BNT-113

悲观者永远正确，乐观者永远前行。 对于刚过去的2024年，无论是欧美抑或本土，生物制药行业都似乎仍陷在某种焦灼里——专利悬崖需要跨过，现金流维系刻不容缓，不断出海寻找商业化机会。 然而，我们也能看到，2024年是突破之年。CRISPR基因编辑技术走向商业化，无药可用的NASH领域迎来首款特异性疗法，而在机器算法解读蛋白质结构方面获得诺奖青睐的推动下，AI与制药结合的产业升级浪潮日渐高涨。 德勤对生物制药领域的上百名高管进行了一次调查，75%的受访者对2025年的行情抱以乐观。这背后，是强劲增长的预期和科技创新的步伐。 来自普华永道的分析也显示，经历2024年并购交易数量和规模的下滑后，生物制药行业有望重新振作起来。 下文，将结合GEN等公开资料，对2025年生物制药的趋势进行梳理。 1 热钱流动，从VC到IPO 如果2024年第三季度的数据继续保持积极方向，那么，初创Biotech有可能在2025年获得更大规模的VC融资，并且融资交易的数量也会更多。 截至目前，2024年全年数据尚未出炉，不过，摩根大通基于DealForma数据发布的第三季度报告显示，去年前三季度，319笔VC融资总额为208亿美元，预计全年425笔融资总额将达到277亿美元。 换言之，这种结果将扭转生物制药行业融资金额连续两年下降的局面。 近年的融资数量并未出现明显波动，但规模的下滑已是有目共睹的现实。从2021年触及440亿美元（756笔交易）的高位后，生物制药的VC市场行情便急转直下，2022年减少至279亿美元（543笔交易），2023年又进一步下滑至235亿美元（464笔交易）。 对于2024年，摩根大通和DealForma都提及“持续的看涨信号”，包括美联储同年9月将基本利率下调0.5%：“过去利率与交易活动呈相关性，因此我们可能会看到生物制药交易和融资活动在2024年第四季度增加。” 具体来看，Xaira Therapeutics获得2024年最大一笔VC融资，筹集超过10亿美元。截至2024年第三季度，有77家Biotech筹集1亿美元或以上的资金，这个表现已优于2023年全年的73轮融资。 IPO市场在过去一年出现复苏迹象后，预计将在2025年进一步反弹。跟VC融资类似，生物制药IPO在2021年达到顶峰，彼时不少Biotech正争夺开发COVID-19药物和疫苗机会，引起投资者对各种其他治疗领域的治疗和疫苗开发商的兴趣。 普华永道预测，IPO市场不会回到2021年的水平，但会从2024年的水平反弹。该机构相关负责人透露：“根据机密文件，很多公司进入了绿色空间，IPO的时机因素也很重要，这很有影响力。” 2024年1月至9月，有16家公司在美国交易所上市，共获得资金30亿美元——已超过2023年全年13家IPO总计的27亿美元。 2024年生物制药IPO排名中，最大一笔是靶向癌症治疗开发商Nuvalent筹集的5.75亿美元，其次，癌症药物开发商CG Oncology募集了4.37亿美元，超过该公司的最初3.8亿美元的计划。 2 中型规模并购将延续 VC和IPO市场的回暖，让市场观察人士对生物制药并购交易反弹抱有希望。长期以来，并购活动一直被投资者视为最有利可图的投资变现途径。 德勤认为，这一方面离不开专利悬崖的推动。MNC急于补充未来几年将萎缩的药物管线，例如强生/拜耳的Xarelto（利伐沙班）、BI/礼来的Jardiance（恩格列净）和阿斯利康Farxiga（达格列净）。Jardiance和Farxiga都是SGLT2抑制剂，用于治疗2型糖尿病、慢性肾病和心力衰竭。 2024年前三个季度，并购交易金额和数量都出现同比下降，预计2025年会迎来反弹。 摩根大通和DealForma报告称，2024年1月至9月期间，生物制药行业共发生71笔并购交易，总额达432亿美元，而2023年前三季度，共发生75笔并购交易，总额达611亿美元。 “原因有几个。首先是总体经济，企业希望了解利率走向何方，利率是否已达到稳定水平？我认为选举和地缘政治环境也对此产生了影响。”德勤相关负责人表示，经济已稳定下来，可以更好地了解利率走向。从美国新一届政府的人员构成看，并购活动也有望复苏。 去年12月，特朗普宣布提名Gail Slater担任司法部反垄断部门助理司法部长。对一些从业者来说，这被解读为一次松绑。 2023年，生物制药领域共发生106笔并购交易，总价值达1179亿美元，而辉瑞斥资430亿美元收购Seagen很大程度推高了该数字。 普华永道分析师表示，到2025年，预计中等规模的并购活动将持续，金额在50亿美元至150亿美元之间——低于辉瑞与Seagen等重磅交易，但高于50亿美元以下的“附加”收购。 2024年最昂贵的收购案，是Vertex Pharmaceuticals斥资49亿美元收购AlpineImmune Sciences，交易于2024年4月宣布，次月完成，扩大了Vertex专科药物产品线。Alpine旗下管线主要是IgA肾病候选药物povetacicept，去年10月，该公司启动povetacicept的III期RAINIER试验。 分析人士指出，2024年交易规模普遍低于50亿美元的部分原因是，小型Biotech越来越多地选择自己将药物推向市场。这意味着，MNC可购买后期产品的选择少了一些，对价也会受到限制。 但从现金角度来看，包括MNC在内，不少公司的资产负债表仍然良好。因此，普华永道称，2025年的中等规模并购活动的趋势还会持续。 3 基因编辑走向商用 2024年，从第一位接受Casgevy治疗的患者那里，Vertex Pharmaceuticals成功实现基因编辑技术商业收入的里程碑突破——根据报告，2024年第三季度，Casgevy营收为200万美元。 Casgevy由Vertex和CRISPR Therapeutics共同开发。自从2023年12月获批用于治疗镰状细胞病、2024年1月获批用于治疗β地中海贫血以来，美国市场标价220万美元的首款CRISPR药物，正在开创自己的版图。 Vertex曾不无期待地表示，Casgevy的势如破竹会延续到2025年。去年9月，该公司与CDMO巨头Lonza签署了一项长期供应协议，后者将帮助Vertex在荷兰的生产基地生产Casgevy。 加州大学伯克利分校分子与细胞生物学教授Fyodor Urnov则断言，CRISPR疗法可能会产生更多的收入，并且可以让更多的此类治疗惠及需要它们的患者。 他呼吁，药企应该将视线延伸到某些罕见病临床项目以外，而监管机构则需要改革其审查方式，以便在单个IND申请中考虑多种向导RNA。跨界合作方面，学术界和行业研究人员创建“CRISPR治疗中心”，通过三级医院在治疗设计、制造、动物研究和临床护理方面进行协同，将有助于基因编辑疗法走向更广阔的市场。 “为了所有目前患有临床可编辑遗传病的患者，以及那些将要生下来就患有这种疾病的人，我们必须给CRISPR编辑技术一个机会，”Urnov说，“现在是进行上述改革的时候了。” CRISPR以外的基因编辑技术，在2024年也取得进展，并有望继续扩大成就。 在2025年，Prime Medicine预计报告PM359首次人体试验的初步临床数据，这是一项I/II期研究，去年获得FDA批准。PM359是一种体外自体造血干细胞（HSC）产品，旨在治疗p47phox突变的慢性肉芽肿病（CGD）患者。 此外，新的一年里，Wave Life Sciences将分享其Ib/IIa期RestorAATion-2试验的多剂量数据，该研究评估了其alpha-1抗胰蛋白酶缺乏症（AATD）候选药物WVE-006。 2024年10月，Wave宣布，在RestorAATion-2中的早期数据证明，WVE-006具有成药的潜力。同时，这也是生物制药行业首次在人体上取得RNA编辑疗法的积极结果。 4 癌症疫苗，临门一脚 2025年，癌症疫苗的研发工作将继续进行后期数据收集。 在领跑的阵营里，2024年10月，Moderna和默沙东启动了其个性化新抗原疗法（INT）的III期试验INTerpath-009，Moderna称之为mRNA-4157，而默沙东称之为V940。 INTerpath-009正在评估INT与Keytruda的组合潜力，用于治疗接受Keytruda和化疗后某些类型的NSCLC。 去年11月，Moderna总裁Stephen Hoge在公司季度财报电话会议上告诉分析师：“我们确实在继续与合作伙伴默沙东讨论额外的III期项目。明年，我们将启动尚未宣布的新项目。” Moderna和默沙东的项目，得到Personalis旗下ImmunoID NeXT综合肿瘤组织分析平台的支持。2024年底，Personalis表示，Moderna将继续跟其合作，默沙东则以12月18日每股3.56美元的收盘价，通过私募购买5000万美元的Personalis股票。这笔交易使默沙东获得Personalis约16.5%的股权（1400多万股）。 另一家巨头BioNTech，有望在2025年报告BNT111与再生元旗下产品Libtayo联用的数据，这项II期临床正探索治疗抗PD-(L)1难治/复发、不可切除的III期或IV期黑色素瘤。BNT111基于BioNTech的现成FixVac平台，并编码共享的黑色素瘤相关抗原。 根据计划表，BioNTech会在今年晚些时候或2026年，披露与基因泰克共同开发的cevumeran（BNT122/RO7198457）II期试验中期数据，该疗法拟用于II期高风险和III期循环肿瘤DNA+（ctDNA）辅助CRC。 BioNTech还在开发第三种癌症疫苗——BNT113，它也是基于FixVac，但编码HPV16抗原。 此外，OSE Immunotherapeutics去年也报告了基于T细胞表位的癌症疫苗Tedopi（OSE2101）的积极成果，这是一种针对五种肿瘤相关抗原的“现货”免疫疗法。 OSE预计，将在2025年上半年完成III期ARTEMIA注册试验的准备工作，并于9月启动，比较Tedopi与标准治疗（多西他赛）在HLA-A2阳性转移性NSCLC患者中对免疫检查点抑制剂产生继发性耐药的疗效和安全性。 业内人士指出，癌症疫苗几十年来一直经受失败，但现在，Moderna和BioNTech等公司的新数据令人重燃希望。 5 AI深度介入制药行业 AI在药物研发领域站稳脚跟后，有望进一步发展。德勤调查的近60%生物制药公司高管表示，他们计划增加其价值链中生成式AI的投资。 “我们正从实验和炒作阶段，转向‘我如何使用它来改善我的业务？’阶段。这种转变发生在今年，我认为明年我们会看到更多。”德勤副主席兼美国生命科学部门负责人Pete Lyons说。 制药高管们计划，将AI的应用范围扩大到药物研发算法之外，扩大到在整个业务运营中大规模使用AI。 