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Information contained in this presentation has been compiled from sources believed to be credible
and reliable. However, we cannot guarantee such credibility and reliability. The forecasts and
projections of events contained herein are based upon subjective valuations, analyses and personal
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Company Highlights
Emerging clinical portfolio of “best‐in‐class” product candidates and technologies
Multiple clinical stage programs in development , strong preclinical pipeline
Focus on biologics (MultiStem ) and pharmaceuticals (for CNS /metabolic
related indications including obesity, cognition and others)
Multiple clinical trials initiated with MultiStem
Highly standardized “Off‐the‐shelf” cell therapy product, produced at scale
Administered without tissue matching or immune suppression
Multiple disease indications in development ‐ multiple mechanisms of benefit
Frost & Sullivan Product Innovation of the Year Award – 10/29/08
Public company with strong cash position
NASDAQ: ATHX
$65 MM financing completed in June ‘07
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Business Strategy
Develop a portfolio of potential of potential best in class opportunities
Maintain lean operational infrastructure / modest core burn
Cost effective portfolio diversification + focused core competencies
Portfolio based approach enables development & partnering flexibility
Advance programs as resources allow
Evaluate partnering opportunities as we advance
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Obesity Program
5
Obesity Market Opportunity
Clinical Landscape
Growing, global health epidemic contributing to heart disease, diabetes, cancer and stroke
Estimated 30% of Americans are clinically obese (BMI > 30); an additional ~30% are
overweight (BMI > 25)
Economic cost in U.S. alone is estimated at $117 billion annually
True blockbuster potential for safe and effective therapies
Therapeutic Landscape
Increasing recognition of obesity as serious medical condition
No highly effective & safe drug therapies currently on market – few in clinical trials, recent
additional attrition due to “demise” of CB‐1 antagonist class
Several targets are well known but have not been effectively exploited to date
Large potential market, patient variability (efficacy and tolerability) creates room for
multiple players and MOA’s
6
Obesity Program – Overview of 5HT2c Agonists
5HT2c (serotonin) receptor agonists suppress appetite & cause weight loss
Mechanism extensively validated in humans (e.g. fenfluramine, dexfenfluramine
recognized as highly effective weight loss agents)…but…
These non‐selective agents also activate the 5HT2b receptor in the heart and cause
cardiovascular toxicity (valvular hypertrophy = valvular regurgitation/heart murmur)
Selective 5HT2c agonists (i.e. that do not stimulate 5HT2b) believed to be safe
Selectivity relative to 5HT2a important to limiting CNS related side effects
Portfolio of potent and selective compounds established
ATHX‐105 has been the lead
‐ Multiple Phase I trials completed in U.K. (good safety & tolerability profile observed)
‐ Excellent regional absorption seen in recent clinical study (important for development of
modified release formulation)
‐ Currently on partial clinical hold – have met with FDA, resolved several issues, but
significant issue remains – could result in suspension or termination of further development
‐ Intend to provide further update on program this quarter after completion of ongoing
work, analysis of results and dialogue with FDA
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Cognition & Wakefulness ‐ H3 Antagonist Program
Histamine H3 Receptor Extensively Studied – Multiple Potential Applications
H3 Receptor Antagonists / Inverse Agonists result in elevated levels of histamine in
certain regions of the brain directly affecting cognitive tone
Compounds improve wakefulness (e.g. Narcolepsy, EDS) and cognition (e.g. ADHD,
Alzheimer’s)
May also have relevance in other indications (e.g. obesity, neuropathic pain)
High quality portfolio of therapeutic compounds established
Multiple compounds currently under evaluation in animal tox, efficacy studies
‐ Potent, highly selective compounds developed by ATHX
Intend to select a clinical candidate and one or more back‐up compounds this
quarter (pending successful completion of ongoing studies)
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MultiStem®: Biologic
Product Platform
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Historical Limitations to Stem Cell Therapy
Requirement for close Donor – Recipient tissue matching
Necessary to avoid transplant rejection
Also needed to reduce incidence of Graft vs. Host Disease
Lack of ability to scale production of cells
One donor for each recipient – logistically difficult and very costly
