A Pilot Study of Safety and Efficacy of the Oral IL-12/23 Inhibitor, STA-5326 Mesylate, for Symptomatic Gastrointestinal Inflammation Associated With Common Variable Immunodeficiency

This study will determine whether an experimental medicine, STA-5326 mesylate, is safe to use in patients with common variable immunodeficiency (CVID) who have inflammation of the gut. It will also determine if patients who take this drug show improvement in their symptoms, decrease in inflammatory chemicals in the gut, changes in their immune cells, and improvement in how their gut is functioning to absorb food.
Patients between 18 and 75 years of age with CVID and chronic diarrhea or involuntary weight loss of more than 5 percent of their past body weight over the past 12 months may be eligible for this study. Candidates are screened with a review of their medical records, a medical history and physical examination, blood, urine and stool tests, chest x-rays and skin test for exposure to tuberculosis, and a hydrogen breath test. For the latter, breath samples are collected before and every 20 minutes (for 2 hours) after the subject drinks a sugar solution. This test determines the digestive effects of bacteria in the upper intestine. Samples are collected by having the subject blow into a balloon.
Participants undergo the following tests and procedures:
Immune System and Gastrointestinal Evaluation
* 48-hour stool fat collection (measures the amount of undigested fat in the stool): Subjects keep a diary of what they eat for a 48-hour period. At the beginning of the 48 hours they take two dye capsules and then take another two capsules 48 hours later. They collect a stool sample when they pass the second set of capsules in their bowel movement. An additional 24-hour stool collection is tested for loss of protein in the stool.
* D-xylose absorption test (measures the ability of the gut to absorb nutrients): Subjects drink a solution of d-xylose (a sugar substitute). Blood samples are collected before and 1 hour after drinking the solution.
* Upper endoscopy: A thin flexible lighted tube is advanced through the mouth to evaluate the esophagus, stomach and beginning of the small intestine.
* Lower endoscopy: A thin flexible lighted tube is advanced through the rectum to evaluate the colon.
Treatment Period (Study days 1 to 57)
* Physical examination - study days 1, 8, 15, 29, 43 and 57
* Blood samples to test the levels of STA-5326 in the blood. On study days 1 and 57, samples are collected before the medication dose and 1, 2, 4, 6 and 8 hours after the dose; on day 29, one sample is collected before the medication dose.
* Blood samples for routine safety testing - study days 1, 8, 15, 29, 43 and 57
* Medication history - study days 1, 8, 15, 29, 43 and 57
* Interview about pain, discomfort, and well being - study days 1, 8, 15, 29, 43 and 57
* Pregnancy test for women who can become pregnant - study days 15, 43, and 57
* D-xylose absorption test - study days 29 and 57
* Electrocardiogram - study days 29 and 57
* Urine test - study days 29 and 57
* Blood test for research on immune cells - study day 57
* Repeat endoscopies and studies of gut function (24- and 48-hour stool collections)
Follow-up period (Day 85 and day 113)
-Physical examination, blood tests, medication history, questions about pain, discomfort and well being

开始日期2005-12-02

申办/合作机构

National Institute of Allergy & Infectious Diseases

NCT00088062

/ Completed临床1/2期

A Phase I/IIa Trial of STA-5326 in Crohn's Disease Patients With CDAI Scores of 220-450

The purpose of this study is to determine the safety and tolerability of STA-5326 given once daily or twice daily to Crohn's Disease patients with moderate disease.

开始日期2004-02-01

申办/合作机构

Synta Pharmaceuticals Corp.

