IDEAYA Biosciences(US:IDYA)2025-02-18 21:00Clinical Development Pipeline - The company has a clinical pipeline with six potential first-in-class product candidates, including darovasertib, IDE397, and IDE849, with all commercial rights owned or controlled outside of Greater China for IDE849[21]. - As of February 7, 2025, over 230 patients have been enrolled in the Phase 2/3 clinical trial for darovasertib, targeting a median progression-free survival readout by year-end 2025[25]. - The IDE397 program is being evaluated in a Phase 1/2 clinical trial, with preliminary clinical efficacy demonstrated in heavily pre-treated MTAP-deletion patients[28]. - The company is targeting IND filings for several development candidates, including IDE892 and IDE034, in the second half of 2025[21]. - The company plans to initiate a neoadjuvant UM trial with approximately 400 patients randomized for treatment in the first half of 2025[25]. - The IDE705 program is in Phase 1 dose escalation, targeting solid tumors with BRCA or other HRD mutations, in collaboration with GSK[31]. - The company aims to enable a clinical combination of IDE397 and IDE892 in the second half of 2025 for MTAP-deletion NSCLC[28]. - The company is targeting a clinical data update for darovasertib in over 75 patients in the first half of 2025, including vision data in plaque brachytherapy patients[25]. - IDE849 is currently in a Phase 1 trial in China for small cell lung cancer, with 8 out of 11 evaluable patients achieving partial response[32]. - A U.S. IND submission for IDE849 as a monotherapy in SCLC is planned for the first half of 2025, with a combination evaluation targeted for the second half of 2025[32]. - GSK initiated a Phase 1 clinical trial for IDE275 (GSK959) in October 2024, with a milestone payment of $7.0 million received for IND clearance[32]. - IDE161 is progressing in a Phase 1/2 clinical trial, with an initial expansion dose selected for endometrial cancer and a Phase 1 expansion targeted for 2025[32]. - The company received Fast Track Designations from the FDA for IDE161 in September 2023 for specific advanced cancer treatments[32]. - IDE892, a potential best-in-class MTA-cooperative PRMT5 inhibitor, is targeted for IND submission in mid-2025[36]. - The company has selected IDE034 as a development candidate, with a potential IND submission targeted for the second half of 2025[36]. - Darovasertib (IDE196) has enrolled over 230 patients in a Phase 2/3 trial, with a median overall survival readout targeted for 2025[40]. - The Phase 2 portion of the clinical trial for darovasertib will randomize approximately 230 patients on a 2:1 basis for treatment with darovasertib and crizotinib or control[52]. - The primary endpoint for the Phase 2 trial is median progression-free survival (PFS), with a goal of supporting potential accelerated approval based on efficacy data from approximately 200 patients[52]. - The FDA has granted darovasertib Orphan Drug designation for uveal melanoma (UM) and Fast Track designation for the development program in metastatic uveal melanoma (MUM)[59][60]. - The Phase 2 clinical trial for darovasertib in neoadjuvant UM is projected to enroll approximately 400 patients, with primary endpoints focused on time to vision loss and eye preservation rate[65][66]. - The company has expanded its relationship with Pfizer to support the Phase 2/3 registrational trial, with Pfizer providing crizotinib at no cost for a defined quantity[55]. - The Phase 2 clinical trial for darovasertib as neoadjuvant therapy has enrolled 95 patients as of December 31, 2024, with ongoing enrollment across multiple clinical sites[62]. - The favorable adverse event profile at the 30 mg QD dose of IDE397 showed only 5.6% of patients experienced Grade 3 or higher drug-related adverse events[73]. - The company anticipates initiating the registrational trial for neoadjuvant UM in the first half of 2025, with a targeted move-forward dose of 300 mg BID for darovasertib[67]. - In the Phase 1 expansion data for IDE397, an overall response rate of approximately 33% was reported among 27 evaluable MTAP-deletion patients, with a disease control rate of 93%[74]. - For MTAP-deletion UC patients, the confirmed overall response rate was 40%, while for squamous NSCLC patients it was approximately 38%, and for adenocarcinoma NSCLC patients it was approximately 22%[74]. - The ctDNA minimal response rate was 81%, with 17 of 21 reportable patients showing a 50% or greater ctDNA reduction, and 33% showing a deep 90% or greater ctDNA reduction[74]. - Approximately 18% of patients experienced a Grade 3 or higher drug-related adverse event at the 30 mg QD dose, with no drug-related serious adverse events observed[75]. - The collaboration with Gilead aims to evaluate IDE397 in combination with Trodelvy for MTAP-deletion UC patients, with the first patient dosed in June 2024[76][77]. - The IDE849 program, licensed from Hengrui Pharma, has shown an overall response rate of approximately 73% in SCLC patients, with 8 partial responses observed among 11 evaluable subjects[86]. - IDE161, a PARG inhibitor, is being evaluated in a Phase 1/2 clinical trial for tumors with homologous recombination deficiency, with a focus on endometrial cancer[96][101]. - The IDE161 development program has received Fast Track Designation from the FDA for advanced ovarian and breast cancer patients with BRCA mutations[98][99]. - The company is targeting a Phase 1 expansion for IDE161 in MSI-High and MSS endometrial cancer in 2025[101]. Collaborations and Partnerships - The company has established collaborations with leading pharmaceutical companies, including Pfizer and Gilead, to support clinical development activities[21]. - An exclusive license agreement with Hengrui Pharma for IDE849 includes potential payments totaling $1.045 billion, with a $75 million upfront fee and milestone payments[28]. - The company has expanded