Biontech SE (BNTX) 2023 Q3 法說會逐字稿

Welcome to the BioNTech Third Quarter 2023 Update Call. I would like to hand the call over to Dr. Victoria Meissner, Vice President of Strategy and Investor Relations. Please go ahead.

歡迎參加 BioNTech 2023 年第三季更新電話會議。我想將電話轉交給策略和投資者關係副總裁維多利亞·邁斯納 (Victoria Meissner) 博士。請繼續。

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

謝謝。早安，下午好。感謝您今天參加我們的 BioNTech 2023 年第三季財報電話會議。提醒一下，本次電話會議附帶的幻燈片以及今天早上發布的新聞稿可以在我們網站的投資者部分找到。

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

在下一張投影片上，您可以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。電話會議中的前瞻性陳述存在重大風險和不確定性，僅在電話會議原始日期發表，我們不承擔更新或修改任何陳述的義務。

On Slide 3, you can find the agenda for today's call. Today, I'm joined by the following members of BioNTech's management team. Our CEO and Co-Founder, Ugur Sahin; Ozlem Tureci, our Chief Medical Officer and Co-Founder; Jens Holstein, our Chief Financial Officer; and Ryan Richardson, our 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。我們的執行長兼聯合創辦人 Ugur Sahin； Ozlem Tureci，我們的首席醫療官兼聯合創始人； Jens Holstein，我們的財務長；以及我們的首席策略長 Ryan Richardson。

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

我想把電話轉給 Ugur Sahin。

Thank you, Victoria. A warm welcome to all those joining us today. I will summarize our third quarter highlights before turning to my colleagues who will provide further details.

謝謝你，維多利亞。熱烈歡迎今天加入我們的所有人。我將總結我們第三季的亮點，然後再向我的同事提供進一步的詳細資訊。

Slide 5. Let me start by providing an overview of our strategic priorities and latest achievements. This quarter, we continued to build on our global COVID-19 vaccine leadership with first-to-market Omicron XBB.1.5-adapted vaccine launches across multiple regions worldwide. I thank our team and collaborators for their tireless efforts to make this accomplishment possible again in such a short period of time. Our COVID-19 influenza combination program run in partnership with Pfizer leveraging our proprietary mRNA technology has also reported positive topline results. The Phase 1/2 study evaluating the safety, tolerability and immunogenicity of co-administered mRNA-based vaccine candidates for COVID-19 and influenza, among healthy adults 18 to 64 years of age when compared to a licensed influenza vaccine demonstrated robust immune responses to influenza A, influenza B and SARS-CoV-2 strains as well as a safety profile consistent with the safety profile of the company's COVID-19 vaccine. A pivotal Phase 3 study will be initiated in the coming months.

投影片 5。首先讓我概述一下我們的策略重點和最新成就。本季度，我們在全球多個地區推出了首個上市的 Omicron XBB.1.5 疫苗，繼續鞏固我們在全球 COVID-19 疫苗方面的領導地位。我感謝我們的團隊和合作者的不懈努力，使這項成就在如此短的時間內再次成為可能。我們與輝瑞合作的 COVID-19 流感聯合計畫利用我們專有的 mRNA 技術也報告了積極的頂線結果。 1/2 期研究評估了18 至64 歲健康成年人中聯合注射的針對COVID-19 和流感的基於mRNA 的候選疫苗的安全性、耐受性和免疫原性，與許可的流感疫苗相比，顯示出強大的免疫反應甲型流感、乙型流感和 SARS-CoV-2 株，以及與該公司的 COVID-19 疫苗的安全性一致的安全性。一項關鍵的第三階段研究將在未來幾個月內啟動。

Our second strategic priority is to advance our oncology platforms by initiating multiple trials with registrational potential. Jointly with our partner Duality Bio, we are initiating a pivotal Phase 3 trial to evaluate our next-generation antibody conjugate BNT323 in patients with hormone receptor positive HER2low breast cancer who progressed on previous standard of care but are chemotherapy naïve.

我們的第二個策略重點是透過啟動具有註冊潛力的多項試驗來推進我們的腫瘤學平台。我們與我們的合作夥伴Duality Bio 聯合啟動了一項關鍵的3 期試驗，以評估我們的下一代抗體偶聯物BNT323 在激素受體陽性HER2low 乳腺癌患者中的作用，這些患者在之前的標準護理中取得了進展，但未接受過化療。

Furthermore, during this quarter, we and our respective collaboration partners published original scientific papers and presented new clinical data across several programs at international scientific congresses, including ESMO and SITC, that will inform our development strategies and next step for these programs.

此外，在本季度，我們和我們各自的合作夥伴在國際科學大會（包括ESMO 和SITC）上發表了原創科學論文，並展示了多個項目的新臨床數據，這將為我們的發展策略和這些項目的下一步提供資訊。

Based on the successful results, we have expanded existing collaborations and made new deals with specialized developers, which add to our proprietary toolkit of technologies and strengthen our therapeutic product candidate portfolio. This covers the in-licensing of 3 targeted antibody drug conjugate from MediLink Therapeutics, and as announced today, our plan to bring forward anti-VEGF, anti-PD-1 bi-specific antibody in collaboration with our partner, Biotheus. Our first strategic priority is to initiate and accelerate clinical programs that target infectious diseases of unmet medical need. In the third quarter, we initiated our first test in-human trial in infectious disease this year, a program aimed at advancing mRNA-based vaccine candidates for the prevention of Mpox, run in partnership with the Coalition for Epidemic Preparedness Innovation.

基於成功的結果，我們擴大了現有的合作，並與專業開發商達成了新的交易，這增加了我們專有的技術工具包，並加強了我們的治療產品候選產品組合。這涵蓋了 MediLink Therapeutics 的 3 種靶向抗體藥物綴合物的許可，正如今天宣布的，我們計劃與我們的合作夥伴 Biotheus 合作推出抗 VEGF、抗 PD-1 雙特異性抗體。我們的首要策略重點是啟動和加速針對未滿足醫療需求的傳染病的臨床計劃。第三季度，我們啟動了今年首次針對傳染病的人體試驗，該計畫旨在推進基於 mRNA 的候選疫苗來預防 Mpox，該計畫與流行病防範創新聯盟合作運作。

In summary, we continued our focused execution against our strategic priorities in the first quarter and look forward to additional progress in all 3 of these areas for the remainder of the year and into 2024. We will share more detail on our oncology as well, infectious disease programs at our Innovation Series Day in Boston tomorrow, an event that I invite you all to attend in person or online.

總而言之，我們在第一季度繼續集中執行我們的戰略重點，並期待在今年剩餘時間和 2024 年在所有這 3 個領域取得更多進展。我們還將分享更多有關腫瘤學、傳染病學的細節明天我們將在波士頓舉行創新系列日的疾病項目，我邀請大家親自或在線上參加這項活動。

Slide 6, focusing on our marketed COVID-19 vaccine, COMIRNATY. We continue to build on our global COVID-19 vaccine leadership with first-to-market Omicron XBB.1.5-adapted vaccine launches. This was preceded by a robust and successful regulatory process. In late August, European Medicines Agency recommended full marketing authorization for our monovalent XBB.1.5-adapted vaccine. This was followed in September by the U.S. Food and Drug Administration authorizing the adaptive vaccine for individuals aged 6 months to 11 years under emergency use authorization and for those aged 12 and above. The vaccines have been approved under supplemental biologics license application.

投影片 6，重點介紹我們已上市的 COVID-19 疫苗 COMIRNATY。我們透過推出首款適應 Omicron XBB.1.5 的疫苗，繼續鞏固我們在全球 COVID-19 疫苗的領導地位。在此之前有一個強而有力且成功的監管流程。 8 月下旬，歐洲藥品管理局建議對我們的單價 XBB.1.5 疫苗進行全面行銷授權。隨後，美國食品藥物管理局於 9 月授權緊急使用授權為 6 個月至 11 歲的個人以及 12 歲及以上的個人使用適應性疫苗。這些疫苗已根據補充生物製品許可證申請獲得批准。

Second, other national health regulators across the globe, including the U.K., Japan, Canada and South Korea have also approved our monovalent adaptive vaccine. Within 2 months, we went from the first regulatory recommendations for an XBB.1.5-adapted vaccine to our first shipment of the respective vaccine. The ability to execute this at such speed was enabled by our continued surveillance and analysis of variance of concern, the strength of our mRNA technology, which allows for scalable production, rapid manufacturing and adaptation and our expertise at navigating the evolving regulatory landscape on a global scale. Historically, we have seen an increase in COVID-19 hospitalizations in the winter, in line with other common respiratory diseases.

其次，包括英國、日本、加拿大和韓國在內的全球其他國家衛生監管機構也批准了我們的單價適應性疫苗。在 2 個月內，我們從針對 XBB.1.5 疫苗的第一個監管建議到我們第一批相應疫苗的發貨。我們能夠以如此快的速度執行此任務，得益於我們對所關注差異的持續監控和分析、我們的mRNA 技術優勢（可實現可擴展生產、快速製造和適應）以及我們在應對全球不斷變化的監管環境方面的專業知識。規模。從歷史上看，與其他常見呼吸道疾病一樣，冬季 COVID-19 住院人數有所增加。

On Slide 7, you can see independent on formal projections across scenarios, assuming different vaccination recommendations and immune escape levels. Based on this, it is expected that weekly hospitalizations are likely to increase this winter and have a healthcare impact similar to last year. COVID-19 burden is currently lower than in previous years. However, the absolute number of hospitalizations and death is still high in certain regions with thousands of hospitalizations and hundreds of deaths each week. The emergence of new variants, coupled with the waning of both vaccine and infection-induced immunity indicates that susceptibility to infection remains a concern and may increase over time. Moreover, the data shown here suggests that providing simple, stable recommendations for updated doses could contribute to improved vaccine coverage over time, mitigating the risk associated with evolving COVID-19 variants.

在投影片 7 上，您可以看到獨立於跨場景的正式預測，假設不同的疫苗接種建議和免疫逃脫程度。據此，預計今年冬季每週住院人數可能會增加，並對醫療保健產生與去年類似的影響。目前，COVID-19 負擔低於前幾年。然而，某些地區的住院和死亡絕對人數仍然很高，每周有數千人住院，數百人死亡。新變種的出現，加上疫苗和感染引起的免疫力的減弱，表明對感染的易感性仍然是一個令人擔憂的問題，並且可能隨著時間的推移而增加。此外，此處顯示的數據表明，為更新劑量提供簡單、穩定的建議可能有助於隨著時間的推移提高疫苗覆蓋率，從而減輕與不斷演變的 COVID-19 變種相關的風險。

As shown on Slide 8, Long COVID has a significant societal and healthcare system impact, the studies indicating that 10% to 20% of SARS-CoV-2 infected inhibitors may develop symptoms recognized as Long COVID. It is estimated that 36 million people across Europe may have experienced complications arising from COVID-19 weeks after infection commonly defined as Long COVID from the start of the pandemic to date. Studies show that mRNA vaccination has a significant impact in reducing the development of Long Covid by 10% to 45% depending on the criteria used to define symptoms. The protective effect of mRNA vaccination is largely attributed to its ability to reduce susceptibility to infection. We continue to look closely at the role of mRNA vaccination in addressing the unmet need of Long COVID.

