Slide 1: Corporate Presentation
Corporate Presentation October 2021
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 is broad coronavirus 3CL non
Slide 5: Pipeline
Pipeline Diversified portfolio with eight positive phase 2B/3 trials Therapeutic Compound Indication Preclinical Phase 1 Phase 2 Phase 2B/3 Confirmatory Phase 3 area Amyotrophic Lateral Sclerosis* First phase 2B/3 completed; 394 patients enrolled. On-going confirmatory study Neurology Alzheimer’s Di
Slide 6: Financial Information
Financial Information ▪ Euronext Paris: AB.PA ▪ Ordinary Shares Outstanding: 46.8M ▪ Cash position (€): 17.6M€ (as of June 30, 2020) ▪ Research Tax Credit 2020 to be received in 2021: 3.3M€ ▪ Debt : State-guaranteed loan of 6M€ received in April 2021 ▪ Off-balance sheet commitments: • 15M€ Loan agre
Slide 7: Masitinib
MASITINIB
Slide 8: 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 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: 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 11: Masitinib Safety Database Across Indications
Masitinib Safety Database Across Indications Well established safety profile with long-term exposure Safety population Patients exposed for at least All ≥ 6 months ≥ 12 months ≥ 2 years ≥ 5 years Healthy Volunteers subjects 114 0 0 0 0 Non Oncology subjects 3,338 2,124 1,519 665 50 Oncology subjects
Slide 12: 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 Severe Asthma 825 000 Blockbuster potential Multiple Sclerosis (PPMS & nSPMS) 500 000 Mast Cell
Slide 13: Masitinib in Neurology Diseases
Masitinib in Neurology Amyotrophic Lateral Sclerosis (ALS) Diseases Alzheimer's Disease (AD) Multiple Sclerosis (PPMS and nSPMS)
Slide 14: Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS) Study AB10015 evaluated two masitinib doses in patients with ALS. Design Main inclusion criteria Pre-specified Analysis Plan Design 1) Patients with probable, or definite ALS, Two distinct populations were differentiated: Prospective, multicenter, randomized, doub
Slide 15: Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS) Phase 2B/3 demonstrated significant delay in disease progression in “Normal” progressors with masitinib 4.5 mg/kg/day 27% slowing of functional deterioration (Primary Endpoint) 25% delay in disease progression (PFS) al) 0.0 Placebo 100 Masitinib 4.5mg Placebo Masi
Slide 16: Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS) Clinical benefit further enhanced when treatment initiated early 42% slowing of functional deterioration (vs 27%) % reduction in change in ALSFRS (primary endpoint – Normal progressors) Masitinib 4.5mg/kg/day Moderate / Severe / Very Moderate / Severe ALS Moderate
Slide 17: Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS) Long-term survival follow-up showed a significant survival benefit of +25 months when treatment was initiated early + 25 months in median Overall Survival in patients with moderate ALS Kaplan–Meier survival curves from masitinib study AB10015 long-term survival an
Slide 18: Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS) On-going confirmatory phase 3 study, with design validated by health authorities through Scientific Advise Confirmatory phase 3 design Optimizations from previous phase 3 Design: Double blind, placebo controlled, randomized 1:1:1:1, Enriched inclusion criteria com
Slide 19: Alzheimer's disease (AD)
Alzheimer’s disease (AD) Masitinib is positioned in patients with mild and moderate dementia, which is different from other compounds MMSE Score Disease severity Aducanumab Masitinib (mini mental state examination) Prodromal > 25 Prodromal AD > 22 / > 24 Mild [21 – 25] Mild & Moderate AD [ 12 – 25]
Slide 20: Alzheimer's disease (AD)
Alzheimer’s disease (AD) Study AB09004 evaluated in patients with mild and moderate AD, three doses of masitinib, each dose having its own placebo control Design Main inclusion criteria Pre-specified Analysis Plan Design 1) Patient with dementia of Alzheimer's type, Statistical analysis: Prospective
Slide 21: Alzheimer's disease (AD)
Alzheimer’s disease (AD) 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) with masitinib 4.5 mg/kg/day Significant effect on cognitive function after 24 weeks of
Slide 22: Alzheimer's disease (AD)
Alzheimer’s disease (AD) 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
Slide 23: 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 24: Multiple Sclerosis
Multiple Sclerosis Study AB7002 evaluated two masitinib doses in patients with PPMS and non-active SPMS. Design Main inclusion criteria Pre-specified Analysis Plan Design 1) Patient with Primary Progressive (PPMS) or Statistical analysis: Prospective, multicenter, randomized, double Non-active secon
