A Phase 2, Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients With Mild Cognitive Impairment (MCI) With Biomarkers of Inflammation

The goal of this Phase 2 MCI study is to determine whether 1.0 mg/kg XPro1595 is superior to placebo at improving measures of cognition, functioning and brain quality in individuals with MCI and biomarkers associated with neuroinflammation (APOE4) and to evaluate safety, tolerability, and efficacy of XPro1595.

开始日期2023-06-01

申办/合作机构

INmune Bio, Inc.

NCT05522387

/ Terminated临床2期

An Open Label Extension of XPro1595 in Patients With Alzheimer's Disease That Have Completed a Phase 1 or Phase 2 Study With XPro1595

The goal of this Phase 2 Open Label study is to evaluate long-term safety, tolerability, and efficacy of XPro1595 on measures of cognition, function and brain quality in individuals with Alzheimer's Disease.

开始日期2023-02-21

申办/合作机构

INmune Bio, Inc.

NCT05318976

/ Completed临床2期

A Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation

The goal of this Phase 2 Alzheimer's study is to determine whether 1.0 mg/kg XPro1595 confers a benefit on cognition, function, and biomarkers of white matter and to further evaluate safety and tolerability. The objectives of this study are to determine the safety, tolerability, and efficacy of XPro1595 in patients with early ADi.

开始日期2022-02-28

申办/合作机构

INmune Bio, Inc.

100 项与 INB-03 相关的临床结果

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100 项与 INB-03 相关的转化医学

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100 项与 INB-03 相关的专利（医药）

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项与 INB-03 相关的文献（医药）

2026-02-01·JOURNAL OF PHYSIOLOGY-LONDON

Targeting necroptosis protects against astrocyte death and hippocampal sclerosis in experimental temporal lobe epilepsy

Article

作者: Lukas Henning ; Christian Steinhäuser ; Zhou Wu ; Peter Bedner

Abstract:

Temporal lobe epilepsy (TLE) is the most common and severe form of adult focal epilepsy and is frequently associated with hippocampal sclerosis (HS). Accumulating evidence suggests that brain inflammation plays an important pathophysiological role in TLE. A key pro‐inflammatory mediator is tumour necrosis factor α (TNFα), which can trigger necroptosis pathways regulated by RIPK1, RIPK3 and MLKL through binding to the TNF receptor 1 (TNFR1). Previously, we detected activation of RIPK1, RIPK3 and MLKL in hippocampal CA1 astrocytes, along with a reduction in astrocyte density, during the early stages of experimentally induced TLE‐HS, providing strong evidence for necroptotic astrocytic cell death. Using immunohistochemistry, pharmacology and long‐term EEG recording, here we unravel the mechanisms underlying necroptosis induction in astrocytes and its role in epileptogenesis. The results show that pharmacological inhibition of necroptosis using Nec‐1s, a specific inhibitor of RIPK1, or selective inhibition of soluble TNFα by XPro1595, as well as genetic knockout of TNFR1, effectively rescued CA1 astrocyte loss caused by kainate‐induced status epilepticus. Furthermore, targeting necroptosis by Nec‐1s administration attenuated CA1 astrogliosis, degeneration of pyramidal neurons, granular cell dispersion and shrinkage of the CA1 subfield. In contrast, Nec‐1s did not affect acute and chronic epileptic activity in the TLE‐HS model. Our findings demonstrate that TNFα‐induced necroptotic astrocyte death is involved in the pathogenesis of TLE. image

Key points:

In the early stage of experimental temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS), we observed activation of RIPK1, RIPK3 and MLKL in CA1 astrocytes, along with a reduction in astrocyte density, providing evidence for necroptotic cell death.Pharmacological inhibition of necroptosis (Nec‐1s), blockade of soluble tumour necrosis factor α (XPro1595) or genetic knockout of TNFR1 prevented astrocyte loss after status epilepticus.Continuous telemetric EEG recordings showed that Nec‐1s has no effect on acute or chronic epileptic activity in the TLE‐HS model.Immunohistochemical analysis revealed that Nec‐1s treatment reduced the extent of hippocampal sclerosis in experimental TLE‐HS.Our results provide further insights into the molecular mechanisms underlying the development and progression of TLE.

2026-01-01·Neurobiology of pain (Cambridge, Mass.)

Xpro®1595 alleviates neuropathic pain by targeting spinal dorsal horn ADAM17-mediated inflammation

Article

作者: Li, Li ; Yao, Wei-Wei ; Sun, Yan-Yan ; Sun, Ling-Ling ; Su, Yidie

A disintegrin and metalloprotease 17 (ADAM17) mediates the shedding of key pro-inflammatory cytokines, yet its specific contribution to neuropathic pain remains elusive. Here, we investigated the role of ADAM17 in the rat spinal nerve ligation (SNL) model. Following nerve injury, ADAM17 expression was significantly upregulated in the spinal dorsal horn (SDH) and dorsal root ganglion (DRG). Specifically, ADAM17 colocalized with TRPV1 and IB4 positive afferents in the superficial SDH, and with IB4, CGRP, and TRPV1 positive neurons in the DRG. Intrathecal administration of exogenous ADAM17 to naive rats recapitulated neuropathic pain behaviors-inducing mechanical and thermal hypersensitivity-and significantly increased the levels of TNF-α, IL-1β, and IL-6 in the SDH. Conversely, therapeutic treatment with Xpro®1595 markedly attenuated SNL-induced pain behaviors. This analgesic effect correlated with the suppression of injury-induced ADAM17 upregulation and a consequent reduction in proinflammatory cytokines. These findings demonstrate that ADAM17 is a critical driver of the neuroinflammatory cascade in neuropathic pain. Moreover, our data suggest that the analgesic efficacy of Xpro®1595 is mediated, at least in part, by disrupting this ADAM17-dependent inflammatory feedback loop.

