Biontech SE (BNTX) 2023 Q2 法說會逐字稿

Welcome to BioNTech Second 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 年第二季度更新電話會議。我想將電話轉交給戰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 Second Quarter 2023 Earnings Call. As a brief reminder, the slides to accompany this call and the second quarter 2023 press release that was issued this morning can be found in the Investors section of our website. As outlined on Slide 2, you can see all our forward-looking statements disclaimer.

謝謝。早上好，下午好。感謝您今天參加我們的 BioNTech 2023 年第二季度收益電話會議。簡單提醒一下，本次電話會議附帶的幻燈片以及今天早上發布的 2023 年第二季度新聞稿可以在我們網站的投資者部分找到。如幻燈片 2 所示，您可以看到我們所有的前瞻性聲明免責聲明。

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

有關聲明和其他風險的更多信息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面臨重大風險和不確定性。我們僅在電話會議最初日期發表意見，並且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'm joined by the following members of BioNtech's management team. Our CEO and Co-Founder; Ugur Sahin, Özlem Türeci; our Chief Medical Officer and Co-Founder, Jens Holstein; our Chief Financial Officer, and Ryan Richardson; our Chief Strategy Officer.

在幻燈片 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。我們的首席執行官兼聯合創始人；烏古爾·沙欣 (Ugur Sahin)、阿茲萊姆·圖雷奇 (Ánzlem Türreci)；我們的首席醫療官兼聯合創始人 Jens Holstein；我們的首席財務官瑞安·理查森 (Ryan Richardson)；我們的首席戰略官。

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 the call participants. We appreciate your continued support. Today, I will summarize our second quarter 2023 highlights and priorities before I pass the call over to my team to provide some further details.

謝謝你，維多利亞。熱烈歡迎各位來電參加者。我們感謝您一如既往的支持。今天，我將總結 2023 年第二季度的亮點和優先事項，然後再將電話轉交給我的團隊以提供更多詳細信息。

Slide 5. Let me start reiterating our 2023 strategic priorities that we set at the beginning of the year and highlight our recent progress executing against that. We pursue our priority to expand and sustain our COVID-19 leadership with Pfizer by advancing our next-generational and combination vaccine candidates and by advancing key commonality features.

幻燈片 5。首先讓我重申我們在年初制定的 2023 年戰略重點，並強調我們最近在執行該戰略方面取得的進展。我們的首要任務是通過推進我們的下一代候選疫苗和組合疫苗以及推進關鍵的共性功能來擴大和維持我們與輝瑞在 COVID-19 領域的領導地位。

During this quarter, we received recommendations from regulatory authorities and the World Health Organization on the composition of the adapted COVID-19 vaccine for the 2023-2024 fall season. Based on these recommendations, we together, with our partner, Pfizer, has submitted regulatory packages for Omicron XBB.1.5 adapted monovalent COVID-19 vaccine to the U.S. FDA, EMA and other regulatory agencies.

在本季度，我們收到了監管機構和世界衛生組織關於 2023-2024 年秋季適應的 COVID-19 疫苗成分的建議。根據這些建議，我們與合作夥伴輝瑞一起向美國 FDA、EMA 和其他監管機構提交了 Omicron XBB.1.5 適應單價 COVID-19 疫苗的監管包。

We have also kicked off commercial launch activities for the Omicron XBB.1.5 adapted monovalent COVID-19 vaccine. Our second 2023 strategic priority is to accelerate our oncology pipeline and initiate multiple trials with registrational potential.

我們還啟動了適用於 Omicron XBB.1.5 的單價 COVID-19 疫苗的商業上市活動。我們 2023 年的第二個戰略重點是加速我們的腫瘤學研發管線並啟動多項具有註冊潛力的試驗。

Our new collaborations with DualityBio and OncoC4 complement our pipeline with multiple mid- to late-stage clinical programs that will help us to achieve this goal in the near term.

我們與 DualityBio 和 OncoC4 的新合作通過多個中後期臨床項目補充了我們的產品線，這將幫助我們在短期內實現這一目標。

In the second quarter at ASCO Annual Meeting, we and our respective collaboration partners presented 3 new clinical datasets that Özlem will cover later. Further, jointly with our partner OncoC4, we began a pivotal Phase III trial evaluating the next-generation anti-CTLA-4 antibody candidate BNT316 Gotistobart as a second-line treatment for patients with non-small cell lung cancer.

