Bavarian Nordic, Inc.

First award under UNICEF emergency tender to secure availability of mpox vaccines for Africa COPENHAGEN, Denmark, September 26, 2024 – Bavarian Nordic A/S (OMX: BAVA) today announced an agreement with UNICEF for the supply of 1 million doses of the MVA-BN® mpox vaccine for countries in Africa impacted by the mpox outbreak. Under the agreement, UNICEF will procure 1 million doses of the vaccine which includes the 500,000 doses that were committed by Gavi and announced on September 18, 2024. As part of Bavarian Nordics commitment to increase and prioritize its production capacity to fulfil the short- and medium-term demand, the Company will make all doses available for supply before the end of 2024 and will work with UNICEF and its partners to swiftly deliver the vaccines upon request. Paul Chaplin, President & CEO of Bavarian Nordic, said: “The agreement with UNICEF represents a significant contribution to the global efforts to combat the mpox outbreak in Africa and we are proud to assist with making our vaccine rapidly available to help where they are needed. Combined with donations by various governments, institutions and Bavarian Nordic, this agreement has helped to secure more than 2.5 million doses of MVA-BN, thus fulfilling the short-term requirement as expressed by the Africa CDC. This is a huge milestone to achieve within such a short timeframe and we applaud UNICEF, Gavi and their partners along with nations who have contributed with donations for their commitments to make this happen. We will continue our efforts together with partners to secure the necessary availability of vaccines beyond 2024.” About the mpox vaccineMVA-BN or Modified Vaccinia Ankara-Bavarian Nordic is the only non-replicating mpox vaccine approved in the U.S., Switzerland, Singapore and Mexico (marketed as JYNNEOS®), Canada (marketed as IMVAMUNE®), and the EU/EAA and United Kingdom (marketed as IMVANEX®). Originally developed as a smallpox vaccine in collaboration with the U.S. government to ensure the supply of a smallpox vaccine for the entire population, including immunocompromised individuals who are not recommended vaccination with traditional replicating smallpox vaccines, MVA-BN has been indicated for use in the general adult population in individuals considered at risk for smallpox or mpox infection. In the EU/EAA, the vaccine has also been approved for adolescents 12-17 years of age. Bavarian Nordic has been a long-term supplier of the vaccine to a number of nations, and during the 2022-2023 mpox outbreak, the Company supported governments and supranational organizations by expanding access to the vaccine to more than 70 countries worldwide. About Bavarian NordicBavarian Nordic is a fully integrated vaccine company with a mission to protect and save lives through innovative vaccines. We are a global leader in smallpox and mpox vaccines, supplied to governments to enhance public health preparedness and have a strong portfolio of vaccines for travelers and endemic diseases. For more information visit www.bavarian-nordic.com. Forward-looking statements This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law. ContactsEurope: Rolf Sass Sørensen, Vice President Investor Relations, rss@bavarian-nordic.com, Tel: +45 61 77 47 43US: Graham Morrell, Paddock Circle Advisors, graham@paddockcircle.com, Tel: +1 781 686 9600 Company Announcement no. 33 / 2024 Attachment 2024-33-en

Pictured: Syringe drawing up vaccine/iStock, Diy13 The competitive race to develop an effective chikungunya vaccine is heating up, after Danish biotech Bavarian Nordic posted positive Phase III results for its vaccine candidate—the second late-stage trial data in as many months. The latest results from Bavarian Nordic’s study of over 3,500 patients found that its virus-like particle (VLP)-based candidate produced strong induction of chikungunya-inducing antibodies in 98% of those who had received the vaccine versus placebo. In addition, 97% of subjects had antibodies induced within two weeks of vaccination “confirming a rapid onset of protective levels of immunity,” the company said in a statement. Bavarian Nordic also noted that the vaccine was “well-tolerated in this adolescent and adult population and adverse events were mainly mild or moderate in nature.” The positive results follow good news from Bavarian Nordic in June, when the company posted similar Phase III study results for an older population. While those results were not as strong, they nevertheless showed chikungunya-neutralizing antibodies in 87% of participants within three weeks of vaccination after a single vaccination, which were also “well-tolerated,” Nordic said. The race to develop an effective chikungunya vaccine has been heating up. French biotech Valneva reported promising Phase III results around the same time Nordic was posting its results in elderly patients. The Valneva study, published in The Lancet, found its vaccine had a 28-day seroprotection rate of 98.9%. In patients aged 18-64, the seroprotection rate was 98.6% and patients aged 65 or older had a 100% seroprotection rate. The study also noted that more than half of patients given the vaccine experienced an adverse event, with two serious adverse events were deemed to be related to it. Valneva’s vaccine was submitted to the FDA’s rolling submissions, which the regulator gave Priority Review, with a decision expected this month. Bavarian Nordic, for its part, will be using the results from its two latest studies to support applications to both the FDA and the European Medicines Agency. “With a fast and durable response, our vaccine has the potential to be the best in class to prevent chikungunya infections in adolescents to elderly adults," Bavarian Nordic CEO Paul Chaplin said in a statement, noting that the company’s “focus remains to finalize the studies and prepare for regulatory submissions next year.” However, the field is less crowded after Merck dropped out of the vaccine race in February, as reported by Fierce Biotech. The decision was made as part “routine pipeline prioritization,” according to a company spokesperson. While serious symptoms and death are rare, chikungunya is a widespread disease present in over 110 countries and there is currently no vaccine, according to the World Health Organization. However, the disease has high morbidity and, consequently, a heavy economic and healthcare burden. Caused by a Togaviridae virus carried by Aedes Aegypti mosquitos, chikungunya causes symptomatic infection in up to 92% of infected humans. Connor Lynch is a freelance writer based in Ottawa, Canada. Reach him at lynchjourno@gmail.com.

