HRAS

ERAS-0015 and ERAS-4001 showed robust anti-tumor activity as monotherapy and combination therapy First-in-class examples of direct SHOC2 binders and modulators of SMP complex assembly identified with potential to block oncogenic RAS/MAPK pathway signaling SAN DIEGO, April 29, 2025 (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 presented new preclinical data reinforcing the best-in-class profiles of Erasca’s RAS-targeting franchise at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, Illinois. The Company also presented potential first-in-class examples of direct SHOC2 binders and modulators of SMP complex assembly, representing a new approach to block oncogenic RAS/MAPK pathway signaling. The posters are available online at Erasca.com/science/#presentations. “We were pleased to present new preclinical data at this year’s AACR meeting further solidifying our understanding of the properties that support the best-in-class potential of our pan-RAS molecular glue ERAS-0015 and the best-in-class/first-in-class potential of our pan-KRAS inhibitor ERAS-4001. We also showcased our research capabilities with, to our knowledge, the first identification of direct SHOC2 binders targeting the RAS/MAPK pathway in collaboration with our scientific advisory board member Pablo Rodriguez-Viciana,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “Importantly, these data reinforce the favorable pharmacokinetic properties that allow for robust anti-tumor activity at significantly lower doses of ERAS-0015 versus the leading pan-RAS molecular glue in development, as well as the potential expanded therapeutic index of ERAS-4001 through selective targeting of key KRAS mutations. We are excited to achieve our goal of advancing development of both RAS-targeting compounds in the clinic this year.” Poster Presentation Highlights Abstract 390 – ERAS-0015 is a pan-RAS molecular glue with best-in-class potential in RAS mutant solid tumors ERAS-0015 demonstrated favorable pharmacokinetic properties including longer residence time and greater tissue exposure that led to robust anti-tumor activity alone and in combination at doses lower than the leading pan-RAS molecular glue in development. ERAS-0015 is a pan-RAS molecular glue designed to shut down pathogenic signaling mediated by mutant and wildtype RAS by targeting RAS in the GTP-bound state. 8-21-fold greater cyclophilin A (CypA) binding for ERAS-0015 vs. pan-RAS molecular glue comparator RMC-6236 ERAS-0015 dose-dependently formed a ternary complex with active state RAS and CypA, which blocks formation of additional downstream effector complexes Potent inhibition of proliferation with ERAS-0015 across a panel of cell lines spanning diverse tumor tissues and RAS mutations Preferential drug distribution into tumor tissues Promising monotherapy and combination activity across multiple RAS mutant models Abstract 4367 – ERAS-4001 is a pan-KRAS inhibitor with robust anti-tumor activity in KRAS altered solid tumors ERAS-4001 potentially has an expanded therapeutic index relative to pan-RAS inhibitors by selectively targeting both mutant and wildtype KRAS, leading to significant tumor growth inhibition alone and in combination. Selectively targeting both wildtype (WT) and oncogenic KRAS may address resistance mechanisms to mutant-selective KRAS inhibitors that are driven by WT KRAS activity. A potential first-in-class pan-KRAS inhibitor, ERAS-4001 is a novel, highly potent pan-KRAS inhibitor that blocks mutant and WT KRAS, potentially offering improved tolerability relative to pan-RAS inhibitors by sparing NRAS and HRAS. ERAS-4001 selectively inhibited KRAS mutant enzymes and WT KRAS over WT HRAS and NRAS ERAS-4001 inhibited 3D cell viability and proliferation in 13 G12X mutant and one wildtype KRAS amplified cell lines across indications with single digit nanomolar IC50s Dose-dependent tumor growth inhibition and significant antitumor efficacy with ERAS-4001 monotherapy in KRAS mutant xenograft models Robust tumor growth inhibition with ERAS-4001 plus anti-PD-1 or cetuximab in KRAS mutant models Promising antitumor monotherapy and combination activity across multiple KRAS mutant models Abstract 3152 – Identification and characterization of inhibitors of SHOC2-MRAS-PP1C complex assembly Identified inhibitors of SMP complex assembly via SHOC2 engagement, representing a potential new approach to attenuate RAS/MAPK pathway signaling. Genetic ablation or protein degradation of SHOC2 can sensitize RAS-driven cells to RAS/MAPK pathway inhibitors and prevent adaptive resistance. Identified two lead series that bind selectively to SHOC2 with low nanomolar affinity, interfere with SMP complex assembly, and inhibit the SMP complex’s phosphatase activity To our knowledge, these compounds represent the first examples of direct modulators of the SMP complex Further optimization of SHOC2 binders for protein-protein inhibitors (PPIs) and degrader modalities is ongoing About Erasca At 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 patients with 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 and early-stage development projects, including ERAS-0015, ERAS-4001, and our SHOC2 binding project; and our ability to achieve our goal of initiating the clinical development of ERAS-0015 and ERAS-4001 this year. 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 development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; results from preclinical studies not necessarily being predictive of future results; 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, 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; 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, 2024, 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. Contact: Joyce Allaire LifeSci Advisors, LLC jallaire@lifesciadvisors.com Source: Erasca, Inc. Source: Erasca, Inc.

