Microsatellite instability-high Endometrial Carcinoma

WILMINGTON, Del.--( BUSINESS WIRE )--Incyte (Nasdaq:INCY) today announced results from the Phase 3 POD1UM-303/InterAACT2 trial of retifanlimab (Zynyz ® ), a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), in combination with platinum-based chemotherapy (carboplatin–paclitaxel) for the treatment of adults with inoperable locally recurrent or metastatic squamous cell anal carcinoma (SCAC). These data were featured today in a Presidential Symposium (LBA 2) at the European Society for Medical Oncology (ESMO) Congress 2024, held in Barcelona and virtually. The POD1UM-303/InterAACT2 trial results build on previously announced topline results, showing that the study met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with SCAC not previously treated with systemic therapy, as assessed by blinded independent central review (BICR) using RECIST v1.1. Adding retifanlimab to standard of care chemotherapy resulted in a clinically meaningful 37% reduction in the risk of progression or death (Hazard Ratio [HR]: 0.63; 95% Confidence Interval [CI] (0.47, 0.84); P =0.0006). Patients in the retifanlimab and chemotherapy combination group achieved a median PFS of 9.3 months compared to 7.4 months for patients in the placebo combination group. “The POD1UM-303/InterAACT2 trial is the first and largest Phase 3 trial evaluating a checkpoint inhibitor for the treatment of patients with squamous cell anal carcinoma, a disease with significant medical need. The positive efficacy and safety data presented today at ESMO illustrate the potential of retifanlimab in combination with carboplatin and paclitaxel to become a new standard-of-care treatment for patients with advanced SCAC,” said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. “We look forward to working with regulatory authorities to progress the supplemental Biologics License Application (sBLA) for retifanlimab and potentially bring the first-ever PD-1 or PD-L1 antibody to patients with SCAC.” The trial also showed improvement in key secondary endpoints, including: In an interim analysis for overall survival (OS), patients that received retifanlimab in combination with chemotherapy achieved an approximately 6-month improvement in median OS versus the placebo combination group, with a strong trend toward statistical significance (median OS 29.2 months vs. 23 months [HR: 0.70; 95% CI (0.49, 1.01); P =0.0273]; OS follow-up is ongoing). Overall response rate (ORR) and duration of response (DOR) by BICR each showed improvement in the retifanlimab and chemotherapy combination group versus the placebo combination group (ORR of 56% vs. 44% [95% CI (48, 64) and (36, 52), respectively; nominal P =0.0129]; DOR of 14 months vs. 7 months [95% CI (8.6, 22.2) and (5.6, 9.3), respectively]). Retifanlimab was generally well-tolerated, and safety was consistent with other chemotherapy plus checkpoint inhibitor regimens. The most common treatment-emergent adverse events (TEAEs) in the retifanlimab and chemotherapy combination group were anemia (66.2%), nausea (56.5%) and alopecia (51.3%). “Advanced SCAC is an often-neglected rare condition that, despite its increasing incidence and the often poor prognosis, has had the same standard-of-care treatment for decades with very few trials,” said Sheela Rao, M.D., Consultant Medical Oncologist, The Royal Marsden National Health Service Foundation Trust. “I believe the positive results from the POD1UM-303/InterAACT2 trial may provide a long-awaited, new treatment option with retifanlimab in addition to platinum-based chemotherapy for adults with inoperable locally recurrent or metastatic SCAC.” About Squamous Cell Anal Carcinoma (SCAC) Squamous cell anal carcinoma (SCAC) is an orphan disease for which the incidence is increasing approximately 3% per year, largely due to endemic human papillomavirus (HPV). 1,2,3,4 Human immunodeficiency virus (HIV) is an important amplifier of SCAC, as people with HIV are 25 to 35 times more likely to develop SCAC. 5,6 Patients with unresectable metastatic SCAC have poor 5-year survival, and there are currently no FDA-approved treatments for patients with advanced disease. 7 About POD1UM The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-303 and several other Phase 1, 2 and 3 studies for patients with solid tumors, including registration-directed trials evaluating retifanlimab as a monotherapy for patients with microsatellite instability-high endometrial cancer; and in combination with platinum-based chemotherapy for patients with non-small cell lung cancer. About POD1UM-303/InterAACT 2 POD1UM-303/InterAACT2 (NCT04472429) is a Phase 3, randomized, multicenter, double-blind, placebo-controlled study evaluating retifanlimab or placebo in combination with platinum-based chemotherapy (carboplatin and paclitaxel) in adult patients with inoperable locally recurrent or metastatic SCAC who have not been previously treated with systemic chemotherapy. During the blinded portion of the study, patients, including those with well-controlled HIV infection, were randomized 1:1 to receive retifanlimab 500 mg intravenously or placebo during each 28-day cycle for up to 6 months in combination with standard therapy of carboplatin and paclitaxel followed by monotherapy for up to 1-year total treatment. Crossover to active therapy retifanlimab was allowed for patients assigned to placebo upon verification of progression by blinded independent central review (BICR). The primary endpoint is progression-free survival (PFS) as determined by BICR using RECIST v1.1. The key secondary endpoint includes overall survival (OS). Secondary objectives include objective response rate (ORR), duration of response (DOR), disease control rate (DCR) by BICR, safety and pharmacokinetics. For more information about the study, please visit https://clinicaltrials.gov/study/NCT04472429 . About Zynyz ® (retifanlimab-dlwr) Zynyz (retifanlimab-dlwr), is an intravenous PD-1 inhibitor indicated in the U.S. for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Zynyz is marketed by Incyte in the U.S. