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July 09, 2025 -- BioVie Inc. (NASDAQ: BIVI) (“BioVie” or the “Company”), a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease, presented “Bezisterim Epigenetic Effects on Aging and Neurodegeneration” at the 7th World Aging and Rejuvenation Conference (ARC-2025) taking place in Vienna, Austria, July 9th –10th, 2025. Unlike historical approach to Alzheimer’s Disease (AD) treatment that focuses on changing one gene product (e.g., amyloid, p-Tau) at a time, bezisterim modulates inflammation and is believed to help reestablish homeostasis and small changes in many genes at the same time. The data suggest that bezisterim may alter biological age by anti-inflammatory epigenetic modifications. Epigenetic biomarkers can measure “Epigenetic Age Acceleration” (EAA), which is defined as the difference between observed biological age as measured by DNA methylation and the chronological age (i.e., years since birth). An analysis of the Company’s Phase 3 NM101 study (NCT04669028) evaluating bezisterim in patients with mild-to-moderate probable AD assessed 33 blood samples of patients treated with bezisterim (n = 17) and placebo (n = 16) using five validated epigenetic “biological” clocks that analyze genes linked to aging, as well as age-related inflammatory markers. In this analysis, treatment with bezisterim demonstrated: Biological Aging Effects. After 30 weeks of treatment, the average difference between the placebo and bezisterim groups was −3.16 years for SBCAge (p = 0.036), −4.12 years for PhenoAge (p = 0.048), −1.38 years for GrimAge (p = 0.148), −4.24 years for Hannum clock (p = 0.015), and −3.77 years for InflammAge (p = 0.050). The various “biological clocks” measure the extent of age deceleration1 advantage bezisterim-treated patients have compared to those treated with placebo. Gene modulation effects. Bezisterim-treated patients experienced decreased activation of various genes associated with inflammatory kinase cascades, aging and cognition, leading to potentially beneficial changes in aging and AD pathophysiology. Metabolic and inflammatory biomarker effects. Bezisterim-treated experienced significant improvements from baseline on metabolic and inflammatory biomarkers compared to those treated with placebo, including -8.5 mg/dL on fasting glucose (p=0.036), -15 mg/dL in cholesterol (p=0.049), and -90.5 pg/mL in MCP (p=0.007). Bezisterim-treated patients also experienced a decrease in carbohydrate metabolism, glycolysis, and Type 2 diabetes pathophysiology. “Biological aging is the single greatest risk factor for the development of dementia, and we believe our work with bezisterim represents a promising strategy to target the underlying mechanisms of neurodegeneration,” said Christopher Reading, PhD, Senior Vice President of BioVie’s Alzheimer’s Program. “We are honored to share these data that may illuminate bezisterim’s potential to target epigenetic-driven age acceleration as a treatment for Alzheimer’s and other neurodegenerative diseases of aging. We are conducting ongoing studies to further explore these intriguing findings and how bezisterim may help everyone improve healthspan in normal aging.” Bezisterim is a unique, stabilized version of Beta AET, a naturally occurring brain metabolite of dehydroepiandrosterone (DHEA), which has demonstrated anti-inflammatory and immunomodulating activity in humans, but that naturally decreases with age. Beta AET itself cannot be