Lonafarnib

Sentynl will acquire full rights to the investigational drug candidate, Progerinin (SLC-D011), adding to its commercial portfolio of rare and ultra-rare disease products March 16, 2026-- Sentynl Therapeutics Inc. (" Sentynl"), a U.S.-based biopharmaceutical company and wholly-owned subsidiary of Zydus Lifesciences Limited (" Zydus"), announced that it is entering into an agreement with PRG S&T, a Korean company specializing in the development of medicine for rare genetic diseases, to license its investigational molecule Progerinin (SLC-D011) for Hutchinson-Gilford Progeria Syndrome (HGPS or "progeria"). The agreement will allow Sentynl to begin working with PRG S&T immediately to advance the clinical development of Progerinin (SLC-D011) for HGPS, which has been designated as an orphan drug by the United States Food and Drug Administration (FDA). Under the conditions that certain milestones are met, Sentynl will acquire full rights to the molecule for HGPS upon closing, making Progerinin the company's second therapy intended for the treatment of HGPS. The program is currently finalizing a Phase 2A clinical trial and data are expected before the end of 1H 2026. "This acquisition marks an important step in growing our portfolio of therapies for Hutchinson-Gilford Progeria Syndrome, which can have severe impacts on patient health if left untreated," said Dr. Sharvil P. Patel, Managing Director, Zydus Lifesciences Limited. "Supporting patients in living healthy, fulfilled lives is core to what we do, and the agreement with PRG S&T directly furthers this mission by advancing orphan therapies for patients and families impacted by rare diseases." "Children with Hutchinson-Gilford Progeria Syndrome face an unforgiving disease. However, we are seeing real progress in progeria research, with new science changing what's possible," said Matt Heck, CEO, Sentynl. "This agreement, which will add Progerinin to our progeria portfolio, represents our commitment to translating that progress into another real therapy for children and families who need them." Progerinin is an investigational, orally active small-molecule drug being developed as a potential treatment for Hutchinson-Gilford Progeria Syndrome, a rare genetic disorder characterized by accelerated aging in children. The disease is caused by the accumulation of progerin, an abnormal form of the lamin A protein produced by mutations in the LMNA gene, which disrupts nuclear structure and leads to premature cellular aging. Progerinin is designed to inhibit the interaction and harmful effects of progerin within cells, thereby improving nuclear integrity and reducing cellular damage. It is not currently approved by FDA or any other health authority. "The Progeria Research Foundation (PRF) is proud to have funded the foundational research that led to the development of Progerinin, and we are happy to see this potential path moving forward," said Leslie