在第二季度的 ASCO 年會上，我們和各自的合作夥伴展示了 äzlem 稍後將介紹的 3 個新的臨床數據集。此外，我們與我們的合作夥伴 OncoC4 聯合開始了一項關鍵的 III 期試驗，評估下一代抗 CTLA-4 候選抗體 BNT316 Gotistobart 作為非小細胞肺癌患者的二線治療。

Our third strategic goal is to initiate and accelerate clinical programs with high medical need in infectious diseases. We are expecting multiple data readouts for our mRNA-based vaccine candidate in the second half of this year.

我們的第三個戰略目標是啟動並加速傳染病方面醫療需求較高的臨床項目。我們預計今年下半年將公佈基於 mRNA 的候選疫苗的多項數據。

In summary, we continued our focused execution against strategic priorities in the second quarter and look forward to additional progress in all 3 of these areas in the remainder of this year.

總之，我們在第二季度繼續集中執行戰略重點，並期待今年剩餘時間在所有這三個領域取得進一步進展。

Slide 6, starting with COVID-19, while variants of concern has emerged in all seasons in the past 2 years, we expect that in the fall and winter in line with other common respiratory diseases such as influenza and RSV, also SARS-CoV-2 hospitalization will increase.

幻燈片 6，從 COVID-19 開始，雖然過去 2 年所有季節都出現了令人擔憂的變種，但我們預計在秋季和冬季，與流感和 RSV 等其他常見呼吸道疾病以及 SARS-CoV 一樣， 2 住院人數將增加。

Slide 7. In 2023, 4 years after the start of the COVID-19 pandemic, there is the highest level prevalence in the global population as a result of vaccinations and/or infection. Profiles of immune responses against SARS-Cov-2 are highly heterogeneous as individuals have been infected with different variants and or vaccinated using a variety of vaccine platform.

幻燈片 7。2023 年，即 COVID-19 大流行開始 4 年後，由於疫苗接種和/或感染，全球人口中的流行率達到最高水平。針對 SARS-Cov-2 的免疫反應特徵具有高度異質性，因為個體已感染不同的變種和/或使用多種疫苗平台接種疫苗。

The substantial genetic and antigenic evolution of SARS-Cov-2 and its spike proteins continues with divergence of the evolution of trajectory from the original (inaudible) virus. Despite increasing gaps in the genomic surveillance globally, the available sequencing data indicates that the original drivers and other early variants such as alpha, beta, gamma, delta are no longer detected in humans.

SARS-Cov-2 及其刺突蛋白的實質性遺傳和抗原進化仍在繼續，其進化軌跡與原始（聽不清）病毒的進化軌蹟有所不同。儘管全球基因組監測的差距越來越大，但現有的測序數據表明，原始驅動程序和其他早期變異（例如α、β、γ、δ）不再在人類中檢測到。

As of July 2023, the XBB1 descendant lineages predominate globally, and they have further antigenic distance from previous variants. Clinical data have shown that currently approved COVID-19 vaccines provide a level of protection against this new variance. However, with the antigenic drift of current variance of concern, signs of waning protections have been observed starting 2 to 4 months after booster with last season B4/B5 adapted vaccine, including against severe COVID-19.

截至 2023 年 7 月，XBB1 後代譜系在全球佔據主導地位，並且與之前的變體有進一步的抗原距離。臨床數據表明，目前批准的 COVID-19 疫苗可以針對這種新變異提供一定程度的保護。然而，隨著當前關注差異的抗原漂移，在上一季 B4/B5 適應疫苗加強接種後 2 至 4 個月開始觀察到保護作用減弱的跡象，包括針對嚴重的 COVID-19。

Due to the greater antigenic distance of this variance of concern and the further immune escape, absolute vaccine effectiveness against hospitalization due to COVID-19 is reduced as time passes between vaccination and subsequent infection.

由於這種關注差異的抗原距離更大以及進一步的免疫逃逸，隨著疫苗接種和隨後感染之間時間的推移，疫苗針對 COVID-19 住院的絕對有效性會降低。

In summary, this data support a rollout of a COVID-19 vaccine adapted to the most recent variance of concerns this fall. We plan to launch an Omicron XBB.1.5 adapted monovalent COVID-19 vaccine this fall, subject to approval by regulatory authorities.

總之，這些數據支持今年秋天推出適應最新擔憂變化的 COVID-19 疫苗。我們計劃於今年秋季推出 Omicron XBB.1.5 適應單價 COVID-19 疫苗，但須經監管機構批准。

Our goal is to maintain protection against severe COVID-19 disease, hospitalization and death by providing a vaccine that is better matched to the currently circulating strain and that is designed to be more closely aligned to the newer evolving lineages.

