Sofosbuvir

Results Demonstrate AT-587 To Be Highly Potent In Vitro Against Hepatitis E Virus Initiation of Phase 1 Clinical Program Anticipated Mid-2026 BOSTON, Feb. 24, 2026 (GLOBE NEWSWIRE) -- Atea Pharmaceuticals, Inc. (Nasdaq: AVIR) (Atea or Company), a late-stage clinical biopharmaceutical company engaged in the discovery and development of oral antiviral therapeutics for serious viral diseases, today announced in vitro results showing that two proprietary oral nucleotide analogs, AT-587 and AT-2490, exhibit promising antiviral profiles as potential first-in-class inhibitors for the treatment of Hepatitis E virus (HEV) infection, a positive-sense, single-stranded RNA virus that primarily infects liver cells. These results were presented at the Conference on Retroviruses and Opportunistic Infections (CROI), taking place February 22-25 in Denver, Colorado. In vitro studies demonstrated that AT-587 and AT-2490 were potent inhibitors of HEV replication. AT-587 and AT-2490 were 30-150-fold more potent against HEV compared to sofosbuvir and ribavirin. Analyses showed the two compounds were also active against other viruses, including all flaviviruses tested, rubella and chikungunya. Antiviral activity of AT-587 and AT-2490 in the tissue of interest -- human liver cells -- was indicated by the formation of high amounts of active metabolite of each compound. Neither compound showed any toxicity. In January, Atea announced the selection of AT-587 as the lead product candidate for the HEV clinical program and plans to initiate a Phase 1 program mid-year. “We are excited to share these preclinical results at CROI showing the potent activity and promising in vitro safety profiles of AT-2490 and AT-587, our HEV product candidate. These results underscore the potential of AT-587 as a first-in-class direct acting antiviral for HEV,” said Jean-Pierre Sommadossi, PhD, Chief Executive Officer and Founder of Atea. “With no antivirals currently marketed for HEV, AT-587 has the potential to address a significant unmet need for a treatment option for patients with chronic HEV infection who are immunocompromised or at high risk for rapid progression to cirrhosis. We look forward to advancing AT-587 to a Phase 1 program mid-year.” HEV, the causative agent of hepatitis E, is a significant public health concern in developing regions of Asia and Africa (genotypes 1 and 2) and is also endemic in industrialized countries, including the US and Europe, where genotypes 3 and 4 predominate. In recent years, chronic HEV genotype 3 and 4 infections have been increasingly recognized as a potentially life-threatening viral infection in immunocompromised individuals — a population that includes solid-organ and hematopoietic stem-cell transplant recipients, and patients with hematologic malignancies or pre-existing liver disease. In these vulnerable populations, chronic HEV can result in rapid progression to cirrhosis within three to five years. There is currently no approved antiviral therapy for HEV, and current off-label treatments have limited efficacy and tolerability, underscoring a clear and urgent unmet medical need. More