Slides
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Web-Conference Clinical Development Update December 2024
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2 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 laws and regulation. This document is solely for your information on a confidential basis and may not be reproduced, redistributed or sent, in whole or in part, to any other person, including by email or by any other means of electronic communication. In particular, neither this document nor any copy of it may be taken, transmitted or distributed, directly or indirectly, in the United States, Canada, Japan or Australia. The distribution of this document in other jurisdictions may be restricted by law and persons into whose possession this document comes should make themselves aware of the existence of, and observe, any such restrictions. Neither the Company, nor any of its advisors and representatives may accept any responsibility for any loss or damage incurred by the use of this document or the information set forth herein. Neither the Company, nor any of its advisors and representatives takes any undertaking nor guarantees, whether explicitly or tacitly, the accuracy or the completeness of the information set forth herein. Neither this document, nor any part of it, shall form the basis of, or be relied upon in connection with, any contract or commitment whatsoever. In particular, in France, any decision to purchase such securities shall rely solely on the documents that have been reviewed by the Autorité des Marchés Financiers (the “AMF”) and/or published by the Company. This document does not constitute an offer to purchase any financial instruments in the United States. Securities mentioned in this document have not been and will not be registered under the Securities Act of 1933, as amended (the “Securities Act”) and may not be offered or sold in the United States absent registration or an exemption from the registration requirements of the Securities Act. The Company does not intend to register any offering in all or in part or to make a public offer of securities in the United States. This document contains information on the objectives of the Company along with some projections and forward-looking statements. The reader’s attention is drawn to the fact that these objectives may not be fulfilled, and the forecasts or information provided may prove erroneous, and the Company is not required to update such information. Past performance is no guide to future performance and persons needing advice should consult an independent financial adviser.
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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 3 Platform Drug Therapeutic area Indication Development Stage Tyrosine Kinase Inhibitor Masitinib (Oral) Neuro-degenerative Diseases (NDD) Amyotrophic Lateral Sclerosis Phase 3 Progressive Forms of Multiple Sclerosis Phase 3 Alzheimer’s Disease Phase 3 Mast Cell Diseases Indolent Systemic Mastocytosis Phase 3 Mast Cell Activation Syndrome Phase 2 Blood diseases Sickle Cell Disease (1) Phase 2 Oncology Platform AB8939 (IV) Hematology Acute Myeloid Leukemia (AML) Phase 1 ABXXXX (oral) Oncology Sarcoma, Solid Tumors Preclinical Drug Discovery Platform Target 1: undisclosed for neurodegenerative diseases Target 2: undisclosed for neurodegenerative diseases Drug Discovery (1) Collaborative programme with Assistance Publique - Hôpitaux de Paris (AP-HP) as sponsor, publicly funded as part of the "hospital-university health research " projects under the Future Investment Programme.
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AB8939 PLATFORM
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5 Target Product Profile Pharmacology Data Preliminary Activity in MECOM Intellectual Property Phase 1 Preliminary Safety and Efficacy Planned Phases 2
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6 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) 1. BLOCKING PROLIFERATING LEUKEMIA CELLS THROUGH MICROTUBULES ▪ AB8939 destabilizes microtubules ▪ AB8939 is not subjected to multidrug resistance (no PgP binding) ▪ AB8939 is not degraded by myeloperoxidase 2. TARGETING OF LEUKEMIA CANCER STEM CELLS THOUGH ALDH ▪ AB8939 inhibits ALDH1 ▪ AB8939 favors the bone marrow repopulation of normal progenitors 3. TREATMENT OF REFRACTORY/RELAPSING AML ▪ AB8939 has activity seen across refractory AML cell lines ▪ AB8939 has an additive effect with cytarabine, azacitidine and venetoclax ▪ AB8939 has shown a signal of efficacy in AML