proposal for cord blood banking and therapeutics business (roll up strategy september 2011)v 6
TRANSCRIPT
Gregory A. BonfiglioProteus Venture Partners
Proposal: Build The Leading International Cryo-Banking and Stem Cell Therapeutics Company
September, 2011
CONFIDENTIAL 2
Proteus: An Investment and Advisory Firm Focused on RM
Proteus, Inc.
Proteus Management, LLC
(Fund Management)
Proteus Insights, LLC
(Consulting Services)
Proteus Advisors, LLC
(Investment Banking Services)
Agenda
I. The Market & Opportunity Broader Regenerative Medicine Market Cord Blood Market: Key Metrics & Market Leaders The Opportunity
II. Phase I: Build A Dominant International Bio-Banking Company Acquire A Market Leader & Roll-Up Small Underperforming Banks Drive Revenues with Aggressive Sales & Marketing Expand Tissue Offering
III. Phase II: Bring RM Therapeutics To Emerging Markets Initial Therapies Leverage Stored Tissue Proven Therapies That Address Unmet Regional Medical Needs
IV. Funding & Exit Strategy Funding Required Exit Strategy
CONFIDENTIAL 3
The Promise of Regenerative Medicine
To Regenerate Heart MuscleTo Replace Entire Organs
CONFIDENTIAL 4
Paralyzed Rat(double click to see video)
Paralyzed Rat Walks(double click to see video)
To Heal Acute Spinal Cord InjuryTo Cure Vision DisordersTo Cure Diabetes
Tools for Drug Discovery
CONFIDENTIAL 5
Development of Regenerative Medicine
1968 – ALL patient irradiated, infused with identical twin BMT
1968 – ALL patient irradiated, infused with identical twin BMT
1973 – First unrelated bone marrow transplant
1973 – First unrelated bone marrow transplant
2001 – RhBMP-7 Approved
2001 – RhBMP-7 Approved
FDA Approves Dermagraft (2001)FDA Approves Dermagraft (2001)
1997 – Dolly the Sheep cloned; –FDA ApprovesCarticel (19997) & Apligraf (1999)
1997 – Dolly the Sheep cloned; –FDA ApprovesCarticel (19997) & Apligraf (1999)
1960s 1990s1970s 1980s 2000s
Source: Company websites, NIH, Pubmed
2005 Use of unrelated cord blood in BMT
2005 Use of unrelated cord blood in BMT
1963 – Mouse ASCs isolated1963 – Mouse ASCs isolated
1981 – Mouse ESCs Isolated1981 – Mouse ESCs Isolated
1998 – Human ESCs isolated
1998 – Human ESCs isolated
2007 – iPSCs from Humans
2007 – iPSCs from Humans
Current technologies build on 50 years of research
1993 – ViaCell Begins Banking Cord Blood
1993 – ViaCell Begins Banking Cord Blood
1989 – First Sibling Cord Blood Transplant (Gluckman)
1989 – First Sibling Cord Blood Transplant (Gluckman)
1986 – First Mouse Cloned1986 – First Mouse Cloned
RM Is Entering A New ERA
RM Market is Maturing: Key Metrics Rapidly Expanding Market:• $1.6B in 2010• $20.0B in 2025 • CAGR of 18.34%
Dramatic Revenue Growth• $130M in 2001• $1.6B+ in 2010
Worldwide funding for research Increasing• $2.5B Now• $14B in 10 Years
Clinical Programs • Over 3600 Clinical Trials• Over 400 ex-Oncology
Commercial Products • 400 on Market (Mostly Skin, Tools Media,
& Devices); – 900+ in Development
• 44 Cell Therapies on Market– $1B Revenues– 400 in Development– 28 in PIII/Pivotal Trials
1.2M+ Patients Treated with RM Products.
• 320K+ Cell Therapy Patients
RM Companies• 700+ Co’s involved in RM • 50+ Public Co’s;
– $8-$10B Total Market Cap • 250+ Private Co’s
CONFIDENTIAL 6
RM Market: Global Company Distribution
5%
Asia32 firms
3%
Canada24 firms
56%
USA386 firms
14%
Europe (ex. UK)93 firms
UK133 firms
19%
2%
Middle East17 firms
700+ RM companies worldwide!