100 项与 Apilimod 相关的临床结果

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100 项与 Apilimod 相关的转化医学

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100 项与 Apilimod 相关的专利（医药）

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项与 Apilimod 相关的文献（医药）

2026-05-01·EXPERIMENTAL EYE RESEARCH

PIKfyve is an essential component of the endolysosomal pathway within photoreceptors and the retinal pigment epithelium

Article

作者: Anjum, Ifrah ; Benson, Matthew D ; Hocking, Jennifer C ; MacDonald, Ian M ; Lingrell, Susanne ; Dworkind, Chavy ; Attia, Karen

Phosphoinositides (PIs) are a family of seven low abundance membrane lipids, each with distinct signaling functions. The phosphoinositide kinase PIKfyve generates phosphoinositide-3,5-bisphosphate (PI(3,5)P₂) and PI5P. Emerging evidence implicates PIKfyve in key cellular processes, including autophagy, phagocytosis, endosomal trafficking, lysosomal maintenance, and melanosome formation. Complete loss of PIKfyve function is embryonic lethal in model organisms. In humans, heterozygous mutations in PIKFYVE are associated with Fleck corneal dystrophy and congenital cataracts. In this study, we investigate the role of PIKfyve in photoreceptors and the adjacent retinal pigment epithelium (RPE), host to dynamic endolysosomal pathways required for enduring the high oxidative stress environment, transporting metabolites and phototransduction components, and the breakdown of outer segment discs. To assess PIKfyve function in the retina and RPE in our zebrafish model, we employed CRISPR/Cas9-mediated gene editing and pharmacological inhibition using the specific PIKfyve inhibitor apilimod. Loss of PIKfyve activity leads to RPE expansion characterized by the accumulation of LC3- and LAMP1-positive vacuoles, along with defects in phagosome degradation and minor changes to melanosome biogenesis. Photoreceptors deprived of PIKfyve function develop a single large vacuole in the inner segment, while the OS remains largely intact over the timespan analyzed. Electroretinography (ERG) recordings revealed complete visual impairment in pikfyve crispant larvae and significantly reduced visual function in larvae treated with apilimod post embryogenesis. These findings highlight the critical role of PIKfyve in the development and homeostasis of the RPE and retina.

2026-03-01·EUROPEAN JOURNAL OF PHARMACOLOGY

Chronic stress-induced depression-like behaviors through Th1-lymphocytes and microglia-mediated neuroinflammation in the mouse

Article

作者: Zhang, Cai ; Song, Cai ; Kunikullaya U, Kirthana ; Li, Xiaohong ; Charlier, Thierry D ; Liu, Baiping ; Steinbusch, HarryW M

Recent studies showed the activation of T helper (Th) 1 and microglia during depression. However, the changes in peripheral and central lymphocyte subtypes, and their relationship with microglia in the depression are still unclear. To answer these questions, this study investigated concurrent alterations in lymphocyte subsets (Th1/Th2), microglial activation, and related neuroinflammation and neuronal changes in a mouse model of depression induced by chronic unpredictable mild stress (CUMS). Furthermore, pharmacological inhibitors targeting Th1 (STA-5326), M1 microglia (minocycline), or p38 MAPK (SB203580) were utilized to assess the contribution of these factors to behavioral and molecular outcomes. CUMS induced significant anhedonia and anxiety-like behaviors. These symptoms were accompanied by a decrease in central CD4 T cells and peripheral CD4/CD8 ratio, alongside an increased Th1/Th2 ratio. Hippocampal levels of cortisol, interleukin (IL)-2, IL-12, and the IFN-γ/IL-4 ratio were elevated. CUMS also activated microglia, P38-MAPK pathway and increased neuronal apoptotic signaling (reduced Bcl-2/Bax ratio), and decreased both 5-HT/5-HIAA ratio and neuroplasticity (PSD-95, DCX) in the hippocampus and prefrontal cortex. Notably, the correlations between microglia (Iba-1) and Th1 cell (IL-12), as well as both of them correlations with p-p38 were found. All these parameters were normalized by the three treatments. Interestingly, STA-5326 showed greater efficacy in restoring anhedonia and meningeal CD4 T cell levels, while SB203580 was most effective in normalizing 5-HT neurotransmitter. In summary, inhibiting Th1 lymphocyte activity, M1-microglia or p-38-MAPK pathways improved depression-like behaviors, which were associated with the normalization of peripheral and central immune imbalances, attenuation of neuroinflammation, and protection of neuroplasticity.

