Losmapimod

― Announced positive 12-week results from the 20 mg dose cohort of the Phase 1b PIONEER trial of pociredir in sickle cell disease (SCD) ― ― 20 mg cohort demonstrated rapid and robust fetal hemoglobin (HbF) induction, with mean absolute HbF increasing by 12.2% from a baseline of 7.1% to 19.3% at Week 12, improvements in markers of hemolysis and anemia, and encouraging trends in vaso-occlusive crisis (VOC) reduction ― ― Fulcrum plans to initiate a potential registration-enabling trial in the second half of 2026 ― ― Ended 2025 with $352.3 million in cash, cash equivalents, and marketable securities; cash runway into 2029 ― CAMBRIDGE, Mass., Feb. 24, 2026 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. ® (Fulcrum) (Nasdaq: FULC), a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases, today reported financial results for the fourth quarter and full year 2025 and provided a business update. “Building on the previously reported interim data presented in December at ASH, the positive 12-week data from the complete 20 mg cohort of the PIONEER trial reinforce our conviction in pociredir’s potential to address the underlying biology of sickle cell disease,” said Alex C. Sapir, Fulcrum’s President and Chief Executive Officer. “The magnitude of HbF induction, progression toward pan-cellular distribution, and improvements in markers of hemolysis and anemia observed to date position us well as we prepare for discussions with the FDA regarding the design of the next study. With a strong balance sheet extending our cash runway into 2029, we believe we are well positioned to continue to advance pociredir and our broader benign hematology pipeline.” Recent Business Highlights Announced positive 12-week results from the 20 mg dose cohort (n=12) of the Phase 1b PIONEER trial in SCD, building upon previously reported interim data presented at the 2025 American Society of Hematology (ASH) Annual Meeting. Mean absolute HbF increased by 12.2% from a baseline of 7.1% to 19.3% at Week 12. Results demonstrated progression toward pan-cellular HbF induction, improvements in markers of hemolysis and anemia, and encouraging trends in VOC reduction. Pociredir continued to be generally well-tolerated, with no treatment-related serious adverse events reported as of the December 23, 2025 data cutoff. In December 2025, completed an underwritten public offering of common stock and pre-funded warrants raising $164.2 million of net proceeds, strengthening Fulcrum's balance sheet to support advancement of pociredir through the next phase of development among other general corporate purposes. Fulcrum expects to provide additional details regarding the design of its next trial in the second quarter of 2026 following receipt of meeting minutes from its End-of-Phase meeting with the FDA. Pending feedback from the FDA, Fulcrum plans to initiate a potential registration-enabling trial in the second half of 2026. Activating sites for an open label extension trial for participants