Malignant melanoma of eye

Phase 2 company-sponsored and IST neoadjuvant uveal melanoma (UM) clinical data update in 49 evaluable patients, demonstrates ~49% of patients with >30% tumor shrinkage by product of diameters, and ~61% eye preservation rate for enucleation patients Targeting to initiate Phase 3 randomized registrational trial in neoadjuvant UM following finalization of the clinical protocol with FDA Clinical endpoints supportive of full approval based on FDA guidance: Eye preservation rate as the primary endpoint for enucleation patients. Time to vision loss as the primary endpoint for plaque brachytherapy patients. No detriment to Event-Free-Survival (EFS) in the treatment arms is a secondary endpoint Discussions ongoing with FDA to include ORR as a potential surrogate and composite endpoint to support earlier approval scenarios Based on FDA meeting, potential for consideration of broad indication label in neoadjuvant UM for subjects with low, intermediate, and high risk for metastatic disease Pending FDA discussions, we project registrational trial enrollment will be ~400 patients North America, Europe, and Australia annual incidence of primary UM is projected to be ~12k patients where there are currently no FDA-approved therapies Investor webcast with Company management and KOL scheduled for Mon Sept 23, at 8am ET SOUTH SAN FRANCISCO, Calif., Sept. 23, 2024 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announced positive interim Phase 2 clinical trial data for darovasertib in neoadjuvant uveal melanoma (UM) and a successful FDA Type C meeting on registrational trial design for regulatory approval in neoadjuvant UM. "Darovasertib has demonstrated compelling preliminary clinical efficacy and a favorable AE profile in the neoadjuvant UM setting, with approximately 49% of patients demonstrating greater than 30% tumor shrinkage and importantly approximately 61% eye preservation rate for enucleation patients. The primary clinical endpoints supported by discussions with the FDA of eye preservation and time to vision loss are clinically meaningful for neoadjuvant UM patients, and darovasertib has the potential to provide a new standard of care in this setting," said Dr. Carol L. Shields, M.D., Chief of the Ocular Oncology Service at Wills Eye Hospital and Professor of Ophthalmology at Thomas Jefferson University. "The successful FDA Type C meeting provides darovasertib a potential registrational path in neoadjuvant UM, using primary clinical endpoints of eye preservation and time to vision loss, with no detriment to EFS in the treatment arms as a secondary endpoint. Based on the highly promising preliminary clinical efficacy and manageable safety profile observed with darovasertib and the high unmet medical need of neoadjuvant UM, we are excited to advance darovasertib rapidly to a registrational trial in this indication," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences. 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, two of which are in collaboration with Pfizer. The darovasertib and crizotinib combination in metastatic uveal melanoma (MUM) has FDA Fast Track designation. IDE196-009 (NCT05907954) is a company-sponsored Phase 2 trial evaluating darovasertib as neoadjuvant treatment for UM prior to primary interventional treatment of enucleation or radiation therapy, and as adjuvant therapy following the primary treatment. In addition, there is an investigator-sponsored trial (IST), NCT05187884, evaluating darovasertib as a neoadjuvant UM treatment. Phase 2 Clinical Data Update – Darovasertib in Neoadjuvant UM The company observed further evidence of encouraging clinical activity from an ongoing company-sponsored Phase 2 trial (NCT05907954) evaluating darovasertib in neoadjuvant uveal melanoma. The data cut-off date is August 15th, 2024, with an enrollment cut-off of May 13th, 2024, for the Phase 2 company-sponsored trial. Collectively, these clinical efficacy data from the Phase 2 company-sponsored and IST further substantiate clinical proof of concept for the use of darovasertib in the neoadjuvant uveal melanoma setting. Clinical data update highlights include: 31 enucleation and 18 plaque brachytherapy evaluable UM patients treated with darovasertib neoadjuvant therapy in Phase 2 company-sponsored and IST trials ~59% (29 of 49) of patients with >20% ocular tumor shrinkage by product of diameters ~49% (24 of 49) of patients with >30% ocular tumor shrinkage by product of diameters ~61% (19 of 31) eye preservation rate observed Evidence of visual preservation observed by reducing the amount of radiation associated with plaque brachytherapy Manageable AE profile observed from Phase 2 company-sponsored trial (n=38), including 