M-102.4

还记得曾经火遍社交网络的“冰桶挑战”吗？意在引起人们对罕见病肌萎缩性侧索硬化症（ALS，也称“渐冻人症”）这种疾病的关注。参与者要将一桶冰水从自己头上倒下，并将过程拍成视频上传至社交网络。过往ALS一直都被外界所忽视。著名物理学家斯蒂芬•霍金及前美国棒球明星卢•贾里格（在美国，此症一直以他而命名）都是ALS患者。肌萎缩侧索硬化肌萎缩侧索硬化（amyotrophic lateral sclerosis，ALS）主要症状为四肢和躯干肌肉表现进行性加重的肌肉无力和萎缩，逐渐失去运动功能，像被“冻住”一般。这是一种病因未明、主要累及大脑皮质、脑干和脊髓运动神经元的神经系统变性疾病。ALS属于罕见病，发病率约为10万分之2到10万分之5，被世界卫生组织列为与艾滋病、癌症等并列的5大绝症之一。中国大约有20万左右的患者，且这个数字还在逐年递增。Pegcetacoplan“折戟”Apellis Pharmaceuticals，Inc.（Nasdaq：APLS）在24号宣布，研究Pegcetacoplan治疗肌萎缩侧索硬化症（ALS）的2期MERIDIAN研究在第52周未达到其功能和生存综合评估（CAFS）等级评分的主要终点。该研究也未达到关键的次要疗效终点。此外，Pegcetacoplan在研究中耐受性良好，数据与既定的安全性一致。也就是说，安全性没有问题，问题出在了疗效上。为什么会这样呢？很大程度的原因在于ALS发病原因未知，没有明确的靶点，对新药的开发造成了很大的困难。各个公司也是进行了多种尝试，摸着石头过河。正是由于这种不确定性，造成了研发过程屡屡受挫，大量公司的研发也因此陷入僵局。基于上述临床结果，Apellis和Sobi计划停止开发用于ALS的全身性治疗的Pegcetacoplan。这一决定并不意外，因为今年4月，根据独立数据监测委员会的建议，Apellis和Sobi就停止了研究开放标签部分的治疗。这次临床试验用药Pegcetacoplan并非籍籍无名之辈。它是一种靶向C3疗法，旨在调节补体级联的过度激活，补体级联是人体免疫系统的一部分，可降低许多严重疾病的发作和进展。今年2月，该药物以商品名Syfovre创造了历史。FDA批准Apellis补体C3环肽抑制剂Pegcetagoplan上市，用于治疗继发于年龄相关性黄斑变性（AMD）的地图样萎缩（GA），这是首款针对该适应症的上市药物。地理萎缩是年龄相关性黄斑变性的晚期阶段，是导致失明的主要原因之一。5月4日，Apellis Pharmaceuticals报告其2023年第一季度财务业绩。其中SYFOVRE™ (Pegcetacoplan injection) 和EMPAVELI®（Pegcetacoplan）在美国的产品净收入分别为1840万美元和2040万美元。不到三个月时间能收获如此高的销售业绩，不可谓不优秀。但面对未知的ALS领域，该药物还是不幸折戟。Apellis表示计划对数据进行彻底分析，以深入了解试验结果，并在未来的医学会议上介绍研究结果。Apellis首席开发官Jeffrey Eisele在一份声明中表示，该公司希望MERIDIAN研究产生的数据“将继续支持ALS的未来研究和开发。已有手段非常有限患者急需新型治疗方式ALS患者的治疗选择非常有限。FDA分别于上世纪90年代和2017年批准了两款ALS治疗药物利鲁唑（Riluzole）和依达拉奉（Edaravone），后于2022年9月批准了Relyvrio。数据来源：药渡数据利鲁唑（Riluzole）利鲁唑（Riluzole）是赛诺菲公司开发的药物，1996年美国FDA批准上市，是第一个获美国FDA和欧盟批准用于治疗ALS的药物。它的主要作用是抑制多种受体和离子通道介导的谷氨酸突触传导和神经元超兴奋性，提高神经营养因子的表达量，保护神经元免受兴奋毒性损伤，保护神经元的存活，从而可以改善ALS患者的生活质量。依达拉奉（Edaravone）依达拉奉（Edaravone）是一种自由基清除剂，由2001年日本田边三菱制药公司研制上市，治疗脑卒中。研究认为，依达拉奉可清除自由基并防止脑细胞（血管内皮细胞/神经细胞）出现氧化损伤，从而延缓ALS的疾病进展。该药用于治疗ALS适应症在日本（2015年）以商品名Radicut获准上市，在美国（2017年）和加拿大（2020年）以商品名Radicava获准上市。2022年9月，Amylyx公司的Relyvrio（苯丁酸钠和牛磺酸二醇口服固定剂量配方）获得了FDA的批准， Relyvrio是两种药物苯丁酸钠（Sodium Phenylbutrate）和牛磺酸二醇（Taurursodiol）的复方制剂。苯丁酸钠是一种组蛋白脱乙酰酶抑制剂，牛磺酸二醇与线粒体凋亡抑制有关。相较于安慰剂，Relyvrio治疗使中位生存期延长了6.5个月。Relyvrio已在美国和加拿大获得对ALS治疗授权。在过去两年中，来自Biogen、Cytokinetics、Alexion Pharmaceuticals和Biohaven等公司的ALS药物都遇到了临床障碍。其中，Biogen的药物临床效果虽然未达预期，但因为显著降低了ALS生物标识物数量，因此获得了FDA的加速审批。4月25日，Biogen/lonis联合宣布FDA已同意加速批准用于治疗超氧化物歧化酶1(SOD1)突变所致肌萎缩侧索硬化（ALS）的反义寡核苷酸疗法Tofersen，这是首款针对ALS的基因靶向疗法。接受Tofersen治疗的患者人群在临床肌萎缩侧索硬化功能评定量表（ALSFRS-R）相较基线下降较少，不具有统计学意义。但在生物标志物研究中，Tofersen可显著降低患者体内SOD1蛋白水平，且降低了与神经轴突损伤相关的神经丝轻链（NfL）的水平。NfL是神经退行性标志物，可作为神经退行性疾病的替代终点。因此，Biogen基于Tofersen能够显著降低NfL水平，向FDA提出加速批准的申请。面对ALS这座大山走到三期却失败的尝试间充质干细胞（MSC）-NTF细胞疗法（NurOwn）间充质干细胞（MSC）-NTF细胞疗法（NurOwn）是首个通过随机安慰剂对照关键试验评估的ALS细胞治疗方案。从患者自己的骨髓中收集成体干细胞，进行扩增和体外操作以分泌NTFs。随后，通过鞘内注射将细胞移植回患者体内。2020年11月17日，Brainstorm公司宣布，在研干细胞产品NurOwn®治疗渐冻人症的3期临床试验中，显示未能达到主要终点指标和关键次要终点。值得一提的是，NurOwn®在病情较轻的患者组中产生了具有临床意义的作用，会使病情较轻的患者受益。AldesleukinAldesleukin，癌症免疫治疗“老兵”，是一种重组人IL-2，与内源性IL-2具有本质上相似的药理学特性。低剂量IL-2可增强自身炎症条件下的调节性T（Treg）细胞功能，而神经炎症是ALS的一个关键致病特征。采用嵌入式实验药物方法的2/3期临床试验（MIROCALS，NCT02059759）正在进行，用于评估低剂量Aldesleukin在36例ALS患者中的作用。该试验涉及220名参与者，为期18个月。该试验的结果目前正在分析中。RavulizumabRavulizumab是一种人源化抗C5抗体，用于治疗ALS和其他罕见疾病。它是一种末端补体抑制剂，特异性地与C5补体蛋白结合，具有高亲和力，从而抑制其切割成C5a和C5b，防止末端膜攻击复合体C5b9的生成和促炎C5a片段的产生。进行了3期CHAMPION-ALS试验（NCT04248465），以评估Rravulizumab治疗ALS的疗效和安全性。在完成预先确定的中期分析后，由于缺乏疗效，于2021年8月停止了这项试验。Verdiperstat靶向神经炎症的Verdiperstat是由Biohaven制药开发的一种口服的髓过氧化物酶（MPO）小分子抑制剂。MPO可促进在大脑中氧化应激和炎症反应，抑制MPO可缓解与神经炎症相关的病理表征。2021年9月27日，Biohaven公布了一项Verdiperstat 治疗多系统萎缩症（MSA）3期研究的分析结果。无论是预先指定的主要疗效指标，亦或是关键的次要疗效指标上，Verdiperstat均未与安慰剂达到统计学显著差异。安全性数据的初步分析与此前的总体情况一致。除上述ALS治疗药物外，临床前研究表明还有包括QRA-244（Kv7离子通道开放剂）、M102（多巴胺受体激动剂）、COYA-201（Treg细胞源性的外泌制备物）对ALS具有潜在的治疗作用。总结近几年有效ALS药物的市场份额呈逐年增长的趋势。根据Grand View Research的一份新报告，2018年全球ALS治疗市场规模约为5.4亿美元，预计到2026年将达到8.9亿美元，2019-2026期间复合年增长率将为5.8%。新药研发从来都不是一件易事，尤其是对ALS这种发病机理不明的疾病来说。长期以来，神经退行性疾病的治疗和缓解药物都非常有限，且效果难以让人满意，而该领域的新药研发同样是令制药行业屡屡受挫。但医药公司在这条赛道上，不断向上进行着攀登，尤其是今年还迎来了第3款获批治疗ALS的药物Relyvrio，都预示着在治疗ALS上又向前跨进了一大步。在这里，我们也许需要对这些“失败者”唱一首赞歌，感谢他们不懈的努力。ALS或许只是一个开始，随着药企和监管机构的更多介入，可以期待未来将会有更多的神经退行性疾病受到大众关注，这类患者也能获得更多更有效更安全的治疗。END👇关注药渡数据媒体矩阵

