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Ab Science Sa — Technical Presentation (March 2020)
36 slides from Ab Science Sa's technical presentation, Mar 6, 2020
Slide 1: Masitinib in Primary Progressive and Non-Active Secondary Progressive Multiple Sclerosis
AB SCIENCE WEBCONFERENCE MASITINIB IN PRIMARY PROGRESSIVE AND NON-ACTIVE SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS 06 MARCH 2020
Slide 2: Disclaimer
Disclaimer This presentation, together with the material set forth herein, does not constitute an offer of securities for sale nor the solicitation of an offer to purchase securities in any jurisdiction. Distribution of such presentation in certain jurisdiction may constitute a breach of applicable
Slide 3: Agenda
AGENDA ❖ Introduction of participating experts ❖ Overview of multiple sclerosis ❖ Overview of masitinib clinical results ❖ Q&A
Slide 4: Participants
Participants MS Experts AB Science Management and Chairman of Scientific Committee Patrick VERMERSCH, MD, PhD Professor of Neurology at Lille University Alain MOUSSY, MBA in France Co-founder and Chief Executive Officer. Bob FOX, MD Staff Neurologist at the Mellen Center for Laurent GUY, MBA Multipl
Slide 5: Principal Investigator of Study AB7002
Principal Investigator of Study AB7002 Patrick VERMERSCH, MD, PhD ❖ About Patrick Vermersch ▪ Professor of Neurology at Lille University in France. ▪ Vice-president for research in biology and health at the University of Lille ▪ Board member of the European Charcot Foundation. ▪ Author or co-author
Slide 6: Clinical Forms of Multiple Sclerosis
Clinical Forms of Multiple Sclerosis Multiple sclerosis has two main forms, relapsing and progressive forms. Relapsing forms of MS1–3 Progressive forms of MS1–3 Relapsing-Remitting Secondary Progressive Primary Progressive Active Non-active CIS Secondary Secondary (RIS) Progressive Progressive Disab
Slide 7: Difference between Progressive and Relapsing Forms of MS
Difference between Progressive and Relapsing Forms of MS PPMS and nSPMS are distinct from RRMS, which may explain why therapies targeting the peripheral adaptive immune system (T and B-cells) proven to be effective in RRMS have failed or had inconclusive results in PPMS and nSPMS. Time to disability
Slide 8: New Scientific Rationale in Progressive Forms MS – Target Mast Cells and Microglia
New Scientific Rationale in Progressive Forms MS – Target Mast Cells and Microglia The innate immune system can play a critical role in the progressive forms of MS. ❖ Progressive forms of MS (PPMS and non active SPMS) are predominantly driven by self- perpetuating innate immunity-related inflammatio
Slide 9: New Scientific Rationale in Progressive Forms MS – Target Mast Cells and Microglia
New Scientific Rationale in Progressive Forms MS – Target Mast Cells and Microglia The innate immune system can play a critical role in the progressive forms of MS. Activated microglia and Macrophages/activated Mast cells release enzymes that can hypertrophic astrocytes found at microglia can cause
Slide 10: Masitinib Inhibits Activated Mast Cells and Microglia
Masitinib Inhibits Activated Mast Cells and Microglia Masitinib targets selected kinases in mast cells and M-CSF1 receptor in microglia. Kinase inhibition profile of masitinib ❖ Masitinib targets mast cells ▪ Masitinib is a potent and selective inhibitor of c-Kit, Lyn, and Fyn kinases. These kinases
Slide 11: Masitinib Positioning in Progressive Forms of Multiple Sclerosis
Masitinib Positioning in Progressive Forms of Multiple Sclerosis Because of its mechanism of action targeting mast cells and microglia, Masitinib is aimed to treat patients with PPMS and non-active SPMS, which is a difficult to treat population representing around 50% of MS patients. ❖ Primary progr
Slide 12: Masitinib Positioning in Progressive Forms of Multiple Sclerosis
Masitinib Positioning in Progressive Forms of Multiple Sclerosis There is a tremendous unmet need, with no approved drugs for nSPMS and only one for PPMS. Masitinib positioning Label First Manufacturer Non-active Active PPMS RRMS approved SPMS* SPMS Distribution of patients 15% 35% 10% 40% (Estimate