Biological limitations of most cells prevent large scale production
Mechanistic focus has been primarily cell / tissue replacement
Most cell types can produce limited repertoire of more differentiated cells
Goal has been to replace lost or damaged cells (e.g. HSC transplantation)
Safety
Rejection, GVHD, Ectopic Tissue, Teratoma / Tumor formation
10
2008 – Pharma‐Biotech Arriving to Party …
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MultiStem®: Best‐in‐Class Cell Therapy Product
“Off the shelf” administration
No tissue matching needed
Non‐immunogenic ‐ No immunosuppression required
Well defined, FDA‐approved manufacturing process in place (with Lonza)
Banked product, highly characterized
Large scale production / yield (100k’s to millions of doses possible from a single donor)
Multiple potential mechanisms of therapeutic benefit
Dynamically responsive biologic therapy = a drug like therapy
Therapeutic effect primarily factor mediated: anti‐inflammatory / immunomodulatory,
cytoprotective, trophic & growth factors, angiogenic / vasculogenic
Direct cell replacement plays a minor role
Leading IP position for pluripotent, multifunctional non‐embryonic stem cells
Multiple IND’s advanced in efficient, cost effective manner
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Overview of MultiStem® Production Process
Lot Release & Product Characterization
Testing
Sterility
Potency
Purity and Viability
Stable Cytogenetics
Absence of tumorigenic potential in vivo
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MultiStem: Additional Safety Studies
▲ GLP Toxicology and Clinical Pathology (2 week, 4 week)
Studies indicate no evidence of acute toxicity or abnormal clinical pathology
▲ Genetic Stability and Tumorigenicity Testing
Karyotypic stability
Clinical product tested in standard Nude mouse tumor models (both i.v. and s.c.)
▲ Long Term GLP Histopathology Analysis (one year for stroke)
Extensive histopathology analysis of animals receiving clinical grade MultiStem
indicates no evidence of tumorigenicity or ectopic tissue after one year
No other abnormalities or other adverse events noted
▲ Immune Sensitization Analysis
Single or repeat administration (5x) of MultiStem does not cause immune
sensitization or abnormal clinical pathology
▲ Gene Expression, Protein Expression and SNP Array Analysis
No evidence of variability between working cell banks and production runs after
significant expansion of clinical grade cellular product
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MultiStem: Multiple Potential Mechanisms of Benefit
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Focused Product Development Approach
o Chronic ischemia / CHF
o Peripheral vascular disease
MultiStem® Treatment o Traumatic brain injury & related
Acute/Ischemic
Injury o Other Neurological Indications
o Other ischemic injury (e.g., kidney)
o Acute Myocardial Infarction
(Ph 1 initiated)
o Ischemic Stroke
o Inflammatory bowel disease
Immune System o Transplantation
Modulation
o Diabetes (type 1)
o HSC / Bone Marrow Transplant Support / o Multiple Sclerosis
GVHD (Ph 1 initiated) o Other autoimmune disorders
o Other Neurological Indications
Next generation
opportunities
Other themes, e.g., protein deficiencies,
bone growth
16
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Accelerating MultiStem Proof‐of‐Concept Path
Proof‐of‐concept with cell‐therapy products
– Standardized and scalable product manufacturing
– Basic safety in humans within desired dose ranges and delivery approaches
• Phase I studies (with potential for efficacy signals)
– Efficacy in humans
• Focus in near term on Phase I/II studies in indications with discreet endpoints / readouts over short
→ showing of desired biological activity and benefit
– Further elucidation of mechanisms of benefit (from animal models, in vitro)
support clinical findings
Fastest path likely infused product in immunomodulatory area
– Leverage IND BB‐13507 (Evaluation of MTD of Single and Repeated Administration
of Allogeneic MultiStem in Patients with AL, CM and Myelodysplasia)
– Treatment of (steroid refractory, or acute) GvHD
• Basically, same patient population with well‐defined shorter‐term endpoints; same sites
– Other immunomodulation indication(s): exploit same therapeutic pathways, and
conditions with similar treatment approaches
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MultiStem for Acute
Myocardial Infarction
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MultiStem®: Acute Myocardial Infarction
AMI remains a major area of need for improved therapies
865,000 heart attacks annually in the U.S.
156,000 deaths
Significant incidence of progression to CHF
Local (catheter) delivery of MultiStem following heart attack
Reduces inflammation‐related damage and promotes revascularization
Also exploring administration via i.v.
