PRESS RELEASE
Amphista Therapeutics unveils new differentiated mechanism of action for BRD9
degradation at 2024 Protein Degradation in Focus Symposium
* First presentation of a novel mechanism of action for the degradation of
BRD9 - completely differentiated from cereblon- or VHL-based PROTACs
* Amphista's bifunctional BRD9 degraders selectively induce BRD9 to DCAF16
proximity and serve as molecular glues, leading to strong and rapid
degradation of BRD9
* Discovery further underscores Amphista's proprietary chemistry and high-
quality science which is being applied to the discovery and development of
additional targeted glues beyond BRD9
Cambridge, UK, May 23, 2024 - Amphista Therapeutics ("Amphista"), a leader in
next generation targeted protein degradation (TPD) approaches, today announces
the unveiling of a new mechanism of action for the degradation of BRD9, an
emerging target in oncology, that is differentiated from cereblon- or VHL-based
PROTACs, during an oral presentation at the 2024 Protein Degradation in Focus
Symposium held in Dundee, UK.
This significant news for the TPD field builds upon an earlier announcement
(https://amphista.com/amphista-therapeutics-announces-new-data-demonstrating-in-
vivo-efficacy-and-cns-activity-of-its-mechanistically-differentiated-targeted-
protein-degraders/) by Amphista of two compelling data sets demonstrating in
vivo efficacy and central nervous system (CNS) activity of its mechanistically
differentiated protein degraders. At today's presentation titled "Degradation of
BRD9 by a novel targeted glue", Dr Andrea Testa, Scientific Co-Founder and
Senior Director, Discovery Chemistry showed data from proteomic and genetic
validation studies which demonstrate that Amphista's bifunctional degraders
induced degradation of BRD9 by target-assisted E3 ligase recruitment. This novel
mechanism selectively induces the proximity of BRD9 to DCAF16 and serves as a
molecular glue. DCAF16 is a cullin-RING E3 ligase which can facilitate
degradation of proteins of interest via ternary complex formation. Induction of
this complex leads to deep and rapid degradation of BRD9 in vivo.
Louise Modis, Chief Scientific Officer of Amphista Therapeutics, said: "The
discovery of a novel mechanism for BRD9 degradation, differentiated from
cereblon- or VHL-based PROTACs, is a testament to Amphista's proprietary
chemistry and know-how. Our ability to translate this novel approach into high-
quality, drug-like compounds with oral bioavailability and activity in vivo is
truly exciting. As we continue to spearhead our efforts to advance new TPD
approaches, our goal remains clear - to expand the offering of TPD medicines
beyond CRBN and VHL-based agents and bring effective treatments to patients in
areas of high unmet need."
In the results presented, Amphista's sub-nanomolar BRD9 degraders showed
activity in both solid and liquid cancer cell lines and demonstrated a high
degree of selectivity over 8,000 proteins quantified by proteomics, including
the closely related proteins BRD7 and BRD4. Notably, these compounds induced
BRD9 degradation in a mouse xenograft model illustrating Amphista's BRD9
degraders are orally bioavailable and active in vivo. This is the first-time in
vivo degradation of BRD9 has been demonstrated via DCAF16, underscoring the
potential therapeutic application of Amphista's bifunctional degraders.
Building on this knowledge, Amphista is applying its proprietary scientific
know-how and expertise to the development of targeted glues which induce
degradation of different targets, expanding the opportunity beyond BRD9. Future
announcements will provide details of additional pipeline targets as part of
Amphista's ambitions to develop a first- and/or best-in-class portfolio of
degraders with leading physicochemical properties.
About Amphista Therapeutics
Amphista Therapeutics is focused on transforming the lives of patients with
severe diseases, including cancer and neurodegenerative disease, through the
advancement of next generation targeted protein degradation (TPD) medicines.
Amphista is applying its proprietary warhead chemistry and mechanistic know-how
to generate bifunctional targeted glues with a differentiated mechanism and
leading physicochemical properties. Its portfolio offers the potential for
first- and/or best-in-class assets and expanding the offering of TPD medicines
beyond CRBN and VHL-based agents. Founded by Advent Life Sciences, Amphista is a
spin-out of TPD expert Professor Alessio Ciulli's laboratories at the University
of Dundee. Amphista is funded by leading life science investors including
Forbion, Gilde Healthcare, Novartis Venture Fund, Advent Life Sciences, Eli
Lilly & Company and The Dementia Discovery Fund, and also has strategic
collaborations with Bristol Myers Squibb and Merck. For more information, please
visit: www.amphista.com (http://www.amphista.com/)
Amphista and the Amphista logo are all trademarks or registered trademarks of
Amphista Therapeutics Limited.
For more information please contact:
ICR Consilium
Amber Fennell, Namrata Taak
Email: Amphista@consilium-comms.com
Tel: +44 (0)20 3709 5813
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