11% grade 3 or higher AEs, and 5% serious AE rate. The discontinuation rate observed was 3%. The most common AEs observed included diarrhea, nausea, vomiting and fatigue. IDEAYA's ocular oncology advisory board recommended product of diameters for tumor measurement to determine overall response rate (ORR) criteria in ocular melanoma. In IDEAYA's ongoing Phase 2 clinical study with darovasertib, a >20% ocular tumor shrinkage by product of diameters correlates to clinical benefit, including eye sparing for enucleation UM patients and visual preservation for plaque brachytherapy UM patients. FDA Guidance in Type C Meeting supports Initiation of Potential Registrational Trial IDEAYA is targeting to initiate a potential registration-enabling Phase 3 randomized clinical trial in neoadjuvant UM patients following finalization of the clinical protocol with the FDA. The randomized Phase 3 clinical trial design incorporates guidance and feedback from the U.S. FDA following a recent Type C meeting. In the Phase 3 clinical trial, we currently project approximately 400 patients will be randomized for treatment with darovasertib in the treatment arm or the control arm, with potential modifications pending further FDA feedback. Based on the currently targeted clinical trial design, there will be 2 cohorts enrolled: 1) enucleation eligible UM patients, 2) plaque brachytherapy eligible UM patients. For the enucleation cohort, the randomization will be with or without darovasertib as neoadjuvant therapy. For the plaque brachytherapy cohort, the randomization will be darovasertib followed by plaque brachytherapy versus plaque brachytherapy alone. Key highlights of the target registrational trial design in neoadjuvant UM, based on FDA guidance and information provided in IDEAYA's FDA briefing book: Eye preservation rate is the primary endpoint for enucleation UM patients. Time to vision loss is the primary endpoint for plaque brachytherapy UM patients No detriment to Event-Free-Survival (EFS) in the treatment arms is a secondary endpoint Discussions ongoing with FDA to include ORR as a potential surrogate and composite endpoint to support earlier approval scenarios. The FDA briefing book notes a >20% ocular tumor shrinkage by product of diameters correlates to clinical benefit in the ongoing Phase 2 clinical study, including eye sparing for enucleation UM patients and visual preservation for plaque brachytherapy UM patients Primary endpoint of % eye preservation rate: The FDA briefing book notes objective to exceed lower bound of 10% eye preservation rate with a 95% confidence interval The registrational study will enroll UM patients with high risk for metastatic disease. Based on our preliminary projections, we anticipate the no detriment to EFS in the treatment arms for this high-risk population will take approximately 2-years of data maturity to initial readout Based on FDA meeting, potential for consideration of broad indication label in neoadjuvant UM for subjects with low, intermediate and high risk for metastatic disease 300mg BID darovasertib noted in FDA briefing book as the move-forward dose for registrational trial Addressable Patient Population in neoadjuvant UM Neoadjuvant UM represents a significant expansion opportunity for darovasertib – with a potential annual incidence of approximately 12,000 patients aggregate in North America, Europe, and Australia. IDEAYA owns or controls all commercial rights in darovasertib, including in MUM and in UM, subject to certain economic obligations pursuant to its exclusive, worldwide license with Novartis. IDEAYA Investor Webcast and Conference Call IDEAYA will host an investor webcast and conference call today, Monday, September 23, 2024 at 8:00 am ET, to present the darovasertib Phase 2 clinical efficacy and tolerability data, and the potential registrational clinical trial design based on guidance and feedback from the recent FDA Type C meeting. Presenters at the investor webcast and conference call will include Dr. Carol L. Shields, M.D., Chief of the Ocular Oncology Service at Wills Eye Hospital and Professor of Ophthalmology at Thomas Jefferson University. IDEAYA management, Yujiro S. Hata, Chief Executive Officer and President of IDEAYA Biosciences, and Darrin Beaupre, M.D., Ph.D., Chief Medical Officer of IDEAYA Biosciences, will also serve as presenters. IDEAYA's darovasertib investor webcast presentation, as well as an updated corporate presentation, will be available on the company's website, at its Investor Relations portal () in advance of the investor webcast presentation today, Monday, September 23, 2024, at approximately 8:00 am ET. 