First in Human Phase 1 Trial of ELI-002 Immunotherapy as Treatment for Subjects With Kirsten Rat Sarcoma (KRAS) Mutated Pancreatic Ductal Adenocarcinoma and Other Solid Tumors

This is a Phase 1 study to assess the safety and efficacy of ELI-002 immunotherapy (a lipid-conjugated immune-stimulatory oligonucleotide [Amph-CpG-7909] plus a mixture of lipid-conjugated peptide-based antigens [Amph-Peptides]) as adjuvant treatment of minimal residual disease (MRD) in subjects with KRAS/neuroblastoma ras viral oncogene homolog (NRAS) mutated PDAC or other solid tumors.

开始日期2021-10-04

申办/合作机构

Elicio Therapeutics, Inc.

100 项与 ELI-002 相关的临床结果

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100 项与 ELI-002 相关的转化医学

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100 项与 ELI-002 相关的专利（医药）

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项与 ELI-002 相关的文献（医药）

2024-02-01·Nature medicine1区 · 医学

Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial

1区 · 医学

Article

作者: Seenappa, Lochana M ; Wainberg, Zev A ; Chung, Vincent ; VanWyk, Haley ; DeMuth, Peter C ; Devoe, Craig E ; Furqan, Muhammad ; Weekes, Colin D ; McNeil, Lisa K ; Kasi, Pashtoon M ; Pant, Shubham ; Tavares, Amy M ; Perry, James R ; Haqq, Christopher M ; Welkowsky, Esther ; O'Reilly, Eileen M ; Kheoh, Thian ; Leal, Alexis D ; Basturk, Olca

Abstract:

Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). We treated 25 patients (20 pancreatic and five colorectal) who were positive for minimal residual mKRAS disease (ctDNA and/or serum tumor antigen) after locoregional treatment in a phase 1 study of fixed-dose Amph-Peptides-2P and ascending-dose Amph-CpG-7909; study enrollment is complete with patient follow-up ongoing. Primary endpoints included safety and recommended phase 2 dose (RP2D). The secondary endpoint was tumor biomarker response (longitudinal ctDNA or tumor antigen), with exploratory endpoints including immunogenicity and relapse-free survival (RFS). No dose-limiting toxicities were observed, and the RP2D was 10.0 mg of Amph-CpG-7909. Direct ex vivo mKRAS-specific T cell responses were observed in 21 of 25 patients (84%; 59% both CD4+ and CD8+); tumor biomarker responses were observed in 21 of 25 patients (84%); biomarker clearance was observed in six of 25 patients (24%; three pancreatic and three colorectal); and the median RFS was 16.33 months. Efficacy correlated with T cell responses above or below the median fold increase over baseline (12.75-fold): median tumor biomarker reduction was −76.0% versus −10.2% (P < 0.0014), and the median RFS was not reached versus 4.01 months (hazard ratio = 0.14; P = 0.0167). ELI-002 2P was safe and induced considerable T cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors. ClinicalTrials.gov identifier: NCT04853017.

Cells

Advances in Non-Small Cell Lung Cancer Cellular Immunotherapy: A Progress in Dendritic Cell, T-Cell, and NK Cell Vaccines

Review

作者: Aslam, Mohammad ; Ayaz, Asma ; Zaman, Wajid ; Masroor Ali Beg, Mirza ; Akhtar, Muhammad Saeed

Over the past decade, cellular immunotherapy has emerged as a transformative strategy for non-small cell lung cancer (NSCLC), with dendritic-cell (DC) vaccines, T-cell vaccines, and natural killer (NK)-cell therapies demonstrating distinct mechanisms and clinical potential. DC vaccines capitalize on antigen presentation to prime tumor-specific T-cell responses, showing excellent safety profiles limited mainly to injection-site reactions and flu-like symptoms. While monotherapy has shown limited efficacy, combinations with checkpoint inhibitors or chemotherapy enhance immune activation and survival outcomes. Recent innovations, including neoantigen-loaded, mRNA-electroporated, and exosome-pulsed DCs, demonstrate improved immunogenicity and personalized approaches. T-cell vaccines, designed to activate cytotoxic CD8+ T-cell responses, have been tested across multiple platforms, including peptide-based (MAGE-A3), viral vector (TG4010/MUC1), and mRNA (CV9201/92) formulations. While the phase III MAGRIT trial presented no disease-free survival (DFS) benefit with adjuvant MAGE-A3 vaccination, the TG4010 vaccine improved progression-free survival (PFS; HR 0.66) and overall survival (OS; HR 0.67) in MUC1-positive NSCLC when combined with chemotherapy. Current strategies focus on personalized neoantigen vaccines and KRAS-targeted approaches (e.g., ELI-002), with ongoing phase III trials evaluating their potential in resectable NSCLC. NK-cell therapies have also shown promise, with early trials establishing the feasibility of autologous and allogeneic infusions, while engineered CAR-NK cells enhance tumor-specific targeting. Combination strategies with checkpoint inhibitors significantly improve response rates and PFS, revealing synergies between innate and adaptive immunity. Recent advances include cytokine-enhanced, memory-like NK cells to overcome immunosuppression and “off-the-shelf” products for broader clinical use. Together, these cellular immunotherapies represent a versatile and evolving frontier in NSCLC treatment, with ongoing research optimizing combinations, delivery platforms, and patient selection to maximize therapeutic benefit.

