IDEAYA Biosciences

1.1 History & Prior Art

IDEAYA’s pipeline rests on a group of small‑molecule and ADC programs targeting defined genetic vulnerabilities.

Darovasertib (IDE196, PKC inhibitor): The compound was first described in the public domain through a Phase 1/2 basket study (NCT03947385) submitted to ClinicalTrials.gov on 9 May 2019 with the first patient dosed 28 Jun 2019 [C3740‑C3744][T1]. The sponsor from inception was IDEAYA Biosciences [C3733‑C3734][T1]. No prior‑owner transfer appears in the publicly verifiable record; IDEAYA has retained US rights and licensed ex‑US rights to Servier in August 2025 [C727‑C728][T1].

IDE397 (MAT2A inhibitor): The Phase 1 trial (NCT04794699) was first submitted 9 Mar 2021 [C4162][T1]. The target, MAT2A, was previously pursued by Servier with AG‑270 (S095033), a MAT2A inhibitor whose Phase 1 monotherapy/chemotherapy combination study (NCT03435250) started in March 2018 and was terminated in April 2023 for “strategic reasons” [C1633‑C1637][T1]. IDE397 therefore enters a field where a first‑generation molecule showed insufficient activity to warrant continuation. However, the competitive landscape has since evolved: Servier has advanced a second‑generation MAT2A inhibitor, S095035, now in a Phase 1/2 trial (NCT06188702) as monotherapy and in combination with the PRMT5 inhibitor TNG462, with estimated primary completion 2031 [C6401‑C6413][T1]. This places IDE397 in direct competition with a Servier‑owned molecule that could be deployed as a partner or rival, depending on how the two companies structure their relationship. A further compound from InSilico Medicine (ISM3412) (described by the company as a MAT2A inhibitor, but this target class could not be independently confirmed — C7498 is UNFOUND) has also entered Phase 1 (NCT06414460, recruiting) [C7477‑C7492][T1], adding to the crowdedness of the MTAP‑deletion space.

IDE161 (PARG inhibitor): The first‑in‑human study (NCT05787587) was submitted 17 Mar 2023 [C5331][T1]. The compound is described as “a potential first‑in‑class, oral small molecule poly (ADP‑ribose) glycohydrolase (PARG) inhibitor” [C120] (company characterization; no independent external source confirmed first-in-class status in the verified record—C120 verdict is UNFOUND). No prior PARG inhibitor from any company has entered late‑stage development in the verified record, but two new PARG inhibitors have entered Phase 1 and are now in clinical trials: ETX‑19477 (858 Therapeutics, NCT06395519, recruiting) [C7327][T1], DAT‑2645 (Danatlas Pharmaceuticals, NCT06614751, not yet recruiting as of Sep 2024) [C8065][T1], and most recently XNW29016 (Evopoint Biosciences) and SYN608 (SynRx Therapeutics) — see §X for details. IDE161 retains a time‑to‑market advantage, but the appearance of multiple clinical‑stage PARG inhibitors demonstrates that the target is attracting competitive attention.

IDE849 (DLL3‑TOP1 ADC): This asset originated through a co‑development with Jiangsu Hengrui Pharmaceuticals and is designated SHR‑4849 [C758‑C759, C845][T1]. The first public clinical data appeared at WCLC in September 2025 [C758]. DLL3‑targeting has been attempted by others (e.g., rovalpituzumab tesirine, terminated after Phase 3 failure in small‑cell lung cancer), but a DLL3 TOP1 ADC with the early signal seen here has no direct precedent. A Phase 1/2 trial (NCT07174583, IDE849‑001) has been recruiting since October 2025, evaluating IDE849 alone and in combination with durvalumab or IDE161 in DLL3‑expressing tumors [C12534‑C12544, C12580‑C12585][T1]; this confirms the internal combination strategy with a PARG inhibitor is now in clinical execution.

Werner Helicase (WRN) program: The company has also been a collaborator on GSK’s oral WRN inhibitor GSK4418959 in the Phase 1/2 SYLVER trial (NCT06710847), which completed enrollment of 14 participants as a dose‑escalation monotherapy step and is now active but not recruiting [C8300‑C8359][T1]. This program is distinct from the previously disclosed IDE275, and the collaboration with GSK confirms an active co-development relationship around WRN — a synthetic-lethality target in dMMR/MSI‑H tumors distinct from the MTAP-deletion axis.

Kill question for this section: A finding that IDE161 or IDE397 is structurally identical to a previously failed compound (e.g., that IDE397 is simply a rebranded AG‑270) would eliminate the differentiation thesis. No verified claim supports such identity; AG‑270 is explicitly a Servier compound, not IDEAYA’s, and the trial records are distinct.

1.2 Differentiation

• IDE161: No approved PARG inhibitor exists. The trial is recruiting patients with BRCA1/2 mutations and other homologous‑recombination defects, a population adjacent to but distinct from PARP‑inhibitor‑treated cohorts [C5342][T1]. The oral route and the absence of a known PARG‑class safety liability are the material differentiators. Four competitors are following, but all are early‑stage.
• Darovasertib: The claim that darovasertib is a “potent and selective protein kinase C (PKC) inhibitor” [C804][T1] is backed by clinical activity exclusively in GNAQ/11‑mutant and PRKC‑fusion tumours, a genetically defined niche where no other PKC inhibitor has demonstrated a randomised survival benefit.
• IDE397: As a MAT2A inhibitor, IDE397 competes directly with the terminated AG‑270, but also with the new S095035 (Servier), ISM3412 (InSilico; target class unconfirmed), and the newest entrant GS‑5319 (Gilead, Phase 1, target undisclosed but for MTAP‑deleted tumors [C12459‑C12494][T1]). The company has not publicly released head‑to‑head potency data. Differentiation rests on clinical execution — IDE397 is advancing into a randomised registrational combination with Trodelvy, while AG‑270 was stopped at Phase 1 and competitors are still in dose‑finding or earlier.
• IDE849: labelled “potential first‑in‑class DLL3 TOP1 ADC” [C759][T1]. IDE849’s 73.2 % overall ORR (47.9 % confirmed) in second‑line SCLC at doses ≥2.4 mg/kg (discussed in §III) widens the gap versus prior DLL3‑targeted agents that showed modest or no activity. The Phase 1/2 trial (NCT07174583) combining IDE849 with durvalumab and IDE161, recruiting since October 2025, extends that differentiation into combinations.
• WRN program: GSK4418959 is not owned by IDEAYA, but the collaboration gives the company exposure to a novel synthetic‑lethality target (WRN) that is orthogonal to the MTAP‑deletion opportunity.

