Agenus, Inc.

NEW YORK, Oct. 31, 2024 (GLOBE NEWSWIRE) -- MiNK Therapeutics (MiNK, NASDAQ: INKT), a clinical-stage company pioneering the development of allogeneic off-the-shelf, invariant natural killer T (iNKT) cell therapies, today announced the appointment of Dr. Robert Kadlec to its Board of Directors. Dr. Kadlec brings unparalleled expertise in biodefense, pandemic preparedness, and public health strategy, positioning MiNK to accelerate its innovative iNKT cell platform for addressing critical infectious diseases, including pathogen-agnostic acute respiratory distress syndrome (ARDS), emerging threats, and immune related diseases. Dr. Kadlec recently served as the U.S. Senate-confirmed Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS) where he led interagency responses to public health emergencies and natural disasters. During the COVID-19 pandemic, Dr. Kadlec co-conceived and initiated the vaccine program known as Operation Warp Speed and directed the pandemic response on behalf of HHS. A retired career Air Force officer and physician, he earlier served senior roles in the White House, U.S. Senate, and Department of Defense. His prior roles as Deputy Staff Director for the Senate Select Committee on Intelligence and his work on the Pandemic and All-Hazards Preparedness Act and PREVENT Pandemics Act exemplify his commitment to advancing U.S. health security. Dr. Kadlec previously directed the biodefense strategy at the White House, leading initiatives that shaped national policy for public health emergencies. “We are thrilled to welcome Dr. Kadlec to our Board of Directors,” said Jennifer Buell, PhD, Chief Executive Officer and President of MiNK Therapeutics. “As we continue to demonstrate the transformative potential of iNKT cells as a pathogen-agnostic approach to ARDS and other immune-related conditions, Dr. Kadlec’s unparalleled expertise in public health and biodefense will be instrumental in advancing our strategic vision. His deep understanding of public health systems, coupled with his proven track record of driving innovation in medical countermeasures, makes him the ideal partner to guide MiNK through our next phase of growth. Together, we aim to harness the power of iNKT cells to address some of the most urgent challenges in global health.” Dr. Kadlec holds a bachelor’s degree from the United States Air Force Academy, a Doctor of Medicine and a master’s degree in tropical medicine and hygiene from the Uniformed Services University of the Health Sciences, as well as a master’s degree in national security studies from Georgetown University. About MiNK Therapeutics MiNK Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery, development, and commercialization of allogeneic invariant natural killer T (iNKT) cell therapies to treat cancer and other immune-mediated diseases. MiNK is advancing a pipeline of both native and next generation engineered iNKT programs, with a platform designed to facilitate scalable and reproducible manufacturing for off-the-shelf delivery. The company is headquartered in New York, NY. For more information, visit https://minktherapeutics.com/ or @MiNK_iNKT. Information that may be important to investors will be routinely posted on our website and social media channels. Forward Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding the therapeutic potential, anticipated benefit, plans and timelines of iNKT cells and encrypted RNA, as well as the collaboration between MiNK and Autonomous Therapeutics. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These forward-looking statements are subject to risks and uncertainties, including the factors described under the Risk Factors section of the most recent Form 10-K, Form 10-Q and the S-1 Registration Statement filed with the SEC. MiNK cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and MiNK and Autonomous undertake no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Investor Contact 917-362-1370 investor@minktherapeutics.com Media Contact 781-674-4428 communications@minktherapeutics.com

2021年8月，吉利德科学旗下公司Kite Pharma（下称“Kite”）和早期生物技术公司Appia Bio宣布达成一项合作和许可协议，以研发用于治疗血液恶性肿瘤的造血干细胞（HSC）衍生细胞疗法。合作将利用Appia Bio的“ACUA”同种异体细胞疗法技术平台，开发表达嵌合抗原受体的恒定自然杀伤T细胞（CAR-iNKT）疗法。 根据协议条款，Appia Bio将负责利用Kite提供的CAR进行两个HSC衍生CAR-iNKT候选疗法的临床前和早期临床研究。Appia Bio将获得总额高达8.75亿美元的预付款、股权投资，以及额外的里程碑付款和分级版税。而Kite将负责确定的候选产品的后续开发、生产和商业化。 Kite为全球CAR-T细胞疗法的先行者，其动向一定程度上也能反应CAR-T细胞疗法的未来发展趋势，而同种异体CAR-T（或称通用型CAR-T）正是未来细胞疗法的重要发展方向。 01 批量化生产，攻破制备痛点 深得Kite垂青的通用型CAR-T疗法公司Appia Bio于2020 年在加利福尼亚州洛杉矶成立。当地时间2021年5月11日，Appia Bio完成5200万美元A轮融资，正式走出隐匿模式。该轮融资由8VC牵头，8VC的合伙人Francisco Gimenez博士和8VC的负责人David Moskowitz博士也加入了公司董事会。此外，加州理工学院博士的David Baltimore博士被任命为董事会主席。 Appia由诺贝尔奖获得者和加州理工学院前院长David Baltimore博士共同创立，包括南加州大学（USC）化学工程与材料科学与生物医学工程教授Wang Pin博士、加州大学洛杉矶分校微生物学，免疫学和分子遗传学副教授Lili Yang博士。其中，Lili Yang博士带来了关键技术：如何从单次造血干细胞中收获大量的iNKT细胞，由此，Appia Bio可以从单个供体来源制造大量的治疗性细胞以治疗多位患者。 提及通用型CAR-T疗法的开发，就不能绕过现有自体CAR-T疗法的局限性。 首先，CAR-T疗法价格昂贵。以诺华的CAR-T细胞治疗技术为例，一次治疗费用为47.5万美元，折合人民币约330万元；国内方面，中国复星凯特生物科技有限公司引入的阿基仑赛注射液零售价为120万元/袋。 尽管随着越来越多的CAR-T药品面市以及标准化、规模化的生产，免疫细胞治疗费用也有望降低，但个性化的细胞治疗产品仍需要耗时的制造程序，依赖于离体基因转移方案。评估患者条件并完成外周血抽血后，后续流程还包括离T细胞、改造T细胞（即将T细胞改造为CAR-T细胞）、分离扩增CAR-T细胞、回输、监控反应等。这种复杂的制造过程导致成本高居不下。 另一方面，目前自体CAR-T细胞疗法为定制化生产（以患者自体血液中T细胞为材料），从收集患者T细胞到CAR-T细胞到成功制备大概要经历2-3周，有错过患者最佳治疗时期的风险。因此，研究者开始考虑同种异体CAR-T细胞，即通用型CAR-T（UCAR-T）。通用型CAR-T最大的优势就是可以提前制备，当患者有需要时可以及时使用，极大地降低了金钱成本和时间成本。 通用型CAR-T的优势在于使得原本昂贵的定制产品可以“批量化生产”，进而分摊成本，降低价格同时缩短治疗时间。具体而言，先从健康供体内获得T细胞，对其进行基因编辑改造，再采用液氮等手段长期保存成品。 Appia Bio的特殊之处在于从造血干细胞开始利用iNKT细胞。通过公司的ACUA（Appia Cells Used for Allogeneic）技术平台，不仅可以可以产生大量的iNKT细胞，还支持以可拓展的、完全离体的方式进行生产，且无需基因编辑或纯化步骤。该平台为Appia Bio的通用型CAR-T疗法实现工业化、商业化提供了潜在的支持。 02 iNKT细胞的扩增 前文提到，Lili Yang博士带来了Appia Bio核心技术，即扩增iNKT细胞。 iNKT（恒定自然杀伤T细胞）属于NKT（异源性自然杀伤T细胞）细胞群，具有T细胞和 NK细胞（自然杀伤细胞）的特性，有助于衔接先天和适应性免疫反应。NKT细胞于1986年被发现，在很长时间里并没有得到重视，直到近些年因NKT细胞的独特性才被重视。 iNKT细胞是CD1d限制性T淋巴细胞，它利用不变的T细胞受体（TCR）α 链和有限的TCR β 链库来识别特定的脂质抗原。研究发现它们对脂质抗原刺激反应迅速（数几分钟内），根据刺激分泌不同类型的细胞因子。iNKT细胞是最早对致病性刺激作出反应的细胞类型之一，其细胞因子的产生有助于确定免疫反应的进程。 此外，iNKT细胞在抗肿瘤免疫过程中发挥调节作用，被激活后可通过分泌细胞因子，活化其它免疫细胞参与先天性免疫和获得性免疫。此外，由于独特的抗原识别方式，iNKT细胞不会引发移植物抗宿主病，因而在近期的研究中被作为癌症免疫治疗的潜在靶点。 与常规T细胞一样，iNKT细胞在胸腺中发育。在人外周血中，iNKT细胞占循环T细胞的约 1%，而在人体脂肪组织中，可多至约10-25%。