On May 7, 2024 IDEAYA Biosciences, Inc., a precision medicine oncology company committed to the discovery and development of targeted therapeutics, provided a business update, and reported financial results for the first quarter ended March 31, 2024 (Press release, Ideaya Biosciences, MAY 7, 2024, View Source [SID1234642774]).
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"This quarter we continued to execute on our strategic vision to build a leading precision medicine oncology company, with the broad advancement of 4 potential first-in-class clinical programs across multiple patient selection biomarker populations, including GNAQ/11, MTAP-deletion, and HRD solid tumors. Next, through our excellence in translational research, we have discovered and enabled what we believe are potential first-in-class rational combinations across our diverse clinical pipeline, including with Pfizer, Amgen, Gilead, GSK, and Merck. IDEAYA’s next generation programs have also made tremendous progress this past quarter, including the Werner Helicase program that is on-track for an IND-filing this year and our second MTAP-deletion program where we anticipate a development candidate in 2024 to enable a potential wholly-owned clinical combination with IDE397," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.
"We are excited to provide a clinical data update from the ongoing investigator-sponsored Phase 2 neoadjuvant uveal melanoma trial as an oral presentation at ASCO (Free ASCO Whitepaper) 2024. In addition,
Exhibit 99.1
we are targeting to provide a clinical data update from our company-sponsored Phase 2 neoadjuvant UM trial and receive FDA regulatory guidance for a potential registrational path in the neoadjuvant uveal melanoma indication in the second half of 2024. In addition, our potential first-in-class clinical pipeline including programs in Phase 1/2 such as the MAT2A inhibitor IDE397 which targets MTAP-deleted solid tumors and PARG inhibitor IDE161 which targets HRD solid tumors, both continue to make important advancements. For IDE397, we have selected a move-forward Phase 2 monotherapy expansion dose in MTAP-deletion squamous non-small cell lung cancer. For the IDE161 program, we are targeting to initiate the Phase 2 monotherapy expansion in HRD solid tumors in the second half of 2024," added Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.
Summary of Recent Key Developments
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Interim data from the investigator-sponsored Phase 2 trial of darovasertib in neoadjuvant UM accepted for an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
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Selected move-forward Phase 2 expansion dose for IDE397 monotherapy in MTAP-deletion squamous NSCLC, based on adverse event profile and preliminary clinical efficacy observed, including multiple partial responses in squamous NSCLC by RECIST 1.1. In addition, multiple partial responses by RECIST 1.1 have also been observed in MTAP-deletion bladder cancer with IDE397 monotherapy and evaluation is ongoing for further potential Phase 2 expansion in this tumor type.
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Enrollment is ongoing in the IDE397 and AMG 193 combination Phase 1 dose escalation.
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IDE161 Phase 1/2 dose escalation is ongoing and targeting initial Phase 2 expansion in HRD solid tumors in H2 2024. Established clinical trial collaboration with MSD International Business GmbH, a subsidiary of Merck & Co., Inc. Rahway, NJ, USA, in March 2024 to evaluate IDE161 in combination with KEYTRUDA in endometrial cancer with a first patient dosing targeted in the second half of 2024.
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IND-enabling GLP toxicology studies have been completed for the Werner Helicase inhibitor development candidate, in collaboration with GSK, representing IDEAYA’s 5th potential first-in-class clinical program. Multiple development candidates targeted in H2 2024, including in MTAP-deletion to enable potential IDE397 clinical combination.
Clinical Programs Update and Upcoming Milestones
Darovasertib (IDE196) Program in Tumors with GNAQ or GNA11 Mutations
Darovasertib is a potent and selective protein kinase C (PKC) inhibitor being developed to broadly address primary and metastatic UM. Darovasertib is currently being evaluated in four ongoing clinical trials, three of which are in collaboration with Pfizer. The darovasertib + crizotinib combination in MUM has U.S. Food & Drug Administration (FDA) Fast Track designation:
Exhibit 99.1
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IDE196-002(NCT05987332) is a Phase 2/3 potentially registration-enabling clinical trial of darovasertib + crizotinib in first-line HLA-A2*02:01(-) MUM. Clinical program update(s) are anticipated in 2024.
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IDE196-001 (NCT03947385) is a Phase 1/2 clinical trial evaluating darovasertib + crizotinib in GNAQ/11 melanomas, including in MUM and metastatic cutaneous melanoma.
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Phase 2 trials of darovasertib as neoadjuvant / adjuvant therapy in primary UM:
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IDE196-009 (NCT05907954) is a company-sponsored Phase 2 trial evaluating darovasertib as neoadjuvant treatment of UM prior to primary interventional treatment of enucleation or radiation therapy, and as adjuvant therapy following the primary treatment. A clinical efficacy update on over 30 patients and an FDA regulatory guidance update are both targeted in the second half of 2024.
