Biontech SE (BNTX) 2023 Q4 法說會逐字稿

Welcome to the BioNTech's Fourth Quarter and Full Year 2023 Earnings Call.

歡迎參加 BioNTech 2023 年第四季和全年財報電話會議。

I would like to hand the call over to Dr. Victoria Meissner, Vice President of Strategy and Investor Relations. Please go ahead.

我想將電話轉交給策略和投資者關係副總裁維多利亞·邁斯納 (Victoria Meissner) 博士。請繼續。

Thank you. Good morning and good afternoon. Thank you for joining BioNTech's fourth quarter and full year 2023 earnings Call. As a reminder, the slides we'll 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 的 2023 年第四季和全年財報電話會議。提醒一下，我們將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 U.S. Securities and Exchange Commission. Forward-looking statements in this call are subject to significant risks and uncertainties, speak only as of the date of this conference call, and we undertake no obligation to update or revise any of these statements. On Slide 3, you can find the agenda for today's call.

在下一張投影片上，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資訊在我們向美國證券交易委員會提交的文件中進行了描述。本次電話會議中的前瞻性陳述存在重大風險和不確定性，僅在本次電話會議之日發表，我們不承擔更新或修改任何這些陳述的義務。在投影片 3 上，您可以找到今天電話會議的議程。

Today, I'm joined by the following members of BioNTech's management team. Ugur Sahin, our CEO and Co-Founder; Ozlem Tureci, Chief Medical Officer and Co-Founder; Jens Holstein, Chief Financial Officer; and Ryan Richardson, Chief Strategy Officer.

今天，BioNTech 管理團隊的以下成員也加入了我的行列。 Ugur Sahin，我們的執行長兼共同創辦人； Ozlem Tureci，首席醫療官兼聯合創始人； Jens Holstein，財務長；瑞安·理查森（Ryan Richardson），首席策略長。

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

說到這裡，我想把事情交給烏古爾。

Thank you, Victoria. A warm welcome to all those joining us today.

謝謝你，維多利亞。熱烈歡迎今天加入我們的所有人。

Slide 5. Let me start by reiterating our vision and company goals. BioNTech was founded 15 years ago with the vision to harness the power of the immune system to fight human diseases, particularly cancer. The emergence of the pandemic accelerates our mission leading to the development of our COVID-19 vaccine. This achievement not only showcased the (inaudible) clarity of our mRNA technology, but also highlighted our unique expertise and ability to execute fast.

投影片 5。首先讓我重申我們的願景和公司目標。 BioNTech 成立於 15 年前，其願景是利用免疫系統的力量來對抗人類疾病，特別是癌症。大流行的出現加速了我們開發 COVID-19 疫苗的使命。這項成就不僅展示了我們 mRNA 技術的（聽不清楚）清晰度，也突顯了我們獨特的專業知識和快速執行的能力。

Our vision was realized and prudent, eliminating the potential of our science across other therapeutic areas. Building on this, our 3 objectives moving forward are to establish a multiproduct company covered by our pioneering technologies and science to address medical needs worldwide.

我們的願景已實現且審慎，消除了我們的科學在其他治療領域的潛力。在此基礎上，我們前進的 3 個目標是建立一家擁有領先技術和科學的多產品公司，以滿足全球醫療需求。

To contribute to the development of innovative precision medicines against cancer, aiming for multiple product approvals in the coming years. And to expand and strengthen our sustainable respiratory infectious disease vaccine business, building on the success of our COVID-19 franchise.

為抗癌創新精準藥物的開發做出貢獻，目標是在未來幾年獲得多項產品批准。並以我們的 COVID-19 特許經營權的成功為基礎，擴大和加強我們可持續的呼吸道傳染病疫苗業務。

Slide 6. On the next slide, I want to talk about our clinical achievements in 2023. We successfully advanced our clinical pipeline and enhance our technology platforms, digital capabilities and infrastructure by executing across our key strategic initiatives. We continue to develop and empower our innovative oncology and infectious disease pipeline.

幻燈片6。在下一張投影片上，我想談談我們在2023 年的臨床成就。透過執行關鍵策略舉措，我們成功推進了我們的臨床管道，並增強了我們的技術平台、數位能力和基礎設施。我們繼續開發和增強我們的創新腫瘤學和傳染病產品線。

Today, we have over 20 programs in oncology and 7 programs in infectious disease being evaluated in more than 40 clinical trials, including multiple Phase II or Phase III clinical trials.

如今，我們有 20 多個腫瘤學課程和 7 個傳染病項目正在 40 多項臨床試驗中進行評估，其中包括多個 II 期或 III 期臨床試驗。

I'm particularly excited about our recent achievements in shaping our oncology pipeline. We started 7 clinical trial, in-licensed 6 clinical assets throughout the year. Most importantly, several assets have advanced to mid- and late-stage development with Phase II and Phase III clinical trials ongoing.

我對我們最近在塑造腫瘤學產品線方面的成就感到特別興奮。全年啟動臨床試驗7項，引進臨床資產6項。最重要的是，多項資產已進入中後期開發階段，第二期和第三期臨床試驗正在進行中。

This task feature antibody-drug conjugate mRNA vaccines and novel IO therapies in indications such as non-small cell lung cancer, breast and endometrial cancer, adjuvant colorectal cancer and adjuvant pancreatic cancer.

此任務的特點是抗體藥物偶聯 mRNA 疫苗和新型 IO 療法，適用於非小細胞肺癌、乳腺癌和子宮內膜癌、輔助結直腸癌和輔助胰腺癌等適應症。

In infectious disease, we started 3 first-in-human Phase I clinical care, leveraging our [proprietary] mRNA vaccine technology including candidates being evaluated against shingles, tuberculosis and mpox.

在傳染病方面，我們利用我們的[專有] mRNA 疫苗技術啟動了 3 項首次人體 I 期臨床護理，包括針對帶狀皰疹、結核病和MPOX 的候選疫苗進行評估。

Over the course of 2024, we aim to advance and prioritize additional product candidates to late-stage development. We expect to have 10 or more potential regulation type earnings.

2024 年，我們的目標是推進並優先考慮更多候選產品進入後期開發。我們預計會有 10 個或更多潛在的監管型收益。

Slide 7. The fleet of oncology is currently undergoing a significant shift away from traditional shingle therapy towards combination therapies. This shift leverages the power of immuno-oncology and antibody drug conjugates to potentially transform also advanced cancer into a manageable condition.

投影片 7. 腫瘤學領域目前正在經歷從傳統帶狀皰疹療法到聯合療法的重大轉變。這種轉變利用了免疫腫瘤學和抗體藥物偶聯物的力量，有可能將晚期癌症轉變為可控制的疾病。

As we reflect on the achievements of 2023, we can proudly say that we have accelerated our IO and ADC programs by not only starting new task, but also successfully recruiting over 2,000 patients in our clinical trials across various indications. This is a testament to the hard work and dedication of our team and our collaboration partners as well as the trust and willingness of patients to participate in our study.

當我們回顧 2023 年的成就時，我們可以自豪地說，我們不僅啟動了新任務，而且在各種適應症的臨床試驗中成功招募了 2,000 多名患者，從而加速了 IO 和 ADC 計畫。這證明了我們團隊和合作夥伴的辛勤工作和奉獻精神，以及患者參與我們研究的信任和意願。

Looking ahead to 2024, we aim to build on the success and recruit patients into our clinical trials across indications such as lung cancer, breast cancer, colorectal cancer and other indications.

展望2024年，我們的目標是在成功的基礎上再接再厲，招募患者參與我們針對肺癌、乳癌、大腸癌和其他適應症等適應症的臨床試驗。

Slide 8. In 2023, we successfully executed strategic investments, acquisitions, licensing agreements and public private partnerships enabling our continued progress towards building a multi-product, AI-powered patient-centric company.

投影片 8。2023 年，我們成功執行了策略性投資、收購、授權協議和公私合作夥伴關係，使我們能夠在建立一家以患者為中心的多產品、人工智慧驅動的公司方面不斷取得進展。

Since our foundation, we have placed a strong emphasis on computational medicine, data science, artificial intelligence and machine learning. With the acquisition of InstaDeep, we are integrating capabilities in supercomputing AI research and generative AI into various processes. For example, to identify and optimize molecules to predict biological and clinical outcomes and to speed up our workflow.

自成立以來，我們非常重視計算醫學、數據科學、人工智慧和機器學習。透過收購 InstaDeep，我們正在將超級運算人工智慧研究和產生人工智慧的能力整合到各種流程中。例如，識別和優化分子以預測生物學和臨床結果並加快我們的工作流程。

In 2023, we expanded our technology base to include ADCs by initiating new collaborations with DualityBio and Medilink Therapeutics. We believe ADCs have the potential to supplement or replace highly toxic chemotherapy regimens as a new combination backbone of cancer treatment.

2023 年，我們透過與 DualityBio 和 Medilink Therapeutics 啟動新的合作，擴大了我們的技術基礎，將 ADC 納入其中。我們相信 ADC 有潛力補充或取代劇毒化療方案，作為癌症治療的新組合支柱。

Our collaborations with OncoC4 and Biotheus complement our toolkit of technologies with next-generation IO antibodies that offer unique mechanisms of action, and have augmented our oncology pipeline with mid- to late-stage clinical programs.

我們與 OncoC4 和 Biotheus 的合作透過下一代 IO 抗體補充了我們的技術工具包，這些抗體提供了獨特的作用機制，並透過中後期臨床計畫增強了我們的腫瘤學管道。

We have started strongly in 2024 on the collaboration front by announcing a strategic alliance with Autolus aimed at advancing both companies, autologous CAR-T cell programs towards commercialization. With this collaboration leads to support the development and commercialization of Autolus lead cell therapy candidate, (inaudible) and retain options to participate in its Auto 122 and Auto [6 mg] programs.

2024 年，我們在合作方面取得了強有力的開端，宣布與 Autolus 結成策略聯盟，旨在推動兩家公司的自體 CAR-T 細胞計畫走向商業化。透過此次合作，將支持 Autolus 主要細胞療法候選藥物的開發和商業化（聽不清楚），並保留參與其 Auto 122 和 Auto [6 mg] 計畫的選擇權。

Importantly, we have the option to use Autolus commercial and cell therapy manufacturing infrastructure in a cost-efficient manner. This is of relevance for our plans to extend the development of BNT211 to additional closing 6 positive tumor types, and thus realize its full potential.