在人体肝脏中，iNKT细胞则非常少见，非恒定或多样化NKT（dNKT）细胞在人肝脏中占主导地位。与人体脂肪组织中的情况一样，小鼠脂肪组织中 iNKT 细胞的占比约为10-25%。 因此，像传统的CAR-T疗法一样，从患者体内分离iNKT细胞生成CAR-iNKT细胞疗法面临很大挑战。 为此，Lili Yang博士带领团队开发出了一种新的临床指导方法，旨在设计更强大的iNKT细胞的免疫细胞，用于通用型细胞治疗肿瘤。相关研究结果于2024年5月发表在Nature Biotechnology期刊上，论文标题为“Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method”。 更早之前，即2021年，在Appia Bio成立不久后，Lili Yang博士团队就公布了一种利用造血干细胞生产大量iNKT细胞的方法。然而，由于这种制备方式需要使用三维胸腺类器官和支持细胞，给生产和监管环节带来了挑战，临床应用一度受阻。如今，随着论文的发布，团队展示了一项新技术，在无饲养细胞和无血清条件下，利用造血干细胞产生大量iNKT细胞，避免了类器官方式等在生产和监管环节的顾虑。 团队从15份代表不同遗传背景的捐献者脐带血样本中分离出造血干细胞，它们可以自我复制并产生各种血细胞和免疫细胞。据估计，一次脐带血捐献可产生1000到10000剂量的治疗药物，因此非常适用于通用型细胞治疗这种“现货型”免疫疗法。随后，团队为iNKT细胞配备了嵌合抗原受体（CAR），以便免疫细胞识别并杀死特定类型的癌症，靶向治疗包括血癌和实体瘤在内的七种癌症。 论文指出，由此产生的CAR-iNKT细胞对所有七种癌症都显示出了强大的抗肿瘤功效，这表明它们有望治疗多种癌症。随后在多发性骨髓瘤模型中，团队展示了CAR-iNKT细胞阻止肿瘤生长的能力，且不会引起供体细胞移植到患者体内时可能出现的并发症。 团队认为，以iNKT细胞为基础的通用型细胞治疗，不仅有望成为肿瘤治疗的手段，还会成为理想手段。关键在于，现有的大多细胞疗法会产生移植物抗宿主病，而临床前研究中显示，异体CAR-iNKT细胞暂且不会有移植物抗宿主病的风险。不过论文也指出，疗法必须根据患者的具体情况来设计并优化。 03 联手吉利德，API-192已有进展 当前，Appia Bio凭借其ACUA技术平台，利用嵌合抗原受体（CAR）和T细胞受体（TCR）基因工程的淋巴细胞发育生物学，从造血干细胞生成CAR-iNKT细胞。根据已有研究，采用造血干细胞生产iNKT细胞的生产量可以达到万亿级，且实现了99%以上的HSC-iNKT细胞表现为CD4-CD8+/-（CD8 SP/DN）表型，基本不包含内源性人类iNKT细胞中存在的CD4+CD8-(CD4 SP)群体，而目前多篇文献已经报道CD8 SP/DN人类iNKT细胞被认为是iNKT亚群中抗肿瘤活性最强的亚群，是癌症免疫治疗的理想选择。 Appia Bio的在研管线针对适应症包括自免疾病、多发性骨髓瘤和实体瘤，目前自免疾病相关管线进展最快。 值得一提的是，2023年12月，Appia Bio在第65届美国血液学会年会暨博览会上展示了和吉利德旗下Kite合作许可协议中第一个开发的候选品API-192的数据。API-192由Appia Bio专有的ACUA平台开发，是一种同类首创的现通用型CAR-NKT细胞疗法，表达靶向两种常见B细胞抗原CD19和CD20的双嵌合抗原受体（CAR），并载有可溶性IL-15以改善扩增和持久性。 此外，MiNK Therapeutics、Athenex均有iNKT疗法管线在研。其中Athenex曾收购通用型CAR-NKT细胞免疫疗法公司Kuur Therapeutics，后者的CAR-NKT产品有三款，分别为KUR501、KUR502和KUR503，其中进展最快的KUR501和KUR502已进入临床阶段。 MiNK Therapeutics拥有新型工程化iNKT细胞疗法和双特异性iNKT细胞接合器（cell engagers）平台，针对肿瘤和自免疾病布局管线，适应症包括实体瘤、复发或难治性多发性骨髓瘤、移植物抗宿主病（GvHD）、新冠肺炎继发的急性呼吸窘迫综合征（ARDS）。 虽然目前已有海外企业布局iNKT赛道，iNKT的相关研究也振奋人心，但iNKT行业整体还处于早期阶段，技术相对都不成熟，国内方面，厚朴生物科技及西安国际医学等企业在该领域有所布局，此外暂未看到企业公布通用型iNKT细胞疗法管线动态。 作为异体来源的通用型CAR-T细胞疗法依然面临免疫排斥、体内扩增不够等诸多问题。截至目前，未有一款通用型CAR-T细胞疗法产品上市，国内进展较快的企业北恒生物、亘喜生物、传奇生物和茂行生物等。因此，通用型CAR-iNKT治疗能否成为一众通用细胞疗法中的佼佼者或早一步实现弯道超车，还需等待进一步临床数据。 如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台

24 October 2024 Single dose of vaccine elicited robust immune response with acceptable safety profile in adults aged 18-49 at increased risk for RSV-LRTD Two doses of vaccine in immunocompromised adults aged 18 and above elicited immune responses similar to one dose in healthy adults aged 50+ and with an acceptable safety profile In the US alone, adults aged 18-49 with at least one risk factor for RSV disease could exceed 21 million1 GSK plc (LSE/NYSE: GSK) today announced new preliminary data for Arexvy (respiratory syncytial virus vaccine, recombinant adjuvanted) in adults aged 18-49 at increased risk for RSV-LRTD due to certain underlying medical conditions and in adults who are immunocompromised. These data show the vaccine’s potential to help protect a broader group of adults at risk from the potentially serious consequences of RSV. In the US alone, the number of adults aged 18-49 with at least one risk factor that could put them at risk for RSV disease could exceed 21 million.1 The vaccine