关键词Abrysvo；Arexvy；呼吸道合胞病毒日前，辉瑞宣布其呼吸道合胞病毒（RSV）二价疫苗Abrysvo（RSVpreF，PF-06928316）已经在美国获批，用于预防60岁及以上人群由RSV引起的急性呼吸道疾病和下呼吸道疾病（LRTI）。RSVpreF是根据美国国立卫生研究院（NIH）建立的RSV融合前（prefusion）F蛋白晶体结构所制造的一款双价重组蛋白疫苗，含有等量、分别来自A与B病毒亚型的重组RSV融合前F蛋白。该融合前蛋白是RSV病毒用以进入人体细胞的F蛋白的主要形态，NIH的研究显示靶向此融合前蛋白形态可以有效阻断病毒感染。2018年11月，RSVpreF被FDA快速通道资格（FTD），通过孕妇主动免疫预防婴儿RSV相关LRTI。2022年3月，RSVpreF先后被FDA授予两项突破性疗法认定（BTD）：1）用于孕妇，进行主动免疫接种，预防从出生至6个月大的婴儿发生与RSV相关的LRTI；2）用于60岁及以上老年人群，进行主动免疫接种，预防由RSV引起的LRTI。此次Abrysvo被FDA批准是基于3期临床试验RENOIR的积极数据。该试验是一项随机、双盲、安慰剂对照试验，共招募37000位受试者，试验中受试者按照1:1的比例接种RSVpreF疫苗或安慰剂，旨在评估60岁以上老年人接种单剂量RSVpreF疫苗的有效性和安全性。2022年4月，RENOIR试验结果荣登国际顶级医学期刊《新英格兰医学杂志》。结果显示：RSVpreF疫苗对预防出现至少两种感染症状的保护力为66.7%，对三种或以上感染症状的保护力为85.7%。同时，RSVpreF疫苗安全性良好。同时，评估怀孕妇女接种RSVpreF疫苗以避免出生6个月内的婴儿因感染RSV引起的相关LRTI的3期临床试验MATISSE的试验结果也荣登《新英格兰医学杂志》。MATISSE试验招募了约7400名孕妇，受试者按照1:1的比例接种RSVpreF疫苗或安慰剂。结果显示，MATISSE试验达成了两个主要终点的其中一项。在婴儿出生后90天，RSVpreF疫苗对RSV引起的相关严重LRTI保护力为81.8%，婴儿出生180天后，RSVpreF疫苗保护力为69.4%。同时，RSVpreF疫苗安全性良好。目前，RSVpreF用于通过孕妇主动免疫，预防从出生到六个月大的婴儿因RSV引起的需要医疗护理的下呼吸道疾病（MA-LRTI）和严重性MA-LRTI的生物制品许可申请（BLA）正在美国接受优先审查，PDUFA日期为2023年8月。今年5月18日，辉瑞宣布该BLA获FDA咨询委员会支持。同月获批，GSK佐剂疫苗Arexvy率先出线，夺得第一Abrysvo是FDA批准的第二款RSV疫苗。GSK的Arexvy（RSVPreF3 OA疫苗）于今年5月3日率先被FDA批准用于预防60岁及以上人群因RSV引起的LRTI。Arexvy包含重组的融合前构象的RSV F糖蛋白抗原（RSVPreF3）和GSK专有佐剂AS01。AS01已被用于GSK已上市的多款佐剂疫苗。抗原加佐剂组合可能帮助克服与年龄相关的免疫力自然下降，这有助于保护老年人免受RSV疾病的挑战。Arexvy获批是基于关键性3期试验AReSVi-006的积极结果。该试验是一项随机、安慰剂对照、多国试验，旨在评价单剂量RSVPreF3 OA试验疫苗对60岁及以上成年人的疗效。结果显示：RSVPreF3对RSV所致下呼吸道疾病（RSV-LRTD）的总体预防效力为82.6%，对严重性RSV-LRTD的预防效力为94.1%。在有基础合并症人群中，RSVPreF3的预防效力为94.6%，其中70-79岁人群为93.8%。此外，RSVPreF3预防RSV-A亚型和RSV-B亚型感染导致的LRTD的效力一致，分别为84.6%和80.9%。在研RSV疫苗类型多样此外，目前全球还有多款在研RSV预防疫苗，详见下表。