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 of FDA regulatory guidance and a potential registration-enabling Phase 3 randomized clinical trial in neoadjuvant UM patients, (ii) the potential therapeutic benefits of IDEAYA therapeutics, (iii) the translation of preliminary clinical trial results into future clinical trial results, and (iv) the estimate of patient populations. 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. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Aura will Host a Virtual Ocular Oncology Investor Event Featuring Key Opinion Leaders at 8:00 am Eastern Time on September 12, 2024BOSTON, Aug. 26, 2024 (GLOBE NEWSWIRE) -- Aura Biosciences, Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing precision therapies to treat a range of solid tumors designed to preserve organ function, today announced that Phase 2 end of study data evaluating suprachoroidal administration of bel-sar for the first-line treatment of patients with small choroidal melanoma and indeterminate lesions will be presented at The Retina Society Annual Meeting being held September 11-15, 2024, in Lisbon, Portugal. The presentation details are as follows: Title: Final Results of a Phase 2 Trial of Suprachoroidal Administration of Belzupacap Sarotalocan (bel-sar, AU-011) for Choroidal MelanomaPresenter: Dr. Ivana Kim, MD, Mass Eye and EarDate/Time: Thursday, September 12, 2024, from 11:04 am to 11:09 am Western European Daylight Time (6:04 am to 6:09 am Eastern Time) The presentation will be available here on Thursday, September 12, 2024, following the presentation. In addition, Aura will host a virtual ocular oncology investor event featuring Dr. Ivana Kim, MD (Mass Eye and Ear) and Dr. Prithvi Mruthyunjaya, MD, MHS (Stanford University Byers Eye Institute) to discuss the Phase 2 end of study data on Thursday, September 12, 2024, at 8:00 am Eastern Time. To register for the event, click here. A live question and answer session will follow the formal discussion. The live webcast of Aura’s virtual ocular oncology investor event will be available on the “Investors & Media” page under the “Events & Presentations” section of Aura’s website at https://ir.aurabiosciences.com/events-and-presentations, where a replay of the webcast will be archived for 90 days following the presentation date. About Ivana K. Kim, MD As a member of Mass Eye and Ear's Retina Service, Ivana K. Kim, MD specializes in the medical and surgical treatment of patients with vitreoretinal diseases, including age-related macular degeneration, retinal detachment, and uveal melanoma. In addition to her clinical responsibilities, Dr. Kim is Co-Director of the Harvard Ophthalmology Age-Related Macular Degeneration (AMD) Center of Excellence-a multidisciplinary collaboration among clinicians and scientists who are pooling their knowledge and resources with the goal of advancing breakthroughs in treatment for patients with AMD. Dr. Kim received her medical training at Harvard Medical School. She deepened her knowledge of the eye as a resident in the Harvard Ophthalmology Residency Training Program, and subsequently, as a retina fellow at Mass Eye and Ear. As a clinician scientist, Dr. Kim investigates genetic risk factors associated with AMD as a means to understand the mechanisms that cause the disease and further refine and advance therapies. In addition, she works to improve visual outcomes in patients with ocular melanoma-investigating strategies to reduce radiation complications-and hopes to help improve survival in these patients by studying frequently occurring mutations in this tumor type. Dr. Kim is Director of the Ocular Oncology Fellowship at Mass Eye and Ear. Her teaching activities involve the medical and surgical training of retina fellows, as well as ophthalmology residents. She also mentors medical students and research fellows in the laboratory setting. She is frequently invited to participate in regional and national continuing education courses, such as the annual Macula course, and the American Academy of Ophthalmology Retina Subspecialty Day. About Prithvi Mruthyunjaya MD, MHS Prithvi Mruthyunjaya MD, MHS is Professor of Ophthalmology and Professor of Radiation Oncology (by courtesy) at Stanford University, Director of Ocular Oncology at the Byers Eye Institute, and member of the Vitreoretinal Surgery Service. He is a board-certified ophthalmologist who has completed two prestigious fellowships: the first in Vitreoretinal Surgery at Duke University and the second in Ocular Oncology at Moorfields Eye Hospital in London, England. Dr. Mruthyunjaya is actively involved in research in ocular cancer imaging, genetics, and new modalities of tumor biopsy. He actively participates in early phase clinical trial development in ocular