Elironrasib

Meg Flippin, Benzinga Staff Writer CHICAGO, IL AND FORT WORTH, TX / ACCESS Newswire / March 24, 2026 / Actuate Therapeutics, Inc. (NASDAQ:ACTU) is a clinical-stage biopharmaceutical company advancing elraglusib, a first-in-class, highly selective small-molecule inhibitor of glycogen synthase kinase-3 beta (GSK-3β). This multimodal agent targets tumor survival pathways, DNA damage response, NF-κB signaling and the tumor immune microenvironment, offering a new potential treatment across multiple difficult-to-treat cancers including metastatic pancreatic ductal adenocarcinoma (mPDAC), melanoma, colorectal cancer and sarcomas. What sets Actuate apart is its dual formulation strategy and recent momentum in pediatrics. While the company reports that the intravenous (IV) form has generated compelling clinical data, it is also advancing an oral tablet version of elraglusib that could significantly expand the drug's utility and commercial appeal. The Oral Compound: Convenience, Compliance And Broader Reach Actuate has successfully completed a phase 1 study of elraglusib oral formulation in healthy volunteers, demonstrating robust bioavailability-approximately 51% relative to IV when dosed with food-and dose-proportional pharmacokinetics without unexpected safety signals. A Phase 1 dose-escalation trial of the oral tablet in advanced cancer patients (Actuate-2401) is planned, with the oral formulation offering key advantages: daily dosing for steady-state exposure, improved patient compliance (especially in long-duration responses), lower manufacturing costs at commercial scale and potential expansion into pediatric populations or adult indications where oral therapies are preferred. This shift to oral could broaden elraglusib's addressable market while maintaining the same potent GSK-3β inhibition that has already shown disease control and responses when combined with chemotherapy backbones. Pediatric Breakthroughs And The Rare Pediatric Disease Priority Review Voucher (PRV) In January 2026, Actuate reported highly encouraging phase 1 data from the open-label Actuate-1902 trial in 40 children and adolescents (ages 3-21) with relapsed/refractory malignancies. Notable highlights included two complete responses in relapsed/refractory metastatic Ewing sarcoma and one complete response in relapsed/refractory metastatic neuroblastoma when elraglusib was combined with cyclophosphamide/topotecan. No maximum tolerated dose was reached, and responses supported plans to advance into Ewing sarcoma (and potentially neuroblastoma) in 2026. Crucially, the FDA first granted Rare Pediatric Disease Designation to elraglusib for neuroblastoma and subsequently for Ewing sarcoma in November 2024. Upon approval of a New Drug Application for either indication, Actuate would