Leading the world in the development of adult stem cell therapies. June 2014

Transcription

1 Leading the world in the development of adult stem cell therapies June 2014

2 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. 1

3 Shareholder value and ownership Market valuation Issued shares 321 million Current share price (market close, 4 June 2014) $4.42 Market capitalization, circa $1.41 billion Cash reserves (at 31 March 2014) $241 million Shareholder ownership 24% 18% Institutions/sophisticated investors Retail investors Management Strategic investors 9% 49% 2

4 Mesoblast s pipeline in key therapeutic areas 3

5 Successful products built on traditional Pharma fundamentals Commercialization strategy Manufacturing capabilities 1 Proprietary platform technology adult vs embryonic vs ips autologous vs allogeneic 1 Defined regulatory path 2 Intellectual property protection of commercial interests 2 Control of manufacturing 3 Strong cash balance strategic needs, product development 3 Product delineation for partners, reimbursement 4 Strategic partnerships product development and commercialisation 4 Commercial scale-up 5 Development of multiple products target unmet medical need technical/competitor advantages pricing strategy 5 Reduction of COGS 4 Product on market

6 1 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 5 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 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 pathway

7 2 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 6

8 3 Strong cash position allows multiple product development 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 7

9 5 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 8

10 Ongoing regulatory interactions essential for successful product launch MOA hypotheses (re-evaluated) In vivo correlation Qualitative based on MOA Assay matrix some are quantifiable Best candidate(s) set quantitative values Finalize potency Commercial manufacturing Product characterization Discovery Preclinical PoC and P/T Pre(pre)-IND IND PI PII PIII BLA PA OS EOP1 EOP2 Pre- BLA 9 Mendicino, 2013, unpublished

11 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 10

12 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 11 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 noninflammatory phenotype inhibit activated T cells and induce regulatory T cells

13 Mesoblast leads the expanding regenerative medicine sector A sample of company sponsored stem cell products in clinical trials Phase 3 Phase 2 Phase

14 Mesoblast s pipeline in key therapeutic areas 13

15 Therapeutic areas of focus 1. Programs in cardiac and vascular conditions Phase 3 Congestive heart failure NYHA Class II/III using MPCs Phase 2 Congestive heart failure NYHA Class IV using MPCs Acute myocardial infarction using MSCs injected intravenously Acute myocardial infarction using MPCs delivered by intracoronary catheter Preclinical Ischemic stroke using MPCs

16 Natural History of Acute Myocardial Injury, Myocardial Inflammation and Heart Failure Normal Heart IC Revascor Initial Myocardial Injury Inflammation & Repair Early Injury Phase IV Prochymal Hyper-acute Injury Phase Adverse LV Remodeling and Dilation Compensatory and Remodeling Phase Transendocardial Revascor Chronic HF Phase 15 Episodes of Decompensated Heart Failure Time Death LVAD + Revascor

17 Change from Baseline in LV End-Systolic Volume (LVESV) and LV End Diastolic Volume (LVEDV) Obtained Using 2-D Echo at Months 6 and 12 Post Treatment

18 Kaplan-Meier Analysis Time-to-First HF-MACE by Treatment (36 Months Follow-up) 150M MPC vs Control P-value = based on log-rank test

19 Phase 3 Chronic Heart Failure Events Driven Trial Phase III morbidity-mortality trial Event driven trial of adjudicated MACE Cardiac death or resuscitated cardiac death Non-fatal decompensated HF event ~ 1700 enrolled patients (~ 850 per treatment group) at ~ 225 sites and ~ 80 injection centers Anticipate 20% MACE rate annually in control group Independent and unblinded DMC will monitor the progress of the trial Adaptive design, two interim analyses 18

20 Therapeutic areas of focus 2. Programs in inflammatory and immune-mediated conditions Phase 3 Crohn s disease using MSCs Phase 2 Type 2 diabetes inadequately controlled by Metformin and other oral glucose-lowering agents using MPCs Chronic kidney disease with type 2 diabetes using MPCs Rheumatoid arthritis using MPCs