– More than $2.6 billion in cash, cash equivalents, investments and profit-share payments to be received from GSK expected to fund the company’s ongoing operations and liabilities for up to five years – – Company provides update on COVID-19 development program and outlines multiple anticipated value drivers from its robust pipeline – SAN FRANCISCO, Aug. 09, 2022 (GLOBE NEWSWIRE) -- VIR BIOTECHNOLOGY Inc. (Nasdaq: VIR) today provided a corporate update and reported financial results for the second quarter ended June 30, 2022. “Vir closed the second quarter with a balance sheet that we believe is sufficient to fund the company for up to five years. During that time, we expect to generate meaningful Phase 2 and Phase 3 data from our programs in COVID-19, hepatitis B, hepatitis D and influenza A, while also advancing multiple early-stage programs into the clinic that have the potential to be significant value drivers,” said George Scangos, Ph.D., chief executive officer of Vir Biotechnology. “With the expectation that there will be an enduring unmet need in the prevention and treatment of COVID-19, we are shifting our strategy from rapidly developing pandemic medicines to a focus on long-term control. With several next-generation antibodies and small molecules moving through R&D, we believe that we are in a strong position to do so. In the near-term, we expect the second half of 2022 to hold many important milestones, including the initiation of our anticipated Phase 2 trial aimed at universal prophylaxis for influenza A, our first trial in hepatitis D and multiple data readouts from our hepatitis B and HIV programs.” Corporate Update During the quarter, the Company continued to deliver on its mission of addressing serious infectious diseases, including bringing sotrovimab to appropriate patients and actively investing in next-generation COVID-19 therapies while simultaneously advancing a robust clinical portfolio aimed at hepatitis B and D, influenza A and human immunodeficiency virus (HIV). COVID-19 In the second quarter of 2022, approximately 265,000 sotrovimab doses were delivered, all to countries outside of the US. This exceeded expectations for delivery of approximately 100,000 doses in the quarter due to additional agreements with countries outside of the US. Sotrovimab currently has Emergency Use Authorization (EUA), temporary authorization or marketing approval (under the brand name Xevudy®️) in more than 40 countries, and remains in use outside of the US. The Company and GlaxoSmithKline (GSK) continue to conduct in vitro testing of sotrovimab against new variants and subvariants as they emerge and plan to submit data in the second half of 2022, including safety at a higher dose and real-world evidence, to regulatory authorities. Due to the evolving COVID-19 landscape and based on discussions with the US Food and Drug Administration (FDA), the Company and GSK do not plan to Biologics License Application for sotrovimab at this time and do not intend to pursue the US-based Phase 3 COMET-STAR prophylaxis trial. Discussions with the FDA remain ongoing regarding the appropriate path forward for sotrovimab in the US. As part of the ongoing COVID-19 development plan for sotrovimab: The PROTECT-V prophylaxis trial, a Phase 3 platform trial of sotrovimab sponsored by Cambridge University Hospitals National Health Service (NHS) Foundation Trust, assessing the use of sotrovimab in uninfected individuals started in August. Initial data are expected in 2023. Sotrovimab is being evaluated at a 1g dose among patients hospitalized with COVID-19 in the United Kingdom (UK) as part of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) Trial. Timing of initial data will depend on continued rate of enrollment. VIR-7832 is being evaluated in the Phase 2a portion of the UK’s NHS-supported AGILE initiative. To date, no safety signals have been reported in the Phase 1b or 2a portions of the trial. Additional safety data from the Phase 1b portion of the trial are expected in the second half of 2022. To prepare for new waves of variants and future pandemics, the Company and GSK continue to actively pursue multiple next-generation broadly neutralizing and highly