Astex Pharmaceuticals to Present Key Data at 36th EORTC-NCI-AACR Symposium

Astex Pharmaceuticals, a company headquartered in Cambridge, UK, and dedicated to discovering and developing new small molecule therapeutics for oncology and central nervous system diseases, has announced its plan to present significant data at the 36th EORTC-NCI-AACR Symposium on molecular targets and cancer therapeutics. The symposium is scheduled to take place from October 23rd to 25th, 2024, in Barcelona, Spain. Astex will deliver five key presentations at this event, focusing on two of its innovative compounds: the CBP/p300 HAT domain inhibitor, ASTX528, and the MDM2 antagonist, ASTX295, which is ready for Phase II trials.

The first presentation is about ASTX528, a novel small-molecule CBP/p300 HAT domain inhibitor. This compound has demonstrated potent in vivo activity and has shown a favorable safety profile in preclinical species. It was discovered through Astex’s proprietary fragment-based drug discovery approach. CBP (CREB binding protein) and its paralog, p300 (EP300), are lysine acetyltransferases involved in human cancers. Previous dual CBP/p300 bromodomain inhibitors have faced dose-limiting tolerability issues, potentially restricting their clinical usefulness. ASTX528 targets the histone acetyltransferase (HAT) domain, which may enhance its therapeutic window. The presentations will explore the effects of inhibiting the CBP/p300 HAT domain in preclinical models of androgen receptor (AR) and estrogen receptor (ER) driven cancers. Additionally, they will discuss the characterization of ASTX528, revealing its low predicted human dose and promising preliminary toxicity evaluation. Astex is interested in further developing ASTX528 with potential partners.

The second compound to be highlighted is ASTX295, an oral inhibitor of the p53-MDM2 protein-protein interaction, discovered using Astex’s structure-based drug design technique. ASTX295 aims to address the on-target toxicity observed in first-generation MDM2 antagonists, which have shown dose-limiting hematological toxicities in clinical settings. ASTX295, however, is a potent MDM2 antagonist with a clean CYP/hERG profile and a shorter human half-life, allowing for pulsatile pathway modulation and avoiding myelosuppression. This bone marrow-sparing characteristic grants ASTX295 a differentiated safety profile. It was developed in collaboration with the Cancer Research UK Drug Discovery Unit at Newcastle University. Astex holds an exclusive license to research, develop, and commercialize ASTX295 under its drug discovery alliance agreement with Newcastle University and Cancer Research Technology Limited.

Astex is recognized as a leader in innovative drug discovery and development, focusing on combating cancer and central nervous system disorders. The company is developing a proprietary pipeline of novel therapies and has several partnered products progressing through collaborations with leading pharmaceutical companies. Astex operates as a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.

Astex’s participation at the EORTC-NCI-AACR Symposium underscores its ongoing commitment to advancing cancer treatment through the development of cutting-edge therapies. By showcasing their latest research and development achievements, Astex aims to foster collaborations and drive forward the clinical potential of their innovative compounds, ASTX528 and ASTX295.