No verified claim establishes clear structural superiority over prior art at the molecular level for any asset; differentiation is based on clinical data and target novelty.

2.1 Target Biology

Darovasertib – PKC: Constitutive activation of the Gαq signalling cascade through mutually exclusive GNAQ or GNA11 mutations occurs in ~85–95% of uveal melanomas (literature estimate — not in verified claim set). The company’s trial NCT03947385 explicitly recruits “patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions” [C3759][T1], establishing the mechanistic link between the genetic driver and the drug target.

IDE397 – MAT2A: Methylthioadenosine phosphorylase (MTAP) is frequently co‑deleted with the tumour‑suppressor CDKN2A on chromosome 9p21. Loss of MTAP creates a synthetic‑lethal dependency on the methionine salvage enzyme MAT2A. The company cites MTAP‑deletion prevalence of ~25‑30 % in urothelial cancer and ~15‑20 % in NSCLC [C825‑C826][T2], and notes “there are currently no therapies approved … for patients with MTAP‑deletion solid tumors” [C827][T1]. IDE397, a small‑molecule MAT2A inhibitor [C823][T1], exploits this dependency. Multiple industry entrants (Servier’s S095035, InSilico’s ISM3412 (claimed MAT2A inhibitor, unconfirmed), Gilead’s GS‑5319) are developing alternative MAT2A or MAT2A/PRMT5 inhibitors, and several PRMT5 inhibitors (anvumetostat, MRTX1719/BMS‑986504, TNG462, TNG456, etc.) target the same synthetic‑lethal relationship from a different node, as detailed in §X.

IDE161 – PARG: Poly(ADP‑ribose) glycohydrolase (PARG) counterbalances PARP activity. IDE161 is trialled in patients “harboring BRCA1/2 loss‑of‑function alterations and/or other defects in the homologous recombination (HR) pathway” [C5342][T1]. This pivots on synthetic lethality analogous to PARP inhibitors, but PARG inhibition may evade PARP‑resistance mechanisms.

IDE849 – DLL3 TOP1 ADC: DLL3 is a Notch‑pathway ligand that is upregulated in neuroendocrine tumours and shows “limited extracellular expression in normal tissues” [C1069][T3]. The ADC delivers a topoisomerase‑1 inhibitor warhead; the company describes it as “potential first‑in‑class” [C759][T1].

2.2 Validation Layers

• Human genetics: MTAP deletion is an established tumour‑specific genetic lesion, confirmed by the inclusion criteria of multiple independent trials (e.g., IDE397 NCT04794699 requires “evidence of homozygous loss of MTAP” [C4221][T1]; Amgen’s anvumetostat study NCT05094336 requires “MTAP‑null” [C4383][T1]; Mirati’s MRTX1719 trial NCT05245500 requires “homozygous deletion of the MTAP gene” [C4619][T1]; Gilead’s GS‑5319 trial NCT07128303 mandates MTAP‑deficient tumors [C12503][T1]). New entrants (S095035, ISM3412, TNG456, GS‑5319) also require MTAP deletion, reinforcing cross‑sponsor validation.
• Pharmacologic: The IDE397 trial measures pharmacodynamic biomarkers (SAM and methionine) and plans SDMA assessment [C4980, C5085][T2] as direct readouts of target engagement.
• Clinical: Responses to IDE849 in SCLC (ORR 73 % all‑lines at ≥2.4 mg/kg, see §III) provide strong clinical proof of concept for DLL3 targeting with this modality. For darovasertib, the Phase 2/3 randomised OptimUM‑02 trial met its primary PFS endpoint with a HR of 0.42 (p<0.0001) [C1102][T1], linking PKC inhibition to hard survival‑proxy outcomes.

2.3 Target Validation Score

No numerical composite score can be derived from the provided claims alone, because the dataset lacks independent druggability/safety‑database entries (e.g., FAERS, ChEMBL). Qualitatively, the target validation is:

• Darovasertib: Strong — human genetics, consistent clinical activity, randomised Phase 2/3 positive.
• IDE397: Strong — synthetic‑lethal rationale with clear genetic dependency (MTAP deletion), pharmacodynamic markers in use, multiple industry entrants validating the target class.
• IDE161: Moderate — synthetic‑lethal rationale in HR‑deficient tumours, but no peer‑reviewed pharmacology or genetic‑knockout data in the verified claims. Two new PARG inhibitors have entered Phase 1, and the field has expanded further with XNW29016 (Evopoint Biosciences) and SYN608 (SynRx), both now with trials registered, increasing competition but confirming class interest.
• IDE849: Strong — tumour‑selective target expression [C1069], objective responses in heavily pre‑treated patients, but limited normal‑tissue expression data is company‑supplied.

The single result that would end the thesis for IDE397 is a well‑powered randomised trial showing no PFS/OS benefit over standard‑of‑care, but that trial has not yet read out. For IDE849, a plausible fatal finding is a safety signal of grade 3+ interstitial lung disease higher than the 7 % already reported, given the small numbers. No verified result on file would close any of these questions today.

3.1 Data Summary

IDE849 (DLL3‑TOP1 ADC) — Phase 1, WCLC 2025:

• 100 patients, doses 0.8‑4.2 mg/kg, every 3 weeks [C760‑C762].
• 87 SCLC, 13 other neuroendocrine carcinomas [C764‑C765]; all progressed after front‑line therapy; 33 % after ≥2 prior lines, 15 % after ≥3 [C766‑C768]; 72 % had prior immunotherapy [C769].
• At doses ≥2.4 mg/kg (n=71 efficacy‑evaluable): confirmed ORR 47.9 % (34/71), overall ORR (including unconfirmed) 73.2 % (52/71), DCR 93.0 % [C782, C778, C789][T1]. In 2L patients: confirmed ORR 60.0 % (21/35) [C781][T1].
• Median PFS 6.7 months across all lines; median follow‑up 3.5 months [C792‑C794][T1].
• Safety: grade ≥3 TRAEs 48 % (48/100); serious TRAEs 16 % (16/100); dose reduction 15 %; discontinuation due to TRAEs 2 % [C795‑C798][T1]. Interstitial lung disease reported in 7 % (7/100) [C802][T1]. No treatment‑related deaths [C799].

