NC-410

▲点击图片，了解详情作者：贝壳社6月16日，先声药业集团旗下的抗肿瘤创新药公司先声再明与美国生物制药公司NextCure, Inc.（以下简称NextCure）宣布，双方已建立战略合作伙伴关系，共同开发针对CDH6靶点的新型抗体药物偶联物（ADC）新药SIM0505，用于治疗实体瘤。在SIM0505项目的潜在开发阶段，先声再明将有权获得最高7.45亿美元的相关款项，这些款项涵盖首付款、开发及销售里程碑付款，并且还将根据该产品在大中华区以外地区的净销售额，额外获得高达双位数的分级特许权使用费。01NextCure：战略转型与ADC布局ADC药物的成功依赖于靶点、抗体、有效载荷三大核心组成部分的协同作用。据悉，SIM0505是由先声再明研发的一款靶向CDH6（钙粘蛋白-6或K-钙粘蛋白）的新型ADC，独特的结合表位对肿瘤抗原的亲和力高于同类候选药物。其中，CDH6在多种癌症中高度表达，而在正常成人组织中表达量有限，使其成为ADC药物的理想靶点。此外，SIM0505采用了先声再明专有的TOPO异构酶1抑制剂（TOPOi）有效载荷，在具有强抗肿瘤活性的同时，具有较高的系统清除率，从而扩大治疗窗口。临床前研究表明，该药物在多种实体瘤模型中均表现出强抑瘤效果，并且在毒理学模型中具有良好的安全性。SIM0505目前正在中国进行I期临床试验。NextCure计划于2025年第三季度在美国启动临床试验。此次合作还包括授权NextCure使用先声再明ADC技术平台专有的连接子和TOPOi有效载荷，用于NextCure一款临床前阶段新型靶点ADC的开发。先声再明将拥有这款新型靶点ADC在大中华区的权利。NextCure是美国一家临床阶段的生物制药公司，聚焦肿瘤IO疗法。目前市值约1400万美元，财务数据显示，近年来，NextCure持续亏损，且现金储备有限。2024年11月，NextCure宣布了一项重大的战略转型，决定降低其临床阶段免疫肿瘤资产NC410（一种LAIR-2融合蛋白）的优先级，转而“全力以赴”投入ADC领域。这一转型表明NextCure急需在ADC领域取得突破，以提升自身竞争力和市场价值。引进SIM0505对NextCure而言是一场豪赌。它为NextCure带来了一款具有‘同类最佳’潜力的资产，以及一个即将到来的临床催化剂。而预计将于2026年上半年公布的初步临床数据，将成为决定此次合作价值乃至NextCure公司未来的关键转折点。02强手如林：CDH6靶向疗法的竞争格局针对CDH6靶点的药物开发正日趋白热化，尤其是在ADC领域，多家公司都在力争证明其候选药物拥有更优的疗效和安全性。除了ADC，其他新兴技术如T细胞衔接器和CAR-T疗法也开始布局此靶点，展现出了巨大的治疗潜力。ADC是当前CDH6靶点竞争最激烈的赛道。各家公司通过优化有效载荷、连接子和抗体技术，力求在疗效和安全性之间找到平衡点，并实现突破。以下是主要临床阶段CDH6 ADC的对比：第一三共/默沙东的DS-6000无疑是该领域的领导者，已进入关键的Ⅲ期临床试验，并以46%的ORR设定了极高的疗效标杆。然而，其致命弱点在于安全性，特别是导致患者死亡的间质性肺病（ILD）风险，这为后来者创造了巨大的机会窗口。SIM0505和CUSP06等挑战者均旨在利用DS-6000的安全性弱点。SIM0505宣称，其有效载荷具备‘较高系统清除率’的特性，从而扩大治疗窗口。CUSP06则已在临床中初步证明了其“可控的安全性”和36%的ORR，显示出强大的潜力。CDH6靶向药的竞争核心很可能取决于最佳的综合治疗指数，而非单纯追求最高的疗效。德琪医药正在开发的ATG-106是一款CDH6/CD3 TCE，拟用于卵巢癌和肾癌。Phrontline Biopharma正在开发的TJ102是一款同时靶向CDH6和FRα的双特异性、双有效载荷ADC，来增强肿瘤特异性并可能克服耐药性。随着全球肿瘤发病率的逐年上升，以及对肿瘤治疗的重视程度不断提高，患者对精准且有效的治疗药物的需求正日益增长。据相关统计，卵巢癌的发病率在2017年到2021年的全球年复合增长率达到了2.5%，且预测该病2025年全球发病人数将达到35万人，在2030年全球发病人数预计将达到37万人。CDH6靶向药在卵巢癌等肿瘤治疗领域的应用前景广阔，有望分享这一市场的增长红利。艾伯维以101亿美元收购ImmunoGen，以获得其靶向FRα ADC药物Elahere，用于卵巢癌的治疗，为该领域成功药物的潜在估值提供了一个强有力的参照。总体而言，NextCure通过与先声再明的合作，获得了具有潜力的CDH6 ADC药物SIM0505，并借助先声再明的技术平台加速自身在ADC领域的研发进程。这一合作将为NextCure提供重要的产品和技术支持，有望改善其在ADC领域的竞争地位。但SIM0505的最终成功将由临床数据决定，SIM0505如果能在提供与DS-6000相当疗效的同时，展现出明显改善的安全性，那么它就有望成为一个极具价值的商业资产。但NextCure能否成功抓住这一机会，还需在研发、商业化等方面不断努力，以应对激烈的市场竞争和技术挑战。往期推荐1医健企业前沿动态2医健行业BD/出海/投融资洞察___*声明：本文仅为作者观点，不构成任何投资建议，且非治疗方案推荐素材来源公司官媒/网络新闻关于贝壳社贝壳社是国内领先的医健创新创业服务平台，构建了"产业空间+创业教育+投资孵化+资本运作"四位一体服务体系，为医健领域创业企业提供全周期赋能。通过深度挖掘高成长项目、精准匹配产业资源及全球化生态网络，覆盖企业从孵化培育到加速发展的全链路，重点提供包括空间落地、创业培训、资本运作及跨境资源链接服务。贝壳社以加速科学技术成果转化与产业升级为目标，致力于成为医健领域的孵化器、加速器、连接器。

Prioritize and focus resources on LNCB74 (B7-H4 ADC) with a planned IND submission by year-endCash of approximately $75 million expected to fund operations into second half of 2026 BELTSVILLE, Md., Nov. 07, 2024 (GLOBE NEWSWIRE) -- NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class, and best-in-class therapies to treat cancer, today provided a business update and reported third-quarter 2024 financial results. “The November SITC presentation of LNCB74 preclinical data will highlight the differentiation of our B7-H4 ADC from other ADC’s that also target B7-H4. We plan to file an IND in the fourth quarter of this year and advance into Phase 1, shortly following receipt of an FDA safe-to-proceed letter,” said Michael Richman, NextCure’s president and CEO. “Additionally, while the NC410 combo has shown encouraging Phase 1b clinical activity in both ovarian cancer and CRC patients, we plan to conclude the current trial and seek a partner to advance the program, allowing us to focus our resources on advancing the development of LNCB74.” Business Highlights and Near-Term