Biontech SE (BNTX) 2024 Q2 法說會逐字稿

Thank you for joining BioNTech second quarter 2024 earnings call. As a reminder, the slides we will be using during this call and the corresponding press release we issued this morning can be found in the Investor Relations section of our website.

感謝您參加 BioNTech 2024 年第二季財報電話會議。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 US Securities and Exchange Commission. Forward-looking statements in this call are subject to significant risks and uncertainties and speak only as of the date of the conference call. We undertake no obligation to update or revise any of these statements.

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，並且僅代表截至電話會議當日的情況。我們不承擔更新或修改任何這些聲明的義務。

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

在投影片 3 上，您可以找到今天電話會議的議程。今天，BioNTech 管理團隊的以下成員也加入了我的行列：執行長兼聯合創始人 Ugur Sahin； 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. I will start with an overview of the quarter's highlights with a focus on COMIRNATY and our late-stage oncology portfolio. Ozlem will talk about some of our recent oncology pipeline advancement in more detail. Jens and Ryan will then provide updates on our financial and corporate progress and the outlook for the remainder of the year.

謝謝你，維多利亞。熱烈歡迎今天加入我們的所有人。我將首先概述本季度的亮點，重點關注 COMIRNATY 和我們的後期腫瘤學產品組合。 Ozlem 將更詳細地討論我們最近的一些腫瘤學研發管線進展。然後 Jens 和 Ryan 將提供有關我們財務和企業進展以及今年剩餘時間前景的最新資訊。

Slide 5. The second quarter of 2024 was marked by a significant execution across our oncology pipeline and our leading COVID-19 franchise. Our progress in the quarter was set up for an impactful end of 2024, as we continue to progress towards our long-term vision. I would like to highlight achievements in three areas.

幻燈片 5。2024 年第二季度，我們的腫瘤產品線和領先的 COVID-19 特許經營業務取得了重大進展。我們在本季度取得的進展是為了在 2024 年底取得具有影響力的成果，因為我們將繼續朝著我們的長期願景邁進。我想強調三個領域的成就。

First, with regard to our COVID-19 vaccine leadership. On the back of the first regional approvals, we have initiated the launch of our new variant-adapted vaccine and expect additional approvals in the coming weeks and months. Second, in oncology, we shared numerous updates at major medical meetings that highlighted our clinical execution and pipeline progress and provided data on several of our assets across modalities. Ozlem will discuss some of these updates in more detail. But I would like to highlight two of those specifically.

首先，關於我們在 COVID-19 疫苗方面的領導地位。在獲得首批地區批准後，我們已開始推出新的變異疫苗，並預計在未來幾週和幾個月內獲得更多批准。其次，在腫瘤學方面，我們在主要醫學會議上分享了許多最新信息，強調了我們的臨床執行和管道進展，並提供了我們跨模式的幾種資產的數據。 Ozlem 將更詳細地討論其中一些更新。但我想特別強調其中兩個。

Last week, we announced that our off-the-shelf FixVac mRNA cancer vaccine for melanoma, BNT111 met the primary endpoint in the ongoing randomized Phase 2 trial, evaluating BNT111 in combination with cemiplimab in patients with Stage III and Stage IV cutaneous melanoma.

上週，我們宣布現成的黑色素瘤 FixVac mRNA 癌症疫苗 BNT111 在正在進行的隨機 2 期試驗中達到了主要終點，該試驗評估了 BNT111 與 cemiplimab 聯合治療 III 期和 IV 期皮膚黑色素瘤患者的效果。

This preliminary result is a significant milestone for our company and underscores our belief in the transformative potential of this new class of medicines and of our mRNA vaccine technology which is a key pillar of our oncology strategic.

這一初步結果對我們公司來說是一個重要的里程碑，並強調了我們對此類新型藥物和我們的 mRNA 疫苗技術的變革潛力的信念，這是我們腫瘤學策略的關鍵支柱。

We have exciting news also with regard to another key pillar of our oncology strategy, namely the development of novel IO ADC combination. This quarter we started the first of several preparatory trials for our combination therapy strategy. The trial evaluates the combination of our anti PD-1 VEGF bispecific antibody BNT327 and our top two ADC, BNT325. We look forward to the initiating additional trials evaluating novel IO ADC combinations over the next 12 months. The third area in which we made progress is our mission towards the creation of sustainable and resilient end-to-end vaccine ecosystem in Africa, by expanding our partnership with CEPI.

我們還有關於我們腫瘤學策略的另一個關鍵支柱的令人興奮的消息，即新型 IO ADC 組合的開發。本季度，我們開始了聯合治療策略的多項準備試驗中的第一項。該試驗評估了我們的抗 PD-1 VEGF 雙特異性抗體 BNT327 和我們前兩位的 ADC BNT325 的組合。我們期待在未來 12 個月內啟動更多試驗來評估新型 IO ADC 組合。我們取得進展的第三個領域是，我們的使命是透過擴大與 CEPI 的合作夥伴關係，在非洲創建可持續且有彈性的端到端疫苗生態系統。

CEPI is committed up to USD145 million to support us to establish mRNA vaccine clinical and commercial-scale manufacturing capabilities at our facility in Kigali, Rwanda. These capabilities will contribute to better prepare for potential future epidemic and pandemic threats in Africa in alignment with our corporate purpose of ensuring equitable access to our medicines.

CEPI 承諾提供高達 1.45 億美元的資金支持我們在盧安達基加利的工廠建立 mRNA 疫苗臨床和商業規模的生產能力。這些能力將有助於更好地應對非洲未來潛在的流行病和疫情威脅，這符合我們確保公平獲得藥物的企業目標。

Slide 6, starting with our COVID-19 franchise. The continuous circulation of SARS-CoV-2 leads to the ongoing evolution and emergence of novel variant of the virus, which we continue to monitor and evaluate further immune evasive potential and virulence.

幻燈片 6，從我們的 COVID-19 特許經營權開始。 SARS-CoV-2的持續傳播導致病毒新變種的不斷進化和出現，我們將繼續監測和評估進一步的免疫逃脫潛力和毒性。

In September 2022, the XBB lineage gradually emerged, dominated globally throughout 2023 with multiple sub- lineages and was successfully addressed by XBB.1.5 variant-adapted COVID-19 vaccine, including our own.

2022 年9 月，XBB 譜系逐漸出現，並在2023 年以多個亞譜系在全球佔據主導地位，並透過XBB.1.5 變體適應的COVID-19 疫苗（包括我們自己的疫苗）成功解決了這一問題。

This year, JN.1-lineage, including KP.2 became the predominant variant globally, leading to the current surge in infections in many regions in the Northern hemisphere. Shown on the right graph, real-world effectiveness data demonstrate that the antigenic shift and the distance of JN.1-lineages from XBB.1.5 has impacted the vaccine effectiveness of the XBB.1.5-adapted vaccine against the now prevalent JN.1-lineages.

今年，包括 KP.2 在內的 JN.1 譜系成為全球主要變種，導致目前北半球許多地區的感染激增。如右圖所示，真實世界的有效性數據表明，JN.1 譜系與 XBB.1.5 的抗原轉變和距離影響了 XBB.1.5 適應疫苗針對目前流行的 JN.1 的疫苗有效性。

Slide 7. Based on these and additional data, regulatory and public health authorities consequently advised vaccine manufacturers to revise the formulation for their authorized COVID-19 vaccines. The WHO and the EMA recommended the use of JN.1-lineage antigen in a monovalent COVID-19 vaccine for the season 2024-2025. And 17 days later, we were able to submit our application to the European regulator. Based on this recommendation and consequently EMA approval on July 3, we have begun rolling out our updated COMIRNATY JN.1 vaccine in Europe. In the United States, the FDA further recommended the use of KP.2 as the preferred JN.1-lineage antigen for the 2024-2025 COVID-19 mRNA vaccines on June 13.

幻燈片 7。 WHO 和 EMA 建議在 2024-2025 年季節的單價 COVID-19 疫苗中使用 JN.1 譜系抗原。 17 天后，我們向歐洲監管機構提交了申請。根據這項建議以及 EMA 於 7 月 3 日獲得的批准，我們已開始在歐洲推出更新的 COMIRNATY JN.1 疫苗。在美國，FDA於6月13日進一步建議使用KP.2作為2024-2025年COVID-19 mRNA疫苗的首選JN.1譜系抗原。

Less than two weeks later, we initiated our rolling submission with the US FDA. We and our partner Pfizer are working hard to enable early availability of variant-adaptive vaccines for people around the world with the aim of reducing or preventing severe disease, hospitalization and COVID-19-related death. We expect the FDA approval of our KP.2-adapted vaccine by mid-September and we aim to deliver the first vaccine doses to the people in the United States shortly thereafter.

不到兩週後，我們開始向美國 FDA 滾動提交申請。我們和我們的合作夥伴輝瑞正在努力為世界各地的人們儘早提供變異適應性疫苗，以減少或預防嚴重疾病、住院治療和與 COVID-19 相關的死亡。我們預計 FDA 會在 9 月中旬批准我們的 KP.2 疫苗，我們的目標是不久後向美國人民提供第一劑疫苗。

Slide 8. The other area I'm highly excited about is the progress on our oncology pipeline. Before I hand over to Ozlem to deep dive into the recent achievements, let me remind you of our overarching oncology strategy.

投影片 8。在我交給 Ozlem 深入探討最近的成就之前，讓我提醒您我們的整體腫瘤學策略。

mRNA cancer immunotherapies were our starting point when we founded BioNTech, and they remain the centerpiece. Ever since we have been pursuing a technology-agnostic approach by not limiting ourselves to any one technology. Over the past two-years, we added platforms to complement the mRNA centerpiece.

mRNA 癌症免疫療法是我們創立 BioNTech 時的起點，而且仍然是核心。從那時起，我們就一直追求一種與科技無關的方法，不將自己局限於任何一種技術。在過去的兩年裡，我們加入了平台來補充 mRNA 的核心內容。

Today, we have an oncology toolkit featuring multiple modalities, including targeted therapies such as ADCs and immunomodulators IOs that open up new combination opportunities through synergistic mechanisms of action. Having this diversity of assets in our pipeline enable us to pursue combination approaches that are proprietary and unique.

如今，我們擁有一個具有多種模式的腫瘤學工具包，包括 ADC 和免疫調節劑 IO 等標靶療法，它們透過協同作用機制開闢了新的組合機會。我們的管道中擁有這種多樣化的資產，使我們能夠追求專有且獨特的組合方法。

This strategic advantage allows us to evaluate the activity of each individual compound and to determine those patient population for which monotherapy or synergistic combinations are best suited. We believe that our strategy has the potential to address fundamental challenges of cancer and to drive meaningful improvement in the long-term survival rates for patients. And as you will hear from Ozlem, the last quarter has been about executing towards this vision.

這項策略優勢使我們能夠評估每種化合物的活性，並確定最適合單一療法或協同組合的患者群體。我們相信，我們的策略有潛力解決癌症的根本挑戰，並推動患者長期存活率的顯著提高。正如您將從 Ozlem 聽到的那樣，上個季度一直致力於實現這一願景。

Before I hand over, I would like to thank you all for your ongoing support as we enter this truly-exciting period for BioNTech and our progress towards our founding vision. Thank you.