WALTHAM, Mass. and BOULDER, Colo., April 25, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced preclinical data from four pipeline programs during poster sessions at the American Association for Cancer Research (AACR) 2025 Annual Meeting taking place in Chicago. “We welcome the opportunity to present updated results from these programs that represent our exciting pipeline of potential best-in-class targeted therapies,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “These data demonstrate Cogent’s ability to discover and advance novel therapies for rare disease populations with high unmet medical need, and we look forward to continuing to advance these candidates.” Poster Details Title: Identification of a potent KRAS (ON) inhibitor with selectivity for mutant KRAS over HRAS and NRASSession Category: ChemistrySession Title: Lead Identification and OptimizationSession Date and Time: April 30, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 25Poster Board Number: 3Published Abstract Number: 6974 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 program with selectivity over HRAS and NRAS and picomolar (pM) activity across KRAS mutations. In response to our 30mg/kg oral dose we observed robust PD including 90% tumor growth inhibition in a mouse TGI model. Lead optimization of this series is ongoing. Title: Preclinical characterization of CGT6297, a novel PI3Kα H1047R mutant-selective inhibitorSession Category: Experimental and Molecular TherapeuticsSession Title: Kinase and Phosphatase Inhibitors 2Session Date and Time: April 28, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 20Poster Board Number: 5Published Abstract Number: 3004 Cogent is developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage for the both the H1047R mutation as well as E542K and E545K helical mutants. 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. In the poster being presented today, Cogent’s preclinical candidate CGT6297 demonstrates broad cellular panel profiling across multiple resistant and mutated cell lines, including, for the first time, efficacy against PI3K helical mutations. The poster also showcases the activity of CGT6297 in both ST1056 (H1047R mutant) and MCF-7 (E545K mutant) breast cancer TGI models. Title: The Reversible and Selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR inhibitorsSession Category: Clinical ResearchSession Title: Targeted Therapies and Combinations 2Session Date and Time: April 29, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 34Poster Board Number: 27Published Abstract Number: 4729 FGFR inhibitors are well-established oncogenic drivers in multiple diseases, but approved medicines fail to capture the full landscape of FGFR altered tumor types, with FGFR1-mediated hyperphosphatemia serving as the most common dose-limiting toxicity for pan-FGFR inhibitors. The poster presented today describes Cogent’s internally-developed FGFR2/3 inhibitor which maintains potency on FGFR2 mutations and is selective against the entire kinome and a broad panel of channels and receptors. Exploratory pharmacokinetics (PK) studies conducted across species showed CGT4859 to be a low-clearance compound with high oral bioavailability. Further, in an AN3 CA model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at >2.5 mg/kg QD or BID and was well-tolerated. Cogent is currently enrolling patients in an ongoing Phase 1 trial with CGT4859 in patients with confirmed FGFR2 or FGFR3 mutations, including patients with advanced cholangiocarcinoma. The trial is designed to explore the safety, tolerability and clinical activity of escalating doses with the goal of selecting an active and well tolerated dose for further clinical investigation. Title: Identification of CGT4255 an EGFR-sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetrationSession Category: Experimental and Molecular TherapeuticsSession Title: Novel Antitumor Agents 3Session Date and Time: April 29, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 21Poster Board Number: 1Published Abstract Number: 5623 Cogent’s potential best-in-class EGFR-sparing, brain-penetrant ErbB2 inhibitor includes potent coverage of key mutations (YVMA, S310F, V842I, L755S) inadequately addressed by currently approved therapies. Activating mutations in the ErbB2 gene have been identified in multiple cancers and demonstrate a tumorigenic role similar to that of ErbB2 amplification. New data presented on this compound describes CGT4255’s exceptional stability in human whole blood and liver cytosol fractions and high oral bioavailability and low clearance across preclinical species. In addition, CGT4255 is expected to have equivalent brain to plasma exposure suggesting potential best-in class properties. All posters will be available on the ‘Posters and Publications’ page of Cogent’s website. New Leadership AppointmentsCogent also announced today that Ray Frost has joined Cogent as Senior Vice President, Market Access and Adam Boyd, Ph.D. has joined Cogent as