2025-12-23·BIOSCIENCE REPORTS

The effect of the nonselective TNF inhibitor etanercept and of the selective TNF inhibitor XPro1595 on lesioned supraspinatus muscle

Article

作者: Nasseri, Sohail ; Aboo, Christopher ; Jensen, Peter Toft ; Ditzel, Nicholas ; Ding, Ming ; Hejbøl, Eva Kildall ; Stensballe, Allan ; Lambertsen, Kate Lykke ; Frich, Lars Henrik ; Schrøder, Henrik Daa ; Linh Ta, Thi My

The cytokine tumor necrosis factor (TNF), a major regulator of inflammatory responses, exists in both a membrane-bound form and a soluble form. We used the nonselective TNF inhibitor etanercept and the selective inhibitor XPro1595 and compared supraspinatus muscle cytokine levels, histology, and proteomic signatures in mice after supraspinatus tendon tear. The aim was to investigate the effect of anti-TNF treatment on the early inflammatory response in the muscle after tendon tear. In addition, the effect on body composition and bone mineral content was compared in naive mice after 2 months of treatment with either etanercept or XPro1595 using dual-energy X-ray absorptiometry (DEXA) and micro-CT. Inhibition of TNF did not significantly affect DEXA indexes of body composition nor bone microarchitecture, apart from increased structure model index and decreased bone surface density at 14 days, and bone surface to volume ratio at 2 months. Supraspinatus tendon tear caused extensive inflammatory changes in the supraspinatus muscle and initiated a regenerative response. However, TNF inhibition did not significantly affect these processes recorded as density in the lesioned supraspinatus muscle of macrophages and myogenin-positive nuclei. Although both inhibitors had an effect on mitochondrial proteins, particularly etanercept tended to modulate mitochondrial function, and eternacept also influenced NF-κB signaling. Modulation of the mitochondrial proteome and the influence on NF-κB signaling seen after etanercept treatment could correspond with its known effect on apoptosis.

154

项与 INB-03 相关的新闻（医药）

2026-06-08

·BiG生物创新社

冲破β-Amyloid圭臬：阿尔茨海默病2026“面壁十年图破壁”

