Cancer Research UK have signed an agreement with ORIC Pharmaceuticals, Inc. to advance ORIC-259, a potential first-in-class CIP2A-targeted therapy, into clinical development.

Under the agreement, Cancer Research UK’s Centre for Drug Development (CDD) will fully fund, sponsor, design and execute a Phase 1/2 clinical trial of ORIC-259, including CTA-enabling studies, for patients with cancer. ORIC retains an option to reacquire rights to ORIC-259 following Phase 1/2 data, with Cancer Research UK eligible to receive downstream milestone payments and royalties. Cancer Research Horizons, Cancer Research UK’s innovation arm, will manage the commercial relationship between Cancer Research UK and ORIC.

ORIC-259 is a splice-modifier directed against CIP2A, a cancer-driving protein that has traditionally been considered undruggable. CIP2A plays multiple roles in cancer progression and is associated with tumour growth and survival across numerous cancer types, making it an attractive target for the development of potential new cancer treatments.

The collaboration aims to accelerate the clinical development of ORIC-259 and evaluate its potential as a new treatment option for patients with cancer. The Phase 1/2 trial will assess the safety, tolerability and preliminary anti-tumour activity of the molecule, generating important data to determine whether targeting CIP2A could offer a new therapeutic approach across a range of tumour types.

A potential area of application is in BRCA-mutant cancers, where research has identified CIP2A as a synthetic lethal vulnerability. PARP inhibitors have significantly improved outcomes for patients with these cancers, but treatment resistance remains a considerable clinical challenge. Because CIP2A targeting has a distinct mechanism from PARP, ORIC-259 could offer a new approach for patients whose cancers have become resistant to PARP inhibitors, while also creating opportunities to combine CIP2A-targeted therapies with PARP inhibitors or other agents.

This programme builds on Cancer Research UK and the UK’s pioneering role in PARP inhibitor development, drawing on deep expertise in translating synthetic lethal approaches into treatments for patients with BRCA-mutant and HRD cancers.

Lars Erwig, Director of the CDD, said: “ORIC-259 represents an innovative approach to targeting CIP2A, a protein with significant potential in cancer but one that has proven difficult to drug. We share ORIC’s mission to overcome treatment resistance in cancer, and we look forward to applying our expertise to explore new treatment options for patients.”

Lori Friedman, Chief Scientific Officer of ORIC, said: “We are excited to partner with Cancer Research UK to advance ORIC-259, a potential first-in-class CIP2A-targeted therapy, into the clinic. Cancer Research UK’s proven expertise and capabilities in developing innovative cancer therapies make it an ideal partner for the program, while this structure allows us to remain disciplined in allocating our internal resources to our late-stage clinical pipeline.”