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab. Zynyz is a registered trademark of Incyte. Important Safety Information What is the most important information I should know about ZYNYZ? ZYNYZ is a medicine that may treat a certain type of skin cancer by working with your immune system. ZYNYZ can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended. Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: Lung problems: cough, shortness of breath, chest pain Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky, or have blood or mucus; severe stomach-area (abdomen) pain or tenderness Liver problems: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach area (abdomen); dark urine (tea colored); bleeding or bruising more easily than normal Hormone gland problems: headaches that will not go away or unusual headaches; eye sensitivity to light; eye problems; rapid heartbeat; increased sweating; extreme tiredness; weight gain or weight loss; feeling more hungry or thirsty than usual; urinating more often than usual; hair loss; feeling cold; constipation; your voice gets deeper; dizziness or fainting; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, loss of appetite Skin problems: rash; itching; skin blistering or peeling; painful sores or ulcers in your mouth or nose, throat, or genital area; fever or flu-like symptoms; swollen lymph nodes Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with ZYNYZ. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath, or swelling of ankles confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight persistent or severe muscle pain or weakness, muscle cramps low red blood cells, bruising Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had. Complications, including graft-versus-host disease, in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with ZYNYZ. Your healthcare provider will monitor you for these complications. Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with ZYNYZ. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with ZYNYZ if you have severe side effects. Before you receive ZYNYZ, tell your healthcare provider about all of your medical conditions, including if you: have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus have received an organ transplant have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic) have received radiation treatment to your chest area have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome are pregnant or plan to become pregnant. ZYNYZ can harm your unborn baby. Females who are able to become pregnant: — Your healthcare provider should do a pregnancy test before you start treatment with ZYNYZ. — You should use an effective method of birth control during your treatment and for 4 months after your last dose of ZYNYZ. Talk to your healthcare provider about birth control methods that you can use during this time. — Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with ZYNYZ. are breastfeeding or plan to breastfeed. It is not known if ZYNYZ passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose of ZYNYZ. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of ZYNYZ include tiredness, muscle and bone pain, itching, diarrhea, rash, fever, nausea These are not all the possible side effects of ZYNYZ. Call your doctor for medical advice about side effects. General information about the safe and effective use of ZYNYZ. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about ZYNYZ, talk with your healthcare provider. You can ask your healthcare provider for information about ZYNYZ that is written for health professionals. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch . You may also report side effects to Incyte Corporation at 1-855-463-3463. Please see the full Prescribing Information for ZYNYZ for additional Important Safety Information. About Incyte A global biopharmaceutical company on a mission to Solve On. , Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia. For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn , X , Instagram , Facebook , YouTube . Incyte Forward-looking Statements Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding retifanlimab, the POD1UM-303 clinical trial, the potential for retifanlimab to become an approved treatment option for SCAC, Incyte’s plans to share data with the scientific community and Incyte’s expectations with respect to filing an sBLA or otherwise engaging with regulators, contain predictions, estimates and other forward-looking statements. These forward-looking statements are based on Incyte's current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the U.S. FDA and other regulatory authorities outside of the United States; the efficacy or safety of Incyte and its partners' products; the acceptance of Incyte and its partners' products in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; and other risks detailed from time to time in Incyte's reports filed with the Securities and Exchange Commission, including its annual report on Form-10K and its report on Form 10-Q for the quarter ended June 30, 2024. Incyte disclaims any intent or obligation to update these forward-looking statements. 1 Gondal TA, et al. Curr Oncol. 2023;30:3232-3250. 2 Islami F, et al. Int J Epidemiol. 2017;46:924-938. 3 Giuliano AR, et al. Int J Cancer . 2015;136:2752-2760. 4 Morris V, Eng C. J Gastrointest Oncol . 2016;7:721-726. 5 Wang C-CJ, et al. Surg Oncol Clin N Am. 2017;26:17-31. 6 NCCN Clinical Practice Guidelines in Oncology: Cancer in People with HIV. Version 1.2021. 2021. 7 Eng C, et al. Oncotarget 2014;5:11133-11142.