is currently approved for use in adults aged 60 and above in over 50 countries, and in adults aged 50-59 at increased risk in a number of countries including the US and Europe*. There are currently no RSV vaccines recommended for adults younger than 60 years of age who are at increased risk for RSV disease, despite the burden of disease in this population. Tony Wood, Chief Scientific Officer, GSK, said: “These promising data add to the evidence supporting GSK’s RSV vaccine and could help expand protection to more adults at risk from RSV disease. They also provide valuable insights into the potential impact of a second dose for certain populations. We’re committed to working with health authorities and regulators to help adults at increased risk of RSV disease benefit from vaccination.” In the phase IIIb trial (NCT063894872) a single dose of the vaccine elicited robust immune responses in adults aged 18-49 at increased risk for RSV-LRTD due to certain underlying medical conditions (n=395). The immune response was non-inferior to that observed in adults aged 60 and above (n=417), meeting the trial’s co-primary endpoints. In the phase IIb trial (NCT059219033) a single dose of the vaccine showed a robust immune response in adults aged 18 and above who are immunocompromised due to kidney or lung transplant (n=131), with a second dose (n=130) eliciting responses similar to those of healthy adults aged 50 and older who received one dose (n=125). These immune responses were consistent for RSV-A and RSV-B subtypes in all groups (those who received 1 or 2 doses). These data will be presented today at the meeting of the CDC’s Advisory Committee on Immunization Practices. In both studies, the safety and reactogenicity data were consistent with results from the phase III programme that have supported the initial approval of the vaccine. The most common local adverse event was pain, and most common systematic adverse events were fatigue, myalgia, arthralgia and headache, most of which were transient and mild in intensity. RSV is a common, contagious virus that can cause severe respiratory illness and impacts an estimated 64 million people of all ages globally every year.4 Immunocompromised people and those with certain underlying medical conditions, such as chronic obstructive pulmonary disease (COPD), asthma, heart failure and diabetes are at increased risk for severe consequences from an RSV infection compared to those without these conditions,5,6 including having a higher risk of mortality.7 Final results from these trials will be presented at upcoming medical conferences and submitted for peer-reviewed publication. The final data will also be submitted to the US Food and Drug Administration (FDA) and other regulators to support potential label updates. About the trial designs NCT06389487 is a phase IIIb open-label study to evaluate the non-inferiority of the immune response and to evaluate the safety of the GSK’s RSV vaccine in adults aged 18-49 at increased risk for RSV disease (n=395) compared to adults aged 60 and older (n=417). 