Biontech SE (BNTX) 2025 Q1 法說會逐字稿

Welcome to BioNTech's first-quarter 2025 earnings call. I would like to hand the call over to Michael Horowicz, Director of Investor Relations. Please go ahead.

歡迎參加 BioNTech 2025 年第一季財報電話會議。我想把電話交給投資者關係總監 Michael Horowicz。請繼續。

Thank you. Good morning and good afternoon. Thank you for joining BioNTech's first-quarter 2025 earnings call. As a reminder, the slides we will be using during this call and the corresponding press release we issued this morning can be found in the Investor Relations section of our website.

謝謝。早安，下午好。感謝您參加 BioNTech 2025 年第一季財報電話會議。提醒一下，我們在本次電話會議中使用的幻燈片以及我們今天早上發布的相應新聞稿可以在我們網站的投資者關係部分找到。

On the next slide, you will see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings with the US Securities and Exchange Commission. Forward-looking statements on this call are subject to significant risks and uncertainties and speak only as of the date of this conference call. We undertake no obligation to update or revise any of these statements.

在下一張投影片中，您將看到我們的前瞻性聲明免責聲明。有關這些聲明和其他風險的更多信息，請參閱我們向美國證券交易委員會提交的文件中。本次電話會議中的前瞻性陳述受重大風險和不確定性的影響，並且僅代表本次電話會議之日的觀點。我們不承擔更新或修改任何這些聲明的義務。

On slide 3, you can find the agenda for today's call. Today, I am joined by the following members of BioNTech's management team. Ugur Sahin, Chief Executive Officer and Co-Founder; Özlem Türeci, Chief Medical Officer and Co-Founder; Jens Holstein, Chief Financial Officer; and Ryan Richardson, Chief Strategy Officer.

在第 3 張投影片上，您可以找到今天電話會議的議程。今天，我與 BioNTech 管理團隊的以下成員一起出席。Ugur Sahin，執行長兼共同創辦人； Ãzlem Türeci，首席醫療官兼共同創辦人； Jens Holstein，財務長；以及首席策略長 Ryan Richardson。

With this, I would like to hand the call over to Ugur.

現在，我想把發言權交給烏古爾 (Ugur)。

Thank you, Michael. A warm welcome to all those joining us today. As BioNTech has grown and evolved significantly over the years, our vision has remained unchanged, to translate science into survival by building an immunotherapy powerhouse and becoming a fully integrated biopharmaceutical company with multiple approved products. In today's call, we will provide updates on key achievements from this quarter related to our strategic goals. In oncology, we presented new clinical data for our two pan tumor priority programs, our bispecific immunomodulator BNT327 and our mRNA cancer immunotherapies at recent medical meetings.

謝謝你，麥可。熱烈歡迎今天與我們一起參加的所有人。BioNTech 多年來不斷發展壯大，但我們的願景始終未變，那就是透過打造免疫療法強國，成為一家擁有多種獲批產品的完全整合的生物製藥公司，將科學轉化為生存之道。在今天的電話會議中，我們將提供本季度與我們的策略目標相關的主要成就的最新情況。在腫瘤學領域，我們在最近的醫學會議上展示了我們的兩個泛腫瘤優先項目、雙特異性免疫調節劑 BNT327 和 mRNA 癌症免疫療法的新臨床數據。

For BNT327, our bispecific entire PD-L1 anti-VEGF antibody, we've presented new Phase 2 data in small cell lung cancer at the European Lung Cancer Congress with preliminary overall survival data in the first-hand setting.

對於我們的雙特異性全 PD-L1 抗 VEGF 抗體 BNT327，我們在歐洲肺癌大會上展示了小細胞肺癌的新 2 期數據，並在第一手環境中提供了初步的總體生存數據。

At AACR, we reported the first data from our Phase 1 trial, evaluating BNT327 in combination with our top two target in ADC BNT325, signaling that this combination appears to have a manageable safety profile and may have synergistic clinical efficacy. This data strengthened our conviction in BNT327 as a next-generation IO-backbone. We will continue to drive its clinical development with the aim to establish a new standard of care for cancer patients, who are currently treated with approved checkpoint inhibitors and for some that are currently not.

在 AACR 上，我們報告了第 1 階段試驗的第一批數據，評估了 BNT327 與 ADC 中的前兩個目標 BNT325 的聯合作用，表明這種組合似乎具有可控的安全性，並且可能具有協同臨床療效。這些數據增強了我們對 BNT327 作為下一代 IO 主幹的信心。我們將繼續推動其臨床開發，旨在為目前正在接受已批准的檢查點抑制劑治療的癌症患者以及一些尚未接受該療法治療的患者建立新的護理標準。

For our mRNA cancer immunotherapies, we reported data from ongoing Phase 1 trial evaluating BNT116, our off-the-shelf FixVac, mRNA immunotherapy candidate in combination with cemiplimab in PD-L1-positive frail patients with non-small cell lung cancer. The data indicate that our off-the-shelf mRNA immunotherapy may be synergistic with checkpoint inhibitor. Likewise, we are progressing our individualized mRNA cancer immunotherapy, autogene cevumeran, in randomized Phase 2 trials.

對於我們的 mRNA 癌症免疫療法，我們報告了正在進行的 1 期試驗的數據，該試驗評估了 BNT116（我們的現成 FixVac、mRNA 免疫療法候選藥物）與 cemiplimab 聯合治療 PD-L1 陽性虛弱非小細胞肺癌患者。數據表明，我們現成的 mRNA 免疫療法可能與檢查點抑制劑具有協同作用。同樣，我們正在隨機 2 期試驗中推進個體化 mRNA 癌症免疫療法自基因 cevumeran。

Early in 2025, we published two manuscripts discussing our insight from two Phase 1 types, which demonstrate the polyspecific induction of long-term neoantigen-specific T cell responses and to support the anticipated mode of action of our initialized mRNA therapy approach in multiple cancer indications. We are also advancing towards commercialization in oncology with the first BLA submission for BNT323, our HER2 ADC planned by the end of 2025 pending regulatory feedback.

2025 年初，我們發表了兩份手稿，討論了我們從兩種 1 期類型中獲得的見解，這些見解證明了長期新抗原特異性 T 細胞反應的多特異性誘導，並支持我們初始化的 mRNA 治療方法在多種癌症適應症中的預期作用模式。我們也在腫瘤學商業化方面取得進展，我們的 HER2 ADC BNT323 首次提交 BLA，等待監管部門的回饋，計劃於 2025 年底完成。

Regarding our COVID-19 vaccine franchise, we initiated preparations to be on track to roll out a variant adapted, COVID-19 vaccine for the upcoming seasons. During the quarter, we closed the Biotheus acquisition and now hold global control over BNT327.

關於我們的 COVID-19 疫苗特許經營權，我們已經開始準備，準備推出適用於未來季節的變體 COVID-19 疫苗。在本季度，我們完成了對 Biotheus 的收購，目前擁有對 BNT327 的全球控制權。

We were able to achieve all this while maintaining a strong financial position. Leveraging our COVID-19 vaccine business and our strong financial position, we are significantly investing in the clinical development of our priority oncology programs across key tumor indications.

我們在保持強勁財務狀況的同時實現了所有這些目標。利用我們的 COVID-19 疫苗業務和強大的財務狀況，我們正在大力投資針對關鍵腫瘤適應症的優先腫瘤學計畫的臨床開發。

Before I continue with our strategy in oncology, I would like to provide an update regarding our management board. Today, we announced our new Chief Financial Officer. We will welcome Ramón Zapata on July 1, 2025. Ramón is an accomplished leader with deep finance experience who will be taking over from Jens at an exciting phase. He will join BioNTech from Novartis global biomedical research organization, where he has been serving as CFO since 2022.

在繼續介紹我們的腫瘤學策略之前，我想先介紹我們的管理委員會的最新情況。今天，我們宣布了新任財務長。我們將於 2025 年 7 月 1 日迎來拉蒙·薩帕塔 (Ramón Zapata)。Ramón 是一位經驗豐富的領導者，擁有豐富的金融經驗，他將在激動人心的階段接替 Jens 的職位。他將從諾華全球生物醫學研究組織加入 BioNTech，自 2022 年起他一直擔任該組織的財務長。

He will introduce himself in the next analyst and investor call in August. With this, and as previously shared, our current CFO, Jens Holstein will retire at the end of his term at the end of June as planned. Jens, thank you for your excellent financial leadership and your significant contributions to BioNTech's successful trajectory. We wish you continued success and fulfillment in the next chapter of your journey.