Slide 25: Multiple Sclerosis
Multiple Sclerosis Phase 2B/3 demonstrated significant benefit on disability progression with masitinib 4.5 mg/kg/day 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 9
Slide 26: 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 27: Masitinib in Inflammatory Diseases
Masitinib in Neurology Indolent Systemic Mastocytosis (ISM) Inflammatory Mast Cell Activation Syndrome (MCAS) Diseases Severe Asthma
Slide 28: Indolent Systemic Mastocytosis (ISM)
Indolent Systemic Mastocytosis (ISM) Study AB06006 evaluated masitinib versus placebo in 135 patients with ISM and severe symptoms at baseline. Design Main inclusion criteria Pre-specified Analysis Plan Design 1) Patient with one of the following Response : documented mastocytosis as per WHO Prospec
Slide 29: Indolent Systemic Mastocytosis
Indolent Systemic Mastocytosis Phase 2 showed masitinib is effective on key disease symptoms, regardless of c-Kit mutation status, and efficacy is sustainable Improvement in disease symptoms Sustained efficacy Reduction in urticaria pigmentosa % Change from baseline at week 12 % of patients still un
Slide 30: Indolent Systemic Mastocytosis
Indolent Systemic Mastocytosis Phase 3 demonstrates significant reduction in symptoms with masitinib 6.0 mg/kg/day 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 - P
Slide 31: Indolent Systemic Mastocytosis
Indolent Systemic Mastocytosis On-going confirmatory phase 3 study, with design validated by key health authorities 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/kg/d
Slide 32: MCAS (Mast Cell Activation Syndrome)
MCAS (Mast Cell Activation Syndrome) MCAS is a disease caused by activation of mast cells Disease Features Treatment Objectives ▪ MCAS is a common disease associated with numerous symptoms. o Symptoms are similar to mastocytosis ones and include - Fatigue, - Neurologic/psychiatric symptoms, - Pain A
Slide 33: MCAS (Mast Cell Activation Syndrome)
MCAS (Mast Cell Activation Syndrome) Study AB20006 is a phase 2 evaluating ascending doses of masitinib Design Main inclusion criteria Design: 1) Patient with severe Mast cell activation syndrome (MCAS) Randomized, double-blind, placebo-controlled, parallel-group, diagnosed based on both clinical an
Slide 34: Severe Asthma Uncontrolled with Oral Corticosteroids
Severe Asthma Uncontrolled with Oral Corticosteroids Study AB07015 evaluated masitinib 6.0 mg/kg/day in patients with severe asthma uncontrolled by OCS Design Main inclusion criteria Pre-specified Analysis Plan Design 1) Oral corticosteroids (OCS) dose ≥ 7.5 mg Primary analysis : Prospective, multic
Slide 35: Severe Asthma Uncontrolled with Oral Corticosteroids
Severe Asthma Uncontrolled with Oral Corticosteroids Significant decreases in asthma exacerbations regardless of eosinophil level Greater benefit in patients with higher cumulative OCS Annualized severe asthma exacerbation rate (>500mg or >1000mg) Primary Analysis Sequential Analysis patients Sensit
Slide 36: Severe Asthma Uncontrolled with Inhaled Corticosteroids
Severe Asthma Uncontrolled with Inhaled Corticosteroïds Study AB14001 evaluated masitinib titration up to 6.0 mg/kg/day in patients with severe asthma uncontrolled by ICS and with elevated eosinophil levels Design Main inclusion criteria Pre-specified Analysis Plan Design 1) Patient with history of
Slide 37: Severe Asthma Uncontrolled with Inhaled Corticosteroids
Severe Asthma Uncontrolled with Inhaled Corticosteroïds Phase 3 AB14001 in severe asthma uncontrolled by high-dose inhaled corticosteroids (ICS) and with high eosinophil level also met its primary endpoint Annualized severe asthma Significant improvement in quality of life exacerbation rate Primary
Slide 38: Inflammatory Diseases
Inflammatory Diseases Strong market potential across three 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 reg
Slide 39: Masitinib in Oncology
Masitinib in Oncology First Line Non Resectable Locally Advanced Pancreatic Cancer (LAPC) First Line Metastatic Castrate Resistant Prostate Cancer (mCRPC)
Slide 40: 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 41: Pain in cancer
Pain in cancer The presence of pain in pancreatic cancer is thought to flag an increased mast cell activity within the tumor microenvironment, which in turn promotes disease progression. Pain therefore effectively identifies those patients with a pro-tumoral immune response ❖ There is evidence that
Slide 42: 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 43: Pancreatic cancer with pain