in the PIONEER trial to evaluate the safety and durability of response with pociredir. Based on results from IND-enabling studies, Fulcrum has decided not to advance its program for bone marrow failure syndromes into clinical development and will focus its resources on advancing pociredir and its core benign hematology programs. Fourth Quarter and Full Year 2025 Financial Results Cash Position: As of December 31, 2025, cash, cash equivalents, and marketable securities were $352.3 million, as compared to $241.0 million as of December 31, 2024. The increase of $111.3 million is primarily due to net proceeds of $164.2 million from the December 2025 public offering of our common stock and pre-funded warrants, partially offset by cash used to fund operating activities in 2025. R&D Expenses: Research and development expenses were $15.4 million for the three months ended December 31, 2025, as compared to $11.7 million for the three months ended December 31, 2024. The increase of $3.7 million was primarily due to increased costs related to the advancement of the PIONEER trial. Research and development expenses were $56.1 million for the year ended December 31, 2025, as compared to $63.4 million for the year ended December 31, 2024. The decrease of $7.3 million was primarily due decreased costs associated with the discontinuation of our losmapimod program and the reimbursement from the global development cost sharing under the now-terminated collaboration with Sanofi, partially offset by increased costs related to the advancement of the PIONEER trial. G&A Expenses: General and administrative expenses were $7.3 million for the three months ended December 31, 2025, as compared to $7.7 million for three months ended December 31, 2024. The decrease of $0.4 million was primarily due to decreased professional services costs. General and administrative expenses were $28.7 million for the year ended December 31, 2025, as compared to $36.4 million for the year ended December 31, 2024. The decrease of $7.7 million was primarily due to decreased professional services costs and decreased employee compensation costs as a result of the reduction in workforce implemented in the third quarter of 2024. Net Loss: Net loss was $20.3 million for the three months ended December 31, 2025, as compared to a net loss of $16.6 million for the three months ended December 31, 2024. Net loss was $74.9 million for the year ended December 31, 2025, as compared to $9.7 million for the year ended December 31, 2024. Cash Runway Guidance Based on its current operating plans, Fulcrum now expects that its current cash, cash equivalents, and marketable securities will be sufficient to fund its operating requirements into 2029. About Fulcrum Therapeutics Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum’s lead clinical program is pociredir, a small molecule designed to increase expression of HbF for the treatment of SCD. Fulcrum uses proprietary technology to identify drug targets that