IDEAYA Biosciences (IDYA) Study Update summary

Market Opportunity and Unmet Need

• Pre-metastatic uveal melanoma has a high unmet need with no FDA-approved systemic therapies in neoadjuvant or adjuvant settings.

• Annual incidence is about 12,000 patients in North America, Europe, and Australia, with total prevalence multiples higher due to untreated small tumors.

• Uveal melanoma is molecularly distinct from cutaneous melanoma, with ~95% of patients harboring GNAQ/GNA11 mutations driving PKC signaling.

• Standard treatments include enucleation and plaque brachytherapy, both associated with significant vision loss or eye removal.

• Darovasertib is positioned as a potential first-line standard of care for all uveal melanoma patients in the neoadjuvant setting.

Clinical Program, Trial Design, and Regulatory Guidance

• Darovasertib is being evaluated in both metastatic and primary uveal melanoma, with ongoing and planned trials covering all disease stages.

• The registrational phase 3 trial will randomize ~400 high-risk localized uveal melanoma patients to immediate local therapy or 6–12 months of neoadjuvant darovasertib, followed by definitive therapy.

• Primary endpoints: eye preservation (enucleation cohort) and time to vision loss (plaque brachytherapy cohort); secondary endpoints include event-free survival and safety.

• FDA agreed on eye preservation and time to vision loss as primary endpoints, with no detriment to event-free survival as a key secondary endpoint; ongoing discussions may allow ORR as a surrogate endpoint for earlier approval.

• 300mg BID darovasertib selected as the dose for the registrational trial, with interim analysis expected at two years.

Phase 2 Clinical Data and Efficacy

• In phase 2 trials, darovasertib showed ~82% of patients had ocular tumor shrinkage and ~61% eye preservation rate in enucleation patients.

• 49% of patients achieved ≥30% tumor reduction; tumor shrinkage correlated with eye and vision preservation.

• Median treatment duration was ~4 months, with 43% of patients still on therapy at data cut-off.

• Typical time to ≥30% tumor shrinkage was about two months; conversion from enucleation to eye-sparing therapy took about 5.5 months.

• Tumor shrinkage correlated with both enucleation sparing and radiation reduction.