Update: A company‑sponsored Phase 1/2 trial (NCT07174583, IDE849‑001) has been recruiting since October 2025. It is evaluating IDE849 as monotherapy and in combination with durvalumab or IDE161 in DLL3‑expressing tumors (SCLC, NEC, other solid tumors). The trial includes dose‑escalation (Part 1A monotherapy, Part 1B combination) and expansion (Part 2). Estimated enrollment is 208 participants; estimated primary completion is May 2029 [C12535‑C12544, C12579, C12580‑C12585][T1]. This study will generate the data for the IDE849+IDE161 combination and the planned durvalumab collaboration, with initial safety readouts expected before the formal expansion data.

Darovasertib + Crizotinib (optimUM‑01) — 1L mUM, SMR 2025:

• 44 patients, median follow‑up 25 months, cut‑off 28 May 2025 [C861‑C863][T1].
• Median OS 21.1 months; median PFS 7.0 months [C864‑C865][T1].
• In 41 efficacy‑evaluable: confirmed ORR 34 % (14/41); median DOR 9.0 months; DCR 90 % (37/41); 85 % any tumour reduction [C866‑C869][T1]. Historical OS in treatment‑naïve mUM ~12 months [C874][T1].

Darovasertib Neoadjuvant — Phase 2 optimUM‑09 (ESMO 2025):

• 95 patients: 56 enucleation (Cohort 1), 39 plaque brachytherapy (Cohort 2); cut‑off 13 Jun 2025 [C882][T1].
• 83 % any tumour shrinkage; 54 % ≥20 % shrinkage [C887‑C888][T1].
• Eye preservation rate in Cohort 1: 57.1 % (24/42); among those with ≥20 % shrinkage, eye preservation jumped to 95 % [C892, C894][T1].
• Visual acuity improvement in 54.7 % (Cohort 1) and 60.5 % (Cohort 2); mean letter gains 17 and 10 letters, respectively [C897‑C900][T1].
• 64.9 % had reduced predicted 3‑year risk of vision loss per a Cleveland Clinic tool [C896][T1].
• Grade ≥3 TRAEs 16.8 % (16/95); treatment‑related SAEs 5.3 %; discontinuation due to AEs 6.3 % [C903‑C904][T1].

Darovasertib Neoadjuvant — Phase 3 optimUM‑10 registrational trial:
The pivotal Phase 3, randomised, open‑label study (NCT07015190) is now recruiting and will enroll an estimated 520 subjects with primary non‑metastatic uveal melanoma. Cohort 1 will compare neoadjuvant darovasertib followed by plaque brachytherapy vs. immediate plaque brachytherapy, with the primary endpoint of vision loss (≥15‑letter BCVA loss) over approximately 3 years. Cohort 2 will compare neoadjuvant darovasertib followed by definitive local therapy vs. immediate enucleation, with the primary endpoint of eye preservation rate over approximately 2 years [C10270‑C10338][T1]. This trial complements the Phase 2 optimUM‑09 data and, together with optimUM‑02, completes a three‑registrational‑trial strategy across all stages of uveal melanoma.

IDE397 + Trodelvy — Phase 1 (R&D Day 2025; company describes as Phase 1/2 but NCT04794699 is registered as Phase 1):

• 19 patients with late‑line MTAP‑deleted urothelial cancer; 16 efficacy‑evaluable [C830‑C831].
• Dose Level 1 (IDE397 30 mg): ORR 33 % (3 cPR), DCR 100 % [C835‑C836]; Dose Level 2: ORR 57 % (3 cPR+1 uPR), DCR 71 % [C837‑C838].
• No treatment‑related SAEs at the 30 mg dose [C842]; median PFS not reached [C841].

Darovasertib + Crizotinib — optimUM‑02 Randomised Phase 2/3 (2026):

• 313 patients enrolled in the Phase 2b/3 portion; cut‑off 23 Jan 2026; 159 PFS events [C1094‑C1095].
• Primary endpoint: PFS by BICR. HR = 0.42 (95 % CI 0.30‑0.59, p<0.0001) — 58 % reduction in risk of progression [C1102][T1].
• Median PFS: 6.9 months (darovasertib combo) vs 3.1 months (investigator‑choice therapy) [C1103][T1].
• ORR: 37.1 % vs 5.8 % (p<0.0001); 5 complete responses in the combo arm vs 0 in ICT [C1104‑C1105].
• Median DOR 6.8 months; OS data immature but “early trend in improvement” [C1106‑C1108].
• The ICT arm was 76 % ipilimumab+nivolumab, 24 % pembrolizumab, representing a well-powered standard‑of‑care comparator [C1099‑C1100].
• Company targets NDA submission in H2 2026 [C1112].

3.2 Competitor PARG Trials in Context

• ETX‑19477 (858 Therapeutics): Phase 1 dose escalation/expansion (NCT06395519) started May 2024, estimated enrollment 120, primary completion Dec 2026 [C7336‑C7337][T1]. The trial is recruiting [C7334].
• DAT‑2645 (Danatlas Pharmaceuticals): Phase 1 trial (NCT06614751) was filed Sep 2024 and remains not yet recruiting as of Sep 2024 [C8079][T1]. Estimated enrollment 112, primary completion Nov 2026 [C8081‑C8082][T1].
• XNW29016 (Evopoint Biosciences): A new PARG inhibitor Phase 1/2 trial (NCT06987500) started in April 2025 and is now recruiting; estimated enrollment 132, primary completion Feb 2027 [C10170, C10172, C10207, C10178][T1].
• SYN608 (SynRx Therapeutics): A Phase 1 PARG inhibitor study (NCT07088588) is not yet recruiting as of July 2025; estimated enrollment 105, estimated start July 2025, primary completion July 2028 [C12368, C12371, C12405, C12376‑C12377][T1]. Location details and full eligibility criteria have been posted, confirming a similar HR‑deficient population focus [C12419‑C12458].

IDE161’s first‑mover advantage is now limited to a modest lead; the appearance of four clinical‑stage PARG inhibitors (including the two new entries) reduces the exclusivity window, though IDE161’s combination studies planned with IDE849 could create a differentiation path.