相应的，随着生物制药领域AI的进一步应用，领跑的AI药物开发商将实现更多增长。2024年11月，Recursion以6.88亿美元的价格与Exscientia合并。 英矽智能也已公布其炎症性肠病项目的细节，并将其产品线扩展到31个项目，其中10个项目正在进入临床阶段。进展最快的是ISM001-055，这是一种特发性肺纤维化候选药物，该公司计划将其推进到潜在的关键试验。 虽然一些药企将继续构建自己的AI平台，但不乏只会与AI公司合作的案例。 “人们已基本转向许可获取这些AI技术，部署到他们自己的内部开发项目中。”普华永道美国合伙人兼该公司制药和生命科学交易负责人Roel Vanden Akker补充说。 生物制药AI领域的不断增长，助力英伟达市值在2024年突破3万亿美元，并于同年6月实施了“10比1”的股票分割。进入2025年，该公司的新股几乎已趋于稳定。 然而，部分投资人预测，英伟达股价“到2025年可能翻一番”，因为市场预计，该公司去年3月发布的下一代NVIDIA Blackwell图形处理器（GPU）架构将需求强劲。最终，这些技术和机会也有望进一步传递到生物制药领域。 参考资料： 1.Seven Biopharma Trends to Watch in 2025 2.Biopharma and medtech venture investments continue to trend upward in Q3 3.Vertex's Casgevy breaks ground with 1st commercial patient infusions as company readies another major launch for 2025 4.2024制药并购：百亿美元难再来 5.生物制药，正在走出并购“大低谷” 同写意媒体矩阵，欢迎关注↓↓↓

Presented clinical data for multiple assets across modalities, including bispecific antibody candidate BNT327/PM8002 and mRNA cancer vaccine candidate BNT113 based on BioNTech’s FixVac platform Initiated two Phase 2 dose optimization trials with BNT327/PM8002 in small-cell lung cancer and in triple-negative breast cancer to inform planned pivotal Phase 3 trials Phase 2 clinical trial on track to evaluate mRNA-based individualized cancer vaccine candidate autogene cevumeran (BNT122/RO7198457) as an adjuvant treatment in patients with high-risk muscle-invasive urothelial cancer Successfully launched variant-adapted COVID-19 vaccines for the 2024/2025 vaccination season in multiple regions Reports third quarter 2024 revenues of €1.2 billion, net profit of €198.1 million and diluted earnings per share of €0.81 ($0.89)1 Ended the third quarter of 2024 with €17.8 billion in cash and cash equivalents plus security investments Expects to be at low end of full year 2024 revenue guidance range (€2.5-3.1 billion) Re-confirms guidance of planned full year 2024 R&D expenses of €2.4-2.6 billion and reduced guidance range for SG&A expenses to €600-700 million and for capital expenditures for operating activities to €300-400 million Conference call and webcast scheduled for November 4, 2024, at 8:00 a.m. EST (2:00 p.m. CET) MAINZ, Germany, November 4, 2024 (GLOBE NEWSWIRE) -- BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) today reported financial results for the three and nine months ended September 30, 2024 and provided an update on its corporate progress. “BioNTech’s achievements during the period were the successful launch of our variant-adapted COVID-19 vaccines and the progress across our oncology pipeline. In particular, we initiated later-stage trials and shared important updates for our PD-L1 x VEGF-A bispecific antibody candidate BNT327/PM8002 and for our mRNA cancer vaccine portfolio. These successes reinforce the potential of our multi-platform technology approach and inform our strategy to pursue novel proprietary combinations,” said Prof. Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. “We remain focused on advancing our late-stage oncology product candidates towards potential registration. We believe our pipeline and capabilities uniquely position us to execute on our vision of becoming a global multiproduct immunotherapy company.” Financial Review for Third Quarter and Nine Months of 2024 Revenues reported were €1,244.8 million for the three months ended September 30, 2024, compared to €895.3 million for the comparative prior year period. For the nine months ended September 30, 2024, revenues were €1,561.1 million, compared to €2,340.0 million for the comparative prior year period. The higher revenues in the third quarter of 2024 as compared to the comparative prior year period can be largely attributed to the earlier approvals received for its variant-adapted COVID-19 vaccines as compared to last year. Cost of sales were €178.9 million for the three months ended September 30, 2024, compared to €161.8 million for the comparative prior year period. For the nine months ended September 30, 2024, cost of sales were €297.8 million, compared to €420.7 million for the comparative prior year period. Research and development (“R&D”) expenses were €550.3 million for the three months ended September 30, 2024, compared to €497.9 million for the comparative prior year period. For the nine months ended September 30, 2024, R&D expenses were €1,642.4 million, compared to €1,205.3 million for the comparative prior year period. R&D expenses were mainly influenced by progressing clinical studies for the Company’s late-stage oncology pipeline candidates. Sales, general and administrative (“SG&A”) expenses2, in