NATURE MEDICINE

Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results

Article

作者: Welkowsky, Esther ; Pant, Shubham ; Kheoh, Thian ; Wainberg, Zev A ; Chung, Vincent ; Furqan, Muhammad ; Weekes, Colin D ; Devoe, Craig E ; DeMuth, Peter C ; O'Reilly, Eileen M ; McNeil, Lisa K ; Perry, James R ; Leal, Alexis D ; Kasi, Pashtoon M ; Haqq, Christopher M

Abstract:

Cellular immunity, mediated by tumor antigen-specific CD4+ and CD8+ T cells, has a critical role in the success of cancer immunotherapy by targeting intracellular driver and passenger tumor mutations. We present the final results of the phase 1 AMPLIFY-201 trial, in which patients who completed standard locoregional treatment, with minimal residual mKRAS disease (n = 25, 20 pancreatic cancer and 5 colorectal cancer), received monotherapy vaccination with lymph node-targeting ELI-002 2P, including mutant KRAS (mKRAS) amphiphile-peptide antigens (G12D, G12R) and amphiphile-adjuvant CpG-7909. At a median follow-up of 19.7 months, efficacy correlated with mKRAS-specific T cell responses above or below a threshold 9.17-fold increase over baseline, with median radiographic relapse-free survival not reached, versus 3.02 months (hazard ratio (HR) = 0.12, P = 0.0002) and median overall survival not reached versus 15.98 months (HR = 0.23, P = 0.0099). Seventy-one percent of evaluable patients induced both CD4+ and CD8+ subsets, with sustained immunogenicity. Following ELI-002 2P treatment, antigen spreading was observed in 67% of patients, with increased T cells reactive to personalized, tumor antigens absent from the ELI-002 2P vaccine. Therefore, lymph node-targeting amphiphile vaccination induces persistent T cell responses targeting oncogenic driver KRAS mutations, alongside personalized, tumor antigen-specific T cells, which may correlate to clinical outcomes in pancreatic and colorectal cancer. ClinicalTrials.gov registration: NCT04853017.

122

项与 ELI-002 相关的新闻（医药）

2025-11-03

·GlobeNewswire-Health Care

Elicio Therapeutics to Present Clinical and Preclinical Data at the SITC 2025 Annual Meeting

Late-breaking poster presentation to highlight new immunogenicity data from ongoing Phase 2 AMPLIFY-7P trial of ELI-002 in patients with mKRAS-driven pancreatic cancerBOSTON, Nov. 03, 2025 (GLOBE NEWSWIRE) -- Elicio Therapeutics, Inc. (Nasdaq: ELTX, “Elicio” or the “Company”), a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer, today announced that the Company will present a late-breaking update on clinical immunogenicity results from its ongoing Phase 2 AMPLIFY-7P trial of ELI-002 in patients with mKRAS-driven pancreatic cancer and preclinical data from ELI-004 for the treatment of advanced solid tumors via two accepted poster presentations at the Society for Immunotherapy of Cancer’s (“SITC”) 40th Anniversary Annual Meeting, taking place November 5–9, 2025, in National Harbor, Maryland. Presentation Details: Late-breaking Abstract (“LBA”) Poster Presentation Title: AMPLIFY-7P Phase 2: T cell responses induced by ELI-002 7P, a lymph node-targeted amphiphile therapeutic cancer vaccine in patients with KRAS mutated pancreatic ductal adenocarcinomaPresenter: Lisa McNeil, Ph.D., Vice President, Translational Medicine at ElicioAbstract Number: 1317Session Date: Friday, Nov. 7, 2025Location: Prince George ABC Exhibit Halls – Gaylord National Resort and Convention Poster Presentation Title: Amphiphile (AMP)-Immunomodulator therapy controls growth and eradicates syngeneic solid tumors Presenter: Martin Steinbuck, Ph.D., Director of Research at ElicioAbstract Number: 946Session Date: Saturday, Nov. 8, 2025Location: Prince George ABC Exhibit Halls – Gaylord National Resort and Convention About Elicio Therapeutics Elicio Therapeutics, Inc. (Nasdaq: ELTX) is a clinical-stage biotechnology company advancing novel immunotherapies for the treatment of high-prevalence cancers, including mKRAS-positive pancreatic and colorectal cancers. Elicio intends to build on recent clinical successes in the personalized cancer immunotherapy space to develop effective, off-the-shelf immunotherapies. Elicio’s Amphiphile (“AMP”) technology aims to enhance the education, activation and amplification of cancer-specific T cells relative to conventional immunotherapy strategies, with the goal of promoting durable cancer immunosurveillance in patients. Elicio’s ELI-002 lead program is an off-the-shelf immunotherapy candidate targeting the most common KRAS mutations, which drive approximately 25% of all solid tumors. Off-the-shelf immunotherapy approaches have the potential benefits of low cost, rapid commercial scale manufacturing, and rapid availability of drug to patients especially in neo-adjuvant settings and for prophylaxis in high-risk patients, contrary to personalized immunotherapy approaches. ELI-002 is being studied in an ongoing, randomized clinical trial in patients with mKRAS-positive pancreatic cancer who completed standard therapy but remain at high risk of relapse. ELI-002 also has been studied in patients with mKRAS-positive colorectal cancer (“CRC”) in Phase 1 studies. The updated AMPLIFY-201 Phase 1 data for PDAC and CRC was presented at the ESMO Immuno-Oncology Congress 2024 and included a 16.3-month median recurrence-free survival and 28.9-month median overall survival for the full study population. In the future, Elicio plans to expand ELI-002 to other indications including mKRAS positive lung cancer and other mKRAS positive cancers. Elicio’s pipeline includes additional off-the-shelf therapeutic cancer immunotherapy candidates, including