Biontech SE (BNTX) 2024 Q3 法說會逐字稿

Welcome to BioNTech's third quarter 2024 earnings call. I would like to hand the call over to Michael Horowicz Director, Investor Relations. Please go ahead.

歡迎參加 BioNTech 2024 年第三季財報電話會議。我想將電話轉給投資者關係總監 Michael Horowicz。請繼續。

Thank you. Good morning and good afternoon. Thank you for joining BioNtech's Third Quarter 2024 Earnings Call. As a reminder, the slide that we will be using during this call and the corresponding press release we issued this morning can be found in the Investor Relations section of our website.

謝謝。早安，下午好。感謝您參加 BioNtech 的 2024 年第三季財報電話會議。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 comments disclaimer. Additional information about these statements and other risks are described in our filings with the U.S. Securities and Exchange Commission. Forward-looking statements in this call are subject to significant risks and uncertainties and speak only as of the date of this conference call. We undertake no obligation to update or revise any of these statements.

在下一張投影片上，您將看到我們的前瞻性評論免責聲明。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，並且僅代表本次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 Biotech's 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，Biotech 管理團隊的以下成員加入了我的行列：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, Michael. Welcome to all with us today. I will be keeping my introduction rather brief today. We made significant achievements during the third quarter, including advancements across our oncology pipeline and a strong start to the season for our COVID-19 vaccine franchise. Our progress in this quarter based on what has already been an impactful year. I would like to highlight achievements in three areas. First, with regard to our COVID-19 vaccine leadership. We have successfully launched updated vaccines targeting the latest variance, distribution now underway in multiple regions globally.

謝謝你，麥可。歡迎大家今天和我們一起來。今天我的介紹將相當短。我們在第三季度取得了重大成就，包括我們的腫瘤學產品線的進步以及我們的 COVID-19 疫苗系列的強勁開局。我們在本季取得的進展是基於已經具有影響力的一年。我想強調三個領域的成就。首先，關於我們在 COVID-19 疫苗方面的領導地位。我們已成功推出針對最新變異的更新疫苗，目前正在全球多個地區進行分發。

In oncology, we have presented our progress in two strategic priority areas, namely our bispecific immunomodulated BNT327, partnered with [ Biocell ] and our mRNA cancer vaccine portfolio. As part of our pipeline progress, we shared numerous clinical updates across our oncology pipeline at the ESMO Congress. (inaudible), our partner bios has kicked off the board global development of BNT327, our bispecific antibody targeting PD-L1 and [ VGFA ]. The data sets presented at ESMO [ a ] conferences earlier this year, support the cancer potential of this priority asset and support our clinical development plans that we will touch on today and discuss in greater detail at our innovation series next week. We took significant steps forward in the execution of our clinical development plan this quarter and dosed the first patients in two optimization studies in small cell lung cancer and triple (inaudible) breast cancer to inform the pivotal studies than in both indications.

在腫瘤學方面，我們展示了我們在兩個策略優先領域的進展，即我們與 [ Biocell ] 合作的雙特異性免疫調節 BNT327 和我們的 mRNA 癌症疫苗產品組合。作為我們管道進展的一部分，我們在 ESMO 大會上分享了我們腫瘤管道的大量臨床更新。 （聽不清楚），我們的合作夥伴 BIOS 已啟動 BNT327 的全球開發，這是我們針對 PD-L1 和 [ VGFA ] 的雙特異性抗體。今年稍早在 ESMO [a] 會議上提出的數據集支持了這項優先資產的癌症潛力，並支持我們今天將討論的臨床開發計劃，並在下週的創新系列中更詳細地討論。本季我們在執行臨床開發計劃方面取得了重大進展，並對小細胞肺癌和三重（聽不清楚）乳腺癌的兩項優化研究中的第一批患者進行了給藥，為這兩種適應症的關鍵研究提供了資訊。

With regard to our mRNA vaccine portfolio, we announced earlier in the quarter that our off-the-shelf FixVac mRNA cancer vaccine candidate, BNT111, met the primary endpoint in the ongoing randomized two trials evaluating BNT111 in combination with a general anti-PD-1 agent [ cemiplimab ] in patients with Stage 3 and Stage 4 cutaneous melanoma. This preliminary result has caused our belief in the transformative potential of our proprietary mRNA vaccine technology, which is a key pillar of our oncology strategy. Moreover, we have taken another step to broaden our personalized mRNA cancer vaccine development program. We and our partner, Genentech have initiated a new randomized controlled Phase II clinical trial evaluating our personalized cancer vaccine candidate in patients with bladder cancer in the (inaudible) setting in combination with immune checkpoint inhibition. Our personalized vaccine program now includes four ongoing Phase II clinical trials.

關於我們的 mRNA 疫苗組合，我們在本季度早些時候宣布，我們的現成 FixVac mRNA 癌症候選疫苗 BNT111 在正在進行的隨機兩項試驗中達到了主要終點，該試驗評估了 BNT111 與通用抗 PD- 1種藥物[cemiplimab] 用於治療3 期和4 期皮膚黑色素瘤患者。這項初步結果讓我們相信我們專有的 mRNA 疫苗技術具有變革潛力，這是我們腫瘤學策略的關鍵支柱。此外，我們採取了進一步擴大我們的個人化 mRNA 癌症疫苗開發計劃的措施。我們和我們的伴侶基因泰克啟動了一項新的隨機對照II 期臨床試驗，評估我們的個人化癌症候選疫苗與免疫檢查點抑制相結合，在（聽不清楚）情況下對膀胱癌患者的影響。我們的個人化疫苗計劃現在包括四項正在進行的第二期臨床試驗。

In addition, during Q3, we had our [ in-house covert AI day ] where we highlighted our in-house AI company, InstaDeep and provided an overview of BioNtech's collective AI capabilities. This was an exciting event where we showcased our commitment to building state of the art AI.

此外，在第三季度，我們舉辦了[內部隱藏人工智慧日]，重點介紹了我們的內部人工智慧公司 InstaDeep，並概述了 BioNtech 的集體人工智慧能力。這是一次令人興奮的活動，我們展示了我們對建造最先進的人工智慧的承諾。

Before turning over to [ Ozlem ] for more detailed coverage of these achievements, let me remind you our overarching strategy for oncology. Biotech was established the ambition to revolutionize cancer treatment to the development of mRNA-based immunotherapies particularly to personalized cancer vaccines. This approach remains at the forefront of our efforts to pioneer next wave of cancer treatments, aiming to tailor therapies to the individual genetic makeup of each patient's tumor. Building on this foundation, we have systematically assessed next-generation immune modulator with a focus on bispecific molecules that can engage more than 1 target. BNT327, our bispecific antibody targeting PD-L1 and VGFA has emerged as a key molecule in our pipeline. We believe that BNT327 has the potential to serve as a foundational component in the treatment of aliments from multiple cancer types, enhancing the effectiveness of our Terra project mRNA cancer vaccines and other therapies to its dual targeting mechanism. Complementing these mechanisms of action we have recently expanded our portfolio to include targets immunotherapies such as antibody drug [ cone new ] gates and CAR-T cell therapies. These modalities offer precise mechanisms for attacking cancers, providing new avenues for combination therapies, particularly for fighting large metastatic tumors.

在轉向 [Ozlem] 更詳細地報道這些成就之前，讓我提醒您我們的腫瘤學總體戰略。 Biotech 立志徹底改變癌症治療，開發基於 mRNA 的免疫療法，特別是個人化癌症疫苗。這種方法仍然處於我們開拓下一波癌症治療的最前沿，旨在根據每位患者腫瘤的個別基因組成客製化治療方案。在此基礎上，我們系統性地評估了下一代免疫調節劑，重點在於可以參與多個標靶的雙特異性分子。 BNT327 是我們針對 PD-L1 和 VGFA 的雙特異性抗體，已成為我們管道中的關鍵分子。我們相信，BNT327 有潛力成為治療多種癌症類型的基礎成分，從而增強我們的 Terra 計畫 mRNA 癌症疫苗和其他療法對其雙重標靶機制的有效性。為了補充這些作用機制，我們最近擴大了我們的產品組合，包括標靶免疫療法，例如抗體藥物 [cone new] 門和 CAR-T 細胞療法。這些方式提供了攻擊癌症的精確機制，為聯合療法，特別是對抗大型轉移性腫瘤提供了新途徑。

Our integrated long-term approach will combine the synergistic therapeutics platform to optimize cancer treatment. Our strategy aims not only to address the existing challenges in cancer care, but also to significantly long-term survival rates even in patients with advanced disease state. By continually evaluating the effectiveness of usual compounds and innovative combinations, we can better identify the most promising treatment strategies for specific patient populations. Today, as (inaudible) discussed in more detail our progress on BNP327 and our outstanding efforts on our therapeutic mRNA cancer vaccine fund, two profit key pillars of our strategy. Before handing over, I would like to thank you all for your ongoing support. We entered a truly exciting period for BioNTech and progress towards our founding vision. Thank you.

我們的綜合長期方法將結合協同治療平台來優化癌症治療。我們的策略不僅旨在解決癌症治療中現有的挑戰，而且旨在提高晚期疾病患者的長期存活率。透過不斷評估常用化合物和創新組合的有效性，我們可以更好地為特定患者群體確定最有希望的治療策略。今天，正如（聽不清楚）更詳細地討論了我們在 BNP327 上的進展以及我們在治療性 mRNA 癌症疫苗基金方面所做的傑出努力，這是我們策略的兩個利潤關鍵支柱。在移交之前，我要感謝大家一直以來的支持。我們進入了 BioNTech 真正激動人心的時期，並朝著我們的創始願景取得了進展。謝謝。

Thank you, Ugur. Glad to be speaking with everyone today. I will begin with our COVID-19 franchise. Ahead of this vaccination season, regulatory and public health authorities at five vaccine manufacturers to revise the antigen composition for the authorized COVID-19 vaccines in line with tenants epidemiologic data. The continuous evolution of SARS-CoV-2 and the emergence of variants have led to regionally different recommendations for the (inaudible) strain selection. We have been able to rapidly meet these different requirements due to the flexibility of our mRNA technology, which enables us to adapt our construct on relatively short notice. .

謝謝你，烏古爾。很高興今天能和大家交談。我將從我們的 COVID-19 特許經營權開始。在本疫苗接種季節到來之前，五家疫苗製造商的監管和公共衛生當局將根據租戶流行病學數據修改授權的 COVID-19 疫苗的抗原成分。 SARS-CoV-2 的不斷進化和變種的出現導致了針對（聽不清楚）菌株選擇的區域性不同建議。由於 mRNA 技術的靈活性，我們能夠快速滿足這些不同的要求，這使我們能夠在相對較短的時間內調整我們的構建體。 。

In Europe, less than three weeks after the regulatory of our year, we commented the use of JN1 spike antigen in the COVID-19 vaccine toward '24, '25 season we were able to submit our application to a European regulator and we began rolling out our update shortly after appropriate (inaudible) are ready to live. Anticipating the regional differences, we followed up with development and submission for our (inaudible) KP2 adapted vaccine.