如投影片 8 所示，長 COVID 具有重大的社會和醫療保健系統影響，研究顯示 10% 至 20% 的 SARS-CoV-2 感染抑制劑可能會出現被識別為長 COVID 的症狀。據估計，從大流行開始至今，歐洲各地有 3600 萬人可能在感染通常被定義為「長新冠病毒」的幾週後經歷了由新冠病毒 (COVID-19) 引起的併發症。研究表明，mRNA 疫苗接種可以顯著減少長新冠病毒的發展，減少 10% 至 45%，具體取決於用於定義症狀的標準。 mRNA疫苗接種的保護作用很大程度上歸因於其降低感染易感性的能力。我們將繼續密切關注 mRNA 疫苗接種在解決長新冠病毒未滿足的需求方面的作用。

Slide 9. Studies have demonstrated that natural immunity acquired by SARS-CoV-2 infection is variable across individuals, and the protection it offers wanes over time. Vaccination can restore and enhance infection acquired immune protection and further reduce the risk of the re-infection. The risk of severe COVID-19 disease remains high in vulnerable populations and that vaccination serves to not only reduce the risk, but can also mitigate the risk of Long COVID. And pre-clinical data demonstrate that vaccination of XBB.1 descendent lineage containing candidate elicit higher neutralizing antibody to currently circulating variant of concern compared to the responses elicited by previously approved COVID-19 vaccine.

投影片 9。研究表明，SARS-CoV-2 感染獲得的自然免疫力在個體之間存在差異，並且其提供的保護作用會隨著時間的推移而減弱。疫苗接種可以恢復和增強感染後天免疫保護，進一步降低再次感染的風險。在弱勢群體中，嚴重 COVID-19 疾病的風險仍然很高，疫苗接種不僅可以降低風險，還可以減輕長期 COVID 的風險。臨床前數據表明，與先前批准的 COVID-19 疫苗引起的反應相比，含有候選疫苗的 XBB.1 後代譜系疫苗接種可引發針對當前流行的關注變異體的更高中和抗體。

Given all this and our current understanding of COVID-19 seasonality and its burden on healthcare systems during autumn and winter season, we anticipate the need for annual adaptive vaccines to be a long-term feature of COVID-19 vaccination practices.

鑑於所有這些以及我們目前對 COVID-19 季節性及其在秋冬季節對醫療系統造成的負擔的了解，我們預計每年接種適應性疫苗的需求將成為 COVID-19 疫苗接種實踐的長期特徵。

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

在此，我要感謝大家對我們成功的信心和持續的支持。我現在將把電話轉給 Ozlem。

Thank you, Ugur. Glad to be speaking with everyone. Today, we will provide a high-level pipeline update. We will delve into the more advanced programs in greater detail at our Innovation Series Day event tomorrow.

謝謝你，烏古爾。很高興與大家交談。今天，我們將提供高級管道更新。我們將在明天的創新系列日活動中更詳細地探討更進階的計畫。

Starting with an overview of our infectious disease pipeline on Slide 11. In addition to our marketed product, COMIRNATY, we continue to pursue our multi-prompt innovation strategy to improve upon our vaccine with next-generation approaches aimed at generating broader and more durable immunity. This includes our stabilized spike vaccine approach being studied in the Phase 2 trial and our Tcell-enhancing vaccine candidate in an ongoing Phase 1 trial. We believe that our COVID-19 vaccine has the potential to be combined with a seasonal flu vaccine. Across many parts of the world, people are currently receiving the Omicron-XBB adapted vaccine boosters at the same time as their flu shots. A combination product has the potential to provide seasonal protection from both viruses with a single shot. We are working together with our partner, Pfizer, to develop an influencer combination vaccine, which leverage our mRNA technology.

首先從幻燈片11 上我們傳染病產品線的概述開始。除了我們的上市產品COMIRNATY 之外，我們還繼續奉行多重即時創新策略，透過下一代方法改進我們的疫苗，旨在產生更廣泛、更持久的免疫力。這包括我們在 2 期試驗中研究的穩定刺突疫苗方法以及我們在正在進行的 1 期試驗中研究的 T 細胞增強候選疫苗。我們相信我們的 COVID-19 疫苗有潛力與季節性流感疫苗結合。在世界許多地區，人們目前在註射流感疫苗的同時接受 Omicron-XBB 改良疫苗加強劑。組合產品有潛力透過單次注射提供對兩種病毒的季節性保護。我們正在與合作夥伴輝瑞合作，利用我們的 mRNA 技術開發一種影響因子組合疫苗。

We recently reported Phase 1/2 results, where our combination candidate showed robust immune responses to influenza A, influenza B and SARS-CoV-2 strains as well as a safety profile consistent with the safety profile of company's COVID-19 vaccine, which met the criteria for advancement to a Phase 3 trial. In addition to the previously mentioned COVID-19 and influenza vaccine program, we started multiple first in-human trials of our mRNA vaccine candidates in the last year that addressed Shingles, HSV, TB and Mpox.

我們最近報告了1/2 期結果，其中我們的聯合候選藥物顯示出對甲型流感、乙型流感和SARS-CoV-2 毒株的強大免疫反應，並且安全性與該公司的COVID-19 疫苗的安全性一致，該疫苗符合進入第三階段試驗的標準。除了前面提到的 COVID-19 和流感疫苗計劃外，我們去年還針對帶狀皰疹、HSV、結核病和 Mpox 啟動了針對 mRNA 候選疫苗的多項首次人體試驗。

On Slide 12, as expected, SARS-CoV-2 continues to evolve. The Omicron XBB sub-lineages currently account for the majority of COVID-19 cases globally, including the XBB-descendent EG.5.1 whose dominance is growing.

在投影片 12 上，正如預期的那樣，SARS-CoV-2 繼續進化。目前，Omicron XBB 亞系佔全球 COVID-19 病例的大多數，其中包括其主導地位正在增長的 XBB 後代 EG.5.1。

Slide 13. We and our partner, Pfizer, tested for potential effectiveness of an Omicron XBB.1.5-adapted monovalent vaccine as a primary series and booster in preclinical models. You can see here the neutralizing antibody response in mice immunized with our Omicron BA.4/BA.5 adapted bivalent vaccine as a booster after 2 doses of the original BNT162b2 vaccine. One group of mice again received the BA.4-5 adapted bivalent COVID-19 vaccine as a fourth dose and the other group received the new XBB.1.5adapted monovalent COVID-19 vaccine as a fourth dose. You can see a 4- to 5-fold increase of neutralization of several XBB-related variants when dose 4 is the XBB.1.5-adapted monovalent vaccine as compared to last season's BA.4-5adapted vaccine.

投影片 13。我們和我們的合作夥伴輝瑞 (Pfizer) 在臨床前模型中測試了 Omicron XBB.1.5 適應單價疫苗作為主要係列和加強疫苗的潛在有效性。您可以在此處看到使用我們的 Omicron BA.4/BA.5 適應二價疫苗作為加強劑免疫的小鼠在接種 2 劑原始 BNT162b2 疫苗後的中和抗體反應。一群小鼠再次接受 BA.4-5 適應的二價 COVID-19 疫苗作為第四劑，另一組接受新的 XBB.1.5 適應的單價 COVID-19 疫苗作為第四劑。與上一季的 BA.4-5 適應疫苗相比，當第 4 劑是 XBB.1.5 適應單價疫苗時，您可以看到幾種 XBB 相關變體的中和作用增加了 4 至 5 倍。

This preclinical data indicate that an XBB.1.5 variant-adapted monovalent vaccine in the pre-vaccinated setting has the potential to induce broad cross-neutralizing antibody titer against multiple XBB sub-lineages. We can also see an increase in geometric mean titers of neutralizing antibodies across XBB lineages, including EG.5.1 and BA.2.86 when compared to the previous bivalent BA.4.5 vaccine comparator.

此臨床前數據表明，在預接種環境中適應 XBB.1.5 變異體的單價疫苗有可能誘導針對多個 XBB 亞譜系的廣泛交叉中和抗體滴度。與先前的二價 BA.4.5 疫苗比較劑相比，我們還可以看到 XBB 譜系（包括 EG.5.1 和 BA.2.86）中和抗體的幾何平均滴度增加。

Slide 14 shows the design of our ongoing Phase 2/3 clinical study, testing the safety, tolerability and immunogenicity of our Omicron XBB.1.5-adapted monovalent vaccine in 700 vaccine-naive and 16 experienced participants. While data from the study will be reported in 2024, there's already clinical real-world data shown on Slide 15, demonstrating that our XBB.1.5-adapted vaccine elicited significantly higher neutralizing antibody responses against XBB.1.5, XBB.2.3, EG.5.1 and BA2.86 compared to pre-vaccination levels.

投影片14 顯示了我們正在進行的2/3 期臨床研究的設計，該研究在700 名未接種過疫苗的參與者和16 名經驗豐富的參與者中測試了我們的Omicron XBB.1.5 適應單價疫苗的安全性、耐受性和免疫原性。雖然研究的數據將於2024 年報告，但投影片15 中已經顯示了臨床真實數據，顯示我們的XBB.1.5 疫苗針對XBB.1.5、XBB.2.3、EG.5.1 引發了顯著更高的中和抗體反應和 BA2.86 與疫苗接種前水準相比。

Moving now to our oncology pipeline on Slide 16, which is grounded in our multi-modality toolbox and is advancing through focused execution. We now have one Phase 3 study ongoing and the second Phase 3 expected to dose its first patient soon. Gotistobart, our anti-CTLA-4 monoclonal antibody, which we believe offers a differentiated safety profile, a Phase 3 clinical trial evaluating its efficacy and safety as monotherapy and metastatic non-small cell lung cancer patients who have progressed on previous IO therapy has started in June this year and will enroll 600 patients. BNT323, our anti-HER2 antibody drug conjugate, also being studied in a Phase 3 clinical trial to assessing its efficacy versus investigator's choice of chemotherapy in patients with hormone receptor positive HER2-low chemotherapy naive breast cancer patients whose disease has progressed on at least 2 lines of prior endocrine therapy or within 6 months of first-line endocrine therapy plus CDK4 inhibitor.

現在轉向幻燈片 16 上的腫瘤學管道，該管道基於我們的多模態工具箱，並透過集中執行來推進。我們現在正在進行一項 3 期研究，第二項 3 期研究預計很快就會給第一位患者用藥。 Gotistobart 是我們的抗CTLA-4 單株抗體，我們相信它具有差異化的安全性，一項3 期臨床試驗已啟動，評估其作為單一療法和在先前IO 治療中出現進展的轉移性非小細胞肺癌患者的療效和安全性今年6月將招募600名患者。 BNT323 是我們的抗HER2 抗體藥物偶聯物，也在一項3 期臨床試驗中進行研究，以評估其在激素受體陽性HER2 低化療初治乳腺癌患者中的療效與研究者選擇的化療的比較，這些患者的疾病在至少2 年內出現進展既往內分泌治療線或一線內分泌治療加上 CDK4 抑制劑 6 個月內。

We've also recently initiated 2 new Phase 2 trials, one in partnership with Genentech. It's evaluating our individualized cancer vaccine candidate, BNT122, in the actual setting for patients with pancreatic cancer. The other in partnership with Genmab is evaluating our BNT311 bispecific, conditionally PD-L1/4-1BB agonistic antibody as a second-line treatment for patients with endometrial cancer. Also, as part of our collaboration with Genmab, BNT314, a bispecific antibody designed to boost antitumor immune response through EpCAM-dependent 4-1BB agonistic activity is ready to move from preclinical to Phase I clinical testing with the first patient dosed expected in the next few months. Within our bispecific portfolio, I'm excited about our expanded collaboration with Biotheus announced today, we've partnered to develop and commercialize PM8002, a bispecific antibody candidate targeting PD-L1 and VEGF, in various cancer indications. PM8002 is currently being tested in a Phase 2/3 study to evaluate the efficacy and safety of a candidate at monotherapy or in combination with chemotherapy in patients with non-small cell lung cancer. PN8002 may lead to reduced systemic toxicity by enriching anti-VEGF activity in the tumor micro environment.

