Slide 1: Web-Conference Clinical Development Update
Web-Conference Clinical Development Update December 2024
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: AB Science has three platforms: masitinib, AB8939 and discovery projects
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 4: AB8939 Platform
AB8939 PLATFORM
Slide 5: Target Product Profile; Pharmacology Data; Phase 1; Planned Phases 2; IP
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Planned Phases 2 Intellectual Property 5
Slide 6: AB8939 is a next generation 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 7: AB8939 has a 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 8: Objective is to position AB8939 combination 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 9: Target Product Profile; Pharmacology Data; Phase 1; Planned Phases 2; IP
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Planned Phases 2 Intellectual Property 9
Slide 10: AB8939 is active against chemotherapy naive or refractory/relapsing AML cells ex vivo
AB8939 is active against chemotherapy naive or chemotherapy refractory/relapsing patient’s AML cancers cells ex vivo ❖ 69% of blasts isolated from a cohort of 99 AML patients at diagnosis are sensitive to AB8939 (IC50<1 µM), ❖ Among the blasts isolated from this cohort that are resistant to Ara-C, 6
Slide 11: AB8939 eradicates blasts in blood and bone marrow in 5-AraC-resistant PDX
AB8939 eradicates blasts in Blood and Bone Marrow in 5-AraC-resistant (Cytarabine) PDX Red luminescence detects cancer cells 11
Slide 12: AB8939 increases survival and has additive effect 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) ZA ZA 39 RL 89 DA A CT ID AB
Slide 13: AB8939 increases survival and has potential additive effect 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 14: ALDHs expression is a hallmark of cancer stem cells and 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 15: AB8939 eradicates Leukemia Cancer Stem Cells in a human 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 16: Target Product Profile; Pharmacology Data; Phase 1; Planned Phases 2; IP
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Planned Phases 2 Intellectual Property 16
Slide 17: The objective of the phase 1 is to determine the 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 18: Case Report 1 in non MECOM patient
Case Report 1 in non MECOM patient: Response in refractory AML patient with intermediate-risk prognosis receiving low dose of AB8939 and stable disease after at least 108 days Step 1, 3 days, single agent AB8939 Dose Cycle 1 Baseline characteristics (GR-04-001) Dose 1 : 0.9 mg/m2 3 days ▪ Patient (8
Slide 19: Case Report 2 in non MECOM patient
Case Report 2 in non MECOM patient: Response after first cycle of 14 days Step 2, 14 days, single agent AB8939 Dose Baseline characteristics (ES-07-006) Dose 1 : 16.0 mg/m2 ▪ Patient (38 years old) with high-risk AML Cycle 1 Dose 2 : 21.3 mg/m2 14 days ▪ Adverse cytogenetic risk 21.3 mg/m2 ▪ Mutatio
Slide 20: Target Product Profile; Pharmacology Data; Phase 1; Planned Phases 2; IP
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Planned Phases 2 Intellectual Property 20
Slide 21: MECOM is associated with a dismal outcome and only 14% response rate
MECOM is associated with a dismal outcome, with short survival and only 14% response rate(1) in relapsed or refractory setting Impact of cytogenetic entities recognized in 2008 WHO classification24 on survival . Survival of AML with 3q abnormality treated with AZA according to prior treatments. Surv
Slide 22: AB8939 is a stem cell ALDH targeted therapy with potential use in AML with MECOM
AB8939 is a stem cell ALDH targeted therapy with potential use in AML with MECOM Scientific Rationale ▪ ALDH gene expression is a marker of survival prognosis in AML. The higher the expression, the worse the prognosis ▪ MECOM is associated with the worst prognosis in AML ▪ Mecom is a rearrangement o
Slide 23: Case Report 1 in MECOM patient
Case Report 1 in MECOM patient: Response in a refractory AML patient with MECOM rearrangement receiving low dose of AB8939 Step 1, 3 days, single agent AB8939 Dose Dose 1 : 0.9 mg/m2 Baseline characteristics (ES-07-001) Cycle 1 ▪ Patient (65 years old) with Secondary AML Dose 2 : 1.8 mg/m2 3 days ▪
Slide 24: Case Report 2 in MECOM patient
Case Report 2 in MECOM patient: Response after first cycle of 14 days Step 2, 14 days, single agent AB8939 Dose Cycle 1 Baseline characteristics (GR-04-001) Dose 1 : 16.0 mg/m2 14 days ▪ Patient (63 years old) with AML with myelodysplasia-related changes 16.0 mg/m2 ▪ add(2)(q13), del(3)(q21q26), add
Slide 25: AB8939 has shown activity on MECOM rearrangement with 50% response rate
AB8939 has shown activity on MECOM rearrangement, based on non-clinical data and early clinical data with 50% response rate observed ▪ 50% response rate in in-vitro tests Drug sensitivity (IC50 µM) in MECOM Karyotype In-vitro, AB8939 was effective (IC50 of 50nM Patient ID AML type AraC AB8939 Azacit
Slide 26: Target Product Profile; Pharmacology Data; Phase 1; Planned Phases 2; IP
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Planned Phases 2 Intellectual Property 26
Slide 27: First step is to capture market potential in MECOM AML via accelerated approval
The first intended step is to capture the market potential of AB8939 in patients with MECOM AML through accelerated approval based on response rate ❖ MECOM accounts for around 5% of AML and is a sizable market >100 million euros Region Incidence Case (1) Market Size (per in in Mio EUR) R/R AML 90,20
Slide 28: First MENIN inhibitor registered based on phase 1/2 study with fewer than 100 patients
the first MENIN inhibitor, targeting AML with specific rearrangement, has been registered based on a phase 1/2 study with less than 100 patients in relapse/refractory patients Trial Patient Drug Phase Regimen Eligibility (ClinicalTrials.gov ID) Population AUGMENT- I/II Revumenib monotherapy 95 Adult
Slide 29: Second objective is to capture full market potential in broader forms of AML
The second objective is to capture the full market potential of AB8939 in broader forms of AML and position AB8939 in relapse/refractory The third objective could be to also position AB8939 in first line A possible design could be the following: ▪ Phase 2 controlled study ▪ Objective #2 : In relapse
Slide 30: Target Product Profile; Pharmacology Data; Phase 1; Planned Phases 2; IP
Target Product Profile Pharmacology Data Phase 1 Preliminary Safety and Efficacy Preliminary Activity in MECOM Planned Phases 2 Intellectual Property 30
Slide 31: AB8939 intellectual property rights in AML secured until 2036
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
Slide 32: Masitinib Platform
MASITINIB PLATFORM
Slide 33: The strategy is to continue masitinib development through partnerships
The strategy is to continue masitinib development through partnerships ▪ Discussion for masitinib partnership is on-going ▪ AB Science will provide an update of masitinib in neuro-degenerative diseases during next communication 33
Slide 34: Finance
FINANCE
Slide 35: Financing strategy
AB Science raised 5 millions euros in Q4 2024, which provides financial runway for more than 12 months Financing Strategy ▪ Neuro-degenerative diseases : Financing through partnership Masitinib ▪ Sickle Cell Disease : Financing of phase 2 through RHU collaborative program with APHP (9.2M€) ▪ Phase 1