Summary
- Asset co-developed by Cancer Research Horizons, Newcastle University and Astex Pharmaceuticals
- MDM2-p53 antagonist increases levels of p53, a key suppressor of tumour growth and survival
- Phase 1/2 clinical study demonstrates potential to overcome limitations observed with other MDM2-p53 antagonists
Cancer Research Horizons, the innovation arm of Cancer Research UK, announces a Phase 1/2 clinical update on ASTX295, a novel MDM2 antagonist, currently being investigated in patients with advanced solid tumours.
The compound was discovered and developed through a multi-project alliance with Astex Pharmaceuticals and Newcastle University, the longest running translational partnership of Cancer Research UK and Cancer Research Horizons. This strategic drug discovery collaboration leverages the expertise in cellular and structural biology, as well as medicinal chemistry, from the Cancer Research Horizons Drug Discovery Group at Newcastle University.
“Everyone involved in this project is highly encouraged by ASTX295’s emerging safety profile and by the early results observed in advanced cancer patients,” said Professor Martin Noble at Newcastle University. “This project exemplifies how industry and academic scientists can work together in partnership to advance life-improving therapies.”
ASTX295 is a potential best-in-class small molecule MDM2 (mouse double minute 2 homolog) antagonist, designed to restore the function of p53, a fundamental tumour-suppressing pathway in cancer biology. ASTX295 distinguishes itself from other MDM2-p53 antagonists with its shorter plasma half-life, resulting in a potentially broader therapeutic window and reduced dose-limiting toxicities on normal blood cells.
Steve Wedge, CSO of Cancer Research Horizons’ Therapeutic Innovation laboratories and Professor of Stratified Cancer Medicine Discovery at Newcastle University, commented: “A number of tumours retain normal p53 protein, but its ability to function as a tumour suppressor is compromised through an interaction with MDM2, which ultimately leads to p53 being destroyed. Inhibiting the interaction between MDM2 and p53 with a drug is therefore an exciting prospect in oncology treatment. Our inhibitor was designed to have a shorter duration of action in patients, to enable activity in tumour cells whilst avoiding longer-term toxic effects in bone marrow. We believe ASTX295 has the potential to be combined with other cancer therapies, and we are looking forward to the next phase of our collaboration.”
Led by Dr Ecaterina Dumbrava, MD (MD Anderson Cancer Centre), the ongoing Phase 1/2 study demonstrated ASTX295's tolerability and identified a Recommended Phase 2 Dose regimen. These findings, along with preliminary patient pharmacodynamic and pharmacokinetic data, support continued clinical development.
Astex Pharmaceuticals holds exclusive worldwide licensing rights for ASTX295 and any other compounds arising from the alliance, with Cancer Research Horizons eligible for milestone and royalty payments upon successful clinical advancement and market introduction.
The Phase 1 trial results were presented at AACR’s annual meeting in April 2024. [2]
ENDS
References
[1] – Phase 1/2 Open-label study of the safety, pharmacokinetics, and preliminary activity of ASTX295 in subjects with wild-type TP53 advanced solid tumors. NCT03975387
About Cancer Research Horizons
Cancer Research Horizons is the innovation engine of Cancer Research UK – the world's largest charitable funder of cancer research. We bring together world-leading minds, bold ideas and the right partners to bridge the gap between academic research and taking drugs to market. We focus on the tougher, more profound ideas that can lead to true innovation, translating them into effective treatments and diagnostics for cancer patients.
To date, we've played an instrumental role in forming over 70 start-ups. We've helped bring 13 cancer drugs to market, borne out of Cancer Research UK's pioneering research. Through these drugs, we have enabled in excess of 6 million courses of treatment for cancer patients across the world.
With access to Cancer Research UK's network of 4,000 exceptional researchers, and £400+ million of annual research spend, we're a powerful partner in the fight to conquer cancer. By uniting our commercial partnerships and therapeutic innovation capabilities, Cancer Research Horizons is uniquely placed to support translational funding, entrepreneurial development, licensing and collaboration, spinout creation, and offer a full spectrum of drug discovery and clinical capabilities.
Every penny we make goes back into funding the next bold steps, to help bring forward the day when all cancers are conquered.
For more information and to get in touch with the team, visit cancerresearchhorizons.com.