NRAS

Positive preliminary Phase 1b SEACRAFT-1 data for naporafenib plus trametinib reinforce therapeutic potential in NRASm melanoma and further support ongoing Phase 3 SEACRAFT-2 trial SEACRAFT-2 has potential for approval based on alignment with US and European regulatory agencies on path for tissue-specific indication in melanoma; Stage 1 randomized data expected in 2025 Rapid progress across RAS targeting franchise; planned IND submissions remain on track Erasca to host investor event today at 8:30 AM Eastern Time SAN DIEGO, Oct. 24, 2024 (GLOBE NEWSWIRE) -- Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced clinical progress for naporafenib and preclinical execution across the company’s RAS targeting franchise. “The SEACRAFT-1 trial in patients with RAS Q61X solid tumors has successfully accomplished several key objectives: delivering clinical data supporting the potential for durable efficacy in patients with NRAS-mutant (NRASm) melanoma, who currently have limited treatment options following frontline immunotherapy; identifying the most promising antitumor signal for the combination, which has been observed in melanoma patients, supporting a tissue-specific approach; and reducing the frequency and severity of dermatologic toxicities through mandatory primary prophylaxis,” said Shannon R. Morris, M.D., Ph.D., Erasca’s chief medical officer. “In totality, these data strengthen our conviction in the ongoing SEACRAFT-2 Phase 3 trial, for which we gained US and European alignment on the regulatory path in patients with NRASm melanoma. We look forward to randomized dose optimization data from Stage 1 of this trial, which is expected in 2025.” Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder, added, “We were excited to bolster our pipeline with the in-licensing of our RAS-targeting franchise in May, including the pan-RAS molecular glue ERAS-0015 and the pan-KRAS inhibitor ERAS-4001. These two assets with competitive profiles, potential for significant patient benefit, and broad application across solid tumors, have become key priorities for the company. In addition to reproducing data in-house supporting the best-in-class potential of both compounds, we continue to execute effectively and efficiently across several functional disciplines, including generating additional in vivo data and progressing the in-life portion of the Good Laboratory Practice (GLP) toxicology studies as anticipated, as well as advancing our drug substance and drug product development and manufacturing activities for both molecules according to plan. Investigational new drug (IND) application submissions remain on track for the first quarter of 2025 for ERAS-4001 and the first half of 2025 for ERAS-0015.” Naporafenib Program Update Naporafenib is a potential first-in-class and best-in-class pan-RAF inhibitor. Naporafenib plus trametinib (MEKINIST®) is being evaluated in the Phase 1b SEACRAFT-1 trial in patients with RAS Q61X mutations and the Phase 3 SEACRAFT-2 trial in patients with NRASm melanoma. In a post-hoc pooled analysis of Phase 1b and Phase 2 data from trials in patients with NRASm melanoma conducted by Novartis, naporafenib in combination with trametinib demonstrated favorable median overall survival (mOS) and median progression free survival (mPFS). The U.S. Food and Drug Administration has granted Fast Track Designation to naporafenib plus trametinib for the treatment of NRASm melanoma. NRASm melanoma has a high unmet medical need 25-30% of melanomas are NRASm, which has a worse prognosis vs. other molecular alterationsCurrent treatment options following frontline immunotherapy are poor: chemotherapy (approved standard of care) demonstrated 7% ORR and 1.5 months mPFS; binimetinib demonstrated 15% ORR and 2.8 months mPFS Promising initial Phase 1b efficacy results in the SEACRAFT-1 melanoma cohort further bolsters rationale for pursuing NRASm melanoma indication*: 40% (4/10) response rate observed in the melanoma cohort, including three confirmed partial responses (cPR) and one unconfirmed partial response (uPR); the melanoma cohort in SEACRAFT-1 is representative of the patient population currently being enrolled in the pivotal SEACRAFT-2 trial70% (7/10) of patients were on treatment as of the data cutoff, including all four responders Generally well-tolerated with mostly low-grade adverse events in the majority of patients* Results suggest that mandatory primary rash prophylaxis helped reduce frequency and severity of dermatological toxicities, reduced drug discontinuation rate due to adverse events, and improved the tolerability profile as measured by an increased relative dose intensity as compared to the prior clinical trials of naporafenib plus trametinib conducted by Novartis, which did not include the use of mandatory primary rash prophylaxis Data reinforce potential of ongoing Phase 3 SEACRAFT-2 trial in patients with NRASm melanoma Potential for approval in both US and Europe based on high unmet need and regulatory alignmentRandomized dose optimization data from Stage 1 of the