IDEAYA Biosciences, Inc. has announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for IDE275 (GSK959), a potential first-in-class Werner Helicase (WRN) inhibitor. This clearance paves the way for a Phase 1 clinical trial evaluating IDE275 in patients with microsatellite instability-high (MSI-High) solid tumors.
The Phase 1 trial is projected to begin in the fourth quarter of 2024. GSK will sponsor the IND application and plans to develop IDE275 (GSK959) as a monotherapy and in combination with a PD-1 inhibitor for patients with MSI-High tumors.
Rationale for WRN Inhibition in MSI-High Tumors
IDE275 (GSK959) was discovered by IDEAYA in collaboration with GSK. Preclinical studies have demonstrated robust and selective synthetic lethality in the MSI-High biomarker setting, including single-agent tumor regressions in vivo in MSI-High CDX and PDX models derived from colorectal, endometrial, and gastric cancers. MSI-High tumors are characterized by a deficiency in DNA mismatch repair, making them particularly sensitive to WRN inhibition.
"IDE275 represents IDEAYA's fifth potential first-in-class clinical program in our precision medicine oncology pipeline and has a potentially differentiated best-in-class profile that we are targeting to present at a future medical conference with GSK," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. He added that the robust preclinical efficacy observed by IDE275 selectively in the MSH-High biomarker setting, including monotherapy regressions, provides a double-digit % prevalence target patient population across several major solid tumor types, including endometrial, colorectal and gastric cancer.
Financial Implications for IDEAYA
Upon acceptance of the IND by the FDA, IDEAYA is eligible to receive a $7 million milestone payment. The company may also receive an additional $10 million milestone payment upon initiation of Phase 1 clinical dose expansion. Furthermore, IDEAYA is potentially eligible to receive up to $465 million in further later-stage development and regulatory milestones and up to $475 million of commercial milestones. IDEAYA will also receive 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of IDE275 (GSK959), ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.
GSK is responsible for 80% of global research and development costs for IDE275 (GSK959), while IDEAYA is responsible for 20% of such costs.
Market Opportunity
The prevalence of MSI-High in solid tumors, including endometrial, colorectal, and gastric cancers, has been reported at approximately 31%, 20%, and 19%, respectively (JCO Precision Oncology, September 2017), underscoring the significant market potential for IDE275.
