ELI-002 7P

近期，全球多肽和寡核苷酸（TIDES）及相关RNA药物领域迎来多项进展。Elicio Therapeutics旗下KRAS靶向癌症多肽疫苗针对胰腺导管腺癌（PDAC）患者的又一项临床试验启动。Silence Therapeutics旗下潜在“first-in-class”siRNA候选药物divesiran用于依赖放血治疗的真性红细胞增多症（PV）患者的2期试验达到主要终点及次要终点。本文将选取其中部分重要进展作简要介绍，仅供读者参阅。 作为全球医药创新的赋能者，药明康德为合作伙伴的寡核苷酸、多肽药物及相关化学偶联物开发提供高效、灵活且高质量的解决方案。针对TIDES类药物从生物分析到工艺开发与生产的不同需求，药明康德生物分析部（BAS）与药明康德旗下WuXi TIDES多肽平台分别建立了专业能力，为相关药物的分析评价、开发及规模化生产提供支持，助力全球合作伙伴持续推进TIDES类药物研发进程。 Divesiran：达2期试验主要终点 Silence Therapeutics旗下潜在“first-in-class”siRNA候选药物divesiran在依赖放血治疗的PV患者中开展的2期SANRECO试验达到主要终点及次要终点。Divesiran是Silence Therapeutics基于其专有mRNAi GOLD平台开发的siRNA候选药物，通过沉默几乎仅在肝脏表达的TMPRSS6发挥作用。 在该试验中，临床应答者被定义为在第18-36周无需接受放血治疗且红细胞比容（HCT）维持在45%以下的患者。分析显示，divesiran治疗组总体应答率为88%，显著高于安慰剂组的19%（p<0.0001），达成试验主要终点。其中，接受每6周一次（Q6W）皮下注射组和每12周一次（Q12W）皮下注射组患者的应答率分别为93.8%和81.3%。关键次要终点方面，在第0-36周期间，divesiran组每名患者平均接受放血治疗0.2次，安慰剂组为2.1次（p<0.0001）。此外，divesiran治疗组在HCT控制、铁蛋白等铁代谢指标，以及基于MPN-SAF总症状评分（MPN-SAF TSS）的患者报告结局方面均显示改善。安全性方面，divesiran总体耐受性良好，与既往试验结果一致，未观察到新的安全性信号；注射部位反应发生率低且可自行缓解，研究者报告了2例1级贫血不良事件。 ELI-002 7P：1期临床试验启动 Elicio Therapeutics宣布，一项研究者发起的1期新辅助临床研究已启动，将评估其在研癌症免疫疗法ELI-002 7P联合化疗及PD-1检查点抑制剂治疗可切除或临界可切除PDAC的潜力。该随机、开放标签研究预计纳入20例携带KRAS突变的可切除或临界可切除PDAC患者，受试者将在手术前接受ELI-002 7P联合标准化疗方案mFOLFIRINOX，并根据分组联合或不联合抗PD-1检查点抑制剂替雷利珠单抗（tislelizumab）。研究期间，研究人员还计划采集肿瘤组织及血液样本，以进一步了解治疗诱导的免疫激活情况、肿瘤微环境变化，并探索可用于指导后续临床研究的生物标志物。 ELI-002是Elicio Therapeutics的核心在研产品，是一款采用该公司专有AMP技术开发、靶向KRAS突变驱动型癌症的癌症免疫疗法，由AMP修饰的突变KRAS多肽抗原和AMP修饰的CpG寡脱氧核苷酸佐剂ELI-004组成，可采用即用型皮下注射方式给药。其中，ELI-002 7P包含7种多肽，旨在覆盖7种最常见的KRAS突变，这些突变存在于约25%的实体瘤中。此前，ELI-002 7P已在随机2期AMPLIFY-7P研究中用于接受标准治疗后仍具有较高复发风险的KRAS突变阳性胰腺癌患者；目前总体生存期数据尚未成熟，公司仍在评估包括R0切除患者在内的预设亚组，以进一步完善3期开发策略。此外，Elicio Therapeutics还计划在转移性PDAC中启动一项开放标签1期研究，通过客观缓解率等指标快速评估临床活性，并据此进一步探索与检查点抑制剂的联合方案，为转移性及辅助治疗阶段PDAC的后续开发提供依据。 ASC36、ASC36_35FDC：1期临床试验启动 歌礼（Ascletis Pharma）宣布，在IND申请获得美国FDA许可后，公司已在美国启动两项针对肥胖症的1期临床研究，分别评估新一代胰淀素受体多肽激动剂ASC36，以及ASC36与GLP-1R/GIPR双重多肽激动剂ASC35组成的固定剂量复方制剂ASC36_35FDC。其中，ASC36旨在实现每月一次至每季度一次给药；ASC36_35FDC则是一款每月一次皮下注射的固定剂量复方制剂。两项研究均采用随机、双盲、安慰剂对照设计，将通过单次和多次剂量递增给药，评估候选疗法的安全性、耐受性、药代动力学和药效学特征，入组对象包括BMI≥30.0 kg/m²的肥胖受试者，以及BMI≥27.0 kg/m²且伴有体重相关合并症的超重受试者。 ASC36_35FDC的1期研究还将比较两种不同的固定剂量复方制剂，即Injection A和Injection B，各计划纳入88例受试者。两种制剂均由两款超长效多肽激动剂组成，分别为胰淀素受体多肽激动剂ASC36和GLP-1R/GIPR双重多肽激动剂ASC35。与此同时，ASC36单药1期研究也将评估Injection A和Injection B两种不同制剂，各计划纳入72例受试者。通过同步推进ASC36单药及其与ASC35组成的固定剂量复方制剂，歌礼正进一步评估不同超长效多肽方案在肥胖及伴体重相关合并症的超重人群中的临床开发潜力。 Rusfertide：达成1亿美元授权协议 Zealand Pharma近日宣布，与Royalty Pharma达成一项特许权使用费购买与出售协议，将其与在研药物rusfertide（PTG-300）相关的部分经济权益出售给后者，交易总额为1亿美元。根据协议，其中5000万美元将在交易完成时支付，另外5000万美元将在交易完成一周年时支付。Rusfertide拟用于治疗罕见慢性血液疾病真性红细胞增多症（PV），美国FDA已将其新药申请（NDA）的PDUFA目标日期设定在2026年第三季度。根据此前合作协议，武田（Takeda）将负责该药物的全球商业化。 Rusfertide是一款潜在“first-in-class”的在研皮下注射疗法，通过模拟天然激素铁调素（hepcidin）的作用，调节铁稳态和红细胞生成。该药旨在针对真性红细胞增多症中铁调节异常这一疾病机制，减少过量红细胞生成，并帮助患者实现持续的红细胞压积控制。目前，rusfertide采用每周一次皮下自行注射的给药方式，在迄今开展的临床试验中总体耐受性良好。2026年3月，美国FDA受理rusfertide的新药申请并授予优先审评资格。该申请主要基于3期全球随机研究VERIFY的积极结果，以及2期REVIVE及长期扩展研究的数据。 一体化平台助力多肽疗法开发 随着多肽药物分子量增加、结构修饰增多及偶联形式日益复杂，其生物分析面临一系列特有挑战：一方面，多肽在液相色谱串联质谱（LC-MS/MS）分析中通常呈现多电荷态分布及电离效率不均一，导致信号分散与离子抑制，从而影响检测灵敏度与方法稳健性；另一方面，多肽分子表位有限且与内源性肽序列高度同源，往往表现为免疫原性较低、特异性抗体制备困难，同时在配体结合分析（LBA）中易出现内源性干扰与交叉反应，增加免疫原性评价的复杂性。