CONFIDENTIAL 7
Shire Acquires ABH for $750M
Big Pharma is Actively Engaged
GSK & HSCI: $25M Deal
Merck, Pfizer & Lily Launch Enlight BioScience
Pfizer RM Division: $111M Deal with Athersys (IBD); UCL (RPE); ViaCyte (Diabetes) GSK, AZN & Roche Help Launch Stem Cells
for Safer Medicine in UK
Johnson & Johnson Invests in Tengion & ViaCyte (NovoCell)
Genzyme & Osiris: $1.25B Deal
CONFIDENTIAL 8
GE & Cytori: StemSource
Cephalon & Mesoblast: $2B Deal
Cord Blood Market: Key Metrics
Cord Blood Market Metrics
Market Size:• $3.4B (2010)• $14.9B (2105) • CAGR: 27.9%
Cord Blood Banks:• 150+ Private Banks• 44 Public Banks • 26 Countries
Total Cord Blood Units Stored• 500,000 Units in Public Banks • 1M+ Units in Private Banks
Market Penetration • 1-6% of All Births (varies by
country/region)
Average Fees: Private Banks • $1,750 Initial Collection & Storage
– Range: $890 - $2300• $125 Annual Fee
– Range: $85-$150
Average Fee: Public Banks• $35,000 per Unit (US/EU)
Public Bank Utilization Rate:• 1-3% of Units per year
CONFIDENTIAL 9
Cord Blood Market: Key Metrics
Cord Blood Market Metrics
Total Cord Blood Transplants: 15,000 in 43 Countries • 1,056 per year (2009) • 10,000 per year (2015)• CAGR: 37.8%
50% of All Patients Seeking a BM/PBSC Transplant Cannot Find a Match
Fastest Growing Segment of Cell Transplant Market
• 25% of All Cell Transplants in 2010• 60% by 2015
Regulatory Framework• Regulated as a “Biologic” by FDA/EMA• By October 2011, All Cord Blood Banks
Must be Licensed (BLA)
Therapeutic Applications• 70+ in Clinical Practice• Leukemia; Lymphoma; Blood
Disorders; Hematopoietic Restoration
Clinical Trials • Over 530 FDA Clinical Trials
– 396 New Therapies – 50 Pivotal/PIII Trials
CONFIDENTIAL 10
Cord Blood Therapeutics: Comparison with Bone Marrow
Confidential 11
Cord Blood v. Bone Marrow
Donor Morbidity
HLA Match Required
Units Available
Search Time
2nd or Double Graft
Engraftment Time
GvHD Risk
Ethnic Match
Cord Blood
None 4/6550,000Units
1 Day Yes 26 Days Minimal Easier
Bone Marrow
50% 8/814.6MDonors
3-4 Months
Possible if donor is available
18 Days 50% Difficult
Banking Other Tissues
• Wharton’s Jelly/Entire Cord • CHORI Technology (www.chori.org)
• Placental Tissue (MSCs) • Pluristem Therapeutics, Inc. (www.pluristem.com) ; LifebankUSA (
www.lifebankusa.com)
• Amniotic Fluid (MSCs & HSCs)
• Biocell Center (www.biocellcenter.com)
• Autologous Marrowized Bone• Arnie Caplan (Cell Bank Technologies)
• iPS Cell Lines• Shinya Yamanaka (Japan)/Janet Rossant (Toronto); iPerian (
www.ipierian.com)
CONFIDENTIAL 12
Banking Other Tissues
• Peripheral Blood/Bone Marrow• Stem Cell Assurance, Inc. (www.stemcellassurance.com)• Oristem (www.oristem.com/)
• ALDH Cells (Hematopoietic Stem And Progenitor Cells)• Aldagen (www.aldagen.com)
• Adipose Derived Mesenchymal Cells (MSCs) • Cytori (www.cytori.com); GE Healthcare • Stem Cell Assurance, Inc. (www.stemcellassurance.com)
• Menstrual Blood • CryoCell (www.cryo-cell.com)
CONFIDENTIAL 13
Current Therapeutic Applications for Cord Blood Market
• 25,000 + Cord Blood Transplant To Date
• 3000+ Transplants in 2010o 9% Increase over 2009o 100% Increase (2X) over 2005
• 10,000 Transplants per year projected by 2015o CAGR: 49.3%
• Multi-Cord Transplants Increased 25% in 2010
• 60+ Diseases Treated
CONFIDENTIAL 14
Key Metrics
Agenda
I. The Market & Opportunity Broader Regenerative Medicine Market Cord Blood Market: Key Metrics & Market Leaders The Opportunity
