Biontech SE (BNTX) 2023 Q1 法說會逐字稿

Welcome to the BioNTech First Quarter 2023 Update Call.

歡迎來到 BioNTech 2023 年第一季度更新電話會議。

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

我想將電話轉交給戰略和投資者關係副總裁 Victoria Meissner 博士。請繼續。

Good morning and afternoon. My name is Victoria Meissner, and I'm the new Head of Investor Relations at BioNTech. I'm a medical doctor by training and have recently joined BioNTech from Healthcare Investment Banking at Jefferies. I look forward to working with you on the corporate side.

早上好，下午好。我叫 Victoria Meissner，是 BioNTech 的新投資者關係主管。我是一名受過培訓的醫生，最近從 Jefferies 的醫療保健投資銀行加入了 BioNTech。我期待與您在公司方面的合作。

Thank you for joining us today for BioNTech's First Quarter 2023 Earnings Call. As a brief reminder, the slides that accompany this call and the first quarter 2023 press release that was issued this morning can be found in the Investors section of our website.

感謝您今天加入我們參加 BioNTech 的 2023 年第一季度收益電話會議。簡短提醒一下，本次電話會議的幻燈片和今天上午發布的 2023 年第一季度新聞稿可以在我們網站的“投資者”部分找到。

As outlined on Slide 2, you can see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings made with the U.S. Securities and Exchange Commission. Forward-looking statements on the call are subject to substantial risks and uncertainties, speak only as of called original date, and we undertake no obligation to update or revise any of the statements.

如幻燈片 2 所述，您可以看到我們的前瞻性聲明免責聲明。我們向美國證券交易委員會提交的文件中描述了有關這些聲明和其他風險的更多信息。電話中的前瞻性陳述受重大風險和不確定性的影響，僅在電話原始日期發表，我們不承擔更新或修改任何陳述的義務。

On Slides 3 and 4, you can see detailed safety information regarding our COVID-19 vaccine.

在幻燈片 3 和 4 上，您可以看到有關我們的 COVID-19 疫苗的詳細安全信息。

On Slide 5, you can find the agenda for today's call.

在幻燈片 5 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: our CEO and Co-Founder, Ugur Sahin; Özlem Türeci, our Chief Medical Officer and Co-Founder; Jens Holstein, our Chief Financial Officer; and Ryan Richardson, our Chief Strategy Officer.

今天，BioNTech 管理團隊的以下成員加入了我的行列：我們的首席執行官兼聯合創始人 Ugur Sahin； Özlem Türeci，我們的首席醫療官兼聯合創始人；我們的首席財務官 Jens Holstein；和我們的首席戰略官 Ryan Richardson。

I would like to turn the call over to Ugur Sahin.

我想把電話轉給 Ugur Sahin。

Thank you, Victoria. Good morning, and good afternoon, and warm welcome to all the call participants. We appreciate your continued support. Today, I will summarize our first quarter 2023 highlights and priorities before I pass the call over to my team to provide further details.

謝謝你，維多利亞。早上好，下午好，熱烈歡迎所有電話會議參與者。感謝您一直以來的支持。今天，在將電話轉交給我的團隊以提供更多詳細信息之前，我將總結我們 2023 年第一季度的亮點和優先事項。

Let me reiterate our strategic goals for 2023 and highlight our first quarter and recent achievements. First, to expand and sustain our leadership in COVID-19 with Pfizer by advancing our next-generation vaccine candidate, developing combination vaccines and advancing key Comirnaty features. This quarter, we maintained our strong COVID-19 vaccine market position, supported by key label expansions in regions around the world.

讓我重申我們 2023 年的戰略目標，並強調我們第一季度和最近取得的成就。首先，通過推進我們的下一代候選疫苗、開發聯合疫苗和推進關鍵的 Comirnaty 功能，擴大和維持我們與輝瑞在 COVID-19 方面的領導地位。本季度，在全球各地區關鍵標籤擴張的支持下，我們保持了強大的 COVID-19 疫苗市場地位。

This month, we published preclinical data in the [Journal] Cell on our next-generation Pfizer's (inaudible) vaccine component in combination with Comirnaty.

本月，我們在 [Journal] Cell 上發布了我們下一代輝瑞（聽不清）疫苗成分與 Comirnaty 的臨床前數據。

Our second goal is to accelerate our oncology pipeline and initiate multiple potentially registrational trials. Our new collaborations with DualityBio and OncoC4 complement our pipeline with multiple mid- to late-stage clinical programs that will help us to achieve this goal in the near term.

我們的第二個目標是加快我們的腫瘤管道並啟動多項潛在的註冊試驗。我們與 DualityBio 和 OncoC4 的新合作通過多個中後期臨床項目補充了我們的管道，這將幫助我們在短期內實現這一目標。

Our third and final strategic goal is to initiate and accelerate clinical programs with high unmet medical need in infectious diseases. In the first quarter, we initiated new clinical vaccine programs namely for shingles and tuberculosis. The first quarter was a strong start to 2023. We plan to continue execution against these strategic goals to continue our development into a fully integrated global multiproduct biotechnology company addressing divesting medical needs worldwide.

我們的第三個也是最後一個戰略目標是啟動和加速具有高度未滿足的傳染病醫療需求的臨床項目。第一季度，我們啟動了針對帶狀皰疹和肺結核的新臨床疫苗計劃。第一季度是 2023 年的一個良好開端。我們計劃繼續執行這些戰略目標，以繼續發展成為一家完全整合的全球多產品生物技術公司，以滿足全球剝離醫療需求。

Cancer remains one of the key unmet medical needs. Our long-term oncology strategy is to expand the treatment options available for cancer patients and become a multiproduct company in the next year. In order to best serve the needs of tumor patients, we aim to address the full continuum of cancer treatment, bring novel therapies to market for patients with adjuvant and late-stage cancer and combining our platforms and programs to translate our science into survival.

癌症仍然是未滿足的主要醫療需求之一。我們的長期腫瘤學戰略是擴大癌症患者的治療選擇，並在明年成為一家多產品公司。為了最好地滿足腫瘤患者的需求，我們的目標是解決癌症治療的完整連續性，為輔助治療和晚期癌症患者將新療法推向市場，並結合我們的平台和計劃，將我們的科學轉化為生存。

Key elements in our oncology pipeline are mRNA cancer vaccines, cell therapies, next-generation checkpoint immune modulators and antibody drug conjugate. We believe that these 5 classes has the potential to drive improved outcomes for solid tumor patients across multiple lines of treatment and tumor types.

我們腫瘤管線的關鍵要素是 mRNA 癌症疫苗、細胞療法、下一代檢查點免疫調節劑和抗體藥物偶聯物。我們相信，這 5 個類別有可能在多種治療方法和腫瘤類型中推動實體瘤患者改善預後。

Our most advanced oncology assets are currently in development for a range of solid tumors at all stage of treatment. We believe that this asset has first-in-class or best-in-class potential and may enable us to drive meaningful change in the treatment of many cancers.

我們最先進的腫瘤學資產目前正在為處於治療各個階段的一系列實體瘤開發。我們相信，這項資產具有一流或一流的潛力，可能使我們能夠在許多癌症的治療中推動有意義的變革。

How are we planning to achieve this? Our technology-agnostic innovation engine leverages modular technology platforms, both developed internally and accessed via collaboration partnerships, to produce novel product candidates.

我們打算如何實現這一目標？我們與技術無關的創新引擎利用內部開發和通過合作夥伴關係訪問的模塊化技術平台來生產新的候選產品。

In the first quarter, we announced 2 new collaborations to give us access to assets and platforms that we believe may be important in how solid tumors are treated in the future. One of those, which I'm particularly excited about is the new collaboration with Duality Biologics, the company focused on the discovery and development of next-generation antibody drug conjugates.

在第一季度，我們宣布了 2 項新的合作，使我們能夠獲得我們認為可能對未來如何治療實體瘤很重要的資產和平台。我特別興奮的其中之一是與 Duality Biologics 的新合作，該公司專注於下一代抗體藥物偶聯物的發現和開發。

In the last few years, advancements in ADC technology has resulted in a potent use for the treatment of solid tumors. We believe that ADCs have the potential to replace highly toxic chemotherapy regimens as the cytotoxic backbone to cancer treatment. ADCs consists of 3 main components: Antibody, Linker and Payload, each of these components has an impact on ADC's pharmacological and clinical properties. ADC is a precision medicine, allowing for targeted graft delivery, particularly to tumor cells with high specificity and potent induced cell death with the benefit of reduced off-target events.

在過去的幾年中，ADC 技術的進步已在實體瘤的治療中發揮了重要作用。我們相信 ADC 有可能取代劇毒化療方案，成為癌症治療的細胞毒性支柱。 ADC 由 3 個主要成分組成：抗體、接頭和有效載荷，這些成分中的每一個都對 ADC 的藥理和臨床特性產生影響。 ADC 是一種精準藥物，允許靶向移植物遞送，特別是具有高特異性和有效誘導細胞死亡的腫瘤細胞，具有減少脫靶事件的好處。

When the monoclonal antibody binds to the target antigen specifically expressed on the tumor cell, the ADC is internalized, allowing for the release of the cytotoxin, which leads to cell death.

當單克隆抗體與腫瘤細胞上特異性表達的靶抗原結合時，ADC 被內化，釋放細胞毒素，導致細胞死亡。

Slide 11. Under the terms of the exclusive worldwide licensing collaboration agreement with DualityBio, excluding Mainland China, Hong Kong region and Macau region, we will gain access to 2 programs: DB-1303 targeting HER2 and DB-1311 driven by Duality Biotech platform and novel, cleavable, linker and payload technologies, this third-generation ADCs have demonstrated pharmacokinetic properties that may contribute to an increased third-party window compared to other ADC platforms. ADCs offer a bold combination potential, especially with various IO agents.

Slide 11. 根據與 DualityBio 的獨家全球許可合作協議條款，不包括中國大陸、香港地區和澳門地區，我們將獲得 2 個項目：針對 HER2 的 DB-1303 和由 Duality Biotech 平台驅動的 DB-1311 和該第三代 ADC 具有新穎、可切割、連接子和有效載荷技術，已證明與其他 ADC 平台相比，可能有助於增加第三方窗口的藥代動力學特性。 ADC 提供了大膽的組合潛力，尤其是與各種 IO 代理。

A Phase I/II clinical trial for DB-1303 is ongoing, which we plan to expand into further tumor indications, and we aim to rapidly advance clinical development of this program.

DB-1303 的 I/II 期臨床試驗正在進行中，我們計劃將其擴展到更多的腫瘤適應症，我們的目標是快速推進該項目的臨床開發。

Slide 12. I want to end where I started, our vision. With our new collaboration, we now have 27 programs. We plan to start multiple potentially registrational trials in the coming years. Within the next years, we aim to become a multiproduct global biotechnology leader, aiming to contribute and address the world's most pressing health challenges with pioneering disruptive technologies delivered at scale.

幻燈片 12。我想在我開始的地方結束，我們的願景。通過我們的新合作，我們現在有 27 個項目。我們計劃在未來幾年開始多項潛在的註冊試驗。在接下來的幾年裡，我們的目標是成為多產品的全球生物技術領導者，旨在通過大規模交付開創性的顛覆性技術來應對世界上最緊迫的健康挑戰。

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 Özlem.