2026 年 4 月，一项 Cochrane 系统评价把 β-amyloid （Aβ）靶向治疗再次推到阿尔茨海默病研发争议的中心。该评价纳入 17 项临床试验、20342 名轻度认知障碍或轻度阿尔茨海默病失智患者，分析对象覆盖多种Aβ 靶向单抗。评价结论认为，这类药物在 18 个月治疗后对记忆和思维能力下降、痴呆严重程度以及日常活动能力的影响有限，临床意义不足，同时增加 amyloid 相关影像异常风险，包括脑水肿和微出血。这一结论之所以迅速引发讨论，是因为它触及了Aβ开发路线最核心的问题：脑内Aβ斑块清除能否稳定转化为患者能够感知、照护者能够观察、支付方愿意承担的临床获益。过去几年，lecanemab 和 donanemab 的获批曾让 Aβ路线获得监管层面的确认，也证明在 biomarker 筛选的早期阿尔茨海默病患者中，抗 Aβ 治疗可以延缓疾病进展。但 Cochrane 评价把这一类药物的总体获益重新拉回临床意义和获益风险平衡的框架中，使行业不得不再次面对疗效幅度、给药负担、安全监测和支付价值之间的矛盾。 Aβ仍然是阿尔茨海默病药物开发的重要方向，但在 2026 年阿尔茨海默病研发管线中，anti-amyloid 药物占比已经降至约 16%，低于十年前的 33%。与此同时，神经递质受体、炎症和免疫系统、tau 蛋白以及 biomarker 驱动的患者筛选正在占据更大比重。这意味着阿尔茨海默病研发已经进入更复杂的多机制阶段。Aβ清除仍有价值，但它更适合作为早期病理干预的一部分。tau 病理、神经炎症、免疫功能异常、突触损伤、代谢压力和神经递质失衡共同参与疾病进展，不同患者、不同病程阶段和不同临床症状需要更精细的治疗策略。疾病修饰治疗继续追求延缓病程，症状治疗则直接面对精神病性症状、激越、认知下降和照护负担。 01 管线扩大背后的机制分化 2026 年阿尔茨海默病药物目前的开发管线包括 158 个在研药物和 192 项临床试验。按临床阶段划分，III 期包含 36 个药物和 54 项试验，II 期包含 84 个药物和 89 项试验，I 期包含 45 个药物和 49 项试验。这一组数据说明，阿尔茨海默病并未因长期失败而被产业放弃，反而在抗 amyloid 药物获批后进入了更大规模的试验探索周期。从机制类别看，Aβ 已经不是 2026 年管线中数量最多的方向。神经递质受体相关药物有 38 个，占 24%；炎症和免疫相关药物有 28 个，占 18%；Aβ 相关药物有 25 个，占 16%；tau 相关药物有 15 个，占 9%。突触可塑性和神经保护、代谢和生物能量、蛋白稳态、氧化应激、血管因素等方向共同构成更分散的研发结构。分阶段看，III 期中神经递质受体类药物有 14 个，占 39%；Aβ 相关药物有 10 个，占 28%；代谢和生物能量相关药物有 3 个，占 8%；炎症/免疫和蛋白稳态各有 2 个，分别占 5%。II 期的非 Aβ 特征更加突出，神经递质受体和炎症/免疫各有 19 个，均占 23%；Aβ 和 tau 各有 8 个，均占 9%。这组数据说明，非 Aβ 方向已经成为 2026 年 AD 管线的主体，真正的新机制密度集中在 II 期。这种结构变化来自疾病生物学本身。Aβ 更接近早期病理沉积环节，tau 病理与神经元损伤和认知下降更直接相关，炎症免疫贯穿疾病进展过程，突触功能和神经递质系统则直接影响认知、行为和照护负担。阿尔茨海默病药物开发正在从单一靶点竞争，转向不同病程阶段、不同症状维度和不同生物学背景下的机制匹配。 02 后期与关键验证项目从Aβ清除扩展至症状、代谢、突触和炎症后期临床和关键验证项目仍然是判断新型AD 药物商业化前景的核心窗口。2026 年非 Aβ 方向的重点项目显示，新型 AD 药物开发已经不再局限于疾病修饰抗体，神经精神症状、代谢调节、突触可塑性、蛋白稳态和小胶质细胞炎症调节都在进入更严格的临床验证阶段。 BMS 的 Cobenfy 是神经精神症状路径中最受关注的项目。 Cobenfy 由 xanomeline 和 trospium chloride 组成，已经获 FDA 批准用于成人精神分裂症。其作用机制不同于传统以多巴胺 D2 受体阻断为核心的抗精神病药物，而是通过中枢 M1 和 M4 毒蕈碱乙酰胆碱受体相关活性发挥作用，trospium chloride 用于限制外周胆碱能不良反应。BMS 通过收购 Karuna 获得该资产后，正在向阿尔茨海默病相关精神病和激越拓展。 Semaglutide 的 III 期研究曾把 AD 开发带入代谢和炎症交叉框架。GLP-1 受体激动剂在代谢疾病和肥胖症中已经形成成熟商业基础，进入 AD 后，其开发逻辑包括改善脑内胰岛素信号、降低神经炎症、影响血管和代谢风险。但 EVOKE 和 EVOKE+ 两项大型 III 期研究的顶线结果显示，口服 semaglutide 14 mg 未能相较安慰剂显著延缓早期症状性 AD 患者的疾病进展。这个结果削弱了 GLP-1 路径在 AD 单药疾病修饰治疗中的短期确定性，也说明代谢和炎症假设仍需要更清晰的人群分层、终点选择和联合治疗策略来验证。 AR1001、Buntanetap 和 Masitinib 代表另一组疾病修饰探索。AR1001 通过 PDE-5 抑制机制改善突触可塑性，关注神经网络功能；Buntanetap 试图抑制 APP、tau 和 α-synuclein mRNA 翻译，触及多种病理蛋白；Masitinib 通过酪氨酸激酶抑制减少小胶质细胞激活，切入神经炎症。它们与 Aβ 抗体的区别在于，治疗目标从清除沉积物扩展到保护突触、控制病理蛋白生成和改变神经炎症环境。 Tau项目 tau 是 Aβ 之后最受关注的病理方向之一。2026 年管线中，tau 相关药物共有 15 个，III 期纯 tau 项目仍少，II 期和 I 期更活跃。这个阶段的技术形态已经明显扩展，从传统抗体、主动免疫，到 ASO 和 RNAi 均有代表性项目。 