II. Phase I: Build A Dominant International Cryo-Banking Company Acquire A Market Leader & Roll-Up Small Underperforming Banks Drive Revenues with Aggressive Sales & Marketing Expand Tissue Offering
III. Phase II: Bring RM Therapeutics To Emerging Markets Initial Therapies Leverage Stored Tissue Proven Therapies That Address Unmet Regional Medical Needs
IV. Funding & Exit Strategy Funding Required Exit Strategy
CONFIDENTIAL 15
Build A Dominant International Cryo-Banking Company: Strategic Plan
#1: Acquire a Market Leader
• Acquisition Candidate: StemCyte (http://www.stemcytefamily.com/)
3rd Largest Cord Blood Company o Cord Blood Registry, and ViaCord Are Largest
Public & Private Banks Proprietary Plasma Reduction Technology Active Therapeutics Program
o 1300+ Transplants to Dateo Clinical Trials in China (Spinal Cord; Stroke)
Facilities in US, Taiwan, and India
CONFIDENTIAL 16
Build A Dominant International Cryo-Banking Company: Strategic Plan
#2: Roll-Up Small Underperforming Banks
• 20-25 Possible Candidates Worldwide Small “Proprietary” Operations Struggling to Achieve Sustained Profitability
o 2500-7500 Units Under Management Limited Budget for Sales & Marketing Facing New Regulatory Environment
o October 2011 – New FDA Regs Become Effective o Need Update Technology to cGMP/cGLP Standards
Facing Potential Long-term Liability o Storage Obligations for 20+ years
• Aggregate All Banking Operations Into One Facility in Each Country/Region
CONFIDENTIAL 17
Build A Dominant International Cryo-Banking Company: Strategic Plan
#3: Drive Revenues and Reduce Expenses
• Drive Revenues In Private Banks Thru Aggressive Sales & Marketing Strategy Internet/Website; Call Center; Professional Sales Team (Nurses) Build Relationships with Maternity Hospitals & OBGYNs
• Drive Revenues in Public Banks Thru Education/Marketing and Product Differentiation Focus on Transplant Physicians & Transplant Coordinators Led By Internal Transplant Surgeon & SAB Members Differentiate Product By Including Data to Improve Patient Match
o Genetic Datao Ethnic Data
Target Utilization Rate: 3-5%
CONFIDENTIAL 18
Build A Dominant International Cryo-Banking Company: Strategic Plan
#3: Drive Revenues and Reduce Expenses
• Reduce Expenses By Improving Collection Technology and Sourcing Materials from India Improved Collection Technologies: Closed Perfusions/Gravity
Systems Acquire Rights to Technology Source Materials & Manufacture in India
• Reduce Expenses By Leveraging Economies of Scale Single, Global Management Team Standardize Processes Common Sales & Marketing Materials
o Modified for Local Markets
CONFIDENTIAL 19
Build A Dominant International Cryo-Banking Company: Strategic Plan
#4: Expand Tissue Offering
• New Tissue Candidates Include:
• Wharton’s Jelly/Entire Cord
• Placental Tissue (MSCs)
• Amniotic Fluid (MSCs & HSCs)
• Autologous Marrowized Bone
• iPS Cell Lines
• Peripheral Blood/Bone Marrow
• ALDH Cells (Hematopoietic Stem And Progenitor Cells)
• Adipose Derived Mesenchymal Cells (MSCs)
CONFIDENTIAL 20
Agenda
I. The Market & Opportunity Broader Regenerative Medicine Market Cord Blood Market: Key Metrics & Market Leaders The Opportunity
II. Phase I: Build A Dominant International Cryo-Banking Company Acquire A Market Leader & Roll-Up Small Underperforming Banks Drive Revenues with Aggressive Sales & Marketing Expand Tissue Offering
III. Phase II: Bring RM Therapeutics To Emerging Markets Initial Therapies Leverage Stored Tissue Proven Therapies That Address Unmet Regional Medical Needs