在我交接之前，我要感謝大家在 BioNTech 進入這個真正令人興奮的時期以及我們在實現我們的創始願景方面取得的進展時給予的持續支持。謝謝。

Thank you, Ugur. Glad to speaking with everyone today. Our multi-platform immunology clinical pipeline is continuing to grow and to progress, and it is a rich source for a rationally planned novel, novel combinations that we consider a key pillar of our strategy.

謝謝你，烏古爾。很高興今天能和大家交談。我們的多平台免疫學臨床管道正在持續成長和進步，它是合理規劃的新穎組合的豐富來源，我們認為這是我們策略的關鍵支柱。

As you can see, two of our modalities, namely mRNA and immunomodulator IOs, are dominantly represented in our pipeline and particularly so in advanced clinical stages. Today, I want to focus on priority assets within these modalities, which have our special attention, our mRNA vaccines and one of our IO compounds BNT327.

正如您所看到的，我們的兩種模式，即 mRNA 和免疫調節劑 IO，在我們的產品線中占主導地位，尤其是在晚期臨床階段。今天，我想專注於這些模式中的優先資產，我們特別關注這些資產，即我們的 mRNA 疫苗和我們的 IO 化合物之一 BNT327。

Before I cover these assets, let me just mention that a rich clinical pipeline and ambitious plans require execution capability, which we are continuously building. As you can see on the slide, we are accelerating the pace of pipeline-wide patient accrual compared to last quarter. Compared to 2022, we and our network of partners are now recruiting 6 times as many patients per quarter to support enrollment into the clinical trials you saw on the previous slide.

在介紹這些資產之前，我想提一下，豐富的臨床管道和雄心勃勃的計劃需要執行能力，而我們正在不斷建立這種能力。正如您在幻燈片中看到的那樣，與上季度相比，我們正在加快整個管道的患者成長速度。與 2022 年相比，我們和我們的合作夥伴網路現在每季招募的患者數量是原來的 6 倍，以支持您在上一張投影片中看到的臨床試驗的註冊。

This increase is a testament of our drive towards more and larger mid to late-stage trials as part of our ambition to achieve multiple product launches in oncology by the year 2030. It also underlines the success of our partnership strategy, which not only gives us access to compounds that complement our own pipeline. But enables us to leverage additional clinical trial execution capacity and know-how and geographic reach.

這一成長證明了我們致力於進行更多、更大規模的中後期試驗，這是我們在2030 年實現腫瘤學領域多種產品推出的雄心壯志的一部分。 ，這不僅使我們能夠獲得補充我們自己的管道的化合物。但使我們能夠利用額外的臨床試驗執行能力、專業知識和地理覆蓋範圍。

Now to a centerpiece of our oncology portfolio, our mRNA cancer vaccine platforms iNeST and FixVac, which differ in the type of tumor antigens they target. iNeST targets neoantigens derived from somatic mutations in cancer cells that are unique to an individual's tumor.

現在我們的腫瘤產品組合的核心是我們的 mRNA 癌症疫苗平台 iNeST 和 FixVac，它們所針對的腫瘤抗原類型有所不同。 iNeST 的目標是源自癌細胞體細胞突變的新抗原，這些突變是個別腫瘤所特有的。

iNeST vaccines are manufactured on-demand and personalized to each individual patient. FixVac vaccines target multiple non-mutated antigens shared by a majority of patients with a given tumor type and are off-the-shelf. The computational approaches to discover and select these two different types of target antigens are one of our core competencies. iNeST and FixVac, both use the same technology, namely our proprietary mRNA LPX platform.

iNeST 疫苗是按需生產的，並針對每位患者進行個人化。 FixVac 疫苗針對大多數特定腫瘤類型患者共有的多種非突變抗原，並且是現成的。發現和選擇這兩種不同類型的目標抗原的計算方法是我們的核心能力之一。 iNeST 和 FixVac 都使用相同的技術，也就是我們專有的 mRNA LPX 平台。

Today, we have ongoing trials in multiple disease settings and indications across both vaccine platforms. We have reported translational and clinical data over the last couple of years and future data updates from multiple trials shown on the slide are planned.

今天，我們正在對兩種疫苗平台的多種疾病環境和適應症進行試驗。我們報告了過去幾年的轉化和臨床數據，並計劃未來對幻燈片上顯示的多項試驗進行數據更新。

Aggregate data that we have reported in the past across iNeST and FixVac trials indicate that uridine mRNA LPX based vaccines have a manageable and largely mild safety profile as single-agent in combination with anti-PD-1, PD-L1 compounds and in combination with chemotherapy.

我們過去在 iNeST 和 FixVac 試驗中報告的匯總數據表明，基於尿苷 mRNA LPX 的疫苗作為單藥與抗 PD-1、PD-L1 化合物組合以及與化療。

Our data also indicates that our uridine mRNA-LPX based vaccines are proficient in inducing and expanding high-magnitude functional and long-lived T-cell responses in the majority of patients, which is a prerequisite for clinical activity. Furthermore, our data from small sample size patient cohorts indicates clinical activity alone and in combination with anti-PD-1, PD-L1 treatment.

我們的數據還表明，我們的基於尿苷 mRNA-LPX 的疫苗能夠熟練地在大多數患者中誘導和擴大高強度的功能性和長壽命的 T 細胞反應，這是臨床活動的先決條件。此外，我們來自小樣本患者群組的數據顯示了單獨治療以及與抗 PD-1、PD-L1 治療聯合治療的臨床活性。

Several of now ongoing trials shown on this slide aim to answer the material question of whether our mRNA vaccines are superior to the respective standard of care. In our FixVac program, here on the right, I would like to highlight three vaccine candidates currently being evaluated in multiple trials in both the metastatic and adjuvant settings.

本投影片中顯示的目前正在進行的幾項試驗旨在回答我們的 mRNA 疫苗是否優於各自的護理標準的重大問題。在我們的 FixVac 計劃中（右側），我想重點介紹三種候選疫苗，目前正在轉移性和佐劑環境的多項試驗中進行評估。

First, BNT113 being well underway in first line HPV16 positive PD-L1 positive head-neck squamous cell carcinoma in a potentially registrational Phase 2 randomized trial. Second, BNT116 being investigated in two trials as single-agent and in various combinations in different non-small-cell lung cancer patient populations and treatment lines. And last but not least, BNT111 being investigated in anti-PD-1 relapsed or refractory melanoma, about which I would like to talk a bit more.

首先，BNT113 正在一項潛在註冊的 2 期隨機試驗中順利進行一線 HPV16 陽性 PD-L1 陽性頭頸鱗狀細胞癌治療。其次，BNT116 正在兩項試驗中作為單藥和不同組合在不同的非小細胞肺癌患者群體和治療線中進行研究。最後但並非最不重要的一點是，BNT111 正在針對抗 PD-1 復發或難治性黑色素瘤進行研究，對此我想多談一點。

BNT111 is a uridine mRNA LPX based vaccine that encodes four melanoma-associated antigens that collectively cover more than 90% of melanoma patients and are highly immunogenic. In the randomized three Arm Phase 2 clinical trial conducted in collaboration with our partner, Regeneron, we are evaluating BNT111 in combination with Regeneron's anti-PD-1 compound cemiplimab, and we measure activity of BNT111 alone or cemiplimab alone in a total of 184 enrolled patients with PD-L1 refractory, unresectable Stage III or Stage IV melanoma.

BNT111是一種以尿苷mRNA LPX為基礎的疫苗，編碼四種黑色素瘤相關抗原，覆蓋了90%以上的黑色素瘤患者，並且具有高度免疫原性。在與我們的合作夥伴Regeneron 合作進行的隨機三臂2 期臨床試驗中，我們正在評估BNT111 與Regeneron 的抗PD-1 化合物cemiplimab 的組合，並測量了總共184 名入組患者單獨使用BNT111 或單獨使用cemiplimab 的活性患有 PD-L1 難治性、不可切除的 III 期或 IV 期黑色素瘤患者。

As Ugur noted earlier, we very recently announced that the trial met its primary endpoint, achieving a statistically significant improvement of overall response rate in the BNT111 cemiplimab combination arm as compared to historical control of anti-PD-1 monotherapy in relapsed refractory patients. The historic control was based on multiple late-stage clinical trials that established the expected objective response rate for monotherapy checkpoint inhibitors in this setting for this patient population. While the data are further maturing, we do see a trend towards improved overall survival.

正如Ugur 先前指出的，我們最近宣布該試驗達到了主要終點，與復發難治性患者中抗PD-1 單藥治療的歷史對照相比，BNT111 cemiplimab 聯合治療組的總體緩解率取得了統計學上的顯著改善。歷史對照基於多項後期臨床試驗，這些試驗確定了單藥治療檢查點抑制劑在這種情況下針對該患者群體的預期客觀緩解率。雖然數據進一步成熟，但我們確實看到了整體存活率提高的趨勢。

The BNT111-01 trial is based on the earlier Lipo-MERIT Phase 1, 2 trial in patients with advanced melanoma who had exhausted treatment options. The trial established the dose and provided initial safety, efficacy and immunogenicity data on BNT111 as single agent and with checkpoint inhibitors approved in this patient population.

BNT111-01 試驗是基於早期 Lipo-MERIT 1、2 期試驗，試驗對像是已用盡的治療方案晚期的黑色素瘤患者。該試驗確定了 BNT111 的劑量，並提供了 BNT111 作為單藥和已在該患者群體中批准的檢查點抑制劑的初步安全性、有效性和免疫原性數據。

In that proof-of-concept study, we observed that treatment with BNT111 alone or in combination with anti-PD-1 could induce strong high magnitude T-cell responses against at least one targeted tumor-associated antigen in all analyzed patients, most of which were not detectable prior to using the vaccine.

在該概念驗證研究中，我們觀察到，在所有分析的患者中，單獨使用BNT111 或與抗PD-1 聯合治療可以誘導針對至少一種靶向腫瘤相關抗原的強烈高強度T 細胞反應，其中大多數患者在使用疫苗前無法檢測到。

As shown here, objective responses by BNT111 were durable with some patients followed up for several years. The safety profile was generally mild and in line with expectations for those patients who were co-treated with checkpoint inhibitors. The results we are seeing in the Phase 2 BNT111-01 study our consistent with these prior results. We plan to present the full data from the primary analysis at the Medical Conference in 2025 and are entering into discussions with regulatory authorities regarding our data and the clinical path forward for this program.

如圖所示，BNT111 的客觀反應是持久的，有些患者追蹤了數年。安全性總體上是溫和的，符合那些接受檢查點抑制劑合併治療的患者的預期。我們在第二階段 BNT111-01 研究中看到的結果與先前的結果一致。我們計劃在 2025 年的醫學會議上展示初步分析的完整數據，並正在與監管機構就我們的數據和該計畫的臨床前景進行討論。

Cutaneous melanoma carries a high and continuously increasing incidence and mortality burden. The introduction of checkpoint inhibitor-directed therapies was a breakthrough for patients that led to significant improvements in survival.

皮膚黑色素瘤的發生率和死亡率負擔較高且持續增加。檢查點抑制劑導向療法的引入對於患者來說是一項突破，可以顯著改善患者的存活率。

Nonetheless, in advanced disease stages, only a third of patients achieve a long-term response and long-term survival. After failure of checkpoint inhibitors, there is no established standard-of-care with only limited and short-lived responses to salvage therapy.