2025-06-01·Science China-Life Sciences

Integrative analysis based on CRISPR screen identifies apilimod as a potential therapeutic agent for cisplatin-induced acute kidney injury treatment

Article

作者: Shen, Lu ; Zhang, Yutong ; Du, Huihui ; Lv, Cai ; Cao, Zhongyu ; Yang, Fan ; Wang, Zhenting ; Tan, Jie ; Zhou, Wei ; Chu, Yunpeng ; Qin, Shengying ; Zhang, Yingtian ; Huai, Cong ; Bao, Wei ; Chen, Luan ; Li, Shiyi ; Wei, Muyun ; Lin, Yunxiao

Acute kidney injury (AKI), a life-threatening side effect of cisplatin therapy, significantly limits the drug's therapeutic potential. In this study, we conducted a genome-wide CRISPR/Cas9 knockout screen in human renal tubular epithelial cells, integrating the results with transcriptome analyses and the Connectivity Map (CMap) database. Apilimod and elacridar emerged as the top two candidates of mitigating cisplatin-induced nephrotoxicity, with apilimod demonstrating superior efficacy in drug matrix experiments. Apilimod reduced cisplatin-induced apoptosis, inflammation and reactive oxygen species (ROS) generation. Transcriptome analyses suggested that apilimod may protect against cisplatin-induced nephrotoxicity via modulating lipid metabolism. In vitro experiments revealed that apilimod significantly ameliorated cisplatin-induced lipotoxicity by enhancing lipid clearance and upregulating PGC1α-mediated fatty acid oxidation. Mechanism experiments showed that apilimod induces the nuclear translocation of TFEB through the inhibition of its target, PIKfyve, thereby enhancing PGC1α expression and ameliorating lipotoxicity. These protective effects of apilimod were simulated by siRNA-mediated PIKfyve knockdown and diminished by the PGC1α inhibitor SR-18292 and siRNA targeting TFEB, confirming the role of the PIKfyve/TFEB/PGC1α signaling axis in apilimod's renoprotective effects. In vivo, apilimod alleviated apoptosis, inflammation, and lipid accumulation in a cisplatin-induced AKI mouse model. Additionally, apilimod treatment did not compromise the antitumor effect of cisplatin in cancer cells or tumor-bearing mice. Overall, our study suggests that apilimod could be a promising therapeutic agent for the treatment of cisplatin-induced AKI and revealed its underlying molecular mechanism.