can modulate gene expression to treat the known root cause of gene mis-expression. For more information, visit and follow us on X (@FulcrumTx) and LinkedIn. About Pociredir Pociredir is an investigational oral small-molecule inhibitor of Embryonic Ectoderm Development (EED) that was discovered using Fulcrum’s proprietary discovery technology. Inhibition of EED leads to potent downregulation of key fetal globin repressors, including BCL11A, thereby causing an increase in HbF. Pociredir is being developed for the treatment of SCD. In the PIONEER Phase 1b clinical trial in people with SCD, pociredir has demonstrated dose-dependent increases in HbF, pan-cellular HbF induction, and improvements in markers of hemolysis and anemia. Across the 12 mg and 20 mg dose cohorts, pociredir has been generally well-tolerated with up to three months of exposure, with no treatment-related serious adverse events reported through the December 23, 2025 data cutoff date. Pociredir has been granted Fast Track and Orphan Drug Designation from the FDA for the treatment of SCD. To learn more about clinical trials of pociredir please visit ClinicalTrials.gov . About Sickle Cell Disease SCD is a genetic disorder of the red blood cells caused by a mutation in the HBB gene. This gene encodes a protein that is a key component of hemoglobin, a protein complex whose function is to transport oxygen in the body. The result of the mutation is less efficient oxygen transport and the formation of red blood cells that have a sickle shape. These sickle shaped cells are much less flexible than healthy cells and can block blood vessels or rupture cells. People with SCD typically suffer from serious clinical consequences, which may include anemia, pain, infections, stroke, heart disease, pulmonary hypertension, kidney failure, liver disease, and reduced life expectancy. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release are forward-looking statements, including express or implied statements regarding Fulcrum’s clinical development of pociredir, including an open-label extension trial and receiving feedback from regulators on trial design and commencing a registrational trial; the potential of pociredir to increase HbF to levels that could ameliorate symptoms of SCD and transform the standard of care; Fulcrum’s ability to progress its early stage development programs and enable IND filings related thereto; and Fulcrum’s projected cash runway, among others. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Fulcrum’s ability to continue to advance its product candidates in clinical trials, including progressing early stage candidates into the clinic; initiating and enrolling clinical trials on the timeline expected or at all; including receiving feedback from, and obtaining and maintaining necessary approvals from the FDA and other regulatory authorities; replicating in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials; obtaining, maintaining or protecting intellectual property rights related to its product candidates; managing expenses; and raising the substantial additional capital needed to achieve its business objectives, among others. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Fulcrum’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties, and other important factors, in Fulcrum’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Fulcrum’s views as of the date hereof and should not be relied upon as representing Fulcrum’s views as of any date subsequent to the date hereof. Fulcrum anticipates that subsequent events and developments will cause Fulcrum’s views to change. However, while Fulcrum may elect to update these forward-looking statements at some point in the future, Fulcrum specifically disclaims any obligation to do so. Fulcrum Therapeutics, Inc. Selected Consolidated Balance Sheet Data (In thousands) (Unaudited) December 31, 2025 December 31, 2024 Cash, cash equivalents, and marketable securities $ 352,306 $ 241,021 Working capital (1) 344,432 238,879 Total assets 366,284 260,718 Total stockholders’ equity 349,000 243,034 (1) Fulcrum defines working capital as current assets minus current liabilities. Fulcrum Therapeutics, Inc. Consolidated Statements of Operations (In thousands, except per share data) (Unaudited) Three Months Ended December 31, Year Ended December 31, 2025 2024 2025 2024 Collaboration revenue — — — 80,000 Operating expenses: Research and development 15,416 11,713 56,103 63,386 General and administrative 7,277 7,716 28,666 36,448 Restructuring expenses — — — 2,063 Total operating expenses 22,693 19,429 84,769 101,897 Loss from operations (22,693) (19,429) (84,769) (21,897) Other income, net 2,359 2,861 9,889 12,172 Net loss $ (20,334) $ (16,568) $ (74,880) $ (9,725) Net loss per share, basic and diluted $ (0.31) $ (0.31) $ (1.18) $ (0.16) Weighted-average common shares outstanding, basic and diluted 65,781 53,954 63,355 61,984 Contact: Kevin Gardner LifeSci Advisors, LLC kgardner@lifesciadvisors.com 617-283-2856

哪些是MNC补位需求迫切的赛道？ 撰文丨拿铁 中国创新药BD交易2025年最新数据出炉。出海授权全年交易总金额达到1356.55亿美元，较2024年的519亿美元大幅增长161%；首付款70亿美元；交易总数量达到157起，较去年94起交易大幅增长67%[1]。 这背后的原因，离不开众多MNC在未来几年将遭遇核心产品专利悬崖压力。预计截至2037年，将有超25款重磅药物面临专利悬崖，合计潜在损失金额超2300亿美元。其中包括辉瑞的阿哌沙班、默沙东的K药、BMS的O药、诺和诺德的司美格鲁肽、艾伯维的利生奇珠单抗、礼来的替尔泊肽等。我们以近年来BD较为活跃的赛诺菲、辉瑞、诺和诺德为例，分析它们如何创造未来BD机遇。这个机会窗口中，中国药企将扮演怎样的角色，2026年还可以有哪些BD交易期待？ 赛诺菲：罕见病、自免领域 赛诺菲的度普利尤单抗核心专利（美国）将于2031年到期，该药物曾是赛诺菲“Play to Win”战略的核心产品，为了打造第二增长曲线，赛诺菲通过多次对外合作以打破困局。 2025年11月19日，赛诺菲对Lifordi公司进行投资，Lifordi的核心产品LFD-200是一款靶向VISTA的自免ADC药物，作用机制为通过高度内化的细胞表面膜蛋白——VISTA，将高效糖皮质激素精准递送至靶细胞，实现持久、局部的免疫抑制效果，在保证疗效的同时，降低脱靶毒性风险。 VISTA具有快速内化和细胞内积累的独特生物学特性，该优势使其成为ADC疗法的理想选择。临床前研究表明，LFD-200具有血清半衰期短、免疫细胞内停留时间长的特点，并且能够在这些细胞内长期发挥免疫抑制功能。在2025年美国风湿病学会（ACR）年会上公布的数据显示，每周皮下注射一次LFD-200，持续13周，可在免疫细胞中维持糖皮质激素暴露，且未见系统性毒性的证据，LFD-200有望解决过去75年来限制糖皮质激素广泛长期使用的问题。 未来，VISTA靶向ADC或许是自免领域下一个待爆方向。近年来，赛诺菲一直在紧密追踪前沿医学动态，前瞻性地锁定未来的合作伙伴，及时充实自身产品管线，应对即将到来的专利悬崖。 2024年1月，赛诺菲与临床阶段生物制药上市公司Inhibrx达成22亿美元的并购协议，强化在罕见病、炎症免疫领域的地位。 