IV. Funding & Exit Strategy Funding Required Exit Strategy
CONFIDENTIAL 21
Phase II: Bring RM Therapeutics to Emerging Markets
Selection Criteria for New RM Therapies
• Leverage Existing Tissues Cord Blood “Concentrated” MSCs & HSCs
• Autolgous Cells; Minimally Manipulated Simple Regulatory Path
• Established Record of Successful Treatments Proven Therapies Faster Time To Market & Revenues Build Track Record of Success
• Reasonable Market Size
CONFIDENTIAL 22
Phase II: Bring RM Therapeutics to Emerging Markets
Potential RM Therapies (Near Term)
• Cord Blood Leukemia Thalassemia; Sickle Cell Anemia Hematopoietic Restoration
• MSCs Peripheral Vascular Disease Cardio GvHD Immune Disorders
• HSCs Hematopoietic Restoration
CONFIDENTIAL 23
Phase II: Bring RM Therapeutics to Emerging Markets
Potential RM Therapies - Aesthetic Medicine
• MSCs (Adipose Derived) Skin Rejuvenation Anti-Wrinkle Reconstructive Surgery (Breast Implants)
• Fibroblasts Dermal Fillers
• Conditioned Media (Histogen; ReGen Biosciences) Hair Regrowth Skin Rejuvenation
CONFIDENTIAL 24
Phase II: Bring RM Therapeutics to Emerging Markets
Potential RM Therapies (Mid Term)
• Engineered Skin Products - Wound Repair Apligraf /Dermagraft Diabetic Foot Ulcers
• Dendritic Cells Prostate Cancer
• Cardio Products MSCs CHF or MI
• Fibroblasts ReCell - Wound Repair
• Vision Disorders• Corneal Transplants; RPEs
CONFIDENTIAL 25
Phase II: Bring RM Therapeutics to Emerging Markets
Potential Therapies (Long Term)
• Diabetes • Other Autoimmune Diseases (MS; Lupus; Crohn’s) • CNS Disorders
Parkinson's Alzheimer's Stroke
• Spinal Cord Repair • Tissue & Organs
Bladder Ligaments; Veins; Valves Cartilage
CONFIDENTIAL 26
Agenda
I. The Market & Opportunity Broader Regenerative Medicine Market Cord Blood Market: Key Metrics & Market Leaders The Opportunity
II. Phase I: Build A Dominant International Cryo-Banking Company Acquire A Market Leader & Roll-Up Small Underperforming Banks Drive Revenues with Aggressive Sales & Marketing Expand Tissue Offering
III. Phase II: Bring RM Therapeutics To Emerging Markets Initial Therapies Leverage Stored Tissue Proven Therapies That Address Unmet Regional Medical Needs
IV. Funding & Exit Strategy Funding Required Exit Strategy
CONFIDENTIAL 27
Funding & Exit Strategy
Funding Required: $75M
• Use of Proceeds: Acquisition of Market Leader Execute Roll-Up Of Small Underperforming Banks Centralize Banking Operations in Country/Region Expand Sales & Marketing Program
o Website Design; Call Center Operationso Expand Sales & Marketing Team o Education/Conferences for Transplant Surgeons & Transplant
Coordinators Acquire New Collection Technologies Bring All Facilities Up To cGMP Standards Fund Research on Cord Blood Therapies
CONFIDENTIAL 28
Funding & Exit Strategy
Exit Strategy: IPO in 24-36 Months
• Drive Revenues to $100M-$150M Revenue Ramp of 25% per Quarter Gross Profit Margins: 60%
• List on Most Favorable Exchange Current Cord Bank Valuations: 4-6X Revenues
• Expected Valuation Range: $300M-$600M Expected ROI: 30+% (3 years; assumes 50% ownership)
• Use Proceeds of IPO to Fund Introduction of RM Therapies
CONFIDENTIAL 29
MAJOR RISKS
• Risk: Decline In Market Price for Public Units Due to Increase in Supply
• 550,000 Units now; growing rapidly
o Risk Mitigation Strategy Product Differentiation: Store Higher Quality Product (TNC & CD34+ Counts) ;
Greater Genetic Diversity Expand Market: Increased Therapeutic Applications Drives Additional Demand
and Offsets Increases in Supply
