Amphista Therapeutics has announced that the US Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for AMX-883 for the treatment of acute myeloid leukaemia (AML).
AMX-883 is an orally available, non-cereblon-degrader of BRD9 and is expected to enter the clinic in H2 2026.
Amphista's Targeted Glue technology drives BRD9 degradation by recruiting DCAF16, a mechanism distinct from cereblon- or VHL-based PROTACs.
AMX-883 achieves nearly complete BRD9 degradation within two hours while maintaining excellent selectivity compared with other bromodomain-containing proteins, as shown by global proteomics.
The IND clearance now allows Amphista to start its Phase I monotherapy dose-escalation and optimisation clinical trial of AMX-883 in patients with relapsed or refractory AML.
The company will also test AMX-883 in patients with high-risk myelodysplastic syndrome (MDS), a related bone marrow disorder that often progresses to AML.
Amphista added that after it has established the monotherapy profile, it intends to explore AMX-883 in combination with venetoclax and azacitidine in early lines of therapy, where treatment resistance remains a major clinical challenge.
Louise Modis, CEO at Amphista, said: "FDA clearance of our IND for AMX-883, our lead Targeted Glue, for acute myeloid leukaemia is a significant milestone as we transition into a clinical-stage company."
AMX-883 is the only BRD9 degrader currently being developed and the compelling preclinical findings submitted to the FDA support its potential as a first-line treatment option in the earlier disease setting in one of the most aggressive blood cancers.
"We look forward to commencing the clinical trial in H2 2026."
Patrick Kelly, Chief Medical Officer at Amphista, added: "AML remains one of the most devastating blood cancers, with a five-year survival rate of just 33% and resistance to standard-of-care treatments such as venetoclax a critical challenge."
FDA clearance of our IND for AMX-883 supports the advancement of a differentiated therapeutic approach, with the potential to establish an important new treatment pathway for patients in urgent need of innovative therapies.