在歐洲，今年監管後不到三週，我們評論了在 24、25 年季節的 COVID-19 疫苗中使用 JN1 刺突抗原，我們能夠向歐洲監管機構提交申請，並開始滾動在適當的（聽不見清）準備好後不久我們就會發布更新。考慮到區域差異，我們跟進了（聽不清楚）KP2 適應疫苗的開發和提交。

In the U.K., the regulator posted our JN1 adapted COVID-19 vaccine in July and our KP2 adapted COVID-19 in early October. In the United States and Canada, regulatory authorities, recommended the use of KP2 as a preferred (inaudible) for the presence (inaudible). Less than 2 weeks after recommendation, we initiated our rolling submission with the U.S. FDA has received approval of our KP2 adaptive vaccine in August.

在英國，監管機構於 7 月發布了我們的 JN1 適應的 COVID-19 疫苗，並於 10 月初發布了我們的 KP2 適應的 COVID-19 疫苗。在美國和加拿大，監管機構建議使用 KP2 作為首選（聽不清楚）的存在（聽不清楚）。推薦後不到兩週，我們就開始向美國 FDA 滾動提交申請，我們的 KP2 適應性疫苗已於 8 月獲得批准。

In Japan, we received our JN1 approval in early August. These early strain recommendations and approval have allowed for the timely delivery and earlier availability of vaccines for four vaccination campaign.

在日本，我們於 8 月初獲得了 JN1 批准。這些早期病毒株建議和批准使得四次疫苗接種活動能夠及時交付和更早獲得疫苗。

Execution at such speed was enabled by our continued surveillance and analysis of areas of concern by the strength of our mRNA technology, which allows for scalable rapid production and due to our expertise in navigating the regulatory landscape on a global scale. We will continue to monitor our evolving epidemiology of COVID-19 and remain prepared to develop vaccines with adapted antigenic composition in line with regulatory recommendations. COVID-19 transitions to an endemic infection pattern. -- data on a weekly new hospital admission due to infections caused by (inaudible) and (inaudible) influenza show different patterns of seasonality. This past season, like in the prior year, COVID-19 disease related hospitalization had two primary peaks, one in the winter and an additional one in summer. In contrast, for influenza, we predominantly see increases in hospitalizations in the winter. The emergence of new variants, coupled with a weighing of both vaccine and infection induced in immunity indicates that the susceptibility to COVID-19 infection remains a concern after the winter vaccination season. These different patterns of seasonality of Influenza and COVID-19 may have an impact on regulatory guidelines to facilitate protection throughout the year.

如此速度的執行得益於我們憑藉 mRNA 技術的優勢對關注領域進行持續監控和分析，從而實現可擴展的快速生產，並且得益於我們在全球範圍內應對監管環境的專業知識。我們將繼續監測不斷變化的 COVID-19 流行病學，並隨時準備根據監管建議開發具有調整抗原成分的疫苗。 COVID-19 轉變為地方性感染模式。 -- 每週因（聽不清楚）和（聽不清楚）流感引起的感染而入院的數據顯示出不同的季節性模式。與去年一樣，上個季度，與 COVID-19 疾病相關的住院有兩個主要高峰，一個在冬季，另一個在夏季。相較之下，對於流感，我們主要看到冬季住院人數的增加。新變種的出現，加上疫苗和免疫誘導感染的權衡表明，冬季疫苗接種季節過後，對 COVID-19 感染的易感性仍然是一個令人擔憂的問題。流感和 COVID-19 的這些不同的季節性模式可能會對促進全年保護的監管指南產生影響。

Recently, U.S. authorities recommended order and immunocompromised individuals received an additional COVID-19 vaccine dose administration of additional doses, (inaudible) season could contribute to improved vaccine coverage over time, mitigating the risks associated with evolving COVID-19 variance. Given our current understanding of COVID-19 seasonality its burden on health care systems, we are proud that our vaccine can contribute to mitigate severe infection and protect people around the world from COVID-19 replacement hospitalizations index.

最近，美國當局建議免疫功能低下的個人接受額外的COVID-19 疫苗劑量管理，（聽不清楚）季節可能有助於隨著時間的推移提高疫苗覆蓋率，從而減輕與不斷變化的COVID-19 變異相關的風險。鑑於我們目前對COVID-19 季節性及其對醫療保健系統負擔的了解，我們感到自豪的是，我們的疫苗有助於減輕嚴重感染並保護世界各地的人們免受COVID-19 替代住院指數的影響。

Turning now to our oncology pipeline. Our multi-platform immuno-oncology clinical pipeline is continuing to advance, and it is a rich source from a strategically planned novel-novel combinations that we consider a key pillar of our vision for oncology. As you can see, two of our modalities, namely mRNA and immune non-ocular [ data IO ] are dominant year represented in our pipeline, and particularly so in the advanced clinical stages. This is a testament to our drive towards mid- to late-stage clients as part of our position to achieve multiple product launches in oncology by 2030. It is (inaudible) a special focus on our mRNA cancer vaccine portfolio and our BNT327 setup clinical development program with the latter becoming our platform for unique combinations with several of our other assets, in particular [OIDC ].

現在轉向我們的腫瘤學管道。我們的多平台免疫腫瘤學臨床管道正在不斷推進，它是策略規劃的新穎組合的豐富來源，我們認為這是我們腫瘤學願景的關鍵支柱。正如您所看到的，我們的兩種模式，即 mRNA 和免疫非眼[數據 IO] 在我們的管道中占主導地位，尤其是在高級臨床階段。這證明了我們對中後期客戶的努力，也是我們在 2030 年實現腫瘤學多種產品推出的目標的一部分。後者成為我們與其他幾個資產（特別是[OIDC]）進行獨特組合的平台。

BNT327 is a bispecific antibody candidate that targets both PD-L1 and VGFA that's combined two complementary functions. The binding of BNT327 to PD-L1 tumor stores effectors (inaudible) of tumor cells and enrich the GLA non-neutralization within the tumor micro environment to create a cycle of ventricular normalization, improved blood flow and reduce hypoxia with the tumors. BNT327 also reverses the negative effect of the GFA signaling on the infiltration and activation of immune cells inter-tumor microenvironment. By co-localizing the blockade of PD-L1 and VGFA signaling to the tumor, BNT327 is designed to deliver superior anti-tumor compared to individual targeting of PD-L1 and VGFA with the potential to minimize worth events associated with systemic anti VGFA (inaudible). With the entire PD-L1 and VGFA antagonistic mechanisms being navigated across numerous tumor types and in some cases, in combination, we have a role for a development of BNT327.

BNT327 是一種雙特異性候選抗體，同時靶向 PD-L1 和 VGFA，結合了兩種互補功能。 BNT327 與 PD-L1 腫瘤的結合可儲存腫瘤細胞的效應子（聽不清楚），並豐富腫瘤微環境內的 GLA 非中和作用，從而創建心室正常化循環、改善血流並減少腫瘤缺氧。 BNT327 還可以逆轉 GFA 訊號傳導對腫瘤間微環境中免疫細胞浸潤和活化的負面影響。透過將PD-L1 和VGFA 訊號傳導共同阻斷至腫瘤，BNT327 旨在提供比單獨靶向PD-L1 和VGFA 更出色的抗腫瘤作用，並有可能最大限度地減少與全身性抗VGFA 相關的價值事件（聽不清楚） ）。隨著整個 PD-L1 和 VGFA 拮抗機制在多種腫瘤類型中發揮作用，在某些情況下，結合起來，我們可以在 BNT327 的開發中發揮作用。

We and our partner (inaudible) have treated over 700 patients in clinical trials across a wide range of clinical indications with BNT327 either as monotherapy or in combination with various standard of care (inaudible). In these early studies, BNT327 demonstrated encouraging activity as mono and combo therapy with a favorable safety profile that was shown to be generally well manageable and in line with worst events and immune related to work observed with other purity targeted PD-L1.

我們和我們的合作夥伴（聽不清楚）已經在臨床試驗中使用 BNT327 作為單一療法或與各種標準護理相結合（聽不清楚）治療了 700 多名患者，涉及廣泛的臨床適應症。在這些早期研究中，BNT327 作為單藥和組合療法表現出令人鼓舞的活性，具有良好的安全性，且總體上易於控制，並且與使用其他純度靶向PD-L1 觀察到的最壞事件和免疫相關的工作一致。

The data also indicates robust single-agent activity for BNT327 and in combination with standard of care chemotherapy across tumor type and treatment plans. This extensive data collection provides us with the foundation for making data-driven decisions on potential indications and patient cohorts for future potentially registrational study. One of the indications we have selected for further development in triple-negative breast cancer, TNBC, the type of breast cancer with the poorest outcomes. In first sign metastatic TNBC, we have observed a high objective response rate with encouraging responses and long progression-free survival for BMT327 in combination with (inaudible). As now this year, we presented updated efficacy and safety findings from the ongoing Phase I/II study in this indication across the 10 to 3 population of 42 patients, we observed a confirmed objective response rate of 74%. Importantly, which posted were shown clinically meaningful irrespective of PD-L1 status. In patients with PD-L1 combined positive score of CPS smaller than one confirmed of objective response rate was 76.9% in patients with PD-L1 CPS between one and 10, the confirmed objective response was 52%. And in patients with tier 1 CPS higher, the control of trend rate was 100%.

數據還表明，BNT327 與跨腫瘤類型和治療計劃的標準護理化療相結合具有強大的單一活性。這種廣泛的數據收集為我們為未來潛在的註冊研究的潛在適應症和患者隊列做出數據驅動的決策奠定了基礎。我們選擇進一步開發三陰性乳癌（TNBC）的適應症之一，這是一種預後最差的乳癌類型。在第一徵兆轉移性 TNBC 中，我們觀察到 BMT327 合併使用（聽不清楚）具有較高的客觀緩解率、令人鼓舞的緩解和較長的無惡化存活期。截至今年，我們在 42 名患者的 10 至 3 組中展示了正在進行的 I/II 期研究的最新療效和安全性結果，我們觀察到經證實的客觀緩解率為 74%。重要的是，無論 PD-L1 狀態如何，發布的內容都顯示出臨床意義。在PD-L1合併CPS陽性評分小於1的患者中，證實的客觀緩解率為76.9%；在PD-L1 CPS在1到10之間的患者中，證實的客觀緩解率為52%。而在1級CPS較高的患者中，趨勢控制率為100%。

We also served record tumor shrinkage with a median time to response of 1.9 months and an encouraging median duration of response of 11.7 in the intense treat population. Treatment-related adverse events of Grade 3 or (inaudible) occurred in 57% of patients leading to treatment less continuation in 4.8%.