儘管如此，在疾病晚期，只有三分之一的患者獲得長期緩解和長期存活。檢查點抑制劑失敗後，沒有既定的護理標準，對挽救治療的反應有限且短暫。

While a new adopted cell therapy has recently become available for this patient population, we do not expect that all patients will be eligible, leaving a significant unmet medical need unaddressed. In this context, our BNT111 may be of interest to potentially help treat this high medical need population.

雖然最近已針對該患者群體採用了新的細胞療法，但我們並不期望所有患者都符合資格，從而導致未滿足的重大醫療需求無法解決。在這種情況下，我們的 BNT111 可能有助於治療這個高醫療需求族群。

Moreover, the BNT111 data is a proof-of-concept in three dimensions. Firstly, a proof-of-concept for our decade-long improved mRNA cancer vaccine technology that uses uridine mRNA chemistry, a non-coding backbone that is engineered for optimal translational performance and our proprietary lipoplex formulation for systemic delivery. Second, this is a proof-of-concept for our computational approaches for selecting suitable tumor antigens and targets for our cancer indication-specific FixVac program candidates. And lastly, it's a proof-of-concept for our strategy to combine synergistic modalities, in this case BNT111, with an established immune checkpoint inhibitor treatment.

此外，BNT111 資料是三維概念驗證。首先，我們長達十年改進的mR​​NA 癌症疫苗技術的概念驗證，該技術使用尿苷mRNA 化學、一種專為實現最佳翻譯性能而設計的非編碼骨架以及我們用於全身遞送的專有lipoplex配方。其次，這是我們為癌症適應症特定 FixVac 計畫候選者選擇合適腫瘤抗原和標靶的計算方法的概念驗證。最後，這是我們將協同模式（在本例中為 BNT111）與已建立的免疫檢查點抑制劑治療相結合的策略的概念驗證。

All three of these also applies to BNT122, our individualized mRNA cancer immunotherapy based on our iNeST platform and the same delivery technology. We consider individualized cancer vaccines as a medical breakthrough in addressing the high unmet medical need of resectable cancer and in adjuvant or minimal residual disease treatment settings. Here, I want to highlight ongoing randomized Phase 2 trials with our individualized vaccine in pancreatic ductal adenocarcinoma and in colorectal cancer.

這三項也適用於 BNT122，這是我們基於 iNeST 平台和相同遞送技術的個體化 mRNA 癌症免疫療法。我們認為個人化癌症疫苗是解決可切除癌症以及輔助或微小殘留疾病治療環境中未滿足的高度醫療需求的醫學突破。在這裡，我想強調正在進行的針對胰腺導管腺癌和結直腸癌的個體化疫苗的隨機 2 期試驗。

The five-year survival rate in pancreatic ductal adenocarcinoma after resection alone is 10% and up to 75% of patients with pancreatic ductal carcinoma relapse even though they appear tumor-free within five years after adjuvant treatment. As for high-risk Stage II or Stage III colorectal cancer, about 35% of patients relapse within five years after resection and adjuvant therapy.

胰臟導管腺癌單獨切除後的五年存活率為 10%，即使胰臟導管癌患者在輔助治療後 5 年內出現無腫瘤，但高達 75% 的患者會復發。對於高風險II期或III期大腸直腸癌，約35%的患者在切除和輔助治療後五年內復發。

As discussed in the last earnings call. We demonstrated that our individualized vaccine used in patients with adjuvant pancreatic cancer can induce de novo T-cell responses that are specific to the individual mutant tumor neoantigens and that the risk of recurrence of cancer for patients with vaccine-induced immune responses was reduced even after a three-year follow-up period.

正如上次財報電話會議中所討論的。我們證明，我們的個人化疫苗用於輔助性胰腺癌患者，可以誘導針對個體突變腫瘤新抗原的從頭T 細胞反應，並且即使在疫苗誘導免疫反應的患者中，癌症復發的風險也降低了。

At the recent ESMO GI Conference, we disclosed findings from the biomarker sub-study of our ongoing Phase 2 iNeST trial, BNT122-01, involving patients with Stage II high-risk of Stage III colorectal cancer who remain ctDNA positive, following the surgical excision of the localized cancer. Upon completion of standard-of-care adjuvant chemotherapy, these patients receive BNT122, our individualized vaccine, in contrast to the conventional wait-and-watch approach.

在最近的ESMO GI 會議上，我們揭露了正在進行的2 期iNeST 試驗BNT122-01 的生物標記子研究的結果，該試驗涉及II 期高風險III 期結直腸癌患者，這些患者在手術切除後仍維持ctDNA 陽性局部癌症。完成標準護理輔助化療後，這些患者將接受我們的個人化疫苗 BNT122，這與傳統的等待觀察方法不同。

In the subset of 12 patients who were accessible for immunogenicity analysis, a high magnitude de novo T-cell response against at least one vaccine-encoded neoantigen was observed in all patients. These T-cell responses were amplified with successive vaccination cycles. Notably, in several patients, the T-cell responses were sustained even after two years of follow-up.

在可進行免疫原性分析的 12 名患者中，所有患者均觀察到針對至少一種疫苗編碼的新抗原的高強度從頭 T 細胞反應。這些 T 細胞反應隨著連續的疫苗接種週期而增強。值得注意的是，在某些患者中，即使在兩年的追蹤後，T 細胞反應仍然持續。

All 12 patients involved in the immunogenicity analysis remained disease-free at the time of data cutoff. Enrollment for the main part of the colorectal cancer study is underway to establish the safety and efficacy of BNT122 in patients with ctDNA positive Stage II, Stage III colorectal cancer as opposed to the standard wait-and-watch strategy. We anticipate presenting the result from this randomized Phase 2 study by late 2025 or early '26.

參與免疫原性分析的所有 12 名患者在數據截止時均保持無病狀態。大腸直腸癌研究的主要部分正在進行招募，以確定 BNT122 在 ctDNA 陽性 II 期、III 期結直腸癌患者中的安全性和有效性，而不是標準的等待觀察策略。我們預計在 2025 年末或 26 年初公佈這項隨機 2 期研究的結果。

As multiple Phase 2 trials are ongoing and our clinical data on mRNA immunotherapies continues to mature, we are scaling up our manufacturing capabilities and capacities for bulk mRNA drug supply for off-the-shelf FixVac vaccines and also for our individualized vaccine programs. To build out our manufacturing capacity for personalized mRNA, we are currently building a pilot facility in Mainz, Germany to support our ongoing late-stage trials and potentially in the future commercialization. We also continue to leverage in study, our wholly-owned AI subsidiary company, to work with our teams in improving both the up and downstream processes in personalized mRNA manufacturing.

隨著多項2 期試驗正在進行，以及我們關於mRNA 免疫療法的臨床數據不斷成熟，我們正在擴大我們的生產能力和批量mRNA 藥物供應能力，用於現成的FixVac 疫苗以及我們的個人化疫苗專案.為了建立個人化 mRNA 的製造能力，我們目前正在德國美因茨建造一個試點設施，以支持我們正在進行的後期試驗以及未來可能的商業化。我們也繼續利用我們的全資人工智慧子公司 in Study 與我們的團隊合作，改進個人化 mRNA 製造的上下游流程。

From our mRNA cancer vaccines, I'm now moving to our immunomodulatory IO compounds, specifically BNT327, which we consider as a key immunomodulatory concept and compelling backbone for novel combination. BNT327 combines two validated mechanisms of action, VEGF-A binding inhibits the VEGF-A with VEGF-R access, blocks tumor angiogenesis, which leads to reduced tumor cell proliferation and survival.

從我們的 mRNA 癌症疫苗，我現在轉向我們的免疫調節 IO 化合物，特別是 BNT327，我們認為它是關鍵的免疫調節概念和新型組合的引人注目的支柱。 BNT327結合了兩種經過驗證的作用機制，VEGF-A結合抑制VEGF-A與VEGF-R的接觸，阻斷腫瘤血管生成，進而導致腫瘤細胞增殖和存活減少。

VEGF-A inhibition also counteracts formation of the immunosuppressive tumor micro-environment as does the PD-L1 arm of a bispecific antibody by reverting PD-L1, PD-1 access mediated T-cell exhaustion. The PD-L1 arm also anchors this bispecific antibody to the tumor bed for efficient and localized scavenging of VEGF-A, which may contribute to mitigate of tumor on-target side effects.

VEGF-A 抑制還可以透過恢復 PD-L1、PD-1 路徑介導的 T 細胞耗竭來抵消免疫抑制性腫瘤微環境的形成，就像雙特異性抗體的 PD-L1 臂一樣。 PD-L1 臂也將這種雙特異性抗體錨定在腫瘤床上，以有效、局部地清除 VEGF-A，這可能有助於減輕腫瘤的靶向副作用。

Given that both the anti-VEGF-A and the anti-PD-1 mechanisms are validated across many tumor types and in some cases as a combination, we have a clear roadmap ahead of us where to develop BNT-327. Beyond these initial indications in which we may combine with standard-of-care chemotherapy, we plan to evaluate novel BNT327 combination, the first of which were started recently. These novel BNT327 combinations may open up new areas of activity for our anti-VEGF-A and anti-PD-L1 molecule.

鑑於抗 VEGF-A 和抗 PD-1 機制均在多種腫瘤類型中得到驗證，並且在某些情況下作為組合，我們面前有一個明確的開發 BNT-327 的路線圖。除了我們可以與標準化療聯合使用的這些初步適應症之外，我們還計劃評估新型 BNT327 組合，其中第一個組合最近已開始。這些新型 BNT327 組合可能為我們的抗 VEGF-A 和抗 PD-L1 分子開闢新的活性領域。

We and our partner, Biotheus, have treated over 600 patients across a wide range of clinical indications with BNT327, either as monotherapy or in combination with various standard-of-care protocols. This extensive data collection effort provides a solid foundation for making informed data-driven decisions on potential indications and patient cohorts for future registration studies.

我們和我們的合作夥伴 Biotheus 已使用 BNT327 治療了 600 多名具有廣泛臨床適應症的患者，無論是作為單一療法還是與各種標準護理方案相結合。這種廣泛的數據收集工作為未來註冊研究的潛在適應症和患者群做出明智的數據驅動決策奠定了堅實的基礎。

Notably, the data demonstrate robust single-agent activity of BNT327 in previously untreated advanced non-small-cell lung cancer and high response rates in combination with standard-of-care chemotherapy in triple-negative breast cancer and small-cell lung cancer.

值得注意的是，數據表明 BNT327 在先前未經治療的晚期非小細胞肺癌中具有強大的單藥活性，並且在三陰性乳腺癌和小細胞肺癌中與標準護理化療相結合具有高緩解率。

Specifically, in first-line triple-negative breast cancer, we observed an objective response rate approaching 80% with durable responses when combined with nab-paclitaxel. The safety profile in these indications was generally well-managed and in line with adverse events observed with other therapies targeting PD-L1 and appears to be more favorable than those seen with anti-VEGF-A agents. These data have driven our strategic decision to initiate registration trials in small-cell lung cancer, non-small-cell lung cancer and in triple-negative breast cancer this year and next year.