我們的目標是通過提供一種與當前流行毒株更匹配且旨在與更新的進化譜系更緊密結合的疫苗，來維持對嚴重 COVID-19 疾病、住院和死亡的保護。

Slide 8, let me remind you of the core principles of our overarching strategy. we pursue a multi-technology driven approach rooted in deep fundamental understanding of biology and immunobiology. We leverage the power of computational science and AI. Our acquisition of InstaDeep has expanded our capabilities in that regard.

第 8 張幻燈片，讓我提醒您我們總體戰略的核心原則。我們追求一種植根於對生物學和免疫生物學的深刻基礎理解的多技術驅動方法。我們利用計算科學和人工智能的力量。我們對 InstaDeep 的收購擴大了我們在這方面的能力。

Together, we aim to become the global leader in applying cutting-edge artificial intelligence and machine learning technology in research to discover, design and develop next-generation immunotherapies at scale. We build novel platforms with the ability to produce multiple product candidates for our clinical pipeline including a [purchase] that enable and accelerate individualization of treatment.

我們共同致力於成為將尖端人工智能和機器學習技術應用於大規模發現、設計和開發下一代免疫療法的研究領域的全球領導者。我們構建了新穎的平台，能夠為我們的臨床管道生產多種候選產品，包括支持和加速個性化治療的[購買]。

To leverage synergistic mode of action, we explore opportunities for combining modalities, both developed internally and access via collaboration partnerships. Last quarter, we announced that we initiated a collaboration with Duality Biologics to access 2 of their next-generation antibody drug conjugates.

為了利用協同行動模式，我們探索組合模式的機會，包括內部開發的和通過合作夥伴關係獲取的。上季度，我們宣布與 Duality Biologics 合作，獲取他們的 2 種下一代抗體藥物偶聯物。

This quarter, we and Duality shared clinical data from one of these programs and expanded our collaboration to a third encouraging program from Duality Biologics pipeline.

本季度，我們和 Duality 共享了其中一個項目的臨床數據，並將我們的合作範圍擴大到 Duality Biologics 管道中的第三個令人鼓舞的項目。

Slide 9. A disease consists of 3 main components: Antibody, Linker, Payload. Each of these components has an impact on ADC's pharmacological and clinical properties. ADCs are precision medicine, allowing for targeted drug delivery, particularly to tumor cells with high specifity and potent in you cell death with the benefit of reduced off-target events.

幻燈片 9。疾病由 3 個主要組成部分組成：抗體、鏈接器、有效負載。這些成分中的每一個都會對 ADC 的藥理學和臨床特性產生影響。 ADC 是精準醫學，可以進行靶向藥物遞送，特別是針對具有高特異性和有效促進細胞死亡的腫瘤細胞，並具有減少脫靶事件的優點。

When the monoclonal antibody binds to the targets expressed on the tumor cell, the ADC is internalized allowing for the release of the cytotoxins which leads to cell death. 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 combination backbone for cancer immunotherapy. Advancements in this technology have resulted in its extended use for the treatment of solid tumors.

當單克隆抗體與腫瘤細胞上表達的靶標結合時，ADC 被內化，從而釋放細胞毒素，從而導致細胞死亡。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，成為癌症免疫治療的新組合支柱。這項技術的進步已使其廣泛用於實體瘤的治療。

ADCs can also [synergize] with various immunotherapy modalities, including those in our current immunotherapy pipeline. Our growing ADC pipeline now includes ADCs directed against 3 distinct targets and is of interest for a broad range of cancer types.

ADC 還可以與各種免疫治療方式[協同]，包括我們當前免疫治療管道中的那些方式。我們不斷增長的 ADC 管道現在包括針對 3 個不同靶點的 ADC，並且對廣泛的癌症類型感興趣。

In the future, we plan to combine these ADCs with our proprietary pipeline programs to maximize the patient impact of this exciting modality. With that, I would like to thank you all for your confidence in our success and your continued support.

未來，我們計劃將這些 ADC 與我們專有的管道項目相結合，以最大限度地提高這種令人興奮的模式對患者的影響。在此，我要感謝大家對我們成功的信心和持續的支持。

I will now turn the call over to Özlem.