此外，脂肪酸修饰、PEG化或蛋白融合等结构改造在延长半衰期的同时，也可能引入新的免疫原性风险（如抗PEG抗体），对抗药抗体（ADA）与中和抗体（NAb）检测提出更高要求。 针对上述行业痛点，药明康德生物分析部整合高灵敏度LC-MS/MS、免疫捕获-质谱、ELISA/MSD平台及细胞功能分析方法，实现PK分析、ADA与NAb评价的一体化支持。通过优化样本前处理策略、建立免疫捕获-质谱联用技术及基于胰蛋白酶消化的bottom-up分析方法，可显著提升检测灵敏度并降低基质干扰，在复杂修饰多肽及长链多肽分析中表现出良好的方法特异性与稳健性。同时，针对多肽药物免疫原性评价中的低免疫原性与高同源性带来的检测难点，团队建立了分层（tiered）免疫原性评价体系，整合桥式（bridging）ADA检测、确认实验及滴度分析，并结合酸解离（ACE）、MRD优化等策略提升药物耐受性与检测灵敏度；通过优化标记试剂设计及方法学条件，有效降低内源性干扰与非特异性结合，并结合细胞功能性NAb分析方法，实现从ADA筛查到中和效应评价的全流程覆盖，从而系统性支持复杂修饰多肽及偶联多肽药物的免疫原性风险评估。 对于结构日趋复杂的多肽药物而言，可靠的生物分析只是开发链条中的重要一环。从候选分子进入临床前开发，到工艺放大、临床供应乃至商业化生产，还需要同步解决复杂序列合成、非天然氨基酸引入、偶联反应、纯化、制剂开发以及规模化生产等一系列挑战。因此，将高质量分析评价能力与覆盖开发和生产全生命周期的工艺及制造能力相衔接，有助于推动复杂多肽分子更加高效地从早期研发走向临床和商业化阶段。 药明康德旗下WuXi TIDES多肽平台为原料药和制剂提供从药物发现到商业化生产的一体化CRDMO服务。平台的多肽开发团队由数百名经验丰富的研发人员组成，能支持从临床前到商业化生产各阶段的各类多肽分子、非天然氨基酸及复杂偶联物的工艺开发，包括但不限于：长肽、环肽、复杂肽（例如通过化学连接得到的长肽、肽核酸、类肽、肽类似物、支链肽和树状聚合物）和多肽偶联药物。 在多肽生产方面，WuXi TIDES定制的合成设备和裂解反应釜可全面降低微生物污染和交叉污染风险。多肽平台可确保在整个产品生命周期内的知识传承及放大生产，同时通过不同职能团队之间的无缝协作加快项目开发进程。 WuXi TIDES的多肽生产平台还配备了最新的技术，包括液相多肽合成，连续反应釜（包括过程分析技术PAT），连续流动色谱法，切向流过滤（TFF）/沉淀等。固相合成反应釜总体积已超过10万L。依托符合全球标准的质量体系，WuXi TIDES有能力成为创新者的战略合作伙伴，提供从克级到吨级规模的可靠且稳健的多肽原料药供应。 参考资料： [1] Silence Therapeutics Announces Positive Topline Results from Phase 2 SANRECO Trial of Divesiran in Polycythemia Vera, Supporting its Potential Best-in-Class Profile. Retrieved August 10, 2026 from https://www.silence-therapeutics.com/investors/press-releases/press-releases-details/2026/Silence-Therapeutics-Announces-Positive-Topline-Results-from-Phase-2-SANRECO-Trial-of-Divesiran-in-Polycythemia-Vera-Supporting-its-Potential-Best-in-Class-Profile/default.aspx [2] Ascletis Announces Initiation of Two Phase I Studies in U.S. for the Treatment of Obesity: ASC36 Once-Monthly Injection, an Amylin Receptor Peptide Agonist, and ASC36_35FDC Once-Monthly Injection, a Co-Formulation of ASC36 and GLP-1R/GIPR Peptide Agonist ASC35. Retrieved August 14, 2026 from https://www.prnewswire.com/news-releases/ascletis-announces-initiation-of-two-phase-i-studies-in-us-for-the-treatment-of-obesity-asc36-once-monthly-injection-an-amylin-receptor-peptide-agonist-and-asc3635fdc-once-monthly-injection-a-co-formulation-of-asc36-and-glp-302847051.html [3] Zealand Pharma enters into a USD 100 million royalty purchase and sale agreement with Royalty Pharma for the economics related to rusfertide. Retrieved August 14, 2026 from https://www.globenewswire.com/news-release/2026/08/12/3344048/0/en/zealand-pharma-enters-into-a-usd-100-million-royalty-purchase-and-sale-agreement-with-royalty-pharma-for-the-economics-related-to-rusfertide.html?_gl=1*k0phv*_up*MQ..*_ga*OTMxODkyMzIuMTc4NjU3NDA2NA..