具體來說，在一線三陰性乳癌中，我們觀察到與白蛋白結合型紫杉醇合併使用時，客觀緩解率接近 80%，且緩解持久。這些適應症的安全性總體上管理良好，並且與其他針對 PD-L1 的療法觀察到的不良事件一致，並且似乎比抗 VEGF-A 藥物所觀察到的不良事件更有利。這些數據推動了我們的策略決策，即在今年和明年啟動小細胞肺癌、非小細胞肺癌和三陰性乳癌的註冊試驗。

In small-cell lung cancer, therapeutic options for the treatment of metastatic disease remain limited with few innovative approaches beyond frontline anti-PD-1 checkpoint inhibitor, which only achieve response rates of around 20%. TNBC patients, particularly those with PD-L1 negative tumors, have few treatment options as they are not eligible for current anti-PD-1 therapies.

在小細胞肺癌中，轉移性疾病的治療選擇仍然有限，除了第一線抗 PD-1 檢查點抑制劑之外，很少有創新方法，其反應率僅達到 20% 左右。 TNBC 患者，特別是 PD-L1 陰性腫瘤患者，幾乎沒有治療選擇，因為他們不符合目前的抗 PD-1 療法。

In metastatic non-small-cell lung cancer, while anti-PD-1 inhibitors have significantly changed the treatment landscape, nearly half of these patients, they do not respond to frontline therapy in combination with chemotherapy. We will soon start two global Phase 2 dose optimization studies to enable selection of a registrational dose for global registrational trials in these particular indications.

在轉移性非小細胞肺癌中，雖然抗 PD-1 抑制劑顯著改變了治療格局，但這些患者中近一半的患者對第一線治療合併化療沒有反應。我們很快將啟動兩項全球 2 期劑量優化研究，以便為這些特定適應症的全球註冊試驗選擇註冊劑量。

At ASCO, we presented updated preliminary efficacy and safety data from an ongoing Phase 1, 2 study in cohorts of advanced cervical cancer, platinum-resistant relapsed ovarian cancer and advanced relapsed non-small-cell lung cancer.

在ASCO 上，我們展示了一項正在進行的1 期、2 期研究的最新初步療效和安全性數據，該研究涉及晚期子宮頸癌、鉑類抗藥性復發性卵巢癌和晚期復發性非小細胞肺癌隊列。

We will be presenting signal finding data from additional tumor indications at upcoming conferences. This will add to our extensive database and is the basis of our plans for further development in key indication. Most importantly, as Ugur also noted, it is a strategic goal for us to explore BNT327 as part of novel and novel combinations, in particular with our ADC assets and mRNA therapies. We have started to implement this strategy by investigating BNT327 in combination with our TROP2 ADC, BNT325, further combinations will be announced in the coming months. We are very excited to advance these combination trials with our partners.

我們將在即將舉行的會議上展示其他腫瘤適應症的訊號發現數據。這將增加我們廣泛的資料庫，並且是我們進一步開發關鍵適應症的計劃的基礎。最重要的是，正如 Ugur 也指出的那樣，探索 BNT327 作為新穎和新穎組合的一部分是我們的策略目標，特別是與我們的 ADC 資產和 mRNA 療法。我們已經開始透過研究 BNT327 與我們的 TROP2 ADC、BNT325 的組合來實施這項策略，進一步的組合將在未來幾個月內公佈。我們非常高興與我們的合作夥伴一起推進這些組合試驗。

On my final slide now, I would like to provide an outlook on upcoming congress presentations in September, with updates on some of our priority assets. At our Annual ESMO Congress in Barcelona, here we will present an update on our two trials evaluating BNT113, FixVac.

在我現在的最後一張投影片上，我想對 9 月即將舉行的大會演講進行展望，並提供我們一些優先資產的更新。在巴塞隆納舉行的年度 ESMO 大會上，我們將在此介紹評估 BNT113、FixVac 的兩項試驗的最新情況。

The first update will include patients with anal head and neck, cervical and other HPV16-driven carcinomas, and we report mainly safety and immunogenicity findings from the Phase 1, 2 trials. The second update from a safety run in cohort of our ongoing Phase 2 trials evaluating BNT113 dosed in combination with pembrolizumab versus pembrolizumab alone will include patients with HPV16 positive head, neck squamous cell carcinoma. This update will focus on the safety, immunogenicity and preliminary activity findings of the cohort.

第一次更新將包括肛頭頸癌、子宮頸癌和其他 HPV16 驅動的癌症患者，我們主要報告 1、2 期試驗的安全性和免疫原性結果。我們正在進行的評估 BNT113 與派姆單抗聯合用藥與單獨使用派姆單抗的 2 期試驗隊列的安全性的第二次更新將包括 HPV16 陽性頭頸鱗狀細胞癌患者。本次更新將重點放在該隊列的安全性、免疫原性和初步活性研究結果。

We will also present the updated results on BNT327 in patients with TNBC, with EGFR-mutated non-small-cell lung cancer and with kidney cancer, together with our partner Biotheus. These updates will contain either initial or follow-up data on safety and efficacy of BNT327 as a monotherapy and as a combination with different chemotherapeutic regimens.

我們也將與我們的合作夥伴 Biotheus 一起展示 BNT327 在 TNBC、EGFR 突變非小細胞肺癌和腎癌患者的最新結果。這些更新將包含有關 BNT327 作為單一療法以及與不同化療方案組合的安全性和有效性的初始或後續數據。

And finally, we will be presenting updated results from our ongoing Phase 1 trial evaluating safety and efficacy of our Claudin 6 CAR-T cells in combination with Claudin 6 encoded mRNA vaccine in patients with relapsed sirefractory Claudin 6 solid tumors. These data will be a follow-up from what was presented at last year's ESMO Congress and will include updated safety and efficacy data, as well as data on CAR-T cell persistence. We will share additional details on these and further congress publication in the near-future.

最後，我們將展示正在進行的1 期試驗的最新結果，該試驗評估了我們的Claudin 6 CAR-T 細胞與Claudin 6 編碼的mRNA 疫苗聯合治療復發性難治性Claudin 6 實體瘤患者的安全性和有效性。這些數據將是去年 ESMO 大會上提交的數據的後續數據，並將包括更新的安全性和有效性數據，以及 CAR-T 細胞持久性數據。我們將在不久的將來分享有關這些內容的更多詳細資訊以及進一步的大會出版物。

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

現在，我將把演講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. Let me start by reviewing our financial results for the three months ended June 30, 2024.

謝謝您，Ozlem，並熱烈歡迎所有撥打今天電話的人。首先讓我回顧一下我們截至 2024 年 6 月 30 日的三個月的財務表現。

Our total revenues reported for the second quarter of 2024 reached approximately EUR129 million compared with approximately EUR168 million for the second quarter of 2023. Our second quarter revenues reflect the current demand of a seasonal endemic COVID-19 vaccine market, and I expect it to be the low point in this year's COVID-19 vaccine uptake. Part of our total revenues are derived from a pandemic preparedness agreement with the German government, which is expected to run until early 2027.

我們報告的2024 年第二季總收入約為1.29 億歐元，而2023 年第二季約為1.68 億歐元。預計今年 COVID-19 疫苗接種量的最低點。我們總收入的一部分來自與德國政府簽訂的流行病防備協議，預計將持續到 2027 年初。

Moving to cost of sales. Cost of sales amounted to approximately EUR60 million for the second quarter of 2024 compared to approximately EUR163 million for the comparative prior-year period. Research and development expenses were approximately EUR585 million for the second quarter of 2024 compared to approximately EUR373 million for the comparative prior-year period. Of the total R&D spend in the second quarter, we invested approximately 90% in our non-COVID business, mainly by initiating larger clinical studies for our late-stage oncology candidates and by investing in additional personnel in our R&D departments to run those clinical trials.

轉向銷售成本。 2024 年第二季的銷售成本約為 6,000 萬歐元，而去年同期約為 1.63 億歐元。 2024 年第二季的研發費用約為 5.85 億歐元，而去年同期約為 3.73 億歐元。在第二季的總研發支出中，我們將約90% 投資於非新冠業務，主要是為我們的晚期腫瘤候選者啟動更大規模的臨床研究，並在研發部門投資更多人員來運作這些臨床試驗。

Sales, general and administrative expenses amounted to approximately EUR184 million in the second quarter of 2024 compared to about EUR138 million in the comparative prior-year period. The increase in SG&A was mainly due to the increased expenses for our IT environment as well as an increase in headcount to support the scaling of our business.

2024 年第二季的銷售、一般和管理費用約為 1.84 億歐元，而去年同期約為 1.38 億歐元。 SG&A 的增加主要是由於我們的 IT 環境費用增加以及支援業務擴展的員工人數增加。

Regarding the company's other operating results during the second quarter of 2024, this amounted to approximately EUR267 million in negative operating results compared to about EUR57 million in negative operating result for the comparative prior-year period. This change was primarily due to the recording of a provision related to a contractual dispute.

至於該公司 2024 年第二季的其他經營業績，負經營業績約為 2.67 億歐元，而去年同期的負經營業績約為 5,700 萬歐元。這項變更主要是由於記錄了與合約糾紛相關的條款。

Income taxes were accrued with an amount of EUR2 million of tax expenses for the second quarter of 2024 compared to approximately EUR222 million of realized tax income for the comparative prior-year period. The effective income tax rate for the first half of 2024 was approximately 1.3%.

2024 年第二季應計所得稅費用為 200 萬歐元，而去年同期已實現的稅收收入約為 2.22 億歐元。 2024年上半年的有效所得稅稅率約為1.3%。

For the second quarter of 2024, we reported a net loss of approximately EUR808 million compared to a net loss of about EUR190 million for the comparative prior-year period. Our loss per share for the second quarter of 2024 amounted to EUR3.36 compared to a loss per share of EUR0.79 for the comparative prior-year period. As of June 30, 2024, our cash and cash equivalents and security investments reached approximately EUR18.5 billion.

2024 年第二季度，我們報告的淨虧損約為 8.08 億歐元，而去年同期淨虧損約為 1.9 億歐元。 2024 年第二季的每股虧損為 3.36 歐元，而去年同期每股虧損為 0.79 歐元。截至2024年6月30日，我們的現金和現金等價物以及證券投資達到約185億歐元。

Our strong balance sheet provides us with a strategic flexibility to invest in our long-term growth strategy. As part of that strategy, we will continue to invest in the development of our individualized therapies and in the buildout of the manufacturing capacities and capabilities to support additional late-stage trials in commercialization. To create long-term value, we aim to advance our clinical programs quickly, yet cost-efficiently towards potential registration.

我們強大的資產負債表為我們提供了投資長期成長策略的策略靈活性。作為該策略的一部分，我們將繼續投資於個體化療法的開發以及製造能力和能力的建設，以支持更多的商業化後期試驗。為了創造長期價值，我們的目標是快速、經濟高效地推進我們的臨床項目，以實現潛在的註冊。

Turning to the next slide. Today, we are reiterating the company's financial guidance for the current financial year. Consistent with the expectations of approval of our variant-adapted COVID-19 vaccine in the United States in mid-September. We expect to recognize the vast majority of our full year revenues mostly in Q4. Independent of the timing of the revenue generation and as communicated earlier in the year, we expect to report a loss for the 2024 financial year, while we continue to invest in our proprietary assets and technologies.

