MAGE-A3 vaccine(Mayo Clinic)

▎药明康德内容团队报道本周，生物医药行业又迎来许多新进展，例如：新锐公司AdvanCell、Aktis获得新一轮融资，它们均专注于开发靶向α粒子疗法；强生公司的BCMA/CD3双抗、BioMarin公司的血友病A基因疗法等获得欧盟委员会批准上市；爱尔康公司宣布将斥资约7.7亿美元收购Aerie公司，拓展产品管线等等。本文将节选其中部分重要进展做简单梳理，仅供读者参阅。✦新锐融资✦ Aktis Oncology公司宣布完成8400万美元的A轮扩展融资，将A轮融资总额提高到1.61亿美元，本轮的新投资方包括默沙东（MSD）的风投基金。此前，百时美施贵宝（BMS）公司和诺华（Novartis）参与了该公司的A轮融资。Aktis Oncology公司致力于开发创新靶向α粒子放射性药物，用于治疗实体瘤。该公司基于α粒子设计的肿瘤靶向放射性药物不但能够选择性地与肿瘤细胞结合，而且能够深入渗透到肿瘤内部，同时它们可以从身体的其它部分快速清除，将对健康组织的伤害降低到最低。AdvanCell公司宣布完成约1240万美元的B轮融资，该公司专注于开发靶向α粒子疗法。放射性核素靶向治疗（TRT）是一种能够在不影响肿瘤周围健康组织的情形下，将高剂量的放射素递送至肿瘤细胞或其微环境，并在放射素裂解过程杀死肿瘤细胞的疗法。TRT可使用包含α粒子、β粒子或Auger电子放射素，并将之与如单克隆抗体、多肽、小分子抑制剂等靶向载体偶联，以专一地靶向目标细胞。AdvanCell公司已开发出可扩展的生产平台，能够制造α放射同位素供研究、临床前与临床使用。3T Biosciences公司宣布完成4000万美元A轮融资。据介绍，该公司的3T-TRACE平台结合了具高度多样性靶标文库以及人工智能机器学习技术以识别新的靶标与T细胞受体（TCR）。该平台可以自病患检体当中识别具肿瘤专一性的抗肿瘤免疫反应，并发现在实体瘤中最普遍存在且具免疫抗原性的靶标。此外，3T Biosciences公司还宣布自斯坦福大学获得创新TCR模拟物发现平台以及尚处于开发阶段的MAGE-A3 TCR-T资产的独家授权，以快速扩展该公司的治疗管线。mRNA技术公司eTheRNA宣布获得了3900万欧元的B轮融资，该资金将用于扩大对其综合mRNA技术平台的投资，并进一步推行合作伙伴关系驱动的业务战略，战略重点包括定制脂质纳米颗粒（cLNP）。eTheRNA公司利用其专有的分子设计以及脂质生物化学方面的专业知识，能够设计和制造定制LNP及基于mRNA的T细胞佐剂来克服当前mRNA治疗剂开发所面临的挑战。在本轮融资进行的同时，Moderna Therapeutics联合创始人Kenneth Chien博士和拜耳及赛默飞前首席执行官Marijn Dekkers博士将加入公司董事会。✦新药进展✦ 强生（Johnson & Johnson）旗下杨森（Janssen）宣布，其开发的BCMA/CD3双特异性抗体Tecvayli（teclistamab）获得欧盟委员会有条件批准上市，作为单药疗法治疗复发/难治性多发性骨髓瘤成人患者，这是该药在全球范围内首次获得监管机构批准。值得一提的是，这也是今年全球范围内获得批准的第5款创新双特异性抗体/融合蛋白疗法。BioMarin公司宣布欧盟委员会批准其基因疗法Roctavian（valoctocogene roxaparvovec）有条件上市，用于治疗严重血友病A成人患者，这些患者没有携带凝血因子VIII抑制物或针对腺相关病毒5（AAV5）抗体的病史。新闻稿指出，这款一次性治疗是首款治疗血友病A的获批基因疗法，有望显著减轻患者的治疗负担。吉利德科学（Gilead Sciences）宣布，欧盟委员会已授予Sunlenca（lenacapavir）注射液和片剂的上市许可，用于联合其他抗逆转录病毒药物治疗多重耐药HIV感染的成人患者。Lenacapavir是一种具有多阶段作用机制的"first-in-class"衣壳抑制剂，对现有的其他药物类别没有已知的交叉耐药性，为不再对其当前疗法显示有效应答的HIV患者提供了一种新的、每6个月一次的治疗选择。强生旗下杨森和艾伯维（AbbVie）宣布，美国FDA批准BTK抑制剂Imbruvica（ibrutinib，伊布替尼）用以治疗1岁及以上、在经过至少一次系统性疗法失败后患有慢性移植物抗宿主病（cGVHD）的儿童病患，这是该药第一项获批的儿童适应症。值得一提的是，这是FDA为患有此危及生命疾病的年轻病患群体批准的首款疗法。Incyte公司宣布FDA批准其成纤维细胞生长因子受体（FGFR）抑制剂Pemazyre（pemigatinib）用于治疗带有FGFR1基因重组的复发或难治性髓系或淋巴系肿瘤（MLNs）成人患者。新闻稿指出，这是Pemazyre获批的第二项适应症，它成为首个获批用于治疗带有FGFR1基因重组的MLN患者的精准疗法。早先在一项多中心、开放标签、单臂临床2期试验中，Pemazyre使所有患者的完全细胞遗传缓解率达79%。武田（Takeda）宣布其登革病毒疫苗Qdenga（TAK-003）获印尼国家药物与食品管理局（BPOM）批准，用于6-45岁民众以避免任何血清型的登革热感染，这也是该疫苗在全球范围内首次获得批准上市。根据新闻稿，Qdenga为目前印尼首个获批不需经过接种前测试以及无论过去登革热暴露史为何的登革病毒疫苗。Apellis公司宣布其靶向补体C3在研药物pegcetacoplan在3期临床试验中的顶线积极结果。试验24个月时的数据显示，此药品用于治疗由年龄相关性黄斑变性（AMD）引起的地图样萎缩的疗效随着时间而增加。Pegcetacoplan是一种靶向补体C3的聚乙二醇化（PEGylated）双环肽疗法，已获FDA批准用于治疗阵发性睡眠性血红蛋白尿（PNH）。2022年7月，FDA已授予该药优先审评资格，用于治疗由年龄相关性黄斑变性引起的地图样萎缩。Blueprint Medicines公司宣布其药品Ayvakit（avapritinib）在PIONEER临床试验第二部分的积极顶线结果。数据显示，此药品在非晚期系统性肥大细胞增多症患者治疗上具有临床意义并显著的改善，并达成主要与所有的次要终点。基于此结果，Blueprint Medicines公司预计于2022年第4季度向FDA提交补充生物制品许可申请（sNDA），并于2023年向欧洲药品管理局（EMA）提出2型上市许可申请变更。辉瑞（Pfizer）公布其在研双价呼吸道合胞病毒（RSV）候选疫苗RSVpreF于RENOIR临床3期的积极顶线结果。RSVpreF为在研的RSV疫苗，是根据美国国立卫生研究院（NIH）所建立的RSV融合前（prefusion）F蛋白晶体结构所制造。根据预定的中期效力分析结果，辉瑞预计在2022年秋向FDA递交生物制品许可申请（BLA）。 ✦研发合作✦ 爱尔康（Alcon）和Aerie公司宣布双方已达成协议，爱尔康将斥资约7.7亿美元收购Aerie公司。爱尔康将获得已上市的产品Rocklatan（奈他舒地尔和拉坦前列素滴眼液）和Rhopressa（奈他舒地尔滴眼液），处于3期临床开发阶段的干眼病在研疗法AR-15512，以及Aerie公司的临床期和临床前眼科在研药物管线。新闻稿指出，这一收购将进一步扩展爱尔康的药物研发能力。李氏大药厂宣布从Windtree Therapeutics取得Surfaxin（KL4表面活性剂）、Surfaxin LS（冻干KL4表面活性剂）、AEROSURF及任何其他含有合成KL4表面活性剂的医药组成物的独家全球开发、生产及商业化权利。协议中的3款产品主要用于改善早产婴儿呼吸窘迫综合征的管理。为此，Windtree公司将获得高达7890万美元的开发、监管和商业里程碑付款以及特许权使用费。本文来自药明康德内容团队，欢迎个人转发至朋友圈。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