他將在八月的下一次分析師和投資者電話會議上介紹自己。正如之前所分享的，我們現任財務長 Jens Holstein 將按計劃於 6 月底任期結束時退休。Jens，感謝您出色的財務領導能力以及對 BioNTech 成功軌蹟的重大貢獻。我們祝福您在旅程的下一篇章中繼續取得成功並取得成就。

Now coming back to our oncology strategy. One of our first convictions for cancer immunotherapy is that we believe that future cancer treatment and particularly the desire to increase cure rates in human cancer will be driven by combination therapy exploiting compound classes is potentially synergistic mode of actions. Driven by our vision, we want to address the full continuum of cancers across different states from resected cancers which are in the adjuvant stage and have a high risk for relapse, to early-stage metastatic cancer as well as the late-stage cancers, which are refractory to different types of treatment.

現在回到我們的腫瘤學策略。我們對癌症免疫療法的首要信念之一是，我們相信未來的癌症治療，特別是提高人類癌症治癒率的願望，將由利用化合物類別具有潛在協同作用模式的聯合療法來驅動。在我們的願景的驅動下，我們希望解決不同狀態下各種癌症的全部問題，從處於輔助階段且復發風險較高的切除癌症，到早期轉移性癌症以及對不同類型治療具有抗藥性的晚期癌症。

We have built a pipeline with compounds from different drug classes that are well suited to achieve this following for novel-novel combinations of immunomodulators with targeted therapies and mRNA cancer immunotherapy. With a clear focus, we will continue to invest in our technologies and drug candidates that have the potential to improve outcomes for patients across wide range of tumor types. We believe that our two priority pan tumor programs, our mRNA cancer immunotherapies, FixVac and iNEST and our bispecific anti-PD-L1, anti-VEGF antibody BNT327 have disruptive potential and are aligned there with our vision. We successfully developed and approved. We believe these programs could establish a new standard of care and enhance patients' outcome in multiple cancer indications globally.

我們已經建立了一條包含不同藥物類別的化合物的管道，這些化合物非常適合實現免疫調節劑與標靶療法和 mRNA 癌症免疫療法的新型組合。我們將以明確的重點，繼續投資於有可能改善各種腫瘤患者治療結果的技術和候選藥物。我們相信，我們的兩個優先泛腫瘤項目、我們的 mRNA 癌症免疫療法、FixVac 和 iNEST 以及我們的雙特異性抗 PD-L1、抗 VEGF 抗體 BNT327 具有顛覆性潛力，並且與我們的願景一致。我們成功開發並獲得批准。我們相信這些項目可以建立新的護理標準並改善全球多種癌症患者的治療效果。

We are significantly investing in the clinical development of this program across various cancer types, building up commercial functions for the future commercialization in key markets and enhancing manufacturing capabilities to support both clinical prices and commercial supply.

我們正在大力投資該計畫針對各種癌症類型的臨床開發，為未來在主要市場的商業化建立商業功能，並增強製造能力以支持臨床價格和商業供應。

I will turn the call over to Özlem to provide more details on select clinical programs.

我將把電話轉給Ãzlem，以提供有關精選臨床項目的更多詳細資訊。

Thank you, Ugur. Glad to be speaking with everyone today. Our first oncology programs are moving towards commercial stage. We continue to advance towards our first BLA submission in oncology with BNT323 in HER2 expressing second-line endometrial cancer, alongside BNT323 and our mRNA cancer immunotherapies BNT327 is a key program in our development pipeline. The first global pivotal clinical trials in triple-negative breast cancer, small cell and non-small cell lung cancer.

謝謝你，烏古爾。很高興今天能與大家交談。我們的首個腫瘤學課程正在走向商業階段。我們繼續推進腫瘤學領域的第一個 BLA 提交，BNT323 針對 HER2 表達的二線子宮內膜癌，同時 BNT323 和我們的 mRNA 癌症免疫療法 BNT327 是我們開發管道中的關鍵項目。首次針對三陰性乳癌、小細胞肺癌和非小細胞肺癌的全球關鍵臨床試驗。

BNT327 by co-localizing the blockade of PD-L1 and VEGF-A signaling to the tumor is being developed with the aim to deliver superior antitumor immunomodulatory and anti-angiogenic effects compared to individual targeting of PD-L1 and VEGF-A, and with the potential to minimize at worst events associated with systemic anti-VEGF-A therapy. We now have data from over 1,000 patients across indications, which further strengthens our conviction in this asset.

BNT327 透過共定位阻斷 PD-L1 和 VEGF-A 訊號傳導至腫瘤而進行開發，旨在與單獨針對 PD-L1 和 VEGF-A 相比，提供更優異的抗腫瘤免疫調節和抗血管生成作用，並有可能最大限度地減少與全身性抗 VEGF-A 治療相關的最壞事件。我們目前擁有超過 1,000 名不同適應症患者的數據，這進一步增強了我們對這項資產的信心。

With the anti-PD-L1 and anti-VEGFA mechanisms being validated across numerous tumor types and in some cases, in combination, we have a clear road map for development. The first wave is focused on small cell and non-small cell lung cancer and TNBC as key indications to establish BNT327 combined with standard of care chemotherapy with first approvals then for the first-line settings of these indications. We have made continuous progress over the past months in researching these clear decisions.

隨著抗 PD-L1 和抗 VEGFA 機制在多種腫瘤類型中得到驗證，並且在某些情況下結合起來，我們擁有清晰的發展路線圖。第一波重點關注小細胞和非小細胞肺癌以及 TNBC 作為關鍵適應症，以建立 BNT327 與標準治療化療的聯合療法，並首先獲得批准，然後用於這些適應症的一線治療。在過去的幾個月裡，我們在研究這些明確的決定方面取得了不斷的進展。

Our second wave of development with BNT327 reflects that IO plus ADC combos emerging treatment paradigm in oncology. We have started exploring combinations of BNT327 with other ADC candidates informed by single agent data for these ADCs. The last wave aims at further broadening our global clinical development program with BNT327 through additional novel combinations across tumor types.

我們對 BNT327 的第二波開發反映了 IO 加 ADC 組合腫瘤學中新興的治療模式。我們已經開始探索 BNT327 與其他 ADC 候選藥物的組合，並根據這些 ADC 的單一藥物數據提供資訊。最後一波旨在透過更多跨腫瘤類型的新組合進一步擴大我們 BNT327 的全球臨床開發計劃。

As mentioned, triple-negative breast cancer is a priority indication for BNT327 based on the unmet need we see for patients and based on the clinical profile observed to date. Stage 4 TNBC patients faced prognosis with a five-year survival rate around 10%. Currently, these patients depending on their PD-L1 status are either treated with checkpoint inhibitor in combination with chemophherapy or with chemotherapy alone.

如上所述，根據我們看到的患者未滿足的需求以及迄今為止觀察到的臨床情況，三陰性乳癌是 BNT327 的優先適應症。4 期 TNBC 患者的預後為五年存活率約為 10%。目前，這些患者根據其 PD-L1 狀態採用檢查點抑制劑聯合化學療法治療或單獨使用化學療法治療。

PD-L1-positive patients have a median overall survival of 23 months, while PD-L1 negative patients have a median overall survival of 15.2 months as observed in the KEYNOTE-355 study. Data from a study in first-line metastatic triple-negative breast cancer showed that BNT327 in combination with chemotherapy has an encouraging high objective response rate of 73.8%, irrespective of PD-L1 status. We also observed in the trial encouraging landmark overall survival rates such as 69.7% at 18 months for BNT327 in this setting, suggesting that effective control of disease can translate into improved overall survival.

KEYNOTE-355 研究觀察到，PD-L1 陽性患者的中位總存活期為 23 個月，而 PD-L1 陰性患者的中位總存活期為 15.2 個月。第一線轉移性三陰性乳癌研究數據顯示，BNT327 合併化療具有令人鼓舞的高客觀緩解率，達到 73.8%，無論 PD-L1 狀態為何。我們也在試驗中觀察到令人鼓舞的里程碑式整體存活率，例如 BNT327 在這種情況下 18 個月的整體存活率達到 69.7%，這表明有效控制疾病可以轉化為提高整體存活率。

In addition to the encouraging efficacy data, the manageable safety profile was observed with no new safety signals beyond those typically described for a standard of care chemotherapy for anti-PD-1, PD-L1, and anti-VEGF-A monotherapies. Based on these data, we believe that BNT327 has the potential to become a first-line treatment option for triple-negative breast cancer patients, including those not currently treated by existing IO therapies. We also plan to start a Phase 3 trial later this year in the first-line setting.

