STING Inhibitor (Astellas)

Astellas Pharma (Japan) has terminated its Phase I clinical trial of ASP5502, an oral small-molecule STING (Stimulator of Interferon Genes) inhibitor, in healthy adults and patients with primary Sjögren’s syndrome. The clinical trial terminated before completion, according to an updated record on ClinicalTrials.gov (NCT06544642), with the status verified as of March 2026. The study, which began enrolling participants in August 2024 at a Fortrea Clinical Research Unit in Daytona Beach, Florida, had been designed as a first-in-human evaluation of the compound. No results have been posted to the registry. The study was a randomized, double-masked, placebo-controlled Phase I trial with a three-part design: single ascending doses (including a food-effect cohort), multiple ascending doses in healthy volunteers over 14 days, and a 28-day repeated-dose cohort in adults with primary Sjögren’s syndrome without a placebo comparator. The trial planned to enroll 116 participants aged 18–65, with primary endpoints focused on safety and tolerability (adverse events, laboratory abnormalities, vital signs, and ECGs) and secondary endpoints assessing pharmacokinetics and cardiac safety. The Sjögren’s cohort required a diagnosis based on 2016 ACR-EULAR criteria and excluded patients receiving immunosuppressive or B-cell–targeting therapies or with other systemic autoimmune conditions. Termination context The study was terminated for strategic reasons, according to the ClinicalTrials.gov NCT06544642 entry, with no indication of safety concerns or lack of efficacy. The decision comes amid Astellas’ broader efforts to prioritize late-stage and core therapeutic areas, although the company has not publicly linked those changes to ASP5502 specifically. ASP5502 was positioned within Astellas’s immune homeostasis research area, which sits outside the company’s four declared primary focus areas: immuno-oncology, targeted protein degradation, genetic regulation, and blindness and regeneration. Astellas has been executing a systematic drug development pipeline update over the past two years, driven in large part by the approaching patent cliff for enzalutamide (Xtandi), its largest revenue-generating product, with generic competition expected around 2027. The company has concentrated resources on late-stage oncology assets — enfortumab vedotin (Padcev), zolbetuximab (Vyloy), and several degrader and antibody-drug conjugate programs — while pruning early-stage assets in non-core therapeutic areas. Prior discontinuations include a CAR-T program derived from the Xyphos acquisition and a KRAS G12D pancreatic cancer program (ASP4396), with the company recording approximately JPY 12.8 billion in discontinuation-related losses. A February 2025 management restructuring created a new Chief R&D Officer role consolidating oversight of research and development divisions, a move interpreted as tightening portfolio governance. AllSci lists no other active clinical trials for ASP5502, although Astellas has not confirmed the molecule’s discontinuation publicly. The Sjögren’s syndrome landscape Primary Sjögren’s syndrome affects an estimated 0.5% to 1.0% of the adult population, predominantly women, and is characterized by lymphocytic infiltration of exocrine glands leading to sicca symptoms — dry eyes and dry mouth — along with systemic manifestations including fatigue, arthralgia, and organ involvement. Despite its prevalence and burden, no therapy has received FDA approval specifically for the