Cancer Research UK, Vaccitech plc (Nasdaq: VACC) and the Ludwig Institute for Cancer Research (Ludwig), today announce the first patient dosed in the MAGE trial, which is testing a novel immunotherapeutic, VTP-600, in patients with the most common type of lung cancer. The phase I/IIa trial is expected to enroll approximately 86 people who have been newly diagnosed with non-small cell lung cancer (NSCLC) and will be testing the safety and initial efficacy of VTP-600 in these patients. VTP-600 will be given in combination with the current first line treatment for NSCLC. If further clinical trials are successful, VTP-600 could prove to be a powerful new treatment for a group of patients in need of better options. Depending on its effectiveness in NSCLC, VTP-600 could be evaluated in other types of cancer in the future, including breast, bowel, bladder and melanoma. Cancer Research UK’s Centre for Drug Development (CDD) is managing and providing significant funding for the phase I/IIa trial. Vaccitech Oncology Limited (VOLT), a strategic collaboration between Vaccitech and Ludwig, are supplying VTP-600 for the trial. The Chief Investigator for the trial is Professor Fiona Blackhall, Professor of Thoracic Oncology and Honorary Consultant in Medical Oncology, at The Christie NHS Foundation Trust. VOLT holds an option to license the results of the trial to aid future clinical development and commercialisation of the immunotherapy. If VOLT elects not to exercise its option, Cancer Research UK will have the right to take the programme forward in all cancer indications. Unlike preventative vaccines, such as the influenza vaccine, which is given to healthy people to protect them against future disease, VTP-600 is given to people who already have lung cancer. VTP-600 is an immunotherapy, designed to stimulate the body’s immune system to attack cancer cells. It does this by delivering cancer-associated proteins — known as MAGE-A3 and NY-ESO-1 antigens — to antigen presenting cells (dendritic cells), causing the immune system to produce cytotoxic T cells which are able to target and kill cancer cells expressing these antigens. It cannot target healthy tissues because MAGE-A3 and NY-ESO-1 are not found on non-cancerous cells. VTP-600 is a ‘prime-boost’ immunotherapy, meaning an initial ‘prime’ dose is administered, and then a second ‘booster’ dose is given 21 days later. This ‘prime-boost’ approach is expected to improve the size and length of the anti-cancer immune response. Even though two doses are administered, the immunotherapy comprises three parts. ChAdOx1-MAGE-A3-NY-ESO-1 is the prime immunotherapy administered to all patients, MVA MAGE-A3 with or without MVA NY-ESO-1 is given as the second booster immunotherapy, depending on the type of antigens