3.3 Source vs. Company Claims

The data presented in the 8‑K filings are numerical extracts that correspond closely to the underlying trial records. No instance of numeric inflation or endpoint switching was detected in the verified claims compared with ClinicalTrials.gov protocol‑specified endpoints. All reported endpoints (PFS, ORR, DCR, OS) are prespecified primary or secondary outcomes in the respective trial registries.

One caveat: the IDE849 data are from a conference presentation; the full publication and longer follow‑up are pending. The median follow‑up of 3.5 months means that PFS and durability estimates are immature.

The single result that would end the darovasertib thesis is a statistically significant absence of benefit in the confirmatory OS analysis of optimUM‑02, given that accelerated approval is being sought on PFS. For IDE849, re‑emergence of a safety concern — particularly an ILD rate comparable to the 7 % already seen — with longer follow‑up could curtail registrational prospects in a second‑line population.

4.1 FAERS Disproportionality

No verified claims in this category. The dossier does not contain FAERS PRR, ROR, or reporting‑denominator data. Safety evaluation rests entirely on trial‑reported adverse events.

4.2 Class-Wide Signals

Across the IDEAYA portfolio, the most consistently reported treatment‑emergent adverse events (TRAEs) are gastrointestinal (diarrhoea, nausea, vomiting), fatigue, and haematological changes — a pattern typical of oral anticancer agents.

• IDE849: Grade ≥3 TRAEs 48 % overall, but only “below 20 %” at the 2.4 mg/kg dose likely to be taken forward [C795, C801][T1]. Interstitial lung disease (any grade) seen in 7 % (7/100); this is a notable class‑aware signal for topoisomerase‑1 ADCs and needs monitoring as patient numbers grow [C802].
• Darovasertib (neoadjuvant): Grade ≥3 TRAEs 16.8 %; low rates of treatment‑related SAEs (5.3 %) and discontinuations (6.3 %) [C903‑C904]. Common low‑grade events: diarrhoea, nausea, fatigue, maculo‑papular rash, hypotension [C819].
• Darovasertib + Crizotinib: Gr ≥3 TRAEs at 5 % each for iron‑deficiency anaemia and pulmonary embolism [C871]; most common TRAEs (>30 %): diarrhoea, nausea, oedema, vomiting, dermatitis, hypoalbuminemia, fatigue [C870]. The serious adverse event rate was 5 % in the combination arm [C1111].
• IDE397 + Trodelvy: “no treatment related serious adverse events observed at the IDE397 30 mg and Trodelvy” dose level [C842][T1]. Larger cohorts are needed to confirm this favourable profile.

No class‑wide finding emerges that would definitively distinguish IDEAYA’s molecules from competitors on safety grounds alone. The ILD signal for IDE849 is the most materially negative safety feature; it is present, quantified, and acknowledged.

4.3 Disqualifying Findings

No adverse event in the verified claims has led to a trial suspension or clinical hold. The 7 % ILD rate for IDE849, if confirmed at a pivotal scale with no grade 5 events, is unlikely to be disqualifying in the SCLC population where the standard of care has significant toxicity. The single result that would disqualify a programme would be an FDA clinical hold due to an unexpected severe safety signal; no such hold appears in the record.

5.1 Chain of Title

• Darovasertib: IDEAYA granted Servier an exclusive license in August 2025 for all countries except the United States, covering all diagnostic, prophylactic, and therapeutic uses in humans [C727‑C728][T1]. IDEAYA retains US rights. The licence includes a $210 million upfront payment, up to $100 million in development/regulatory milestones, up to $220 million in commercial milestones, and mid‑teen to low‑twenties royalties on ex‑US net sales [C729‑C733][T1]. This confirms IDEAYA’s ownership and ability to license.
• IDE275 (Werner Helicase) and IDE705 (Pol Theta): These programmes originated from a June 2020 collaboration with GSK. GSK served notice of termination in December 2025, with effect March 9 2026 [C941, C962‑C965][T1]. During a 90‑day transition, GSK will transfer the clinical programmes back to IDEAYA [C944][T1]. The company plans to evaluate options for these programmes in 2026 [C946]. This termination eliminates a partner‑controlled development path but returns full IP and control to IDEAYA without compromising cash runway (the company states the update “does not change its expectation of cash runway into 2030” [C947]).
• GSK Collaboration on WRN inhibitor (GSK4418959): Separately, IDEAYA is listed as a collaborator on GSK’s Phase 1/2 SYLVER trial (NCT06710847) evaluating the oral WRN inhibitor GSK4418959 in dMMR/MSI‑H solid tumors [C8327‑C8328][T1]. This confirms an ongoing partnership distinct from the terminated IDE275 agreement, and gives IDEAYA exposure to a novel synthetic‑lethality target. The enrolled cohort of 14 participants is now in active, not‑recruiting status [C8309, C8358][T1].
• Other programmes: No licensing‑out or in‑licensing events for IDE397, IDE161, IDE849, IDE034, IDE892, or IDE574 appear in the verified claims. The absence of disclosed third‑party foundation IP does not confirm freedom‑to‑operate, but indicates that these programmes are internally originated or fully licensed by IDEAYA.

5.2 Maintenance & Lapse Risk

No verified claims address patent annuity payments, expiry dates, or jurisdictional scope. The existence of exclusive licenses and terminated collaborations provides indirect evidence that relevant IP estates are maintained but does not confirm active prosecution in all key territories.

5.3 Freedom to Operate

The Servier license for darovasertib removes the partner from the US market, giving IDEAYA exclusive commercial rights in its home territory. The GSK termination returns IDE275 and IDE705, removing a potential blocking collaborator. No third‑party patents or pending applications that could block these programmes are cited in the verified claims, but the dossier cannot certify a formal clearance opinion. This is an open, material IP risk: a blocking patent held by a competitor targeting the same genetic dependency (e.g., MAT2A or PRMT5) could complicate IDE397’s development, though the broad industry activity may indicate a crowded field rather than a single dominant patent holder.

The single result that would end the IP thesis for any programme is a successful validity challenge or a finding of infringement of a third‑party patent covering the composition of matter; no such litigation or opposition appears in the record.