我現在將把電話轉給阿茲萊姆。

Thank you, Ugur. I'm delighted to speak with everyone today and to provide our pipeline update. Slide 11. Starting with our COVID-19 vaccine. We expect that as the SARS-Cov-2 continues to evolve and the risk of severe COVID-19 disease and death continues, there will be persisting demand for vaccine boosting and vaccinations, especially for at-risk and immunocompromised groups.

謝謝你，烏古爾。我很高興今天與大家交談並提供我們的管道更新。幻燈片 11。從我們的 COVID-19 疫苗開始。我們預計，隨著SARS-Cov-2 的不斷發展以及嚴重的COVID-19 疾病和死亡的風險持續存在，對疫苗加強和疫苗接種的需求將會持續存在，特別是對於高危群體和免疫功能低下的群體。

The Omicron XBB sublineages currently account for the majority of COVID-19 cases globally and are antigenically distant from prior circulating SARS-Cov-2 lineages, including Omicron BA4/5 and original SARS-CoV-2 strain.

Omicron XBB 亞系目前佔全球 COVID-19 病例的大多數，並且在抗原上與先前流行的 SARS-Cov-2 譜系（包括 Omicron BA4/5 和原始 SARS-CoV-2 毒株）相距甚遠。

Although Omicron BA4/5 adapted bivalent vaccines provide some protection against the range of outcomes from XBB-related COVID-19, evidence suggests that vaccine better match to currently circulating sublineages can help further improve protection against symptomatic disease and severe COVID-19.

儘管Omicron BA4/5 適應的二價疫苗對XBB 相關的COVID-19 的一系列後果提供了一定的保護，但有證據表明，疫苗與當前流行的亞譜系更好地匹配可以幫助進一步提高對症狀性疾病和嚴重COVID-19 的保護。

XBB lineage viruses have reduced neutralization in comparison to earlier Omicron lineages but have similar neutralization profiles to each other. Despite sequence of XBB.1.5 and XBB.1.16 differ in only 2 mutations highlighted here.

與早期的 Omicron 譜系病毒相比，XBB 譜系病毒的中和作用有所減少，但彼此具有相似的中和特性。儘管 XBB.1.5 和 XBB.1.16 的序列僅存在此處突出顯示的 2 個突變不同。

In May, the EMA and other health authorities provided guidance highlighting that updated vaccines targeting Omicron XBB 1 sublineages may help to maintain protection against COVID-19 during the upcoming fall and winter season, when COVID-19 case rates and hospitalizations are expected to increase.

5 月份，EMA 和其他衛生當局提供了指導意見，強調針對Omicron XBB 1 亞系的更新疫苗可能有助於在即將到來的秋冬季節保持對COVID-19 的保護，屆時COVID-19 病例率和住院人數預計將增加。

Also, the FDA vaccines and related Biological Products Advisory Committee, the VRBPAC, issued guidance recommending manufacture of an Omicron XBB.1.5 adapted monovalent COVID-19 vaccine for the 2023 and 2024 fall and winter seasons.

此外，FDA 疫苗和相關生物產品諮詢委員會 VRBPAC 發布了指南，建議在 2023 年和 2024 年秋冬季節生產適用於 Omicron XBB.1.5 的單價 COVID-19 疫苗。

We and Pfizer submitted regulatory applications to the EMA and to the FDA for our Omicron XBB.1.5 adapted monovalent COVID-19 vaccine for individual 6 months of age and older. Following guidance from regulatory authorities on the requirements for strain changes, where applications include data suggesting that Omicron XBB.1.5 adapted monovalent COVID-19 vaccine may generate improved responses against circulating XBB sublineages compared to the current Omicron BA4/5 adapted bivalent COVID-19 vaccine.

我們和輝瑞向 EMA 和 FDA 提交了針對 6 個月及以上個體的 Omicron XBB.1.5 適應單價 COVID-19 疫苗的監管申請。遵循監管機構關於毒株變更要求的指導，其中應用中包含的數據表明，與當前Omicron BA4/5 適應的二價COVID-19 疫苗相比，Omicron XBB.1.5 適應的單價COVID-19 疫苗可能對循環XBB 亞系產生更好的反應。

Moving to Slide 12. We and our partner, Pfizer, tested the potential effectiveness of an Omicron XBB.1.5 adapted monovalent vaccine as a primary series and booster in mice. Here, you see the neutralizing antibody response in mice immunized with Omicron BA4/5 adapted bivalent vaccines as booster after 2 doses of original vaccine.

