Ribavirin

Phase 1 Study Designed to Evaluate the Safety, Tolerability and Pharmacokinetics of AT-587 in Healthy Volunteers AT-587 is a Potential First-in Class Treatment for Hepatitis E Virus, a Serious Liver Disease with No Approved Therapies Study Initiation Represents an Important Milestone Advancing Atea’s Antiviral Pipeline Focusing on First- or Best-in-Class Product Candidates in Areas of High Unmet Medical Need BOSTON, July 14, 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 the initiation of a first-in-human Phase 1 clinical trial evaluating AT-587, for the treatment of hepatitis E virus (HEV) infection. AT-587 is a proprietary oral antiviral nucleotide analog being developed for the treatment of HEV, a potentially serious liver disease that can lead to chronic infection, cirrhosis and liver failure in certain patient populations. In particular, at-risk populations include immunocompromised individuals, such as transplant recipients and patients taking immunosuppressants, among others. There are currently no approved treatments for HEV. “HEV is a significant health concern, particularly among immunocompromised patients who are at heightened risk for chronic infection and rapidly progressive liver disease, and the initiation of our Phase 1 trial represents an opportunity to address a substantial unmet need,” said Jean-Pierre Sommadossi, PhD, founder and chief executive officer of Atea Pharmaceuticals. “Supported by encouraging preclinical data demonstrating potent antiviral activity, we believe AT-587 has the potential to become an important therapeutic option for patients, particularly transplant recipients and immunocompromised patients living with HEV. Advancing AT-587 into the clinic builds on our deep expertise in antiviral drug development and represents another step in expanding Atea’s viral hepatitis franchise.” The Phase 1 trial is a randomized, double-blind, placebo-controlled, sequential dose-escalation study designed to evaluate the safety, tolerability and pharmacokinetics (PK) of AT-587 in healthy volunteers. The study includes both single ascending dose (SAD) and multiple ascending dose (MAD) components, as well as an embedded food-effect assessment. Part A of the study will evaluate single ascending doses of AT-587 administered under fasting conditions, with one cohort incorporating both fasting and fed administration to assess food effect. Part B of the study will evaluate multiple ascending doses of AT-587 administered once daily or twice daily for seven days, with dose selection informed by safety and PK data generated in Part A. Dose escalation decisions will be guided by ongoing review of emerging safety and PK data, providing flexibility to adapt the doses as clinical experience with AT-587 evolves. EASL 2026: AT-587 In Vitro Results Demonstrate High Antiviral Potency Against HEV and In Vivo Efficacy Results presented at EASL Congress 2026 demonstrated the promising preclinical antiviral potency of AT-587 against HEV. Studies demonstrated that AT-587 