重要的是，我們可以選擇以經濟高效的方式使用 Autolus 商業和細胞治療製造基礎設施。這與我們將 BNT211 的開發擴展到另外 6 種陽性腫瘤類型的計劃有關，從而充分發揮其潛力。

Slide 9. BNT211 is our CAR-T cell therapy targeting Claudin-6. To improve CAR-T cell in (inaudible) and persistence, we codevelop a CAR-T cell amplifying RNA vaccine or CARVac for short. BNT211 is one example of BioNTech's novel company. The goal is to enhance the system and effector function of CAR-T cell by repeated administration of CARVac.

幻燈片 9。BNT211 是我們針對 Claudin-6 的 CAR-T 細胞療法。為了提高 CAR-T 細胞的（聽不清楚）和持久性，我們共同開發了 CAR-T 細胞放大 RNA 疫苗或簡稱 CARVac。 BNT211 是 BioNTech 的新型態公司之一。目標是透過重複施用CARVac來增強CAR-T細胞的系統和效應器功能。

Recently, we presented data suggesting a favorable effect of CARVac on CAR-T cell persistence in our clinical trial with Claudin-6 tumors. Based on the promising early clinical results, we believe that BNT211 has the potential to make a significant impact in patients with Claudin-6 positive tumors.

最近，我們提供的數據表明，在針對 Claudin-6 腫瘤的臨床試驗中，CARVac 對 CAR-T 細胞的持久性具有良好的影響。基於有希望的早期臨床結果，我們相信 BNT211 有潛力對 Claudin-6 陽性腫瘤患者產生重大影響。

Our new term strategy is to establish Claudin-6 as a proven target in solid tumors and to establish BNT211 as the first CAR-T cell therapy in gene cell tumors. Claudin-6 is both to be expressed in solid cancers, including ovarian, lung, gastric, pediatric, cancers and other. Upcoming data will inform the development path for other tumor indications.

我們的新學期策略是將 Claudin-6 確立為實體瘤的經過驗證的靶點，並將 BNT211 確立為基因細胞腫瘤的第一個 CAR-T 細胞療法。 Claudin-6在實體癌中均有表達，包括卵巢癌、肺癌、胃癌、兒科癌症等。即將發布的數據將為其他腫瘤適應症的開發路徑提供資訊。

Slide 10. In 2024, we will continue building a portfolio of compound classes that have been adjusted mechanisms of action, including immunomodulators, targeted therapies and mRNA vaccines. We believe that combination of these therapies, if approved, could play an important role in the efforts towards potentially curative approaches.

投影片 10. 2024 年，我們將繼續建構經過調整作用機制的化合物類別組合，包括免疫調節劑、標靶治療和 mRNA 疫苗。我們相信，這些療法的組合如果獲得批准，可能會在潛在治癒方法的努力中發揮重要作用。

With that, I would like to thank you all for your confidence in our success and your continued support. I will now turn the call over to Ozlem, who will speak about our oncology pipeline.

在此，我要感謝大家對我們成功的信心和持續的支持。我現在將把電話轉給 Ozlem，他將談論我們的腫瘤學管道。

Thank you, Ugur. Glad to be speaking with everyone today.

謝謝你，烏古爾。很高興今天能和大家交談。

Starting on Slide 12, with an overview of our oncology pipeline. In 2023, we and our partners reported data across our portfolio at multiple medical meetings, including ASCO and ESMO. And we published manuscript in (inaudible) journal.

從投影片 12 開始，概述我們的腫瘤學研發管線。 2023 年，我們和我們的合作夥伴在多個醫學會議（包括 ASCO 和 ESMO）上報告了我們產品組合的數據。我們在（聽不清楚）雜誌上發表了手稿。

More data readouts are expected this year, starting at AACR on the BNT122, our individualized neoantigen-based cancer vaccine in adjuvant PDAC and on BNT116, our off-the-shelf cancer vaccine in non-small cell lung cancer.

預計今年將公佈更多數據，從 AACR 開始，我們將公佈 BNT122（我們的佐劑 PDAC 中基於新抗原的個體化癌症疫苗）和 BNT116（我們的現成非小細胞肺癌癌症疫苗）的數據。

In 2023, we advanced and expanded our pipeline considerably and now have multiple mid- to late-stage trials ongoing. Our aim is to continue to progress our oncology pipeline towards pivotal data readouts and submissions for regulatory approvals in the next 18 months.

2023 年，我們大幅推進並擴展了我們的產品線，目前正在進行多項中後期試驗。我們的目標是在未來 18 個月內繼續推進我們的腫瘤學管道，以獲取關鍵數據並提交監管部門批准。

Slide 13. Here on the left are the ongoing trials in mid- to late-stage development. The 3 on top of this were initiated in 2023. BNT316, an anti-CTLA-4 and IO experience on non-small cell lung cancer. BNT323, an anti-HER2-low ADC in HER2-low low breast cancer, and BNT122, our individualized cancer vaccine in the SCLC pancreatic cancer space.

投影片 13。左邊是正在進行的中後期開發試驗。除此之外的 3 個計畫於 2023 年啟動。BNT316，一種抗 CTLA-4 和 IO 治療非小細胞肺癌的經驗。 BNT323 是一種用於 HER2 低乳癌的抗 HER2 低 ADC，而 BNT122 是我們在 SCLC 胰臟癌領域的個人化癌症疫苗。

On the right are the product candidate based on ADC IO mRNA cancer vaccine modalities for which we are planning to initiate additional Phase II and Phase III trials. These programs include validated and novel targets as well as in-house and in-licensed assets with unique mode of action.

右側是基於 ADC IO mRNA 癌症疫苗模式的候選產品，我們計劃啟動額外的 II 期和 III 期試驗。這些計劃包括經過驗證的新穎目標以及具有獨特行動模式的內部和許可資產。

We believe we have multiple shots on goal. Our in-licensed assets are starting to contribute to value creation and towards derisking our pipeline. We plan to explore potential combination product candidates, featuring these assets based on the scientific rationale, preclinical and clinical evidence and also thinking of future treatment sequencing in different indications to provide options for patients along their disease journey.

我們相信我們有多次射門。我們的授權資產開始為價值創造和降低管道風險做出貢獻。我們計劃探索潛在的組合產品候選者，以基於科學原理、臨床前和臨床證據的這些資產為特色，並考慮不同適應症的未來治療順序，為患者在疾病歷程中提供選擇。

As shown in Slide 14, in 2023, we began building a pipeline of ADC candidates that now includes third-generation ADC directed against 4 distinct targets. These 4 targets collectively cover a wide range of cancer types. Our reason for adding this modality to our clinical multi-platform pipeline is that we believe ADCs will transform the oncology space and become broadly used backbone of combination treatment.

如幻燈片 14 所示，2023 年，我們開始建立候選 ADC 管道，其中包括針對 4 個不同目標的第三代 ADC。這 4 個目標共同涵蓋了多種癌症類型。我們將這種模式添加到我們的臨床多平台管道中的原因是，我們相信 ADC 將改變腫瘤學領域並成為廣泛使用的聯合治療的支柱。

Our strategy for acquiring these specific assets was based on their potentially differentiated profile, the objective of covering multiple cancer attacks and the broad market they may address. BNT323, a HER2 targeting ADC, is our most advanced ADC. It also is one of our frontrunners in our clinical pipeline.

我們收購這些特定資產的策略是基於它們潛在的差異化特徵、覆蓋多種癌症攻擊的目標以及它們可能涉及的廣泛市場。 BNT323 是一款針對 HER2 的 ADC，是我們最先進的 ADC。它也是我們臨床管道中的領導者之一。

Now on Slide 15, BNT323 is a 3rd generation ADC that aims to overcome the drawbacks of first- and second-generation ADCs to achieve high stability in such relation, low risk of target halo delivery, a high drug antibody ratio of 8 and an expanded therapeutic window. It is comprised of a humanized anti-HER2 IgG antibodies, covalently attached to a potent proprietary DNA topoisomerase I inhibitor. We -- via a stable maleimide tetrapeptide linker selectively achievable by pyrimidine that are operate regulated in tumor cell.

現在在幻燈片15 上，BNT323 是第三代ADC，旨在克服第一代和第二代ADC 的缺點，以實現這種關係的高穩定性、目標光環傳遞的低風險、8 的高藥物抗體比率和擴展的治療窗口。它由人源化抗 HER2 IgG 抗體組成，共價連接到有效的專有 DNA 拓樸異構酶 I 抑制劑。我們透過嘧啶選擇性地實現穩定的馬來酰亞胺四肽接頭，在腫瘤細胞中進行操作調節。

BNT323 binding to HER2 on the surface of tumor cells inhibit HER2 signaling followed by internalization of a ADC HER2 receptor contact, cleavage of the linker and release of the membrane permeable payload. The effect is not only killing of these tumor cells, but also bystander killing of neighboring tumor cells, regardless of their HER2 expression levels.

BNT323 與腫瘤細胞表面的 HER2 結合，抑制 HER2 訊號傳導，隨後內化 ADC HER2 受體接觸，裂解接頭並釋放膜滲透性有效負載。其效果不僅是殺死這些腫瘤細胞，而且是旁觀者殺死鄰近的腫瘤細胞，無論它們的 HER2 表現量如何。

In preclinical studies with other 3rd generation ADCs in animal models, BNT323 was observed to have higher stability, lower levels of free payload and circulation and more efficient payload release within tumor cells and stronger antitumor activity, including in HER2-low model.

在動物模型中與其他第三代ADC 進行的臨床前研究中，觀察到BNT323 具有更高的穩定性、更低水平的遊離有效負載和循環、腫瘤細胞內更有效的有效負載釋放以及更強的抗腫瘤活性，包括在HER2-low 模型中。

On Slide 16 now, BNT323 is currently being evaluated in a signal seeking Phase I/II clinical trial forward to expressing advanced solid tumor. The dose expansion part of the Phase I/II study is enrolling pretreated patients with advanced or metastatic HER2 expressing solid tumors.

現在在投影片 16 上，BNT323 目前正在一項訊號尋求 I/II 期臨床試驗中進行評估，以表達晚期實體瘤。 I/II 期研究的劑量擴展部分是招募已接受過治療的晚期或轉移性 HER2 表達實體瘤的患者。

As of February of this year, more than 300 patients have received BNT323 in this Phase I/II trial. The first data from this study were presented at ASCO last year. We reported preliminary antitumor activity in heavily pretreated patients with HER2 expressed in solid tumors.

截至今年2月，已有超過300名患者在該I/II期試驗中接受了BNT323。這項研究的第一個數據於去年在 ASCO 上發表。我們報告了在實體瘤中表達 HER2 的經過大量治療的患者中的初步抗腫瘤活性。

Responses were observed in patients treated with different dose levels and with different HER2 expression status. Based on our findings, in these dark green marked cohort on the right, we have initiated potentially registrational trials in patients with endometrial cancer and breast cancer.

