IDE397 / Ideaya Biosci - LARVOL DELTA

IDE892 monotherapy and combination with IDE397 in methylthioadenosine phosphorylase-deleted (MTAPdel) advanced solid tumors (IDE892-001) (ESMO 2026) - No abstract available

Metastases • Monotherapy • Oncology • Solid Tumor • MTAP

Phase 1 expansion results of IDE397, a first-in-class, oral, MAT2A inhibitor (MAT2Ai) in MTAP deleted(del) non-small cell lung cancer (NSCLC) and urothelial cancer (UC) (EORTC-NCI-AACR 2024) - P1, P1/2 | "IDE397 provides preliminary clinical proof of concept for MAT2A inhibition in MTAPdel tumors with manageable safety & antitumor activity in pre-treated NSCLC & UC. Expansion of IDE397 monotherapy is ongoing, as well as in combination with sacituzumab-govitecan (Trodelvy®) (NCT04794699), and AMG 193 (NCT05975073)."

Late-breaking abstract • P1 data • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • MAT2A • MTAP

Proteome-wide mapping of S-adenosylmethionine interactions reveals novel regulatory targets (SSIEM 2026) - "Lysates were treated with 0.01-1 mM SAM, S-adenosylhomocysteine (SAH), methylthioadenosine (MTA), or DMSO, together with two structurally distinct methionine adenosyltransferase 2A inhibitors (AG-270 and IDE397) as binding selectivity controls. This study provides a proteome-wide view of SAM-binding proteins, offering new insights into its role as a global allosteric regulator. Ongoing work will determine how SAM binding influences the function of these newly identified targets. Overall, our findings expand the current understanding of SAM-mediated regulation in human cells."

Metabolic Disorders • MAT2A • MTHFR

In May, IDEAYA entered into a clinical trial collaboration with Roche to explore IDE892 in combination with RG6505, Roche's proprietary Phase 1 pan-RAS inhibitor, in MTAP-deleted, RAS-mutant PDAC to target the genetic co-alterations of MTAP and KRAS in this indication. (PRNewswire) - "IDEAYA plans to begin a Phase 1 combination trial in the second half of 2026. Upon joint IDEAYA and Roche approval, the collaboration may also evaluate a combination triplet with IDE892, RG6505, and IDE397, IDEAYA's proprietary Phase 1/2 MAT2A inhibitor."

Licensing / partnership • New P1 trial • Pancreatic Ductal Adenocarcinoma

A Phase 1/2 combination cohort was initiated to evaluate IDE892 with IDE397, IDEAYA's proprietary MAT2A inhibitor, in MTAP-deleted cancers. (PRNewswire) - "Expansion is planned by year end 2026 or early 2027, with an initial clinical focus on MTAP-deleted NSCLC."

Trial status • Non Small Cell Lung Cancer

IDE892 as monotherapy and in combination with IDE397 in patients with 5-methylthioadenosine phosphorylase-deleted (MTAP-Del) advanced solid tumors (IDE892001): Phase 1 trial. (ASCO 2026) - P1 | "Exploratory assessments include progression free survival, changes in circulating and tumor‑based markers of PRMT5 pathway modulation, molecular predictors of response, exposure–response relationships, and metabolite characterization. Clinical trial information: NCT07277413."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Heart Failure • Infectious Disease • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MAT2A • MTAP

IDE892 (PRMT5):…IDEAYA is planning to initiate a Phase 1 combination cohort with IDE397, its proprietary MAT2A inhibitor, in MTAP-deleted cancers in mid-2026 and expansion in the second half of 2026. (IDEAYA Biosciences Press Release) - "Dual inhibition of IDE892 and IDE397 has demonstrated durable and well-tolerated tumor regressions in preclinical MTAP-deleted tumor models, including in NSCLC."

New trial • Preclinical • Solid Tumor

IDEAYA Biosciences Announces First-Patient-In for Phase 1 Trial of IDE892, a Potential Best-In-Class PRMT5 Inhibitor for MTAP-Deleted Solid Tumors, and Provides MTAP and CDKN2A Pipeline Update (PRNewswire) - "IDE892 is being evaluated as a monotherapy agent in MTAP-deleted solid tumors, including NSCLC and PDAC, and targeting combination FPI with IDE397 (MAT2A) in mid-2026; Targeting nomination of a first-in-class CDKN2A development candidate in H2 2026 and IND in H1 2027; prevalence of CDKN2A-deficiency has been reported at over 80% in PDAC; IDEAYA will deprioritize combination activities with Trodelvy as part of a strategic prioritization of its proprietary MTAP-deleted and CDKN2A pipeline."