information about the CROI presentation is below: Poster Number: 596 Title: Discovery and Preclinical Profiles of Potent Pan-Genotypic Hepatitis E Virus Inhibitors Poster Session: (I-01) Beyond the C: Hepatitis D, B, and E Lead Author: Qi Huang, PhD About HEV HEV is a positive-sense, single-stranded RNA virus which infects the liver and remains an under-recognized global health challenge with an estimated 20 million infections annually. While typically self-limiting in healthy individuals, HEV can cause chronic disease in those with compromised immunity, including solid organ and stem cell transplant recipients, people living with HIV, and those with hematologic or rheumatic conditions, often progressing rapidly to cirrhosis. HEV genotypes 1 and 2 drive waterborne, acute epidemics in developing regions, whereas genotypes 3 and 4 predominate in high-income countries with expanding at-risk populations through zoonotic, foodborne transmission that can lead to chronic infection. Despite this burden, no antiviral therapy is approved for the treatment of HEV, and current off-label treatments have limited efficacy and tolerability. Atea’s initial HEV clinical efforts will focus on developing AT-587 for the treatment of immunocompromised patients with chronic HEV genotype 3 and 4 infections. About Atea Pharmaceuticals Atea is a late-stage clinical biopharmaceutical company focused on discovering, developing and commercializing oral antiviral therapies to address the unmet medical needs of patients with serious viral infections. Leveraging Atea’s deep understanding of antiviral drug development, nucleos(t)ide chemistry, biology, biochemistry and virology, Atea has built a proprietary nucleos(t)ide prodrug platform to develop novel product candidates to treat single stranded ribonucleic acid, or ssRNA, viruses, which are a prevalent cause of serious viral diseases. Atea plans to continue to build its pipeline of antiviral product candidates by augmenting its nucleos(t)ide platform with other classes of antivirals that may be used in combination with its nucleos(t)ide product candidates. Atea’s Phase 3 program is evaluating the regimen of bemnifosbuvir, a nucleotide analog polymerase inhibitor, and ruzasvir, an NS5A inhibitor, to treat HCV. Atea anticipates advancing AT-587, a nucleotide analog, into Phase 1 for the treatment of HEV. For more information, please visit . Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include but are not limited to statements regarding the potential development of AT-587 for the treatment of HEV and anticipated milestone events and timelines for initiation of the HEV Phase 1 program. When used herein, words including “expected,” “should,” “anticipated,” “believe,” “will,” “plans”, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Atea’s current expectations and various assumptions. Atea believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Atea may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, uncertainties inherent in the drug discovery and development process and the regulatory submission or approval process, unexpected or unfavorable safety or