在此，我要感謝大家對我們成功的信心和一如既往的支持。我現在將把電話轉給 Özlem。

Thank you, Ugur. I'm delighted to speak with everyone today and provide our pipeline update.

謝謝你，烏古爾。我很高興今天能與大家交談並提供我們的管道更新。

Starting on Slide 14. Not only since BioNTech's founding, we have firmly believed in the potential for mRNA cancer vaccines to have a place in the future of cancer treatment. We have built our personalized and off the shelf platforms and initiated a broad clinical program to evaluate the full utility of our approaches.

從幻燈片 14 開始。不僅自 BioNTech 成立以來，我們還堅信 mRNA 癌症疫苗在未來癌症治療中佔有一席之地的潛力。我們已經建立了個性化的現成平台，並啟動了廣泛的臨床計劃來評估我們方法的全部效用。

Today, we have a broad cancer vaccine's development program with 4 ongoing randomized Phase II clinical trials in both the adjuvant and metastatic disease settings. The iNeST program includes 4 clinical studies, the Phase II clinical trial with autogene cevumeran, BNT122 monotherapy in adjuvant CRC started in 2020 and is recruiting patients with CTDNA positive the resected Stage 2 high-risk and Stage 3 colorectal cancer.

今天，我們有一個廣泛的癌症疫苗開發計劃，其中有 4 個正在進行的隨機 II 期臨床試驗，包括輔助和轉移性疾病設置。 iNeST 項目包括 4 項臨床研究，2020 年開始的自體基因 cevumeran 的 II 期臨床試驗，BNT122單藥治療結直腸癌的輔助治療，正在招募 CTDNA 陽性且已切除的第 2 期高危和第 3 期結直腸癌患者。

Data from an investigator initiated Phase I clinical trials evaluating BNT122, autogene cevumeran, and onetime dosing of atezolizumab in adjuvant pancreatic ductal adenocarcinoma were presented at ASCO last year. A Phase II clinical trial in this patient population is planned to start in 2023. A randomized Phase II clinical trial evaluating our agent in combination with pembrolizumab in first-line melanoma patients has finished enrollment. Analysis of PFS as primary endpoint will be triggered event-based.

去年在 ASCO 上公佈了一項研究者啟動的 I 期臨床試驗的數據，該試驗評估了 BNT122、自體基因 cevumeran 和一次劑量的 atezolizumab 在輔助胰腺導管腺癌中的作用。該患者群體的 II 期臨床試驗計劃於 2023 年開始。一項隨機 II 期臨床試驗評估了我們的藥物與 pembrolizumab 在一線黑色素瘤患者中的聯合作用，該試驗已完成入組。作為主要終點的 PFS 分析將基於事件觸發。

Data from a Phase I clinical trial with BNT122 autogene cevumeran, a single agent and in combination with atezolizumab in patients with locally advanced disease and metastatic disease across multiple tumor types, was presented previously. We are preparing a manuscript summarizing the Phase I data for publication.

來自 BNT122 autogene cevumeran 的 I 期臨床試驗的數據，這是一種單一藥物，並與 atezolizumab 聯合治療患有局部晚期疾病和多種腫瘤類型的轉移性疾病的患者，先前已提供。我們正在準備一份總結第一階段數據的手稿以供發表。

In our FixVac program that is comprised of 4 different indication-specific product candidates, we have ongoing clinical studies. We have a first-in-human Phase I/II clinical trial, evaluating BNT112 monotherapy and in combination with cemiplimab in 2 cohorts of patients, namely with metastatic castration-resistant prostate cancer and with high-risk localized prostate cancer, who are eligible for treatment with androgen-deprivation therapy is ongoing.

在我們的 FixVac 計劃中，該計劃由 4 種不同的適應症特定候選產品組成，我們正在進行臨床研究。我們進行了首次人體 I/II 期臨床試驗，評估 BNT112 單一療法和與 cemiplimab 聯合治療 2 組患者，即轉移性去勢抵抗性前列腺癌和高危局限性前列腺癌，他們有資格正在進行雄激素剝奪療法的治療。

A randomized Phase II clinical trials evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with PD-L1 positive unresectable recurrent or metastatic HPV-16 positive head, neck squamous cell carcinoma is ongoing.

一項隨機 II 期臨床試驗正在評估 BNT113 聯合帕博利珠單抗與帕博利珠單抗單一療法作為 PD-L1 陽性、不可切除的複發性或轉移性 HPV-16 陽性頭頸部鱗狀細胞癌患者的一線治療。

A randomized Phase II clinical trial evaluating BNT111 in combination with cemiplimab, whereas both agents as monotherapy in patients with refractory/relapsed unresectable Stage 3 or 4 melanoma is ongoing, conducted in collaboration with Regeneron. Data from the first-in-human open-label Phase I clinical trial evaluating BNT111 in patients with advanced melanoma have been published and presented.

一項評估 BNT111 聯合 cemiplimab 的隨機 II 期臨床試驗正在與再生元合作進行，而這兩種藥物作為難治性/復發性不可切除的 3 期或 4 期黑色素瘤患者的單一療法正在進行中。來自評估晚期黑色素瘤患者 BNT111 的第一個人體開放標籤 I 期臨床試驗的數據已經發表和呈現。

A Phase I basket clinical trial evaluating BNT116 alone and in combination with cemiplimab in patients with non-small cell lung cancer in various settings is ongoing. For example, patients, who have progressed on prior PD-1 inhibitor treatment or are not eligible for chemotherapy, and in combination with the docetaxel in patients, who have received prior platinum-based chemotherapy.

正在進行一項 I 期籃子臨床試驗，評估 BNT116 單獨和聯合 cemiplimab 在各種環境下的非小細胞肺癌患者中的作用。例如，既往 PD-1 抑製劑治療進展或不適合化療的患者，以及與多西紫杉醇聯合用於既往接受過鉑類化療的患者。

The second trial is planned to start this year to evaluate the combination of BNT116 and cemiplimab and cemiplimab alone as first-line treatment of patients with non-small cell lung cancer.

第二項試驗計劃於今年開始，以評估 BNT116 與 cemiplimab 聯合使用以及 cemiplimab 單獨作為非小細胞肺癌患者的一線治療藥物。

Based on the data collected from these trials, we plan to continue the clinical trial advancement and expansion of both our mRNA cancer vaccine program.

根據從這些試驗中收集的數據，我們計劃繼續推進和擴展我們的 mRNA 癌症疫苗計劃的臨床試驗。

I'd like to put our first quarter pipeline advancements and additions into the broader context of our clinical stage pipeline, which is depicted on Slide 15. In the first quarter, we added to our pipeline the new assets. Ugur already mentioned. The HER2 targeting ADC, DB-1303 developed by our colleagues at DualityBio, which has recently started the Phase II portion of the ongoing Phase I/II clinical trial.

我想將我們第一季度管道的進步和補充放在我們臨床階段管道的更廣泛背景下，如幻燈片 15 所示。在第一季度，我們將新資產添加到我們的管道中。烏古爾已經提到了。我們在 DualityBio 的同事開發的 HER2 靶向 ADC，DB-1303，最近開始了正在進行的 I/II 期臨床試驗的 II 期部分。

Also in the first quarter, we added ONC-392 to our pipeline, the PH sensitive anti-CTLA4 antibody developed by our partner, OncoC4. ONC-392 is being tested in 2 ongoing clinical trials, the first in [multiple solid tumors] as monotherapy and in combination with pembrolizumab; and the second trial in platinum-resistant ovarian cancer patients in combination with pembrolizumab. We are excited about accelerating and broadening the clinical development for both of these programs based on the data we've seen in the pre-clinic and clinic.

同樣在第一季度，我們將 ONC-392 添加到我們的管道中，這是由我們的合作夥伴 OncoC4 開發的 PH 敏感抗 CTLA4 抗體。 ONC-392 正在 2 項正在進行的臨床試驗中進行測試，第一項是 [多發實體瘤] 作為單一療法並與 pembrolizumab 聯合使用；以及聯合 pembrolizumab 在鉑耐藥卵巢癌患者中進行的第二項試驗。我們很高興能夠根據我們在臨床前和臨床中看到的數據加速和擴大這兩個項目的臨床開發。

On Slide 16, I want to briefly highlight the mechanism of action and clinical data of ONC-392. CTLA-4 recycles continuously between the cell surface and the endosomes as it does not undergo lysosomal degradation. Interruption of this process is associated with the development of autoimmunity. Autoimmunity and immune-related adverse events are a major limitation of approved anti-CTLA-4 antibodies, such as ipilimumab that disrupts CTLA-4 recycling by promoting lysosomal degradation of this important immune checkpoint modulators.

在幻燈片 16 上，我想簡要強調一下 ONC-392 的作用機制和臨床數據。 CTLA-4 在細胞表面和核內體之間不斷循環，因為它不經歷溶酶體降解。這個過程的中斷與自身免疫的發展有關。自身免疫和免疫相關的不良事件是批准的抗 CTLA-4 抗體的主要限制，例如 ipilimumab 通過促進這種重要的免疫檢查點調節劑的溶酶體降解來破壞 CTLA-4 循環。

ONC-392 does not interpret with the recycling it dissociates from the CTLA-4 molecule in the endosome and allows normal recycling of both the antibody and the CTLA-4 molecule, and thus is designed for stronger cancer furopoletic effect and less immune-related adverse effects. ONC-392 is being tested in the trial that investigated dose escalation, a single agent and in combination with pembrolizumab. Multiple indications, such as [IO] and resistant non-small cell lung cancer and melanoma are being treated with RP2D. Preliminary data shows that ONC-392 is well tolerated with no DLTs, and the RP2D was determined to be 10 mg/kg without MTDs being reached.

ONC-392 不解釋它與核內體中的 CTLA-4 分子解離的再循環，並允許抗體和 CTLA-4 分子的正常再循環，因此設計用於更強的癌症 furopoletic 效應和更少的免疫相關不良反應效果。 ONC-392 正在試驗中進行測試，該試驗研究了劑量遞增、單一藥物以及與 pembrolizumab 的組合。多種適應症，例如 [IO] 和耐藥性非小細胞肺癌和黑色素瘤正在使用 RP2D 進行治療。初步數據顯示，ONC-392耐受性良好，無 DLT，RP2D 確定為 10 mg/kg，未達到 MTD。

Severe immune-related grade-free adverse event rate in the combo dose escalation was 23%, which is considered lower than what was reported for comparable IO/IO combination. The RP2D dose for combination is 6 mg/kg. In summary, ONC-392 dose as monotherapy or in combination was well tolerated, and the safety profile appears to allow higher dosing for a longer duration of treatment as compared to ipilimumab.

組合劑量遞增中與免疫相關的嚴重無等級不良事件發生率為 23%，這被認為低於可比較的 IO/IO 組合所報告的情況。組合的 RP2D 劑量為 6 mg/kg。總之，與易普利姆瑪相比，ONC-392 劑量作為單一療法或聯合療法具有良好的耐受性，並且安全性似乎允許更高的劑量和更長的治療持續時間。

Early efficacy data as monotherapy in platinum-resistant ovarian cancer patients and in combination with pembrolizumab in multiple solid tumors were promising. Presentation of the first data from the NSCLC expansion cohort of the Phase I/II PRESERVE-001 study is planned at ASCO next month.