IND • Pipeline update • Trial status • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

A Phase 1/2 Study of Anvumetostat in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov) - P1/2 | N=53 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

Synergistic antitumor activity of the MTA-cooperative PRMT5 inhibitor ABSK131 in combination with multiple therapeutic agents in diverse cancer models (AACR 2026) - "In KRAS-mutant and MTAP-deleted models, ABSK131 led to robust tumor growth inhibition when combined with KRAS G12C inhibitor AMG510 or KRAS G12D inhibitor ABSK141. In EGFR-mutant and MTAP-deleted NSCLC, ABSK131 combined with osimertinib produced enhanced anti-proliferative and in vivo antitumor efficacy. ABSK131 synergizes with multiple therapeutic classes across MTAP-deleted models, providing compelling preclinical support for developing ABSK131-based combination strategies in genetically defined patient populations in clinic."

Combination therapy • IO biomarker • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • MAT2A • MTAP

IDE892 is a highly potent and selective PRMT5 inhibitor, with MTA-positive and SAM-negative cooperativity, optimized for development in MTAPdel cancers in combination with the allosteric MAT2A inhibitor IDE397 (AACR 2026) - "Whole transcriptome, proteome, and mRNA/tRNA methylome analyses indicated both shared and distinct contributions of IDE397 and IDE892 to perturbation of MTAPdel cellular systems which translated to robust combination benefit in MTAPdel CDX and PDX models. These preclinical studies indicate that the combination of IDE892/IDE397 has the potential to deliver durable therapeutic activity for patients harboring MTAPdel tumors; an opportunity that is currently under evaluation in phase 1 clinical trials."

Combination therapy • Oncology • CDKN2A • MAT2A • MTAP

IDE397-001: Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion (clinicaltrials.gov) - P1 | N=169 | Active, not recruiting | Sponsor: IDEAYA Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

The impact of metabolite kinetics on dysregulation of essential enzymes in cancers with MTAP deficiencies (AACR 2025) - "This study provides novel insights into the metabolic vulnerabilities of MTAP-deficient cancers and the mechanisms underlying the efficacy of targeted therapies. The discovery of the metabolite exchange channel in PRMT5 and the impact of MTA/SAM ratios on inhibitor efficacy offer new avenues for drug design and combination strategies. The synergistic effect observed with concurrent MAT2A and PRMT5 inhibition presents a promising approach with the potential to profoundly alter the treatment landscape for patients with MTAP deleted cancers.Our novel findings in this study provide mechanistic support for the importance of understanding metabolite exchange in PRMT5, the crucial impact of MTA/SAM ratios on the potency of MTA-cooperative PRMT5 inhibitors, and the benefit of combination therapy with the MAT2A inhibitor IDE397."

Oncology • MAT2A • MTAP

The allosteric MAT2A inhibitor IDE397 uniquely exploits metabolic liabilities associated with MTAP deletion to perturb DNA replication and repair (AACR 2025) - P1, P1/2 | "Observations of adaptive compensation within distinct methyltransferase pathways, such as polyamine synthesis, suggest this hierarchy is dynamic and orchestrated. The metabolic liabilities arising from MAT2A inhibition in MTAP deleted cancer cells provide a mechanistic rationale for unique therapeutic opportunities for IDE397 as a single-agent and in combination which are now being evaluated in patients (NCT04794699 and NCT05975073)."

Oncology • Solid Tumor • CDKN2A • MAT2A • MTAP

Development of SY-9453, a novel MAT2A inhibitor, for the treatment of MTAP-deficient cancers (AACR 2025) - "The encouraging clinical activity of IDE397 provides further proof-of-concept for MAT2A inhibitors in the treatment of MTAP-deficient cancers. Furthermore, SY-9453 revealed favorable PK properties and tolerability in preclinical studies. In conclusion, the current results demonstrate that SY-9453 is a novel small molecule MAT2A inhibitor with high activity in vitro and in vivo, providing a rational option for treating cancers with MTAP deficiency."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CDKN2A • MAT2A • MTAP

The MTA-cooperative PRMT5 inhibitor ABSK131 exhibits potent activity and broad synergistic potential in MTAP-deleted cancer models (AACR 2025) - "ABSK131 exhibits strong anti-tumor activity in MTAP-deleted lung and pancreatic cancer models and synergizes effectively with multiple therapeutic agents. These findings support the continued clinical development of ABSK131 as both a monotherapy and in combination regimens for MTAP-deleted cancers."