SEACRAFT-2 Phase 3 trial expected in 2025 * Safety data cutoff date was September 3, 2024. Efficacy data cutoff date was September 5, 2024 RAS Targeting Franchise Update (ERAS-0015 and ERAS-4001) ERAS-0015 is a preclinical pan-RAS molecular glue with best-in-class potential for patients with RASm solid tumors that showed up to 10-fold greater potency and favorable absorption, distribution, metabolism, and excretion (ADME) properties and pharmacokinetics (PK) performance in preclinical studies when compared to another pan-RAS molecular glue currently in clinical development. ERAS-4001 is a preclinical pan-KRAS inhibitor that has shown first-in-class and best-in-class potential with high potency, strong antitumor activity, favorable ADME and PK properties in preclinical studies, including oral bioavailability, and ability to spare H/NRAS while limiting resistance through KRAS wild type activation. Nonclinical data continue to support potential best-in-class profiles, including data generated in-houseIn-life portion of Good Laboratory Practice (GLP) toxicology studies tracking as anticipated: ERAS-0015 completed, ERAS-4001 near completionOn track to achieve previously articulated guidance of IND filing in H1 2025 for ERAS-0015 and Q1 2025 for ERAS-4001 About ErascaAt Erasca, our name is our mission: To erase cancer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of cancer. We have assembled one of the deepest RAS/MAPK pathway-focused pipelines in the industry. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer.Cautionary Note Regarding Forward-Looking Statements Erasca cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: our expectations regarding the potential therapeutic benefits of our product candidates, including naporafenib, ERAS-0015, and ERAS-4001; the planned advancement of our development pipeline, including the anticipated timing of the data readout for Stage 1 of the SEACRAFT-2 trial, our alignment with regulatory authorities on the regulatory pathway for naporafenib, and the anticipated timing of the IND filings for ERAS-0015 and ERAS-4001. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: our approach to the discovery and development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; preliminary results of clinical trials are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data and more patient data become available; the analysis of pooled Phase 1 and Phase 2 naporafenib plus trametinib data covers two clinical trials with different designs and inclusion criteria, which cannot be directly compared, and therefore may not be a reliable indicator of survival data; due to differences between trial designs and subject characteristics, comparing data across different trials may not be a reliable indicator of data; our assumptions about ERAS-0015’s and ERAS-4001’s development potential are based in part on the preclinical data generated by the licensors and we may observe materially and adversely different results as we conduct our planned studies and trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; we only have one product candidate in clinical development and all of our other development efforts are in the preclinical or development stage; our SEACRAFT trials may not support the registration of naporafenib; our assumptions around which programs may have a higher probability of success may not be accurate, and we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; potential delays in the commencement, enrollment, data readout, and completion of clinical trials and preclinical studies; our dependence on third parties in connection with manufacturing, research, and preclinical and clinical testing; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization, or may result in recalls or product liability claims; unfavorable results from preclinical studies or clinical trials; the inability to realize any benefits from our current licenses, acquisitions, and collaborations, and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; regulatory developments in the United States and foreign countries; later developments with the FDA or EU health authorities may be inconsistent with the feedback received to date regarding our development plans and trial designs; Fast Track Designation may not lead to a faster development or regulatory review or approval process, and does not increase the likelihood that our product candidates will receive marketing approval; our ability to obtain and maintain intellectual property protection for our product candidates and maintain our rights under intellectual property licenses; our ability to fund our operating plans with our current cash, cash equivalents, and marketable securities; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K for the year ended December 31, 2023, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. MEKINIST® is a registered trademark owned by or licensed to Novartis AG, its subsidiaries, or affiliates. Contact:Joyce AllaireLifeSci Advisors, LLCjallaire@lifesciadvisors.com Source: Erasca, Inc.

