Ab Science Sa · EURONEXT:AB
Ab Science Sa — Investor Presentation (March 2025)
59 slides from Ab Science Sa's investor presentation, March 2025
Slide 1: Corporate Presentation
Corporate Presentation March 2025
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: Overview: Management Team and Stock Information
Overview Management Team Stock Information ALAIN MOUSSY OLIVIER HERMINE, Co-founder and MD, PhD ▪ Listed on Euronext Compartment B CEO Co-founder and Chairman of ▪ ISIN : FR0010557264 Former strategic consultant at Booz, Scientific Allen & Hamilton and former Head of Committee ▪ Tickers : AB.PA (Reu
Slide 4: AB Science has three platforms, masitinib, AB8939 and discovery
AB Science has three platforms, platform 1with masitinib, in phase 3, primarily centered around neuro-degenerative diseases, platform 2 with AB8939 in AML and platform 3 with new discovery projects Platform Drug Therapeutic area Indication Development Stage Amyotrophic Lateral Sclerosis Phase 3 Neur
Slide 5: Masitinib Platform
MASITINIB PLATEFORM
Slide 6: Target Product Profile: Amyotrophic Lateral Sclerosis
Target Product Profile Amyotrophic Lateral Sclerosis Multiple Sclerosis Alzheimer’s Disease Other indications Intellectual Property 6
Slide 7: Masitinib is an orally-administered kinase inhibitor targeting mast cells and macrophages
Masitinib is an 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 critical roles in the activatio
Slide 8: Masitinib's dual-targeting strategy in neurodegenerative diseases
Masitinib’s dual-targeting strategy, targeting mast cells and macrophages, is uniquely positioned to realize this therapeutic potential in neurodegenerative diseases (NDDs) Microglia and mast cells are at the cutting edge of research Masitinib has demonstrated neuroprotective benefits in regarding N
Slide 9: Target Product Profile: Amyotrophic Lateral Sclerosis
Target Product Profile Amyotrophic Lateral Sclerosis Multiple Sclerosis Alzheimer’s Disease Other indications Intellectual Property 9
Slide 10: In ALS, competitive programs failed and masitinib is the most advanced
In ALS, all competitive programs with different approaches failed and Masitinib is today the most advanced compound in clinical development with a validated scientific approach and positive clinical data Drug Sponsor • Approved by the FDA in 1995 and EMA in 1997 with Riluzole Generic modest OS benef
Slide 11: Masitinib has a proven mechanism of action via mast cells and microglia
Masitinib has a proven mechanism of actions acting via mast cells inhibition and microglia modulation, as published in several peer-reviewed journals There is a Strong Scientific Rationale There is a Well Demonstrated Mechanism of Action Masitinib exerts a protective effect on the central nervous Ma
Slide 12: Phase 2B enrolled patients with broad inclusion criteria
Phase 2B enrolled 394 patients with broad inclusion criteria and evaluated Masitinib after 48 weeks of treatment. The primary analysis was preplanned in the population defined as “Normal” progressors, following an early protocol amendment Design Statistical analysis Design: Two distinct populations
Slide 13: First phase 2B/3 met its primary analysis in ALS
A first phase 2B/3 (394 patients) met its primary analysis, slowing down functional decline at week 48, and generated a strong hypothesis for confirmatory phase 3 with the identification of an optimal population (normal progressor prior to loss of function) AB10015 – Subgroup Analysis AB10015 - Prim
Slide 14: Survival benefit of +12 months in patients prior to loss of function
In particular, in this population prior a complete loss of function, a significant survival benefit of +12 months was observed based on long-term follow-up Overall Survival - KM Curves - Patients prior to any complete loss of function - Masitinib 4.5 vs placebo 100 Placebo Masitinib 4.5 90 Survival
Slide 15: Very long-term survivors under compassionate use program
Following patients under compassionate use program, we observe very long-term survivors that are not explained by the published model that predicts survival based on baseline characteristics A large proportion of patients treated with masitinib Survival for these patients is not explained by the 4.5