total, amounted to €150.5 million for the three months ended September 30, 2024, compared to €153.5 million for the comparative prior year period. For the nine months ended September 30, 2024, SG&A expenses were €466.9 million, compared to €415.4 million for the comparative prior year period. SG&A expenses were mainly influenced by personnel expenses. Other operating result amounted to negative €354.6 million during the three months ended September 30, 2024, compared to negative €9.0 million for the comparative prior year period. For the nine months ended September 30, 2024, other operating result amounted to negative €616.9 million compared to negative €134.4 million for the prior year period. Other operating result was primarily influenced by provisions for contractual disputes. Income taxes were realized with an amount of €39.4 million in tax income for the three months ended September 30, 2024, compared to €66.8 million in accrued tax expenses for the comparative prior year period. For the nine months ended September 30, 2024, income taxes were realized with an amount of €54.1 million in tax income for the nine months ended September 30, 2024, compared to €50.5 million of accrued tax expenses for the comparative prior year period. Net profit was €198.1 million for the three months ended September 30, 2024, compared to €160.6 million net profit for the comparative prior year period. For the nine months ended September 30, 2024, net loss was €924.8 million, compared to a net profit of €472.4 million for the comparative prior year period. Cash and cash equivalents plus security investments as of September 30, 2024, reached €17,839.8 million, comprising €9,624.6 million in cash and cash equivalents, €7,078.0 million in current security investments and €1,137.2 million in non-current security investments. Diluted earnings per share was €0.81 for the three months ended September 30, 2024, compared to €0.66 for the comparative prior year period. For the nine months ended September 30, 2024, loss per share was €3.83, compared to diluted earnings per share of €1.94 for the comparative prior year period. Shares outstanding as of September 30, 2024, were 239,739,752, excluding 8,812,448 shares held in treasury. “We successfully launched our variant-adapted COVID-19 vaccines upon receipt of earlier approvals as compared to last year. This drove our strong revenues in the third quarter,” said Jens Holstein, CFO of BioNTech. “Our cost discipline in combination with our financial position allow us to continue to focus on those assets that we believe offer a fast path to market and the highest potential to generate value for patients and shareholders.” 2024 Financial Year Guidance3 The Company expects its revenues for the full 2024 financial year to be at the low end of the guidance range provided in its outlook: The range reflects certain assumptions and expectations, including, but not limited to: COVID-19 vaccine uptake and price levels, including seasonal variations; inventory write-downs and other charges by BioNTech’s collaboration partner Pfizer Inc. (“Pfizer”) that negatively influence BioNTech’s revenues; anticipated revenues from a pandemic preparedness contract with the German government; and revenues from the BioNTech Group service businesses, namely InstaDeep Ltd (“InstaDeep”), JPT Peptide Technologies GmbH, and BioNTech Innovative Manufacturing Services GmbH. Generally, the Company continues to remain largely dependent on revenues generated in its collaboration partner’s territories in 2024. 2024 Financial Year Expenses and Capex The Company has reduced its previous guidance for expected SG&A expenses and capital expenditures for operating activities for the 2024 financial year: The full interim unaudited condensed consolidated financial statements can be found in BioNTech’s Report on Form 6-K for the period ended September 30, 2024, filed today with the United States Securities and Exchange Commission (“SEC”) and available at https://www.sec.gov/. Endnotes1Calculated applying the average foreign exchange rate for the nine months ended September 30, 2024, as published by the German Central Bank (Deutsche Bundesbank). 2 SG&A expenses include sales and marketing expenses as well as general and administrative expenses. 