with MECOM gene rearrangement, a subset of patients that show extreme resistance to chemotherapies 4. LOW HEMATOLOGICAL TOXICITY ▪ AB8939 shows absence of hematological toxicity based on clinical data AB8939 Target Product Profile Targeted Indications Acute Myeloid Leukemia: ▪ relapsed or refractory patients and ▪ AML patients with MECOM gene rearrangement Cancer cells and Microtubule Scientific Rationale Cancer stem cells and ALDH ▪ Microtubules are critical for cell division ▪ Microtubule targeting chemotherapies are gold standard in many cancers, but, subjected to multidrug resistance (efflux by PgP) and are degraded by myeloperoxidase (produced by cancer cells) in AML ▪ ALDH plays critical role in cancer stem cells ▪ AML cells with high ALDH activity are more resistant to chemotherapeutic agents ▪ ALDH is over-expressed in MECOM
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7 AB8939 has a potential to improve treatment of relapsed / refractory AML Relapsed / refractory AML (R/R AML) * Line 1 Line 2 Line 3 Patients eligible to high dose chemotherapy Anthracyclines + cytarabine + targeted therapies (IDH/FLT3) High dose chemotherapy or Low dose chemotherapy No approved drug Low dose chemotherapy or Best supportive care Patients ineligible to high dose chemotherapy Hypomethylating agents (azacitidine / venetoclax) + targeted therapies (IDH/FLT3) No approved drug Low dose chemotherapy or Best supportive care No approved drug Best supportive care AB8939 current positioning in AML * One Menin inhibitors recently registered for R/R AML patients with KMT2Ar rearrangement or NPM1 mutation Anthracyclines = Daunorubicin or Idarubicin Cytarabine = Ara C Azacitidine = Vidaza Venetoclax = Venclyxto
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8 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 (1) Zhou, Y et al. Global, regional, and national burden of acute myeloid leukemia, 1990 –2021: a systematic analysis for the global burden of disease study 2021. Biomark Res 12, 101 (2024). (2) Ravandi F. Relapsed acute myeloid leukemia: Why is there no standard of care Best Pract Res Clin Haematol. 2013;26(3):253-9 (3) Walter RB et al. Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SA KK, SWOG and MD Anderson Cancer Center. Leukemia (2015) 29:312–20. . (4) Estimated (5) Choi M. et al. Costs per patient achieving remission with venetoclax-based combinations i n newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemotherapy. Journal of Managed Care & Specialty Pharmacy Volume 28, Number 9. https://doi.org/10.18553/jmcp.2022.22021 Region Incidence Case (1) % Relapse or Refractory (2,3) % Insured Patients (4) Drug Price (€) Market Size (per in in Mio EUR) USA / CANADA 23,700 50% 90% 100,000(5) 1 000 000 EUROPE 27,600 90% 60,000 770 000 APAC 27,800 30% 60,000 250 000 INDIA 11,000 30% 60,000 100,000 LATAM 7,200 30% 60,000 65 000 MENA 3,900 30% 60,000 35 000 TOTAL 90,200 2 200 000 EUROPE = EU27 + Norway + United Kingdom + Switzerland ; APAC = Australia, People’s Republic of China , Japan, New Zealand, Singapore, Taiwan ; LATAM = Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico ; MENA = Algeria, Bahrain, Egypt, Israel, Kuwait, Morocco, Oman, Qatar, Saudi Arabia, Tunisia, United Arab Emirates.
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9 Target Product Profile Pharmacology Data Preliminary Activity in MECOM Intellectual Property Phase 1 Preliminary Safety and Efficacy Planned Phases 2
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10 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, 66% remain sensitive to AB8939
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11 AB8939 eradicates blasts in Blood and Bone Marrow in 5-AraC-resistant (Cytarabine) PDX Red luminescence detects cancer cells
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12 AB8939 increase survival and has an additive effect in combination with reference treatment Azacitidine 0 10 20 80 90 100 110 Weight Curve Days post treatment % weight before treatment AB8939/VIDAZA VIDAZA AB8939 CTRL Spleen CTRL AB8939 VIDAZA AB/VIDAZA 0 10 20 30 40 50 9092949698100 % hCD33/µL Blood CTRL AB8939 VIDAZA AB/VIDAZA 0 5 10 15 20 40 60 80 100 % hCD33/µL Bone Marrow CTRL AB8939 VIDAZA AB/VIDAZA 0.00.20.40.60.81.0 20 40 60 80 100 % hCD33/µL ControlAB8939VIDAZA AB8939/VIDAZA 0 500 1000 1500 2000mCD45/µL A. Study Design B. Unlike Vidaza, AB8939 does not induce any hematotoxicity C. • AB8939/ vidaza combination allows the clearing of leukemia blasts in blood, spleen and bone marrow (C) without adding toxicities.
