BNT-211

据BBC 2024年4月26日报道， mRNA-4157 （一种个性化癌症疫苗）与 派姆单抗 （Keytruda）联用，治疗 已经切除的高风险IIB至IV期黑色素瘤的3期临床试验 ， 已在伦敦大学学院（UCL）医院招募了首批患者。 去年美国癌症研究协会（AACR）大会报告的数据显示，与单独使用Keytruda治疗相比， mRNA-4157可在18个月内将复发或死亡率降低62% 。 其中，音乐家史蒂夫·杨（Steve Young）作为首批报名参加临床试验的患者，已顺利完成了疫苗接种治疗。现年52岁的Steve于去年8月确诊为 II期黑色素瘤 ，尽管当时接受了手术切除治疗，但仍然可能存在尚未被发现的癌细胞。他在接受英国BBC节目采访时表示“ 我很幸运能参与这项临床试验，这让我并没有坐以待毙，而是真正做一些事情来对抗一个潜在的、看不见的敌人，这是我阻止癌症复发的最好机会！ ” ▲图源“BBC”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 mRNA-4157显著延长生存期，远处转移/死亡风险降低62% mRNA-4157（V940）是一种 新型mRNA个体化新抗原疗法（INT） ，根据患者肿瘤DNA序列的独特突变特征设计并生产的，由合成mRNA（编码34种新抗原）组成。注射到体内后，会产生特定的T细胞反应，使其训练和激活抗肿瘤免疫反应，从而识别和攻击特定的癌细胞，最终达到防治黑色素瘤的目的。 在2023年ASCO（美国临床肿瘤学会）会议上，公布了“ mRNA-4157（V940）联合派姆单抗（Keytruda），治疗高危III/IV期黑色素瘤 ”的IIb期临床试验结果。基于该惊艳结果，mRNA-4157疫苗已 被美国FDA授予“突破性认定” 。 本次研究共纳入157例 完全切除的高风险皮肤黑色素瘤（Ⅲ B/C/D和Ⅳ期） 患者，并将其分为两组，即 派姆单抗单药治疗组 (n=50)、 mRNA-4157疫苗与派姆单抗联合治疗组 （n=107）。治疗18个月后结果显示： 1、 无复发生存期（RFS） ：与派姆单抗单药治疗组相比，mRNA-4157联合治疗组患者的 无复发生存期明显延长 ，18个月RFS率分别为 62.2% （单药治疗组）、 78.6% （联合治疗组）。 2、 无远处转移生存期（DMFS） ：与派姆单抗单药治疗组相比，mRNA-4157联合治疗组患者的 无远处转移生存期明显延长 。18个月DMFS率分别为 76.8% （单药治疗组）、 91.8% （联合治疗组）。 综上，mRNA-4157疫苗与派姆单抗联用， 将高危III/IV期黑色素瘤患者的远处转移或死亡风险降低了62%，复发或死亡风险降低了49% ，显著改善了患者的生存期！ 据全球肿瘤医生网小编获悉，目前 mRNA-4157的Ⅲ期临床试验（V940-001，NCT05933577）已经启动 ，旨在评估mRNA-4157与派姆单抗联合应用，治疗1089例高风险（IIB-IV期）黑色素瘤的疗效及安全性，并计划迅速扩展到非小细胞肺癌等其他肿瘤类型。本文开头提到的Steve，参加的就是mRNA-4157的Ⅲ期临床试验，并且幸运的成为了首批接种者。mRNA-4157也有望成为首款上市的mRNA肿瘤疫苗，最早将于2025年问世！ 如何寻求mRNA或其他癌症疫苗帮助？ 目前有两款mRNA癌症疫苗（JCXH-211注射液、ABO2011注射液）的临床试验，正在招募 肺鳞癌、肝癌、结直肠癌、黑色素瘤、食道癌、三阴性乳腺癌、头颈部肿瘤 等多款恶性实体瘤患者。 想参加上述临床试验的病友，可将近期病理报告、影像学或血液检查、治疗经历等相关资料，提交至全球肿瘤医生网医学部！ mRNA抗癌疫苗：“定制版”新型免疫治疗方法 mRNA（信使核糖核酸疫苗）疫苗是一类 新型免疫治疗策略 ，通过编码 免疫反应过程的关键成分 ，包括 肿瘤特异性抗原（TSA）、肿瘤相关抗原（TAA）、免疫调节因子 ，每种类型都涉及疫苗内化到细胞中、转录编码选定靶标的mRNA序列、递送至免疫细胞，从而促进免疫系统激活，以达到杀伤肿瘤细胞的目的（详见图1）。 图1 mRNA癌症疫苗的作用机制 ▲图源“frontiers”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 与传统的灭活病原体或基于蛋白质的疫苗相比，治疗性mRNA癌症疫苗能 提供更强的细胞或体液免疫 ，而且具有 免疫原性强、开发快速、成本低、安全灵活 等优点。目前，多款mRNA癌症疫苗的I/II期临床试验正在进行中，早期结果令人鼓舞，适用于 黑色素瘤、非小细胞肺癌（NSCLC）、结直肠癌（CRC） 等多款侵袭性/转移性实体瘤。下图展示了mRNA癌症疫苗的综合设计和生产过程，主要包括 样本采集、基因测序和靶标识别、mRNA序列设计、疫苗生产、最终疫苗产品给药 等治疗流程。 图2 mRNA癌症疫苗的综合设计和生产过程 ▲图源“frontiers”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 多款mRNA疫苗，精准打击实体瘤 BNT122：胰腺癌新利器，中位无复发生存时间长达13.4个月 BNT122（RO7198457，自体cevumeran）是一款可 编码20余种特异性新抗原的个体化新抗原mRNA疫苗 ，可用于治疗 胰腺导管腺癌（PDAC） ，以 降低复发率，延长生存时间 。 世界权威期刊《Nature》报道了“ BNT122治疗胰腺导管腺癌的Ⅰ期惊艳临床研究结果 ”，本次共入组34例患者（其中28例接受过手术治疗）。19例患者在术后接受 Atezolizumab（阿替利珠单抗） 治疗，其中部分患者随后接受 BNT122疫苗接种 （16例）、 改良版四药化疗方案 （mFOLFIRINOX，包括亚叶酸、氟尿嘧啶、奥沙利铂、伊立替康）治疗（15例）。 结果显示，8例无应答患者的 中位无复发生存时间（RFS）达13.4个月之久 。值得一提的是，其中29号患者治疗后短暂出现血清CA19-9水平升高、新的肝脏病变（7mm），但该病变在随后的影像学检查中消失了，这表明该疫苗可能具有 根除微转移病灶的能力 （详见图2）。 图2 接种BNT122疫苗前后患者腹部MRI对比 ▲图源“nature”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 总之，上述Ⅰ期临床数据表明，BNT122与mFOLFIRINOX+Atezolizumab联用是安全可行的，且疫苗扩增的T细胞，有助于预防肿瘤复发。 BNT211：mRNA疫苗联合CAR-T暴击实体瘤，疾病控制率达67% BNT211是BioNTech公司研发的一款 独特的CAR-T细胞扩增mRNA疫苗相结合的治疗方法 ，将 靶向CLDN6 （癌胚抗原的一种，在多种实体瘤中高度特异性表达） 抗原的CAR-T细胞疗法 ，与 表达CLDN6抗原的mRNA疫苗（CARVac） 相结合，疫苗的注射有助于将全身RNA，递送至淋巴器官中的抗原呈递细胞（APC），从而增强抗癌效果。 世界知名期刊《自然医学（nature medicine）》报道了“ BNT211-01的1/2期临床试验结果（NCT04503278） ”，旨在评估CLDN6 CAR-T细胞单独使用，及与CARVac联合使用，对复发或难治性CLDN6阳性实体瘤的治疗效果。本次接受治疗的22名复发或难治性CLDN6阳性实体瘤患者中，13例为 睾丸癌 、4例为 浆液性癌 ，此外， 胃腺癌、子宫内膜癌、促纤维化小圆细胞瘤（DSRCT）、输卵管浆液性癌、原发性不明癌 各1例。 治疗后，在21可评估疗效的患者中，结果显示， 客观缓解率（ORR）达到33% （详见下图）。在较高剂量水平下治疗的生殖细胞肿瘤患者的反应率最高， ORR高达57% 。其中， 6例患者达到部分缓解（PR） ；另有 1例 幸运患者奇迹般的获得 完全缓解（CR） 。数据截止时， CR持续了10.5个月 。 疾病控制率（DCR）为67% ， 7名患者显示病情稳定（SD），5名患者靶病变缩小可量化 。