Phase1a, Randomized Placebo-controlled, Single and Multiple Dose, Dose-escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Oral NNI-362 in Healthy Aged Volunteers 50 to 72 Years of Age

The purpose of this study is to examine the safety, tolerability and pharmacokinetics of single and multiple doses of NNI-362 in healthy aged population.

开始日期2019-08-01

申办/合作机构

NeuroNascent, Inc.

[+1]

100 项与 NNI-362 相关的临床结果

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100 项与 NNI-362 相关的转化医学

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100 项与 NNI-362 相关的专利（医药）

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项与 NNI-362 相关的文献（医药）

2021-12-01·Stem cell research & therapy2区 · 医学

Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease

2区 · 医学

ArticleOA

作者: Wong, Jessica M ; Wells, Matthew S ; Kelleher-Andersson, Judith A ; Sidhu, Akram ; Zheng, Qiao-Xi ; Forster, Michael J ; Sumien, Nathalie

Abstract:

Aging is known to slow the neurogenic capacity of the hippocampus, one of only two mammalian adult neurogenic niches. The reduction of adult-born neurons with age may initiate cognitive decline progression which is exacerbated in chronic neurodegenerative disorders, e.g., Alzheimer’s disease (AD). With physiologic neurogenesis diminished, but still viable in aging, non-invasive therapeutic modulation of this neuron regeneration process remains possible. The discovery of truly novel neuron regenerative therapies could be identified through phenotypic screening of small molecules that promote adult-born neurons from human neural progenitor cells (hNPCs). By identifying neuron-generating therapeutics and potentially novel mechanism of actions, therapeutic benefit could be confirmed through in vivo proof-of-concept studies. The key aging and longevity mTOR/p70S6 kinase axis, a commonly targeted pathway, is substrate for potential selective kinase modulators to promote new hippocampal neurons from NPCs. The highly regulated downstream substrate of mTOR, p70S6 kinase, directly controls pleiotropic cellular activities, including translation and cell growth. Stimulating this kinase, selectively in an adult neurogenic niche, should promote NPC proliferation, and cell growth and survival in the hippocampus. Studies of kinase profiling and immunocytochemistry of human progenitor neurogenesis suggest that the novel small molecule NNI-362 stimulates p70S6 kinase phosphorylation, which, in turn, promotes proliferation and differentiation of NPCs to neurons. NNI-362 promoted the associative reversal of age- and disease-related cognitive deficits in aged mice and Down syndrome-modeled mice. This oral, allosteric modulator may ultimately be beneficial for age-related neurodegenerative disorders involving hippocampal-dependent cognitive impairment, specifically AD, by promoting endogenous hippocampal regeneration.

Alzheimers Research & Therapy

First-in-human study of neuron regenerative therapy NNI-362 to evaluate the safety, pharmacokinetics, and pharmacodynamics in healthy aged population

Article

作者: McFarlane, Claire ; Green, Carol ; Turner, R Scott ; Kelleher-Andersson, Judith ; Bagheri, Donya ; Yoon, Esther ; Thomas, Lynn Parker

BACKGROUND:

A placebo-controlled, double-blind Phase 1a trial examined the safety, tolerability, and pharmacokinetics of NNI-362 as well as the pharmacodynamic outcome of plasma phosphorylated tau¹⁸¹ (p-tau¹⁸¹).

METHODS:

Oral NNI-362 and placebo were randomized in healthy, cognitively-unimpaired individuals (ages 50-72) at a 3:1 ratio, with sponsor, principal investigator, and subjects all blinded. Plasma levels of p-tau¹⁸¹ were determined in the placebo and the two highest arms of 120 and 240 mg NNI-362. Plasma biomarker was examined for statistical change from baseline.

RESULTS:

NNI-362 treatment was safe and well tolerated in older individuals. NNI-362, at the two highest multiple doses, significantly reduced plasma p-tau¹⁸¹ levels compared to pretreatment levels (P < 0.0012 to P < 0.0009), while no change occurred in placebo groups.

CONCLUSIONS:

These findings suggest in older subjects, oral NNI-362 appeared safe, well tolerated and reduced plasma p-tau¹⁸¹. Phase 2 studies of NNI-362 are warranted for Alzheimer's disease and age-related degenerative disorders.

TRIAL REGISTRY NUMBER:

NCT04074837. First registered: 2019-08-27.

