Mesoblast Limited · ASX:MSB
Mesoblast — 2018 ISSCR Annual Scientific Meeting
31 slides from Mesoblast's conference presentation, Jun 22, 2018
Slide 1: Road to Commercialization for Mesenchymal Lineage Cells
For personal use only Road to Commercialization for Mesenchymal Lineage Cells 2018 ISSCR Annual Scientific Meeting Melbourne June 21, 2018
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: Mesoblast is committed to bringing to market disruptive cellular medicines
For personal use only Mesoblast is committed to bringing to market disruptive cellular medicines to treat serious and life-threatening illnesses.
Slide 4: Lengthy, Complex Process to Bring a New Medicine to Patients
Lengthy, Complex Process to Bring a New Medicine to Patients Ethically and with Integrity For personal use only Discovery Stage Development Stage Source: Scientifist.com |4
Slide 5: Implementation of Regulatory Environment to Protect Patients
Implementation of Regulatory Environment to Protect Patients For personal use only Section What it covers Demonstration that the proposed manufacturing process produces consistent quality product, Quality controlled by in-process and finished product acceptance criteria; a controlled environment, GM
Slide 6: Regulatory Filing Requirements (FDA): Common Technical Documents for a BLA
Regulatory Filing Requirements (FDA): Common Technical Documents for a Biologics License Application For personal use only The CTD triangle. The Common Technical Document is organized into five modules. Module 1 is region specific and modules 2, 3, 4 and 5 are intended to be common for all regions.
Slide 7: Mesoblast: A Leading Global Cellular Medicines Company
Mesoblast: A Leading Global Cellular Medicines Company For personal use only Disruptive Technology Industrial Scale Multiple Revenue Platform1 Manufacturing Generating Products & Phase 3 Assets • Immuno-selected, culture • Unique cell properties enable • 2 approved products expanded cellular medicin
Slide 8: STRO-1+ Mesenchymal Precursor Cells (MPCs)
STRO-1+ Mesenchymal Precursor Cells (MPCs) At the apex of the entire mesenchymal lineage, irrespective of source of derivation For personal use only Bone Cultured Expanded Immunoselection Progeny Cartilage of MPC MPC MSC Bone Marrow Adipose Fibroblast STRO-1 Differentiation Smooth muscle STRO-1 Simm
Slide 9: Immunomodulatory Actions of MPCs and MSCs
The Immunomodulatory Actions of MPCs and MSCs are Triggered by Their Receptor Initiated Responses to Inflammatory Cues: Paracrine-mediated alteration of the function of multiple cellular constituents For personal use only of the innate and adaptive immune systems IL-10 Breg TH1 Proliferation Cytokin
Slide 10: Global IP Estate Provides Substantial Competitive Advantage
Global IP Estate Provides Substantial Competitive Advantage For personal use only • ~800 Patents and patent applications (69 Patent families) across all major jurisdictions • Covers composition of matter, manufacturing, and therapeutic applications of Mesenchymal Lineage Cells Diseases • Provides st
Slide 11: Industrial Scale Manufacturing
Industrial Scale Manufacturing For personal use only • Cellular technology platform enables immune privileged, allogeneic ‘off the shelf’ product candidates • Delineated products with specific potency assays, batch to batch consistency and reproducibility • Scalable culture expansion sufficient to p
Slide 12: Clinical Pipeline and Products Commercialized by Licensees
Clinical Pipeline and Products Commercialized by Licensees For personal use only PLATFORM PRODUCT THERAPEUTIC AREA APPROVAL COMMERCIAL RIGHTS MARKETED MSC TEMCELL® Acute GVHD Japan Only (Bone Marrow) HS Inj1 MSC (Adipose) Alofisel2 Perianal Fistula World Wide PRODUCT PRE-CLINICAL PLATFORM THERAP
Slide 13: Acute Graft vs Host Disease
For personal use only Acute Graft vs Host Disease Remestemcel-L (MSC-100-IV) for Steroid-Refractory aGVHD |8
Slide 14: Acute Graft Versus Host Disease (aGVHD) Background
Acute Graft Versus Host Disease (aGVHD) Background For personal use only • Acute graft-versus-host disease (aGVHD) is associated with significant morbidity and is a leading cause of mortality after allogeneic hematopoietic stem cell transplantation • Severe aGVHD (determined by grade C/D, visceral o
Slide 15: Visceral Organ Involvement Predicts High Mortality in aGVHD
Visceral Organ Involvement Predicts High Mortality in aGVHD For personal use only Univerate Analysis Multiverate Analysis Organ Involvement (n) P Value P Value Hazard Ratio Hazard Ratio Skin Only (1010) 1 1 Gut Only (266) 1.11 0.448 0.80 0.139 Liver Only (28) 4.11 <0.001 2.22 0.013 Skin and Gut, No
Slide 16: MSC-100-IV: Multiple MOA pathways addressing inflammatory response in GVHD
