Obexelimab

▎药明康德内容团队编辑 神经生物学领域内疾病影响广泛且未竟治疗需求巨大，该领域的创新药物研发具有显著价值。从帕金森病的干细胞疗法到癫痫的再生细胞药物，从渐冻症的基因编辑突破到精神疾病的AI精准诊疗，神经疾病的治疗边界正在被不断拓展。回顾2024年，全球至少有223家神经生物学创新药公司获得融资。值得关注的亮点包括： 多家公司成功IPO：其中有15家公司成功IPO上市，以登陆纳斯达克为主，包括Kyverna Therapeutics、Septerna、Zenas BioPharma等。 一年内完成多轮融资：至少19家公司在2024年内完成2轮或以上融资，包括宁丹新药先后完成了B轮、B+轮及C轮三轮融资，Seaport Therapeutics完成A、B两轮融资共获3.25亿美元支持等。 细胞与基因疗法（CGT）备受关注：通过根源性修复和再生，CGT疗法有望为神经生物疾病提供突破性治疗手段。至少54家获融资公司是CGT疗法研发企业，其中Neurona Therapeutics单轮融资达1.2亿美元，推动即用型细胞疗法迈入临床新阶段。 Kyverna Therapeutics成功登陆纳斯达克 Kyverna Therapeutics是一家临床阶段的细胞疗法研发公司，致力于为自身免疫性疾病和炎症疾病研发新疗法。其治疗平台结合T细胞工程和合成生物学技术，可抑制和消除导致疾病的自身反应性免疫细胞。Kyverna Therapeutics的候选管线KYV-101及其异构体KYV-201是一种CAR-T细胞疗法，旨在治疗B细胞介导的自身免疫性疾病。KYV-101特异性地靶向CD19，这是一种在B细胞表面表达的蛋白，参与各类恶性肿瘤及自身免疫性疾病。该药物已在美国启动针对狼疮性肾炎的1期临床试验，并在德国启动1/2期临床试验。而且在神经生物学领域，KYV-101还获得了美国FDA授予的快速通道资格，用于治疗重症肌无力和多发性硬化。 2月，Kyverna Therapeutics宣布完成3.19亿美元的超额IPO。 GondolaBio获3亿美元A轮融资 GondolaBio是BridgeBio Pharma公司成立的一家新公司。BridgeBio Pharma公司将把针对红细胞生成性原卟啉症、α-1抗胰蛋白酶缺乏症和结节性硬化症的早期临床期和临床前项目转移到GondolaBio公司并由其继续进行开发。 8月，公司在Viking Global Investors LP、Patient Square Capital、红杉资本（Sequoia Capital）等投资机构的支持下成立并获得3亿美元的分期融资。 Septerna纳斯达克成功上市 Septerna成立于2019年，最初名称为GPCR NewCo，2021年6月，公司正式更名为Septerna。正如公司初始名字所示，Septerna是一家致力于开发靶向G蛋白偶联受体（GPCR）小分子药物的公司，由Robert J. Lefkowitz博士与著名投资机构Third Rock Ventures联合创办，Robert J. Lefkowitz博士是GPCR领域的先驱，因为揭秘了GPCR的研究与Brian Kobilka博士一同获得了2012年诺贝尔化学奖。Septerna开发了专有技术，用于分离、纯化细胞外的GPCR，并将其与配体、转导蛋白和模拟细胞膜的脂质双分子层重组为复合物，这些重组的复合物称为原生复合物。公司的Native Complex平台可针对特定的GPCR，发现已验证受体的新结合口袋，并采用各种药理学方法，包括激动剂、拮抗剂和变构调节剂，以不同的方式影响GPCR信号，从而达到预期的治疗效果。 10月，公司宣布在美国纳斯达克上市，预计IPO获得2.88亿美元资金支持。 Alumis一年内从C轮到IPO Alumis由Foresite Labs孵化，旨在利用精准数据分析和多平台方法，优化治疗结果，解决免疫功能紊乱的口服疗法管线。Alumis的候选产品ESK-001是一种口服、高选择性、小分子、变构的TYK2抑制剂，目前正在评估用于治疗中度至重度斑块状银屑病和系统性红斑狼疮患者。Alumis还在开发A-005，一种中枢神经系统渗透性变构TYK2抑制剂，用于治疗神经炎症和神经退行性疾病。 3月，公司完成了2.59亿美元的C轮融资。仅3个月后，公司便成功登陆纳斯达克。 Zenas BioPharma连续完成两轮融资 Zenas成立于2021年，致力于开发免疫治疗药物。公司主要管线Obexelimab是一种双功能单克隆抗体，旨在同时靶向CD19和FcγRIIb，以抑制B细胞、浆母细胞和表达CD19的浆细胞的活性。Obexelimab的临床开发计划包括正在进行的针对IgG4相关疾病的3期注册性临床试验，该疗法已经在五项包括198名受试者的临床试验中显示出显著的临床疗效和安全性，尤其是在自身免疫性疾病方面。其中，针对神经类自身免疫性疾病多发性硬化的临床研究已推进至2期，预计2025年第三季度达到主要临床终点。 5月公司完成2亿美元的C轮融资，并在9月成功登陆纳斯达克。 Seaport Therapeutics两轮融资共获3.25亿美元支持 Seaport Therapeutics聚焦推进其专有Glyph技术平台驱动的创新神经精神疾病药物的开发。该平台旨在提高药物口服生物利用度，避免首过代谢，减少肝毒性和其他副作用，以推进之前因这些限制而被搁置的活性药物。Seaport进展最快的候选药物是SPT-300，它是一种别孕烷醇酮（allopregnanolone）的口服前药，正在开发用于治疗焦虑和抑郁。在2a期临床试验中，SPT-300已在健康志愿者中进行的一个临床焦虑模型中获得了概念验证。 Seaport于4月宣布完成1亿美元的A轮融资，仅半年后便完成了超额认购的2.25亿美元B轮融资。公司将利用这笔资金推进其临床阶段的创新药物管线，并进一步提升Glyph技术平台的能力。 读者们请星标⭐创鉴汇，第一时间收到推送 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：本文由药明康德内容团队根据公开资料整理编辑，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发/复制至其他平台。转发授权请在「创鉴汇」微信公众号留言联系我们。 更多数据内容推荐 点击“在看”，分享创鉴汇健康新动态

- Advancing Phase 2 and Phase 3 trials of obexelimab, a unique CD-19 x FcγRIIb inhibitor of B cell function- -Topline results from Phase 2 Trial in Relapsing Multiple Sclerosis (MoonStone) expected in third quarter 2025- -Topline results from pivotal Phase 3 Trial in Immunoglobulin G4-Related Disease (INDIGO) expected year-end 2025- - Enrollment of Phase 2 Trial in Systemic Lupus Erythematosus (SunStone) expected to be completed in 2025- - Out-licensed greater-China anti-IGF-1R Thyroid Eye Disease programs to Zai Lab - Feb. 05, 2025 -- Zenas BioPharma, Inc. (“Zenas” or the “Company”) (Nasdaq: ZBIO), a clinical-stage global biopharmaceutical company committed to being a leader in the development and commercialization of therapies for autoimmune diseases, today announced its 2024 accomplishments, outlined its key business objectives for 2025 and announced preliminary unaudited cash balance as of year-end 2024. “Based upon the progress achieved across all of our corporate goals and objectives during 2024, we enter 2025 with an opportunity to achieve major value-driving milestones with the anticipated results from our ongoing obexelimab Phase 2 and Phase 3 clinical trials,” said Lonnie Moulder, Founder and Chief Executive Officer of Zenas. “We are extremely proud of the