Amphista Therapeutics recently announced the nomination of AMX-883; a potent, selective and orally bioavailable degrader of BRD9, as its first clinical development candidate. Amphista is advancing AMX-883 for the treatment of acute myeloid leukaemia (AML).

Leveraging Amphista’s Eclipsys platform and proprietary Targeted Glue technology, AMX-883 induces the degradation of BRD9 via induction of the E3 ligase DCAF16, a completely novel mechanism, distinct from CRBN and VHL-based technologies. AMX-883 is a highly potent and rapid degrader, inducing almost complete degradation of BRD9 within just two hours of treatment, whilst retaining exquisite selectivity over all other bromodomain containing proteins, and beyond, as illustrated by global proteomics. This profile translates into robust in vivo efficacy, including in disseminated patient derived xenograft models. Amphista plans to initiate its first clinical trial with AMX-833 in the second half of 2026.

“Nominating AMX-883 as our first clinical candidate, marking the first time a BRD9 degrader has been developed in AML, is a key milestone for Amphista and the TPD field. Our preclinical data package underlines the fundamental role BRD9 plays in the pathogenesis of AML. AMX-883 has the potential to transform the treatment paradigm for this terrible disease, where 5-year survival rates remain at just 33% and is the cause of death for an estimated 130,000 patients globally each year. As a broad-acting, pro-differentiation agent, AMX-883 has the potential to treat AML in a karyotype-independent way, bringing benefit to a larger patient population than current treatments,” said Martin Pass, Chief Development Officer at Amphista.

The nomination of AMX-883 triggers the drawdown of the third tranche of Amphista’s Series B financing, enabling the continued progression of the Company’s portfolio of next generation Targeted Glue™ therapeutics towards clinical stage development.

Antony Mattessich, Chief Executive Officer at Amphista, said “We have built a truly unique discovery platform in Eclipsys, which offers the opportunity to deliver advanced protein degraders with performance characteristics beyond what has been achievable with earlier generation approaches. The nomination of AMX-883 as our first development candidate is a testament to our capabilities and we now look forward to filing an IND application in early 2026.”

This news follows an announcement in May 2024 when Amphista unveiled its discovery of a new differentiated mechanism of action for BRD9 degradation. This year, the Company also unveiled a new mechanism of action for TEAD degradation via FBXO22, and for SMARCA2 degradation via induction E3 ligase DCAF16.

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. 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

At Amphista Therapeutics, we are focused on transforming the lives of patients with severe diseases, including cancer and neurodegenerative disorders, through the discovery 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’s Dementia Discovery Fund and Eli Lilly. For more information, visit www.amphista.com.