Amphista Therapeutics

Amphista Therapeutics announces three presentations at the American Association for Cancer Research Annual Meeting on its next-generation Targeted Glue™ degrader programs

Cambridge, UK, 23^rd March 2026 – Amphista Therapeutics (“the Company” or “Amphista”), a leader in the discovery and development of non-cereblon/non-VHL Targeted Glue™ degraders, today announces three upcoming presentations at the American Association for Cancer Research (AACR) 2026 Annual meeting being held in San Diego on 17-22 April, including an invited presentation on the discovery of AMX-883, Amphista’s BRD9 clinical candidate, at the New Drugs on the Horizon: Part 3 session.

Oral presentation details:

Title: Discovery of AMX-883: an orally bioavailable, novel degrader of BRD9 as a karyotype-independent pro-differentiation agent for the potential treatment of AML

Session: New Drugs on the Horizon: Part 3

Date: Monday 20 April | 10:15-11:45 AM PST

Presenter: Martin Pass, Chief Development Officer, Amphista Therapeutics

Poster presentations details:

Title: Rational development of novel DCAF16-mediated SMARCA2 selective Targeted Glues™ for the treatment of SMARCA4 deficient tumors

Session: Proximity-Induced Drug Discovery 1

Date: Tuesday 21 April | 9:00 AM – 12:00 PM PST

Presenter: James Lynch, Senior Director Bioscience, Amphista Therapeutics

Abstract:

SMARCA2 and SMARCA4 are mutually exclusive catalytic subunits of the SWI/SNF chromatin remodelling complex. In non-small cell lung cancer (NSCLC), SMARCA4 mutations are observed in >5% patients and are associated with poor prognosis and advanced disease. Selective degradation of SMARCA2 exploits paralogue dependency in SMARCA4-deficient tumors to impact disease burden with minimal toxicity in normal tissues. 
Here, we report the rational design and optimisation of a novel class of SMARCA2 degraders that exploit a Targeted Glue™ mechanism to induce DCAF16-dependent proteasomal degradation. Amphista’s degraders potently drive >95% SMARCA2 degradation within 4 hours, resulting in deep suppression of biomarkers KRT80 and PLAU in vitro. Further, we observe exceptional degradation specificity for SMARCA2, as revealed by global proteomics and, critical for a best-in-class molecule, achieve near complete selectivity over SMARCA4 in a SMARCA4 WT model. 

Comprehensive mode of action studies, including E3-ligase knock-out and cysteine mutant rescue experiments demonstrate that our SMARCA2 Targeted Glues™ induce degradation via selective recruitment of DCAF16 and covalent interaction with a single DCAF16 cysteine residue. Structural studies, including generation of multiple high resolution (sub-3Å) cryo-EM ternary complex structures have enabled informed structure-activity relationship optimisations of degradation potency, kinetics and selectivity. Consequently, optimised compounds can deliver fast, deep degradation of SMARCA2 as demonstrated in-vivo in a disease-relevant SMARCA4 mutant model. 

We have achieved compound profiles that uniquely position Amphista to deliver class-leading SMARCA2 degraders for the treatment of SMARCA4-mutant NSCLC. 

Title: Rational development of novel FBXO22-mediated TEAD Targeted Glues™ for Mesothelioma and NSCLC Treatment 

Session: Targeted Protein Degradation and Induced Proximity

Date: Tuesday 21 April | 9:00 AM – 12:00 PM PST

Presenter: Marta Carrara, Associate Director Bioscience, Amphista Therapeutics

Abstract:

TEAD transcription factors are emerging oncology targets due to their function as key effectors of the Hippo signalling pathway, which is frequently dysregulated in cancer. Here, we report the discovery and development of potent, deep, and rapid-acting TEAD Targeted Glue degraders that leverage an aldehyde-mediated degron mechanism. Our compounds demonstrate exceptional on-pathway selectivity profiles and exhibit the expected Hippo signalling modulation.

Mechanistically, we demonstrate that amine-based TEAD degrader amine scaffolds undergo extracellular conversion to reactive aldehyde species, which mediate covalent engagement of FBXO22 C326, triggering TEAD proteasomal degradation. The degraders identified were able to be rationally and systematically optimised for both degradation potency and kinetics, achieving enhanced degradation profiles compared to previously reported FBXO22-targeting approaches, establishing design principles for this degrader class.

Our findings highlight aldehyde-mediated degrons as a viable strategy for targeted protein degradation, enabling rational design of degraders that hijack endogenous protein quality control machinery for precision medicine applications.

Ends

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 and development 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 Health Investors’ 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.

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. Five-year survival rates remain at just 33% and is the cause of death for an estimated 130,000 patients globally each year. 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

For more information please contact:

Amphista Therapeutics
John Goodall
Email: Info@amphista.com

ICR Healthcare
Namrata Taak, Ashley Tapp, Emily Johnson
Email: Amphista@icrhealthcare.com
Tel: +44 (0)20 3709 5813