Tau 方向的核心挑战仍然是临床转化。降低 tau 或阻断 tau 传播能否稳定延缓认知下降，需要更长期、更清晰的人群分层和 biomarker 证据支持。BIIB080 和 posdinemab 的最新读出给出了不同方向的信号：前者显示 tau pathology 降低和认知下降减缓的积极趋势，但主要终点未达成；后者未能显著延缓临床下降并终止研究。tau 病理与神经元损伤和认知衰退关系更紧密，未来仍可能成为早期 Aβ 清除之后的病程控制方向，也可能与 Aβ 药物形成更合理的联合治疗组合，但这一方向仍处于临床有效性继续验证阶段。 II期炎症/免疫项目 2026 年管线中，炎症/免疫相关药物有 28 个，占 18%，仅次于神经递质受体方向。 AD 进展受到神经免疫微环境持续影响。小胶质细胞既可能参与清除病理蛋白，也可能在慢性激活状态下推动突触损伤和神经炎症。TREM2、progranulin、TNF、JAK、NLRP3、CSF-1R 和 S1P 等机制，分别从吞噬功能、细胞因子信号、炎症小体、免疫细胞迁移和小胶质细胞状态调节切入。VHB937、Foralumab、Enrupatinib、XPro1595 等项目继续代表 AD 免疫状态调节方向的临床探索。AL101 / nivisnebart 的终止则提示，progranulin 提升和 sortilin 阻断机制虽然具有明确生物学依据，但仍未在 Phase 2 临床中证明可以延缓早期 AD 疾病进展。炎症/免疫药物仍处于验证早期。其难点在于免疫调节存在双向性，过度抑制可能影响清除功能，过度激活可能加剧损伤。未来临床开发需要更明确的 biomarker，证明药物确实改变了目标免疫通路，并且这种改变能够转化为认知或功能获益。 03 II期神经递质和症状治疗直接面对照护负担神经递质受体是 2026 年 AD 管线中数量最多的机制类别，共 38 个药物，占 24%。这一方向的意义在于，它直接对应患者和照护者最容易感受到的临床问题。Aβ、tau 和炎症免疫药物主要关注病程进展，神经递质和神经精神症状药物则聚焦幻觉、妄想、激越、冷漠、认知下降等现实症状。 BMS 的 Cobenfy/KarXT不是传统意义上的 Aβ 或 tau 疾病修饰药物，但它可能切中 AD 临床照护中最难处理的一类症状。ML-007C-MA 与 Cobenfy 同样围绕 M1/M4 毒蕈碱受体机制展开，说明 muscarinic receptor agonism 正在成为 AD 精神行为症状和认知改善中的重要方向。 ITI-1284、BMS-986368、Dexmedetomidine 和 Cannabidiol 则从 5-HT2A/D1/D2、内源性大麻素系统、α2 肾上腺素能受体等路径切入激越和精神病性症状。症状治疗的商业和临床价值不应被低估。AD 患者进入中后期后，照护负担往往不只来自记忆下降，也来自激越、幻觉、妄想、睡眠紊乱和行为异常。能够降低这些症状的药物，即使不直接改变病理进程，也可能显著影响患者安全、家庭照护压力、机构护理需求和医疗资源使用。 04 新型AD药物开发的真正变化 2026 年的 AD 管线已经给出清晰信号：Aβ 仍是重要方向，但非 Aβ 已经成为管线主体。神经递质受体和炎症/免疫的药物数量均超过 Aβ，tau 方向虽然总量较小，却在 I/II 期形成了 ASO、RNAi、单抗和主动免疫并行的技术格局。突触可塑性、代谢、蛋白稳态和药物再开发共同补充了疾病修饰和症状治疗之间的空白。与此同时，semaglutide 和 posdinemab 的最新结果也提醒行业，多机制扩展并不天然意味着更高成功率，真正决定价值的仍是临床终点、患者分层和 biomarker 转化之间能否形成一致证据链。新型 AD 药物开发的重点，已经从寻找单一替代靶点，转向为不同临床问题匹配不同机制。早期患者需要更精准的筛查和病程延缓策略，轻中度患者需要认知和功能获益，伴精神行为症状患者需要安全有效的症状控制，医疗系统需要可执行的诊断、给药和监测路径。 Cobenfy、BIIB080、ARO-MAPT、BMS-986446、Masitinib、AR1001、Buntanetap 和 Metformin 等项目的价值，正是在不同维度上检验 AD 药物开发的新方向。Semaglutide 和 posdinemab 则更适合作为机制假设进入临床后接受严格验证的案例：前者提示代谢路径在 AD 中仍需重新审视临床转化逻辑，后者提示 tau 单抗阻断传播策略仍需更精准的人群和终点设计。阿尔茨海默病研发正在进入多机制验证期。这个阶段的关键不在于用某一个新靶点取代 Aβ，而在于用更精细的患者分层、更可靠的 biomarker 和更贴近临床需求的终点，证明药物能够在复杂患者群体中产生可观察、可复制、可支付的治疗获益。未来几年，行业信心将由一组不同机制项目共同塑造，而不再由单一病理路径决定。 Ref. Bilodeau, K. As amyloid falls out of favor, here’s where Alzheimer’s R&D is headed next. Pharma Voice. 02. 06. 2026. Bell, J. In Alzheimer’s, Bristol Myers sees big promise beyond amyloid. Pharma Voice. 27. 05. 2026. Cummings JL, Zhou Y, Yang Y, et al. Alzheimer's disease drug development pipeline: 2026. Alzheimer's Dement. 2026;12:e70251. https://doi.org/10.1002/trc2.70251 共建Biomedical创新生态圈！如何加入BiG会员？