Gordon, MD, PhD, Medical Director at Progeria Research Foundation. "PRF's mission is to find treatments and the cure for Progeria, and we are grateful for the efforts of PRG S&T and Sentynl to improve the lives of the children and young adults in our Progeria patient community." Early research and clinical trials aim to determine whether Progerinin can slow disease progression and improve survival in HGPS patients, potentially offering another therapeutic option. Currently, Zokinvy® (lonafarnib) is the only approved treatment for HGPS and certain processing-deficient Progeroid Laminopathies in the U.S., European Union, Great Britan, Israel, and Japan. Progerinin is a small-molecule drug candidate being developed to treat Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder that causes rapid aging in children. It works by targeting progerin, an abnormal protein produced from a mutation in the LMNA gene. In HGPS, this mutation causes cells to produce progerin instead of normal lamin A, which leads to defects in the cell nucleus and accelerates aging symptoms. In mouse models of HGPS, progerinin demonstrated encouraging outcomes. In mice with a severe form of the disease, treatment increased lifespan by 8–10 weeks and improved body weight. The untreated control group had a shorter lifespan (average = 16.8 weeks; maximum = 18 weeks), whereas the treated group exhibited a significantly extended lifespan (average = 25.2 weeks; maximum = 26 weeks; p LMNA point mutation that produces the farnesylated lamin A variant, progerin, via aberrant splicing. Progeroid laminopathies are genetic disorders of accelerated aging caused by mutations in LMNA and/or ZMPSTE24 that impair lamin A processing, resulting in the accumulation of farnesylated prelamin A proteins including progerin.2,3 Children with HGPS commonly die of atherosclerosis, the same heart disease that affects millions of normally aging adults by an average age of 14.5 years. Disease manifestations include severe failure to thrive, scleroderma-like skin, global lipodystrophy, alopecia, joint contractures, skeletal dysplasia, global accelerated atherosclerosis with cardiovascular decline, and debilitating strokes.1 Zydus Lifesciences Limited is an innovation-led life-sciences company with leadership positions across pharmaceuticals and consumer wellness, supported by an emerging MedTech franchise and a global footprint across the United States, India and other international markets. As of September 30, 2025, the group employs 29,000 people worldwide including 1,500 scientists engaged in R&D and is driven by its mission to unlock new possibilities in life sciences through quality healthcare solutions that impact lives. The group aspires to transform lives through path-breaking discoveries. Sentynl Therapeutics Inc. (" Sentynl") is a commercial stage U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. Recognized for its commitment to the rare