轉到幻燈片 12。我們和我們的合作夥伴輝瑞 (Pfizer) 在小鼠中測試了 Omicron XBB.1.5 改造單價疫苗作為初級系列疫苗和加強疫苗的潛在有效性。在這裡，您可以看到使用 Omicron BA4/5 適應二價疫苗作為加強劑免疫的小鼠在接種 2 劑原始疫苗後出現的中和抗體反應。

One group of mice again received a BA4/5 adapted bivalent COVID-19 vaccine as a fourth dose, and the other group received the new XBB.1.5-adapted 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 bivalent vaccine, indicating that XBB.1.5 variant adapted monovalent vaccine in the prevaccinated setting has the potential to induce broad cross neutralizing antibody titers against multiple XBB sublineages.

一組小鼠再次接受 BA4/5 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。您可以看到，與上一季二價疫苗相比，當第4 劑是XBB.1.5 適應單價疫苗時，幾種XBB 相關變體的中和作用增加了4 至5 倍，這表明預接種中的XBB.1.5 變體適應單價疫苗設置有可能誘導針對多個 XBB 亞系的廣泛交叉中和抗體滴度。

We made significant progress towards monovalent COVID-19 vaccine against Omicron XBB.1.5 with regulatory submissions to the U.S. FDA, EMA and other regulatory authorities, and we are well prepared to launch an adapted COVID-19 vaccine if approved in early fall this year.

我們在針對Omicron XBB.1.5 的單價COVID-19 疫苗方面取得了重大進展，並向美國FDA、EMA 和其他監管機構提交了監管申請，如果在今年初秋獲得批准，我們已做好充分準備推出改良的COVID-19 疫苗。

Moving to our oncology pipeline. Let me put our second quarter pipeline advancements into the broader context of our clinical stage pipeline, which is depicted on Slide 13.

轉向我們的腫瘤學管道。讓我將我們第二季度的產品線進展放到更廣泛的臨床階段產品線背景中，如幻燈片 13 所示。

In the second quarter, the initiation of our pivotal Phase III trial in non-small cell lung cancer marks the first landmark in our strategic collaboration with OncoC4. The randomized Phase III trial is evaluating BNT316, the pH sensitive anti-CTLA-4 antibody with distinctive mode of action and is expected to enroll approximately 600 patients with metastatic immunotherapy-resistant non-small cell lung cancer.

第二季度，我們針對非小細胞肺癌的關鍵 III 期試驗的啟動，標誌著我們與 OncoC4 戰略合作的第一個里程碑。這項隨機 III 期試驗正在評估 BNT316，這是一種具有獨特作用模式的 pH 敏感抗 CTLA-4 抗體，預計將招募約 600 名轉移性免疫治療耐藥的非小細胞肺癌患者。

The trial initiation follows for FDA Fast Track designation granted in 2022 and is based on Phase I/II safety and efficacy data for the monotherapy in metastatic immune checkpoint inhibitor-resistant non-small cell lung cancer.

該試驗是在 2022 年獲得 FDA 快速通道指定後啟動的，並且基於轉移性免疫檢查點抑製劑耐藥非小細胞肺癌單一療法的 I/II 期安全性和有效性數據。

Further, we expanded our collaboration with Duality and added a third ADC to our oncology pipeline. DB-1305 is currently in a Phase I/II clinical trial for solid tumors. Then I have news from BNT116, our lung cancer antigen-based FixVac candidate.

此外，我們擴大了與 Duality 的合作，並在我們的腫瘤學產品線中添加了第三個 ADC。 DB-1305目前正在進行針對實體瘤的I/II期臨床試驗。然後我收到了來自 BNT116 的消息，BNT116 是我們基於肺癌抗原的 FixVac 候選藥物。

A second trial with BNT116 has dosed its first patient end of July. Together with our partner, Regeneron, we will evaluate BNT116 in combination with cemiplimab versus cemiplimab monotherapy alone in treatment-naive patients with Stage IIIB, Stage IIIC or Stage IV squamous or non-squamous non-small cell lung cancer patients with at least 50% PD-L1 expression in a randomized multicenter open-label Phase II study.

BNT116 的第二次試驗已於 7 月底對第一位患者進行了給藥。我們將與我們的合作夥伴Regeneron 一起，在患有至少50% 的IIIB 期、IIIC 期或IV 期鱗狀或非鱗狀非小細胞肺癌的初治患者中評估BNT116 聯合cemiplimab 與單獨cemiplimab 單藥治療的情況隨機多中心開放標籤 II 期研究中的 PD-L1 表達。

The Phase I clinical trial is ongoing with BNT116 to evaluate the safety, tolerability and preliminary efficacy of BNT116 alone and in combination with cemiplimab in patients who have progressed on prior PD-1 inhibitor treatment or are not eligible for chemotherapy and in combination with docetaxel in patients who have received prior PD-1 inhibitor therapy and platinum-based chemotherapy.