Preclinical data highlight company’s fourth discovery stage program, a novel potent and selective KRAS(ON) inhibitor Updated preclinical data from CGT6297, Cogent’s H1047R mutant-selective PI3Kα inhibitor demonstrates robust inhibition of downstream signaling and efficacy WALTHAM, Mass. and BOULDER, Colo., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced the addition of a potent and selective KRAS inhibitor to its pipeline. Preclinical data from this program as well as its newly announced H1047R mutant-selective PI3Kα clinical candidate will be presented in two poster presentations at the 2024 EORTC-NCI-AACR International Symposium on Molecular Targets and Cancer Therapeutics taking place in Barcelona, Spain October 23-25, 2024. “Our Research team continues to make amazing progress, and we are excited to announce our third clinical candidate and fourth preclinical program today,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “Building upon earlier data presentations and recent advancements in the field, our first poster describes the properties of CGT6297, which we believe has the potential to emerge as a best-in-class H1047R mutant-selective PI3Kα inhibitor. Separately, for the first time, we outline our progress toward developing a potential best-in-class KRAS(ON) inhibitor, which in addition to its mechanistic attributes, has pharmacological properties differentiated from existing compounds in the class. Each of these programs align with our long-term strategy of creating and developing best-in-class molecules with the potential to have a broad impact on patients with genetically defined diseases.” Poster DetailsThe posters can be accessed in the ‘Posters and Publications’ page of Cogent’s website. Title: Identification of a Pan KRAS(On) Inhibitor with Selectivity Over KRAS over H/NRAS and pM Activity Across Prevalent KRAS MutationsSession Date and Time: Wednesday, October 23, 2024 – 12.00 - 19.00 CESTLocation: Exhibition Hall, Centre de convencions internacional Barcelona (CCIB), Barcelona, SpainPoster Number: PB108Abstract Number: 120 Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. The poster presented today describes Cogent’s internally-developed pan KRAS(ON) inhibitor with selectivity over HRAS and NRAS and picomolar (pM) activity across KRAS mutations without the potential liabilities of molecules in the class. Following oral administration, CGT6737 demonstrated robust PK/PD and tumor growth inhibition with 90% PD inhibition in mouse xenograft models. Lead optimization of CGT6737 is ongoing. Title: Preclinical Characterization of a Novel PI3Kα H1047R Mutant Selective Inhibitor Session Date and Time: Wednesday, October 23, 2024 – 12.00 - 19.00 CESTLocation: Exhibition Hall, Centre de convencions internacional Barcelona (CCIB) Barcelona, SpainPoster Number: PB133Abstract Number: 145 Cogent is also developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage for the H1047R mutation, which affects >55,000 cancer patients each year. The phosphoinositide 3-kinase (PI3K) pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. The approved agents for these patients often lead to dose limitations, resulting from activity against wild-type PI3Kα. The poster presented today highlights Cogent’s clinical candidate CGT6297, a potent allosteric inhibitor of PI3K, with 25-fold selectivity over PI3Kα WT. CGT6297 has high oral bioavailability and low clearance across species, providing robust inhibition of downstream signaling and efficacy in animal models. Importantly, when compared to a clinically relevant dose of a currently approved therapy in a mouse tumor model, CGT6297 demonstrated superior efficacy with no increase in insulin. IND-enabling studies are expected to be initiated in 2025. Upcoming Investor ConferenceCogent will participate in the following upcoming investor conference: Guggenheim Healthcare Innovation Conference - November 12, 2024 at 10:30 a.m. ET. A live webcast of the fireside discussion will be available in the Investors & Media section of Cogent’s website at investors.cogentbio.com/events. A replay of the event will be archived on Cogent’s website for up to 30 days. About Cogent Biosciences, Inc.  Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2, ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X.  Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the potential for CGT6297 to be a best-in-class H1047R mutant-selective PI3Kα inhibitor, the expectation that the company will initiate IND-enabling studies for CGT6297 in 2025, and the potential for the company’s KRAS program to produce a best-in-class KRAS(ON) inhibitor with pharmacological properties differentiated from existing compounds in the class and without the potential liabilities of molecules in the class. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof. Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