MSC-100-IV (remestemcel-L): In vitro/in vivo studies demonstrate multiple MOA pathways For personal use only addressing underlying inflammatory response in GVHD In vitro studies demonstrate that remestemcel-L • Inhibits alloantigen- and mitogen-driven T cell proliferation in vitro • Decreases secret
Slide 17: Relationship Between TNFR1 Expression on MSC and Inhibition of T Cell Proliferation
Relationship Between TNFR1 Expression on MSC and Inhibition of T Cell Proliferation1 For personal use only 60 77 80 71 67 50 70 49 % inhibition of proliferation TNFRI (pg/mil cells) 40 60 38 30 44 50 28 20 40 10 30 11 0 20 TNFRI 0 1.25 2.5 5 Proliferation TNFRI antisense oligonucleotide (um) US PTO,
Slide 18: Remestemcel-L: Expanded Access Program
Remestemcel-L (MSC-100-IV):Expanded Access Program Overall Day 28 response in pediatric aGVHD patients receiving remestemcel-L For personal use only (MSC-100-IV) as first-line or salvage therapy after failing steroids Population: steroid-refractory 100% aGVHD pediatric patients • 241 pediatric patie
Slide 19: Remestemcel-L: Expanded Access Program Survival Correlation
Remestemcel-L (MSC-100-IV):Expanded Access Program Correlation of Day 28 overall response with Day 100 survival, using remestemcel-L For personal use only (MSC-100-IV) as first-line or salvage therapy after failing steroids and/or additional treatments MSC-100-IV in Children with SR-aGVHD who failed
Slide 20: MSC-100-IV: Study Adult Population
MSC-100-IV: Study 280 Adult Population Randomized controlled data in patients who failed steroids and received For personal use only no additional GVHD treatment prior to enrollment Overall Response (CR + PR) by Organ Involvement – mITT population Remestemcel-L Placebo P Value Liver 32/42 (76.2%) 9/
Slide 21: Remestemcel-L for GVHD: Product development strategy
Remestemcel-L for GVHD: Mesoblast’s product development strategy For personal use only 1. Target pediatric patients with steroid refractory-aGVHD first 2. Seek label extension for high-risk adult patients with steroid refractory-aGVHD 3. Lifecycle potential in chronic GVHD (cGVHD) | 21
Slide 22: Phase 3 Pediatric Trial GVHD001 Design
Remestemcel-L (MSC-100-IV): Phase 3 Phase 3 pediatric trial GVHD001 as first-line therapy in aGVHD For personal use only after failing steroids Patient screening/enrollment • Multi-center, single-Arm, open-label to evaluate efficacy and safety to Day 100 (GVHD001) and from Day 100 to Day 180 (GVHD00
Slide 23: Protocol GVHD001: Demographics
Protocol GVHD001: Demographics For personal use only Subjects enrolled 55 Age (Years) Mean (SD) 7.8 (5.44) Median (minimum, maximum) 7.6 (0.6, 17.9) Gender Male 35 (63.6%) Female 20 (36.4%) Underlying Disease AML 18 (32.7%) ALL 12 (21.8%) Anemia 5 (9.1%) CML 4 (7.3%) Sickle Cell 3 (5.5%) JML 2 (3.6%
Slide 24: Protocol GVHD001: Transplant Characteristics Reflect aGVHD Risk Factors
Protocol GVHD001:Transplant Characteristics Reflect aGVHD Risk Factors For personal use only Conditioning Regimen Donor Compatibility Myeloablative Matched Reduced Intensity Mismatched Non-Myeoablative 87% of subjects received myeloablative conditioning regimen 51% of subjects received an HLA-mismat
Slide 25: Protocol GVHD001: Disease Characteristics Reflect aGVHD Severity
Protocol GVHD001: Disease Characteristics Reflect aGVHD Severity For personal use only GVHD Grade at Baseline Baseline Organ Involvement Grade B Skin Only Grade C Lower GI Only Grade D Two Organs Three Organs 26% of subjects had Skin involvement only 47% of subjects had Grade D disease All had stage
Slide 26: Consistency of the Manufacturing Process in Phase 3
Consistency of the Manufacturing Process in Phase 3: Remestemcel-L demonstrates consistent lot to lot expression of TNFR1 For personal use only and high level inhibition of T cell activation % Inhibition T-cell activation 400 100 350 90 80 300 TNFR1 (pg/ml) 70 250 60 200 50 150 40 30 100 20 50 10 0
Slide 27: Protocol GVHD001: Primary Efficacy Outcome
Protocol GVHD001:Primary Efficacy Outcome Overall response at Day 28 was 69%, p=0.0003 For personal use only 80% 70% 60% 50% 40% 30% 20% 10% 0% | 27
Slide 28: Protocol GVHD001: Summary of Phase 3 Trial Results
Protocol GVHD001: Summary of Phase 3 Trial Results For personal use only • Multi-dose regimen of remestemcel-L infusions was well tolerated • Day 28 Overall Response was 69% • Day 28 Overall Response was significantly greater than theoretical control rate of 45% (p=0.0003) • Overall survival at Day
Slide 29: Remestemcel-L as First Line in Steroid Refractory Acute GVHD: Conclusions
Remestemcel-L as First Line in Steroid Refractory Acute GVHD For personal use only Phase 3 Conclusions • Multi-dose regimen of remestemcel-L infusions was well tolerated • Remestemcel-L successfully achieved the pre-specified primary endpoint of Day 28 Overall Response • Remestemcel-L demonstrated s
Slide 30: Thank you
For personal use only Thank you
Slide 31: Questions?
For personal use only Questions? | 31 | 31