在研RSV疫苗类型多样，包括减毒活疫苗（如MV-012-968）、载体疫苗（如JNJ-64400141、MVA-BN RSV）、亚单位疫苗（如GSK3888550A）、颗粒疫苗（如IVX-121）。全球部分在研RSV疫苗来源：药渡数据库GSKGSK在RSV领域布局广泛，除了Arexvy，还包括GSK3389245A和GSK3888550A。其中GSK3389245A是一款腺病毒疫苗，适用于婴幼儿和成人，但GSK于2021年自愿停止了临床研究。GSK3888550A是一款母体疫苗，2022年2月基于独立数据监测委员会（IDMC）常规安全评估观察结果，GSK宣布自愿暂停其用于母体免疫的3期GRACE试验入组和接种，同时暂停了另外两项在孕妇群体开展的临床试验。强生强生在RSV领域也有布局，其JNJ-64400141是应用腺病毒载体开发的一种RSV候选疫苗，2019年被FDA授予的突破性疗法认定。2021年强生宣布该疫苗在以65岁以上老年人为对象的2b期临床试验中达到了主要和关键性次要终点，预防下呼吸道疾病效力为80%。遗憾的是，今年3月，强生终止了JNJ-64400141的开发。公司表示此决定是为对管线和研发投资进行战略选择所做的更大的努力，以期专注于开发对患者有最大潜在益处的药物。ModernaModerna的mRNA-1345是一款编码病毒稳定融合前F糖蛋白的mRNA疫苗，其使用与Moderna的COVID-19疫苗相同的脂质纳米颗粒（LNP），并包含优化的蛋白质和密码子序列。2023年1月，Moderna宣布mRNA-2345的3期临床达到主要终点，对于2种或2种以上症状的保护率为83.7%。同月，mRNA-2345被FDA授予突破性疗法认定，用于预防60岁或以上成年人因RSV引起的LRTD。据悉，Moderna已决定于今年上半年向监管机构提交mRNA-1345的上市申请。Bavarian NordicBavarian Nordic开发MVA-BN RSV是一种基于MVA-BN载体的疫苗，能够进入哺乳动物细胞，表达病毒蛋白，但不能复制。MVA-BN RSV表达5种不同的RSV抗原，能够同时覆盖A型和B型RSV，这也是该产品与其他在研RSV疫苗的不同之处。2022年3月，优锐医药与Bavarian Nordic达成协议，以2.25亿美元获得Bavarian Nordic开发在中国、韩国和东南亚地区的开发和商业化权益。2023年4月，Bavarian Nordic宣布MVA-BN RSV全球3期临床试验已完成主要疗效分析所需的病例数积累，预计将于今年中完成该疫苗3期临床试验的主要疗效分析。经裁定的数据已经证实有足够的病例具有符合实验要求的2+和3+症状。CodagenixCodagenix的CodaVax-RSV™和Meissa的MV-012-968都属于减毒活疫苗，通过鼻喷给药。其中CodaVax-RSV™采用基因编辑的方式，可防止野生型回归。2022年11月，CodaVax-RSV被FDA授予快速通道资格。国内企业我国药企也积极布局RSV疫苗，其中艾棣维欣的ADV110进展较快，目前已进入2期临床。ADV110是一种含新型佐剂的RSV蛋白亚单位候选疫苗，旨在保护6个月至5岁的儿童及65岁以上的老年人。此前，艾棣维欣在澳大利亚完成的1期临床试验结果表明：ADV110在低剂量、高剂量，以及单次接种和两次接种均具备良好的安全性及耐受性，并且绝大多数受试者表现出显著的抗体应答，其中低剂量组达到90%、高剂量组达到100%的比例。RSV预防性抗体药物更早获批早在Abrysvo和Arexvy之前，RSV预防领域已批准3款药物，即RespiGam、Synagis（palivizumab）和Beyfortus（nirsevimab）。RespiGamRespiGam是含有高滴度RSV中和抗体的免疫球蛋白——RSV-IVIG，是各种抗体的混合物，1995年被FDA批准用于两岁以下高风险新生儿的RSV预防。