Amphista Therapeutics unveils new differentiated mechanism of action for BRD9 degradation at 2024 Protein Degradation in Focus Symposium
2024年5月23日 - 8:00PM
Amphista Therapeutics unveils new differentiated mechanism of
action for BRD9 degradation at 2024 Protein Degradation in Focus
Symposium
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 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
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