Slide 16: EMA considered the safety of masitinib acceptable in ALS
In its benefit-risk assessment, EMA considered the safety of Masitinib acceptable in ALS Masitinib Safety Benefits from a Large Database Masitinib Safety is Deemed Acceptable in ALS Number of Patients Randomized in Masitinib Treatment Arms CHMP Latest Assessment Report Safety Population Safety popul
Slide 17: Results published in two peer-reviewed journals
Results from phase 2B/3 and long-term survival were published in two peer-reviewed journals 17
Slide 18: Confirmatory phase authorized by FDA and approved through CTIS
A confirmatory phase 3 has been authorized by FDA and harmonized protocol has been approved through step 1 of CTIS 204 Masitinib 4.5mg/kg/day + Optional Extension Riluzole Randomizatioion Last patient Last visit week 48 Screening Concomitant treatment with edaravone authorized if initiated prior to
Slide 19: Target Product Profile: Multiple Sclerosis
Target Product Profile Amyotrophic Lateral Sclerosis Multiple Sclerosis Alzheimer’s Disease Other indications Intellectual Property 19
Slide 20: Unmet need in progressive MS
There is a tremendous unmet need in progressive MS, with no approved drugs for non-active secondary progressive MS and one for primary progressive MS ▪ Vast majority of drugs are effective only in active MS patients because these drugs stop immune attacks (active inflammation) but cannot repair myel
Slide 21: Tolebrutinib success validates targeting microglia
The recent success of tolebrutinib in secondary progressive MS, a BTK inhibitor targeting microglia, validates the strategy of targeting microglia, although BTKi have a safety class effect Tolebrutinib* 24% risk reduction of time to 3 months confirmed disability BKT inhibitors Safety Class Effect pr
Slide 22: Masitinib showed activity in animal model of multiple sclerosis
Masitinib’s targeting of the innate immune system showed activity in animal model of multiple sclerosis In EAE mouse model of MS, masitinib showed significant reduction in disease. Masitinib lowered blood levels of NfL in a EAE model The potential of masitinib in MS was explored using a MOG-EAE mode
Slide 23: Phase 2B/3 enrolled 656 patients
Phase 2B/3 enrolled 656 patients Sub-study I Sub-study II Dosing Dosing Dosing Masitinib 4.5 mg/kg/day vs Masitinib 4.5 to 6.0 mg/kg/day 6.0 mg/kg/day matching placebo titration vs matching placebo ITT population ITT population N=301 N=45 N=310 (M=200 ; P=101) (M=203 ; P=107) mITT population* Stoppe
Slide 24: Significant benefit on disability progression in advanced stage patients
Phase 2B/3 demonstrated a significant benefit on disability progression with masitinib 4.5 mg/kg/day in patients with advanced stage of the disease Significant reduction in progression on EDSS Patients were enrolled at advanced disease stage (Primary Endpoint*) 0.2 ▪ Median age (years) : 50.0 (both
Slide 25: Phase 2B reduction of risk of disability progression
Phase 2B demonstrated a significant reduction of risk of first disability progression by 42% and a reduction of risk of confirmed (12-week) disability progression by 37% 37% risk reduction of time to confirmed disability 42% risk reduction of time to disability progression (12 weeks) progression (12
Slide 26: Masitinib potential best-in-class for PPMS and nSPMS
Masitinib has the potential to become a best-in-class drug for PPMS and nSPMS comparison of 3- month confirmed disability progression Time to confirmed disability progression (CDP) Study Size Drug Type of Progressive MS Hazard Ratio Reduction in risk of CDP (patients) Masitinib 4.5 mg/kg/day 300 PPM
Slide 27: Results published in peer-reviewed journal
Results from phase 2B/3 were published in peer-reviewed journal 27
Slide 28: Confirmatory phase study authorized by FDA and European countries
Confirmatory phase 3 study is authorized by FDA and key European countries Primary endpoint 400 Randomizatioion Masitinib 4.5mg/kg/day ▪ Time to confirmed EDSS progression End of Study Screening Main secondary endpoints ▪ Change in EDSS from baseline considering all measurements from baseline up to
Slide 29: Target Product Profile: Alzheimer's Disease
Target Product Profile Amyotrophic Lateral Sclerosis Multiple Sclerosis Alzheimer’s Disease Other indications Intellectual Property 29
