PM-8002

MAINZ, Germany, May 27, 2025 -- BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) will present clinical trial data from select pipeline candidates across the Company’s diversified oncology portfolio at the American Society of Clinical Oncology (“ASCO”) Annual Meeting, to be held in Chicago, IL, from May 30 to June 3, 2025. The data highlight continued progress of the Company’s clinical programs consisting of complementary therapeutic modalities, including mRNA cancer immunotherapies, next-generation immunomodulators, and targeted therapies, including antibody-drug conjugates (“ADCs”). “We believe that the next era of cancer medicine will be defined by the interplay of complementary mechanisms and innovative molecules, unlocking their full potential through synergy. Our data presentations at this year's ASCO Annual Meeting show how we aim to help shape this era,” said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. “We will present clinical progress with two of our therapeutic modalities: our next generation immunomodulators, most notably our investigational anti-PD-L1xVEGF-A antibody BNT327, and for one of our ADC programs, which are an important pillar of our combination strategy. These data underline the potential of our assets to improve outcomes for patients.” Highlights of BioNTech’s oncology programs to be presented at ASCO 2025: Three presentations on BNT3271, an investigational anti-PD-L1xVEGF-A antibody, will detail data from ongoing later-stage and potentially registrational clinical trials: An oral presentation will feature the first data from a Phase 2 clinical trial (NCT05918107) of BNT327 in combination with chemotherapy as first-line treatment for patients with unresectable malignant mesothelioma. Malignant mesothelioma is a type of cancer that develops in the tissue that covers the lung or the abdomen. The preliminary data indicated anti-tumor activity and a manageable safety profile. Two posters will detail the ongoing global Phase 3 and Phase 2/3 clinical trials, ROSETTA Lung-01 (NCT06712355) in extensive-stage small cell lung cancer (“ES-SCLC”) and ROSETTA Lung-02 (NCT06712316) in non-small cell lung cancer (“NSCLC”). BNT327 combines the two complementary anti-tumor mechanisms of PD-L1 checkpoint and VEGF-A signaling blockade in the tumor microenvironment, thereby aiming to enhance anti-tumor activity. Data on BNT324/DB-1311, a B7H3-targeted ADC candidate, from an ongoing Phase 1/2 clinical trial (NCT05914116) in patients with heavily pre-treated castration-resistant prostate cancer (“CRPC”) will be presented during an oral session. The data indicated early clinical activity and a manageable safety profile. BNT324/DB-1311 received Fast Track Designation by the U.S. Food & Drug Administration (“FDA”) for this patient population in 2024 and is being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. (“DualityBio”). Preliminary data on BNT316/ONC-392 (gotistobart), an investigational anti-CTLA-4 antibody, from two ongoing Phase 1/2 clinical trials evaluating the antibody candidate in combination with current standard of care treatments will be presented. Data from the PRESERVE-001 clinical trial (NCT04140526) in patients with advanced melanoma indicated a manageable safety profile and early signs of anti-tumor activity. The data included an analysis of overall survival (“OS”) and an ad-hoc analysis of next-treatment free survival (“NTFS”), a measure for potential long-lasting benefit after initial treatment. Data from the PRESERVE-006 clinical trial (NCT05682443) in patients with metastatic CRPC indicated a manageable safety profile and preliminary efficacy. BNT316/ONC-392 is being developed in collaboration with OncoC4, Inc. (“OncoC4”).Data on BNT142 from an exploratory Phase 1/2 dose finding trial (NCT05262530) in patients with CLDN6-positive advanced solid tumors will be featured in an oral presentation. BNT142 is an investigational lipid nanoparticle-formulated mRNA immunotherapy that encodes a CD3xCDLN6 T cell engager antibody. Preliminary data indicated a manageable safety profile and early signs of clinical activity, supporting scientific proof-of-concept and underscoring the potential of mRNA-encoded bispecific antibodies. BioNTech has established a diversified oncology portfolio to develop novel treatment approaches for patients living with cancer. The Company is advancing its oncology pipeline across multiple solid tumor indications, including more than 20 active Phase 2 and 3 clinical trials with a strategic focus on two pan-tumor priority programs: investigational mRNA cancer immunotherapies and the next-generation immunomodulator candidate BNT327. BioNTech expects multiple data readouts in 2025 and 2026 aimed at supporting its strategy and advancing the Company towards becoming a diversified multi-product oncology company. The