BNT116 的I 期臨床試驗正在進行中，以評估BNT116 單獨使用以及與cemiplimab 聯合治療在既往PD-1 抑製劑治療中出現進展或不適合化療的患者以及與多西他賽聯合治療的安全性、耐受性和初步療效。既往接受過PD-1抑製劑治療和鉑類化療的患者。

We are planning to start several trials with our partners imminently. Firstly, building on compelling Phase I data in patients with resectable PDAC in the adjuvant setting that we recently reported in Nature, a Phase II trial with Autogene cevumeran BNT122, our individualized cancer vaccine candidate is planned with our partner, Genentech, evaluating the efficacy and safety of autogene cevumeran in combination with atezolizumab and modified FOLFIRINOX compared to modified FOLFIRINOX as standard of care alone.

我們計劃立即與合作夥伴開始多項試驗。首先，基於我們最近在《自然》雜誌上報導的可切除PDAC 患者的輔助治療中令人信服的I 期數據，一項Autogene cevumeran BNT122 的II 期試驗，我們與我們的合作夥伴Genentech 一起計劃了個體化癌症候選疫苗，評估其功效和與單獨使用改良 FOLFIRINOX 作為護理標準相比，autogene cevumeran 與 atezolizumab 和改良 FOLFIRINOX 聯合使用的安全性。

Second, another trial is planned to start with our second ADC developed by DualityBio. BNT324 is a humanized antibody conjugated to a novel DNA Topoisomerase 1 inhibitor via cleavable linker. The Phase I part of the study will evaluate the safety in all comers and determine the recommended Phase II dose. In the Phase II dose expansion part, we aim to evaluate safety and efficacy in small cell and non-small cell lung cancer, esophageal cancer, prostate cancer, melanoma and other solid tumors.

其次，計劃從 DualityBio 開發的第二個 ADC 開始另一項試驗。 BNT324 是一種人源化抗體，通過可裂解接頭與新型 DNA 拓撲異構酶 1 抑製劑綴合。該研究的第一階段部分將評估所有參與者的安全性並確定推薦的第二階段劑量。在II期劑量擴展部分，我們的目標是評估小細胞和非小細胞肺癌、食管癌、前列腺癌、黑色素瘤和其他實體瘤的安全性和有效性。

On the next couple of slides, I want to summarize the recently presented data from 3 of our programs at the ASCO Annual Meeting.

在接下來的幾張幻燈片中，我想總結一下我們最近在 ASCO 年會上提供的 3 個項目的數據。

On Slide 14, starting with BNT316 ONC-392. Antibody targeting of CTLA-4 works primarily by depleting regulatory T cells and thus, the suppression of tumor-specific immunity. Physiologically, CTLA-4 recycles continuously between the self-service in the endosome. Interruption of this process by a binding antibody is associated with the development of autoimmunity.

在幻燈片 14 上，從 BNT316 ONC-392 開始。 CTLA-4 抗體的靶向作用主要是通過消耗調節性 T 細胞，從而抑制腫瘤特異性免疫。生理上，CTLA-4在內體內的自助服務之間不斷循環。結合抗體對該過程的中斷與自身免疫的發展相關。

Autoimmunity and immune-related adverse events are a major limitation of approved anti-CTLA-4 antibodies that disrupt CTLA-4 recycling by promoting lysosomal degradation of its important immune checkpoint molecule. BNT316 in contrast dissociates from the CTLA molecule in the endosome, allows normal recycling of both the antibody and the CTLA-4 molecule and thus is designed for stronger cancer therapeutic effect and less immune-related adverse effects. Preliminary data showed that BNT316 is well tolerated with no dose-limiting toxicities.

自身免疫和免疫相關不良事件是已批准的抗 CTLA-4 抗體的主要限制，這些抗體通過促進重要免疫檢查點分子的溶酶體降解來破壞 CTLA-4 的循環。相比之下，BNT316 在內體中與 CTLA 分子解離，允許抗體和 CTLA-4 分子正常循環，因此旨在實現更強的癌症治療效果和更少的免疫相關副作用。初步數據顯示，BNT316 耐受性良好，沒有劑量限制性毒性。

The single-agent recommended Phase II dose was determined to be 10 mg per kg without MTD being reached. Severe immune-related grade 3 adverse event rate in the combo dose escalation with pembrolizumab was 23%, which is considered lower than what was reported for comparable IO-IO combination. The recommended Phase II dose for combination is 6 mg per kg.

