Breakthrough Clinical Results
IDEAYA Biosciences, Inc. announced the agenda for its 10-year anniversary R&D Day on September 8, 2025. The event will feature presentations on the company's progress, including new clinical data on darovasertib in neoadjuvant uveal melanoma, IDE849 (DLL3 TOP1 ADC), and IDE397 (MAT2A). Key areas of future growth strategy will also be outlined. Presentations will cover Phase 2 data for darovasertib, Phase 1 data for IDE849, mechanistic data supporting combinations of TOP1-ADCs with IDE161/PARG, and initial Phase 1 data from the IDE397/Trodelvy combination. Dr. Arun D. Singh will present data from IDEAYA's Phase 2 trial of darovasertib and discuss the Phase 3 OptimUM-10 trial.
Key Highlights
- Presentation of new clinical data on darovasertib in neoadjuvant uveal melanoma
- Presentation of data on IDE849 (DLL3 TOP1 ADC) and IDE397 (MAT2A)
- Outline of key areas of focus for future growth strategy
- Live Q&A session with IDEAYA's leadership team and Dr. Arun D. Singh
Incidence and Prevalence
Global Incidence and Prevalence of Uveal Melanoma
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, despite comprising less than 5% of all melanomas. This rare disease has significant mortality implications, with approximately 50% of patients developing metastatic disease, predominantly in the liver, and those with metastatic disease having a median survival of less than one year.
Incidence Rates
The mean age-adjusted incidence of uveal melanoma in the United States was 5.1 per million (95% CI 4.2-6.1) according to data from 1973-2012. This represents a slight increase from the 4.3 per million (4.1-4.5; 95% CI) reported over the 25-year period from 1973 to 1997.
Gender disparities are evident in the incidence rates, with higher rates in males (5.9, CI=4.4-7.6) compared to females (4.5, CI=3.3-5.8), P<0.001. This gender difference was also observed in earlier data (males: 4.9 [4.6-5.2] 95% CI; females: 3.7 [3.5-3.9] 95% CI).
Racial and Ethnic Distribution
Uveal melanoma occurs most commonly among Caucasians (94.7%), with most cases (97.8%) reported in the white population. The annual age-adjusted incidence (per million population) shows significant racial disparities: - 0.31 for black individuals - 0.38 for Asian individuals - 1.67 for Hispanic individuals - 6.02 for non-Hispanic white individuals
The relative risk compared to black patients was: - 1.2 for Asian and Pacific Islander patients - 5.4 for Hispanic patients - 19.2 for non-Hispanic white patients
When combining non-Hispanic white and Hispanic populations, the overall white:black ratio was 18:1.
Geographic Distribution
In the United States, 52.3% of cases were reported in the Western US, with 35.7% in California alone. However, earlier studies found no significant variation of incidence by geographic location within the US.
The mean age-adjusted incidence in the US is similar to that reported from European countries, suggesting some consistency across Western nations.
In Malaysia, there is an increasing number of cases of choroidal melanoma (a subtype of uveal melanoma). A 2022 Malaysian study identified eight cases with a median age of 65 years, predominantly in females (six females, two males) and among Malay ethnicity (five Malay, three Chinese).
Survival Rates
The 5-year cancer-specific survival rate for uveal melanoma patients was 76%±5.3%, while the overall 5-year relative survival rate was 79.8%±5.8%. The mean 5-year cancer-specific survival rate remained stable during the study period between 1973 and 2012.
Metastasis occurs in 28% of patients treated with plaque radiotherapy by 5 years. Among patients who underwent enucleation, those with low nuclear BAP1 expression had significantly higher rates of metastasis (68%) compared to those with high nuclear expression (9%).
Uveal melanoma is considered a rare disease with 90% of affected patients dying within 15 years.
Emerging Mechanism of Action
Emerging Mechanisms of Action in Uveal Melanoma
Genetic Drivers and Signaling Pathways
Recent research has identified several critical genetic factors in uveal melanoma (UM). GNAQ and GNA11 mutations, present in over 90% of UM patients, serve as oncogenic drivers and indicators for circulating tumor DNA (ctDNA). These mutations activate important signaling pathways including phospholipase C and the transcription factor YAP. BAP1 mutations, particularly germline BAP1 mutations, are associated with bilateral UM and should prompt evaluation in patients with family history of cancer.
