Cambridge, UK, 21^st October 2024 – Astex Pharmaceuticals, a pharmaceutical company based in Cambridge, UK, dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, announced today that it will make five key data presentations at the 36^th EORTC-NCI-AACR Symposium on molecular targets and cancer therapeutics, 23^rd-25^th October 2024, Barcelona, Spain.  The Astex presentations will focus on its novel small-molecule CBP/p300 HAT domain inhibitor, ASTX528 in preclinical development and its Phase II-ready MDM2 antagonist, ASTX295.

Astex data presentations at 36th EORTC-NCI-AACR Symposium, 23rd-25th October 2024, Barcelona

Title	Presentation	Date/Time/Session Title/Presenter	Presentation number
A Novel Small-Molecule CBP/p300 HAT Domain Inhibitor Demonstrates Potent In Vivo Activity and a Favourable Safety Profile in Preclinical Species	Poster	Date: Wed, 23rd Oct 2024 Time: 12:00 – 19:00 Session Title: Molecular Targeted Agents Presenter: Gianni Chessari, Astex Pharmaceuticals, UK	Catalog #42 Presentation #PB030
Targeting the Catalytic HAT Domain of CBP/p300 for the Treatment of Hormone-Dependent Breast and Prostate Cancers	Poster	Date: Wed, 23rd Oct 2024 Time: 12:00 – 19:00 Session Title: Molecular Targeted Agents Presenter: John Lyons, Astex Pharmaceuticals, UK	Catalog #73 Presentation #PB061
From a Preclinical Therapeutic Concept to the Clinic. ASTX295: Discovery of a bone marrow sparing MDM2 antagonist	Oral	Date: Wed, 23rd Oct 2024 Time: 16:55 -17:15 Session Title: Optimising of preclinical models for drug development Presenter: Maria Ahn, Astex Pharmaceuticals, UK	Workshop 2 Room 113+114
Identification of Biomarkers Predictive of Response to ASTX295, a Next-Generation MDM2 Antagonist, in Solid Tumors Carrying Wild-type p53	Poster	Date: Wed, 23rd Oct 2024 Time: 12:00 – 19:00 Session Title: Molecular Targeted Agents Presenter: Maria Ahn, Astex Pharmaceuticals, UK	Catalog #28 Presentation #PB016
Pulsatile Induction of the p53 Pathway by MDM2 Antagonist ASTX295 Shows an Enhanced Therapeutic Index in vivo	Poster	Date: Thu, 24th Oct 2024 Time: 9:00 – 17:30 Session Title: Translational Studies Presenter: Andrea Biondo, Astex Pharmaceuticals, UK	Catalog #289 Presentation #PB277

ASTX528 – CBP/p300 HAT Domain Inhibitor – Preclinical

ASTX528 is a novel small molecule CBP/p300 HAT domain inhibitor with potent in vivo activity and a favourable safety profile in preclinical species that was discovered by Astex using its proprietary fragment-based drug discovery approach.  CREB binding protein (CBP) and its paralog, EP300 (p300), are lysine acetyltransferases and transcriptional cofactors implicated in human cancers.  Dose-limiting tolerability issues have been observed with dual CBP/p300 bromodomain (BRD) inhibitors, which may limit their clinical utility.  We hypothesised that a dual inhibitor targeting the histone acetyltransferase (HAT) domain may improve the therapeutic window.  Our presentations will describe the effects of CBP/p300 HAT domain inhibition in preclinical models of AR- and ER-driven cancers and the characterisation of ASTX528, a potent, fragment-derived CBP/p300 HAT domain inhibitor with a low predicted human dose and promising preliminary toxicity evaluation.  Astex is interested in discussing the further development of ASTX528 with potential partners.

ASTX295 – Bone Marrow-Sparing MDM2 Antagonist, Phase II-ready

ASTX295 is an oral, potent inhibitor of the p53-MDM2 protein-protein interaction that was discovered by Astex using its proprietary structure-based drug design approach.  The compound was specifically designed to overcome the on-target toxicity seen in the first generation MDM2 antagonist compounds which have shown dose-limiting haematological toxicities in the clinic.  In contrast, ASTX295 is a potent MDM2 antagonist with a clean CYP/hERG profile and a shorter human half-life allowing for pulsatile pathway modulation while avoiding myelosuppression.   ASTX295 therefore has bone-marrow sparing characteristics which permit a differentiated safety profile.  ASTX295 was discovered by Astex in collaboration with the Cancer Research UK Drug Discovery Unit at Newcastle University.  Astex has an exclusive license to research, develop and commercialise ASTX295 under its drug discovery alliance agreement with Newcastle University and Cancer Research Technology Limited.

-ENDS-

 

About Astex Pharmaceuticals

Astex is a leader in innovative drug discovery and development, committed to the fight against cancer and diseases of the central nervous system.  Astex is developing a proprietary pipeline of novel therapies and has several partnered products being developed under collaborations with leading pharmaceutical companies.  Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.

For more information about Astex Pharmaceuticals please visit: http://www.astx.com

For more information about Otsuka Pharmaceutical, please visit: https://www.otsuka.co.jp/en/

Contact
At the Company: Jeremy Carmichael SVP Corporate Development Head of Business Development Tel: +44(0)1223 226289 Email:  jeremy.carmichael@astx.com	For Media Enquiries: Sue Charles Charles Consultants Tel : +44(0)7968 726585 Email:  sue@charles-consultants.com