我們也實現了創紀錄的腫瘤縮小，在強化治療族群中，中位反應時間為 1.9 個月，中位反應持續時間令人鼓舞，為 11.7 個月。 57% 的患者發生 3 級或（聽不清楚）的治療相關不良事件，導致 4.8% 的患者減少繼續治療。

In summary, we are encouraged by the potential of BNT327 in combination with chemotherapy to offer clinically meaningful antitumor activity regard to of PD-L1 status and by manageable toxicity. We have prioritized the planning of global trials in TNBC where unmatched needs remains high, particularly for the with PD-L1 negative tumors, if they are not eligible for current anti-PD-1 treatment.

總而言之，我們對 BNT327 與化療聯合使用的潛力感到鼓舞，在 PD-L1 狀態方面提供具有臨床意義的抗腫瘤活性，並且毒性可控。我們優先規劃 TNBC 的全球試驗，因為 TNBC 的需求仍然很高，特別是對於 PD-L1 陰性腫瘤，如果它們不符合目前的抗 PD-1 治療條件的話。

We will be presenting additional data in first line TNBC at the San Antonio Breast Cancer Conference next month. We believe that BNT327 and this (inaudible) class at large are showing a single validated mechanism of action, where dose optimization price in the U.S. initiated recently allow us to create a robust scientific data package to inform the global development of (inaudible) and tick off three waves of focus development.

我們將在下個月的聖安東尼奧乳癌會議上展示更多第一線 TNBC 的數據。我們相信BNT327 和這一類（聽不清楚）總體上顯示出一種經過驗證的單一作用機制，美國最近發起的劑量優化價格使我們能夠創建一個強大的科學資料包，為（聽不清楚）和蜱蟲的全球發展提供資訊掀起三波重點發展浪潮。

We plan to execute (inaudible) and move broadly into three ways. First, we are investigating the BNT327 combination in standard of care chemotherapies as an (inaudible) fast-to-market approach. The data generated by our partner, (inaudible), that have driven our decision to prioritize the planning of registrational trials in small cell lung cancer, TNBC and non-(inaudible) lung cancer due to start in the next few months. Second, we plan to evaluate BNT327 with our ADC isolate tumor types and additional key indications. The first exploratory trial evaluating novel BNT327 commissions was started earlier this year with our proprietary TROP2, ADC '23, '25. These non combinations may open up new areas of activity for BNT327. We plan to initiate additional trials evaluating other proprietary combinations of BNT327 with before year-end and over the next 12 months.

我們計劃執行（聽不清楚）並大致分為三種方式。首先，我們正在研究標準護理化療中的 BNT327 組合作為一種（聽不清楚）快速上市方法。我們的合作夥伴（聽不清楚）產生的數據促使我們決定優先規劃小細胞肺癌、TNBC 和非（聽不清楚）肺癌的註冊試驗，這些試驗將於未來幾個月開始。其次，我們計劃使用我們的 ADC 分離腫瘤類型和其他關鍵適應症來評估 BNT327。評估新型 BNT327 委託的第一個探索性試驗於今年早些時候開始，使用我們專有的 TROP2、ADC '23、'25。這些非組合可能為 BNT327 開闢新的活動領域。我們計劃在年底前和未來 12 個月內啟動更多試驗，評估 BNT327 的其他專有組合。

Lastly, we aim to expand with standard of care chemotherapy and moral combinations beyond ADCs across (inaudible) and treatment settings. It is a strategic goal for us to explore BNT327 as part of normal and other combinations.

最後，我們的目標是將標準護理化療和道德組合擴展到 ADC 以外的（聽不清楚）和治療環境。探索BNT327作為普通組合和其他組合的一部分是我們的策略目標。

Given our experienced clinical development team, which has an increasingly global footprint, our strong financial position and unique pipeline. We are confident that we are well positioned to efficiently execute on this comprehensive clinical development strategy. Now to the other cornerstone of our oncology portfolio, our mRNA cancer vaccine platform, IMS and (inaudible). (inaudible) target neoantigens necrosometic mutations in cancer cells that are unique to the individual tumor. I see our investigational vaccines that are being codeveloped with our partner Genentech and are manufactured on-demand and personalized to win with your patients. FixVac vaccines target mitosis non-mutated tumor antigens shared by the majority of patients with a given tumor type and are also shared cancer vaccine chemicals. The computational approaches to discovering and testing these to different types of target antigens of our core company IMS and FixVac both use the same vaccine and delivery technology minor proprietary MRAS platform. Today, we have ongoing trials in multiple disease settings and indications across on we have reported relation in clinical data over the last couple of years and future data updates from multiple trials shown on this plan. aggregate data that we have reported in the past across IMS and FixVac trials indicate that Urogen mRNA LPS-based vaccines are a manageable and much we might safety profile as single agents in combination with anti-PD-1, PD-L1 compound and in combination with chemotherapy. Our data also indicates that our uridine mRNA LP based vaccine platform is highly proficient in inducing and expanding high magnitude functional and longest T cell responses in the majority of patients, which is a prerequisite for clinical activity.

鑑於我們經驗豐富的臨床開發團隊（其業務遍及全球）、強大的財務狀況和獨特的產品線。我們相信，我們有能力有效地執行這項全面的臨床開發策略。現在談談我們腫瘤學產品組合的另一個基石，我們的 mRNA 癌症疫苗平台、IMS 和（聽不清楚）。 （聽不清楚）針對單一腫瘤特有的癌細胞中的新抗原壞死體突變。我看到我們的研究性疫苗正在與我們的合作夥伴基因泰克共同開發，並且是按需和個性化生產的，以贏得您的患者的支持。 FixVac 疫苗針對大多數特定腫瘤類型患者共有的有絲分裂非突變腫瘤抗原，也是共有的癌症疫苗化學物質。我們的核心公司 IMS 和 FixVac 發現和測試不同類型目標抗原的計算方法都使用相同的疫苗和交付技術（次要專有 MRAS 平台）。今天，我們正在對多種疾病環境和適應症進行試驗，我們報告了過去幾年臨床數據的關係以及該計劃中顯示的多項試驗的未來數據更新。我們過去在IMS 和FixVac 試驗中報告的匯總數據表明，基於Urogen mRNA LPS 的疫苗是一種易於管理的藥物，並且作為單一藥物與抗PD-1、PD-L1 化合物組合以及聯合用藥，我們可能會對其安全性進行評估。我們的數據還表明，我們基於尿苷 mRNA LP 的疫苗平台能夠高度熟練地在大多數患者中誘導和擴大高強度的功能性和最長的 T 細胞反應，這是臨床活動的先決條件。

Furthermore, our data from small (inaudible) patient cohorts indicates clinical activity alone and in combination with (inaudible) PD-L1 and PD-1 treatment. In our fixed back program, I would like to highlight two vaccine candidates for which we have important updates during the quarter. For BNT113, our mRNA vaccine candidate against HPV16-positive cancer, we presented data from (inaudible) at the ESMO conference. One data set was from the safety run in cohort of or potentially registrational Phase II randomized trial and had merit. This trial evaluates BNT113 in combination with emporium net versus payroll alone in first-line HPV16-positive PD-L1 positive had in net came sarcolemma. The data supports the tolerability of BNT113 and clinical activity in combination with pembro and the induction of higher magnitude de novo T cell responses against HPV16 antigens encoded in this vaccine. In summary, we are encouraged by the data in the safety cohort.

此外，我們來自小型（聽不清楚）患者群組的數據表明單獨的臨床活性以及與（聽不清楚）PD-L1 和 PD-1 治療相結合的臨床活性。在我們的固定背部計劃中，我想重點介紹兩種候選疫苗，我們在本季有重要更新。對於 BNT113（我們針對 HPV16 陽性癌症的 mRNA 候選疫苗），我們在 ESMO 會議上提供了（聽不清楚）數據。一組數據來自一組或可能註冊的 II 期隨機試驗的安全性運行，並且具有優點。該試驗評估了 BNT113 合併商場網與單獨薪資治療第一線 HPV16 陽性 PD-L1 陽性網來肌膜的情況。該數據支持 BNT113 的耐受性和與 pembro 組合的臨床活性，以及​​針對該疫苗中編碼的 HPV16 抗原誘導更高強度的從頭 T 細胞反應。總之，我們對安全隊列中的資料感到鼓舞。

The second data set from investigator initiated Phase I/II trials, exploring the NT1 person as single agent in patients localized in metastatic (inaudible) and (inaudible) other HPV16 driven carcinoma, further confirmed positive safety and immunogenicity finding. We have reported top line findings for BNT111, which is being investigated in patients with anti-1 relapsed or refractory melanoma BNT111 includes four melanoma associated antigens, which collectively cover more than 90% of melanoma patients and are highly immunogenic. In the randomized two clinical trial conducted in collaboration with Regeneron, BNT111 is being evaluated in combination with their anti-PD-1 contain. The trade in more 184 patients with PD-L1 refractory unresectable Stage 3 or 4 for and comprises prearm of which one evaluates the combination and the other to measure the activity of BNT111 alone or simply map. The trial met its primary endpoint, achieving a statistically significant improvement in ORR objective response rate in BNT111 similar combination as compared to a historical control of anti-PD-1 monotherapy in relapsed refractory patients based on live-stage chemical trials that established make business ORR for monotherapy checkpoint inhibitors in this setting for patient population.

研究者發起的I/II 期試驗的第二個數據集，探索NT1 作為單一藥物治療轉移性（聽不清楚）和（聽不清楚）其他HPV16 驅動的癌症患者，進一步證實了積極的安全性和免疫原性發現。我們報告了BNT111 的主要發現，該藥物正在抗1 復發或難治性黑色素瘤患者中進行研究。性。在與 Regeneron 合作進行的隨機兩項臨床試驗中，BNT111 正在與其抗 PD-1 藥物聯合進行評估。對超過 184 名 PD-L1 難治性不可切除的 3 期或 4 期患者進行了交易，包括預先治療，其中一個評估組合，另一個單獨測量 BNT111 的活性或簡單繪製圖譜。該試驗達到了其主要終點，與復發難治性患者中抗PD-1 單藥治療的歷史對照相比，BNT111 類似組合的ORR 客觀緩解率取得了統計學上的顯著改善，這是基於建立了商業ORR 的活體階段化學試驗在這種情況下，針對患者族群進行單藥治療檢查點抑制劑。

The results we saw in the Phase II study are consistent with results seen and we're proceeding on two trial in patients with advanced melanoma who have exhausted frequent option. BNT111 a lower oil combination with anti-PD-1 compound induced high magnitude T-cell responses against at least one targeted tumor related antigen in all analyzed patients, most of which were not detected prior to losing (inaudible). We plan to present the full data from the primary levers at a medical conference.