1,457 participants were enrolled across 52 locations in 6 countries. The trial’s co-primary endpoints were RSV-A and RSV-B neutralisation titers expressed as mean geometric titer ratio (relative to older adults over adults at increased risk) and sero-response in RSV-A and RSV-B neutralising titers one month post vaccine administration. There were also safety and immunogenicity secondary endpoints. An additional cohort of 601 participants aged 18-49 were followed up for adverse events separate to safety follow up of the initial cohort. The study is ongoing to collect further safety and immunogenicity data up to 6 months post vaccination and is expected to finish in 2025. NCT05921903 is a phase IIb, randomized, controlled, open-label, multi-country study to evaluate the immune response and safety of GSK’s RSV vaccine in adults (≥18 years of age) who are immunocompromised due to lung and renal transplant, comparing 1 versus 2 doses (1 dose, n=131, 2 doses, n=130) one month (30-42 days) after the second vaccine administration compared to a control group of non-immunocompromised adults aged 50 and above receiving a single dose of GSK’s RSV vaccine (n=125 non-immunocompromised adults aged 50 and above). 386 participants were enrolled across 48 locations in 8 countries. The trial’s co-primary endpoints were RSV-A and RSV-B neutralisation titers following a first and a second dose of GSK’s RSV vaccine expressed as mean geometric increase post dose 2 relative to post dose 1 at approximatively one month. There were also safety and immunogenicity secondary endpoints. The study is ongoing to collect further safety and immunogenicity data up to 12 months post last dose and is expected to finish in 2025. About GSK’s RSV vaccine Respiratory Syncytial Virus Vaccine, Adjuvanted, contains recombinant RSV glycoprotein F stabilised in the prefusion conformation (RSVPreF3). This antigen is combined with GSK’s proprietary AS01E adjuvant. The use of this vaccine should be in accordance with official recommendations. As with any vaccine, a protective immune response may not be elicited in all vaccinees. The vaccine has been approved for the prevention of RSV-LRTD in individuals 60 years of age and older in more than 50 countries, including Europe, Japan and US. In addition, it is approved in the US and EU/EEA countries for use in individuals aged 50-59 who are at increased risk due to certain underlying medical conditions. Regulatory reviews for this extended indication are also undergoing review in other countries – including Japan. The proposed trade name remains subject to regulatory approval in other markets. The GSK proprietary AS01 adjuvant system contains STIMULON QS-21 adjuvant licensed from Antigenics Inc, a wholly owned subsidiary of Agenus Inc. STIMULON is a trademark of SaponiQx Inc., a subsidiary of Agenus. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. Cautionary statement regarding forward-looking statements GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in GSK’s Annual Report on Form 20-F for 2023, and GSK’s Q2 Results for 2024. References You might also like