• Risk: Cost of Roll-Up Increases Due to Market Pressures• Acquisition Targets Increase Demands with Knowledge of Roll-Up
Strategy
o Risk Mitigation Strategy Close on Initial Acquisition Targets Simultaneously
CONFIDENTIAL 30
MAJOR RISKS
• Risk: Failure to Execute • Typical Roll-Up Execution Risk
o Risk Mitigation Strategy Assemble World-Class Acquisition Team – Technical & Business (Chris
Mason; Melissa Carpenter) Leverage Proteus Team & Network
• Risk: Competition In Market • Other Groups Looking at Roll-Up Strategy (DW Harper; Cord Blood
America)
o Risk Mitigation Strategy Move Quickly to Acquire Key Targets : 18 Month Window
CONFIDENTIAL 31
CONFIDENTIAL 32
Proposal Re Cryo-Banking and Stem Cell Therapeutics Business
APPENIDX
Cord Blood Transplants Have Doubled In Last 5 Years (NMDP Data)
CONFIDENTIAL 33
Cord Blood Is the Preferred Cell Source for Pediatric Patients (NMDP Data)
CONFIDENTIAL 34
Adult Patients Are the Fastest Growing Population: 58% 0f 2010 Cord Transplants
CONFIDENTIAL 35
0
200
400
600
800
1,000
1,200
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
0-17 18+
Cord Blood Transplants By Patient Age (NMDP Data)
Transplant Outcomes Have Improved Dramatically in Last 5 Years
CONFIDENTIAL 36
• Improved HLA Matching;
• Advances in Conditioning Regimes; KEY FACTORS
• Advances in Post-Transplant Supportive Care
Report Year Period One-Year Survival
2008 2002-2006 54.0%
2007 2001-2005 51.5%
2006 2000-2004 48.8%
2003 1996-2001 42.2%
Clinical Outcomes Related to Quality of Tissue & Match
Quality of Tissue• TNC Count (150+)• CD34+ Count • Size of Unit
Matching Criteria • HLA Match (4/6 Min)• Race & Ethnicity Match • Genetic Match (DNA tissue typing)
CONFIDENTIAL 37
Key Metrics
Cord Shipments By TNC Count for Adults
CONFIDENTIAL 38
0
200
400
600
800
1,000
1,200
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
150+
125-149
90-124
<90
Most Units (77%) for Adults Had TNC >150 (NMDP Data)
82% of all 2010 shipments came from 31% of the available inventory. (NMDP Data)
Less than 12518%
Greater than or equal to
12582%
TNC of Shipments -CY 2010
Less than 12569%
Greater than or equal to
12531%
TNC of Inventory as of June 30, 2010
Public Bank Utilization Rates: 2010 Inventory and Shipments
CONFIDENTIAL 39
Current Therapeutic Applications for Cord Blood
60+ Diseases Treated• Leukemias And Lymphomas, Including:
– Acute Myelogenous Leukemia
– Acute Lymphoblastic Leukemia• Multiple Myeloma And Other Plasma Cell Disorders• Severe Aplastic Anemia And Other Marrow Failure States, Including:
– Severe Aplastic Anemia
– Fanconi Anemia • SCID And Other Inherited Immune System Disorders, Including:
– Severe Combined Immunodeficiency (SCID, All Sub-types)
– Wiskott-aldrich Syndrome • Hemoglobinopathies, Including:
– Beta Thalassemia Major
– Sickle Cell Disease
CONFIDENTIAL 40
Diseases Treated: Hematologic Malignancies (NMDP Data)
CONFIDENTIAL 41
Diseases Treated:Non-Malignant Disorders (NMDP Data)
CONFIDENTIAL 42
Cord Blood Therapies in Clinical Development: 426 Ongoing FDA Trials
CONFIDENTIAL 43Source: ClinicalTrials.gov (www.clinicaltrials.gov)
FDA Trials Involving Cord Blood Address Numerous Conditions & Diseases
Source: ClinicalTrials.gov (www.clinicaltrials.gov)
• Bacterial and Fungal Diseases• Behaviors and Mental Disorders• Blood and Lymph Conditions• Cancers and Other Neoplasms• Digestive System Diseases• Diseases and Abnormalities at or
before Birth• Ear, Nose, and Throat Diseases• Eye Diseases• Gland and Hormone Related