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NADOM (NCT05187884) is a Phase 2 neoadjuvant / adjuvant trial of darovasertib in ocular melanoma. This is an investigator-sponsored trial (IST) led by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent’s Hospital in Sydney with additional participating sites in Melbourne, Australia. The interim results from the trial have been accepted for an oral presentation at the upcoming 2024 ASCO (Free ASCO Whitepaper) annual meeting on June 3, 2024.
IDE397 Program in Solid Tumors and Bladder Cancer with MTAP Deletion
IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion. The Company continues to focus on evaluating IDE397 in two trials in select monotherapy indications and in high conviction clinical combinations:
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IDE397-001 (NCT04794699) is a Phase 2 monotherapy expansion of IDE397 in MTAP-deletion NSCLC and bladder cancer.
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Selected a move-forward Phase 2 expansion dose for IDE397 monotherapy in MTAP-deletion squamous NSCLC, based on adverse event profile and preliminary clinical efficacy observed, including multiple partial responses by RECIST 1.1 in squamous NSCLC. MTAP-deletion squamous NSCLC is estimated to have a global annual incidence greater than 100,000 patients.
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Multiple partial responses by RECIST 1.1 have also been observed in MTAP-deletion bladder cancer with IDE397 monotherapy and evaluation is ongoing for further potential Phase 2 expansion in this tumor type.
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Phase 1/2 trial of IDE397 + AMG 193 in MTAP-Deletion NSCLC (Amgen-sponsored study, NCT05975073):
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Enrollment is ongoing in the dose escalation portion.
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Joint publication strategy on IDE397 and AMG 193 combination targeted in 2024
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Phase 1 trial of IDE397 + Trodelvy in MTAP-deletion bladder cancer (IDEAYA-sponsored, NCT04794699). Trial initiation activities for the IDE397 and Trodelvy clinical combination
Exhibit 99.1
are ongoing and the dosing of a first patient is anticipated in mid-year (second or third quarter) 2024.
IDE161 Program in Tumors with Homologous Recombination Deficiency
IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a novel, mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDE161 received two FDA Fast Track designations in platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations, and in pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer. IDE161 is currently being evaluated in IDE161-001 (NCT05787587), a Phase 1/2 trial of IDE161 in solid tumors with HRD.
Early clinical data from the dose escalation cohorts were reported and the Phase 1 dose optimization portion of the trial is ongoing with the goal to select an initial Phase 2 expansion dose. Solid tumor types of focus, include ER+ HER-breast, colorectal, endometrial, and prostate cancers. Selection of an initial Phase 2 monotherapy expansion dose in HRD solid tumors is targeted in the second half of 2024. The Company is currently validating IDE161 combination opportunities preclinically and targeting identification of additional combination(s) in 2024.
In March 2024, the Company entered into the Clinical Trial Collaboration and Supply Agreement with MSD International Business GmbH, a subsidiary of Merck & Co., Inc. Rahway, NJ, USA. The Company is planning to evaluate IDE161 in a combination study with KEYTRUDA in patients with MSI-high and MSS endometrial cancer. A first-patient-in for this study is targeted in the second half of 2024.
KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
GSK-Partnered Programs
GSK101 (IDE705) Program in Tumors with HRD
GSK101 (IDE705) is a potential first-in-class small molecule inhibitor of Pol Theta Helicase being developed as a combination treatment with niraparib for advanced solid tumors with HRD. IND clearance was obtained from the FDA to enable the GSK-sponsored Phase 1/2 clinical trial to evaluate GSK101 in combination with niraparib, the GSK small molecule inhibitor of PARP, for patients having solid tumors with BRCA or other HR mutations, or with HRD. GSK is the sponsor of the Phase 1/2 clinical trial. GSK has dosed the first patient and enrollment is ongoing in the dose escalation portion of this study. Upon initiation of the Phase 1 dose expansion trial, IDEAYA will be eligible to receive a $10.0 million milestone payment, with the collaboration having a potential further aggregate later-stage development and regulatory milestones of up to $465.0 million. GSK is responsible for all research and development costs for the program. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, and tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.
Werner Helicase Inhibitor in Tumors with High Microsatellite Instability
Exhibit 99.1
IDEAYA and GSK are on track for an IND filing later in 2024 for the selected Werner Helicase inhibitor announced in December 2023. The IND-enabling GLP toxicology studies have been completed for the Werner Helicase inhibitor development candidate. IDEAYA has the potential to earn up to an additional $17.0 million in aggregate milestones through early Phase 1, including $7.0 million upon IND clearance, and is entitled to receive up to $465.0 million in further later-stage development and regulatory milestones. GSK is responsible for 80% of global research and development costs and IDEAYA is responsible for 20% of such costs. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase Inhibitor DC – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.
Next-Generation Precision Medicine Pipeline Programs
Early preclinical research programs focused on pharmacological inhibition of several new targets for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures are ongoing. These programs have the potential for discovery and development of first-in-class or best-in-class therapeutics with multiple wholly owned development candidate nominations targeted in the second half of 2024, including in MTAP-deletion solid tumors indications to enable potential wholly-owned clinical combination with IDE397.