full abstracts are available on the ASCO Annual Meeting website. Click here for further information on BioNTech’s pipeline assets. Full presentation details: Oral presentations Asset: BNT327Session Title: Clinical Science Symposium | Two Targets, One Goal: The Potential for Bispecific Antibodies in Thoracic MalignanciesAbstract Title: First report of efficacy and safety results from a phase 2 trial evaluating BNT327/PM8002 plus chemotherapy (chemo) as first-line (1L) treatment in unresectable malignant mesothelioma Location: E451Abstract Number: 8511Date: June 3, 2025Time: 9:45 AM – 11:15 AM CDT Asset: BNT324/DB-1311Session Title: Rapid Oral Abstract Session | Genitourinary Cancer—Prostate, Testicular, and PenileAbstract Title: DB-1311/BNT324 (a novel B7H3 ADC) in patients with castrate-resistant prostate cancer (CRPC)Location: Hall D2Abstract Number: 5015Date: June 1, 2025Time: 4:30 PM – 6:00 PM CDT Asset: BNT142Session Title: Oral Abstract Session | Developmental Therapeutics—ImmunotherapyAbstract Title: First-in-human phase I/II trial evaluating BNT142, a first-in-class mRNA encoded, bispecific antibody targeting Claudin 6 (CLDN6) and CD3, in patients (pts) with CLDN6-positive advanced solid tumors.Location: Hall D2Abstract Number: 2501Date: May 31, 2025Time: 3:00 PM - 6:00 PM CDT Poster Presentations Asset: BNT327Session Title: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic CancersAbstract Title: A global Phase 3 double-blind, randomized trial of BNT327/PM8002 plus chemotherapy (chemo) compared to atezolizumab plus chemo in patients (pts) with first-line (1L) extensive-stage small cell lung cancer (ES-SCLC)Poster Board: #242aAbstract Number: TPS8129Date: May 31, 2025Time: 1:30 PM – 4:30 PM CDT Asset: BNT327Session Title: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic CancersAbstract Title: Phase 2/3, global, multisite, randomized, open-label trial of BNT327/PM8002 in combination with chemotherapy (chemo) in first-line (1L) non-small cell lung cancer (NSCLC)Poster Board: #138bAbstract Number: TPS8670Date: May 31, 2025Time: 1:30 PM – 4:30 PM CDT Asset: BNT316/ONC-392 (gotistobart)Session Title: Melanoma/Skin CancersAbstract Title: Gotistobart in combination with pembrolizumab in patients with advanced melanoma who have progressed on PD-1 inhibitors with or without CTLA-4 inhibitorsPoster Board: #34Abstract Number: 9551Date: June 1, 2025Time: 9:00 AM – 12:00 PM CDT Asset: BNT316/ONC-392 (gotistobart)Session Title: Genitourinary Cancer—Prostate, Testicular, and PenileAbstract Title: Phase 1 study of gotistobart (BNT316/ONC-392) in combination with lutetium Lu 177 vipivotide tetraxetan (Lu 177) in patients with metastatic castration-resistant prostate cancer (mCRPC)Poster Board: #266Abstract Number: 5067Date: June 2, 2025Time: 9:00 AM – 12:00 PM CDT About BioNTechBiopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel investigative therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic modalities with the intent of rapid development of novel biopharmaceuticals. Its diversified portfolio of oncology product candidates aiming to address the full continuum of cancer includes mRNA cancer immunotherapies, next-generation immunomodulators and targeted therapies such as antibody-drug conjugates (ADCs) and innovative chimeric antigen receptor (CAR) T cell therapies. Based on its deep expertise in mRNA development and in-house manufacturing capabilities, BioNTech and its collaborators are researching and 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 Duality Biologics, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron. For more information, please visit www.BioNTech.com. BioNTech Forward-Looking StatementsThis 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: 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 and its collaborators’ current and future preclinical studies and clinical trials in oncology, including the investigational bispecific antibody BNT327 in various indications, the B7H3-targeted ADC candidate BNT324/DB-1311 in advanced solid tumors, the anti-CTLA-4 antibody candidate BNT316/ONC-392 in advanced melanoma, and the mRNA-based RiboMab candidate BNT142 in CLDN6-positive advanced solid tumors; 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, 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; the impact of tariffs and escalations in trade policy; 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 and regions; 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 March 31, 2025 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 Media Relations Jasmina Alatovic Media@biontech.de Investor Relations Michael Horowicz Investors@biontech.de 1 BNT327, formerly also known as PM8002, was initially jointly developed by BioNTech and Biotheus Inc (“Biotheus”). Since February 2025, Biotheus is a member of the BioNTech Group.

