NC-318

▎药明康德内容团队编辑近日，NextCure公司公布了一项2期临床试验的积极结果，对PD-1通路抑制剂耐药的难治性非小细胞肺癌（NSCLC）晚期患者在接受其靶向Siglec-15（S15）的单克隆抗体NC318联用默沙东（MSD）的PD-1抗体帕博利珠单抗后可获得临床获益。NextCure是一家专注于发现并开发下一代免疫药物治疗癌症和其他疾病的生物医药公司，陈列平博士是该公司的科学创始人。通过其专有的FIND-IO平台，NextCure致力于研究各种免疫细胞，发现并了解免疫细胞的靶点和结构成分及其对疾病的功能影响，从而开发免疫药物。该公司的工作重点是为那些对目前的癌症疗法没有应答的患者、尽管接受治疗但癌症仍在进展的患者，以及现有疗法无法充分治疗的癌症患者带来希望和新疗法。虽然靶向PD-1/PD-L1的免疫检查点抑制剂疗法给癌症治疗带来了革命性的变更，然而依然有很多癌症患者无法从这些疗法中获益。有些患者的肿瘤PD-L1表达水平很低，这些患者通常对PD-1/PD-L1免疫疗法响应不良。NC318是一款潜在“first-in-class”的单克隆抗体，它的靶点是名为Siglec-15的细胞表面蛋白。这种蛋白表达在肿瘤细胞和M2巨噬细胞表面，能够强有力地抑制T细胞的激活，从而抑制人体对癌症细胞的免疫反应。重要的一点是，在NSCLC和其它癌症类型中，Siglec-15的表达与PD-L1的表达并不重叠。这意味着靶向Siglec-15的疗法可能用于治疗那些对PD-1/PD-L1抑制剂反应不佳的患者。在NextCure早先进行的一项单药治疗研究中，NC318在针对晚期实体瘤患者的1/2期剂量递增试验中显示出了单药活性。相关阅读：对PD-1疗法产生抗性怎么办？来自美国免疫疗法学会年会的答案此次公布的2期临床试验的疗效数据表明，NC318联用帕博利珠单抗在晚期PD-1通路抑制剂难治性NSCLC中具有活性：28%的患者（5/18）获得了持久的临床获益（经RECIST和/或irRC检测，部分缓解或疾病稳定超过6个月），其中3名患者获得了确认的缓解。所有确认的缓解均发生在PD-L1阴性肿瘤患者身上，PD-L1阳性和阴性肿瘤患者均可获益。其他生物标志物和药效学研究正在进行中。截至目前，单药治疗和联合用药两臂的耐受性均良好，两臂共发生6起3级治疗相关不良事件（TRAE）：横贯性脊髓炎（1起）、输液反应（3起）、皮疹（1起）和肺炎（1起）；4起2级TRAE：输液反应（2起）、心包炎（1起）和银屑病（1起）。7名患者出现了NC318输液反应（3名3级，4名2级），其中6名为接受联合用药的患者，1名为单用NC318的患者。NC318的输注时间从30分钟延长到60分钟后，没有再出现输液反应。药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] A Phase 2 Study of Anti-Siglec-15 Antibody, NC318, in Combination with Pembrolizumab (NCT04699123) Demonstrates Clinical Activity in Patients with Advanced PD-1 Axis Inhibitor Refractory NSCLC. Retrieved September 14，2023，from https://www.globenewswire.com/news-release/2023/09/12/2741628/0/en/A-Phase-2-Study-of-Anti-Siglec-15-Antibody-NC318-in-Combination-with-Pembrolizumab-NCT04699123-Demonstrates-Clinical-Activity-in-Patients-with-Advanced-PD-1-Axis-Inhibitor-Refracto.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。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：本文来自药明康德内容团队，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

• Data presented at the 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Singapore BELTSVILLE, Md., Sept. 12, 2023 (GLOBE NEWSWIRE) -- NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases, today announced the presentation of Phase 2 clinical data by collaborators at the Yale Cancer Center demonstrating clinical benefit in patients with advanced, PD-1 axis inhibitor refractory non-small cell lung cancer (NSCLC) treated with a combination regimen of NC318, a Siglec-15 (S15) monoclonal antibody (mAb), and pembrolizumab, an anti-PD-1 antibody. NC318 is a humanized IgG1 mAb against S15 that blocks interactions of S15 with myeloid cells and T lymphocytes within the tumor microenvironment, relieving immune inhibitory signaling. In an earlier monotherapy study from NextCure, NC318 demonstrated single agent activity in a Phase 1/2 dose escalation trial (NCT03665285) for patients with advanced solid tumors (Tolcher et al, SITC 2019). The ongoing NCT04699123 study is a randomized trial designed to assess the safety and efficacy of NC318 alone or in combination with pembrolizumab. The combination portion of the study is assessing efficacy in NSCLC subjects who have experienced disease progression on, or after, PD-1 axis inhibitor therapy. Key findings from the trial include: Efficacy data demonstrate that the combination of NC318 and pembrolizumab is active in advanced PD-1 axis inhibitor refractory NSCLC: 28% of patients (5/18) had durable clinical benefit (partial response or stable disease lasting greater than 6 months by RECIST and/or irRC) with three of these being confirmed responses.To date, both monotherapy and combination arms have been well tolerated, with six Grade 3 treatment-related adverse events (TRAEs) [transverse myelitis (1), infusion reactions (3), rash (1) and pneumonitis (1)] and four Grade 2 TRAEs [infusion reactions (2), pericarditis (1) and psoriasis (1)] between both arms. NC318 infusion reactions were seen in seven patients (three Grade 3, four Grade 2), six receiving the combination and one NC318 alone. No additional infusion reactions occurred once NC318 infusion time was increased from 30 to 60 minutes.All confirmed responses were in patients with PD-L1 negative tumors, and benefits were seen in patients with both PD-L1 positive and negative tumors. Additional biomarker and pharmacodynamic studies are ongoing. “Based on these early encouraging results, Yale is