ELI-007 and ELI-008, that target BRAF-driven cancers and p53 hotspot mutations, respectively. For more information, please visit www.elicio.com. About ELI-002 Elicio’s lead product candidate, ELI-002, is a structurally novel investigational AMP cancer immunotherapy that targets cancers that are driven by mutations in the KRAS-gene—a prevalent driver of many human cancers. ELI-002 is comprised of two powerful components that are built with Elicio’s AMP technology consisting of AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified CpG oligodeoxynucleotide adjuvant that is available as an off-the-shelf subcutaneous administration. ELI-002 2P (2-peptide formulation) has been studied in the Phase 1 (AMPLIFY-201) trial in patients with high relapse risk mKRAS-driven solid tumors, following surgery and chemotherapy (NCT04853017). ELI-002 7P (7-peptide formulation) is currently being studied in a Phase 1/2 (AMPLIFY-7P) trial in patients with mKRAS-driven pancreatic cancer (NCT05726864). The ELI-002 7P formulation is designed to provide immune response coverage against seven of the most common KRAS mutations present in 25% of all solid tumors, thereby increasing the potential patient population for ELI-002. About ELI-004 ELI-004 is a structurally novel, investigational AMP-modified immune-stimulatory CpG oligonucleotide. CpG oligonucleotide sequences are potent stimulators of TLR-9 which induce activation of innate immune cells, and production of supportive inflammatory effector molecules critical for enhancing innate and adaptive immunity. AMP-modification of CpG oligonucleotides promotes several mechanisms which may enhance tumor-directed immune responses: as an adjuvant administered with an antigen to the peripheral tissue, association with tissue albumin promotes delivery from the injection site to the lymph nodes where targeted uptake can enhance action on key immune cells which promote anti-tumor activity; following local injection into a solid tumor, AMP-mediated retention of CpG sequences concentrates immune activation within the target tumor, likely restricting systemic dissemination to irrelevant or toxicity-inducing sites throughout the body. About the Amphiphile Platform Elicio’s proprietary AMP platform delivers investigational immunotherapeutics directly to the “brain center” of the immune system – the lymph nodes. Elicio believes this site-specific delivery of disease-specific antigens, adjuvants and other immunomodulators may efficiently educate, activate and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, Elicio observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability. Elicio believes its AMP lymph node-targeted approach will produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes based on preclinical studies. Elicio’s AMP platform, originally developed at the Massachusetts Institute of Technology, has broad potential in the cancer space to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships. The AMP platform has been shown to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the local injection site, as it travels to lymphatic tissue. Cautionary Note on Forward-Looking Statements Certain statements contained in this communication regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, known as the PSLRA. These include statements regarding Elicio’s planned clinical programs, including planned clinical trials; the potential of Elicio’s product candidates and platform; the potential for future expansion of ELI-002 to other indications; the potential benefits and effectiveness of off-the-shelf immunotherapy approaches; the potential participation and presentation at upcoming conferences and medical meetings; and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Elicio undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law. We use words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions of the PSLRA. Such forward-looking statements are based on our expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, Elicio’s plans to develop and commercialize its product candidates, including ELI-002; the timing of initiation of Elicio’s planned clinical trials; the timing of the availability of data from Elicio’s clinical trials; the timing of any planned investigational new drug application or new drug application; Elicio’s plans to research, develop and commercialize its current and future product candidates; and Elicio’s estimates regarding future revenue, expenses, capital requirements and need for additional financing. New factors emerge from time to time, and it is not possible for Elicio to predict all such factors, nor can Elicio assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. These risks are more fully discussed under the heading “Risk Factors” in Elicio’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 31, 2025, Elicio’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, filed with the SEC on May 13, 2025, and Elicio’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, filed with the SEC on August 7, 2025, as updated by subsequent reports and other documents filed from time to time with the SEC. Forward-looking statements included in this release are based on information available to Elicio as of the date of this release. Elicio does not undertake any obligation to update such forward-looking statements to reflect events or circumstances after the date of this release, except to the extent required by law. Investor Relations Contact Brian RitchieLifeSci Advisors(212) 915-2578britchie@lifesciadvisors.com