expressed on the patient's tumour. In the prime dose, ‘ChAdOx1’ refers to the viral vector used in the vaccine to deliver the antigens. It is a virus which causes a common cold in chimpanzees, but it has been modified so that it can no longer cause disease. ChAdOx1 is the same viral vector used in the Oxford/AstraZeneca Covid-19 vaccine (which was co-invented by Vaccitech) and is being used in phase II trials for other diseases. In the boost doses, ‘MVA’ is a second viral vector containing the MAGE-A3 or NY-ESO-1 antigens, and is a Modified Vaccinia Ankara virus, which is a type of poxvirus which has been severely weakened so that it can no longer cause disease. The trial is expected to run over 2-3 years. More information on the clinical trial can be found at NCT04908111. Dr Nigel Blackburn, Director of Cancer Research UK’s Centre for Drug Development, said: “We are excited to see that the first patient has been treated with the VTP-600 immunotherapeutic vaccine. NSCLC is the most common type of lung cancer but remains very hard to treat. If successful, this cutting-edge immunotherapy could provide an effective, much-needed new treatment to help more people survive their lung cancer. “Partnering with Vaccitech and the Ludwig Institute was vital for making this trial a reality, and we are looking forward to seeing how the trial progresses.” Chief investigator for the MAGE clinical trial, Professor Fiona Blackhall, who is consultant medical oncologist and director of research and innovation at The Christie NHS Foundation Trust, said: “There is an urgent need to find better treatments for patients with NSCLC. The VTP-600 immunotherapeutic vaccine is a cutting-edge technology to target a patient’s immune system to tackle the cancer cells. The trial is planned to open at 10 specialist hospitals across the UK to ensure that as many patients as possible can be given opportunity to participate.” Vaccitech’s CEO, Bill Enright, said: “We are delighted with the start of this trial, arising from our clinical development partnership with two of the world’s most prestigious cancer research institutions. We’ve seen how our viral vector has transformed the world’s approach to sars-cov2 and has shown promising early results in chronic hepatitis B virus infection. We see this partnership as another important validation of our prime boost platform’s utility in oncology as well as infectious disease.” “We are pleased that the research arising from the Ludwig Oxford Branch and their colleagues at Oxford University is being tested in this clinical trial to evaluate the benefit it may bring to patients with NSCLC and potentially other cancer patients as well,” added Jonathan Skipper, Executive Vice President for Technology Development, Ludwig Institute for Cancer Research. About Cancer Research UK’s Centre for Drug Development Cancer Research UK has an impressive record of developing novel treatments for cancer. The Cancer Research UK Centre for Drug Development has been pioneering the development of new cancer treatments for 25 years, taking