▎药明康德内容团队报道 8月7日消息，葛兰素史克（GSK）新加坡公司宣布，新加坡卫生科学管理局（HSA）已批准Jemperli（dostarlimab）的一项新适应症，即与卡铂和紫杉醇联合使用，随后Jemperli作为单一药物用于治疗原发性晚期或复发性子宫内膜癌患者，这些患者存在错配修复缺陷（dMMR）或高度微卫星不稳定性高（MSI-H）。 根据GSK新闻稿介绍，此次获批使得Jemperli成为新加坡dMMR/MSI-H原发性晚期或复发性子宫内膜癌的首个一线免疫肿瘤治疗药物，可用于该类患者的早期治疗。Jemperli早前已获得新加坡HSA的批准，作为dMMR复发或晚期子宫内膜癌成人患者的单药治疗，这些患者在任何情况下在先前含铂方案中或之后进展，并且不适合治疗性手术或放疗。 Dostarlimab（商品名：Jemperli）是一种程序性死亡受体-1（PD-1）阻断抗体，可结合PD-1受体并阻断其与PD-1配体PD-L1和PD-L2的相互作用。该产品最早于2021年4月获美国FDA加速批准，随后陆续获批多项肿瘤适应症，涵盖dMMR晚期或复发性子宫内膜癌、dMMR或MSI-H原发性晚期或复发性子宫内膜癌、dMMR复发或晚期实体瘤、所有的原发性晚期或复发性子宫内膜癌成人患者。 本次GSK向新加坡监管机构提交的文件包括3期RUBY/ENGOT-EN6/GOG3031/NSGO试验第一部分的中期分析结果，中位随访时间为25个月。该试验达到了研究者评估的无进展生存期（PFS）的主要终点，表明在dMMR/MSI-H人群中，接受Jemperli +卡铂和紫杉醇治疗的患者具有统计学意义和临床意义的益处。在dMMR/MSI-H人群中，观察到疾病进展或死亡风险降低72%。Jemperli联合卡铂和紫杉醇的安全性和耐受性与已知的单个药物的安全性基本一致。 GSK新加坡医疗总监Stephanie Cinthu Stephen Ambrose博士表示：“新加坡扩大对Jemperli的监管批准重新定义了新加坡dMMR/MSI-H原发性晚期或复发子宫内膜癌患者的治疗前景。到目前为止，化疗一直是许多疾病进展患者的标准治疗方法。在GSK的RUBY试验中，与化疗相比，Jemperli+化疗在该患者群体中显示出72%的疾病进展或死亡风险降低，提供了具有统计学意义和临床意义的益处。这些结果强调了Jemperli将癌症治疗转变为骨干免疫肿瘤治疗的潜力。 参考资料： [1]GSK's Jemperli (dostarlimab) plus chemotherapy approved in Singapore as the first frontline immuno-oncology treatment for dMMR/MSI-H primary advanced or recurrent endometrial cancer. Retrieved Aug 7，2024,from https://en.prnasia.com/releases/apac/gsk-s-jemperli-dostarlimab-plus-chemotherapy-approved-in-singapore-as-the-first-frontline-immuno-oncology-treatment-for-dmmr-msi-h-primary-advanced-or-recurrent-endometrial-cancer-456494.shtml 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

Darovasertib achieves triple-digit enrollment in Phase 2/3 trial in 1L HLA-A2*02:01(-) MUM; and >50 patients enrolled in Phase 2 neoadjuvant UM study ASCO 2024 oral presentation of darovasertib in neoadjuvant UM; FDA Type C meeting for neoadjuvant UM in Q3'24 and targeting Phase 2 neoadjuvant UM data update in H2'24 Demonstrated preliminary proof-of-concept for IDE397 in MTAP urothelial and lung cancer; 1 PR awaiting confirmation has confirmed and 1 additional PR still awaiting confirmation, from the 2 uPRs noted in the July 8, 2024 webcast IDEAYA, in consultation with Amgen, has now financially budgeted to support its obligations for target IDE397 / AMG 193 clinical combination expansion in NSCLC Phase 1 FPI achieved for IDE397 and Trodelvy® combo in MTAP-deletion urothelial cancer Targeting initial IDE161 Ph 1/2 expansion and Phase 1 FPI for IDE161 in combination with Merck's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in endometrial cancer in H2'24 Targeting Werner IND in H2'24, and MTAP and KAT6 pathway DCs in H2'24 Targeting B7H3/PTK7 Topo-Payload Bispecific-ADC DC nomination in H2'24 IDEAYA to host an Investor R&D Day in Q4 2024 $952.7 million of cash, cash equivalents and marketable securities as of June 30, 2024, supplemented by net proceeds of $283.8 million from July 2024 public offering, anticipated to fund operations into at least 2028 SOUTH SAN FRANCISCO, Calif., Aug. 6, 2024 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, provided a business update, and announced financial results for the second quarter ended June 30, 2024. "We made significant progress advancing four potential first-in-class precision medicine oncology clinical programs this past quarter, and we are on-track to deliver our fifth potential first-in-class program to the clinic this year in Werner Helicase. Importantly, we presented preliminary clinical proof of concept data for IDE397 monotherapy in MTAP-deletion urothelial and lung cancer, demonstrating the ability to deliver confirmed RECIST responses with a favorable AE profile. The IDE397 combination therapy trials in MTAP-deletion solid tumors with our collaborators continue to progress, with the first patient dosed in the Phase 1 trial evaluating IDE397 with Gilead's Trodelvy, and continued dose escalation in the AMG 193 clinical combination with Amgen. We look forward to hosting an investor R&D Day that will profile our rapidly advancing potential first-in-class precision medicine oncology pipeline, where we are targeting multiple additional development candidates by the end of this year," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. "We