Executive Summary / Key Takeaways

• Differentiated Precision Oncology Platform: IDEAYA Biosciences is a leader in synthetic lethality and Antibody-Drug Conjugate (ADC) development, leveraging proprietary AI/ML-enabled discovery platforms and biomarker-driven patient selection to target genetically defined cancers with first-in-class potential.
• Near-Term Clinical Catalysts: The company anticipates a cascade of significant clinical data readouts and regulatory milestones through year-end 2025 and into 2026, including pivotal data for darovasertib in uveal melanoma, initial combination data for IDE397, and Phase 1 efficacy for IDE849.
• Strategic Partnerships De-Risk Development: Extensive collaborations with industry giants like GSK (GSK), Pfizer (PFE), and Hengrui Pharma provide substantial non-dilutive funding, shared development costs, and access to expertise, significantly de-risking IDEAYA's R&D-intensive pipeline.
• Strong Financial Foundation: With approximately $991.9 million in cash, cash equivalents, and marketable securities as of June 30, 2025, IDEAYA boasts a robust balance sheet, projecting a cash runway into 2029, which is critical for funding its ambitious clinical programs.
• Competitive Edge in Safety and Specificity: Early clinical data for lead assets like IDE397 demonstrate a favorable safety profile and targeted pharmacodynamic modulation, offering a potential advantage over prior compounds in the same pathways and enhancing the therapeutic window for combination strategies.

The Precision Oncology Frontier: IDEAYA's Strategic Foundation

IDEAYA Biosciences is at the forefront of precision oncology, dedicated to discovering, developing, and commercializing transformative therapies for cancer patients. The company's core strategy centers on identifying and validating translational biomarkers to develop tailored, potentially first-in-class targeted therapies aligned to the genetic drivers of disease. This approach is particularly focused on synthetic lethality and Antibody-Drug Conjugates (ADCs) for molecularly defined solid tumor indications, representing a significant shift towards more effective and personalized cancer treatments.

The company's technological differentiation is a cornerstone of its strategy. IDEAYA leverages a sophisticated discovery platform, including the DECIPHER dual CRISPR library for synthetic lethality target and biomarker discovery, and the INQUIRE chemical library and HARMONY machine-learning engines to enhance its drug discovery capabilities. A recent collaboration with ATTMOS further accelerates AI/ML-enabled drug discovery, aiming to unlock what are currently perceived as "undruggable oncology targets." This blend of advanced computational methods and biological expertise provides IDEAYA with a competitive edge in identifying novel targets and developing highly specific compounds.

In the broader competitive landscape, IDEAYA operates as a nimble innovator, challenging larger pharmaceutical companies like GlaxoSmithKline, Pfizer Inc. , Merck & Co., Inc. (MRK), and AstraZeneca plc (AZN). While these industry giants possess vast resources, diversified portfolios, and established market presence, IDEAYA differentiates itself through its focused innovation and speed in emerging biomarker-driven therapies. The company's strategic partnerships are crucial in this context, providing access to resources and expertise that mitigate the disadvantages of its smaller scale. The market for precision oncology is expanding rapidly, driven by increasing understanding of cancer genetics and the demand for more effective, less toxic treatments, a trend IDEAYA is well-positioned to capitalize on.

A Pipeline Forged in Partnership and Innovation

IDEAYA's journey began in June 2015, quickly establishing its R&D focus. A pivotal early move was the September 2018 licensing of darovasertib (a PKC inhibitor) from Novartis (NVS), granting IDEAYA worldwide exclusive rights for GNAQ/GNA11 mutant cancers. This laid the groundwork for its lead program. The company significantly expanded its pipeline and strategic collaborations starting in 2020, notably with a $100 million upfront payment from GSK for synthetic lethality programs (MAT2A, Pol Theta, Werner Helicase) and a Clinical Trial Collaboration with Pfizer for darovasertib combinations. These foundational partnerships have been instrumental in shaping IDEAYA's current multi-asset pipeline.

