Obexelimab

- Obexelimab met the primary endpoint demonstrating a clinically meaningful and highly statistically significant 56% reduction in risk of IgG4-RD flare - - Obexelimab also met and demonstrated statistically significant activity on all four key secondary efficacy endpoints - - Obexelimab was well tolerated and no new safety signals were observed - - Zenas anticipates submitting a Biologics License Application (BLA) to the FDA in the second quarter of 2026 and a Marketing Authorization Application (MAA) to the EMA in the second half of 2026 - - Zenas to host a conference call today, January 5, 2026, at 8:00 a.m. ET - Jan. 05, 2026 -- Zenas BioPharma, Inc. (“Zenas,” “Zenas BioPharma” or the “Company”) (Nasdaq: ZBIO), a clinical-stage global biopharmaceutical company committed to being a leader in the development and commercialization of transformative therapies for patients living with autoimmune diseases, today announced positive results from the Phase 3 INDIGO trial of obexelimab in Immunoglobulin G4-Related Disease (IgG4-RD). Obexelimab met the primary endpoint, demonstrating a highly statistically significant and clinically meaningful 56% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.44, p=0.0005) during the 52-week randomized placebo-controlled period. Obexelimab also met and demonstrated highly statistically significant activity compared to placebo on all four key secondary endpoints, which were reduction in investigator assessed IgG4-RD flare, the number of flares requiring rescue therapy, the proportion of patients achieving complete remission and the cumulative use of IgG4-RD rescue therapy. Rates of infections, including Grade 3, were lower in the obexelimab arm compared to placebo, and the incidence of injection site reactions was similar across both study arms. The Company expects that full data from the INDIGO trial will be presented at a future medical meeting. “Given obexelimab’s significant clinical activity and the compelling safety and tolerability profile observed in the INDIGO trial, we believe obexelimab may have an important role as a first line therapy in the long-term management of IgG4-RD,” said Lonnie Moulder, Founder and Chief Executive Officer of Zenas. “With its unique inhibitory mechanism, tolerability profile, at-home subcutaneous self-administration and potential to pause for vaccination or management of intercurrent illness, obexelimab has the potential to be a meaningful treatment option for patients. IgG4-RD represents a significant commercial opportunity for obexelimab and Zenas, and today’s data support obexelimab as a potential franchise molecule for rheumatic diseases. We look forward to submitting our Biologics License Application to the FDA in the second quarter of 2026 and our Marketing Authorization Application to the EMA in the second half of this year.” “Patients living with IgG4-RD have faced limited treatment choices for far too long,” said John Stone, M.D., M.P.H., Professor of Medicine at Harvard Medical School and the Edward A. Fox Chair in Medicine at Massachusetts General Hospital. “The INDIGO study results suggest that obexelimab, with its intriguing mechanism of action – emphasizing B cell inhibition rather than B cell depletion – and self-administration by patients, may be an important new therapy for people living