Amphista Therapeutics presents new preclinical data showing the potential of its BRD9 Targeted Glue™, AMX-883, to transform the treatment paradigm for acute myeloid leukaemia
- AMX-883-induced BRD9 degradation is sufficient to block patient-derived tumour growth in vivo as a monotherapy, with superiority to venetoclax
- AMX-883-induced BRD9 degradation synergises with venetoclax to block tumour growth in vivo
- AMX-883-induced degradation of BRD9 prevents emergence of resistance to venetoclax in vitro
- Data supports progression of AMX-883 into clinical development with the first trial planned in AML for H2 2026
Cambridge, UK, 8 December 2025 – Amphista Therapeutics (“the Company” or “Amphista”), a leader in the discovery of next generation targeted protein degradation (TPD) medicines, today announces that full details of its new preclinical data with its lead Targeted Glue™ AMX-883, an orally bioavailable, potent and selective degrader of BRD9 were presented on 6 December during the 67th American Society of Haematology (ASH) Annual Meeting and Exposition in Orlando, Florida.
The compelling findings support the potential of AMX-883 as a first-line treatment option in the earlier disease setting of acute myeloid leukaemia (AML), one of the most aggressive blood cancers where 5-year survival rates remain at just 33% and where resistance to standard of care treatments like venetoclax remains a major clinical challenge. Based on these data, the Company will advance AMX-883 as a karyotype-independent, pro-differentiation agent into the clinic for AML in H2 2026.
The key data presented at ASH showed that:
AMX-883 demonstrates potent degradation as a monotherapy and synergistic benefit in combination with venetoclax
- AMX-883 (30mg/kg twice daily and 100mg/kg once daily) significantly reduced cancer growth by achieving picomolar potency degradation of BRD9 across a panel of AML cell lines and significantly reduced leukemic burden in bone marrow and blood in vivo, compared to venetoclax alone.
- Synergistic efficacy was observed when each dose of AMX-883 was combined with venetoclax (75mg/kg once daily), leading to significant blocking of tumour growth at therapeutically relevant concentrations.
AMX-883 prevents resistance to venetoclax when dosed in combination
- The combination of AMX-883 with venetoclax in a venetoclax resistant cell line, prevented the emergence of resistance, and cells had comparable sensitivity to venetoclax from their first exposure.
- AMX-883 actively degrades BRD9 in venetoclax resistant cells, prevents upregulation of key resistance markers, including MCL-1 and BCL-2, and increases levels of cell death markers.
Martin Pass, Chief Development Officer at Amphista Therapeutics said, “The important preclinical data presented for the first time show that our Targeted Glue™ AMX-883, a selective degrader of BRD9, extends the durability and efficacy of combination therapy with venetoclax and prevents AML cancer cells from becoming resistant to venetoclax. We are very pleased to receive positive feedback from experts in the field on this compelling profile, which gives us strong reason to believe that AMX-883 could be a viable treatment option for patients with AML. We look forward to commencing the first clinical trial for this devastating blood cancer in H2 2026.”
To deliver the first clinical study of AMX-883, Amphista has built its development capabilities with three key strategic leadership appointments, including Dr. Lisa Butler, Senior Vice President of Clinical Operations who was previously Head of Study Leadership, early Oncology Clinical at AstraZeneca.
The abstract presented at ASH is available on the congress website here.
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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. 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
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 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, 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.
For more information please contact:
Amphista Therapeutics
John Goodall
Email: Info@amphista.com
ICR Healthcare
Namrata Taak, Emily Johnson
Email: Amphista@icrhealthcare.com
Tel: +44 (0)20 3709 5813