be eligible to receive a Priority Review Voucher (PRV). The PRV program incentivizes development for rare pediatric diseases (affecting fewer than 200,000 U.S. children) by granting the sponsor a voucher redeemable for a six-month priority FDA review of any future marketing application-potentially shaving four months off the standard 10-month timeline. Vouchers are fully transferable and can be sold to other companies, providing a non-dilutive financing mechanism that has historically delivered substantial value. The High Value Of Pediatric Review Vouchers And Recent Sales Actuate reports that PRVs have traded at premium prices in recent years, reflecting their ability to accelerate revenue for blockbuster candidates. Following the program's reauthorization through September 2029 via the Consolidated Appropriations Act of 2026, transaction values have remained strong: Jazz Pharmaceuticals sold a voucher for $200 million (January 2026) Fortress Biotech reportedly sold one for $205 million (February 2026) Abeona Therapeutics: $155 million (June 2025) Zevra Therapeutics: $150 million (April 2025) Ipsen: $158 million (August 2024) Acadia Pharmaceuticals and PTC Therapeutics: $150 million each (late 2024) Average recent sales have clustered around $150-200 million, with some exceeding that level. For a small-cap company like Actuate, monetizing a PRV could represent transformative non-dilutive capital to fund late-stage development, oral formulation advancement or strategic partnerships-without relying solely on equity raises or debt. Why RAS Inhibitor Leaders Like Revolution Medicines (RVMD) And Erasca (ERAS) May Need To Combine With Elraglusib RAS mutations drive ~30% of all human cancers, including the majority of pancreatic, colorectal and certain lung cancers-areas where single-agent RAS(ON) or RAS pathway inhibitors have shown promise but face adaptive resistance. In March 2026, Actuate launched a dedicated research initiative evaluating elraglusib in combination with emerging RAS-targeted therapies. Preclinical combination data are expected in the second half of 2026. The scientific rationale is compelling and multi-pronged, reports Actuate. Elraglusib's GSK-3β inhibition disrupts downstream survival signaling (via NF-κB and MYC suppression), impairs DNA damage repair and enhances anti-tumor immunity by boosting antigen presentation and activating T- and NK-cell responses. When paired with RAS(ON) inhibitors-which potently block proliferative RAS-GTP signaling-the combination can push tumor cells past the apoptotic threshold and overcome resistance mechanisms that limit monotherapy durability. Revolution Medicines (RVMD) is advancing a leading RAS(ON) portfolio, including the multi-selective inhibitor daraxonrasib (RMC-6236), G12C-selective elironrasib