- AMX-883 shows synergistic efficacy in combination with venetoclax in vivo and prevents the emergence of resistance to venetoclax in vitro, addressing a major clinical challenge in acute myeloid leukaemia (AML)
- AMX-883 showed a significant survival benefit and reduced disease burden compared to control treatments, while being well tolerated in a murine pre-clinical experiment
- Data provides compelling evidence of BRD9's critical role in AML and supports progression of AMX-883, as a karyotype-independent pro-differentiation agent, into clinical development, with the first trial planned for H2 2026
Cambridge, UK, 25 November 2025 – Amphista Therapeutics (“the Company” or “Amphista”), a leader in the discovery of next generation targeted protein degradation (TPD) medicines, today announces the presentation of new preclinical data with its lead Targeted Glue™ AMX-883, an orally bioavailable, potent and selective degrader of BRD9 at the upcoming 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, 6-9 December 2025, and provides a business progress update ahead of its leadership team attending the 44th Annual J.P. Morgan Healthcare Conference in San Francisco, 12-15 January 2026.
The abstract reports:
- AMX-883 time dependently increases the expression of key proteins associated with myeloid cell differentiation and maturation in vitro.
- Using patient derived samples in disseminated xenograft models, AMX-883 significantly reduced leukemic burden in bone marrow and blood over the treatment period and resulted in a significant increase in survival compared to venetoclax.
- The combination of AMX-883 with venetoclax resulted in synergistic efficacy in leukemic cell lines. AMX-883 co-dosed with venetoclax and azacitidine resulted in synergy with significant cell death at therapeutically relevant concentrations. Combination benefit was also observed with a range of other commonly used AML therapies in vitro.
- A cell line co-cultured with venetoclax and AMX-883 did not develop resistance to venetoclax and had comparable sensitivity to cells on their first exposure to venetoclax. The venetoclax-resistant line exhibited a significant increase in the anti-apoptotic proteins MCL-1 and BCL-2, an effect that was prevented when AMX-883 was included during venetoclax treatment.
- The data demonstrates the potent, selective BRD9 degrader AMX-883 induces significant differentiation and preclinical efficacy in AML cell lines and in primary AML cell lines.
"There is a critical unmet need for novel therapies that can augment the efficacy of anti-proliferative and cytotoxic agents in AML. The data to be presented at ASH demonstrates that AMX-883 prevented the development of resistance to venetoclax in vitro and AMX-883 delivered synergistic efficacy when combined with venetoclax, achieving significant cancer cell death at therapeutically relevant concentrations,” said Martin Pass, Chief Development Officer at Amphista Therapeutics. "These compelling results provide further strong preclinical evidence supporting the advancement of AMX-883 into the clinic for AML patients.”
“Amphista has made significant progress this year in advancing a new generation of targeted protein degraders designed to address serious diseases with high unmet need,” said Antony Mattessich, Chief Executive Officer of Amphista Therapeutics. “This is exemplified by the key data to be presented at ASH, alongside the nomination of AMX-883 as our first clinical candidate and the unveiling of distinct mechanisms of action across BRD9, SMARCA2, and TEAD. We look forward to 2026 when we will advance AMX-883 into the clinic and nominate our next clinical candidates.”
2025 business highlights:
- Nominated AMX-883, an orally available Targeted Glue™ degrader of BRD9, as the Company’s first clinical development candidate for the treatment of AML.
- Amphista received additional funding as part of its Series B financing following AMX-883 nomination, supporting plans to initiate the Company’s first clinical trial in H2 2026.
- Disclosed a novel mechanism of action for TEAD degradation by selectively inducing its proximity to FBXO22 as a targeted molecular glue, resulting in strong and rapid degradation.
- Reported first data from the SMARCA2 program, demonstrating exquisite selectivity of Amphista’s bifunctional Targeted Glues™ for SMARCA2 over the closely related homolog, SMARCA4.
- Achieved a discovery milestone under Amphista’s exclusive research collaboration and license agreement with Merck KGaA.
- Showcased Amphista’s cryo-EM enabled Eclipsys® platform at SLAS Europe 2025, highlighting its unique approach to constructing novel, orally bioavailable Targeted Glue™ degraders with mechanisms distinct from traditional cereblon (CRBN) or VHL approaches.
- Presented a differentiated mechanism for BRD9 degradation distinct from CRBN- or VHL-based PROTACs using Amphista’s Targeted Glue™ technology at the 2nd SMR Molecular Glues Meeting and the 5th Annual TPD and Induced Proximity Summit Europe.
Poster presentation details:
Title: AMX-883, a Potent and Selective Degrader of BRD9 Drives Differentiation in Acute Myeloid Leukaemia and Shows Synergistic Efficacy in Combination with venetoclax In Vivo and Prevents the Emergence of Resistance to venetoclax In Vitro.
Speaker: Martin Pass
Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster I
Session Date and Time: December 6, 2025 at 5:30 PM - 7:30 PM
Room: OCCC - West Halls B3-B4
Presentation ID: 1489
Abstract Number: abs25-2358
The online abstract is available on the ASH website here.
Ends
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
Amber Fennell, Namrata Taak
Emily Johnson
Email: Amphista@icrhealthcare.com
Tel: +44 (0)20 3709 5813
