Vericel Corporation · NASDAQ:VCEL
Vericel — Technical Presentation (April 2016)
32 slides from Vericel's technical presentation, April 2016
Slide 1: The ixCELL-DCM Trial: Transendocardial Injection of ixmyelocel-T
The ixCELL-DCM Trial: Transendocardial Injection of ixmyelocel-T in Patients with Ischemic Dilated Cardiomyopathy Timothy D. Henry, MD, FACC on behalf of Arshed A. Quyyumi, Gary L. Schaer, David R. Anderson, Catalin Toma, Cara East, David P. Recker, Ann Remmers, James Goodrich, Amit N. Patel and the
Slide 2: Lancet publication: Ixmyelocel-T for ischaemic heart failure
Lancet CrossMark Ixmyelocel-T for patients with ischaemic heart failure: I@k® a prospective randomised double blind trial Amit N Patel*, Timothy D Henry*, Arshed A Quyyumi, Gary L Schaer, R David Anderson, Catalin Toma, Cara East, Ann E Remmers, James Goodrich, Akshay S Desai, David Recker, Anthony
Slide 3: Disclosures
Disclosures • Trial sponsored by Vericel Corporation • Steering Committee – Amit N. Patel, Chair – Timothy D. Henry, PI – Gary L. Schaer – Anthony N. DeMaria – David P. Recker • Clinical Endpoint Committee: Brigham & Women’s Hospital – Ashkay S. Desai, Chair • DSMB: University of California, San Fra
Slide 4: Clinical Sites
Clinical Sites Steering Committee • Amit N. Patel (Chair) • Timothy D. Henry (PI) • Gary L. Schaer • Anthony N. DeMaria • David P. Recker
Slide 5: Investigators
Investigators # Subjects # Subjects Principal Investigator Study Coordinator Randomized Principal Investigator Study Coordinator Randomized Arshed Quyyumi Kareem Hosney 12 Amish Raval Cathlyn Leitzke 3 Amit Patel Patty Meldrum 11 Guy Reeder Cindy Woltman 3 Gary Schaer Jon Learoyd 10 Safwan Kassas Va
Slide 6: Introduction
Introduction • Heart failure is a leading cause of morbidity and mortality in the U.S. • Patients with Class III/IV heart failure, despite optimal medical and device therapy, have limited options beyond cardiac transplantation and LVAD • Preclinical studies suggest regenerative therapies are an attr
Slide 7: Background
Background • Ixmyelocel-T is an autologous, bone marrow derived, multicellular therapy expanded over 2 weeks to increase: – CD90+ mesenchymal stem cells (MSC) – CD45+ CD14+ M2-like macrophages • Phase 2a IMPACT-DCM and Catheter-DCM (n=59): – Improved safety with percutaneous vs. surgical delivery –
Slide 8: Ixmyelocel-T: Expanded Multicellular Therapy
Ixmyelocel-T: Expanded Multicellular Therapy Two-Week Expansion Increases: 1. CD45+ CD14+ M2-like macrophages 2. CD90+ MSCs Potential Mechanisms: 1. Anti-Inflammatory 2. Tissue Remodeling 3. Endothelial Protection 4. Angiogenesis
Slide 9: Phase 2a Results
Phase 2a Results IMPACT-DCM (n=39) Catheter-DCM (n=22) 75% fewer patients treated with ixmyelocel-T experienced a MACE (* p < 0.05) MACE = cardiac death, cardiac arrest, MI, HF hospitalization, or major bleeding Henry TD, et al. Circ Res 2014;115:730-737.
