Pharma Focus America

IND Application Approval for Development Candidate GSK101 (IDE705) Targeting Pol Theta Helicase

Monday, August 21, 2023

IDEAYA Biosciences Obtains IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a company specializing in precision medicine oncology and dedicated to the research and development of targeted therapeutics, has announced the approval of an Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA). This approval paves the way for the initiation of a Phase 1/2 clinical trial, sponsored by GSK, to evaluate GSK101 (IDE705). GSK101 is a small molecule inhibitor targeting Pol Theta Helicase. The trial will investigate the combination of GSK101 with niraparib, a GSK-developed small molecule inhibitor of poly-(ADP-ribose) polymerase (PARP), for treating patients with tumors harboring BRCA or other homologous recombination (HR) mutations, as well as homologous recombination deficiency (HRD).

Dr. Ramon Kemp, Vice President and Global Head of Oncology Early Development at GSK, emphasized the potential significance of the GSK101 and niraparib combination in addressing the medical needs of patients with homologous recombination mutations. He highlighted the role of Pol Theta in microhomology-mediated end joining and its connection to resistance mechanisms against PARP inhibitors. The combination therapy aims to enhance thlkoe depth and duration of tumor responses, potentially improving outcomes for these cancer patients.

Yujiro S. Hata, Chief Executive Officer of IDEAYA Biosciences, expressed enthusiasm for the advancement of GSK101 into clinical trials, considering it the fourth potential first-in-class program for the company. He emphasized GSK's strategic role in optimizing the value of GSK101 through its combination with niraparib, positioning it as a promising treatment for solid tumors. Additionally, Hata mentioned the company's focus on the Werner Helicase development candidate nomination, which could mark their fifth potential first-in-class program.

GSK101, a potential first-in-class small molecule inhibitor, targets the helicase domain of DNA Polymerase Theta (Pol Theta). This enzyme is involved in DNA repair through microhomology-mediated end joining (MMEJ), which allows for the reversion of BRCA mutations. Notably, around 30% of patients who experience progression after PARP inhibitor treatment have tumors with MMEJ signatures at reversion sites, underscoring the medical need for a combination therapy involving GSK101 and niraparib.

The development of GSK101 was a collaborative effort between IDEAYA and GSK, involving its discovery and preclinical evaluation. Preclinical studies demonstrated that the combination of GSK101 and niraparib led to more profound and durable responses in BRCA mutant models compared to either agent alone.

GSK is aiming to initiate first-in-human studies for GSK101 in the fourth quarter of 2023. The company will lead the clinical development of the Pol Theta program under its exclusive license agreement, the GSK Pol Theta License. This license grants GSK global rights to develop and commercialize the Pol Theta Helicase Inhibitor DC. GSK will be responsible for all associated research and development costs.

IDEAYA is set to receive a $7 million milestone payment upon the FDA's acceptance of the IND, along with a potential additional $10 million milestone payment upon the initiation of Phase 1 clinical dose expansion. Further down the line, IDEAYA may also receive later-stage development and regulatory milestones totaling up to $465 million. In the event of successful commercialization, IDEAYA could gain up to $475 million in commercial milestones and tiered royalties based on global net sales by GSK, its affiliates, and sublicensees, subject to certain adjustments.

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