- First public disclosure of the chemical structure of AMX-883, an orally bioavailable, highly potent and selective DCAF16-dependent Targeted Glue™ degrader of BRD9
- AMX-883 is the Company’s lead asset entering a Phase I clinical trial for acute myeloid leukaemia in H2 2026
Cambridge, UK, 21st April 2026 – Amphista Therapeutics (“the Company” or “Amphista”), a leader in the discovery and development of non-cereblon/non-VHL Targeted Glue™ degraders, today announced 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) Annual Meeting 2026 in San Diego, California yesterday.
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. 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.
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About Amphista Therapeutics
At Amphista Therapeutics, we are focused on transforming the lives of patients with severe diseases, including cancer and neurodegenerative disorders, through the discovery and development of advanced, next generation targeted protein degradation (TPD) medicines. Amphista applies its proprietary Eclipsys® platform to generate unique, sequentially bifunctional Targeted Glue™ therapeutics with a differentiated mechanism and leading drug-like properties. Our portfolio offers the potential to deliver first- and/or best-in-class therapeutics with performance characteristics beyond the limitations of CRBN and VHL-based agents. Amphista was co-founded by Advent Life Sciences and is additionally funded by a premier group of investors including Forbion, Gilde Healthcare, Novartis Venture Fund, SV Health Investors’ Dementia Discovery Fund and Eli Lilly. For more information, please visit: www.amphista.com
Amphista, Eclipsys, Targeted Glue, Targeted Glues and the Amphista logo are all trademarks or registered trademarks of Amphista Therapeutics Limited.
About BRD9 and Acute Myeloid Leukaemia
Acute Myeloid Leukaemia (AML) is one of the most aggressive blood cancers and despite the availability of anti-proliferative treatments, patient survival rates remain alarmingly low. Five-year survival rates remain at just 33% and is the cause of death for an estimated 130,000 patients globally each year. The disease is characterized by a differentiation block which prevents myeloid cell maturation and results in an accumulation of immature cells/AML blasts. Therapies which remove the differentiation block and allow maturation of these AML blasts including ATRA, FLT-3 inhibitors, and most recently menin inhibitors have demonstrated clinical benefit in several sub-sets of AML. However, there is a pressing need for broader-acting treatments that can benefit patients regardless of their genetic profile.
BRD9 is a subunit of the non-canonical BAF complex where it plays a key structural and functional role, being linked to regulation of chromatin structure and maintaining genomic stability in AML. Degradation of BRD9 releases the differentiation block and leads to the differentiation and death of AML blasts
For more information please contact:
Amphista Therapeutics
John Goodall
Email: Info@amphista.com
ICR Healthcare
Namrata Taak, Ashley Tapp, Emily Johnson
Email: Amphista@icrhealthcare.com
Tel: +44 (0)20 3709 5813