临床2期

2026-06-04

·阿尔茨海默病研究

INmune Bio双喜临门：XPro1595 FDA快速通道获批+2期白质生物标志物显著改善，炎症型AD治疗路径正式打通

关键词：阿尔茨海默病，XPro1595，可溶性TNF，神经炎症，FDA快速通道认定，白质生物标志物，MINDFuL，临床二期，早期AD Keyword: AD, XPro1595, soluble TNF inhibitor, neuroinflammation, FDA Fast Track Designation, white matter biomarker, MINDFuL, Phase 2, early Alzheimer's disease 新闻发生时间： FDA快速通道认定：2026年5月14日 MINDFuL 2期白质MRI显著疗效数据公布：2026年6月2日XPro1595：靶向神经炎症的可溶性TNF抑制剂在当前AD药物研发领域，以Aβ和tau为核心靶点的路线主导了过去二十年的投入，但神经炎症作为AD病理的独立驱动因子正获得越来越多的临床证据支撑。INmune Bio旗下候选药物XPro1595（pegipanermin）是一种选择性可溶性TNF（soluble TNF, sTNF）抑制剂，通过竞争性置换的方式特异性中和sTNF——这是TNF家族中与小胶质细胞激活、突触损伤和白质病变最密切相关的亚型——而不影响跨膜TNF（tmTNF）介导的正常免疫防御功能[1][2]。这一"选择性"设计规避了传统TNF全面拮抗剂（如依那西普）在CNS应用中的安全性顾虑，是XPro1595的核心差异化优势[3]。里程碑一：2026年5月14日——FDA授予XPro1595快速通道认定 2026年5月14日，INmune Bio宣布FDA正式授予XPro1595快速通道认定（Fast Track Designation, FTD），适应症覆盖轻度认知障碍（MCI due to AD）和轻度AD痴呆两个早期AD阶段[1][4]。快速通道认定使INmune Bio得以享有与FDA更频繁的沟通机会（rolling review机制）、优先审评资格申请权及加速审批通道，将显著压缩XPro1595从关键性试验完成到NDA/BLA获批的时间线[1]。此次认定的授予，建立在此前2026年2月INmune Bio宣布与FDA就XPro1595 2b/3期注册路径达成一致的基础之上——FDA已认可以整合性2b/3期设计（adaptive Phase 2b/3）推进XPro1595的注册申请，规避了传统"先完整2期再启动3期"的冗长路径[5]。两个监管节点的相继落地，意味着XPro1595向注册性临床的推进已获得充分的法规框架支撑。里程碑二：2026年6月2日——MINDFuL 2期白质MRI生物标志物达到统计学显著 2026年6月2日，INmune Bio发布来自MINDFuL 2期试验的白质MRI生物标志物关键补充数据，这是该试验迄今最具说服力的疗效信号[6]：全mITT人群（n=200）：XPro1595治疗组在高级白质MRI生物标志物（Advanced White Matter MRI Biomarker）上显示出高度显著的治疗效应，p=0.0028，效应量d=0.46，达到中等效应规模[6] 这一结果在全人群层面（非预设亚组）实现统计学显著，克服了此前2025年6月MINDFuL顶线数据发布时主要认知终点"混合结果"所带来的市场顾虑[3][6] 白质病变（White Matter Lesions/Hyperintensities）是神经炎症和小血管损伤在影像上的直接体现，在早期AD患者中普遍存在，且与认知衰退速率独立相关。XPro1595在白质MRI指标上的显著改善，为其"抗炎→白质修复→认知获益"的作用链条提供了关键影像学证据，也为此前认知功能指标上的混合结果提供了机制层面的解释框架[2][6]。值得特别关注的是，整个MINDFuL试验过程中未观察到ARIA（淀粉样蛋白相关影像学异常）事件，这与lecanemab、donanemab等抗Aβ抗体普遍存在ARIA风险形成鲜明对比，进一步凸显了XPro1595的安全性优势[3]。MINDFuL试验背景与整体数据回顾 MINDFuL（Modulating INnate Immune Function to Limit Alzheimer's disease）是一项在早期炎症型AD患者中开展的随机双盲安慰剂对照2期试验，共入组200名MCI或轻度AD患者，研究持续18个月，主要考察XPro1595皮下注射给药（每周一次）的安全性及疗效[3][6]。2025年6月：顶线数据发布，主要认知终点结果"混合"，XPro1595未达预设主要终点，股价单日跌逾50%，但炎症标志物（IL-6、TNF）和白质生物标志物显示积极趋势[3]2025年9月：完整MINDFuL数据向 npj Dementia（Nature Portfolio）投稿[7]2026年2月：FDA就整合性2b/3期注册路径达成一致[5]2026年5月14日：FDA授予快速通道认定[1]2026年6月2日：白质MRI生物标志物显著疗效数据补充发布[6]相关内容2024年12月：FDA授予XPro1595罕见儿科病认定（RPDD），用于Down综合征相关AD[8]2025年1月：FDA授予XPro1595孤儿药认定（ODD）[8]2026年2月：INmune Bio宣布FDA就XPro1595整合性2b/3期注册路径达成一致，为快速通道申请奠定基础[5]2026年5月7日：INmune Bio发布Q1 2026财报，同步更新XPro1595开发进展[8]相关介绍 INmune Bio：美国纳斯达克上市生物技术公司（NASDAQ: INMB），总部位于佛罗里达州博卡拉顿，专注于通过调节先天免疫系统（Innate Immune System）治疗神经退行性疾病，核心管线包括XPro1595（AD、唐氏综合征相关AD）和INB-03（AD合并抑郁），以及CORDStrom（脊髓损伤间充质干细胞疗法）。 XPro1595（pegipanermin）：选择性可溶性TNF（sTNF）抑制剂，通过PEGylated dominant-negative TNF技术平台开发，特异性中和sTNF而保留tmTNF功能，以皮下注射每周给药，已获FDA快速通道、孤儿药、罕见儿科病三项认定。 FDA快速通道认定（Fast Track Designation）：FDA为治疗严重疾病且可能填补未满足医疗需求的候选药物授予的加速开发机制，持有者享有与FDA频繁沟通权、滚动审查资格及优先审评申请权，可显著缩短从临床开发到上市的总时间线。白质MRI生物标志物（Advanced White Matter MRI Biomarker）：通过弥散张量成像（DTI）或其他高级MRI序列量化白质完整性的影像学指标，在AD及相关神经退行性疾病中是神经炎症和小血管损伤的客观体现，与认知功能独立相关，INmune Bio将其作为XPro1595疗效评估的关键影像终点。参考文献 [1] "INmune Bio Receives FDA Fast Track Designation for XPro1595 in Early Alzheimer's Disease." GlobeNewswire / INmune Bio Official, May 14, 2026. https://www.inmunebio.com/index.php/newsroom/2026-news/muneioeceivesastrackesignationforro159520260514050502 [2] "INmune Bio Receives FDA Fast Track Designation for XPro1595 in Early Alzheimer's Disease." Yahoo Finance, May 14, 2026. https://finance.yahoo.com/sectors/healthcare/articles/inmune-bio-receives-fda-fast-120000037.html [3] "Phase 2 MINDFuL Trial Results on XPro1595 for Early Alzheimer Disease with Inflammation." Psychiatric Times, 2025. https://www.psychiatrictimes.com/view/phase-2-mindful-trial-results-on-xpro1595-for-early-alzheimer-disease-with-inflammation [4] "FDA Grants Fast Track Designation to XPro1595 for Early Alzheimer's Disease." PharmaCallly, May 2026. https://pharmacally.com/fda-grants-fast-track-designation-to-xpro1595-for-early-alzheimers-disease/ [5] "INmune Bio Announces FDA Alignment on Integrated Phase 2b/3 Registration Pathway for XPro1595 in Early Alzheimer's Disease." INmune Bio Official, February 12, 2026. https://www.inmunebio.com/index.php/newsroom/2026-news/muneionnounceslignmentonntegratedhase2b320260212040512 [6] "INmune Bio Reports Statistically Significant Treatment Effect on Advanced White Matter MRI Biomarker in Phase 2 MINDFuL Alzheimer's Trial." GlobeNewswire, June 2, 2026. https://www.globenewswire.com/news-release/2026/06/02/3305058/0/en/inmune-bio-reports-statistically-significant-treatment-effect-on-advanced-white-matter-mri-biomarker-in-phase-2-mindful-alzheimer-s-trial.html [7] "INmune Bio Announces Submission of Phase 2 MINDFuL Trial Results in Alzheimer's Disease to npj Dementia." INmune Bio Official, September 29, 2025. https://www.inmunebio.com/index.php/newsroom/2025-news/muneionnouncesubmissionofhase2uriales20250929050505 [8] "INmune Bio Corporate Deck." INmune Bio Official, March 2026. https://www.inmunebio.com/images/pdf/presentation/2026/INMD%20corporate%20deck_3.10.2026_Website.pdf 本文内容来自公开信息及研究文献，不代表临床建议。如需投稿、转载、商务合作后台留言，回复有一定延迟敬请谅解。辅助编辑：腾讯元宝or（GPT、Gemini、Claude等）扫码加入ima知识库，获取本公众号所有文献全文资料，AI问答了解更多信息，文献实时更新