轉到下一張投影片。今天，我們重申公司本財年的財務指引。與我們的變體適應的 COVID-19 疫苗於 9 月中旬在美國獲得批准的預期一致。我們預計全年收入的絕大部分將在第四季度確認。無論收入產生的時間如何，正如今年早些時候所傳達的那樣，我們預計將在 2024 財年報告虧損，同時繼續投資於我們的專有資產和技術。

As such, we also reiterate our R&D and SG&A guidance with EUR2.4 billion to EUR2.6 billion for R&D and EUR700 million to EUR800 million for SG&A expenses. Those expenses are expected to increase in the second half compared to the first half of 2024.

因此，我們也重申了我們的研發和銷售及管理費用指引，研發費用為 24 億至 26 億歐元，銷售費用為 7 億歐元至 8 億歐元。與 2024 年上半年相比，這些費用預計在下半年將會增加。

Please note that this guidance does not include any M&A transactions, payment for collaboration agreements or licensing deals not yet disclosed, nor any potential payments resulting from the outcomes of ongoing and/or future legal disputes or related activities such as judgment or settlements, which may have a material effect on our results of operations or cash flows.

請注意，本指南不包括任何尚未披露的併購交易、合作協議付款或許可交易，也不包括因正在進行和/或未來的法律糾紛或相關活動（例如判決或和解）的結果而產生的任何潛在付款，這些付款可能對我們的經營業績或現金流量產生重大影響。

In summary, our focus so far has been on executing the company's strategy, highlighted by the progress in our pipeline. We've advanced and started new potentially registrational trials and have shared encouraging data that demonstrates the potential of our pipeline.

總之，到目前為止，我們的重點是執行公司的策略，我們的管道進展突顯了這一點。我們已經推進並開始了新的潛在註冊試驗，並分享了令人鼓舞的數據，證明了我們的管道的潛力。

Our focus in oncology remains on investing in our innovative technologies that we believe can make a difference while progressing our late-stage programs towards potential market authorizations. Supported by our strong cash position and demonstrated financial discipline, we will continue to invest in our pipeline and focus on generating value for patients and our shareholders.

我們在腫瘤學方面的重點仍然是投資我們的創新技術，我們相信這些技術可以發揮作用，同時推進我們的後期專案以獲得潛在的市場授權。在我們強大的現金狀況和良好的財務紀律的支持下，我們將繼續投資於我們的產品線，並專注於為患者和股東創造價值。

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

在此，我想將電話轉給我們的首席策略長 Ryan Richardson，以了解我們策略前景的最新情況和總結發言。謝謝。

Thank you, Jens. Our efforts over the last few months have put us in a strong position to execute our COVID-19 vaccine launches this fall season. In June, the European Medicines Agency recommended marketing authorization for our JN.1-adapted COVID-19 vaccine, followed by European Commission approval on July 3. We started distributing vaccine doses to EU member states shortly thereafter.

謝謝你，延斯。過去幾個月的努力使我們處於有利地位，可以在今年秋季推出 COVID-19 疫苗。 6 月，歐洲藥品管理局建議對我們的 JN.1 適應的 COVID-19 疫苗進行行銷授權，隨後歐盟委員會於 7 月 3 日批准。

We expect the earlier launch of our updated COVID-19 vaccine Europe relative to last year will allow vaccination campaigns this year to be more closely aligned with seasonal influenza vaccination campaigns. In the United States, the FDA has recommended the use of KP.2 as the preferred strain for the '24, '25 season.

我們預計，與去年相比，歐洲更新的 COVID-19 疫苗的推出將使今年的疫苗接種活動與季節性流感疫苗接種活動更加緊密地結合。在美國，FDA已建議使用KP.2作為'24、'25季節的首選菌株。

We and our partner Pfizer have initiated a rolling submission with the FDA for our KP.2-adapted COVID-19 vaccine and expect to be in a position to begin vaccine distribution in the US following regulatory approval, with first shipments expected in September. COVID-19 vaccine demand continues to be globally distributed. We and our partner Pfizer are preparing to launch our variant-adapted COVID-19 vaccine in over 40 countries and regions worldwide. We expect approximately two-thirds of demand potential to reside outside the United States.

我們和我們的合作夥伴輝瑞已開始向 FDA 滾動提交我們的 KP.2 適應的 COVID-19 疫苗，並預計在獲得監管部門批准後能夠開始在美國分發疫苗，預計將於 9 月首批發貨。 COVID-19 疫苗需求持續分佈在全球。我們和我們的合作夥伴輝瑞正準備在全球 40 多個國家和地區推出我們的變體適應的 COVID-19 疫苗。我們預計大約三分之二的需求潛力來自美國境外。

While some regions outside the US continue to be served by government contracts, we anticipate several newly established private markets to open up in regions like the UK and Japan. This could enable broader access to COVID-19 vaccines for individuals who may not qualify under local immunization recommendations, which tend to focus on the higher-risk population segments.

雖然美國以外的一些地區繼續接受政府合約的服務，但我們預計英國和日本等地區將開放幾個新建立的私人市場。這可以使那些可能不符合當地免疫建議的個人更廣泛地獲得 COVID-19 疫苗，這些建議往往側重於高風險族群。

In addition, we have increased our supply of pre-filled syringes, but we'll continue to offer a mix of pre-filled syringes, single-dose vials and multi-dose vials across regions. We believe the COMIRNATY franchise is well-positioned to maintain its leading position globally in the continued fight against COVID-19.

此外，我們也增加了預充式註射器的供應，但我們將繼續在各地區提供預充式註射器、單劑量小瓶和多劑量小瓶的組合。我們相信，COMIRNATY 特許經營權處於有利位置，可以在持續對抗 COVID-19 的鬥爭中保持其全球領先地位。

Moving to oncology on the next slide. We will continue to invest in our mRNA cancer vaccine platforms based on our belief that personalized mRNA cancer vaccines have potential to establish a new paradigm in cancer treatment. These vaccines employ cutting-edge mRNA technology, which aims to address the root cause of cancer, genomic mutations or neoantigens that are largely specific to each individual's tumor. Neoantigen selection for each patient is today driven by AI algorithms and a fully in silico process.

下一張投影片轉向腫瘤學。我們將繼續投資我們的 mRNA 癌症疫苗平台，因為我們相信個人化 mRNA 癌症疫苗有潛力建立癌症治療的新範例。這些疫苗採用尖端的 mRNA 技術，旨在解決癌症、基因組突變或新抗原的根本原因，這些新抗原很大程度上針對每個個體的腫瘤。如今，每個患者的新抗原選擇都是由人工智慧演算法和完全電腦化的過程所驅動的。

We believe this is fundamentally distinct from other pharmaceutical products and that it will allow for iterative improvement over time, powered by data assets. In addition to their ability to be combined with other therapies with complementary mechanisms of action, we believe these therapies have potential to extend beyond the product life-cycle of a traditional off-the-shelf pharmaceutical product.

我們相信這與其他醫藥產品有著根本的區別，並且它將允許在數據資產的支持下隨著時間的推移進行迭代改進。除了能夠與具有互補作用機制的其他療法結合外，我們相信這些療法還有可能超越傳統現成藥品的產品生命週期。

The next slide highlights the key pipeline milestones to focus on as we look ahead to '24 and '25. We are entering a catalyst-rich period over the next 18 months with data updates and regulatory submissions expected from multiple product candidates. This includes but is not limited to Phase-3 COVID flu combination vaccine topline data expected this year. And data expected in 2025 from both our mRNA cancer vaccine platforms FixVac and iNeST.

下一張投影片重點介紹了我們展望 24 年和 25 年時需要關注的關鍵管道里程碑。未來 18 個月，我們將進入催化劑豐富的時期，預計多個候選產品將進行資料更新和監管提交。這包括但不限於今年預計的第三階段新冠流感聯合疫苗的主要數據。我們的 mRNA 癌症疫苗平台 FixVac 和 iNeST 預計將於 2025 年提供數據。

We also expect data updates for BNT327, our anti-PD-L1 VEGF bispecific antibody, and BNT323, our HER2 ADC in a variety of solid tumor indications. Finally, we plan to initiate multiple combination trials in solid tumor indications over the next 12 months, consistent with our strategy to develop novel combinations, which leverage complementary mechanisms of action.

我們也預期 BNT327（我們的抗 PD-L1 VEGF 雙特異性抗體）和 BNT323（我們的 HER2 ADC）在多種實體腫瘤適應症中的數據更新。最後，我們計劃在未來 12 個月內針對實體腫瘤適應症啟動多項組合試驗，這與我們開發利用互補作用機制的新型組合的策略一致。

Turning to the next slide, we continue to focus on our late-stage oncology portfolio in line with our near-term goal to have 10 potentially registrational trials active by the end of the year. While still in the early stages, we are making progress in attracting talented professionals to join our commercial organization to support our first wave of anticipated oncology product launches. We believe that focusing execution on our diverse late-stage pipeline will bring significant potential for mid- and long-term value creation.

轉向下一張投影片，我們繼續專注於我們的後期腫瘤學產品組合，這符合我們的近期目標，即今年年底有 10 項潛在的註冊試驗處於活動狀態。雖然仍處於早期階段，但我們在吸引有才華的專業人士加入我們的商業組織以支持我們第一波預期的腫瘤產品發布方面正在取得進展。我們相信，將執行重點放在多元化的後期管道上將為中長期價值創造帶來巨大潛力。

On the next slide, I would like to remind everyone that we plan to hold our first Artificial Intelligence Innovation Series event via webcast on October 1, followed by our Annual Innovation Series event on November 14. Further details will be released soon. We welcome you to join these events for a deeper look at the exciting developments taking place at BioNTech.

在下一張投影片中，我想提醒大家，我們計劃於 10 月 1 日透過網路直播舉辦首屆人工智慧創新系列活動，隨後於 11 月 14 日舉辦年度創新系列活動。我們歡迎您參加這些活動，更深入地了解 BioNTech 正在發生的令人興奮的發展。

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

現在我想開始提問。

(Operator Instructions).

（操作員說明）。

Daina Graybosch, Leerink Partners.

戴娜‧格雷博斯 (Daina Graybosch)，Leerink 合夥人。

Hi, thank you guys, and thanks for the question. This one is on the launches early as 2026. I wonder if you could talk about what specific programs and settings trials you think are most likely to be able to launch in 2026? And if that's dependent on accelerated approval, what gives you confidence in accelerated approvals by that date? I guess, I'm specifically referencing whether any of those are your Phase 2 vaccine trials? Thank you.

你好，謝謝大家，也謝謝你的提問。這個最早將於 2026 年推出。如果這取決於加速批准，那麼是什麼讓您對在那一天之前加速批准充滿信心？我想，我具體指的是你們的第二期疫苗試驗中是否有任何一個？謝謝。

Yeah. Thank you, Daina. I'll start briefly (inaudible). So, I think, for 2026, we have a couple of different programs that potentially could launch in that timeframe. And the first of which is BNT323, our HER2 ADC, and we've highlighted the potential for -- we think for an accelerated approval in second and third line endometrial cancer. So that would be one asset where we're expecting data next year. And if that timeline is confirmed with further FDA discussions, we think that could be a '26 launch opportunity.

