EGFR x VHL

Cambridge, UK, 24 th April 2026 - Amphista Therapeutics (“the Company” or “Amphista”), a leader in the discovery and development of non-cereblon/non-VHL Targeted Glue™ degraders, today announces the presentation of new pre-clinical data on its orally bioavailable SMARCA2 and TEAD Targeted Glue™ programs at the American Association for Cancer Research (AACR) Annual Meeting in San Diego, US, and publication in bioRxiv of the optimization of early TEAD Targeted Glues™. Selective SMARCA2 Targeted Glue™ degraders: Robust SMARCA2 selectivity over SMARCA4 maintained over time Deep degradation of SMARCA2 following oral delivery New data from the DCAF16-dependent SMARCA2 program demonstrated deep in vivo degradation of SMARCA2 following oral dosing. In vivo SMARCA2 degradation translated into suppression of downstream biomarkers, including KRT80 and PLAU , reinforcing the therapeutic relevance of the approach. The program leverages insights gained from multiple high-resolution cryo-electron microscopy structures of the ternary complex, enabling improvements in the speed and depth of SMARCA2, as well as high degradation selectivity over the closely related SMARCA4 paralog. Together, these data support a best-in-class potential for Amphista’s SMARCA2 Targeted Glue™ degraders. TEAD Targeted Glue™ degraders: Oral in vivo tumor regression following intermittent dosing bioRxiv publication on the rational and systematic optimization of early TEAD Targeted Glues™ New data from the FBXO22-dependent TEAD program demonstrated anti-proliferative activity in mesothelioma cell lines, with synergistic efficacy observed in combination with osimertinib in vitro in an EGFR-mutant NSCLC model. Further data showcased how a degradation-based modality, combined with the long half-life of TEAD, drives extended pharmacodynamic effects, enabling an efficacious once-every-three-day dosing schedule and tumor regression in vivo in a mesothelioma xenograft model. The bioRxiv publication describes the rational and systematic optimization of early FBXO22 Cys326-mediated TEAD Targeted Glues™, achieving enhanced degradation potency and kinetics compared to previously reported FBXO22-targeting approaches. These findings establish important design principles for this emerging degrader class and validate FBXO22-TEAD degradation as a therapeutically relevant approach for Hippo pathway-driven cancers, with promise in mesothelioma and combination strategies for EGFR-mutant NSCLC. Dr. Louise Modis, Chief Executive Officer at Amphista Therapeutics, commented : “The positive preclinical data on two of our programs, SMARCA2 and TEAD, reflect the strength of our unique approach and proprietary technology, and the great progress we are making as we advance towards the clinic. We are actively seeking partners to collaborate on our SMARCA2 and TEAD programs as they progress towards candidate selection in the second half of 2026.” Today’s announcement builds on the progress Amphista has made since it disclosed its SMARCA2 and TEAD programs in September 2025 and follows the recent presentation of AMX-883, an orally bioavailable, highly potent and selective degrader of BRD9, at AACR 2026. BioRxiv publication details: Title: Identification and SAR optimization of FBXO22-mediated TEAD Targeted Glue™ degraders DOI: 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 Presenter: James Lynch, Senior Director Bioscience, Amphista Therapeutics Title: Rational development of novel FBXO22-mediated TEAD Targeted Glues™ for Mesothelioma and NSCLC Treatment Session: Targeted Protein Degradation and Induced Proximity Presenter: Marta Carrara, Associate Director Bioscience, Amphista Therapeutics 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: 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, Ashley Tapp, Emily Johnson Email: Amphista@icrhealthcare.com Tel: +44 (0)20 3709 5813