Slide 1: MPC-300-IV: Week 39 Results in Biological Refractory Rheumatoid Arthritis
For personal use only MPC-300-IV: Week 39 Results in Biological Refractory Rheumatoid Arthritis February 2017
Slide 2: Cautionary Note Regarding Forward-Looking Statements
For personal use only CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This presentation includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, le
Slide 3: Compelling Investment Proposition: Building a Leading Franchise of Cellular Medicines
Compelling Investment Proposition: Building a Leading Franchise of Cellular Medicines For personal use only Leader in Disruptive Proven Capability for Advanced Pipeline of Cellular Technology Commercial Translation Cellular Medicines Platform Extensive patent portfolio Scalable industrialized
Slide 4: Biologic Refractory RA – Market Landscape: Market Size
MPC-300-IV: Biologic Refractory Rheumatoid Arthritis (RA) – Market Landscape For personal use only Market Size • There are 6.0 million prevalent cases in the US, Japan, and EU5, of which there were 2.9 million in the US alone in 20161 • Incidence increases with age – 8.7 per 100,000 for ages 18-34 v
Slide 5: Biologic Refractory RA – Significant Unmet Need
MPC-300-IV: Biologic Refractory Rheumatoid Arthritis (RA) – Market Landscape For personal use only Significant Unmet Need • One third of RA patients do not respond or cannot tolerate current biologic therapies – Sustained low disease activity or remission is seen in low numbers of patients who are r
Slide 6: MPC-300-IV for Treatment of Chronic Inflammatory Diseases through Immunomodulation
MPC-300-IV for treatment of Chronic Inflammatory Diseases through Immunomodulation For personal use only Inflammation induces production of immuno-modulatory factors by STRO-1+ Mesenchymal Precursor Cells (MPCs), which regulate multiple immune pathways concurrently • MPCs have receptors that respond
Slide 7: STRO-1+ MPCs are more immunosuppressive than plastic adherent mesenchymal lineage cells
STRO-1+ MPCs are more immunosuppressive than plastic adherent mesenchymal lineage cells For personal use only A. Mixed Lymphocyte Culture B. Mitogen Stimulation • STRO-1 selected MPC elicit approximately 10-fold greater levels of inhibition of T-cell proliferation in vitro than MSC from the same don
Slide 8: MPC-300-IV for modulation of cytokine production by synoviocytes in RA
MPC-300-IV for modulation of Cytokine production by For personal use only Synoviocytes/Synovial fibroblasts in Rheumatoid Arthritis • PGE2 and TGFβ secreted by MPCs following surface signaling in inflamed joint • Both act directly on synovial fibroblasts to increase IkappaB and inhibit NFkappaB • Se
Slide 9: A sheep model of Collagen-Induced Arthritis (CIA)
A sheep model of Collagen-Induced Arthritis (CIA)* For personal use only Aim: to determine the anti-inflammatory effects and dose ranging of ovine MPCs in an ovine model of collagen-induced acute arthritis (CIA) and systemic inflammation Dosed: administered by IV injection: 150 million ovine allogen
Slide 10: Features of CIA and Human RA: Invading Synovial Pannus and Cartilage Erosion
Features of CIA and Human RA: Invading Synovial Pannus and Cartilage Erosion For personal use only Col II Injected Normal joint Joint (Day 42) Inflammatory Erosion of Cell Pannus Cartilage |9
Slide 11: Allogeneic sheep MPCs reduce synovial pannus and inflammatory cytokines, improve symptoms in CIA
Allogeneic sheep MPCs reduce Synovial Pannus / Inflammatory Cytokines, improve symptoms in CIA For personal use only Pain on Flexion Joint Swelling Total Clinical Score | 10
Slide 12: MSB-RA001: Study design
MSB-RA001: Study design For personal use only • Phase 2 double-blind, randomized, placebo-controlled, dose-escalating study comparing a single infusion of two MPC doses (1M/kg and 2M/kg) with placebo in patients with active RA – Inadequate response to at least 1 anti-TNF +/- other biologics – On a s
Slide 13: MSB-RA001: Study design – Objectives