disease community, Sentynl leverages its global operations as well as its parent organization, Zydus Group, to advance the development, manufacturing, and delivery of treatments to patients who need them in numerous countries worldwide. Sentynl is dedicated to improving patient outcomes and access while upholding ethical standards and operating in compliance with applicable laws, regulations, and industry guidelines. For more information, visit https://sentynl.com. PRG S&T is a research & development company specializing in the treatment of rare genetic diseases. PRG S&T has been developing therapeutics for rare genetic diseases (laminopathies, neurodegenerative diseases, neuro-oncology etc.) with small molecules, which are derived from target sites on aberrant Protein-Protein Interactions (PPI). Resources 1. Gordon LB, Brown WT, Collins FS. Hutchinson-Gilford Progeria Syndrome. 2003 Dec 12 [Updated 2019 Jan 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. 2. Gordon LB, Shappell H, Massaro J, et al. Association of lonafarnib treatment vs no treatment with mortality rate in patients with Hutchinson-Gilford progeria syndrome. JAMA. 2018;319(16):1687-1695. doi:10.1001/jama.2018.3264. 3. Marcelot A, Worman HJ, and Zinn-Justin S. Protein structural and mechanistic basis of progeroid laminopathies. FEBS Journal. 2021:288:2757-2772. Doi:10.111/febs.15526. The content above comes from the network. if any infringement, please contact us to modify.

点击蓝字 关注我们  导读 乙肝病毒（HBV）感染是全球主要公共卫生问题之一，有超过2.5亿人慢性感染HBV。而其中有超三分之一的人口集中在我国，人数接近1亿人。NTCP工具细胞，特别是外源表达NTCP的肝癌细胞系如HepG2-NTCP和Huh7-NTCP，因其易操作、短周期、重现性佳的特点，在乙肝病毒（HBV）研究中扮演着至关重要的角色。这些细胞模型能够有效模拟HBV的感染过程，为研究HBV的生命周期、宿主限制因子、病毒复制以及药物筛选提供了一个强大而便捷的体外平台。它们不仅有助于揭示HBV感染的分子机制，如DDX3作为宿主限制因子阻碍cccDNA转录，GPC5作为附着因子在感染入胞过程中的作用，还能通过直接与NTCP相互作用或下调NTCP表达来筛选和验证抗病毒药物的活性，例如环孢菌素A及其衍生物、雷帕霉素及其衍生物等。此外，这些工具细胞还促进了对HBV宿主特异性分子的发现，为发展支持HBV感染的小动物模型提供了可能，这对于乙肝相关研究和药物开发具有重大意义。 本周推荐  PART.01  基本信息 英文标题：Advances and Challenges in Managing Hepatitis D Virus: Evolving Strategies 中文标题：丁型肝炎病毒管理的进展与挑战：不断发展的策略 发表期刊：《Curr Hepatol Rep》 影响因子：1.02 作者单位： 1.Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA 2.The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA 3.Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 4-5722, Bethesda, MD 20892-1800, USA 作者信息： Harish Gopalakrishna¹, Maria Mironova¹, Harel Dahari², Christopher Koh¹, Theo Heller¹,³ PART.02  研究背景 丁型肝炎病毒（HDV）是一种缺陷病毒，需依赖乙型肝炎病毒（HBV）完成生命周期，其感染会导致侵袭性更强的病毒性肝炎，加速疾病进展，约 70%-80% 的患者在感染数十年内会发展为肝硬化，且患肝细胞癌（HCC）的风险显著升高。全球约有 1200 万 HBV 感染者合并 HDV 感染，但由于筛查不足，实际患病率可能更高。尽管 HDV 已被发现四十余年，但针对它的美国食品药品监督管理局（FDA）批准疗法仍较为匮乏，临床常用的聚乙二醇干扰素 α（PEG-IFNα）疗效有限、复发率高，仅欧洲于 2020 年批准了布列维肽（bulevirtide）用于 HDV 治疗，仍缺乏根治手段。此外，HDV 的流行病学复杂，诊断和疾病分层缺乏统一标准，监测指南不完善，高风险人群筛查率低，这些因素共同构成了 HDV 管理的重大挑战。随着对 HDV 生物学特性和临床行为的认识不断深入，靶向性治疗策略逐步涌现，为改善 HDV 管理提供了新的可能，本综述旨在系统梳理 HDV 的生物学特征、诊断筛查方法、当前及新兴治疗策略，探讨其管理中的关键问题与未来方向。 PART.03  研究方法 本综述通过系统性检索丁型肝炎病毒相关的基础研究、临床研究及指南文献，全面整合了 HDV 的生物学特性、流行病学数据、诊断技术、治疗策略及预后监测等方面的研究成果。