除了令人鼓舞的療效數據外，還觀察到可控的安全性，除了抗 PD-1、PD-L1 和抗 VEGF-A 單一療法的標準化療通常描述的安全信號外，沒有出現新的安全信號。基於這些數據，我們認為 BNT327 有潛力成為三陰性乳癌患者的第一線治療選擇，包括目前未接受現有 IO 療法治療的患者。我們也計劃在今年稍後在一線環境中啟動第三階段試驗。

Moving to extensive stage small cell lung cancer and immunologically cold tumor for which high unmet need remains. With current standard of care treatment, the durability of responses is quite short and five-year survival rate is only 3%. Today, these patients are treated with a combination of atezolizumab in chemotherapy and experienced a median overall survival of 12.3 months as observed in the IMpower133 clinical trial.

轉向廣泛期小細胞肺癌和免疫學冷腫瘤，這些腫瘤仍有大量未滿足的需求。採用目前的標準治療，治療效果持續時間很短，五年存活率僅 3%。如今，這些患者接受了阿替利珠單抗聯合化療的治療，IMpower133 臨床試驗觀察到他們的中位總存活期為 12.3 個月。

Based on our emerging data, we believe that BNT327 has the potential to improve clinical outcomes for patients with small cell lung cancer. At the European Lung Cancer Congress, we disclosed interim data from a Phase 2 clinical trial evaluating BNT327 in combination with chemotherapy as a first-line treatment for patients with extensive stage non-cell lung cancer. Beyond the response rate of 85.4% and median progression-free survival of 6.9 months, but ELCC data also included for the first time, median overall survival data with a median overall survival of 16.8 months. In addition, a manageable safety profile was observed with no new safety signals beyond those typically described for chemotherapy agents and anti-PD-L1 and anti-VEGF monotherapies.

根據我們新出現的數據，我們相信 BNT327 有可能改善小細胞肺癌患者的臨床結果。在歐洲肺癌大會上，我們揭露了評估 BNT327 聯合化療作為廣泛期非細胞肺癌患者一線治療的 2 期臨床試驗的中期數據。除了 85.4% 的緩解率和 6.9 個月的中位無惡化存活期之外，ELCC 數據還首次納入了中位總存活期數據，中位總存活期為 16.8 個月。此外，觀察到可控的安全性，除了化療藥物和抗 PD-L1 和抗 VEGF 單一療法通常描述的安全訊號外，沒有新的安全訊號。

While these data are still immature, we are encouraged by the findings. These data support our decision to evaluate BNT327 in combination with chemotherapy in the ongoing global randomized Phase 3 clinical trial, ROSETTA Lung-01. We view non-small cell lung cancer as one of our priority indications as it's the most prevalent cancer globally. Over 80% of patients are diagnosed at late stages. Long-term outcomes depend on PD-L1 status and histology, but overall, remain poor despite improvements in care by checkpoint inhibitors.

雖然這些數據還不成熟，但我們對這些發現感到鼓舞。這些數據支持我們決定在正在進行的全球隨機 3 期臨床試驗 ROSETTA Lung-01 中評估 BNT327 與化療的聯合作用。我們將非小細胞肺癌視為我們的優先適應症之一，因為它是全球最常見的癌症。超過80%的患者在確診時已是晚期。長期結果取決於 PD-L1 狀態和組織學，但總體而言，儘管檢查點抑制劑改善了治療效果，但結果仍然不佳。

At the ASCO Annual Meeting last year, we presented data from the Phase 1 trial, evaluating BNT327 as a monotherapy first-line treatment in metastatic PD-L1 positive non-small cell lung cancer. BNT327 monotherapy treatment resulted in an overall response rate of 47%, a DCR of 100% and the MPFS of 13.6 months.

在去年的 ASCO 年會上，我們展示了第 1 階段試驗的數據，評估了 BNT327 作為轉移性 PD-L1 陽性非小細胞肺癌單一療法一線治療的效果。BNT327 單藥治療的整體反應率為 47%，DCR 為 100%，MPFS 為 13.6 個月。

In summary, BNT327 indicated encouraging antitumor activity and manageable safety in this patient population. Safety events were consistent with those described for anti-PD-L1 and anti-VEGF monotherapy. These data support our decision to start our global Phase 3 trial in non-small cell lung cancer, which is named Rosetta Lung-02. Rosetta Lung-02 is designed to evaluate the potential of BNT327 dosed in combination with chemotherapy to improve on survival outcomes when compared to standard of care pembrolizumab in combination with chemotherapy as a first-line therapy for non-small cell lung cancer patients without actionable genomic alterations. This trial is enrolling both non-squamous and squamous histologies in two separately powered sub-studies, and each sub study will enroll patients across all PD-L1 status.

總之，BNT327 在該患者群體中表現出令人鼓舞的抗腫瘤活性和可控制的安全性。安全事件與抗 PD-L1 和抗 VEGF 單一療法所描述的安全事件一致。這些數據支持我們啟動非小細胞肺癌全球 3 期試驗的決定，該試驗名為 Rosetta Lung-02。Rosetta Lung-02 旨在評估 BNT327 與化療聯合使用作為無可操作基因組改變的非小細胞肺癌患者的一線治療，與標準治療方案 pembrolizumab 與化療聯合使用相比，改善生存結果的潛力。該試驗在兩個單獨進行研究的子研究中招募非鱗狀和鱗狀組織學患者，每個子研究將招募所有 PD-L1 狀態的患者。

The study includes the Phase 2 part with 40 patients seeking to establish the dose for the Phase 3 randomized part in 942 patients. The co-primary end points up progression-free survival and overall survival. Today, we are enrolling patients in the Phase 2 part and expect to progress to the Phase 3 part data. We will present the complete trial design for our two ongoing BNT327 global Phase 3 studies, Rosetta Lung-01 and Rosetta Lung-02, which are evaluating BNT327 dosed in combination with chemotherapy in first-line small cell and non-small cell lung cancer at the ASCO annual meeting at the end of this month. We plan to have a significant presence at the ASCO annual meeting, including five clinical data updates across our oncology pipeline, ensuring not only our immunomodulator BNT327, but also our anti-CTLA-4 BNT316, our B7-H3 targeting ADC BNT324 and BNT142, our Claudin 6 T-cell engager, RiboMabs.

研究包括第 2 階段，其中有 40 名患者參與，旨在確定第 3 階段隨機階段（942 名患者）的劑量。共同主要終點是無惡化存活期和總體存活期。今天，我們正在招募第 2 階段的患者，並期望取得第 3 階段的數據。我們將在本月底的 ASCO 年會上展示我們正在進行的兩項 BNT327 全球 3 期研究 Rosetta Lung-01 和 Rosetta Lung-02 的完整試驗設計，這兩項研究旨在評估 BNT327 與化療聯合治療一線小細胞和非小細胞肺癌的效果。我們計劃在 ASCO 年會上進行重要展示，包括更新我們腫瘤學產品線的五項臨床數據，不僅確保我們的免疫調節劑 BNT327，還確保我們的抗 CTLA-4 BNT316、我們的 B7-H3 靶向 ADC BNT324 和 BNT142、我們的 Claudin 6 TMabsRibo.Ribo.

We look forward to this and other conferences this year during which we plan to share more data updates across our investigational oncology pipeline as we continue our progress towards becoming a multiproduct oncology company. To conclude, as I highlighted at the beginning of my section, we remain strongly convinced that our combination-based pipeline offers this potential to positively impact the future outcomes for patients in key indications such as in breast and lung cancer.

我們期待今年的這次會議和其他會議，在此期間，我們計劃在我們的研究腫瘤學管道中分享更多數據更新，我們將繼續朝著成為多產品腫瘤學公司的方向前進。總而言之，正如我在本部分開頭所強調的那樣，我們仍然堅信，我們的組合療法產品線具有對乳癌和肺癌等關鍵適應症患者的未來結果產生積極影響的潛力。

With that, I will now pass the presentation to our CFO, Jens Holstein.

現在，我將把簡報交給我們的財務長 Jens Holstein。

Thank you, Özlem, and a warm welcome to everyone who has dialed in today's call. Let me begin my section with our Q1 2025 financial results. In the first quarter of 2025, we reported total revenues of approximately EUR183 million, driven mostly by the sale of our COVID-19 vaccines compared with EUR188 million for the first quarter of 2024. This revenue figure is consistent with our expectations and reflects the seasonality that we expect in an endemic COVID-19 environment. Research and development expenses reached EUR526 million for the first quarter of 2025 compared to EUR508 million for the comparative prior year period. The increase was mainly driven by progressing late-stage clinical studies for pipeline candidates, including BNT327 in our ADC portfolio.