氨基观察-创新药组原创出品作者 | 武月2024年，吉利德堪称水逆王者。重金收购的Trodelvy，在非小细胞肺癌和尿路上皮癌的三期临床试验中接连失利，并撤回尿路上皮癌适应症的加速批准，一度被贴上“水逆”标签。戏剧性的是，在2025年，这款Trop2 ADC却在三阴性乳腺癌（TNBC）领域接连取胜：2025年4月21日，Trodelvy联合K药一线治疗转移性TNBC的ASCENT-04试验成功；5月23日，单药一线治疗PD-L1阴性TNBC的ASCENT-03试验再传捷报。这两项关键3期临床的胜利，有可能让Trodelvy成为一线mTNBC所有患者的骨干疗法，巩固其在首发适应症三阴乳腺癌的优势，更让吉利德的肿瘤管线重燃希望。但这并非终点。在ADC赛道“内卷”加剧的当下，Trodelvy既要面对同靶点竞品的围剿，又要警惕HER2 ADC的“跨界打击”。更紧迫的是，吉利德必须尽快突破乳腺癌的“舒适区”。Trodelvy在肺癌领域的失利阴影尚未消散，而小细胞肺癌、子宫内膜癌等新战场的开拓能否成功，将决定其能否真正走出水逆。当然，这不只决定Trodelvy处境，可能决定了Trop2 ADC的命运。/ 01 /一线突破三阴性乳腺癌因缺乏治疗靶点、预后极差，号称“乳腺癌之王”，给年轻女性的健康造成极大威胁。过去20年，化疗始终是标准疗法，但中位生存期仅1-2年。Trodelvy的崛起，始于2021年ASCENT试验中二线治疗的突破，而2025年的两项三期临床胜利，则将其推向了更前线的战场。4月21日，吉利德宣布，Trodelvy+K药联合一线治疗转移性三阴乳腺癌的ASCENT-04试验获得成功。该研究针对既往未接受过治疗的PD-L1高表达（CPS≥10）不可切除局部晚期或转移性三阴性乳腺癌（mTNBC）患者，结果显示，相较于K药联合化疗，Trodelvy+K药的方案在无进展生存期（PFS）方面展现出统计学及临床意义的显著改善，OS作为关键次要终点其数据尚未成熟，但呈现早期积极趋势。安全性方面，联合疗法未出现新的安全信号，与单药已知特性一致，具体数据将在即将举行的ASCO会议上披露。这也是mTNBC首个达到PFS终点的PD-1+Trop2 ADC联合治疗的三期临床试验。5月23日，吉利德再次宣布，Trodelvy单药一线治疗PD-L1阴性TNBC的ASCENT-03试验成功，与化疗相比，在不适合PD-1/PD-1的mTNBC患者中，经过Trodelvy治疗的患者PFS具有高度统计学意义和临床意义的改善。安全性方面也与之前的试验表现相同。传统化疗一直是mTNBC早期治疗的标准护理，但是化疗的效果亟待改善，并且吉利德表示，在mTNBC中，大约50%的患者没有接受超过1线的治疗，这表明需要额外的有效早线治疗选择。吉利德首席医疗官Dietmar Berger表示：“与化疗相比，ASCENT-03结果代表了20多年来这一患者群体的首次临床上有意义的进步。通过更早地解决这种侵袭性和难以治疗的疾病，我们有可能改善转移性三阴性乳腺癌患者面临的高未满足需求的治疗方案。”更重要的是，这两项关键三期临床的成功，使Trodelvy有望覆盖所有一线TNBC患者，成为新的“骨干疗法”。2024年，Trodelvy的销售额为13.15亿美元，若成功拓展至一线三阴乳腺癌，对吉利德显然是一大步。花旗分析师甚至预测，2030年Trodelvy的峰值销售额或达32亿美元。/ 02 /TNBC攻防战2025年一季度，Trodelvy的销售额出现了下滑，尽管吉利德表示这是库存调整所导致的，但市场竞争的压力不言而喻。能否借临床胜利保持增势，将是吉利德的下一个考验。毕竟，TROP2这个靶点在乳腺癌中的前景并不是十分明朗，不仅要面对同靶点药物的竞争，还要担心HER2 ADC的“背刺”，后来者的超车。即使是在Trodelvy已经建立先发优势的TNBC领域，HER2 ADC、后来者的攻势已箭在弦上。首先是双抗药物的进击。康方生物的PD-1/VEGF双抗AK112，普米斯/BioNTech的PD-L1/VEGF双抗PM8002以及康宁杰瑞的PD-1/CTLA-4双抗KN046，也正在加速探索TNBC适应症，AK112、PM8002已在2期试验中展现出对PD-L1高/低表达TNBC的强势疗效，并启动三期临床。在去年底召开的圣安东尼奥乳腺癌研讨会(SABCS)会上，AK112、PM8002更新了其一线治疗三阴乳腺癌的数据，前者的mPFS为9.3个月，后者为13.5个月。由于研发进度更快，PM8002已经读出部分OS数据，12个月和15个月的OS率分别为80.8%和78.1%。如果能够延续这样的临床表现，双抗无疑将为TNBC患者带来新的选择。