在接受不同劑量水平和不同 HER2 表達狀態的患者中觀察到反應。根據我們的研究結果，在右側這些深綠色標記的隊列中，我們已經啟動了針對子宮內膜癌和乳癌患者的潛在註冊試驗。

On Slide 17, in the breast cancer cohort of our Phase I/II trial with 26 patients with HER2-positive cancer, which means high and intermediate levels of HER2 expression, showed an objective response rate of 50% and a disease control rate of 96.2%. The 13 patients refer to low breast cancer that have a particularly high medical need, had an objective response rate of 38.5%, and thus disease control rate of 84.6%.

在幻燈片17 上，在我們的I/II 期試驗的乳癌群組中，有26 名HER2 陽性癌症患者（這意味著HER2 表達高和中等水平）顯示出50% 的客觀緩解率和96.2 的疾病控制率%。這13名患者屬於低度乳癌，醫療需求特別高，客觀緩解率為38.5%，疾病控制率為84.6%。

BNT323 was observed to be well tolerated and all adverse events were manageable. [Interspecial] lung disease of Grade 1 occurred in 2 out of these 85 patients. Based on this data, we initiated a Phase III study of BNT323 in chemotherapy naive patients with hormone receptor positive HER2-low breast cancer, whose disease has progressed on prior endocrine therapy with or without CDK4/6 inhibition in the metastatic setting versus investigator charge of chemotherapy.

據觀察，BNT323 具有良好的耐受性，所有不良事件均可控制。 [專業間] 這 85 名患者中有 2 名出現 1 級肺部疾病。基於這些數據，我們在未接受化療的荷爾蒙受體陽性HER2-low 乳癌患者中啟動了一項BNT323 的III 期研究，這些患者在轉移性環境中接受或不接受CDK4/6 抑制的既往內分泌治療後疾病已進展，而研究者負責化療。

As shown on Slide 18, in the U.S., the U.K., the EU4 and Japan, approximately 700,000 patients per year are diagnosed with breast cancer. The majority of those achieved remission for territory of the initial therapy. Those that do not get cured are being treated with hormonal and targeted therapies and chemotherapy.

如投影片 18 所示，在美國、英國、歐盟四國和日本，每年約有 70 萬名患者被診斷出罹患乳癌。其中大多數患者在初始治療範圍內獲得了緩解。那些沒有治癒的人正在接受荷爾蒙療法、標靶療法和化療。

3rd generations of HER2 targeting antibodies only benefited both 30% of patients with high or intermediate expression levels of HER2, designated as HER2 positive. More recently, patients with HER2-low expression that comprise 2/3 of the remaining 70% breast cancer patients have been shown to benefit substantially from new generation HER2-targeted ADC therapy.

第三代 HER2 標靶抗體僅使 30% HER2 高或中等表現量的患者受益，即 HER2 陽性。最近，HER2 低表達患者（佔剩餘 70% 乳癌患者的 2/3）已被證明可從新一代 HER2 標靶 ADC 療法中受益匪淺。

HER2 directed ADCs are currently only approved for chemotherapy experienced patients, meaning from first line onwards. In our ongoing Phase III study, we are targeting chemo-naive patients from second line onwards, as marked here in dark green.

HER2 導引的 ADC 目前僅被核准用於有化療經驗的患者，也就是從第一線開始。在我們正在進行的 III 期研究中，我們的目標是從二線開始接受化療的患者，如深綠色所示。

Slide 19, coming back to our Phase I/II trial and the findings in endometrial cancer patients with advanced recurrent or metastatic HER2-positive and HER2-low. For endometrial cancer, we received fast track designation and breakthrough designation from the FDA in 2023. In September 2023, clinical data from 17 patients with endometrial cancer were presented at the ASCO Annual Meeting. All patients had received one or more treatment lines, including immunotherapy anti-HER2 antibody or endocrine therapy.

投影片 19，回到我們的 I/II 期試驗以及晚期復發或轉移性 HER2 陽性和 HER2 低的子宮內膜癌患者的研究結果。對於子宮內膜癌，我們於2023年獲得了FDA的快速通道認定和突破性認定。2023年9月，17名子宮內膜癌患者的臨床數據在ASCO年會上公佈。所有患者均接受過一種或多種治療方案，包括抗 HER2 抗體免疫療法或內分泌治療。

BNT323 shows promising antitumor activity across different HER2 expression levels, including IHC 1+ expression, which is low expression with an objective response rate of 58.8%, of which 35.5% are pending confirmation. The disease control rate was 94.1%.

BNT323 在不同 HER2 表達水平上顯示出有希望的抗腫瘤活性，包括 IHC 1+ 表達，這是低表達，客觀緩解率為 58.8%，其中 35.5% 正在等待確認。疾病控制率為94.1%。

While the synthesis is just small and data cutoff is too early to draw conclusions on less frequent treatment emergent adverse events and TEAEs with protracted manifestation, the safety profile was manageable and no new safety signals were observed.

雖然綜合規模很小，而且數據截止還為時過早，無法就不太常見的治療緊急不良事件和長期表現的 TEAE 得出結論，但安全性是可控的，沒有觀察到新的安全信號。

Slide 20, patients with advanced unresectable or recurrent endometrial cancer receive treatments based on their molecular profile. The latest clinical data support adding immunotherapy to chemotherapy as a frontline treatment for patients with Stage 4 endometrial cancer and dMMR status. Patients who overexpress HER2 can be treated with HER2 targeting therapies such as HER2 tumor in combination with chemotherapy as a frontline treatment.

幻燈片 20，晚期不可切除或復發性子宮內膜癌患者根據其分子譜接受治療。最新的臨床數據支持將免疫療法添加到化療中作為 4 期子宮內膜癌和 dMMR 狀態患者的一線治療。 HER2過度表現的患者可以接受HER2標靶治療，例如HER2腫瘤合併化療作為第一線治療。

Despite the recent advancements in first-line treatment, most patients relapse. At present, there is no targeted therapy approved for patients who progressed on first-line treatment and post tumor expressed HER2. This is the patient population we are currently focusing on with the BNT323.

儘管一線治療最近取得了進展，但大多數患者都會復發。目前，對於第一線治療中進展且腫瘤後表達 HER2 的患者，尚無核准的標靶治療。這是我們目前 BNT323 重點關注的患者群體。

Slide 21. I would like to reemphasize that our aim for 2024 is to further advance our key programs into late-stage development with the aim of contributing to the next generation of oncology medicines that could include candidates featured on this slide. We believe our investments and efforts will pave the way for an initial wave of oncology product launches from 2026 onwards.

投影片 21。我想再次強調，我們 2024 年的目標是進一步推進我們的關鍵項目進入後期開發，旨在為下一代腫瘤藥物做出貢獻，其中可能包括本幻燈片上介紹的候選藥物。我們相信，我們的投資和努力將為 2026 年起第一波腫瘤產品的推出鋪平道路。

I'll now pass the presentation to our CFO, Jens Holstein.

現在我將把簡報轉交給我們的財務長 Jens Holstein。

Thank you, Ozlem, and a warm welcome to everyone who has dialed in today's call.

謝謝您，Ozlem，並熱烈歡迎所有撥打今天電話的人。

2023 was another successful year for BioNTech on its journey to develop novel therapies for cancer and infectious diseases. Let me highlight 3 main points here.

2023 年是 BioNTech 在開發癌症和傳染病新療法的道路上又一個成功的一年。我在這裡強調 3 個要點。

We kept our global COVID-19 vaccine market leadership. We grew and advanced our late-stage pipeline. And we, again, delivered a strong financial performance, highlighted by EUR 3.8 billion of total recognized revenues, EUR 1.2 billion of profit before tax, resulting in earnings per share on a fully diluted basis of EUR 3.83. With this, we ended the 2023 financial year with approximately EUR 17.7 million of cash, cash equivalents and security investments.

我們保持了全球 COVID-19 疫苗市場的領先地位。我們發展並推進了我們的後期研發管線。我們再次實現了強勁的財務業績，其中體現為 38 億歐元的總確認收入、12 億歐元的稅前利潤，以及完全攤薄後的每股收益為 3.83 歐元。至此，我們在 2023 財年結束時擁有約 1,770 萬歐元的現金、現金等價物和證券投資。

Turning to the next slide. While our financial performance in 2023 was strong, and we were able to maintain profitability, there were also some financial challenges that we had to navigate through. In our third quarter earnings call last year, we updated our full year 2023 COVID-19 vaccine revenue guidance to around EUR 4 billion, reflecting write-downs in the amount of approximately EUR 600 million by our collaboration partner, Pfizer.

轉到下一張投影片。雖然我們 2023 年的財務表現強勁，並且能夠保持獲利能力，但我們也必須應對一些財務挑戰。在去年第三季的財報電話會議上，我們將 2023 年全年 COVID-19 疫苗收入指引更新為約 40 億歐元，反映出我們的合作夥伴輝瑞 (Pfizer) 進行了約 6 億歐元的減記。

In Q4, Pfizer recognized additional write-downs of approximately EUR 300 million, that negatively impacted our top line figure compared to our initial expectations for Q4. The negative impact on our revenue for 2023 accumulated to a total of approximately EUR 900 million.

在第四季度，輝瑞確認了約 3 億歐元的額外減記，與我們對第四季的最初預期相比，這對我們的營收數字產生了負面影響。對我們 2023 年收入的負面影響累計約為 9 億歐元。

Write-downs related to [each] inventory would typically have a negative impact on the gross profit in the P&L. Following our gross profit share agreement for Pfizer, write-downs by our partner have a negative effect on BioNTech's revenue figure. That made our revenue guidance for 2023 challenging.

與[每個]庫存相關的減記通常會對損益表中的毛利產生負面影響。根據我們與輝瑞的毛利分享協議，我們合作夥伴的減記對 BioNTech 的收入數字產生了負面影響。這使得我們 2023 年的收入指引充滿挑戰。

Having said that, the agreement has an important advantage. BioNTech only requires very little commercial infrastructure in the COVID-19 vaccine franchise, and with this, has low expenses related to sales and marketing in comparison to other players in the field. This is, we believe, favorable as COMIRNATY is a leading brand in the global COVID-19 vaccine market.

話雖如此，該協議有一個重要的優勢。 BioNTech 在 COVID-19 疫苗特許經營中只需要很少的商業基礎設施，因此與該領域的其他參與者相比，與銷售和行銷相關的費用較低。我們認為，這是有利的，因為 COMIRNATY 是全球 COVID-19 疫苗市場的領導品牌。

Despite the decrease in our revenues in 2023 and despite the negative impact of these write-downs, we were able to both remain profitable in 2023 and grew our year-end financial position in respect of cash, cash equivalents and security investments to EUR 17.7 billion compared to EUR 13.9 billion at the end of 2022.

