- AMX-883, Amphista’s first asset to enter the clinic, is a potent, selective, orally bioavailable DCAF16-mediated BRD9 degrader targeting acute myeloid leukaemia (AML)
- The first-in-human ‘BRAMLIE’ (BR(D9) AML Interventional Evaluation) trial will assess the safety, pharmacokinetics and preliminary efficacy of AMX-883 monotherapy in participants with AML and high-risk myelodysplastic syndrome (MDS)
- AMX-883 demonstrates karyotype-independent pro-differentiation activity pre-clinically, with trial enrolling patients regardless of mutational status
Amphista Therapeutics Limited (‘Amphista’ or ‘the Company’), a leader in the discovery and development of non-cereblon / VHL targeted protein degradation (TPD) medicines, today announced dosing of the first patient in a Phase 1 trial for its lead candidate, AMX-883. Initiated following authorisation from the U.S. Food and Drug Administration in June 2026, the BRAMLIE trial will investigate the safety, pharmacokinetics and preliminary efficacy of AMX-883 monotherapy in participants with AMLand high-risk MDS1.
BRAMLIE is expected to enroll approximately 54 patients across multiple sites. After establishing the monotherapy profile, a multi-centre dose-escalation study would evaluate AMX-883 in combination with current standards of care in participants with relapsed/refractory AML as well as in earlier lines of therapy.
AML is an aggressive blood cancer causing ~130,000 deaths globally each year, with most patients receiving traditional cytotoxic chemotherapy. Although novel targeted agents can be effective, the use of these is restricted to specific mutations, and therefore target only a subset of AML patients, highlighting a need for broad-acting therapeutics.
Acting via a targeted protein degradation (TPD) mechanism, Amphista’s Targeted GlueTM degraders are highly selective small molecule therapeutics with properties optimised for human medicines. AMX-883 is a potent, selective, orally bioavailable Targeted GlueTM for BRD9, a subunit of the chromatin remodeling complex involved in maintaining leukemic stemness and blocking of myeloid cell differentiation. Rapid BRD9 degradation is induced via AMX-883’s novel mechanism of action by which it recruits the E3 ligase DCAF16, enabling exceptional selectivity. Preclinically, AMX-883 has demonstrated activity across diverse AML subtypes, independent of mutation status2.
Dr Eytan Stein, Director, Program for Drug Development in Leukaemia, Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Centre, and Lead Investigator for this trial, said: “With a five-year survival rate of just 33% and emerging resistance to standard-of-care treatments like venetoclax, AML is one of the most devastating blood cancers and there is an urgent need for innovative new therapeutics. AMX-883 is the only BRD9 degrader currently in development and I look forward to seeing what this clinical stage research will reveal.”
Dr Louise Modis, Chief Executive Officer at Amphista, said: “The progression of our lead asset into the clinic marks a significant milestone for Amphista in our mission to transform the lives of patients with severe diseases. This study will help us better understand the potential of AMX-883, our lead Targeted Glue™ and how it could establish an important new treatment pathway for patients facing this very difficult disease with high unmet medical need.”