Milestones LNCB74 (B7-H4 ADC) Leveraging LigaChem Biosciences, Inc. glucuronidase cleavable site-specific linkage as part of a collaboration agreement that includes a 50-50 cost sharing of external development expenses and certain internal cost sharing associated with the development of the antibody- drug conjugate (ADC) program.Preclinical data from LNCB74 (B7-H4 ADC) will be presented at the Society of Immunotherapy of Cancer (SITC) annual meeting in November.Planned submission of an Investigational New Drug (IND) application in the fourth quarter of this year. NC410 (LAIR-2 fusion) Additional colorectal cancer (CRC) patient Phase 1b clinical data along with biomarker data supporting mechanism of action to be presented at SITC annual meeting in November.As of October 14, 2024 (the cut-off date), 11 patients (4 with ovarian cancer and 7 with CRC) remain in the Phase 1b study evaluating NC410 in combination with pembrolizumab and will continue to be monitored while the study concludes.As of the cut-off date, the response rate for the ovarian cancer patients that were immune checkpoint inhibitor (ICI) naïve was 25% based on 5 out of 20 patients, which consisted of 2 partial responses (PRs) at 200 mg, and 3 PRs at 100mg in ICI naïve.As of the cut-off date, the 100 mg cohort CRC response rate was 8.3% based on 3 out of 36 patients, which consisted of 3 PRs in ICI naïve, MSS/microsatellite instability-low with a disease control rate (DCR) of 47% (17/36), median disease control (mDC) duration of 8.5 months, and median duration of response of 15.2 months. A 200 mg CRC cohort of 7 showed no clinical responses with a DCR of 86% (6/7) and a mDC duration of 8.3 months.Will seek a partner or pursue third party financing to advance NC410 in further clinical trials. Preclinical Non-Oncology Programs Seeking Third Party Financing NC181 (ApoE4), a humanized antibody for the treatment of Alzheimer’s disease (AD). In preclinical AD animal models, NC181 has demonstrated amyloid clearance, prevention of amyloid deposition, plaque clearance and reduced neuroinflammation.NC605 (Siglec-15), a humanized antibody for the treatment of osteogenesis Imperfecta (OI). Preclinical data reported that NC605 treatment reduced bone loss and enhanced bone quality in mice with OI.Both programs could lead to IND filings within 12 to 18 months if financial support from third parties is secured. Financial Results for Quarter Ended September 30, 2024 Cash, cash equivalents, and marketable securities as of September 30, 2024 were $75.3 million as compared to $108.3 million as of December 31, 2023. The decrease of $33.0 million was primarily due to cash used to fund operations. NextCure expects financial resources to fund operating expenses and capital expenditures into the second half of 2026.Research and development expenses were $8.8 million for the three months ended September 30, 2024, as compared to $11.0 million for the three months ended September 30, 2023. Net costs on the LNCB74 program were more than offset by lower costs on other programs and preclinical development and lower personnel-related costs.General and administrative expenses were $3.7 million for the three months ended September 30, 2024, as compared to $4.6 million for the three months ended September 30, 2023. The decrease of $0.9 million was primarily related to lower payroll, lower stock compensation expense and lower insurance costs.Net loss was $11.5 million for the three months ended September 30, 2024, as compared to