potent COVID-19 antibodies, leveraging the Company’s robust antibody platform, with the aim of generating a pipeline of variant-proof antibodies, as well as small molecules aimed at treating COVID-19 and potentially other respiratory diseases. Hepatitis B Virus (HBV) In June, at the International Liver Congress™ 2022, the Annual Meeting of the European Association for the Study of the Liver (EASL), the Company announced encouraging new data from its robust HBV program. Results from the Phase 2 monotherapy trial of VIR-2218 demonstrated that a six-dose regimen provided greater and more durable reductions in hepatitis B surface antigen (HBsAg) than a two-dose regimen, with all participants achieving a >1 log10 IU/mL reduction during the trial. Results from the Phase 1 monotherapy trial of VIR-3434 demonstrated that a single dose (6 mg, 18 mg, 75 mg or 300 mg) resulted in a rapid reduction of HBsAg, with the largest and most durable response noted with the 300 mg dose. Pharmacokinetic (PK) analyses and HBsAg profiles support evaluation of monthly dosing of VIR-3434. Preclinical in vivo data evaluating both VIR-2218 and VIR-3434 as monotherapy and in combination demonstrated that the combination of both compounds resulted in greater HBsAg and HBV DNA reductions than either alone. In June, the first patient was dosed in Part B of the Phase 2 Monoclonal Antibody siRNA Combination against Hepatitis B (MARCH) trial evaluating VIR-2218 in combination with VIR-3434 for 24 and 48 weeks, and in triple combination with VIR-3434 and interferon. Initial data are expected in the second half of 2023. Previously reported results from Part A suggested that VIR-2218 and VIR-3434 are additive in reducing HBsAg, with no drug-related safety signals reported to date. Additional data from Part A are expected later this year. In July, Brii Biosciences exercised its option to acquire exclusive development and commercialization rights to VIR-3434 in China, Hong Kong, Macau and Taiwan, providing the Company with an option exercise fee. Pending VIR-3434’s development progression in these regions, the Company could receive future milestone payments and royalties. Additional HBV milestones expected in 2022 include: Additional data from the Phase 2 trial of VIR-2218 alone and in combination with PEG-IFN-α. Initial data from the Phase 2 trial led by Brii Biosciences evaluating VIR-2218 in combination with BRII-179, an investigational T cell vaccine, for the potential treatment of chronic HBV infection. Initiation of a Phase 2 platform trial of VIR-2218 in combination with VIR-3434 in viremic patients (THRIVE/STRIVE sub-protocols), with initial data expected in the second half of 2023. Hepatitis D Virus (HDV) The Company expects to initiate a Phase 2 trial of VIR-2218 in combination with VIR-3434 for the treatment of chronic HDV infection called SOLSTICE in the second half of 2022, with initial data expected in 2023. Recent findings indicate that treatment approaches that reduce HBsAg production and block HDV entry into hepatocytes could provide an effective method for HDV management, thus supporting the investigation of the combination of VIR-3434 and VIR-2218 in this high unmet need disease. Influenza Aligned with the start of the North American influenza season in the second half of 2022, the Company expects to initiate a Phase 2 prophylaxis healthy volunteer trial evaluating the safety and efficacy of two different doses of VIR-2482, an intramuscularly administered influenza A-neutralizing monoclonal antibody, with the aim to reduce the rate of infection. The primary efficacy endpoint is confirmation of symptomatic influenza A illness with key secondary endpoints of severity and duration of illness due to influenza A. Initial data are expected in mid-2023. Also in the second half of 2022, the Company expects to initiate a Phase 1b prophylaxis trial evaluating the safety of VIR-2482 in elderly (>65 years old) participants who will receive a flu vaccine. This population is representative of the Company’s anticipated Phase 3 trial population. Initial data are