Pipeline

Precision Medicine Approach

IDEAYA is applying its capabilities and approach to a portfolio of targeted therapeutics for defined patient populations, including based on direct targeting of oncogenic pathways (DT), synthetic lethality (SL), and immuno-oncology (IO). For each program in our pipeline, we are discovering novel therapeutics and identifying biomarkers with an objective of enabling biomarker-driven clinical trials.

Our lead product candidate, IDE196, has shown clinical activity in metastatic uveal melanoma patients whose tumors harbor mutations in GNAQ or GNA11 that activate the PKC signaling pathway. Our pipeline in synthetic lethality comprises multiple preclinical small molecule therapeutics against known and novel targets for defined patient populations, including patients with tumors having MTAP gene deletion, and tumors with genetic mutations in homologous recombination deficiency (HRD), including BRCA mutations, or base excision repair (BER), and tumors having high microsatellite instability (MSI). Our product candidate IDE697 targets AhR, which antagonizes a known pathway of immuno-suppression in the tumor microenvironment that we are pursuing with a clinical biomarker strategy.

For many of our programs, a diagnostic is commercially available, for example, on a tumor-profiling panel. In some cases, we coordinate or support development of a diagnostic with selected partners.

IDEAYA Precision Medicine Approach

Precision Medicine Pipeline

Our clinical stage precision medicine pipeline contains product candidates in distinct classes of biomarker-enabled targeted therapies, including direct targeting of oncogenic pathways (DT), synthetic lethality (SL), and immuno-oncology (IO). This pipeline is supplemented by a proprietary target discovery platform, including our Dual CRISPR combinatorial approach for evaluating potential synthetic lethality relationships between potential drug targets and tumor suppressor genes, or TSG.

We are developing IDE196, a protein kinase C (PKC) inhibitor, for the treatment of cancers with GNAQ and GNA11 mutations. This targeted therapeutic is a potent and selective small molecule inhibitor of PKC. IDE196 is demonstrating early clinical activity and tolerability in an ongoing Phase 1 clinical study being conducted by Novartis in patients with metastatic uveal melanoma (MUM). In the ongoing trial, IDE196 is being studied as a single-agent and in combination therapy with HDM201, Novartis’ human double minute 2 (HDM2) inhibitor, an important negative regulator of the p53 tumor suppressor. We are also planning to evaluate IDE196 in a broader patient population in a basket trial in multiple solid tumor types which have GNAQ or GNA11 mutations or PKC gene fusions.

Our pipeline in synthetic lethality comprises multiple preclinical small molecule therapeutics against known and novel targets for defined patient populations having a prevalence of over 10% in certain solid tumors, including for example patients with tumors having MTAP gene deletion, and tumors with genetic mutations in homologous recombination deficiency (HRD), including BRCA mutations, or base excision repair (BER), and tumors having high microsatellite instability (MSI).

IDEAYA is also developing an aryl hydrocarbon receptor (AhR) antagonist for treatment of various solid tumors. Our development candidate, IDE697, is a highly potent and selective small-molecule antagonist of AhR. In vivo, IDE697 demonstrates tumor growth inhibition in mouse models. The compound inhibits activation of its target AhR receptor by endogenous and exogenous ligands in-vitro and in-vivo. In ex-vivo human cell cultures, IDE697 demonstrates an immune response profile evidencing a mode of action consistent with the mechanistic understanding of this immune suppression pathway – including increase in tumor infiltrated activated CD8 T-cells, and inhibition of Treg cell and M2 macrophage cell suppressive activities.