Amphiphile-CpG

近期，全球多肽和寡核苷酸（TIDES）领域迎来系列进展。诺和诺德（Novo Nordisk）公司的重磅疗法Wegovy（2.4 mg司美格鲁肽）获得美国FDA加速批准，成为首个获批用于治疗代谢功能障碍相关脂肪性肝炎（MASH）的胰高血糖素样肽-1（GLP-1）疗法。Elicio Therapeutics针对KRAS突变体的癌症疫苗ELI-002的1期临床试验结果在Nature Medicine期刊上发表。在T细胞免疫应答超过抗肿瘤疗效阈值的患者中，疾病进展或死亡风险降低88%，死亡风险降低77%。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。 Wegovy：FDA批准治疗MASH 诺和诺德（Novo Nordisk）宣布，美国FDA已加速批准其重磅疗法Wegovy（2.4 mg司美格鲁肽）的补充新药申请（sNDA），用于联合低热量饮食及增加体育活动，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。 此次批准主要基于ESSENCE试验的第一部分结果，该结果已发布于《新英格兰医学杂志》。在第72周时，第一个主要终点数据显示，接受司美格鲁肽治疗的患者中，62.9%达到脂肪性肝炎缓解且肝纤维化未恶化，而安慰剂组为34.3%。两组间应答患者比例的估计差值（EDP）为28.7%（95% CI：21.1-36.2；P<0.001）。第二个主要终点显示，司美格鲁肽治疗组有36.8%的患者肝纤维化得到改善且脂肪性肝炎未恶化，而安慰剂组为22.4%（EDP为14.4%；95% CI：7.5-21.3；P<0.001）。 此外，第72周时的一个次要终点表明，接受司美格鲁肽治疗的患者中有32.7%同时达到脂肪性肝炎缓解及肝纤维化改善，而安慰剂组仅为16.1%（EDP为16.5%；95% CI：10.2-22.8；P<0.001）。 ELI-002：1期临床试验结果发表 Elicio Therapeutics公司日前宣布，在研疗法ELI-002的1期临床试验AMPLIFY-201的随访数据已发表于科学期刊Nature Medicine。数据显示，在T细胞应答超过抗肿瘤疗效阈值的受试者中，其疾病进展或死亡风险显著降低。 这项试验入组了25例处于辅助治疗阶段的实体瘤患者（20例胰腺癌，5例结直肠癌），他们在接受局部治疗后仍存在KRAS突变阳性的微量残留病（MRD）。在84%接受ELI-002治疗的患者中检测到突变KRAS特异性的外周T细胞应答，其中71%患者同时产生CD4阳性和CD8阳性T细胞应答。通过量化循环肿瘤DNA（ctDNA）检测，84%的患者观察到肿瘤生物标志物应答。中位随访时间为19.7个月时，25例患者的中位无复发生存期（RFS）为16.33个月，中位总生存期（OS）为28.94个月。 ELI-002的疗效与其诱导的突变KRAS特异性T细胞应答显著相关，在T细胞应答高于抗肿瘤疗效阈值的17名患者中，11名患者疾病无影像学进展，而应答低于阈值的8名患者均出现影像学进展。高于阈值组患者与低于阈值组相比，疾病进展或死亡风险降低88%，死亡风险降低77%。 ELI-002是一种基于Elicio公司淋巴结靶向两亲性（AMP）技术构建的癌症疫苗，专门靶向由KRAS基因突变驱动的癌症。ELI-002包含两种重要成分：基于AMP技术改造的KRAS突变多肽抗原和AMP改造的寡脱氧核苷酸佐剂ELI-004。 Cylembio：公布关键性3期临床试验结果 IO Biotech公布了在研癌症疫苗Cylembio（imsapepimut与etimupepimut，配合佐剂）关键性3期临床试验的主要结果。该试验在407例不可切除或转移性黑色素瘤患者中，评估Cylembio联合默沙东（MSD）的PD-1抑制剂Keytruda（pembrolizumab）与pembrolizumab单药作为一线治疗的疗效。 分析显示，联合治疗组在无进展生存期（PFS）方面较单药组有所改善，风险比为0.77（95% CI：0.58-1.00），中位PFS分别为19.4个月与11.0个月，但主要终点的统计学显著性（p=0.056）略低于预设阈值（p≤0.045）。在未接受过新辅助/辅助PD-1抑制剂治疗的患者亚组（n=371）中，联合治疗的风险比为0.74（95% CI：0.56-0.98，p=0.037），中位PFS延长至24.8个月，相较对照组的11.0个月有所提升。几乎所有亚组均观察到PFS改善，其中PD-L1阴性肿瘤患者的受益尤为显著（HR=0.54，95% CI：0.35-0.85，p=0.006），联合治疗组中位PFS为16.6个月，对照组为3.0个月。研究还观察到联合治疗组在总生存期（OS）方面呈改善趋势（HR=0.79，95% CI：0.57-1.10），但数据尚未成熟。Cylembio联合pembrolizumab耐受性良好，未发现新的安全性信号。IO Biotech计划于今年秋季与美国FDA会面，讨论该研究数据及潜在上市申请途径。 Cylembio是一款在研的免疫调节、现货型治疗用多肽癌症疫苗，通过激活并扩增针对IDO1阳性和/或PD-L1阳性细胞的T细胞，旨在同时杀灭肿瘤细胞和肿瘤微环境中的免疫抑制细胞。 Zorevunersen：3期临床试验完成首位患者给药 渤健（Biogen）与Stoke Therapeutics公司宣布，全球性3期临床试验EMPEROR的首位患者已接受zorevunersen给药，用于治疗Dravet综合征。Zorevunersen是一种在研反义寡核苷酸（ASO）药物，有望成为首个可改变Dravet综合征疾病进程的治疗方案。 Dravet综合征是一种严重且进展性的遗传性癫痫，其特征是患儿在出生后第一年即出现频繁、长期且难治的癫痫发作，导致发育迟缓和认知障碍。该病通常与编码NaV1.1通道α亚基的SCN1A基因突变有关。当人体中两个SCN1A基因拷贝中的一份因突变而无法产生功能性蛋白时，NaV1.1蛋白水平便会下降，从而引发疾病。 Zorevunersen旨在增强患者体内没有突变的SCN1A等位基因的表达，从而提高NaV1.1蛋白水平。它已经获得美国FDA授予的突破性疗法认定，用于治疗Dravet综合征。渤健与Stoke Therapeutics在今年年初就zorevunersen达成超5亿美元的开发和商业化合作协议。 参考资料： [1] Elicio Therapeutics Announces Publication of ELI-002 Updated AMPLIFY-201 Phase 1 Follow-up Data in Nature Medicine for Minimal Residual Disease (“MRD”) Positive, Adjuvant-Stage Patients. Retrieved August 13, 2025, from https://www.globenewswire.com/news-release/2025/08/12/3131607/0/en/Elicio-Therapeutics-Announces-Publication-of-ELI-002-Updated-AMPLIFY-201-Phase-1-Follow-up-Data-in-Nature-Medicine-for-Minimal-Residual-Disease-MRD-Positive-Adjuvant-Stage-Patients.html [2] IO Biotech Announces Clinical Improvement in Progression Free Survival Demonstrated in Pivotal Phase 3 Trial of Cylembio® plus KEYTRUDA® (Pembrolizumab) for the Treatment of First-line Advanced Melanoma, but Statistical Significance Narrowly Missed. Retrieved August 13, 2025, from https://iobiotech.com/press-releases/?workflow=6562e614-30a0-4300-9a37-ab75253933a2 [3] Biogen and Stoke Therapeutics Announce First Patient Dosed in Phase 3 EMPEROR