我們最近也啟動了 2 項新的 2 期試驗，其中一項是與 Genentech 合作的。它正在針對胰腺癌患者在實際環境中評估我們的個人化癌症候選疫苗 BNT122。與 Genmab 合作的另一個項目正在評估我們的 BNT311 雙特異性、條件性 PD-L1/4-1BB 激動性抗體作為子宮內膜癌患者的二線治療。此外，作為我們與Genmab 合作的一部分，BNT314 是一種雙特異性抗體，旨在透過EpCAM 依賴性4-1BB 激動活性增強抗腫瘤免疫反應，已準備好從臨床前轉移到I 期臨床測試，預計在下一個患者中接受給藥幾個月。在我們的雙特異性產品組合中，我對今天宣布的與Biotheus 的擴大合作感到興奮，我們合作開發和商業化PM8002，這是一種針對PD-L1 和VEGF 的雙特異性抗體候選藥物，用於各種癌症適應症。 PM8002 目前正在一項 2/3 期研究中進行測試，以評估候選藥物單一療法或與化療聯合治療非小細胞肺癌患者的療效和安全性。 PN8002 可能透過增強腫瘤微環境中的抗 VEGF 活性來降低全身毒性。

Now moving on to our antibody drug conjugate portfolio. During the quarter, one of our [antibody] -- ADCs, BNT324, entered Phase I/II basket trial. Furthermore, on the ADC front, I would like to note our latest addition, YL202 candidate being developed in partnership with MediLink. We continue to broaden our access to ADCs because we believe this technology has the potential to replace highly toxic chemotherapy regimens to become a new commoditized combination backbone of cancer treatment.

現在轉向我們的抗體藥物偶聯物產品組合。本季度，我們的一種[抗體]—ADC，BNT324，進入 I/II 期籃子試驗。此外，在 ADC 方面，我想指出我們最新添加的產品，即與 MediLink 合作開發的 YL202 候選藥物。我們繼續擴大 ADC 的使用範圍，因為我們相信這項技術有潛力取代劇毒化療方案，成為癌症治療的新商品化組合骨幹。

In summary, we can see a diversified clinical oncology pipeline and solid tumor indications of high unmatched medical needs and more than 30 clinical studies.

總而言之，我們可以看到多元化的臨床腫瘤產品管線和具有高度無與倫比的醫療需求的實體瘤適應症以及30多項臨床研究。

On Slide 17, I would like to highlight 5 across our multiple platforms that have disclosed clinical data in recent medical conferences this autumn. In September, clinical data from the ongoing Phase 1/2 clinical trial, evaluating BNT323 in patients with advanced and unresectable recurrent or metastatic HER2expressing solid tumors were presented at the ESGO Annual Meeting. BNT323 was shown to have a manageable safety profile and no new safety signals were observed. It also demonstrated promising anti-tumor activity in patients with advanced recurrent or metastatic HER2expressing endometrial cancer with an objective response rate confirmed and unconfirmed of 58.8% and disease control rate of 94.1%.

在投影片 17 上，我想重點介紹我們多個平台上的 5 個平台，這些平台在今年秋天最近的醫學會議上揭露了臨床數據。 9 月，ESGO 年會上發表了正在進行的 1/2 期臨床試驗的臨床數據，該試驗評估了 BNT323 在晚期和不可切除的複發性或轉移性 HER2 表達實體瘤患者中的作用。 BNT323 已被證明具有可控的安全性，並且沒有觀察到新的安全訊號。它還在晚期復發或轉移性表達 HER2 的子宮內膜癌患者中表現出良好的抗腫瘤活性，經證實和未經證實的客觀緩解率為 58.8%，疾病控制率為 94.1%。

Data at ESMO, we presented alongside our partner, DualityBio, clinical data from the ongoing Phase 1/2 trial, evaluating our TROP-2 targeted ADC candidate in patients with advanced solid tumors. The data suggests that a manageable safety profile at lower dosages and encouraging efficacy sickness were observed in non-small cell lung cancer patients with unconfirmed objective response rate of 46.2% in 6 out of 13 evaluated patients and an unconfirmed CCR of 92.3% in 12 out of 13 patients.

在 ESMO 數據上，我們與合作夥伴 DualityBio 一起展示了正在進行的 1/2 期試驗的臨床數據，評估了我們的 TROP-2 靶向 ADC 候選藥物對晚期實體瘤患者的作用。數據表明，在非小細胞肺癌患者中觀察到較低劑量的可控安全性和令人鼓舞的療效，13 名接受評估的患者中有6 名未經證實的客觀緩解率為46.2%，12 名未經證實的CCR 為92.3%共 13 名患者。

We also reported data from the ongoing Phase 1/2 clinical trial with BNT211, detailing the new dose escalation of Claudin-6 CAR-T cells with and without a Claudin-6-encoding mRNA vaccine for the treatment of Claudin-6 positive relapsed/refractory solid tumors using an automated manufacturing process. BNT211 demonstrated an encouraging anti-tumor activity, and in patients treated at a higher dose level, the additional CARVac improved CAR-Tcell persistence.

我們也報告了正在進行的BNT211 1/2 期臨床試驗的數據，詳細介紹了使用和不使用Claudin-6 編碼mRNA 疫苗的Claudin-6 CAR-T 細胞的新劑量遞增，用於治療Claudin-6 陽性復發/使用自動化製造製程治療難治性實體瘤。 BNT211 表現出令人鼓舞的抗腫瘤活性，並且在接受較高劑量水平治療的患者中，額外的 CARVac 改善了 CAR-T 細胞的持久性。

The rate of treatment dependent adverse events was dose dependent. After determination of a recommended Phase 2 dose, BioNTech plans to initiate a pivotal trial in germ cell tumors. Also at ESMO, we presented initial data from our first-in-human Phase 1 dose escalation trial, evaluating BNT221. Our autologous fully personalized T-cell therapy directed against selected sets of individualized neoantigens. Using our proprietary NEOSTIM technology on the patient's peripheral blood test, we expand memory T-cells and induce naive T-cells with the aim of generating a strong polyclonal immune response to overcome antigen escape. The initial results showed a manageable safety profile and tumor regression in several patients with anti-PD-1 and anti-CTLA-4 pretreated advanced or metastatic melanoma.

治療依賴性不良事件的發生率是劑量依賴性的。在確定建議的 2 期劑量後，BioNTech 計劃啟動生殖細胞腫瘤的關鍵試驗。同樣在 ESMO，我們展示了首次人體 1 期劑量遞增試驗的初步數據，該試驗評估了 BNT221。我們的自體完全個人化 T 細胞療法針對選定的個人化新抗原。我們在患者的周邊血液測試中使用我們專有的 NEOSTIM 技術，擴增記憶 T 細胞並誘導幼稚 T 細胞，目的是產生強大的多克隆免疫反應以克服抗原逃脫。初步結果顯示，幾名接受抗 PD-1 和抗 CTLA-4 預處理的晚期或轉移性黑色素瘤患者的安全性可控，腫瘤消退。

This past weekend at the SITC, clinical data was shown from the ongoing Phase 1 clinical trial evaluating BNT116, our off-the-shelf mRNA-based cancer vaccine candidate for non-small cell lung cancer patients. The trial evaluates BNT116 alone and in combination with cemiplimab or docetaxel across multiple settings. BNT116 was generally well tolerated with an expected safety profile as monotherapy and in combination with cemiplimab. In heavily pretreated non-small cell lung cancer patients, treatment with BNT116 with an optional addition of cemiplimab from cycle 3 onwards showed early clinical activity. These updates show the momentum across our cancer pipeline. This year and next year, we plan to advance our key programs into late-stage development, including multiple programs towards the pivotal stage with the aim to deliver the next generation of oncology medicines.

上週末在 SITC，顯示了正在進行的評估 BNT116 的 1 期臨床試驗的臨床數據，BNT116 是我們針對非小細胞肺癌患者的現成的基於 mRNA 的癌症候選疫苗。該試驗在多種環境下單獨評估 BNT116 以及與 cemiplimab 或多西他賽聯合使用。 BNT116 作為單一療法以及與 cemiplimab 聯合用藥時整體耐受性良好，具有預期的安全性。在經過大量預處理的非小細胞肺癌患者中，從第 3 個週期開始使用 BNT116 並可選添加 cemiplimab 治療顯示出早期臨床活性。這些更新顯示了我們整個癌症管道的勢頭。今年和明年，我們計劃將重點項目推進到後期開發，包括多個項目邁向關鍵階段，旨在提供下一代腫瘤藥物。

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

現在，我將把簡報交給我們的財務長 Jens Holstein。

Thank you, Ozlem, and a warm welcome to everyone who dialed in today's call. Before we go into the financial details for the third quarter and the first 9 months of 2023, I'll start by giving you an overview on some key financial highlights, which you can find on the next slide. Our total revenues reached EUR 2.3 billion for the first 9 months of 2023 and were significantly derived from sales of our recently approved Omicron XBB.1.5adapted monovalent vaccine, which started to pick up at the end of the third quarter of 2023 and are expected to accelerate for the remainder of the year.

謝謝您，Ozlem，並熱烈歡迎所有撥打今天電話的人。在我們討論 2023 年第三季和前 9 個月的財務細節之前，我將首先向您概述一些關鍵的財務亮點，您可以在下一張幻燈片中找到這些亮點。 2023 年前 9 個月，我們的總收入達到 23 億歐元，主要來自我們最近批准的 Omicron XBB.1.5 適應單價疫苗的銷售，該疫苗於 2023 年第三季末開始回升，預計今年剩餘時間內加速。

Our revenues during the first 9 months of 2023 were negatively influenced in the amount of approximately EUR 0.6 billion triggered by write-downs and other charges reported by our collaboration partner, Pfizer. As a reminder, as part of our gross profit share arrangement at Pfizer, write-downs and similar charges by Pfizer reduced the gross profit, which both parties generally share equally. And this ultimately impacts BioNTech's revenue figure. As part of this contractual model, we own and commercialize COMIRNATY in Germany and Turkey, and commercialization costs remain with the party being responsible for its respective markets.

由於我們的合作夥伴輝瑞報告的減記和其他費用，我們在 2023 年前 9 個月的收入受到了約 6 億歐元的負面影響。提醒一下，作為我們在輝瑞的毛利分享安排的一部分，輝瑞的減記和類似費用減少了毛利，而雙方通常平等分享毛利。這最終會影響 BioNTech 的收入數據。作為此合約模式的一部分，我們在德國和土耳其擁有 COMIRNATY 並將其商業化，商業化成本仍由負責各自市場的一方承擔。

While we have impacted by such write-downs on the top line, our sales and marketing expenses remain low. As we have outlined in earlier earnings calls, the revenue development for COVID-19 vaccines is expected to mimic a flu-like setting. I will go into more details concerning our financial guidance in the course of the call, but I want to emphasize now that taking the Pfizer announcement and its implications on to the 2023 revenues into account, we have updated our 2023 COVID-19 vaccine revenue guidance of around EUR 5 billion to somewhere around EUR 4 billion for the full financial year 2023.