项与 Apilimod 相关的新闻（医药）

2025-07-14

·精准药物

【Nature】合成致死新靶点: PIKfyve

胰腺导管腺癌 (PDAC) 存在于代谢失调的微环境中，这使其特别容易受到干扰癌症代谢的治疗的影响。尽管针对代谢途径已在临床前研究中显示出潜力，但由于难以识别和表征有利的药物开发靶点，药物研发受到阻碍。最新的一篇 Nature 文章表征了 PDAC 中的新可成药靶点： PIKfyve，一种对溶酶体功能不可或缺的脂质激酶。通过抑制 PIKfyve 来破坏脂质代谢，与 KRAS-MAPK 靶向疗法联合应用，可诱导 PDAC 的合成致死。1. 背景介绍PDAC 是最致命的癌症之一，五年生存率仅为 13%。这在很大程度上是由于缺乏有效的治疗选择。PDAC 肿瘤微环境是这种抗药性的核心，其特点是大量基质成纤维细胞和细胞外基质沉积，导致 PDAC 经历间质压力升高、血管分布低和营养利用中断。为了避免这种营养不良的获取，PDAC 细胞成为优秀的清道夫，利用细胞内和细胞外循环途径，通过表达高亲和力营养转运蛋白、大量吞噬、和与其他促肿瘤细胞类型的串扰从其环境中获取非经典营养物质（如谷氨酸）。溶酶体依赖性途径在 PDAC 中发挥多种作用。例如，这些途径已被证明能维持生物合成中间体的可用性，调节铁稳态，降解 MHC-1，增强免疫逃逸，并适应对KRAS 或下游MAPK 通路的抑制。当前，已开展了许多临床试验靶向自噬和溶酶体依赖性途径，使用自噬和溶酶体抑制剂羟氯喹、或 MAPK 抑制剂。脂质激酶 PIKfyve 是细胞中磷脂酰肌醇 3,5-二磷酸（PtdIns(3,5)P2）和磷脂酰肌醇 5-磷酸（PtdIns5P）的唯一来源，对溶酶体活性和自噬至关重要的信号脂质。先前的研究表明，抑制 PIKfyve 会降低 PtdIns(3,5)P2和 PtdIns5P 的细胞水平，并破坏自噬通量和溶酶体功能，从而导致多种癌症模型中的免疫活性增强和肿瘤抑制。示意图显示各种磷脂酰肌醇之间的相互转化。PIKfyve 是一种激酶，可磷酸化PI(3)P（右下）生成 PI(3,5)P2（左下）。Fig4是一种磷酸酶，它能去除磷酸基团。重要的是，两种 PIKfyve 抑制剂 apilimod 和 ESK981 已经通过了 I 期临床试验（NCT02594384和NCT00875264），进入临床2期研究，凸显了靶向 PIKfyve 破坏癌症中的自噬和溶酶体过程的快速转化潜力。为此，作者试图评估 PIKfyve 作为 PDAC 治疗靶点的作用，并发现基因敲除或药物抑制 PIKfyve 可显著减缓 PDAC 肿瘤的发展和生长。Apilimod ( STA-5326， PIKfyve 抑制剂，ID50 = 0.4 nM) CEP-11981 (ESK981，靶向PIKfyve，TIE2, VEGFR1-3、和FGFR1) 2. Pikfyve 在健康的胰腺中是可有可无的首先评估了Pikfyve在原发性 PDAC 基因工程小鼠模型 KPC 中的表达情况。Pikfyve在胰腺上皮内瘤变(PanIN)和 PDAC 组织中的表达显著，且持续高于其在周围健康原位组织中的表达（图1a-c）。表明，与健康胰腺组织相比，PanIN 和 PDAC 可能更高地利用 PIKfyve 驱动的过程来适应营养破坏的微环境。为了评估了 PIKfyve 在正常胰腺发育中的重要性。在条件性胰腺Pikfyve 敲除小鼠中，确认了胰腺组织中 PIKfyve 蛋白的缺失后，不会影响胰腺的重量、形态或胰岛素生成功能。图 1： Pikfyve 对于前体 PanIN 病变发展为 PDAC 至关重要。3. PDAC 肿瘤发生需要 Pikfyve随后，评估 Pikfyve 条件性缺失与 KC 模型（Ptf1a-Cre;LSL-KrasG12D/+）杂交，以评估胰腺肿瘤发生（图1d）。Pikfyve缺失显著延长了 KC 基因型小鼠的生存期（图1e）。Pikfyve 缺失的 KC 小鼠的胰腺保留了更高程度的正常组织学结构。 KPC-Pikfyvef /f小鼠的胰腺重量显著低于 KPC-Pikfyve+/+小鼠，相对于其总体重而言（图1f）。对胰腺进行了组织病理学分析，并观察到 KPC-Pikfyvef /f小鼠的胰腺表现出的疾病发生和进展程度明显低于相似年龄的 KPC-Pikfyve+/+小鼠（图1g,h）。