AB SCIENCE (AB) Status Update summary

Clinical development update

• AB8939 is being developed for acute myeloid leukemia (AML), targeting high-risk genetic subtypes with poor prognosis, such as TP53 mutations, MECOM rearrangements, NRAS/KRAS mutations, and complex karyotypes.

• The drug offers a novel mechanism by destabilizing microtubules and inhibiting ALDH, aiming to overcome resistance and eradicate leukemic stem cells.

• Preclinical studies show AB8939 is effective in vitro and in vivo against resistant AML cell lines, including those with adverse genetics.

• Early phase I monotherapy data in humans show promising responses in MECOM patients, with survival extending beyond typical expectations.

• Combination therapy with venetoclax in heavily pretreated, high-risk patients resulted in 100% disease control and partial response rate after one cycle, including one complete remission, with no hematological toxicity and good tolerability.

Clinical trial progression and next steps

• The ongoing phase I trial completed monotherapy dose-finding, establishing a maximum tolerated dose of 21.3 mg/m².

• The trial is progressing to combination arms, first with venetoclax, then a triplet with azacitidine.

• An expansion study with about 15 selected AML patients is planned to confirm efficacy and inform registrational trial design.

• Next phase will test a higher dose of AB8939 in combination with venetoclax.

• Regulatory discussions are underway for potential registration strategies in both frontline and relapsed/refractory settings, focusing on adverse genetic subtypes.

Mechanism and regulatory status

• AB8939 targets cancer cells by destabilizing microtubules and inhibiting enzymes essential for cancer stem cell survival, evading multi-drug resistance.

• Intellectual property is secured with patents extending to 2041 and 2044, and orphan drug status from FDA and EMA.

• The addressable market for high-risk AML is estimated at over $2 billion globally.