我們在 II 期研究中看到的結果與所看到的結果一致，我們正在對已用盡常見選擇的晚期黑色素瘤患者進行兩項試驗。 BNT111 是一種低油與抗PD-1 化合物的組合，在所有分析的患者中誘導針對至少一種靶向腫瘤相關抗原的高強度T 細胞反應，其中大多數在失去之前未檢測到（聽不見清）。我們計劃在醫學會議上展示主要槓桿的完整數據。

The various FixVac data updates provided in Q3 are a proof of concept in three dimensions. Firstly, for our mRNA cancer vaccine technology that uses uridine mRNA chemistry. A noncoding (inaudible) that is engineered for commercialization performance and our proprietary like formulation for systemic delivery, which we are using in both IMS and FixVac vaccine.

第三季提供的各種 FixVac 資料更新是三個維度的概念驗證。首先，我們的 mRNA 癌症疫苗技術使用尿苷 mRNA 化學。一種非編碼（聽不清楚），專為商業化性能而設計，以及我們用於全身遞送的專有配方，我們在 IMS 和 FixVac 疫苗中使用。

Secondly, for our computational approaches for the activities and targets for our indication specific fixed red program candidates. Now see a proof of concept for our strategy to combine synergistic modalities in the case of BNT111 and (inaudible) with established immune (inaudible) inhibitor treatment.

其次，對於我們針對特定固定紅色計劃候選者的活動和目標的計算方法。現在看到我們策略的概念證明，該策略將 BNT111 和（聽不清楚）的協同模式與已建立的免疫（聽不清楚）抑制劑治療相結合。

Moving to [Outogen Saunoral], also BNT122, our individualized mRNA cancer vaccine candidate based on our IMS platform in development with our partner Genentech. We consider individualized cancer vaccines as a potential medical breakthrough is addressing by high under medical need of resectable cancer and acumen or minimal disease treatment setting. We have demonstrated that our individualized vaccine can be deduced in patients with atomic pancreatic cancer can induce de novo responses that are specific to the individual muting tumor neoantigens and that the risk of recurrence of cancer for patients when they're being induced immune responses was reduced over a 3-year follow-up period. We have two active randomized Phase II price evaluating our individual cancer vaccine in the (inaudible) setting. Mainly pancreatic factors, adenocarcinoma aqueduct and in colorectal cancer. The 5 years elaborate in (inaudible) after resection is 10% and up to 75% of patients with PDP relapse even though the (inaudible) within 5 years after adjuvant treatment.

轉向 [Outogen Saunoral]，還有 BNT122，這是我們與合作夥伴 Genentech 共同開發的基於 IMS 平台的個人化 mRNA 癌症候選疫苗。我們認為個人化癌症疫苗是一項潛在的醫學突破，正在解決可切除癌症和敏銳或最小疾病治療環境的高醫療需求。我們已經證明，我們的個人化疫苗可以在原子胰腺癌患者中誘導出針對個體突變腫瘤新抗原的從頭反應，並且當患者被誘導免疫反應時，癌症復發的風險降低了超過3年的隨訪期。我們有兩個活躍的隨機 II 期價格在（聽不清楚）環境中評估我們的個體癌症疫苗。主要是胰臟因素、腺癌導水管和大腸直腸癌。切除後（聽不清楚）的 5 年內，有 10% 和高達 75% 的 PDP 患者復發，即使在輔助治療後（聽不清楚）5 年內也是如此。

For high-risk colorectal cancer, about 35% of patients elect within 5 years after resection and accelerate. So to summarize, we aim to bring endometrial cancer vaccine into (inaudible) treatment setting in tumor tracts where unmet medical need is (inaudible). As such, we have expanded into a new indication with the start of a Phase II trial evaluating our individualized cancer vaccine candidate in the active treatment master-invasive urothelial carcinoma, which has started screening patients.

對於高風險大腸直腸癌，約35%的患者選擇在切除後5年內加速。總而言之，我們的目標是將子宮內膜癌疫苗引入（聽不清楚）未滿足醫療需求（聽不清楚）的腫瘤區域的治療環境。因此，我們已經擴展到新的適應症，啟動了一項II 期試驗，評估我們的個人化癌症候選疫苗在積極治療主侵襲性尿路上皮癌中的作用，該試驗已開始對患者進行篩檢。

The current treatment includes neutrals chemotherapy followed by cystectomy and for eligible patients. This is followed by actual treatment with an induced checkpoint inhibitor. The (inaudible) survival among issues with metastatic greater cancer is about 8% Excellent treatment of master evasive disease is an important opportunity to potentially avoid recurrent metastases and improve overall survival. The randomized (inaudible) multi-cite Phase I clinical trials into they make [ autogenounoran ] as an adjuvant treatment with the on checkpoint in (inaudible) patients with (inaudible). The trial is expected to enroll about 360 patients to evaluate the efficacy of BNT122 in combination with novo compared to (inaudible), the standard of care product indication in the U.S. The primary point for study is investigator-assessed disease suite provider secondary objectives include our survival and safety.

目前的治療方法包括中性化療，然後針對符合條件的患者進行膀胱切除術。接下來是用誘導檢查點抑制劑進行實際治療。轉移性較大癌症的（聽不清楚）存活率約為 8%。隨機（聽不清楚）多引用 I 期臨床試驗將 [autogenounoran] 作為檢查點的輔助治療用於（聽不清楚）患有（聽不清楚）的患者。該試驗預計將招募約 360 名患者，以評估 BNT122 合併 novo 與美國護理產品適應症標準（聽不清楚）的療效。生存和安全。

Lastly, as a final note, I would like to invite you to our upcoming innovation period day next week, where we will share additional details on needs and other programs of our PRP pipeline.

最後，作為最後一點，我想邀請您參加下週即將到來的創新日，我們將在會議上分享有關 PRP 管道的需求和其他計劃的更多詳細資訊。

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 have done in today's call. Let me start by reviewing our financial results for the 3 -- ended September 30, 2024. The total revenues reported for the period were approximately EUR 1.245 billion. mostly recorded in September compared to approximately EUR 895 million for the third quarter of 2023. The increase compared to the same period last year can be largely attributed to early approvals of our variant adapted COVID-19 vaccines this year versus last year.

謝謝 Ozlem，並熱烈歡迎參加今天電話會議的所有人。首先讓我回顧一下我們截至 2024 年 9 月 30 日的第三季財務業績。與2023 年第三季的約8.95 億歐元相比，大部分記錄在9 月。批准。

Moving to cost of sales. Cost of sales amounted to approximately EUR 179 million for the third quarter of 2024 compared to approximately EUR 162 million for the comparative prior year period. Research and development expenses were approximately EUR 550 million for the third quarter of 2024 compared to approximately EUR 498 million for the comparative prior year period. These expenses were mainly influenced by progressing clinical trials for our late-stage oncology pipeline candidates.

轉向銷售成本。 2024 年第三季的銷售成本約為 1.79 億歐元，而去年同期約為 1.62 億歐元。 2024 年第三季的研發費用約為 5.5 億歐元，而去年同期約為 4.98 億歐元。這些費用主要受到我們後期腫瘤候選藥物正在進行的臨床試驗的影響。

Sales, general and administrative expenses amounted to approximately EUR 151 million for the third quarter of 2024 compared to about EUR 164 million for the comparative prior year period. SG&A expenses were primarily driven by personnel expenses. The company's other operating results amounted to approximately negative EUR 355 million in the third quarter of 2024 compared to negative EUR 9 million for the comparative prior year period. The other operating result was primarily influenced by accruals for contractual disputes.

2024 年第三季的銷售、一般和管理費用約為 1.51 億歐元，而去年同期約為 1.64 億歐元。 SG&A 費用主要由人員費用驅動。 2024 年第三季度，該公司的其他經營業績約為負 3.55 億歐元，而去年同期為負 900 萬歐元。其他經營績效主要受到合約糾紛應計費用的影響。

Income taxes were realized with an amount of about EUR 39 million in the third quarter of 2024 compared to approximately EUR 67 million of accrued tax expenses for the comparative prior year period.

2024 年第三季實現的所得稅金額約為 3,900 萬歐元，而去年同期的應計稅費約為 6,700 萬歐元。

For the third quarter of 2024, we reported a net income of approximately EUR 198 million compared to about EUR 161 million for the comparative prior year period. Our diluted earnings per share for the third quarter of 2024 amounted to EUR 0.81 compared to EUR 0.66 for the comparative prior year period. As of September 30, 2024, our cash and cash equivalents plus security investments reached approximately EUR 17.8 billion.

2024 年第三季度，我們報告的淨利潤約為 1.98 億歐元，而去年同期約為 1.61 億歐元。我們 2024 年第三季的攤薄每股收益為 0.81 歐元，去年同期為 0.66 歐元。截至 2024 年 9 月 30 日，我們的現金和現金等價物加上證券投資達到約 178 億歐元。

Our strong balance sheet allows us to invest in future value creation. Consequently, we will continue to invest in maintaining a lean cash generative COVID-19 vaccine business. In the development of our (inaudible) therapies and in our core capabilities to sort additional late-stage trials and potential commercialization of our most encouraging oncology assets. We will continue to assume a rigorous go/no-go decision-making across all development stages as part of our portfolio prioritization strategy. This allows us to maintain our focus on materializing the value in our pipeline.

我們強大的資產負債表使我們能夠投資於未來的價值創造。因此，我們將繼續投資維持精益現金產生的 COVID-19 疫苗業務。在我們（聽不清楚）療法的開發中，以及我們對更多後期試驗和我們最令人鼓舞的腫瘤學資產的潛在商業化進行分類的核心能力中。作為我們的投資組合優先策略的一部分，我們將繼續在所有開發階段採取嚴格的進行/不進行決策。這使我們能夠繼續專注於實現管道中的價值。

Turning to the next slide, we see financial guidance for the full year of 2024. We saw a strong quarter in terms of revenues, which included certain revenues that we previously anticipated in the last quarter of 2024. With this, we expect full 2024 financial year revenues to be at the low end of the guidance range provided in our outlook. Our guidance reflects some risk of write-downs and other charges by our collaboration for the Pfizer, which we estimate to approximately 10% of company revenues. We will continue to monitor the risk of potential write-downs to determine the full scope of charges related to the 2024, 2025 vaccination season. In line with our disclosure earlier in the year, we expect to report a loss for the 2024 financial year as we continue to invest in our most differentiating assets and technologies.