作為鉑類耐藥卵巢癌患者的單一療法以及與 pembrolizumab 聯合治療多種實體瘤的早期療效數據很有希望。 I / II 期 PRESERVE-001 研究的 NSCLC 擴展隊列的第一批數據計劃於下個月在 ASCO 上公佈。

Building on this data, we are planning to start a Phase III clinical trial in non-small cell lung cancer patients without driver mutations, who have progressed following anti-PD-1. After progressing on an anti-PD-1 treatment, non-small cell lung cancer patients have 8 to 11 months median overall survival and 3 to 4.5 months progression-free survival with a response rate of around 10% when treated with the second-line standard of care docetaxel. With ONC-392, we hope to offer a promising new second-line treatment option for these patients.

基於這些數據，我們計劃在抗 PD-1 治療後取得進展的無驅動突變的非小細胞肺癌患者中開展 III 期臨床試驗。在抗 PD-1 治療取得進展後，非小細胞肺癌患者的中位總生存期為 8 至 11 個月，無進展生存期為 3 至 4.5 個月，二線治療的緩解率約為 10%標準護理多西紫杉醇。通過 ONC-392，我們希望為這些患者提供一種有前途的新二線治療選擇。

The randomized open-label controlled multicenter Phase III RESERVE-003 study is planned to treat IO resistant non-small cell lung cancer patients in the dose confirmation part we and OncoC4 plan to assess the efficacy and safety of ONC-392 given at 2 dose levels in comparison to docetaxel. In the subsequent part of the trial, we intend to assess the safety and efficacy of ONC-392 at the collective dose regimen versus docetaxel.

隨機開放標籤對照多中心 III 期 RESERVE-003 研究計劃在劑量確認部分治療 IO 耐藥的非小細胞肺癌患者，我們和 OncoC4 計劃評估以 2 個劑量水平給予的 ONC-392 的療效和安全性與多西紫杉醇相比。在試驗的後續部分，我們打算評估 ONC-392 在集體劑量方案中與多西紫杉醇相比的安全性和有效性。

Patients with Stage 4 non-small cell lung cancer, who progressed on prior IO treatment with or without chemotherapy and ECOG status of 0 or 1 can be enrolled via IO-IO therapy is allowed. A total of about 600 patients are planned to be enrolled and randomized 1:1 to receive either ONC-392 or docetaxel in this 2-stage study. The primary endpoint is overall survival with objective response rate, PFS and safety as secondary endpoints.

4 期非小細胞肺癌患者，在既往 IO 治療中有或沒有化療進展且 ECOG 狀態為 0 或 1 的患者可以通過 IO-IO 治療入組。在這項兩階段研究中，計劃總共招募約 600 名患者，並以 1:1 的比例隨機分配接受 ONC-392 或多西紫杉醇。主要終點是總生存期，客觀緩解率、PFS 和安全性作為次要終點。

The study is planned to start enrolling patients within the next few weeks. The trial in progress poster will be presented at the 2023 ASCO Annual Meeting.

該研究計劃在未來幾週內開始招募患者。正在進行的試驗海報將在 2023 年 ASCO 年會上展示。

Moving to our collaboration with our partner, DualityBio, on Slide 18. As part of the collaboration, we will gain access to DualityBio's lead candidate, DB-1303, a HER2 targeting ADC comprised of the trastuzumab, biosimilar covalently linked to a proprietary DNA topoisomerase-1 inhibitor, P1003 via retrievable linker L101.

轉到幻燈片 18 上我們與合作夥伴 DualityBio 的合作。作為合作的一部分，我們將獲得 DualityBio 的主要候選藥物 DB-1303，這是一種 HER2 靶向 ADC，由曲妥珠單抗組成，生物仿製藥與專有 DNA 拓撲異構酶共價連接-1 抑製劑，P1003 通過可回收接頭 L101。

Approved ADCs have shown antitumor activity and clinical benefits and multiple types of cancer. While current generations of anti-HER2 ADCs have an improved overall therapeutic index, more efficacious and safer anti-HER2 ADCs, for example, regarding potential lung toxicity, such as the severe life-threatening or fatal interspecial lung disease, including pneumonitis may add further clinical benefit.

批准的 ADC 已顯示出抗腫瘤活性和臨床益處以及多種類型的癌症。雖然當前幾代抗 HER2 ADC 的總體治療指數有所提高，但更有效和更安全的抗 HER2 ADC，例如，潛在的肺毒性，如嚴重危及生命或致命的特殊間肺病，包括肺炎可能會進一步增加臨床效益。

The first data for DB-1303 were presented at the t EORTC-NCI-AACR conference last October and describe to significantly improved therapeutic window of DB-1303 preclinically as compared to DS-8201a or TDM-1 analogs to trastuzumab deruxtecan and trastuzumab emtansin, respectively. In [red] monkey and human plasma, DB-1303 demonstrated high drug to antibody ratio and outstanding plasma stability.

DB-1303 的第一個數據於去年 10 月在 t EORTC-NCI-AACR 會議上公佈，並描述了與 DS-8201a 或 TDM-1 類似物相比，DB-1303 的臨床前治療窗口顯著改善，曲妥珠單抗 deruxtecan 和曲妥珠單抗 emtansin，分別。在 [紅色] 猴子和人血漿中，DB-1303 表現出高藥物抗體比和出色的血漿穩定性。

In HER2-positive and HER2 negative mixed cell cultures, DB-1303 inhibited the proliferation of both cell types, demonstrating its bi-standard effect. Pharmacokinetic and pharmacodynamic analysis of DB-1303 in xenograft mouse models showed targeted delivery of the toxin into tumor tissue. Further in VIVO studies in monkeys showed a superior stability of DB-1303 and rapid systemic clearance of the toxin. These pharmacokinetic properties result in maintenance of efficacy and reduction of systemic toxicity in animal models, which are shown on the next slide.

在 HER2 陽性和 HER2 陰性混合細胞培養物中，DB-1303 抑制兩種細胞類型的增殖，證明其雙標準效應。 DB-1303 在異種移植小鼠模型中的藥代動力學和藥效學分析表明，該毒素可靶向遞送至腫瘤組織。進一步在猴子體內進行的研究表明 DB-1303 具有出色的穩定性和毒素的快速全身清除率。這些藥代動力學特性導致在動物模型中維持療效並降低全身毒性，如下一張幻燈片所示。

Slide 19, DB-1303 exhibited potent antitumor activity in both HER2-positive and HER2-low tumor models, potentially expanding the benefit population of HER2-targeted therapy. Preclinical studies in monkeys demonstrated an improved safety profile compared to DS-8201 with the highest non-severely toxic dose of 80 mg/kg.

幻燈片 19，DB-1303 在 HER2 陽性和 HER2 低腫瘤模型中均表現出強大的抗腫瘤活性，可能擴大 HER2 靶向治療的受益人群。猴子臨床前研究表明，與 DS-8201 相比，最高非嚴重毒性劑量為 80 mg/kg，安全性有所提高。

Further, DB-1303 showed lower risk of causing lung inflammation with no ILD-like lung toxicity. The pharmacokinetic properties of DB-1303 may contribute to a superior safety profile observed in monkeys.

此外，DB-1303 顯示出較低的引起肺部炎症的風險，並且沒有類似間質性肺病的肺毒性。 DB-1303 的藥代動力學特性可能有助於在猴子中觀察到優異的安全性。

Slide 20. The program has received Fast Track Designation from the FDA and is currently being evaluated in a Phase I/II clinical trial for HER2-positive advanced solid tumors. The study is enrolling pretreated patients with advanced or metastatic HER2-positive or HER2-expressing solid tumors. Data from this study will be presented at ASCO this year. After determination of the recommended Phase II dose, further dose expansion cohorts are planned, including tastuzumab-treated HER2 gastric or the gastric esophageal adenocarcinoma, esophageal carcinoma and CRC. HER2 over-expressing and HER2-low endometrial carcinoma, hormone receptor positive HER2-low breast cancer as well as HER2-positive breast cancer and non-small cell lung cancer with activating HER2 mutations.

幻燈片 20。該項目已獲得 FDA 的快速通道指定，目前正在 HER2 陽性晚期實體瘤的 I/II 期臨床試驗中進行評估。該研究正在招募既往接受過治療的晚期或轉移性 HER2 陽性或 HER2 表達實體瘤患者。這項研究的數據將在今年的 ASCO 上公佈。在確定推薦的 II 期劑量後，計劃進行進一步的劑量擴展隊列，包括他妥珠單抗治療的 HER2 胃癌或胃食管腺癌、食管癌和 CRC。 HER2 過表達和 HER2-low 子宮內膜癌、激素受體陽性 HER2-low 乳腺癌以及 HER2 陽性乳腺癌和 HER2 突變激活的非小細胞肺癌。

Slide 21 highlights our infectious disease pipeline. In December of last year, we initiated the first clinical trials, investigating an mRNA-based vaccine for malaria prevention. Consistent with our 2023 strategic priorities, we started first in human clinical trials testing new mRNA vaccine candidates in the first quarter of 2023. One is a vaccine against tuberculosis and the other with our partner, Pfizer, a vaccine for shingles.

幻燈片 21 重點介紹了我們的傳染病管道。去年 12 月，我們啟動了第一次臨床試驗，研究一種基於 mRNA 的瘧疾預防疫苗。根據我們 2023 年的戰略重點，我們首先在 2023 年第一季度開始了人體臨床試驗，測試新的 mRNA 候選疫苗。一種是結核病疫苗，另一種是與我們的合作夥伴輝瑞公司合作的帶狀皰疹疫苗。

These programs built on our validated platform of mRNA-LNPs that have a backbone optimized design and our nucleos got modified to address diseases with a significant global need. The World Health Organization estimates that about 25% of the world population is latently infected with mycobacterium tuberculosis, the bacterium responsible for the tuberculosis disease. 10.6 million people developed active tuberculosis in 2021 and a total of 1.6 million people died of tuberculosis worldwide.

這些程序建立在我們經過驗證的 mRNA-LNP 平台上，該平台具有骨幹優化設計，我們的核仁經過修改以解決具有重大全球需求的疾病。世界衛生組織估計，世界上約有 25% 的人口潛伏感染結核分枝桿菌，這種細菌會導致結核病。 2021 年有 1060 萬人患上活動性結核病，全球共有 160 萬人死於結核病。

There are limited prophylactic treatment options for tuberculosis and cases of multidrug-resistant mycobacterium tuberculosis strains are increasing worldwide. The only licensed, tuberculosis vaccine, is the mycrobacterium bovis derived and attenuated BCG, which was first introduced in the 1920s and is still routinely administered to newborns in most tuberculosis endemic countries.

結核病的預防性治療選擇有限，全球範圍內耐多藥結核分枝桿菌菌株的病例正在增加。唯一獲得許可的結核病疫苗是牛分枝桿菌衍生和減毒的 BCG，它於 1920 年代首次推出，在大多數結核病流行國家仍常規用於新生兒。

While BCG provides time protection from severe forms of tuberculosis in childhood, the high number of pulmonary tuberculosis cases that emerge every year illustrates the limited durability and protective efficacy of BCG against tuberculosis disease and transmission in adolescents and adults. Vaccine technology advances are seen as important to ending the tuberculosis epidemic by 2030, which is the United Nations Sustainable Development Goal.