2026-06-02

·BioSpace

INmune Bio Reports Statistically Significant Treatment Effect on Advanced White Matter MRI Biomarker in Phase 2 MINDFuL Alzheimer’s Trial

XPro1595 showed a highly significant treatment effect in the full mITT population (p=0.0028; d=0.46; n=200), demonstrating broad tissue-level target engagement and treatment-related biological effect. Efficacy was further strengthened in biomarker-enriched patients with elevated levels of inflammation (p=0.0098; d=0.59; n=100) validating INmune’s precision-medicine approach and directly aligning with the design of the Phase 2b/3 registrational program. BOCA RATON, FL , June 02, 2026 (GLOBE NEWSWIRE) -- INmune Bio Inc. (NASDAQ: INMB), a late-stage biotechnology company focused on inflammation and immunology, today announced results from exploratory chi-separation (χ-separation) MRI imaging analyses from the MINDFuL Phase 2 clinical trial of XPro™ (XPro1595) in patients with early Alzheimer's disease encompassing both mild cognitive impairment (MCI) and mild Alzheimer’s disease dementia. The new MRI findings add to a growing body of evidence supporting XPro™’s precision-medicine development strategy, including the peer-reviewed publication of the Phase 2 MINDFuL results in NPJ Dementia, FDA End-of-Phase 2 alignment on an integrated Phase 2b/3 registrational pathway, and the recent grant of FDA Fast Track designation for XPro™ in early Alzheimer’s disease. CJ Barnum, VP of Neuroscience at INmune Bio, further added, "What we are seeing in MINDFuL is consistency across nearly every domain we measured: cognition, neuropsychiatric symptoms, blood biomarkers, patient-reported outcomes, and now both MRI measures of brain quality, gray matter and white matter. The chi-separation result is the latest signal in that convergent picture, and it carries an additional layer of significance: across multiple independent preclinical models, XPro’s most reliable and reproducible effect has been on myelin biology. The MINDFuL chi-separation result demonstrates a treatment effect on myelin in the full study population that strengthens in patients with elevated inflammatory biomarkers. This is not a surprise finding. It is exactly what the preclinical work predicted. We look forward to presenting the complete dataset at AAIC 2026." BACKGROUND: White Matter Opportunity in Neurodegenerative Disease Across multiple independent preclinical models of demyelination and neurological injury, white matter has consistently emerged as the most reliable and reproducible target of XPro™ response, with clear, documented effects on myelin volume and quality. While historical industry efforts in AD have focused heavily on gray matter pathology, white matter (WM) degeneration and myelin loss are increasingly recognized as fundamental, early contributors to cognitive decline. This structural degradation is not unique to Alzheimer's; it represents a primary pathological signature across a broad spectrum of neurological and neurodegenerative conditions such as Multiple Sclerosis (MS), Vascular Dementia, traumatic brain injury, and many rare CNS diseases where neuroinflammation drives destruction of oligodendrocytes and myelin integrity. Chi-separation MRI was included in the MINDFuL Phase 2 trial as a target engagement biomarker for white matter. This method was chosen given that the trial enrolled patients with MCI and mild AD, the disease stage at which white matter abnormalities are prominent and highly clinically relevant. Chi-separation is a recently validated imaging technique that resolves key challenges of conventional MRI myelin measurement and can be deployed across standard multi-site clinical infrastructure without requiring specialty scanners, making it a methodologically superior and operationally scalable measure of white matter biology. Statistically Significant Biomarker Results The blinded analysis, performed by an independent imaging core laboratory, revealed statistically significant treatment effect on myelin: Full mITT Population (N=200): After 24 weeks of treatment, XPro™-treated participants showed a statistically significant difference in myelin compared to placebo ( p=0.0028 ) with a medium effect size ( Cohen's d=0.46 ). This effect across the full treatment population reproduces XPro™'s most reliable preclinical signature, establishing target engagement in AD patients with a high degree of confidence. Biomarker-Enriched AD Population (N=100): In patients with amyloid-positivity and two or more elevated inflammatory biomarkers at baseline, the treatment effect strengthened further to a medium-to-large effect size ( Cohen's d=0.59; p=0.0098 ). This is the patient pro directly aligned with XPro™'s anti-neuroinflammatory mechanism. "A statistically significant treatment effect on white matter across the full mITT population, strengthening further in inflammation-enriched patients, tells us that XPro™ is doing exactly what it is designed to do, with increased effect in patients we intend to treat in the registrational study,” said David Moss, Chief Executive Officer of INmune Bio. “Importantly, by successfully targeting neuroinflammation to preserve and potentially repair white matter, these data do more than validate our current program, they provide a robust mechanistic foundation that expands the opportunities for XPro™ across a spectrum of other neurodegenerative and neuroinflammatory disease states where pathology is driven by the same inflammatory cascade. With FDA Fast Track designation in hand, End-of-Phase 2 alignment secured, and an additional imaging biomarker result that further reinforces our patient selection strategy, we have systematically addressed several of the key uncertainties that have historically derailed programs in this space. We are building the registrational program on our strongest scientific footing to date and for our broader pipeline potential with XPro." AAIC 2026 Presentation INmune Bio will present the complete chi-separation dataset from the MINDFuL study, including