Slide 1: MultiStem Clinical Programs: An In-Depth Look
MultiStem® Clinical Programs: An In-Depth Look February 2, 2022
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation has been prepared solely for informational purposes. This presentation includes, and our responses to various questions may include, “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securitie
Slide 3: Clinical Program Update Agenda
Clinical Program Update Agenda Topic Ischemic Stroke Program ARDS Program Other Programs Q&A 3
Slide 4: Clinical Program Update Participants
Clinical Program Update Participants Participants Title William (B.J.) Lehmann, JD, MBA Chief Operating Officer John Harrington, PhD Chief Scientific Officer Robert Mays, PhD Head Regenerative Medicine Research Eric Jenkins, MD Senior Medical Director Ivor Macleod, MBA, CPA Chief Financial Officer 4
Slide 5: Unique Attributes of MultiStem Cell Therapy Provide a Competitive Edge
Unique Attributes of MultiStem® Cell Therapy (invimestrocel) Provide a Competitive Edge Promotes healing and tissue repair Off-the-shelf and easy administration By regulating the overactive immune response after an MultiStem is easily administered intravenously or injury, our therapy can potentially
Slide 6: Advanced Portfolio Targeting Areas of Substantial Unmet Need
Advanced Portfolio Targeting Areas of Substantial Unmet Need KEY: = Enrolling; in progress = Completed enrollment / study Indication Clinical Trial Phase 2 Phase 3 BLA Target Market MASTERS-1 • ~800K annual cases in the U.S. • ~2.2MM annual cases in the U.S., Europe and Japan Ischemic Stroke MASTERS
Slide 7: Substantial Market Opportunity for MultiStem Therapy
Substantial Market Opportunity for MultiStem Therapy Annual Revenue Frontier $90,000 U.S. Ischemic Stroke + ARDS: $75,000 Potential $5-10 billion annual market opportunity $60,000 Price $45,000 $30,000 $15,000 50,000 150,000 250,000 350,000 450,000 Annual Treatments $2 billion $4 billion $6 billion
Slide 8: Ischemic Stroke
Ischemic Stroke 8
Slide 9: Objective: Dramatically Improve the Recovery Path
Objective: Dramatically Improve the Recovery Path Our data show that early intervention with MultiStem therapy after an acute injury enhances healing by regulating an overactive immune response and re-establishing homeostasis. 4. MultiStem cell Supports preservation of therapy intervention life and
Slide 10: Potential Treatment Benefits
Potential Treatment Benefits • Ischemia may cause loss of brain tissue with associated loss of neurological function, and Recovery of neurological function in severe cases, death. • Secondary inflammation-mediated damage can contribute to additional tissue loss, scar Survival formation and expanded
Slide 11: Key Design Features for the Pivotal MultiStem Stroke Studies
Key Design Features for the Pivotal MultiStem Stroke Studies – TREASURE and MASTERS-2 Single cell therapy dose (1.2B cells) delivered intravenously within 18-36 hours following stroke onset or LKN Targeted to patients most likely to benefit – moderate to moderate-severe stroke patients – baseline NI
Slide 12: MASTERS-1: Phase 2 Ischemic Stroke Trial Results
MASTERS-1: Phase 2 Ischemic Stroke Trial Results Treatment with MultiStem Shows Meaningful Benefit Proportion of Subjects Treated within 36 Hours Achieving Excellent Outcome Increases Over Time (Excellent Outcome = Patients Achieving NIHSS 0 or 1 and mRS 0 or 1, and Barthel Index >95) Excellent Outc
Slide 13: MASTERS-1: Impact Across Outcome Measures
MASTERS-1: Impact Across Outcome Measures Patients who received treatment ≤ 36 hours after stroke onset Placebo group (n=61) MultiStem treatment group (n=31) p = 0.03* p < 0.01* 25% p = 0.09 10% p = 0.14 29% 32% Day 90 % Patients - Death or life- 16.1% 13% threatening adverse events 6.6% 8.2% (60% d
Slide 14: MASTERS-1: Clinical Improvement Observed Across the Severity Spectrum
MASTERS-1: Clinical Improvement Observed Across the Severity Spectrum Patients who received treatment ≤ 36 hours after stroke onset Distribution of Subjects by Group using mRS scores – mRS "shift" analysis – over time 0 1 2 3 4 5/6 0 1 2 3 4 5/6 3.2% 3.2% 9.7% 22.6% 16.1% 38.7% 9.7% MultiStem 12.9%
Slide 15: Patient Characteristics: TREASURE v. MASTERS Studies
Patient Characteristics: TREASURE v. MASTERS Studies Age – stroke patients older in Japan, meaning TREASURE forecasted to have older patients than MASTERS-1 and MASTERS-2 Reperfusion therapy – utilization in TREASURE forecasted to be modestly lower or generally comparable to MASTERS-1 – MultiStem tr