taken in oral form, a major limitation that Bezisterim may address. Unlike its naturally occurring counterpart, Bezisterim is metabolically stable, orally available, and able to cross the blood-brain barrier. It has demonstrated anti-inflammatory effects through inhibition of NF-kappa B, a central mediator of inflammation, and has shown insulin-sensitizing properties. Notably, Bezisterim is not immunosuppressive, and has demonstrated favorable safety and tolerability profiles across in-vivo clinical trials in AD and Parkinson’s Disease (PD). Bezisterim (NE3107) is an orally bioavailable, blood-brain barrier (BBB)-permeable modulator of inflammation and insulin-sensitizer. In addition, it is not immunosuppressive and has a low risk of drug-drug interaction. By binding to ERK and selectively modulating NFκB activation and TNF-α production, BioVie believes that bezisterim may offer clinical improvements in several disease indications, including Alzheimer’s disease, Parkinson’s disease and long COVID. In Parkinson’s disease, BioVie is currently enrolling patients in the Phase 2 SUNRISE-PD clinical trial evaluating the safety and efficacy of bezisterim on motor and non-motor symptoms in patients who have not been treated with carbidopa/levodopa, with topline data expected in late 2025 or early 2026. A previous Phase 2 study of bezisterim in Parkinson’s disease (NCT05083260) completed in 2022, and data presented at the AD/PD™ 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders in Gothenburg, Sweden in March 2023, showed significant improvements in “morning on” symptoms and clinically meaningful improvement in motor control in patients treated with a combination of bezisterim and levodopa versus patients treated with levodopa alone, and no drug-related adverse events. In long COVID, bezisterim has the potential to reduce neurological symptoms, including fatigue and cognitive dysfunction. Persistently circulating viral spike proteins are believed to trigger TLR-4 driven activation of NFκB and the subsequent expression of inflammatory cytokines (IL-6, TNF, IFNg). BioVie’s Phase 2 ADDRESS-LC study, is a randomized (1:1), placebo-controlled, multicenter trial in approximately 200 patients to evaluate the safety, tolerability and potential efficacy of 3 months of treatment with bezisterim to reduce the neurocognitive symptoms associated with long COVID, including difficulty concentrating or remembering things (“brain fog”) and fatigue. In Alzheimer’s disease, BioVie conducted and reported efficacy data on its Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate bezisterim in patients who have mild-to-moderate Alzheimer’s disease (NCT04669028) in 2023. Results of a Phase 2 investigator-initiated trial (NCT05227820) showing bezisterim-treated patients experienced improved cognition and biomarker levels were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) annual conference in December 2022. An estimated six million Americans suffer from Alzheimer’s disease. BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders (AD, Parkinson’s disease and long COVID) and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate bezisterim inhibits inflammatory activation of extracellular signal-regulated kinase and the transcription factor nuclear factor-κB, and the associated neuroinflammation and insulin resistance but not ERK and NFκB homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both neuroinflammation and insulin resistance are drivers of AD and PD. Persistent systematic inflammation and neuroinflammation are key features in patients with neurological symptoms of long COVID. