IDEAYA Biosciences Gains IND Clearance for Werner Helicase Candidate IDE275 (GSK959) in Phase 1 MSI-High Tumor Study

IDEAYA Biosciences, based in South San Francisco, has announced the FDA approval of an IND application for their novel drug IDE275 (GSK959), aiming to commence Phase 1 clinical trials by the end of 2024. This investigational treatment is a pioneering Werner Helicase (WRN) inhibitor specifically designed for patients with tumors exhibiting high microsatellite instability (MSI-High). This approval marks a significant milestone as IDE275 (GSK959) becomes the company's fifth potential first-in-class clinical program in the pipeline of precision medicine oncology.

According to Yujiro S. Hata, IDEAYA’s President and CEO, the preclinical data for IDE275 is promising. The drug has demonstrated significant efficacy selectively in MSI-High settings, showing tumor regressions even as a monotherapy. This is particularly relevant for patients with endometrial, colorectal, and gastric cancers, where MSI-High prevalence rates are approximately 31%, 20%, and 19%, respectively. Given this, IDE275 has the potential to address a substantial patient population across these tumor types.

Developed in collaboration with GSK, IDE275 (GSK959) has shown strong and selective synthetic lethality in preclinical models, including in-vivo studies involving MSI-High CDX and PDX models derived from colorectal, endometrial, and gastric cancers. The forthcoming Phase 1 trial, sponsored by GSK, will explore IDE275 both as a standalone treatment and in combination with a PD-1 inhibitor for patients with MSI-High tumors.

From a financial perspective, IDEAYA stands to benefit significantly from this development. The company will receive a $7 million milestone payment upon the FDA's IND acceptance and potentially another $10 million upon the start of Phase 1 dose expansion. Additional future milestones could yield up to $465 million in later-stage development and regulatory achievements. Upon commercialization, IDEAYA could gain up to $475 million in commercial milestones, half of the U.S. net profits, and tiered royalties on global non-U.S. net sales, ranging from high single-digit to sub-teen double-digit percentages, subject to customary reductions.

In terms of cost-sharing, GSK will handle 80% of the global research and development expenses for IDE275 (GSK959), while IDEAYA will cover the remaining 20%. This collaboration underscores the strategic partnership between IDEAYA and GSK, leveraging their combined expertise to advance this promising therapeutic candidate.

IDEAYA Biosciences is a precision medicine oncology firm focused on developing targeted therapies based on molecular diagnostics. Their approach integrates the identification and validation of translational biomarkers with drug discovery to tailor treatments for patient populations most likely to benefit. This strategy is especially pertinent to synthetic lethality, a burgeoning area in precision medicine that IDEAYA is actively pursuing.

Overall, IDEAYA Biosciences' advancement of IDE275 (GSK959) into clinical trials represents a significant step forward in precision oncology, potentially offering new hope for patients with MSI-High tumors. The strategic collaboration with GSK and the promising preclinical data underscore the potential impact of IDE275 on various solid tumor types, particularly endometrial, colorectal, and gastric cancers.