雖然 BCG 可以為兒童時期的嚴重結核病提供時間保護，但每年出現的大量肺結核病例表明 BCG 在青少年和成人中對結核病和傳播的持久性和保護效果有限。疫苗技術的進步被視為對到 2030 年結束結核病流行很重要，這是聯合國可持續發展目標。

Given the major global unmet medical need for tuberculosis vaccines, we and the Bill and Melinda Gates Foundation are working on multi-antigen our aided lipid nanoparticle vaccine candidates against tuberculosis. The target population of a BNT164 program will include IGRA-negative and positive BCG naive and vaccinated healthy adults. The clinical program in Germany and South Africa, thereby including a non-endemic and endemic country, will investigate with safety, reactogenicity and tolerability of the BNT164 vaccine candidates.

鑑於全球對結核病疫苗的主要醫療需求未得到滿足，我們和比爾及梅琳達·蓋茨基金會正在研究多抗原我們輔助的脂質納米顆粒候選疫苗以對抗結核病。 BNT164計劃的目標人群將包括 IGRA 陰性和陽性 BCG 幼稚和接種疫苗的健康成年人。德國和南非的臨床計劃，因此包括一個非地方病和地方病國家，將調查 BNT164 候選疫苗的安全性、反應原性和耐受性。

The Phase I program is intended to have select for optimal mRNA vaccine candidate and the dose level for advancement to Phase II. The vaccine may prevent infection and subsequent transmission, and when applied to a large enough proportion of the target population that constitutes the infectious reservoir, could enable interruption of transmission. And that bring us closer to the elimination of tuberculosis.

I 期計劃旨在選擇最佳 mRNA 候選疫苗和推進到 II 期的劑量水平。疫苗可以預防感染和隨後的傳播，並且當應用於構成傳染源的足夠大比例的目標人群時，可以阻斷傳播。這使我們更接近於消除結核病。

We believe that even a vaccine that is only 50% efficacious would be a critical intervention and a success in contributing to the WHO tuberculosis elimination target by 2030.

我們相信，即使只有 50% 有效的疫苗也將是一項關鍵干預措施，並成功地為世衛組織到 2030 年消除結核病的目標做出貢獻。

Slide 23. Dynamic evolution of COVID-19 strain requires care vaccine adaptations and innovative next-generation vaccines. We are pursuing several next-gen vaccine concepts. One of these is a T-cell string vaccine component, aka BNT162b4. As shown on the left-hand side, along the evolution of SARS-CoV-2 and particularly pronounced in the omicron sublineages, there has been progressive loss of concert spike protein neutralizing antibody sites.

幻燈片 23。COVID-19 毒株的動態進化需要護理疫苗適應性和創新的下一代疫苗。我們正在研究幾種下一代疫苗概念。其中之一是 T 細胞串疫苗成分，又名 BNT162b4。如左圖所示，隨著 SARS-CoV-2 的進化，在 omicron 亞系中尤為明顯，音樂會刺突蛋白中和抗體位點逐漸丟失。

In contrast, HLA Class 1 and 2 presented T-cell epitopes of the spike protein remained mostly unaltered the process of virus evolution. This is not surprising. Indeed, a fundamental difference of T-cell versus B cell-mediated immunity is that owing to their very nature, T-cell epitopes are less likely to be impacted by mutations. And the T cell-mediated layer of immunity is more robust against immunization.

相比之下，HLA 1 類和 2 類呈遞的刺突蛋白的 T 細胞表位在病毒進化過程中基本保持不變。這並不奇怪。事實上，T 細胞與 B 細胞介導的免疫的一個根本區別在於，由於它們的性質，T 細胞表位不太可能受到突變的影響。而 T 細胞介導的免疫層對免疫的抵抗力更強。

T-cell response is likely to remain much less impacted than neutralizing antibodies by new variants of concern and may contribute to prevention or limitation of severe COVID-19 manifestation. Based on this rationale, we are developing BNT162b4, an mRNA that encodes variant conserve immunogenic segment of non-spike proteins of SARS-CoV-2, mainly of nuclear captured membrane and ORF1ab proteins was binding to diverse HLA alleles. For design of this strain, we have built on our platforms and skills developed in the context of designing [thematic] mutation-based cancer vaccines.

與中和抗體相比，受關注的新變體對 T 細胞反應的影響可能要小得多，並且可能有助於預防或限制嚴重的 COVID-19 表現。基於這個原理，我們正在開發 BNT162b4，這是一種編碼 SARS-CoV-2 非刺突蛋白的變異保守免疫原性片段的 mRNA，主要是核捕獲膜和 ORF1ab 蛋白，與多種 HLA 等位基因結合。對於這種菌株的設計，我們建立在我們在設計基於[主題]突變的癌症疫苗的背景下開發的平台和技能的基礎上。

Our BNT162b4 T-cell strain vaccine component is designed to enhance T-cell immunity and is intended to be combined with variant adapted Comirnaty. We believe we can improve immunity that is variant independent. Our preclinical data was recently published in Cells. In a mouse animal model, we demonstrated that mice immunized with BNT162b2, which is (inaudible) without BNT162b4, which is the T-cell strain non-strong polyfunctional and polyepitopic CD4 and CD8 T-cell responses to the N, M, and ORF1ab proteins of SARS-CoV-2.

我們的 BNT162b4 T 細胞株疫苗成分旨在增強 T 細胞免疫力，旨在與適應變體的 Comirnaty 結合使用。我們相信我們可以提高獨立於變體的免疫力。我們的臨床前數據最近發表在 Cells 上。在小鼠動物模型中，我們證明了用 BNT162b2 免疫的小鼠（聽不清）沒有 BNT162b4，BNT162b4 是 T 細胞株非強多功能和多表位 CD4 和 CD8 T 細胞對 N、M 和 ORF1ab 的反應SARS-CoV-2 的蛋白質。

Thus broadening the T Cell with (inaudible) beyond the spike protein.

從而擴大 T 細胞（聽不清）超出刺突蛋白。

Data from Syrian hamsters that were immunized with BNT162b4 alone or in combination with BNT162b2 and then challenged with [White] SARS-CoV-2 of the delta variants demonstrate that BNT162b4 alone and in combination protects animals from severe disease and enhances viral clearance. The clinical study investigating this next-generation COVID-19 vaccine component candidate in combination with Comirnaty is ongoing.

來自敘利亞倉鼠的數據表明，單獨使用 BNT162b4 或與 BNT162b2 聯合免疫，然後用 [白色] SARS-CoV-2 的 delta 變體進行攻擊，表明 BNT162b4 單獨和聯合使用可保護動物免受嚴重疾病並增強病毒清除率。結合 Comirnaty 調查這種下一代 COVID-19候選疫苗成分的臨床研究正在進行中。

I look forward to providing additional program updates in the coming months. I will now pass the presentation to our CFO, Jens Holstein, who will present our financial results.

我期待在接下來的幾個月中提供更多的程序更新。我現在將演示文稿交給我們的首席財務官 Jens Holstein，他將介紹我們的財務結果。

Thank you, Özlem, and a warm welcome to everyone who dialed in today's call. I'll start my section with the key highlights for the first quarter of 2023, which you can find on Slide 26.

謝謝 Özlem，並熱烈歡迎今天撥通電話的每一個人。我將從 2023 年第一季度的主要亮點開始我的部分，您可以在幻燈片 26 上找到這些亮點。

The first quarter of 2023 started strong and fully to our expectations. The quarter was driven by seasonal and some carryover effects from the previous year. As an example, we generated revenues from sales in countries with late approvals of our BA.4/ 5-adapted bivalent COVID-19 vaccine. For the rest of the year, we are expecting an increase in vaccine sales towards the Northern Hemisphere winter season in the countries which are our key markets. As a consequence, we expect the second quarter to be the weakest quarter in 2023.

2023 年第一季度開局強勁，完全符合我們的預期。該季度受到季節性和上一年的一些結轉影響的推動。例如，我們的 BA.4 / 5 適應雙價 COVID-19 疫苗的批准較晚的國家/地區的銷售產生了收入。在今年餘下的時間裡，我們預計在我們的主要市場國家/地區，北半球冬季的疫苗銷量將會增加。因此，我們預計第二季度將是 2023 年最疲軟的季度。

Overall, we reiterate our COVID-19 vaccine revenue guidance of around EUR 5 billion for the full 2023 financial year.

總體而言，我們重申 2023 年整個財政年度的 COVID-19 疫苗收入指引約為 50 億歐元。

I would now like to dive into some key financial figures that underline our successful first quarter. Our total revenues reported for the first quarter of 2023 reached EUR 1.3 billion, mainly related to our share of gross profit from COVID-19 vaccine sales in the collaboration partner territories. These revenues represent a net figure, meaning that we generate a 100% gross margin on those.

我現在想深入探討一些強調我們第一季度成功的關鍵財務數據。我們報告的 2023 年第一季度總收入達到 13 億歐元，主要與我們在合作夥伴地區的 COVID-19 疫苗銷售毛利中所佔份額有關。這些收入代表一個淨數字，這意味著我們產生了 100% 的毛利率。

As a reminder, under our COVID-19 vaccine collaboration, territories have been allocated between us, Pfizer and Fosun Pharma based on marketing and distribution rights. Please keep in mind that Pfizer's fiscal quarter for subsidiaries outside the United States differs from our financial reporting cycle. Hence, Pfizer's international operations from December 2022 will be reflected in their Q1 2023 earnings, whereas we have included the respective estimate already in our Q4 2022 financial figures. This creates a deviation between the numbers of our partner Pfizer publishers versus our numbers on a quarterly and a full year basis.

提醒一下，根據我們的 COVID-19 疫苗合作，我們、輝瑞和復星醫藥根據營銷和分銷權分配了區域。請記住，輝瑞美國以外子公司的財政季度與我們的財務報告週期不同。因此，輝瑞從 2022 年 12 月開始的國際業務將反映在其 2023 年第一季度的收益中，而我們已經將相應的估計包括在我們的 2022 年第四季度財務數據中。這導致我們的合作夥伴輝瑞出版商的數量與我們的季度和全年數字之間存在偏差。

With EUR 1.3 billion in revenues, we ended the first quarter with an operating result of EUR 654.4 million and generated earnings per share on a fully diluted basis of EUR 2.05.

憑藉 13 億歐元的收入，我們在第一季度結束時的經營業績為 6.544 億歐元，在完全攤薄的基礎上產生的每股收益為 2.05 歐元。

With respect to the company's financial position, we ended the first quarter of 2023 with EUR 12.8 billion, comprising EUR 12.1 billion cash and cash equivalents as well as EUR 0.7 billion security investment with a longer time horizon, which we made as part of our investment strategy.