謝謝你，Ãzlem，並熱烈歡迎今天撥打電話的所有人。讓我從 2025 年第一季的財務表現開始我的部分。2025 年第一季度，我們的總收入約為 1.83 億歐元，主要來自 COVID-19 疫苗的銷售，而 2024 年第一季的總收入為 1.88 億歐元。這個收入數字與我們的預期一致，反映了我們在 COVID-19 流行環境中預期的季節性。2025 年第一季研發費用達 5.26 億歐元，去年同期為 5.08 億歐元。這一增長主要得益於包括我們 ADC 產品組合中的 BNT327 在內的候選藥物的後期臨床研究的進展。

SG&A expenses amounted to approximately EUR121 million in the first quarter of 2025 compared to EUR133 million in the comparative prior year period. The decrease was primarily driven by a reduction in external services. For the first quarter of 2025, we reported a net loss of EUR416 million compared to a net loss of EUR350 million for the comparative prior year period. Our basic and diluted loss per share for the first quarter of 2025 was EUR1.73 compared to a basic and diluted loss per share of EUR1.31 in the comparative prior year period. As indicated in our full year earnings call in March, 2025 will be a year of transition for BioNTech with the aim of becoming a multiproduct oncology company.

2025 年第一季銷售、一般及行政費用約為 1.21 億歐元，去年同期為 1.33 億歐元。下降的主要原因是外部服務的減少。2025 年第一季度，我們報告淨虧損 4.16 億歐元，而去年同期淨虧損 3.5 億歐元。2025 年第一季度，我們的每股基本虧損和稀釋虧損為 1.73 歐元，而去年同期的每股基本虧損和稀釋虧損為 1.31 歐元。正如我們 3 月全年財報電話會議中所指出的，2025 年將是 BioNTech 的轉型之年，目標是成為一家多產品腫瘤學公司。

We will continue to invest with discipline in our long-term growth strategy, namely by advancing BNT327 and our mRNA cancer immunotherapies. We believe that these two programs have disruptive pan-tumor potential. We ended the quarter in a strong financial position with EUR15.9 billion in total cash plus security investments. Among other things, the reduction compared to the year-end figure is due to the payment of approximately USD800 million as part of the Biotheus acquisition. It also reflects the payment made in connection with the settlement of a contractual dispute with NIH of about USD792 million. We expect an additional payment of USD400 million associated with the settlement with the University of Pennsylvania to be reflected in our second quarter 2025 financial position.

我們將繼續嚴格投資於我們的長期成長策略，即推進 BNT327 和我們的 mRNA 癌症免疫療法。我們相信這兩個項目具有顛覆性的泛腫瘤潛力。本季結束時，我們的財務狀況良好，總現金和證券投資為 159 億歐元。除其他因素外，與年底數字相比的減少是由於作為 Biotheus 收購的一部分支付了約 8 億美元。它還反映了與 NIH 解決合約糾紛所支付的約 7.92 億美元的款項。我們預計與賓州大學達成的和解協議相關的 4 億美元額外付款將反映在我們 2025 年第二季的財務狀況中。

With respect to both these settlements, we expect to be reimbursed partially by our partner, Pfizer, during 2025 and 2026. Building on our strong cash position and track record of financial discipline, we will continue to invest in our pan-tumor oncology programs, which we believe position us well to achieve sustainable growth. Turning to the next slide. We're confirming the company financial guidance for the 2025 financial year with revenue expected to be in the range of EUR1.7 billion to EUR2.2 billion. R&D expenses expected to be in the range of EUR2.6 billion to EUR2.8 billion.

對於這兩項和解，我們預計將在 2025 年和 2026 年期間從合作夥伴輝瑞公司獲得部分補償。憑藉我們強大的現金狀況和良好的財務紀律記錄，我們將繼續投資於我們的泛腫瘤學項目，我們相信這將使我們實現可持續成長。翻到下一張投影片。我們確認了公司 2025 財年的財務指導，預計收入在 17 億歐元至 22 億歐元之間。研發預計支出將在26億歐元至28億歐元之間。

SG&A expense is expected to be in the range of EUR650 million to EUR750 million and capital expenditures expected to be in the range of EUR250 million to EUR350 million. Our revenue guidance assumes relatively stable vaccination rates, pricing and market share as compared to 2024.

銷售、一般及行政費用預計支出將在 6.5 億歐元至 7.5 億歐元之間，資本支出預計將在 2.5 億歐元至 3.5 億歐元之間。我們的收入指導假設與 2024 年相比，疫苗接種率、價格和市場份額相對穩定。

We anticipate a revenue phasing similar to last year with the last three to four months of the year driving the full year revenue figure. Please note that potential changes in law or government policy, including tariffs and public health policy and evolving public sentiment around vaccines and mRNA technology worldwide could further negatively impact our anticipated COVID-19 vaccine revenues and expenses. While it is premature to comment specifically on the potential impact of tariffs on the pharmaceutical industry at this stage, we're actively monitoring the situation and are evaluating potential risk mitigation strategies.

我們預計收入分階段與去年類似，今年最後三到四個月將推動全年收入數字。請注意，法律或政府政策的潛在變化，包括關稅和公共衛生政策以及全球圍繞疫苗和 mRNA 技術的不斷變化的公眾情緒，可能會進一步對我們預期的 COVID-19 疫苗收入和支出產生負面影響。雖然現階段就關稅對製藥業的潛在影響發表具體評論還為時過早，但我們正在積極監測局勢並評估潛在的風險緩解策略。

In addition, we estimate some inventory write-downs and other charges in the range of roughly 15% of BioNTech's share of gross profit from COVID-19 vaccine sales in the Pfizer territory. We also expect revenues related to our service businesses as well as revenues from the German pandemic preparedness agreement to contribute to our overall group revenues. We continue to diligently invest in our long-term growth strategy while maintaining financial discipline. We remain focused on achieving long-term sustainable growth and generating value for patients and shareholders.

此外，我們估計，一些庫存減記和其他費用約佔 BioNTech 在輝瑞地區 COVID-19 疫苗銷售毛利份額的 15%。我們也預計與我們的服務業務相關的收入以及來自德國大流行病防備協議的收入將有助於我們集團的整體收入。我們在保持財務紀律的同時，繼續努力投資我們的長期成長策略。我們始終致力於實現長期可持續成長並為患者和股東創造價值。

Today, I will close my section on a personal note. As Ugur mentioned, I will retire from my executive role at BioNTech at the end of June and will focus on nonexecutive Board roles in the future. As this is my last earnings call as CFO of BioNTech, I would like to take this opportunity to thank the investor and analyst community for their trust.

今天，我將以個人觀點結束我的部分。正如 Ugur 所提到的，我將於 6 月底從 BioNTech 的執行職位上退休，並將在未來專注於非執行董事會職位。這是我擔任 BioNTech 財務長的最後一次財報電話會議，我想藉此機會感謝投資者和分析師社群的信任。

I also thank my colleagues on the Supervisory and Management Board as well as my teams for their dedication and collaboration during this remarkable growth journey. It has been a privilege to be part of the development of BioNTech into one of the largest global biotechnology companies. I'm confident that BioNTech is well positioned for continued success.

我還要感謝監事會和管理委員會的同事以及我的團隊在這非凡的成長歷程中的奉獻和合作。我很榮幸能夠參與 BioNTech 發展成為全球最大的生技公司之一。我相信 BioNTech 已做好準備繼續取得成功。

And with that, I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for our strategic outlook and concluding remarks. Thank you.

接下來，我想將電話交給我們的首席策略長瑞安·理查森 (Ryan Richardson)，請他介紹我們的策略展望並作總結發言。謝謝。

Thank you, Jens. I will close our prepared remarks with a brief summary of our 2025 strategic priorities. We are continuing to focus on executing against two pan-tumor product opportunities, BNT327 and our mRNA cancer immunotherapies, FixVac and iNeST. Both of these programs are currently in multiple ongoing Phase 2 and 3 trials, reflecting our strategy to bring novel combinations to patients. We expect to generate additional meaningful data for these programs throughout this year.