轉向下一張投影片，我們看到2024 年全年的財務指引。我們預計2024 年全年財務指引年收入將處於我們展望中提供的指導範圍的低端。我們的指導反映了我們與輝瑞公司的合作帶來的一些減記和其他費用的風險，我們估計輝瑞的收入約占公司收入的 10%。我們將繼續監控潛在的減記風險，以確定與 2024 年、2025 年疫苗接種季節相關的全部費用範圍。根據我們今年稍早披露的信息，隨著我們繼續投資於最具差異化的資產和技術，我們預計 2024 財年將出現虧損。

We are committed to responsible and sustainable growth. And with this, updating our full 2024 financial year expenses guidance to indicate a decrease in estimated SG&A expenses and capital expenditures. Reflecting our focus on continued investment in our pipeline, we're maintaining our R&D expense guidance. We have lowered the initial full 2024 financial year SG&A expense guidance by EUR 100 million from EUR 700 million to EUR 800 million to now EUR 600 million to EUR 700 million. We also reduced our capital expenditures guidance by EUR 100 million from the initial 2024 guidance range of between EUR 400 million and EUR 500 million to between EUR 300 million and EUR 400 million.

我們致力於負責任和可持續的成長。由此，我們更新了完整的 2024 財年支出指南，以顯示估計的 SG&A 支出和資本支出減少。我們維持研發費用指導，這反映了我們對管道持續投資的關注。我們已將最初的 2024 財年全年 SG&A 支出指引降低了 1 億歐元，從 7 億歐元至 8 億歐元降至目前的 6 億歐元至 7 億歐元。我們也將資本支出指引減少了 1 億歐元，從 2024 年最初的 4 億至 5 億歐元指引範圍減少到 3 億至 4 億歐元。

Please note that these guidance update for SG&A expenses and CapEx do not reflect any M&A, collaborational licensing transaction that we may enter into in the future, nor any potential payments resulting from the outcomes of ongoing and/or future legal disputes or related activities such as judgments or settlements or other extraordinary items all of which may have a material effect on our results of operations and cash flows. In summary, we remain focused on executing the company strategy highlighted by the progress across our pipeline. We have advanced and started new dose optimization and potentially registrational trials and have shared encouragingly (inaudible) has to demonstrate the potential of our product candidate.

請注意，這些SG&A費用和資本支出的指導更新並不反映我們未來可能進行的任何併購、合作許可交易，也不反映因持續和/或未來法律糾紛或相關活動的結果而產生的任何潛在付款，例如判決或和解或其他非常項目，所有這些都可能對我們的經營業績和現金流量產生重大影響。總之，我們仍然專注於執行我們管道的進展所強調的公司策略。我們已經推進並開始了新的劑量優化和潛在的註冊試驗，並令人鼓舞地（聽不清楚）分享了我們候選產品的潛力。

In our oncology portfolio, our focus remains on investing in our innovative technologies that we believe can have the greatest impact on medical practice while progressing our late-stage programs efficiently towards potential approvals. Our cash position and financial discipline allows us to continue to invest in those assets with the highest disruptive potential and focus on generating value for patients and our shareholders. With that, I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for our strategic outlook and concluding remarks.

在我們的腫瘤學產品組合中，我們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對醫療實踐產生最大的影響，同時有效地推進我們的後期專案以獲得潛在的批准。我們的現金狀況和財務紀律使我們能夠繼續投資於那些具有最高顛覆潛力的資產，並專注於為患者和股東創造價值。在此，我想將電話轉給我們的首席策略長瑞安·理查森（Ryan Richardson），聽取我們的策略展望和總結發言。

Thank you, Jens. Starting with COVID-19, we continue to execute on our successful launch of this season's JN1 and KP2 variant adaptive vaccines in more than 40 countries and regions around the world. In September, we began distribution of our KP2 variant adaptive vaccine in Europe following the initial rollout of JN1 vaccines in July. We expect additional markets including the U.K. that received initial shipments of JN1 vaccine to transition to KP2 deliveries in November.

謝謝你，延斯。從COVID-19開始，我們繼續執行本季JN1和KP2變異適應性疫苗在全球40多個國家和地區的成功上市。繼 7 月首次推出 JN1 疫苗後，我們於 9 月開始在歐洲分發 KP2 變異體適應性疫苗。我們預計包括英國在內的其他市場將在 11 月收到首批 JN1 疫苗出貨，轉為 KP2 出貨。

In the United States, we continue to expect vaccination rates this year that are generally comparable to last year. with potential for slightly higher volumes due in part to the earlier approval and rollout of vaccines and supported by ACIP's recommendation in October for a second dose of COVID-19 vaccine for individuals who are 65 or older or immunocompromised.

在美國，我們仍然預期今年的疫苗接種率與去年大致相當。銷售量可能會略有增加，部分原因是疫苗的較早批准和推出，以及 ACIP 在 10 月建議為 65 歲或以上或免疫功能低下的個人接種第二劑 COVID-19 疫苗的建議。

Internationally, we have seen the opening up of several private meets in countries like the U.K., Japan, Switzerland, Australia, South Korea, Singapore and Brazil. This year, we have also increased our supply of prefilled syringes in a number of international markets. The epidemiology of COVID-19 over the last 2 years and the associated global demand for vaccination continue to support our view that COVID-19 vaccines will be a sustainable market for the foreseeable future. We expect to maintain or even gain market share in (inaudible) key markets this year. versus last year and believe that we are likely to enter a period with improved visibility into vaccine demand. One of the unique features of our COVID-19 vaccine business is its lean cost structure.

在國際上，我們看到英國、日本、瑞士、澳洲、韓國、新加坡和巴西等國家舉辦了幾場私人會議。今年，我們也增加了在許多國際市場的預充式註射器的供應。過去 2 年 COVID-19 的流行病學以及相關的全球疫苗接種需求繼續支持我們的觀點，即在可預見的未來，COVID-19 疫苗將是一個可持續的市場。我們預計今年將在（聽不清楚）關鍵市場保持甚至增加市場份額。與去年相比，我們相信我們可能會進入一個疫苗需求可見度提高的時期。我們的 COVID-19 疫苗業務的獨特之處之一是其精益的成本結構。

Our partnership with Pfizer allows us to leverage its manufacturing infrastructure and global commercial capabilities, which we will continue to enable us to limit the OpEx flowing through our P&L. These features create the potential for us to generate significant cash flow from our COVID-19 business, a feature we expect to benefit from in the future.

我們與輝瑞的合作關係使我們能夠利用其製造基礎設施和全球商業能力，我們將繼續使我們能夠限制流經損益表的營運支出。這些功能為我們創造了從 COVID-19 業務中產生大量現金流的潛力，我們預計未來將從中受益。

Turning to the next slide. We are entering a catalyst-rich period for our company, in particular, for our oncology portfolio. Today, we have more than 10 Phase II and III trials ongoing across multiple tumor types. In the next 18 months, we expect multiple clinical data updates from these trials, and we'll initiate several additional trials with registrational potential. Data is expected in 2025 from both our mRNA cancer vaccine platforms, FixVac and iNeST. We also expect data updates for BNT327, our anti-PD-L1 VGFA bispecific antibody and BNT323, our HER2 ADC.

轉到下一張投影片。我們公司正在進入一個充滿催化劑的時期，特別是我們的腫瘤學產品組合。如今，我們正在進行超過 10 項針對多種腫瘤類型的 II 期和 III 期試驗。在接下來的 18 個月中，我們預計這些試驗將更新多項臨床數據，並且我們將啟動幾項具有註冊潛力的額外試驗。我們的 mRNA 癌症疫苗平台 FixVac 和 iNeST 預計將於 2025 年提供數據。我們也預期 BNT327（我們的抗 PD-L1 VGFA 雙特異性抗體）和 BNT323（我們的 HER2 ADC）的數據更新。

Before we conclude our planned remarks, I would like to invite everyone to watch our annual Innovation Series event on November 14. This will include a deeper dive into our oncology strategy, including plans for BNT327 and our mRNA cancer vaccine candidates. We look forward to engaging with you later this month to share more on our plans to create value for patients, society and shareholders. With that, we would like to open the floor for questions.

在我們結束計劃演講之前，我想邀請大家觀看我們 11 月 14 日舉行的年度創新系列活動。我們期待本月稍後與您接觸，並更多地分享我們為患者、社會和股東創造價值的計劃。現在，我們想開始提問。

(Operator Instructions). Tazeen Ahmad, Bank of America Securities.

（操作員說明）。塔津‧艾哈邁德，美國銀行證券公司。

I appreciate your time. I wanted to ask you about one of the data catalysts that you mentioned that's upcoming in 2025. Perhaps we'll talk about this more in detail next week but for 323, specifically, I believe you've got data coming for endometrial cancer. Can you talk about the level of data you expect to show next year for that program and what you're looking for in order to move forward?

我很感激你的時間。我想向您詢問您提到的2025 年即將推出的數據催化劑之一。數據。您能否談談您預計明年該計劃顯示的數據水平以及您正在尋找什麼以便繼續前進？

Katin, thank you for this question. The question was about our mitral cancer data with BNT323. And what I can tell you about that is that in 2025, we expect to share data from our single-arm trial in second-line endometrial cancer, we will be able to show efficacy data and safety data across different HR positivity, populations, and this will be presented at one-off of major cancer conferences.

卡廷，謝謝你提出這個問題。問題是關於 BNT323 的二尖瓣癌數據。我可以告訴你的是，到 2025 年，我們期望分享二線子宮內膜癌單臂試驗的數據，我們將能夠展示不同 HR 陽性、人群和人群的療效數據和安全性數據。主要癌症會議上提出。

And also what would be positive data in your mind for that program?

您認為該計劃的正面數據是什麼？

Can you repeat?

你能重複一下嗎？

What would be positive data for that study in your mind data?

在您的心目中，該研究的正面數據是什麼？

What would justify to continue with the compound is a strong clinical activity profile and a favorable safety. And this is also what we see in the data, and we see this across different HER2 expression levels. .

繼續使用該化合物的理由是其強大的臨床活性和良好的安全性。這也是我們在數據中看到的，我們在不同的 HER2 表達水平上都看到了這一點。 。

Daina Graybosch, Leerink Partners.