是的。謝謝你，戴娜。我將簡短地開始（聽不清楚）。因此，我認為，到 2026 年，我們可能會在該時間範圍內啟動幾個不同的計劃。第一個是 BNT323，我們的 HER2 ADC，我們強調了二線和三線子宮內膜癌的加速核准潛力。因此，這將是我們預計明年數據的資產。如果 FDA 的進一步討論確認了這一時間表，我們認為這可能是 26 年的發布機會。

In addition, we've highlighted the potential for an accelerated pathway with our BNT122, iNeST in adjuvant colorectal cancer. We still have further discussions to take place with the FDA, but based on the current study design and the pace of enrollment, we do think that there is the potential if the data is strong also for data to be for submission and potentially launch in that sort of timeframe, most likely towards the end of the year or early '27, but it could fall in '26.

此外，我們也強調了 BNT122、iNeST 在輔助大腸直腸癌中加速路徑的潛力。我們仍需與 FDA 進行進一步的討論，但根據當前的研究設計和入組速度，我們確實認為，如果數據強勁，也有可能提交數據並可能在該領域推出某種時間框架，最有可能是在今年年底或27 年初，但也可能在26 年。

Yaron Werber, TD Cowen.

亞龍·韋伯，TD·考恩。

Yeah, hi. Thanks for taking my question. Maybe just a quick question. I know you probably can't say a lot, but BNT111 FixVac. When you're looking at historical controls and you're looking at sort of the overall survival sort of trend, can you give us a sense what -- which historical control do you think are most appropriate just to kind of help gauge what the efficacy could be? Thank you.

是的，嗨。感謝您提出我的問題。也許只是一個簡單的問題。我知道你可能不能說太多，但 BNT111 FixVac。當您查看歷史對照並且查看某種總體生存趨勢時，您能否讓我們了解您認為哪種歷史對照最合適，以幫助衡量功效可能？謝謝。

Yeah. Sure. This is a very dire indication, CPI refractory resistant melanoma and the controls against which we compare anti-PD-1, PD-L1 treatments, which have been tested in this indication are chemotherapies, which have been tested in this indication. And as compared to those, we see a clinically meaningful benefit with regard to objective response rate. There is a trend for overall survival, but it is too early to be more specific about PFS and OS now. The data will mature and at the time, when we present the data next year, we will be able to be more specific.

是的。當然。這是一個非常可怕的適應症，CPI 難治性黑色素瘤和我們比較抗PD-1、PD-L1 治療（已在該適應症中進行測試）的對照是化療，已在該適應症中進行了測試。與這些相比，我們在客觀緩解率方面看到了具有臨床意義的益處。總存活率存在趨勢，但現在更具體地了解 PFS 和 OS 還為時過早。數據將會成熟，到時候，當我們明年提供數據時，我們將能夠更加具體。

Tazeen Ahmad, Bank of America Securities.

塔津‧艾哈邁德，美國銀行證券公司。

Hi, good morning. Thanks for taking my question. Regarding the upcoming Phase 3 COVID flu combo data later this year, can you frame for us what would be good data? And how would you think that would impact the demand for the regular COVID vaccine going forward? And then, also related to that, how long before you think that this product, the combo product, would be able to launch? Thanks.

早安.感謝您提出我的問題。關於今年稍後即將發布的第三階段新冠流感組合數據，您能為我們框架什麼是好的數據？您認為這將如何影響未來常規新冠疫苗的需求？然後，也與此相關，您認為這個產品，組合產品，需要多長時間才能推出？謝謝。

Hi, it's Ugur. Yeah, thanks for your question. So, we are expecting that timeframe with safety, immunogenicity data and efficacy data end of this year. And based on the results, we have to see whether the data qualify for submission and potential approval for the season 2025-2026.

嗨，我是烏古爾。是的，謝謝你的提問。因此，我們預計安全性、免疫原性數據和療效數據的時間表將在今年底公佈。根據結果，我們必須查看數據是否符合提交條件以及是否有可能獲得 2025-2026 年賽季的批准。

What would you consider good data though, Ugur, to be an improvement over the regular COVID vaccine?

Ugur，您認為好的數據對常規新冠疫苗有何改進？

Can you repeat your question? I didn't get that.

你能重複一下你的問題嗎？我沒明白。

What would you consider to be good data relative to the COVID-only vaccine in order to.

您認為與新冠疫苗相關的良好數據是什麼？

I think the data is very clear. There is an efficacy trial, yeah. It's about comparability with the COVID-19 plus efficacy in the flu arm, and additional immunogenicity data supporting the mode of action of the vaccine.

我認為數據非常清楚。有一個功效試驗，是的。它涉及與 COVID-19 的可比性以及在流感組中的功效，以及支持疫苗作用模式的其他免疫原性數據。

Etzer Darout, BMO Capital Markets.

Etzer Darout，BMO 資本市場。

Hi, thanks for taking the question. Just wondering sort of in the wake of the cemiplimab update and your maintenance of R&D guidance, is there a specific internal oncology program that potentially benefits here, in other words, maybe potential of acceleration of investments or broadening out of the program? Just so curious your thoughts around who maybe -- what programs may benefit from this internally?

您好，感謝您提出問題。只是想知道在 cemiplimab 更新和您對研發指導的維護之後，是否有一個特定的內部腫瘤學計劃可能會從中受益，換句話說，也許有加速投資或擴大該計劃的潛力？只是很好奇您對誰可能 - 哪些程式可以從內部受益的想法？

Yeah. Thank you for that question. Ultimately, this does come down to portfolio strategy, as I think your question alludes to. And the fact is that we have multiple programs that we think could have potential in non-small-cell lung cancer. We've already started a Phase 3 for BNT316. We've just brought out data at ASCO for BNT327, which albeit early, we do think is quite promising. And we also have a FixVac program that's also in NSCLC. So, we've got already critical mass on our portfolio in the non-small-cell lung cancer indication and we are planning a multi-pronged strategy to execute against.

是的。謝謝你提出這個問題。最終，這確實取決於投資組合策略，正如我認為你的問題所暗示的那樣。事實上，我們有多個項目，我們認為這些項目可能對非小細胞肺癌具有潛力。我們已經開始了 BNT316 的第三階段。我們剛剛在 ASCO 上公佈了 BNT327 的數據，儘管還為時過早，但我們確實認為很有希望。我們還有一個針對 NSCLC 的 FixVac 計畫。因此，我們的產品組合在非小細胞肺癌適應症方面已經達到了臨界點，我們正在計劃採取多管齊下的策略來執行。

So, while we found the data encouraging for cemiplimab, we decided to prioritize other programs, frankly, over this in the next phase. I think the important takeaway here though, of course, is that as Genmab now takes this program forward into Phase 3. We will still retain a economic stake in the program and a stake in the success, the future success of the program, but we won't fund Phase 3. And we think that's the right balance given the many shots on goal and exciting data that we're seeing from the portfolio.

因此，雖然我們發現 cemiplimab 的數據令人鼓舞，但坦白說，我們決定在下一階段優先考慮其他項目。當然，我認為這裡重要的一點是，隨著 Genmab 現在將該計劃推進到第三階段。 。

Thank you.

謝謝。

Yifeng Liu, HSBC Bank Plc.

劉一峰，匯豐銀行

Hello. Thank you for taking my question. I've got a question on margin progression. So, just how should we think about -- as your oncology pipeline progresses and also in the meantime, you've scaling up manufacturing and potentially investing in R&D and then SG&A, how should we think about that margin progression especially as you're launching your oncology for that in the future?

你好。謝謝你回答我的問題。我有一個關於保證金進展的問題。因此，我們應該如何考慮—隨著您的腫瘤學管道的進展，同時，您擴大了生產規模並可能投資於研發，然後是銷售、一般管理費用（SG&A），我們應該如何考慮利潤率的進展，特別是當您推出產品時您未來的腫瘤學方向是什麼？

Yeah. We couldn't hear you very well there, but just want to make sure we get the question right. So, your question is about how do we see margin progression over the next couple of years, specifically as it relates to oncology? Is that right?

是的。我們在那裡聽不清楚，但只是想確保我們正確回答問題。那麼，您的問題是我們如何看待未來幾年的利潤率進展，特別是與腫瘤學相關的利潤率進展？是對的嗎？

Yeah, I think the launches predominantly we see sort of in oncology space. And yeah, just the question on margin progression. Thank you.

是的，我認為我們看到的發布主要是在腫瘤學領域。是的，只是關於利潤進展的問題。謝謝。

Maybe I'll start. It's awfully difficult actually to understand you. You're fading away somewhat. I mean we're seeing that, of course, the margin that we have with our -- in our partnership with Pfizer is extremely good. I mean, we're close to 100% given the gross margin share structure that we have with Pfizer, so that's outstanding and certainly not normal.

也許我會開始。其實要理解你是非常困難的。你正在漸漸消失。我的意思是，我們當然看到，我們與輝瑞的合作關係中的利潤非常好。我的意思是，考慮到我們與輝瑞的毛利率份額結構，我們接近 100%，所以這是很突出的，當然也不正常。

In terms of oncology, going forward, we would expect that we see similar sort of margins as you see, with other companies. I think in looking forward in terms of internalized medicine, I think we got to wait a little bit on how we can -- when we can make some statements. In terms of the margin, but we're working very hard. We can assure you, we're working very hard to bring the costs down for internalized medicine candidates.

在腫瘤學方面，展望未來，我們預計我們會看到與其他公司類似的利潤率。我認為，在展望內化醫學方面，我認為我們必須等待一段時間，看看我們可以如何做——當我們可以發表一些聲明時。就利潤率而言，我們正在非常努力地工作。我們可以向您保證，我們正在非常努力地降低內化醫學候選人的成本。

Yeah, I would just add one point to that. So, in addition to what Jens just said about oncology, I think we're still expecting, of course, that our COVID business is going to still be for the next couple of years still a driver of our overall margins. And I think there we've got, as we pointed out in the past, a very attractive economic model vis-a-vis our partner, Pfizer, that we think will allow us to keep our overall operating profile quite attractive.

是的，我只想補充一點。因此，除了 Jens 剛才所說的關於腫瘤學的內容之外，我認為我們當然仍然期望我們的新冠業務在未來幾年內仍然是我們整體利潤的驅動力。我認為，正如我們過去指出的那樣，相對於我們的合作夥伴輝瑞，我們擁有一個非常有吸引力的經濟模式，我們認為這將使我們的整體營運狀況保持相當有吸引力。

Thank you.

謝謝。

Manoj Eradath, Jefferies.

馬諾傑·埃拉達斯，杰弗里斯。

Hi, this is actually Akash. So, you recently toplined data from your 111 trial in cutaneous melanoma. Our analysis suggests that combo arm would have a 24% delta versus roughly the 11% historical control rate for anti-PD-1 monotherapy in relapsed refractory patients. Is that the ballpark way to think about the ORR delta in this study?

嗨，這實際上是阿卡什。因此，您最近列出了 111 項皮膚黑色素瘤試驗的數據。我們的分析表明，對於復發難治性患者，聯合治療組的控制率將達到 24%，而抗 PD-1 單藥治療的歷史控制率約為 11%。這是本研究中考慮 ORR 增量的大致方法嗎？

And what would you have to see on PFS and OS to justify moving this forward into a Phase 3? And maybe just stepping back, what does this trial teach the BioNTech team about the ideal place for cancer vaccines? I feel like one of the lessons from your early iNeST data was that cancer vaccines were perhaps not well-suited for patients with metastatic late-stage disease and yet these patients were PD-1 refractory. So, how should we interpret that? Thank you.