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13 AB8939 increase survival and has a potential additive effect in combination with reference treatment Venetoclax BLOOD CTRL AB8939 Venetoclax AB/Venetoclax 0 50 100 150 5000 10000 15000hCD33 (cell/µL) SPLEEN CTRL AB8939 Venetoclax AB/Venetoclax 0 2×105 4×105 6×105 8×105 1×106 2×1074×1076×1078×1071×108 hCD33 (cell/µL) BONE MARROW CTRL AB8939 Venetoclax AB/Venetoclax 0 1000000 2000000 3000000 4000000 hCD33 (cell/µL) C. AB8939/ Venetoclax combination allows the clearing of leukemia blasts in blood, spleen and bone marrow without adding toxicities. B. AB8939 monotherapy or combined with Venetoclax is well-tolerated: absence of any toxicity (left: weight curves) or hematotoxicity (right: hematopoietic progenitors mCD45) A. Study Design 0 10 20 30 80 90 100 110 CTRL AB8939 Venetoclax AB8939/Venetoclax Days post treatment % weight before treatment control AB8939 VENETOCLAX AB8939/VENETOCLAX 0 500 1000 1500mCD45 (cell/µL) ns ✱ ns
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14 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 both recombinant ALDH1A1 and ALDH2 with a sub-micromolar potency ❖ Reverse proteomic analysis revealed ALDHs as main AB8939 interactors 10 -6 10 -4 10 -2 10 0 10 2 0 50 100 150 Log [AB8939] (µM) NADH (FI 340 nm) ALDH1A1 ALDH2 ALDH1A1 ALDH2 IC50 (nM) 500 340 R squared 0,96 0,99 Accession number Gene AB8939 beads peptides count Control beads peptides count Ratio 8939/contr ol Experiment 1 (Pool of 33 cell lines lysates) P05091 ALDH2 34,5 1 34,5 P47895 ALDH1A3 4,5 1 4,5 P30837 ALDH1B1 7 1 7 P00352 ALDH1A1 2 1 2 Experiment 2 (CLS354-4 cell lysate) P30837 ALDH1B1 60 1 60 P05091 ALDH2 178 4 45 P47895 ALDH1A3 102 33 3 P30838 ALDH3A1 7 3 2
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15 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 both leukemic blast and leukemia cancer stem cells(Step 2). ▪ AB8939 is likely to kill highly dividing blasts through microtubule disruption while it kills resting cancer Stem cells through inhibition of ALDHs.
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16 Target Product Profile Pharmacology Data Preliminary Activity in MECOM Intellectual Property Phase 1 Preliminary Safety and Efficacy Planned Phases 2
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17 The objective of the phase 1 is to determine the maximum tolerated dose (MTD) for three different cycles of AB8939 Step 1 MTD* 3 DAYS AB8939 alone Step 2 MTD 14 DAYS AB8939 alone # Dose Patients DLT 1 0.9 mg/m 2 3 0 2 1.8 mg/m 2 3 0 3 3.6 mg/m 2 3 0 4 6.0 mg/m 2 3 0 5 9.0 mg/m 2 3 0 6 12.0 mg/m 2 3 0 7 16.0 mg/m 2 3 0 8 21.3 mg/m 2 4 1 MTD 3D 9 28.3 mg/m 2 3 2 Completed 28 patients randomized (some patients received several cycles at increased dose following observed clinical benefit) On-going Near completion # Dose Patients DLT 1 16.0 mg/m 2 7 1 2 21.3 mg/m 2 On-going Step 3 MTD 14 DAYS AB8939 Combination ▪ AB8939 + Venetoclax / Azacitidine ▪ AB8939 + Venetoclax + Azacitidine Next Steps
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18 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 Dose 4 : 6.0 mg/m2 Dose 2 : 1.8 mg/m2 Dose 3 : 3.6 mg/m2 Dose 5 : 9.0 mg/m2 Dose 6 : 12.0 mg/m2 Dose 7 : 16.0 mg/m2 Step 1, 3 days, single agent AB8939 Dose Dose 1 : 0.9 mg/m2 Dose 8 : 21.3 mg/m2 Cycle 1 3 days 0.9 mg/m2 Baseline characteristics (GR-04-001) ▪ Patient (81 years old) with De novo AML ▪ Intermediate-risk prognosis ▪ No additional mutation reported ▪ Refractory to Azacitidine, Venetoclax, Aracytine treatments Response after 1 cycle of 28 days with 3 consecutive daily injections at 0,9 mg/m² ▪ Decrease of % blasts in bone marrow after 1 cycle from 15% at baseline to 9% ▪ Decrease of % blasts in blood after 2 cycles: 1.5% to 0.9% ▪ Stability of neutrophils: From 1,960/µL to 2,100/µL after 2 cycles ▪ Increase of platelets: From 70,000/µL to 110,000/µL after 2 cycles ▪ Death occurred 418 days after the 1st injection
