Amphista Therapeutics has 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).
AML is one of the most aggressive blood cancers and despite the availability of anti-proliferative treatments, patient survival rates remain alarmingly low.
Leveraging Amphista’s Eclipsys platform and proprietary Targeted Glue technology, AMX-883 induces the degradation of BRD9 via induction of the E3 ligase DCAF16.
DCAF16 is 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.
It still retains 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," said Martin Pass, Chief Development Officer at Amphista.
"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 five-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.”
The nomination of AMX-883 triggers the drawdown of the third tranche of Amphista’s Series B financing.
This enables the continued progression of the Company’s portfolio of next-generation Targeted Glue therapeutics towards clinical stage development.
Antony Mattessich, CEO at Amphista, said: “We have built a truly unique discovery platform in Eclipsys."
"It 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 the induction of E3 ligase DCAF16.