Senior Vice President, Corporate Strategy. Mr. Frost joins Cogent with over 20 years of industry experience. Previously he served as Vice President Market Access at Ono Pharma USA and Zealand Pharma (Zealand). While at Zealand he played an integral part in building the commercial infrastructure to support the launch of their first product. Prior to Zealand he held roles of increasing responsibility in Market Access and Health Policy at Melinta Therapeutics, The Medicines Company, Bayer Healthcare, Eisai and MGI PHARMA. Mr. Frost is a graduate of Hofstra University. Dr. Boyd joins Cogent with nearly 25 years of industry experience building and leading global teams across Development functions including Biostatistics, Clinical Pharmacology, Clinical Operations, and Data Management. In these roles, he was instrumental in bringing several products to market, including Mektovi® (binimetinib), Braftovi® (encorafenib), Jakafi® (ruxolitinib), and Folotyn® (pralatrexate). Prior to joining Cogent, Dr. Boyd was Vice President, Biometrics at Intellia Therapeutics, and prior to that, held various roles of increasing responsibility at Pfizer, Array BioPharma, Novartis, and Allos Therapeutics. Dr. Boyd earned his Ph.D. in Biostatistics from the University of Colorado, where he is currently a member of the Colorado School of Public Health’s Dean’s Advisory Board. Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that, on April 14, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of “inducement” equity awards to five new employees, including Mr. Frost and Dr. Boyd, under the company’s 2020 Inducement Plan with a grant date of April 21, 2025. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 446,000 shares of Cogent common stock. Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date. 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. The company also has an ongoing Phase 1 study of its novel internally discovered FGFR2 inhibitor. In addition, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases targeting mutations in 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 best-in-class therapeutic potential of the company’s pre-clinical pipeline candidates. 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 Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings 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. Investor Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

WALTHAM, Mass. and BOULDER, Colo., March 25, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced four preclinical poster presentations at the upcoming 2025 AACR Annual Meeting being held in Chicago, IL April 25-30, 2025. Poster Details Title: Identification of a potent KRAS (ON) inhibitor with selectivity for mutant KRAS over HRAS and NRASSession Category: ChemistrySession Title: Lead Identification and OptimizationSession Date and Time: April 30, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 25Poster Board Number: 3Published Abstract Number: 6974 Title: Preclinical characterization of CGT6297, a novel PI3Kα H1047R mutant-selective inhibitorSession Category: Experimental and Molecular TherapeuticsSession Title: Kinase and Phosphatase Inhibitors 2Session Date and Time: April 28, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 20Poster Board Number: 5Published Abstract Number: 3004 Title: The Reversible and Selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR inhibitorsSession Category: Clinical ResearchSession Title: Targeted Therapies and Combinations 2Session Start: April 29, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 34Poster Board Number: 27Published Abstract Number: 4729 Title: Identification of CGT4255 an EGFR sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetrationSession Category: Experimental and Molecular TherapeuticsSession Title: Novel Antitumor Agents 3Session Start: April 29, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 21Poster Board Number: 1Published Abstract Number: 5623 Inducement Grant Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grant of an “inducement” equity award on March 21, 2025 to one new employee under the company’s 2020 Inducement Plan. The award was approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employee received a nonqualified option to purchase 9,700 shares of Cogent common stock. The option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date. 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. The company also has an ongoing Phase 1 study of its novel internally discovered FGFR2 inhibitor. In addition, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases targeting mutations in 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 clinical development plans and timelines and the potential of the company’s pipeline programs. 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 Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings 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. Investor Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com