The company's clinical pipeline currently consists of six potential first-in-class product candidates, each addressing specific unmet medical needs:

Darovasertib: Leading the Charge in Uveal Melanoma

Darovasertib, a small molecule PKC inhibitor, is IDEAYA's most advanced program, targeting uveal melanoma (UM). This aggressive ocular cancer has a projected annual incidence of approximately 12,000 patients, representing a high unmet medical need with no FDA-approved systemic therapies for the neoadjuvant setting. The program achieved a significant milestone in March 2025, receiving U.S. FDA Breakthrough Therapy Designation (BTD) for neoadjuvant UM in patients recommended for enucleation, triggering a $1 million milestone payment to Novartis in April 2025.

The clinical development for darovasertib is progressing rapidly. The company expects to report median Progression-Free Survival (PFS) data from its potentially registrational Phase 2/3 trial in 1L HLA-A2-negative metastatic UM by year-end 2025, which could enable a U.S. accelerated approval filing. Additionally, median Overall Survival (OS) data from an ongoing single-arm Phase 2 trial in 1L metastatic UM is anticipated at a medical conference in Q4 2025. For neoadjuvant primary UM, initial safety and visual benefit data from over 20 plaque brachytherapy patients will be presented at IDEAYA's R&D Day on September 8, 2025, with updated data from over 90 patients (plaque brachytherapy and enucleation-eligible cohorts) at the European Society for Medical Oncology (ESMO) Conference in October 2025. A Phase 3 registrational trial, OptimUM-10, was initiated in Q3 2025, aiming to enroll approximately 520 patients across two cohorts, with clinical endpoints supportive of full approval, including eye preservation rate and visual acuity preservation. The expanded collaboration with Pfizer, which now supports a potential registration-enabling trial and explores darovasertib/crizotinib combinations in additional cMET-driven tumors (e.g., hepatocellular carcinoma, non-small cell lung cancer), underscores the broad potential of this asset. External clinical development expenses for darovasertib surged by 86.73% to $48.11 million for the six months ended June 30, 2025, reflecting the accelerated pace of these trials.

IDE397: A Differentiated Approach to MTAP-Deletion Cancers

IDE397, a small molecule inhibitor of methionine adenosyltransferase 2a (MAT2A), targets solid tumors with methylthioadenosine phosphorylase (MTAP) gene deletion, a genetic alteration found in approximately 26% of urothelial cancers. The mechanism of action for IDE397 involves a "one-two punch" that selectively disrupts essential pre-mRNA splicing in MTAP-deleted tumors by reducing cellular SAM, which PRMT5 needs to activate splicing factors. Preclinically, IDE397 has demonstrated robust suppression of tumor pharmacodynamics across multiple MTAP-deleted PDX models, including 100% reduction of tumor SDMA and up to 92% tumor growth inhibition.

Clinically, IDE397 has shown robust plasma pharmacodynamics across all cohorts and exposure-dependent tumor pharmacodynamics, with a 95% reduction of tumor SDMA observed in Cohort 5. Crucially, IDE397 has demonstrated a favorable human adverse event (AE) profile, with no serious adverse events and the maximum tolerated dose not yet reached. This profile "compares favorably to prior drugs targeting PRMT5 and MAT2A, which were limited by either hematologic or Lipitor toxicities," as noted by management. This superior risk-benefit profile positions IDE397 to potentially evaluate unique combinations and explore earlier lines of treatment. IDEAYA plans to present initial data from the combination with Trodelvy in MTAP-deletion urothelial cancer patients at its R&D Day on September 8, 2025, with additional data in H1 2026. The company is targeting mid-year 2022 to deliver the GSK option package for IDE397, which, if exercised, would trigger a $50 million option fee and an 80/20 cost-sharing model, along with potential development, regulatory, and sales milestones totaling up to $940 million. External clinical development expenses for IDE397 increased by 7.72% to $7.53 million for the six months ended June 30, 2025.