在生物学研究方面，总结了 HDV 依赖 HBV 的生命周期机制，包括病毒结构、入侵受体（NTCP）、复制过程及抗原功能等；在流行病学与筛查部分，分析了全球及不同地区的 HDV 患病率、传播途径（胃肠外传播、垂直传播等）、高风险人群特征，对比了不同地区（美国、欧洲、亚洲）的筛查指南差异；诊断与分期方面，梳理了血清学检测（抗 - HDV 抗体、HDV RNA 定量）、非侵入性纤维化评估（FIB-4、APRI、VCTE、SWE 等）及新型纤维化评分系统（DFS、D4FS）的应用效果与局限性；治疗策略部分，汇总了干扰素类（PEG-IFNα、IFN-λ）、entry 抑制剂（bulevirtide）、法尼基转移酶抑制剂（lonafarnib）、核酸聚合物（REP 2139-Ca）等单药及联合治疗的临床 trial 数据，包括疗效指标（HDV RNA 下降幅度、SVR 率）、安全性及复发情况；同时，整合了治疗响应监测（HBsAg、HBcrAg 动力学）、HCC 筛查及肝移植相关的临床研究结果，最后通过归纳现有研究的不足，提出了 HDV 管理中亟待解决的关键问题。 PART.04  实验结果 图1：HDV 生命周期及药物作用靶点示意图 该图清晰展示了 HDV 的完整生命周期及各类药物的作用靶点：HDV 病毒粒子通过肝细胞表面的钠 - 牛磺胆酸共转运多肽（NTCP）受体附着并进入肝细胞，其核糖核蛋白（RNP）转运至细胞核，通过滚环复制机制完成基因组复制，HDV 抗基因组转运至内质网（ER）后，与 HBV 包膜蛋白结合组装为新的病毒粒子并释放；图中标注了已应用或处于研究阶段的药物作用位点：经专家指南推荐使用的干扰素 α（IFN-α）、欧洲有条件批准的 entry 抑制剂布列维肽（bulevirtide，靶向 NTCP 受体结合），以及处于研究阶段的核酸聚合物（NAP）、法尼基转移酶抑制剂 lonafarnib（靶向 HDV 组装过程中的异戊烯化步骤）和干扰素 λ（IFN-λ），明确了不同药物干预 HDV 生命周期的关键环节。 图2：HDV 感染的诊断与管理流程示意图 该图呈现了 HDV 感染的标准化诊断与管理路径：首先对乙肝表面抗原（HBsAg）阳性者进行抗 - HDV 抗体筛查，抗体阴性者排除 HDV 感染，仅需管理 HBV；抗体阳性者需进一步通过灵敏的 HDV RNA 检测确认是否为活动性感染（非洲地区患者需重复检测以排除假阴性），RNA 阴性提示 HDV 感染已清除或受控；对于活动性 HDV 感染患者，采用非侵入性血清学纤维化标志物（FIB-4、APRI、AAR、API）或影像学方法（VCTE、SWE）评估纤维化程度，必要时通过肝穿刺活检明确分期；无 / 轻度纤维化且丙氨酸氨基转移酶（ALT）正常者可给予支持治疗并定期监测，代偿期肝硬化患者需评估抗病毒治疗指征，符合条件者可选择指南推荐疗法或参与临床 trial，终末期患者可考虑肝移植；治疗期间需每 3-6 个月监测 AST、ALT、HBsAg 及 HDV RNA 水平，每 6 个月通过超声（USS）和甲胎蛋白（AFP）筛查 HCC。 PART.05  研究结论 本综述系统阐述了丁型肝炎病毒（HDV）的管理进展与挑战，HDV 作为依赖 HBV 的缺陷病毒，全球感染人数约 1200 万，易导致快速进展为肝硬化和 HCC，但其筛查率低、诊断分层标准不统一，治疗手段长期匮乏。在诊断方面，HDV 的诊断需先通过抗 - HDV 抗体筛查，再经 HDV RNA 定量确认活动性感染，非侵入性纤维化评估工具（FIB-4、VCTE 等）及新型纤维化评分（DFS、D4FS）为疾病分期提供了有效手段；治疗领域，现有疗法包括 PEG-IFNα、欧洲批准的 bulevirtide，以及处于研究阶段的 lonafarnib、REP 2139-Ca 等，联合治疗（如 bulevirtide+PEG-IFNα、lonafarnib+ritonavir+PEG-IFNλ）展现出更优的抗病毒效果，可显著降低 HDV RNA 水平，部分患者能实现持续病毒学应答（SVR）；治疗响应监测中，HBsAg、HBcrAg 动力学及 HDV RNA 变化可作为关键评估指标，HDV 感染患者需加强 HCC 筛查，终末期患者肝移植联合预防方案可降低术后复发风险。然而，HDV 的真实患病率尚不明确，治疗终点的合理性、最佳治疗时长、基因型对疾病进展及治疗响应的影响等问题仍需进一步研究，未来需通过推广普遍筛查、优化联合治疗策略、明确个体化治疗方案，提升 HDV 感染的精准管理水平。 往期推荐 ▶从分子机制到临床潜力：NTCP 如何成为抗 HBV 治疗的核心靶点 ▶表观遗传调控新发现！HDAC 抑制剂可恢复 HBV 受体 hNTCP 表达 ▶逸漠生物NTCP细胞助力乙肝疾病研究丨亚洲人专属保护基因！NTCP S267F 变异可降低乙肝进展至肝硬化、肝癌风险 ▶逸漠生物NTCP细胞助力乙肝疾病研究丨越南人群HBV防控新发现！NTCP S267F变异可降低肝硬化风险，基因型C需重点警惕 ▶逸漠生物NTCP细胞助力乙肝疾病研究丨人类胆盐转运体 NTCP 结构新发现：闭合构象是惰性状态，面板域移动调控通道开关 ▶逸漠生物NTCP细胞助力乙肝疾病研究丨慢性乙肝 LLV 难题破解：脱氧胆酸促进 HBV 颗粒形成，竟是肠道菌群在 “助攻”！ ▶逸漠生物NTCP细胞助力乙肝疾病研究丨栀子苷致肝损伤真相：抑制 FXR 打乱胆汁酸，还激活炎性小体！ ▶逸漠生物NTCP细胞助力乙肝疾病研究丨不杀细胞也能抗 HBV？IFI27 的 “绝招”：靶向 C/EBPα 泛素化降解 ▶逸漠生物NTCP细胞助力乙肝疾病研究丨打破“开关”认知！NTCP的G102位点竟是“功能变阻器”，影响胆汁酸转运与细胞表达 ▶逸漠生物NTCP细胞助力乙肝疾病研究丨1484 例患者验证！深度学习 NTCP 模型提升头颈部癌放疗毒性预测  ▎企业介绍 厦门逸漠生物科技有限公司 厦门逸漠生物科技有限公司坐落于厦门国家留学创业园(翔安)产业园，是一家专注于细胞生物学领域新产品、新技术开发的高新技术企业。公司产品涵盖：细胞系、原代细胞、标记细胞、耐药细胞、免疫细胞及胎牛血清、培养基、胰酶、双抗、无血清冷冻液、支原体/黑胶虫清除剂、细胞因子等产品，提供细胞形态和免疫相关检测、流式细胞检测 、细胞学服务、分子生物学检测等多种技术服务。 逸漠生物(IMMOCELL)拥有一支具有深厚造诣和丰富经验的高端技术人才，建设了高规格的研发实验室与生产车间，建立了规范的研发、生产、销售、客服管理体系。公司与国内外多家医院、高等院校、科研院所、生物医药公司建立了良好的合作关系，赢得了良好的市场声誉和广泛的客户认可，努力成为生命科学界可靠的合作伙伴和坚强的技术后盾。 END 逸漠生物 构建专业的细胞资源平台 涵盖细胞系、原代细胞 标记细胞、耐药细胞 培养相关产品 400-080-3389 www.immocell.com 深耕细胞技术 · 共筑人类健康 immocell丨逸漠资源平台