關於公司的財務狀況，我們在 2023 年第一季度結束時為 128 億歐元，包括 121 億歐元的現金和現金等價物以及 7 億歐元的長期證券投資，這是我們投資的一部分戰略。

When looking at our cash burn during the first quarter of 2023, the cash movement was negatively impacted, for example, due to a onetime payment settling our wage tax liability incurred in the context of our 2022 share-based payment settlement significant tax prepayments relating to the full financial year of 2023 as well as amounts spent as part of our share repurchase program.

在查看我們 2023 年第一季度的現金消耗時，現金流動受到了負面影響，例如，由於一次性付款結算了我們在 2022 年以股份為基礎的付款結算中產生的工資稅負債，與2023 年的整個財政年度以及作為我們股票回購計劃一部分的支出金額。

Subsequent to the end of the quarter, in April 2023, we have received approximately EUR 4 billion in cash from our collaboration partner, Pfizer, settling our gross profit share for the fourth quarter of 2022.

在本季度末，即 2023 年 4 月，我們從合作夥伴輝瑞公司收到了約 40 億歐元的現金，用於結算我們 2022 年第四季度的毛利份額。

Our M&A activities and recent collaboration license agreements announced in the first quarter did not lead to cash outflows during the quarter. In connection with the planned acquisition of InstaDeep and the upfront payments of the collaboration and license agreements with OncoC4 and Duality Biologics, we expect approximately EUR 0.8 billion to be invested in cash and by exchanging shares in the course of 2023. Please note the final InstaDeep purchase price will be determined on closing, and the mentioned amount for M&A does not comprise future earnout and milestone payments.

我們在第一季度宣布的併購活動和最近的合作許可協議並未導致本季度出現現金流出。關於計劃收購 InstaDeep 以及與 OncoC4 和 Duality Biologics 的合作和許可協議的預付款，我們預計將在 2023 年期間以現金和交換股份的方式投資約 8 億歐元。請注意 InstaDeep 的最終結果購買價格將在交易結束時確定，上述併購金額不包括未來收益和里程碑付款。

I'll be moving to our financial results for the first quarter of 2023, as shown on Slide 27. Having explained our revenues on the previous slide, let me move to cost of sales that amounted to EUR 0.1 billion in the first quarter of 2023 compared to EUR 1.3 billion for the comparative prior year period. The drop was mainly due to the decrease in COVID-19 vaccine sales.

我將轉到 2023 年第一季度的財務業績，如幻燈片 27 所示。在上一張幻燈片中解釋了我們的收入之後，讓我轉到 2023 年第一季度的銷售成本為 1 億歐元上年同期為 13 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 334 million for the first quarter of 2023 compared to EUR 285.8 million for the comparative prior year period. The increase was mainly due to higher expenses incurred from progressing the clinical studies for pipeline candidates. The increase was further driven by an increase in wages, benefits and social security expenses resulting from an increase in headcount.

2023 年第一季度研發費用達到 3.34 億歐元，而去年同期為 2.858 億歐元。增加的主要原因是為進行在研候選藥物的臨床研究而產生的費用增加。員工人數增加導致工資、福利和社會保障支出增加，進一步推動了這一增長。

General and administrative expenses amounted to EUR 119.4 million for the first quarter of 2023 compared to EUR 90.8 million for the comparative prior year period. The increase in G&A was mainly due to increased expenses for IT consulting and IT services as well as an increase in wages, benefits and social security expenses, resulting mainly from an increase in headcount.

2023 年第一季度的一般和行政費用為 1.194 億歐元，而去年同期為 9080 萬歐元。 G&A 的增加主要是由於 IT 諮詢和 IT 服務的費用增加以及工資、福利和社會保障費用的增加，這主要是由於員工人數的增加。

Income taxes were accrued with an amount of EUR 205.5 million for the first quarter of 2023 compared to EUR 1.3 billion for the comparative prior year period. The derived effective income tax rate for the first quarter of 2023 was approximately 29%, which is expected to decrease over the 2023 financial year to be in line with our guidance.

2023 年第一季度應計所得稅為 2.055 億歐元，而去年同期為 13 億歐元。得出的 2023 年第一季度實際所得稅率約為 29%，預計 2023 財年將下降，以符合我們的指引。

For the first quarter of 2023, net profit reached EUR 502.2 million compared to EUR 3.7 billion for the comparative prior year period. Our diluted earnings per share for the first quarter of 2023 amounted to EUR 2.05 compared to EUR 14.24 for the comparative prior year period.

2023 年第一季度，淨利潤達到 5.022 億歐元，而去年同期為 37 億歐元。我們 2023 年第一季度的攤薄後每股收益為 2.05 歐元，而去年同期為 14.24 歐元。

Now turning to Slide 28. I would like to emphasize that we are reiterating the company's outlook for the 2023 financial year. Please note, the following number reflects current base case projections and are calculated based on the constant currency rate. As stated before, we reiterate our estimated COVID-19 vaccine revenues of around EUR 5 billion for the full 2023 financial year.

現在轉到幻燈片 28。我想強調的是，我們重申了公司對 2023 財年的展望。請注意，以下數字反映了當前的基本情況預測，並根據恆定匯率計算得出。如前所述，我們重申我們估計 2023 年整個財政年度的 COVID-19 疫苗收入約為 50 億歐元。

Our capital allocation strategy includes a strong investment in M&A transactions to the extent disclosed. They have been, as far as known, reflected in the R&D expenses and will be updated as needed. Overall, we maintain our guidance for client expenses and growth and maintenance CapEx for operating activities as well as the estimated annual effective income tax rate, which we have summarized for you on the slide.

我們的資本配置策略包括在披露的範圍內對併購交易進行大量投資。據了解，它們已反映在研發費用中，並將根據需要進行更新。總體而言，我們保持對客戶支出和運營活動的增長和維護資本支出的指導，以及我們在幻燈片中為您總結的估計年度有效所得稅率。

And with that, I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for an update on our strategic outlook for 2023 and concluding remarks. Thank you.

因此，我想將電話轉給我們的首席戰略官 Ryan Richardson，以了解我們 2023 年戰略展望的最新情況和結束語。謝謝。

Thank you, Jens. To wrap up our prepared remarks, I'll provide a brief summary of the commercial outlook for our COVID-19 vaccine franchise 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評論，我將簡要概述我們的 COVID-19 疫苗特許經營權的商業前景，然後以幾個重要的日期結束，以便在您的日曆上標記。

In 2023, we aim to develop, manufacture and deploy a seasonal adapted Comirnaty vaccine. We expect a recommendation from governmental authorities regarding vaccine strain composition midyear with a potential approval for an adapted vaccine by the end of this summer. Broad vaccination is planned to start early fall.

2023 年，我們的目標是開發、製造和部署季節性適應的 Comirnaty 疫苗。我們期待政府當局在年中就疫苗株組成提出建議，並可能在今年夏末批准一種適應性疫苗。計劃在初秋開始廣泛接種疫苗。

In addition, we aim to introduce a single-dose, ready-to-use vial, and will continue to improve key Comirnaty features such as shelf stability. In addition, we plan to advance our next-generation COVID-19 vaccine candidates throughout the year. We expect that COVID demand in 2023 will continue to come from a broad range of regions globally. Since the beginning of the first quarter, we have shipped COVID-19 vaccine doses to more than 70 countries and regions. Since the start of the year, our deliveries to middle-income and low-income countries have increased. We have also seen a greater contribution from the pediatric segment so far this year.

此外，我們的目標是推出單劑量、即用型小瓶，並將繼續改進關鍵的 Comirnaty 特性，例如貨架穩定性。此外，我們計劃在全年推進我們的下一代 COVID-19 候選疫苗。我們預計 2023 年的 COVID 需求將繼續來自全球範圍廣泛的地區。自第一季度初以來，我們已向 70 多個國家和地區運送了 COVID-19 疫苗。自今年年初以來，我們對中等收入和低收入國家的交付量有所增加。今年到目前為止，我們還看到兒科部門做出了更大的貢獻。

For the full year 2023, we expect global demand to be driven by existing signed government contracts, which we anticipate will be augmented by the opening of a commercial market in the U.S. in the second half. In the midterm, we see multiple potential growth drivers for our COVID-19 vaccine franchise. These include the potential for volume growth as the seasonal market is established, particularly in high-risk population segments.

對於 2023 年全年，我們預計全球需求將受到現有簽署的政府合同的推動，我們預計下半年美國商業市場的開放將增加這一需求。在中期，我們看到我們的 COVID-19 疫苗特許經營權有多種潛在的增長動力。其中包括隨著季節性市場的建立，銷量增長的潛力，特別是在高風險人群中。

In addition, we believe continued innovation from variant-adapted vaccines, next-generation vaccines and possible respiratory combination vaccines have the potential to support future franchise growth. The transition to private markets in certain regions is likely to take several years. We believe the shift to commercial pricing will provide further midterm growth potential.

此外，我們相信變異適應疫苗、下一代疫苗和可能的呼吸道聯合疫苗的持續創新有可能支持未來的特許經營增長。某些地區向私人市場的過渡可能需要數年時間。我們相信向商業定價的轉變將提供進一步的中期增長潛力。

We and our partner, Pfizer, believe in the value that our COVID-19 vaccines provide both to individuals and health systems, and we will continue to invest to maintain our leadership position in the market.

我們和我們的合作夥伴輝瑞相信我們的 COVID-19 疫苗為個人和衛生系統提供的價值，我們將繼續投資以保持我們在市場上的領先地位。

The next slide summarizes our pipeline news flow for 2023. Some of these points have been covered, so I won't go through them in detail again here. What is clear is that our pipeline of 27 clinical-stage programs is expected to produce several readouts throughout the year across a range of technologies. We expect data updates for our CAR-T cell program, targeting Claudin-6, our anti-CTLA-4 program and our new HER2 antibody-drug conjugate at ASCO, in addition to multiple further updates for other programs later in the year.

下一張幻燈片總結了我們 2023 年的管道新聞流。其中一些要點已經涵蓋，因此我不會在這裡再次詳細介紹。顯而易見的是，我們的 27 個臨床階段項目管道預計將在全年通過一系列技術產生多個讀數。我們預計我們的 CAR-T 細胞計劃（針對 Claudin-6）、我們的抗 CTLA-4 計劃和我們在 ASCO 的新 HER2 抗體藥物偶聯物的數據更新，以及今年晚些時候其他計劃的多個進一步更新。

Before concluding and opening up the floor for questions, I would like to reiterate that we will hold our AGM on May 25 and our next innovation series event on November 7. We'll provide further details in the coming weeks on both events.

在結束和開始提問之前，我想重申，我們將在 5 月 25 日舉行我們的年度股東大會，在 11 月 7 日舉行我們的下一次創新系列活動。我們將在未來幾週內提供有關這兩個活動的更多詳細信息。

With that, I'd like to thank our shareholders for their continued support, and I'll conclude our remarks and open up the floor for questions.

至此，我要感謝我們的股東一直以來的支持，我將結束我們的發言並開始提問。

(Operator Instructions) And your first question comes from the line of Tazeen Ahmad from Bank of America.

（操作員說明）您的第一個問題來自美國銀行的 Tazeen Ahmad。

I have one on pipeline as it relates to the partnership with Pfizer. On the iNeST program for first-line melanoma, can you give us a sense of when exactly this year that data could be presented, if it's still this year? And what level of data we should expect at the top line? And then I have a follow-up.