您在 PFS 和 OS 上需要看到什麼才能證明將其推進到第 3 階段是合理的？或許退一步來說，這次試驗讓 BioNTech 團隊了解到癌症疫苗的理想地點是什麼？我覺得你們早期 iNeST 數據的教訓之一是，癌症疫苗可能不太適合患有轉移性晚期疾病的患者，但這些患者對 PD-1 有抗藥性。那麼，我們該如何解釋呢？謝謝。

Okay. Thank you. It's a great question. So, the personalized cancer vaccines have a manufacturing turnaround time in the range of six weeks to eight weeks. And therefore, in the metastatic setting, this type of vaccines are difficult to provide a clinical benefit since these patients rapidly progress. So, the statement of refers to the personalized vaccines.

好的。謝謝。這是一個很好的問題。因此，個人化癌症疫苗的生產週轉時間在六週到八週範圍內。因此，在轉移性環境中，此類疫苗很難提供臨床益處，因為這些患者進展迅速。因此，該聲明指的是個人化疫苗。

With regard to FixVac, we have seen that FixVac has two activities on the one side, the direct activity due to the adjuvant function. We are seeing a type-1 interferon response and have seen now in a number of indications, not only in melanoma, but also in lung cancer, objective responses in patients with advanced cancers. And we expect that the combination, particularly with a treatment that is able to control the disease for a certain time and we are particularly interested here in our ADC mRNA vaccine combinations, we will see a number of trials coming up in 2025 for this (technical difficulty) would be an exciting opportunity for our FixVac approach.

關於FixVac，我們看到FixVac一方面有兩種活性，一種是因為輔助功能而產生的直接活性。我們看到了 1 型乾擾素反應，現在已經在許多適應症中看到了晚期癌症患者的客觀反應，不僅在黑色素瘤中，而且在肺癌中。我們預計這種組合，特別是能夠在一定時間內控制疾病的治療方法，我們對我們的 ADC mRNA 疫苗組合特別感興趣，我們將在 2025 年看到對此進行大量試驗（技術難度）對於我們的FixVac 方法來說將是一個令人興奮的機會。

And maybe for the other part, I'll give to Ozlem.

也許另一部分，我會捐給奧茲萊姆。

Yes. Your question regarding BNT111 was about the clinical benefit which we would like to see as compared to standard-of-care. I cannot pre-empt our disclosures, which will come when we have mature data. But what I can say is, as, you know, standard-of-care objective response rate for this patient population is around 10%-ish. So, what we would like to see is something well above that, and this is also what our data shows us.

是的。您關於 BNT111 的問題是關於我們希望看到與標準護理相比的臨床益處。我無法阻止我們的揭露，當我們擁有成熟的數據時，我們就會進行披露。但我可以說的是，如您所知，該患者群體的標準護理客觀緩解率約為 10% 左右。因此，我們希望看到的是遠高於此的東西，這也是我們的數據向我們展示的。

We also want to see duration of response and also this looks clinically meaningful in the current dataset, which we have and then it's obviously also about safety. And what we see is that BNT111 as a FixVac based on RNA-lipoplex technology has a very manageable safety profile, and in combination with cemiplimab, we don't see anything which is surprising. So, there is no additive toxicity or so, which for us means that the clinical profile looks very promising for this patient population.

我們還希望看到反應的持續時間，而且這在我們擁有的當前資料集中看起來具有臨床意義，而且顯然也與安全性有關。我們看到的是，BNT111 作為基於 RNA-lipoplex 技術的 FixVac 具有非常易於管理的安全性，並且與 cemiplimab 結合使用，我們沒有看到任何令人驚訝的情況。因此，不存在附加毒性等，這對我們來說意味著該患者群體的臨床特徵看起來非常有希望。

Jessica Fye, JPMorgan Chase.

潔西卡‧菲伊，摩根大通。

Hey guys, good morning. Thanks for taking my question. It looks like the BioNTech topline guidance reflects a different expectation for 2024 COMIRNATY sales than what Pfizer's guidance would imply. What gives you confidence in achieving this result? And to the extent that part of the delta is driven by German pandemic preparedness contract, which I believe falls outside the collaboration, can you quantify what that is contributing to the guidance? Thank you.

嘿夥計們，早安。感謝您提出我的問題。看起來 BioNTech 的頂線指引反映了對 2024 年 COMIRNATY 銷售額的預期，與輝瑞的指引所暗示的不同。是什麼讓您有信心實現這項成果？在某種程度上，三角洲的一部分是由德國大流行病防備合約驅動的，我認為該合約不屬於合作範圍，您能否量化這對指導有何貢獻？謝謝。

Yeah, let me start and maybe Ryan want to jump in. So, I think we are very much aligned with Pfizer, in terms of our COMIRNATY expectations. We should keep in mind that Pfizer has reiterated its guidance. We did the same today. You should be aware that and take into account that we have a contract together with the European Union. They have approval in the UK, so I think for Europe this gives us some comfort in terms of how the full year should look like. Of course, there's always some insecurity in that respect, but in that sense, we feel good about it.

是的，讓我開始，也許瑞安想加入進來。我們應該記住，輝瑞重申了其指導。今天我們也做了同樣的事情。您應該意識到這一點並考慮到我們與歐盟簽訂了合約。他們在英國獲得了批准，所以我認為對於歐洲來說，這讓我們對全年的情況感到一些安慰。當然，在這方面總是存在一些不安全感，但從這個意義上說，我們對此感覺良好。

And in terms of the pandemic preparedness contract, we have confidentiality with the German government. So, we are a bit limited in really stating here some numbers. But you should expect that there is a significant amount of money being part of what we have reported in the first half. So, we have reported outside of COMIRNATY, if you look into the documents, [120 million]. So a big chunk of that in the first half comes from that pandemic preparedness contract.

就大流行防範合約而言，我們對德國政府保密。因此，我們在這裡實際陳述一些數字有點有限。但你應該預料到，我們上半年報告的內容中有大量資金。因此，如果您查看文件，我們已經在 COMIRNATY 之外進行了報告，[1.2 億]。因此，上半年的很大一部分來自大流行病防備合約。

Thank you.

謝謝。

Cory Kasimov, Evercore ISI.

科里·卡西莫夫，Evercore ISI。

Hi, thanks for taking the question. So, regarding the upcoming data at ESMO for BNT327 in EGFR-mutated non-small-cell lung cancer, there's obviously been a lot of attention of late on the competitive PD-1 VEGF bispecific that's out there. I'm curious like kind of based on what you know about that compound and the data presented to date, how similar or different do you expect your approach to be and how confident are you in having competitive data in this population? Thank you.

您好，感謝您提出問題。因此，關於 ESMO 即將公佈的 BNT327 在 EGFR 突變非小細胞肺癌中的數據，顯然最近人們對競爭性 PD-1 VEGF 雙特異性藥物給予了許多關注。我很好奇，根據您對該化合物的了解以及迄今為止提供的數據，您期望您的方法有多相似或不同，以及您對在這一人群中擁有競爭性數據有多大信心？謝謝。

Yeah. Thank you for the question. I can keep it short. I think the data that we are going to present will be competitive. And as you know, and the asset that BNT327 is now a molecule that is currently in evaluation in multiple indications at BioNTech and our collaboration partner Biotheus. And we will see additional studies to be announced end of this year, beginning next year.

是的。感謝你的提問。我可以保持簡短。我認為我們將提供的數據將具有競爭力。如您所知，BNT327 現在是一種分子，目前 BioNTech 和我們的合作夥伴 Biotheus 正在對多種適應症進行評估。我們將看到今年年底、明年開始將公佈更多研究。

Okay. Thank you.

好的。謝謝。

Chris Shibutani, Goldman Sachs.

克里斯·澀谷，高盛。

Yeah. Thank you. If I could just follow-up on the BNT327, noting from slide 10, it appears from the change in your pipeline plans are some additional trials there, which seem to signal that BioNTech is quite enthusiastic in that regard. I think it would be helpful the investor community was certainly attentive during ASCO to understand how your approach may differ from that of a competitor [Summit Therapeutics]? And in particular, can I ask you, are you looking to do any head-to-head trial involving KEYTRUDA? How are you thinking about sort of clinical development strategy that we can understand to be differentiated? Thank you.

是的。謝謝。如果我可以跟進 BNT327，從幻燈片 10 中註意到，從您的管道計劃的變化看來，那裡有一些額外的試驗，這似乎表明 BioNTech 在這方面相當熱情。我認為投資者群體在 ASCO 期間的關注肯定會有所幫助，以了解您的方法與競爭對手 [Summit Therapeutics] 的方法有何不同？特別是，我可以問您，您是否打算進行涉及 KEYTRUDA 的頭對頭試驗？您如何考慮我們可以理解的差異化臨床開發策略？謝謝。

Thank you for this question, Chris. We cannot comment on the strategy of others. But what we can say is that we think that BNT327 and this concept is highly compelling and qualifies as IO backbone for various combinations. And our approach here to be -- is to be broad with regard to the indications, which we will pursue also in potentially registrational trials.

謝謝你提出這個問題，克里斯。我們不能評論別人的策略。但我們可以說的是，我們認為 BNT327 和這個概念非常引人注目，並且有資格作為各種組合的 IO 骨幹。我們的方法是對適應症進行廣泛的研究，我們也將在潛在的註冊試驗中追求這一點。

We are well poised for that because our partner Biotheus has already a broad multi-indication program ongoing with a number of signal seeking cohorts in various indications with various standard-of-care regimen, so that we have a wealth of data already and can pick the indications and expand that as they mature.

我們已經為此做好了準備，因為我們的合作夥伴Biotheus 已經開展了一項廣泛的多適應症計劃，其中有許多針對不同適應症和標準護理方案的信號尋求隊列，因此我們已經擁有大量數據，可以選擇適應症並隨著它們的成熟而擴展。

And another dimension of diversification is that we see BNT327 as a backbone for many of our pipeline assets, our wholly-owned ones, but also those we have partnered because it has such a permissive synergistic prone mode of action.

多元化的另一個面向是，我們將 BNT327 視為我們許多管道資產、我們的全資管道資產以及我們合作夥伴的支柱，因為它具有如此寬鬆的協同作用模式。

Yeah. And regarding pembro. So we are seeing, of course, data from now a number of indications coming in and continue to mature. And yes, we have seen for data for which, for example, historical benchmark data are available for example, in triple negative breast cancer.

是的。關於彭布羅。當然，我們現在看到的數據有許多跡象正在出現並繼續成熟。是的，我們已經看到了一些數據，例如，三陰性乳癌的歷史基準數據。

And the extent of clinical benefit that we are observing BNT327 is really encouraging. And for any indication in which pembro is approved as a backbone, our plan would be of course to compare efficacy of BNT327 against the counterpart standard-of-care and pembro, we would compare against pembro.

我們觀察到 BNT327 的臨床效益程度確實令人鼓舞。對於 pembro 被批准為骨幹的任何跡象，我們的計劃當然是將 BNT327 與對應的護理標準和 pembro 的功效進行比較，我們將與 pembro 進行比較。

Thank you.