Slide 10: ixCELL-DCM Study Objective
ixCELL-DCM Study Objective • The ixCELL-DCM clinical trial is a multicenter, prospective, randomized, double-blind, placebo-controlled Phase 2b study designed to evaluate the efficacy, safety, and tolerability of ixmyelocel-T compared to placebo when injected transendocardially in patients with Clas
Slide 11: ixCELL-DCM Eligibility
ixCELL–DCM Eligibility Inclusion Criteria Exclusion Criteria • Age 30 to 86 • MI, Stroke, TIA within 3 months • NYHA Class III/IV heart failure • LV thrombus/ineligible for NOGA • Diagnosis of ischemic cardiomyopathy • PCI, CABG within 30 days • LVEF ≤35% • Status 1A or 1B on heart transplant list •
Slide 12: Protocol
Protocol Ixmyelocel-T 12 Day ± 1 Expansion R Randomization/Aspiration Injection Month 12 Month 24 Month 3 Month 6 Day -14 Day 1 Data Analysis Safety Follow-up Screening Days -30 to -15 Placebo
Slide 13: Primary Endpoint
Primary Endpoint • The Primary Endpoint was a composite of: – All-cause death – Cardiovascular hospitalization – Unplanned clinical visits to treat acute decompensated HF Excluding procedure-related events within 7 days of injection (sensitivity analysis) All events adjudicated by independent Cl
Slide 14: Secondary Endpoints
Secondary Endpoints • Win ratio • LVEF, LVESV, and LVEDV measured by echocardiogram • NYHA class • Six-minute walk distance • Time to First Event
Slide 15: Safety Endpoints
Safety Endpoints • Serious Adverse Events – MACE – Cardiovascular death – MI – CVA – HF requiring hospitalization – UA requiring hospitalization – Resuscitated sudden death – LVAD – Heart transplantation
Slide 16: Enrollment Curve
Enrollment Curve 140 ixCELL-DCM Enrollment Subjects Subjects 120 Month Randomized Treated Randomized Feb-14 3 7 100 Mar-14 12 4 Treated Apr-14 8 7 80 May-14 6 10 Jun-14 12 15 60 Jul-14 5 4 Aug-14 8 6 40 Sep-14 11 8 Oct-14 12 9 20 Nov-14 8 11 Dec-14 9 8 Jan-15 10 11 0 Feb-15 0 1 May-13 Dec-13 May-14
Slide 17: Patient Enrollment
189 patients assessed for eligibility Patient Enrollment 63 excluded 57 did not meeting eligibility criteria 5 declined to participate 1 other reason: central reader unable to provide LVEF because of poor images 126 randomised 60 assigned to placebo 66 assigned to ixmyelocel-T 7 not treated 5 not tr
Slide 18: Patient Demographics
Patient Demographics Category Placebo (N=51) Ixmyelocel-T (N=58) P value Demographics Sex (%) Male 88% 95% 0.30 Age (years) Mean 64.7 65.3 0.69 Race (%) White 88% 91% 0.75* Risk Factors Hypertension % 90% 81% 0.28 Hyperlipidemia % 96% 97% 1.00 Diabetes % 51% 41% 0.34 CV Medical History Previous CABG
Slide 19: Baseline Data & Medications
Baseline Data & Medications Category Placebo (N=51) Ixmyelocel-T (N=58) P value Baseline NYHA Class III % 92% 90% 0.88* LVEF (%) Mean 24.4% (+/-6.0) 26.5% (+/-5.1) 0.05 Creatinine Clearance (mL/min) Mean 61.9 (+/-19.0) 61.8 (+/-21.4) 0.83 Six Minute Walk Test (meters) Mean 301.6 (+/-104.8) 313.4 (+/
Slide 20: Primary Endpoint: Per Protocol (n=109)
Primary Endpoint: Per Protocol (n=109) _____Primary Endpoint_____ _____Sensitivity Endpoint_____ Without IP Procedure Related Events With IP Procedure Related Events Placebo Ixmyelocel-T Placebo Ixmyelocel-T (N=51) (N=58) (N=51) (N=58) P-Value 0.0344 0.0267 Rate Ratio [95% CI] 0.63 [0.42, 0.97] 0.62