儘管我們 2023 年的收入有所下降，儘管這些減記產生了負面影響，但我們仍能夠在 2023 年保持盈利，並將現金、現金等價物和證券投資方面的年終財務狀況增加至 177 億歐元相比之下，2022 年底為139 億歐元。

Please note that the contractual settlement of the gross profit share has a temporary offset of more than 1 calendar quarter. In addition, Pfizer financial quarter for the subsidiaries outside the United States differs from ours.

請注意，毛利份額的合約結算具有超過 1 個日曆季度的臨時抵銷。此外，輝瑞美國以外子公司的財務季度與我們不同。

I'll be moving now to the summary of our financial results for the fourth quarter of 2023 and full year of 2023, as shown on the next slide. For the 3 months ended December 31, 2023, we recognized EUR 1.5 billion in COVID-19 vaccine revenues compared to EUR 4.3 billion for the comparative period in 2022.

我現在將總結 2023 年第四季和 2023 年全年的財務業績，如下一張投影片所示。截至 2023 年 12 月 31 日的三個月，我們確認了 15 億歐元的 COVID-19 疫苗收入，而 2022 年同期為 43 億歐元。

For the financial year 2023, our total reported revenues reached EUR 3.8 billion compared to EUR 17.3 billion in 2022. This was primarily driven by lower COVID-19 vaccine market demand, and as stated before, write-downs reported by our collaboration with Pfizer, which negatively influenced our revenues.

2023 財年，我們報告的總收入達到 38 億歐元，而 2022 年為 173 億歐元。這主要是由於 COVID-19 疫苗市場需求下降，以及如前所述，我們與輝瑞合作報告的減記，這對我們的收入產生了負面影響。

Moving to cost of sales. Cost of sales amounted to EUR 179 million in the fourth quarter of 2023, in line with the EUR 183.5 million for the comparative prior year period. For the 2023 financial year, the cost of sales amounted to close to EUR 600 million compared to approximately EUR 3 billion in 2022. The drop was mainly caused by the decrease in COVID-19 vaccine sales.

轉向銷售成本。 2023 年第四季的銷售成本為 1.79 億歐元，與去年同期的 1.835 億歐元持平。 2023 財年，銷售成本接近 6 億歐元，而 2022 年約為 30 億歐元。下降的主要原因是 COVID-19 疫苗銷量下降。

Research and development expenses reached EUR 578 million for the fourth quarter of 2023 compared to EUR 510 million for the comparative period in 2022. For the 2023 financial year, research and development expenses amounted to approximately EUR 1.8 billion compared to EUR 1.5 billion in 2022. The increase was mainly influenced by progressing clinical studies for pipeline candidates as well as by our newly acquired product candidates and the development of variant adapted COVID-19 vaccines.

2023 年第四季的研發費用達到 5.78 億歐元，而 2022 年同期為 5.1 億歐元。2023 財年的研發費用約為 18 億歐元，而 2022 年為 15 億歐元。這一增長主要受到管道候選產品臨床研究進展以及我們新收購的候選產品和變異適應的COVID-19 疫苗開發的影響。

In line with the higher head count compared to the previous year to -- for example, support our existing clinical trials and future growth initiatives, we also saw respective higher costs in wages, benefits and social security expenses in the financial year 2023.

與前一年相比，員工人數增加，例如支持我們現有的臨床試驗和未來的成長計劃，我們還看到 2023 財年的工資、福利和社會安全費用相應增加。

General and administrative expenses amounted to approximately EUR 0.1 million for both the fourth quarter of 2023 as well as for the comparative period in 2022. For the 2023 financial year, general and administrative expenses remained at EUR 0.5 billion, around the same level as in the previous year. The slight increase in G&A was mainly influenced by increased expenses for IT services as well as by wages, benefits and social security expenses, resulting from an increase in headcount.

2023 年第四季以及 2022 年同期的一般和管理費用約為 10 萬歐元。2023 財年，一般和管理費用保持在 5 億歐元，與上一財年的水平大致相同。前一年。 G&A 的小幅增長主要是由於員工人數增加導致 IT 服務費用增加以及工資、福利和社會安全費用增加的影響。

Income taxes were accrued with an amount of EUR 205.3 million for the fourth quarter of 2023 compared to EUR 893.9 million for the comparative period in 2022. For the 2023 financial year, income taxes were accrued with an amount of EUR 255.8 million compared to EUR 3.5 billion in 2022. The derived effective income tax rate for the 2023 financial year was 21.6%, roughly in line with our expectations of around 21%, improved versus last year's tax rate of 27%.

2023 年第四季應計所得稅為 2.053 億歐元，而 2022 年同期為 8.939 億歐元。2023 財年，應計所得稅為 2.558 億歐元，而 2022 年同期為 3.5 歐元2022 年將實現10 億美元。由此得出的2023 財年有效所得稅率為21.6%，大致符合我們21% 左右的預期，較去年27% 的稅率有所改善。

For the fourth quarter of 2023, net profit reached EUR 457.9 million compared to EUR 2.3 billion in the comparative period in 2022. For the year ended December 31, 2023, net profit reached EUR 0.9 billion compared to EUR 9.4 billion in 2022.

2023年第四季，淨利達4.579億歐元，而2022年同期為23億歐元。截至2023年12月31日止年度，淨利達9億歐元，而2022年同期為94億歐元。

Our diluted earnings per share for the fourth quarter of 2023 amounted to EUR 1.90 compared to EUR 9.26 for the comparative period in 2022. For the 2023 financial year, our diluted earnings per share amounted to EUR 3.83 compared to EUR 37.77 in 2022.

我們 2023 年第四季的稀釋每股收益為 1.90 歐元，而 2022 年同期為 9.26 歐元。2023 財年，我們的稀釋每股收益為 3.83 歐元，而 2022 年為 37.77 歐元。

Let's continue with the next slide. This shows the 2023 financial guidance provided to you during our Q3 earnings call in November 2023 in comparison with the actuals for the 2023 financial year.

讓我們繼續看下一張投影片。這顯示了我們在 2023 年 11 月第三季財報電話會議期間向您提供的 2023 年財務指導，並與 2023 財年的實際情況進行了比較。

Starting from the top. We recognized EUR 3.8 billion of COVID-19 vaccine revenues compared to our guidance of around EUR 4 billion. Approximately EUR 300 million additional write-downs by our collaboration partner had to be unexpectedly recognized in Q4.

從頂部開始。我們確認了 38 億歐元的 COVID-19 疫苗收入，而我們的指導值為約 40 億歐元。我們的合作夥伴在第四季度意外確認了約 3 億歐元的額外減記。

Moving to R&D expenses. During the 2023 financial year, our R&D expenses were nearly EUR 1.8 billion, slightly below our amended guidance from November of 2023 of EUR 1.82 billion. Lower spending in, for example, our collaborations have been a main contributor as well as strong cost control measures. Our co-R&D activities in 2023 focused on broadening and accelerating our existing pipeline of product candidates in oncology and infectious diseases in line with our expectations.

轉向研發費用。在 2023 財年，我們的研發費用接近 18 億歐元，略低於 2023 年 11 月修訂後的指引價值 18.2 億歐元。例如，我們的合作支出減少以及強有力的成本控制措施是主要原因。我們 2023 年的聯合研發活動重點是擴大和加速我們現有的腫瘤學和傳染病候選產品管線，以符合我們的預期。

Moving to SG&A expenses. During the 2023 financial year, we recognized EUR 558 million in SG&A expenses, slightly below the lower end of our amended guidance of EUR 600 million to EUR 650 million. Again, we were closely monitoring our spending to reflect the uncertainty on the revenues without jeopardizing the future needs in this area.

轉到SG&A 費用。在 2023 財年，我們確認了 5.58 億歐元的 SG&A 費用，略低於我們修訂後的指導方針的下限（6 億至 6.5 億歐元）。同樣，我們正在密切監控我們的支出，以反映收入的不確定性，而不危及該領域的未來需求。

Moving to CapEx. Our 2023 financial year capital expenditures for operating activities amounted to EUR 276 million, whereof the majority was related to investments in building our laboratory and office facilities in Mainz, Germany. The spending is in line with our expectations, ranging from EUR 200 million to EUR 300 million.

轉向資本支出。我們 2023 財年的營運活動資本支出為 2.76 億歐元，其中大部分與在德國美因茨建造實驗室和辦公設施的投資有關。支出在 2 億歐元到 3 億歐元之間，符合我們的預期。

Lastly, tax. As already mentioned during the 2023 financial year, we reached an annual effective income tax rate of 21.6%, which is roughly in line with our amended guidance of around 21%.

最後，稅收。如同在 2023 財年期間已經提到的，我們的年度有效所得稅率為 21.6%，這與我們 21% 左右的修訂指導大致一致。

Turning to the next slide, showing the 2024 financial year guidance. Let me highlight now some key aspects of the company's outlook for the 2024 financial year. Starting with total revenues for the BioNTech Group.

轉向下一張投影片，顯示 2024 財年指引。現在讓我重點介紹公司 2024 財年展望的一些關鍵面向。從 BioNTech 集團的總收入開始。

We expect total revenues in the range of EUR 2.5 billion to EUR 3.1 billion for 2024. In providing a range estimate today, we take, to some extent, potential up and downsides into account. For example, we assume largely the same vaccination rate for the U.S. market, but have seen some price pressure in the U.S. in Q4, some smaller inventory write-down with -- by our collaboration partner, Pfizer, as we have faced, again, additional write-downs above the previous announced ones that hit our revenues again in Q4 2023.

我們預計 2024 年總收入將在 25 億歐元至 31 億歐元之間。在今天提供範圍估計時，我們在某種程度上考慮了潛在的上升和下降。例如，我們假設美國市場的疫苗接種率大致相同，但在第四季度美國出現了一些價格壓力，我們的合作夥伴輝瑞（Pfizer）進行了一些較小的庫存減記，正如我們再次面臨的那樣，高於先前宣布的額外減記，這再次影響了我們2023 年第四季的營收。

We also assume that we generate revenues from a pandemic preparedness contract with the German government in 2024. For the 2024 financial guidance, we expect our R&D expenses to be in the range of EUR 2.4 billion to EUR 2.6 billion, while our SG&A expenses are expected to be in the range of EUR 700 million to EUR 800 million.

我們也假設我們將在2024 年從與德國政府簽訂的大流行病防備合約中獲得收入。對於2024 年財務指導，我們預計我們的研發費用將在24 億歐元至26 億歐元之間，而我們的SG&A 費用預計將在24 億歐元至26 億歐元之間介於 7 億歐元至 8 億歐元之間。

Please note that anticipated expenses related to the external legal advice in connection with legal litigations is not reflected in SG&A, but in other operating expenses.