謝謝。

Terence Flynn, Morgan Stanley.

特倫斯‧弗林，摩根士丹利。

Hi, thanks for taking our questions. This is Chris on for Terence. We have a two-part question on BNT122 in colorectal cancer. You guided data by the end of 2025 or early 2026, but is there a potential for an interim analysis that would allow you to look at the data earlier? And then second, what will you and your partner Roche need to see in this trial in order to advance it into Phase 3? Thank you.

您好，感謝您回答我們的問題。這是克里斯替補特倫斯。我們有一個關於 BNT122 在結直腸癌中的問題，分為兩部分。您在 2025 年底或 2026 年初指導了數據，但是是否有可能進行中期分析，讓您能夠更早查看數據？其次，您和您的伴侶羅氏需要在這次試驗中看到什麼才能將其推進到第三階段？謝謝。

Yeah, we have hinted toward the potential analysis in end of 2025. As you know, the study is -- the endpoint is disease-free survival in this indication. And the general principle that we expect from individual cancer vaccines is that metastatic tumor cells which are present after surgery could be removed by inducing a T-cell response.

是的，我們已經暗示了 2025 年底的潛在分析。我們預期個別癌症疫苗的一般原則是，手術後存在的轉移性腫瘤細胞可以透過誘導 T 細胞反應來去除。

The indication that we have chosen is a ctDNA positive indication. That means based on the published data, we know that this patient population, who are ctDNA positive after surgery with the Stage II, Stage III colorectal cancer have a PFS in the range of 10 months to 12 months. And after chemotherapy and PFS, it's more around medium PFS is around more six months to eight months.

我們選擇的適應症是 ctDNA 陽性適應症。這意味著根據已發表的數據，我們知道，II 期、III 期結直腸癌手術後 ctDNA 呈陽性的患者群體的 PFS 在 10 個月至 12 個月範圍內。在化療和 PFS 之後，中等 PFS 約為六個月到八個月。

So that means at that time point, we would expect that at least part of the data would be matured, and then based on the results, we -- it will depend how the results are whether additional studies would be required at that time point or whether the data would be sufficient to continue and request potential regulatory steps.

因此，這意味著在那個時間點，我們預計至少部分數據將會成熟，然後根據結果，我們將取決於結果如何，是否需要在該時間點進行額外的研究，或者這些數據是否足以繼續並要求採取潛在的監管措施。

Great. Thank you.

偉大的。謝謝。

Simon Baker, Redburn Atlantic.

西蒙貝克，雷德本大西洋月刊。

Thank you for taking my question. It's a question on iNeST capacity. I wonder if you could give us an idea of the capacity that Mainz facility will give you in 2027. And also, you mentioned the ability to reduce the bottlenecks in vein-to-vein time. I wonder if you could give us an idea of where they stand and where this could currently go to. And just related to this, based on your comments on 122, is it right to assume that completion of that facility is rather 122 approval is not contingent on a completion of that facility? Thanks so much.

謝謝你回答我的問題。這是一個關於 iNeST 容量的問題。我想知道您能否向我們介紹美因茨工廠在 2027 年將為您提供的產能。我想知道您能否告訴我們他們的立場以及目前的發展方向。與此相關的是，根據您對 122 的評論，是否可以假設該設施的完成是正確的？非常感謝。

Yeah. So at the moment, we can't comment on the capacity of the facility that is being built, because we are still in process, further process improvements, increasing the overall capacity. And so, reliable numbers will be available end of 2025 for the capacity.

是的。因此，目前我們無法評論正在建設的設施的產能，因為我們仍在進行中，進一步改進工藝，提高整體產能。因此，到 2025 年底，我們將獲得可靠的容量數據。

But facility has been built with the idea that it could act as a pilot facility if one of the personalized vaccine products is approved at that time point. So, this is ongoing work and parallel for building this facility, which is intended to act as a potential pilot facility, we are expanding currently our clinical trial capacity to ensure that we can start additional trials in 2025 and later on.

但該設施的建設理念是，如果其中一種個人化疫苗產品當時獲得批准，它可以作為試點設施。因此，這是一項正在進行的工作，與建造該設施並行，旨在作為潛在的試點設施，我們目前正在擴大我們的臨床試驗能力，以確保我們可以在 2025 年及以後開始更多試驗。

And then, I think, as, Simon, you asked about bottlenecks in terms of vein-to-vein time.

然後，我想，正如西蒙，您詢問了靜脈間時間方面的瓶頸問題。

Yes, please.

是的，請。

Bottlenecks, yeah, so this is of course a completely new process, manufacturing a vaccine in real-time, and you can imagine and that every step must be validated. So this is -- we have established personalized manufacturing of mRNA vaccines for the first time in 2014. Since then we have been to two additional innovation cycles.

是的，瓶頸，所以這當然是一個全新的過程，即時製造疫苗，你可以想像，每一步都必須經過驗證。所以，我們在 2014 年首次建立了 mRNA 疫苗的個人化生產。

We have recently implemented additional change in their manufacturing, further reducing the turnaround plan. But still a manufacturing release of such a vaccine comes with multiple release tests for the individual batches. So, we are working on making these steps more robust, reducing the cost, and this will become more or less also the value driver of this approach being able to reduce the cost substantially and thereby allowing that this is an affordable approach, both be available for a large population of patients.

我們最近對他們的製造進行了額外的改變，進一步減少了周轉計畫。但這種疫苗的生產發布仍需要對各個批次進行多次發布測試。因此，我們正在努力使這些步驟更加穩健，降低成本，這或多或少也將成為該方法的價值驅動因素，能夠大幅降低成本，從而使這是一種負擔得起的方法，兩者都可用對於大量患者。

Thanks so much.

非常感謝。

Eliana Merle, UBS.

埃利安娜梅爾，瑞銀。

Hi, guys. Thanks so much for taking my question. Your slides mentioned starting the first novel combo trials at oncology this year. I guess just a strategic question in terms of your oncology combination strategy given the breadth of your portfolio. I guess, what are the programs that you are most excited about or prioritizing for combinations? Thanks.

嗨，大家好。非常感謝您提出我的問題。您的投影片提到今年開始在腫瘤學領域進行第一個新穎的組合試驗。考慮到您的投資組合的廣度，我想這只是您的腫瘤學組合策略的策略問題。我想，您最感興趣或最優先組合的項目是什麼？謝謝。

Thank you for the question, Eliana. We are in principle very excited about the IO ADC combination concept because we expect and also our preclinical data supports this that this is highly synergistic. And as you pointed out, we have started our first trial, which is the first of the series you will see where we use BNT327 as the IO backbone, which in the first trial is combined with our top two ADC from our partnership with Duality in multiple solid cancers. And this will be extended to additional ADCs from our pipeline to be combined with BNT327.

謝謝你的提問，艾利安娜。原則上我們對 IO ADC 組合概念感到非常興奮，因為我們期望並且我們的臨床前數據也支持這一點，即這是高度協同的。正如您所指出的，我們已經開始了第一個試驗，這是您將看到的系列中的第一個，我們使用BNT327 作為IO 主幹，在第一個試驗中，它與我們與Duality 合作的兩個頂級ADC 相結合。這將擴展到我們管道中的其他 ADC，與 BNT327 結合。

We are also very excited about a combination which is ongoing for quite some time, namely one of our priority assets, BNT211, which is our Claudin 6 CAR-T cell in combination with our vaccine. Which is designed in this case in a way that it specifically acts on the adoptively transferred CAR-T cells, and our data which shows that the vaccine in fact adds to the persistence and duration of adoptively transferred CAR-T cells is getting stronger and stronger with data maturing.

我們也對正在進行相當長一段時間的組合感到非常興奮，即我們的優先資產之一 BNT211，它是我們的 Claudin 6 CAR-T 細胞與我們的疫苗的組合。在這種情況下，它的設計方式是專門作用於過繼轉移的CAR-T 細胞，我們的數據表明，疫苗實際上增加了過繼轉移的CAR-T 細胞的持久性和持續時間，而且越來越強隨著數據的成熟。

Great. Thank you.

偉大的。謝謝。

John Newman, Canaccord Genuity.

約翰紐曼，Canaccord Genuity。

Hi, there. Thanks very much for taking my question. You're obviously in the midst of very active development for BNT327. I'm wondering specifically for the trials where you're combining with BNT325 your TROP2 ADC, do you see the potential down the road for accelerated approval in some of those indications? Thank you.

你好呀。非常感謝您提出我的問題。顯然，您正處於非常積極的 BNT327 開發之中。我特別想知道，對於您將 BNT325 與 TROP2 ADC 結合使用的試驗，您是否認為其中一些適應症有加速批准的潛力？謝謝。

Thank you. I think this is too early to say.

謝謝。我認為現在說這個還為時過早。

Okay. Thanks.

好的。謝謝。

Manos Mastorakis, Deutsche Bank.

馬諾斯‧馬斯托拉基斯，德意志銀行。

Hello, thank you for taking my question. Again on BNT327, just wanted to understand how you're thinking about the clinical trial design. Are you hoping or aiming to study mainly PD-L1 positive populations, or are you keen to keep that open and see what the data looks like after the fact? Thank you.

您好，謝謝您回答我的問題。再次關於 BNT327，只是想了解您如何看待臨床試驗設計。您是否希望或打算主要研究 PD-L1 陽性人群，或者您是否熱衷於保持開放並在事後查看數據是什麼樣的？謝謝。

Yeah, see, this is a good question. Let me share our view. So, the introduction of anti-PD-1 treatments led to the division of patient populations in PD-L1 high, PD-L1 low and PD-L1 negative population. The exciting observation that we made now in two indications is that the combination of tumor therapy plus BNT327 appears to be effective in a highly clinically meaningful manner also in the PD-L1 negative population. And this really provides the great opportunity.

是的，你看，這是個好問題。讓我分享我們的觀點。因此，抗PD-1治療的引入導致患者群體分為PD-L1高、PD-L1低和PD-L1陰性群體。我們現在在兩個適應症中進行的令人興奮的觀察是，腫瘤治療加 BNT327 的組合似乎在 PD-L1 陰性人群中也以具有高度臨床意義的方式有效。這確實提供了絕佳的機會。

So, we believe that BNT327 is not only something which is -- which could be better than existing PD-1 treatment, but we see the chance that we overcome the current classification of the patients into PD-L1 negative and PD-L1 positive patient population. This is exciting. And by this, of course, the patient populations would dramatically increase, and clinical trials could be done in a much easier way and standard-of-care could become easier manageable based on treatment combinations that are independent of PD-L1 [staining].

因此，我們相信 BNT327 不僅可能比現有的 PD-1 治療更好，而且我們有機會克服目前將患者分為 PD-L1 陰性和 PD-L1 陽性患者的分類人口。這真讓人興奮。當然，透過這種方式，患者群體將急劇增加，臨床試驗可以以更簡單的方式進行，並且基於獨立於 PD-L1 [染色] 的治療組合，護理標準可以變得更容易管理。

Thank you.

謝謝。

Thank you. This is all the time we have for questions today. I would like to hand back over to the speakers.

謝謝。這是我們今天所有的提問時間。我想將會議交還給發言者。

Yeah. Thank you very much for joining us today.

是的。非常感謝您今天加入我們。