所有7名反应者的 中位缓解持续时间（DOR）为2.8个月 。 ▼所有疗效可评估患者（n=21）治疗后的反应示例图 ▲图源“nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 LK101注射液：国内首款获批进入临床阶段的个性化肿瘤新抗原疫苗 2023年3月15日，我国“北京立康生命”自主研发的一款个性化肿瘤新抗原疫苗——“LK101注射液”， 新药临床试验申请（IND）获国家药品监督管理局药品审评中心（CDE）批准 ，用于治疗 晚期实体瘤 。据悉，它是 我国首款获批进入临床阶段的个性化肿瘤新生抗原疫苗！ 在我国mRNA癌症疫苗的研发领域中，留下了浓墨重彩的一笔！ ▲图源“NMPA”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 小编寄语 mRNA癌症疫苗既可 刺激强大的免疫反应 ，又可 降低不良反应，增强机体抗癌的能力！ 迄今为止，美国国立卫生研究院（NIH）临床试验网站上收录了7000余项处于研发阶段的肿瘤疫苗项目，其中，mRNA疫苗多达600余项，涉及新抗原疫苗的项目包括190余项，此外还包括树突细胞（DC）疫苗等。目前，疗效及预防复发效果较为突出几款癌症疫苗包括古巴肺癌疫苗、树突状细胞（DC）疫苗、个性化新抗原疫苗等，为 肺癌、黑色素瘤、肝癌、肾癌、乳腺癌 等实体瘤患者，带来了新的希望 近日更是迎来了mRNA-4157三期临床试验的开展，以及首批接种该疫苗患者的积极反馈，这无疑为癌症疫苗研发打了一剂“强心针”！小编也期望mRNA及更多癌症疫苗能尽快问世，让更多实体瘤患者获益，最终实现“打一针就能精准抗癌”的美好愿景！ 参考资料 [1]Khattak A,et al.Distant metastasis-free survival results from the randomized,phase 2 mRNA-4157-P201/KEYNOTE-942 trial[J].2023. https://ascopubs-org.libproxy1.nus.edu.sg/doi/abs/10.1200/JCO.2023.41.17_suppl.LBA9503 [2]Wang B,et al.Recent advances in mRNA cancer vaccines: meeting challenges and embracing opportunities[J].Frontiers in immunology,2023,14:1246682. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1246682/full [3]Rojas L A,et al.Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer[J]. Nature,2023,618(7963):144-150. https://www-nature-com.libproxy1.nus.edu.sg/articles/s41586-023-06063-y [4]Mackensen A,et al.CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial[J].Nature Medicine,2023,29(11):2844-2853. https://www-nature-com.libproxy1.nus.edu.sg/articles/s41591-023-02612-0 [5]https://www.bbc.com/news/health-68897731 [6]https://www.uclh.nhs.uk/news/first-patients-getting-individualised-risk-reducing-therapy-melanoma [7]https://www-merck-com.libproxy1.nus.edu.sg/news/merck-and-moderna-initiate-phase-3-study-evaluating-v940-mrna-4157-in-combination-with-keytruda-pembrolizumab-for-adjuvant-treatment-of-patients-with-resected-high-riskstage-iib-iv-melanom/

MAINZ, Germany, May 21, 2024 – BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) will present clinical trial data for selected programs from the Company’s diversified immuno-oncology pipeline at the American Society of Clinical Oncology (“ASCO”) Annual Meeting in Chicago, Illinois, from May 31 to June 4, 2024. Moreover, in support of the Company’s ongoing CAR-T cell and individualized mRNA programs, BioNTech will also present epidemiological and real-world data from two observational studies in patient populations for which product candidates are being developed in the Company’s respective clinical programs. “Our aim is to develop innovative treatment options across the continuum of cancer disease and establish new treatment paradigms that have the potential to address the fundamental challenges of treating cancer to drive meaningful improvements in the long-term survival rates for patients,” said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. “The data from the interventional and observational studies that we will present at this year’s ASCO are of relevance for progress towards our goal as they will contribute to informing the direction of further development of several of our priority product candidates as well as the design of planned pivotal and later-stage clinical trials across all three key pillars of our diversified oncology pipeline, including novel immunomodulators, targeted therapies such as cell therapies and ADCs, and mRNA-based