請注意，與法律訴訟相關的外部法律諮詢相關的預期費用並不反映在銷售管理費用中，而是反映在其他營運費用中。

Additionally, the guidance does not include, but may be impacted by potential payments resulting from any collaboration agreements or in-licensing deals, M&A transactions or outcomes of ongoing or future legal disputes or related activities such as judgment for settlements.

此外，該指南不包括但可能受到任何合作協議或許可交易、併購交易或正在進行或未來法律糾紛或相關活動（例如和解判決）的結果所產生的潛在付款的影響。

Lastly, capital expenditures for the 2024 financial year are expected to be in the range of EUR 400 million to EUR 500 million. In 2024, we will be increasing our operating expenses in R&D and SG&A to accelerate BioNTech's transition into a multiproduct oncology and infectious disease company with a commercial footprint. For that, we want to increase our investments to lift the potential value that we see in our portfolio of product candidates.

最後，2024財年的資本支出預計在4億至5億歐元之間。 2024 年，我們將增加研發和銷售、一般行政費用的營運費用，以加速 BioNTech 轉型為具有商業足跡的多產品腫瘤和傳染病公司。為此，我們希望增加投資，以提升我們在候選產品組合中看到的潛在價值。

In 2023, we in-licensed multiple assets to bolster our late-stage pipeline. This year, we will invest in progressing our candidates into later-stage trials to fuel BioNTech's next stage of growth. As previously mentioned, we aim to have 10 or more potentially registration of clinical trials ongoing by the end of 2024. With this, we paved the way for multiple potential product approvals, estimated to begin with first launch in 2026.

2023 年，我們獲得了多項資產的許可，以加強我們的後期研發管線。今年，我們將投資候選藥物推進後期試驗，以推動 BioNTech 下一階段的成長。如前所述，我們的目標是到 2024 年底進行 10 個或更多潛在的臨床試驗註冊。這樣，我們為多個潛在產品的批准鋪平了道路，預計將於 2026 年首次推出。

As previously indicated, 2024 will be a transition year for our company, during which, we will continue to invest in our long-term growth strategy while maintaining strict cost discipline.

如前所述，2024 年將是我們公司的過渡年，在此期間，我們將繼續投資於我們的長期成長策略，同時保持嚴格的成本紀律。

Overall, during this transition year, our revenues will be driven largely by the uptake of our COVID-19 vaccines in the second half of 2024. As a consequence of the expected revenue range and taking into account cost of sales, R&D and all other expenses, we do not expect to be profitable in 2024.

總體而言，在這個過渡年中，我們的收入將主要由 2024 年下半年 COVID-19 疫苗的使用推動。由於預期收入範圍並考慮到銷售成本、研發和所有其他費用，我們預計2024 年不會盈利。

Turning to the next slide. Today, BioNTech has a leading and profitable COVID-19 vaccine business. As you can see on this slide, our COVID-19 vaccine business benefited from its lean fixed cost structure in 2023 and generates very attractive positive results.

轉到下一張投影片。如今，BioNTech 擁有領先且獲利的 COVID-19 疫苗業務。正如您在這張幻燈片中看到的，我們的 COVID-19 疫苗業務受益於 2023 年的精益固定成本結構，並產生了非常有吸引力的積極成果。

In the coming years, we aim to invest alongside our partner in bringing variant adapted and potentially combination vaccines to market with the goal to further contributing to our future value generation. In addition to our value contributing COVID-19 vaccine franchise, we are investing into long-term value creation with our multiple product oncology pipeline.

未來幾年，我們的目標是與合作夥伴一起投資，將變異疫苗和潛在的組合疫苗推向市場，以期進一步為我們未來的價值創造做出貢獻。除了我們貢獻價值的 COVID-19 疫苗特許經營權外，我們還投資於透過我們的多種腫瘤產品線創造長期價值。

Let me highlight 3 value drivers. We plan to have 10 or more potentially registrational trials ongoing by the end of 2024. We aim to have a first potential oncology launch in 2026, adding to our top line. And thirdly, we believe to have a diversified clinical pipeline that offers multiple product growth opportunities for the years to come.

讓我重點介紹 3 個價值驅動因素。我們計劃在 2024 年底進行 10 項或更多潛在的註冊試驗。我們的目標是在 2026 年推出第一個潛在的腫瘤學試驗，從而增加我們的營收。第三，我們相信擁有多元化的臨床管道，可以在未來幾年提供多種產品成長機會。

Summarizing, we believe that our COVID-19 vaccine franchise and our innovative pipeline of product candidates will drive long-term value creation for the company.

總而言之，我們相信我們的 COVID-19 疫苗專營權和創新的候選產品系列將推動公司創造長期價值。

Our Chief Strategy Officer, Ryan Richardson, will now talk you through some of the strategic drivers for this transformation. Thank you.

我們的首席策略長 Ryan Richardson 現在將向您介紹這項轉型的一些策略驅動因素。謝謝。

Thank you, Jens. To wrap up our prepared remarks, I'll provide a high-level overview of our 2030 strategy and the path to value creation from our mid- and late-stage oncology pipeline programs before concluding with a few important dates to mark on your calendars.

謝謝你，延斯。為了結束我們準備好的發言，我將簡要概述我們的 2030 年策略以及我們的中後期腫瘤管道項目的價值創造之路，然後最後列出一些要在日曆上標記的重要日期。

On the next slide, we highlight the broad value creation opportunities underpinning our 2030 strategy. Our balance sheet has been further strengthened in 2023, and we'll continue to serve as a strategic asset to fuel long-term growth.

在下一張投影片中，我們重點介紹了支撐我們 2030 年策略的廣泛價值創造機會。 2023 年，我們的資產負債表進一步加強，我們將繼續作為策略資產來推動長期成長。

We will continue to invest behind our market-leading COVID-19 vaccine franchise, leveraging our partnership with Pfizer across R&D, manufacturing and commercial functions. On a product contribution basis, we expect this franchise to continue to be highly cash generative.

我們將利用與輝瑞在研發、製造和商業職能方面的合作夥伴關係，繼續投資於我們市場領先的 COVID-19 疫苗特許經營權。在產品貢獻的基礎上，我們預計該特許經營權將繼續產生大量現金。

We are working with Pfizer to develop a COVID-19 and Influenza combination vaccine, which is successful in late-stage trials, could reach the market as early as fall 2025. We are ramping up our investments into our expanding and diverse late-stage oncology pipeline.

我們正在與輝瑞合作開發一種 COVID-19 和流感聯合疫苗，該疫苗在後期試驗中取得了成功，最早可能在 2025 年秋季上市。我們正在加大對不斷擴大和多樣化的後期腫瘤學的投資管道。

Our goal is to have at least 10 trials initiated with registrational potential by the end of this year. We believe this broad pipeline can deliver multiple new commercial product launches in the years ahead.

我們的目標是在今年年底前啟動至少 10 項具有註冊潛力的試驗。我們相信，這條廣泛的產品線可以在未來幾年推出多種新的商業產品。

Finally, we will continue to invest to industrialize our mRNA vaccine platform to address infectious diseases with high unmet global need. Today, we have 5 infectious disease vaccines beyond COVID-19 in Phase I clinical trials. By 2030, we aim to bring our first vaccines from this pipeline to market, complemented by an expanding late-stage infectious disease vaccine pipeline.

最後，我們將繼續投資將我們的 mRNA 疫苗平台工業化，以應對全球需求未被​​滿足的傳染病。如今，除了 COVID-19 之外，我們還有 5 種傳染病疫苗處於 I 期臨床試驗中。到 2030 年，我們的目標是將該管道中的第一批疫苗推向市場，並輔以不斷擴大的後期傳染病疫苗管道。

Our 2030 strategy aims to transform BioNTech into a diversified cash flow-generating multiproduct company that can deliver sustained long-term growth.

我們的 2030 年策略旨在將 BioNTech 轉型為一家能夠產生持續長期成長的多元化現金流生成多產品公司。

Turning to the next slide. I would like to spend a little more time today on the growth potential of our expanding late-stage pipeline. This pipeline includes 7 mid- and late-stage programs that are currently in Phase II and III trials.

轉到下一張投影片。今天我想多花一點時間來談談我們不斷擴大的後期產品線的成長潛力。該管道包括 7 個中後期項目，目前正處於 II 期和 III 期試驗。

We have mentioned our goal to have 10-plus trials with registrational potential initiated by the end of 2024. We also expect a busy calendar program updates this year. These include updates on several cancer vaccine programs at AACR, which were announced last week and further anticipated updates for specific IO and ADC programs at other major medical conferences throughout the year.

我們已經提到我們的目標是在 2024 年底之前啟動 10 多項具有註冊潛力的試驗。我們也預計今年的日曆計畫更新會很繁忙。其中包括上周宣布的 AACR 多個癌症疫苗項目的更新，以及全年其他主要醫學會議上特定 IO 和 ADC 項目的進一步預期更新。

2024 will therefore be an important year of execution as we transition toward our goal of commercializing our oncology portfolio. We are looking forward to sharing further details on these programs throughout the course of the year.

因此，2024 年將是我們向腫瘤產品組合商業化目標過渡的重要執行年。我們期待在這一年中分享有關這些計劃的更多細節。

Ultimately, we believe our oncology pipeline can deliver one or more indication launches per year from 2026 onwards. We see significant potential for our mid- and late-stage programs to address unmet medical need across a broad range of cancer types and across the cancer treatment continuum. We are truly excited by the potential our oncology pipeline holds to expand and improve on cancer treatment options for people around the world.

最終，我們相信從 2026 年起，我們的腫瘤學產品線每年可以推出一個或多個適應症。我們看到我們的中後期計畫在解決廣泛的癌症類型和整個癌症治療連續體中未滿足的醫療需求方面具有巨大的潛力。我們對我們的腫瘤學產品線在擴大和改善世界各地人們的癌症治療選擇方面的潛力感到非常興奮。

In closing, I would like to highlight on the next slide a few important investor events we will be holding this year. Our Annual General Meeting will take place on May 17, and the next Innovation Series event on November 14.

最後，我想在下一張投影片上強調我們今年將舉辦的一些重要的投資人活動。我們的年度股東大會將於 5 月 17 日舉行，下一次創新系列活動將於 11 月 14 日舉行。

This year, we will also introduce a new and exciting event, focused on our expanding work in the field of artificial intelligence and machine learning, which will take place on October 1. We look forward to sharing further details on both events in the near future.

今年，我們還將推出一項令人興奮的新活動，重點關注我們在人工智慧和機器學習領域的擴展工作，該活動將於10 月1 日舉行。我們期待在不久的將來分享這兩項活動的更多詳細資訊。

With that, I would like to thank our shareholders for their continued support and open the floor for questions.

