Astex Pharmaceuticals Announce Key Data Presentations at the 36th EORTC-NCI-AACR Symposium
Cambridge, UK, 21 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 36th EORTC-NCI-AACR Symposium on molecular targets and cancer therapeutics, 23-25 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, 23-25 October 2024, Barcelona
- 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 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.