我有一個正在籌備中，因為它與輝瑞公司的合作有關。關於一線黑色素瘤的 iNeST 計劃，您能否告訴我們今年具體什麼時候可以提供數據，如果還是今年的話？我們應該期望在頂線獲得什麼級別的數據？然後我有一個後續行動。

Yes, sure. Thank you, Tazeen. I'll start and maybe, Ugur, you want to add. So we've retained our guidance for an update in the first-line melanoma setting for this year. And we've also -- we've stated previously, and it's still the case, that our expectation is that the update would speak to both ORR and also PFS.

是的，當然。謝謝你，塔贊。我會開始，也許，Ugur，你想補充一下。因此，我們保留了對今年一線黑色素瘤設置更新的指導。我們也——我們之前已經說過，現在仍然如此，我們的期望是更新將同時涉及 ORR 和 PFS。

Ugur, anything you'd like to add?

Ugur，你有什麼要補充的嗎？

No, that's it.

不，就是這樣。

Okay. And then as it relates to HER2 with your ADC program, so this is [competitive space] there's multiple candidates that are in development. Can you just talk to us about how you think your program could be differentiated and how you're thinking about the general competitive landscape and what indications could we got served?

好的。然後因為它與 HER2 和你的 ADC 程序有關，所以這是[競爭空間]，有多個候選人正在開發中。您能否與我們談談您認為您的項目如何與眾不同，您如何看待總體競爭格局以及我們可以得到哪些指示？

Yes, maybe I can take this question. So the generation of ADCs, particularly if HER2 provided a massive improvement on existing ADC compounds. We believe that there is still room for improvement, and we also believe that there is room for multiple lines of development, including, for example, HER2 gynecological tumors like ovarian cancer, endometrial cancer, HER2-positive non-small cell lung cancer, but even in the breast cancer space, with a compound that comes with a differentiated safety profile. That could add additional safety features and tolerability features.

是的，也許我可以回答這個問題。因此，ADC 的產生，特別是如果 HER2 對現有 ADC 化合物提供了巨大的改進。我們認為還有改進的空間，我們也相信有多線發展的空間，包括像卵巢癌、子宮內膜癌、HER2陽性非小細胞肺癌等HER2婦科腫瘤，但即使在乳腺癌領域，化合物也具有差異化的安全性。這可能會增加額外的安全特性和耐受性特性。

I would like to mention that we will have a poster at ASCO, which would provide data generated in a larger breast cancer cohort. And that -- and this data could be informative about how this product could be positioned.

我想提一下，我們將在 ASCO 上發布一張海報，其中將提供在更大的乳腺癌隊列中生成的數據。而且 - 這些數據可以提供有關如何定位該產品的信息。

And the next question comes from the line of Daina Graybosch, SVB Securities.

下一個問題來自 SVB 證券公司的 Daina Graybosch。

I have -- I'll take 2 questions, too. The first one, I wonder if you could talk about the payload in the immunity -- sorry, in the DualityBio programs, and whether you think that this payload will be as synergistic with IO as some of the other payloads that we've seen late-stage clinical trials and how -- whether its synergy is great or less great, how that will impact your development in combination with your other programs? And then I have a follow-up.

我也有——我會回答 2 個問題。第一個，我想知道你是否可以談談免疫力中的有效載荷——抱歉，在 DualityBio 程序中，以及你是否認為這個有效載荷會像我們最近看到的其他一些有效載荷一樣與 IO 協同作用- 階段臨床試驗以及如何 - 它的協同作用是好是壞，這將如何影響你與其他項目的發展？然後我有一個後續行動。

Yes, Daina, thank you for the excellent question. Actually, you bring up a key point by we are interested in these ADCs. So the payload is based on topoisomerase inhibitor and linker technology is differentiated, providing a more stable linker with even more reduced release of the spontaneous release of the toxin. And yes, the key aspects of bringing in this new compound class is that we believe that these new compounds would be highly synergistic with our IO pipeline, including the next-generation immune modulators and bispecific antibodies as well as our personalized vaccines and fixed back applications.

是的，戴娜，謝謝你提出的很好的問題。實際上，您通過我們對這些 ADC 感興趣提出了一個關鍵點。因此，有效負載基於拓撲異構酶抑製劑和連接器技術進行區分，提供更穩定的連接器，進一步減少毒素的自發釋放。是的，引入這種新化合物類別的關鍵方面是我們相信這些新化合物將與我們的 IO 管線高度協同，包括下一代免疫調節劑和雙特異性抗體以及我們的個性化疫苗和固定後備應用.

Great. And then my second question is on the flu vaccine. And I wonder how much degree of freedom there was and is in designing an mRNA-based flu vaccine? And essentially, I'm trying to get at, how similar or different should we expect Pfizer BioNTech vaccine from the Moderna vaccine in its outcome?

偉大的。然後我的第二個問題是關於流感疫苗。我想知道在設計基於 mRNA 的流感疫苗時有多少自由度？從本質上講，我試圖弄清楚，我們應該期望輝瑞 BioNTech 疫苗與 Moderna 疫苗的結果有何相似或不同？

So there is always flexibility. If you use this mRNA technology, there's a lot of flexibility in having a vaccine with a differentiated profile. As you know, there are challenges in the field of influenza vaccines, particularly if you address the question of influenza A versus B immune responses. Therefore, I believe that the design of these vaccines could provide additional features that can overcome limitations in the field.

所以總是有靈活性。如果你使用這種 mRNA 技術，就可以非常靈活地開發出具有差異化特徵的疫苗。如您所知，流感疫苗領域存在挑戰，尤其是當您解決甲型流感與乙型流感免疫反應的問題時。因此，我相信這些疫苗的設計可以提供額外的功能來克服該領域的局限性。

And your next question comes from the line of Akash Tewari from Jefferies.

你的下一個問題來自 Jefferies 的 Akash Tewari。

This is Ivy on for Akash. We have 2 actually. First is for COVID. So for your EU government orders, I guess, how many doses have been delivered so far? Because the tracker we follow use to suggest there's around 900 million that has been delivered, but now it's only showing around 700 million BioNTech Pfizer doses delivered, with around like 200 million unknown categories. So I guess, any clarification you can give me will be super helpful. Then I have a follow-up question on your IMS program.

這是阿卡什的常春藤。我們實際上有 2 個。首先是針對 COVID。那麼對於你們的歐盟政府訂單，我猜，到目前為止已經交付了多少劑？因為我們跟踪的跟踪器表明已經交付了大約 9 億劑，但現在它只顯示交付了大約 7 億劑 BioNTech Pfizer 劑量，大約有 2 億劑未知類別。所以我想，你能給我的任何澄清都會非常有幫助。然後我有一個關於你的 IMS 程序的後續問題。

Yes. Yes, thanks for the question. I mean, as you know, we are currently in discussions with the EU regarding the renegotiation of the contract. And given that we're in the middle of these discussions, we don't want to give any details on this. We don't want to put any burden on those discussions. So please bear with us. We expect that we have some more clarity on the discussions in the course of Q2. That's our expectation, and then we're happy to share the results on those negotiations with you, of course.

是的。是的，謝謝你的提問。我的意思是，正如你所知，我們目前正在與歐盟就合同的重新談判進行討論。鑑於我們正在進行這些討論，我們不想提供任何細節。我們不想給這些討論增加任何負擔。所以請耐心等待。我們希望我們對第二季度的討論有更多的了解。這是我們的期望，當然，我們很樂意與您分享這些談判的結果。

Got it. So my second question is for BNT122. So for the melanoma data readout this year, I guess you just reiterate that this will be limited to PFS and ORR. Is there any specific reason on why there won't be any OS data? Does that imply a potential longer duration of result?

知道了。所以我的第二個問題是關於 BNT122。所以對於今年的黑色素瘤數據讀出，我猜你只是重申這將僅限於 PFS 和 ORR。為什麼沒有任何操作系統數據有什麼具體原因嗎？這是否意味著結果的持續時間可能會更長？

I can take this question. The maturation of the data is -- will most likely not allow to generate OS data.

我可以回答這個問題。數據的成熟度很可能不允許生成操作系統數據。

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

你的下一個問題來自高盛的 Chris Shibutani。

Some clarifying questions in terms of how we should think about your results and financials through the year, if I could. The reiteration of the EUR 5 billion of guidance, can you tell us what does that take into account embedded in your base case assumption here, particularly as I recognize that you have the EC contract negotiations are going through? You did mention the second quarter is going to delight us, but then the deliveries, again, in the assumption for the EUR 5 billion through the balance of the year.

如果可以的話，一些關於我們應該如何考慮您全年的業績和財務狀況的澄清問題。重申 50 億歐元的指導意見，你能告訴我們你的基本案例假設中考慮了什麼，特別是當我認識到你正在進行 EC 合同談判時？您確實提到第二季度會讓我們感到高興，但是在今年餘下的時間裡，交付量再次假設為 50 億歐元。

Similarly to the financials on the R&D-related expense, you have the outlining of the full year level in the first quarter. It was quite a bit less than we had been expecting, and I believe consensus as well. Help us with the sort of the cadence and the shape of spending through the year. And then I have one other follow-up.

與研發相關費用的財務數據類似，您可以概述第一季度的全年水平。這比我們預期的要少很多，我相信共識也是如此。幫助我們了解全年支出的節奏和形式。然後我有另一個後續行動。

Yes, Chris, happy to take that question, and Ryan will chime in. Maybe starting with the top line guidance. We reiterated the guidance, as I stated in my speech, before we had a good start in Q1. We believe, Q2, and that's not a surprise to you, will be weaker. I mean it's not really the season for vaccinations as we see it for flu. We assume that the development in terms of how people will get vaccinated is comparable to some extent to what we see in flu. So specifically looking at the Northern Hemisphere, so our expectations for Q3 and Q4 is that these will be the 2 quarters of relevance for us for the full year.

是的，Chris，很高興回答這個問題，Ryan 會插話。也許從頂線指導開始。正如我在演講中所說，在第一季度取得良好開端之前，我們重申了指導方針。我們相信，第二季度，這對你來說並不奇怪，會更弱。我的意思是，現在並不是真正的流感疫苗接種季節。我們假設人們接種疫苗的方式在某種程度上與我們在流感中看到的情況相當。因此，特別關注北半球，我們對第三季度和第四季度的預期是，這將是我們全年的兩個相關季度。

We have, of course, seen already before we went out with the guidance that the discussions with the EU will be discussions, where we might have to face, and we stated that when we went out with the guidance that we might have to face some reduction in the total volume for '23 versus what has been negotiated before, that we might have some other implications in some other countries potentially as well, and we try to reflect this accordingly.

當然，在我們走出去之前，我們已經看到與歐盟的討論將是討論，我們可能不得不面對的地方，我們表示，當我們走出去時，我們可能不得不面對一些指導與之前談判的相比，'23 的總量減少，我們可能也會對其他一些國家產生一些其他影響，我們試圖相應地反映這一點。

I would like to reiterate that if you compare the Pfizer guidance of $13.5 billion, if you take that, I think they're also reflected those discussions and negotiations ongoing. And if you translate that, taking into account the currency implication, taking into account that Pfizer reflects their December revenue figure of 2022 in their Q1 figure, and December 2022 has been a very strong month, we -- whereas we have to reflect this month in our full year figures for 2022, so we have from January to December, our revenue figures were at Pfizer for the international part is just looking at November to November.