Slide 13: Pharmacology Data - Masitinib improves MS Symptoms in Mice
Pharmacology Data - Masitinib improves MS Symptoms in Mice In a mouse model of MS, masitinib showed significant reduction in disease. ❖ The potential of masitinib in MS was explored using a MOG-EAE model (MOG-induced experimental allergic encephalomyelitis). ▪ It is established that mast cells are n
Slide 14: Masitinib Clinical Development Plan in Progressive Forms of MS
Masitinib Clinical Development Plan in Progressive Forms of MS The current development program in progressive forms of MS is comprised of one proof of concept study (published), and one pivotal study. Study Primary Patient IDMC Study Related Phase Design Population code endpoint Enrolled recommendat
Slide 15: Proof of concept study – 2012 Publication
Proof of concept study – 2012 Publication Proof of concept in progressive MS has been established through a study evaluating masitinib effect on the multiple sclerosis functional composite score (MSFC). ❖ Positive effect on MS-related impairment for PPMS and nSPMS patients. ▪ Improvement in MSFC sco
Slide 16: Study AB7002 - Phase 2B/3 Design
Study AB7002 - Phase 2B/3 Design Study AB7002 evaluated two masitinib doses in patients with PPMS and non-active SPMS. ❖ Double blind, placebo controlled, 2-parallel groups ▪ Two doses tested independently, each with its own placebo control group (i.e. 4 arms study) 1. Masitinib 4.5 mg/kg/day versus
Slide 17: Phase 2B/3 - Design
Phase 2B/3 - Design The primary endpoint was absolute change from baseline on Expanded Disability Status Scale (EDSS) averaged for all time points over 2 years, with a sensitivity analysis based on the ordinal EDSS change. ❖ Pre-specified Primary Endpoint: Change from baseline in absolute EDSS value
Slide 18: Phase 2B/3 - Design
Phase 2B/3 - Design Time to first EDSS progression and time to confirmed EDSS progression were pre-specified for sensitivity analysis although the study was not powered to detect an effect on these endpoints. ❖ Pre-specified Sensitivity analysis based on time to first EDSS progression and confirmed
Slide 19: Phase 2B/3 - Disposition of patients
Phase 2B/3 - Disposition of patients The study was comprised of two independent sub-studies testing two distinct dosing regimens Analyses were performed on the mITT* population. Study AB7002 Dosing Dosing Dosing Masitinib 4.5 to 6.0 Masitinib 4.5 mg/kg/day vs Masitinib 6.0 mg/kg/day vs mg/kg/day tit
Slide 20: Phase 2B/3 - Masitinib 4.5mg/kg/day - Baseline Characteristics
Phase 2B/3 - Masitinib 4.5mg/kg/day - Baseline Characteristics Patients were enrolled at an advanced stage of disease, reflecting a difficult-to-treat population. Baseline Characteristics (M4.5 mg/kg/day vs placebo) Masitinib Placebo ❖ Baseline characteristics were Number of Randomised Patients 200
Slide 21: Phase 2B/3 - Met Primary Analysis at 4.5 mg/kg/day
Phase 2B/3 - Met Primary Analysis at 4.5 mg/kg/day The study met its primary analysis, demonstrating a statistically significant reduction in disability progression on EDSS (p=0.0256) . Primary analysis – Visualization of absolute changes from baseline in EDSS measured at 8 time points every 12 week
Slide 22: Phase 2B/3 – Subgroup Analysis by Disease Category
Phase 2B/3 – Subgroup Analysis by Disease Category This treatment-effect was consistent for PPMS and nSPMS, supportive of the case for registration of masitinib in the two populations. Assessment of consistency of the primary endpoint for each population (PPMS and sSPMS) Means Treatment N (all chang
Slide 23: Phase 2B/3 - Masitinib 4.5mg/kg/day - Ordinal EDSS
Phase 2B/3 - Masitinib 4.5mg/kg/day - Ordinal EDSS The sensitivity analysis based on ordinal EDSS change showed a significant 39% increased probability with masitinib of having either more disease improvements or fewer disease progressions. Prespecified Analysis on EDSS – Ordinal EDSS Mean of 8 time
Slide 24: Phase 2B/3 - Masitinib 4.5mg/kg/day - Time to EDSS progression