continuing to enroll patients to gain further evidence of clinical activity of NC318,” said Solomon Langermann, Ph.D., NextCure’s chief scientific officer. “We look forward to continuing our collaboration with Drs. Herbst and Gettinger and the Yale Cancer Center. “We are excited that this investigator-initiated trial, part of our NCI Lung SPORE (Specialized Program of Research Excellence), is providing new insights into the mechanisms and treatment of immune therapy resistance. We look forward to reporting more data in the future,” said Roy Herbst, M.D., Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology; Deputy Director, Yale Cancer Center; Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; Assistant Dean for Translational Research, Yale School of Medicine; Director, Center for Thoracic Cancers, Yale Cancer Center and Smilow Cancer Hospital. Details of the presentation are as follows: Title: A Phase 2 study of NC318 alone or in combination with pembrolizumab in patients with advanced NSCLCPresenter: Roy Herbst, MDPresentation No: MA15.07Session Title: Bringing New Discoveries into Early Phase Clinical TrialsSession Time: September 12, 2023, 10:45AM - 11:45AM SGT NextCure has maintained a longstanding relationship with clinician scientists at Yale University stretching back to the company’s founding. NextCure’s scientific founder Dr. Lieping Chen, a leader in immunology and medical oncology, is the United Technologies Corporation Professor in Cancer Research and Professor of Immunobiology, Dermatology and Medicine (Medical Oncology) at Yale University. The immunosuppressive properties of S15 were discovered by Dr. Chen at Yale University. NextCure has exclusively licensed technologies relating to S15 from Yale University, and has since collaborated with Yale University to continue development of NC318, as well as other immuno-oncology candidates, through sponsored research and clinical trial agreements. About NextCure, Inc.NextCure is a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases. Through our proprietary FIND-IO™ platform, we study various immune cells to discover and understand targets and structural components of immune cells and their functional impact in disease in order to develop immunomedicines. Our focus is to bring hope and new treatments to patients who do not respond to current cancer therapies, patients whose cancer progresses despite treatment and patients with cancer types not adequately addressed by available therapies. http://www.nextcure.com Cautionary Statement Regarding Forward-Looking StatementsStatements made in this press release that are not historical facts are forward-looking statements. Words such as “expects,” “believes,” “intends,” “hope,” “forward” and similar expressions are intended to identify forward-looking statements. Examples of forward-looking statements in this press release include, among others, statements about NextCure’s plans, objectives, and intentions with respect to the discovery of immunomedicine targets and the discovery and development of immunomedicines. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those projected in any forward-looking statement. Such risks and uncertainties include, among others: our limited operating history and no products approved for commercial sale; our history of significant losses; our need to obtain additional financing; risks related to clinical development, including that early clinical data may not be confirmed by later clinical results; risks that pre-clinical research may not be confirmed in clinical trials; risks related to marketing approval and commercialization; and the unproven approach to the discovery and development of product candidates based on our FIND-IO platform. More detailed information on these and additional factors that could affect NextCure’s actual results are described in NextCure’s filings with the Securities and Exchange Commission (the “SEC”), including NextCure’s most recent Form 10-K and subsequent Form 10-Q. You should not place undue reliance on any forward-looking statements. NextCure assumes no obligation to update any forward-looking statements, even if expectations change. Investor InquiriesTimothy Mayer, Ph.D.NextCure, Inc.Chief Operating Officer(240) 762-6486IR@nextcure.com