with IgG4-RD.” “These INDIGO trial results build upon the highly positive results observed in our Phase 2 MoonStone trial in Relapsing Multiple Sclerosis and further validate obexelimab’s mechanism of action, optimized subcutaneous dosing and its potential to address the unmet medical needs of patients living with autoimmune diseases,” said Lisa von Moltke, M.D., Head of Research and Development and Chief Medical Officer of Zenas. “Without treatment, IgG4-RD meaningfully contributes to organ fibrosis, damage and failure. Obexelimab’s unique inhibitory mechanism, combined with its weekly subcutaneous dosing chosen for optimal pharmacokinetic and clinical activity, has the potential to sustain B cell inhibition and durably impact disease activity. The INDIGO trial results are supported by the largest body of clinical data ever reported in this indication and strengthen confidence in the ongoing Phase 2 SunStone trial in Systemic Lupus Erythematosus (SLE), which remains on track to report data later this year. On behalf of the Zenas team, I would like to thank the patients and healthcare professionals who took part in the INDIGO trial.” Following these positive Phase 3 INDIGO results, Zenas anticipates submitting the obexelimab Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for the treatment of IgG4-RD in the second quarter of 2026. Zenas also intends to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the second half of 2026. Zenas’ partner Bristol Myers Squibb holds exclusive development and commercialization rights for obexelimab in Japan, South Korea, Taiwan, Hong Kong, Singapore and Australia. Zenas also expects to report topline results, including a biomarker analysis, of the obexelimab Phase 2 SunStone trial in SLE in the fourth quarter of 2026. In addition, orelabrutinib, a potentially best-in-class, highly selective central nervous system (CNS)-penetrant, oral, small molecule Bruton’s Tyrosine Kinase (BTK) inhibitor, is being studied in a global Phase 3 clinical trial in patients with Primary Progressive Multiple Sclerosis (PPMS). A global Phase 3 trial of orelabrutinib in patients with non-active Secondary Progressive Multiple Sclerosis (naSPMS) is expected to initiate in the first quarter of 2026. Subject to Investigational New Drug (IND) clearance, Zenas expects to initiate Phase 1 clinical development for ZB021, a potentially best-in-class oral IL-17AA/AF inhibitor, in 2026. Pending Phase 1 data, Zenas expects to advance development of ZB021 for rheumatic and/or dermatologic diseases. In addition, subject to IND clearance, Zenas expects to initiate Phase 1 clinical development for ZB022, a potentially best-in-class brain penetrant TYK2 inhibitor, in 2026. Pending Phase 1 data, Zenas expects to advance development of ZB022 for neurologic diseases. Immunoglobulin G4-Related Disease (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 may 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, treatment options are limited. The pathogenesis of IgG4-RD suggests that B cell-targeted therapies may provide therapeutic benefit. One B cell depleting agent is currently approved to treat IgG4-RD in the U.S. and others (e.g., rituximab) are occasionally administered to patients with IgG4-RD. However, B cell depleting agents can compromise a patient’s ability to mount a response to