AB Science reports completion of the step 3 of phase 1, evaluating the combination of AB8939 with venetoclax for the treatment of refractory or relapsed AML

PRESS RELEASE AB SCIENCE REPORTS COMPLETION OF THE STEP 3 OF PHASE 1, EVALUATING THE COMBIN ATION OF AB8939 WITH VENETOCLAX FOR THE TREATMENT OF REFRACTORY OR RELAPSED ACUTE MYELOI D LEUKEMIA THE COMBINATION OF AB8939 WITH VENETOCLAX GENERATED A 67% OVERALL RESPONSE RATE (ORR) AND A 100% DISEASE CONTROL RATE (DCR), WITH NO DOSE-LIMITING TOXICITIES (DLT) OBSERVED, IN A POOR-PROGNOSIS POPULATION WITH ADVERSE GENETICS TREATED IN THE SECOND - TO FOURTH-LINE RELAPSED OR REFRACTORY SETTING Paris, June 29, 2026, 8am CET AB Science SA (Euronext - FR0010557264 - AB) today provides an update on the Phase 1 study of the molecule AB8939 and the completion of Step 3, evaluating the combination o f AB8939 + venetoclax in patients with acute myeloid leukemia (AML) associated with a very unfavorable genetic profile. Step 3 evaluated the combination of AB8939 plus venetoclax administered over a 14-day cycle. A total of six patients were treated across two dose levels of AB8939 (16 mg/m² and 21.3 mg/m ²), each in combination with venetoclax. The combination was well-tolerated, with no dose-limiting toxicity (DLT) and no hematological toxicity observed at either dose level, allowing selection of the recommended Phase 2 dose (RP2D). Encouraging preliminary signs of efficacy were observed. Of the six patients treated, four achieved an objective response (one complete remission with incomplete hematologic recover y and three partial responses), corresponding to a 67% overall response rate (ORR). The two remaining patients achieved stable disease, resulting in a 100% disease control rate (CDR). These responses were achieved after a single cycle of treatment (14 days) in heavily pre-treated patients receiving second- to fourth-line therapy. Notably, two of the responding patients had previously progressed on venetoclax in combination with other chemotherapies. The patients treated all have very difficult to treat cytogenetic profiles, includi ng complex karyotype, TP53 mutation, NRAS mutation, monosomy 5 and 7 and MECOM-rearrangement, that ty pically have a poor prognosis due to their aggressive disease course and treatment resistance This is a high response rate in a population where standard- of-care therapies achieve ORR of 10 –30% in adverse-risk, multiply pre-treated AML (Gill H, et al. Cancer Med. 2020;9(10):3371-3382). Response after the first 14 days cycle in the six patients treated in Step 3 (AB8939 + venetoclax) Patient AB8939 dose Line of therapy Key adverse genetics Best response Patient 1 16 mg/m² 2nd RUNX1 and NRAS mutations CRi Patient 2 16 mg/m² 2nd MECOM-rearrangement, complex karyotype, monosomy 5 and 7 PR Patient 3 16 mg/m² 4th TP53 mutation, complex karyotype, monosomy 5 and 7 PR Patient 4 21.3 mg/m² 3rd TP53 mutation, complex karyotype, monosomy 5 and 7 PR Patient 5 21.3 mg/m² 2nd TP53 mutation SD Patient 6 21.3 mg/m² 2nd TP53 mutation (very high-risk MDS) SD Complete remission (CRc) is defined as CRc = CR + CRh + CRi + CRp • CR=Bone marrow blasts <5%; of circulating blasts; low level (<5%); extramedullary disease; ANC ≥1.0 x 109/L (1000/μL); platelet count ≥100 x 109/L (100 000/μL). • CRh =ANC ≥ 0.5 × 109/L (500/μL) and platelet count ≥ 50 × 109/L (50 000/μL), otherwise all other CR criteria met • CRi =All CR criteria except for residual neutropenia (<1.0 x 109/L [1000/μL]) or thrombocytopenia (<100 x 109/L [100 000/μL]). • CRp =All CR criteria except platelet count < 100 × 109/L (100 000/μL) Partial remission (PR) requires bone marrow response of at least 50% with a residual % between 5% and 25%. Progressive disease (PD): > 50% increase in marrow blasts over baseline (a minimum 15% increase is required in cases <30% blasts at baseline). This diversity of responsive patients appears to corroborate the mechanism of action of AB8939, which is capable of destabilizing microtubules while evading multi-drug resistance and also targeting cancer stem cells without eliminating non tumoral stem cells These results corroborate the positioning of AB8939 in patients with adverse genetics, complex karyotypes, TP53 mutations, NRAS and KRAS mutations, monosomy 5 and 7, and MECOM-rearrang ement, which represents the highest