On April 24, 2026 Amphista Therapeutics ("the Company" or "Amphista"), a leader in the discovery and development of non-cereblon/non-VHL Targeted Glue degraders, reported 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) (Free AACR Whitepaper) Annual Meeting in San Diego, US, and publication in bioRxiv of the optimization of early TEAD Targeted Glues.
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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 (Free AACR Whitepaper) 2026.
BioRxiv publication details:
Title: Identification and SAR optimization of FBXO22-mediated TEAD Targeted Glue degraders
DOI: View Source
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
(Press release, Amphista Therapeutics, APR 24, 2026, View Source [SID1234664752])