SAN DIEGO--( BUSINESS WIRE )-- Curebound , a philanthropic organization that invests in innovative cancer research , announces eight grants for a total of $2M in funding. The funding is made available through two new Curebound programs – Catalyst Grants , which support exciting projects within early-stage life science companies that are seeking to take innovative discoveries to commercially approved products, and Equity Grants , which focus on overcoming disparities in cancer research and treatment in underserved populations. Catalyst Grants award funds of up to $250,000 to San Diego-based pre-series A companies to conduct innovative oncology-based projects that hold promise for translation to clinic. Applications that advance transformative ideas and/or concepts to therapeutics, products, and/or services are prioritized. These grants are a new slant on the work of Curebound, which typically funds academic research, but is now looking to early-stage life sciences companies working on promising cancer solutions that have potential to become commercialized medicines and products. “These two new programs are the next evolution for Curebound’s mission to mobilize San Diego to accelerate cancer cures across populations,” says Curebound CEO Anne Marbarger . “We have a rigorous review process. Each application is reviewed by at least three peer reviewer experts and the Curebound scientific advisory board, which looks specifically for projects that have potential to make it to patients.” Catalyst Grant Recipients Include: Beken Bio “Liquid Biopsy Detection of Ovarian Cancer Targeting Novel Extracellular Vesicle Biomarkers” Investigator: Christopher Millan, PhD Pillar: Prevention and Diagnostic Tools Palm Therapeutics “Preclinical Development of NRAS Palmitoylation Inhibitors for NRAS Mutant Cancers” Investigator: Andrew Rudd, PhD Pillar: Novel Approaches and New Therapeutic Platforms Resolute Science “Targeting Macrophages to Treat Glioblastoma” Investigators: Faith Barnett, MD, PhD, Andre Basbaum Pillar: Novel Approaches and New Therapeutic Platforms Seren Bio “Development of DMGV analogs as a first-in-class, small molecule therapy for colorectal cancer” Investigators: Jongdae Lee, PhD Pillar: Novel Approaches and New Therapeutic Platforms Equity Grants address disparities in research and treatment in underserved populations , a key initiative for Curebound. These grants award up to $250,000 for high-impact research conducted by individual researchers aimed at reducing cancer-related health disparities by increasing access to high-quality care and by promoting cancer prevention, screening, and detection within medically underrepresented or underserved communities. Equity Grant Recipients Include: “Enhancing Lung Cancer Screening Engagement for Primary Care Patients in Low Income Communities” Investigators: David Strong, PhD (UC San Diego), Job Godino, PhD (Family Health Center of San Diego) Pillar: Cancer Equities, Prevention and Diagnostic Tool “Screening with Liquid Biopsies to Address Colorectal Cancer Inequities” Investigators: Samir Gupta, MD (UC San Diego), Job Godino, PhD (Family Health Center of San Diego) Pillar: Cancer Equities, Prevention and Diagnostic Tools “COMPRENDO-A: Peer-Navigation to Improve Accrual of Adolescents with cancer into Clinical Trials” Investigators: Paula Aristizabal, MD (Rady Children’s Hospital) Jesse Nodora, DrPH (UC San Diego) Pillar: Cancer Equities, Pediatric Cancers “Improving Health Equity and Cancer Care Quality through Tailored Navigation” Investigators: Matthew Banegas, PhD (UC San Diego), Corinne McDaniels-Davidson, PhD (San Diego State University), Jesse Nodora, DrPH (UC San Diego) Pillar: Cancer Equities “Curebound's scientific advisory board looks for areas of emerging research where the greatest opportunity exists including high-risk/high-reward research that can disrupt traditional approaches. These Catalyst and Equity Grant winners represent that and we are excited to see the results of their work,” says Ezra Cohen, MD, FRCPSC, FASCO, Chief Science Advisor, Curebound. More information on the Curebound Catalyst and Equity Grant recipients is available here. To apply for a 2025 Curebound Catalyst or Equity Grant, visit: https://curebound.org/what-we-do#research-program About Curebound Curebound is a philanthropic organization that invests in cancer research with the power to save lives. Through collaborative grants, corporate partnerships, and strategic investments, Curebound’s aim is to significantly accelerate better prevention, detection, and treatments for cancer. Headquartered in the major U.S. biotech hub of San Diego, amid 3,000+ life sciences companies, leading health systems, and world-class research institutions, Curebound partners with these organizations to forge interdisciplinary collaboration, foster knowledge sharing, and fund pioneering cancer research. So far, Curebound has funded $35+ million in cancer research, awarding 123 study grants for 17 types of pediatric and adult cancers with one vision: cures in our lifetime. Join us - www.curebound.org .