MultiStem demonstrated safe and effective in multiple pre‐clinical models
IND approved, clinical trial initiated with co‐development partner (Angiotech)
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Innovative Approach: Standardized Product + Efficient Local Delivery
Standardized product (administered without matching or immunosuppressive agents)
Reduces inflammation‐related damage and promotes revascularization
Targeted, local delivery in coronary arteries with transarterial catheter
Administration of cell product into perivascular region
Relative ease of use, comparable to standard angioplasty
Strong partners and leading investigational sites
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Allogeneic MultiStem Delivers Functional Improvement in Pig
Models of Cardiovascular Ischemia
Transient ischemia, catheter delivery
p-value < .005 P-value < .02
60
55
E je c tio n F ra c tio n %
50
45
40
35
30
25
20
Baseline 1 Wk post-MI 4 Wk post MI
• Consistent improvement across multiple functional parameters
with single dose administered post‐MI
• No observed safety issues
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Transarterial Catheter Delivery Approach
Mercator MedSystems, 510(k) approved MicroSyringe Infusion Catheter
• Site‐specific delivery into perivascular space and adventitia
– Retain greater number of cells at/near injury site (reduce wash‐away of cells into bloodstream)
– Relative ease‐of‐use
• Good cell viability, efficient ease of use
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Phase I Clinical Protocol Summary ‐ AMI
Phase I Study, open label, dose escalation
STEMI, LVEF between 30‐45%
Administration of MultiStem in coronary artery (via transarterial catheter)
delivered on day 2‐5 after Acute MI
‐ Three dose groups (6 patients each) plus 10‐patient registry cohort
Multiple sites, largely regional
Objectives
Primary endpoints: safety (arrhythmias, acute toxicity, hospitalization, death,
mechanical complication)
Secondary endpoints: functionality measures (e.g. LVEF)
Strategy
Provide safety foundation and information to enable design of meaningful
Phase II exploratory study (e.g., dose levels, delivery timing)
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Delivery of MultiStem in AMI patient
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MultiStem for Support of
Hematological Stem Cell Transplants
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MultiStem®: Transplantation (GvHD)
Frequent, potentially life threatening consequence of HSC / BM transplants
Clear need for improved treatments beyond broad immunosuppression
Limited treatment options for complications (e.g., GvHD)
Other problems associated with conditioning regimen (e.g., GI function)
IV delivery of MultiStem in conjunction with HSC / BM transplant
Reduction of GvHD impact and promotion of tissue regeneration and engraftment
Potential for GvHD intervention
MultiStem demonstrated safe and effective in pre‐clinical models
IND approved, clinical trial initiated
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MultiStem® Immuno‐Privileged In Vitro
Mixture
Allogeneic T-
cell controls
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MultiStem® Immunosuppress Alloreactive T Cells
160,000
3H-thymidine counts
100,000
0.25x10^5 0.5x10^5
80,000
1x10^5 2x10^5
60,000
40,000
20,000
0
R (Lewis )+ S (DA) R (Lewis ) No responder or s tim ulator
MAPC (MultiStem) Dose Dependent
Suppresses Immune Effect
Response
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MultiStem® Does Not Induce Immune Response in vivo
Serial administration of MultiStem does not result in detectable allo‐
antibody or T cell sensitization response
‐ Serial administration is safe
‐ Positive control = splenocytes (which do elicit alloreactivity)
FDA review of pre‐clinical data approved use of single universal donor
in multiple indications
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MultiStem Provides Survival Advantage in Rat Acute GvHD Model
Design
Survival
• Rats sublethally irradiated and injected 100%
with bone marrow cells and T‐cells 90%
Graft vs. Host immune response 70%
or at days 1 and 8 50%
40%
No treatment
30%
Treatment, day 1
Results 20%
Treatment days 1+8
10%
• MultiStem provides significant survival 0%
benefit versus animals receiving no 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
treatment Days
• Benefits observable for other GvHD Significant survival advantage in MultiStem treated animals
indicators (body weight, activity,
posture, fur texture, skin)
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Gut Pathology in Rat Acute GVHD Model
Day 15 Pathology, Multi‐treatment Group
GVHD, MultiStem
Treated
GVHD, PBS Control Substantially less
Treated
gastro‐intestinal damage
in MultiStem‐treated
animals
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Phase I Clinical Protocol Summary – Transplantation / GvHD
Phase I study, open label, dose escalation