accomplishments of our dedicated team as we enter the year well-financed and able to focus on execution, and achievement of our key objectives for the year.” The Company enters 2025 well-capitalized to deliver its key milestones with approximately $350 million in cash, cash equivalents, and short-term investments as of December 31, 2024, 1 which is expected to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2026. During 2024, the Company achieved the following objectives and announced a recent business development transaction: Completed enrollment of the Phase 3 INDIGO trial, a global Phase 3 registration-directed, randomized, double-blind placebo-controlled trial of obexelimab in patients with Immunoglobulin-G4 Related Disease (IgG4-RD), the largest clinical trial ever conducted in this patient population. Initiated the Phase 2 MoonStone trial, a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and safety of obexelimab in patients with Relapsing Multiple Sclerosis (RMS). Initiated the Phase 2 SunStone trial, a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and safety of obexelimab to reduce disease activity in patients with Systemic Lupus Erythematosus (SLE). Provided initial data from the Phase 2 SApHiAre trial, a global, multicenter, open-label safety and dose confirmation run-in period (SRP) to evaluate the safety and activity of obexelimab in patients with warm Autoimmune Hemolytic Anemia (wAIHA). Obexelimab achieved clinical proof-of-mechanism by increasing hemoglobin levels and red blood cells, and decreasing LDH and total bilirubin levels. Obexelimab was well tolerated in the SRP. Completed an upsized Series C and initial public offering, raising approximately $458.7 million in aggregate gross proceeds to fund its planned activities for obexelimab and the Company’s growth strategy. Bolstered its leadership team with the appointments of Chief Commercial Officer, Orlando Oliveira, and Chief Legal Officer, Jeff Held. Out-licensed ZB005, a human IgG4 monoclonal antibody designed to bind only to the active form of C1s, for which Zenas held the development and commercialization rights in China, Hong Kong, Macau and Taiwan (Greater China) through an exclusive license with Dianthus. The Company recently out-licensed regional rights to its thyroid eye disease programs, including ZB001, an insulin-like growth factor-1 receptor (anti-IGF-1R) monoclonal antibody, to Zai Lab (Zai). Zenas received an upfront fee and is eligible to receive milestone payments and royalties in the future, as consideration for an exclusive sublicense to Zai to develop and commercialize ZB001 and related programs in Greater China. Obexelimab is a bifunctional monoclonal antibody designed to bind both CD19 and FcγRIIb, which are broadly present across B cell lineage, to inhibit the activity of cells that are implicated in many autoimmune diseases without depleting them. This unique mechanism of action and self-administered, subcutaneous once-weekly injection regimen may broadly and effectively address the pathogenic role of B cell lineage in chronic autoimmune disease. Obexelimab has been evaluated in five completed clinical trials in a total of 198 patients who received obexelimab either as an intravenous infusion or as a subcutaneous injection. Obexelimab was well tolerated and demonstrated clinical activity across these five clinical trials, providing the Company an initial clinical proof of concept for obexelimab as a potent B cell inhibitor for the treatment of patients living with certain autoimmune diseases. During 2025, the Company expects to achieve the following key clinical milestones: Report the 12-week primary endpoint results in the third quarter of 2025 from the Phase 2 MoonStone trial in patients with RMS. The role of B cells in the pathogenesis of multiple sclerosis including RMS has been demonstrated through the successful clinical development, approval and clinical use of anti-CD20 B cell targeting therapies of other companies, including