and G12D-selective zoldonrasib, with strong focus on KRAS-mutant pancreatic ductal adenocarcinoma (PDAC), NSCLC and colorectal cancer. Erasca (ERAS) is similarly pursuing RAS/MAPK pathway inhibitors. Both companies' assets excel at shutting down oncogenic RAS signaling but may benefit from orthogonal mechanisms like GSK-3β blockade to address tumor intrinsic resistance, immune evasion and microenvironment support. Actuate's initiative positions elraglusib as a natural complementary agent. In RAS-addicted tumors, the combination strategy could deliver deeper, more durable responses - potentially expanding the clinical and commercial opportunity for RVMD, ERAS and other RAS-focused players while creating high-value partnership or licensing opportunities for Actuate. Outlook: Multiple Catalysts And Strategic Optionality With positive pediatric data, an advancing oral formulation, mPDAC phase 2 overall survival signals and a new RAS combination program, Actuate is entering a high-impact period. A potential PRV monetization upon pediatric approvals could provide immediate capital, while the oral program and RAS research initiative open doors to broader adult oncology markets and collaborations. As the only clinical-stage GSK-3β inhibitor with this breadth of mechanistic and clinical support, Actuate believes elraglusib could become a backbone therapy in both rare pediatric cancers and the much larger RAS-mutant solid tumor landscape. For investors and patients alike, Actuate Therapeutics may deserve a closer look as a rather compelling case where scientific innovation, regulatory incentives and strategic positioning converge. Click here for more information on Actuate Therapeutics. Featured image from Shutterstock . This post contains sponsored content and was created in collaboration with a third-party partner. Benzinga is a publisher and does not provide personalized investment advice or act as a broker or dealer. This content is for informational purposes only and is not intended to be investing advice or an offer or solicitation to buy or sell any security. Contact: Investor Relations info@actuatetherapeutics.com SOURCE: Actuate Therapeutics, Inc. View the original press release on ACCESS Newswire

点击蓝字 关注我们 特别福利：通过平台指定基因检测公司进行基因检测并成功入组临床的患者，基因检测费用可以全额退款（限额5000元），具体请咨询平台医生（联系方式见文末）。 新 药 临 床 “一个新的药物就是一个新的希望！！！”                                     ------引言 温馨提示 更多新药免费临床试验信息，请访问下方网站： www.onc123.com/cpy.html 网站内可以直接按病种检索，无需爬楼梯！ 前言 在肿瘤治疗领域，KRAS突变一直是令人头疼的“硬骨头”——它被称为“不可成药”靶点，驱动着多种恶性肿瘤的发生发展，且长期缺乏针对性靶向药物。在这样的背景下，一款专门针对KRAS G12V突变的新型抑制剂RMC-5127，正式迈入人体临床试验阶段，为全球尤其是中国大量肿瘤患者带来了新的生存希望。 先搞懂：KRAS G12V突变，到底有多“棘手”？ 首先我们简单科普下核心靶点：致癌性RAS信号被激活后，会通过MAPK和PI3K两条关键通路驱动肿瘤发生发展；同时它会抑制机体干扰素信号、调控免疫抑制性细胞因子，并下调免疫识别分子，帮助肿瘤实现免疫逃逸，使免疫系统无法有效识别和清除肿瘤细胞。 