is a potent inhibitor of HEV replication being 30- to 150-fold more potent in vitro against HEV than sofosbuvir and ribavirin. Ribavirin is currently used off label as a treatment for HEV. AT-587 showed no toxicity in in vitro studies. AT-587 was also active against flaviviruses, rubella and chikungunya. Additional data presented at EASL Congress 2026 showed that AT-587 inhibits HEV genotype 3 activity in vivo . Using an HEV genotype 3 infected gerbil model, samples from the treated groups had significantly lower HEV RNA levels than the control group. Notably, AT-587 also retained high potency against ribavirin (G1634R) and sofosbuvir (A1343V) clinical resistance strains in vitro , further underscoring the potential of AT-587 as a first-in-class therapy and differentiating its pro existing off-label treatment options. About HEV HEV is a single stranded ribonucleic acid (ssRNA) virus which infects the liver and remains an under-recognized global health challenge with an estimated 20 million acute infections annually. Waterborne transmission of HEV genotypes 1 and 2 causes mostly acute self-limiting hepatitis in developing regions, whereas foodborne transmission of HEV genotype 3 predominates in the US and Europe and may cause chronic hepatitis in immunocompromised patients, which can lead to cirrhosis in three to five years. There is a growing number of immunocompromised patients, a population that includes solid organ transplant and hematopoietic stem cell transplant recipients and patients with hematologic malignancies such as multiple myeloma. Each year, in the US and Europe, 3% of the approximately 665,000 patients who have these underlying medical conditions are at risk of developing chronic HEV. There is currently no approved antiviral therapy for HEV, and current off-label treatments, including ribavirin, have limited efficacy and tolerability, underscoring a clear and urgent unmet medical need. Atea’s initial HEV clinical efforts will focus on developing AT-587 for the treatment of immunocompromised patients with chronic HEV. 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 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 FDC regimen of BEM, a nucleotide analog polymerase inhibitor, and RZR, an NS5A inhibitor, to treat HCV. AT-587, a nucleotide analog, is in Phase 1 development 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 to develop a product for the treatment of HEV, anticipated milestone events and timelines for clinical trials, future results of operations and business strategy. 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 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; dependence on the success of Atea’s most advanced product candidate, in particular the regimen of bemnifosbuvir and ruzasvir for the treatment of HCV; 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 March 31, 2026 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