expected in mid-2023. HIV Additional safety and immunology data from the proof-of-concept Phase 1 trial of VIR-1111, an HIV T cell vaccine based on human cytomegalovirus (HCMV), are expected in the second half of 2022. To date, no safety signals have been reported. Management In July, the Company announced that Herbert “Skip” Virgin, M.D., Ph.D., executive vice president, research and chief scientific officer, will step down effective August 30, 2022, to pursue a new position with Altos Labs. He will be a member of the Company’s Scientific Advisory Board. Phil Pang, M.D., Ph.D., executive vice president and chief medical officer, will take on overall responsibility for research and development on an interim basis while the Company identifies a permanent successor. Second Quarter 2022 Financial Results Revenues: Total revenues for the quarter ended June 30, 2022, were ($40.6 million), compared to $177.1 million for the same period in 2021. The profit-sharing amount under the collaboration with GSK for the quarter ended June 30, 2022, was $342.5 million, which was offset by a non-cash charge of $397.4 million for potential write-offs related to excess sotrovimab supply and manufacturing capacity against uncertain future pandemic demand. As a result, collaboration revenue for the second quarter was ($54.9 million), compared with $5.3 million for the same period in 2021. Collaboration revenue reflects the delivery in the second quarter of approximately 265,000 sotrovimab doses, which exceeded expectations of approximately 100,000 doses due to additional agreements with countries outside the US. The $342.5 million profit-sharing amount due from GSK is expected to be received during the third quarter. Collaboration revenue is calculated by applying the Company’s contractual share of 72.5% to the revenue reported in the period by GSK, $551.9 million for the second quarter, net of cost of goods sold and allowable expenses from both GSK and the Company (e.g., medical affairs, selling and marketing expenses), and adding back the Company’s expenses that appear elsewhere in the consolidated statement of operations (e.g., cost of revenue). Contract revenue for the quarter ended June 30, 2022, was $12.3 million, compared to $168.7 million for the same period in 2021. The decrease for the quarter was primarily due to $168.3 million of revenue related to the license granted to GSK under the Company’s 2021 agreement with GSK recognized in the quarter ended June 30, 2021, partially offset by $7.0 million related to the additional license granted to GSK applicable in mainland China, Hong Kong, Macau and Taiwan upon execution of Amendment No. 1 to the Company’s 2020 agreement with GSK in the quarter ended June 30, 2022. Grant revenue for the quarter ended June 30, 2022, was $2.1 million, compared to $3.1 million for the same period in 2021. The decrease for the quarter was primarily due to the timing of research activities under the grant agreements with the Bill & Melinda Gates Foundation. Cost of Revenue: Cost of revenue for the quarter ended June 30, 2022, was $27.9 million, compared with $1.1 million for the same period in 2021. The increase was due to third-party royalties owed based on the sales of sotrovimab. Research and Development Expenses: Research and development expenses for the quarter ended June 30, 2022, were $115.1 million, which included $14.1 million of non-cash stock-based compensation expense, compared to $86.1 million for the same period in 2021, which included $10.9 million of non-cash stock-based compensation expense. The increase for the quarter was primarily due to higher personnel-related expenses resulting from higher headcount, the change in fair value of the contingent consideration from the acquisition of Humabs, an increase in manufacturing activities for the Company’s product candidates and an increase in the allocation of facilities and other costs, partially offset by a decrease in costs under the collaboration arrangements with GSK and other R&D collaborators and a decrease in clinical trial costs for