On April 21, 2026 Amphista Therapeutics ("the Company" or "Amphista"), a leader in the discovery and development of non-cereblon/non-VHL Targeted Glue degraders, reported the first public disclosure of the chemical structure of its lead Targeted Glue AMX-883, a novel DCAF16-dependent protein degrader of BRD9, during the New Drugs on the Horizon session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026 in San Diego, California yesterday.
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The oral presentation titled "Discovery of AMX-883: an orally bioavailable, novel degrader of BRD9 as a karyotype-independent pro-differentiation agent for the potential treatment of acute myeloid leukaemia", detailed the discovery and optimisation of a series of DCAF16-recruiting BRD9 degraders which yielded AMX-883, an orally bioavailable clinical candidate with picomolar potency and exquisite selectivity over the related bromodomain proteins BRD4 and BRD7. The DCAF16-dependent mechanism of action of AMX-883 was structurally confirmed by high-resolution cryo-EM of the ternary complex, revealing true glue-like interactions that stabilize the complex.
Amphista nominated AMX-883 as its first clinical development candidate in October 2025, based on a preclinical data package which expands the growing evidence base defining a critical role for BRD9 in maintaining acute myeloid leukaemia (AML) blast stemness and survival.
Martin Pass, Chief Development Officer at Amphista Therapeutics, said: "I’m delighted to be able to share the preclinical characterization data for AMX-883, our BRD9 Targeted Glue degrader, for the first time at AACR (Free AACR Whitepaper). Not only does it showcase the ability of our Eclipsys platform to deliver truly differentiated and high-quality molecules, but it also brings new insight and mechanistic understanding to BRD9’s role in AML and the hope that targeted removal from AML blasts may bring profound benefit to patients".
The data presented demonstrate that by degrading BRD9, AMX-883 relieves the differentiation block characteristic of AML, inducing expression of myeloid differentiation genes and repressing pro-proliferative programmes. AMX-883 increases markers of myeloid maturation across a range of AML cell lines representing diverse cytogenetic backgrounds, including TP53-mutant disease. This underlines its potential as a broad-acting, pro-differentiation agent and karyotype-independent therapeutic with the potential to benefit a wider population of AML patients than current treatments.
Critically, through BRD9 degradation, AMX-883 blocks patient-derived tumour growth in vivo as a monotherapy and demonstrated synergistic efficacy while in combination with venetoclax and prevented the emergence of resistance to venetoclax in vitro, addressing a major clinical challenge in AML.
Patrick Kelly, Chief Medical Officer at Amphista Therapeutics, added: "AML is a devastating disease with a poor prognosis, and most patients will relapse or become refractory to current treatments within a matter of months. As a karyotype-independent, pro-differentiation agent, AMX-883 has the potential to address a critical unmet need in AML by offering a broadly applicable treatment option. We are excited to advance this highly differentiated molecule into clinical trials in the second half of this year bringing new hope to patients facing this serious disease."
The Company is advancing AMX-883 into a Phase I clinical trial for AML in H2 2026.
(Press release, Amphista Therapeutics, APR 21, 2026, View Source [SID1234664596])