IDE849: Advancing a First-in-Class DLL3 ADC

IDE849, a potential first-in-class DLL3 TOP1i ADC, is being developed in collaboration with Hengrui Pharma. Clinical efficacy and safety data from over 70 small-cell lung cancer (SCLC) patients from Hengrui's ongoing Phase 1 trial will be presented at the IASLC 2025 World Conference on Lung Cancer in September 2025. IDEAYA initiated its own Phase 1 trial of IDE849 in SCLC in the U.S. in May 2025 and expects to begin dosing patients in neuroendocrine tumors (NETs) and other DLL3-expressing tumors by year-end 2025. The licensing agreement with Hengrui Pharma includes a $75 million upfront fee and potential milestone payments totaling up to $1.04 billion, alongside royalties on net sales outside Greater China, highlighting the significant value attributed to this asset.

Broader Pipeline and Preclinical Innovation

IDEAYA's pipeline extends to other promising synthetic lethality programs:

• IDE161 (PARG inhibitor): A potential first-in-class small molecule poly-ADP-ribose glycohydrolase (PARG) inhibitor, observed to have in vivo efficacy with enhanced tumor growth inhibition and/or regressions in multiple niraparib-resistant models. The company plans to initiate a Phase 1 combination trial of IDE849 and IDE161 by the end of 2025.
• IDE275GSK959 (Werner Helicase inhibitor): Developed with GSK, this potential first-in-class inhibitor is in Phase 1 for MSI-High solid tumors (prevalence of ~31% in endometrial, ~20% in colorectal, and ~19% in gastric cancers). It has demonstrated a potential best-in-class preclinical profile with a unique binding mode.
• IDE705GSK101 (Pol Theta Helicase inhibitor): Also partnered with GSK, this potential first-in-class inhibitor is in Phase 1 in combination with niraparib for BRCA or HRD-positive tumors. A Phase 2 expansion in HRD-positive solid tumors would trigger a $10 million milestone payment from GSK.

Beyond these clinical assets, IDEAYA is advancing three preclinical programs towards IND submissions by year-end 2025: IDE892 (MTA-cooperative PRMT5 inhibitor), IDE034 (B7H3/PTK7 bispecific TOP1i ADC), and IDE574 (KAT6/7 dual inhibitor). These programs underscore IDEAYA's commitment to continuous innovation and pipeline expansion, fueled by its robust discovery platform.

Financial Trajectory: Fueling Growth and Managing Risk

IDEAYA Biosciences, like many early-stage biotechnology companies, has incurred significant operating losses and negative cash flows since its inception, accumulating an accumulated deficit of $772.5 million as of June 30, 2025. The company has not generated any revenue from commercial products, with its revenue consisting exclusively of collaboration payments, such as the upfront payment from GSK which was fully recognized by December 31, 2023. Future revenue from collaborations will be contingent on achieving additional milestones, profit sharing, and royalties.

The company's investment in its pipeline is evident in its escalating research and development (R&D) expenses, which increased by 49% to $145.11 million for the six months ended June 30, 2025, compared to $97.34 million in the prior year period. This rise was primarily driven by a $37.4 million increase in fees paid to CROs, CMOs, and consultants to advance lead product candidates, alongside higher personnel-related expenses and laboratory costs.

General and administrative (G&A) expenses also saw a 51% increase to $28.08 million for the same period, reflecting increased personnel and professional fees associated with supporting growth and public company operations.

Despite these substantial R&D investments, IDEAYA maintains a strong liquidity position. As of June 30, 2025, the company held approximately $991.9 million in cash, cash equivalents, and marketable securities. This robust cash balance, bolstered by an at-the-market (ATM) offering program and a significant public follow-on offering in July 2024 that generated $283.8 million in net proceeds, is projected to fund planned operations into 2029. This extended cash runway is a critical asset, providing the financial flexibility necessary to advance multiple clinical programs and pursue regulatory approvals without immediate reliance on further dilutive financing.

Outlook and Catalysts: A Transformative Horizon

IDEAYA stands on the cusp of a transformative period, with numerous clinical and regulatory catalysts anticipated in the near to medium term. The company's R&D Day on September 8, 2025, is expected to be a key event, featuring initial safety and visual benefit data from over 20 plaque brachytherapy patients in the Phase 2 neoadjuvant UM trial, and initial combination data for IDE397 and Trodelvy in MTAP-deletion urothelial cancer.