Patients (leukemia, myelodysplasia) undergoing PBSC / bone marrow transplantation
Administration of MultiStem intravenously
‐ Two treatment arms: Single dose co‐administered with transplant, multiple doses
administered over first 30 days
‐ Continual reassessment methodology
Objectives
Primary endpoints: safety: maximum tolerated dose based on composite of DLTs and
AEs through 30 days
Secondary endpoints: incidence and severity of GVHD, survival, infection
Strategy
Provide safety foundation to allow for (a) prophylactic treatment and intervention for
GVHD, and (b) single and multiple dose treatment approaches
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Opportunities in Other Autoimmune Disease
Treating emergent or chronic autoimmune disease
Immunomodulatory activity of MultiStem for GVHD is mechanistically similar
to biological conditions for other autoimmune conditions
Rapid clinical entry is possible (leveraging off of existing pre‐clinical and
clinical data)
Manufacturing capability already in place
Multiple indications possible
Wide range of autoimmune conditions with unmet medical need as potential
therapeutic targets for MultiStem
I.V. delivery
Other potential benefits to help address tissue damage
33
MultiStem for Ischemic Stroke
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MultiStem®: Ischemic Stroke
Substantial unmet need in the treatment of Ischemic Stroke
Over 700,000 strokes annually in U.S., and ~80%+ ischemic strokes
Substantial functional loss and rehabilitation and follow‐up care costs
Limited treatment options, tPA must be administered within 3 – 4.5 hrs of stroke
IV delivery of MultiStem 48 hours (+/‐) following Ischemic Stroke
Broad potential treatment window
Benefit trophic‐factor mediated: reduce inflammation, stimulate revascularization,
override processes of cell / tissue decline & contribute to tissue regeneration
MultiStem demonstrated safe and effective in pre‐clinical models
IND filing planned for 2H, 2008
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Animal Models of Cerebral Ischemia
MCA Occlusion
MCA Ligation
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Pre‐Clinical Experimental Approach
Key results
• Immunosuppression not required for safe improvement to
neurological function
Experimental approach • Significant functional improvement (locomoter, neurological)
statistically over control
1. Immunosuppression (+/‐) with allo‐/
xenogeneic cells, intracranial delivery • Comparable improvement in locomotor or neurological
function observed among animals receiving cells at 1, 2 or 7
2. Route of administration: viability of IV‐ days
delivery
• Dose response observed with IV‐infused cells, as measured by
3. Delivery window: 1‐7 days post‐stroke neurological improvement
4. Dose escalation • Engrafted cells display neuronal markers in neonatal model
• No abnormal tissues or abnormal pathology observed in
animals kept on study for 1 year post cell transplantation
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Single Dose of Human MultiStem Provides Robust, Durable Improvement
in Rodent Model of Ischemic Stroke
• Dose response –
Mean Neurological Score
2.5
Therapeutic benefit
2
proportional to dose
delivered
1.5 • Treatment timing –
Improvement
1 whether delivery at
day 1, 2 or 7
0.5
Day 42
Day 14
Day 28
Day 56
Stroke
Post-
Baseline
Broad MultiStem product platform for cell‐based therapy initiating clinical trials
Standardized, off‐the‐shelf product (a product, not a procedure)
First truly scalable manufacturing platform for cell therapy
Strong IP position
2008 Focus: Initiating clinical development activities
Ischemic injury: AMI (possibly ischemic stroke)
Immunomodulation and tissue damage: Bone Marrow / HSC Transplantation / GvHD
Potential for broad development program
Other neurological indications, autoimmune disease, other areas
Single “master file” approach = highly efficient development
Progress will be based on validation in appropriate models, collaboration with experts
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Financials & Milestones
40
Summary Financial Data
Revenues $2,846
Debt 0
41
Athersys – Key Milestones
2007
√ Begin ATHX‐105 Phase I study
√ IND approval for MultiStem ‐ HSC transplant support / GvHD
√ IND approval for MultiStem ‐ AMI
√ NASDAQ listing and share registration
√ Evaluate H3 antagonist compounds for multiple indications
2008
√ Review/evaluate ATHX‐105 Phase I top line results
√ Submit ATHX‐105 Phase II plan to FDA
√ Complete additional ATHX‐105 clinical studies re: safety, regional drug absorption
√ Launch MultiStem GVHD / Oncology Support Phase I clinical trial
√ Launch MultiStem AMI Phase I clinical trial
□ Resolve Partial Clinical Hold with FDA
□ Complete further pre‐clinical studies for H3 antagonist program/select candidate
□ IND Approval for MultiStem ‐ Stroke (Initiate trial depending on resource 42
availability)
Athersys, Inc.