Ab Science Sa · EURONEXT:AB
Ab Science Sa — Investor Presentation (December 2020)
49 slides from Ab Science Sa's investor presentation, December 2020
Slide 1: Corporate Presentation
Corporate Presentation December 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: Experienced Management Team
Experienced Management Team ALAIN MOUSSY CHRISTIAN FASSOTTE OLIVIER HERMINE, MD, PHD LAURENT GUY Co-founder and CEO Global Chief Medical Officer Chief Financial Officer Chairman of Scientific Committee Former strategic consultant at Booz, Allen Former positions in the banking industry Medical Doctor
Slide 4: Investment Highlights
Investment Highlights Portfolio based on Diversified and Multiple Late-Stage Programs • Lead compound: Masitinib, kinase inhibitor selectively targeting mast cells and macrophages/microglia Breakthrough mechanism of action • New opportunity in viral diseases as masitinib has been shown in vitro to b
Slide 5: Pipeline
Pipeline Diversified portfolio with seven positive phase 2B or phase 3 trials Confirmatory Compound Therapeutic area Indication Preclinical Phase 1/2 Phase 2B/3 Phase 3 Amyotrophic Lateral Sclerosis* Neurology Diseases Progressive forms of Multiple Sclerosis* Alzheimer’s Disease* Indolent Systemic M
Slide 6: Pathway to Registration
Pathway to Registration Interaction with health • Pancreatic Cancer – Decision 2021 authorities for NDA filing or confirmatory phase 3 study • Severe asthma – Decision 2021 • Amyotrophic Lateral Sclerosis – Initiated, expected completion early 2023 • Indolent Systemic Mastocytosis – Initiated, expec
Slide 7: Market Potential
Market Potential Blockbuster potential but also addressing orphan diseases Estimated Number of patients (USA and EU) in targeted indications with masitinib Alzheimer’s disease 5 000 000 Covid-19 2 300 000 Blockbuster potential Severe Asthma 825 000 Multiple Sclerosis (PPMS & nSPMS) 500 000 Metastati
Slide 8: Rationale
Rationale The clinical development is primarily based on the targeting of Mast Cells & Macrophages/Microglia Compound Therapeutic area Indication Cellular (Molectular) Target Amyotrophic Lateral Sclerosis ▪ Mast Cells (c-Kit, Lyn, Fyn kinases) Neurology Diseases Progressive forms of Multiple Scleros
Slide 9: Critical Role of Mast Cells & Macrophages / Microglia
Critical Role of Mast Cells & Macrophages / Microglia Mast cells and microglia contribute to neuro-inflammation, which is strongly influenced by their potential for mutual interaction and exacerbation of pathology Activation of mast cells leads to degranulation and secretion of numerous mediators th
Slide 10: Masitinib Profile and Mechanism of Action
Masitinib Profile and Mechanism of Action Orally-administered kinase inhibitor selectively targeting mast cells and macrophages Masitinib targets mast cells Kinase inhibition profile of masitinib • Masitinib is a potent and selective inhibitor of c-Kit, Lyn, and Fyn kinases. These kinases play criti
Slide 11: Masitinib Safety Database Across Indications
Masitinib Safety Database Across Indications Well established safety profile with long-term exposure Safety Patients exposed for at least population All ≥ 6 months ≥ 12 months ≥ 2 years ≥ 5 years Healthy Volunteers subjects 114 0 0 0 0 Non Oncology subjects 3,317 2,120 1,515 662 50 Oncology subjects
Slide 12: AB8939
AB8939 Novel Microtubule-destabilizing Agent for Acute Myeloid Leukemia Detection of AMKL26 PDX blasts in mice Activity of AB8939 in Ara-C Key Differentiating factors following single agent AB8939 treatment resistant/refractory AML patent blasts • Overcomes P-glycoprotein (Pgp) and myeloperoxidase (
Slide 13: Upcoming newsflow
Upcoming newsflow Two important catalysts are expected in 2021 ❖ Report top-line results from phase 3 with masitinib + docetaxel in metastatic prostate cancer (n=470) ❖ Report top-line results from phase 2 with masitinib + Isoquercetin in COVID-19 patients (n=200) 13
Slide 14: Neurology Diseases
Multiple Sclerosis (PPMS and nSPMS) Neurology Amyotrophic Lateral Sclerosis (ALS) Diseases Alzheimer's Disease (AD)
Slide 15: Multiple Sclerosis
Multiple Sclerosis Tremendous unmet need, with no approved drugs for non-active SPMS and only one for PPMS Masitinib Positioning Label Manufacturer First approved Non-active Primary Active Secondary Relapsing Secondary Progressive MS Progressive MS Remitting MS Progressive MS* Distribution of patien
Slide 16: Multiple Sclerosis
Multiple Sclerosis Phase 2B/3 demonstrated significant benefit on disability progression Significant reduction in progression on EDSS (Primary Endpoint) 42% risk reduction of time to disability progression 0.2 P=0.0256 P=0.0342 LSM Change 0.1 0.0 0 12 24 36 48 60 72 84 96 Weeks in Treatment Masitini
Slide 17: ALS