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

I have one on the VEGF PD-L1, BNT327. I think we're all aware of a similar bispecific that has a PD-1 side, whereas you have a PD-L1 side and in small trials in similar indications like triple-negative breast cancer, the two bispecifics look to have similar outcomes, was that expected? And what does that tell you about the mechanism? And do you believe BNT327 could be differentiated in any indications?

我有一個 VEGF PD-L1，BNT327。我想我們都知道有一個類似的雙特異性藥物，它有PD-1 一側，而你有PD-L1 一側，並且在三陰性乳癌等類似適應症的小型試驗中，這兩種雙特異性藥物看起來有類似的結果，這是預期的嗎？這告訴你關於這個機制的什麼資訊？您認為 BNT327 可以在任何適應症上實現差異化嗎？

In, thanks for the question. Yes, this is a good question. And at the end of the day, both by specific link these activities of notarizing VEGF and authorizing PD-1, PD-L1 interaction, they have this in common. The biggest distance is that BNT327 is directed against PD-1, which comes with the potential advantage of being further enriched in the tumor micro environment by binding to PD-L1 or vice versa enabling or adding to the binding of VEGF and (inaudible). The data that we have so far, these are -- there are some overlapping clinical trial. As you as we mentioned, look similar. And they have to see whether this potential mechanistic difference could translate into better response rate and better durability, particularly in PD-L1 positive tumors. So we have to see that there is a slight trend in this direction, but it's too early to, yes, to validate it.

在，謝謝你的提問。是的，這是一個好問題。歸根結底，透過將公證 VEGF 和授權 PD-1、PD-L1 相互作用的這些活動具體聯繫起來，它們有這一點。最大的距離是 BNT327 是針對 PD-1，它具有透過與 PD-L1 結合而在腫瘤微環境中進一步富集的潛在優勢，反之亦然，從而啟用或增加 VEGF 的結合（聽不清楚）。到目前為止，我們掌握的數據是──有一些重疊的臨床試驗。正如我們所提到的，你看起來很相似。他們必須看看這種潛在的機制差異是否可以轉化為更好的緩解率和更好的持久性，特別是在 PD-L1 陽性腫瘤中。所以我們必須看到這個方向有輕微的趨勢，但現在驗證它還為時過早。

Akash Tewari, Jefferies.

阿卡什·特瓦里，杰弗里斯。

This is Kathy on for Akash. So for your VEGF PD-L1 bispecific BNT327, when do the AEs and reductions in dose for hypertension proteinuria job in comparison to what we've seen historically for VEGF PD-L1 when co-administrated as two separate drugs. And additionally, weren't you going forward with it to first-line NSCLC in all-comers population? And what's the rationale for going as a biomarker selected population..

這是阿卡什的凱西。因此，對於您的VEGF PD-L1 雙特異性BNT327，與我們歷史上看到的VEGF PD-L1 作為兩種單獨藥物共同給藥時的不良事件和減少高血壓蛋白尿劑量相比，何時會發揮作用。此外，您不是打算將其用於所有人群的一線 NSCLC 治療嗎？作為生物標誌物選擇人群的理由是什麼？

Okay. I take both parts of the question. So the first question was the comparison with the historical starting to safety profile, particularly with bevacizumab. Yes. So yes, now more than 700 patients treated either as mono-compound or in combination. And the comparison to historical to the historical safety profile clearly shows reduced side effect profile with regard to the key concern in side effects of bevacizumab bleeding hypertension of the formation of fistulas. We have not seen any significant increase of bleeding cases in this cohort, which goes beyond what is observed in this population, for example, for PD-1 antibody and hypotension rate is significantly lower than the historical (inaudible) of (inaudible). The mechanism for this can only be speculated and that by linking the entire body with the VEGF part to PD-1 and the anti-VEGF interaction is more targeted to the tumor site and that's less active in PD-L1 negative areas. And this is, of course, encouraging and provides an additional argument beyond increased so far increased clinical activity for this compound class. So this was the first part.

好的。我回答了問題的兩個部分。因此，第一個問題是與歷史起始安全性的比較，特別是與貝伐珠單抗的比較。是的。所以，是的，現在有 700 多名患者接受單一化合物或合併治療。與歷史安全性概況的比較清楚地表明，關於貝伐珠單抗出血性高血壓的副作用以及瘻管形成的關鍵問題，副作用概況有所減少。我們沒有看到該群組中出血病例有任何顯著增加，這超出了在該族群中觀察到的情況，例如，PD-1 抗體和低血壓率顯著低於（聽不清楚）的歷史（聽不清）。其機制只能推測，將整個身體與 VEGF 部分連接到 PD-1，抗 VEGF 相互作用更有針對性地針對腫瘤部位，而在 PD-L1 陰性區域中活性較低。當然，這是令人鼓舞的，除了迄今為止增加的此類化合物的臨床活性之外，還提供了額外的論點。這是第一部分。

And the second part is why we prefer to go into outcome population. The response to that is that our bispecific has shown a clinical activity, not only in PD-L1 positive and we have run low population, but also in populations, which do not express PD-L1 or CPS. I would refer to our data set that we generate in TNBC where the objective response rate in the TNBC or current population with extremely intelligent. We see something similar with a clear indication of clinical activity in the PD-L1 negative population in the second 9 months announced small cell lung cancer and (inaudible) positive population.

第二部分是為什麼我們更喜歡進入結果人群。對此的回應是，我們的雙特異性抗體不僅在 PD-L1 陽性且我們的人群較少的情況下表現出臨床活性，而且在不表達 PD-L1 或 CPS 的人群中也表現出臨床活性。我會參考我們在 TNBC 中產生的資料集，其中 TNBC 或當前人口中非常聰明的客觀反應率。我們在宣布的小細胞肺癌和（聽不清楚）陽性人群的後 9 個月內看到了類似的情況，明確表明 PD-L1 陰性人群的臨床活動。

So the working hypothesis that we have is that this bispecific antibody, fully comes -- overcomes the limitation, the rotation of pure clinical activity in PD-L1 positive tumors and opens up the potential to bring check point blockade plus VEGF activity into tumors that are also PDL negative. So the clinical trial in non-small cell lung cancer is an (inaudible) trial, but we are documenting and collecting standards for TD evaluation, and we are stratifying patients accordingly the (inaudible) positivity.

因此，我們的工作假設是，這種雙特異性抗體完全克服了 PD-L1 陽性腫瘤中純臨床活性輪換的限制，並開闢了將檢查點阻斷加上 VEGF 活性引入腫瘤的潛力。陰性。因此，非小細胞肺癌的臨床試驗是一項（聽不清楚）試驗，但我們正在記錄和收集 TD 評估標準，我們正在根據（聽不清楚）陽性對患者進行分層。

Suzanne van Voorthuizen, VLK. .

蘇珊娜‧範‧福爾特赫伊森 (Suzanne van Voorthuizen)，VLK。 。

This is Suzanne. Maybe I missed it, but can you clarify what the exact amount is that you have taken as a provision for contractual disputes this year? Is this it? Or will there be more and can you indicate what this relates to, if this is the ongoing patent dispute with other mRNA players on the COVID vaccine? Or if there are other contractual disagreements you are dealing with?

這是蘇珊娜。也許我錯過了，但你能澄清一下今年作為合約糾紛準備金的具體金額是多少嗎？是這個嗎？或者還會有更多嗎？或者您正在處理其他合約分歧？

Yes. Happy, Susanne, to take the question. So as you stated, the other operating result is reflecting these provisions that we have taken care of for contractual disputes with licenses and collaborators. We -- at this point in time, given the legal situation that we're in, cannot give precise messaging and for what this is. There are a couple of disputes that are related, as I stated with some of the players and collaborators that we're working with. In total, we have accrued around about EUR 600 million year-to-date for this, and this is the amount that we feel is accurate at this point in time.

是的。蘇珊娜，很高興回答這個問題。正如您所說，其他營運結果反映了我們針對與許可和合作者的合約糾紛所處理的這些條款。目前，考慮到我們所處的法律狀況，我們無法給出準確的資訊以及這是什麼。正如我與我們正在合作的一些參與者和合作者所說，存在一些相關的爭議。到目前為止，我們總共為此籌集了約 6 億歐元，這是我們目前認為準確的金額。

Terence Flynn, Morgan Stanley. .

特倫斯‧弗林，摩根士丹利。 。

I was just wondering if you can tell us what you think the relevant benchmark is for survival for the upcoming BNT327-TNBC data that we're going to see at the San Antonio conference in December?

我只是想知道您是否可以告訴我們，您認為我們將在 12 月的聖安東尼奧會議上看到的即將發布的 BNT327-TNBC 數據的生存相關基準是什麼？

Were you able to hear my question?

你聽得到我的問題嗎？

Can you just repeat that? Sorry.

你能重複一遍嗎？對不起。

Survival benchmarks for the upcoming BNT327-TNBC data at the San Antonio conference in December. And then the second part of the question is, is it reasonable to expect some interim data from your global Phase II lung cancer trial next year?

12 月聖安東尼奧會議上即將發布的 BNT327-TNBC 數據的生存基準。問題的第二部分是，預計明年全球二期肺癌試驗的一些中期數據是否合理？

Okay. I can take the question. The trial will be an against chemotherapy standard of care. And the private sales is powered for PFS and OS -- the PFS is in this indication in the range of 4 to 5 months as I can't recall at the moment.

好的。我可以回答這個問題。該試驗將是一項反對化療的護理標準。私人銷售是為 PFS 和 OS 提供支援的——PFS 處於 4 到 5 個月的範圍內，我目前不記得了。

Right. I think we're going to have updates plant to provide an update at the 15 and 18-month OS mark in terms of percentage of patients read. And that's starting to get into a relevant one, Terence, when you look at the what pembro has achieved in a similar indication, which is basically in the 15 to 23 -- up to 23-month median OS, depending on the patient, CPS patient model.

正確的。我認為我們將擁有更新工廠，以患者閱讀百分比的形式提供 15 個月和 18 個月 OS 標記的更新。 Terence，當您查看pembro 在類似適應症中所取得的成就時，這開始進入相關的主題，基本上是15 至23 個月的中位OS，最長可達23 個月，具體取決於患者， CPS患者模型。

Absolutely. And we have recently reported PFS data in the single region, reaching now about 13 months and still ongoing.

絕對地。我們最近報告了單一地區的 PFS 數據，目前已達到約 13 個月，並且仍在持續進行中。

Yaron Werber, TD Cowen.

亞龍·韋伯，TD·考恩。

Great. Maybe just a follow-on Terence's question. on TNBC is the starting Phase IIIs to go for CPS less than 10 specifically in that cohort? Or would you go across all CPS levels in Phase III. And then secondly, on small cell, is the primary going to be head-to-head against chemo to centric or is it going to be against chemo alone? Thank you so much.