Diseases• Heart and Blood Diseases• Immune System Diseases• Wounds and Injuries
• Mouth and Tooth Diseases• Muscle, Bone, and Cartilage Diseases• Nervous System Diseases• Nutritional and Metabolic Diseases• Parasitic Diseases• Respiratory Tract (Lung and Bronchial)
Diseases• Skin and Connective Tissue Diseases• Substance Related Disorders• Symptoms and General Pathology• Urinary Tract, Sexual Organs, and
Pregnancy Conditions• Viral Diseases
CONFIDENTIAL 44
NMDP Data
CONFIDENTIAL 45
NMDP Data
CONFIDENTIAL 46
NMDP Data
CONFIDENTIAL 47
Adult Patients Are the Fastest Growing Population: 58% 0f 2010 Cord Transplants
CONFIDENTIAL 48
Tissue Engineering: Skin Substitute/Wound Healing Products
EpiCel® CorMatrix ®
Apligraf ®
CONFIDENTIAL 49
RM Applications:Tissue Engineering – Skin & Wound Repair
Company Product Product Type Status IndicationOther
InformationPros/Cons
Organo-genesis
Apligraf®
Allogeneic neonatal fibroblasts/keratinoc
ytes on scaffoldCommercial
Diabetic skin ulcers
1st cell-based regenerative
product approved in 1998 in the
U.S.
3 times faster healing in
difficult wounds/Most
expensive, short shelf-life
LifeCell Corporation
AlloDerm® Acellular dermal allograft
Commercial
Abdominal wall
repair/breast reconstruction
Can be grafted simultaneously with epithelial
autografts; shelf life 2 yrs
No refrigeration or
freezing required/Potential for disease transmission
TengionNeo-
Bladder Augment™
Autologous urothelial and
muscle cells on biodegradable
scaffold for implantation
Phase II complete
(October 2008)
Bio-engineered
organs
12-month data presented at AUA
2009 annual conference
No immunosuppressive drugs/2 safety events
Osiris Therapeutics,
Inc.Prochymal®
Allogeneic adult mesenchymal stem
cell therapy
Phase III complete (May
2009)
Graft versus host disease
Fast Track designation
(FDA), Orphan Drug (FDA &
EMEA)
Large-scale production/P3
data: not statistically better than
placebo
RM Applications: Orthopedic
Company Product Product Type Status Indication Other Information Pros/Cons
TiGenixChondro-Celect®
Autologous chondrocytes
injection
EU approval (Oct 2009)
Cartilage repair
1st approved cell therapy by EMEA
More durable hyaline cartilage*/separate
periosteal** patch, 4-6 wks culture time
Genzyme Carticel®Autologous
chondrocytes injection
CommercialCartilage
repair Cell therapy in use for
10+ yrs in the U.S.
3-4 wks culture time/separate
periosteal patch
Aesculap Implant
Systems, Inc.
Novocart ®
3D
Autologous chondrocytes on 3D bioscaffold
Commercial in EU
Cartilage repair
Will be a biologic-device combination product in the U.S.
No periosteal patch/2-step process, biopsy &
implantation
Osiris Therapeutics
, Inc.Chondrogen®
Allogeneic adult mesenchymal
stem cell therapy
Phase I/II complete
(Feb 2008)
Osteoarthris and knee
injury
Alliance between Osiris and Genzyme
Off-the-shelf product potential; preliminary data: significant pain improvement/in-vitro
MSC proliferation could be limited
RM Applications: Cardiovascular
Company Product Product Type Indication Status Other Information Pros/Cons
Kensey Nash
CorporationAngio-Seal™
Vascular closure device
Arterial seal CommercialClass III device, in market since 1996
Easy to use/vascular
complications in 0.2-2% of patients*
Cytori
Adipose-derived stem
and regenerative
cells (ADRCs)
Autologous adult stem cell therapy
Heart failurePhase I in EU
(2007)Official data to be
reported in 1Q 2010
No cell culture; P1 met safety &
feasibility goal/
Advanced Cell
Technology, Inc.