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with FDA Fast Track status, is being evaluated and discussed with guidance received from the FDA regarding the design of Phase 3 clinical testing of BIV201 for the reduction of further decompensation in participants with liver cirrhosis and ascites. The active agent is approved in the U.S. and in about 40 countries for related complications of advanced liver cirrhosis. The content above comes from the network. if any infringement, please contact us to modify.

用干细胞培育神经元，有望治疗癫痫GABA能中间神经元MGE-pIN是大脑皮层回路的重要调节器，它们的功能障碍与神经系统疾病有关。近日，在一项发表在Neuron的研究中，科学家们成功从多能干细胞中培育出了人MGE-pIN，用于治疗耐药性癫痫。在这项研究中，科学家们将培育出的MGE-pIN移植到健康与癫痫模型小鼠脑内进行观察与分析。图片来源：123RF分析显示，97%的移植细胞成功发育成生长激素抑制素（SST）和小清蛋白（PVALB）亚型神经元。移植的hMGE-pIN表现出快速的亚型特征形成过程，依次经历了神经元迁移、突触结构形成和膜成熟等不同转录状态。分子、电生理和形态学数据共同证实，这些移植细胞能够发育成多种真实的人类SST和PVALB神经元。该研究不仅为研究hMGE-pIN的发育提供了一个高保真模型，也为耐药性癫痫等神经系统疾病领域的细胞治疗提供了重要的组成图谱。论文标题：Human stem cell-derived GABAergic interneuron development reveals early emergence of subtype diversity and gradual electrochemical maturationDOI: 10.1016/j.neuron.2025.06.010衰老细胞"传染"的机制揭晓细胞衰老是机体衰老和多种疾病的重要驱动因素。此前研究已证实，在体外培养条件下，衰老细胞可以通过衰老相关分泌表型等机制"传染"周围细胞，导致非细胞自主发生的继发性衰老。然而，这种现象在活体中的发生机制和生理意义一直是个谜。近期发表在Nature Aging杂志上的研究构建了两种衰老诱导小鼠模型，并通过模型成功绘制了原发性和继发性衰老细胞在体内的分布图谱。研究发现，原发和继发性衰老表型具有高度的组织特异性和诱导方式依赖性。即使是同一种细胞类型，不同诱导方式产生的衰老细胞也展现出独特的基因表达特征，这解释了体内衰老细胞的异质性。此外，这项研究还发现，巨噬细胞来源的白细胞介素-1β是诱导继发性衰老的关键因子。这些研究结果不仅深化了我们对衰老扩散机制的理解，还为开发靶向衰老细胞的干预策略提供了理论基础。论文标题：Characterizing primary and secondary senescence in vivoDOI: 10.1038/s43587-025-00917-y产生新生T细胞应答的联合疗法虽然个体化新抗原靶向疫苗在癌症治疗领域展现出巨大潜力，但其免疫原性仍有待提高。为此，研究人员开发了一种新型联合疗法：将Montanide、poly-ICLC佐剂以及局部注射的ipilimumab配制成新型肽类疫苗，患者在接受这种新型疫苗治疗的同时接受系统性nivolumab治疗。这种联合疗法在10名黑色素瘤患者中进行的试验取得了积极结果，相关研究成果于近日发布在Cell杂志。研究显示，完成全程疫苗接种的9名患者，都产生了针对大多数免疫新表位的新生T细胞应答，其中6人还检测到了CD8+ T细胞应答。疫苗接种还诱导了数百种循环和肿瘤内T细胞受体克隆型，这些克隆型与PD-1抑制后产生的克隆型截然不同。通过将T细胞克隆的新抗原特异性与其在肿瘤中的单细胞表型相关联，研究人员证实疫苗接种能够重塑肿瘤内的T细胞库。这些发现表明，“多管齐下”的免疫佐剂策略可以有效增强新抗原靶向疫苗的T细胞应答，为开发更有效的个体化癌症疫苗提供了重要依据。论文标题：A multi-adjuvant personal neoantigen vaccine generates potent immunity in melanomaDOI: 10.1016/j.cell.2025.06.019乳腺癌早期转移的“帮凶”找到了乳腺癌转移是导致患者死亡的主要原因之一，但在早期的微转移阶段，肿瘤细胞如何与免疫系统相互作用仍不清楚。最新发表在Cancer Cell的一项研究发现，T细胞免疫球蛋白和黏蛋白结构域分子3（TIM3）在乳腺癌微转移过程中起着重要作用。研究人员利用乳腺癌转移小鼠模型发现，TIM3在微转移灶中表达显著上调，帮助肿瘤细胞存活、维持干性特征并逃避免疫监视。在微转移早期，TIM3阳性的肿瘤细胞会被优先选择。机制研究表明，TIM3通过增强β-catenin/白细胞介素-1β（IL-1β）信号通路，诱导免疫抑制性γδ T细胞并减少CD8+ T细胞，从而促进肿瘤干性和免疫逃逸。临床数据证实，乳腺癌转移灶中TIM3阳性肿瘤细胞增多，且这类细胞可作为患者不良预后的生物标志物。在临床前模型中，新辅助或辅助治疗中使用TIM3阻断剂可减少转移灶的形成和发生率。这些发现揭示了微转移免疫逃逸的特异机制，为亚临床转移的治疗提供了潜在靶点。论文标题：TIM3 breast cancer cells license immune evasion during micrometastasis outbreak +DOI: 10.1016/j.ccell.2025.06.015SCN2A缺失引发自闭症自闭症谱系障碍（ASD）是一种与基因突变密切相关的神经发育疾病，多巴胺假说被认为是其潜在机制之一。SCN2A基因的功能缺失突变是自闭症的高风险因素，但其致病机制是否与多巴胺系统功能障碍有关尚不清楚。  最新发表在Neuron的一项研究发现，在小鼠腹侧被盖区（VTA）的多巴胺能神经元中，Scn2a是主要的钠离子通道亚型。当VTA多巴胺能神经元完全缺失Scn2a后，神经元的放电活动和多巴胺释放减少，导致小鼠出现多动、社交能力受损和焦虑感不足等自闭症样行为。Scn2a杂合突变小鼠也表现出类似的行为变化。值得注意的是，给予左旋多巴急性治疗能够缓解这些非运动行为缺陷。  这项研究揭示了SCN2A基因缺陷通过多巴胺功能低下机制直接导致自闭症样行为，并为携带SCN2A突变的自闭症患者提供了多巴胺替代疗法的潜在治疗策略。论文标题：Selective loss of Scn2a in ventral tegmental area dopaminergic neurons leads to dopamine system hypofunction and autistic-like behaviorsDOI: 10.1016/j.neuron.2025.06.003欢迎转发到朋友圈，谢绝转载到其他平台。如有开设白名单需求，请在“学术经纬”公众号主页回复“转载”获取转载须知。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：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。更多推荐点个“在看”再走吧~