OCREVUS® (ocrelizumab) and KESIMPTA® (ofatumumab), which selectively deplete CD20-expressing B cells. The Company believes obexelimab’s unique mechanism of action to potently inhibit but not deplete a broader B cell lineage than CD20, nonclinical data, and a subcutaneous injection regimen, supports its potential for the treatment of RMS. Following an initial screening period, patients in the MoonStone trial are being randomized 2:1 to 250 mg of obexelimab or placebo administered as a subcutaneous injection every seven days for a 12-week treatment period. The primary objective of this double-blinded portion of the trial will be to assess the change from baseline in the cumulative number of gadolinium (Gd) enhancing lesions identified on T1-weighted magnetic resonance imaging (MRI). Upon completion of the 12-week period, patients will enter an open-label period where patients on placebo will receive obexelimab treatment for at least three months, and patients initially randomized to obexelimab will continue treatment. Important secondary endpoints during this open-label period include using standardized assessments, novel 3D imaging and biomarkers, including serum neurofilament light chain (NfL), to evaluate the impact of obexelimab on disease progression. More information on the Phase 2 MoonStone trial (NCT06564311) is available at clinicaltrials.gov Report topline results year-end 2025 from the Phase 3 INDIGO trial in patients with IgG4-RD. IgG4-RD is a chronic fibro-inflammatory disease that can affect virtually all organ systems, including the pancreas, biliary tract, salivary and lacrimal glands, lungs, and kidneys. Patients with IgG4-RD may present with a single organ involved but more frequently present with multiple organ involvement. As the disease progresses and patients experience new or worsening symptoms (i.e., flares), lesions develop in additional organs and the cellular inflammation characterizing early disease moves toward a more fibrotic stage, which can lead to major irreversible tissue damage and ultimately organ failure. We estimate that the currently diagnosed population of IgG4-RD patients in the U.S. is approximately 20,000, with comparable prevalence rates globally. Despite the growing recognition of IgG4-RD and advances in the understanding of its pathophysiology, there are no approved therapies for the treatment of this disease and there remains high unmet medical need. The current standard of care is treatment with glucocorticoids (GCs). Although GCs are initially effective, treatment with GCs can often result in various complications and co-morbidities. Most patients can relapse within 12 months of discontinuing GC treatment, and maintenance therapy with GCs has not been shown to prevent recurrence of disease. The pathogenesis of IgG4-RD suggests that B cell-targeted therapies may provide therapeutic benefit. Although not approved by any regulatory authorities to treat IgG4-RD, certain B cell depleting agents (e.g., rituximab) are occasionally administered to patients with IgG4-RD. However, B cell depleting agents are often associated with infections, including serious opportunistic infections, and can compromise a patient’s ability to mount a response to vaccinations. The reported evidence for the role of B cells in the pathogenesis of IgG4-RD, the observed effects of B cell targeting agents in previous trials in IgG4-RD, the data from our Phase 2 IgG4-RD trials with obexelimab, and its unique, non-depleting mechanism and once-weekly, subcutaneous injection regimen support its development in patients with IgG4-RD. INDIGO is the largest clinical trial conducted in patients living with IgG4-RD and is designed to evaluate the safety and efficacy of obexelimab in approximately 190 patients with active IgG4-RD and being conducted at approximately 100 sites in 20 countries. Following an initial screening period, patients were randomized 1:1 to 250 mg of obexelimab or placebo administered as a