儘管我們的營收受到此類減記的影響，但我們的銷售和行銷費用仍然很低。正如我們在先前的財報電話會議中所概述的那樣，COVID-19 疫苗的收入發展預計將模仿流感的情況。我將在電話會議中詳細介紹我們的財務指引，但我現在想強調的是，考慮到輝瑞的公告及其對 2023 年收入的影響，我們已經更新了 2023 年 COVID-19 疫苗收入指引2023 年整個財政年度約50 億歐元至40 億歐元左右。

During the first 9 months of 2023, we generated a profit before tax of EUR 0.5 billion, which on top of our operating results, demonstrates our positive financial results generated from our strong financial position, overall, resulting in earnings per share on a fully diluted basis of EUR 1.94.

2023 年前9 個月，我們實現了5 億歐元的稅前利潤，除了我們的經營業績之外，這也證明了我們強勁的財務狀況所帶來的積極的財務業績，總體而言，我們實現了完全攤薄後的每股收益基礎為 1.94 歐元。

We started into the financial year 2023 with a total amount of EUR 13.9 billion in cash and cash equivalents, which we significantly increased due to our steady cash collection. Hence, we have now ended the third quarter of 2023 with EUR 17 billion. This amount comprises approximately EUR 13.5 billion reflected as cash and cash equivalents in our financial statements as well as approximately EUR 3.5 billion, partly current and partly non-current security investments.

進入 2023 財年，我們的現金和現金等價物總額為 139 億歐元，由於我們穩定的現金回收，我們的現金和現金等價物總額大幅增加。因此，截至 2023 年第三季度，我們的營收為 170 億歐元。該金額包括約 135 億歐元（在我們的財務報表中反映為現金和現金等價物）以及約 35 億歐元（部分流動和部分非流動證券投資）。

Subsequent to the end of the quarter in October 2023, we received EUR 565 million in cash from our collaboration partner, Pfizer, settling our gross profit share for the second quarter of 2023, our strong financial position as a strategic advantage. These days where financial stability is key for companies in this industry, a cash surplus is a tremendous asset. Our cash position offers us opportunities to invest in capabilities and assets to build a highly innovative later-stage R&D pipeline.

2023 年 10 月季度末後，我們從合作夥伴輝瑞收到了 5.65 億歐元現金，結算了 2023 年第二季度的毛利份額，這是我們強大的財務狀況的戰略優勢。如今，財務穩定對於該行業的公司至關重要，現金盈餘是一筆巨大的資產。我們的現金狀況為我們提供了投資能力和資產的機會，以建立高度創新的後期研發管道。

Help me move into our financial results for the third quarter of 2023 as shown on the next slide. Our total revenues reported reached EUR 0.9 billion for the third quarter compared to EUR 3.5 billion for the comparative prior year period and decreased corresponding with a lower COVID-19 vaccine market demand. The already mentioned write-downs by Pfizer reduced our gross profit share in the third quarter by approximately EUR 0.5 billion.

請幫我了解 2023 年第三季的財務業績，如下一張投影片所示。我們第三季的總營收達到 9 億歐元，而去年同期為 35 億歐元，並隨著 COVID-19 疫苗市場需求的下降而下降。前面提到的輝瑞減記使我們第三季的毛利份額減少了約 5 億歐元。

Let me move to cost of sales, which amounted to EUR 161.8 million in the third quarter of 2023 compared to EUR 752.8 million for the comparative prior year period. For the first 9 months of 2023, the cost of sales reached EUR 420.7 million compared to EUR 2.8 billion for the comparative prior year period. The change is in line with decreasing COVID-19 vaccine revenues. Research and development expenses reached EUR 497.9 million for the third quarter of 2023 compared to EUR 341.8 million for the comparative prior year period.

讓我們來談談銷售成本，2023 年第三季的銷售成本為 1.618 億歐元，而去年同期為 7.528 億歐元。 2023 年前 9 個月，銷售成本達到 4.207 億歐元，去年同期為 28 億歐元。這項變化與 COVID-19 疫苗收入的減少一致。 2023 年第三季的研發費用達到 4.979 億歐元，去年同期為 3.418 億歐元。

For the first 9 months of 2023, research and development expenses amounted to EUR 1.2 billion compared to EUR 1 billion for the comparative prior year period. Our R&D expenses are mainly influenced by progressing clinical studies for pipeline candidates, the development of varied adapted as well as next-generation COVID-19 vaccines and the expansion of our R&D headcount.

2023 年前 9 個月，研發費用達 12 億歐元，去年同期為 10 億歐元。我們的研發費用主要受到管道候選藥物臨床研究進展、各種適應性疫苗和下一代 COVID-19 疫苗的開發以及研發人員規模擴大的影響。

General and administrative expenses amounted to EUR 144.5 million for the third quarter of 2023 compared to EUR 141 million for the comparative prior year period. For the first 9 months of 2023, G&A expenses reached EUR 386.6 million compared to EUR 361.8 million for the comparative prior year period. G&A expenses for the first 9 months were mainly influenced by increased expenses for IT services as well as expanding the G&A headcount.

2023 年第三季的一般及管理費用為 1.445 億歐元，去年同期為 1.41 億歐元。 2023 年前 9 個月，一般管理費用達到 3.866 億歐元，去年同期為 3.618 億歐元。前 9 個月的一般管理費用主要受到 IT 服務費用增加以及一般管理人員人數擴大的影響。

Our profit before tax amounted to EUR 227.4 million for the third quarter of 2023 compared to EUR 2.4 billion for the comparative prior year period. As mentioned, this reflects the performance in our financial results derived from our strong financial position. Income taxes were accrued with an amount of EUR 66.8 million for the third quarter of 2023 compared to EUR 0.7 billion for the comparative prior year period. In total, for the first 9 months of 2023, income taxes were accrued with an amount of EUR 50.5 million compared to EUR 2.6 billion for the comparative prior year period. The derived effective income tax rate for the first 9 months of 2023 were approximately 9.7%, which is expected to change over the 2023 financial year to be in line with the estimated annual cash effective income tax rate of somewhere around 21% for the BioNTech's growth.

2023 年第三季度，我們的稅前利潤為 2.274 億歐元，而去年同期為 24 億歐元。如前所述，這反映了我們強勁的財務狀況所帶來的財務表現。 2023 年第三季應計所得稅為 6,680 萬歐元，而去年同期為 7 億歐元。 2023 年前 9 個月，應計所得稅總額為 5,050 萬歐元，而去年同期為 26 億歐元。 2023 年前 9 個月的有效所得稅率約為 9.7%，預計在 2023 財年將發生變化，與 BioNTech 增長的預計年度現金有效所得稅率約 21% 一致。

We recognized a net profit during the third quarter of 2023 amounting to EUR 160.6 million compared to EUR 1.8 billion for the comparative prior year period. For the first 9 months of 2023, net profit reached EUR 0.5 billion compared to EUR 7.2 billion for the comparative prior year period. Our earnings per share on a fully diluted basis for the third quarter of 2023 amounted to EUR 0.67 compared to a diluted earnings per share of EUR 6.98 for the comparative prior year period. For the first 9 months of 2023, our diluted earnings per share was EUR 1.94 compared to EUR 27.70 for the comparative prior year period.

我們確認 2023 年第三季淨利為 1.606 億歐元，而去年同期為 18 億歐元。 2023 年頭 9 個月，淨利達 5 億歐元，而去年同期淨利為 72 億歐元。 2023 年第三季完全稀釋後的每股收益為 0.67 歐元，而去年同期的稀釋後每股收益為 6.98 歐元。 2023 年前 9 個月，我們的稀釋每股收益為 1.94 歐元，去年同期為 27.70 歐元。

As mentioned in the beginning, please allow me now to address the inventory write-downs and other charges related to COMIRNATY recently announced by our collaboration partner Pfizer in more detail. Please note, those charges were mainly triggered when the world moves from a pandemic environment into an endemic flu-like setting. In this context, we announced on October 16, an estimated impact of up to EUR 0.9 billion. We have assessed the initially announced estimate further, particularly to address the question whether those inventory write-downs and other charges indicated by Pfizer have already been reflected in our accounts. The good news is the charges which originated at BioNTech's end have largely already been reflected in our 2022 financial results, and to a small extent, will continue to be reflected during 2023. Ultimately, the impact from our collaboration partners, charges onto our revenues have been identified to be roughly EUR 0.6 billion for the first 9 months of 2023 and EUR 0.5 billion for the third quarter of 2023.

如同開頭所提到的，現在請允許我更詳細地討論我們的合作夥伴輝瑞最近宣布的與 COMIRNATY 相關的庫存減記和其他費用。請注意，這些指控主要是在世界從大流行環境轉變為地方性流感環境時引發的。在此背景下，我們在10月16日宣布，預計影響高達9億歐元。我們進一步評估了最初宣布的估計，特別是為了解決輝瑞公司指出的庫存減記和其他費用是否已經反映在我們的帳目中的問題。好消息是 BioNTech 端產生的費用已在很大程度上反映在我們 2022 年的財務業績中，並且在一小部分程度上將在 2023 年繼續反映。最終，我們的合作夥伴對我們收入的影響預計2023 年前9 個月約6 億歐元，2023 年第三季約5 億歐元。

To explain the partnership mechanism in respect of write-downs and comparable charges, please remember that risks are borne by both partners equally. As a part of our shared responsibilities, both partners are responsible for manufacturing activities. Hence, Pfizer is responsible for a certain level of inventories and so are we. If, for example, Pfizer writes down inventories under its control, those charges reduce the gross profit that is shared with us. As a result, we are affected by half of those charges. Those charges lead to a decrease in our revenues according to IFRS accounting rules. In cases where we have to book charges for [EG] write-downs, at our end, those charges lower the gross profit that we share with Pfizer.

為了解釋減記和可比較費用方面的合夥機制，請記住，風險由雙方平等承擔。作為我們共同責任的一部分，雙方都負責製造活動。因此，輝瑞負責一定水準的庫存，我們也是如此。例如，如果輝瑞公司減記其控制下的庫存，這些費用就會減少與我們分享的毛利。因此，我們受到其中一半費用的影響。根據國際財務報告準則會計規則，這些費用導致我們的收入減少。如果我們必須記入 [EG] 減記費用，那麼這些費用最終會降低我們與輝瑞分享的毛利。

Let me now turn to the next slide. As stated before, based on what we know of the expected market development in our partners' guidance for their market, we update our estimated COVID-19 vaccine revenues from previously around EUR 5 billion to somewhere around EUR 4 billion for the full 2023 financial year. Our guidance is influenced by the mentioned write-downs and charges on the Pfizer side in the amount of EUR 0.6 billion as well as our partners reduced expectation on 2023 COVID-19 vaccine sales. We, at BioNTech, reacted on the volatility around the COVID-19 vaccine market and adapted our cost base in the course of 2023. Our strategic collaboration model with big pharma supports drug development and delivery at scale, but it also provides us additional financial flexibility by leveraging the global clinical trial network of our partners as well as their commercial network and their internal resources.