除此之外，BioNtech还在全速推进PD-L1/VEGF+ADC策略，这无疑也会对吉利德的PD-1+TROP-2 ADC联用造成冲击。其次是HER2 ADC的“背刺”。虽然TNBC不适用于传统HER2靶向药，但有着旁观者效应的HER2 ADC，能对其中占比约30%的HER2低表达TNBC患者发挥作用。DS-8201率先在HER2低表达中取得突破。在一项3期临床DESTINY-Breast04中，纳入既往接受过1-2线化疗的低表达HER2的不可切除性或转移性乳腺癌患者，结果表明相比化疗组，DS-8201组ORR达50%，接受化疗的患者仅为16%，PFS更是增长了近3倍，OS也获益翻倍。尽管该研究样本数有限，但虑到目前TNBC治疗选择的有限性，以及DS-8201在低水平表达HER2的TNBC患者中的显著疗效，这也为TNBC提供了新方向。作为首发阵地，吉利德围绕三阴乳腺癌进行了全方位布局，除了前述的两项3期临床，还在开展PD-1+Trop2 ADC用于三阴乳腺癌术后辅助治疗的3期临床试验。除此之外，吉利德表示，正在对Trodelvy开展的一系列Trop-2高表达的肿瘤3期试验进行评估，包括单药及与K药的联用，涉及TNBC和HR+/HER2-乳腺癌的早期治疗。但是，在强手林立的世界，真正的护城河不在于数量，而是临床数据的深度，能否在OS/PFS最终分析中保持优势，并证明其在真实世界中的成本效益，将决定Trodelvy的长期竞争力。/ 03 /不能止于乳腺癌作为自己重金收购而来的ADC，吉利德没有理由、也不能放弃对它的潜力挖掘。换句话说，Trodelvy不能止于乳腺癌，倘若能在肺癌领域取得突破，必将开拓更大的市场。只不过，在非小细胞肺癌（NSCLC）领域，Trodelvy已经有了一次重大失利。2024年1月22日，名为EVOKE-01的研究没有达到OS的主要终点。在与对照组化疗相比，Trodelvy并未为晚期NSCLC患者带来OS改善，这也导致市场对Trodelvy预期的走低。目前其进度大为落后对手，科伦博泰的SKB264已经获批用于三线EGFR突变NSCLC，成功突围肺癌；第一三共的Dato-DXd也在失败之后，从广泛探索到“锚定”EGFR突变的NSCLC，并重新提交了新的上市申请，也获得了FDA的突破性疗法认定。对于Trodelvy来说，EVOKE-01研究也并非一无所获。通过该研究，吉利德发现患者此前接受PD-(L)1抑制剂治疗时的应答状态，会对Trodelvy治疗效果产生影响。简单来说，对于PD-(L)1抑制剂无应答的患者，相比经过PD-(L)1抑制剂治疗达成完全缓解或部分缓解的患者，或许能够在Trodelvy的治疗中获益更多。这也为TROP2 ADC在肺癌领域的应用提供了新的思路和方向。默沙东则在开展Trodelvy联合K药对比K药单药一线治疗PD-L1≥50%的NSCLC患者的3期临床。此前，联合治疗组在治疗PD-L1高表达患者的ORR达到69%，疾病控制率达到86%。Trodelvy能否在细分人群中扳回一城，仍是未知数。与此同时，吉利德也在推进Trodelvy在肺癌领域的其他研究。2024年国际肺癌研究协会世界肺癌大会上，吉利德公布了2期临床试验TROPiCS-03中广泛期小细胞肺癌（ES-SCLC）队列的结果。结果显示，43例小细胞肺癌患者，均为一线化疗联合免疫治疗耐药，该临床经确认的缓解率为41.9%，即43例患者中有18例达到PR，mPFS为4.4个月，中位OS为13.6个月。2024年底，FDA授予Trodelvy突破性疗法认定，用于治疗接受铂类化疗后疾病进展的ES-SCLC患者；今年2月份，Trodelvy已经登记了二线小细胞肺癌3期临床。小细胞肺癌约占肺癌病例的15%，其中约70%的患者在确诊时处于广泛期。对于ES-SCLC患者来说，当疾病对当前一线标准治疗（铂类化疗或免疫疗法）无应答时，预后通常较差且治疗选择有限。这意味着，若最终临床成功，吉利德无疑会开辟一片新市场，也能让市场重拾对Trodelvy的预期。/ 04 /总结肺癌领域足够宽广，但也已经足够内卷。去年7月，吉利德还启动了Trodelvy在子宫内膜癌患者中的三期临床，此外，其在胃癌、膀胱癌的早期探索也在进行中，只不过前路漫漫。总体来看，Trodelvy的三阴乳腺癌连续胜利，为吉利德赢得了喘息之机，但远非终局。在ADC赛道，既有DS-8201这样的超级明星，也有SKB264等本土黑马。若不能尽快在肺癌、妇科肿瘤等领域复制成功，Trodelvy恐难逃被替代的宿命。这就是ADC江湖的生存法则，不进则退。PS：欢迎扫描下方二维码，添加氨基君微信号交流。