免疫疗法临床1期疫苗临床2期临床结果

2025-11-02

·伍的解读

Daraxonrasib(RMC-6236)获FDA授予胰腺癌孤儿药资格认定

前言胰腺癌是我公众号的核心话题，可参考： "万癌之王"胰腺癌治疗药物大全(2025) 胰腺癌新药Certepetide最新数据 Elicio Therapeutics公司宣布继续推进针对胰腺癌疫苗ELI-002 7P的II期研究胰腺癌和结直肠癌肿瘤疫苗ELI-002 2P 1期研究的最终结果 Atebimetinib(IMM-1-104)胰腺癌新数据公布 Claudin18.2(CLDN18.2)，可能不是胰腺癌的答案？很遗憾，胰腺癌似乎还停在化疗时代为什么我认为胰腺癌仍在化疗时代？胰腺癌又一个顶刊的化疗III期研究 [上述文章即为我最新版胰腺癌综述和之后的几篇文章] 还可关注我之前的一篇综述翻译： 2025年最新胰腺癌柳叶刀本刊综述正文 2025年10月27日，Revolution Medicines发布新闻稿[1]，宣布其RAS(ON)多靶选择性抑制剂Daraxonrasib获FDA授予胰腺癌孤儿药资格认定(ODD)。 Revolution Medicines(RVMD)是一家处于晚期阶段的临床肿瘤公司，致力于为RAS依赖型癌症患者开发靶向疗法。该公司宣布，FDA已授予其RAS(ON)多靶选择性抑制剂Daraxonrasib用于治疗胰腺癌的ODD。 “我们非常欣慰FDA已授予Daraxonrasib用于治疗胰腺癌的ODD。这是一种毁灭性的疾病，治疗选择有限，代表着巨大的未满足医疗需求，”Revolution Medicines首席执行官兼董事长Mark A. Goldsmith表示。“RAS驱动突变几乎存在于所有胰腺癌病例中，这凸显了迫切需要能够靶向这一关键疾病进展驱动因素的创新疗法。” Daraxonrasib目前正在一项名为RASolute 302的全球性III期临床试验中进行研究，该试验面向二线转移性胰腺导管腺癌(PDAC)患者。公司还宣布计划启动另外两项针对胰腺癌的III期临床试验：一项用于转移性PDAC患者的一线治疗试验，另一项用于可切除PDAC患者的辅助治疗试验。 ODD由FDA授予特定研究性药物，旨在鼓励用于治疗罕见疾病的疗法开发。罕见疾病被定义为在美国影响人数少于20万的疾病。该认定为申办方提供多项激励措施，包括临床试验费用的税收抵免、豁免部分FDA费用，以及在获批后最长可达七年的市场独占期。点评和观点刚看到这个新闻，我首先揉了揉眼睛，然后看下新闻稿发布时间。确实是最近。然后我迷茫了：我记得ODD是药物研发很早期的时候FDA授予的资格，而Daraxonrasib明显不属于"很早期"。所以我问了问某个AI：大概的答案是：大多数ODD都是研发的最早阶段授予的，但ODD实际上可在任何研发阶段申请。关于该药物，还可参考：胰腺癌新药Daraxonrasib(RMC-6236)监管里程碑——获得FDA授予的BTD Daraxonrasib(RMC-6236)胰腺癌新数据公布胰腺癌的希望——Daraxonrasib(RMC-6236)——将可能更快获得FDA批准？拥有"姓名"的RMC-6236/RMC-6291/RMC-9805，是否意味着离批准更近一步？结语希望Daraxonrasib(RMC-6236) III期成功，并尽快获得监管批准，尤其是国内。参考资料 1.https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-rason-multi-selective-inhibitor/ 欢迎关注本公众号的核心文章(超过6w字) 非小细胞肺癌(NSCLC)治疗药物大全(2025)[药物推荐分级] 非小细胞肺癌(NSCLC)治疗药物大全(2025)——提纲和解析最新基础知识肿瘤/医药名词解释(科普+专业版) 最新胰腺癌综述 "万癌之王"胰腺癌治疗药物大全(2025) 最新乳腺癌综述乳腺癌(BC)治疗药物大全(2025) 最新卵巢癌综述卵巢癌(OC)治疗药物大全(2025) 和其它文章《伍的解读》2025年10月文章按癌种等分类总结《伍的解读》2025年9月文章按癌种等分类总结和400篇里程碑《伍的解读》2025年8月文章按癌种等分类总结《伍的解读》2025年7月文章按癌种等分类总结《伍的解读》2025年6月文章按癌种等分类总结《伍的解读》2025年5月文章按癌种等分类总结《伍的解读》2025年4月文章按癌种等分类总结《伍的解读》2025年3月文章按癌种等分类总结《伍的解读》2025年1-2月文章按癌种等分类总结《伍的解读》2024年文章按癌种等分类简单总结最近的综述文献翻译非小细胞肺癌化疗免疫治疗后线治疗[顶刊综述全文翻译与解读] "最顶刊"CA综述：EGFR突变非小细胞肺癌(NSCLC) 2025年最新胰腺癌柳叶刀本刊综述 HER2检测：伴随诊断检测方法的演变与更新(顶刊综述全文翻译) EGFR/ALK阳性非小细胞肺癌脑转移的治疗管理不可切除的III期非小细胞肺癌在同步放化疗前应该新辅助化免治疗？[JCO评论文章翻译] 韩国、日本、欧洲和美国：为何胃癌诊疗指南存在差异？我写本公众号的原因我的公众号写了4年+第200篇文章——简单谈谈我为什么写了这个号患者和家属应该学着用AI，但注意应用范围人工智能(AI)与肿瘤——打破信息不对称的利器免疫治疗有可能可以降低剂量使用超低剂量免疫治疗也可用？来自一篇JCO的老文章低剂量免疫治疗，可行？[2025 ESMO系列报道之六] "玄学"的使用情绪焦虑会影响NSCLC免疫治疗疗效？(同时是我选文章的思路) 百年"神药"，阿司匹林(aspirin)，焕发新生？ NEJM为一代"神药"阿司匹林正名 Nature本刊震惊体研究——阿司匹林在小鼠中抑制癌症转移上午(11:30之前)接受一线免疫联合化疗治疗，疗效更好？非小细胞肺癌免疫治疗，尽量在上午？运动可能改善癌症预后？来自NEJM的研究 2025 ESMO专题简述20个2025 ESMO上值得关注的研究结果 DESTINY-Breast11简单结果[2025 ESMO系列报道之一] TIGIT希望又回来了？[2025 ESMO系列报道之二] BRAF V600E NSCLC一线治疗还得是靶向治疗？[2025 ESMO系列报道之三] III期ALINA研究更新结果[2025 ESMO系列报道之四] 胃癌围术期III期研究MATTERHORN最终OS数据发布[2025 ESMO系列报道之五] KEYNOTE-B96——免疫治疗正式可用于卵巢癌的标志[2025 ESMO系列报道] HER2靶向治疗Sevabertinib登顶NEJM[2025 ESMO系列报道之八] FLAURA2 OS结果登顶NEJM/2025 ESMO数据更新国产创新药芦康沙妥珠单抗III期研究登顶NEJM 中国的"老药"维迪西妥单抗+特瑞普利单抗登顶NEJM 戈沙妥珠单抗一线治疗三阴性乳腺癌登顶NEJM #胰腺癌 #PDAC #胰腺导管腺癌 #KRAS #RAS