Pikfyve 缺失分别抑制了 KC 和 KPC 模型中胰腺癌的发生和进展，而不会影响正常胰腺组织。总之，PIKfyve 驱动了 PDAC 进程。4. PIKfyve 抑制可抑制 PDAC 生长接下来药理学评估 PIKfyve 抑制是否会引起类似的效果。首先使用细胞热位移分析（CETSA）来确认apilimod和 ESK981与小鼠 PIKfyve 蛋白结合（图2a）。重要的是，PIKfyve 抑制以时间依赖性方式降低了 PtdIns(3,5)P2和 PtdIns5P 的水平，时间点短至 30 分钟（图2b、c）。为了评估 PIKfyve 抑制对 PDAC 发育的影响，用 ESK981 对 KPC 小鼠进行了四周的预防性治疗（图2d）。在十周结束时， ESK981 处理的 KPC 胰腺的重量降低到接近野生型胰腺的水平（图2e）。此外，ESK981 处理的胰腺保留了更高程度的组织病理学上无显著特征的胰腺组织，并且 PanIN 和 PDAC 负担相对减少（图2f）。为了确定 PIKfyve 抑制对 PDAC 肿瘤生长的影响，在体内同种异体移植、异种移植、和原位移植模型中，ESK981 治疗也显著降低了肿瘤负担。图 2：PIKfyve 的药理抑制可阻止体内胰腺癌进展。5. PIKfyve 驱动 PDAC 溶酶体过程为了确定 PIKfyve 抑制对 PDAC 细胞的分子效应，使用了一系列方法来扰乱 PIKfyve。首先，在人 PDAC 细胞系 MIA PaCa-2 和 PANC1 中，CRISPR 干扰介导的 PIKFYVE敲低降低了自噬通量。用 apilimod 或 ESK981 药理学抑制 PIKfyve 在 7940B 和 Panc 04.03（人 PDAC）细胞中以及在UM-2pCDX 肿瘤中体内也显示出类似的效果。用 apilimod、ESK981 或氯喹治疗会降低基础自噬通量，以及由 torin-1 抑制 mTORC 诱导的自噬通量。最后，为了进一步确认靶标特异性，作者开发了第二代靶向蛋白水解的 PIKfyve 嵌合降解剂（PROTAC） PIK5-33d，它基于之前描述的 PIKfyve 降解剂（扩展数据图4g，来自国内有机所丁克研究组，参考先前报道：蛋白降解剂 PROTAC的设计-靶向PIKfyve）。PIK5-33d 强效降解 PIKfyve，这表型复制了由PIKFYVE敲低或其酶抑制引起的自噬抑制和 PIP 水平变化。与之前研究一致，用 PIKfyve 抑制剂或降解剂治疗，或敲低 PIKFYVE，会在 PDAC 细胞中诱导空泡化表型（扩展数据图4n,o）。通过PIKFYVE敲低对 PIKfyve 的干扰也显著减缓了 PDAC 细胞的增殖，PIKfyve 抑制降低了 PDAC 细胞活力，对于大多数细胞系，半数最大抑制浓度 (IC50) 在纳摩尔范围内。6. 脂肪生成回补 PIKfyve 的缺失为了客观评估 PIKfyve 在 PDAC 中的功能相关代谢作用，在 MIA PaCa-2 细胞中进行了两次平行的以代谢为重点的 CRISPR 筛选，并使用不同剂量的 PIKfyve 抑制（图 3a）。有趣的是，高剂量筛选中消耗最显著的sgRNA靶向的基因核心，与从头胆固醇、脂肪酸合成、脂肪酸延长和鞘脂合成途径有关，即SLC25A1、FDFT1、SQLE、FDPS、LSS、FASN、ACACA、ELOVL1、HSD17B12、TECR、SPTLC1、SPTLC2和KDSR（图3b-d）。值得注意的是，在两次筛选中，完成脂质 β-氧化第一步的ACOX1都是筛选中一些最显著富集的 sgRNA 的靶标。这些数据支持 PIKfyve 与从头脂质合成之间的合成致死关系。图 3：PIKfyve 抑制迫使 PDAC 细胞刺激脂肪生成的转录和代谢程序。７. KRAS–MAPK 驱动 PDAC 中的脂肪生成利用 PIKfyve 和脂质合成的合成致死性的途径。作者特别关注从头脂肪酸合成的调控，因为在 CRISPR 筛选中，PIKfyve 抑制后，该途径被强烈地提名为合成必需途径。已知 KRAS 通过 MAPK 信号传导和 MYC 驱动的转录调控，是 PDAC 代谢稳态的核心驱动因素。与先前研究一致，KRAS 抑制（使用 KRASG12D抑制剂 MRTX1133 或 KRASG12C抑制剂 AMG510）或 MEK 抑制（Trametinib，曲美替尼）降低了 PDAC 细胞中 MYC 转录本的表达和蛋白质水平。