Slide 30: Masitinib developed in more advanced forms of Alzheimer's
Masitinib is developed in more advanced forms of Alzheimer’s disease as compare with biologics recently approved AD severity based on MMSE score 30 26 20 10 Prodromal Mild Moderate Severe Lecanemab (Eisai/Biogen): MMSE [22 – 30] Approved Donanemag (Eli Lilly): MMSE [20 – 28] Phase 3 * Masitinib: MMS
Slide 31: Masitinib has a differentiating positioning
Masitinib has a differentiating positioning Strategy Approved Drugs Sponsor ▪ Currently the main strategy for early AD Main Strategy 1 Donanemab (Kisunla) Eli Lilly ▪ Class-effect warning for amyloid-related imaging abnormalities (ARIA) beta amyloid ▪ ARIA can be life-threatening (swelling in areas
Slide 32: Phase 2B/3 enrolled 718 patients from 118 sites
Phase 2B/3 enrolled 718 patients from 118 sites in 21 countries Sub-study I Sub-study II Dosing Dosing Dosing Dosing Masitinib 4.5 mg/kg/day vs Masitinib 4.5 to 6.0 mg/kg/day 3.0 mg/kg/day 6.0 mg/kg/day matching placebo titration vs matching placebo ITT population ITT population N=58 N=370 N=12 N=27
Slide 33: Significant reduction in cognitive impairment on ADAS-Cog
Phase 2B/3 study demonstrated a 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 treatment Change in ADAS-Cog - ANCOVA Ana
Slide 34: Treatment effect on cognition sustained at week 48
The treatment effect on COG was sustained at week 48 Significant effect on cognitive function after 48 weeks of treatment LSM of ADAS-Cog Change from Baseline - Masitinib 4.5 versus Placebo (Full Analysis Set Population) Mastinib 4.5 mg (N=182) Placebo 3/4.5 mg (N=176) 3 2 LS Mean (+/- SE) 1 0 -1 -2
Slide 35: Results published in peer-reviewed journal
Results from phase 2B/3 were published in peer-reviewed journal 35
Slide 36: Confirmatory phase study authorized by FDA and European countries
Confirmatory phase 3 study is authorized by FDA and key European countries Primary endpoint 300 ▪ Change from baseline in ADCS-ADL score at week 24, Extension period Randomizatioion Masitinib 4.5mg/kg/day End of Study and Screening ▪ Change from baseline in ADAS-Cog 11 score at week 24 Main secondar
Slide 37: Target Product Profile: Other Indications
Target Product Profile Amyotrophic Lateral Sclerosis Multiple Sclerosis Alzheimer’s Disease Other indications Intellectual Property 37
Slide 38: Masitinib Platform – Sickle Cell Disease
Masitinib Platform – Sickle Cell Disease SCD is the largest monogenic disease worldwide, with a disproportionate burden on Black communities and masitinib will address severe form of SCD Growing Market, driven by the high cost of novel drugs and Major Health Problem rising awareness SCD is a group o
Slide 39: Masitinib Platform – Sickle Cell Disease phase 2 funded
Masitinib Platform – Sickle Cell Disease Phase 2 of masitinib as a new treatment of SCD for patients harboring a specific biomarker is funded through public collaborative program ▪ Mast cells appear to play a critical role for the severe forms of SCD Scientific ▪ Masitinib has demonstrated in an SCD
Slide 40: Masitinib Platform – Other programs
Masitinib Platform – Other programs Masitinib pipeline in oncology and inflammatory diseases can add value to the neurology platform Therapeutic Indication Results Development Status area ▪ First phase 3 completed (135 patients) ▪ Confirmatory phase 3 ongoing Indolent systemic mastocytosis ▪ Signifi
Slide 41: Target Product Profile: Intellectual Property
Target Product Profile Amyotrophic Lateral Sclerosis Multiple Sclerosis Alzheimer’s Disease Other indications Intellectual Property 41
Slide 42: Masitinib IP rights secured through use patents
Masitinib IP rights are secured through use patent until 2037 in ALS and up to 2041 in MS and AD Scope Protection Title Reference Duration of protection Treatment of multiple sclerosis with masitinib WO2011131705 2031 Multiple Use patent Sclerosis Masitinib for the treatment of a multiple sclerosis
Slide 43: AB8939 Platform
AB8939 PLATEFORM
Slide 44: Target Product Profile
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Intellectual Property 44
Slide 45: AB8939 is a synthetic microtubule destabilizer and ALDH1/2 inhibitor