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19 Case Report 2 in non MECOM patient: Response after first cycle of 14 days Step 2, 14 days, single agent AB8939 Dose Cycle 1 14 days 21.3 mg/m2 Dose 1 : 16.0 mg/m2 Dose 2 : 21.3 mg/m2 Baseline characteristics (ES-07-006) ▪ Patient (38 years old) with high-risk AML ▪ Adverse cytogenetic risk ▪ Mutation :+8,+21[10] ▪ In relapse from previous treatments (LMA flow and Flag –Ida) Response achieved after 1 cycles of 28 days with 14 consecutive daily injections at 21.3 mg/m² ▪ Dramatic decrease of % blast in bone marrow after 1 cycle from 55% at baseline to 8% ▪ Decrease of % blasts in blood in after 1 cycle from 3,3% to 0.6% ▪ Only neutrophils met hematological criteria (>1G/L) after 28 days,
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20 Target Product Profile Pharmacology Data Preliminary Activity in MECOM Intellectual Property Phase 1 Preliminary Safety and Efficacy Planned Phases 2
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21 MECOM is associated with a dismal outcome, with short survival and only 14% response rate(1) in relapsed or refractory setting *Excluding patients with t(15;17), t(8;21), inv(16), t(9;11), t(6;9),inv(3)/t(3;3). **Excluding patients with any other abnormalities listed previously. MECOM Grimwade et al. Blood. 2010 Jul 22;116(3):354-65. doi: 10.1182/blood-2009-11-254441. Impact of cytogenetic entities recognized in 2008 WHO classification24 on survival . Survival of AML with 3q abnormality treated with AZA according to prior treatments. Survival was expressed in months and calculated using Kaplan Meier estimate. AML: acute myeloid leukemia; IC: intensive chemotherapy. Wanquet et al. Am. J. Hematol. 90:859–863, 2015. (1) G. Richard-Carpentier et al. Characteristics and clinical outcomes of patients with acute m yeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2). Haematologica | 108 September 2023. https://doi.org/10.3324/haematol.2022.282030
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22 AB8939 is a stem cell ALDH targeted therapy with potential use in AML with MECOM ▪ 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 or a mutation of the chromosome 3 locus Q26 that codes for the transcription factor gene EVI1 (Ecotropic virus integration site-1) ▪ The expression of ALDH1A1 is regulated by EVI1 and has an outstanding role in the formation and transformation of hematopoietic cells and in particular leukemia stem cells ▪ The hypothesis is that: o in MECOM, the rearrangement of chromosome 3 Q26 lead to EVI1 over-expressing ALDH1A and induce high resistance of leukemia stem cells o AB8939 should have an impact on leukaemia stem cells by inhibiting ALDH1 o This is what we observe in the experiment described in slide 15 Scientific Rationale Garrett M. Dancik. medRxiv preprint doi: https://doi.org/10.1101/2021.10.20.21265241
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23 Case Report 1 in MECOM patient: Response in a refractory AML patient with MECOM rearrangement receiving low dose of AB8939 Dose 1 : 0.9 mg/m2 Dose 2 : 1.8 mg/m2 Step 1, 3 days, single agent AB8939 Dose Cycle 1 3 days 1.8 mg/m2 Dose 4 : 6.0 mg/m2 Dose 3 : 3.6 mg/m2 Dose 5 : 9.0 mg/m2 Dose 6 : 12.0 mg/m2 Dose 7 : 16.0 mg/m2 Dose 8 : 21.3 mg/m2 Dose 9 : 28.3 mg/m2 Baseline characteristics (ES-07-001) ▪ Patient (65 years old) with Secondary AML ▪ Adverse prognostic factors with MECOM rearrangement, del(11)(q12)[4]/46,XX,idem,t(3;8)(q26;q24)[6] ▪ Refractory to Azacitidine treatment Response after 1 cycle of 28 days with 3 consecutive daily injection at 1.8 mg/m² ▪ Drastic decrease of blasts in bone marrow after 1 cycle: from 55% at baseline to 5% ▪ Stability of blasts in bone marrow after a second cycle: 10% at the end of the cycle ▪ Increase of neutrophils: From 200 to 260/µL after 1 cycle and to 480/µL after the end of the second cycle ▪ Increase of platelets: From 3,000 to 11,000/µL after 1 cycle and to 12,000/µL after the end of the second cycle ▪ Death occurred 536 days after the 1st injection