表明 KRAS-MAPK 信号传导驱动 PDAC 中从头脂肪酸合成基因的表达。用 MRTX1133、AMG51、或曲美替尼治疗可降低 PDAC 细胞系中 FASN 和 ACACA 的 mRNA 和蛋白质水平（图4a）。综上所述，KRAS–MAPK 信号调节 PDAC 中 FASN 和 ACC1 的表达。图 4：KRAS-MAPK 和 PIKfyve 双重抑制导致 PDAC 发生代谢危机和协同生长抑制。接下来，评估了 PIKfyve 和 KRAS 双重抑制对 FASN 和 ACC1 的影响。PIKfyve 抑制会增加 FASN 和 ACC1 的转录本和蛋白质水平，而同时抑制 Kras OFF 和 PIKfyve 导致 FASN 和 ACC1 的增幅与基线相比较小（图 4b-c ）。抑制 PIKfyve 和 KRAS 或 MEK 会使脂质谱向相反方向移动，但 PIKfyve 和 KRAS/MEK 抑制的组合在任一方向上的移动幅度均较小。具体而言，单独抑制 KRAS/MEK 会降低鞘脂水平，并减弱 PIKfyve 抑制引起的鞘脂水平升高。总体而言，KRAS-MAPK 调节从头脂质合成，并且 KRAS-MAPK 抑制会阻止 PDAC 细胞利用鞘脂等脂质的从头合成来适应 PIKfyve 抑制。８. PIKfyve 与 KRAS–MAPK 抑制剂的协同作用那么同时抑制 PIKfyve 和 KRAS-MAPK 所引发的代谢危机是否可用于抑制 PDAC 细胞增殖？协同作用试验证实，PIKfyve 抑制（使用 apilimod或 ESK981）和 KRAS-MAPK 抑制（使用 MRTX1133 或曲美替尼）的任何组合均能产生显著的协同效应，降低 PDAC 细胞增殖和活力。在同基因原位临床前模型、和人类 PDAC 模型中，用 ESK981 和/或曲美替尼治疗不会影响小鼠的体重。PIKfyve 抑制剂和 MEK 抑制剂联合治疗可消除免疫功能正常的原位 PDAC 模型中的肿瘤负担。９.　讨论鉴于 PDAC 已知的代谢脆弱性，以溶酶体功能和自噬途径为目标的治疗策略在临床前研究中已显示出良好的前景。然而，羟氯喹是唯一可用于靶向这些途径的临床级化合物，但疗效有限。在本研究表明 PIKfyve 和 KRAS-MAPK 具有双向合成致死关系：首先，PIKfyve 功能是溶酶体依赖性脂质稳态所必需的，而 KRAS-MAPK 信号传导调节 PDAC 细胞中的从头脂肪生成；其次，PIKfyve 抑制会导致溶酶体脂质代谢中断，迫使 PDAC 细胞上调并依赖于从头脂肪生成；第三，PIKfyve 和 KRAS–MAPK 的双重抑制会导致 PDAC 因无法获得细胞功能所需的脂质而陷入代谢危机（图 5）。鉴于突变型 KRAS 、泛KRAS和 MAPK 通路抑制剂的开发形势迅速发展，以及 PIKfyve 抑制剂 ESK981（目前正在进行多中心 II 期临床试验，NCT05988918 ），这凸显了 PIKfyve 和 KRAS–MAPK 抑制剂的组合是治疗 PDAC 的一种极有前景且可快速转化的治疗策略。图 5：PIKfyve 抑制和 KRAS-MAPK 抑制效果的示意图。左图：在 PIKfyve 和 KRAS-MAPK 信号传导功能正常的情况下，PDAC 处于代谢稳态，能够通过从头合成和溶酶体获取与循环过程生成脂质。中图：PIKfyve 被抑制后，溶酶体功能被破坏，导致溶酶体肿胀或空泡化，脂质被隔离在溶酶体膜上。这导致细胞脂质可用性相对降低，迫使 PDAC 细胞启动从头脂质合成，从而激活 SREBP 以及促脂生成的转录和代谢程序。右图：同时抑制 PIKfyve 和 KRAS-MAPK 会阻断溶酶体循环和获取以及获取脂质的从头合成途径，从而导致合成致死。仔细阅读后觉得这是一篇中规中矩的文章，略表失望，能上Nature有肿瘤代谢领域的大牛加持的成分。只能说从药理研究和靶点验证方面出了更加充分的工作，位临床研究给了很好的意见。此外，将合成致死概念更好的引入到了肿瘤代谢领域，不止是叶酸代谢中的MAT2A和PRMT5。参考：10.1038/s41586-025-08917-z 声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