在未達到 MTD 的情況下，II 期單藥推薦劑量確定為 10 mg/kg。派姆單抗組合劑量遞增中的嚴重免疫相關 3 級不良事件發生率為 23%，這被認為低於報導的可比 IO-IO 組合的發生率。 II 期聯合用藥的推薦劑量為 6 mg/kg。

Overall, BNT316 dosed as monotherapy and in combination was well tolerated, and the safety profile appears to allow higher dosing for a longer duration of treatment as compared, for example, to ipilimumab. Early efficacy data as monotherapy and platinum-resistant ovarian cancer patients and in combination with pembrolizumab in multiple solid tumors were promising.

總體而言，BNT316 作為單一療法和聯合療法的劑量均具有良好的耐受性，並且與伊匹單抗(ipilimumab) 等相比，其安全性似乎允許在更長的治療時間內使用更高的劑量。單藥治療和鉑耐藥卵巢癌患者以及與派姆單抗聯合治療多種實體瘤的早期療效數據是有希望的。

Slide 15. With our colleagues from OncoC4, we presented data from the Phase I/II study, investigating BNT316 in 35 non-small cell lung cancer patients with metastatic lesions that progressed on immune checkpoint inhibition in previous lines. The majority of patients had an ECOG [intensity] of 1. The objective response rate was about 30% and disease control rate was 70%. Patients that responded to BNT316 had previously failed multiple lines of treatment, including several immune checkpoint inhibitors.

幻燈片15。我們與OncoC4 的同事一起展示了I/II 期研究的數據，該研究在35 名患有轉移性病變的非小細胞肺癌患者中研究了BNT316，這些轉移性病變在先前的細胞系中因免疫檢查點抑製而進展。大多數患者的ECOG[強度]為1。客觀緩解率約為30%，疾病控制率為70%。對 BNT316 有反應的患者此前曾多次治療失敗，包括幾種免疫檢查點抑製劑。

In this cohort, BNT316 has shown manageable safety and tolerability when dosed at 10 mg per kg twice and followed with 6 mg per kg every 3 weeks. Immune-related adverse events of grade 3/4 were observed in 34% of patients and included immune-mediated colitis ALT/AST increase and immune hepatitis.

在該隊列中，BNT316 按 10 毫克/公斤劑量兩次給藥，隨後每 3 週服用 6 毫克/公斤，顯示出可控的安全性和耐受性。 34% 的患者觀察到 3/4 級免疫相關不良事件，包括免疫介導的結腸炎 ALT/AST 升高和免疫性肝炎。

Our findings support the further development of BNT316 in non-small cell lung cancer in the Phase III study, preserve-free.

我們的研究結果支持 BNT316 在非小細胞肺癌 III 期研究中的進一步開發，不含防腐劑。

Slide 16. Our second presentation at ASCO was together with our colleagues from DualityBio and about our first clinical data for BNT323, our next-generation HER2-targeting ADC. BNT323 is comprised of a HER2-targeting antibody, covalently linked to the proprietary DNA topoisomerase 1 inhibitor via a cleavable linker.

幻燈片 16。我們在 ASCO 上的第二次演講是與 DualityBio 的同事一起進行的，內容涉及我們的下一代 HER2 靶向 ADC BNT323 的第一個臨床數據。 BNT323 由 HER2 靶向抗體組成，通過可裂解接頭與專有的 DNA 拓撲異構酶 1 抑製劑共價連接。

Approved ADCs have shown antitumor activity and clinical benefit in multiple types of cancer. And we believe that midterm ADCs as a modality will become a broadly used backbone for combos in oncology. More efficacious and safer anti-HER2 ADCs for example, regarding potential lung toxicity may add further clinical benefit.

批准的 ADC 已在多種類型的癌症中顯示出抗腫瘤活性和臨床益處。我們相信，中期 ADC 作為一種模式將成為腫瘤學組合中廣泛使用的支柱。例如，針對潛在的肺毒性，更有效、更安全的抗 HER2 ADC 可能會增加更多的臨床益處。

Preclinical data for BNT323 distracted significantly improved therapeutic window as compared DS-8201a or TDM-1 analogues to approved HER2 ADC Trastuzumab deruxtecan and Trastuzumab-Emtansin respectively.