longitudinal trajectory analysis, subgroup characterization, dose-response analyses, and mechanistic interpretation at the Alzheimer's Association International Conference (AAIC) 2026 which will take place July 12–15, 2026 in London, UK. The presentation will also include data from complementary advanced MRI endpoints in the MINDFuL imaging package. Additional details will be announced following the presentation. Accelerated Registration Program Architecture Following a successfully completed End-of-Phase 2 meeting, INmune Bio has secured regulatory alignment with the FDA on the design of its upcoming registrational program, establishing a clear, de-risked pathway toward commercial submission. Supported by FDA Fast Track designation granted on May 14, 2026, the Phase 2b/3 seamless adaptive trial is engineered to support the registration of XPro™ in patients with early Alzheimer's disease who carry biomarkers of inflammation. The registrational strategy is also supported by the favorable safety pro in the Phase 2 MINDFuL trial, including no observed ARIA-E or ARIA-H, an important differentiating feature for a disease-modifying Alzheimer’s program focused on neuroinflammation rather than amyloid clearance. Phase 2b Adaptive Advancement: The Phase 2b portion of the study will utilize the Early Alzheimer's Disease Cognitive Composite (EMACC) and plasma pTau217 as rigorous, decision-gating endpoints. These metrics will dictate the adaptive advancement of the program into the Phase 3 cohort. Phase 3 Registrational Evaluation: The Phase 3 portion is expected to evaluate definitive clinical outcomes, including the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB), which the FDA has raised no objections to using as the sole primary efficacy endpoint for the Phase 3 registrational portion of the program. About XPro1595 XPro1595 is a next-generation inflammatory cytokine modulator that neutralizes soluble TNF (sTNF) without affecting transmembrane TNF (tmTNF) or its receptors. This selective targeting is designed to reduce neuroinflammation, a key driver of neurodegeneration in Alzheimer’s disease, while maintaining the protective immune functions of the body. About INmune Bio Inc. INmune Bio Inc. is a publicly traded (NASDAQ: INMB), late-stage biotechnology company focused on developing treatments that target the innate immune system to fight disease. Moving beyond early-stage exploration, the company’s clinical-development strategy centers on advanced precision medicine, matching drug mechanisms directly to patient biology to optimize clinical outcomes. INmune Bio is actively advancing two late-stage product platforms toward registrational milestones: 1. CORDStrom™: A proprietary, pooled, allogeneic, human umbilical cord-derived mesenchymal stromal cell (hucMSC) platform engineered to address the historical clinical challenges of donor variability and manufacturing inconsistency. Following successful clinical readouts in Recessive Dystrophic Epidermolysis Bullosa (RDEB), the platform is transitioning to regulatory filing phases, with a Marketing Authorization Application (MAA) scheduled for the UK MHRA and EU EMA in 2026, alongside a planned U.S. Biologics License Application (BLA) submission. 2. XPro™: A Dominant-Negative Tumor Necrosis Factor (DN-TNF) platform that selectively neutralizes soluble TNF (sTNF) to eliminate neuroinflammation without compromising protective immune function. Backed by recently granted FDA Fast Track designation and successful regulatory alignment from an End-of-Phase 2 meeting, XPro™ is positioned for an integrated Phase 2b/3 seamless adaptive registrational program in neuroinflammation-enriched early Alzheimer's disease. To learn more about INmune Bio's pipeline and its approach to harnessing the innate immune system, please visit . Forward Looking Statements Clinical trials are in early stages and there is no assurance that any specific outcome will be achieved. Any statements contained in this press release related to the development or commercialization of product candidates and other business and financial matters, including without limitation, trial results and data, including trial results, timing of key milestones, future plans or expectations, and the prospects for receiving regulatory approval or commercializing or selling any product or drug candidates, may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements contained herein are based on current expectations but are subject to several risks and uncertainties. Actual results and the timing of certain events and circumstances may differ materially from those described by the forward-looking statements because of these risks and uncertainties. CORDStrom™, XPro1595™ (XPro™, pegipanermin), and INKmune™ have either finished clinical trials, are still in clinical trials or are preparing to start clinical trials and have not been approved by the US Food and Drug Administration (FDA), the UK MHRA or any regulatory body and there cannot be any assurance that they will be approved by the FDA, the UK MHRA or any regulatory body or that any specific results will be achieved. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the Company’s ability to produce more drug for clinical trials; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and the Company’s business, research, product development, regulatory approval, marketing and distribution plans and strategies. These and other factors are identified and described in more detail in the Company’s filings with the Securities and Exchange Commission, including the Company’s Annual Report on Form 10-K, the Company’s Quarterly Reports on Form 10-Q and the Company’s Current Reports on Form 8-K. The Company assumes no obligation to update any forward-looking statements to reflect any event or circumstance that may arise after the date of this release. INmune Bio Contacts: David Moss Chief Executive Officer (561) 710-0512 info@inmunebio.com Daniel Carlson Head of Investor Relations (415) 509-4590 dcarlson@inmunebio.com