6.1 Verified Credentials

• Yujiro Hata, President & CEO: Age 51; launched IDEAYA as its first employee and CEO while an Executive‑in‑Residence at 5AM Ventures (2015‑2018) [C1292][T1]. Former COO at Flexus Biosciences (acquired by Bristol‑Myers Squibb, April 2015) and FLX Bio [C1293‑C1294]. Previously VP Corporate Development & Strategy at Onyx Pharmaceuticals during its acquisition by Amgen (October 2013) [C1295‑C1296]. Earlier, SVP and Chief Business Officer at Enanta Pharmaceuticals (2002‑2010) [C1297]. Education: MBA, Wharton; BA Chemistry, Colorado College [C1300].
• Board of Directors: Seven seated directors as of the 2026 proxy statement [C1281]. Class I (up for re‑election in 2026): Hata, M. Garret Hampton, Catherine J. Mackey. Class II (expiring 2027): Terry J. Rosen (Chair), Wendy L. Yarno. Class III (expiring 2028): Scott W. Morrison, Jeffrey L. Stein [C1282‑C1284]. Susan L. Kelley, M.D., opted not to stand for re‑election and will transition to Chair of a new Clinical Advisory Board [C614‑C617].
• CFO: Joshua Bleharski, Ph.D., appointed 26 Jun 2025 [C689].
• Clinical leadership: Darrin Beaupre, MD, PhD, is listed as Study Director on IDE161 (NCT05787587) with affiliation IDEAYA Biosciences [C5430‑C5431]; Jasgit Sachdev, MD, serves as Study Director on IDE397 and darovasertib neoadjuvant trials, indicating a built‑out clinical operations team. Newly verified: Hetal Patel, MD, MSHS, CHCQM is Study Director on the optimUM‑02 trial (NCT05987332) [C5975][T1], reinforcing the depth of clinical operations.

The team demonstrates a track record of successful company creation, M&A exits (two acquisitions in which Hata played a senior role), and public‑company operations. No litigation, clawbacks, or credential mismatches are in the record.

6.2 Publication Record

No verified claims substantiate peer‑reviewed publications by the executive team. The dossier cannot grade academic output.

6.3 Flags

• Board turnover: Susan Kelley’s departure from the board, while stated as “not the result of any disagreement” [C619], is a director‑level exit that warrants monitoring for further governance changes. The simultaneous transition to an advisory role mitigates the concern somewhat.
• No public first‑author papers by key executives: this is typical for biotech executives but leaves the scientific depth of the leadership untestable via publication record.

The single result that would break confidence in the team is an SEC investigation or a material restatement; none appears.

7.1 Capital Raised vs. Claimed

• Net loss for the twelve months ended 31 Dec 2025: $113.7 million [C181] (UNVERIFIABLE verdict—source not retrievable; figure consistent with SEC EDGAR confirmation [E004]). The SEC EDGAR net income line confirms –$113,698,000 [E004].
• The company has filed a new shelf registration on Form S‑3ASR (May 2026) and maintains an at‑the‑market (ATM) sales agreement with Jefferies LLC that has $156.6 million in remaining capacity as of that date [C1142‑C1144][T1]. Prior to termination of the old shelf, $193.4 million had been sold under the same ATM [C1143][T1]. No equity raise beyond the ATM has been executed recently.
• The Servier upfront payment of $210 million was received in 2025 [C729][T1]. This is the single largest capital inflow in the verified period.
• Common shares outstanding were 87,577,550 as of 28 Apr 2025 [C654] and increased slightly to 87,860,920 as of 1 May 2026, reflecting a small amount of subsequent dilution [MQ002][T1].

No Form D‑filed private placement or PIPE is evident in the claims, indicating that recent financing has been via the ATM and partnership.

7.2 Cash Runway

• Cash, cash equivalents, and marketable securities were approximately $1.1 billion as of 30 Sep 2025 [C1002][T1].
• The company projects that this balance, together with the Servier upfront and expected cost savings, will fund the current operating plan into 2030 [C1003, C735][T1]. The Servier deal alone is expected to extend runway by “at least twelve months” [C734][T1].
• The GSK collaboration termination “does not change its expectation of cash runway into 2030” [C947][T1].

The projected runway beyond the next data readouts (optimUM‑02 NDA in H2 2026, IDE849 registrational initiation) places IDEAYA in a position of financial independence relative to its near‑term milestones.

7.3 Insider Transactions

No verified claims of Form 4 filings, insider sales, purchases, or holdings are included in the dossier. This item cannot be assessed from the available evidence.

7.4 Implied Valuation

Based on the last closing price of $28.21 on 15 May 2026 (T3 source: Stooq daily close) [MQ001][T3] and the most recent shares outstanding of 87,860,920 from the 10‑Q as of 1 May 2026 [MQ002][T1], the implied market capitalisation is approximately $2.48 billion. No last‑round private post‑money valuation is available in the verified claims; therefore a step‑up history cannot be derived. The public‑company market capitalisation provides a current value benchmark, but any intrinsic valuation model must rely on external assumptions about future revenues and probabilities.

8.1 FDA Precedent

Uveal melanoma has two precedents of relevance:

• Tebentafusp (Kimmtrak) received FDA approval in 2022 for HLA‑A*02:01‑positive metastatic uveal melanoma based on an overall survival benefit in a randomised trial.
• No drug is approved for the neoadjuvant setting or for HLA‑A*02:01‑negative mUM. Darovasertib’s optimUM‑02 trial enrolled exclusively the HLAA*02:01‑negative population [C876], aiming for a first indication.

For IDE849 in SCLC, the precedent is the accelerated approval of tarlatamab (DLL3xCD3 bispecific) in 2024 for third‑line SCLC, demonstrating that the FDA is willing to approve a DLL3‑targeted agent on response rate in a post‑platinum population. IDE849’s higher ORR in an earlier line (second‑line) could support a similar pathway, and the new Phase 1/2 combination study (NCT07174583) with durvalumab and IDE161 may provide expansion data for a frontline‑maintenance setting.

8.2 Designation Status

• Darovasertib has received FDA Breakthrough Therapy Designation “in the neoadjuvant setting of primary uveal melanoma for EN eligible patients” [C905][T1]. The company explicitly cautions: “Neither Breakthrough Therapy, Orphan Drug Designation, nor an accelerated approval filing necessarily translates into approval of a drug” [C909][T1].
• No RMAT, Fast Track, or Orphan Drug designation letters are verified in the claims (though the company may hold them; they are not in the dossier).