謝謝你，詹斯。我將以我們 2025 年策略重點的簡要總結來結束我們的準備好的發言。我們將繼續專注於針對兩種泛腫瘤產品機會的執行，即 BNT327 和我們的 mRNA 癌症免疫療法 FixVac 和 iNeST。這兩個項目目前都處於多個正在進行的 2 期和 3 期試驗中，體現了我們為患者帶來新型組合的策略。我們希望今年能為這些專案產生更多有意義的數據。

We are also continuing to build out our commercial capabilities in oncology to support our goal of becoming a fully integrated biopharmaceutical company. These include a US General Manager and broader global commercial leadership team with the goal of commercial readiness to support our transition to a commercial stage in oncology, starting with the potential launch of BNT323 as early as 2026, if approved.

我們也將繼續增強我們在腫瘤學領域的商業能力，以支持我們成為一家完全整合的生物製藥公司的目標。其中包括一名美國總經理和更廣泛的全球商業領導團隊，其目標是做好商業準備，支持我們向腫瘤學商業階段的過渡，如果獲得批准，最早可能在 2026 年推出 BNT323。

In infectious diseases, we will continue to invest to maintain our and Pfizer's global leadership position in the COVID-19 vaccine market while advancing next-generation and combination vaccines in the clinic. We expect to provide multiple updates from our early-stage infectious disease pipeline this year.

在傳染病領域，我們將繼續投資，維持我們和輝瑞在新冠疫苗市場的全球領導地位，同時推動下一代疫苗和聯合疫苗的臨床研發。我們預計今年將提供早期傳染病研究管道的多項更新。

In closing, I would like to highlight on the next slide important investor events we will be holding this year. Our Annual General Meeting will take place on May 16. We also plan to hold our Innovation Series event in the fall, and we'll share more details later in the year.

最後，我想在下一張投影片中強調我們今年將舉辦的重要投資人活動。我們的年度股東大會將於 5 月 16 日舉行。我們還計劃在秋季舉辦創新系列活動，並將在今年稍後分享更多細節。

With that, we would like to open the floor for questions.

現在，我們願意開始回答問題。

(Operator Instructions) Tazeen Ahmad, Bank of America.

（操作員指示） Tazeen Ahmad，美國銀行。

As you prepare for your first launch for endometrial cancer, can you talk to us about how big do you think that particular addressable population is? And then related to that, can you remind us where manufacturing of 327 is expected to take place? And if you expect any impact on those tariffs?

當您準備首次推出針對子宮內膜癌的藥物時，能否告訴我們您認為特定的可針對人群有多大？與此相關，您能否提醒我們 327 的製造預計將在哪裡進行？您預計這些關稅會受到什麼影響？

Yeah. Thank you, Tazeen. So we estimate that the second-line market in endometrial cancer is about 10,000 patients in the US and Europe. So it is a sizable potential market opportunity.

是的。謝謝你，塔津。因此，我們估計美國和歐洲子宮內膜癌的二線市場約為 10,000 名患者。因此，這是一個巨大的潛在市場機會。

In regards to manufacturing, so we licensed this program, BNT323, as you know, from Duality Biologics. Manufacturing is currently supplied out of China, and we are in the process of diversifying our supply base and our plans over the next couple of years are to establish multiple supply nodes, including outside of China. But for the time being, it is -- we're reliant on a China-based CDMO.

關於製造，如您所知，我們從 Duality Biologics 獲得了 BNT323 專案的許可。目前，製造業的供應來自中國，我們正在實現供應基礎的多元化，未來幾年我們的計畫是建立多個供應節點，包括中國以外的供應節點。但就目前而言，我們依賴中國的 CDMO。

I'll just say that -- maybe, Jens, you can say a few things about tariffs for our broader business. But we don't anticipate at the current time, significant impact, financial impact from the tariffs that have been announced. Obviously, we're continuing to track policies and responses to US policy in that regard.

我只是想說——也許，詹斯，你可以談談我們更廣泛業務的關稅問題。但我們目前預計，已宣布的關稅不會產生重大影響，也不會對財務造成重大影響。顯然，我們將繼續關注美國在這方面的政策和回應。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞。

So this is more long term. In NSCLC, let's say, five years down the road, what do you think is the more likely outcome? The VEGF bispecifics changed standard of care in chemo combo or you really actually needed a novel ADC along with the bispecific to beat pembro chemo? And then kind of as an add-on, how do you expect the safety profile of 327 to evolve in chemo combo versus some of the early data you've seen with the TROP2 ADC?

所以這是更長期的。對於 NSCLC 來說，假設五年後，您認為更可能的結果是什麼？VEGF 雙特異性抗體改變了化療組合的治療標準，還是您真的需要一種新型 ADC 和雙特異性抗體來擊敗派姆化療？然後作為補充，與您在 TROP2 ADC 中看到的一些早期數據相比，您認為 327 的安全性在化療組合中會如何發展？

Yeah. Thanks, Akash. So I think you're asking -- yes, just to clarify the question. So you're asking in five years, how do we see the NSCLC market evolving? Do we see this evolving where an ADC will be a necessary component on top of a next-generation immunomodulator? Is that fair?

是的。謝謝，阿卡什。所以我認為你問的是——是的，只是為了澄清這個問題。所以您想問，五年後，我們會看到 NSCLC 市場如何發展？我們是否看到了這種發展趨勢，即 ADC 將成為下一代免疫調節劑的必要組成部分？這樣公平嗎？

We'll go with that.

我們會這麼做。

That was the question. Akash, we think that actually both will be the case. On the one hand, we, as you know, are developing -- our bispecific 327 in combination with chemotherapy to replace first-generation CPIs in non-small cell lung cancer. However, we expect that the clinical benefit threshold to be reached, will be moving over time.

這就是問題所在。Akash，我們認為實際上兩種情況都是如此。一方面，如您所知，我們正在開發雙特異性 327 與化療相結合，以取代非小細胞肺癌中的第一代 CPI。然而，我們預期達到的臨床獲益閾值將會隨著時間的推移而變化。

And therefore, also ADCs in combination with our bispecifics or with such PD-1, PD-L1 VEGF bispecifics will also have a role. That's the reason why we are following both streams of development. In a sort of sequential manner.

因此，ADC 與我們的雙特異性抗體或 PD-1、PD-L1 VEGF 雙特異性抗體的結合也將發揮作用。這就是我們追隨這兩條發展潮流的原因。以某種連續的方式。

And with regard to the ADCs, as you know, we have several ADCs that in principle, can be combined in the non-small cell lung cancer indications, including our TROP2 ADC, B7-H3 as well as our HER3 ADC BNT326.

關於 ADC，如您所知，我們有幾種 ADC 原則上可以結合用於非小細胞肺癌適應症，包括我們的 TROP2 ADC、B7-H3 以及我們的 HER3 ADC BNT326。

Daina Graybosch, Leerink Partners.

Daina Graybosch，Leerink Partners。

CDC's ACIP is going to have a vote in June on the recommendation of COVID boosters. And my interpretation of their pre-meeting was there is a likelihood that they narrow the US recommendation to a risk-based. And I wonder if you could talk about that meeting, what you anticipate the vote will be? And if they do narrow it, what that might -- how that might impact your COVID-19 vaccine sales in the US?

CDC 的 ACIP 將於 6 月就 COVID 加強劑的建議進行投票。我對他們會前會議的解讀是，他們有可能將美國的建議縮小到基於風險的程度。我想知道您是否可以談談那次會議，您預計投票結果會如何？如果他們確實縮小了範圍，這可能會對您在美國的 COVID-19 疫苗銷售產生什麼影響？

Yes. Thanks for the question, Daina. Indeed, (technical difficulty) the world, not just in the United States, but also in other regions. And we are expecting actually the first wave of decisions regarding strain selection and policy for the COVID season in 2025 that take place actually in the next couple of weeks in May already in some regions. And we're going to be tracking that very closely. So I think we'll have within the next four to six weeks, we already have some additional clarity in terms of the picture.

是的。謝謝你的提問，戴娜。確實，(技術難度)全球都存在，不只在美國，也在其他地區。實際上，我們預計，有關 2025 年 COVID 季節的病毒株選擇和政策的第一波決策將在未來幾週（即 5 月）在某些地區做出。我們將密切關注此事。因此我認為我們將在接下來的四到六週內對情況有更清晰的了解。

I think in regards to the US policy specifically, it's already been the case that the majority of vaccinations in the United States have gone into the older 65-plus populations along with the immunocompromised, which together account for about 20% of the US population, about 18% of the US population is 65-plus, and there's a couple more percent that take into account the immunocompromised.