現在讓我轉到下一張投影片。如前所述，根據我們對合作夥伴市場指南中預期市場發展的了解，我們將 2023 年整個財年的 COVID-19 疫苗收入預估從之前的 50 億歐元左右更新為 40 億歐元左右。我們的指引受到上述輝瑞方面 6 億歐元的減記和費用以及我們的合作夥伴降低的 2023 年 COVID-19 疫苗銷售預期的影響。 BioNTech 針對COVID-19 疫苗市場的波動做出了反應，並在2023 年調整了我們的成本基礎。我們與大型製藥公司的策略合作模式支持大規模藥物開發和交付，同時也為我們提供了額外的財務靈活性透過利用我們合作夥伴的全球臨床試驗網絡及其商業網絡和內部資源。

In comparison to other models, this collaboration setup allows us to accelerate our development initiatives while having a lower level of expenses. Our updated financial outlook for the 2023 financial year excludes effects caused by, but not limited to, events like in-licensing arrangements, collaborations for M&A transactions that might take place until the year-end.

與其他模型相比，這種協作設定使我們能夠加快開發計劃，同時降低費用。我們更新的 2023 財年財務展望不包括但不限於年底前可能發生的授權安排、併購交易合作等事件造成的影響。

As summarized for you on this slide, we reduced the initial 2023 R&D expense guidance range from initially between EUR 2.4 billion and EUR 2.6 billion to between EUR 1.8 billion and EUR 2 billion, including the R&D costs identified from our latest publicly announced M&A activities. We also updated our SG&A expenses and narrow the initial 2023 guidance range from between EUR 650 million and EUR 750 million, down to between EUR 600 million and EUR 650 million. Lastly, we reduced our spending for growth and maintenance CapEx for operating activities from the initial 2023 guidance range of between EUR 500 million and EUR 600 million to between EUR 200 million and EUR 300 million.

正如本投影片中為您總結的那樣，我們將2023 年最初的研發費用指引範圍從最初的24 億歐元至26 億歐元之間減少到18 億歐元至20 億歐元之間，其中包括從我們最新公開宣布的併購活動中確定的研發成本。我們也更新了 SG&A 支出，並將 2023 年初步指引範圍從 6.5 億歐元至 7.5 億歐元縮小至 6 億歐元至 6.5 億歐元。最後，我們將營運活動的成長和維護資本支出從最初的 2023 年指引範圍 5 億至 6 億歐元減少到 2 億至 3 億歐元。

Comparing the initial 2023 guidance to our updated guidance announced today, we are significantly decreasing our spend as we effectively manage our expenditures as part of our ongoing cost revenue procedures. Nonetheless, let me clarify here as well that we further intend to invest in our capabilities, in our pipeline of product candidates as those will create the value of the company in the future. As noted before, we have updated our group estimated annual cash effective income tax rate in Q2 from around 27% to around 21%, excluding potential effects from share-based payment settlements in the course of 2023.

將 2023 年初始指導與今天宣布的更新指導進行比較，我們正在大幅減少支出，因為我們有效地管理支出，作為我們持續成本收入程序的一部分。儘管如此，我還是在這裡澄清一下，我們進一步打算投資我們的能力、我們的候選產品管道，因為這些將在未來創造公司的價值。如前所述，我們已將第二季集團預期的年度現金有效所得稅率從約 27% 更新至約 21%，不包括 2023 年股權支付和解的潛在影響。

And with that, I would now like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for the corporate overview and concluding remarks. Thank you very much.

說到這裡，我現在想將電話轉給我們的首席策略長 Ryan Richardson，了解公司概況和總結發言。非常感謝。

Thank you, Jens. I'll now provide a brief summary of the outlook for our updated COVID-19 vaccine franchise and an overview of our latest progress in oncology before concluding with our strategic outlook for the remainder of the year.

謝謝你，延斯。現在，我將簡要總結我們更新的 COVID-19 疫苗系列的前景，並概述我們在腫瘤學方面的最新進展，然後再總結我們今年剩餘時間的戰略展望。

We're making good progress on our 3 main strategic objectives. Regarding our COVID-19 vaccine franchise, we look forward to advancing our COVID-19 influenza combination vaccine into a Phase 3 trial in the coming months. If successful, we believe simplifying immunization practices for health care providers could positively impact compliance and help reduce the burden of these diseases and its impact on health care systems.

我們在三大戰略目標上取得了良好進展。關於我們的 COVID-19 疫苗特許經營權，我們期待在未來幾個月內將我們的 COVID-19 流感組合疫苗推進到 3 期試驗。如果成功，我們相信簡化醫療保健提供者的免疫接種做法可以對依從性產生積極影響，並有助於減輕這些疾病的負擔及其對醫療保健系統的影響。

In immuno-oncology, we are building a unique and powerful portfolio of complementary therapies. We expect to start multiple trials with registrational potential over the next 12 months to 18 months, while continuing to generate data that inform our go/no-go development decisions. In infectious diseases, we plan to broaden our pipeline with new therapies that target high medical need indications.

在免疫腫瘤學領域，我們正在建立獨特而強大的補充療法組合。我們預計在未來 12 個月至 18 個月內啟動多項具有註冊潛力的試驗，同時繼續產生為我們的繼續/不繼續開發決策提供資訊的數據。在傳染病方面，我們計劃透過針對高醫療需求適應症的新療法來擴大我們的產品線。

Now moving to the next slide on the ongoing global rollout of our adaptive vaccine. In the 2.5 months following regulatory recommendation for an XBB.1.5-adaptive monovalent vaccine, we and Pfizer have shipped vaccine doses to more than 40 geographies around the world. Across key markets, we continue to benefit from a strong market position. In some regions, such as Europe and Japan, we have gained considerable share. In the U.S., where we leverage our partner Pfizer's commercial capabilities, we are seeing approximately 50% of vaccines going through the retail channel. We expect the vaccine uptake will continue to increase through the end of the year. In a recent national immunization survey in the U.S. by the CDC published last month, more than 30% of adults reported to have received or planned to receive an XBB.1.5 variant-adaptive vaccine. We believe this data reflects the potential baseline demand for an annual vaccination.

現在轉到下一張投影片，介紹我們正在全球推出的適應性疫苗。在監管機構建議採用 XBB.1.5 適應性單價疫苗後的 2.5 個月內，我們和輝瑞已將疫苗劑量運送到全球 40 多個地區。在主要市場，我們繼續受益於強大的市場地位。在一些地區，例如歐洲和日本，我們已經獲得了相當大的份額。在美國，我們利用合作夥伴輝瑞的商業能力，看到大約 50% 的疫苗通過零售通路。我們預計到今年底疫苗的使用量將繼續增加。 CDC 上個月發布的美國全國免疫調查顯示，超過 30% 的成年人已接種或計劃接種 XBB.1.5 變異體適應性疫苗。我們認為該數據反映了每年疫苗接種的潛在基線需求。

As outlined in the next slide, we expect our COMIRNATY franchise will be a long-term source of revenue. We expect to enter 2024 with a manufacturing base which has been reset to serve the future endemic market. In the next 2 years, we expect the continuation of several market shifts to play out. Those include the continued opening of private markets and the shift to commercial pricing globally, along with the continued transition from multi-dose vials to single-dose vials and prefilled syringes, which could bring upside opportunity to the franchise. We also expect the combination vaccines, if successful in late-stage trials, could present growth opportunities for the franchise from 2025 onwards.

正如下一張幻燈片所述，我們預計 COMIRNATY 特許經營權將成為長期收入來源。我們預計到 2024 年，我們的製造基地已重新調整，以服務未來的流行市場。在未來兩年中，我們預計將繼續出現一些市場轉變。其中包括私人市場的持續開放和全球商業定價的轉變，以及從多劑量小瓶到單劑量小瓶和預充式註射器的持續過渡，這可能會為特許經營帶來上行機會。我們也預計，如果聯合疫苗在後期試驗中取得成功，從 2025 年起將為該系列帶來成長機會。

We see the potential for increased vaccine uptake from a potential combination flu and COVID vaccine by connecting protection from COVID to a well-accepted paradigm of annual flu vaccination. We will continue to invest for the long term in next-generation COVID-19 vaccines with the aim of increasing robustness and durability of immune response.

我們看到，透過將新冠病毒 (COVID-19) 保護與公認的年度流感疫苗接種模式聯繫起來，流感和新冠肺炎聯合疫苗有可能增加疫苗接種量。我們將繼續對下一代 COVID-19 疫苗進行長期投資，旨在提高免疫反應的穩健性和持久性。

Now turning to the next slide. I'd like to wrap up with a snapshot of the progress we're making in accelerating our innovative oncology portfolio toward the market. So far in 2023, we and our partners have initiated 11 oncology trials, including 6 Phase 2 or 3 trials. We plan to continue this trend through the initiation of additional late-stage trials in the next 12 months to 18 months. We will continue to look for additive bolt-on BD and M&A opportunities that fit with our strategy while reinvesting to build world-class capabilities and accelerate our growth. We remain as optimistic as ever on our ability to continue to create long-term value for patients, our shareholders and society.

現在轉到下一張投影片。最後，我想簡要介紹一下我們在加速創新腫瘤產品組合推向市場方面所取得的進展。 2023 年到目前為止，我們和我們的合作夥伴已啟動 11 項腫瘤學試驗，其中包括 6 項 2 期或 3 期試驗。我們計劃在未來 12 個月至 18 個月內啟動額外的後期試驗來延續這一趨勢。我們將繼續尋找符合我們策略的附加補充業務拓展和併購機會，同時進行再投資以建立世界一流的能力並加速我們的成長。我們一如既往地對我們繼續為患者、股東和社會創造長期價值的能力感到樂觀。

Before concluding, I would like to remind and invite you all to attend our Innovation Series event tomorrow, starting 9 a.m. Eastern Time where we will provide further details on our pipeline and corporate strategy.

在結束之前，我想提醒並邀請大家參加我們明天東部時間上午 9 點開始的創新系列活動，屆時我們將提供有關我們的產品線和公司策略的更多詳細資訊。

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

在此，我要感謝大家一直以來的支持，並歡迎大家提問。

(Operator Instructions) We'll now take our first question. This is from the line of Daina Graybosch from Leerink Partners.

（操作員說明）我們現在回答第一個問題。這是來自 Leerink Partners 的 Daina Graybosch 的血統。

I have 2 financial questions. One, you have many programs going into Phase 3, and that's certainly going to increase your R&D expenses. And I wonder if you can give us any guidance on sort of the near to mid-term and how much R&D we should expect in our model? And the second one is whether you could help us at all with any inventory write-down, understanding more predictability behind how we might see that next year and then through 2 years after that.

我有 2 個財務問題。第一，您有許多專案進入第三階段，這肯定會增加您的研發費用。我想知道您是否可以就我們的模型中的近期和中期以及我們應該期望多少研發提供任何指導？第二個問題是，您是否可以幫助我們進行庫存減記，了解我們明年以及之後兩年的情況背後的更多可預測性。

Thanks, Daina. Thanks for the question. And let me start with the second one maybe first with the inventory write-offs. As I stated in my speech, I think this EUR 600 million that we had to face from Pfizer this year has been really a reflection of the situation that we moved from the pandemic into an endemic situation. Going forward, of course, if we have to, with new variants coming up, always have some sort of write-offs to be reflected, be it on Pfizer side or on our side. So there will be something, but not at all at that magnitude that we have seen now with the shift in '23. So, I think from our perspective going forward, the magnitude is a fraction of what we had to announce unfortunately for '23.