its relationship with Pfizer to support the Phase 2/3 registrational trial, with Pfizer providing crizotinib at no cost for a defined quantity[55]. - The company has established strategic partnerships for clinical evaluations, including an exclusive license agreement with Novartis for darovasertib and collaborations with Gilead and Merck for IDE397 and IDE161, respectively[161]. - The company has entered into strategic collaborations with Hengrui Pharma for IDE849 and Biocytogen for IDE034, focusing on selective evaluations of partnerships for targeted product candidates[139]. - The company has formed joint development committees with Pfizer and Gilead to coordinate regulatory and other activities under their respective agreements[168][180]. - The company will bear all internal and external costs associated with the conduct of the combination studies with Gilead and Amgen[179][180]. - The company has a license agreement with Novartis for darovasertib, which includes an upfront payment of $2.5 million and potential milestone payments totaling up to $29 million[176]. - The company entered into a collaboration agreement with GSK, receiving $100 million upfront and being eligible for up to $485 million in development and regulatory milestones for Pol Theta products[192][194]. - The company has the potential to achieve an additional $10.0 million development milestone upon initiation of Phase 1 clinical dose expansion, with further aggregate late-stage development and regulatory milestones of up to $465.0 million[197]. - Under the GSK Collaboration Agreement, the company is eligible to receive total development milestones of up to $485.0 million for each WRN product, along with up to $475.0 million in commercial milestones[199]. - In October 2023, the company earned a $3.0 million milestone from GSK for IND-enabling studies and a $7.0 million milestone for IND clearance of IDE275, with potential for an additional $10.0 million milestone[200]. - The Biocytogen Option and License Agreement includes total potential milestone payments of $400.0 million, with development and regulatory milestones of up to $100.0 million[206]. - The Hengrui Pharma License Agreement includes upfront and milestone payments totaling $1.045 billion, with a $75.0 million upfront fee and up to $200.0 million in development and regulatory milestones[209]. Financial and Regulatory Milestones - The company incurred an obligation to pay milestone payments totaling £750,000 to CRT for achieving specific milestones in the Phase 1 clinical trial of IDE161-001[104]. - The company has the potential to earn up to $10.0 million in milestone payments upon the initiation of Phase 1 clinical dose expansion, with a recent achievement of a $7.0 million milestone based on FDA IND acceptance[111]. - The company is eligible to receive up to $475.0 million in commercial milestones and tiered royalties on global net sales of GSK101, ranging from high single-digit to sub-teen double-digit percentages[112]. - The company is obligated to make milestone payments totaling up to £19.5 million to CRT based on specific development events for PARG inhibitors[188]. Market Position and Competition - The company faces substantial competition from major pharmaceutical and biotechnology companies, with many competitors having significantly greater financial and technical resources[140]. - For darovasertib, the company is not aware of other companies developing clinical-stage therapeutics directed to PKC as a target for solid tumors, indicating a unique position in this area[142]. Intellectual Property - The patent portfolio includes approximately 59 distinct patent families, with 18 issued U.S. patents and 35 pending U.S. applications, protecting technology across the pipeline[154]. - As of January 26, 2025, the PKC program includes approximately six issued U.S. patents and 33 issued foreign patents, with expiration dates ranging from 2035 to 2045[155]. - The MAT2A program has approximately four issued U.S. patents and 50 pending foreign applications, with expiration dates between 2039 and 2044[157]. Research and Development Strategy - The company has established a robust precision medicine research platform, integrating drug discovery with biomarker identification to develop targeted therapies[125]. - The company has established collaborative relationships for access to proprietary databases and genetic screening services, supporting its research and development activities[164]. - The company has various agreements with service providers for research and development activities, including chemistry, compound synthesis, and clinical trial support[165]. - The company plans to selectively evaluate strategic collaborations with biopharmaceutical partners to accelerate development timelines and maximize commercial potential[166]. - In May 2023, the company entered into Amendment No. 4 to the Pfizer Agreement for the supply of crizotinib in support of a Phase 2 clinical trial, with Pfizer providing additional crizotinib at no cost[170]. Manufacturing and Commercialization - The company plans to build its own sales force to commercialize approved medicines in the U.S. and potentially in Europe and other selected countries[212]. - The company currently relies on third parties for the manufacture of product candidates and biomarker diagnostics, with plans to establish agreements with contract manufacturing organizations[213]. - The company intends to retain significant rights in key markets for its products, including worldwide commercialization rights for darovasertib, IDE397, and IDE161[211]. - The GSK Collaboration Agreement will continue until the expiration of payment obligations for each product in each country, unless terminated earlier by either party[203]. - The company has the right to terminate the Biocytogen Option and License Agreement for any reason upon ninety days written notice[207].