efficacy data or results observed during preclinical development, clinical trials or in data readouts; delays in or disruptions to clinical trials or our business; our reliance on third parties over which we may not always have full control; our ability to manufacture sufficient clinical supply and commercial product; as well as the other important factors discussed under the caption “Risk Factors” in Atea’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2025 as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SEC’s website at These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While Atea may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing Atea’s views as of any date subsequent to the date of this press release. Contacts Jonae Barnes SVP, Investor Relations and Corporate Communications 617-818-2985 Barnes.jonae@ateapharma.com Joyce Allaire LifeSci Advisors jallaire@lifesciadvisors.com

1957年，伦敦国立医学研究所的病毒学家阿利克·艾萨克和瑞士裔同事让·林登曼正在研究一个看似平凡的现象：为什么细胞感染一种病毒后，就不容易被第二种病毒感染？这个被称为“病毒干扰”的现象，自1930年代就被观察记录，但原因成谜。 他们设计了一个精妙的实验：用热灭活的流感病毒先处理鸡胚绒毛尿囊膜细胞，再将这些细胞破碎，提取其中的液体，添加到新鲜的细胞培养中。然后，他们用活的水泡性口炎病毒攻击这些新鲜细胞。 按照当时的主流观点，热灭活的病毒不可能在新鲜细胞中复制，因此不应该有任何保护作用。然而，令人困惑的结果出现了：那些接受了“处理过”细胞提取液的新鲜细胞，竟然真的抵抗了活病毒的攻击！ 两人面面相觑。这不可能来自残留的灭活病毒，那么，细胞里究竟产生了什么物质，能够“干扰”后续病毒的感染？经过一系列严谨的排除实验，他们得出一个革命性的结论：被病毒感染的细胞，会释放出一种可溶性的、能够传递给其他细胞、使其获得抗病毒能力的“因子”。 1957年，他们在《英国皇家学会学报》上发表了这一发现，并将其命名为 “干扰素” 。这个平淡无奇的名字下，隐藏着人类对抗病毒和癌症的全新武器库的第一把钥匙。当时没有人能预料到，这个源于基础研究的好奇心，将开启生物制药史上最艰辛、最昂贵，也最富戏剧性的篇章之一。 1 “白色黄金”的炼金术: 前基因工程时代的艰难求索 干扰素的发现激起了科学界的巨大热情。它似乎提供了一个理想的抗病毒方案：一种由人体自身细胞产生的天然防御物质，理论上应该高效且低毒。然而，通往临床应用的道路上横亘着一座几乎无法逾越的大山：如何获得足够用于治疗的干扰素？ 在1970年代，生产干扰素的过程堪称一场“现代炼金术”，其成本与难度令人咋舌： 原料的奢侈：最初，科学家发现人白细胞——主要是血液中的白细胞层（“白膜层”）——是干扰素-α的良好来源。这意味着，生产原料是人血。芬兰科学家卡里·坎特尔发展了一套相对高效的方法：用仙台病毒刺激从献血者血液中分离出的白细胞，诱使其产生干扰素。但即便如此，产量也低得可怜。 数字的震撼：据估算，从4.5万升人血（约需6万名献血者）的白细胞中，仅能提取出约0.4克纯度不足1%的干扰素粗品。为了治疗一名癌症患者一个疗程，可能需要数百名献血者的血液。其稀缺性和生产成本，使其价格一度远超黄金，被誉为 “白色黄金”。 应用的悲壮：由于数量极度有限，早期的干扰素临床试验充满了悲壮色彩。它被优先用于那些常规治疗全部失败、濒临死亡的癌症患者。剂量微小，疗效不确定，但这是绝望中的唯一曙光。1970年代和80年代初，干扰素治疗成了医学界一个既充满希望又令人心酸的符号——它代表了一种革命性的治疗理念，却被现实的生产技术牢牢锁在实验室的保险柜里。 这场“炼金术”的困境，清晰地暴露了传统生物提取法的极限，也催生了对技术革命的迫切呼唤。 2 基因工程的救赎与“多面手”的证明 转机出现在生物技术革命的黎明。1970年代末至1980年代初，重组DNA技术（基因工程）日趋成熟。科学家们开始思考：如果能找到编码干扰素的基因，将其插入细菌或哺乳动物细胞中，不就可以像工厂一样大规模生产了吗？ 这是一场激烈的国际竞赛。多家生物技术公司（如基因泰克、百健）和学术机构投入巨资。1979–1980年，多个团队几乎同时克隆出第一个人干扰素基因。到1982年，采用基因工程大肠杆菌生产的重组人干扰素-α 首次进入临床试验。这是历史性的一刻：曾经比黄金还贵重的物质，终于有可能实现工业化、规模化生产。生物制药的新纪元，随着干扰素的量产而真正开启。 有了充足的“弹药”，医学家们开始系统地探索干扰素这位“多面手”的真正实力。临床试验的结果，描绘出一幅复杂而振奋人心的图景： 1. 对抗血液肿瘤的“奇兵”： 干扰素最早获得确凿胜利的领域是某些血液肿瘤。1980年代中期，研究表明，高剂量的干扰素-α对毛细胞白血病——一种罕见但难治的B细胞肿瘤——疗效显著，能诱导大部分患者获得长期缓解乃至接近治愈。对于慢性髓性白血病，干扰素-α也能诱导部分细胞遗传学缓解，在格列卫问世前，它是重要的治疗选择。此外，它对滤泡性淋巴瘤、多发性骨髓瘤等也有一定作用。其抗肿瘤机制复杂，包括直接抑制肿瘤细胞增殖、增强免疫细胞（如NK细胞、巨噬细胞）的杀伤活性、抑制血管生成等。 2. 抗击慢性病毒感染的“主力”： 干扰素的本职是抗病毒，它在这一领域确立了长达二十余年的统治地位。 · 慢性乙型肝炎：干扰素-α（特别是聚乙二醇化长效剂型）能够抑制乙肝病毒复制，促使部分患者实现e抗原甚至乙肝表面抗原（HBsAg）清除±抗-HBs阳转（即“临床治愈”），疗效持久。 · 慢性丙型肝炎：干扰素-α联合利巴韦林，曾是数十年间全球唯一的丙肝标准疗法。尽管治愈率（约40%-60%不等，取决于基因型）远非完美，且副作用显著，但它为数百万患者延缓了肝硬化、肝癌的进程，守住了生命防线。 干扰素的临床应用远不止于此，它还曾用于治疗尖锐湿疣（一种HPV病毒感染）、卡波西肉瘤（一种与HIV相关的肿瘤）等。 然而，这位“多面手”有着一张众所周知的、令人望而生畏的“价签”——其副作用谱。 几乎所有患者都会经历类似重流感的“急性反应”：高烧、寒战、剧烈头痛、肌肉酸痛。长期治疗则可能导致持续疲劳、抑郁、食欲不振、骨髓抑制（白细胞、血小板减少）、甲状腺功能紊乱，甚至诱发自身免疫性疾病。