a net loss of $14.3 million for the three months ended September 30, 2023. About NextCure, Inc. NextCure is a clinical-stage biopharmaceutical company that is focused on advancing innovative medicines that treat cancer patients that do not respond to, or have disease progression on, current therapies, through the use of differentiated mechanisms of actions including antibody-drug conjugates, antibodies and proteins. We focus on advancing therapies that leverage our core strengths in understanding biological pathways and biomarkers, the interactions of cells, including in the tumor microenvironment, and the role each interaction plays in a biologic response. www.nextcure.com Forward-Looking Statements Some of the statements contained in this press release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including with respect to funding for our operations, objectives and expectations for our business, operations and financial performance and condition, including the progress and results of clinical trials, development plans and upcoming milestones regarding our therapies. Any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “continue,” “could,” “should,” “due,” “estimate,” “expect,” “intend,” “hope,” “may,” “objective,” “plan,” “predict,” “potential,” “positioned,” “seek,” “target,” “towards,” “forward,” “later,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or similar language. 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: positive results in preclinical studies may not be predictive of the results of clinical trials; NextCure’s limited operating history and not having any products approved for commercial sale; NextCure’s history of significant losses; NextCure’s need and ability to obtain additional financing on acceptable terms or at all; risks related to clinical development, marketing approval and commercialization; and NextCure’s dependence on key personnel. More detailed information on these and additional factors that could affect NextCure’s actual results are described under the heading “Risk Factors” in NextCure’s most recent Annual Report on Form 10-K and in NextCure’s other filings with the Securities and Exchange Commission. You should not place undue reliance on any forward-looking statements. Forward-looking statements speak only as of the date of this press release, and NextCure assumes no obligation to update any forward-looking statements, even if expectations change. Selected Financial Information Selected Statement of Operations Items:Three Months Ended Nine Months Ended September 30, September 30,(in thousands, except share and per share amounts)2024 2023 2024 2023Operating expenses: Research and development$8,770 $11,010 $32,586 $36,104 General and administrative 3,725 4,608 12,165 15,743 Restructuring and asset impairment — — 2,542 — Loss from operations (12,495) (15,618) (47,293) (51,847)Other income, net 955 1,317 3,242 3,591 Net loss$(11,540) $(14,301) $(44,051) $(48,256)Net loss per common share - basic and diluted$(0.41) $(0.51) $(1.58) $(1.73)Weighted-average shares outstanding - basic and diluted 27,975,840 27,839,968 27,950,634 27,814,655 Selected Balance Sheet Items: September 30, December 31,(in thousands) 2024 2023Cash, cash equivalents, and marketable securities $75,308 $108,299 Total assets $90,345 $128,038 Accounts payable and accrued liabilities $8,672 $6,883 Total stockholders' equity $75,592 $114,421 Investor InquiriesTimothy Mayer, Ph.D.NextCure, Inc.Chief Operating Officer(240) 762-6486IR@nextcure.com