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The Adult Stem Cell Company
Building Blocks for Better Health
Our Mission
“Mesoblast Limited aims to become the world leader in novel
therapeutic treatments for patients with bone and joint diseases.
Our primary focus is the rapid and successful commercialisation
of a proprietary, high-margin, adult stem cell platform for the
treatment of conditions with very large, unmet global markets,
including bone fractures, spinal disease, damaged joint cartilage,
and intervertebral disc disease”.
Stem Cells Are Human Building Blocks
Stem Cells
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building blocks for blood, bone, cartilage, fat, vasculature, heart
muscle
can be extracted from various sites
can be used to repair and regenerate a wide range of tissues and
organs
Advantages Of Stem Cells Over Other Medical Therapies
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natural biologicals, safer, less likely to have side-effects
regenerate tissues, reducing long-term health care costs
restore function and quality of life
Adult Stem Cells: The Right Building Blocks
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Advantages Of Adult Stem Cells Over Embryonic Stem Cells
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no ethical issues surrounding embryo creation and destruction
more mature, hence shorter and less costly development processes
significantly reduced risk of cancer formation
not recognized as foreign by immune system of an unrelated party
Therefore, Adult Stem Cells Are Much Closer To Market
Adult Stem Cells:
Haematopoietic vs Mesenchymal
Adult Tissue Contains Two Types of Stem Cells:
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haematopoietic precursor cells:
frequent; blood, bone marrow precursors
mesenchymal precursor cells (MPC):
rare; bone, cartilage, fat, muscle, artery precursors
Advantages Of Mesenchymal Precursors Over Haematopoietic Precursors:
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if isolated, can be easily cultured and expanded
can generate various tissue types needed for functional restoration
not recognized as foreign by immune system of an unrelated party
Proprietary MPC Isolation
Bone
Marrow
spin
adhere
to dish
Bone Marrow (BM)
BM + stem cell-binding antibody
1 hour, on ice
second binding reagent
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density
solution
1/2 hour, on ice
microbeads (Miltenyi)
mixed cell
culture
Historical Isolation Method
1/4 hour, on ice
MACS
magnet
Competitive Advantages:
Precise identification, ease of isolation and scale-up
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1000-fold purer initial stem cell pool
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homogeneous population, high rate cell division
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efficient large-scale expansion
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lower costs of cell culture process
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greater potency of expanded, cultured product
MPCs Give Rise To Various Tissue Types:
Potential Therapeutic Markets!
Mesenchymal
Precursor Cell,
MPC
MPC
Isolated
and Cultured
bone
Orthopaedic
cartilage
other cell types
Adult Stem Cell
Self-Renewing
Stem cell
heart muscle
smooth muscle
Cardiac
Differentiated cell
arteriole
Very Large, Unmet Orthopaedic Markets
1.
Bone Regeneration/Fracture Repair:
(a) delayed or non-union fractures (>500,000 in US annually)
(b) vertebral fusion (300,000 in US annually)
(c) osteoporosis-related fractures (>700,000 vertebral, femoral neck in US annually)
existing therapies inadequate, use of own bone traumatic, MPC regenerate bone
2.
Vertebral Disc Regeneration
affects 20% of population, results in back pain and nerve impingement
existing therapies inadequate, MPC produce material similar to disc cartilage
3.
Cartilage Regeneration in Joints
(a) chronic arthritis of knee ( >800,000 arthroscopic knee surgery in US annually)
(b) acute meniscal tears
existing therapies inadequate, MPC produce material similar to articular cartilage
Very Large, Unmet Cardiovascular Markets
1. Acute Myocardial Infarction (AMI or Heart Attack)
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>1.1 million heart attacks in US annually
46% develop heart failure due to loss of heart muscle <6 years
existing therapies inadequate
MPC can increase blood vessels, protect and rebuild heart muscle
2. Congestive Heart Failure (CHF)
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affects 5 million Americans (2% of the population)
550,000 new US cases annually
existing therapies modest efficacy, symptomatic relief only
MPC can rebuild heart muscle, alleviating the condition
3. Peripheral Artery Disease (PAD) and Wound Healing
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>8 million in US suffer from PAD
>400,000 angioplasties annually to prevent limb amputation
>800,000 diabetic foot ulcers annually
MPC likely to improve blood flow to limbs
Delivering A High-Margin Business Model:
An “Off-the-Shelf” Product
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lack of immune activation:
one “universal” donor provides MPC for multiple unrelated recipients
(allogeneic), contrasting with other cell therapies (autologous)
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purity of MPC starting material:
one “universal” donor can provide easy scale-up, many dosages
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easy access to source material:
pay “universal” donors using existing FDA guidelines
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centralised manufacture and distribution:
commercial quantities of clinical-grade MPC product easily delivered to
market as an “off the shelf” product
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pharmaceutical range profit margins
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proprietary MPC technology -- long term market protection
Strategic Vision: Biological Therapy To Complement
Existing Device Markets
Orthopaedics
MPC may be combined with
• cements/polymers for fractures (e.g Zimmer, Smith & Nephew, Johnson & Johnson)
• fracture repair devices (e.g. Kyphon)
• vertebral cages for vertebral fusion (e.g. Medtronic)
• other biologicals for bone/cartilage regeneration (e.g. Medtronic, Stryker)
• delivery devices for percutaneous injection into vertebral disc/knee cartilage
Cardiovascular
MPC may be combined with
• catheters for coronary/myocardial injection (e.g Johnson & Johnson, Guidant, Medtronic)
• minimally invasive surgical delivery devices (e.g. Ethicon, Guidant, Medtronic)
• devices/biomaterials for wound healing (e.g. Johnson & Johnson)
Executing Results-Oriented Commercial Strategy
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milestone-driven and outcome-focused
