• ~39% Overall Response Rate (ORR): 1 CR and 6 PRs (2 awaiting confirmation) by RECIST 1.1 out of 18 evaluable MTAP-deletion urothelial and NSCLC patients
• ~94% Disease Control Rate (DCR): 1 CR and 6 PRs and 10 SD by RECIST 1.1
• ~78% of Patients with Tumor Shrinkage: 14 patients observed tumor shrinkage
• ~81% ctDNA Molecular Response Rate (MRR): 13 of 16 patients with > 50% ctDNA reduction
• AE Profile: ~5.6% drug-related grade >3 AEs and no drug-related SAEs or discontinuations at 30 mg once-a-day expansion dose
• IDE397 expansion dose of 30 mg once-a-day achieved target drug coverage and plasma SAM pharmacodynamic reduction associated with preclinical tumor regressions
• ~48k U.S. annual incidence of MTAP-deletion urothelial cancer and NSCLC, with high unmet need and no FDA-approved therapies for MTAP-deletion solid tumors
• Investor webcast scheduled for today, Monday, July 8, 2024, at 8:00 am ET

SOUTH SAN FRANCISCO, Calif., July 8, 2024 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, today announced positive clinical data for the IDE397 Phase 2 monotherapy expansion dose in methylthioadenosine phosphorylase (MTAP)-deletion urothelial and non-small cell lung cancer (NSCLC) patients. IDE397 is a potent and selective potential first-in-class methionine adenosyltransferase 2 alpha (MAT2A) inhibitor in Phase 2 clinical trials for the treatment of MTAP-deletion solid tumors.

"We are highly encouraged by the preliminary clinical efficacy and favorable safety profile observed with IDE397 at the 30mg once-a-day expansion dose, including multiple partial responses and one complete response by RECIST 1.1 in MTAP-deletion urothelial and lung cancer patients. In addition, at this expansion dose we observed a favorable adverse event profile with no drug-related serious adverse events and mid-single digit percent grade 3 or higher drug-related adverse events, which we believe has the potential to enable longer duration dosing as well as combinations," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"IDE397 is a potential first-in-class MAT2A inhibitor, that is being advanced as a monotherapy agent in priority MTAP-deletion solid tumor types and in high conviction rational combinations, including with Amgen's investigational MTA-cooperative protein arginine methytranferase 5 inhibitor AMG 193 in NSCLC and with Gilead's Trop-2 directed anti-body conjugate Trodelvy in urothelial cancer. The IDE397 clinical data update demonstrates important clinical proof-of-concept in MTAP-deletion solid tumors to deliver RECIST responses and encouraging preliminary durability, with a convenient 30mg once-a-day tablet and favorable adverse event profile," said Yujiro S. Hata, Chief Executive Officer and Founder, IDEAYA Biosciences.

There are currently no FDA-approved therapies for patients with MTAP-deletion solid tumors, highlighting the unmet medical need. The priority MTAP-deletion solid tumor types for the IDE397 Phase 2 monotherapy program are urothelial cancer and NSCLC. MTAP-deletion prevalence has been reported at over 15% in NSCLC and over 25% in urothelial cancer, based on The Cancer Genome Atlas (TCGA) database. We estimate that the MTAP-deletion annual incidence in the U.S. in NSCLC and urothelial cancer is approximately 48,000 patients, based on the 2024 Surveillance, Epidemiology, and End Results (SEER) database. In addition, there are several potential expansion MTAP-deletion solid tumor types that are also being considered for monotherapy and combination development, including pancreatic, gastric, esophageal, and head and neck cancer, among others. Based on the TCGA database, MTAP-deletion prevalence in pancreatic cancer has been reported at over 20%, representing a U.S. annual incidence of approximately 14,000 patients.

Clinical Data Update – IDE397 at 30mg QD Phase 2 Expansion Dose in MTAP-Deletion Urothelial Cancer and NSCLC Patients

The company observed encouraging clinical activity at the 30 mg expansion dose in its Phase 2 clinical trial evaluating its potential first-in-class MAT2A inhibitor IDE397 in heavily pre-treated MTAP-deletion urothelial cancer and NSCLC patients. The patients evaluated had a median of two (2) prior lines of therapy, ranging from one (1) to seven (7) prior lines of treatment. The reported Phase 2 clinical data are based on eighteen (18) evaluable MTAP-deletion patients, including seven (7) urothelial cancer, four (4) adenocarcinoma NSCLC, and seven (7) squamous NSCLC patients at the expansion dose of 30 mg once-a-day of IDE397. 

Reported clinical efficacy and tolerability data are preliminary and based on investigator review from an unlocked database as of the data analysis cutoff date of June 21, 2024. 