were excited to share the compelling interim clinical data from the investigator- and company-sponsored Phase 2 trials of darovasertib in neoadjuvant UM, and look forward to discussing the registrational path forward with the FDA and providing our company-sponsored Phase 2 trial update in over 30 patients during the second half of this year. In addition, the most recent positive interim results observed with IDE397 monotherapy, in addition to the ongoing combination trials, bring us closer to potentially addressing a high unmet need in MTAP-deletion NSCLC, urothelial cancer and other solid tumors, and we are targeting developing a registrational plan in 2025. Separately, we anticipate initiating both the Phase 2 IDE161 monotherapy expansion cohort and the IDE161 in combination with KEYTRUDA cohort in the second half of 2024," said Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences. Summary of Q2 and Recent Key Developments Research and Clinical Development Darovasertib in neoadjuvant uveal melanoma (UM) Interim data from the investigator-sponsored Phase 2 trial were presented at the American Society of Clinical Oncology (ASCO) 2024 meeting by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent's Hospital in Sydney, and the lead principal investigator of the study. The company-sponsored Phase 2 trial has enrolled over 50 patients in 20 sites globally as of July 31, 2024; a clinical update from eight patients was provided. An additional clinical data update in over 30 patients is planned in the second half of 2024. IDEAYA has scheduled a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss a potential registrational trial for darovasertib in the neoadjuvant UM setting in the third quarter of 2024. IDE397 in MTAP-Deletion Solid Tumors Selected 30 mg as move-forward Phase 2 expansion dose in MTAP-deletion urothelial cancer and squamous non-small cell lung cancer (NSCLC). Reported positive interim data from 18 evaluable urothelial cancer and NSCLC patients. Announced first-patient-in (FPI) for Phase 1 trial evaluating IDE397 in combination with Gilead's Trodelvy in MTAP-deletion urothelial cancer. The IDE397 / AMG 193 clinical combination dose escalation is ongoing. In the past quarter, IDEAYA, in consultation with Amgen, has now financially budgeted to support its obligations for target IDE397 / AMG 193 clinical combination expansion in NSCLC. Entered into an option and license agreement for a potential first-in-class B7H3/PTK7 topo-I-payload bispecific antibody drug conjugate (B7H3/PTK7 Topo-Payload BsADC) program with Biocytogen Pharmaceuticals (Beijing) Co., Ltd. (Biocytogen) in July 2024. A development candidate nomination is targeted for the second half of 2024. IDEAYA plans to host an Investor R&D Day in Q4 2024. Corporate Development Raised gross proceeds of approximately $302.4 million in July 2024 through public offering, generating net proceeds of approximately $283.8 million. Appointed Daniel A. Simon as Chief Business officer. Mr. Simon brings over 18 years of experience at leading life science and strategy consulting companies. Clinical Programs 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. The darovasertib and crizotinib combination in MUM has FDA Fast Track designation: IDE196-002 (NCT05987332) is a Phase 2/3 potentially registration-enabling clinical trial of darovasertib + crizotinib in first-line human leukocyte antigens HLA-A2*02:01(-) MUM. Triple digit patient enrollment has been achieved as of July 31, 2024. IDE196-001 (NCT03947385) is a Phase 1/2 clinical trial evaluating darovasertib + crizotinib in GNAQ/11 melanomas, including in MUM and metastatic cutaneous melanoma. Phase 2 trials of darovasertib as neoadjuvant / adjuvant therapy in primary UM: 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. Interim efficacy and safety results were reported in conjunction with the Phase 2 investigator-initiated trial (IST) interim data ASCO 2024 presentation. Data from eight patients (six enucleation and two plaque eligible) who have been on darovasertib treatment for 4 months or more as of the database lock of May 24, 2024 demonstrated a median tumor