MyoblastAutologous
skeletal myoblasts stem cell therapy
Heart failurePhase I
completed (2007)
Injection via a catheter,
1-yr data presented at 2007 AHA annual
meeting
No in-vitro differentiation; 1-yr
data: significant improvement in
tissue regrowth and function/requires
tissue culture, depends on in-vivo transdifferentiation
*Published data from Kadner K; et. al, Vasc Endovascular Surg 2008; 42; 225
CONFIDENTIAL 52
RM Applications: Cardiovascular
Company Product Product TypeIndicatio
nStatus Other Information Pros/Cons
Osiris Therapeutics,
Inc.Prochymal®
Allogeneic adult mesenchymal
stem cell therapy
Heart failure
Phase II (May 2009)
Intravenous infusion,
Phase I data in JACC (May 2009)
No in-vitro differentiation; 2-yr P1 data: 6.6 point
improvement in LVEF*; reduction in
arrhythmias (p<0.006)/cell
culture needed, limited in-vitro
MSC propagation
Geron GRNCM1hESC-derived cardiomyocytes
Heart failure
Pre-clinical
Intracardiac injection,
Data published in Nat Biot, 2007**
Successful engraftment and heart function in 100% of rats/in-
vitro differentiation; potential for
teratoma
*LVEF: Left Ventricular Ejection Fraction, a measure of overall heart function**Laflamme MA, et. al, Nature Biotechnology, 2007, 25: 1015-1024
CONFIDENTIAL 53
RM Applications: Diabetes
Company Product Product Type Indication Status Other Information Pros/Cons
NovocellHuman islets
encapsulated in PEG
Allogeneic cell therapy
Type 1 diabetes
Phase I/II complete (started in
2006)
Preliminary data presented in 66th
ADA
Results marginal/regular
insulin shots needed
NovocellhESC-derived human islets
Allogeneic cell therapy
Type 1and 2 diabetes
R&D2-yr drug discovery agreement w/ Pfizer
(Dec 2008)
Insulin production in mice/tumors
developed in 5% of treated mice*
*Nature Reports Stem Cells, 28 May 2009
CONFIDENTIAL 54
RM Applications: Diabetes
Company Product Product Type Indication Status Other Information Pros/Cons
Osiris Therapeutics,
Inc.Prochymal®
Allogeneic adult mesenchymal
stem cell therapy
Type 1 diabetes
Phase II (started in Jun 2008)
Collaborative agreement with JCR
Pharmaceuticals (2003), Japan &
JDRF (2007)
Good safety profile to
date/in-vitro MSC
proliferation could be limited
Harvard Stem Cell Institute
Induced pluripotent stem (iPS)
cells
Cell therapyType 1 and 2
diabetesR&D
Proc Natl Acad Sci USA (2009)
Differentiate mature cells
into beta cells/ low efficiency**
** Proceedings of National Academic Sciences USA (Sep 15 2009, Vol 106, 15768-15773)
CONFIDENTIAL 55
RM Applications: CNS
Company Product Product Type Indication Status Other Information Pros/Cons
Integra Life Sciences
CorporationNeuraWrapTM Collagen sleeve
implant
Peripheral nerve
protectionCommercial
Pre-cut*; bio-absorbable; easy
placement/repairs < 30-40mm
Opexa Therapeutics
Tovaxin® vaccine
Autologous myelin-reactive T
cell therapy
Multiple Sclerosis
Phase I/II complete
(Dec 2008)
Increased baseline disease burden in all
trial patients
55% reduction in relapses/primary and secondary endpoints
not met
* http://www.podiatrytoday.com/article/8978
Company ProductProduct
TypeIndicatio
nStatus
Other Information
Pros/Cons
GeronhESC-derived
oligodendrocytesAllogeneic cell therapy
Spinal cord
injuries
IND put on 2nd clinical hold (Aug
2009)*
More preclinical studies done
Locomotive function in animal model/high frequency of cysts in one preclinical study
Neuralstem, Inc.