我想重申，如果你比較輝瑞 135 億美元的指導，如果你接受的話，我認為它們也反映了正在進行的討論和談判。如果你將其轉換，考慮到貨幣影響，考慮到輝瑞在其第一季度數據中反映了他們 2022 年 12 月的收入數字，而 2022 年 12 月是一個非常強勁的月份，我們 - 而我們必須反映這個月在我們 2022 年的全年數據中，從 1 月到 12 月，我們的收入數據是在輝瑞公司，國際部分只看 11 月到 11 月。

So these things caused some differences, quite significant differences in our estimation, if you compare the December 2022 versus our expectation for December 2023. So there is a big impact coming from this. And if you then take this into account, we feel that the EUR 5 billion that we have reiterated today is something that we can live with. It could be that -- and that has been our assumption that there might be a new variant that we will adapt the existing vaccine that we produce. That's our assumption to reach the EUR 5 billion. And we're -- our assumption in that respect remains valid at this point in time. I hope that helps you.

因此，如果將 2022 年 12 月與我們對 2023 年 12 月的預期進行比較，這些事情會導致一些差異，我們的估計存在相當大的差異。因此，這會產生很大的影響。如果你再考慮到這一點，我們認為我們今天重申的 50 億歐元是我們可以接受的。可能是——這一直是我們的假設，即可能會有一種新的變體，我們將採用我們生產的現有疫苗。這是我們達到 50 億歐元的假設。而且我們 - 我們在這方面的假設在這個時間點仍然有效。我希望這對你有幫助。

And maybe -- I would just add, and maybe you can come back as well to the R&D point.

也許 - 我只想補充一點，也許你也可以回到研發點。

Yes, I'll come back to the R&D part.

是的，我會回到研發部分。

Just to add two points to that. So first is actually the volumes, while we're not disclosing volumes in the first quarter, we were shipping to quite a broad range of countries in the first quarter, over 70 countries we mentioned. There's still some carryover there to pandemic contracts. And so as I mentioned in the prepared remarks, we did see some significant volumes in particular to low and middle income countries in the first quarter.

只是為了補充兩點。所以首先實際上是數量，雖然我們沒有披露第一季度的數量，但我們在第一季度向相當廣泛的國家發貨，我們提到了 70 多個國家。流行病合同仍有一些結轉。因此，正如我在準備好的發言中提到的那樣，我們確實在第一季度看到了一些重要的交易量，特別是對低收入和中等收入國家的交易量。

Yes. And then maybe to add on the R&D costs, Chris, so the first quarter has been relatively light if you see (inaudible) that we have booked for Q1, if you put that into relation of the EUR 2.4 billion to EUR 2.6 billion of our guidance. But this is, to a great extent, some sort of phasing implication to a great extent, also coming from our various programs that we have together with our collaboration partner, Pfizer.

是的。然後可能會增加研發成本，克里斯，所以第一季度相對較少，如果你看到（聽不清）我們已經為第一季度預訂，如果你把它與我們的 24 億歐元到 26 億歐元相關聯指導。但這在很大程度上是某種分階段的影響，也來自我們與合作夥伴輝瑞公司一起開展的各種項目。

So I wouldn't read too much into this. I would -- we reiterated that guidance. Please also take into account that we have reflected under and already in there and to a great extent duality, spending for our clinical studies here. So we feel comfortable with the EUR 2.4 billion to EUR 2.6 billion in the course of the next quarters.

所以我不會對此讀太多。我會 - 我們重申了該指導。還請考慮到我們已經在很大程度上反映了二元性，我們在這裡進行臨床研究。因此，我們對接下來幾個季度的 24 億至 26 億歐元感到滿意。

And then to follow-on, Pfizer during their meeting in December outlined their vision for what the vaccines for COVID could look like usage, particularly in the U.S. out for the next 3 or 4 years. There was a factor in there in terms of potential for combination with flu. Can you talk to what the BioNTech house view is? Were you involved with these projections? If there's any fundamental differences in your point of view, where might they lie?

接下來，輝瑞公司在 12 月的會議上概述了他們對 COVID 疫苗使用情況的願景，特別是未來 3 或 4 年在美國的使用情況。就與流感結合的可能性而言，其中有一個因素。你能談談 BioNTech 的觀點是什麼嗎？你參與了這些預測嗎？如果您的觀點存在任何根本差異，它們可能存在於何處？

Yes, thanks for the question. So yes, we're very involved with Pfizer on an operational level and also on the commercial planning level globally as a co-commercialization partner. I think it's fair to say that Pfizer has taken the driver's seat in the U.S. commercial sphere. We've been very involved in Europe and also in other geographies.

是的，謝謝你的提問。所以是的，我們在運營層面和全球商業規劃層面都與輝瑞密切合作，作為共同商業化合作夥伴。我認為可以公平地說，輝瑞公司已經在美國商業領域佔據了主導地位。我們一直積極參與歐洲和其他地區的活動。

I think how we look at it, this is that it's a little too early to be precise and prescribe a factor to the contribution from combinations at this point. I think we need to see more data. I think what we outlined today is that we do see combinations, respiratory combination specifically as a potential, one of multiple potential growth drivers over the mid- to longer term for the franchise. So that is something that we're looking very closely at with our partner, multiple angles there. And I think Pfizer brings a lot to the table there, but so do we in terms of thinking about how combinations could be best deployed to meet patient need.

我認為我們如何看待它，現在要準確地為組合的貢獻規定一個因素還為時過早。我認為我們需要查看更多數據。我認為我們今天概述的是，我們確實看到組合，特別是呼吸組合作為一種潛力，是特許經營中長期的多種潛在增長動力之一。所以這是我們正在與我們的合作夥伴密切關注的事情，那裡有多個角度。我認為輝瑞（Pfizer）在那裡帶來了很多東西，但我們在思考如何最好地部署組合以滿足患者需求方面也是如此。

Great. Thanks. We'll look for the data as it progresses.

偉大的。謝謝。隨著數據的進展，我們將尋找數據。

And your next question comes from the line of Yaron Werber from Cowen. As there is no response, I will go to the next question, and your next question comes from the line of Terence Flynn, Morgan Stanley.

你的下一個問題來自 Cowen 的 Yaron Werber。由於沒有回應，我將轉到下一個問題，你的下一個問題來自摩根士丹利的特倫斯弗林。

Just had a follow-up on the iNeST vaccine program. I was wondering if you can just discuss high level about how you're thinking about likelihood of success in the adjuvant versus the metastatic setting. I think Merck and Moderna have focused more on the adjuvant setting, but obviously, you're taking a more broader approach. So just wondering if you could elaborate there.

剛剛對 iNeST 疫苗計劃進行了跟進。我想知道你是否可以高層次地討論你如何考慮在輔助治療和轉移治療中成功的可能性。我認為 Merck 和 Moderna 更關注輔助設置，但顯然，你們正在採取更廣泛的方法。所以只是想知道你是否可以在那裡詳細說明。

Yes, I can take this question. And the question is a very important one. With regard for the development, we have an early adjuvant study in melanoma, and we have initiated 2 additional adjuvant stage trials, one in triple-negative breast cancer, for which we do not yet have reports; and the second one in pancreatic cancer, which we have reported at ASCO last year and where we are expecting a publication in the next few weeks.

是的，我可以回答這個問題。這個問題非常重要。關於發展，我們有黑色素瘤的早期輔助研究，我們已經啟動了另外兩個輔助階段試驗，一個是三陰性乳腺癌，我們還沒有報告；第二個是關於胰腺癌的，我們去年在 ASCO 上報告過，我們期待在接下來的幾週內發表。

And in the adjuvant setting, the clear understanding is that we have, as compared to the metastatic setting, a higher immunogenicity rate even though using the same vaccine platform. And in the melanoma and now previously reported contract at cancer study, we have shown that immune responses are correlated, this prevention of relapses or with a reduced relapse rate in this patient population.

在佐劑環境中，清楚的理解是，與轉移環境相比，即使使用相同的疫苗平台，我們也有更高的免疫原性。在黑色素瘤和現在之前報導的癌症研究合同中，我們已經證明免疫反應是相關的，這種預防復發或降低該患者群體的複發率。

We have also reported the metastatic study, Phase I study, which yielded also immunogenicity, but to a much weaker extent than the actual setting. And based on this, we can clearly say that at least in the setting, how the vaccines are used so far, we see an improved activity in the adjuvant-stage. There are other reasons why adjuvant-stage cancers could be more eligible. This is, first of all, the lack of heavily established tumor micro environment, the lower tumor load and most importantly in the adjuvant setting, there is a window of opportunity, so the tumors do not progress in the first 6 to -- or in the first 3 months, giving the opportunity to build an immune response, which can then deal with the tumor.

我們還報告了轉移研究，I 期研究，該研究也產生了免疫原性，但程度比實際環境弱得多。基於此，我們可以清楚地說，至少在目前疫苗的使用情況下，我們看到佐劑階段的活動有所改善。輔助階段的癌症可能更符合條件還有其他原因。這是，首先，缺乏高度成熟的腫瘤微環境，較低的腫瘤負荷，最重要的是在輔助環境中，有一個機會窗口，所以腫瘤在前 6 到 - 或前 3 個月，有機會建立免疫反應，然後可以對付腫瘤。

So in the totality, we believe that the adjuvant stage is the type of diseases to go. We have, as you know, randomized clinical trial in colorectal cancers running since 2019. We expect here readout data from this randomized colorectal cancer trial in 2024, yes. And we are planning a Phase II study based -- randomized Phase II study in pancreatic cancer based on the data that we have observed.

所以總的來說，我們認為輔助階段是要治療的疾病類型。如您所知，自 2019 年以來，我們開展了結直腸癌隨機臨床試驗。我們希望在 2024 年從該隨機結直腸癌試驗中讀出數據，是的。我們正在計劃一項基於 II 期研究的隨機化 II 期胰腺癌研究，該研究基於我們觀察到的數據。

And your next question comes from the line of Yaron Werber, Cowen.

你的下一個問題來自 Cowen 的 Yaron Werber。

I got a quick question on Pfizer and your flu vaccine, 161. The 25,000 patients -- I'm sorry, U.S. healthy adult study is ongoing. Any sense as to when you think we might be able to see data this year? Is it -- are you thinking sort of in the fall? And is that sufficient to follow? Do you need to run an additional study potentially in the rest of the world or even in the Southern Hemisphere?

我有一個關于輝瑞和你們的流感疫苗 161 的快速問題。25,000 名患者——對不起，美國健康成人研究正在進行中。關於您認為我們今年什麼時候可以看到數據，有什麼感覺嗎？是——你在考慮秋天嗎？這足以遵循嗎？您是否需要在世界其他地區甚至南半球進行額外的研究？

And then secondly, my understanding that's the quadrant modified RNA vaccine. Any update on the self-amplifying mRNA vaccine for flu as well?