8.3 Approval Path

• Darovasertib in mUM: The Phase 2/3 optimUM‑02 trial’s PFS primary endpoint was met. The company targets topline PFS data by year‑end 2025 to Q1 2026 to support a potential accelerated approval filing in the US [C877], and subsequently announced an NDA submission target in H2 2026 [C1112]. A confirmatory trial (optimUM‑02 itself enrolling 437 patients as of Dec 2025, with OS data planned for full approval) is ongoing [C987‑C988].
• Darovasertib in neoadjuvant UM: The Phase 3 optimUM‑10 trial (NCT07015190) was initiated during Q2 2025 and is now recruiting, with an estimated enrollment of 520 patients; primary completion is estimated October 2030 [C820, C906, C10270, C10318, C10277][T1]. This will be a separate registrational package. The company expects to have three randomised Phase 3 registrational trials across all stages of uveal melanoma by H1 2026 [C986].
• IDE849: The company plans to initiate a monotherapy registrational study in second‑line/refractory SCLC and/or neuroendocrine carcinomas [C993]. The Phase 1/2 trial (NCT07174583) already recruiting includes monotherapy and combination arms that will inform the registrational path. No specific FDA meeting minutes or surrogate‑endpoint confirmation is cited.

The single result that would close the regulatory path for darovasertib: FDA refusal to file the NDA, or a Complete Response Letter. The submitted Phase 2/3 data, with a statistically significant PFS benefit (HR 0.42, p<0.0001) over a real‑world standard‑of‑care comparator, make this outcome appear low‑probability, but definitive confirmation requires the acceptance of the submission.

9.1 Verified TAM

No claim in the dossier provides a TAM (total addressable market) derived from prevalence, price, and penetration. The company has not, through the verified filings, broken out a quantitative market‑size model that can be independently crossed‑checked. This absence is a meaningful information gap.

9.2 Prevalence Data

• MTAP deletion: reported to occur in ~25‑30 % of urothelial cancer and ~15‑20 % of NSCLC [C825‑C826][T3]. These percentages are company‑cited estimates; a primary epidemiological source is not provided.
• Uveal melanoma: described as “rare” [C875][T1], with no incidence or prevalence figure in the verified claims. The overall population of HLA‑A*02:01‑negative mUM (the initial registrational population for darovasertib) is a subset of an already small patient pool, implying a niche‑to‑orphan market size.

9.3 Standard of Care & Pricing

• 1L mUM: investigator‑choice therapy in the optimUM‑02 comparator arm was dominated by ipilimumab+nivolumab (76 %) and pembrolizumab (24 %) [C1099‑C1100], reflecting US guideline‑recommended immunotherapy. No pricing for darovasertib or comparators is in the claims.
• For IDE849, the 2L+ SCLC standard of care is lurbinectedin, topotecan, or platinum re‑challenge; DLL3‑targeting with tarlatamab is approved in third‑line. Pricing benchmarks for ADCs in this setting exist (e.g., tarlatamab ~$24,000/month (approximate external estimate — not in verified claim set)), but no IDE849 pricing strategy is available.

The absence of verified pricing and market‑size data makes any DCF‑style valuation reliant on external assumptions.

10.1 Competitor Stage Map

MAT2A / MTAP‑deletion space (IDE397):

Key observation: The MAT2A‑PRMT5 field has grown to more than 13 compounds in Phase 1 or later. Servier’s S095035 and Gilead’s GS‑5319 represent new direct competitors, and BeOne’s BGB‑58067 (PRMT5) plus Tango’s TNG456 (PRMT5 with CDK4/6 combo) add to the PRMT5 layer. Bayer’s BAY 3713372 and Haisco’s HSK41959 are now also in Phase 1, alongside the Tango TNG462 combination trial and PharmaEngine’s PEP08. IDE397 remains the most clinically advanced MAT2A inhibitor, but the number of PRMT5 inhibitors that could substitute for MAT2A in the same patient population is growing, and the entry of Gilead (a large oncology company) into this space intensifies competitive pressure.

The Amgen anvumetostat Phase 2 in NSCLC (MTAPESTRY 201) and BMS’s randomized Phase 2/3 MountainTAP‑29 trial (NCT07063745) in first‑line MTAP‑deleted NSCLC, combining the PRMT5 inhibitor BMS‑986504 with pembrolizumab and chemotherapy, will directly stress‑test the MTAP‑deletion hypothesis in a large‑scale controlled setting; MountainTAP‑29 started enrolling in January 2026 and has an estimated enrollment of 590 patients with primary completion in 2031. Its results will provide a benchmark for IDE397’s eventual registrational plans and could establish PRMT5 inhibition as a new standard in this population, potentially narrowing the window for a MAT2A inhibitor.

Uveal Melanoma (darovasertib):

• Tebentafusp (Immunocore) is the only FDA‑approved therapy for HLA‑A*02:01‑positive mUM. Darovasertib is initially pursuing the complementary HLA‑negative population where tebentafusp is ineffective. In the HLA‑positive setting, the company is enrolling a separate single‑arm Phase 2 cohort [C991] and a combination with crizotinib.
• No other PKC inhibitor is in late‑stage development for UM. The competitive moat is therefore based on target biology and the genetic stratification, not direct head‑to‑head data.

DLL3‑Targeted Therapies (IDE849):

• Tarlatamab (Amgen DLL3xCD3 bispecific T‑cell engager) approved for third‑line SCLC; response rates ~40% in the pivotal trial (approximate external estimate — not in verified claim set). IDE849, a DLL3 ADC, has demonstrated a ≥60 % confirmed ORR in second‑line, suggesting a potential efficacy advantage, but no direct comparison exists.
• Rovalpituzumab tesirine (Rova‑T, AbbVie) was a DLL3 ADC that failed due to toxicity and limited efficacy, highlighting the historical difficulty of this target with an ADC modality. IDE849’s manageable safety and high response rates differentiate it from that precedent.

PARG Inhibitors (IDE161):

IDE161 was first‑mover among PARG inhibitors, but the competitive set has now grown to four other clinical‑stage PARG inhibitors, narrowing its lead time. The primary differentiator will be clinical data: IDE161 has yet to produce public efficacy results, while the followers are also early‑stage. The emerging trial details for SYN608 indicate a focus on the same HR‑deficient population, which could intensify competition for patients and future market share.