*_ga_B6167QB2TF*czE3ODY1NzQwNjMkbzEkZzAkdDE3ODY1NzQwNjMkajYwJGwwJGgyMDQzOTYyMzYw*_ga_ERWPGTJ5X8*czE3ODY1NzQwNjMkbzEkZzAkdDE3ODY1NzQwNjMkajYwJGwwJGgw [4] Elicio Therapeutics Announces Activation of the Investigator-Initiated Phase 1 Study of Neoadjuvant ELI-002 7P for Pancreatic Ductal Adenocarcinoma. Retrieved August 14, 2026 from https://www.globenewswire.com/news-release/2026/08/10/3341758/0/en/elicio-therapeutics-announces-activation-of-the-investigator-initiated-phase-1-study-of-neoadjuvant-eli-002-7p-for-pancreatic-ductal-adenocarcinoma.html [5] Aligos Therapeutics Announces First Participant Dosed in the Phase 1 Study of its Potentially Best-in-Class Antisense Oligonucleotide ALG-170675 by its Partner Amoytop in China. Retrieved August 14, 2026 from https://aligostherapeutics.gcs-web.com/news-releases/news-release-details/aligos-therapeutics-announces-first-participant-dosed-phase-1 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

Phase 1 study conducted by Memorial Sloan Kettering (“MSK”) Cancer Center and funded by The Lustgarten Foundation Study to evaluate ELI-002 7P in combination with chemotherapy and checkpoint inhibition in the neoadjuvant setting Expected to enroll 20 patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (“PDAC”) BOSTON, Aug. 10, 2026 (GLOBE NEWSWIRE) — Elicio Therapeutics, Inc. (Nasdaq: ELTX) (“Elicio” or the “Company”), a clinical-stage biotechnology company developing next-generation immunotherapies for KRAS-driven cancers, today announced the opening of the investigator-initiated (“IIT”) Phase 1 neoadjuvant study (NCT07671339) evaluating ELI-002 7P in combination with chemotherapy and an anti-PD1 checkpoint inhibitor in borderline resectable and resectable PDAC. The multi-center IIT is being conducted by MSK Cancer Center and is being funded by a strategic partnership between The Lustgarten Foundation and Break Through Cancer. “The activation of this study marks an important milestone as we prepare to evaluate the potential of ELI-002 7P across multiple stages of pancreatic cancer,” said Christopher Haqq, M.D., Ph.D., Executive Vice President, Head of Research and Development and Chief Medical Officer of Elicio. “Building on the complete responses observed in patients with metastatic PDAC treated with sequential ELI-002 7P followed by checkpoint inhibitor and chemotherapy, this study prospectively evaluates the combination beginning in the neoadjuvant setting and continuing after surgery. We hope to generate important clinical insights into ELI-002 7P’s potential to harness the immune system and improve surgical outcomes and long-term survival for patients facing this devastating disease.” Kevin Soares, MD, Assistant Attending Surgeon Hepatopancreatobiliary Service, MSK and Principal Investigator of the Phase 1 study added, “Despite advances in the treatment of pancreatic cancer, patients with resectable and borderline resectable disease continue to face a high risk of recurrence, highlighting the need for new therapeutic strategies. This trial offers an important opportunity to investigate how ELI-002 7P may reshape the tumor immune environment when initially combined with neoadjuvant therapy, while offering the potential to generate valuable translational data that could inform future treatment strategies.” The randomized, open-label Phase 1 trial aims to enroll 20 patients with resectable or borderline resectable KRAS-mutant PDAC. Participants will receive ELI-002 7P with standard chemotherapy, mFOLFIRINOX, with or without tislelizumab, an anti-PD1 checkpoint inhibitor, starting before surgery. Throughout treatment, researchers plan to collect tumor tissue and blood samples to better understand immune activation, characterize changes within the tumor microenvironment, and identify biomarkers that could guide future clinical trials. 