ALS Phase 2B/3 demonstrated significant delay in disease progression 27% slowing of functional deterioration (Primary Endpoint) 25% delay in disease progression (PFS) al) 0.0 Placebo 100 Masitinib 4.5mg Placebo Masitinib 4,5 Placebo Masitinib 4,5 -2.0 90 80 LS Means ALSFRS change from baseline -4.0
Slide 18: ALS
ALS Clinical benefit further enhanced when treatment initiated early 51% slowing of functional deterioration (vs 27%) Significant improvement on Combined Assessment of Function & Survival % reduction in change in ALSFRS (primary endpoint) At least 1 subgroup Diff. of means p-value Primary Analysis S
Slide 19: ALS
ALS Next Step Confirmatory phase 3 study, with design optimized based on first phase 3 study Confirmatory phase 3 design Optimizations from previous phase 3 Design: Double blind, placebo controlled, randomized 1:1:1:1, Enriched inclusion criteria comparing masitinib titration up to 6.0 mg/kg/day wit
Slide 20: Alzheimer's disease
Alzheimer’s disease The Phase 2B/3 study demonstrated a statistically significant reduction in Cognitive impairment based on ADAS-COG (p=0.0003) and improvement on daily activity based on ADCS-ADL (p=0.0381) Significant effect on cognitive function after 24 weeks of treatment Change in ADAS-Cog - AN
Slide 21: Alzheimer's disease
Alzheimer’s disease There were significantly fewer patients reaching severe dementia stage (MMSE<10) and a significant decrease in time to severe dementia with masitinib 4.5 mg/kg/day compared with the pooled placebo arms Significant effect on severe dementia (MMSE<10) with masitinib 4.5 versus comb
Slide 22: Neurology
Neurology Blockbuster Opportunity across three indications Annual cost of Market Market Phase of No No Indication registered Drugs Penetration Opportunity US Opportunity EU Development US Patients EU Patients (USD) (M€) (M€) Positive phase 2/3 study 800 1,200 ALS Launch of confirmatory • Radicava (1
Slide 23: Viral Diseases
Viral COVID-19 Diseases
Slide 24: COVID-19
COVID-19 Cytokine storm syndrome and lung injury may be avoided by inhibiting mast cell and macrophage activity Innate Implication in cytokine storm Evidence of masitinib activity immune Cells ▪ Mast cells contribute to COVID-19-induced inflammation by ▪ Masitinib inhibits mast cells activity throug
Slide 25: COVID-19
COVID-19 Phase 2 initiated in moderate and severe forms of the COVID-19 without limitation of age (i.e. patients above 80 will be enrolled) Phase 2 design Key differentiating factors Design: Double blind, placebo controlled, randomized 1:1, The combination masitinib + IsoQuercetin differentiates fro
Slide 26: COVID-19
COVID-19 In addition, an independent drug repurposing screen identified masitinib as the most potent drug blocking replication of SARS-CoV-2 in vitro • Drug reprofiling screening of around 12,000 drugs, using SARS-CoV-2 infected SARS-CoV-2 Progeny VERO6 cells-based assay, identified masitinib among
Slide 27: COVID-19
COVID-19 Masitinib completely inhibited in multiple assays 3CLpro activity, the SARS-CoV-2 main protease necessary for its viral replication cycle SARS-Cov-2 Virus • The 3CL-protease is the main protease found in Replication coronaviruses and is a key enzyme, as it cleaves several sites to produce n
Slide 28: COVID-19
COVID-19 X-ray crystallography revealed that masitinib directly binds to the active site of 3CLpro, thereby having a direct antiviral activity by blocking its enzymatic activity • Masitinib’s three active groups (pyridine, aminothiazole and toluene rings) contribute to the majority of interactions b
Slide 29: COVID-19
COVID-19 Blockbuster Opportunity Market Market Phase of Treatment cost of authorized No No Indication Penetration Opportunity US Opportunity EU Development drugs (USD) US Patients EU Patients (M€) (M€) • Phase 2 study in the moderate and severe forms of Covid-19 with Patients infected by • Eli Lilly
Slide 30: Oncology
First Line Non Resectable Locally Advanced Pancreatic Cancer First Line Metastatic Castrate Resistant Prostate Cancer (mCRPC) Oncology
Slide 31: Pharmacology Data - Masitinib targets tumor microenvironment
Pharmacology Data - Masitinib targets tumor microenvronment Masitinib has no direct “tumor killer” general activity but has shown efficacy on tumor proliferation in vivo, mediated through the tumor micro-environment No direct effect on tumor cells in vitro… …but decreases tumor volume growth in vivo
Slide 32: Scientific Rationale
Scientific Rationale Innate immune cells, in particular mast cells and macrophages, are critical components of the tumor microenvironment, promoting angiogenesis and tumor growth, and also contribute to tumorigenesis by suppression of the immune response ❖ There is a compelling body of evidence impl
Slide 33: Pancreatic cancer
Pancreatic cancer Study AB12005 evaluated masitinib 6.0mg/kg/day in first line pancreatic cancer patients with pain. Design Main inclusion criteria Design: 1) Histologically or cytologically confirmed adenocarcinoma of the Double-blind, 2-parallel Groups, Phase 3 Study to Compare as First Line pancr