vaccinations and can compromise response to infections including serious and opportunistic infections should they occur. Glucocorticoids (GCs), while not approved for the treatment of IgG4-RD, are commonly used to treat disease flares. Although GC treatment is initially effective, long-term treatment can often result in various complications and co-morbidities. GCs do not address underlying disease activity that can meaningfully contribute to organ fibrosis, damage and failure. Most patients treated with GCs relapse within 12 months of discontinuing treatment, and maintenance therapy with GCs has not been shown to prevent recurrence of disease. The Phase 3 INDIGO trial, which enrolled 194 patients, is a global, registration-directed, double-blind, placebo-controlled trial, designed to evaluate the safety and efficacy of obexelimab in patients with IgG4-RD. After 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, that requires initiation of rescue therapy as determined by the investigator and the adjudication committee (AC) from randomization to week 52. Key secondary endpoints included time to first IgG4-RD flare as determined per protocol, that requires initiation of rescue therapy as determined by the investigator from randomization to week 52; the number of investigator and AC-determined flares requiring initiation of rescue therapy from randomization to week 52; the proportion of patients achieving complete remission at week 52; and the cumulative dose of IgG4-RD rescue therapy from randomization to week 52. 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 inhibitory mechanism of action and self-administered, subcutaneous injection regimen may broadly and effectively address the pathogenic role of the B cell lineage in chronic autoimmune disease. Obexelimab has been evaluated in eight clinical trials in a total of 383 subjects, including INDIGO. Obexelimab was well tolerated and demonstrated clinical activity across these clinical trials. The registrational Phase 3 INDIGO trial for Immunoglobulin G4-Related Disease met its primary endpoint and all four key secondary endpoints with high statistical significance. The trial continues to evaluate patients in the 3-year open label extension period which will further build upon the largest body of clinical data reported for IgG4-RD patients to date. In October 2025, Zenas reported that the Phase 2 MoonStone trial for Relapsing Multiple Sclerosis met its 12-week primary endpoint demonstrating a highly statistically significant 95% relative reduction in the cumulative number of new gadolinium-enhancing T1 hyperintense lesions over week 8 and week 12 compared with placebo (p=0.0009). A randomized Phase 2 trial for Systemic Lupus Erythematosus is ongoing and Zenas expects to report topline results, including biomarker data from this trial in the fourth quarter of 2026. Zenas is a clinical-stage global biopharmaceutical company committed to becoming a leader in the development and commercialization of transformative therapies for patients living 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 meaningful clinical benefits to patients living with autoimmune diseases. Zenas is advancing two late-stage, potential franchise molecules, obexelimab and orelabrutinib. Obexelimab, Zenas’ lead product candidate, 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 