Neural stem cellsAllogeneic fetal neural stem cells
ALS
Phase I approved
(December 2009)
Preclinical data in J of Comp
Neu Jun 2009,Tumor-free
pigs**
Neuroprotective effect seen in
rats***/in-vitro MSC propagation could be
limited
RM Applications: CNS
* http://www.stemcellresearchnews.com/absolutenm/anmviewer.asp?a=1768&z=9** http://money.cnn.com/2008/04/08/news/companies/stem_cell/index.htm*** Journal of Comparative Neurology, 514: 297-309 (2009)
CONFIDENTIAL 57
RM Applications: Oncology
Cancer Vaccines• Vaccine that uses greater concentration of tumor antigens to
give a boost to the immune systemTumor-specific antigensCells loaded with tumor-specific antigens
Adoptive T Cell Therapy• Isolation, ex-vivo expansion and activation, & infusion of T-
cells into patientTumor-infiltrating lymphocytes (TIL; lymchocytes inside the tumor)Engineered/genetically modified T cells
CONFIDENTIAL 58
Cancer: Adoptive T-Cell Therapy (TIL & T-Cells)
Source: J Clin Invest 2007 117:1466-76CONFIDENTIAL 59
RM Applications: Oncology/Hematology
Company/Institute
Product Product Type IndicationDevelopment
StageOther
InformationPros/Cons
Aastrom BioSciences,
Inc.
Vascular repair cells
Bone-marrow-derived adult stem
and progenitor cells
Vascular regeneration
Phase II started in Apr 2007
Data to be analyzed in 4Q
2009
Off-the-shelf potential; 9.5 mo data: evidence of
blood flow and wound healing/need
differentiation; in-vitro propagation could be limited
Dendreon Provenge®
Autologous dendritic cells
against prostatic acid phosphatase
Prostate cancer
BLA submitted (Nov 2009)
GMP facility
P3 data showed safety; reduced the
risk of death by 22.5%/treatment repeated 3 times
RM Applications: Oncology/Hematology
Company/Institute
Product Product Type IndicationDevelopment
StageOther Information Pros/Cons
U.S. National Cancer Institute
Tumor-infiltrating
lymphocytes (TIL)
Autologous T cell from melanoma tumor
MelanomaPhase II complete
(started in Jun 2003)
Treatment offered after a brief
chemotherapy
Tumor-specific T cells, T cell persistence post infusion/30-40% efficiency in producing TILs; long
culture time (wks); multiple rounds of T cell activation; requires IL-2 support
Roger William Medical Center
Designer/Engineered T
cells
Autologous T cell transduced to express
receptor for PSMA antibody
Prostate cancer
Phase I started April 2008
Retroviral transduction
No tumor tissue needed; short culture time (days); independent of TCR-MHC interaction/in-vivo antigen escape or poor expression; potential of genetic
mutagenesis
CONFIDENTIAL 61
RM Applications: Eye
Company ProductProduct
TypeIndication Status Other Information Pros/Cons
Advanced Cell Technology,
Inc.
hESC-derived retinal
pigmented epithelial
(RPE) cells
Allogeneic cell therapy
Adult macular degeneration
IND filed (Nov 2009)
GMP-compliant RPE cell line
(cryopreserved)
100% vision improvement in rats, no
ASE*, hESC line w/o embryo
destruction/potential for teratomas
Intercytex
hESC-derived retinal
pigmented epithelial
(RPE) cells on a synthetic
matrix
Allogeneic cell therapy
Adult macular degeneration
PreclinicalPhase I/II in UK in
late 2010
Vision improvement, no ASE in
preclinical/potential for teratomas
*ASE = Adverse Safety Event
RM Applications: Aesthetic Medicine
Source: Intercytex
Company Product Product Type Indication Status Other Information Pros/Cons
Fibrocell Science
Laviv™Autologous cell
therapyFacial
wrinkles
BLA review in progress (due
Jan 2010)cGMP facility
Significant wrinkle improvement
(p<0.0001)/exact mechanism of
action unknown
Intercytex ICX-TRCAutologous dermal papilla cell therapy
Male baldness and female hair
thinning
Phase II completed in
UK (Mar 2008)
Looking for partner for further clinical
development
Increase in hair count in 78% of
subjects/culture time
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