但由于免疫球蛋白制备、使用不便，后来RespiGam被停用。SynagisSynagis是一种人源化的鼠单克隆抗体，通过结合病毒表面上的RSV融合蛋白而阻断膜融合过程，1998年6月被FDA批准用于支气管肺发育异常的婴幼儿、早产婴幼儿和血液动力学异常的先心病儿童预防下呼吸道RSV感染。Synagis（palivizumab）仅限于高危婴儿，只能提供一个月的保护，需要注射5次才能覆盖一个典型的RSV流行季。BeyfortusBeyfortus是赛诺菲和阿斯利康联合开发的的一款长效单克隆抗体，专为所有婴儿设计。2022年11月，该药被欧盟批准用于新生儿和婴儿，帮助他们在第一个RSV流行季到来时预防RSV引起的LRTI。此外，目前全球还有几款RSV预防性药物，如默沙东的MK-1654、泰诺麦博的TNM001。其中TNM001是我国首款独立自主开发的长效全人源抗RSV中和抗体药物，2021年8月在国内获批临床。TNM001将首先用于0-24个月的早产儿及婴幼儿的RSV感染的预防，只需要打一针即可保护整个RSV流行季。治疗、预防同等重要，RSV多款治疗药物取得新进展除了预防，RSV感染的治疗也很重要。据不完全统计，目前全球已有多款RSV治疗药物进入临床试验阶段，详见下表。这些药物除了干扰素制剂（如XW001），大多为RSV融合蛋白抑制剂，如AK0529、JNJ-53718678和Sisunatovir。全球部分在研RSV治疗药物来源：药渡数据库爱科百发的齐瑞索韦（AK0529）进展最快，目前已申报上市。该药是一种结构新颖的RSV融合蛋白小分子抑制剂，与病毒的融合蛋白结合从而阻止病毒侵入人体细胞，防止感染引起的疾病。同时，齐瑞索韦也可以阻止病毒通过细胞与细胞间的融合（即形成“合胞体”，一种RSV感染细胞的特征），从而实现抗病毒效果。2022年4月，齐瑞索韦在一项名为AirFLO的多中心3期临床试验获得积极结果，达到主要终点及关键次要终点。该试验旨在评估齐瑞索韦在中国1~24月大的中重度RSV感染住院婴幼儿中的疗效和安全性。在AIRFLO试验中，齐瑞索韦显示出快速的临床效果，在治疗第3天，齐瑞索韦的症状评分与安慰剂组相比多改善了30%。在RSV的重症高风险危险人群（即6个月以下的婴幼儿）中，齐瑞索韦表现出更显著的临床获益，症状评分与安慰剂相比多改善了55%。此外，在因RSV相关的严重疾病而收住ICU的患者中，齐瑞索韦显示出明显缩短ICU治疗时间的临床获益、减轻医疗经济负担的潜在效果，齐瑞索韦组ICU治疗时间平均为3天，安慰剂组为8天。同时，齐瑞索韦显示了明显的抗病毒效果：齐瑞索韦组在治疗第5天的病毒载量与对安慰剂组相比进一步降低77%；并且在整个治疗期间，齐瑞索韦组相对安慰剂组的病毒载量有显著降低。此外，治疗后6个月的随访数据显示，如果一开始就对于6个月或以下婴幼儿使用齐瑞索韦进行治疗，其后续出现再发喘息的几率明显低于安慰剂组（9.0% vs. 26.3%）。我国先为达生物的XW001是一种干扰素λ的吸入溶液，其在人源干扰素λ 1的基础上，经蛋白质工程优化，使得雾化吸入给药更加稳定。XW001具有独特的广谱抗病毒优势，临床前研究显示其可显著降低呼吸道合胞病毒、流感病毒、偏肺病毒等的复制。总结呼吸道合胞病毒（RSV）是一种常见的通过空气传播的RNA呼吸道病毒，是引起婴幼儿、老年人及免疫功能缺陷患者下呼吸道感染的重要病原体。据统计，每年RSV在全球成人中造成36万多人住院、2.4万多人死亡。自上世纪50年代发现RSV以来，由于安全性问题，RSV疫苗的开发多年没有取得突破性进展。纵观当前RSV预防治疗疫苗/药物进展，近两年RSV领域可谓喜讯连连，1款预防性抗体和2款预防性疫苗先后获批，治疗药物齐瑞索韦也已报产，而且多款在研产品处于临床后期。此外，鉴于丰富的在研RSV管线，未来RSV领域的竞争势必将非常激烈。END👇关注药渡数据媒体矩阵