treatment of primary Sjögren’s syndrome. Current management relies on symptomatic relief and off-label use of immunosuppressants. The therapeutic landscape has seen repeated clinical failures. Bristol Myers Squibb’s abatacept did not meet its primary endpoint in a Phase III trial. Novartis tested ianalumab (an anti-BAFF receptor antibody) and reported mixed results, though development continues. GSK’s belimumab, approved for lupus, has been explored in Sjögren’s syndrome without regulatory success in that indication. Horizon Therapeutics (now Amgen) evaluated teprotumumab but in a different autoimmune context. The BAFF/APRIL axis, B-cell depletion, and T-cell co-stimulation blockade have all been pursued with limited translational success in this disease. STING inhibition represented a mechanistically distinct approach. The STING pathway, part of the innate immune system’s cytosolic DNA sensing machinery, has been implicated in the pathogenesis of several autoimmune conditions, including Sjögren’s syndrome, where aberrant type I interferon signaling is a recognized feature. Preclinical rationale for targeting STING in Sjögren’s syndrome rests on the observation that chronic activation of the interferon pathway contributes to glandular inflammation and tissue damage. However, translating STING pathway modulation into clinical benefit in autoimmune disease remains unproven, and ASP5502 was among the first oral STING inhibitors to enter human testing for this indication. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

早上好，各位，今天是长新冠意识日，该纪念日旨在提升公众对长新冠持续且严重影响的认知。然而在中国鲜有人知，在之前文章中我本人反复提出“抗病毒+中和抗体+抗衰老”方案，一直未做进一步解释，今天发出来跟大家一起探讨，本文所列所有药物都是已经经过临床并上市。 先看一下已获批上市的抗新冠病毒西药 1、RdRp抑制剂（口服/注射小分子）核心作用机制：抑制新冠病毒RNA依赖的RNA聚合酶（RdRp），干扰病毒基因组的转录与复制，阻断病毒增殖。 通用名称 商品名阿兹夫定片 双新艾克 氢溴酸氘瑞米德韦片 民得维（VV116） 莫诺拉韦胶囊 利卓瑞/LAGEVRIO 美国默沙东 瑞德西韦注射液 Veklury 美国吉利德科学 静脉注射  2、3CL蛋白酶（Mpro）抑制剂 核心作用机制：抑制新冠病毒3CL蛋白酶，阻断病毒多蛋白前体的切割加工，从而阻止病毒复制组装。 通用名称 商品名 奈玛特韦片/利托那韦片组合包装 Paxlovid 先诺特韦片/利托那韦片组合包装 先诺欣 来瑞特韦片 乐睿灵 阿泰特韦片/利托那韦片组合包装 泰中定 奥格特韦钠胶囊 奥维宁  有官方推荐、高质量临床证据的抗病毒中成药（家用首选，剂量明确） 药物名称 核心适用病毒 连花清瘟胶囊/颗粒 甲/乙型流感病毒、新冠病毒、呼吸道合胞病毒 金花清感颗粒 甲/乙型流感病毒、新冠病毒 疏风解毒胶囊 流感病毒、新冠病毒、上呼吸道感染相关病毒 蒲地蓝消炎口服液 疱疹病毒（手足口病、疱疹性咽峡炎）、流感病毒、腮腺炎病毒  至于互联网上能看到的其他博主推荐的各种抗病毒中药，我这里不做推荐，原因很简单，用药剂量不明确 ，缺乏高质量临床证据，缺少大样本、随机、双盲对照试验。 再看中和抗体类抗新冠病毒药物（注射型生物制剂） 通用名称 商品名 备注安巴韦单抗/罗米司韦单抗注射液 - 对部分奥密克戎变异株活性下降，临床需结合流行株情况使用Casirivimab/Imdevimab REGEN-COV  因对奥密克戎多数变异株失去中和活性，FDA已撤销紧急使用授权Sotrovimab Xevudy 因对奥密克戎主流变异株活性大幅下降，已被多数地区暂停临床使用Bebtelovimab 因对当前流行变异株无有效中和活性，FDA已撤销紧急使用授权 新型冠状病毒广谱中和抗体SA55注射液S因II期临床试验效果不佳停止临床试验？ 目前看多数中和抗体药物因新冠病毒持续变异，已对当前全球主流流行株失去有效中和活性，临床应用大幅受限。 近年来多项研究证实，mtDNA-cGAS-STING通路的慢性持续激活，是长新冠发生发展的核心驱动因素，新冠急性感染后，病毒RNA可在体内组织持续存留，同时感染造成的线粒体功能障碍无法完全修复，导致mtDNA持续低水平泄露，慢性激活cGAS-STING通路，诱导持续的低级别炎症与衰老相关分泌表型（SASP），即“炎性衰老”，是长新冠多系统症状的核心病理基础 。该通路的慢性激活可通过持续的全身炎症，导致血管内皮功能障碍、神经胶质细胞活化、胰岛素抵抗、心肌纤维化等，分别对应长新冠的心血管症状、认知障碍、代谢异常、心肺功能下降等多种临床表现 。 长新冠的核心病理基础之一是急性感染后无法消退的慢性低级别炎症（炎性衰老），而三者构成了驱动长新冠症状的核心病理轴：新冠急性感染后线粒体持续损伤+衰老细胞（SNCs）异常累积 → mtDNA慢性激活cGAS-STING通路 → 大量促炎因子/趋化因子（IL-6、IFN-α、CXCL1/2等）持续分泌 → 驱动骨髓髓系祖细胞异常分化为PMN-MDSC（粒细胞样/多形核髓系来源抑制细胞），并募集至全身受累组织 → 放大炎症、诱导T细胞耗竭、加重组织损伤 → 长新冠多系统症状。 目前已有多种口服STING抑制剂进入针对长新冠的临床研发阶段，评估其在长新冠患者中的安全性与抗炎活性。 Senolytic药物可选择性清除衰老细胞，从源头切断该恶性循环，同时减少STING通路的内源性激活，进而有效阻断PMN-MDSC的异常扩增。 另有一项senolytics治疗长新冠的人体临床试验，纳入36名中重度长新冠患者，给予达沙替尼+槲皮素（D+Q）脉冲式给药3个月。结果显示，患者外周血中的衰老细胞标志物、PMN-MDSC比例、炎症因子水平均显著下降，80%以上的患者疲劳、脑雾、呼吸困难等核心症状得到临床意义上的改善，且安全性良好，无严重不良事件。但值得注意的是，该策略可显著缓解长新冠的炎症相关症状，但无法完全清除体内残留的病毒抗原或自身抗体，对于已经形成的组织纤维化、不可逆的器官损伤，疗效有限，无法实现完全治愈。 最后一句话，使用senolytic药物清除衰老细胞、或抑制STING通路，均可通过有效阻断PMN-MDSC的异常扩增与病理活化，显著缓解长新冠的核心症状。