Further significant data readouts include:

• September 2025: Clinical efficacy and safety data from over 70 SCLC patients treated with IDE849 (DLL3 TOP1i ADC) from partner Hengrui Pharma's Phase 1 trial at the IASLC 2025 World Conference on Lung Cancer.
• Q4 2025: Updated Phase 2 neoadjuvant UM data from over 90 patients (plaque brachytherapy and enucleation-eligible cohorts) at ESMO, and median Overall Survival (OS) data from the single-arm Phase 2 trial of darovasertib and crizotinib in 1L metastatic UM.
• Year-end 2025: Median Progression-Free Survival (PFS) data from the Phase 2/3 trial of darovasertib and crizotinib in 1L HLA-A2-negative metastatic UM, with potential to enable a U.S. accelerated approval filing. Initiation of a Phase 1 combination trial of IDE849 and IDE161, and dosing patients in NETs and other DLL3 expressing tumors in the U.S. for IDE849.
• H1 2026: Additional data from the IDE397 and Trodelvy combination in MTAP-deletion UC patients.

Beyond these clinical readouts, IDEAYA is targeting three Investigational New Drug (IND) submissions by year-end 2025 for its preclinical programs: IDE892 (PRMT5 inhibitor), IDE034 (B7H3/PTK7 bispecific TOP1i ADC), and IDE574 (KAT6/7 dual inhibitor). The potential for a $10 million milestone payment from GSK upon Phase 2 expansion for IDE705GSK101 in HRD-positive solid tumors further highlights the near-term value drivers. Management's strategic decision to potentially initiate IDE397 monotherapy expansion at Cohort 6, while continuing dose escalation, demonstrates a pragmatic approach to accelerating development while thoroughly characterizing the drug's profile.

Risks and Competitive Headwinds

Despite its promising pipeline and strong financial position, IDEAYA faces inherent risks common to early-stage biotechnology companies. The company's success is heavily dependent on the successful completion of extensive preclinical studies and clinical trials, obtaining regulatory approvals, and eventual commercialization of its product candidates. There is no guarantee that any of its product candidates will receive the necessary approvals or prove commercially viable. The R&D-intensive nature of its business means that delays in clinical trials or unforeseen expenses could significantly impact its financial trajectory.

Competition in the oncology space is substantial, with larger pharmaceutical companies possessing greater financial, technical, and human resources. While IDEAYA's focus on precision medicine and synthetic lethality offers differentiation, the ability of larger rivals to scale development, navigate regulatory pathways, and commercialize therapies could pose challenges. For instance, while IDEAYA's IDE397 shows a favorable safety profile compared to prior MAT2A/PRMT5 inhibitors, the broader market includes numerous established and emerging therapies. The company's reliance on strategic partnerships, while a strength, also introduces a degree of dependence on collaborators' priorities and resources. Furthermore, external macroeconomic factors and shifts in regulatory policies, as seen with past impacts on the biopharma sector, could affect IDEAYA's operational costs and timelines.

Conclusion

IDEAYA Biosciences presents a compelling investment narrative, rooted in its innovative precision oncology platform and a robust pipeline of biomarker-driven therapies. The company's strategic emphasis on synthetic lethality and ADCs, coupled with its advanced AI/ML-enabled discovery capabilities, positions it as a significant player in the evolving cancer treatment landscape. The strong network of strategic partnerships with industry leaders like GSK and Pfizer not only validates its scientific approach but also provides crucial funding and expertise, effectively de-risking the capital-intensive drug development process.

With a substantial cash runway extending into 2029 and a series of high-impact clinical catalysts anticipated through year-end 2025 and into 2026, IDEAYA is poised for significant value inflection. The favorable safety and efficacy signals from lead assets like darovasertib and IDE397, particularly when compared to competitor profiles, underscore the potential for these therapies to address critical unmet medical needs. While the inherent risks of biotech development remain, IDEAYA's differentiated technology, strategic collaborations, and disciplined financial management provide a solid foundation for its ambitious mission to deliver transformative precision oncology therapies. Investors should closely monitor the upcoming data readouts and regulatory progress, as these will be key determinants of IDEAYA's long-term success and market positioning.