Phase 2B/3 - Masitinib 4.5mg/kg/day - Time to EDSS progression Masitinib reduced the risk of first disability progression by 42% and the risk of confirmed disability progression by 37%. Prespecified Analysis on EDSS Prespecified Analysis on EDSS Kaplan Meier plot of Analysis of time to Kaplan Meier
Slide 25: Phase 2B/3 - Masitinib 4.5mg/kg/day - Time to EDSS 7.0 (wheelchair)
Phase 2B/3 - Masitinib 4.5mg/kg/day - Time to EDSS 7.0 (wheelchair) Masitinib also significantly reduced the risk of reaching an EDSS score of 7.0, corresponding to disability severe enough that the patient is restricted to a wheelchair. Kaplan Meier plot of Analysis of time to First Kaplan Meier pl
Slide 26: Phase 2B/3 - Masitinib 4.5mg/kg/day – Comparison to Other Drugs
Phase 2B/3 - Masitinib 4.5mg/kg/day – Comparison to Other Drugs Masitinib has the potential for a best-in-class profile for treating PPMS and nSPMS. Time to confirmed disability Ordinal EDSS change progression Average of Reduction in Change in EDSS Type of Probability to have Treatment versus Study
Slide 27: Phase 2B/3 study - Masitinib 4.5mg/kg/day - Safety
Phase 2B/3 study - Masitinib 4.5mg/kg/day - Safety Safety was consistent with the known profile for masitinib. ❖ Common treatment-emergent AEs were diarrhea, rash, edema, nausea and hematological assessments ❖ Most Frequent Severe Adverse Events were hematological assessments and rash – Most Frequen
Slide 28: Phase 2B/3 - Masitinib 6.0mg/kg/day - Primary Analysis
Phase 2B/3 - Masitinib 6.0mg/kg/day - Primary Analysis No significant treatment-effect on EDSS was observed for high-dose masitinib (6 mg/kg/day). ❖ Numerically, masitinib 6.0 mg/kg/day titration was comparable to masitinib 4.5 mg/kg/day ❖ However, the placebo comparator for the 6.0 mg/kg/day titrat
Slide 29: Next steps
Next steps ❖ AB Science intends to present detailed study results at one or more major scientific conference in the next 6 months. ❖ AB Science will consult with the FDA (through EOP2 meeting) and with the EMA (through Scientific Advice) to discuss the appropriate pathway forward for masitinib in th
Slide 30: Intellectual Property
Intellectual Property Masitinib IP rights are secured up to 2031 in multiple sclerosis, and potentially until 2040 with patent recently filed based on AB07002 study results. Protection Item Duration of protection Status Phase 2/3 ‘Method of Multiple sclerosis Until 2031 Delivered use’ patents Phase
Slide 31: Discussion
Discussion The clinical data are extremely encouraging and provide new hope for progressive MS patients. ❖ There is a high unmet medical need for people with PPMS and nSPMS ▪ PPMS and nSPMS account for half of all MS patients. ▪ Numerous treatments based on targeting of B-cells and T-cells of the ad
Slide 32: Discussion
Discussion Robert FOX, MD ❖ About Bob Fox ▪ Staff Neurologist at the Mellen Center for Multiple Sclerosis. ▪ Professor of Neurology at Cleveland Clinic Lerner College of Medicine ▪ Vice-Chair for Research of the Neurological Institute, Cleveland Clinic ▪ Board member of the European Charcot Foundati
Slide 33: Discussion
Discussion These results represent a significant advancement for progressive forms of MS. ❖ There is a high unmet medical need for people with PPMS and nSPMS ▪ About half of MS patients have PPMS and nSPMS. ▪ Numerous treatments target the adaptive immune system in relapsing forms of MS. These strat
Slide 34: Discussion
Discussion Friedemann PAUL, MD ❖ About Friedemann Paul ▪ Professor of Clinical Neuroimmunology and head of the neuroimmunology outpatient clinic at the Experimental and Clinical Research Centre (Berlin, Germany). ▪ Co-chairs Charité’s Clinical and Experimental Multiple Sclerosis (MS) Research Centre
Slide 35: Friedemann Paul
Friedemann Paul The clinical results obtained with masitinib validate the relevance of targeting mast cells and microglia in progressive forms of multiple sclerosis. ❖ The medical need for people with PPMS and nSPMS is still very high ▪ Patients PPMS and nSPMS are severely disabled by the progressio
Slide 36: Q&A
Q&A Cession 36