项与 NNI-362 相关的新闻（医药）

2025-08-16

·药明康德

100%临床应答的小分子疗法；降低近90%癌症复发风险的突变KRAS靶向多肽疫苗…… | 一周盘点

本期看点 1. Palisade Bio公司公布了其在研潜在“first-in-class”疗法PDE4抑制剂PALI-2108的最新临床数据。分析显示，在1b期溃疡性结肠炎（UC）队列中，PALI-2108实现了100%（5/5）临床应答。 2. Elicio Therapeutics近日宣布，其靶向突变KRAS（mKRAS）的多肽疫苗ELI-002在胰腺癌和结直肠癌患者中展现积极疗效，在T细胞免疫应答超过抗肿瘤疗效阈值的患者中，死亡风险降低77%，复发风险降低88%。 PALI-2108：1b期试验结果公布 Palisade Bio公司公布了其在研潜在“first-in-class”疗法PDE4抑制剂PALI-2108的最新临床数据，包括在中重度溃疡性结肠炎患者中开展的1b期开放标签队列研究积极的主要结果，以及来自1a期多次递增给药（MAD）队列的结肠组织药代动力学（PK）数据。在1b期UC队列中，PALI-2108实现了100%（5/5）临床应答（修订Mayo评分降低30%或3分，且直肠出血评分≤1），平均修订Mayo评分下降62.8%，其中1名患者达到临床缓解。药物在试验中表现出良好的安全性与耐受性，未发生严重不良事件。研究还显示，PALI-2108具有延长的半衰期及局部生物活性，支持其在溃疡性结肠炎及纤维狭窄型克罗恩病（FSCD）中的每日一次给药方案。在已完成的1a期MAD队列中，结肠组织中药物水平在给药36小时后仍高于目标阈值。公司计划在2026年上半年推进PALI-2108的2期临床研究，并提交IND申请。 ELI-002：1期试验结果发布 Elicio Therapeutics近日宣布，其在《自然》子刊Nature Medicine发表了1期AMPLIFY-201研究的随访数据。该研究评估了靶向mKRAS的多肽疫苗ELI-002在胰腺癌和结直肠癌患者中的疗效。结果显示，在中位随访19.7个月时，T细胞反应水平超过抗肿瘤疗效阈值的受试者在复发或死亡风险方面显著降低。死亡风险降低77%，复发风险降低88%。此外，ELI-002在大多数患者中诱导了mKRAS特异性的CD4+和CD8+T细胞反应，并观察到患者的免疫系统对特异性新抗原产生反应，这些新抗原未包含于原初疫苗的设计当中。 ELI-002是一种在研癌症多肽疫苗，旨在靶向由KRAS基因突变驱动的多种人类癌症。该疫苗由Elicio的Amphiphile（AMP）技术构建，包括AMP修饰的mKRAS肽抗原以及AMP修饰的CpG寡脱氧核苷酸佐剂ELI-004，可作为现成的皮下注射制剂使用。研究结果表明，ELI-002不仅能引发强烈且持久的免疫应答，还显示出通过增强T细胞反应降低肿瘤复发与死亡风险的潜力，为KRAS突变相关癌症的治疗提供了新的方向。 NNI-362：1a期试验结果发布 Neuronascent公司宣布，其研发的口服疗法NNI-362的1a期临床试验结果已发表于Alzheimer’s Research and Therapy期刊。NNI-362是该公司专有主打小分子药物，旨在通过生成新神经元替代慢性与年龄相关的神经退行性疾病中丢失的神经元，从而逆转与衰老相关的疾病。该1a期临床试验的研究对象为健康老年志愿者，主要评估其安全性、药代动力学特征以及阿尔茨海默病进展的血浆生物标志物。试验结果显示，NNI-362在老年受试者中安全且耐受性良好。在两种最高多剂量组中，NNI-362可显著降低血浆p-tau181水平，与治疗前相比差异具有高度统计学显著性（P<0.0012至P<0.0009），而安慰剂组未观察到显著变化。这一结果为NNI-362在改善年龄相关神经退行性疾病方面的潜力提供了初步临床支持。 NT-0796：1b/2a期试验结果发布 NodThera公司宣布，其口服、可穿越血脑屏障的NLRP3炎性小体抑制剂NT-0796在帕金森病1b/2a期研究中的积极数据已发表于Movement Disorders期刊。数据显示，NT-0796在健康志愿者及帕金森病患者中均表现出良好的安全性与耐受性，具有优异的中枢及全身药代动力学特征，并实现了较高的靶点结合率。研究结果显示，NLRP3抑制在降低神经炎症方面具有明确作用，显示可减少神经炎症相关生物标志物。在脑脊液（CSF）中，与NLRP3相关的细胞因子IL-1β水平下降，同时相关下游标志物CSF CCL2、IL-6、IL-8和CXCL1亦同步降低；神经炎症CSF标志物sTREM2和神经丝轻链（NfL）水平也持续下降。此外，对于基线存在全身炎症的受试者，NT-0796还能降低多种全身炎症标志物，包括超敏C反应蛋白、纤维蛋白原、IL-6和IL-18。 ST-01156：IND申请获得FDA许可日前，SEED Therapeutics宣布，美国FDA已批准其在研分子胶药物ST-01156的IND申请。这一批准将支持针对晚期实体瘤和血液恶性肿瘤患者的首次人体1期临床试验的启动，公司将优先聚焦于多种在临床前研究中显示对RBM39依赖性有明确证据的癌症类型。公司预计将在2026年第一季度完成首例患者给药。 SEED自主研发的RITE3平台可通过理性设计筛选出靶向致病蛋白的E3连接酶，并发现具成药性质的分子胶药物，用以治疗多种适应症。ST-01156是SEED的首个进入临床阶段的候选药物，已获FDA授予孤儿药资格和罕见儿科疾病资格，用以治疗尤因肉瘤（Ewing sarcoma）。尤因肉瘤是一种罕见的儿科恶性肿瘤，三十多年来无新疗法获批。 Bulumtatug fuvedotin：1b期试验首位患者给药迈威生物（Mabwell）公司宣布，其在研抗体偶联药物（ADC）bulumtatug fuvedotin（BFv）在三阴性乳腺癌（TNBC）患者中启动1期临床研究，并已完成首例患者给药。该临床研究旨在评估BFv在既往接受过紫杉类药物及拓扑异构酶抑制剂载荷ADC治疗的TNBC患者中的疗效与安全性。 BFv是一款新型Nectin-4靶向ADC，采用新一代位点特异性偶联技术，由创新抗体、优化连接子及细胞毒载荷MMAE组成，具备良好的肿瘤结合力与靶点特异性。研究显示，BFv具有高组分均一性、可显著降低血浆毒素释放并具有更高效的细胞毒载荷递送能力，从而实现肿瘤内药物浓度的大幅提升。鉴于TNBC患者中Nectin-4高表达，BFv在TNBC的临床研究不设生物标志物筛查要求，有望覆盖更广泛的患者群体，为TNBC患者提供全新的治疗选择。