CAMBRIDGE, UK, April 24, 2026

Amphista Therapeutics has unveiled new preclinical data demonstrating the therapeutic potential of its SMARCA2 and TEAD Targeted Glue™ degrader programs, highlighting robust tumor suppression and selective protein degradation across multiple cancer models. Presented at the American Association for Cancer Research (AACR) 2026 Annual Meeting, the findings underscore Amphista’s leadership in next-generation targeted protein degradation (TPD) technologies, positioning its pipeline as a promising source of first- and best-in-class oncology therapies. The data also include the first published insights into its TEAD program, further validating its innovative drug discovery platform and accelerating its progress toward clinical candidate selection in late 2026.

SMARCA2 Program Demonstrates Selective and Deep Degradation

Amphista’s SMARCA2 Targeted Glue™ degraders showed high selectivity and sustained degradation of the SMARCA2 protein while maintaining minimal impact on the closely related SMARCA4 protein, a critical factor in reducing off-target effects. Preclinical studies demonstrated deep in vivo degradation following oral administration, leading to suppression of key downstream biomarkers such as KRT80 and PLAU, which are associated with tumor progression.

The program leverages advanced cryo-electron microscopy insights to optimize the formation of the ternary complex, enhancing both the speed and depth of protein degradation. These results suggest a best-in-class potential for SMARCA2 degraders, particularly in cancers characterized by SMARCA4 deficiency, where targeted degradation strategies may offer a highly effective and selective therapeutic approach.

TEAD Program Shows Tumor Regression and Combination Potential

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The TEAD Targeted Glue™ program demonstrated significant anti-tumor activity, including oral in vivo tumor regression in mesothelioma models and anti-proliferative effects in cancer cell lines. Notably, the therapy exhibited synergistic efficacy when combined with osimertinib in EGFR-mutant non-small cell lung cancer (NSCLC) models, highlighting its potential for combination treatment strategies.

The program also benefits from a unique degradation-based mechanism, enabling extended pharmacodynamic effects and flexible dosing schedules, such as once-every-three-day administration. Amphista’s published research further outlines the rational optimization of TEAD degraders, achieving improved potency, degradation kinetics, and therapeutic selectivity, and establishing key design principles for this emerging drug class. These findings validate the FBXO22-TEAD degradation pathway as a promising target in Hippo pathway-driven cancers, opening new avenues for treating difficult-to-target malignancies.

Advancing Targeted Protein Degradation Innovation

Amphista’s research is powered by its proprietary Eclipsys® platform, which enables the development of sequentially bifunctional Targeted Glue™ therapeutics with enhanced drug-like properties compared to traditional degradation approaches. Unlike conventional CRBN or VHL-based systems, Amphista’s platform offers greater flexibility, selectivity, and efficacy, addressing limitations in current TPD technologies. The company is actively seeking strategic partnerships to advance its SMARCA2 and TEAD programs into clinical development, reflecting growing industry interest in targeted protein degradation as a transformative approach in oncology and beyond.

With additional programs such as BRD9 degraders also progressing, Amphista is building a diversified pipeline of innovative therapies aimed at addressing unmet needs in cancer and neurodegenerative diseases. These advancements highlight the rapid evolution of precision medicine, where novel molecular mechanisms are redefining drug discovery and therapeutic potential.

Source: Amphista Therapeutics press release