shrinkage (maximum height/base/volume change) of approximately 40%/25%/72% and the majority of the six enucleation patients had reported Eye Saved (i.e., converted to plaque brachytherapy or external beam radiotherapy (EBRT) eligible). Darovasertib had a manageable adverse events (AEs) profile with no drug-related serious adverse events (SAEs) observed; drug-related AEs were predominantly Grade 1 or Grade 2 and approximately 13% of patients reported at least one drug-related Grade 3 AE. The trial has enrolled over 50 patients in 20 sites globally, as of July 31, 2024. An amendment to the study protocol was submitted to the FDA in July 2024 to enable dosing of darovasertib as neoadjuvant and adjuvant therapy up to 12 months each. As part of this amendment the number of patients in the study was increased from 82 to 122 patients and the part 2 of the study will, once the amendment is effective, consist of adjuvant treatment with darovasertib in combination with crizotinib for patients with disease characteristics suggesting high or intermediate risk of metastasis. Additional clinical efficacy update from the company-sponsored Phase 2 of darovasertib neoadjuvant UM trial in over 30 patients is anticipated in the second half of 2024. NADOM (NCT05187884) is a Phase 2 neoadjuvant / adjuvant trial of darovasertib in ocular melanoma. This is an 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. Interim efficacy and safety results were presented at the ASCO 2024 meeting. As of the database lock on May 14, 2024, 13 patients had completed neoadjuvant treatment, 11 patients received adjuvant darovasertib after primary treatment of their UM, with five patients completing the planned six months of therapy. At that time, 75% (nine out of 12 enucleation patients) had confirmed Eye Saved (i.e., converted to plaque brachytherapy or EBRT). After six months, approximately 67% (eight out of 12 enucleation patients) observed greater than 30% tumor shrinkage (maximum volume change) and median tumor shrinkage (maximum volume change) was approximately 47%. Darovasertib monotherapy neoadjuvant treatment had a manageable AE profile with no drug-related SAEs observed. Drug-related AEs were predominantly Grade 1 or Grade 2 and 20% of patients reported at least one drug-related Grade 3 AE. IDEAYA has scheduled a Type C meeting with the FDA in the third quarter of 2024 to discuss a potential registrational trial for darovasertib in the neoadjuvant UM setting. IDE397 Program in Tumors 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. IDEAYA continues to focus on evaluating IDE397 in two trials in select monotherapy indications and in high conviction clinical combinations: IDE397-001 (NCT04794699) is a Phase 1/2 treatment study with monotherapy expansion in MTAP-deletion NSCLC and urothelial cancer. The estimated U.S. MTAP-deletion annual incidence in NSCLC and urothelial cancer is approximately 48,000 patients. Selected 30 mg as the move-forward expansion dose for IDE397 monotherapy in MTAP-deletion urothelial cancer and squamous NSCLC based on adverse event profile and preliminary clinical efficacy observed. Over 35 global clinical trial sites activated to enable rapid enrollment. Reported positive interim data from 18 evaluable MTAP-deletion urothelial and NSCLC patients by RECIST 1.1: ~39% Overall Response Rate (ORR) observed with one complete response and six partial responses. Two partial responses were awaiting confirmation at the time of the update (July 8, 2024), and one urothelial cancer patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment has now been confirmed. The second adenocarcinoma NSCLC patient is still awaiting confirmation as of July 31, 2024 In patients with urothelial cancer: One complete response and two partial responses were observed. In patients with lung cancer: three partial responses were seen in squamous NSCLC patients, and one partial response seen in adenocarcinoma NSCLC patient. There was one 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) seen with one complete response, six partial responses, and 10 stable disease. ~78% of patients (14/18) experienced tumor