oncology and has brought cutting-edge treatment options to his patients at Stanford. He has published extensively in the field of ocular oncology, ophthalmic imaging, and complex retinal surgery. In addition, he holds leadership positions in the American Academy of Ophthalmology (AAO), the Retina Society, and the International Society of Ocular Oncology. He joined the faculty of the Byers Eye Institute where he established a state-of-the-art ocular oncology service at Stanford University in Palo Alto, CA. His passion includes teaching the next generation of students, residents and fellows and currently serves as the retinal surgery fellowship director at Stanford. About Aura Biosciences Aura Biosciences is a clinical-stage biotechnology company developing precision therapies to treat a range of solid tumors designed to preserve organ function. Our lead candidate bel-sar is in late-stage clinical development for the treatment of patients with primary choroidal melanoma, and other ocular oncology indications as well as in early-stage clinical development in bladder cancer. We are evaluating the safety and efficacy of bel-sar as a potential vision-sparing therapy in an ongoing global Phase 3 CoMpass trial for the first-line treatment of adult patients with early-stage choroidal melanoma. Bel-sar is also being evaluated in additional solid cancers, including bladder cancer. Our mission is to develop vision and organ-sparing therapies to improve patient outcomes in cancer. Aura is headquartered in Boston, MA. For more information, visit aurabiosciences.com. Visit us @AuraBiosciences and on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, and other federal securities laws. Any statements that are not statements of historical fact may be deemed to be forward looking statements. Words such as “may,” “will,” “could,” “should,” “expects,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “seeks,” “endeavor,” “potential,” “continue” or the negative of such words or other similar expressions that can be used to identify forward-looking statements. These forward-looking statements include express or implied statements regarding Aura’s future expectations, plans and prospects, including, without limitation, statements regarding the therapeutic potential of bel-sar for the treatment of cancers including early-stage choroidal melanoma and statements regarding the timing of the announcement of end of study data for the Phase 2 clinical trial of bel-sar for the treatment of early-stage choroidal melanoma. The forward-looking statements in this press release are neither promises nor guarantees, and investors should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties and other factors, many of which are beyond Aura’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements, including, without limitation, uncertainties inherent in clinical trials and in the availability and timing of data from ongoing clinical trials; the expected timing for submissions for regulatory approval or review by governmental authorities; the risk that the results of Aura’s preclinical and clinical trials may not be predictive of future results in connection with future clinical trials; the risk that interim data from ongoing clinical trials may not be predictive of final data from completed clinical trials; the risk that governmental authorities may disagree with Aura’s clinical trial designs, even where Aura has obtained agreement with governmental authorities on the design of such trials, such as the Phase 3 special protocol assessment agreement with the U.S. Food and Drug Administration; whether Aura will receive regulatory approvals to conduct trials or to market products; whether Aura’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; Aura’s ongoing and planned preclinical activities; and Aura’s ability to initiate, enroll, conduct or complete ongoing and planned clinical trials. These risks, uncertainties and other factors include those risks and uncertainties described under the heading “Risk Factors” in Aura’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the United States Securities and Exchange Commission (SEC) and in subsequent filings made by Aura with the SEC, which are available on the SEC’s website at www.sec.gov. Except as required by law, Aura disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Aura’s current expectations and speak only as of the date hereof and no representations or warranties (express or implied) are made about the accuracy of any such forward-looking statements. Investor and Media Contact: Alex DasallaHead of Investor Relations and Corporate CommunicationsIR@aurabiosciences.com

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.