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24 Case Report 2 in MECOM patient: Response after first cycle of 14 days Step 2, 14 days, single agent AB8939 Dose Cycle 1 14 days 16.0 mg/m2 Dose 1 : 16.0 mg/m2 Dose 2 : 21.3 mg/m2 Baseline characteristics (GR-04-001) ▪ Patient (63 years old) with AML with myelodysplasia-related changes ▪ add(2)(q13), del(3)(q21q26), add(5)(q11.2), add(12)(p13), der(13)t(2;13), (q24;q22), dlc(17;20)(p12;11.2)[13]/45,idem, -7, [13]/45, idem, der(8)t(1;8)(p32;24)[2], TP53 (VAF 75.5%) ▪ Adverse Cytogenetic risk category (MECOM) ▪ Refractory to azacitidine treatment Response after 1 cycles of 14 consecutive daily injections at 16 mg/m² ▪ Reduction of blast bone marrow blast from 13% to 3% ▪ Decrease of % blasts in blood in after 1 cycle from 3,3% to 0.6% ▪ Increase of neutrophils: From 2,900/µL to 10,600/µL after first cycle ▪ Stability of platelets: From 26,000/µL to 23,000/µL after first cycle
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25 AB8939 has shown activity on MECOM rearrangement, based on non-clinical data and early clinical data with 50% response rate observed Clinical evidence in MECOM ▪ 50% response rate in early phase 1 2 out of 4 patients with MECOM after 1 cycle of 3 days or 14 days AB8939 treatment below the MTD Patient ID AB8939 Best Response ES-12-001 0,9 mg/m2, 3 days Early discontinuation ES-07-001 1.8 mg/m2, 3 days, Response (BM blast from 55% to 5%) ES-07-002 16 mg/m2, 14 days Stable disease GR-04-001 16 mg/m2,14 days Response (BM blast from 13% to 3%) ▪ 50% response rate in in-vitro tests In-vitro, AB8939 was effective (IC50 of 50nM and 13nM) against 2 out of 4 patient blasts with MECOM rearrangement Non clinical in vitro evidence Drug sensitivity (IC50 µM) in MECOM Karyotype Patient ID AML type AraC AB8939 Azacitidine 1135 M0 >20 >2 49,90 1156 M0 >20 >5 >50 C1005 M1 refractory 4,1 0,05 NT C1012 M4 refractory 7,9 0,013 9,7
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26 Target Product Profile Pharmacology Data Preliminary Activity in MECOM Intellectual Property Phase 1 Preliminary Safety and Efficacy Planned Phases 2
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27 The first intended step is to capture the market potential of AB8939 in patients with MECOM AML through accelerated approval based on response rate (1) G. Richard-Carpentier et al. Characteristics and clinical outcomes of patients with acute m yeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2). Haematologica | 108 September 2023. https://doi.org/10.3324/haematol.2022.282030 A possible design could be the following: ▪ Phase 2 single arm study ▪ Less than 60 patients ▪ AB8939 single agent or in combination (venetoclax / azacitidine) ▪ Objective: beat response rate of 14% based on literature (1) ▪ Preliminary evidence indicate 50% response rate with AB8939 single agent Region Incidence Case (1) Market Size (per in in Mio EUR) R/R AML 90,200 2 200 000 AML with MECOM gene rearrangement 5% ≈ 100 ❖ MECOM accounts for around 5% of AML and is a sizable market >100 million euros ❖ Seek accelerated approval based on phase 2