在此，我要感謝我們的股東一直以來的支持，並歡迎提問。

(Operator Instructions) And your first question comes from the line of Daina Graybosch from Leerink Partners.

（操作員說明）您的第一個問題來自 Leerink Partners 的 Daina Graybosch。

Yes. I look forward to these 10 potential registrational trials, I wonder if you can talk about maybe even a range of revenue expectations that you could be looking at by 2030 from the oncology portfolio? And then I have a follow-up.

是的。我期待著這 10 個潛在的註冊試驗，我想知道您是否可以談談到 2030 年您可能從腫瘤學組合中看到的一系列收入預期？然後我有一個後續行動。

Yes. Thanks, Daina. I think the pipeline is quite broad. And one of the criteria that is common among most of those assets in that list is actually that they can target multiple solid tumors. And so that means that, that actually, the peak sales estimate for those -- for that collection of assets is actually well over EUR 10 billion in our range long-term -- in our estimates long-term.

是的。謝謝，戴娜。我認為管道相當廣泛。該清單中大多數資產的共同標準之一實際上是它們可以針對多種實體瘤。因此，這意味著，實際上，在我們的長期估計中，這些資產的高峰銷售估計實際上遠超過我們長期範圍內的 100 億歐元。

And -- but I think we're focused now on executing in those first launches. So I think we're not prepared yet to give you a 2030 number. But we do think that we're talking here about double-digit indications that we can address across the solid tumor landscape.

而且 - 但我認為我們現在的重點是在首次發布中執行。所以我認為我們還沒準備好給你一個 2030 年的數字。但我們確實認為我們在這裡談論的是我們可以在實體瘤領域解決的兩位數適應症。

Great. And then my follow-up is more specific on the Autolus collaboration. I wonder if you could talk about potential scenarios for how you see your CAR-T business with Autolus maturing and advancing in the next 5 years?

偉大的。然後我的後續行動更具體地介紹了與 Autolus 的合作。我想知道您是否可以談談您如何看待 Autolus 的 CAR-T 業務在未來 5 年內成熟和發展的潛在情景？

Sure. So I'll start with that, too. So the primary rationale for Autolus was that, as we ended 2023, we actually had higher conviction on moving forward more aggressively with BNT211, which is our lead cell therapy CAR-T program, as you know, targeting Claudin-6 with an mRNA vaccine amplifier.

當然。所以我也將從這個開始。因此，Autolus 的主要理由是，在2023 年結束時，我們實際上更有信心更積極地推進BNT211，這是我們的領先細胞療法CAR-T 項目，如你所知，用mRNA 疫苗靶向Claudin- 6放大器。

And so we've talked about testicular future being a potential lead indication and faster -- a potential fast-to-market path given the high unmet need in the refractory setting, but we're also seeing strong and encouraging data in other indications such as refractory ovarian cancer and even in responses in lung cancer and other Claudin-6 positive tumors.

因此，我們討論了睪丸的未來是一個潛在的領先適應症，而且速度更快——考慮到難治性環境中未滿足的高度需求，這是一條潛在的快速上市路徑，但我們也在其他適應症中看到了強勁和令人鼓舞的數據，例如例如難治性卵巢癌，甚至肺癌和其他 Claudin-6 陽性腫瘤的反應。

And so the Autolus collaboration gives us a sort of runway to more aggressively explore multiple pivotal trials in parallel, leveraging the manufacturing infrastructure that we have in the United States, through the Kite acquisition of assets that we had 2.5 years ago, but also combined with the Autolus state-of-the-art manufacturing infrastructure in the United Kingdom. So that's the first rationale.

因此，與 Autolus 的合作為我們提供了一條跑道，可以透過 Kite 收購我們 2.5 年前擁有的資產，利用我們在美國擁有的製造基礎設施，更積極地並行探索多個關鍵試驗，但也結合了Autolus在英國擁有最先進的製造基礎設施。這就是第一個理由。

And then in addition to that, the deal incorporates some options where we could come in at the pivotal trial stage into a couple of Autolus' programs. We find their Phase I data for our CD19/22 very encouraging. It's early, but it's encouraging. And also the GD2 CAR, we think, is an interesting approach that could be complementary.

除此之外，交易還包含一些選項，我們可以在關鍵試驗階段加入 Autolus 的幾個項目。我們發現他們的 CD19/22 第一階段數據非常令人鼓舞。雖然還早，但令人鼓舞。我們認為，GD2 CAR 是一種有趣的方法，可以起到補充作用。

So the collaboration contract gives us the optionality to actually scale into a multiproduct franchise in cell therapy while keeping our fixed cost lean and allowing us to accelerate BNT211 forward.

因此，合作合約使我們可以選擇實際擴展到細胞治療領域的多產品特許經營權，同時保持我們的固定成本精簡，並使我們能夠加速 BNT211 的發展。

And your next question comes from the line of Chris Shibutani from Goldman Sachs.

你的下一個問題來自高盛的 Chris Shibutani。

This is Steven on for Chris. I had one on the financial side. Can you just give a little bit of color about what's driving the increase in SG&A guidance? I think at the midpoint, it's about over a 30% increase from the prior year. So just wondering if that's related to COVID or if that's more related to building out the oncology franchise?

這是史蒂文替克里斯發言。我在財務方面有一個。能否簡單介紹一下推動 SG&A 指導增加的因素？我認為在中期，比前一年增長了 30% 以上。所以只是想知道這與新冠病毒有關，還是與建立腫瘤專營權更相關？

And then specifically on your HER2 ADC, can you just talk about what type of clinical profile would be attractive in that HER2-low breast cancer indication?

然後，特別是關於您的 HER2 ADC，您能否談談在 HER2 低乳癌適應症中哪種類型的臨床特徵會有吸引力？

Yes. I'll take the first one on the SG&A expense increase that we anticipate for 2024. You have heard from us that we're planning to launch potentially our first product in 2026. Of course, we've got to build up the infrastructure to be able to commercialize those compounds that are coming then in 2016 and onwards. And therefore, we intend to invest in infrastructure, specifically also in the commercial setup in the U.S. going forward.

是的。我將討論第一個關於我們預計 2024 年 SG&A 費用增加的問題。您已經聽說我們計劃在 2026 年推出我們的第一個產品。當然，我們必須建立基礎設施來能夠將2016 年及以後即將推出的化合物商業化。因此，我們打算投資基礎設施，特別是未來美國的商業設施。

The second question was, what makes for HER2 ADC, the indication of hormone receptor positive HER2 to low breast cancer interesting. Did I get that right?

第二個問題是，是什麼讓 HER2 ADC（激素​​受體陽性 HER2 對低乳癌的指示）變得有趣。我做對了嗎？

More kind of expectations for what type of clinical profile would be attractive in that space.

在該領域，對哪種類型的臨床特徵的更多期望會更有吸引力。

[Oh, COVID as a TPP]. So our HER2 ADC, we think, has a differentiable safety efficacy profile. And this is what we want to see in our Phase III trial, which is ongoing.

[哦，新冠病毒作為 TPP]。因此，我們認為我們的 HER2 ADC 具有可區分的安全功效。這就是我們希望在正在進行的第三階段試驗中看到的。

Yes. And just to add on that, what Ozlem shared is, we have a profile allowing us to dose -- to provide higher doses. And we believe that this is particularly important in the HER2 1+ population, which is around half of the HER2-low population.

是的。除此之外，Ozlem 分享的是，我們有一個配置文件，允許我們劑量——提供更高的劑量。我們認為，這對 HER2 1+ 族群尤其重要，該族群約佔 HER2-low 族群的一半。

So particularly, this is interesting in breast cancer as well in endometrial cancer and other HER2 positive tumors. And we believe that we can position here the product with higher objective response rate plus higher durability at this point.

尤其是，這對乳癌、子宮內膜癌和其他 HER2 陽性腫瘤很有意義。我們相信，此時我們可以將具有更高客觀反應率和更高耐用性的產品定位在這裡。

Your next question comes from the line of Bill Maughan from Canaccord.

您的下一個問題來自 Canaccord 的 Bill Maughan。

So I have kind of a two-part question about your ability to maintain market share on the COVID vaccine going forward. Just wondering how you're thinking about your ability to, I guess, defend and/or grow that just given, for example, I know tourists is in Japan with a self-amplifying RNA for COVID.

我有一個由兩部分組成的問題，關於你們未來維持新冠疫苗市場份額的能力。只是想知道你如何看待你的能力，我猜，捍衛和/或發展剛剛給出的，例如，我知道日本的遊客攜帶了針對新冠病毒的自我放大RNA。

And Moderna has previously made a lot of noise about their prefilled syringe. I know that there's that Pfizer is rolling out a prefilled syringe, but I guess, I'm just wondering how widespread that is? And if you've seen any competitive advantage where that has become available?

Moderna 先前曾就其預充式註射器發出許多噪音。我知道輝瑞正在推出預裝注射器，但我想，我只是想知道這種情況有多普遍？如果您看到了任何可用的競爭優勢？

Yes. So we believe that we still [outperformed] very strong in 2023 and having globally above a 50% market share for the COVID franchise. We did see some market share pressure in a couple of markets like the United States. As you point out, we've also had market share gains in a number of other geographies.

是的。因此，我們相信，到 2023 年，我們的表現仍然非常強勁，並且在全球範圍內擁有超過 50% 的新冠肺炎市場份額。我們確實在美國等幾個市場看到了一些市場份額壓力。正如您所指出的，我們在許多其他地區的市場份額也有所增加。

We maintained a very high market share above 85% in Europe, and also grew our market share in countries like Japan, which have actually been pretty sizable from a volume perspective over the last 12 months.

我們在歐洲保持著 85% 以上的很高市場份額，在日本等國家的市場份額也有所增長，從過去 12 個月的銷售來看，這些國家的市場份額實際上相當大。

Going into 2024, we do feel confident that we can continue to maintain a leadership position above the 50% mark globally. To your question on competition, yes, we do expect there to be some new entrants, mostly niche players in some of the peripheral markets.

進入 2024 年，我們確實有信心能夠繼續保持全球 50% 以上的領導地位。對於你關於競爭的問題，是的，我們確實預計會有一些新進入者，其中大部分是一些外圍市場的利基參與者。

I think that you pointed out also the role of prefilled syringes, which is an important point. I think last year, it is fair to say that part of the reduction in market share in the United States that we experienced was due to a -- sort of lack of or limited supply of prefilled syringes.

我認為您也指出了預充式註射器的作用，這是很重要的一點。我認為去年，可以公平地說，我們在美國市場份額下降的部分原因是預充式註射器的缺乏或供應有限。

Last year, we did have some supply in the United States, but we also had single-dose files as well. And clearly, the market preference was for prefilled syringes. As we go into 2024, we have taken steps with Pfizer to dramatically increase our supply of prefilled syringes in the United States, but also elsewhere.