我認為，具體到美國的政策，美國的大部分疫苗接種已經針對 65 歲以上的老年人群和免疫功能低下的人群，這部分人群約占美國人口的 20%，其中 65 歲以上的人口約佔 18%，另有幾個百分點的人口則考慮到了免疫功能低下人群。

So that that's already been the majority of vaccinations in the US for the last couple of years. So while, of course, we're going to track the outcome of the meeting that you mentioned, we think that the market is already oriented in that direction. And so our base scenario here is that we think that the vaccination rates in the US around 20% that we've seen over the last couple of years is still our sort of base scenario going into the end of this year.

因此，這已經成為過去幾年美國大部分疫苗接種的情況。因此，當然，我們會追蹤您提到的會議結果，但我們認為市場已經朝著這個方向發展。因此，我們的基本情境是，我們認為過去幾年美國約 20% 的疫苗接種率仍然是我們今年年底的基本情境。

And in addition, maybe Daina, could just add, we've seen such a development in other jurisdictions before as well. So it's nothing new. What we experienced is, of course, the recommendation goes for (inaudible) population, it goes for the immunosuppressive population. And there will be a chunk of people that will -- and that's difficult to predict -- chunk of people that will get vaccinations nonetheless, independent of the recommendation of the age. That's the experience that we had in the past to a great extent.

此外，戴娜也許可以補充一點，我們以前在其他司法管轄區也看到過這樣的發展。所以這並不是什麼新鮮事。當然，我們的經驗是，該建議適用於（聽不清楚）人群，適用於免疫抑制人群。但仍會有一部分人——這很難預測——無論如何都會接種疫苗，與年齡建議無關。這在很大程度上是我們過去的經驗。

So we got to -- it has to be seen how the implications will look like, could have a negative implication, but it's very difficult to predict at this point in time.

所以我們必須——看看其影響會是什麼樣的，可能會有負面影響，但目前很難預測。

Cory Kasimov, Evercore.

科里·卡西莫夫（Cory Kasimov），Evercore。

Jens, congratulations on your retirement. So I wanted to -- I recognize it's difficult to comment on programs at another company, but I'd be interested in your perspective on Akeso's preliminary overall survival data that recently came out. I mean, is this something that's in line with your expectations? And maybe more specifically as it relates to 327, does it have any impact at all in how you think about designing your own trials in non-small cell lung cancer? Thank you.

詹斯，恭喜你退休。所以我想——我認識到對另一家公司的專案發表評論很困難，但我對你對康方生物最近發布的初步總體生存數據的看法很感興趣。我的意思是，這符合你的預期嗎？也許更具體地說，就 327 而言，它對您如何設計自己的非小細胞肺癌試驗有任何影響嗎？謝謝。

Yes. Thank you, Cory, for the question. We are also strong believers of the VEGF, PD-1, PD-L1 bispecific concept. Therefore, we find the data, which has been reported from HARMONi-2 very encouraging. The PFS, which was the primary endpoint is -- speaks for itself.

是的。謝謝 Cory 提出的問題。我們也堅信 VEGF、PD-1、PD-L1 雙特異性概念。因此，我們發現 HARMONi-2 報告的數據非常令人鼓舞。PFS 是主要終點，其意義不言而喻。

The OS trend, which is based on a premature analysis of an immature information fraction with very low alpha, also this is encouraging. It has not direct impact on our program. ROSETTA Lung-02 is in a different population and it's in combination with chemotherapy. However, as I said, seeing that the concept as such is producing encouraging data and clinical benefit is also very positive for us.

OS 趨勢是基於對不成熟資訊部分的過早分析，其 alpha 值非常低，這也是令人鼓舞的。它對我們的計劃沒有直接影響。ROSETTA Lung-02 適用於不同的族群，並與化療結合。然而，正如我所說，看到這個概念本身正在產生令人鼓舞的數據和臨床效益，對我們來說也是非常積極的。

Terence Flynn, Morgan Stanley.

摩根士丹利的特倫斯弗林。

Two part for me on 327. Thanks for the details on the ROSETTA Lung-02 study. I was just wondering if you could elaborate in terms of the doses that are being studied exactly in the Phase 2 portion and when we might see some of the Phase 2 data? And then can you disclose the powering of the Phase 3 portion of that trial?

327 上有兩個部分。感謝您提供有關 ROSETTA Lung-02 研究的詳細資訊。我只是想知道您是否可以詳細說明第二階段正在研究的劑量以及我們何時可以看到第二階段的一些數據？那麼，您能透露一下該試驗第三階段部分的動力狀況嗎？

We cannot comment at this point on the doses we are exploring. You might get more information on that later this year when we will present that trial design on conferences. The second question was -- can you repeat the second question?

目前我們無法對我們正在探索的劑量發表評論。今年稍後我們將在會議上展示該試驗設計，屆時您可能會獲得更多相關資訊。第二個問題是──您能重複第二個問題嗎？

The timing of the data for Phase 2 and the powering of the Phase 3 portion?

第 2 階段的資料時間和第 3 階段部分的供電時間？

Yes. So the data for Phase 2, we will see some data later this year, beginning of next year. And the powering for the Phase 3 portion is to accommodate co-primary PFS OS.

是的。因此，我們將在今年稍後、明年年初看到第二階段的數據。第 3 階段部分的供電是為了容納共同主要的 PFS OS。

Jessica Fye, JPMorgan.

潔西卡費伊（Jessica Fye），摩根大通。

Ryan, I think earlier in the call, you mentioned minimal impact from current tariffs. But can you speak to how the potential implementation of future biopharma tariffs in the US might impact BioNTech? Is COMIRNATY for the US market made in the US?

瑞安，我想在早些時候的通話中，您提到了當前關稅的影響微乎其微。但是您能否談談美國未來實施的生物製藥關稅將如何影響 BioNTech？COMIRNATY 是針對美國市場在美國製造的嗎？

And second, can you just recap what you guys see as the key similarities or maybe more importantly, the key areas of differentiation of your development plans for 327 relative to the ivonescimab development program?

其次，您能否簡單概括一下您認為 327 開發計劃與 ivonescimab 開發計劃之間的主要相似之處，或者更重要的是，主要的區別領域？

Yes, sure. Thanks, Jessica. So on the tariff point, my reference to limited near-term financial impact was related mainly to the fact that we've got one commercial stage product in COMIRNATY. Currently, where we have production infrastructure and capability through our partnership with Pfizer on both sides of the Atlantic. So we've got -- we have the ability to produce that vaccine in the United States.

是的，當然。謝謝，傑西卡。因此，在關稅問題上，我提到有限的短期財務影響主要與我們在 COMIRNATY 中擁有商業階段產品有關。目前，透過與輝瑞公司的合作，我們在大西洋兩岸都擁有生產基礎設施和生產能力。因此，我們有能力在美國生產這種疫苗。

We also have the ability to produce it in Europe, and we have sufficient capacity to manage that accordingly. I don't know, Jens, would you add anything?

我們也有能力在歐洲生產，我們有足夠的能力進行相應的管理。我不知道，詹斯，你還有什麼要補充嗎？

No, it just -- there are existing tariffs already for China, 20% at this point in time that we've got to cover and the financial implications so far have been really minor for us going forward, and that makes life a little bit difficult in terms of predictions, of course, how that will evolve over time and pharmaceuticals will be challenged, then costs could go up for clinical trials and for research work. But overall, at this point in time, we would estimate that as not being really critical for us. We can't talk for anyone else, of course. I mean you've seen a lot of statements from other companies in terms of the tariffs. We've got to wait how things are evolving over time and how severe financial implications can look like.

不，只是——中國目前已經徵收了 20% 的關稅，我們必須承擔，到目前為止，這對我們未來的財務影響真的很小，當然，這在預測方面有點困難，隨著時間的推移，這種情況將如何發展，製藥業將面臨挑戰，那麼臨床試驗和研究工作的成本可能會上升。但總體而言，目前我們估計這對我們來說並不是很關鍵。當然，我們不能代表任何人發言。我的意思是你已經看到很多其他公司關於關稅的聲明。我們必須等待事態隨著時間的推移如何發展，以及嚴重的財務影響會有多大。

And with regard to your second question, Jessica, on BNT327 development strategy, I would just note that our strategy is based on a couple of key pillars. The first of which is to establish BNT327 as an approved therapy in a number of solid tumor indications. We've announced publicly three of those indications. A couple of those where we think we're positioned if we can execute well to be potentially first to market. So TNBC and small cell lung cancer being two of those potential indications.