快速通道孤儿药临床2期临床3期临床1期

2025-10-06

·药明康德

同行致远 | 全球首款！这项无药可医的疾病终于迎来FDA批准新药；首个口服PCSK9抑制剂3期结果积极……| Bilingual

编者按：多肽药物已成为治疗多种疾病的重要手段。目前，全球已有约100款多肽药物获批上市，覆盖糖尿病、肥胖症、癌症及罕见疾病等多个领域，为患者带来了全新的治疗策略。然而与传统的小分子药物相比，多肽药物更为复杂，涉及非天然氨基酸（UAA）合成、肽库合成、偶联化合物合成、放大生产工艺开发以及制剂开发等多个环节，对专业技术能力提出了更高要求。为更好地满足全球合作伙伴在多肽药物研发方面的需求，药明康德旗下WuXi TIDES围绕多肽药物建立了一体化CRDMO平台，提供包括线性、环状和高度修饰的多肽，以及非天然氨基酸、连接子、毒素和多肽偶联物的合成服务，支持从药物发现、CMC开发到商业化生产的各个阶段。本文将回顾2025年第三季度多肽领域的最新进展，并介绍药明康德的一体化CRDMO平台如何高效解决该领域药物开发过程中的诸多挑战。 GLP-1类多肽疗法持续进展在2025年第三季度，GLP-1类多肽疗法在代谢与心血管领域持续进展。今年8月，美国FDA加速批准Wegovy（2.4 mg司美格鲁肽）用于联合低热量饮食及增加体能活动，治疗伴有中度至重度肝纤维化（2期或3期）的非肝硬化型代谢功能障碍相关脂肪性肝炎（MASH）成人患者。根据新闻稿，Wegovy为首个获批用于治疗MASH的GLP-1疗法。今年9月，欧洲药品管理局（EMA）人用药品委员会（CHMP）批准更新诺和诺德旗下Rybelsus（口服司美格鲁肽）的标签，使其成为欧盟范围内在2型糖尿病治疗中证实具有心血管获益的首个口服GLP-1受体激动剂。该批准主要根据3b期临床试验SOUL的结果。分析显示，在标准治疗基础上加用口服司美格鲁肽可使主要不良心血管事件（MACE）风险较安慰剂显著降低14%。诺和诺德在7月也向EMA提交了Wegovy 7.2 mg新剂量的监管申请，旨在为肥胖患者进一步提升体重管理效果。与此同时，礼来（Eli Lilly and Company）也公布了其GIP/GLP-1双重受体激动剂Mounjaro（tirzepatide）与GLP-1受体激动剂Trulicity（dulaglutide）相较，在2型糖尿病合并动脉粥样硬化性心血管疾病成人患者中的疗效。临床3期研究结果显示，Mounjaro在降低主要不良心血管事件风险方面不劣于Trulicity，后者曾在REWIND研究中证实具有明确的心血管获益。Mounjaro也在这个季度获加拿大卫生部批准上市。根据新闻稿，该疗法是首个获得加拿大卫生部批准用于慢性体重管理的双重受体激动剂。多肽疫苗在癌症领域取得成果部分多肽疫苗也在癌症领域取得进展。例如，PDS Biotechnology旗下多肽癌症疫苗PDS0101（Versamune HPV）联合PD-1抑制剂Keytruda（pembrolizumab），在2期试验当中，作为一线疗法时，患者的中位总生存期达39.3个月（95% CI：23.9-尚未可估）。根据新闻稿，该类患者在接受标准治疗联合化疗时已公布的最佳中位总生存期为17.9个月。而Elicio Therapeutics旗下靶向突变KRAS的多肽疫苗ELI-002在1期AMPLIFY-201研究中，在中位随访19.7个月时，将胰腺癌和结直肠癌患者的死亡风险降低77%，复发风险降低88%。多肽疗法在罕见病领域获得突破此外，多肽疗法在本季度也于罕见病领域有许多突破。今年7月，美国FDA批准Apellis Pharmaceuticals旗下双环肽疗法Empaveli（pegcetacoplan）扩展适应症，用于治疗C3肾小球病（C3G）和原发性免疫复合物膜增生性肾小球肾炎（IC-MPGN），以减少患者的蛋白尿。根据新闻稿，该疗法是获FDA批准用以治疗这两类罕见肾病的首款疗法。此外，Stealth BioTherapeutics所开发的Forzinity（elamipretide）也在今年9月迎来FDA批准，成为巴思综合征全球首款获批疗法。其他领域的进展其他领域方面，强生（Johnson & Johnson）与Protagonist Therapeutics也已向美国FDA递交新药申请（NDA），寻求批准其联合开发的口服多肽疗法icotrokinra，用于治疗12岁及以上中度至重度斑块状银屑病（PsO）成人与儿科患者。默沙东（MSD）在今年9月宣布在研口服大环肽enlicitide decanoate在3期试验中，能够显著降低高胆固醇血症患者的低密度脂蛋白胆固醇（LDL-C）水平。根据新闻稿，该疗法是在3期试验中显示能显著降低LDL-C水平的首个口服PCSK9抑制剂。商业研发合作进展今年9月，辉瑞（Pfizer）与Metsera达成总额达数十亿美元的收购协议。此次收购将使辉瑞获得后者旗下具差异化的口服与注射型肠促胰岛素和胰淀素类候选药物以及联合疗法，这些项目在有效性与安全性方面具备“best-in-class”潜力。Unnatural Products（UNP）与argenx则在7月达成一项多靶点战略合作研究项目，旨在发现和开发针对“不可成药”疾病靶点的口服大环肽药物。该合作将利用UNP公司的专有药物发现平台，生成针对argenx公司所选定的多个靶点的高效、高选择性且可口服的大环肽分子。综上，2025年三季度多肽疗法多线跃进：GLP-1版图延伸至MASH，肿瘤多肽疫苗在延长生存与降低复发方面表现亮眼，多项罕见病亦迎来首款获批疗法，口服多肽赛道持续升温。随着临床证据不断积累与产业协同加速推进，多肽疗法有望在代谢、肿瘤及罕见病等领域实现更多里程碑。 WuXi TIDES高效赋能合作伙伴开发复杂多肽偶联药物药明康德旗下WuXi TIDES平台支持各类多肽药物从发现、CMC开发到商业化生产的各个阶段，致力赋能全球客户推动创新疗法问世。以下案例将展示WuXi TIDES的一体化平台如何高效推动合作伙伴复杂多肽偶联药物的开发进程。在该案例中，客户所开发的一款多肽偶联药物结构复杂，由两个短环肽片段和一个长线性多肽组成，合成步骤多达87步。初期合成方案的总体产率不足0.1%，难以满足临床试验的需求。同时，该药物所需的3种UAA原料供应紧张，若从外部采购可能严重延误研发进度。面对上述挑战，WuXi TIDES团队提出了多项针对性解决方案。针对UAA原料短缺问题，团队充分发挥自身生产UAA的能力，迅速开发出可行的合成工艺，并成功制备了超过3公斤的UAA原料，从源头保障了项目的顺利推进。这一内部合成策略不仅降低了对外部供应商的依赖，还显著优化了进度管理，大幅缩短整体项目周期。与此同时，WuXi TIDES团队致力于提升多肽合成效率。考虑到传统固相合成方法合成超过50个氨基酸的多肽时，往往面临效率与产率下降的挑战，WuXi TIDES团队采用了“片段合成+化学连接”策略，将目标多肽拆分成多个适合固相合成的小片段，分别合成后再通过化学连接形成完整多肽分子。这一策略将总体产率从不足0.1%提升至3%，并使多个团队能够同时进行片段合成，显著加快了项目推进速度。在复杂冗长的合成路线中，每一个细节都可能影响最终质量与产率。为进一步优化工艺，WuXi TIDES团队对多个关键步骤的合成和纯化条件进行了反复筛选与优化。在放大生产阶段，团队专门设计了定制的纯化材料，使杂质水平下降80%，最终产率提升20%。得益于UAA合成团队、多肽合成团队和分析团队的高效执行及并行作业，WuXi TIDES团队仅用4个月即完成了工艺开发与优化，7个月内交付了两批各100克的GLP样品，随后又在3个月内顺利生产出1千克GMP级原料药，产率达3%，纯度达97.4%。项目整体进度比合作伙伴预期提前4个月，为临床试验的及时启动提供了强有力保障。化学合成能力之外，WuXi TIDES还可赋能多肽药物从临床前到商业化阶段的口服和注射制剂的开发和生产。口服制剂平台支持包括片剂、胶囊、脂质体、粉末、颗粒和口服液等各类剂型的开发和生产；注射剂平台则支持多种剂型和灌装形式的无菌制剂生产。展望未来，WuXi TIDES团队将持续依托其一体化CRDMO平台，助力全球合作伙伴充分发挥多肽疗法的巨大潜力，为患者带来更多创新药物。 CRDMO: Q3 2025 Review of Peptide Therapeutics Peptide drugs have emerged as an important therapeutic modality for a broad spectrum of diseases. To date, approximately 100 peptide-based medicines have received global regulatory approval, providing new treatment options for conditions such as diabetes, obesity, cancer, and rare diseases. However, compared to traditional small-molecule drugs, peptides present greater structural complexity. Their development requires advanced capabilities in areas such as unnatural amino acid (UAA) synthesis, peptide library design, conjugation chemistry, scale-up process development, and formulation support. To address these challenges and better support global partners, WuXi TIDES, an integral part of WuXi AppTec, has established an integrated CRDMO platform. The platform offers comprehensive synthesis services for linear, cyclic, and highly modified peptides, as well as UAAs, linkers, payloads, and peptide conjugates. Covering the full development spectrum from drug discovery and CMC development to commercial-scale manufacturing, the platform enables efficient and flexible solutions tailored to each stage of the pipeline. Here we summarize key developments in the peptide space during Q3 2025 and share a case study that illustrates how WuXi TIDES helps accelerate progress in this dynamic area. Sustained Momentum for GLP-1–Based Therapeutics