Novel Therapeutic Targets
Aurora kinase B (AURKB) plays a significant oncogenic role in UM, with overexpression resulting in poor prognosis. The AURKB-specific inhibitor, hesperadin, has shown promising efficiency both in vitro and in vivo. Mechanistically, it compromises phosphorylation of histone H3 and promotes chromatin condensation, epigenetically silencing the expression of oncogenic telomerase reverse transcriptase.
MSK1 (Mitogen- and stress-activated protein kinase 1) is strongly up-regulated in UM tissues and promotes proliferation and metastasis through phosphorylation of CREB at Ser133 residues. In vivo experiments confirmed that tumors grew more slowly with MSK1 inhibition, making it a promising therapeutic candidate.
Researchers have developed imidazopiperazine derivatives as Gαq/11 inhibitors, with GQ262 showing improved inhibitory activity and favorable pharmacokinetics. GQ262 efficiently blocked UM cell proliferation and migration while inducing apoptosis by directly targeting Gαq/11.
Metabolism-Related Mechanisms
Three metabolism-related genes have been identified as prognostic factors: Carbonic anhydrase 12, Acyl-CoA synthetase long-chain family member 3, and Synaptojanin 2. A novel metabolism-based prognostic model accurately predicts UM prognosis.
Immunotherapy Approaches
Immune checkpoint inhibitors (ICIs) have demonstrated lower response rates in UM compared to cutaneous melanoma. However, Tebentafusp, a novel bispecific immune mobilizing T cell receptor (TCR)-based agent, has shown improved overall survival compared to standard care in a phase III trial and is expected to become the standard first-line treatment for metastatic UM.
Diagnostic and Prognostic Approaches
Circulating cell-free plasma DNA analysis shows promise as a noninvasive approach for prognostic testing. ctDNA was detected in 31% of patients during brachytherapy, with the variant allele fraction correlating with tumor size. The endo-lysosomal system affects melanoma progression, with UM cells showing higher receptor-mediated endocytic trafficking associated with caveolae than normal choroidal melanocytes.
Angiogenesis and Immune Profiles
Angiogenesis and vasculogenic mimicry play important roles in UM tumors. Combining immune strategies with drugs targeting angiogenesis offers a new therapeutic paradigm. UM liver metastases preserve the genomic and immune characteristics of primary UM but show lower infiltration of several immune cells and a greater proportion of M2 macrophages. Longer median overall survival was observed in metastatic UM patients with higher expression of LAG3, HLA class I, or HLA class II.
Drug used in other indications
Darovasertib Clinical Trials Beyond Uveal Melanoma
Based on the comprehensive review of available information, there is no evidence that darovasertib is currently being trialed for any indications other than uveal melanoma.
Darovasertib, also known as IDE196 or LXS196, is characterized as a first-in-class oral, small molecular inhibitor of protein kinase C (PKC). In 2022, specifically on May 2, 2022, this compound received orphan drug designation specifically for the treatment of uveal melanoma.
The available data only mentions darovasertib's development and clinical investigation in the context of uveal melanoma treatment. The compound has demonstrated effectiveness in inhibiting both conventional and novel PKC proteins, and research has explored its combination with MEK inhibitors specifically for uveal melanoma patients.
There is one documented intervention model mentioned in the context - the use of darovasertib as a neoadjuvant treatment for uveal melanoma in combination with crizotinib. However, no information is available regarding intervention models for trials in other indications, as there is no evidence that such trials exist.
The mechanism of action of darovasertib as a PKC inhibitor appears to be particularly relevant to uveal melanoma, which is often characterized by GNAQ/GNA11 mutations. No information is provided about its potential application to other disease states or cancer types based on this mechanism.
In summary, according to the available information, darovasertib's clinical development remains focused exclusively on uveal melanoma with no documented expansion into other oncological or non-oncological indications.