2024年5月，赛诺菲与生物制药公司Fulcrum就后者在研新药Losmapimod达成合作，赛诺菲获得Losmapimod在美国以外所有地区的独家商业化权益，Fulcrum保留Losmapimod在美国的商业化权益，并将获得8000万美元首付款等。Losmapimod是一种选择性p38α/β丝裂原活化蛋白激酶（MAPK）抑制剂，针对面肩肱型肌营养不良症（FSHD），曾有望成为全球首个获批的FSHD治疗药物。但在2024年9月公布的III期临床结果中，Losmapimod治疗FSHD未能达到主要终点，赛诺菲终止合作。 2024年9月，赛诺菲与天境生物合作，以不超过20亿人民币，获得天境生物的CD73单抗——尤莱利单抗（uliledimab）在大中华区的开发与商业化权益。 可以看出，赛诺菲正在努力通过对外合作来提升自己在罕见病和自免等领域的实力，以期寻找到下一个具有差异化优势的重磅产品。 辉瑞：肿瘤、代谢领域 辉瑞在疫情期间凭借新冠疫苗赚得盆满钵满。如今业界传出辉瑞计划出售所持新冠疫苗合伙人——BioNTech的455万股存托凭证，这意味着曾经的疫情红利不再，辉瑞失去了一个强大的利润引擎。 更让辉瑞“揪心”的是，核心产品阿哌沙班将在2026年专利到期，这款由辉瑞/BMS共同开发的口服Xa因子抑制剂，自上市以来销售额不断增长，2024年达到206亿美元，2025年上半年销售超110亿美元，是小分子药物销量王者。 面对失去的新冠疫苗红利和核心产品的专利悬崖，辉瑞迫切需要找到下一个增长引擎。于是，在短短两年内，我们就看到辉瑞发起了多个百亿美元并购案。 最近一次是关注度极高的Metsera并购案。这家公司布局了极具差异化的代谢管线，其核心资产MET-097i是一款每月仅需注射一次的超长效GLP-1受体激动剂（GLP-1RA），在2025美国肥胖周（Obesity Week 2025）上，MET-097i用于减肥适应症的两项IIb期临床试验（VESPER-1和VESPER-3）取得积极结果，疗效与礼来公司的“当家花旦”Zepbound相当。治疗28周时，MET-097i相较于安慰剂的平均减重幅度最高达14.1%，部分受试者减重比例甚至高达26.5%，而且具有出色的耐受性。 这些积极结果引得诺和诺德前来竞争，最终在公平贸易委员会（FTC）的介入下，辉瑞以近100亿美元将Metsera收入囊中。对于在GLP-1领域自研产品遇到较多挫折的辉瑞来说，Metsera或将为其带来翻身机会。 在肿瘤领域，2025年5月，辉瑞与三生制药合作，以首付款12.5亿美元、里程碑款最高可达48亿美元的价格，获得后者PD-1/VEGF双抗——SSGJ-707（PF-08634404）在中国大陆以外全球范围的独家开发、生产及商业化权利。 在近期举办的投资者活动上，辉瑞明确表示了对PF-08634404的重视，宣布即将启动PF-08634404相关的7项近期临床，包括一线非小细胞肺癌（NSCLC）和一线结直肠癌的两项全球多中心III期临床试验，以及其他5项研究。 在NSCLC方面，辉瑞将开展PF-08634404联合化疗头对头Keytruda联合化疗，在一线治疗NSCLC上的研究。并且将计划探索PF-08634404与公司内部vedotin ADC的联用，以及探索PF-08634404在新辅助和辅助治疗阶段的应用等。 除了非小细胞肺癌、结直肠癌，辉瑞还将开展PF-08634404在广泛期小细胞肺癌、肝癌、尿路上皮癌和肾癌的应用。辉瑞预计，2026年底PF-08634404的全球多中心临床数量将超过20个，力图将其打造成管线网络中的基石产品。 更早之前，辉瑞还以430亿美元收购ADC领头羊Seagen，将Padcev、Adcetris等核心资产收入囊中，一跃成为ADC领域龙头。 辉瑞凭借“钞能力”和高效的执行效率，立志在肿瘤和代谢领域迎头赶上。 诺和诺德：减重、降糖及相关并发症 丹麦制药巨头诺和诺德凭借GLP-1RA——司美格鲁肽（Ozempic、Rybelsus、Wegovy），曾经富可敌国，然而随着礼来替尔泊肽的后来居上、诺和诺德下一代减肥药CagriSema疗效未达预期，以及美国本土市场仿制药挤压，诺和诺德的股价出现下滑。更紧迫的是，司美格鲁肽的美国专利将在2032年到期，诺和诺德亟需下一个接棒产品。 为了快速开启新篇章，诺和诺德采取了相对激进的措施。首先在2025年5月，前CEO周赋德（Lars Fruergaard Jørgensen）因市场表现不佳而离职，由公司内部人员杜麦克（Maziar Mike Doustdar）接任。接着，杜麦克在上任后迅速推出了大规模重组计划，包括在全球范围内裁员约9000人，以削减成本并重新聚焦业务。 变动之际，诺和诺德也从原来依赖内部研发，转向更开放的姿态。2024年2月，诺和诺德与Neomorph合作，共同发现、开发和商业化多个分子胶降解剂，潜在交易总价值高达14.6亿美元。2025年3月，诺和诺德以最高20亿美元，获得联拓生物的GLP-1/GIP/GCG三重受体激动剂Ubt-251除中国以外的独家权益。2025年10月，诺和诺德以高达52亿美元的总额，收购Akero Therapeutics，用于开发与肥胖相关的肝病MASH的治疗药物。2025年11月，诺和诺德与辉瑞竞购Metsera。 同时，围绕司美格鲁肽，诺和诺德还在推进多个适应症的临床试验，包括糖尿病相关的慢性肾病、心血管疾病以及阿尔茨海默症等。 总的来说，诺和诺德聚焦的仍是降糖、减重这一代谢领域，未来能否走出新的篇章，值得期待。 中国创新药企的机会 药品专利悬崖是各大药企都绕不过的关键挑战之一，而中国药企可能会在未来全球创新生态中扮演重要角色。主要源于三方面原因：首先，自从中国在2017年加入ICH后，国内临床数据的完整性、临床试验的质量得到显著改善，逐步获得海外同行认可。这一变化在近两年不断发生的出海交易中得到体现。 临床质量提高之外，国内药企越来越注重创新质量。在过去十年，中国构建了与FDA类似的创新政策体系，创新药企从以前的改进型、BIC型创新逐步过渡到源头创新。这些创新正在被MNC看见，一年多来，在对外授权交易中，国产ADC引领风潮，双抗成为BD新宠，而独特的NewCo和Co-Co模式也正在改写国际化合作路径。 成本优势也是MNC在中国加大“扫货”力度的主要原因之一。据摩根士丹利推算，中国临床III期受试者的直接成本为2.5万美元/人，美国为6.9万美元/人，药物研发平均回报率（IRR）约8.5%，是美国纯本土研发（3.6%）的2.4倍。 一系列因素驱动下，MNC开始与中国创新药产业深度绑定，并在国内新建多个研发中心，中国的创新药资产正向全球创新舞台中央走去。从近期密集发生的交易情况来看，自免、代谢、肿瘤、罕见病或是MNC补位需求迫切的赛道，短短数年内行业市场格局或将迎来变革性重塑。而中国药企如何抓住这波风口，MNC如何妥当处理专利悬崖，2026年值得继续期待。 数据来源：【1】医药魔方数据库 END 往期精彩内容 替尔泊肽在华获批新适应症；中国小核酸管线44亿美元出海 长期主义深耕，阿斯利康呼吸赛道的“解题思路” 2025药企肿瘤收入TOP5：默沙东仍霸榜，阿斯利康升至第2，强生大涨22%