關於您的第二個問題，傑西卡，關於 BNT327 發展策略，我只想指出，我們的策略是基於幾個關鍵支柱。其中第一步是將 BNT327 確立為多種實體腫瘤適應症的核准療法。我們已經公開宣布了其中三項跡象。我們認為，如果我們能夠很好地執行，我們就有可能率先進入市場。因此，TNBC 和小細胞肺癌是其中兩種潛在適應症。

Those first wave of trials are with chemotherapy backbones. We think that's the fastest path to market. But the broader and longer-term strategy is to combine BNT327 with other agents, including ADCs. And there, we think we have a differentiated strategy by virtue of our broad pipeline and the ADCs and other therapies that we have in-house that could be combined with it.

第一波試驗以化療為主。我們認為這是進入市場的最快途徑。但更廣泛和長期的策略是將 BNT327 與其他藥物（包括 ADC）結合。我們認為，憑藉我們廣泛的產品線以及我們內部可以與之結合的 ADC 和其他療法，我們擁有差異化策略。

I don't have much to add. Thank you, Ryan. I think that summarizes our differentiation strategy.

我沒有什麼好補充的。謝謝你，瑞安。我認為這概括了我們的差異化策略。

Evan Seigerman, BMO Capital Markets.

艾文‧塞格曼 (Evan Seigerman)，蒙特婁銀行資本市場。

I wanted to take a higher-level question. With varying views on mRNA technology, how are you thinking about the potential of your therapeutic vaccine franchise? There's a lot of resistance building up in the United States. Do you still see this as a core component of your strategy? Are you more focused on the bispecifics?

我想問一個更高層次的問題。鑑於人們對 mRNA 技術的看法各不相同，您如何看待治療性疫苗特許經營的潛力？美國國內正在出現強烈的抵抗。您是否仍將此視為您策略的核心組成部分？您是否更關注雙特異性抗體？

Definitely, we have a core interest in our mRNA therapeutics. As we have alluded today, we have two pan-tumor opportunities as BNT327, which gives us the opportunity to develop the product as potential new IO-backbone in multiple indications. And the same is true for the pan-tumor potential for our therapeutic mRNA immunotherapies based on our neoantigen as well as our FixVac approach. We believe that this approaches have a huge potential, particularly in the patient population with a higher risk of relapse, either in the adjuvant setting or in the minimal residual disease setting. But we also believe that the combination of both compounds, BNT327 as well as our vaccine -- mRNA therapeutics vaccine provide a huge opportunity.

毫無疑問，我們對 mRNA 療法有著核心興趣。正如我們今天所提到的，我們擁有 BNT327 兩種泛腫瘤機會，這使我們有機會將該產品開發為多種適應症的潛在新 IO 骨架。我們的基於新抗原和 FixVac 方法的治療性 mRNA 免疫療法的泛腫瘤潛力也是如此。我們相信這種方法具有巨大的潛力，特別是對於復發風險較高的患者群體，無論是在輔助治療中還是在微小殘留病灶治療中。但我們也相信，BNT327 這兩種化合物以及我們的疫苗——mRNA 治療疫苗的結合提供了巨大的機會。

So the science is clearly stating that mRNA therapeutics are going to be a disruptive platform of the future, and we believe it's even more the time to invest into the technologies and further -- further leverage our strength here.

因此，科學清楚地表明，mRNA 療法將成為未來的顛覆性平台，我們相信現在正是投資該技術並進一步發揮我們優勢的時候。

Yaron Werber, TD Cowen.

Yaron Werber，TD Cowen。

I have a couple of interrelated questions. The first one is you've been very clear and everything you said made a lot of sense on how you're going to develop 327, small cell TNBC, non-small cell. What about second-line EGFR mutant? Any thoughts on that indication? Obviously, we're waiting for the Phase 3 from the competitor.

我有幾個相互關聯的問題。首先，您說得非常清楚，您關於如何開發 327、小型細胞 TNBC、非小型細胞的說法也很有道理。那麼二線EGFR突變患者呢？對於這個跡象，您有什麼看法嗎？顯然，我們正在等待競爭對手的第三階段。

And then secondly, can you just remind us for 323 for second-line endometrial, what data are we expecting this year and filing for accelerated approval is going to be based on which endpoint specifically? And if you can, just the powering for that study?

其次，您能否提醒我們，對於二線子宮內膜癌 323，我們今年預計會得到哪些數據，以及申請加速批准將具體基於哪個終點？如果可以的話，您願意為這項研究提供動力嗎？

Yes. For second-line non-small cell lung cancer, I believe you referred to the EGFR mutant population, right? We have recently published data in this population, including response and PFS data based also with differentiation into patient populations with PD-L1 positive and PD-L1 negative populations. The data are very encouraging. We have currently also running ADC trials in this population and see encouraging data here as well.

是的。對於二線非小細胞肺癌，我相信您指的是 EGFR 突變族群，對嗎？我們最近發布了該族群的數據，包括基於反應和 PFS 數據，同時也區分了 PD-L1 陽性和 PD-L1 陰性患者群體。這些數據非常令人鼓舞。我們目前也在該族群中進行 ADC 試驗，也看到了令人鼓舞的數據。

And we will consider -- we are considering to combine both to -- as we expect synergistic activity here, while we also keep our option to BNT327 in the subpopulation of EGFR mutant tumors based on their PD-L1 positivity.

我們正在考慮將兩者結合起來，因為我們預期會產生協同作用，同時我們也根據 PD-L1 陽性情況，在 EGFR 突變腫瘤亞群中保留 BNT327 的選擇權。

I think in regards to your second question, which I believe was what are the endpoints in the data package that we expect for BNT323 later this year. Ozlem, do you want to comment?

關於您的第二個問題，我認為我們預計今年稍後 BNT323 的資料包端點是什麼。Ozlem，你想發表評論嗎？

Yes. So our -- you are referring to our second-line endometrial cancer trial, which is a single-arm trial, which comes basically out of our basket trial across solid cancers, which we are conducting -- have conducted together with Duality. And the endpoint is objective response rate. We are in discussion with regulatory authorities to better understand the expectations for BLA and are progressing in these discussions. I might also add, I forgot to say that the population is across all HER2 positivity scores.

是的。所以我們的——您指的是我們的二線子宮內膜癌試驗，這是一項單臂試驗，基本上來自我們正在進行的針對實體癌的籃子試驗——是與 Duality 一起進行的。終點是客觀響應率。我們正在與監管機構進行討論，以更好地了解對 BLA 的預期，而這些討論正在取得進展。我還要補充一點，我忘了說人群涵蓋了所有 HER2 陽性評分。

So it's the broader second-line endometrial cancer population.

因此，這是更廣泛的二線子宮內膜癌族群。

Mohit Bansal, Wells Fargo.

富國銀行的 Mohit Bansal。

Congrats on all the progress. I have two questions. So one is with ROSETTA Lung-02, could you give us some timelines when should we expect Phase 2 portion of the study to be over and you're moving formally into Phase 3? And second one, you get a lot of questions around the differences between -- different bispecifics for your Summit and Merck. And the key difference I see, like one is that you are the only one using a PD-L1.

祝賀你取得的所有進展。我有兩個問題。其中一個是關於 ROSETTA Lung-02 的，您能否給我們一些時間表，我們預計研究的第 2 階段何時結束，然後正式進入第 3 階段？第二，您會問很多關於 Summit 和 Merck 的不同雙特異性抗體之間的差異的問題。我看到的關鍵區別在於，你是唯一一個使用 PD-L1 的人。

And you also have the very, very heavy chain, so VHH. So could you talk a little bit about these differences and how much could they matter in the real world, actually PD-L1 given that the experience with PD-L1 antibodies has not been that fruitful.

而且你還擁有非常非常重的鏈條，所以是 VHH。那麼，您能否稍微談談這些差異以及它們在現實世界中有多大影響，實際上是 PD-L1，因為 PD-L1 抗體的經驗並沒有那麼富有成效。

Okay. So I think the first question was when do we expect the Phase 2 portion of the ROSETTA Lung trial to be complete?

好的。所以我認為第一個問題是我們預期 ROSETTA Lung 試驗的第 2 階段何時完成？

The Phase 2 portion of ROSETTA will be completed later this year or we will have data to inform -- to put it in this way, to inform the Phase 3 portion of the trial, defining the dose, which will be then used in the Phase 3 portion, which will start this year.