inhibitory 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. Orelabrutinib is a potentially best-in-class, highly selective central nervous system (CNS)-penetrant, oral, small molecule BTK inhibitor. Orelabrutinib’s mechanism of action targets pathogenic B cells not only in the periphery but also within the CNS. Additionally, it directly modulates macrophages and microglial cells in the CNS, with the potential to address compartmentalized inflammation and disease progression in Multiple Sclerosis (MS). Zenas’ earlier stage programs include ZB021, a preclinical, potentially best-in-class, oral, IL-17AA/AF inhibitor, and ZB022, a preclinical, potentially best-in-class, oral, brain-penetrant, TYK2 inhibitor. The content above comes from the network. if any infringement, please contact us to modify.

2026年1月5日，Zenas Biopharma公布了核心产品Obexelimab在治疗IgG4相关疾病（IgG4-RD）的III期研究结果。 从公告来看，这项名为INDIGO的研究非常漂亮，不仅达到了主要终点，连带着四个关键的次要终点也全线飘红。这本来意味着全球即将迎来首个靶向B细胞通路的一线新疗法，公司也紧接着宣布要在今年二季度向FDA提交上市申请。 然而，资本市场的反应却像一盆冷水：消息公布当天，Zenas的股价直接暴跌了52%。在现在的生物医药圈，仅仅拿到一个统计学上的“成功”已经远远不够了，市场更看重你在这个赛道里到底有没有稀缺性和统治力。 我们要先聊聊IgG4-RD这个病。它是一种慢性炎症，会引起组织纤维化，累及全身多个器官。这个病的驱动核心是体内一种特定的B细胞和浆细胞乱跑，在组织中引发炎症。 虽然这个病挺折磨人，但在美国只有2到4万名患者，属于典型的小众市场、小适应症。目前，FDA只批准了一款药物，就是安进的CD19单抗Uplizna。Uplizna于2025年4月获FDA批准率先上市，今年该适应症销售额预计在1亿美元左右。这意味着Obexelimab得在疗效、安全性或依从性上超过Uplizna才能有市场。 Obexelimab的机理确实很独特，它不是那种简单的“杀伤性”武器。它是一种双功能抗体，一边结合CD19，一边结合B细胞表面的抑制性受体FcγRIIb。 简单来说，它利用了人体自身的免疫反馈机制：当系统觉得抗体够多时，就给B细胞发信号让它“安静”下来。 相比传统的疗法直接把B细胞杀光（耗竭），Obexelimab只是在病理活动期“灭活”B细胞，等警报解除了，B细胞还能恢复自然功能。这种“非耗竭性”抑制听起来非常高级，理论上安全性也更高。 这个机制可以说是全新的，也符合逻辑的。正是这个原因，才有了市场对Obexelimab的极高期待：一是其创新的作用机制具备显著的差异化优势，二是该产品已成功吸引了多家重量级资本的战略投入与支持。 值得一提的是Obexelimab其实并不是 Zenas 自己开发的，而是从 Xencor 公司BD过来的。早在 2021 年底，刚起步的 Zenas 就砸下总价 4.8 亿美元的重金，拿下了这款药的全球开发权益。在那时候的市场环境下，Zenas 显然是想靠 Obexelimab 这种“不伤敌一千也能自损八百”的差异化机理，在自免赛道里讲出一个全新的故事。 靠着这个独特的作用机理，Zenas的 BD能力确实拉满了，到处寻找合作。2023 年 9 月，他们先把亚太六国的权益卖给了大厂 BMS，换回了 5000 万美元的真金白银；到了 2025 年 9 月，更是以5.5% 未来销售分成为代价和 Royalty Pharma 签了一份高达 3 亿美元的“对赌”融资。 那临床数据到底怎么样呢？ 在这次III期试验里，Obexelimab把复发风险降低了56%，看着还行，但对比一下对手就尴尬了。安进的Uplizna能把复发风险降低87%，而且Uplizna治疗组的复发比例只有10%左右，Obexelimab却高达27%。 这说明Obexelimab这种温和的“抑制”在力度上确实不如直接“清空”B细胞来得干脆。在IgG4-RD这种容易导致器官受损的病面前，医生和患者显然更看重谁能更彻底地防止复发。 再看给药方式，Obexelimab主打的是“居家皮下注射”，每周打一针。而Uplizna是每半年打一次。虽然居家注射看似方便，但由于Obexelimab为了增强抑制力对Fc段做了改造，反而牺牲了抗体的半衰期，导致给药频率非常高。对于患者来说，一年打52针和一年跑两趟医院，后者的依从性其实更高。 另外，相比半年一次的Uplizna，周制剂Obexelimab的药物成本要上升数十倍。 而且，Obexelimab除了这个小众病，还布局了红斑狼疮（SLE）和多发性硬化症（RMS），但在红斑狼疮的IIa期临床里，它连统计学终点都没达到。在这些大赛道上，它面对的是已经成名的阿达木单抗或者贝利尤单抗，赢面非常小。 除了这个核心产品，Zenas手里还有从诺诚健华引进的BTK抑制剂奥布替尼。这个药主要攻坚多发性硬化症（MS）里最难啃的两个地盘：PPMS和非活动性SPMS。 奥布替尼的优势在于它入脑能力极强，能穿透血脑屏障去清理大脑内部的炎症，这比那些进不去的单抗类药物更有想象力。 然而，BTK抑制剂现在面临一个全行业的“死穴”，就是MS患者肝毒性。就在2026年1月，FDA刚刚拒绝了赛诺菲同类药物Tolebrutinib的上市申请，原因就是出现了严重的肝损伤甚至肝移植病例。 虽然奥布替尼在血液瘤患者身上很安全，但在MS患者这种特定的免疫背景下，它在II期试验里也出现了类似的安全信号。对于需要几十年服药的自免病人来说，监管机构对肝毒性的容忍度极低。即使奥布替尼的病灶减少率比对手高，但只要安全性这把达摩克利斯之剑悬在头上，它的获批和商业化就存在巨大的变量。 Zenas剩下的管线，比如同样BD自诺诚健华的口服IL-17抑制剂ZB021，虽然口服药在百亿美金规模的IL-17市场很有诱惑力，但它的进度实在太慢了。目前ZB021还处于IND阶段，而前面礼来、赛诺菲、歌礼制药的产品已经跑到了二期甚至三期。等ZB021出来，市场可能早就被瓜分完了。 至于那个透脑TYK2抑制剂ZB022，神经炎症领域本身就是研发的“坟场”，机理复杂且失败率极高，目前连临床疗效数据都没有，很难评估成药性。 最后看估值，连续大跌之后，Zenas的市值来到了9亿美金左右。虽然跌了一半，但结合现有资产来看，它依然不便宜。 核心产品Obexelimab在小赛道里打不过安进，在大赛道里又缺乏统治力。 奥布替尼治疗MS虽然有潜力，但肝毒性这道红线极难跨越。剩下的管线要么进度落后，要么风险巨大。对于这种核心资产竞争力被证伪、后续管线又接不上的公司，9亿美金的市值暂时还看不到足够的吸引力。 最后，创新药行业规则就是这么简单而残酷，对未满足市场的绝对统治力才能有高溢价。