21 Therapeutic areas of focus 3. Programs in orthopedic conditions of the spine Phase 3-ready Degenerative intervertebral disc disease using MPCs (non-surgical) Lumbar spinal fusion using MPCs (surgical)

22 Degenerative disc repair Phase 2 trial in patients >6 months discogenic low back pain failing all other therapies 100-patient Phase 2 trial randomized, placebo-controlled comparison of saline, HA, HA + 6M MPC, HA + 18M MPCs injected into culprit painful disc 12-month outcome results of Phase 2 trial in 100 patients showed that compared to controls both MPC-treated groups had: improvement in chronic low back pain (reduction in mean pain score; increased proportion of patients achieving >50% reduction in pain score; increased proportion of patients achieving minimal residual back pain) reduced opioid use for pain relief reduced need for additional surgical and non-surgical interventions for persistent pain improvement in function (reduction in mean disability score and increased proportion of patients achieving minimal residual functional disability) radiographically-determined improvement in disc stability Phase 3 trials planned for intervertebral disc repair, EOP2 FDA meeting in Q2 21

23 Both MPC groups demonstrate a statistically significant increase in patients with at least a 50% improvement of VAS back pain at 12 months 80.0% Overall p = % 69.2% 60.0% 50.0% 61.5% p = p = % 33.3% 30.0% 20.0% Pooled Controls 6M MPCs 18M MPCs 22

24 Mean Translational/Angular Motion Correlates With Disc Height 23

25 Time to Treatment Failure p = M vs. Saline p = M vs. Saline 24 Treatment failure defined as the occurrence of any of the following at the treated level: surgical intervention (spine fusion, discectomy or artificial disc replacement) or injection (epidural steroid injection, rhizotomy or transforaminal injections)

26 Therapeutic areas of focus 4. Programs in oncology conditions associated with bone marrow transplantation Commercial Ready Pediatric GVHD (Canada & New Zealand) using MSCs Phase 3 Cord blood expansion for hematological malignancies using MPCs

27 Acute GVHD - Prochymal Patients who responded to therapy by day 28 had a higher Kaplan-Meier estimated probability of 100- day survival than patients who did not respond (78% vs. 28%, p<0.001) 26

28 Oncology acute Graft Versus Host Disease (GVHD) ~29,500 allogeneic hematopoietic stem cell transplants (HSCTs) performed annually for treatment of hematologic malignancies, certain forms of anemia, and immunological deficiencies GVHD is a potentially life-threatening complication that arises in approximately 50% of all patients who receive an HSCT and affects the skin, gastrointestinal tract, and liver Mortality can reach 85% in patients with liver and gut complications In Phase 3 trial, Prochymal significantly improved overall responses in the adult subset with gut or liver GVHD and resulted in improved survival In open-label pediatric study, at day 28 61% of patients were responders to Prochymal Response at day 28 to Prochymal therapy was a significant predictor of improved day 100 survival (p<0.001) Day 100 survival was 78% in Prochymal responders, compared to 28% in non-responders (p value <0.001, log rank test) Conditionally approved for use in children in Canada and New Zealand Ongoing regulatory discussions regarding accelerated product approvals in major markets: Impetus for accelerating commercial manufacturing 27

29 Mesoblast s alliances include: 28 4 Strategic partnerships manufacturing scale-up, product distribution capabilities, additional sources of funding, other strategic areas of partners expertise strategic relationship with biologics manufacturer Lonza to ensure commercial scale-up and supply, product delineation, COGS reductions, and expansion of clinical manufacturing exclusive rights to Lonza s existing state of the art facilities in Singapore for allogeneic stem cell therapy 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

30 Singapore alliance integral to global operations Mesoblast is bringing forward plans for its commercial manufacturing operations in line with anticipated product launches in the United States and other major markets. Mesoblast will receive incentives from from the Singapore Economic Development Board (EDB) for activities in Singapore related to manufacturing operations as well as product research and development. EDB and A*STAR offer Mesoblast important benefits for its commercial, manufacturing and research operations, including: business friendly environment strong scientific base focus on cellular therapies expertise in research, development and manufacture of biopharmaceuticals 29

31 Leading the world in the development of adult stem cell therapies June 2014