患者们常常形容干扰素治疗是一场“与魔鬼的交易”：用数月乃至数年的极度不适，去换取一个不确定的、延缓疾病进展的机会。许多患者因无法耐受而中途放弃。 3 辉煌谢幕： 被更精准的武器取代的传奇 科学和技术从不停止进步。干扰素疗法虽然有效，但其广谱激活式的机制（诱导细胞产生数百种抗病毒与免疫调节蛋白）和显著的副作用，促使科学家寻找更精准、更温和的武器。 在丙肝战场，这场更替尤为彻底和迅速： 2011年，直接抗病毒药物特拉匹韦和博赛匹韦上市，与干扰素联合，首次将部分基因型丙肝的治愈率提升至接近70%。这仅仅是开始。2013年，索磷布韦——一种高效、高耐药屏障的NS5B聚合酶核苷类似物抑制剂——的横空出世，敲响了干扰素疗法在丙肝领域的丧钟。以索磷布韦为基础的全口服、无干扰素方案，在随后的几年里将丙肝的治愈率推向了惊人的95%以上，疗程缩短至8-12周，副作用轻微。 几乎在一夜之间，曾经需要每周打针、忍受严重副作用、疗程长达一年的干扰素方案，从全球各大肝病治疗指南中黯然退场。丙肝从一个需要艰苦卓绝斗争、仍有失败风险的慢性病，变成了一个几乎可以轻松治愈的感染。这是现代药物史上一次干净利落、近乎完美的 “技术性击倒”。 在乙肝领域，情况略有不同： 虽然强效、低耐药的口服核苷（酸）类似物（如恩替卡韦、替诺福韦）已成为一线治疗，能极好地抑制病毒复制，但它们很难实现停药后持久的免疫控制（即“临床治愈”）。因此，干扰素-α（特别是聚乙二醇干扰素）凭借其免疫调节作用、有机会获得持久应答的优势，仍在一定范围的患者（如年轻、高ALT、低病毒载量）中作为有限疗程的选择，与口服药联合或序贯使用，追求更高的治疗目标。它在这里的角色，从一个“主力”变成了一个追求特定战略目标的“特种部队”。 在肿瘤领域： 随着各种高度特异性的靶向药物（如BCR-ABL抑制剂、CD20单抗等）和免疫检查point抑制剂的兴起，干扰素在大多数肿瘤治疗中的一线地位已被取代。但它仍未完全退出舞台，在一些特定情况（如高危黑色素瘤的辅助治疗）或作为联合方案的组成部分，仍有其应用价值。 4 活化石的遗产与不朽的精神 今天，当我们回顾干扰素-α的故事，它仿佛生物医药领域的一块 “活化石” 。它记录了一段完整的技术史：从偶然的实验室发现，到依赖人血制品的“前工业时代”，再到基因工程带来的第一次生产力解放，最终因更精准的第二代、第三代技术的出现而让出舞台中心。 它的“过时”，恰恰是医学进步最有力的证明。它的遗产丰厚而深刻： 1. 概念的奠基：它是第一个被明确界定和命名的细胞因子，开启了细胞因子与干扰素研究的大门，让人们认识到细胞间可以通过分泌蛋白质进行复杂的通讯和防御。 2. 技术的先驱：它是第一批通过基因工程技术实现工业化生产的蛋白质药物之一，为整个生物制药产业（包括后来的EPO、G-CSF、胰岛素、单克隆抗体）铺平了产业化道路，验证了从基因到药物的可行性。 3. 治疗的启蒙：它证明了免疫调节和生物治疗可以有效地对抗病毒和肿瘤，为后续所有免疫疗法（如白细胞介素-2、肿瘤疫苗、免疫检查点抑制剂、CAR-T）的探索提供了最初的信心和范式。 4. 标准的塑造：在长达二三十年的时间里，它定义了慢性病毒性肝炎和某些血液肿瘤的治疗标准，拯救和延长了无数生命，直到被更好的药物取代。 干扰素的故事，是一个关于科学好奇心如何发现宝藏、人类智慧如何克服生产难关、医学需求如何驱动技术迭代的经典叙事。它从实验室的意外中走来，背负着“白色黄金”的盛名与重担，经历了临床的辉煌与争议，最终在更优秀的后辈面前优雅地转换角色。它的核心精神——利用和增强人体自身的防御系统来对抗疾病——早已融入现代医学的血液，并在新一代免疫疗法中发扬光大。 在药柜里，它的身影或许不再常见；但在医学发展的丰碑上，干扰素-α的名字，将永远镌刻在基石之上。 向下滑动查看 参考文献 1. 奠基性发现： Isaacs, A., & Lindenmann, J. (1957). Virus interference. I. The interferon. Proceedings of the Royal Society of London. Series B, Biological Sciences, 147(927), 258-267. 2. 早期生产与临床试验： Cantell, K., Hirvonen, S., & Koistinen, V. (1981). Partial purification of human leukocyte interferon on a large scale. Methods in Enzymology, 78, 499-505. Quesada, J. R., Reuben, J., Manning, J. T., Hersh, E. M., & Gutterman, J. U. (1984). Alpha interferon for induction of remission in hairy-cell leukemia. The New England Journal of Medicine, 310(1), 15-18. 3. 在病毒性肝炎治疗中的关键作用： Hoofnagle, J. H., et al. (1986). Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon: a preliminary report. The New England Journal of Medicine, 315(25), 1575-1578. Wong, D. K., et al. (1993). Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B: a meta-analysis. Annals of Internal Medicine, 119(4), 312-320. 4. 聚乙二醇化与长效制剂： Zeuzem, S., et al. (2000). Peginterferon alfa-2a in patients with chronic hepatitis C. The New England Journal of Medicine, 343(23), 1666-1672. 5. 被直接抗病毒药物取代的转折点： Lawitz, E., et al. (2013). Sofosbuvir for previously untreated chronic hepatitis C infection. The New England Journal of Medicine, 368(20), 1878-1887. 6. 历史回顾与综合评述： Pestka, S. (2007). The interferons: 50 years after their discovery, there is much more to learn. Journal of Biological Chemistry, 282(28), 20047-20051. Ivashkiv, L. B., & Donlin, L. T. (2014). Regulation of type I interferon responses. Nature Reviews Immunology, 14(1), 36-49. END 温馨提醒：本账号所有内容仅为科普分享，不能代替任何专业医疗建议。 封面图片为AI生成，请注意甄别。