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28 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 Drug Trial (ClinicalTrials.gov ID) Phase Regimen Patient Population Eligibility Revumenib (SNDX -5613) AUGMENT- 101 (NCT04065399) I/II Revumenib monotherapy 95 Adults and 57 in phase 2 R/R KMT2Ar AL, NPM1c AML AUGMENT-102 (NCT05326516) I -AML: Revumenib/FLA ± Revumenib/FLA -ALL/MPAL: Revumenib/Pred/VCR/ASP/DNR 30 Adults and children R/R KMT2Ar AL, NPM1c or NUP98r AML (NCT05761171) II Revumenib/FLA, MTX Children (recruiting) R/R KMT2Ar ALL SAVE ( NCT05360160) I/II Revumenib/ASTX727/VEN 8 Adults and children (recruiting) R/R AML or MPAL BeatAML substudy (NCT03013998) I Revumenib/VEN/AZA 13 Adults Newly diagnosed KMT2Ar or NPM1c AML Ziftomenib (KO -539) KOMET-001 (NCT 04067336) I/II Ziftomenib monotherapy 30 Adults Phase 1a: R/R AML Phase 1b/2: KMT2Ar or NPM1c AML KOMET-007 (NCT05735184) I -Newly diagnosed AML: Ziftomenib/7 + 3 -R/R AML: ziftomenib/VEN/AZA 20 Adults Newly diagnosed and R/R KMT2Ar or NPM1c AML Revumenib, from the American biotech Syndax, has been registered in AML with KMT2Ar rearrangement or NPM1 mutation with ▪ a phase 1/2 study of 95 adult patients including an efficacy population of 57 evaluable patients. ▪ complete or near-complete response rate of 23% Ziftomenib developed by Kuva is the second Menin inhibitor in development and, like AB8939, has done phase 1 with limited number of patients
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29 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 (1) Salvage Therapy Outcomes in a Historical Cohort of Pa tients With Relapsed or Refractory Acute Myeloid Leukaemia Ravandi, Farhad et al. Clinical Lymphoma, Myeloma and Leukaemia, Volume 20, Issue 11, e871 - e882 (2) DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971. PMID: 32786187. A possible design could be the following: ▪ Phase 2 controlled study ▪ Objective #2 : In relapsed or refractory AML as single agent or in combination, with 17,5% complete response rate as a historical control to beat based on literature (1) ▪ Objective #3 : Followed with First line AML in combination (venetoclax and azacitidine), with 37% complete response rate as a historical control to beat based on literature (2)
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30 Target Product Profile Pharmacology Data Preliminary Activity in MECOM Intellectual Property Phase 1 Preliminary Safety and Efficacy Planned Phases 2
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31 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 Orphan drug status Composition of Matter patent Protection Exclusivity period Enforcement Until February 2036 ▪ Granted in the USA ▪ To be filed with EMA ▪ Granted (United States / Europe / China / Hong Kong / Japan / South Korea / India / Mexico / Israel / Brazil / South Africa / Russia / Australia) 7-year protection as of FDA approval 10-year protection as of EMA approval Second Medical Use patent Until February 2044 (if granted) ▪ PCT patent application filed for AML subpopulation with chromosome abnormality
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MASITINIB PLATFORM
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33 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
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FINANCE
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AB Science raised 5 millions euros in Q4 2024, which provides financial runway for more than 12 months 35 ▪ Neuro-degenerative diseases : Financing through partnership ▪ Sickle Cell Disease : Financing of phase 2 through RHU collaborative program with APHP (9.2M€)Masitinib AB8939 ▪ Phase 1 : Financing through equity ▪ Phase 2 : Financing through equity or partnership Financing Strategy