Late-breaking abstract • Preclinical • Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • MAT2A • MTAP • PARP1

A Study of IDE892 as Monotherapy and Combination in MTAP-deleted Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: IDEAYA Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Bladder Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Peritoneal Mesothelioma • Pleural Mesothelioma • Solid Tumor • Urothelial Cancer • MTAP

2026 Corporate Objectives:…MTAP Pathway (PRNewswire) - "(i) IDE397 (MAT2A): provide updated data from Phase 1/2 combination trial with Trodelvy in MTAP-deleted urothelial cancer (UC) at a medical conference in 2026; (ii) IDE892 (PRMT5): initiate a Phase 1 monotherapy dose escalation trial in Q1 '26 to enable a combination trial with IDE397 in MTAP-deleted non-small cell lung cancer (NSCLC) in Q2 '26; (iii) Submit an investigational new drug (IND) application for a potential first-in-class program targeting CDKN2A, the most common co-alteration of MTAP, by the end of 2026."

IND • New P1 trial • P1/2 data • Non Small Cell Lung Cancer • Urothelial Cancer

MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario. (PubMed, Cancer Res) - "MTA-cooperative PRMT5 inhibitors such as BMS-986504/MRTX1719 and AMG 193 target the PRMT5-MTA complex, while inhibitors of the SAM synthetase methionine adenosyl transferase 2A (MAT2A), such as IDE397, deprive PRMT5 of its methyl donor SAM. In this review article, we summarize the mechanisms of action, preclinical data, and clinical data available thus far for these novel classes of oncology precision medicine and discuss potential future directions relevant to MTAP deletion as a promising synthetic lethal vulnerability for cancer therapy."

Journal • Hematological Disorders • Oncology • MAT2A • MTAP

A Study of IDE892 as Monotherapy and Combination in MTAP-deleted Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Not yet recruiting | Sponsor: IDEAYA Biosciences

Monotherapy • New P1 trial • Bladder Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Peritoneal Mesothelioma • Pleural Mesothelioma • Solid Tumor • Urothelial Cancer

IDE397 (MAT2A) (PRNewswire) - "IDEAYA has selected Dose level 2 as the go-forward dose for the IDE397 and Trodelvy clinical combination in MTAP-deleted UC and has achieved first-patient-in (FPI) in NSCLC. The next clinical update from the combination trial is planned for a medical conference in the first half of 2026."

Trial status • Non Small Cell Lung Cancer • Urothelial Cancer

IDEAYA Biosciences Announces Agenda for 10-Year Anniversary R&D Day on September 8, 2025 (PRNewswire) - "Members of IDEAYA's senior leadership team will provide an overview of the company's progress to date, including presentation of new clinical data on darovasertib in neoadjuvant uveal melanoma (UM), IDE849 (DLL3 TOP1 ADC) and IDE397 (MAT2A)..."

Clinical data • Uveal Melanoma

IDEAYA Biosciences Announces IND Submission for IDE892, a Potential Best-In-Class PRMT5 Inhibitor for MTAP-Deletion Solid Tumors (PRNewswire) - "The company is targeting to begin a Phase 1 dose escalation trial of IDE892 in MTAP-deleted lung cancer in the fourth quarter of 2025, with the goal of advancing into combination trials with IDE397...in the first half of 2026....Preclinical profile of IDE892 and mechanistic combination rationale with IDE397...inhibitor, will be presented at the 10-Year Anniversary R&D Day on September 8th."

IND • New P1 trial • Preclinical • Solid Tumor

IDEAYA Biosciences Announces Positive Data From Phase 1/2 Combination Trial of IDE397, a potential first-in-class MAT2A inhibitor, and Trodelvy in MTAP-Deletion Urothelial Cancer (PRNewswire) - "Selection of recommended Phase 2 dose is targeted by end of 2025, with next update planned for a medical conference in H1 2026....33% ORR at DL1 (3/9); 3 confirmed partial responses (cPR), including one patient with a confirmed response after the cut-off date, and 57% ORR at DL2 (3 cPR and 1 unconfirmed partial response (uPR)). The preliminary combination data is trending favorably versus historical Trodelvy monotherapy efficacy reported in metastatic UC, including 11% ORR in patients post-EV therapy (Sternschuss et al., 2025) and 23% ORR in predominantly EV-naïve patients (Powles et al., 2025)."

P1 data • Trial status • Urothelial Cancer

IDEAYA Biosciences Announces First-Patient-In for Phase 1/2 Combination Trial of IDE397, A Potential First-in-Class MAT2A Inhibitor, and Trodelvy in MTAP-Deletion Non-Small Cell Lung Cancer (PRNewswire) - "IDEAYA is conducting the trial pursuant to a clinical study collaboration and supply agreement with Gilead..."

Trial status • Non Small Cell Lung Cancer