临床2期临床1期

2024-02-16

·GlobeNewswire-Health Care

OrphAI Therapeutics receives Orphan Drug Designation for AIT-101 as a treatment for amyotrophic lateral sclerosis in the European Union

Feb. 15, 2024 -- OrphAI Therapeutics Inc. (“OrphAI”), a clinical-stage biopharmaceutical company developing novel therapeutics for rare diseases, announced today that it has received Orphan Drug Designation (ODD) in the European Union (EU) for the treatment of amyotrophic lateral sclerosis (ALS). AIT-101 previously received ODD from the U.S. FDA in June 2023 for the treatment of ALS. “OrphAI Therapeutics now has orphan designation for AIT-101 both in the US and the EU for the treatment of ALS, an important step toward bringing the drug to patients suffering from this neurodegenerative disorder,” said Dr. Brigette Roberts, CEO and Director of OrphAI. “AIT-101 has demonstrated compelling activity in its ability to clear toxic aggregates, which are a hallmark of ALS and other neurodegenerative diseases. We look forward to moving AIT-101 into the next stage of clinical development." AIT-101 is a first-in-class, potent and highly selective inhibitor of the lipid kinase PIKfyve. Inhibition of PIKfyve leads to activation of the transcription factor TFEB which drives the increased clearance of toxic protein aggregates via the lysosomal autophagy pathway. AIT-101 has now been demonstrated to reduce aggregates in human subjects, to improve the survival of motor neurons in in vitro models of familial and sporadic ALS, and to ameliorate functional deficits in a mutant TDP-43 animal model of ALS. AIT-101 is the most clinically advanced PIKfyve inhibitor in development. OrphAI Therapeutics’ mission is to transform the lives of patients with rare diseases. The company is currently developing three investigational therapies across multiple orphan indications: AIT-101, a first-in-class PIKfyve inhibitor, which recently completed a Phase 2a clinical trial in amyotrophic lateral sclerosis (ALS); LAM-001, a proprietary inhaled form of rapamycin, currently in Phase 2 for Group 1 and 3 pulmonary hypertension and bronchiolitis obliterans syndrome (BOS); and AIT-102, a proprietary analogue of mithramycin, in preclinical development, for the treatment of SWI/SNF mutated or dysregulated tumors. The content above comes from the network. if any infringement, please contact us to modify.