B型胰岛素抵抗综合征( type B insulin resistance syndrome, TBIRS)是一种罕见的自身免疫疾病,由于体内存在胰岛素受体抗体(insulin receptor antibody, IRA)而引起的一种临床综合征，多见于中年女性（平均年龄约44岁）,常表现为高血糖和严重的胰岛素抵抗，多伴有黑棘皮症和自身免疫性疾病；并在非裔美国人中具有较高的患病率。IRA阳性是TBIRS的确诊标准,但IRA的检测仅在少数实验室中进行,诊断仍主要依靠临床表现。由于无特定的治疗方法，TBIRS预后较差。目前该病的诊断和治疗是临床的一项重大挑战。它与多种其他自身免疫性疾病密切相关，最显著的是系统性红斑狼疮，此外还包括类风湿性关节炎和混合性结缔组织病。 1）IRA产生的诱因  1.自身免疫调节紊乱：曾报道 1例1型糖尿病患者发病数月后出现严重的胰岛素抵抗,诊断为TBIRS。此外，在接受骨髓移植治疗的严重联合免疫缺陷儿童中也出现了TBIRS。可能与自身免疫调节紊乱诱发IRA产生有关。 2.细菌或病毒感染：幽门螺杆菌感染可能诱发TBIRS。幽门螺杆菌感染引起的炎性反应可导致交叉反应型抗体的产生。此外,人类免疫缺陷病毒感染后发生的免疫重建炎症综合征可能诱发TBIRS。曾报道1例携带人类免疫缺陷病毒的非洲糖尿病妇女在开始高效抗逆转录病毒治疗后出现严重胰岛素抵抗。 3.药物二肽基肽酶-4抑制剂有可能诱导TBIRS：曾报道1例糖尿病患者在服用西格列汀6个月后出现严重的胰岛素抵抗，不排除西格列汀参与了TBIRS的发生。抗病毒药物如利巴韦林和干扰素 可能诱发TBIRS。曾报道1 例慢性丙型肝炎患者在接受干扰素和利巴韦林治疗过程中发生难治性高血糖,其IRA检测阳性。 2）IRA的作用机制 1.竞争性结合抑制：Flier等研究表明，IRA为多克隆IgG 抗体，每种抗体都有各自的表位特异性，可能对受体上的不同抗原位点发生反应。抗体与胰岛素竞争性结合胰岛素受体，通过占据抗原位点，引起胰岛素结合和解离动力学的改变 。 2.胰岛素受体下调：抗体可能通过拟胰岛素样反应加速细胞表面受体的降解，导致受体下调，降低胰岛素对靶器官的敏感性，引起胰岛素抵抗。 3.双向作用：患者的免疫系统“叛变”，产生了针对自身胰岛素受体的IgG抗体。这种抗体是个“双面人”（具有双相效应）：在高滴度时，它像口香糖一样堵住受体，导致胰岛素无法发挥作用，引发极度的高血糖；而在滴度下降时，它又可能模拟胰岛素的作用，异常激活受体，引发严重的低血糖。尽管大多数患者表现为严重的胰岛素抵抗和高血糖，但有一部分患者仅表现为低血糖和胰岛素水平抑制，这反映出其为间歇性受体激活而非受体阻滞。尽管低血糖为TBIRS不常见的首发表现，但许多患者在自发缓解或治疗诱导的缓解期、抗体滴度较低时会出现低血糖。 TBIRS的其他生化特征还包括脂联素水平升高，以及尽管存在严重胰岛素抵抗，甘油三酯水平仍处于正常或偏低范围。值得注意的是，目前尚无被普遍接受的用于临床诊断的生化标准。 早期识别至关重要，因为及时的免疫抑制治疗能够逆转严重的代谢紊乱。美国国立卫生研究院（NIH）的一项前瞻性临床试验表明，联合免疫抑制治疗的缓解率达到86%，且无死亡病例、治疗周期更短，这提示TBIRS可能是一种可治愈的糖尿病类型。一项近期的系统综述报告称，其病死率约为15%，缓解率为70%，复发率仅为7%。 03 ）治疗 1. 核心治疗原则治疗目标：改善糖代谢异常（严重高血糖或低血糖）及解除自身免疫反应（清除抗胰岛素受体抗体）。主要手段：免疫抑制治疗是根本措施；对症治疗（胰岛素、饮食调整）为辅助手段。预后特点：部分患者可自发缓解，但重症患者需积极干预，死亡率约为15.38%。2. 免疫抑制治疗（首选方案） 由于TBIR是自身免疫性疾病，免疫调节是治疗的关键。2.1 糖皮质激素地位：常作为一线免疫抑制药物，尤其是对于合并系统性红斑狼疮（SLE等）的患者。方案：大剂量冲击疗法 北京协和医院研究显示，5例患者接受大剂量糖皮质激素冲击治疗后继以常规剂量维持，均在2-4周内达到部分缓解。常规剂量部分患者仅使用常规剂量激素也可在2-4周内获得部分缓解。注意：激素可能加重胰岛素抵抗和高血糖，需密切监测血糖并配合胰岛素治疗。2.2 联合免疫抑制剂 当单用激素效果不佳或为减少激素副作用时，常联合其他免疫抑制剂。常用药物：硫唑嘌呤（Azathioprine）、环磷酰胺（Cyclophosphamide）、霉酚酸酯（Mycophenolate mofetil）等。疗效证据： 系统综述显示，联合免疫抑制治疗与疾病缓解呈正相关（p = 0.002）。 一例合并SLE和干燥综合征的患者，在使用利妥昔单抗和脉冲地塞米松后，继以硫唑嘌呤维持治疗1年，实现了无外源性胰岛素的正常血糖缓解。 环磷酰胺短程治疗可使高血糖显著改善，黑棘皮病消退，抗体转阴。2.3 生物制剂（利妥昔单抗 Rituximab）机制：抗CD20单克隆抗体，清除B细胞，减少抗体产生。应用： 一例66岁男性TBIR合并SLE患者，采用双滤过血浆置换（DFPP）联合利妥昔单抗，未使用激素，7个月后抗体转阴，糖尿病缓解。 另有病例报道利妥昔单抗联合激素治疗有效。2.4 静脉注射免疫球蛋白（IVIG）适用场景：可作为替代或补充治疗，尤其在其他免疫抑制治疗效果不佳或需要快速起效时。疗效：一例中国女性TBIR合并SLE患者，经脉冲式IVIG治疗后完全康复。文献指出IVIG对胰岛素抵抗有显著快速的效果。3. 血糖管理： 胰岛素治疗挑战：由于存在抗受体抗体，患者通常表现为极度胰岛素抵抗，可能需要极大剂量的胰岛素（文献报道最高达57,600 IU/天）。策略： 尽管抵抗严重，仍常需大剂量胰岛素控制高血糖，尤其是在急性期（如酮症酸中毒）。 部分患者在抗体滴度波动时可能出现严重低血糖，需警惕。 使用传感器增强型胰岛素泵（SAP）有助于预防低血糖并精细调节剂量。4. 治疗流程建议（基于证据整合） 治疗阶段 推荐措施 证据等级/来源一线治疗糖皮质激素 （如泼尼松、甲泼尼龙），可单独或联合使用。 专家共识/病例系列 二线/联合治疗 若激素效果不佳或需减量，联合免疫抑制剂（硫唑嘌呤、环磷酰胺、霉酚酸酯）或利妥昔单抗。 系统综述/病例报告 重症/难治性血浆置换 （特别是双滤过血浆置换DFPP）或静脉注射免疫球蛋白（IVIG）。 病例报告 特殊情形 若上述治疗无效，可尝试IGF-1治疗（需警惕过敏）。 病例报告 辅助治疗 大剂量胰岛素（必要时）、分餐饮食、根除H. pylori（若阳性）。 病例报告/综述  B型胰岛素抵抗综合征的治疗应以免疫抑制为核心。糖皮质激素联合免疫抑制剂是目前最常用的有效方案。利妥昔单抗和血浆置换为难治性或重症患者提供了重要选择。治疗过程中需密切监测血糖波动（高血糖与低血糖交替出现），并根据抗体滴度和临床症状调整方案。 TBIRS是一种罕见性疾病，死亡率较高，预后不佳。诊断的金标准是IRA阳性。但由于实验条件限制，抗体的检测只能在少数实验室中进行，目前该病的诊断仍主要依靠临床表现。联合免疫治疗是一种新的治疗方案，和单一免疫治疗相比，具有更高的缓解率、更短的缓解时间和更低的死亡率。但需注意应用免疫治疗过程中出现的不良反应。新型治疗方法不断出现，为TBIRS的治疗带来了曙光。目前该病的诊断和治疗仍是临床的一项重大挑战，需要研究者探索新的诊断技术与治疗方法。TBIR具有特殊的“双相”病程，在诱导缓解期必须极其严密地监测血糖，防止致死性低血糖的发生。 慢性肾脏病相关性瘙痒