其中，RAS G12V是第二常见的RAS依赖型癌症驱动突变，美国每年新增约4.8万例相关患者，涉及的主要癌种为胰腺导管腺癌、结直肠癌及非小细胞肺癌，这些也是我国肿瘤患者的高发癌种。 重点关注：中国患者的“特殊困境”，50万+人面临无药可治 根据中国人群大样本二代测序（NGS）数据显示，我国肿瘤患者整体KRAS突变率约为16.6%~19.97%，和西方人群的突变亚型分布有显著差异，核心特点的是：以G12D、G12V亚型为主，二者合计占比超70%。 具体来看不同癌种的突变情况，更能体现中国患者的需求紧迫性： 胰腺癌：KRAS突变率最高，达73.5%~88%，其中G12V占32%，是主要亚型之一，而西方人群常见的G12C突变在此极为罕见； 结直肠癌：KRAS突变率37.6%~41.45%，G12V占18.0%，位列主流亚型第二； 非小细胞肺癌：KRAS突变率约11.2%~12.8%，虽低于西方人群，但仍有部分患者携带G12V突变。 更关键的是，我国每年新发KRAS G12V、G12D相关癌症患者超50万，而目前这两种亚型尚无任何获批的靶向药物，患者只能依赖传统化疗、免疫治疗，疗效有限，存在极大的未满足临床需求——这也是RMC-5127的研发意义所在。 重磅登场：RMC-5127，针对性破解G12V突变的“精准武器” RMC-5127 是 Revolution Medicines在研的一款口服可利用、突变体选择性的三元复合物抑制剂，靶向结合处于活化 GTP 结合状态（ON 态）的 RAS G12V。 它的作用机制很巧妙，通俗来说就是“釜底抽薪”： 先与细胞内高丰度的伴侣蛋白亲环蛋白A结合，形成一个“二元复合物”； 这个复合物再与活化状态的RAS G12V结合，形成高亲和力的“三元复合物”； 通过空间位阻的方式，阻断下游效应蛋白与RAS G12V结合，从而彻底抑制致癌信号传导，让肿瘤细胞停止生长。 值得一提的是，这款药物具备口服可利用的优势，且有研究显示其具备穿透血脑屏障的能力，未来或可用于治疗脑转移患者，进一步拓宽适用范围。 临床进展：首例患者已给药，联合PD-1疗效惊艳 2026年1月29日，Revolution Medicines宣布，RMC-5127的首次人体临床试验（编号RMC-5127-001，临床试验登记号：NCT07349537）已完成首例患者给药，标志着这款药物正式进入临床验证阶段。 这项临床试验为开放标签设计，核心目的是评估RMC-5127单药及联合用药的安全性、耐受性和初步抗肿瘤活性，入组人群主要是携带RAS G12V突变的实体瘤患者，包括胰腺导管腺癌、结直肠癌、非小细胞肺癌，且患者需是既往标准治疗（含靶向治疗）后疾病进展或无法耐受的人群——这意味着，它将为晚期耐药患者提供新的治疗选择。 而在今年的美国癌症研究协会免疫肿瘤学会议（AACR IO）上，RMC-5127公布的临床前数据更是让人眼前一亮： 在KRAS G12V驱动的结直肠癌模型中，口服RMC-5127可使40%的肿瘤完全消退； 对于对抗PD-1单药治疗耐药的模型，RMC-5127联合抗PD-1治疗可实现100%的持久完全消退，且肿瘤再攻击实验证实，机体形成了免疫记忆，意味着患者可能获得长期获益； 在胰腺癌、肺癌的相关模型中，无论肿瘤免疫微环境是高T细胞浸润还是低T细胞浸润，RMC-5127都能快速诱导肿瘤消退，还能增加T细胞浸润、上调免疫识别分子，帮免疫系统“认出”并清除肿瘤细胞。 背后力量：Revolution Medicines，深耕RAS突变的“研发巨头” 研发出RMC-5127的Revolution Medicines，是美国一家处于临床后期的肿瘤药物研发公司，核心使命就是为RAS依赖型癌症患者开发新型靶向治疗药物，打破“不可成药”的困境。 目前，该公司拥有一条丰富的RAS（ON）抑制剂研发管线，涵盖多种KRAS突变亚型，形成了“全面覆盖”的布局，其中进入临床阶段的就有4款，包括： daraxonrasib（RMC‑6236）：多选择性RAS抑制剂，可覆盖多种突变亚型； elironrasib（RMC‑6291）：专门针对G12C突变； zoldonrasib（RMC‑9805）：专门针对G12D突变； RMC‑5127：专门针对G12V突变。 除此之外，公司还有针对Q61H、G13C等其他RAS突变亚型的在研项目，未来有望打造出“全方位破解RAS突变”的治疗矩阵。截至2026年3月20日，Revolution Medicines的总市值已达189.81亿美元，彰显了市场对其研发实力的认可。 总结：不止是一款新药，更是50万中国患者的新希望 RMC-5127的临床推进，不仅进一步拓宽了RAS突变亚型的靶向治疗覆盖范围，更精准击中了中国患者的核心需求——我国50万+KRAS G12V、G12D突变患者，终于有望告别“无药可治”的困境。 更值得期待的是，RMC-5127联合PD-1的临床前数据表现惊艳，未来若能在临床试验中验证这一疗效，将为晚期肿瘤患者提供“靶向+免疫”的全新联合方案，进一步提升治疗效果、延长患者生存期。 随着医学研究的不断突破，曾经的“不可成药”靶点正在被逐一攻克。我们将持续关注RMC-5127的临床试验进展，第一时间为大家带来最新消息，也祝愿这款药物早日落地，为更多肿瘤患者带来生的希望。 免责声明：本文仅作信息交流之目的，文中观点不代表平台立场，亦不代表平台支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 我们的优势 最后，我们强烈建议选择我们的渠道进行临床报名，相比其他招募渠道，我们有更完整的临床项目库，我们了解病情、了解各个招募项目的入排要求、更了解项目之间的合理搭配，能让患者大大增加连续入组的成功率！通过我们报名的临床，入组成功率更高、获益更大! 欢迎在其他渠道报名失败的患者和家属联系我们！ 目前有肺癌、肝癌、肾癌、胃癌、肠癌、胰腺癌、妇瘤、泌尿肿瘤、血液肿瘤......等几乎涵盖所有癌种的临床试验正在招募患者！ 而且每一个在我们这里报名的患者，通过平台进行基因检测并成功入组患者，全额退还基因检测费用。 平台福利 福利一、免费基因检测（限初诊或耐药肿瘤患者，生活能自理且有意愿参加临床试验） 免费基因检测 长按左侧二维码报名 福利二、免费临床试验入组 免费临床试验入组 长按左侧二维码报名 基 因         免费基因检测咨询       18024087280        （微信手机同号）          长按上方二维码咨询 肿 瘤         免费临床试验入组咨询       13022079715        （微信手机同号）          长按上方二维码咨询 #临床试验#KRAS突变#实体瘤#胰腺癌