therapeutic cancer vaccines.” Highlights of BioNTech’s updates to be presented at the ASCO Annual Meeting 2024: Updates on several Phase 1b/2a trials investigating BNT327/PM8002 as a monotherapy in patients with solid tumors will be presented. BNT327/PM8002 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with VEGF-A neutralization to create a cycle of vascular normalization and immunostimulation in the microenvironment of the tumor. Two posters will provide clinical data updates for cohorts with advanced cervical cancer, platinum-resistant recurrent ovarian cancer and advanced non-small cell lung cancer (“NSCLC”). The product candidate is being developed in collaboration with Biotheus Inc. (“Biotheus”). Initial results from the randomized, open-label, Phase 2 trial (NCT05117242) with the bispecific antibody candidate BNT311/GEN1046 (acasunlimab) alone or in combination with pembrolizumab in patients with previously treated metastatic NSCLC (“mNSCLC”) will be presented. BNT311/GEN1046 combines PD-L1 checkpoint inhibition with 4-1BB costimulatory activation. The product candidate is being developed in collaboration with Genmab S/A (“Genmab”). BioNTech will present preliminary data of an epidemiological study (NCT04813627) that correlates post-operative circulating tumor DNA (“ctDNA”), a cancer biomarker for minimal residual disease, with disease-free survival in patients with colorectal cancer (“CRC”). This observational study provides supportive epidemiological and prognostic data for the ongoing interventional Phase 2 trial (NCT04486378) with the individualized neoantigen-specific immunotherapy (“iNeST”) candidate autogene cevumeran (BNT122, RO7198457) in ctDNA-positive, high-risk stage II/stage III adjuvant CRC. Autogene cevumeran is jointly being developed by BioNTech and Genentech Inc. (“Genentech”), a member of the Roche Group. BioNTech will present an analysis of real-world data that investigated the overall survival, treatment patterns and prognostic variables of patients with testicular germ cell tumors receiving palliative chemotherapy. This analysis will inform the design of BioNTech’s planned pivotal trial with the Company’s CAR-T cell therapy candidate BNT211 in patients with germ cell tumors. BNT211 combines an autologous CAR-T cell therapy candidate targeting the oncofetal antigen Claudin-6 (“CLDN6”) and an investigational CLDN6-encoding CAR-T cell amplifying RNA vaccine (“CARVac”). BioNTech has established a diversified clinical oncology pipeline based on its modular multi-platform approach. The Company is advancing more than 20 clinical programs in unmet medical need solid tumor indications, including mRNA-based immunotherapies, targeted therapies entailing cell therapies and antibody-drug conjugates (ADCs), and novel immunomodulators. These candidates are currently being evaluated in more than 30 clinical studies, including nine programs in advanced Phase 2 trials and two candidates in pivotal Phase 3 trials. BioNTech is advancing key programs into late-stage development with the aim to have ten or more potentially registrational trials in its oncology pipeline by the end of 2024. The Company aims to launch its first cancer immunotherapy in 2026. By 2030, BioNTech plans to obtain approvals for a total of ten cancer indications across various drug classes. The full abstracts will be available on the ASCO Annual Meeting website. Click here for