6) 0 (0) -w/o endpoint 3 (6) 1 (4) Patient Disposition – All Treated Patients (n=72)
Slide 15: Patient Demographics – All Treated Patients
Parameter* (Mean values) Ixmyelocel-T N = 48 Control N = 24 % Male 71 58 Age 69 67 % Current, % Past smokers 17, 67 38, 46 % Current, % Past alcohol 44, 23 29, 33 BMI 27 28 Creatinine mg/dL 1.2 1.1 N (%) with known Diabetes 21 (44) 15 (63) Patient Demographics– All Treated Patients (n=72) *No signif
Slide 16: Time to First Occurrence of Treatment Failure
Time to First Occurrence of Treatment Failure – All Treated Patients (N=72) 62% risk reduction: HR 0.38, 95%CI = (0.20-0.74) 15
Slide 17: First Event Contributed to Treatment Failure
First Event Contributed to Treatment Failure – All Treated Patients (N=72) Ixmyelocel-T N = 48 Control N = 24 Endpoint (n) Major amputation 6 4 All-cause mortality 2 1 Doubling in total wound surface area* 5 7 De novo gangrene 6 4 Total n(%) 19 (39.6%)** 16 (66.7%)** *For wound size doubling: patien
Slide 18: Amputation-Free Survival – All Treated Patients
Amputation-Free Survival – All Treated Patients (N=72) 32% risk reduction: HR 0.68, 95%CI = (0.28-1.65) 17
Slide 19: Post Hoc Analysis – Patients with Baseline Wounds
18 Patients with Baseline Wounds – 45 of 72 treated patients Ixmyelocel-T: 29 / 48 patients (60.4%) Control: 16 / 24 patients (66.7%) Repeat analysis for only those patients with baseline wounds TTF AFS Post Hoc Analysis – Patients with Baseline Wounds
Slide 20: TTF and AFS – Baseline Wound Patients
TTF and AFS – Baseline Wound Patients (N=45) 19 77% risk reduction: HR = 0.225 95% CI = (0.103, 0.490) Cox PH p-value for treatment = 0.0002 61% risk reduction: HR = 0.391 95% CI = (0.131, 1.164) Cox PH p-value for treatment = 0.0915
Slide 21: Safety Overview: All Aspirated Patients
20 Safety Overview: All Aspirated Patients (N=77) Safety Parameter Ixmyelocel-T N = 53 Control N = 24 P-value** N (%) with Adverse Events 47 (89) 23 (96) 0.424 N (%) Serious Adverse Event 23 (43) 12 (50) 0.628 N (%) withdrawal due to AE 2 (4) 0 (0) 1.000 N (%) Deaths * 3 (6) 2 (8) 1.000 * An additio
Slide 22: Safety Overview: AEs in >10% of Aspirated Patients
21 21 Safety Overview: AEs in > 10% of Aspirated Patients Preferred Term n (%) Ixmyelocel-T N = 53 Control N = 24 P-value** Pain in extremity 17 (32) 4 (17) 0.181 Gangrene 7 (13) 6 (25) 0.209 Cellulitis 5 (9) 6 (25) 0.087 Skin Ulcer 6 (11) 5 (21) 0.303 Hypertension 6 (11) 2 (8) 1.000 Nausea 5 (9) 3
Slide 23: Summary: RESTORE-CLI
Summary: RESTORE-CLI Safety profile for aspiration, injection and treatment with ixmyelocel-T favorable No increased adverse events compared to placebo TTF primary endpoint positive Significantly fewer adverse limb events 32% reduction in AFS in all treated patients Not significant difference Study
Slide 24: Ixmyelocel-T Development Plan: Phase 3 REVIVE-CLI
Ixmyelocel-T Development Plan: Phase 3 REVIVE – CLI 594 no-option CLI patients with tissue loss followed for 18 months Primary Efficacy Endpoint: AFS at 12 months 80 sites (site selection ongoing); US only 1:1 randomization to ixmyelocel-T or placebo Special Protocol Assessment (SPA) concurrence wit
Aastrom Biosciences — American Heart Association Scientific Sessions 2011 on 6ix