subcutaneous injection every seven days for 52 weeks, followed by an opportunity for eligible patients to continue in an open-label extension period where all patients will receive treatment with obexelimab. The primary efficacy endpoint of INDIGO is the time to first IgG4-RD flare, as determined per protocol by the investigator and the adjudication committee. Secondary endpoints include annualized flare rate, the proportion of patients achieving complete remission, and use and quantity of rescue medication, including GCs. More information on the Phase 3 INDIGO trial (NCT05662241) is available at clinicaltrials.gov Complete enrollment in 2025 in the Phase 2 SunStone trial in patients with SLE and report topline results in the first half of 2026. The crucial role of B cells in SLE pathogenesis is well recognized, from producing autoantibodies to abnormal regulation of immune responses. Moreover, SLE is an autoimmune disease characterized by B cell dysfunction, the production of autoantibodies toward cellular and nuclear components, and multiorgan damage caused by immune complex deposition and inflammation within affected tissues. Current treatments are limited in number and modestly effective. Obexelimab has demonstrated clinical activity in a prior Phase 2 double-blind, randomized trial demonstrating proof-of-concept in the overall trial population and increased response in patients who maintained higher systemic exposure to obexelimab, and also in biomarker-defined subpopulations. Coupled with the safety data obtained to date, we believe these data provide support for the development of obexelimab in patients with SLE. Patients with active SLE determined at screening by the investigator and adjudication committee are randomized 1:1 to obexelimab 250 mg or placebo administered as a subcutaneous injection every seven days for 24 weeks. The 250 mg once-weekly subcutaneous injection dose has been selected to maximize the potential for clinical activity as higher systemic exposure (Ctrough) correlated with greater clinical activity in the prior Phase 2 trial in SLE. The primary endpoint is the percentage of responders, defined by BILAG-based Composite Lupus Assessment, with a reduction of SLE disease activity at week 24. Biomarker analysis is planned to be conducted in all patients, including baseline RNA expression profiles to immunophenotype patients and evaluation of their differential responses to treatment. More information on the Phase 2 SunStone trial (NCT06559163) is available at clinicaltrials.gov Zenas is a clinical-stage global biopharmaceutical company committed to becoming a leader in the development and commercialization of transformative therapies for patients with autoimmune diseases. Our core business strategy combines our experienced leadership team with a disciplined product candidate acquisition approach to identify, acquire and develop product candidates globally that we believe can provide superior clinical benefits to patients living with autoimmune diseases. Zenas’ lead product candidate, obexelimab, is a bifunctional monoclonal antibody designed to bind both CD19 and FcγRIIb, which are broadly present across B cell lineage, to inhibit the activity of cells that are implicated in many autoimmune diseases without depleting them. We believe that obexelimab’s unique mechanism of action and self-administered, subcutaneous injection regimen may broadly and effectively address the pathogenic role of B cell lineage in chronic autoimmune disease. For more information about Zenas BioPharma, please visit www.zenasbio.com and follow us on LinkedIn. 1 This amount is preliminary and unaudited and is subject to completion of the Company’s financial closing procedures. As a result, this amount may differ materially from the amount that will be reflected in the Company’s consolidated financial statements for the year ended December 31, 2024. The content above comes from the network. if any infringement, please contact us to modify.