IDEAYA Biosciences, Inc. (Nasdaq: IDYA) has announced its third-quarter 2024 financial results and provided a business update, highlighting advancements across its precision medicine oncology pipeline. The company is focused on the discovery and development of targeted therapeutics, leveraging molecular diagnostics to select patient populations most likely to benefit from its therapies.
Darovasertib Program in Uveal Melanoma
The darovasertib program, targeting tumors with GNAQ or GNA11 mutations, is progressing with enrollment in the Phase 2/3 registration-enabling trial of darovasertib plus crizotinib in first-line human leukocyte antigens (HLA)-A2*02:01 negative (-) metastatic uveal melanoma (MUM) ahead of schedule, exceeding 150 patients. Interim Phase 2 results of darovasertib (IDE196) from company-sponsored and investigator-sponsored trials (IST) were highlighted in September 2024, with over 75 patients enrolled in the company-sponsored trial. These trials are evaluating darovasertib as neoadjuvant/adjuvant therapy in primary uveal melanoma (UM).
Following a successful Type C meeting with the FDA, IDEAYA is finalizing the Phase 3 registrational trial protocol and is targeting to initiate its potential registration-enabling trial in the first half of 2025. The planned trial aims to enroll approximately 400 patients in two cohorts: cohort 1 of plaque brachytherapy eligible UM patients, and cohort 2 of enucleation eligible UM patients. Cohort 1 will be randomized to darovasertib followed by plaque brachytherapy versus plaque brachytherapy alone, and cohort 2 will be randomized with or without darovasertib as neoadjuvant therapy. The primary endpoint of the trial is planned to be time to vision loss and eye preservation rate for cohort 1 and 2, respectively. The secondary endpoint for the trial is no detriment to Event-Free-Survival (EFS).
Interim efficacy data from both company-sponsored and IST trials showed promising results:
- Approximately 59% of patients with >20% ocular tumor shrinkage.
- Approximately 49% of patients with >30% ocular tumor shrinkage.
- Approximately 61% eye preservation rate observed.
IDE397 Program in MTAP-Deletion Solid Tumors
IDE397, a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients with MTAP-deletion solid tumors, is being evaluated in two trials. Phase 1 expansion results of IDE397 in 27 evaluable MTAP-deletion urothelial cancer (UC) and non-small cell lung cancer (NSCLC) patients were presented at ENA 2024. The patients evaluated had a median of two to three prior lines-of-therapy, ranging from one to seven. The reported Phase 1 clinical expansion data was based on 27 evaluable MTAP-deletion patients, including 10 UC, nine adenocarcinoma (Adeno) NSCLC, and eight squamous (Sq) NSCLC patients at the expansion dose of 30 mg once-a-day of IDE397.
Encouraging clinical activity at the 30 mg once-a-day Phase 2 monotherapy expansion dose was observed in the Phase 1 clinical trial evaluating IDE397 in heavily pre-treated MTAP-deletion UC and NSCLC patients presented at ENA 2024 in October 2024:
- ~33% Overall Response Rate (ORR). One complete response (CR) and eight partial responses (PRs) by RECIST 1.1 evaluation out of 27 evaluable patients. Nine of nine responses have been confirmed by RECIST 1.1, including four UC patients, of which one was a CR, three squamous NSCLC patients, and two adenocarcinoma NSCLC patients. Two patients confirmed after the data cutoff date.
- Confirmed ORR% by RECIST 1.1 by Solid Tumor Type: MTAP-deletion UC = 40% (4 of 10) confirmed ORR%; MTAP-deletion squamous NSCLC = ~38% (3 of 8) confirmed ORR%; MTAP-deletion adenocarcinoma NSCLC = ~22% (2 of 9) confirmed ORR%.
- ~93% Disease Control Rate (DCR). One CR, eight PRs, and 16 stable disease (SD) by RECIST 1.1 evaluation out of 27 evaluable patients.
IDEAYA is also exploring IDE397 in combination with AMG 193 (Amgen-sponsored study) in MTAP-Deletion NSCLC and with Trodelvy in MTAP-deletion UC. The PR reported at ENA 2024 has now confirmed by RECIST 1.1.
IDE161 Program in Tumors with Homologous Recombination Deficiency
IDE161, a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), is being evaluated in a Phase 1 trial in solid tumors with homologous recombination deficiency (HRD) and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) in microsatellite instability high (MSI-High) and microsatellite stable (MSS) endometrial cancer. Selection of an initial Phase 1/2 IDE161 monotherapy expansion dose in priority solid tumors type(s) is targeted in the fourth quarter of 2024. Separately, a first-patient-in for IDE161 in combination with KEYTRUDA is targeted in the fourth quarter of 2024.
GSK-Partnered Programs
IDEAYA's partnered programs with GSK are also advancing. IDE275 (GSK959), a potential first-in-class Werner helicase inhibitor, received FDA IND clearance for a Phase 1 trial in October 2024. The GSK-sponsored Phase 1 trial will evaluate IDE275 (GSK959) in patients having MSI-High tumors, as a monotherapy and in combination with a PD-1 inhibitor.
Financial Position
As of September 30, 2024, IDEAYA had cash, cash equivalents, and marketable securities totaling $1.2 billion, anticipated to fund operations into at least 2028.