3Guidance excludes external risks that are not yet known and/or quantifiable. It does not include potential payments resulting from the outcomes of ongoing and/or future legal disputes or related activity, such as judgements or settlements, or other extraordinary items, all of which may have a material effect on the Company’s results of operations and/or cash flows. BioNTech continues to expect to report a loss for the 2024 financial year. 4 Guidance for R&D expenses reflects the expected impact of collaborations and potential M&A transactions, in each case to the extent disclosed, and which are subject to change based on future developments. Guidance does not otherwise reflect M&A, collaboration or licensing transactions that the Company may enter into in the future. Operational Review of the Third Quarter 2024, Key Post Period-End Events and Outlook Variant-adapted COVID-19 Vaccines In the third quarter of 2024, BioNTech and Pfizer executed the commercial launch of their variant-adapted COVID-19 vaccines for the 2024/2025 vaccination season. On July 3, 2024, BioNTech and Pfizer’s Omicron JN.1-adapted COVID-19 vaccine was approved by the European Commission (“EC”). Shortly following approval, the updated vaccines were made available to European Union (“EU”) member states. The EC approved the co-administration of the companies’ COVID-19 vaccine with approved seasonal influenza vaccines in individuals 12 years of age and older and also authorized glass pre-filled syringes, a new presentation of the vaccine that allows for refrigerated storage conditions. On September 24, 2024, the EC approved BioNTech and Pfizer’s Omicron KP.2-adapted COVID-19 vaccine. The companies began shipments of their KP.2-adapted COVID-19 vaccine to EU member states that ordered this formulation. On August 22, 2024, the U.S. Food and Drug Administration (“FDA”) approved the companies’ KP.2-adapted COVID-19 vaccine. The vaccines were shipped immediately following approval and made available in pharmacies, hospitals, and clinics across the U.S. On July 24, 2024, the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (“MHRA”) approved the companies’ JN.1-adapted vaccine and post period, on October 10, 2024, approved the companies’ KP.2-adapted COVID-19 vaccine. BioNTech and Pfizer will continue to monitor the evolving epidemiology of COVID-19 and remain prepared to develop modified vaccine formulas as the data support and as regulatory agencies recommend. COVID-19 – Influenza Combination Vaccine Program An mRNA-based combination vaccine candidate (BNT162b2 + BNT161) against COVID-19 and influenza is in development in collaboration with Pfizer. In August 2024, BioNTech and Pfizer provided topline results from the Phase 3 trial (NCT06178991) evaluating the companies’ mRNA combination vaccine candidate in healthy individuals 18-64 years of age. The vaccine candidate was compared to the co-administration of a licensed influenza vaccine with the companies’ licensed COVID-19 vaccine. The primary immunogenicity objectives were non-inferiority of the antibody responses to influenza (hemagglutination inhibition) and to SARS-CoV-2 (neutralizing titer) elicited by the combination vaccine candidate as compared to standard of care. The trial showed higher influenza A responses and comparable COVID-19 responses versus the comparator vaccines but did not meet one of its primary immunogenicity objectives of non-inferiority against the influenza B strain. No safety signals with the combination vaccine candidate have been identified in an ongoing safety data review. BioNTech and Pfizer are evaluating adjustments to the candidate and will discuss next steps with health authorities. Select Oncology Pipeline Updates Next-Generation Immune Checkpoint Immunomodulator Programs BNT327/PM8002 is a bispecific antibody candidate combining Programmed Cell Death Ligand-1 (“PD-L1”) checkpoint inhibition with Vascular Endothelial Growth Factor A (“VEGF-A”) neutralization and is being developed in collaboration with Biotheus Inc. (“Biotheus”). In October 2024, the first patient was dosed in a multi-site, open-label Phase 2 clinical trial (NCT06449222) to evaluate the safety, efficacy, and pharmacokinetics of BNT327/PM8002 at two dose levels in combination with chemotherapy in the first- and second-line treatment of patients with locally advanced/metastatic triple negative breast cancer (“TNBC”). These data will inform a Phase 3 clinical trial in first-line TNBC that is expected to start in 2025. In September 2024, the first patient was dosed in a multi-site, open-label Phase 2 clinical trial (NCT06449209) to evaluate BNT327/PM8002 in combination with chemotherapy in patients with untreated extensive-stage small-cell lung cancer (“ES-SCLC”), and in patients with SCLC that progressed