Title to go here

1
The Adult Stem Cell Company Building Blocks for
Better Health
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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.

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Stem Cells Are Human Building Blocks

• Stem Cells
• 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
• natural biologicals, safer, less likely to have
  side-effects
• regenerate tissues, reducing long-term health
  care costs
• restore function and quality of life

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Adult Stem Cells The Right Building Blocks

• Advantages Of Adult Stem Cells Over Embryonic
  Stem Cells
• 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

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Adult Stem Cells Haematopoietic vs Mesenchymal

• Adult Tissue Contains Two Types of Stem Cells
• 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
• 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

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Proprietary MPC Isolation
Bone Marrow
Bone Marrow (BM)
adhere to dish
spin
BM stem cell-binding antibody
1 hour, on ice
second binding reagent
density solution
1/2 hour, on ice

microbeads (Miltenyi)
mixed cell culture
1/4 hour, on ice
MACS magnet
Historical Isolation Method

• Competitive Advantages
• Precise identification, ease of isolation and
  scale-up
• 1000-fold purer initial stem cell pool
• homogeneous population, high rate cell division
• efficient large-scale expansion
• lower costs of cell culture process
• greater potency of expanded, cultured product

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MPCs Give Rise To Various Tissue
Types Potential Therapeutic Markets!
Orthopaedic
Mesenchymal Precursor Cell, MPC
bone
MPC Isolated and Cultured
cartilage
other cell types
heart muscle
Adult Stem Cell Self-Renewing
Cardiac
smooth muscle
Stem cell
Differentiated cell
arteriole
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Very Large, Unmet Orthopaedic Markets

• Bone Regeneration/Fracture Repair
• (a) delayed or non-union fractures (gt500,000 in
  US annually)
• (b) vertebral fusion (300,000 in US annually)
• (c) osteoporosis-related fractures (gt700,000
  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 ( gt800,000
  arthroscopic knee surgery in US annually)
• (b) acute meniscal tears
• existing therapies inadequate, MPC produce
  material similar to articular cartilage

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Very Large, Unmet Cardiovascular Markets

• 1. Acute Myocardial Infarction (AMI or Heart
  Attack)
• gt1.1 million heart attacks in US annually
• 46 develop heart failure due to loss of heart
  muscle lt6 years
• existing therapies inadequate
• MPC can increase blood vessels, protect and
  rebuild heart muscle
• 2. Congestive Heart Failure (CHF)
• 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
• gt8 million in US suffer from PAD
• gt400,000 angioplasties annually to prevent limb
  amputation
• gt800,000 diabetic foot ulcers annually
• MPC likely to improve blood flow to limbs

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Delivering A High-Margin Business Model An
Off-the-Shelf Product

• lack of immune activation
• one universal donor provides MPC for multiple
  unrelated recipients (allogeneic), contrasting
  with other cell therapies (autologous)
• purity of MPC starting material
• one universal donor can provide easy
  scale-up, many dosages
• easy access to source material
• pay universal donors using existing FDA
  guidelines
• centralised manufacture and distribution
• commercial quantities of clinical-grade MPC
  product easily delivered to market as an off
  the shelf product
• pharmaceutical range profit margins
• proprietary MPC technology -- long term market
  protection

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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)

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Executing Results-Oriented Commercial Strategy

• milestone-driven and outcome-focused
• continuous engagement of strategic corporate
  partners to generate early revenues in multiple
  fields, geographies
• e.g. orthopaedic delivery companies,
• cardiac catheter companies,
• Big pharma
• minimise corporate costs, whilst maximising
  intelligent use of outsourcing
• deliver therapeutic products to increase
  quality of life and materially reduce health
  care costs

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• 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
• Corporate partnerships

Milestone-Driven, Rapid Commercialisation
2006
2005
2007
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FDA IND
GMP Process for Allogeneic cells mAb
production immunoselection serum-free
culture, batch scale-up
Clinical Studies Allogeneic Ib/IIa randomised,
controlled
Cardiovascular myocardial infarct,
catheter delivery
Orthopedic
bone fracture, spine fusion
GMP process for Autologous cells
immunoselection,
culture, scale-up
Clinical Studies Autologous Ib open label
Orthopedic bone fracture, spine fusion
Cardiovascular chronic ischemia, catheter
delivery
Large Animal Studies (sheep) Allogeneic Tox/Effic
acy
Cardiovascular acute ischemia, heart failure
Orthopedic long bone fracture, vertebral
disc knee OA
GMP facility immunoselection,
batch scale-up
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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)

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Benefits of Autologous Human Clinical Trials

• optimise ex vivo culture process
• 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

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Early Achievements

• External Validation
• December 2004, floated with exceptional
  institutional and retail investment support,
  share price has remained significantly above
  issue.
• Mesoblast Chief Scientific Advisor awarded
  1.5 million grant from Australian National
  Health Research Medical Council for mesenchymal
  adult stem cells.
• substantial early interest from a number of
  leading global medical device and
  pharmaceutical companies re possible
  collaborative and commercial relationships.
• Organisational
• project management, regulatory, and clinical
  groups established, working in concert with
  Angioblast team to ensure efficient execution of
  the Joint Expenditure Program.
• February 2005, Mesoblast regulatory team
  attended FDA advisory meeting, which served to
  reinforce regulatory pathway for cellular therapy
  in orthopedic indications.

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Early Achievements, Ctd.

• Regulatory
• 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.
• key US orthopaedic and cardiovascular opinion
  leaders with extensive FDA experience in
  pre-clinical safety and toxicologic studies have
  been identified. 
• Pilot Clinical Trials
• Pilot Clinical Trials will commence in
  Australia this year, evaluating safety and
  efficacy of autologous (patients own) MPC.
  Specific advances include
• o identification of lead orthopaedic and
  cardiovascular clinical indications o
  selection of key Australian opinion leaders and
  hospital sites
• o preparation of Ethics Committee Submissions
  well advanced  
• o 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.

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Market Guidance For Second Quarter 2005

• Regulatory
• 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.
• formalise contractual arrangements with key US
  orthopaedic and cardiovascular opinion leaders
  to perform pre-clinical safety and toxicologic
  studies. 
• Pilot Clinical Trials
• 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.
• while timing of ethics approval, patient
  recruitment and enrolment will be at sole
  discretion of the medical centres and the
  clinicians involved, Mesoblasts 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 ODwyer -
ex worldwide President Cordis (JJ) 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 LillyCo., Merck,
GlaxoSmithKline