ROSETTA 的第 2 階段部分將於今年稍後完成，或者我們將獲得數據來告知 - 換句話說，告知試驗的第 3 階段部分，確定劑量，然後該劑量將用於今年開始的第 3 階段部分。

The other question, I think, was about molecular differentiation between different bispecific molecules with this mode of action. We cannot comment others molecules, obviously. We have deliberately chosen when we were assessing different external opportunities bispecific with PD-L1 versus the PD-1 portion because we expect from PD-L1 that it might be superior to PD-1 in anchoring in particular, in the tumor microenvironment where we want to have the bispecific. That was one of the reasons. And also the molecular format with full IgG anti-VEGF portion and the VHH PD-L1 portion was compelling to us because we think that we get the right pattern of cross ligation in the tumor micro environment.

我認為，另一個問題是關於具有這種作用模式的不同雙特異性分子之間的分子區分。顯然，我們無法評論其他分子。當我們評估不同的外在機會時，我們特意選擇了 PD-L1 與 PD-1 部分的雙特異性，因為我們預期 PD-L1 可能優於 PD-1，特別是在錨定方面，在我們希望具有雙特異性的腫瘤微環境中。這是原因之一。而且，具有完整 IgG 抗 VEGF 部分和 VHH PD-L1 部分的分子格式對我們來說也很有吸引力，因為我們認為我們在腫瘤微環境中獲得了正確的交叉連接模式。

Geoff Meacham, Citigroup.

花旗集團的傑夫‧米查姆。

This is [Nishant] on for Jeff. So on 327, you also highlight potential to kind of combine with other modalities, including ADCs and cell therapies. I wanted to ask what are the key factors driving the selection of these specific combinations? And what is the overall kind of rationale for this kind of combinations?

我是 [Nishant]，代表 Jeff 發言。因此，在 327 上，您也強調了與其他方式結合的潛力，包括 ADC 和細胞療法。我想問一下，選擇這些特定組合的關鍵因素是什麼？那麼這種組合的整體原理是什麼呢？

Yes, I can take the question. I think with regard to the combination, our portfolio, anticancer portfolio has three categories of products, which are all suitable as combination therapies. First of all, our IO pipeline. So we have multiple additional bispecifics, particularly also after acquisition of Biotheus in the pipeline, including, for example, (inaudible) antibody, bispecific antibody and other bispecific antibodies. So these are -- we will engage into clinical trials.

是的，我可以回答這個問題。我認為就組合而言，我們的產品組合、抗癌產品組合有三類產品，都適合作為聯合療法。首先，我們的 IO 管道。因此，我們有多個額外的雙特異性抗體，特別是在收購 Biotheus 之後，包括例如（聽不清楚）抗體、雙特異性抗體和其他雙特異性抗體。所以這些——我們將參與臨床試驗。

We have in preclinical context a mode of action synergy for this compound. The second class, which we find very exciting is our mRNA vaccines and mRNA immunotherapies.

我們在臨床前環境中對這種化合物的作用協同模式進行了研究。第二類，我們發現非常令人興奮的是我們的 mRNA 疫苗和 mRNA 免疫療法。

We believe that this modality could have the advantage not only to delay PFS and improve OS, but also have to completely eradicate basically tumor cells, which remain after checkpoint blockade. We have been engaging into a number of preclinical studies and our first clinical cohorts are going to start this year -- later this year. And we have recently demonstrated preclinical proof of concept of combination of BNT327 with our ADC portfolio. which provides the opportunity to reduce tumor burden with the ADCs to benefit from the immunogenic cell that's mediated by ADCs and build on the superior effect of the bispecific combining VEGF -- anti-VEGF and PD-L1 activities.

我們相信這種方式不僅可以延長 PFS 和改善 OS，而且還可以徹底根除檢查點阻斷後殘留的腫瘤細胞。我們已經開展了多項臨床前研究，我們的第一批臨床試驗將於今年稍後開始。我們最近展示了 BNT327 與我們的 ADC 產品組合相結合的臨床前概念驗證。這提供了利用 ADC 減輕腫瘤負擔的機會，從而受益於 ADC 介導的免疫原性細胞，並建立在雙特異性結合 VEGF——抗 VEGF 和 PD-L1 活性的卓越效果之上。

Asthika Goonewardene, Truist.

Asthika Goonewardene，Truist。

This is Karina for Asthika. I have a question on the initial ACR data for BNT327, which was combined with TROP2 ADC. There was notable rate of stomatitis, which included Grade 3 events. How do you plan to manage this toxicity going forward? And was this also observed with other ADCs from DualityBio?

我是 Karina，為 Asthika 服務。我對與 TROP2 ADC 結合的 BNT327 的初始 ACR 數據有疑問。口腔炎發生率顯著，其中包括 3 級事件。您計劃如何控制這種毒性？在 DualityBio 的其他 ADC 中也觀察到了這種情況嗎？

Actually, the stomatitis rate in the combination was very comparable to the stomatitis rate that is observed with BNT325, our anti-TROP2 ADC alone, which is very encouraging that we don't see additional additive toxicity.

實際上，組合療法中的口腔炎發生率與單獨使用 BNT325（我們的抗 TROP2 ADC）觀察到的口腔炎發生率非常相似，這非常令人鼓舞，因為我們沒有看到額外的附加毒性。

Harry Gillis, Berenberg.

哈里·吉利斯 (Harry Gillis)，貝倫貝格 (Berenberg)。

Could you please comment on the extent of global Phase 2 BNT327 data you've seen internally that informs your decision for Phase 3 entry in small cell lung and TNBC? And then related to that, is Phase 3 entry in TNBC still contingent on any Phase 2 global data? And finally, when could we expect the Phase 2 global data for BNT327 in small cell or TNBC this year? Could we see it at ESMO or World Lung?

您能否評論一下您內部看到的全球第 2 階段 BNT327 數據的範圍，這些數據有助於您決定在小細胞肺和 TNBC 中進入第 3 階段？與此相關的是，TNBC 進入第 3 階段是否仍取決於任何第 2 階段的全球數據？最後，我們什麼時候可以期待今年 BNT327 在小型蜂窩或 TNBC 中的第 2 階段全球數據？我們可以在 ESMO 或世界肺臟大會上看到它嗎？

Yes. As you might see from the clinical trial data base, we are doing now our clinical trials in this indication in a global manner in the US, in Europe, in multiple centers in Turkey and recapitulating data identified -- identified or previously presented from China patients. We are very confident that this -- the findings of the China trial will be more or less fully recapitulated in this global trial.

是的。正如您可能從臨床試驗資料庫中看到的，我們目前正在美國、歐洲、土耳其的多個中心以全球方式開展此適應症的臨床試驗，並重現已確定的或先前從中國患者那裡提供的數據。我們非常有信心，中國試驗的結果將或多或少在這次全球試驗中完全重現。

John Newman, Canaccord Genuity.

約翰紐曼，Canaccord Genuity。

I'm just curious regarding the development of the COVID-19 vaccine at Pfizer. I wonder if you have any thoughts on some of the recent comments coming out of FDA regarding the possibility of looking at randomized studies for the yearly strain update. I'm wondering if you think that's feasible or likely if it were to move forward, what your strategy might be.

我只是對輝瑞的 COVID-19 疫苗研發感到好奇。我想知道您對 FDA 最近發表的一些關於對年度菌株更新進行隨機研究的可能性的評論有何看法。我想知道您是否認為這是可行的，或者如果繼續前進的話，您的策略是什麼。

Yes. Thanks, John. So I think that -- I would note that the COVID-19 vaccine was first approved after a study of 43,000 participants, very large global study where we demonstrated efficacy in that study. And obviously, we're continuing to track all policy -- potential policies out of FDA, but we don't expect that, that talk is going to have a near-term impact on our COVID vaccine franchise given it's been approved for multiple years. Our expectation is that there's going to be multiple regions selecting strains for the fall '25, '26 season. That's our focus at the moment.

是的。謝謝，約翰。因此我認為——我想指出的是，COVID-19 疫苗是在對 43,000 名參與者進行研究後首次獲得批准的，這是一項非常大規模的全球性研究，我們在該研究中證明了疫苗的有效性。顯然，我們將繼續追蹤 FDA 的所有政策——潛在政策，但考慮到該疫苗已獲批准多年，我們預計這些討論不會對我們的 COVID 疫苗特許經營權產生短期影響。我們預計，將會有多個地區為 2025 年和 2026 年秋季季節選擇菌株。這是我們目前的重點。

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

謝謝。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。