UK-based Amphista Therapeutics has dosed the first patient in a Phase I trial of AMX-883, an oral DCAF16-mediated BRD9 degrader being evaluated in acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The news marks the company's first asset to enter clinical development.
The BRAMLIE trial (BR(D9) AML Interventional Evaluation) is a multisite Phase I monotherapy study of AMX-883 that is expected to enroll approximately 54 patients with AML or high-risk MDS, regardless of mutational status; it will assess safety, pharmacokinetics, and preliminary efficacy, and no clinical results have been reported. The trial was initiated following US FDA authorization of Amphista's investigational new drug (IND) application in June 2026.
AMX-883 recruits the E3 ligase DCAF16 to induce rapid degradation of BRD9, a subunit of the non-canonical BAF chromatin-remodelling complex that maintains leukemic stemness and blocks myeloid cell differentiation; degradation of BRD9 removes this differentiation block and drives the differentiation and death of AML blasts. Preclinical data presented by Amphista showed that AMX-883 blocked patient-derived tumor growth in vivo as a monotherapy, showed synergistic efficacy with venetoclax, and prevented the emergence of venetoclax resistance in vitro.
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