謝謝，戴娜。謝謝你的提問。讓我從第二個開始，也許首先是庫存沖銷。正如我在演講中所說，我認為今年輝瑞給我們的6億歐元確實反映了我們從疫情轉向流行的情況。當然，展望未來，如果我們必須這樣做，隨著新變體的出現，總是會有某種沖銷需要反映，無論是輝瑞這邊還是我們這邊。因此，將會發生一些事情，但根本不會像我們現在在 23 年看到的轉變那麼嚴重。因此，我認為從我們未來的角度來看，其規模只是我們不幸在 23 年宣布的規模的一小部分。

Then in terms of the R&D expenses, Ryan was alluding to additional clinical trials, further late-stage trials. Of course, that means that our R&D expenses are expected to go up. That's something that we envisage and want because we believe strongly that we have valuable compounds that we need to invest money in. So those numbers will go up. In terms of the magnitude for the next couple of years, you got to bear with us a little bit until we give our guidance. But we have -- and I think we have highlighted that in terms of all our costs for '23 that we are carefully looking at how much money do we want to spend or do we need to spend, but first and foremost, we want to create value with a cash position that we'll have. And that, of course, goes hand-in-hand with increased R&D expenses going forward.

然後在研發費用方面，瑞安提到了額外的臨床試驗，進一步的後期試驗。當然，這意味著我們的研發費用預計會增加。這是我們所設想和想要的，因為我們堅信我們擁有需要投資的有價值的化合物。因此這些數字將會上升。就未來幾年的規模而言，在我們給予指導之前，您必須耐心等待我們。但我們已經 - 我認為我們已經強調，就 23 年的所有成本而言，我們正在仔細考慮我們想要花多少錢或我們需要花多少錢，但首先也是最重要的是，我們想要利用我們擁有的現金頭寸創造價值。當然，這與未來研發費用的增加密切相關。

And maybe, Daina, just to add one point to Jens's remarks on the R&D line, I think it's important to remember as well that on a number of these pivotal stage or soon to be pivotal programs, we do expect to share R&D expenses with the partner. So that's the case in the Pfizer collaboration, of course, where we share R&D expenses 50-50. And we talked -- we mentioned today that we expect a couple of pivotal trials to start with combination vaccines that could become a midterm growth driver as successful. And similarly, on the oncology side, we have a number of programs that are partnered as well where we share expense.

也許，戴娜，只是為了在延斯關於研發方面的評論中補充一點，我認為記住這一點也很重要，在這些關鍵階段或即將成為關鍵的項目中，我們確實希望與夥伴。當然，輝瑞合作就是這種情況，我們以 50-50 分擔研發費用。我們今天提到，我們預計將從組合疫苗開始進行幾項關鍵試驗，這些試驗可能會成功成為中期成長動力。同樣，在腫瘤學方面，我們也有許多合作項目，我們分擔費用。

We'll now take our next question. This is from the line of Tazeen Ahmad from Bank of America Securities.

我們現在來回答下一個問題。這是來自美國銀行證券公司的 Tazeen Ahmad 的電話。

Okay. I have a couple of questions. It was encouraging to see that the safety profile in general for the COVID and flu combo vacs resembles what you saw just for the regular COVID vaccine. But I'm wondering if you could just provide any additional data, particularly on what reactogenicity might have looked at, and what you we found, for example? And then secondly, a financial question. On R&D, can you elaborate on whether some of your expenses have come from deprioritizing certain programs? And if so, can you talk to us about what programs those were?

好的。我有一些問題。令人鼓舞的是，新冠肺炎和流感組合疫苗的整體安全性與常規新冠疫苗的安全性相似。但我想知道您是否可以提供任何額外的數據，特別是關於反應原性可能觀察到的數據，以及您我們發現的數據，例如？其次是財務問題。在研發方面，您能否詳細說明您的某些費用是否來自於降低某些項目的優先順序？如果是這樣，您能告訴我們這些是什麼程式嗎？

Do you want to take the first one?

你想拿第一個嗎？

Yes, we were struggling with unmuting. The first one was about reactogenicity profile for our variant-adapted vaccine. And that is, in principle, more or less equal to the (inaudible) type vaccine. We have developed to BA.4, BA.5 adapted version and what we see with the flu and RNA vaccine in the respective dose levels. And that supports the safety profile, including the reactogenicity as a platform characteristic. So in all that regard.

是的，我們在取消靜音方面遇到了困難。第一個是關於我們的變異體適應疫苗的反應原性概況。也就是說，原則上或多或少等於（聽不清楚）型疫苗。我們已經開發出 BA.4、BA.5 適應版本以及我們在流感和 RNA 疫苗各自劑量水平上看到的情況。這支持了安全性，包括作為平台特徵的反應原性。所以在這方面。

Yes. So the combo vaccine with regard to the safety and the reactogenicity profile does not differ from the dose-dependent reactogenicity profile of the COVID-19 vaccine. (technical difficulty) answer the second question goes to the prioritized program?

是的。因此，組合疫苗的安全性和反應原性特徵與 COVID-19 疫苗的劑量依賴性反應原性特徵沒有什麼不同。 （技術難度）回答第二個問題去優先考慮的方案是什麼？

Do you want to say something? Otherwise, shall I jump in, Ugur?

你想說些什麼嗎？否則，我應該跳進去嗎，烏古爾？

You can jump in, yes.

你可以跳進去，是的。

I'll jump in. So, I mean there is -- it's a couple of activities that we undertook during our review of activities. We have de-prioritized a few programs, earlier stuff as well. Of course, we'll keep you updated in terms of updates if they are of relevance in terms of our later-stage programs, but there's nothing that I can report at this point in time. We have also in terms of the collaboration with Pfizer on the programs at a very close look as for other programs of how much money do we really need to spend to come to the desired outcomes. So that's another part that plays a role a little bit of shifting from '23 to '24. So as always, there are a couple of things. But those costs, I wouldn't call as something where you save money. De-prioritization as well as maybe being able to run clinical trials at a cheaper scale is something that we take as real cost savings. And that has been a big chunk of what we have -- where we can explain for the cost reductions.

我會插話。所以，我的意思是，這是我們在活動審查期間進行的幾項活動。我們取消了一些程式的優先級，包括早期的程序。當然，如果更新與我們的後期計劃相關，我們會及時通知您，但目前我無法報告任何內容。我們也非常仔細地了解了與輝瑞公司在這些項目上的合作，以及其他項目，我們真正需要花多少錢才能達到預期的結果。這是另一個在從 23 世紀到 24 世紀的轉變中發揮著一定作用的部分。一如既往，有幾件事。但這些成本，我不會稱之為省錢的東西。我們認為，取消優先順序以及也許能夠以更便宜的規模進行臨床試驗是真正的成本節省。這是我們所擁有的很大一部分——我們可以在其中解釋成本的降低。

We'll now take our next question. This is from the line of Chris Shibutani from Goldman Sachs.

我們現在來回答下一個問題。這是高盛 (Goldman Sachs) 克里斯‧涉谷 (Chris Shibutani) 的發言。

Two questions, if I may. First, on the oncology program, BNT122, the iNeST cancer vaccine ongoing melanoma study. But we noticed that there was an absence of commentary in the press release. Should we still expect a study to report top line results by year-end? And perhaps you can comment on what your expectations are for this program and if they've changed.

如果可以的話，有兩個問題。首先，關於腫瘤學項目，BNT122，iNeST 癌症疫苗正在進行黑色素瘤研究。但我們注意到新聞稿中沒有評論。我們是否還應該期待一項研究在年底前報告頂線結果？也許您可以評論一下您對此計劃的期望以及它們是否發生了變化。

My second question is on the COVID flu combination data. To make sure in terms of immunogenicity, the press release mentioned titers generated by lead formulations were compared to concomitant administration of COVID and flu vaccines. Is that the immunogenicity comparison that the FDA will be evaluating in Phase 3? Or are they looking for titers compared to monotherapy vaccination of COVID and flu separately?

我的第二個問題是關於新冠流感組合數據。為了確保免疫原性，新聞稿中提到的先導製劑產生的滴度與同時接種新冠疫苗和流感疫苗進行了比較。這是 FDA 將在第 3 階段評估的免疫原性比較嗎？或者他們是否正在尋找與分別接種新冠病毒和流感疫苗的單一療法疫苗相比的效價？

Maybe I'll take the iNest question first and then turn it over to Ugur and Ozlem for the fluCOVID. So on BNT122, actually, on our last earnings call, we provided revised guidance that we did not expect data this year. As you remember, the trial is randomized and has a PFS threshold to trigger the PFS analysis, which had not been met and which we didn't anticipate would be met this year. We do plan to provide a trial update this year, but we're not expecting data this year.

也許我會先回答 iNest 問題，然後將其轉交給 Ugur 和 Ozlem 來解決流感問題。因此，實際上，在 BNT122 上，在我們上次的財報電話會議上，我們提供了今年我們預計不會出現的修訂後的指引。如您所知，該試驗是隨機的，並且有一個 PFS 閾值來觸發 PFS 分析，該閾值尚未達到，我們預計今年也不會達到。我們確實計劃今年提供試用更新，但我們預計今年不會提供數據。

And the second question was related to the...

第二個問題與…有關。

To the comparator to the flu combo vaccine.

與流感組合疫苗進行比較。

Yes, yes. This is -- so we are comparing both -- comparing flu mRNA, COVID mRNA as comparator as established flu vaccines, and that are based on proteins or inactivated flu vaccines. Both comparisons will be in the study.

是的是的。這是——所以我們正在比較兩者——將流感 mRNA、新冠病毒 mRNA 作為比較物與已建立的流感疫苗進行比較，並且基於蛋白質或滅活流感疫苗。這兩種比較都將在研究中進行。

And that's what the FDA will be evaluating in the Phase 3?

這就是 FDA 將在第三階段評估的內容？

At least in our case.

至少在我們的例子中是如此。

We'll now move to our next question. This is from the line of Akash Tewari from Jefferies.

現在我們將討論下一個問題。這是來自 Jefferies 的 Akash Tewari 的作品。

This is Amy on for Akash. So just 2 from us. Number one, we've seen Pfizer reduced cost in the face of reducing COVID vaccine demand, while at the same time, we're seeing Moderna increase cost. What do you think about BioNTech planned spend over the next 3 to 4 years? How willing are you to eat into the cash generated during COVID? Should we expect it to decline on an annual basis, or will the team aim to sustain R&D solely off of residual vaccine demand? And then number two, on the COVID flu program, given the economics between you and Pfizer are 50% right now and they drop to potentially in the 30% range, if this program does become a success for BioNTech, do you anticipate it being net positive, net negative or breakeven for BioNTech's cash generation? How should we think about the increased demand potentially being offset by lower economics?