sotrovimab. Selling, General and Administrative Expenses: Selling, general and administrative expenses for the quarter ended June 30, 2022, were $41.6 million, which included $13.0 million of non-cash stock-based compensation expense, compared to $28.8 million for the same period in 2021, which included $10.1 million of non-cash stock-based compensation expense. The increase for the quarter was primarily due to higher personnel-related expenses related to additional headcount, external consulting services, business tax expenses related to increased revenue from the sale of sotrovimab and allocated facilities costs due to higher lease expense. Other (Expense) Income: Other expense for the quarter ended June 30, 2022, was ($8.5 million), compared to income of $0.8 million for the same period in 2021. The increase for the quarter was primarily due to the unrealized loss of $11.4 million resulting from the change in fair value of the Company's equity investment in Brii Biosciences, partially offset by higher interest income. Benefit from (Provision for) Income Taxes: Benefit from income taxes for the quarter ended June 30, 2022, was $157.2 million, compared to a ($53,000) provision for income taxes for the same period in 2021. The increase in benefit from income taxes for the quarter was primarily due to the Company’s pre-tax book loss and the decrease in the estimated 2022 annual effective tax rate. Net (Loss) Income: Net loss for the quarter ended June 30, 2022, was ($76.5 million), or ($0.58) per share, basic and diluted, compared to net income of $61.8 million, or $0.48 per share, basic, and $0.46 per share, diluted, for the same period in 2021. Cash, Cash Equivalents, Investments, and Profit-Share Payments: As of June 30, 2022, excluding restricted cash, the Company had more than $2.6 billion in cash, cash equivalents, investments and profit-share payments to be received from GSK. Sotrovimab in the United States The following is a summary of information for sotrovimab. Healthcare providers in the US should review the Fact Sheets for information about the authorized use of sotrovimab and mandatory requirements of the Emergency Use Authorization (EUA). Please see the Food and Drug Administration (FDA) Letter of Authorization, full Fact Sheet for Healthcare Providers and full Fact Sheet for Patients, Parents, and Caregivers. Sotrovimab has been authorized by the FDA for the emergency use described below. Sotrovimab is not FDA-approved for this use. Sotrovimab is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of sotrovimab under section 564(b)(1) of the Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner. Due to the continued proportion of COVID-19 cases caused by certain Omicron subvariants, sotrovimab is not currently authorized in any US region. Authorized use The FDA has issued an EUA to permit the emergency use of the unapproved product sotrovimab for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. Limitations of authorized use Sotrovimab is not authorized for treatment of mild to moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency. FDA’s determination and any updates will be available at: . Sotrovimab is not authorized for use in adult or pediatric patients who: are hospitalized due to COVID-19, OR require oxygen therapy and/or respiratory support due to COVID-19, OR require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19 in those on chronic oxygen. Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Important Safety Information CONTRAINDICATIONS Sotrovimab is contraindicated in patients who have a history of anaphylaxis to sotrovimab or to any of the excipients in the formulation. WARNINGS AND PRECAUTIONS There are limited clinical data available for sotrovimab. Serious and unexpected adverse events may occur that have not been previously reported with sotrovimab use. Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of sotrovimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of sotrovimab. These reactions may be severe or life-threatening. Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vaso-vagal reactions (e.g., pre-syncope, syncope), dizziness and diaphoresis. If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care. Clinically monitor patients for at least 1 hour after completion of the infusion for signs and symptoms of hypersensitivity. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization. Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration Clinical worsening of COVID-19 after administration of SARS-CoV-2 monoclonal antibody treatment has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue and altered mental status. Some of these events required hospitalization. It is not known if these events were related to SARS-CoV-2 monoclonal antibody use or were due to progression of COVID-19. Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19 Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Therefore, sotrovimab is not authorized for use in patients: who are hospitalized due to COVID-19, OR who require oxygen therapy due to COVID-19 OR who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity. ADVERSE EVENTS Infusion-related reactions, including immediate hypersensitivity reactions, were observed in subjects treated with sotrovimab in COMET-ICE (1%) and in COMET-TAIL (<1%). Events reported within 24 hours of study treatment were pyrexia, chills, dizziness, dyspnea, pruritus, rash, and infusion-related reactions; all events were Grade 1 (mild) or Grade 2 (moderate). Hypersensitivity adverse reactions were observed in 2% of patients treated with sotrovimab in COMET-ICE and in <1% of subjects treated with sotrovimab in COMET-TAIL. All were Grade 1 (mild) or Grade 2 (moderate). One reaction led to temporary pausing of the infusion. The most common treatment-emergent adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhea (2%), all of which were Grade 1 (mild) or Grade 2 (moderate). USE IN SPECIFIC POPULATIONS Pregnancy A pregnancy exposure registry monitors pregnancy outcomes in women exposed to sotrovimab during pregnancy. To enroll, go to or call 1-800-616-3791 to obtain information about the registry. There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcome. Sotrovimab should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy. Lactation There are no available data on the presence of sotrovimab in human milk, the effects on the breastfed infant or the effects on milk production. Individuals with COVID-19 who are breastfeeding should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. About VIR-7832 VIR-7832 is an investigational dual-action SARS-CoV-2 monoclonal antibody. Preclinical data suggest it has the potential to both block viral entry into healthy cells and an enhanced ability to clear infected cells. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (the virus that causes SARS), indicating that the epitope is highly conserved, which may make it more difficult for resistance to develop. VIR-7832, which incorporates Xencor’s Xtend™ and other Fc technologies, has been designed to have an extended half-life. Importantly, VIR-7832 also has been engineered to potentially enhance virus-specific T cell function, which could help treat and/or prevent COVID-19 infection. About VIR-2218 VIR-2218 is an investigational subcutaneously administered HBV-targeting siRNA that has the potential to stimulate an effective immune response and have direct antiviral activity against HBV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus (ESC+) technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index. VIR-2218 is the first asset in the Company’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical trials. About VIR-3434 VIR-3434 is an investigational subcutaneously administered HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and also to reduce the level of virions and subviral particles in the blood. VIR-3434, which incorporates Xencor’s Xtend™ and other Fc technologies, has been engineered to potentially function as a T cell vaccine against HBV in infected patients, as well as to have an extended half-life. About VIR-1111 VIR-1111 is an investigational subcutaneously administered