Study of Zorevunersen, a Potential Disease-Modifying Treatment for Dravet Syndrome. Retrieved August 13, 2025, from https://www.globenewswire.com/news-release/2025/08/11/3130760/0/en/Biogen-and-Stoke-Therapeutics-Announce-First-Patient-Dosed-in-Phase-3-EMPEROR-Study-of-Zorevunersen-a-Potential-Disease-Modifying-Treatment-for-Dravet-Syndrome.html [4] Cue Biopharma Announces Initiation of Investigator Sponsored Trial of CUE-102 in Recurrent Glioblastoma Multiforme. Retrieved August 14, 2025, from https://www.globenewswire.com/news-release/2025/08/13/3132505/0/en/Cue-Biopharma-Announces-Initiation-of-Investigator-Sponsored-Trial-of-CUE-102-in-Recurrent-Glioblastoma-Multiforme.html [5] ProteinQure Receives Regulatory Clearance to Initiate Phase I Trial for PQ203 in the U.S. and Canada; Granted FDA Fast Track Designation. Retrieved August 14, 2025, from https://www.proteinqure.com/proteinqure-receives-regulatory-clearance-to-initiate-phase-i-trial-for-pq203-in-the-u-s-and-canada-granted-fda-fast-track-designation/ [6] Novo Nordisk A/S: Wegovy® approved in the US for the treatment of MASH. Retrieved August 15, 2025 from https://www.globenewswire.com/news-release/2025/08/15/3134494/0/en/Novo-Nordisk-A-S-Wegovy-approved-in-the-US-for-the-treatment-of-MASH.html 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

At extended median follow-up of 19.7 months, median overall survival (“OS”) increased from 16.33 to 28.94 months Clinical efficacy correlated with the magnitude of T cell responses specific to mutant-KRAS (“mKRAS”) induced by ELI-002 77% reduction in the risk of death and 88% reduction in the risk of relapse, associated with T cell responses above the threshold for anti-tumor efficacy ELI-002 induced both CD4+ and CD8+ mKRAS-specific T cell responses in most patients, and evidence of antigen-spreading to patient-specific neoantigens not included in ELI-002 was observed Final event-driven disease-free survival (“DFS”) analysis for the randomized Phase 2 AMPLIFY-7P study evaluating ELI-002 7P monotherapy in pancreatic ductal adenocarcinoma (“PDAC”) is anticipated in Q4 2025 Aug. 12, 2025 -- 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 the publication of follow-up data from the Phase 1 AMPLIFY-201 study evaluating ELI-002 in the peer-reviewed scientific journal, Nature Medicine. The article, entitled, “Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: Phase 1 AMPLIFY-201 trial final results,” highlights that with extended follow-up, more than two-thirds of participants (17 of 25) whose T cell responses exceeded the antitumor efficacy threshold experienced a significantly reduced risk for relapse or death. “This publication, combined with the early promising clinical data we’ve generated to date, further strengthens our belief that our Amphiphile (“AMP”) platform represents a potentially transformative approach in the treatment of mKRAS-driven tumors,” commented Robert Connelly, Chief Executive Officer of Elicio. Chris Haqq, MD, Ph.D., Chief Medical Officer of Elicio, added, “The updated Phase 1 AMPLIFY-201 data further demonstrate that the AMP platform has the potential to provide durable benefit to PDAC patients in the adjuvant setting. These promising results together with the recent positive recommendation from the Independent Data Monitoring Committee that the randomized ongoing Phase 2 AMPLIFY-7P study should continue without modification to final DFS analysis, represent critical advancements for our promising lead program.” 