shrinkage. Preliminary durability assessment showed 11 of the 18 patients are still on treatment, and five of seven RECIST 1.1 responses remain in response. Median duration of treatment, median duration of response, and median progression free survival not yet reached. ~81% circulating tumor DNA (ctDNA) Molecular Response (MR) Rate observed in evaluable subjects with 13 of 16 patients with 50% or greater ctDNA reduction. There were several quality control failures of patient samples that led to unavailability for MR analysis. Overall favorable AE profile. Approximately 5.6% grade 3 or higher drug-related AEs and no drug-related SAEs reported at IDE397 30 mg 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. 30 mg once daily expansion dose achieves target drug coverage and plasma S-adenosyl-l-methionine (SAM) pharmacodynamic reduction associated with preclinical tumor regressions. Targeting development of IDE397 registrational plan in MTAP-deletion solid tumors in 2025. Phase 1/2 trial of IDE397 and AMG 193 in MTAP-Deletion NSCLC (Amgen-sponsored study, NCT05975073) Targeting development of joint publication strategy on IDE397 and AMG193 combination in 2024. At this time, the IDE397 / AMG 193 clinical combination dose escalation is ongoing. In the past quarter, IDEAYA, in consultation with Amgen, has now financially budgeted to support its obligations for target IDE397 / AMG 193 clinical combination expansion in NSCLC. First patient dosed in the Phase 1 trial of IDE397 and Trodelvy in MTAP-deletion urothelial cancer (IDEAYA-sponsored, NCT04794699) evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy. The MAT2A-Trop2 antibody-drug conjugate (ADC) combination targets two distinct, yet complementary nodes in the 26% of patients with MTAP-deleted urothelial cancer and has first-in-class potential to improve clinical outcomes for urothelial cancer patients. 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 as a monotherapy in IDE161-001 (NCT05787587), a Phase 1 trial of IDE161 in solid tumors with homologous recombination deficiency (HRD). Selection of an initial Phase 1/2 monotherapy expansion dose in HRD solid tumors remains on track for the second half of 2024. IDEAYA is currently validating IDE161 combination opportunities preclinically and targeting identification of additional combination(s) in 2024. Additionally, IDEAYA is planning to evaluate IDE161 in combination with KEYTRUDA® in patients with microsatellite instability (MSI)-high and microsatellite stable (MSS) endometrial cancer. Clinical first-patient-in for the IDE161 and KEYTRUDA® combination 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. The dose escalation portion of 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 is currently ongoing. Upon initiation of the Phase 1 dose expansion, 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 MSI IDEAYA and GSK remain on track for an IND filing in the second half of 2024 for the selected Werner Helicase inhibitor announced in December 2023. The IND-enabling Good Laboratory Practice (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 development candidate (DC) – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions. B7H3/PTK7 Topo-Payload BsADC Program IDEAYA entered into an option and license agreement for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program with Biocytogen in July 2024. The agreement grants IDEAYA an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 Topo-Payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in IDEAYA's pipeline targeting DDR-based therapies, including PARG inhibitor IDE161. A development candidate nomination for the B7H3/PTK7 Topo-Payload BsADC program is targeted for the second half of 2024. Under the terms of the agreement, Biocytogen will receive an upfront fee and, upon an option exercise by IDEAYA, be entitled to receive an option exercise fee, development and regulatory milestones and commercial milestone payments, as well as single-digit royalties on net sales. Total potential upfront, option exercise and milestone payments equal an aggregate of $406.5 million, including development and regulatory milestones of $100.0 million. 