further information on BioNTech’s pipeline candidates. Full poster details: Candidate: BNT327/PM8002 Session title: Lung Cancer—Non-Small Cell Metastatic Abstract Title: A Phase Ib/IIa Trial to Evaluate the Safety and Efficacy of PM8002, a Bispecific Antibody Targeting PD-L1 and VEGF-A, as a Monotherapy in Patients with advanced NSCLC Location: Hall A, Poster Board 397 Abstract Number: 8533 Date: Monday, June 3, 2024 Time: 1.30 PM-4.30 PM CDT Candidate: BNT327/PM8002 Session title: Gynecologic Cancer Abstract Title: Efficacy and Safety of PM8002, a Bispecific Antibody Targeting PD-L1 and VEGF-A, as a Monotherapy in Patients with Solid Tumors: Clinical Data from Advanced Cervical Cancer and Platinum-resistant Recurrent Ovarian Cancer Cohorts Location: Hall A, Poster Board 395 Abstract Number: 5524 Date: Monday, June 3, 2024 Time: 9.00 AM-12.00 PM CDT Candidate: BNT326/YL202 Session title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Abstract Title: YL202/BNT326, a HER3-targeted ADC, in patients with locally advanced or metastatic non-small cell lung cancer and breast cancer: Preliminary results from a first-in human phase I trial Location: Hall A, Poster Board 179 Abstract Number: 3034 Date: Saturday, June 1, 2024 Time: 09:00 AM – 12:00 PM CDT Candidate: BNT311/GEN1046 (acasunlimab) Session Title: Developmental Therapeutics—Immunotherapy Abstract Title: Acasunlimab (DuoBody-PD-L1x4-1BB) alone or in combination with pembrolizumab (pembro) in patients (pts) with previously treated metastatic non-small cell lung cancer (mNSCLC): initial results of a randomized, open-label, phase 2 trial Location: Hall A, Poster Board 12 Abstract Number: 2533 Date: Saturday, June 1, 2024 Time: 9.00 AM-12.00 PM CDT Candidate: Autogene cevumeran (BNT122, RO7198457) Session Title: Gastrointestinal Cancer—Colorectal and Anal Abstract Title: Preliminary results correlating post-operative ctDNA status with disease-free survival in Stage II (high risk) / III Colorectal Cancer Patients in the BNT000-001 epidemiology study Location: Hall A, Poster board 189 Abstract Number: 3526 Date: Saturday, June 1, 2024 Time: 1.30 PM-4.30 PM CDT Candidate: BNT211 Session Title: Genitourinary Cancer—Prostate, Testicular, and Penile Abstract Title: Real-world evidence of overall survival (OS) and treatment patterns of patients (pts) with testicular germ cell tumors (DCT) receiving palliative chemotherapy in the United States Location: Poster board 356 Abstract Number: 5038 Date: Sunday, June 2, 2024 Time: 9.00 AM – 12.00 PM CDT About BioNTech Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Biotheus, DualityBio, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron. For more information, please visit . BioNTech Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not be limited to, statements concerning: the initiation, timing, progress and results of BioNTech’s research and development programs in oncology, including the targeted timing and number of additional potentially registrational trials; BioNTech’s current and future preclinical studies and clinical trials in oncology, including the bispecific antibody candidates BNT311/GEN1046 (acasunlimab) in patients with mNSCLC and BNT327/PM8002 in patients with advanced cervical cancer, platinum-resistant recurrent ovarian cancer and advanced NSCLC, iNeST candidate autogene cevumeran (BNT122, RO7198457) in patients with colorectal cancer, the CAR-T