参考资料： [1] Elicio Therapeutics Announces Publication of ELI-002 Updated AMPLIFY-201 Phase 1 Follow-up Data in Nature Medicine for Minimal Residual Disease (“MRD”) Positive, Adjuvant-Stage Patients. Retrieved August 15, 2025 from https://elicio.com/press_releases/elicio-therapeutics-announces-publication-of-eli-002-updated-amplify-201-phase-1-follow-up-data-in-nature-medicine-for-minimal-residual-disease-mrd-positive-adjuvant-stage-patient/ [2] Neuronascent Announces Progress for Lead Candidate NNI-362: Publication of Phase 1a Clinical Trial Results and FDA Grants Waiver of Fee for Canine Cognitive Disorder 2025 Submissions. Retrieved August 15, 2025 from https://www.globenewswire.com/news-release/2025/08/13/3132372/0/en/Neuronascent-Announces-Progress-for-Lead-Candidate-NNI-362-Publication-of-Phase-1a-Clinical-Trial-Results-and-FDA-Grants-Waiver-of-Fee-for-Canine-Cognitive-Disorder-2025-Submission.html [3] Kelleher-Andersson J, Yoon E, Green C, McFarlane C, Bagheri D, Thomas LP, Turner RS. First-in-human study of neuron regenerative therapy NNI-362 to evaluate the safety, pharmacokinetics, and pharmacodynamics in healthy aged population. Alzheimers Res Ther. 2025 Aug 7;17(1):185. doi: 10.1186/s13195-025-01837-0. PMID: 40775373; PMCID: PMC12330068. [4] NodThera Demonstrates Reversal of Neuroinflammation and Inflammation in Parkinson’s Disease with Oral NLRP3 Inhibitor. Retrieved August 15, 2025 from https://www.nodthera.com/news/nodthera-demonstrates-reversal-of-neuroinflammation-and-inflammation-in-parkinsons-disease-with-oral-nlrp3-inhibitor/ [5] Assembly Biosciences Reports Positive Interim Results from Phase 1b Clinical Study of Long-Acting Helicase-Primase Inhibitor Candidate ABI-5366 Showing Reductions in Viral Shedding Rate and Genital Lesion Rate in Recurrent Genital Herpes. Retrieved August 15, 2025 from https://investor.assemblybio.com/news-releases/news-release-details/assembly-biosciences-reports-positive-interim-results-phase-1b [6] FDA Clears IND for SEED Therapeutics’ RBM39 Degrader ST-01156. Retrieved August 15, 2025 from https://www.globenewswire.com/news-release/2025/08/11/3130780/0/en/FDA-Clears-IND-for-SEED-Therapeutics-RBM39-Degrader-ST-01156.html [7] Mabwell Announces First Patient Dosed in the US Clinical Study of Bulumtatug Fuvedotin in TNBC Patients Previously Treated with ADCs. Retrieved August 15, 2025 from https://www.prnewswire.com/news-releases/mabwell-announces-first-patient-dosed-in-the-us-clinical-study-of-bulumtatug-fuvedotin-in-tnbc-patients-previously-treated-with-adcs-302527599.html 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。版权说明：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载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期临床结果疫苗临床1期临床申请