Slide 21: Primary Endpoint Components: Per Protocol (n=109)
Primary Endpoint Components: Per Protocol (n=109) P=0.0344 Rate Ratio [95% CI]: 0.63 [0.42-0.97]
Slide 22: Primary Endpoint: Modified ITT (n=114)
Primary Endpoint: Modified ITT (n=114) _____Primary Endpoint_____ _____Sensitivity Endpoint_____ Without IP Procedure Related Events With IP Procedure Related Events Placebo Ixmyelocel-T Placebo Ixmyelocel-T (N=55) (N=59) (N=55) (N=59) P-Valuea 0.0107 0.0082 Rate Ratio [95% CI] 0.59 [0.40, 0.89] 0.5
Slide 23: Time to First Event: Per Protocol (n=109)
Time to First Event: Per Protocol (n=109) Ixmyelocel-T p=0.1667 Placebo
Slide 24: Time to First Event: Modified ITT (n=114)
Time to First Event: Modified ITT (n=114) Ixmyelocel-T p=0.1434 Placebo
Slide 25: Safety Analysis
Safety Analysis Placebo Ixmyelocel-T (N=55) (N=59) Adverse Events (% patients) 51 (92.7%) 52 (88.1%) Total # 344 323 Serious Adverse Events (% patients) 41 (74.5%) 31 (52.5%) Total # 124 73 Major Adverse Cardiovascular Events (% 23 (41.8%) 16 (27.1%) patients) Total # 38 31
Slide 26: LVEF and Volumes
xs m LVEF and Volumes LVEDV (mL, mean and SEM) Change from Baseline LVESV (mL, mean and SEM) Change from Baseline » 36 |-o— Placebo |-e— Ixmyelocel-T| ey 2 = 2 0 3 6 9 12 Time post treatment (months) 20-|-<— Placebo |-®— Ixmyelocel-T| 0 T T T T 0 3 6 9 12 Time post treatment (months) LVEF (%, mean a
Slide 27: Six-Minute Walk Test & NYHA
Six-Minute Walk Test & NYHA = So i=) —6— Placebo —e— Ixmyelocel-T —6— Placebo —e— kxmyelocel-T > ¢ bi > i=] 2 w ms w S f + N ° 6 Minute Walk Distance (meters, mean and SEM) o i) 3 T T T T 0 3 6 9 12 3 6 9 12 Time post treatment (months) Time post treatment (months) NYHA Class I/II (% of Subjects) a
Slide 28: Summary
Summary • Patients treated with ixmyelocel-T had a significant reduction in the primary endpoint on both per protocol and modified ITT analysis • 37% to 41% reduction in cardiac events compared to placebo; similar to the Phase 2a clinical trials • Driven by a reduction in mortality and cardiac hospi
Slide 29: Conclusions
Conclusions • The transendocardial delivery of ixmyelocel-T resulted in a significant reduction in cardiac events driven by both mortality and cardiac hospitalizations at 12 months compared to placebo • Results suggest that ixmyelocel-T may be an attractive option for NYHA Class III/IV patients with
Slide 30: Appendix
Appendix ixCELL|DCM
Slide 31: Win Ratio: Per Protocol (n=109)
Win Ratio: Per Protocol (n=109) Placebo Ixmyelocel-T n/N (%) n/N (%) Incidence of Individual Components*: All-cause Deaths/LVAD/Heart Transplants 8/51(15.7) 6/58(10.3) Death 7/51(13.7) 2/58(3.4) LVAD Insertion 0/51 3/58(5.2) Heart Transplant 1/51(2.0) 1/58(1.7) CV Hospitalization 24/51(47.1) 22/58(3
Slide 32: ixCELL-DCM Study Design
ixCELL-DCM Study Design Phase 2b ixCELL–DCM Study Design Design • Multicenter, randomized (1:1), double-blind, placebo-controlled phase 2b trial Patient Population • NYHA Class III/IV ischemic dilated cardiomyopathy Treatment • Intramyocardial ixmyelocel-T vs. placebo Study Size • 126 patients rando