10.2 Differentiator Durability

• IDE849’s advantage would survive a competitive positive readout from another DLL3 ADC only if the competitor’s efficacy is lower or its safety profile is inferior. The high DCR and manageable ILD rate at the 2.4 mg/kg dose are strong, but the durability of response and PFS — with a median follow‑up of just 3.5 months — remain uncertain. A mature competitor dataset showing deeper and more durable responses could erode IDE849’s edge. The initiation of the IDE849+IDE161 and IDE849+durvalumab arms in the Phase 1/2 trial (NCT07174583) provides an internal differentiation path if combination activity is high.
• IDE397’s position as a MAT2A inhibitor is challenged by the emergence of S095035, ISM3412, and now GS‑5319 (Gilead). While IDE397 is on a combination path with Trodelvy, the field now has multiple MAT2A inhibitors and many PRMT5 inhibitors targeting the same MTAP‑deleted population. The initiation of the randomized Phase 2/3 MountainTAP‑29 trial for the PRMT5 inhibitor BMS‑986504 in frontline NSCLC adds a high‑visibility benchmark — positive data from that study could accelerate PRMT5 inhibitors as a therapeutic option, potentially narrowing the addressable market for a MAT2A‑targeted therapy. Which target proves superior clinically is unknown.
• IDE161’s lead in PARG is narrow and shrinking; four other PARG inhibitors are now in the clinic, with two actively recruiting and one more (SYN608) in startup. If IDE161 can generate clinical proof‑of‑concept data before the competitors report mature efficacy, it could secure a standard‑of‑care position.
• Darovasertib’s exclusive licence in the US and the lack of a direct competitor for HLA‑negative mUM provide a strong competitive barrier for at least the first approval cycle.

11.1 Contradicted Findings

• C127 — IDE397 + Trodelvy trial phase designation: ClinicalTrials.gov record for NCT04794699 designates this trial as Phase 1. IDEAYA’s R&D Day 2025 presentation and the §III subsection header describe it as “Phase 1/2.” The registry is the authoritative source; the company’s phase framing overstates the trial design.

  Source disagreement: Company characterizes IDE397 + Trodelvy as Phase 1/2. NCT04794699 is registered as Phase 1 only. See §III.

• C514 — optimUM-10 enrollment count: The company stated “approximately 450 patients” for the optimUM-10 registrational trial. The NCT07015190 registry record specifies an estimated enrollment of 520 subjects. The discrepancy of ~70 patients is material for a pivotal trial’s power calculation. This report uses the registry figure (520) in §III and §VIII.

  Source disagreement: Company claims ≈450; ClinicalTrials.gov states 520.

• C518 — IDE849-001 combination trial start date: The company communicated that the IDE849-001 trial (NCT07174583) would initiate in Q1 2026. The NCT07174583 registry record shows an actual start date of October 14, 2025 — approximately one quarter earlier than company guidance.

  Source disagreement: Company guided Q1 2026 start; registry records October 2025 actual start. The combination program is further advanced than company communications indicated.

11.2 Unsupported Claims

Material unsupported claims (UNFOUND or UNVERIFIABLE verdicts) are flagged inline with their claim IDs where relevant. Investors should treat any citation where the claim verdict is UNFOUND as a company assertion pending independent confirmation.

11.3 Risk Severity

Program‑Ending Risks:

1. Inefficacy in confirmatory trial for darovasertib: If the OS analysis of optimUM‑02 does not trend positive or shows a detriment, the accelerated approval based on PFS could be rescinded. This is the most consequential binary risk and can only be resolved when the OS data mature.
2. IDE849 safety signal expansion: If the 7 % ILD rate increases with larger exposure and includes grade 5 events, a clinical hold or withdrawal of interest from AstraZeneca (the combination partner) could derail registrational plans. The next data update from the ongoing Phase 1/2 trial will be critical.
3. Regulatory refusal for darovasertib NDA: The FDA may require OS data or a larger randomised trial before accepting an NDA, despite the statistically significant PFS benefit. The uncertainty is mitigated by the breakthrough designation, but the final decision is binary.
4. Competitive pressure on IDE397: The expansion of MAT2A and PRMT5 inhibitors with significant Phase 2 investments (Amgen, BMS, BeOne, Tango, Bayer, Haisco, PharmaEngine, Gilead) could make the MTAP‑deletion space crowded. The initiation of BMS’s MountainTAP‑29 randomized Phase 2/3 trial in first‑line NSCLC — which could establish PRMT5 inhibition as a standard of care — and the entry of Gilead’s GS‑5319 add new dimensions of competitive risk. If a PRMT5 inhibitor demonstrates compelling Phase 2/3 data before IDE397’s registrational plan is finalised, the commercial opportunity for a MAT2A inhibitor may narrow. The terminated BG‑89894 (BeOne) highlights that failure is also possible, but the sheer number of active programs and the entry of a large‑scale pivotal trial raise the bar for IDE397 to be a differentiated product.
5. Prior failed MAT2A inhibitor (AG‑270): Servier terminated AG‑270, its first-generation MAT2A inhibitor, in Phase 1, citing “strategic reasons” [C1633‑C1634], raising the risk that IDE397 may similarly prove insufficiently active.
6. Crowding in PARG space: The emergence of four additional clinical‑stage PARG inhibitors (XNW29016, SYN608, ETX‑19477, DAT‑2645) reduces IDE161’s first‑mover advantage. If any of these competitors generate positive monotherapy data quickly, differentiation becomes more difficult, though IDE161’s planned combination with IDE849 provides a unique potential path.

Manageable Risks:

• GSK termination return of IDE275/IDE705 adds no cash burden; the company plans to evaluate options in 2026 [C946]. These are early‑stage assets that do not meaningfully change the valuation thesis.
• Board turnover (Kelley departure) appears orderly with a transition to an advisory role, not indicative of internal conflict.
• The ATM dilution risk is $156.6 million remaining capacity, small relative to a $1.1 billion cash reserve; the impact on equity is minimal.
• The trial‑enrollment contradiction for optimUM‑01 in HLA‑positive patients could signal that the dataset for the subgroup is smaller or different from what has been publicly disclosed, potentially affecting the filing strategy; this can be resolved with a company clarification at the next medical meeting.
• The emergence of a Servier‑owned MAT2A inhibitor (S095035) and Gilead’s GS‑5319 could, if developed in the US, create direct competitors to IDE397 in its home market; however, the current license arrangement with Servier for darovasertib suggests the parties have a cooperative relationship, and Gilead’s entry is too early to assess competitive impact.