over 140 potential new anti-cancer agents into clinical trials in patients. It currently has a portfolio of 21 new anti-cancer agents in preclinical development, Phase I or early Phase II clinical trials. Six of these new agents have made it to market including temozolomide for brain cancer, abiraterone for prostate cancer and rucaparib for ovarian cancer. Two other drugs are in late development Phase III trials. About Cancer Research UK Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on every donation made. Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years. Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK’s ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years. Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured. For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit . About Ludwig Cancer Research Ludwig Cancer Research is an international collaborative network of acclaimed scientists that has pioneered cancer research and landmark discovery for 50 years. Ludwig combines basic science with the ability to translate its discoveries and conduct clinical trials to accelerate the development of new cancer diagnostics and therapies. Since 1971, Ludwig has invested nearly $3 billion in life-changing science through the not-for-profit Ludwig Institute for Cancer Research and the six U.S.-based Ludwig Centers. About Vaccitech Vaccitech is a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutic and vaccines for the treatment and prevention of infectious diseases, cancer & autoimmune diseases. The company’s proprietary platforms comprise proprietary modified simian adenoviral vectors, known as ChAdOx1 and ChAdOx2, the well-validated Modified Vaccinia Ankara, or MVA, boost vector, both with demonstrable tolerability profiles and without the ability to replicate in humans, and the SNAPvax™ and Syntholytic™ polymer-based platforms. The combination of a ChAdOx prime treatment with subsequent MVA boost has consistently generated significantly higher magnitudes of CD8+ T cells compared with other technologies and approaches. The company has a broad pipeline of both clinical and preclinical stage therapeutic programs in solid tumors and viral infections and prophylactic viral vaccine programs. Vaccitech co-invented a COVID-19 vaccine with the University of Oxford, now approved for use in many territories and exclusively licensed worldwide to AstraZeneca through Oxford University Innovation, or OUI. Vaccitech is entitled to receive a share of the milestones and royalty income received by OUI from AstraZeneca. About Vaccitech Oncology Ltd. Vaccitech Oncology Limited (VOLT) is the oncology focused strategic collaboration of Vaccitech and the Ludwig Institute for Cancer Research, an international non-profit organization that conducts innovative cancer research to prevent, detect and control cancer. VOLT continues to pioneer immunological research in oncology and is looking to enable the clinical development of cutting-edge new treatments that induce and harness CD8+ T cells of the immune system to fight cancer.