Keynote Presentation for Alliance for Regenerative's RegenMed Investor Day

Building out a multi-product
regenerative medicine company
Keynote presentation to Alliance for Regenerative Medicine Investor Day
New York, 26 March 2014

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
This presentation, including any comments made during or following the presentation, may contain forward-looking statements that
are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. These statements may relate to, but
are not limited to: expectations regarding the safety or efficacy of, or potential applications for, Mesoblast's adult stem cell
technologies; expectations regarding the strength of Mesoblast's intellectual property, the timeline for Mesoblast's regulatory
approval process, and the scalability and efficiency of manufacturing processes; expectations about Mesoblast's ability to grow its
business and statements regarding its relationships with Teva Pharmaceutical Industries, and Lonza and future benefits of those
relationships; statements concerning Mesoblast's share price or potential market capitalization; and statements concerning
Mesoblast's capital requirements and ability to raise future capital, among others. Actual results may differ from the results
anticipated in these forward-looking statements, and the differences may be material and adverse. Factors and risks that may cause
Mesoblast's actual results, performance or achievements to be materially different from those which may be expressed or implied by
such statements, include, without limitation: risks inherent in the development and commercialization of potential products;
uncertainty of clinical trial results or regulatory approvals or clearances; government regulation; the need for future capital;
dependence upon collaborators; and protection of our intellectual property rights, among others. Accordingly, you should not place
undue reliance on these forward-looking statements.
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Successful products built on traditional Pharma fundamentals
2
Proprietary platform technology
 adult vs embryonic vs iPS
 autologous vs allogeneic
Intellectual property
 protection of commercial interests
Strong cash balance
 strategic needs, product development
Strategic partnerships
 product development and
commercialisation
Development of multiple products
 target unmet medical need
 technical/competitor advantages
 pricing strategy
Defined regulatory path
Control of manufacturing
Product delineation for partners,
reimbursement
Commercial scale-up
Reduction of COGS
Commercialization strategy Manufacturing capabilities
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3
4
5
Product on market
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2
3
4
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Proprietary platform technology – must carry inherent
success factors to support product development and business
model
 Mesoblast developing proprietary adult mesenchymal lineage cells,
including Mesenchymal Precursor Cells (MPCs), Mesenchymal Stem Cells
(MSCs), Dental Pulp cells and Adipose cells
– IP protection for cell type, manufacturing process, indication
– Adult stem cells not associated with ethical or safety issues of embryonic
stem cells and iPS cells
– excellent safety profile across multiple clinical indications
– easy to expand in large numbers
- low cost of goods, no supply constraints
- high margin business model
– relatively non-immunogenic, can be used from one donor for many
recipients
- “off the shelf”, classic pharmaceutical drug model
- batch to batch consistency
- clear, rapid regulatory pathway3
1

Intellectual property (IP) – protects commercial interests
 Mesoblast owns or has exclusive rights to more than 60 patent families
covering mesenchymal lineage cells, which provide commercial advantages
and long-term protection across its technology platforms
 Acquisition of Osiris culture-expanded MSCs business was complementary
and additive to Mesoblast’s existing patent position on MPCs, Dental Pulp
and Adipose cells
 IP covers compositions-of-matter, cell extraction processes for purification
and manufacturing scale-up, and a broad range of applications in key
markets including the United States, Europe, Japan and China
4
2

Strong cash position – allows multiple product development
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Commercial success of platform technology developer is critically
dependent on having access to substantial sources of funds, in order to
– ensure timely, optimal product clinical development
– enable multiple clinical development programs in parallel
– allow maximal exploitation of patent life
– facilitate establishment of more balanced partnering relationships
3

 Mesoblast’s alliances include:
– cardiovascular and neurological MPC programs being developed in
partnership with Teva Pharmaceutical Industries Ltd
– Graft Versus Host Disease MSC programs in children and adults in Japan
being developed in partnership with JCR Pharmaceuticals
– strategic relationship with biologics manufacturer Lonza to ensure
commercial scale-up and supply, product delineation, COGS reductions,
and expansion of clinical manufacturing
6
4 Strategic partnerships – additional sources of funding,
validation of technology, access to product commercialization
and other areas of partners’ expertise

