AB Science reports fourth consecutive case of response from Phase 1 data for the combination of AB8939 with venetoclax for the treatment of refractory or relapsed acute myeloid leukemia

Core Viewpoint - AB Science reports a fourth consecutive positive response in a Phase 1 study for the combination of AB8939 and venetoclax in treating refractory or relapsed acute myeloid leukemia (AML) with a very unfavorable genetic profile [2][3]. Summary by Sections Clinical Trial Results - The fourth patient treated with AB8939 (21.3 mg/m²) plus venetoclax for 14 days achieved a partial response, consistent with previous results from three other patients [2][3]. - The combination treatment has shown a 100% response rate (4 out of 4 patients), including one complete remission, one near complete response, and two partial responses [5]. Patient Profile and Treatment Context - The fourth patient had a complex karyotype with a monosomy of chromosome 5 and a TP53 mutation, indicating a very adverse risk profile [5][6]. - All four patients had difficult-to-treat cytogenetic profiles, which typically correlate with poor prognosis due to aggressive disease and treatment resistance [5]. Mechanism of Action - AB8939 destabilizes microtubules and targets cancer stem cells by inhibiting ALDH1A1 and ALDH2, which are essential for cancer cell survival [7][13]. - The combination of AB8939 and venetoclax is expected to have additive or synergistic effects, enhancing treatment efficacy against AML [17]. Future Development Plans - The next steps include completing the Phase 1 trial and launching an expansion study involving approximately 15 AML patients eligible for the AB8939 and venetoclax combination [14]. - AB Science is in discussions with the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) regarding potential registration studies for AB8939 in relapsed/refractory AML, with a market size potential exceeding EUR 2 billion annually [15][21]. Market and Competitive Landscape - The estimated market size for treatments targeting relapsed or refractory AML is projected to be over EUR 2 billion per annum, highlighting a significant unmet medical need [15]. - The combination of AB8939 and venetoclax is anticipated to be less toxic than existing treatments, positioning it favorably in the competitive landscape of AML therapies [17]. Intellectual Property and Regulatory Status - AB8939 has secured intellectual property rights until 2036, with potential extensions through additional patent applications [20]. - The drug has received orphan drug designation from both the EMA and FDA, granting it marketing exclusivity for 10 years in Europe and 7 years in the US [21].