2023-08-22

·BioSpace

Neuronascent Announces NIA Grant Award for NNI-362 to Reach Phase 2 Clinical Trials for Mild to Moderate Alzheimer’s Disease

ROCKVILLE, Md., Aug. 22, 2023 (GLOBE NEWSWIRE) -- Neuronascent Inc., a privately-held neuron regeneration therapeutics company, today announced that the National Institute of Aging (NIA), has awarded a U01 grant to Neuronascent, with the CEO, Dr. Judith Kelleher-Andersson being the principal investigator. The grant, titled “Completion of Non-clinical long-term GLP safety and GMP manufacture for first-in-class neuron regenerative therapy, NNI-362 Phase 2 POC AD trial,” will allow for the longer-term assessment of Neuronascent’s investigational drug, in a proof-of-concept clinical trial. Neuronascent discovered experimental therapeutic NNI-362 through a novel screening program aimed at identifying small molecules that should enter the human brain and promote new adult-born neurons to replace those lost in aging and disease. Key to its efficacy is the unique allosteric modulation of the pleiotropic kinase, p70S6 kinase, where this mechanism-of-action avoids the safety concerns observed with many kinase inhibitors. This first-in-class investigational therapy has received support from the NIA twice previously, first to complete short term GLP safety testing for submission of the Investigational New Drug application, and secondly for the completion of the Phase 1a clinical safety trial in healthy aged population. Alzheimer’s is a disease of aging, the greatest risk-factor, and even with new therapies aimed at slowing early progression into Alzheimer’s disease, there remains a great unmet need for a disease-modifying treatment for the 6.7 million patients, in the United States alone, already suffering from cognitive and functional deficits. Dr. R. Scott Turner, Prof. Neurology and Director Memory Disorders Program at Georgetown University said, “There is still a need for therapies to actually halt and potentially reverse the disease at the next stage of disease progression from pre-AD to severe AD.” This grant award should allow the further long-term safety testing and further GMP manufacture of NNI-362 required before running a critical trial to assess whether NNI-362 will indeed address the next stage of AD disease progression by halting and potentially reversing disease back to a time when the patient had greater memory and executive function. Neuronascent expects that NNI-362 will provide benefit for any number of age-related disorders beyond just Alzheimer’s; that is, those disorders that occur due to loss of adult-born neurons in cognitive and motor regions of the brain. Neuronascent’s Dr. Kelleher-Andersson said, “With therapeutics that address the different stages of disease, we may finally be at the point of obtaining precision medicine for age-related neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.” About NNI-362 NNI-362 is Neuronascent’s lead patented investigational therapeutic aimed at reversing age-related disorders by producing new neurons to replace those lost in chronic age-related neurodegenerative disorders. Orally delivered NNI-362 has completed a NIA-supported and FDA-cleared Phase 1a clinical trial in healthy aged volunteers that assessed safety, pharmacokinetics and a plasma biomarker of Alzheimer’s disease progression. About Neuronascent, Inc. Neuronascent was founded to discover and develop novel therapies to halt and/or reverse diseases of the central nervous system, an area of vast unmet need. Through its proprietary phenotypic screening platform, Neuronascent has discovered a pipeline of small molecule oral regenerative candidates with patents issued. Corporate Contact: Judith Kelleher-Andersson, PhD. Founder and CEO jkelleher@neuronascent.com Media Contact: Nick Veronico Nickver@sbcglobal.net Safe Harbor Statement This release contains forward-looking statements, which are made pursuant to the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements are commonly identified by words such as “would,” “may,” “will,” “expects,” and other terms with similar meaning. Forward-looking statements are based on current beliefs, assumptions and expectations and speak only as of the date of this release and involve risks and uncertainties that could cause actual results to differ materially from current expectations.

