Cambridge, UK, 8 June 2026 — Amphista Therapeutics said on Monday that the U.S. Food and Drug Administration has cleared its investigational new drug application for AMX-883, its lead Targeted Glue degrader for acute myeloid leukaemia . The clearance allows the company to advance AMX-883 into the clinic, with first-in-human testing expected in the second half of 2026 .
AMX-883 is an orally available, non-cereblon degrader of BRD9 that uses Amphista’s Targeted Glue technology to recruit DCAF16 and drive degradation of the BRD9 protein . Amphista says the mechanism is distinct from cereblon- or VHL-based PROTAC approaches, and that the candidate is designed as a potent, rapid and selective degrader with drug-like properties intended for oral dosing .
The planned Phase 1 study will evaluate AMX-883 in patients with relapsed or refractory AML and high-risk MDS . Amphista said the trial will begin with monotherapy dose escalation and optimisation before the company explores combination development with venetoclax and azacitidine in earlier lines of therapy . The company framed that strategy as a response to persistent treatment resistance in AML, where deeper and broader responses remain a major unmet need .
Chief Executive Officer Louise Modis said FDA clearance marks a “significant milestone” as Amphista transitions into a clinical-stage company . She said AMX-883 is the only BRD9 degrader currently being developed and argued that preclinical data submitted to the FDA support its potential as a first-line option in earlier disease settings . Chief Medical Officer Patrick Kelly said AML remains one of the most devastating blood cancers, citing a five-year survival rate of 33% and describing resistance to standard therapies such as venetoclax as a critical challenge .
Amphista’s disease background section says AML is among the most aggressive blood cancers and is characterised by a differentiation block that prevents normal myeloid cell maturation . The company said therapies that reverse that block have already shown clinical benefit in some AML subtypes, but broader-acting treatments are still needed regardless of genetic profile . It added that BRD9 is a subunit of the non-canonical BAF complex and plays a structural and functional role in chromatin regulation and genomic stability in AML .
In its description of AMX-883, Amphista said the candidate can achieve near-complete BRD9 degradation within two hours of treatment and shows exquisite selectivity over other bromodomain-containing proteins in global proteomics studies . The company said preclinical models support activity both as a monotherapy and in combination with venetoclax, where the drug showed synergy in vivo and reduced the emergence of venetoclax resistance in vitro . Amphista said those findings support development of AMX-883 as a karyotype-independent, pro-differentiation agent .
The company has positioned AMX-883 as a key step in its broader targeted protein degradation strategy, which it says is built on its proprietary Eclipsys platform . Amphista said the platform is intended to produce differentiated therapeutics with properties beyond CRBN- and VHL-based agents . The company also listed backing from investors including Advent Life Sciences, Forbion, Gilde Healthcare, Novartis Venture Fund, SV’s Dementia Discovery Fund and Eli Lilly .
For AML developers and investors, the IND clearance is notable because it advances a BRD9-targeting approach into human testing at a time when differentiation therapies remain a major area of interest in hematologic malignancies . Amphista’s move also adds momentum to the broader protein degradation field, where companies are increasingly exploring novel ligase recruitment strategies beyond the best-known E3 ligase systems . The first clinical data from the H2 2026 trial will likely be watched closely for early signals on safety, pharmacodynamics and signs of activity in heavily pretreated AML .