去年，我們在美國確實有一些供應，但我們也有單劑量文件。顯然，市場偏好的是預充式註射器。進入 2024 年，我們已與輝瑞採取措施，大幅增加我們在美國以及其他地方的預充式註射器供應。

Your next question, case from the line of Akash Tewari from Jefferies.

你的下一個問題是來自 Jefferies 的 Akash Tewari 的案例。

This is [Alvina] for Akash. We have two. The first one is on COVID. So for COVID vaccines gross margin, given that Pfizer reported EUR 5.4 billion for revenue versus your EUR 1.5 billion, and that you're exploiting gross profit with Pfizer, it seems to imply a gross margin of 60%, which is lower than previous levels of around 80%. So is this just because of the additional write-off Pfizer has in Q4?

這是阿卡什的[阿爾維娜]。我們有兩個。第一個是關於新冠肺炎的。因此，對於新冠疫苗的毛利率，鑑於輝瑞報告的收入為54 億歐元，而您的收入為15 億歐元，並且您正在利用輝瑞的毛利潤，這似乎意味著毛利率為60%，低於之前的水平約80%。那麼這僅僅是因為輝瑞在第四季進行了額外的沖銷嗎？

Additionally, I think, what's your view on gross margin in '24 and beyond for your COVID business, especially when the competitor seems to talk about a higher [GPN] discount?

此外，我想，您對 24 年及以後的新冠業務毛利率有何看法，尤其是當競爭對手似乎在談論更高的 [GPN] 折扣時？

And my second question is quickly for pipeline. I guess how encouraged are you with the early signals of BNT122 in other consumers outside of pancreatic? And is there any read across from the pancreatic data that will be presented at AACR soon?

我的第二個問題是快速管道。我猜您對 BNT122 在胰臟以外的其他消費者中的早期訊號感到鼓舞嗎？即將在 AACR 上公佈的胰臟數據是否有任何解讀？

Yes. Let me take the first question. To just clarify, Pfizer is, as you know, responsible for the commercialization of COMIRNATY in most markets, with the exception of Germany and Turkey, and we have a gross profit share. And that methodology works in a way that, of course, whatever Pfizer is writing-off on -- in write-offs on inventories or something that is, we're going a gross profit share and will reduce our revenue figure.

是的。讓我回答第一個問題。澄清一下，如您所知，輝瑞負責 COMIRNATY 在大多數市場（德國和土耳其除外）的商業化，並且我們有毛利分成。當然，無論輝瑞公司沖銷的是庫存還是其他什麼，這種方法的運作方式都是如此，我們都會獲得毛利份額，並會減少我們的收入數字。

That is what we are trying to highlight for the last quarters because we have been hit by around about EUR 900 million due to that procedure. This means for us, this is basically 100% profit for us before COGS that come across due to the manufacturing activities that we are responsible for. And they are limited.

這就是我們在過去幾個季度試圖強調的，因為我們因該程序而遭受了約 9 億歐元的損失。這對我們來說意味著，這基本上是我們負責的製造活動帶來的不計銷貨成本 (COGS) 之前 100% 的利潤。而且它們是有限的。

And if you compare the margin development that we'll have in '23 versus '22, you will see that we are above 80% margin. So you can't really read through from what Pfizer is reporting and really to our numbers that we report.

如果您比較我們 23 年和 22 年的利潤率發展情況，您會發現我們的利潤率高於 80%。因此，您無法真正閱讀輝瑞報告的內容以及我們報告的數據。

With regard to your question to our BNT122 and its performance in PDAC, we are very encouraged, not surprised, but really encouraged, and this is also the reason why following the data disclosure of our Phase I PDAC trial. We have initiated a Phase II PDAC trial in the adjuvant setting with BNT122, which is enrolling patients.

關於您對我們的BNT122及其在PDAC中的表現提出的問題，我們感到非常鼓舞，不是驚訝，而是真正的鼓舞，這也是為什麼我們後續公佈我們的一期PDAC試驗數據的原因。我們已經啟動了 BNT122 輔助治療的 II 期 PDAC 試驗，正在招募患者。

The results we saw in this cancer type, which is considered as immune-suppressive and cold and low in tumor mutational load is encouraging us also to go into other cancer indications with this type of immunological profile. And in fact, in our Phase I trials in other such indications we have collected data, which supports the PDAC findings and which we currently are compiling to be published as manuscripts.

我們在這種被認為具有免疫抑制性、冷性和腫瘤突變負荷低的癌症類型中看到的結果鼓勵我們也進入具有此類免疫學特徵的其他癌症適應症。事實上，在其他此類適應症的第一階段試驗中，我們已經收集了數據，這些數據支持 PDAC 的研究結果，我們目前正在將這些數據彙編為手稿出版。

Your next question comes from the line of Yaron Werber from TD Cowen.

您的下一個問題來自 TD Cowen 的 Yaron Werber。

Right. I have a couple of questions as well. So maybe the first one is on 323. The ongoing Phase III study, the DYNASTY-Breast02. Can you talk a little bit about the powering and the PFS, and it sounds like if I remember correctly, chemo, the ORR that historically is 11% to 36%, PFS is about 3% to 8%. You showed a 39% ORR some sort of -- it depends how that chemo is going to do, which is kind of -- will determine kind of how the study works.

正確的。我也有幾個問題。所以也許第一個是 323。正在進行的 III 期研究 DYNASTY-Breast02。可以談談動力和 PFS 嗎？如果我沒記錯的話，化療的 ORR 歷史上是 11% 到 36%，PFS 大約是 3% 到 8%。你顯示了 39% 的 ORR，這取決於化療將如何進行，這將決定研究的運作方式。

So maybe if you can talk about the powering of the study and maybe a little bit if you can share any Phase I/II data on PFS so we can kind of just get a sense of what you're expecting?

那麼，也許您可以談談這項研究的動力，也許您可以分享有關 PFS 的任何 I/II 期數據，以便我們能夠了解您的期望？

And then secondly, just curious, you have such a huge pipeline already and you've executed and you're obviously continuing to execute, and you need to grow the company a lot to continue to execute. What's the purpose to do and potentially more BD given that you have so much already?

其次，只是好奇，你已經有瞭如此龐大的管道，而且你已經執行了，而且顯然你還在繼續執行，你需要讓公司大幅發展才能繼續執行。鑑於您已經有這麼多 BD，那麼這樣做的目的是什麼？可能會有更多 BD？

Yaron. So I'll start with the second question, then we'll come into the first.

亞龍.我將從第二個問題開始，然後我們將討論第一個問題。

So I think we were obviously very active last year on the BD front, bringing us 6 clinical stage or near clinical stage assets. We are going to continue to be active, but Yaron, I think we would agree that we feel that we already have actually now a very broad toolkit that allows us to do a lot. And so we are focused increasingly on execution.

所以我認為去年我們在 BD 方面顯然非常活躍，為我們帶來了 6 個臨床階段或接近臨床階段的資產。我們將繼續保持活躍，但是 Yaron，我想我們會同意，我們認為我們現在實際上已經擁有了一個非常廣泛的工具包，可以讓我們做很多事情。因此，我們越來越注重執行力。

So I do think that we're going to continue to be active in BD, but probably not as active in terms of the number of clinical stage assets that we're looking to bring on board. We're -- the focus this year is going to be more on executing and getting the pivotal trials initiated and enrolled.

因此，我確實認為我們將繼續活躍在 BD 領域，但就我們希望引入的臨床階段資產數量而言，可能不會那麼活躍。我們今年的重點將更多地放在執行和啟動和註冊關鍵試驗上。

Yes. To your second question, I think the second question can be better answered with the powering for a hazard ratio, which we usually do around 0.7, 0.65. And with that, we have a power of 90%. And this is -- this gives us to a study of around 530 patients that we will enroll.

是的。對於你的第二個問題，我認為第二個問題可以透過風險比的動力來更好地回答，我們通常在 0.7、0.65 左右。這樣，我們就有了 90% 的力量。這使我們能夠開展一項針對約 530 名患者的研究，我們將招募這些患者。

And your next question comes from the line of Etzer Darout from BMO Capital.

您的下一個問題來自 BMO Capital 的 Etzer Darout。

Great. Just one question for me. On BNT327, (inaudible) VEGF PD-L1, you highlighted the program sort of prominently a couple of slides and looking at sort of Phase III 2024 and beyond.

偉大的。只是問我一個問題。在 BNT327（聽不清楚）VEGF PD-L1 上，您透過幾張投影片突顯了該計劃，並著眼於 2024 年及以後的 III 期試驗。

Just wondered if you would be providing any clinical updates for this program in 2024, and then what we could expect to see there? And any more specifics as well on sort of the potential path to Phase III and what programs? Or what indications specifically you might be able to sort of pursue with this molecule?

只是想知道您是否會在 2024 年為該計劃提供任何臨床更新，然後我們可以期待在那裡看到什麼？關於第三階段的潛在路徑以及哪些計劃還有更多細節嗎？或者你可以用這個分子來具體研究什麼跡象？

Yes. Indeed, we will see a number of clinical trial updates on this molecule, not only indications. Just to remind everyone, this is a [biospecific molecule, which has PD-L1 for PD-1 blocking and VG -- anti-VEGF arm, yes.

是的。事實上，我們將看到該分子的許多臨床試驗更新，而不僅僅是適應症。只是提醒大家，這是一種[生物特異性分子，其中具有用於PD-1阻斷的PD-L1和VG——抗VEGF臂，是的。

What we have seen so far consistently in a number of cohorts is the objective response rates, which are very encouraging in various indications. And what we have also reported already, our first combination trails in small-cell lung cancer and in triple-negative breast cancer for cancer patients.

到目前為止，我們在許多隊列中一致看到的是客觀反應率，這在各種跡像上都非常令人鼓舞。我們也已經報道過，我們的第一個組合試驗針對癌症患者的小細胞肺癌和三陰性乳癌。

And what is really exciting in these indications is it's not only the high response rates in the range of 60% to 75% in triple-negative breast cancer patients, but also the response rate in the patient population who are negative for immune infiltrates, which is unusual for checkpoint blockade.

這些適應症中真正令人興奮的是，不僅是三陰性乳癌患者 60% 至 75% 的高緩解率，而且是免疫浸潤陰性患者群體的緩解率，這使得檢查站封鎖是不尋常的。

So we believe that this molecule -- that we can replicate this molecule, not only in these 2 indications, small-cell lung cancer and triple-negative breast cancer, but also in a wider range of indications. The results, allowing us to position the molecule as a combination partner for classical immune therapy and even more importantly, for our ADC portfolio.