In the third quarter of 2025, GLP-1 peptide therapeutics continued to advance in the fields of metabolic and cardiovascular diseases. In August, the U.S. FDA granted accelerated approval to Wegovy (semaglutide 2.4 mg) for use in combination with a reduced-calorie diet and increased physical activity to treat adult patients with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (stage 2 or 3). According to the company, Wegovy is the first GLP-1 therapy approved for the treatment of MASH. In September, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) approved an update to the label of Novo Nordisk’s Rybelsus (oral semaglutide), making it the first oral GLP-1 receptor agonist approved for type 2 diabetes in the European Union, with proven cardiovascular benefit. The decision was based on results from the Phase 3b SOUL trial, which demonstrated that adding oral semaglutide to standard therapy reduced the risk of major adverse cardiovascular events (MACE) by 14% compared with placebo. In July, Novo Nordisk also submitted a regulatory application to the EMA for a new 7.2 mg dose of Wegovy, aiming to further enhance weight management outcomes for patients with obesity. Meanwhile, Eli Lilly and Company reported data comparing its dual GIP/GLP-1 receptor agonist Mounjaro (tirzepatide) with the GLP-1 receptor agonist Trulicity (dulaglutide) in adults with type 2 diabetes and atherosclerotic cardiovascular disease. Results from a Phase 3 trial showed that Mounjaro was non-inferior to Trulicity in reducing the risk of major adverse cardiovascular events. Trulicity had previously demonstrated clear cardiovascular benefit in the REWIND trial. Mounjaro also gained approval from Health Canada this quarter, becoming the first dual receptor agonist authorized in Canada for chronic weight management. Breakthroughs for Peptide Vaccines in Oncology Peptide vaccines also achieved important milestones in oncology. PDS Biotechnology’s peptide-based cancer vaccine PDS0101 (Versamune HPV), in combination with the PD-1 inhibitor Keytruda (pembrolizumab), delivered a median overall survival (mOS) of 39.3 months (95% CI: 23.9–not estimable) as a first-line therapy in a Phase 2 trial. By comparison, previously reported standard therapy plus chemotherapy in this patient group achieved a best mOS of 17.9 months. Elicio Therapeutics also reported promising results for its mutant KRAS-targeted peptide vaccine ELI-002. In the Phase 1 AMPLIFY-201 study, at a median follow-up of 19.7 months, ELI-002 reduced the risk of death by 77% and recurrence by 88% in patients with pancreatic and colorectal cancers. Advances in Peptide Therapeutics for Rare Diseases Significant progress was also made in rare diseases this quarter. In July, the U.S. FDA approved Apellis Pharmaceuticals’ cyclic peptide therapy Empaveli (pegcetacoplan) for the treatment of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) to reduce proteinuria. According to the company, this is the first FDA-approved therapy for these two rare kidney disorders. In September, Stealth BioTherapeutics secured FDA approval for Forzinity (elamipretide), marking the world’s first approved treatment for Barth syndrome. Expanding Applications in Other Fields In addition, Johnson & Johnson and Protagonist Therapeutics have submitted a New Drug Application (NDA) to the U.S. FDA for their jointly developed oral peptide therapy icotrokinra, seeking approval for the treatment of adults and adolescents aged 12 years and older with moderate-to-severe plaque psoriasis (PsO). Merck (known as MSD outside of the U.S. and Canada) announced in September that its investigational oral macrocyclic peptide enlicitide decanoate achieved a significant reduction in low-density lipoprotein cholesterol (LDL-C) in a Phase 3 trial in patients with hypercholesterolemia. According to the company’s release, this marks the first oral PCSK9 inhibitor to demonstrate a significant LDL-C reduction in a Phase 3 study. Progress in Partnerships and Collaborations September also saw major business developments, including Pfizer’s acquisition agreement with Metsera. The deal grants Pfizer access to Metsera’s differentiated oral and injectable incretin and amylin candidates, as well as combination therapies, which hold best-in-class potential in both efficacy and safety. In July, Unnatural Products (UNP) entered into a multi-target strategic research collaboration with argenx to discover and develop orally available macrocyclic peptide drugs for previously “undruggable” disease targets. The collaboration will leverage UNP’s proprietary drug discovery platform to generate potent, selective, and orally bioavailable macrocyclic peptides against multiple targets selected by argenx. In summary, Q3 2025 saw peptide therapeutics advance on multiple fronts: the GLP-1 landscape expanded into MASH; peptide cancer