AB8939 is a next generation synthetic microtubule destabilizer and targeted stem cell ALDH1/2 inhibitor with key differentiating factors for treatment of refractory/relapsing acute myeloid leukemia (AML) Scientific Rationale AB8939 Target Product Profile Targeted Indications ▪ Microtubules are criti
Slide 46: AB8939 potential to improve treatment of relapsed/refractory AML
AB8939 has a potential to improve treatment of relapsed / refractory AML Relapsed / refractory AML (R/R AML) * Line 1 Line 2 Line 3 No approved drug Patients eligible to high Anthracyclines + cytarabine + High dose chemotherapy or dose chemotherapy Low dose chemotherapy or targeted therapies (IDH/FL
Slide 47: Position AB8939 as standard of care in refractory/relapsing AML
The objective is to position AB8939 combination treatment to be the standard of care in refractory/relapsing AML, which represents a market size potential above EUR 2 billions per annum, including EUR 100 millions for AML with MECOM gene rearrangement Incidence Case % Relapse or % Insured Patients M
Slide 48: Pharmacology Data
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Intellectual Property 48
Slide 49: AB8939 eradicates blasts in blood and bone marrow in resistant PDX
AB8939 eradicates blasts in Blood and Bone Marrow in 5-AraC-resistant (Cytarabine) PDX Red luminescence detects cancer cells 49
Slide 50: AB8939 increases survival and is additive with azacitidine
AB8939 increase survival and has an additive effect in combination with reference treatment Azacitidine A. Study Design C. Blood 100 80 • AB8939/ vidaza 60 40 % hCD33/µL 20 combination allows 15 the clearing of 10 leukemia blasts in 5 blood, spleen and 0 bone marrow (C) TR L 89 39 A ZA A ZA C B ID I
Slide 51: AB8939 additive effect in combination with venetoclax
AB8939 increase survival and has a potential additive effect in combination with reference treatment Venetoclax A. Study Design C. BLOOD 15000 10000 AB8939/ Venetoclax 5000 hCD33 (cell/µL) 150 combination allows the 100 clearing of leukemia blasts in blood, spleen 50 and bone marrow 0 without adding
Slide 52: ALDH expression is a hallmark of cancer stem cells; AB8939 inhibits ALDH1/2
ALDHs expression is a hallmark of cancer stem cells (CSCs) and AB8939 is an inhibitor of ALDH1/2 ❖ Preliminary in vitro studies have shown that AB8939 inhibits ❖ Reverse proteomic analysis revealed ALDHs as both recombinant ALDH1A1 and ALDH2 with a sub-micromolar main AB8939 interactors potency 150
Slide 53: AB8939 eradicates leukemia cancer stem cells in PDX AML model
AB8939 eradicates Leukemia Cancer Stem Cells in a human PDX AML model ▪ Preliminary AB8939 treatment eradicates most of leukemia cells in the bone marrow (step 1). ▪ AB8939 reduces the re-occurrence of leukemia following re-transplanted of leukemia cells indicating that AB8939 treatment eradicates b
Slide 54: Phase 1 Preliminary Safety and Efficacy
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Intellectual Property 54
Slide 55: Phase 1 objective: determine maximum tolerated dose
The objective of the phase 1 is to determine the maximum tolerated dose (MTD) for three different cycles of AB8939 Step 1 Step 2 Step 3 MTD* 3 DAYS MTD 14 DAYS MTD 14 DAYS AB8939 alone AB8939 alone AB8939 Combination Completed On-going Next Steps 28 patients randomized Near completion (some patients
Slide 56: Preliminary Activity in MECOM
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Intellectual Property 56
Slide 57: MECOM associated with dismal outcome; AB8939 shows activity
MECOM is associated with a dismal outcome, with short survival and only 14% response rate(1) in relapsed or refractory setting AB8939 has shown activity on MECOM rearrangement, based on non-clinical data and early clinical data with 50% response rate observed Impact of cytogenetic entities recognize
Slide 58: Intellectual Property
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Intellectual Property 58
Slide 59: AB8939 intellectual property rights in AML
AB8939 intellectual property rights in AML are secured until 2036 through a ‘composition of matter’ patent and potentially until 2044 in AML with chromosome abnormality through a ‘second medical use’ patent. AB Science is the sole proprietary holder of AB8939 and its family of compounds Protection E