這是艾米為阿卡什主持的節目。所以我們只有 2 個。第一，我們看到輝瑞在面對新冠疫苗需求減少的情況下降低了成本，而同時，我們看到莫德納公司增加了成本。您如何看待 BioNTech 未來 3 到 4 年的計畫支出？您是否願意吃掉新冠疫情期間產生的現金？我們是否應該預期它會逐年下降，還是團隊的目標是只依靠剩餘疫苗需求來維持研發？第二，關於新冠流感計劃，考慮到您和輝瑞之間的經濟效益目前為 50%，並且可能會下降到 30% 的範圍，如果該計劃確實對 BioNTech 取得成功，您是否預計它會淨收益BioNTech的現金產生能力是正值、淨負值還是損益兩平？我們該如何看待需求的增加可能會被經濟下滑所抵銷？

Amy, can you just clarify the second question you asked. Was that in reference to a combination vaccine?

艾米，你能澄清一下你問的第二個問題嗎？這是指聯合疫苗嗎？

Yes, yes, the cover-flu combo vaccine.

是的，是的，流感聯合疫苗。

Okay. So, I'll take the first one and maybe...

好的。所以，我會選第一個，也許......

Yes, I'll chime in.

是的，我會插話。

Jens can chime in. Yes. So we see that -- we're in the midst of a transition period right now. Our COVID vaccine franchise is transitioning from pandemic to endemic market. This is, of course, happening this year, but we also expect that transition to continue next year. And we're also transitioning to become a commercial stage oncology company, and we've outlined some of the programs that we think are going to drive that transition. As we go through this transition, we think it's an immense asset to the company to have a strong balance sheet. And we're very happy with our ability this year if we meet revenue guidance to maintain profitability. That's an important point for us. As we go into the next couple of years through this transition, we expect to continue to maintain a very strong balance sheet, and that's going to continue to be a priority for us.

Jens 可以插話。是的。所以我們看到——我們現在正處於過渡期。我們的新冠疫苗專營權正在從大流行市場過渡到地方病市場。當然，這種情況今年就會發生，但我們也預期這種轉變明年還會持續。我們也正在轉型成為一家商業階段的腫瘤公司，我們已經概述了一些我們認為將推動這項轉型的計劃。當我們經歷這項轉變時，我們認為擁有強大的資產負債表對公司來說是一筆巨大的資產。如果我們達到收入指引以保持獲利能力，我們對今年的能力感到非常滿意。這對我們來說很重要。當我們進入未來幾年的過渡期時，我們預計將繼續保持非常強勁的資產負債表，這將繼續成為我們的首要任務。

Yes. Ryan expressed it very nicely. It's not much to add. I mean, going forward, of course, with the collaboration, we first and foremost, got to invest in these combination trials currently. Flu, COVID, flu COVID RSV. Those settings will eat up some cash, but we're very positive in terms of our expectations on the profitability share that we will get out of that collaborations and those combinations. In our view, this will that -- will create new markets and we'll secure, of course, the existing part and business that we have for COVID. So we think economically that should be something of great value for the company going forward.

是的。 Ryan 表達得非常好。沒什麼好補充的。我的意思是，當然，隨著合作的推進，我們首先必須投資目前的這些組合試驗。流感，新冠病毒，流感新冠病毒RSV。這些設定將消耗一些現金，但我們對從這些合作和這些組合中獲得的獲利份額的預期非常樂觀。我們認為，這將創造新的市場，當然，我們將確保我們針對新冠病毒的現有部分和業務。因此，我們認為從經濟角度來看，這對公司的未來發展應該具有巨大的價值。

And to your question on the combination vaccines, we haven't yet disclosed the full economics with Pfizer on combination vaccines. We plan to do that in the near future. We have communicated today that we intend with Pfizer to embark on pivotal trials, Phase 3 trials with those combination vaccines. And we do think that there is substantial potential for combination vaccines, if successful, to improve uptake of our COVID vaccine based on the rates that we're seeing now in terms of uptake. There's a large difference between, for example, where flu vaccines are in terms of uptake versus what we're expecting this year for COVID. So, we do think the combination vaccines can play an important role in terms of offering convenience and added benefit to increase the franchise over time. And we think that from a time line perspective, if successful, that those vaccines could be -- start to have an impact for us from 2025 onwards.

至於你關於聯合疫苗的問題，我們尚未透露與輝瑞聯合疫苗的全部經濟效益。我們計劃在不久的將來這樣做。今天我們已告知，我們打算與輝瑞一起進行關鍵試驗，即使用這些組合疫苗進行的第三階段試驗。我們確實認為，根據我們現在看到的使用率，如果成功的話，聯合疫苗有很大的潛力可以提高我們的新冠疫苗的使用率。例如，流感疫苗的使用情況與我們今年對新冠疫苗的預期有很大差異。因此，我們確實認為組合疫苗可以在提供便利性和增加收益方面發揮重要作用，從而隨著時間的推移增加特許經營權。我們認為，從時間軸的角度來看，如果成功，這些疫苗可能會從 2025 年開始對我們產生影響。

We'll now move to our next question. Please stand by. This is from the line of Yaron Werber from TD Cowen.

現在我們將討論下一個問題。請稍候。這是來自 TD Cowen 的 Yaron Werber 血系。

Great. I have a couple. Just on 1046, the PDL combo, you mentioned moving to a second line endometrial study in combination with pembro. Just any update -- and I'm not sure on a front around to more, but just any update on the checkpoint experience, non-small cell lung cancer cohort. And is that still sort of in the cards? And then secondly, for 323, BNT323, on the HER2 low side, how do you define HER2 low? Is it histology? Do they have to have any expression at all? And why do you think you're confirming activity in a population that sort of failed (inaudible) before?

偉大的。我有一對。就在 1046（PDL 組合）上，您提到與 pembro 聯合進行二線子宮內膜研究。只是任何更新——我不確定是否有更多更新，但只是關於檢查站經驗、非小細胞肺癌隊列的任何更新。這仍然是可能的嗎？其次，對於 323、BNT323，在 HER2 低的一側，您如何定義 HER2 低？是組織學嗎？他們必須有任何表情嗎？為什麼你認為你要確認之前失敗（聽不清楚）的人群中的活動？

Yes. To your first question, 1046, yes, the lung cancer costs are continuing, and we will most likely report data on this cohort in the next year, mid next year. And it's still a target for follow-up...

是的。對於你的第一個問題，1046，是的，肺癌的費用仍在繼續，我們很可能會在明年、明年年中報告這一隊列的數據。而且還是後續的目標…

Target of interest.

興趣目標。

Target of interest in lung cancer. For BNT 323, yes, low is defined as staining, which is -- and 2 plus without any amplification and activity of the ADC compound in this patient population, which is clearly better than trastuzumab alone is based on the highly potent ADC activity and on the bystander activity, allowing not only to remove antigen-positive tumor cells but also the tumor cells in the surrounding, which are negative.

肺癌的興趣標靶。對於 BNT 323，是的，低定義為染色，即 2+，在該患者群體中 ADC 化合物沒有任何擴增和活性，這明顯優於單獨使用曲妥珠單抗，這是基於高效的 ADC 活性和旁觀者的活動，不僅可以去除抗原陽性的腫瘤細胞，還可以去除周圍的陰性腫瘤細胞。

Thank you. We'll now move to our next question. This is from the line of Jessica Fye from JPMorgan.

謝謝。現在我們將討論下一個問題。這是來自摩根大通的 Jessica Fye 的電話。

Can you outline what key pipeline updates we should expect between now and year-end? You mentioned an update on the iNest melanoma trial. What else should we be looking forward to whether from the 4-1BB programs or otherwise? And then related to iNest, with the new trial starting in the adjuvant pancreatic cancer, can you talk about what drove that decision? And was it based on something you're seeing? And then lastly, just a financial question. You lowered OpEx guidance again this quarter, but also suggested that from here, R&D will likely grow to support these pipeline investments. What about SG&A? That guidance didn't change as much. Is there less flexibility in that line if expenses need to be cut again?

您能否概述從現在到年底我們應該期待哪些關鍵的管道更新？您提到了 iNest 黑色素瘤試驗的最新情況。無論是 4-1BB 計劃還是其他計劃，我們還應該期待什麼？然後與 iNest 相關，新的試驗開始於輔助胰腺癌，您能談談是什麼推動了這一決定嗎？它是基於你所看到的嗎？最後，只是一個財務問題。您本季再次降低了營運支出指引，但也表示，從現在開始，研發可能會成長以支持這些管道投資。 SG&A 怎麼樣？該指導意見沒有太大變化。如果需要再次削減開支，該領域的彈性是否會降低？

Ryan, please go ahead.

瑞安，請繼續。

On the pipeline update, I was just going to say on the pipeline update that we do expect data on BNT116 at SITC just around the corner. And of course, tomorrow, we will have -- we do expect to give a pretty wholesome update across our late-stage oncology pipeline as well.

關於管道更新，我只是想說關於管道更新，我們確實預計 SITC 的 BNT116 數據即將到來。當然，明天，我們確實希望對我們的後期腫瘤學管道進行相當全面的更新。

And then what about on the new iNest trial in adjuvant pancreatic? Can you talk about what drove the decision to start that up, and SG&A flexibility question.

那麼新的 iNest 輔助胰臟試驗又如何呢？您能否談談是什麼促使我們決定啟動該項目，以及 SG&A 靈活性問題。

Maybe I can take this one. We will also talk about that trial tomorrow in our Innovation Day set up. We (technical difficulty) an IIT, an investigator-initiated trial, a small one, which, however, showed very promising results in terms of anti -- the immune responses and the magnitude of immune responses induced in pancreatic cancer patients, which are traditionally always seen as immune suppressed. We also could see that the success of inducing immune responses in half of this population was correlated with prolonged time to recurrence. And this data has motivated us to now set up a Phase 2 trial, which has already dosed first patients.

也許我可以接受這個。我們也將在明天的創新日活動中討論該試驗。我們（技術難度）是一項IIT，一項研究者發起的試驗，一項小型試驗，然而，在抗胰腺癌患者的免疫反應和誘導的免疫反應的強度方面顯示出非常有希望的結果，傳統上這些結果是總是被視為免疫抑制。我們也可以看到，在該族群中成功誘導免疫反應與延長復發時間有關。這些數據促使我們現在開展一項 2 期試驗，該試驗已經對第一批患者進行了給藥。

And then on the SG&A question, Jessica, we have reduced the cost here as well. Of course, we need to support the growth of the business going forward. Here, specifically, in the years to come, we need to set up a sales and marketing organization for our parts where we commercialize and all. So, in that respect, we need to invest as well. But you see, I mean, the scale of cost here is relatively small in comparison to what you see at competitors' levels. And therefore, if you look at the basis currently that we're having here, I think we are already relatively lean. But most important really is to set up a sales and marketing organization. So that will be something where we have to invest going forward, some money.

然後，關於 SG&A 問題，傑西卡，我們也降低了這裡的成本。當然，我們需要支持業務的未來成長。具體來說，在未來的幾年裡，我們需要為我們的零件建立一個銷售和行銷組織，以便我們將其商業化。所以，在這方面，我們也需要投資。但你看，我的意思是，與競爭對手的水平相比，這裡的成本規模相對較小。因此，如果你看看我們目前的基礎，我認為我們已經相對精簡了。但最重要的是建立一個銷售和行銷組織。因此，這將是我們未來必須投資的地方，一些錢。

We'll now move to our next question. This is from the line of Bill Maughan from Canaccord Genuity.

