Amphista Therapeutics Discloses First Details Of Its TEAD Targeted Gluetm Program And Unveils New Mechanism Of Action For TEAD Degradation Via FBXO22

• First disclosure of a novel mechanism of action for the degradation of TEAD by selectively inducing its proximity to FBXO22 as a targeted molecular glue, leading to strong and rapid degradation of TEAD.
• Structurally-guided discovery using high-resolution cryo-EM has delivered TEAD Targeted GluesTM with exceptional potency.
• First in vivo demonstration of FBXO22-mediated protein degradation following oral dosing. TEAD Targeted GluesTM show rapid degradation dynamics with near-maximal effect at 2 hours, sustained for at least 72 hours.
  

Cambridge, UK, 23 September 2025 – Amphista Therapeutics (“the Company” or“Amphista”), a leader in the discovery of next generation targeted protein degradation (TPD) medicines, today disclosed first data on its TEAD oncology therapeutic program including unveiling a new mechanism of action for the degradation of TEAD that is differentiated from cereblon- or VHL-based PROTACs. Amphista's novel TEAD Targeted GluesTM, which are inherently smaller and more drug like molecules than conventional PROTAC binders, have demonstrated:

• Novel mechanism of degradation : Amphista's pan-TEAD Targeted GlueTM series induces degradation via functional recruitment of the E3 ligase FBXO22 (F-Box Protein 22), a mechanism of degradation that has not previously been described for TEAD.
• Highly specific degradation of TEAD: Global proteomics demonstrates complete, and statistically significant, selective, degradation of TEAD vs >7000 other proteins.
• Deep target degradation via oral dosing: Leveraging high-resolution cryo-EM, Amphista has designed sub-nM degraders of TEAD which induce >95% degradation of TEAD in vivo after a single oral dose.
• Exceptional degradation dynamics: Amphista's Targeted GluesTM achieve >90% TEAD degradation within 2 hours (the first time point measured) of single dosing, sustained at >70% through to at least 72 hours.

Louise Modis, Chief Scientific Officer of Amphista Therapeutics, said: “Soon after disclosing initial details of our SMARCA2 oncology program, the first unveiling of a completely novel mechanism of action for the degradation of TEAD, represents another significant milestone for Amphista, as well as the wider targeted protein degradation field. The development of potent, rapid, orally bioavailable Targeted GlueTM degraders of TEAD that work via FBXO22 is testament to the power of our Eclipsys® platform and our brilliant multidisciplinary team. What is particularly exciting are the structural insights that we are gaining from our technology as we build our cryo-EM datasets. Not only are these helping Amphista generate differentiated, higher quality molecules with the properties that will enable them to become medicines, but they are also unlocking mechanistic insights into the development and optimisation of Amphista's Targeted GluesTM which operate through diverse ligases. The progress we have made across our portfolio this year, which includes the disclosure of two completely novel mechanisms for the degradation of therapeutically relevant targets is exceptional. I am looking forward to sharing further data and updates as we look to select our clinical candidates for TEAD and SMARCA next year.”

Amphista plans to present data from its TEAD Targeted GlueTM program at a key forthcoming TPD scientific conference.

This news on Amphista's TEAD Targeted GlueTM program follows an announcement by the Company on 17 September 2025, which disclosed first data on its SMARCA2 program including demonstrating exquisite selectivity of its sequentially bifunctional Targeted GluesTM for SMARCA2 over the closely related homolog, SMARCA4.

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 GlueTM 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:

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
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Amber Fennell, Namrata Taak, Emily Johnson
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