Pancreatic cancer with pain Study AB12005 evaluated masitinib 6.0 mg/kg/day in first line pancreatic cancer patients with pain Design Main inclusion criteria Pre-specified Analysis Plan Design 1) Histologically or cytologically confirmed Statistical analysis: Alpha spending split between Prospective
Slide 44: Pancreatic cancer with pain
Pancreatic cancer with pain There was no benefit in the overall population, yet 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 tumors No benefit on survival in the Overall Population 54% risk reduction of
Slide 45: Pancreatic cancer with pain
Pancreatic cancer with pain Progression free survival and response rate were in favor of masitinib and consistent with survival results 53% risk reduction of time to progression in locally advanced ORR 14.5% (M) vs 3.3% (P) in locally advanced Locally advanced – KM Analysis of PFS 100 Masitinib Plac
Slide 46: Pancreatic cancer with pain
Pancreatic cancer with pain Masitinib reduced pain in patients with locally advanced tumors, supporting the rationale for targeting this population having pain at baseline Significant improvement vs control in pain in locally advanced Numerical improvement vs control in pain in overall population Lo
Slide 47: Metastatic Castrate Refractory Prostate Cancer (mCRPC)
Metastatic Castrate Refractory Prostate Cancer (mCRPC) Masitinib is positioned in combination with docetaxel as first-line treatment of mCRPC eligible to chemotherapy Stage of the desease Registered Drug1 Enzalutamide (Xtandi) 1 High-risk non Metastatic Castration Resistant Prostate Cancer (before c
Slide 48: Metastatic Castrate Refractory Prostate Cancer (mCRPC)
Metastatic Castrate Refractory Prostate Cancer (mCRPC) Study AB12003 evaluated masitinib 6.0 mg/kg/day in combination with docetaxel versus docetaxel alone in first-line treatment of mCRPC Design Main inclusion criteria Pre-specified Analysis Plan Design 1) Patient with histologically or cytological
Slide 49: Metastatic Castrate Refractory Prostate Cancer (mCRPC)
Metastatic Castrate Refractory Prostate Cancer (mCRPC) There was no benefit in the overall population, yet the study met its primary analysis in the pre-specified targeted subgroup, demonstrating a statistically significant increase in PFS (p=0.0272) 21% risk reduction of time to progression in pati
Slide 50: 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 51: Masitinib in Viral Diseases
Masitinib in Viral COVID-19 Diseases
Slide 52: 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 inflammation by activating ▪ Inhibition of mast cells activity through c-Kit, LY
Slide 53: COVID-19
COVID-19 First Phase 2 evaluating masitinib anti-inflammatory activity in adult hospitalized patients with moderate and severe COVID-19 without limitation of age (i.e. patients above 80 enrolled) Phase 2 design Key differentiating factors Design: Double blind, placebo controlled, randomized 1:1, The
Slide 54: COVID-19
COVID-19 Publication in Science shows that masitinib completely inhibited in multiple assays 3CLpro activity, the SARS- CoV-2 main protease necessary for its viral replication cycle Masitinib directly binds to the active site of Masitinib inhibits efficiently the replication Masitinib inhibits SARS-
Slide 55: COVID-19
COVID-19 Second Phase 2 evaluating masitinib anti-viral activity in ambulatory or hospitalized patients with symptomatic mild and moderate COVID-19 Phase 2 design Key differentiating factors Design: Double-Blind, Placebo-Controlled, Multiple Doses, ▪ Well established pharmacokinetic profile is at mu
Slide 56: 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 to evaluate efficacy of masitinib • Eli Lilly monoclonal antibody Hospitalized Patie
Slide 57: Masitinib – Main Publications
Masitinib – Main 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 pa
Slide 58: Masitinib – Main Publications
Masitinib – Main Publications Immunology, oncology and viral diseases Program Data Publications Phase 2 • Paul et al, 2010 : Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study Mastocytosis • Lortholary et al, 2017 (Lancet) : Masitinib for treatment of
Slide 59: AB8939
AB8939
Slide 60: 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 61: Relapsed/Refractory Acute Myeloid Leukemia (AML)
Relapsed/ Refractory Acute Myeloid Leukemia (AML) Phase 1/2 to assess the safety, pharmacokinetics, and efficacy of AB8939 in patients with Relapsed/ Refractory AML Phase 1/2 design Phase 1/2 Objectives Design: Open-label, Uncontrolled, Multiple Doses, phase 1 study Main inclusion criteria: ▪ Patien