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continuous engagement of strategic corporate partners to
generate early revenues in multiple fields, geographies
e.g. orthopaedic delivery companies,
cardiac catheter companies,
Big pharma
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minimise corporate costs, whilst maximising intelligent use of
outsourcing
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deliver therapeutic products to increase quality of life and
materially reduce health care costs
Milestone-Driven, Rapid Commercialisation
Clinical trial protocol
Australian human trials
• orthopaedic (auto)
• cardiovascular (auto)
Safety/toxicology
GMP process
FDA/IND filing (allo)
• orthopaedic
• cardiovascular
IND approval/US trials
IP development
2005
Corporate partnerships
2006
2007
FDA IND
GMP Process for
Allogeneic cells
Clinical Studies
Allogeneic Ib/IIa
randomised,
controlled
Clinical Studies
Autologous Ib
open label
Large Animal
Studies (sheep)
Allogeneic
Tox/Efficacy
Orthopedic
bone fracture,
spine fusion
Orthopedic
bone fracture,
spine fusion
Orthopedic
long bone fracture,
vertebral disc
knee OA
Cardiovascular
myocardial infarct,
catheter delivery
Cardiovascular
chronic ischemia,
catheter delivery
Cardiovascular
acute ischemia,
heart failure
mAb production
immunoselection
serum-free culture,
batch scale-up
GMP process for
Autologous cells
immunoselection,
culture, scale-up
GMP facility
immunoselection,
batch scale-up
IND Development Plan
• contract development and supply agreement for GMP mAb for cell isolation
• contract FDA-licensed cell culture facility in US for allogeneic batch production
• contract Australian cell culture facility for autologous cell production
• optimise cell culture conditions, including serum-free media
• contract Australian medical centres for autologous clinical trials
• contract US and other medical centres for allogeneic clinical trials
• contract GMP facility for analogous mAb/cell culture conditions for sheep cells
• contract animal facilities for orthopedic/cardiac sheep studies (tox/efficacy)
Benefits of Autologous Human Clinical Trials
• optimise ex vivo culture process
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improve cell engraftment and survival (e.g. matrix)
identify appropriate clinical indications amenable to therapy
determine optimal cell dose for safety/efficacy
maintain careful registry of adverse events
determine best route of administration
early validation of technology
Data valuable for inclusion in FDA dossier for IND application
to initiate safety/efficacy trials with allogeneic cells
Early Achievements
External Validation
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December 2004, floated with exceptional institutional and retail investment support,
share price has remained significantly above issue.
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Mesoblast Chief Scientific Advisor awarded $1.5 million grant from Australian
National Health & Research Medical Council for mesenchymal adult stem cells.
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substantial early interest from a number of leading global medical device and
pharmaceutical companies re possible collaborative and commercial relationships.
Organisational
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project management, regulatory, and clinical groups established, working in concert
with Angioblast team to ensure efficient execution of the Joint Expenditure Program.
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February 2005, Mesoblast regulatory team attended FDA advisory meeting, which
served to reinforce regulatory pathway for cellular therapy in orthopedic indications.
Early Achievements, C’td.
Regulatory
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FDA-licensed manufacturing facilities have been identified for large-scale GMP
production of MPC to be used in pivotal, multi-center clinical trials for FDA approval.
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key US orthopaedic and cardiovascular opinion leaders with extensive FDA
experience in pre-clinical safety and toxicologic studies have been identified.
Pilot Clinical Trials
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Pilot Clinical Trials will commence in Australia this year, evaluating safety and
efficacy of autologous (patients’ own) MPC. Specific advances include:
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identification of lead orthopaedic and cardiovascular clinical indications
selection of key Australian opinion leaders and hospital sites
preparation of Ethics Committee Submissions well advanced
contracting of Cell Therapies Pty Ltd, the cell processing facility of the Peter
MacCallum Cancer Centre in Melbourne, to manufacture MPC for these trials
Mesoblast has developed a communications strategy to ensure that the market is
thoroughly informed in a timely basis on the progress of the Pilot Clinical Trials.
Market Guidance For Second Quarter 2005
Regulatory
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formalise contractual arrangements with FDA-licensed manufacturing facilities for
large-scale GMP production of MPC to be used in pivotal, multi-centre clinical trials
for FDA marketing approval.
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formalise contractual arrangements with key US orthopaedic and cardiovascular
opinion leaders to perform pre-clinical safety and toxicologic studies.
Pilot Clinical Trials
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complete Ethics Committee submissions to multiple Australian hospitals for Pilot
Clinical Trials evaluating safety and efficacy of autologous (patients’ own) MPC in
lead orthopaedic and cardiovascular clinical indications.
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while timing of ethics approval, patient recruitment and enrolment will be at sole
discretion of the medical centres and the clinicians involved, Mesoblast’s goal is to
commence Pilot Clinical Trials in as short a timeframe as possible.
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Experienced Board of Directors
Chair Mesoblast: Michael Spooner - ex Ventracor MD & CEO
Directors:
Donal O’Dwyer - ex worldwide President Cordis (J&J)
Byron McAllister - ex VP Ares-Serono (FDA expert)
Prof. Silviu Itescu - Columbia (USA) and Melb. Uni., Corp & FDA advisor
Chair Angioblast: Carter Eckert - ex CEO Knoll, ex Pres Baxter Pharmaceuticals
Chair SAB:
Prof. Silviu Itescu
Members:
Prof. Stephen Graves - Director Orthopaedic Research, Royal Melbourne
Prof. Robert Graham - Exec. Director Victor Chang Institute, Sydney
Prof. Henry Krum - Pfizer Global Advisory Board
Prof. Richard Gilbert - Consultant Lilly&Co., Merck, GlaxoSmithKline