所以我們相信這個分子——我們可以複製這個分子，不僅在小細胞肺癌和三陰性乳癌這兩個適應症中，而且在更廣泛的適應症中。結果使我們能夠將該分子定位為經典免疫療法的組合夥伴，更重要的是，我們的 ADC 產品組合。

Your next question comes from the line of Jessica Fye from JPMorgan.

您的下一個問題來自摩根大通的 Jessica Fye。

First, on the top line guidance. I think you previously talked about roughly a EUR 3 billion top line just a couple of months ago, and I appreciate you highlighting the variables that factor into the guidance. But can you just expand on which of those assumptions drove the change?

一是頂層指導。我想您幾個月前曾談到大約 30 億歐元的營收，我感謝您強調了指導中所考慮的變數。但您能否詳細說明哪些假設推動了這項改變？

And then second, on the pipeline related to the HER2 space, what are you guys going to be watching for in the DYNASTY-Breast06 readout as it relates to your HER2 ADC?

其次，在與 HER2 空間相關的管道上，你們會在 DYNASTY-Breast06 讀數中關注什麼，因為它與您的 HER2 ADC 相關？

So yes, let me take the first question. So we brought in the range. We felt that the top line guidance should reflect the assumption that we've made with respect to the vaccination rates and the price levels that we currently have seen -- we're significant aware commonality of course, is significantly relevant.

所以，是的，讓我回答第一個問題。所以我們引入了這個範圍。我們認為，頂線指導應該反映我們對疫苗接種率和我們目前看到的價格水平所做的假設——我們非常清楚，當然，共通性是非常相關的。

We also have made assumptions related to the inventory write-offs that it hasn't back in '23. And there will be some write-offs that we've got to anticipate going forward. So we've done some -- included here some assumptions. And of course, there are also some additional anticipated revenues related to our service business and the German Pandemic Preparedness contract that we have in hand, or we are finalizing currently with the government. So therefore, we feel we have -- that was driving basically the broadening of that range.

我們也做出了與 23 年庫存註銷相關的假設。我們必須預見未來將會有一些沖銷。所以我們做了一些——包括一些假設。當然，還有一些與我們的服務業務和我們手頭上的德國流行病防範合約相關的額外預期收入，或者我們目前正在與政府敲定合約。因此，我們認為我們已經——這基本上推動了該範圍的擴大。

So each of those really factored into the broadening.

因此，每一個因素確實影響了擴大。

This is this -- there are some upsides, there are some downside that I mentioned, and we'll try to work it in with, of course, current assumptions that could vary over time, but that's what we've done, yes.

就是這樣——有一些優點，也有一些我提到的缺點，當然，我們會嘗試根據當前的假設來解決它，這些假設可能會隨著時間的推移而變化，但這就是我們所做的，是的。

Got it.

知道了。

Yes, with regard to our HER2 ADC, the concept of HER2 ADCs and the molecules, which are around, that's a great concept. That's very obvious. And we are very excited about our HER2 ADC, the molecule BNT323, which we have partnered with Duality.

是的，關於我們的 HER2 ADC，HER2 ADC 的概念和周圍的分子，這是一個很棒的概念。這是非常明顯的。我們對與 Duality 合作的 HER2 ADC（分子 BNT323）感到非常興奮。

And as Ugur pointed out earlier, in HER2-low breast cancer are looking for making a difference in this high medical need population. You also have heard about our target of the hazard ratio, which we are targeting.

正如 Ugur 之前指出的那樣，HER2 低乳癌正在尋求在這一高醫療需求族群中發揮作用。您也聽過我們的風險比目標。

Yes. And we can't, of course, comment on the clinical price of third parties.

是的。當然，我們不能評論第三方的臨床價格。

Your next question comes from the line of Simon Baker from Redburn.

您的下一個問題來自 Redburn 的 Simon Baker。

Two quick ones, if I may. The 2024 R&D guidance of EUR 2.4 billion to EUR 2.6 billion is a step-up on '23. And against the plethora of studies you're running, that makes perfect sense. But I was wondering, is this the new normal? I was wondering what you could say about the anticipated levels of R&D expense beyond 2024.

如果可以的話，兩個快點。 2024 年的研發指引為 24 億歐元至 26 億歐元，較 23 年有所提升。與您正在進行的大量研究相比，這是完全合理的。但我想知道，這是新常態嗎？我想知道您對 2024 年以後研發費用的預期水準有何看法。

And finally, there's been an awful lot of deal activity in the radiopharmaceutical space of late. I'd be interested to get your thoughts on the attractiveness of that modality.

最後，最近放射性藥物領域發生了大量交易活動。我很想了解您對這種方式的吸引力的看法。

Yes. Happy to take the first question. So as you pointed out correctly, of course, we have broadened our portfolio. We have more and more late-stage clinical trials running, and those drive the cost up to a great extent, yes. And going forward, we haven't given any guidance here yet for '25, for the following years. So you've got to bear with us a little bit.

是的。很高興回答第一個問題。正如您正確指出的那樣，我們當然擴大了我們的投資組合。我們正在進行越來越多的後期臨床試驗，這在很大程度上推高了成本，是的。展望未來，我們還沒有為 25 年以及接下來的幾年提供任何指導。所以你必須對我們多一點寬容。

But of course, late-stage clinical trials will cost some money. We will carefully look where we invest our money. We have shown that in '23 already where we had the same sort of range at the beginning and then we reduced costs, also reflecting the pressure that we have faced on the top line regarding the COVID revenue figures that we had to adjust during 2023.

當然，後期臨床試驗需要花費一些錢。我們會仔細檢視我們的資金投資方向。我們已經證明，在 23 年，我們一開始就擁有相同的範圍，然後我們降低了成本，這也反映了我們在 2023 年期間必須調整的新冠收入數據方面面臨的壓力。

So there is some level of insecurity. I think it's part of our job to manage our costs here. And of course, we will do that in '24 in the ongoing years. But we will invest in the areas where we feel we create value for the company and value for the shareholders. That remains on top of our list going forward.

所以存在一定程度的不安全感。我認為管理成本是我們工作的一部分。當然，我們將在接下來的幾年中在 24 年做到這一點。但我們會投資於我們認為能為公司和股東創造價值的領域。這仍然是我們未來的首要任務。

Yes. And the second part of your question about attractiveness of regular (inaudible), I would like to say, and I'm repeating myself is that oncology is being in a transformation, and we will see this transformation ongoing in the next 10 to 15 years.

是的。關於你關於常規藥物吸引力的問題的第二部分（聽不清楚），我想說的是，我重複一遍，腫瘤學正在發生轉變，我們將看到這種轉變在未來10 到15 年裡持續進行。 。

And the transformation happens because they are new concepts. And one of the new concept is targeting tumor cells, but having bystander effect. And this is what we are seeing in value limits. So we have this targeting of tumor cells plus the additional bystander effect. And this is even more pronounced in the ADC field.

轉變的發生是因為它們是新概念。新概念之一是針對腫瘤細胞，但具有旁觀者效應。這就是我們在價值限制中看到的情況。所以我們有針對腫瘤細胞的這種標靶作用以及額外的旁觀者效應。而這一點在ADC領域表現得更加明顯。

So we will see really tremendous transformation in the oncology, providing us the opportunity to open up indications where we believe in the past, patients -- we can't offer patients anything. And this is offering now the opportunity to treat patients with advanced diseases, and not only with their disease, but bring in combinations and thereby ensure that even in patients with advanced disease, we really get a considerable clinical benefit.

因此，我們將看到腫瘤學領域真正的巨大轉變，為我們提供了開闢適應症的機會，而我們過去相信患者——我們無法為患者提供任何東西。現在，這為治療晚期疾病患者提供了機會，不僅是治療他們的疾病，而且是聯合治療，從而確保即使是晚期疾病患者，我們也能真正獲得可觀的臨床益處。

Your next question comes from the line of Ellie Merle from UBS.

您的下一個問題來自瑞銀集團 (UBS) 的 Ellie Merle。

This is [Sarah] on for Ellie. Could you remind us the latest thinking about when we could see data from iNeST Phase II randomized trial and what you're hoping to see there that would continue to give you guys confidence in the program and moving forward?

這是埃莉的[莎拉]。您能否提醒我們最新的想法，即我們何時可以看到 iNeST II 期隨機試驗的數據，以及您希望在那裡看到什麼，這將繼續為您帶來對該計劃和前進的信心？

Okay. Yes. So shortly, we will report iNeST data on our melanoma trial this year, latest in the second half of this year. And we expect the next update for our colorectal cancer study end of 2025.

好的。是的。很快，我們將報告今年黑色素瘤試驗的 iNeST 數據，最新時間是今年下半年。我們預計大腸直腸癌研究的下一次更新將於 2025 年底發布。

And your final question comes from the line of Manos Mastorakis from Deutsche Bank.

你的最後一個問題來自德意志銀行的馬諾斯·馬斯托拉基斯。

So a quick question from us, Manos Mastorakis, Deutsche Bank. So just wanted to know what are the first Phase III readouts we will see for the rest of the portfolio in 2025 or beyond? And I'm assuming nothing major in 2024? Please correct me if I'm wrong.

我們德意志銀行的 Manos Mastorakis 提出了一個簡短的問題。所以我只是想知道 2025 年或以後我們將看到該投資組合其餘部分的第一個 III 期數據是什麼？我假設 2024 年不會發生什麼大事？如果我錯了，請糾正我。

Yes. So we talked about a couple of different trials that we think could produce data in 2025 ahead of product approvals and successful. And that includes the Phase II randomized trial for iNeST and CRC, which Ugur just mentioned, there's the potential for an interim update in the second half of 2025 or early 2026.

是的。因此，我們討論了一些不同的試驗，我們認為這些試驗可以在 2025 年產品獲得批准之前產生數據並取得成功。其中包括 Ugur 剛剛提到的 iNeST 和 CRC II 期隨機試驗，有可能在 2025 年下半年或 2026 年初進行中期更新。

And we've also talked about the BNT323 program in refractory -- in second and third-line endometrial cancer. So those initial readouts are likely to be Phase II, but we think they could have registrational potential if the data is strong. I think obviously, the goal by the end of this year is to start many Phase III. Some of those have already started so we could have further data updates as well on the pipeline. But those are the 2 that I would point you to.

我們也討論了 BNT323 項目在難治性 - 二線和三線子宮內膜癌的應用。因此，這些最初的讀數可能是第二階段，但我們認為，如果數據強勁，它們可能具有註冊潛力。我認為顯然，今年年底的目標是啟動許多第三階段。其中一些已經開始，因此我們也可以在管道上進行進一步的數據更新。但這是我要向您指出的兩個。

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。