現在我們將討論下一個問題。這是來自 Canaccord Genuity 的 Bill Maughan 的作品。

So looking at the ongoing evolution of SARS-CoV-2, do you expect the virus evolution to slow down to the point where annual strain updates aren't necessary? And if that does happen, how strong is the proposition for annual boosters if the strain update isn't needed? And then a second question. Looking more broadly, with the broad -- the multiplicity of platforms that you have, how do you think about bringing a specific modality into the clinic against the tumor target when you have the option of using an ADC or bispecific or anything or several different options here?

那麼，看看 SARS-CoV-2 的持續進化，您是否預計病毒進化會減慢到不需要每年進行病毒株更新的程度？如果這種情況確實發生，如果不需要菌株更新，年度加強劑的提議有多強？然後是第二個問題。從更廣泛的角度來看，您擁有多種平台，當您可以選擇使用 ADC 或雙特異性或任何其他或幾種不同的選擇時，您如何考慮將針對腫瘤標靶的特定模式引入臨床這裡？

I can take the question. So, with regard to the evolution of SARS-CoV-2, we have to consider 2 BRAF mutation patterns. We have (technical difficulty) a vertical mutation of an existing variant, which is continuing in more or less changing of single spike protein amino acids in various positions. This is what we have observed for the alpha, beta variants and now observing for the Omicron variant. But there is also a second mutational pattern, which are variants that evolve with dozens of additional mutations. We have seen that for the first time (technical difficulty) but we have also seen it most recently with a variant which is called BA286 which is actually covering more than 30 additional mutations as compared to the Omicron strain. It is still called Omicron, but if we look closer, it is actually really a new variant. And this is something that we would also expect in future. So, this pattern will continue also in the future, whereas the mutations based on single changes will not foster the generation of a new variant-adaptive vaccine. I expect that the major changes [will require] variant adapted vaccines, and we have also to consider that the antibody titers decline over time. So, we have 2 mechanisms. One is the erosion of the immune response itself, which is associated with a higher rate of infections and also associated with higher severity. And the second is the evolvement of new variants.

我可以回答這個問題。因此，關於SARS-CoV-2的演化，我們必須考慮2種BRAF突變模式。我們對現有變體進行了（技術難度）垂直突變，該突變繼續或多或少地改變單個刺突蛋白氨基酸在各個位置的變化。這就是我們在 alpha、beta 變異體中觀察到的情況，以及現在在 Omicron 變異體中觀察到的情況。但還有第二種突變模式，即隨著數十個額外突變而進化的變異。我們第一次看到了這一點（技術難度），但我們最近也看到了一種名為 BA286 的變體，與 Omicron 菌株相比，它實際上涵蓋了 30 多個額外的突變。它仍然被稱為 Omicron，但如果我們仔細觀察，它實際上是一個新的變體。這也是我們未來所期待的。因此，這種模式在未來也將繼續下去，而基於單一變化的突變不會促進新的變異適應性疫苗的產生。我預計重大變化將需要變體適應疫苗，而且我們還必須考慮到抗體滴度隨著時間的推移而下降。所以，我們有兩種機制。一是免疫反應本身受到侵蝕，這與較高的感染率和較高的嚴重程度有關。其次是新變種的演變。

So, in short, yes, we expect that also, also in the future, we will -- we have to (technical difficulty) of 2 variants. And this patterns, the space, might differ from season to season like we are seeing that for flu infection.

所以，簡而言之，是的，我們預計，在未來，我們也將——我們必須（技術難度）有兩種變體。這種模式、空間可能會因季節而異，就像我們在流感感染中看到的那樣。

And the second question was about our interest in ADC technology and whether we would like to combine that with our expertise in target identification and antibody generation. And the answer is yes. This is something we are working on.

第二個問題是我們對 ADC 技術的興趣，以及我們是否願意將其與我們在目標識別和抗體生成方面的專業知識相結合。答案是肯定的。這是我們正在努力的事情。

We'll now take our next question. This is from the line of Simon Baker from Redburn Atlantic.

我們現在來回答下一個問題。這是來自 Redburn Atlantic 的 Simon Baker 的作品。

Two very quick ones, if I may. Just going back to R&D spend. From what I can gather from what you were saying, it sounds like essentially, you're doing the same for less rather than delaying or deferring. But I wonder if you could just give us a little bit more color on CapEx, whether that's savings driven or whether there are some deferrals in there? And then secondly, on PM8002, you highlight the non-small cell lung indication, but that molecule is in, I think, about half a dozen other tumor types. So I was just wondering what your interest in the other tumor types is for PM8002. Is that something you're looking to develop? And do you have the rights across all tumors?

如果可以的話，兩個非常快的。回到研發支出。從我從你所說的話中可以看出，聽起來本質上你是在以更少的成本做同樣的事情，而不是拖延或推遲。但我想知道您是否可以給我們更多關於資本支出的信息，無論是節省驅動的還是其中是否有一些延期？其次，在 PM8002 上，您強調了非小細胞肺適應症，但我認為該分子存在於大約六種其他腫瘤類型中。所以我只是想知道您對 PM8002 其他腫瘤類型的興趣是什麼。這是你想要發展的嗎？您是否擁有針對所有腫瘤的權利？

Yes, let me maybe quickly start with the CapEx question. So indeed here, we have some savings, but we also have, to some extent, some shift here. So, we're delaying some investments going forward, specifically in terms of the production area where we anticipated to invest maybe a bit more in '23, given where we stand with COVID, the activities around other programs in the infection disease area. We said, we watch how and when we actually invest, and in that respect, we have some lower spend than anticipated. But of course, also when you go through the cost base, you try to figure out if there are some savings here and there.

是的，讓我快速開始討論資本支出問題。因此，我們確實在這裡有一些節省，但在某種程度上，我們也有一些轉變。因此，我們推遲了一些未來的投資，特別是在生產領域，考慮到我們在新冠肺炎方面的立場以及圍繞感染性疾病領域其他項目的活動，我們預計在 23 年可能會多投資一點。我們說，我們會觀察實際投資的方式和時間，在這方面，我們的支出低於預期。當然，當您查看成本基礎時，您也會嘗試找出是否可以節省一些成本。

Can you shortly repeat on which compound you referred in your question? In the first part.

您能否簡單地重複一下您在問題中提到的化合物？在第一部分中。

Yes, it was the Biotheus PM8002.

是的，它就是 Biotheus PM8002。

Yes, yes. The Biotheus PM8002 is a bispecific antibody which combines and neutralizing anti-VEGF arm. There's a blocking PD-L1 arm. The antibody has been evaluated in more than 500 patients and shows a very favorable safety profile and has shown activity in multiple indications, also combination therapies with chemotherapy. And we see this molecule indeed as an opportunity, a new generation IO, which combines bispecific activity for multiple indications. And we are seeing particularly an opportunity to combine this with our ADC portfolio. It's well known that anti-VEGF treatment is synergetic to chemotherapy by improving the penetration of chemotherapeutics and modifying the tumor microenvironment, and thereby increasing the efficacy of chemotherapy. And this is something that we are also expecting (technical difficulty) partner for our ADCs.

是的是的。 Biotheus PM8002 是一種雙特異性抗體，可結合併中和抗 VEGF 臂。有一個阻斷 PD-L1 臂。該抗體已在 500 多名患者中進行了評估，顯示出非常良好的安全性，並在多種適應症以及與化療的聯合治療中顯示出活性。我們確實將這種分子視為一個機會，新一代 IO，它結合了多種適應症的雙特異性活性。我們尤其看到了將其與我們的 ADC 產品組合相結合的機會。眾所周知，抗VEGF治療與化療具有協同作用，透過提高化療藥物的滲透性和改變腫瘤微環境，進而提高化療的療效。這也是我們 ADC 所期待的（技術難度）合作夥伴。

We will now take one more question. The last question is from the line of Ellie Merle from UBS.

我們現在再回答一個問題。最後一個問題來自瑞銀集團 (UBS) 的 Ellie Merle。

Just in terms of thinking about the profitability of the COVID vaccine business, just how should we think about the Pfizer COVID vaccine gross profit margins going forward just given the endemic market and the impact this has on the revenue you recognize? You mentioned the continued shift to single-dose vials and prefilled syringes. Just trying to think about how you're thinking about long-term potential margins for that business and the impact on the revenues that you'd recognize as part of the profit share.

就考慮新冠疫苗業務的獲利能力而言，考慮到疫情市場及其對您所確認的收入的影響，我們應該如何考慮輝瑞新冠疫苗未來的毛利率？您提到繼續轉向單劑量小瓶和預充式註射器。只是想想您如何考慮該業務的長期潛在利潤率以及您將其視為利潤分成的一部分對收入的影響。

I'll start, and then Jens I think can come in. So, I think the short answer is that we expect the COVID vaccine franchise to continue to be highly cash generative and highly profitable on a product basis for us going forward. You rightly point out the shift to endemic market that we've talked about today. You have to remember that because we share gross profits 50-50 with Pfizer and the bulk of our revenue comes in the form of a Pfizer gross profit share from countries outside of Germany and Turkey, which are our revenue reporting regions, because of that, we don't expect the direct shift to single-dose vial and prefilled syringes to have a significant effect on our gross margins. Because it's already -- most of that revenue is already coming to us net of cost of goods. It's rather the mix between Germany and Turkey -- the relative contribution of Germany, Turkey to the total that would affect the gross margins.

我先開始，然後延斯（Jens）我認為可以進來。所以，我認為簡短的答案是，我們預計新冠疫苗特許經營權將繼續在產品基礎上為我們帶來高現金產出和高利潤。您正確地指出了我們今天討論的向流行市場的轉變。您必須記住，因為我們與輝瑞以 50-50 的比例分享毛利潤，並且我們的大部分收入來自德國和土耳其以外國家（我們的收入報告區域）的輝瑞毛利潤份額，因此，我們預計直接轉向單劑量小瓶和預充式註射器不會對我們的毛利率產生重大影響。因為大部分收入已經扣除商品成本後再歸我們所有。相反，德國和土耳其之間的混合——德國和土耳其對總利潤的相對貢獻會影響毛利率。

Yes. I think you said it basically. So, everything that comes from Pfizer is 100% profit for us. So the relation between what we generate as revenue and what Pfizer generates is actually driving the story here at the end of the day. Remember, we have multi-dose contracts anyway for the next couple of years for the COVID stand-alone solution at this point in time. So, Ryan made the point.

是的。我想你基本上都說了。所以，來自輝瑞的一切對我們來說都是100%的利潤。因此，我們產生的收入與輝瑞產生的收入之間的關係實際上是最終推動故事發展的因素。請記住，無論如何，我們目前都簽訂了未來幾年新冠獨立解決方案的多劑量合約。所以，瑞安提出了這一點。

Does that answer your question? Okay. Thank you.

這是否回答你的問題？好的。謝謝。

Thank you. And that concludes the question-and-answer session. I will now hand back to the speakers for any closing remarks.

謝謝。問答環節到此結束。我現在將請發言者發表結束語。

Thank you very much for joining our call. We look forward to speaking with you again tomorrow.

非常感謝您加入我們的通話。我們期待明天再次與您交談。

Thank you. That does conclude the conference for today. Thank you for participating, and you may now disconnect.

謝謝。今天的會議到此結束。感謝您的參與，您現在可以斷開連接。