IDEAYA Biosciences, Inc. (IDYA)
First Day Turnover
We are an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. Our approach integrates extensive capabilities in identifying and validating translational biomarkers with small molecule drug discovery to select patient populations most likely to benefit from the targeted therapies we are developing.
We are applying these capabilities across multiple classes of precision medicine, including direct targeting of oncogenic pathways and synthetic lethality – which represents an emerging class of precision medicine targets. We believe this diversified approach will enable us to deliver the right medicine to the right patient to drive a more robust clinical response.
Our most advanced product candidate is IDE196, a protein kinase C, or PKC, inhibitor for genetically-defined cancers having GNAQ or GNA11 gene mutations. We obtained an exclusive, worldwide license to IDE196 from Novartis International Pharmaceutical Ltd., or Novartis, with the right of reference to certain data from its ongoing Phase 1 clinical trial in metastatic uveal melanoma, a cancer of the eye with a high frequency of GNAQ or GNA11 gene mutations, pursuant to which we may rely on and incorporate data previously submitted to the U.S. Food and Drug Administration, or FDA, by Novartis into our own regulatory submissions.
We have filed an Investigational New Drug Application or, IND, with the FDA and plan to broaden the potentially addressable patient population by initiating our own Phase 1/2 basket trial in the second or third quarter of 2019 to evaluate IDE196 in solid tumors harboring GNAQ or GNA11 mutations, including metastatic uveal melanoma, cutaneous melanoma, colorectal cancer, non-small cell lung cancer, or NSCLC, and pancreatic cancer, and potentially other mutations and gene fusions that activate the PKC signaling pathway.
Subject to completion of and satisfactory results from preclinical studies, we also plan to evaluate the safety and efficacy of IDE196, potentially in combination with an epidermal growth factor receptor or EGFR inhibitor, in a clinical trial in NSCLC patients with tumors resistant to an EGFR inhibitor mediated by PKC. Subject to the same conditions, we also plan to evaluate IDE196 in combination with one or more additional anti-cancer agent(s), such as an inhibitor of MEK, mTOR, FAK, and/or CDK4/6, in a Phase 1/2 clinical trial in patients with metastatic uveal melanoma.
Our pipeline in synthetic lethality comprises multiple preclinical programs against both known and novel targets. Synthetic lethality is an emerging field of oncology with significant potential, as evidenced by the success of PARP inhibitors, including the recent approvals of Zejula, Lynparza, Rubraca, and Talzenna across multiple oncology indications.
Synthetic lethality occurs between two genes when the loss of function of either gene alone does not affect cell viability, but the simultaneous loss of function of both genes leads to cancer cell death. Our pipeline applies synthetic lethality to targets beyond PARP, including MAT2A for solid tumors with MTAP deletions and Pol-theta for solid tumors with homologous recombination deficiency, or HRD, including BRCA mutations. The synthetic lethal relationship between each of these gene pairs has been established and we have observed single agent in vivo efficacy of a MAT2A inhibitor in a MTAP-null model. We are also pursuing programs against PARG in tumors with impaired base excision repair, or BER, and Werner helicase, or WRN, in tumors with high microsatellite instability, or MSI.
We expect to select a development candidate for a MAT2A inhibitor in the second half of 2019 and file an IND for such MAT2A inhibitor in the first half of 2020, and also expect to designate a product candidate for a second synthetic lethality program in the first half of 2020 and file an IND for such second program in synthetic lethality in the second half of 2020. We believe this class of precision medicine targets represents one of the most exciting, potentially impactful new areas of development in oncology, and we are investing a significant portion of our resources to be a leader in this emerging field.