临床1期临床2期

2023-04-12

·BioSpace

Neuronascent Announces the Expansion of its Board of Directors

Dr Emer Leahy, a leader with over 30 years of CNS drug discovery and business development experience joins the Board ROCKVILLE, Md., April 12, 2023 (GLOBE NEWSWIRE) -- Neuronascent Inc., a clinical-stage, neuron generating, biopharmaceutical company, is pleased to announce the addition of industry leader Emer Leahy, Ph.D., MBA, to its Board of Directors. This is a key time for Neuronascent, following the successful completion of its Phase 1a randomized clinical trial of NNI-362 in healthy aged subjects for Alzheimer’s disease, and potentially other age-related disorders, and with NNI-351’s recent designation by the U.S. Food and Drug Administration (FDA) for both orphan and rare pediatric drug development for Fragile X syndrome. The guidance of Dr. Leahy at the board level will be invaluable as Neuronascent aims to advance its novel neuron generating therapies further into clinical trials. “The appointment of Dr. Emer Leahy to our board of directors adds tremendous expertise in the development of central nervous system therapies toward commercialization, as well as guiding Neuronascent in developing pharmaceutical industry partnerships,” said founder and CEO Judith Kelleher-Andersson, PhD. Dr. Leahy holds a PhD in neuropharmacology from University College Dublin, Ireland, and an MBA from Columbia University. She is the long-standing President and CEO of PsychoGenics, Inc., as well as an adjunct associate professor of Neuroscience at Mount Sinai School of Medicine in New York City. Dr. Leahy has more than 30 years of experience in drug discovery, clinical development and business development for pharmaceutical and biotechnology companies, including extensive knowledge of technology assessment, licensing, mergers and acquisitions, and strategic planning. “I am honored to join the Neuronascent Board. I have long been impressed with the company’s novel platform that has identified multiple development candidates including NNI-362 with phase 1 clinical data and the potential to transform the way we think about, and treat, neurodegenerative conditions,” said Dr Leahy. “I have been inspired by what has been accomplished to date, and I look forward to working alongside Judy and the rest of the board to bring these innovative treatment options to those living with severely disabling neurodegenerative conditions.” About Neuronascent, Inc. Neuronascent, Inc., [ ] a privately-held, clinical-stage pharmaceutical company, was founded to discover and develop novel therapies that treat central nervous system disorders with high-unmet need by replacing and enhancing neuron numbers, not just neural connections. Through its proprietary phenotypic screening platform, Neuronascent has discovered a pipeline of small molecule regenerative candidates with patents issued, including NNI-351 for Fragile X syndrome, a rare pediatric disorder. NNI-362, Neuronascent’s lead, patented, new chemical entity, was developed to reverse age-related disorders by producing new neurons to replace those lost due to chronic neurodegeneration. Safe Harbor Statement This release contains forward-looking statements, which are made pursuant to the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements are commonly identified by words such as “would,” “may,” “will,” “expects,” and other terms with similar meaning. Forward-looking statements are based on current beliefs, assumptions and expectations and speak only as of the date of this release and involve risks and uncertainties that could cause actual results to differ materially from current expectations. Corporate Contact: Judith Kelleher-Andersson, PhD. Founder and CEO jkelleher@neuronascent.com Media Contact: Nick Veronico Nickver@sbcglobal.net

临床1期高管变更临床2期快速通道

100 项与 NNI-362 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床1期	美国	NeuroNascent, Inc.	2019-08-01
亨廷顿舞蹈病	药物发现	美国	NeuroNascent, Inc.	-

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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


Phase 1a trial (CTAD2022)	临床1期	老化 plasma p-tau181 -	-	NNI-362	獵蓋艱餘窪鬱鹽窪鏇糧(壓艱繭鹽鏇築鑰製構夢) = 醖醖鹽遞築鏇憲製醖簾鹹襯簾鹹廠積觸鏇顧製 (遞艱範願衊齋窪鑰鏇艱 )	积极	2022-12-03
				Placebo	獵蓋艱餘窪鬱鹽窪鏇糧(壓艱繭鹽鏇築鑰製構夢) = 鏇願襯築淵鏇鏇網淵鹹鹹襯簾鹹廠積觸鏇顧製 (遞艱範願衊齋窪鑰鏇艱 )
NCT04074837 (PRNewswire) 人工标引	临床1期	阿尔茨海默症	56	NNI-362	憲齋鬱醖鹽淵網構醖構(鏇構廠淵襯廠憲膚簾糧) = 膚襯憲壓鑰糧鑰淵觸築獵憲顧壓鹹鹽網網蓋膚 (積遞餘獵鹹遞積醖醖膚 ) 更多	积极	2021-09-29
				Placebo	-