The clinical data update in the eighteen (18) evaluable patients by RECIST 1.1 include:

• ~39% Overall Response Rate (ORR). One (1) complete response and six (6) partial responses by RECIST 1.1 evaluation out of eighteen (18) evaluable patients. Two (2) partial responses are awaiting confirmation, including one (1) urothelial cancer patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment and one (1) adenocarcinoma NSCLC patient. One (1) complete response and two (2) partial responses were urothelial cancer patients. Among patients with lung cancer, three (3) partial responses were squamous NSCLC patients, and one (1) partial response was an adenocarcinoma NSCLC patient. There was one (1) non-evaluable patient who discontinued due to rapid clinical progression of cancer fatigue and drug-unrelated adverse events in cycle 1 of treatment
• 94% Disease Control Rate (DCR). One (1) complete response, six (6) partial responses, and ten (10) stable disease by RECIST 1.1 evaluation out of eighteen (18) evaluable patients
• 78% of patients with tumor shrinkage. Fourteen (14) out of eighteen (18) evaluable patients observed tumor shrinkage
• Swim lane plot by CT-scan evaluation and preliminary durability assessment: Eleven (11) of eighteen (18) patients still on treatment. Five (5) of seven (7) RECIST 1.1 responses remain in response. Median duration of treatment, median duration of response, and median progression free survival not yet reached
• 81% ctDNA Molecular Response (MR) Rate. Thirteen (13) of sixteen (16) patients with 50% or greater ctDNA reduction. There were several quality control failures of patient samples that led to unavailability for MR analysis
• Favorable adverse event (AE) profile. Approximately 5.6% grade 3 or higher drug-related AEs and no drug-related serious adverse events (SAEs) observed at IDE397 30mg once-a-day expansion dose. No drug-related AEs leading to discontinuations observed. We anticipate that the favorable AE profile and dosing convenience of a 30 mg once-a-day tablet has the potential to enable long-term dosing and combination development
• 30mg once daily expansion dose achieves target drug coverage and plasma S-adenosyl-l-methionine (SAM) pharmacodynamic reduction associated with preclinical tumor regressions

IDEAYA has activated over 35 clinical trial sites globally in the U.S., Canada, Europe, and Asia Pacific to enable potential rapid enrollment for the IDE397 Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer in its ongoing trial (NCT04794699). There is also an Amgen-sponsored Phase 1/2 trial of IDE397 and AMG 193 combination in MTAP-Deletion NSCLC (NCT05975073) for which the companies intend to develop a joint publication strategy in 2024. In addition, IDEAYA has initiated enrollment in a Phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with Trodelvy (NCT04794699). IDEAYA is also advancing multiple preclinical stage MTAP-deletion programs to enable wholly-owned combinations with IDE397, including a program targeting a development candidate nomination in the second half of 2024.

IDEAYA Investor Webcast and Conference Call

IDEAYA will host an investor webcast today, Monday, July 8, at 8:00 am Eastern Time (ET), to present the clinical data update for the IDE397 Phase 2 monotherapy expansion dose in MTAP-deletion urothelial cancer and NSCLC patients.

Presenters at the investor webcast will include IDEAYA Biosciences management, including Yujiro S. Hata, Chief Executive Officer, Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, and Michael White, Ph.D., Chief Scientific Officer. 

The IDE397 investor webcast presentation, as well as an updated corporate presentation, which will incorporate the IDE397 Phase 2 clinical data update at the 30mg expansion dose in urothelial cancer and NSCLC patients, will be available on the company's website, at its Investor Relations portal at approximately 8:00 am ET on Monday, July 8, 2024.

About IDEAYA Biosciences

IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets.

Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to (i) expectations regarding the clinical activity profile and potential advantages of IDEAYA's clinical programs, (ii) the timing for the development of a joint Amgen/IDEAYA publication strategy for the Phase 1/2 IDE397 and AMG 193 combination, (iii) the timing of preclinical stage MTAP-deletion programs in combination with IDE397 and (iv) nomination of an IDE397 combination development candidate in the second half of 2024. Such forward-looking statements involve substantial risks and uncertainties that could cause actual events and results to differ from those expressed in these forward-looking statements, including those related to IDEAYA's preclinical and clinical development programs. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, serious adverse events, undesirable side effects or unexpected characteristics of drug development programs, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, the sufficiency of existing cash to fund operations, and other matters that could affect the company's business, financial condition, results of operations and prospects. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual events and results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Annual Report on Form 10-K filed on February 20, 2024, Quarterly Report on Form 10-Q filed on May 7, 2024 and any additional current and periodic reports filed with the U.S. Securities and Exchange Commission. 

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