after first- or second-line treatment. These data will inform a Phase 3 clinical trial in first-line SCLC that is expected to start in 2024. A Phase 2/3 clinical trial in first-line non-small cell lung cancer (“NSCLC”) is expected to start in 2024. In June 2024, evaluation of BNT327/PM8002 in combination with BNT325/DB-1305, a Trophoblast Cell-Surface Antigen 2 (“TROP2”)-targeted antibody-drug conjugate (“ADC”) candidate, was initiated as part of an ongoing Phase 1/2 clinical trial (NCT05438329). The clinical trial evaluates the safety and tolerability of BNT325/DB-1305 alone and in combination with BNT327/PM8002 in various solid tumor indications. Additional trials of novel BNT327/PM8002 combinations with proprietary ADCs are planned to start in 2024. In September 2024, data were presented from three clinical trials evaluating BNT327/PM8002 in patients with advanced TNBC, Epidermal Growth Factor Receptor (“EGFR”)-mutated NSCLC and renal cell carcinoma (“RCC”) at the 2024 Congress of the European Society for Medical Oncology (“ESMO”): Data from an ongoing open-label, single-arm Phase 1/2 clinical trial (NCT05918133) evaluating BNT327/PM8002 in combination with chemotherapy as first-line treatment in patients with advanced or metastatic TNBC showed clinically meaningful anti-tumor activity regardless of PD-L1 status and a manageable safety profile with no new safety signals observed beyond those typically described for anti-PD-(L)1 therapies, anti-VEGF therapies, and chemotherapy. Data from a Phase 2 clinical trial (NCT05756972) evaluating BNT327/PM8002 in combination with chemotherapy in patients with advanced EGFR-mutated NSCLC who progressed after EGFR-tyrosine kinase inhibitor treatment showed encouraging anti-tumor activity regardless of PD-L1 status and a generally manageable safety profile. Data from an open-label multi-cohort Phase 1/2 clinical trial (NCT05918445) evaluating BNT327/PM8002 monotherapy showed encouraging anti-tumor activity and a manageable safety profile in patients with previously untreated advanced non clear cell RCC or treated advanced clear cell RCC. Data in first-line TNBC are planned to be presented at the San Antonio Breast Cancer Symposium, taking place from December 10 to December 13 in San Antonio, Texas, U.S. Additional data are expected to be presented in 2025. Data from an ongoing open-label, single-arm Phase 1/2 clinical trial (NCT05918133) evaluating BNT327/PM8002 in combination with chemotherapy as first-line treatment in patients with advanced or metastatic TNBC showed clinically meaningful anti-tumor activity regardless of PD-L1 status and a manageable safety profile with no new safety signals observed beyond those typically described for anti-PD-(L)1 therapies, anti-VEGF therapies, and chemotherapy. Data from a Phase 2 clinical trial (NCT05756972) evaluating BNT327/PM8002 in combination with chemotherapy in patients with advanced EGFR-mutated NSCLC who progressed after EGFR-tyrosine kinase inhibitor treatment showed encouraging anti-tumor activity regardless of PD-L1 status and a generally manageable safety profile. Data from an open-label multi-cohort Phase 1/2 clinical trial (NCT05918445) evaluating BNT327/PM8002 monotherapy showed encouraging anti-tumor activity and a manageable safety profile in patients with previously untreated advanced non clear cell RCC or treated advanced clear cell RCC. BNT316/ONC-392 (gotistobart) is an anti-cytotoxic T-lymphocyte Associated Protein 4 (“CTLA-4”) monoclonal antibody candidate being developed in collaboration with OncoC4, Inc. (“OncoC4”). In October 2024, the FDA placed a partial clinical hold on the Phase 3 trial (PRESERVE-003; NCT05671510) due to varying results between patient populations. The trial assesses the efficacy and safety of BNT316/ONC-392 as monotherapy in patients with metastatic NSCLC that progressed under previous PD-(L)1-inhibitor treatment. Enrollment of new patients has been paused while patients already enrolled in the trial will continue to receive treatment. Trials evaluating BNT316/ONC-392 in other indications remain unaffected. In September 2024, preliminary data from the Phase 2 (PRESERVE-004; NCT05446298) clinical trial evaluating BNT316/ONC-392 in combination with pembrolizumab in patients with platinum-resistant ovarian cancer were presented at ESMO. The data suggest encouraging preliminary clinical activity and a manageable tolerability profile with no new safety signals detected for the combination. mRNA Cancer Vaccine Programs BNT111, BNT113 and autogene