12.1 Platform Beyond Lead

IDEAYA’s pipeline extends well beyond the lead darovasertib programme, with multiple programmes in clinical trials that have a credible evidence trail:

• IDE849 (DLL3‑TOP1 ADC): Phase 1 data support a registrational programme; the company plans a monotherapy registrational study in SCLC and/or NEC [C993]. A Phase 1/2 trial (NCT07174583) has been recruiting since October 2025 evaluating IDE849 alone and in combination with durvalumab or IDE161 in DLL3‑expressing tumors (SCLC, NEC, others). Estimated enrollment is 208 participants; primary completion is May 2029 [C12534‑C12544, C12579–C12585][T1]. This trial operationalizes the AstraZeneca clinical collaboration (Imfinzi supplied) and the IDE849+IDE161 internal combination, providing a clinical readout pathway for both combinations.
• IDE397 (MAT2A): Updated data from the Trodelvy combination in MTAP‑deleted urothelial cancer are planned for a 2026 medical conference [C996]. A Phase 1 expansion in NSCLC is also enrolling [C828]. The next step is RP2D selection by end‑2025 [C843] and then potential registrational intent. The recent surge of competitors (S095035, ISM3412, GS‑5319, and the BMS MountainTAP‑29 pivotal trial) increases competitive risk, but IDE397’s head start and Trodelvy combination path provide a differentiated strategy.
• IDE161 (PARG): Combination studies with IDE849 in SCLC, NEC, and other DLL3‑overexpressing tumours have now entered clinical evaluation via the NCT07174583 trial (IDE849‑001), earlier than the Q2 2026 target initially communicated [C995]. This gives IDE161 a chance to generate internal combination data before external PARG monotherapy competitors reach maturity.
• IDE892 (PRMT5): A Phase 1 monotherapy dose‑escalation trial is planned for Q1 2026, followed by a combination trial with IDE397 in MTAP‑deleted NSCLC in Q2 2026 [C997‑C998]. This addresses the same synthetic‑lethal pathway as IDE397, potentially capturing patients who may not respond to MAT2A inhibition alone. The presence of many PRMT5 inhibitors broadens the competitive field, but IDE892’s internal combination with IDE397 is unique.
• IDE034 (B7H3/PTK7 bispecific ADC): Phase 1 initiation in Q1 2026 [C994].
• IDE574 (KAT6/7): Phase 1 initiation in Q1 2026 [C1001].
• CDKN2A‑targeting programme: The company plans to submit an IND by end‑2026 for a “potential first‑in‑class program targeting CDKN2A, the most common co‑alteration of MTAP” [C999‑C1000].

All of these programmes have at least a planned Phase 1 start or a disclosed timeline, providing a structured optionality layer beyond the lead asset. The cash runway into 2030 ensures these early‑stage programmes can be advanced without immediate financing risk.

Additionally, the collaboration with GSK on the WRN inhibitor GSK4418959 (SYLVER trial) provides optionality in WRN inhibition — a new synthetic‑lethality target in dMMR/MSI‑H tumors — without requiring IDEAYA to bear the full cost of development.

12.2 Repurposing Potential

Darovasertib is being explored across the entire spectrum of uveal melanoma:

• Neoadjuvant: Phase 3 optimUM‑10 [C906, C989].
• Metastatic 1L HLA‑negative: Phase 2/3 optimUM‑02 (registrational).
• Metastatic 1L HLA‑positive: Phase 2 optimUM‑01 (single‑arm, with a planned NDA filing based on data) [C991‑C992].
• Adjuvant: Phase 3 optimUM‑11, to be initiated with Servier in Q2 2026 [C990]. This exhaustive coverage captures every stage of the same disease, but does not extend to non‑uveal melanoma indications (cutaneous melanoma with GNAQ/11 mutations are rare). The repurposing potential is therefore confined to uveal melanoma but is deep.

For IDE849, the trial is enrolling in multiple DLL3‑upregulated tumour types: SCLC, NEC, NETs, and melanoma [C1062‑C1065]. If activity is observed in NETs or melanoma, the addressable market could expand meaningfully. The ongoing Phase 1/2 combination trial also addresses the possibility of moving into the frontline maintenance setting in SCLC.

12.3 Acquirer Profile

The Servier transaction (up to $320 million in milestones plus royalties ($100M development/regulatory milestones [C730] + $220M commercial milestones [C731], confirmed by C15223)) demonstrates that a global pharmaceutical company sees darovasertib as a commercial‑stage asset worth investing in. Servier’s decision to take ex‑US rights and share clinical trial costs implies a long‑term commitment. For a potential full acquisition of IDEAYA, logical acquirers would be:

• Companies with an existing oncology portfolio in melanoma (e.g., Merck, Bristol‑Myers Squibb, Novartis) that could benefit from adding a genetically‑defined therapy for a population where no drug is approved for HLA‑negative mUM.
• Companies investing in the MTAP‑deletion space (Amgen, Bristol‑Myers Squibb via Mirati, BeOne, Gilead) that could consolidate the MAT2A/PRMT5 landscape by acquiring IDE397, IDE892, and the internal combination capability.
• AstraZeneca’s clinical collaboration for IDE849 signals acquisition interest in the DLL3 ADC field; an acquisition of the entire company would bring in‑house a promising ADC and a synthetic‑lethality pipeline.
• GSK’s collaboration on the WRN inhibitor adds to the acquisition rationale: a company with a deep oncology franchise could acquire IDEAYA to capture a broad pipeline of synthetic‑lethality assets.

No definitive unsolicited bid or formal M&A offer is in the verified claims; the acquirer profile is based on observable partnerships and pipeline gaps.

The single event that would collapse the optionality thesis: Darovasertib OS futility confirmed in the optimUM-02 confirmatory trial, triggering Servier to terminate the license agreement. Servier has an at‑will termination right [C740], and while the upfront payment is non‑refundable, the loss of the partnership would eliminate the ex‑US revenue stream and potentially impair the overall enterprise value if the pipeline is not yet independently validated. Currently, no verified result on file would trigger such termination.

End of dossier.