孤儿药临床结果

2024-01-24

·GlobeNewswire-Health Care

OrphAI Therapeutics Announces Appointment of Jay Fine to Board of Directors

Seasoned leader in drug discovery and developmentGUILFORD, Conn., Jan. 24, 2024 (GLOBE NEWSWIRE) -- OrphAI Therapeutics Inc. (“OrphAI”), a clinical-stage biopharmaceutical company developing novel therapeutics for rare diseases, announced today the appointment of Jay S. Fine, Ph.D. to its Board of Directors. Dr. Fine has a strong track record of drug discovery and development leadership in respiratory diseases, oncology, immunology and fibrotic disease indications. His leadership has contributed to the progression of over 30 new molecular entities into clinical development, leading to the commercial launch of multiple products including Skyrizi™ for Plaque Psoriasis, Psoriatic Arthritis and Crohn’s Disease and Spevigo™ for Generalized Pustular Psoriasis. He has chaired various governance and steering committees at several global pharmaceutical companies. Dr. Fine currently serves as President of Research and Development at EvolveImmune Therapeutics, a development-stage company focused on advancing differentiated immunotherapeutic approaches for the treatment of cancer. Previously, he served as Senior Vice President and Global Therapeutic Area Head for Immunology and Respiratory Diseases Research at Boehringer Ingelheim and as the Discovery Research Site Head at their Ridgefield, CT location. Dr. Fine also served as Head of Translational Biology at Roche Pharmaceuticals, was a Director in the Inflammation department at Schering-Plough and worked in the Biologic Response Modifiers Program at the National Cancer Institute. He holds a B.S. degree from Cornell University and a Ph.D. from the University of Rochester School of Medicine. Dr. Fine has authored over 75 scientific publications and patents and has been the recipient of numerous honors and awards during his career. “Jay Fine represents an extraordinary resource both for the Board as well as for the OrphAI management team, given his years of experience and success in the operational leadership of drug discovery and development. I am personally excited to work with him in this capacity,” said Dr. Brigette Roberts, CEO and Director of OrphAI. “I am very pleased to join the OrphAI Therapeutics’ Board of Directors,” said Dr. Fine. “The company has established an exciting product pipeline which holds tremendous potential to meaningfully improve the lives of patients with rare diseases. I look forward to working closely with the OrphAI team and its board to accelerate the progress of its promising pipeline.” “We are excited to welcome Jay Fine to our Board of Directors,” said David Scheer, Chairman of the Board of Directors at OrphAI. “Jay’s extensive leadership experience and drug development insights will be especially valuable to OrphAI and our Board as we collectively embark on this next stage of the company’s growth.” About OrphAI Therapeutics OrphAI Therapeutics’ mission is to transform the lives of patients with rare diseases. The company is currently developing three investigational therapies across multiple orphan indications: AIT-101, a first-in-class PIKfyve inhibitor, which recently completed a Phase 2a clinical trial in amyotrophic lateral sclerosis (ALS); LAM-001, a proprietary inhaled form of rapamycin, currently in Phase 2 for bronchiolitis obliterans syndrome (BOS) and pulmonary arterial hypertension (PAH); and AIT-102, a proprietary analogue of mithramycin, in preclinical development for the treatment of SWI/SNF mutated or dysregulated tumors. To learn more, please visit: OrphAI-Therapeutics.com

临床2期高管变更

100 项与 Apilimod 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
-	Apilimod	-	DB05611

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
肌萎缩侧索硬化	临床2期	美国	OrphAI Therapeutics, Inc.	2022-07-27
克罗恩病	临床2期	美国	Synta Pharmaceuticals Corp.	2004-02-01
葡萄膜炎	临床前	美国	Synta Pharmaceuticals Corp.	2008-05-01