cell candidate BNT211 in multiple solid tumor types, and the ADC candidate BNT326/YL202 in patients with locally advanced or metastatic NSCLC and breast cancer; the nature and characterization of and timing for release of clinical data across BioNTech’s platforms, which is subject to peer review, regulatory review and market interpretation; the planned next steps in BioNTech’s pipeline programs, including, but not limited to, statements regarding timing or plans for initiation or enrollment of clinical trials, or submission for and receipt of product approvals and potential commercialization with respect to BioNTech’s product candidates; the ability of BioNTech’s mRNA technology to demonstrate clinical efficacy outside of BioNTech’s infectious disease platform; and the potential safety and efficacy of BioNTech’s product candidates. In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are based on BioNTech’s current expectations and beliefs of future events, and are neither promises nor guarantees. You should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond BioNTech’s control and which could cause actual results to differ materially and adversely from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to: the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the data discussed in this release, and including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the nature of clinical data, which is subject to ongoing peer review, regulatory review and market interpretation; the ability to produce comparable clinical results in future clinical trials; the timing of and BioNTech’s ability to obtain and maintain regulatory approval for its product candidates; discussions with regulatory agencies regarding timing and requirements for additional clinical trials; BioNTech’s and its counterparties’ ability to manage and source necessary energy resources; BioNTech’s ability to identify research opportunities and discover and develop investigational medicines; the ability and willingness of BioNTech’s third-party collaborators to continue research and development activities relating to BioNTech’s development candidates and investigational medicines; unforeseen safety issues and potential claims that are alleged to arise from the use of products and product candidates developed or manufactured by BioNTech; BioNTech’s and its collaborators’ ability to commercialize and market, if approved, its product candidates; BioNTech’s ability to manage its development and expansion; regulatory developments in the United States and other countries; BioNTech’s ability to effectively scale BioNTech’s production capabilities and manufacture BioNTech’s products and BioNTech’s product candidates; risks relating to the global financial system and markets; and other factors not known to BioNTech at this time. You should review the risks and uncertainties described under the heading “Risk Factors” in BioNTech's Report on Form 6-K for the period ended March 31, 2024 and in subsequent filings made by BioNTech with the SEC, which are available on the SEC’s website at . These forward-looking statements speak only as of the date hereof. Except as required by law, BioNTech disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. CONTACTS Media Relations Jasmina Alatovic +49 (0)6131 9084 1513 Media@biontech.de Investor Relations Victoria Meissner, M.D. +1 617 528 8293 Investors@biontech.de