Manufacturing capabilities – define ability to commercialize
cell-based products
 Manufacturing strategy must incorporate regulatory, commercial, and R&D
strategies and consider:
– Control of manufacturing
– Regulatory compliance with best practice
– Commercial scale-up with capacity for commercial product supply
– Product delineation to support and separate partner markets and
optimise reimbursement
– Profitability variables including reduction of COGS
– Management of product lifecycles and new product development
- changes in formulation or dosage
- products derived from different tissue sources (e.g. bone marrow,
adipose, dental pulp),
- combination therapies using different modes of delivery or devices,
biologic modifications of cells
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Concurrent development of multiple products
 Increases risk-adjusted probability of success
 Leverages safety data across technology platform
 Allows re-focusing of clinical strategy as results become
available
 Leverages IP protection maximally
 Early success may validate rest of pipeline
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65

Defined product regulatory path – continues to evolve for cell-based
products, combining traditional approval process with unique features
9
PACT Website, Accessed on March 25, 2014
https://secure.emmes.com/pactweb/system/files/evaluation_criteria_v3_0.pdf
Discover; proof of
concept; cell product
potential; therapeutic
mechanism and
pathway; cell and
disease interaction
Basic Research

Cell variability drives regulatory paradigm
 Cell variability at a number of levels
 Donor - allogeneic/autologous, gender,
age, health?
 Tissue source – bone marrow, adipose,
cardiac, neural?
 How are the cells isolated/processed?
Manual or device?
 Are the cells cultured? If so, how?
Serum y/n? PD? Scale-up?
 Product characterization – surface
markers for identity and purity?
 Potency (biological activity) assay
candidates?
 Cryropreservation? Final formulation?
Stability?
 Comparability between lots and
between products?
10 © Nat Rev Mol Cell Biol. 2011 February ; 12(2): 126–131

Ongoing regulatory interactions essential for successful product launch
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Assay matrix – some are quantifiable
Qualitative based on MOA
MOA hypotheses (re-evaluated)
Best candidate(s) – set quantitative values
In vivo correlation
Finalize potency
Discovery
Preclinical PoC and P/T
Pre(pre)-IND IND PI PII PIII BLA
EOP2EOP1 Pre-
BLA
OS
PA
Product characterization
© Mendicino, 2013, unpublished
Commercial manufacturing

Mechanisms of Action (MOA) drive product development
 Must understand well the unique MOAs and scientific advantages
attributable to the particular cell therapy being developed
 Is the proposed MOA replacement of damaged tissue by engraftment of
differentiated or undifferentiated cells?
 Is the proposed MOA repair of endogenous tissue by secretion of paracrine
factors?
 Product MOA must provide rationale for specific disease indication being
targeted
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Mesenchymal lineage cells secrete multiple paracrine factors,
giving rise to complex MOAs
Mesoblast's strategic product focus is guided by specific MOAs of our cellular
therapies
The mesenchymal lineage stem cells respond to signals from inflammation and
/or tissue damage by releasing a range of factors which act on endogenous
tissues to
– stimulate blood vessel growth and maturation
– reverse endothelial dysfunction
– increase survival and improve function of various cell lineages, including
cardiac muscle cells, cells of central nervous system, bone-forming cells,
and cartilage-producing cells
– reduce scar formation and fibrosis
– induce polarization of pro-inflammatory monocytes to a non-
inflammatory phenotype
– inhibit activated T cells and induce regulatory T cells
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Mesoblast’s pipeline in key therapeutic areas
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6

How is the regenerative medicine sector performing?
Source: Acuity Technology Management
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0
2
4
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10
12
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A sample of company sponsored stem cell products in clinical trials 2014
Phase 3
Phase 2
Phase 1

Leveraging strengths
 Probability of success enhanced by:
– proprietary technology offering unique scientific and clinical advantages
– strong IP position
– products specifically targeting major medical conditions
– strong cash position enabling simultaneous product development where
multiple products developed in parallel to increase probability of success
– strategic partnerships providing additional sources of funding and
expertise
– manufacturing operations which are profitable and aligned to the
commercial strategy
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Leading the development of
adult stem cell therapies

Keynote Presentation for Alliance for Regenerative's RegenMed Investor Day

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