MSB-RA001: Study design For personal use only • Objectives – Primary: Evaluate safety and tolerability of a single intravenous MPC infusion in biologic refractory RA patients through a 12-week primary endpoint – Secondary: Evaluate clinical efficacy at week 4, 12, 39 and 52 and assess durability of
Slide 14: MSB-RA001: Safety conclusions through 39 weeks
MSB-RA001: Safety conclusions through 39 weeks For personal use only • Infusions were well-tolerated without any acute infusion reactions or adverse events (AEs) reported either during infusion or the 6-h post-infusion monitoring period • No treatment related SAEs reported during the 39 week period
Slide 15: RA001: Percent Achieving ACR20 and Response over Weeks
RA001: For personal use only Percent Achieving ACR20, 50 and 70 Response over 39 Weeks All Subjects 1-2 Prior Biologics 1. Values are observed n/N (%) at each time point | 14 2. *P values vs. Placebo computed using Fisher exact test
Slide 16: Analysis of ACR-N in all subjects
Analysis of ACR-N in all subjects For personal use only * p=0.004 for 2M MPCs/kg vs. placebo through 39 weeks * p-values vs. placebo for difference in Area Under the Curve (AUC) over 39 weeks using t-test on log-transformed geometric mean for ACR-N. Siegel JN, Zhen BG. Arthritis Rheum. 2005 Jun;52(6
Slide 17: Analysis of ACR-N in subjects treated with 1-2 prior biologics
Analysis of ACR-N in subjects treated with 1-2 prior biologics For personal use only * p=0.012 2M MPCs/kg vs. placebo through 39 weeks p=0.019 1M MPCs/kg vs. placebo through 39 weeks ** p=0.0097 for2M/kg vs. placebo at 39 weeks * p-values vs. placebo for difference in Area Under the Curve (AUC) over
Slide 18: Health Assessment Questionnaire – Disability Index (HAQ-DI)
Health Assessment Questionnaire – Disability Index (HAQ-DI) Least Squares Mean (SE) Change from Baseline at 4 , 12 and 39 Weeks For personal use only All Subjects 1-2 Prior Biologics P la c e b o (n = 8 ) B a s e lin e : 1 .3 P la c e b o B a s e lin e : 1 .3 M P C 1 M / k g ( n = 1 0 ) B a s
Slide 19: HAQ-DI: Percent reaching minimal clinically important reduction
Health Assessment Questionnaire – Disability Index (HAQ-DI) Percent that reached minimal clinically important reduction For personal use only of -0.22 at 4, 12 and 39 weeks All Subjects 1-2 Prior Biologics P la c e b o P la c e b o % R e a c h in g - 0 .2 2 R e d u c t io n in H A Q - D I * p = 0 .0
Slide 20: Percent of patients achieving Low Disease Activity Score (DAS28-CRP <3.2)
Percent of patients achieving Low Disease Activity Score For personal use only (DAS28-CRP <3.2) All Subjects 1-2 Prior Biologics 7/13 6/12 4/10 3/9 5/9 6/9 3/16 4/15 5/14 4/14 2/9 3/10 80 80 3 3 .3 % 5 5 .6 % 6 6 .7 % 1 8 .8 % 2 6 .7 % 3 5 .7 % 2 8 .6 % 5 3 .8 % 5 0 .0 % 2 2 .2 % 3 0 .0 % 4 0 .0 % 6
Slide 21: Summary of Key Efficacy Responses at 12 and 39 Weeks – All Subjects
Summary of Key Efficacy Responses at 3 and 9 Months For personal use only All Subjects Week 12 Week 39 Placebo 1M/kg 2M/kg Placebo 1M/kg 2M/kg N=16 N=16 N=16 N=16 N=16 N=16 ACR20 50% 47% 53% 36% 69% 57% ACR50 19% 27% 40% 14% 31% 21% ACR70 0% 20% 27%* 0% 23% 21% ACR-N median 20% 11% 28% 9% 27% 27% AC
Slide 22: Summary of Key Efficacy Responses for Subgroup with Prior Use of 1-2 Biologics
Summary of Key Efficacy Responses at 3 and 9 Months For personal use only for Subgroup with Prior Use of 1-2 Biologics Week 12 Week 39 Placebo 1M/kg 2M/kg Placebo 1M/kg 2M/kg N=9 N=10 N=11 N=9 N=10 N=11 ACR20 33% 60% 55% 22% 67% 60% ACR50 11% 30% 55% 0% 33% 30% ACR70 0% 20% 36% 0% 22% 30% ACR-N medi
Slide 23: MPC-300-IV: Phase 2 Trial Results Update
MPC-300-IV: Phase 2 Trial Results Update For personal use only • The Phase 2 trial of Mesoblast’s allogeneic product candidate, MPC-300-IV, in biologic refractory rheumatoid arthritis will complete when all patients have been followed for 52 weeks • A single intravenous MPC infusion in biologic refr
Slide 24: Thank you
For personal use only Thank you