Slide 16: Summary Outcome Data from MASTERS-1 Study – Projecting Impact of Older Population in TREASURE
Summary Outcome Data from MASTERS-1 Study – Projecting Impact of Older Population in TREASURE Patients 65 years and older Placebo group (n=24) MultiStem treatment group (n=24) p<0.01* p=0.14 p=0.19 41.7% 29.2% 29.2% p<0.05* 20.8% 12.5% 8.3% 4.2% 0.0% Day 90 Day 365 Day 365 Day 90 % Patients Reaching
Slide 17: MASTERS-1: Reduction in T-cell Levels Following MultiStem Treatment
MASTERS-1: Reduction in T-cell Levels Following MultiStem Treatment All Subjects, Circulating CD3+ T-cell Levels* MultiStem Placebo Day 0 18.5% 18.8% Day 2 18.4% 23.3% Change (0.1%) 4.5% p=0.001 * % of circulating leukocytes (WBC) CD3+ Associated with T-cell Activation an inflammatory and immune sys
Slide 18: MASTERS-1: Reduction in Inflammatory Biomarkers Associated with MultiStem Treatment
MASTERS-1: Reduction in Inflammatory Biomarkers Associated with MultiStem Treatment Biomarker p-value IFNg 0.13 TNFa 0.03 IL-6 <0.01 IL-1b 0.04 IL-12 0.09 Analysis of variance model for the log of ratios as factor, with control for outliers IFNg TNFa IL-6 IL-1b IL-12 MultiStem (51-56) Placebo (48-52
Slide 19: MASTERS-1: Reduction in Inflammatory Biomarkers Associated with MultiStem Treatment
MASTERS-1: Reduction in Inflammatory Biomarkers Associated with MultiStem Treatment MultiStem Subjects with Administration <36 hours IFNg TNFa IL-6 IL-1b IL-12 MultiStem (24-27) Placebo (48-52) 19
Slide 20: Therapeutic Hypothesis
Therapeutic Hypothesis Intravenous (IV) administration of MultiStem cells in the acute time frame after injury to the central nervous system (CNS) provides long term neurological benefit by mitigation of the overt impact of the peripheral immune response, in part originating from the spleen. MultiSt
Slide 21: Temporal Aspects of the Immune Response Following Acute Injury
Temporal Aspects of the Immune Response Following Acute Injury Initial Injury Scar Formation Histopathological Events after Injury Peripheral Immune System Responses after Injury Cellular Events that Follow the Initial Injury Time Course Following the Initial Injury 21 Adapted from Simon et al., Nat
Slide 22: Multimodal Mechanism of Action: Interaction with Multiple Cells of the Immune System
Multimodal Mechanism of Action: Interaction with Multiple Cells of the Immune System MultiStem® Endothelial cells T cells Neutrophils M1 M2 Regulatory Tolerogenic Macrophages Macrophages T cells mDCs DCs Reduces endothelial Reduces neutrophil: Promotes MΦ2: Promotes DCs: cell activation: • Infiltrat
Slide 23: MultiStem Prevents Splenic Atrophy after Stroke
MultiStem Prevents Splenic Atrophy after Stroke Spleen size change 1200.0 ** * 1000.0 Absolute Weights (mg) 800.0 600.0 400.0 200.0 0.0 MAPC+Stroke Vehicle+Stroke Vehicle+Sham stroke Similar CNS injury induced splenic atrophy (and MAPC-mediated recovery) has been published by our collaborators in is
Slide 24: Effect of Splenectomy on Blood Cytokines
Effect of Splenectomy on Blood Cytokines *# Through Day 4 following Stroke * * *# IL-6 IL-10 Spleen Increase Relative No Increase * Intact reduction change No Small Reduction Decrease Decrease Spleen increase to normal Multi- Multi- Vehicle Stem Vehicle Stem *# * *# Intact spleen: n=5 per group; spl
Slide 25: Splenectomy Impacts MultiStem-Mediated Functional Improvements Post-Stroke
Splenectomy Impacts MultiStem-Mediated Functional Improvements Post-Stroke Intact spleen Splenectomy Composite neurological score consisting of motor, sensory and balance tests – higher score means * greater severity; 0=normal n=6 for vehicle group, n=7 for MultiStem group. * p<0.05, ANOVA with post
Slide 26: Acute Respiratory Distress Syndrome (ARDS)
Acute Respiratory Distress Syndrome (ARDS) 26
Slide 27: Potential Treatment Benefits
Potential Treatment Benefits • Damage to the lung's air sacs allows fluid to leak into the lungs. Recovery of pulmonary function (faster) • Most patients placed on mechanical ventilation to help them breathe, often requiring sedation. Survival • Extended, intensive hospitalized care in ICU • Patient
Slide 28: MUST-ARDS: Results from Exploratory Clinical Study in ARDS
MUST-ARDS: Results from Exploratory Clinical Study in ARDS All Subjects (in efficacy cohort) MultiStem Placebo Patients who rated complete independence Number of Patients 20 10 in self care at 1 year Ventilator-free days (median) 18.5 6.5 40% Placebo Mortality (d28) 25% 40% 80% MultiStem-treated Pat