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 DC nominations targeted in the second half of 2024, including in MTAP-deletion solid tumors indications to enable a potential wholly-owned clinical combination with IDE397 and the lysine acetyltransferase 6 (KAT6) pathway. Financial Results As of June 30, 2024, IDEAYA had cash, cash equivalents and marketable securities totaling $952.7 million. This compared to cash, cash equivalents and marketable securities of $941.4 million as of March 31, 2024. The increase was primarily attributable to net proceeds of $36.5 million from the sale of common stock shares through IDEAYA's at-the-market offering program during the period from April 1, 2024 to June 30, 2024, partially offset by net cash used in operations. Subsequent to the reporting period for the quarter ended June 30, 2024, IDEAYA announced the closing in July 2024 of an underwritten public offering of common stock and pre-funded warrants to purchase common stock, generating net proceeds of approximately $283.8 million, after deducting the underwriting discounts and commissions and estimated offering expenses payable by IDEAYA. There was no collaboration revenue recognized for the three months ended June 30, 2024 similar to the three months ended March 31, 2024. We completed all performance obligations related to the upfront payment under the GSK collaboration agreement as of December 31, 2023. Future collaboration revenue recognized under the GSK collaboration agreement will be related to future milestone payments as they are earned. Research and development (R&D) expenses for the three months ended June 30, 2024 totaled $54.5 million compared to $42.8 million for the three months ended March 31, 2024. The increase was primarily due to higher stock-based compensation expenses, clinical trial expenses, professional and outside services and consulting expenses. General and administrative (G&A) expenses for the three months ended June 30, 2024 totaled $10.4 million compared to $8.2 million for the three months ended March 31, 2024. The increase was primarily due to higher stock-based compensation expenses, audit fees and consulting expenses. The net loss for the three months ended June 30, 2024 was $52.8 million compared to the net loss of $39.6 million for the three months ended March 31, 2024. Total stock compensation expense for the three months ended June 30, 2024 was $9.7 million compared to $6.3 million for the three months ended March 31, 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. IDEAYA's updated corporate presentation is available on its website, at its Investor Relations page: . Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to (i) the timing, content and venue of clinical program updates, (ii) the timing for the development of a joint Amgen/IDEAYA publication strategy, (iii) the timing of an FDA Type C meeting for neoadjuvant UM, (iv) the timing of initial Phase 1/2 monotherapy expansion for IDE161 in HRD solid tumors, (v) the timing of a first-patient-in in the IDE161 and KEYTRUDA combination study, (vi) the timing of IND submission for the Werner Helicase inhibitor DC, (vii) the timing of designation of next generation development candidates, (viii) the extent to which IDEAYA's existing cash, cash equivalents, and marketable securities will fund its planned operations, (ix) the estimate of patient populations, (x) additional clinical combinations, and (xi) the receipt of development and regulatory milestones. Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. 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, 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, and other matters that could affect the sufficiency of existing cash to fund operations. 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 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 dated February 20, 2024 and any current and periodic reports filed with the U.S. Securities and Exchange Commission. Investor and Media Contact IDEAYA Biosciences Andres Ruiz Briseno SVP, Head of Finance and Investor Relations [email protected] SOURCE IDEAYA Biosciences, Inc.