Pralatrexate

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

2025年3月31日，CASI制药正式发布截至2024年12月31日的年度财务报告，并同步披露核心产品管线亮点及业务进展。 CASI制药董事长兼首席执行官何为无博士表示：“2024年是CASI的重要转型之年，我们通过战略性聚焦CID-103的开发，深化布局器官移植排斥反应及自身免疫疾病领域。CID-103是一种抗CD38抗体，有望成为治疗多种自身免疫性疾病和抗体介导的排斥反应(AMR)的突破性疗法。2025年1月完成的免疫性血小板减少症（ITP）首例患者给药，标志着全球临床开发进程的重要里程碑。目前，我们正与美国食品药品监督管理局（FDA）保持密切沟通，积极推进AMR临床试验暂停事项的解决方案。” 何博士补充道：“展望2025年，我们将继续推进CID-103的临床开发，并预计实现多个关键里程碑。我们将继续贯彻聚焦核心管线的战略，通过审慎的资本配置和高效的执行能力，持续造福患者、创造股东价值。 关键业务进展 • 2024年第四季度收入为1,340万美元，全年累计营收2,850万美元。 • 2024年6月21日，收到何为无博士发出的收购 CASI中国业务的要约。 • 2024年7月15日，与Venrock Healthcare Capital Partners、Foresite Capital、Panacea Venture及何为无博士达成1,500万美元私募融资协议。 核心管线进展 • 2024年5月15日，CID-103治疗ITP的临床试验获得FDA新药临床试验（IND）批准。 • 2024年10月24日，CID-103治疗ITP的临床试验获得中国国家药品监督管理局（NMPA）临床试验申请（CTA）批准。 • 2025年1月3日，CID-103在中国开展的I/II期临床试验完成首例患者给药，患者招募及治疗仍在进行中。 2025年预期里程碑 • 预计2025年第二季度FDA将对AMR临床试验暂停问题作出反馈。 • 计划于2025年第二季度提交CID-103用于再生障碍性贫血的IND申请。 • 预计2025年年中公布CID-103 ITP I期研究的中期数据。 • 计划于2025年第二季度完成Precision Autoimmune Therapeutics（PAT）的股权转让协议，届时CASI将获得CID-103所有适应症的全球独家权益。 产品亮点 CID-103 (抗CD38单克隆抗体) CID-103是一种全人源IgG1抗CD38单克隆抗体，可识别CD38分子上的独特表位。与其他抗CD38单抗相比，CID-103的临床前数据显示出更好的疗效和安全性。CASI拥有CID-103的全球独家权益，并正在推进其在慢性ITP、AMR等适应症的开发。2024年5月，CID-103 治疗成人ITP的I/II期临床试验获得FDA批准。2024年10月，中国CDE批准该研究在中国慢性ITP患者中开展。中国获批的临床试验，是CID-103全球临床试验的重要组成部分。2025年1月，该临床试验完成首例患者给药。此外，我们正全力协同FDA推进AMR临床试验暂停问题的解决。 迈维宁® (注射用盐酸美法仑) 迈维宁®于2018年12月获得中国国家药监局批准进口并上市，2019年8月正式商业化。迈维宁®进入中国市场之前，全国每年仅有800名多发性骨髓瘤患者接受自体移植。而自2019年迈维宁®上市以来，经过CASI团队的不懈努力，2023年已有近10,000名患者因迈维宁®而得到治疗获益。2024年，国内一家生产商推出同质化的注射用美法仑仿制药，导致市场竞争加剧，并对迈维宁®的销售造成一定影响。 富洛特® (普拉曲沙注射液) 2023年7月31日，CASI与Mundipharma International Corporation Limited（MICL），Mundipharma Medical Company (MMCo)及Acrotech Biopharma Inc.(Acrotech)达成转让协议，获得FOLOTYN® （富洛特®）在中国的商业化权益。富洛特®是一种二氢叶酸还原酶抑制剂，已获FDA和NMPA批准用于治疗复发或难治性外周T细胞淋巴瘤（PTCL）。2024年2月15日，富洛特®完成首例中国患者给药。 2024年第四季度及全年财务业绩 • 2024年第四季度收入1,340万美元，较2023年同期的690万美元增长94%，反映出公司下半年商业战略的成功执行。2024年全年收入为2,850万美元，较2023年的3,390万美元下降16%，主要受国产注射用美法仑竞争影响。 • 2024年第四季度研发支出370万美元，较2023年同期的230万美元增长61%，主要用于开发CID-103，以支持公司战略重点转向器官移植排斥和自身免疫疾病。2024年全年研发支出890万美元，较2023年990万美元下降10%，主要因2023年底注销仿制药组合，降低了摊销费用。 • 2024年第四季度管理与行政开支710万美元，较2023年640万美元增长11%，主要因合源生物仲裁相关法律费用增加。2024年全年管理与行政开支2,360万美元，较2023年2,540万美元下降7%，反映出公司在运营效率和成本控制方面的持续优化。 • 2024年净亏损为3,930万美元，2023年为2,630万美元。 • 截至2024年12月31日，公司现金及现金等价物总计1,350万美元，而2023年底为2,910万美元（包含短期投资）。 • 截至2024年12月31日的完整版20-F年报已发布于公司官网 www.casipharmaceuticals.com。需获取纸质版年度报告者，请致函：北京市朝阳区建国路81号华贸写字楼1座1701-1702室，CASI Pharmaceuticals, Inc. 投资者关系部，邮编：100025。