25 adjuvant-stage patients with solid tumors (20 PDAC, 5 colorectal) were enrolled for treatment based on positive for minimal residual mKRAS disease after locoregional treatment, with data reported through September 24, 2024. Direct ex vivo mKRAS-specific T cell responses were observed in 21/25 patients (84%), including both CD4+ and CD8+ T cell responses in 71% of patients, and 6/6 patients (100%) treated at the recommended Phase 2 dose (“RPD2”); the induction of both CD4+ and CD8+ T cells correlated with overall tumor biomarker response (pTumor biomarker responses were observed in 21/25 patients (84%), with complete biomarker clearance observed in 6/25 patients, as determined by tumor-informed circulating tumor DNA analysis (24%; 3 PDAC, 3 colorectal). At 19.7 months median follow-up (compared to 8.5 months previously), the median relapse-free survival (“RFS”) was 16.33 months, and the median OS was 28.94 months for the 25-patient cohort. Efficacy correlated with ELI-002-induced mKRAS-specific T cell response (≥ versus Median tumor biomarker reduction was 55.2% compared to 36.7% in above versus below threshold T cell responders, respectively (p11/17 patients with T cell response above threshold remained free from radiographic progression while 8/8 patients with below threshold T cell responses had confirm radiographic progression (7/8 had died); Relative Risk of Progression or Death in below threshold T cell responders was 2.96. Median RFS was not reached compared to 3.02 months in above versus below threshold T cell responders, respectively (HR 0.12, 95% CI 0.02 to 0.62, p=0.0002); patients with greater than threshold T cell response had an 88% reduction in the risk of progression or death. Median OS was not reached compared to 15.98 months in above versus below threshold T cell responders, respectively (HR 0.23, 95% CI 0.06 to 0.85, p=0.0099); patients with greater than threshold T cell response had an 77% reduction in the risk of death. Antigen-spreading, a process where the immune system, initially targeting the mKRAS antigens in ELI-002, expands its response to recognize additional antigens in the patient’s tumor leading to a broader and more effective anti-tumor response, was observed in 67% of patients, with increased T cells reactive to personalized, tumor neoantigens absent from ELI-002; overall, increased T cell responses were observed in 13/52 (25%) of evaluated tumor neoantigens. ELI-002 was well tolerated, with no safety concerns identified, and no dose-limiting toxicities or ≥ Grade 3 treatment-related adverse events were observed. DCO: Data cut-off; RFS: Relapse-free survival; OS: Overall survival; ROC: Receiver-operating curve; NR: Not reported 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 vaccine space to develop effective, off-the-shelf vaccines. Elicio’s Amphiphile (“AMP”) technology aims to enhance the education, activation and amplification of cancer-specific T cells relative to conventional vaccination strategies, with the goal of promoting durable cancer immunosurveillance in patients. Elicio’s ELI-002 lead program is an off-the-shelf vaccine candidate targeting the most common KRAS mutations, which drive approximately 25% of all solid tumors. Off-the-shelf vaccine 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 vaccines 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 vaccines candidates, including ELI-007 and ELI-008, that target BRAF-driven cancers and p53 hotspot mutations, respectively. Elicio’s lead product candidate, ELI-002, is a structurally novel investigational AMP cancer vaccine 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. 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. The content above comes from the network. if any infringement, please contact us to modify.