vaccines showed compelling benefits in extending survival and reducing recurrence; several rare diseases welcomed their first approved therapies; and the oral-peptide continued to gain momentum. As clinical evidence builds and industry collaboration accelerates, peptide therapeutics are poised to deliver further milestones across metabolic, oncology, and rare disease fields. WuXi TIDES Empowering Global Innovation WuXi AppTec’s WuXi TIDES platform provides end-to-end support for peptide therapeutics—from discovery and CMC development through commercial manufacturing—helping global partners speed innovative therapies to patients. To demonstrate how this integrated model translates into execution, one representative case is outlined below. In this program, the candidate molecule comprised two short cyclic peptide fragments and one long linear peptide, requiring an intricate synthesis involving up to 87 steps. The initial synthetic route yielded less than 0.1% overall, insufficient to meet clinical trial demands. Additionally, the project was hampered by the limited availability of three critical UAAs, with external sourcing posing a risk of significant delays. To overcome these obstacles, the WuXi TIDES team implemented several targeted solutions. First, the team addressed the UAA supply bottleneck by leveraging its internal UAA synthesis capabilities. They quickly developed viable synthetic pathways and produced over 3 kilograms of UAAs, securing raw material availability and safeguarding project timelines. This internal manufacturing strategy not only reduced dependency on external suppliers but also significantly improved timeline control and shortened the overall project duration. Concurrently, efforts were directed at improving the efficiency of peptide synthesis. Given the challenges of efficiency and yield declines when traditional solid-phase peptide synthesis (SPPS) techniques are used for sequencing longer than 50 amino acids, the WuXi TIDES team adopted a "fragment synthesis + chemical ligation" strategy—breaking down the target peptide into shorter fragments suitable for SPPS, synthesizing them individually, and then linking them chemically into the full-length peptide. This approach improved the overall yield from under 0.1% to 3%, while enabling multiple teams to work in parallel, significantly accelerating development timelines. Given the complexity and length of the synthesis route, process optimization was critical. The WuXi TIDES team conducted extensive rounds of screening and refinement for key synthesis and purification steps. During scale-up, the team introduced customized purification materials that reduced impurity levels by 80% and improved yield by 20%. Through efficient execution and parallel activities between the UAA synthesis, peptide synthesis, and analytical teams, process development and optimization were completed in just four months. The WuXi TIDES team delivered two batches of 100 grams of GLP-grade material within seven months, followed by the production of 1 kilogram of GMP-grade API in an additional three months. The final process achieved a 3% yield with 97.4% purity. Overall, the project was completed four months ahead of schedule, ensuring timely clinical trial initiation with a secure and robust supply. Beyond peptide API synthesis, WuXi TIDES also supports both oral and parenteral drug product development and manufacturing for peptide drugs from preclinical to commercial stages. The oral solid platform supports a diverse array of dosage forms such as tablets, capsules, lipid formulations, powders, granules, and liquid-in-bottle, while the parenteral dosage platform accommodates various injectable drug forms and filling formats. Looking forward, the WuXi TIDES team will continue to leverage its integrated CRDMO platform to accelerate the development of peptide therapeutics. By enabling global partners to unlock the full potential of peptide drugs, WuXi TIDES is helping bring more innovative medicines to patients around the world. 参考资料： [1] FDA Approves Apellis’ EMPAVELI® (pegcetacoplan) as the First C3G and Primary IC-MPGN Treatment for Patients 12 and Older. Retrieved September 25, 2025 from https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and [2] Merck’s Investigational Oral PCSK9 Inhibitor Enlicitide Decanoate Met All Primary and Key Secondary Endpoints in Adults with Hypercholesterolemia in Pivotal CORALreef Lipids Study. Retrieved September 25, 2025 from https://www.merck.com/news/mercks-investigational-oral-pcsk9-inhibitor-enlicitide-decanoate-met-all-primary-and-key-secondary-endpoints-in-adults-with-hypercholesterolemia-in-pivotal-coralreef-lipids-study/ 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德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。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床3期上市批准加速审批临床结果临床2期