Slide 34: Pancreatic cancer
Pancreatic cancer Study AB12005 was positive and reached its primary objective to show statistically significant increase in survival Primary Analysis ❖ The study met its primary endpoint with significant OS increase (+1.8 months median, p=0.007, below 2.5%) in population with locally advanced tumor
Slide 35: Prostate cancer – Study Design
Prostate cancer – Study Design Study AB12003 is evaluating masitinib 6.0mg/kg/day in first line metastatic Castrate Resistant Prostate Cancer. Design Main inclusion criteria Design: 1) Histologically or cytologically confirmed mCRPC with one of the Double-blind, controlled study comparing masitinib
Slide 36: Oncology
Oncology Strong market potential across indications Annual cost of drugs Market Market Opportunity Phase of No No Indication registered in similar Penetration Opportunity US EU Development US Patients EU Patients indication (USD) (M€) (M€) • Xtandi (90,000) Positive phase 2/3 • Jevtana (48,000) 1,00
Slide 37: Inflammatory Diseases
Inflammatory Indolent Systemic Mastocytosis (ISM) Diseases Severe Asthma
Slide 38: Indolent Systemic Mastocytosis
Indolent Systemic Mastocytosis Masitinib inhibits mast cells, regardless of c-Kit mutation status, through c-Kit, Lyn and Fyn kinases The c-Kit receptor is primarily responsible for mast cell growth, differentiation and survival with mast cell mediator release being initiated through the integration
Slide 39: Indolent Systemic Mastocytosis
Indolent Systemic Mastocytosis Effectiveness regardless of c-Kit mutation status confirmed in phase 2 and sustainable Improvement in disease symptoms Reduction in urticaria pigmentosa Sustained efficacy % Change from baseline at week 12 % of patients still under treatment Flush (per day) Pruritus De
Slide 40: Indolent Systemic Mastocytosis
Indolent Systemic Mastocytosis Phase 3 demonstrates significant reduction in symptoms 3.6 fold improvement in most prevalent symptoms Improvement in objective markers of the disease Masitinib Placebo p-value Odds ratio Masitinib Placebo p-value 4H75% Primary Tryptase - Patients with baseline tryptas
Slide 41: Indolent Systemic Mastocytosis
Indolent Systemic Mastocytosis Next Step Confirmatory phase 3 study, with design optimized based on first phase 3 study Confirmatory phase 3 design Optimizations from previous phase 3 Design: Double blind, placebo controlled, randomized 1:1, Dose Titration comparing masitinib titration up to 6.0 mg/
Slide 42: Severe Asthma Uncontrolled with Oral Corticosteroids
Severe Asthma Uncontrolled with Oral Corticosteroids Significant decreases in asthma exacerbations regardless of eosinophil level Annualized severe asthma exacerbation rate Greater benefit in patients with higher cumulative OCS Primary Analysis Sequential Analysis Sensitivity Analysis Sensitivity An
Slide 43: Severe Asthma Uncontrolled with Inhaled Corticosteroids
Severe Asthma Uncontrolled with Inhaled Corticosteroïds Phase 3 study evaluating masitinib in severe asthma uncontrolled by high-dose inhaled corticosteroids (ICS) and with high eosinophil level also met its primary endpoint Positive results of study AB14001 ❖ Significant 29% reduction in severe exa
Slide 44: Inflammatory Diseases
Inflammatory Diseases Strong market potential across two indications Annual cost of drugs Market Market Opportunity Phase of No No Indication registered in similar Penetration Opportunity US EU Development US Patients EU Patients indication (USD) (M€) (M€) Launch of 500 800 ISM confirmatory No regis
Slide 45: Back-up
Back-up
Slide 46: Financial Information
Financial Information • Euronext Paris: AB.PA • Ordinary Shares Outstanding: 44.8M • Cash position (€): 10.6M (as of June 30, 2020) • Convertible Bond (€): 4.5 M issued on October 2020 46
Slide 47: Masitinib - Intellectual Property
Masitinib - Intellectual Property Masitinib IP rights are secured until 2037 in ALS and between 2031 and 2036 in other indications Protection Item Duration of protection Status Patent on composition of Patent on composition of matter has been filed and delivered. It will Until 2028 Delivered matter
Slide 48: Masitinib - Publications
Masitinib - Publications Neurology Program Data Publications • Trias et al, 2020 : Schwann Cells Orchestrate Peripheral Nerve Inflammation Through the Expression of CSF1, IL-34, and SCF in Amyotrophic Lateral Sclerosis • Trias et al, 2018 : Mast cells and neutrophils mediate peripheral motor pathway
Slide 49: Masitinib - Publications
Masitinib - Publications Immunology & Oncology Program Data Publications • Humber et al, 2010 : Masitinib combined with standard gemcitabine chemotherapy: in vitro and in vivo studies in human pancreatic Preclinical tumour cell lines and ectopic mouse model Pancreatic Cancer Phase 2 • Mitry et al, 2