HIV T cell vaccine based on HCMV that has been designed to elicit abundant T cells that recognize HIV epitopes in a way that differs from prior HIV vaccines. About VIR-2482 VIR-2482 is an investigational intramuscularly administered influenza A-neutralizing monoclonal antibody. In vitro, it has been shown to cover all major strains of influenza A that have arisen since the 1918 Spanish flu pandemic. VIR-2482 is designed as a universal prophylactic for influenza A. It has the potential to overcome the limitations of current flu vaccines and lead to meaningfully higher levels of protection due to its broad strain coverage and because it does not rely on an individual to create their own protective antibody response. VIR-2482, which incorporates Xencor’s Xtend™ technology, also has been half-life engineered so that a single dose has the potential to last the entire flu season. Vir’s Commitment to COVID-19 Vir was founded with the mission of addressing the world’s most serious infectious diseases. In 2020, Vir responded rapidly to the COVID-19 pandemic by leveraging our unique scientific insights and industry-leading antibody platform to explore multiple monoclonal antibodies as potential therapeutic or preventive options for COVID-19. Sotrovimab is the first SARS-CoV-2-targeting antibody Vir advanced into the clinic. It was carefully selected for its demonstrated promise in pre-clinical research, including an anticipated high barrier to resistance and potential ability to both block the virus from entering healthy cells and clear infected cells. Vir is continuing to pursue novel therapeutic and prophylactic solutions to combat SARS-CoV-2 and future coronavirus pandemics, both independently and in collaboration with its partners. About Vir Biotechnology Vir Biotechnology is a commercial-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. Vir has assembled four technology platforms that are designed to stimulate and enhance the immune system by exploiting critical observations of natural immune processes. Its current development pipeline consists of product candidates targeting COVID-19, hepatitis B and hepatitis D viruses, influenza A and human immunodeficiency virus. Vir routinely posts information that may be important to investors on its website. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “plan,” “potential,” “aim,” “expect,” “anticipate,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Vir’s expectations and assumptions as of the date of this press release. Forward-looking statements contained in this press release include, but are not limited to, statements regarding Vir’s strategy and plans; Vir’s capital allocation; Vir’s future financial and operating results and its expectations related thereto; potential of, and expectations for, Vir’s pipeline; Vir’s clinical development programs, clinical trials, including the enrollment of Vir’s clinical trials, and data readouts and presentations; testing the ability of sotrovimab to maintain activity against new variants and subvariants; Vir’s plans for sotrovimab and its COVID-19 portfolio; clinical data from Vir’s ongoing trials of VIR-2218 and VIR-3434; the ability of VIR-2218 and VIR-3434 (as monotherapies or combination therapies) to treat and/or prevent chronic HBV infection or treat HDV infection; the timing of Brii Biosciences’ Phase 2 trial evaluating VIR-2218 in a combination trial with BRII-179; and Vir’s plans for its HBV, HDV, influenza and HIV portfolios. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data or results observed during clinical trials or in data readouts; the timing and outcome of Vir’s planned interactions with regulatory authorities; difficulties in obtaining regulatory approval; difficulties in collaborating with other companies; challenges in accessing manufacturing capacity; clinical site activation rates or clinical trial enrollment rates that are lower than expected; successful development and/or commercialization of alternative product candidates by Vir’s competitors; changes in expected or existing competition; delays in or disruptions to Vir’s business or clinical trials due to the COVID-19 pandemic, geopolitical changes (including the war in Ukraine) or other external factors; and unexpected litigation or other disputes. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Vir’s filings with the US Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, Vir assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. Vir Biotechnology, Inc. Condensed Consolidated Statements of Operations (unaudited; in thousands, except share and per share data) Three Months Ended June 30, Six Months Ended June 30, 2022 2021 2022 2021 Revenue: Collaboration revenue $ (54,941 ) $ 5,333 $ 1,174,715 $ 5,333 Contract revenue 12,254 168,653 12,536 169,266 Grant revenue 2,058 3,082 4,579 4,453 Total revenue (40,629 ) 177,068 1,191,830 179,052 Operating expenses: Cost of revenue 27,921 1,144 118,070 1,152 Research and development 115,082 86,126 205,309 220,996 Selling, general and administrative 41,590 28,781 79,845 54,520 Total operating expenses 184,593 116,051 403,224 276,668 (Loss) income from operations (225,222 ) 61,017 788,606 (97,616 ) Other (expense) income: Change in fair value of equity investments (11,390 ) — (106,429 ) — Interest income 2,200 97 2,588 261 Other income (expense), net 691 752 3,421 (9,494 ) Total other (expense) income (8,499 ) 849 (100,420 ) (9,233 ) (Loss) income before benefit from (provision for) income taxes (233,721 ) 61,866 688,186 (106,849 ) Benefit from (provision) for income taxes 157,228 (53 ) (246,058 ) (249 ) Net (loss) income $ (76,493 ) $ 61,813 $ 442,128 $ (107,098 ) Net (loss) income per share, basic $ (0.58 ) $ 0.48 $ 3.34 $ (0.83 ) Net (loss) income per share, diluted $ (0.58 ) $ 0.46 $ 3.28 $ (0.83 ) Weighted-average shares outstanding, basic 132,450,018 130,121,943 132,326,244 128,938,851 Weighted-average shares outstanding, diluted 132,450,018 133,789,977 134,643,840 128,938,851 Vir Biotechnology, Inc. Condensed Consolidated Balance Sheets (unaudited; in thousands, except share and per share data) June 30, 2022 December 31, 2021 ASSETS CURRENT ASSETS: Cash and cash equivalents $ 1,505,183 $ 347,815 Short-term investments 654,113 217,182 Restricted cash and cash equivalents, current 13,147 8,594 Receivable from collaboration 7,000 773,079 Equity investments 36,407 143,148 Prepaid expenses and other current assets 72,417 73,003 Total current assets 2,288,267 1,562,821 Intangible assets, net 33,021 33,287 Goodwill 16,937 16,937 Property and equipment, net 85,135 42,834 Operating right-of-use assets 86,879 87,220 Restricted cash and cash equivalents, noncurrent 8,354 7,006 Long-term investments 97,585 201,388 Other assets 2,816 2,775 TOTAL ASSETS $ 2,618,994 $ 1,954,268 LIABILITIES AND STOCKHOLDERS’ EQUITY CURRENT LIABILITIES: Accounts payable $ 10,618 $ 6,521 Accrued and other liabilities 354,086 236,512 Deferred revenue, current portion 113,164 98,209 Total current liabilities 477,868 341,242 Deferred revenue, noncurrent 4,419 3,815 Operating lease liabilities, noncurrent 130,205 133,561 Contingent consideration, noncurrent 28,455 22,822 Deferred tax liability 18,439 18,439 Other long-term liabilities 7,596 2,540 TOTAL LIABILITIES 666,982 522,419 STOCKHOLDERS’ EQUITY: Preferred stock, $0.0001 par value; 10,000,000 shares authorized as of June 30, 2022 and December 31, 2021; no shares issued and outstanding as of June 30, 2022 and December 31, 2021 — — Common stock, $0.0001 par value; 300,000,000 shares authorized as of June 30, 2022 and December 31, 2021; 132,597,812 and 131,161,404 shares issued and outstanding as of June 30, 2022 and December 31, 2021, respectively 13 13 Additional paid-in capital 1,656,024 1,571,535 Accumulated other comprehensive loss (7,553 ) (1,099 ) Retained earnings (accumulated deficit) 303,528 (138,600 ) TOTAL STOCKHOLDERS’ EQUITY 1,952,012 1,431,849 TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY $ 2,618,994 $ 1,954,268 Contacts: Investors Heather Rowe Armstrong VP, Investor Relations harmstrong@vir.bio +1-415-915-4228 Media Cara Miller VP, Corporate Communications cmiller@vir.bio +1-415-941-6746