unmet medical need. Nicholas J. Short, MD, Associate Professor and Co-Lead of the Section of Develop mental Therapeutics, Department of Leukemia, MD Anderson Cancer Center, said, "This new data is very encouraging, particularly considering the very adverse risk profile of this patient’s leukemia. These early efficacy and safety data suggest that AB8939 can be combined with venetoclax and could have significant activity in the highest-risk subtypes of AML. There is a strong interest in continuing the development of this combination in patients whose AML has high-risk features that are expected to lead to resistance to venetoclax + azacitidine." Professor Olivier Hermine, MD, President of the Scientific Committee of AB Science and member of the Académie des Sciences in France, said, " There is a strong rationale to combine AB8939 and venetoclax as both molecules have low hematologic toxicity and complementary mode of actions. These first resul ts are supportive of this rationale." With Step 3 completed, the next step is Step 4, evaluating the triple combination of AB8 939 + venetoclax + azacitidine. About AB8939 AB8939 is a drug candidate that targets (i) cancer cells by destabilizing microtub ules (essential for cell division) and (ii) cancer stem cells by inhibiting ALDH1A1 and ALDH2 (enzymes essential for maintaining their physiological state and survival). - AB8939 has shown in vitro activity in Ara-C (cytarabine, which is one of the standards of care) resistant patient cell lines, including adverse genetic MECOM and TP53 mutations. - Analysis of cell lines responsive to AB8939 showed that AB8939 is effective in cell lines with TP53 mutations, MECOM, and complex karyotypes, whereas ARAC and azacitidine are not effective. - AB8939 increased survival and had an additive effect in combination with venetoclax (another standard of care) in vivo in a MECOM-grafted PDX mouse model. - AB8939 increased survival and had an additive effect in combination with Vidaza (azacitidine, another standard of care) in vivo in the MECOM PDX#C1005 mouse model of leukemia. - AB8939 eradicated Leukemia Cancer Stem Cells in vivo in a human PDX AML mouse model, which is compatible with targeting stem cells via ALDH. AB8939 is currently being evaluated in a Phase 1 clinical trial (study AB18001, NCT05211570) in patients with refractory and relapsed AML. The Phase 1 clinical trial of AB8939 has completed its first three steps. The first tw o steps determined the maximum tolerated dose (MTD) after 3 and 14 consecutive days of monotherapy. In b oth cases, the MTD was 21.3 mg/m². The third step, now completed, evaluated the combination of AB8939 and ven etoclax. Six patients were treated across two dose levels (AB8939 14 days at a dose of 16 mg/m² + venetoclax 14 days, then AB8939 14 days at a dose of 21.3 mg/m² + venetoclax 14 days), with no dose-lim iting toxicity observed, supporting selection of the recommended Phase 2 dose. The next step (Step 4) will evalu ate the triple combination of AB8939 + venetoclax + azacitidine. Medical need in AML and AB8939 mechanism of action Although several drugs have been registered for AML, 70% of patients still relapse and d ie, creating a persistent unmet medical need for effective treatments. Acute myeloid leukemia remains the most lethal form of leukemia in humans. AML is a heterogeneous disease, and its outcome is highly dependent on genetic factors. TP53 mutation has a very poor prognosis, with a median overall survival (OS) of 5.5 months. N RAS and KRAS mutants have a poor prognosis, with a median OS of 12.1 months. MECOM also has a very po or prognosis in AML, with a median OS of 5.5 months in relapsed or refractory settings. The challenge in AML is the recurrence of tumors due to a combination of two factors: the resistance of cancer cells to chemotherapy and relapse due to the persistence of cancer stem cells. This challenge may be overcome by AB8939’s dual mechanism of action. - First, AB8939 blocks the proliferation of leukemia cells through microtubule disrup tion. It is not subject to multi-drug resistance as it does not bind to PgP, which is responsible for efflux outside the cells, and is not degraded by myeloperoxidase. - Second, AB8939 targets leukemia cancer stem cells by inhibiting ALDH an d promotes bone marrow repopulation of