临床2期快速通道临床结果临床3期

100 项与 INB-03 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
并发症	临床3期	美国	INmune Bio, Inc.	2020-10-21
新型冠状病毒感染	临床3期	美国	INmune Bio, Inc.	2020-10-21
阿尔茨海默症	临床2期	澳大利亚	INmune Bio, Inc.	2022-02-28
阿尔茨海默症	临床2期	加拿大	INmune Bio, Inc.	2022-02-28
阿尔茨海默症	临床2期	捷克	INmune Bio, Inc.	2022-02-28
阿尔茨海默症	临床2期	法国	INmune Bio, Inc.	2022-02-28
阿尔茨海默症	临床2期	德国	INmune Bio, Inc.	2022-02-28
阿尔茨海默症	临床2期	波兰	INmune Bio, Inc.	2022-02-28
阿尔茨海默症	临床2期	西班牙	INmune Bio, Inc.	2022-02-28
阿尔茨海默症	临床2期	英国	INmune Bio, Inc.	2022-02-28

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04370236 (CTgov)	临床2/3期	新型冠状病毒感染 \| 并发症	79	INB03 (INB03 + Standard of Care)	蓋簾膚願鬱顧顧觸餘壓 = 襯襯積簾鬱積壓製廠艱構遞壓鹽簾餘獵築壓構 (糧淵簾積築憲醖糧網簾, 鏇選製遞鹹網範顧鹽願 ~ 齋醖膚範鏇窪鏇艱夢獵) 更多	-	2026-05-19
				Placebo (Placebo + Standard of Care)	蓋簾膚願鬱顧顧觸餘壓 = 願窪獵簾蓋廠製觸遞艱構遞壓鹽簾餘獵築壓構 (糧淵簾積築憲醖糧網簾, 醖艱鹹獵衊壓鬱範觸觸 ~ 鬱壓蓋鏇築憲鑰遞製鹽) 更多
NCT05318976 (MINDFuL, GlobeNewswire) 人工标引	临床2期	阿尔茨海默症	208	XPro1595	鏇簾鑰窪製顧遞構製鹹(繭廠齋築遞憲醖糧遞獵) = was not met 淵構網積廠糧鹽窪壓醖 (積獵糧膚膚鏇餘遞鏇膚 ) 未达到更多	积极	2025-07-24
				Placebo
NCT05318976 (MINDFuL, PipelineReview) 人工标引	临床2期	阿尔茨海默症	208	XPro™	鏇選構製願膚鏇繭選獵(夢觸壓獵鬱獵齋鏇簾鏇) = did not meet the primary cognitive endpoint. 鏇襯艱壓膚願選壓醖憲 (鑰糧遞艱鹹壓壓製膚艱 ) 未达到更多	不佳	2025-06-30
				Placebo
GlobeNewswire 人工标引	临床2期	阿尔茨海默症	7	XPro1595	觸鹽獵蓋壓繭廠糧膚鏇(鬱遞醖淵壓憲鑰構築鏇) = statistically significant increase in Alpha wave frequency and power (p<0.05) 蓋艱壓餘糧構築築鏇積 (憲構製鬱繭築遞蓋獵蓋 )	积极	2024-03-05
				placebo
NCT03943264 (CTAD2023)	临床1期	阿尔茨海默症	9	XPRO1595 0.3 mg/kg/wk	網廠蓋膚網憲簾簾廠鏇(淵繭鏇積鑰獵築醖簾淵) = 積襯構壓鹽顧鑰齋憲醖窪鹹鏇鬱繭選繭鑰鹽齋 (選繭襯糧積膚築壓簾糧 )	积极	2023-10-24
NCT03943264 (CTAD2023)	临床1期	阿尔茨海默症 inflammation	3	XPro1595	齋顧窪壓積醖膚簾夢蓋(廠齋醖鑰網壓膚夢淵網) = 艱衊範夢餘壓糧繭築鹹網齋餘網選築獵積顧餘 (獵鑰齋構鑰顧憲繭獵製 )	积极	2023-10-24