IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company dedicated to discovering and developing targeted therapeutics, has initiated a Phase 1 monotherapy expansion in its first-in-human clinical trial assessing IDE161 (NCT 05787587).

"We are pleased to advance IDE161, a potential first-in-class PARG inhibitor, into an expansion phase of our Phase 1 clinical trial and are excited to explore its potential in cancer patients with homologous recombination deficiency (HRD). Based on extensive preclinical studies, we are focusing this expansion in several priority tumor types, including ER+, Her2(-) breast cancer and ovarian cancer subjects with tumors that harbor HRD," said Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer of IDEAYA Biosciences.

"The clinical update today on IDE161 represents the first reported preliminary clinical proof-of-concept for a PARG inhibitor in HRD solid tumors. We look forward to the continued evaluation of IDE161 as a monotherapy in high unmet medical need HRD solid tumor indications," said Yujiro S. Hata, Chief Executive Officer of IDEAYA Biosciences.

The Phase 1 first-in-human clinical trial is evaluating the safety, tolerability, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of IDE161 in patients with tumors exhibiting homologous recombination deficiency (HRD). Early clinical data from the dose escalation cohorts showed dose-dependent pharmacodynamic modulation of poly-ADP ribose (PAR) proteins in peripheral blood, demonstrating IDE161's target engagement. These clinical data also demonstrated IDE161 exposure levels in humans which correlate with preclinical exposures that were efficacious, achieving tumor regressions in xenograft models.

The Phase 1 expansion is based on preliminary tumor shrinkage observed in multiple HRD solid tumor patients, including a BRCA1/2 endometrial cancer subject with a first imaging assessment of a partial response in the target lesion, a complete response in the non-target lesion, and an 87% reduction in the CA-125 tumor marker (2,638 units/ml at baseline to 360 units/ml at 6 weeks). The company is also continuing to evaluate the optimal dose for Phase 2 expansion. The expansion portion of the Phase 1 trial will include patients with HRD-associated breast cancer and ovarian cancer, as well as a basket of other selected solid tumors. The breast cancer focus is on estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (Her2-), HRD+ tumors, which represent approximately 10% to 14% of breast cancer patients. The ovarian cancer focus represents approximately 50% of ovarian cancer cases where HRD is observed. IDEAYA is targeting clinical program updates for IDE161 in the second half of 2023.

IDE161 is a potent, selective, small-molecule inhibitor of PARG, a novel and mechanistically differentiated target in the same clinically validated pathway as poly (ADP-ribose) polymerase (PARP). IDEAYA presented a poster with preclinical data profiling IDE161 at the 2023 Annual Meeting of the American Association for Cancer Research (AACR) in April 2023. The IDE161 poster is available online on the company's website.

IDEAYA owns or controls all commercial rights in IDE161, subject to certain economic obligations under its exclusive, worldwide license with Cancer Research UK and University of Manchester.

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