偉大的。也許只是特倫斯的後續問題。 TNBC 上的第 3 期臨床試驗是否是針對 CPS 低於 10 的開始，特別是在該群體中？或者您會瀏覽第三階段的所有 CPS 等級嗎？其次，在小細胞上，主要針對中心化療進行正面交鋒還是單獨針對化療？太感謝了。

So the first trial is intended in the patient population below 10% and will be against chemotherapy alone. But we plan also further or we are in the evaluation of additional cars going to the above 10% population.

因此，第一項試驗針對的是 10% 以下的患者群體，並將針對單獨的化療。但我們也進一步規劃，或者我們正在評估為這 10% 以上的人口提供更多汽車。

And can you just repeat the second part of your question?

您能重複問題的第二部分嗎？

Yes. And just switching to small cell lung cancer is the Phase III going to be head-to-head against chemo or against chemo to centric. Thank you in small cell lung cancer.

是的。只是轉向小細胞肺癌，第三階段將與化療進行正面交鋒，或以化療為中心。謝謝小細胞肺癌。

Chemo to centric.

化療至中心。

Jessica Fye, JPMorgan Chase.

潔西卡‧菲伊，摩根大通。

Two first on guidance of the various assumptions factoring into your guidance what changed to lead you to guide the low end of the range, even though Pfizer, I believe, maintained its community guidance last week? And then on the pipeline for BNT327, the VEGF PD-L1 bispecific, what do you see as the fastest to market indications? And what's the right way to think about R&D spend as the company expands trials for this product?

首先是關於各種假設的指導，考慮到您的指導發生了什麼變化，導致您指導範圍的低端，儘管我相信輝瑞上週維持了其社區指導？然後，在 VEGF PD-L1 雙特異性藥物 BNT327 的研發管線中，您認為最快上市的適應症是什麼？當公司擴大該產品的試驗範圍時，考慮研發支出的正確方法是什麼？

Yes, Jessica, let me take the first part of the question. So we've guided at the beginning of the year, EUR 2.5 billion to EUR 3.1 billion based on, of course, certain scenarios. Year-to-date, Q3 has been very, very good. And Q3 so far or the year-to-date figures so far have been generated dominantly by revenues that we generated in high-income countries. We have seen, though, low demand and also low pricing in some of the low and middle income countries within the Pfizer territory, and therefore, we specified our guidance to the low end for this year.

是的，傑西卡，讓我回答問題的第一部分。因此，我們在年初指導了 25 億至 31 億歐元，當然是基於某些情景。今年迄今為止，第三季的表現非常非常好。到目前為止，第三季或年初至今的數據主要是由我們在高收入國家創造的收入所產生的。不過，我們已經看到輝瑞旗下一些低收入和中等收入國家的需求較低且定價較低，因此，我們將今年的指導意見明確為低端。

And then second question?

然後第二個問題？

I think your second question was speed to market. What we think would be the fastest to market for 327 is that correct?

我認為你的第二個問題是上市速度。我們認為 327 上市最快的產品是這樣嗎？

Yes.

是的。

So I think we're going to provide more details at our innovation series week in terms of the paths to market. But I think what we can see is that we do think that small cell lung cancer to be one of the leading indications that we're looking at very closely. We initiated a Phase II trial and believe that we can start a Phase III trial. It's a Phase II/III effectively, so Phase III portion of that trial in the coming months. by first of next year. So that could represent one fast path to market. But of course, we're looking at others as well.

因此，我認為我們將在創新系列週上提供有關市場路徑的更多詳細資訊。但我認為我們可以看到的是，我們確實認為小細胞肺癌是我們正在密切關注的主要適應症之一。我們啟動了二期試驗，並相信我們可以啟動三期試驗。這實際上是第二/第三階段，因此該試驗的第三階段部分將在未來幾個月內進行。到明年年初。因此，這可能是一種快速進入市場的途徑。但當然，我們也在關注其他人。

Cory Kasimov, Evercore ISI. .

科里·卡西莫夫，Evercore ISI。 。

So your Trop-2 ADC BT looks like an important part of your emerging combination strategy with 327, looking at the clinical trial posting shows that you're evaluating a variety of different dosing combinations. So wondering if you can add some color on the dosing strategies in your content level. that all three mechanisms together will not compromise safety?

因此，您的 Trop-2 ADC BT 看起來像是您與 327 的新興組合策略的重要組成部分，查看臨床試驗帖子表明您正在評估各種不同的劑量組合。所以想知道是否可以在內容等級的劑量策略上添加一些顏色。這三種機制一起不會損害安全嗎？

Yes. The current exploration of combination is exactly also directed to explore the safety of the molecule in combination -- so 325 that to ADC comes with a safety profile that is characterized by stomatitis. And one of the questions that we want to ask is what is the combination with built, what he have an additive toxicity effect, that is something that we would like to understand. We do not expect any other overlapping toxicity since the BNT327 a table the safety profile. We will start with lower doses and then escalate to higher doses and assess and safe those identity space dose profile in explore cohort for also determining the contribution of efficacy PERC. .

是的。目前對組合的探索也正是針對探索組合中分子的安全性——因此 325 ADC 具有以口腔炎為特徵的安全性。我們想問的問題之一是與內建的組合是什麼，他有什麼附加毒性作用，這是我們想了解的。自從 BNT327 列出安全概況以來，我們預計不會有任何其他重疊毒性。我們將從較低劑量開始，然後升級到較高劑量，並在探索隊列中評估和保護這些相同空間劑量分佈，以確定 PERC 功效的貢獻。 。

Chris Shibutani from Goldman Sachs. .

來自高盛的克里斯·澀谷。 。

This is Kevin on for Chris. Just wanted to ask another one on the PD-L1 VEGF 327. So you touched on potential mechanistic differences with bevacizumab earlier, if we can assume that the clinical profiles remain relatively similar, do you believe this is a story more about clinical execution? And if so, how can you differentiate there?

這是凱文替克里斯發言。只是想問另一個關於PD-L1 VEGF 327 的問題。所以您之前談到了與貝伐單抗的潛在機制差異，如果我們可以假設臨床特徵保持相對相似，您是否認為這是一個更多關於臨床執行的故事？如果是這樣，你如何區分？

Yes. Thank you for the question, Kevin. I'll start and then to add to it. So I think that -- we do think that there's sufficient -- actually, there's significant room for differentiation in clinical strategy. And that's actually one of the main drivers that we're evaluating now because we do see applicability across many different tumor types, and as Ugur also alluded across different patient segments within tumor types. And I think one of the unique features of our portfolio in oncology is the combination agents that we could bring to bear with 327. So I think we've talked about chemo combinations being likely the fastest path to market initially. And we've guided to a couple of early indications, but we're definitely thinking broader than that. We're thinking about BDC, 327 combinations to follow shortly thereafter. Our current thoughts would be to initiate those trials already in 2025. The first combination potentially in 2025 rather than waiting to do those in sequence. And we're also going to be evaluating other combinations as well. down the road. So I do think that, that's a differentiation angle that we can -- we're well positioned to exploit. So it really comes down to a combination of combination strategy and also clinical execution indeed as potential differentiators for this large opportunity that we see.

是的。謝謝你的提問，凱文。我將開始然後添加它。所以我認為——我們確實認為已經足夠了——實際上，臨床策略有很大的差異化空間。這實際上是我們現在正在評估的主要驅動因素之一，因為我們確實看到了它在許多不同腫瘤類型中的適用性，正如 Ugur 也提到了在腫瘤類型中不同患者群體中的應用。我認為我們在腫瘤學領域的產品組合的獨特之處之一是我們可以與 327 一起使用的組合藥物 所以我認為我們已經討論過化療組合可能是最初進入市場的最快途徑。我們已經引導了一些早期跡象，但我們的思考肯定比這更廣泛。我們正在考慮不久後推出的 BDC、327 組合。我們目前的想法是在 2025 年就開始這些試驗。我們還將評估其他組合。沿著路。所以我確實認為，這是我們可以利用的一個差異化角度——我們已經做好了充分利用的準備。因此，這實際上取決於組合策略和臨床執行的結合，這確實是我們看到的這一巨大機會的潛在差異化因素。

Etzer Darout, BMO Capital Markets. .

Etzer Darout，BMO 資本市場。 。

This is [Luke] on for Etzer. So what are you learning about a survival cause brand leases that you're looking at? I mean what's your level of confidence that you can beat standard of care given the importance of that endpoint to regulators?

這是埃澤爾的[盧克]。那麼，對於您正在考慮的生存原因品牌租賃，您了解到了什麼？我的意思是，考慮到該終點對監管機構的重要性，您對能夠超越護理標準的信心有多大？

So I think we had a little bit of a buzz in the question. I think you were asking about the importance of overall survival. Is that correct? .

所以我認為我們對這個問題有一些爭議。我認為您是在問整體生存的重要性。這是正確的嗎？ 。

Yes. So like when we are for overall survival across breast and money and like what level of confidence you have given the importance of that endpoint to regulators?

是的。那麼，就像我們關心乳房和金錢方面的整體生存一樣，就像您對監管機構對該終點的重要性給予了多大程度的信心一樣？

Yes. Yes. So we completely understand the rational of this creating particularly based on disappointing (inaudible) coming within many indications at an improved PRS, but did not translate into an OS. And there are, of course, of course, collecting our own in-house data. And and we clearly see that this maturing OS data, unpublished (inaudible) data, we are getting more and more encouraged and that improved PFS is translating also into an OS. I would like to remind you that PFS improvement that we are seeing, for example, in TNDC is more than substantial, okay? So it's not the pan and that is usually observed with usually bevacizumab added 2 to 3 months additional PFS and then the drop in was steep this following the pattern that is observed with chemotherapy alone. We are not seeing this pattern we are seeing that particularly in locations where there the combined BNT327 this chemotherapy that there is a sustained PFS and the PFS does not drop in the term like a steep curve that goes slowly down. And this is the best -- this is the best thing that we have so far for that we can translate to OS. And I think we can definitely answer the question in the next 3 months for the first indications in which we are TNBC, small cell lung cancer and second months of the lung company. .

