Cambridge-based biotech Amphista Therapeutics has received FDA clearance for its investigational new drug application for AMX-883, a targeted protein degrader designed to treat acute myeloid leukaemia (AML). The decision clears the way for the company’s first clinical trial of the asset, which Amphista says it expects to begin in the second half of 2026.
AMX-883 is Amphista’s lead Targeted Glue™ degrader and is described by the company as a potent, orally bioavailable, DCAF16-dependent degrader of BRD9. The programme has been built around the idea of exploiting a novel degradation pathway rather than relying on the more established CRBN or VHL-based mechanisms used in other protein degrader approaches.
The planned trial is a Phase 1 monotherapy dose-escalation and optimisation study. According to the company, it will enrol patients with relapsed or refractory AML, as well as patients with high-risk myelodysplastic syndrome, a condition that can progress to AML.
Amphista says the programme is intended to address major unmet need in AML, a disease that remains difficult to treat because of resistance, relapse and the limitations of current regimens. The company has also indicated that, after establishing the monotherapy safety and dose profile, it plans to evaluate AMX-883 in combination with venetoclax and azacitidine.
The latest regulatory milestone follows a year of development activity around the candidate. In October 2025, Amphista nominated AMX-883 as its first clinical development candidate and said at the time that it planned to file an IND application in early 2026. By April 2026, the company had already presented the discovery, characterisation and chemical structure of AMX-883 at AACR 2026, underscoring the pace of progress toward the clinic.
Preclinical data have been central to the programme’s advance. Amphista has reported that AMX-883 achieves near-complete BRD9 degradation within two hours, with high selectivity across bromodomain-containing proteins. The company has also said the compound showed in vivo tumour growth inhibition in patient-derived models and demonstrated synergy with venetoclax in vitro.
Those preclinical findings have been presented as especially relevant to resistance in AML treatment. Amphista said AMX-883 may help prevent the emergence of venetoclax resistance, one of the clinical challenges it is seeking to address, and the company has described the asset as a broad-acting, pro-differentiation therapy with potential activity beyond specific karyotype subtypes.
The FDA clearance also marks a transition point for Amphista itself. Chief executive Louise Modis said the IND approval represents a pivotal moment as the company evolves into a clinical-stage organisation and added that the encouraging preclinical data support AMX-883’s potential as a first-line treatment concept for AML.
AMX-883 is notable in the targeted protein degradation field because it is positioned as the only BRD9 degrader currently under development, according to Amphista’s statement. The company says the programme uses its Eclipsys platform and proprietary Targeted Glue technology, which recruits DCAF16 to drive BRD9 degradation.
For AML drug development, the move is significant because BRD9 has been explored as a target for promoting myeloid differentiation, but clinical validation has been limited. Amphista’s entry into human testing will therefore be watched closely by investors and drug developers following the broader protein degradation space.
If the trial starts as planned in H2 2026, AMX-883 will become one of the first BRD9-directed degraders to reach patients with AML. The outcome will help determine whether the preclinical promise of a DCAF16-based molecular glue can translate into a workable clinical strategy for a hard-to-treat blood cancer.