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 proprietary 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 7P (7-peptide formulation) was evaluated in the randomized Phase 2 AMPLIFY-7P trial in patients with mKRAS-driven pancreatic cancer (NCT05726864). The Phase 2 AMPLIFY-7P trial included patients with mKRAS-positive pancreatic cancer who completed standard therapy but remain at high risk of relapse. Elicio continues to evaluate pre-specified subgroups, including the R0 resected population, to further inform a refined Phase 3 development strategy. Elicio intends to initiate a Phase 1 study in metastatic PDAC designed to provide a rapid assessment of clinical activity using an open label design to assess the objective response rate including partial and complete radiographic responses. Elicio plans to use the study findings to further evaluate checkpoint inhibitor combinations and help inform future development strategies in metastatic PDAC and the adjuvant PDAC Phase 3 trial. At the time of the Phase 2 AMPLIFY-7P analysis, data for overall survival remained immature. 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 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 findings in the personalized cancer immunotherapy space to develop effective, off-the-shelf immunotherapies. Elicio’s 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 7P 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 7P was evaluated in the randomized Phase 2 AMPLIFY-7P trial in patients with mKRAS-positive pancreatic cancer who completed standard therapy but remain at high risk of relapse. Elicio continues to evaluate pre-specified subgroups, including the R0 resected population, to further inform a refined Phase 3 development strategy. Elicio intends to initiate a Phase 1 study in metastatic PDAC designed to provide a rapid assessment of clinical activity using an open label design to assess the objective response rate including partial and complete radiographic responses. Elicio plans to use the study findings to further evaluate checkpoint inhibitor combinations and help inform future development strategies in metastatic PDAC and the adjuvant PDAC Phase 3 trial. ELI-002 also has been studied in patients with mKRAS-positive colorectal cancer in Phase 1 studies. In the future, Elicio plans to expand ELI-002 7P 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. About Break Through Cancer Founded in 2021, Break Through Cancer empowers outstanding researchers and physicians to both intercept and find cures for several of the deadliest cancers by stimulating radical collaboration among outstanding cancer research institutions, including its founding partners: Dana-Farber