Amphista Therapeutics Discloses First Details Of Its SMARCA2 Degrader Program

• Structurally-guided discovery using high-resolution cryo-EM has delivered potent, DCAF16-dependent Targeted GluesTM of SMARCA2, with exquisite selectivity over close homolog, SMARCA4.
• Rapid, deep and sustained degradation of SMARCA2 has been achieved, with a wide margin over SMARCA4.
  • CNS penetrant SMARCA2 Targeted GluesTM have been identified within the program, offering the potential for differentiation to all other agents on this critical parameter.
    

Cambridge, UK, 17 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 SMARCA2 program including demonstrating exquisite selectivity of its sequentially bifunctional Targeted GluesTM for SMARCA2 over the closely related homolog, SMARCA4.

Amphista has identified SMARCA2 Targeted GluesTM, which induce protein degradation via a novel mechanism and enable the development of smaller and more drug like molecules than conventional PROTAC binders. Amphista's SMARCA2 Targeted GluesTM have demonstrated:

• Novel mechanism of degradation : Amphista's SMARCA2 Targeted GlueTM series induce degradation via induction of the E3 ligase DCAF16, a novel mechanism of degradation that goes beyond traditional TPD technologies.
• Exquisite selectivity over SMARCA4: Through the generation of high-resolution cryo-EM, Amphista has learnt the structural basis for selectivity over SMARCA4 and has been able to design molecules with near complete selectivity for SMARCA2, with <5% SMARCA4 degradation observed.
• Highly specific degradation of SMARCA2: Global proteomics profiling demonstrates statistically significant degradation of SMARCA2 vs >8000 other proteins, including SMARCA4.
• Exceptional degradation kinetics: Amphista's Targeted GluesTM are able to potently degrade >95% SMARCA2 within 4 hours.
• CNS penetrance: Amphista has identified a series of SMARCA2 degraders that have demonstrated CNS penetration in vivo. This offers the potential to develop medicines which can treat CNS metastasis, which frequently occur in lung cancer.
  

Louise Modis, Chief Scientific Officer of Amphista Therapeutics, said: “We are excited by the quality of the profile we have been able to achieve with our selective SMARCA2 degraders. The bar for success is very high in this area and we believe achieving sufficient selectivity over SMARCA4 is absolutely critical to generate a best-in-class molecule. Through the extensive deployment of cutting-edge cryo-EM structures, we have been able to do just that – to generate Targeted GluesTM which degrade SMARCA2, and only SMARCA2, over sustained timepoints. In addition, we believe the impressive degradation kinetics we are able to achieve with our technology will give us a significant advantage clinically.”

Amphista plans to present data from its SMARCA2 Targeted GlueTM program at a key forthcoming scientific conference.

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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ICR Healthcare
Amber Fennell, Namrata Taak, Emily Johnson
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Tel: +44 (0)20 3709 5813

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