100 项与 ELI-002 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
胰腺导管腺癌	临床2期	-	Elicio Therapeutics, Inc.	-
胆管癌	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04
结直肠癌	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04
胆囊癌	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04
KRAS突变胰腺导管腺癌	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04
KRAS突变肿瘤	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04
神经母细胞瘤	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04
非小细胞肺癌	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04
卵巢癌	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04
残留肿瘤	临床1期	美国	Elicio Therapeutics, Inc.	2021-10-04

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04853017 (AMPLIFY-201, Pubmed \| GlobeNewswire \| Nat Med) 人工标引	临床1期	结直肠癌 \| 胰腺癌 KRAS G12R \| KRAS G12D	25	ELI-002 2P (mKRAS-specific T cell responses above a threshold 9.17-fold increase over baseline)	選夢膚鹽簾餘鹹鏇積蓋(簾糧壓壓衊齋鹹醖獵願) = 夢鏇壓鬱選壓範願醖壓壓顧艱選顧網鑰製範壓 (鹽齋醖網鏇憲鹹製願鹽 ) 更多	积极	2025-08-11
	临床1期	结直肠癌 \| 胰腺癌 KRAS G12R \| KRAS G12D	25	ELI-002 2P (mKRAS-specific T cell responses below a threshold 9.17-fold increase over baseline)	選夢膚鹽簾餘鹹鏇積蓋(簾糧壓壓衊齋鹹醖獵願) = 鬱鹹壓艱窪膚餘憲淵憲壓顧艱選顧網鑰製範壓 (鹽齋醖網鏇憲鹹製願鹽 ) 更多	积极	2025-08-11
NCT04853017 (AMPLIFY-201, GlobeNewswire) 人工标引	临床1期	胰腺导管腺癌 \| 结直肠癌 \| KRAS突变肿瘤 KRAS Mutation	25	ELI-002 2P	衊淵觸鑰襯憲艱觸壓蓋(艱餘顧選壓襯壓壓鏇餘) = 顧糧齋觸築遞築衊製顧鹹淵醖顧醖壓願顧壓鑰 (獵觸糧夢築齋齋衊製鑰 ) 更多	积极	2024-12-12
NCT04853017 (AMPLIFY-201, GlobeNewswire) 人工标引	临床1期	胰腺导管腺癌 \| 结直肠癌 \| KRAS突变肿瘤 KRAS Mutation	25	ELI-002 2P (PDAC)	衊淵觸鑰襯憲艱觸壓蓋(艱餘顧選壓襯壓壓鏇餘) = 鹽構餘蓋淵顧壓艱觸艱鹹淵醖顧醖壓願顧壓鑰 (獵觸糧夢築齋齋衊製鑰 ) 更多	积极	2024-12-12
NCT04853017 (AMPLIFY-201, AACR 12024 \| AACR 22024) 人工标引	临床1期	结直肠癌 \| 胰腺癌	-	ELI-002	夢醖淵鹽構繭夢觸觸構(醖簾糧蓋網鹹製餘膚構) = A majority of patients maintained or increased relative to baseline. 築鏇醖簾網蓋蓋壓遞窪 (醖鑰鑰襯糧築淵築醖襯 )	积极	2024-04-01
NCT04853017 (AMPLIFY-201, Pubmed \| Nat Med) 人工标引	临床1期	KRAS突变胰腺癌 \| KRAS 突变结直肠癌 KRAS Mutation	25	ELI-002	構憲壓餘艱簾糧獵廠築(艱積廠製顧壓範憲襯築) = 鏇願顧顧範選鏇鹹願膚鹽壓製鑰遞鏇繭鹽築觸 (選醖顧襯壓窪糧餘衊顧 ) 更多	积极	2024-01-09
NCT04853017 (AMPLIFY-201, Corporate Publications) 人工标引	临床1期	胰腺癌 KRAS Mutation	23	ELI-002 2P	積廠繭鬱獵遞網鹹築顧(艱醖網製製壓糧襯齋遞) = 積簾壓顧艱範遞鬱蓋築淵衊鑰繭廠蓋製衊獵鹽 (鬱繭襯鑰醖構製鏇窪廠 ) 更多	积极	2023-11-09
NCT04853017 (AMPLIFY-201, ASCO 12023 \| ASCO 22023) 人工标引	临床1期	KRAS G12D突变结直肠癌	-	ELI-002	膚鹹選鹹鑰蓋鬱膚餘蓋(繭簾糧願繭網鏇鑰鹹淵) = all grade 1, fatigue (19%), headache (19%), and injection site reaction (9.5%) 遞餘艱鹽觸窪齋願淵觸 (觸醖築衊齋顧衊蓋齋製 ) 更多	积极	2023-05-26