cevumeran (BNT122/RO7198457) are investigational vaccines for the treatment of cancer based on BioNTech’s systemically administered uridine mRNA-lipoplex technology. BNT111 is based on BioNTech’s wholly owned, off-the-shelf FixVac platform, and encodes shared melanoma associated antigens. A randomized Phase 2 clinical trial (BNT111-01; NCT04526899) is being conducted in collaboration with Regeneron Pharmaceuticals Inc. (“Regeneron”) to evaluate BNT111 in combination with cemiplimab in patients with anti-PD-(L)1 refractory/relapsed, unresectable stage III or IV melanoma. In July 2024, BioNTech announced that the trial met its primary efficacy outcome measure, demonstrating a statistically significant improvement in overall response rate (“ORR”) in patients treated with BNT111 in combination with cemiplimab, as compared to an historical control in this indication and treatment setting. The ORR in the cemiplimab monotherapy arm was in line with the historical control of anti-PD-(L)1 or anti-CTLA-4 treatments in this patient group. The treatment was generally well tolerated and the safety profile of BNT111 in combination with cemiplimab in this trial was consistent with previous clinical trials assessing BNT111 in combination with anti-PD-(L)1-containing treatments. The Phase 2 trial will continue as planned to further assess the secondary endpoints which were not mature at the time of the primary analysis. BioNTech plans to present data from this trial at an upcoming medical conference in 2025. BNT113 is based on BioNTech’s FixVac platform encoding Human Papilloma Virus 16 (“HPV16”) antigens. A global, randomized Phase 2 clinical trial (AHEAD-MERIT; NCT04534205) is being conducted to evaluate BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable, recurrent or metastatic, PD-L1+, HPV16+ head and neck squamous cell carcinoma. In September 2024, an exploratory analysis of antitumor activity (15 patients) and immunogenicity (3 patients) from the safety run-in of AHEAD-MERIT was presented at ESMO. The data support the tolerability of BNT113 and clinical activity in combination with pembrolizumab was observed. In addition, BNT113 was found to induce de novo T-cell responses against HPV16 antigens. Also at ESMO, results were presented from an investigator-sponsored Phase 1/2 dose escalation clinical trial (HARE-40; NCT03418480) evaluating BNT113 alone in the post-adjuvant and metastatic settings in patients with HPV16+ head and neck and other cancers. BNT113 was shown to induce immune responses in patients in the adjuvant and end-stage clinical settings and to be overall well tolerated with a manageable safety profile. Autogene cevumeran (BNT122/RO7198457) is an mRNA cancer vaccine candidate for individualized neoantigen-specific immunotherapy (“iNeST”) being developed in collaboration with Genentech, Inc. (“Genentech”), a member of the Roche Group (“Roche”). A randomized, double-blind, multi-site Phase 2 clinical trial (IMCODE-004; NCT06534983) evaluating autogene cevumeran as an adjuvant treatment with nivolumab in patients with high-risk muscle-invasive urothelial cancer (“MIUC”) is enrolling patients. The trial aims to evaluate the efficacy of autogene cevumeran in combination with nivolumab compared to nivolumab alone in approximately 360 patients. The primary endpoint for the study is investigator-assessed disease-free survival (“DFS”). Secondary objectives include overall survival (“OS”) and safety. Autogene cevumeran is also being evaluated in ongoing Phase 2 trials in adjuvant resected pancreatic ductal adenocarcinoma (“PDAC”) (NCT05968326), adjuvant colorectal cancer (“CRC”) (NCT04486378) and first-line advanced melanoma (NCT03815058). BioNTech plans to disclose interim data from the Phase 2 clinical trial (NCT04486378) in stage II (high-risk) and III circulating tumor DNA+ (“ctDNA”) adjuvant CRC, which is projected for late 2025 or 2026. ADC Programs BNT323/DB-1303 (trastuzumab pamirtecan) is an ADC candidate targeting Human Epidermal Growth Factor 2 (“HER2”) that is being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. (“DualityBio”). BNT323/DB-1303 is being evaluated in a Phase 1/2 clinical trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic HER2-expressing solid tumors. A potentially registrational cohort of patients with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) advanced/recurrent endometrial carcinoma has completed enrollment. Data from this cohort are expected in 2025. A confirmatory Phase 3 trial (NCT06340568) in patients with advanced