normal progenitors. AB8939 + venetoclax combination There is a strong rationale to combine AB8939 with venetoclax - Both molecules exhibit low hematologic toxicity. This combination is ex pected to be less toxic than azacitidine + venetoclax as first-line treatment for AML - These molecules have different and complementary targets in cancer cells. There is an add itive, even synergistic, efficacy potential for the combination, with three mechanisms of action in a single treatment. o Venetoclax’s mechanism of action inhibits the BCL2 pathway, a protein that prevents apo ptosis (programmed cell death) in cancer cells. BCL2 is a key factor in AML resistance, as it allows cancer cells to survive despite treatment o AB8939 is pro-apoptotic, destabilizing microtubules, and would benefit from BCL2 inhibition to optimize apoptosis o In addition, AB8939 specifically targets cancer stem cells by inhibiting ALDH, reducing resistance to treatment and limiting the risk of relapse Next steps Following completion of Step 3, the next step is to initiate Step 4, evaluating the triple combination of AB8939 + venetoclax + azacitidine, and to launch an expansion study in approximately 1 5 AML patients eligible for AB8939 + venetoclax at the appropriate dose. The expansion phase is expected to generate robust preliminary evidence of efficacy in the AML label, sufficient to support the clin ical development plan and a beneficial partnership agreement. AB Science has started to discuss three possibilities for registration studies, which are not mutually exclusive, with the European Medicines Agency (EMA) and US Food and Drug Administration (FDA): - AB8939 + venetoclax as first-line treatment, with aged patients and/or patients with adverse genetics (complex karyotypes, TP53 mutations, NRAS and KRAS mutations, monosomy 5 and 7, and MECOM- rearrangement) - AB8939 + venetoclax as a second- or third-line treatment, in all patients or patients wi th adverse genetics - AB8939 as a single agent in MECOM as a second or third-line treatment. Addressable market with AB8939 in relapsed/refractory AML Treatments for relapsed or refractory AML represent an estimated market size potential of greater than EUR 2 billion per annum. Region Incidence Case (1) % Relapse or Refractory (2,3) % Insured Patients (4) Drug Price (€) Market Size (per 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 (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 patien ts from MRC/NCRI, HOVON/SAKK, 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 in newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemo therapy. Journal of Managed Care & Specialty Pharmacy Volume 28, Number 9. https://doi.org/10.18553/jmcp.2022.22021 Intellectual property AB8939 intellectual property rights in AML are secured until 2036 through a ‘composition of matter’ patent and potentially until 2041 with a 5 years extension. Two additional ‘second medical use’ patent applications have been filed to protect the use of AB8939 in the treatment of AML with specific chromos omal abnormalities. If these applications are accepted, the protection for AB8939 will be extended until 2044 and 2046 for these AML subpopulations. AB8939 has also received orphan drug designation for AML by both the EMA and FDA. This orphan drug designation confers 10 and 7 years of marketing exclusivity in Europe and the US, respectively, from the date of product registration. AB Science is the sole proprietary holder of AB8939 and its family of compounds. About AB Science Founded in 2001, AB Science is a pharmaceutical company specializing in the re search, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unm et medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquar tered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB Science This press release contains forward-looking statements. These sta tements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions a nd expectations regarding financial results, events, operations, futu re services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking stateme nts are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those express ed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB Science Financial Communication & Media Relations [email protected]

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