Cancer Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Memorial Sloan Kettering Cancer Center, MIT’s Koch Institute for Integrative Cancer Research, and The University of Texas MD Anderson Cancer Center. The Foundation is supported by a Board of Directors from the five partner institutions and a Scientific Advisory Board of U.S. cancer experts. The Foundation was launched with an extraordinary challenge pledge of $250 million from Mr. and Mrs. William H. Goodwin, Jr. and their family, and the estate of William Hunter Goodwin III. For further information, please visit the Foundation’s website at www.breakthroughcancer.org. About The Lustgarten Foundation The Lustgarten Foundation is the largest private funder of pancreatic cancer research in the world, funding preeminent pancreatic cancer research, driving the pursuit of bold and innovative science toward earlier detection and better treatments, and transforming pancreatic cancer into a curable disease. The Foundation funds research where creative risks yield high rewards to accelerate and expand life-saving treatment options. The Lustgarten foundation believes time is everything to patients and their families, and that community is power. Lustgarten programs and events provide people affected by pancreatic cancer a voice and a place to create hope, together. For more information about the Lustgarten Foundation, visit lustgarten.org and follow us on Facebook, Instagram, Bluesky, LinkedIn, and YouTube. Elicio 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 the IIT; the timing, enrollment, and outcome of Elicio’s planned clinical trials; the potential of Elicio’s product candidates and platform; the potential to generate important clinical insights into ELI-002 7P’s potential to harness the immune system and improve surgical outcomes and long-term survival for patients with PDAC; the potential benefits of combining standard neoadjuvant chemotherapy with immunotherapies, including the combination of mFOLFIRINOX with ELI-002 7P, with or without tislelizumab; the potential for ELI-002 7P to reshape the tumor immune environment when combined with neoadjuvant therapy; the potential for the IIT to generate valuable translational data to inform future treatment strategies; the potential for future expansion of ELI-002 to other indications, including mKRAS positive lung cancer and other mKRAS positive cancers; the potential benefits and effectiveness of off-the-shelf vaccine approaches; 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 Elicio’s 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 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, 2025, filed with the SEC on March 12, 2026, as amended on April 29, 2026, its Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, filed with the SEC on May 11, 2026, and any 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. Elicio Investor Relations Contact Brian RitchieLifeSci Advisors(212) 915-2578britchie@lifesciadvisors.com Elicio Media Contact Michael FitzhughLifeSci Communications(415) 269-7757mfitzhugh@lifescicomms.com