Slide 29: ONE-BRIDGE: Healios study in Japan for the treatment of ARDS
ONE-BRIDGE: Healios study in Japan for the treatment of ARDS MultiStem-treated patients experienced: Cohort 1 - Pneumonia-induced ARDS Patients MultiStem SOC Number of Patients 20 10 Ventilator-free days (median) 20 11 Mortality (d90) 26% 43% 82% Increase in Ventilator-free Cohort 2 – COVID-19 Induc
Slide 30: Analysis of Pooled MUST-ARDS & ONE-BRIDGE Data
Analysis of Pooled MUST-ARDS & ONE-BRIDGE Data – Results Signal MultiStem Treatment Potential • 60 ARDS (non-Covid) ARDS patients – 40 receiving MultiStem treatment – 20 placebo or standard of care • Mostly pneumonia-induced ARDS (85% MultiStem-treated subjects; 90% placebo / SOC subjects) • MultiSt
Slide 31: Analysis of Pooled, MUST-ARDS & ONE-BRIDGE Data
Analysis of Pooled, MUST-ARDS & ONE-BRIDGE Data Mortality, 90d EQ5D Index, 90d Favors MultiStem Favors Placebo Favors Placebo Favors MultiStem Note: Mean outcomes and 90% confidence intervals; black: unadjusted in study-specific analysis or adjusted for study in pooled analysis; red: adjusted for co
Slide 32: Evaluating Treatment Effects across Multiple Outcomes in Each Study
Evaluating Treatment Effects across Multiple Outcomes in Each of MUST-ARDS and ONE-BRIDGE Studies Evaluation of Overall Treatment Effect* • Evaluate impact across outcomes and studies • Standardize scores from disparate Chance of observing these positive results outcomes (using z-score) if there wer
Slide 33: Pooled Analysis: Reduction in Inflammation-related Biomarkers
Pooled Analysis: Reduction in Inflammation-related Biomarkers IL-6 MMP-2 MultiStem (38) Placebo (16) 33
Slide 34: Development Strategy
Development Strategy Focus on ARDS and non-ventilated patients with ARDS-like physiology – i.e. acute hypoxemic respiratory failure caused by noncardiogenic pulmonary edema associated with severe inflammation Treatment of the condition no matter the infectious cause (e.g., pneumonia, COVID, influenz
Slide 35: Other Programs
Athersys Other Programs
Slide 36: Expansive Therapeutic Opportunity
Expansive Therapeutic Opportunity : Over 17 Years of Preclinical and Clinical Research Publications Years of preclinical research and data support mechanism of action hypothesis and demonstrates that MultiStem has the potential to treat a variety of clinical indications with unmet need. • Ischemic S
Slide 37: Highlighting Other MultiStem Development Programs
Highlighting Other MultiStem Development Programs = POP established / designation achieved Est.Target Patients Indication Need Preclinical Clinical Orphan Annually (US) Trauma • High 200,000 (hemorrhagic shock) • Accidents, battlefield Hemorrhagic Stroke 50-100,000 • High – limited alternatives Hypo
Slide 38: Highlights – Neonatal Hypoxic Ischemia (PreClinical)
Highlights – Neonatal Hypoxic Ischemia (PreClinical): Potential to Improve Functional and Structural Outcomes Global hypoxic ischemia in preterm ovine model Reduction of HI- induced microglial proliferation and hypomyelination Modulation of peripheral (splenic) MultiStem treatment (iv) inflammatory
Slide 39: Highlights – Spinal Cord Injury (PreClinical)
Highlights – Spinal Cord Injury (PreClinical): Potential to Improve Function and Quality of Life Rat contusion model of SCI Gross Locomotor Behavior MultiStem treatment (iv) improves locomotor function Tissue Integrity Improvement in bladder function (data not shown) Fine Locomotor Behavior Local (i
Slide 40: Exciting Pipeline Opportunities with Potential for Rapid Advancement
Exciting Pipeline Opportunities with Potential for Rapid Advancement Strong scientific rationale for therapeutic potential in multiple high value areas – Acute, critical care – Chronic conditions Established MultiStem (Invimestrocel) Product Candidate – Characterization / tolerability profile – Unde
Slide 41: Summary
Summary 41
Slide 42: Key Takeaways from Clinical Program Update
Key Takeaways from Clinical Program Update Establish New Category – Off-the-shelf cell therapy for treating severe, critical, high- burden conditions – Substantial Unmet Needs in Lead Indications (and in other indications in portfolio) – Large potential business opportunity – $5-10 billion annual U.
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Slide 44: Thank you
Thank you