其次，我的理解是像限修飾的 RNA 疫苗。流感的自擴增 mRNA 疫苗也有更新嗎？

Yes, Yaron, I'll start and, Ugur, you may want to add to this. But I think it's -- just to start off, it's important to reiterate that we licensed that program in 2018 to Pfizer. So they're really in the driver's seat in terms of development. We do have rights to royalties and milestones upon success. And so of course, we're tracking that with them and working with them on the broader program. But I think Pfizer has guided to an update this year. I don't think they've specified in that we don't want to contradict what they put out. So I'll leave it at that. And the same goes, Yaron, for the self-amplifying program, both are -- fall under our collaboration agreement with Pfizer.

是的，Yaron，我會開始，Ugur，你可能想補充一下。但我認為——只是開始，重要的是要重申我們在 2018 年將該項目授權給了輝瑞。因此，就開發而言，他們確實處於主導地位。我們確實有權獲得成功後的版稅和里程碑。因此，當然，我們正在與他們一起跟踪並與他們合作開展更廣泛的計劃。但我認為輝瑞今年已經指導了更新。我認為他們沒有具體說明我們不想與他們提出的內容相矛盾。所以我會保留它。同樣，Yaron，對於自我增強計劃，兩者都屬於我們與輝瑞公司的合作協議。

So Ryan, maybe just a follow-up, when for the flu-COVID combo, can you give us any sense at all as to whether your royalty is going to be sort of a blended between your low teens, let's say, for flu and you're 50-50 for COVID?

所以瑞安，也許只是一個後續行動，當流感 - COVID 組合時，你能給我們任何關於你的版稅是否會在你的青少年之間混合的任何感覺，比方說，流感和你是 50-50 的 COVID？

Yes, it's a great question. And I think blended is the right way to think about it. We haven't disclosed with Pfizer the specific economics, but I think it's fair to assume that would be a blend. As you know, we have a 50% gross profit share on the COVID-19 vaccine, and we do have a royalty on flu. And so there are still ongoing discussions about that. But I think we'll leave that for now until we can present some data and discuss next steps for the programs.

是的，這是一個很好的問題。我認為混合是正確的思考方式。我們還沒有向輝瑞披露具體的經濟效益，但我認為可以公平地假設這將是一種混合。如您所知，我們在 COVID-19 疫苗上有 50% 的毛利份額，而且我們確實有流感特許權使用費。因此，關於這一點的討論仍在進行中。但我認為我們暫時保留這一點，直到我們可以提供一些數據並討論計劃的後續步驟。

And your next question comes from the line of Jessica Fye from JPMorgan.

你的下一個問題來自摩根大通的 Jessica Fye。

This is [Nasan] on for Jessica Fye. I think I want to ask about the FixVac program and the progress there and when we might get to see initial data on that program. And then whether like in light of the comment on metastatic versus adjuvant setting, how you're thinking about the development for FixVac?

這是 Jessica Fye 的 [Nasan]。我想我想問一下 FixVac 計劃及其進展情況，以及我們何時可以看到該計劃的初始數據。然後是否像關於轉移與輔助設置的評論一樣，您如何考慮 FixVac 的開發？

Maybe I'll take the second question on, Ryan, if you could take the first question would be great. Yes. So for 6 Vac, we have some generated data in the metastatic setting in patients with melanoma, particularly with a high proportion of patients, who did (inaudible) under existing PD-1 therapy and have seen in objective responses and high rate of [immunogens] of captive responses in combination with anti-PD1 in the range of 35% to 40% with vaccine alone in the range of 20%.

也許我會回答第二個問題，Ryan，如果你能回答第一個問題就太好了。是的。因此，對於 6 Vac，我們在黑色素瘤患者的轉移環境中獲得了一些生成的數據，特別是在現有 PD-1 治療下（聽不清）的患者比例很高，並且已經看到客觀反應和高[免疫原率] 與抗 PD1 組合的圈養反應在 35% 至 40% 的範圍內，而單獨使用疫苗的範圍為 20%。

The key advantage of FixVac as compared to the customer life the antigen vaccine is the availability of the vaccine directly after patient inclusion. So that means we do not have this 4 to 6 weeks of waiting time until patients can be dosed. Therefore, in principle, FixVac could be an option for patients with advanced metastatic disease.

與客戶生命抗原疫苗相比，FixVac 的主要優勢是在患者加入後可直接獲得疫苗。所以這意味著我們沒有這 4 到 6 週的等待時間，直到患者可以給藥。因此，原則上，FixVac 可以成為晚期轉移性疾病患者的一種選擇。

But again, here, it's a question of the combination compound. And this is something that is now in the focus of our upcoming studies evaluating the use of this vaccines in combination with our checkpoint immune model later, for example, the bispecific BNT312 and BNT311 molecules, but as well as our rybocytokine molecules, the modified IL-2, IL-7 have an approach.

但這裡又是一個組合化合物的問題。這是我們即將進行的研究的重點，該研究評估了這種疫苗與我們後來的檢查點免疫模型的結合使用，例如，雙特異性 BNT312 和 BNT311 分子，以及我們的核細胞因子分子，修飾的 IL -2，IL-7有辦法。

Yes. And in terms of the time lines, we haven't guided any fixed date updates this year. So I would say that 2024 is the most likely. And as you know, we have multiple trials ongoing, multiple trials, so recruiting in NSCLC in refractory melanoma, head and neck squamous cell carcinoma may name a few, so likely 2024.

是的。在時間線方面，我們今年沒有指導任何固定日期更新。所以我會說 2024 年是最有可能的。如您所知，我們正在進行多項試驗，多項試驗，因此在 NSCLC 中招募難治性黑色素瘤、頭頸部鱗狀細胞癌可能僅舉幾例，很可能在 2024 年進行。

And your next question comes from the line of Bill Maughan from Canaccord.

你的下一個問題來自 Canaccord 的 Bill Maughan。

So I have 2 on the broader strategy. So first of all, some of the more recent BD, the partnerships our focus to look more on late-stage clinical programs and less on massive paradigm shifting earlier stage programs. So is there an internal push to reach profitability on some certain time line on the non-COVID portfolio?

所以我有 2 個更廣泛的戰略。因此，首先，一些最近的 BD，我們的合作夥伴關係更多地關注後期臨床項目，而不是大規模範式轉變的早期項目。那麼，是否有內部推動力在非 COVID 投資組合的某個特定時間線上實現盈利？

And then second related question is, are there any other technology platforms that you want to get into that you don't have that technology yet?

然後第二個相關問題是，是否有任何其他技術平台您想進入但您還沒有該技術？

Yes, thank you. So maybe I'll take the first one and then, Ugur, if you want to speak to the technology platforms piece. In terms of the rationale for the recent deals, I think what we have been is clear about our intention to go commercial in the oncology portfolio by 2026 onwards. And so we have multiple internal programs that if successful in late-stage trials could give us opportunities around that time period to bring products to market.

是的，謝謝。因此，如果您想談談技術平台部分，也許我會接受第一個，然後，Ugur。就最近交易的理由而言，我認為我們很清楚我們打算在 2026 年之前將腫瘤產品組合商業化。因此，我們有多個內部計劃，如果在後期試驗中取得成功，我們將有機會在那個時期將產品推向市場。

And so what you've seen us do with these BD deals is basically add depth, further depth to that sort of wave 1 of oncology programs that have potential to be successful to get to market around that same time frame. In addition, we've gone for programs that can serve as backbones. So we've really tried to maximize synergy rather than solving for profitability near term, mid- to long-term synergy with our own pipeline. And so you see that with the anti-CTLA-4 molecule. You see that also with the HER2 ADC with ADC modalities in general. Again, programs and technologies that we think could combine very well with our existing pipeline.

因此，您看到我們對這些 BD 交易所做的基本上是增加深度，進一步深入那種有可能在同一時間框架內成功進入市場的腫瘤學項目的第一波。此外，我們已經開始尋找可以作為骨幹的程序。因此，我們真的試圖最大限度地發揮協同作用，而不是通過我們自己的管道解決近期、中長期的盈利能力問題。所以你會看到抗 CTLA-4 分子。你也看到了 HER2 ADC 和一般的 ADC 模式。同樣，我們認為可以與我們現有的管道很好地結合的程序和技術。

Yes. Thank you, Ryan. With regard to technologies, no, we are not looking to any disruptive technology. We have a number on disruptive technologies in-house. But what we are clearly doing is we are evaluating technology modules and that could close gaps in our technology platforms or further augment the activity of our technology platforms.

是的。謝謝你，瑞安。關於技術，不，我們不尋求任何顛覆性技術。我們內部有很多顛覆性技術。但我們顯然正在做的是我們正在評估技術模塊，這可以縮小我們技術平台的差距或進一步增強我們技術平台的活動。

And your next question comes from the line of Zhiqiang Shu from Berenberg.

你的下一個問題來自貝倫貝格的舒志強。

I have 2. First, I wanted to ask about the FixVac BNT116. I think you mentioned you're going to start a Phase II program in first-line lung cancer. I wonder if you can comment on any signals from Phase I that gives you the confidence to start a Phase II?

我有 2 個。首先，我想問一下 FixVac BNT116。我想你提到過你將開始一線肺癌的 II 期項目。我想知道您是否可以評論第一階段的任何信號，讓您有信心開始第二階段？

Short answer, no, we do not have any updates so far from the running clinical type that is expected end of the season.

簡短的回答，不，到目前為止，我們還沒有從預計本賽季結束的跑步臨床類型中獲得任何更新。

Got it. And then a quick follow-up on the -- your ADC deal. Can you talk about the, I guess, the comparison in top 1 pier at the payload versus microtubule inhibitors payload in terms of the combination with IO differences and similarities there?

知道了。然後快速跟進您的 ADC 交易。我想，你能談談有效載荷與微管抑製劑有效載荷的前 1 碼頭在 IO 異同組合方面的比較嗎？

Yes. One, I think the most important aspect is for getting ADC technologies is that we believe that in the next 6, 7, 8 years, this ADC technologies will more or less complete the -- completely replace chemotherapy. So that means any type of combination therapy, which requires chemotherapy backbone might end up in an ADC approach.

是的。第一，我認為最重要的方面是獲得 ADC 技術，我們相信在未來 6、7、8 年內，這種 ADC 技術將或多或少地完成——完全取代化療。所以這意味著任何類型的聯合療法，需要化療骨幹，最終可能會採用 ADC 方法。

With regard to the currently evaluated compounds and TOP2 inhibitors come with a profile allowing sustainable and also long-term application. And we have also seen now in several studies that they are ideally suited as backbone for combinations with IO compounds. We do not exclude that we could be -- we might be also interested in microtubule inhibitors, but several of the microtubular inhibitors have been in the past, at least in the chemotherapeutic setting associated with (inaudible), and we believe that this new compound class should give the opportunity to develop treatments, which do not come with dose-limiting toxicity with regard to repeated application.

關於目前評估的化合物和 TOP2 抑製劑具有允許可持續和長期應用的特性。我們現在還在幾項研究中看到，它們非常適合作為與 IO 化合物組合的主鏈。我們不排除我們可能 - 我們可能也對微管抑製劑感興趣，但過去有幾種微管抑製劑，至少在與（聽不清）相關的化療環境中，我們相信這種新化合物課程應該提供開發治療方法的機會，這些治療方法在重複應用方面不會產生劑量限制性毒性。

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。您現在可以斷開連接。