endometrial cancer is in planning. A pivotal Phase 3 trial (DYNASTY-Breast02; NCT06018337) is being conducted in patients with Hormone Receptor-positive (“HR+”) and HER2-low metastatic breast cancer that progressed on hormone therapy and/or Cyclin-Dependent Kinase 4/6 (“CDK4/6”) inhibition. In September 2024, a Trial-in-Progress poster was presented at ESMO. Topline data from the ongoing Phase 3 trial in HR+ and HER2-low metastatic breast cancer that have progressed on hormone therapy and/or CDK4/6 inhibition are expected in 2026. BNT324/DB-1311 is an ADC candidate targeting B7H3 that is being developed in collaboration with DualityBio. A first-in-human, open-label Phase 1/2 clinical trial (NCT05914116) in patients with advanced solid tumors is ongoing. In July 2024, the FDA granted Orphan Drug designation to BNT324/DB-1311 for the treatment of advanced or metastatic esophageal squamous cell carcinoma. The first preliminary data update from this trial is expected to be presented at the ESMO Asia Congress (December 6-8, 2024 in Singapore). BNT326/YL202 is an ADC candidate targeting Human Epidermal Growth Factor 3 (“HER3”) that is being developed in collaboration with MediLink Therapeutics (Suzhou) Co., Ltd. (“MediLink”). A multi-site, international, open-label, first-in-human Phase 1 clinical trial (NCT05653752) sponsored by MediLink evaluating BNT326/YL202 as a later-line treatment in patients with locally advanced or metastatic EGFR-mutated NSCLC or HR+/HER2-negative breast cancer is ongoing. On August 15, 2024, the FDA lifted the partial clinical hold that was placed on this trial, initially announced on June 17, 2024. Trial recruitment has been reinitiated with a focus on dose levels no higher than 3 mg/kg, where the safety profile was manageable and encouraging clinical activity was observed. Cell Therapy Programs BNT211 consists of a chimeric antigen receptor (“CAR”)-T cell product candidate targeting Claudin-6 (“CLDN6”)-positive solid tumors in combination with a CAR-T cell-amplifying RNA vaccine (“CARVac”) encoding CLDN6. A first-in-human, open-label, multi-site Phase 1 dose escalation and dose expansion basket trial (NCT04503278) is being conducted to evaluate BNT211 in patients with CLDN6-positive relapsed or refractory solid tumors, including ovarian cancers and testicular germ cell tumors. In September 2024, data from the ongoing trial presented at ESMO showed signs of antitumor activity across indications. CARVac was shown to improve CAR-T persistence in some patients. The data also suggested that the safety profile of CLDN6 CAR T cells with and without CARVac is consistent with the previously published effects of CAR T therapies and that repeated CARVac administration does not significantly increase toxicity. A pivotal Phase 2 trial in patients with testicular germ cell tumors is expected to start in 2025 based on encouraging activity observed in this patient group. Corporate Update for the Third Quarter 2024 and Key Post Period-End Events On October 1, 2024, BioNTech, alongside its artificial intelligence (“AI”) subsidiary InstaDeep, presented an overview of its AI approach during an edition of the Company’s Innovation Series called AI Day. As part of the event, BioNTech showcased the Company’s approach to AI capability scaling and deployment across its pipeline. These updates covered the introduction of a new near exascale supercomputer, the launch of a novel Bayesian Flow Network (“BFN”) generative model, and multiple updates on the deployment of AI across BioNTech’s preclinical and clinical operations. Upcoming Investor and Analyst Events Innovation Series R&D Day: November 14, 2024 Fourth Quarter and Full Year 2024 Financial Results and Corporate Update: March 10, 2025 Conference Call and Webcast Information BioNTech invites investors and the general public to join a conference call and webcast with investment analysts today, November 4, 2024, at 8:00 a.m. EST (2:00 p.m. CET) to report its financial results and provide a corporate update for the third quarter of 2024. To access the live conference call via telephone, please register via this link. Once registered, dial-in numbers and a PIN number will be provided. The slide presentation and audio of the webcast will be available via this link. Participants may also access the slides and the webcast of the conference call via the “Events & Presentations” page of the Investors' section of the Company’s website at www.BioNTech.com. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call. About BioNTechBiopharmaceutical 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 www.BioNTech.com. 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 limited to, statements concerning: BioNTech’s expected revenues related to sales of BioNTech’s COVID-19 vaccine, referred to as COMIRNATY where approved for use under full or conditional marketing authorization, in territories controlled by BioNTech’s collaboration partners, particularly for those figures that are derived from preliminary estimates provided by BioNTech’s partners; the rate and degree of market acceptance of BioNTech’s COVID-19 vaccine and, if approved, BioNTech’s investigational medicines; expectations regarding anticipated changes in COVID-19 vaccine demand, including changes to the ordering environment and expected regulatory recommendations to adapt vaccines to address new variants or sublineages; the initiation, timing, progress, results, and cost of BioNTech’s research and development programs, including BioNTech’s current and future preclinical studies and clinical trials, including statements regarding the expected timing of initiation, enrollment, and completion of studies or trials and related preparatory work and the availability of results, and the timing and outcome of applications for regulatory approvals and marketing authorizations; BioNTech’s expectations regarding potential future commercialization in oncology, including goals regarding timing and indications; the targeted timing and number of additional potentially registrational trials, and the registrational potential of any trial BioNTech may initiate; discussions with regulatory agencies; BioNTech’s expectations with respect to intellectual property; the impact of BioNTech’s collaboration and licensing agreements; the development, nature and feasibility of sustainable vaccine production and supply solutions; the deployment of AI across BioNTech’s preclinical and clinical operations; BioNTech’s estimates of revenues, research and development expenses, selling, general and administrative expenses and capital expenditures for operating activities; and BioNTech’s expectations of net profit / (loss). 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, projected data release timelines, 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 the clinical data, which is subject to ongoing peer review, regulatory review and market interpretation; BioNTech’s pricing and coverage negotiations regarding its COVID-19 vaccine with governmental authorities, private health insurers and other third-party payors; the future commercial demand and medical need for initial or booster doses of a COVID-19 vaccine; competition from other COVID-19 vaccines or related to BioNTech’s other product candidates, including those with different mechanisms of action and different manufacturing and distribution constraints, on the basis of, among other things, efficacy, cost, convenience of storage and distribution, breadth of approved use, side-effect profile and durability of immune response; the timing of and BioNTech’s ability to obtain and maintain regulatory approval for its product candidates; the ability of BioNTech’s COVID-19 vaccines to prevent COVID-19 caused by emerging virus variants; 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; the impact of COVID-19 on BioNTech’s development programs, supply chain, collaborators and financial performance; 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 BioNTech’s COVID-19 vaccine and, if approved, its product candidates; BioNTech’s ability to manage its development and related expenses; regulatory developments in the United States and other countries; BioNTech’s ability to effectively scale its production capabilities and manufacture its products and 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 September 30, 2024 and in subsequent filings made by BioNTech with the SEC, which are available on the SEC’s website at www.sec.gov. 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 Investor RelationsMichael HorowiczInvestors@biontech.de Media Relations Jasmina Alatovic Media@biontech.de Interim Consolidated Statements of Profit or Loss (1) Adjustments to prior-year figures due to change in functional allocation of general and administrative expenses and other operating expenses. Interim Consolidated Statements of Financial Position Interim Consolidated Statements of Cash Flows (1) Adjustments to prior-year figures relate to reclassifications within the cash flows from operating and investing activities, respectively.