是的。是的。因此，我們完全理解這種創建的合理性，特別是基於改進的 PRS 的許多跡象令人失望（聽不清楚），但沒有轉化為作業系統。當然，當然還有收集我們自己的內部數據。而且我們清楚地看到，這些成熟的作業系統數據、未發布的（聽不清楚）數據，我們越來越受到鼓舞，改進的 PFS 也正在轉化為作業系統。我想提醒您，我們看到的 PFS 改善（例如在 TNDC）不僅僅是實質性的，好嗎？因此，這不是普遍現象，通常是在貝伐珠單抗添加 2 至 3 個月的額外 PFS 後觀察到的，然後按照單獨化療觀察到的模式，急劇下降。我們沒有看到這種模式，特別是在聯合 BNT327 這種化療的地方，有持續的 PFS，並且 PFS 不會像一條緩慢下降的陡峭曲線一樣在期限內下降。這是最好的——這是我們迄今為止可以轉化為作業系統的最好的東西。我認為我們絕對可以在未來 3 個月內回答這個問題，我們的第一個適應症是 TNBC、小細胞肺癌和肺公司的第二個月。 。

Ellie Merle, UBS.

艾莉·梅爾，瑞銀。

So the flu COVID combo program, I guess, what's the latest on this program after the Phase III missed d1 of the endpoints? And what's your latest thinking around the time lines for the second-gen program with the trivalent mRNA flu vaccine just given Moderna expects to launch its combo next year, curious dilutes on your strategy with your combination?

那麼，我想，流感 COVID 組合計劃在第三階段錯過了 d1 終點後，該計劃的最新進展是什麼？鑑於 Moderna 預計明年推出其組合疫苗，您對三價 mRNA 流感疫苗第二代計畫的時間線有什麼最新想法，好奇會稀釋您的組合策略嗎？

Yes, Ellie, thanks for the question. So we're working with Pfizer now on our next-generation flu covid vaccine combination a combination vaccine program. And I think it's a little too early to give you a precise road map, but we're hoping to give you -- and planning to give you updates over the course of 2025. I think needless to say, I think it is a program that has or the full weight of Pfizer and biotech R&D teams behind it. And we do think that some of the problems that have been -- we're seeing in an initial trial that those can be addressed through further optimization of the construct. And we have early evidence that supports that. But I think before we give you a definitive road map, I think we'd like to generate a little more data and hopefully come out with that next year.

是的，艾莉，謝謝你的提問。因此，我們現在正在與輝瑞合作開發下一代流感新冠疫苗組合疫苗計畫。我認為現在為您提供精確的路線圖還為時過早，但我們希望為您提供，併計劃在 2025 年期間為您提供更新。生物技術研發團隊的全力支持。我們確實認為，我們在初步試驗中看到，一些問題可以透過進一步優化結構來解決。我們有早期證據支持這一點。但我認為，在我們給你一個明確的路線圖之前，我想我們希望產生更多的數據，並希望明年能拿出來。

Yifeng Liu, HSBC Bank plc.

劉一峰，匯豐銀行。

I have one on your oncology portfolio. Just wondered for the other assets, apart from BNT327, 325 especially on the IO space. In the next 12, what are we going to hear your update on specifically things like 312 or 314, those early stage -- early mid-stage assets. So I think.

我在你的腫瘤學作品集中有一份。只是想知道除了 BNT327、325 之外的其他資產，特別是在 IO 空間上。在接下來的 12 年裡，我們將聽到您對 312 或 314 等早期階段、早期中期資產的具體更新。所以我認為。

At 312, of course, is the CD44BB program with [ Genmab ], and that's an ongoing trials right now. I think our intention is to bring data forward upon that trial's completion. We don't yet have dates for that, but it's likely going to be next year. And I think the other programs, generally speaking, our intention is to bring data out when we think we have something relevant to share. We tend to do that in our preferred mode of data disclosure is in medical meetings. And so of course, that requires that you've got data in hand that it's clean and been analyzed and is accepted by public auction. So we can't always give precise guidance on when every program will read out. But I think those other programs are progressing, and I think we plan to update our pipeline disclosure schedule going into early next year.

當然，312 是 [ Genmab ] 的 CD44BB 程序，目前正在進行試驗。我認為我們的目的是在試驗完成後提供數據。我們還沒有確定具體日期，但很可能是明年。我認為其他項目一般來說，我們的目的是在我們認為有相關內容可以分享時將數據拿出來。我們傾向於在醫療會議中首選的數據揭露方式中做到這一點。當然，這要求您手頭上有乾淨的數據，經過分析並被公開拍賣接受。因此，我們不能總是對每個節目何時讀出給予精確的指導。但我認為其他計劃正在取得進展，我認為我們計劃在明年初更新我們的管道披露時間表。

Simon Baker, Redburn Atlantic.

西蒙貝克，雷德本大西洋月刊。

Another one on BMT327. And going back to Terence's question. I just wanted to double check that the comments you made with respect to trial design were related to triple-negative breast rather than the planned non-small cell lung cancer study. If that is indeed because is there anything you can shed on the design of the upcoming first-line study in terms of geography comparator arm, I think you mentioned stratification and interim results, but any detail would be much appreciated.

BMT327 上的另一張。回到特倫斯的問題。我只是想仔細檢查您對試驗設計的評論是否與三陰性乳癌有關，而不是與計劃中的非小細胞肺癌研究有關。如果這確實是因為您可以就即將進行的地理比較臂方面的一線研究的設計提供任何信息，我認為您提到了分層和中期結果，但任何細節都將不勝感激。

Simon, I would like to refer you to our Innovation Day next week, where we will disclose in more detail a couple of study designs and benchmarks we are comparing against also contextualized to our entire trial were also questions around BNT327 pivotal trials we are planning will be disclosed. .

Simon，我想向您推薦下週的創新日，屆時我們將更詳細地披露我們正在比較的一些研究設計和基準，這些設計和基準也與我們整個試驗的背景相關，也是我們計劃的有關BNT327 關鍵試驗的問題被揭露。 。

Manos Mastorakis, Deutsche Bank. .

馬諾斯‧馬斯托拉基斯，德意志銀行。 。

Since my question was stolen. Basically, I just wanted to ask on your ongoing confidence on your TROP-2 program, but also your nest meal program as well? Thank you very much.

因為我的問題被偷了。基本上，我只是想問一下您對 TROP-2 計劃以及巢餐計劃的持續信心如何？非常感謝。

So first question was about ADC. I get that right. So we -- as you know, our TROP2 ADC 327 is at an early stage of testing. And in particular, we see potential in combination with BNT327, which we see as we have already dust as a platform to combine with different ADCs and the combination trial. We just have started to explore first of all, safe combination doses is going into this direction and is exploring TNBC on small cell lung cancer and ovarian cancer and cervical cancer cohorts up for TROP2 and the ADC and combination. .

所以第一個問題是關於ADC的。我明白了。如您所知，我們的 TROP2 ADC 327 正處於測試的早期階段。特別是，我們看到了與 BNT327 結合的潛力，因為我們已經將其作為與不同 ADC 和組合試驗相結合的平台。首先，我們剛開始探索，安全組合劑量正在朝這個方向發展，正在探索 TNBC 在小細胞肺癌、卵巢癌和子宮頸癌隊列中的 TROP2 和 ADC 及其組合。 。

The second question was about our Nestor individualized platform. We are continuing to expand into the adjuvant space. As you might know, we have adjuvant -- we have trials running in adjuvant colorectal cancer with an upcoming interim analysis end of next year. We have started with our partner Genentech a trial in the actual setting of pancreatic cancer, motivated and informed by small Phase I trial with however, exciting data. And we just have started a third trial in this in the adjuvant setting with muscle invasive urothelial cancer or also a randomized, potentially pivotal trial. So these are the ongoing trials. And we are reading out our trial in first-line melanoma, and we'll be able to disclose more about that in our upcoming innovation day next week.

第二個問題是關於我們的 Nestor 個人化平台。我們正在繼續擴展到輔助領域。正如您可能知道的，我們有佐劑——我們正在進行佐劑結直腸癌試驗，並將於明年年底進行中期分析。我們已經與我們的合作夥伴基因泰克開始了一項針對胰腺癌的實際試驗，受到小型 I 期試驗的推動和啟發，但數據令人興奮。我們剛開始了第三項試驗，在肌肉浸潤性尿路上皮癌的輔助治療中，或是一項隨機的、潛在的關鍵試驗。這些都是正在進行的試驗。我們正在宣讀我們在一線黑色素瘤中的試驗，我們將能夠在下週即將到來的創新日中披露更多相關資訊。

And I would just add to that, that in summary that we continue to believe that INS has disruptive potential in particular in those adjuvant settings that (inaudible) mentioned, and we're investing accordingly in the program. .

我想補充一點，總而言之，我們仍然相信 INS 具有顛覆性潛力，特別是在提到的（聽不清楚）輔助設定中，並且我們正在對該計劃進行相應投資。 。

Jay Olson, Oppenheimer. .

傑·奧爾森，奧本海默。 。

Congrats on the progress, and thank you for providing this update. Can you comment on the approximate level of R&D spending increase you expect in the next few years considering how rapidly you're expanding the number of Phase III programs in oncology? And is there an ideal number of Phase III trials that would optimize your organizational and financial resources?

恭喜您取得的進展，並感謝您提供此更新。考慮到您擴大腫瘤學 III 期項目數量的速度，您能否評論一下您預計未來幾年研發支出增長的大致水平？是否有理想數量的 III 期試驗可以優化您的組織和財務資源？

Yes, thanks for the question. I mean it's a bit early for any guidances that we are not intending to give now in November. I think we feel comfortable with the 2.4%, 2.6% that we currently have running. And on one hand, we want to control costs, on the other hand, of course, we want to invest wisely. If we talk about 37 and the potential, of course, it would be not very clever to not invest in that compound to just use this example, specifically. So -- but be assured that we control our costs going forward, being at SG&A expenses will be in an R&D expenses.

是的，謝謝你的提問。我的意思是，對於我們現在不打算在 11 月提供的任何指導，現在還為時過早。我認為我們對目前的 2.4%、2.6% 感到滿意。一方面，我們要控製成本，另一方面，我們當然要明智地投資。當然，如果我們談論 37 及其潛力，那麼不投資該化合物而僅使用這個例子並不是很明智。所以，但請放心，我們將掌控未來的成本，SG&A 費用將計入研發費用。

Yes. And with regard to the target pipeline, I think it's a very good question. I would just note that with the current level of R&D spend that Jens has just alluded to, and we currently have 10 ongoing Phase II or III trials. Some of those are with partners. Some of those are fully bio-type self-funded. But I think it already shows you that we've already reached at this current R&D level pretty significant scale in the mid- and late-stage pipeline.

是的。關於目標管道，我認為這是一個非常好的問題。我只想指出，按照 Jens 剛才提到的當前研發支出水平，我們目前有 10 項正在進行的 II 期或 III 期試驗。其中一些是與合作夥伴一起進行的。其中一些是完全生物型自籌資金的。但我認為它已經向您表明，我們在目前的研發水平上已經在中後期管道中達到了相當大的規模。

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

謝謝。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。