與 DS-8201a 或 TDM-1 類似物分別與已批准的 HER2 ADC Trastuzumab deruxtecan 和 Trastuzumab-Emtansin 相比，BNT323 的臨床前數據顯著改善了治療窗。

BNT323 has a high drug-to-antibody ratio and when incubated with red monkey and human plasma demonstrated outstanding plasma stability. In HER2 positive and HER2 negative mixed cell cultures, BNT323 inhibited the proliferation of both cell types, demonstrating its bystander effect.

BNT323 具有較高的藥物抗體比，當與紅猴和人血漿一起孵育時，表現出出色的血漿穩定性。在 HER2 陽性和 HER2 陰性混合細胞培養物中，BNT323 抑制兩種細胞類型的增殖，證明了其旁觀者效應。

Pharmacokinetic and pharmacodynamic analysis of BNT323 and xenograft mouse models showed targeted delivery of the toxin into tumor tissue. In vivo studies in monkeys showed a superior stability of BNT323 and rapid systemic clearance of the toxin. Altogether, these properties result in maintenance of efficacy and reduction of systemic toxicity in animal models.

BNT323 和異種移植小鼠模型的藥代動力學和藥效學分析表明，毒素被靶向遞送至腫瘤組織中。猴子體內研究顯示 BNT323 具有卓越的穩定性，並且毒素可快速全身清除。總而言之，這些特性可以在動物模型中維持功效並減少全身毒性。

Slide 17. The program has received Fast Track designation from the FDA and is being evaluated in a Phase I/II clinical trial. The study is enrolling pretreated patients with advanced or metastatic HER2 targetable solid tumors. HER2 status is identified via IHC or ISH for expression level via NGS for HER2 amplification or HER2 mutation.

幻燈片 17。該項目已獲得 FDA 的快速通道指定，並正在 I/II 期臨床試驗中進行評估。該研究正在招募接受過治療的晚期或轉移性 HER2 靶向實體瘤患者。 HER2 狀態通過 IHC 或 ISH 確定表達水平，通過 NGS 進行 HER2 擴增或 HER2 突變。

The majority of patients had the HER2 expression by IHC of 2 plus of status. We showed preliminary antitumor activity in heavily pretreated HER2-expressing patients with a median of 7 prior systemic treatment lines, including other anti-HER2 ADCs, anti-HER2 antibody therapy or anti-HER2 TKI therapy.

根據 IHC 檢測，大多數患者的 HER2 表達為 2+ 狀態。我們在接受過大量預處理的 HER2 表達患者中顯示了初步的抗腫瘤活性，這些患者之前接受過 7 種全身治療線，包括其他抗 HER2 ADC、抗 HER2 抗體療法或抗 HER2 TKI 療法。

In HER2-positive breast cancer patients for objective response rate is 50%, the disease control rate is 96%. In HER2 low breast cancer patients, objective response rate is 38%, the disease control rate is 84%. Antitumor activity of BNT323 was also observed in non-breast cancer tumor types, such as colorectal cancer, ovarian cancer and endometrial cancer.

在HER2陽性乳腺癌患者中，客觀緩解率為50%，疾病控制率為96%。在HER2低乳腺癌患者中，客觀緩解率為38%，疾病控制率為84%。 BNT323 的抗腫瘤活性也在非乳腺癌腫瘤類型中觀察到，例如結直腸癌、卵巢癌和子宮內膜癌。

Responses were observed in patients treated with different dose levels and HER2 expression status. BNT323 was well tolerated and all adverse events were manageable so far. Interstitial lung disease of grade 1 occurred in 2 patients out of 85 patients.

觀察接受不同劑量水平和 HER2 表達狀態治療的患者的反應。 BNT323 的耐受性良好，迄今為止所有不良事件均可控。 85 名患者中有 2 名患者出現 1 級間質性肺疾病。

Expansion cohorts are ongoing in selected tumor patients treated at recombinant Phase II dose, and we expect further data this year.

正在以重組 II 期劑量治療的選定腫瘤患者中進行擴展隊列，我們​​預計今年會有更多數據。

Slide 18. Finally, we presented data on our cell therapy product candidate BNT211. We developed a highly sensitive second-generation CAR targeting CLDN6 with high specificity. The carcinoembryonic antigen CLDN6 is an ideal target for cell therapy as it is absent in healthy tissues, but highly expressed in many high medical need cancers.

幻燈片 18。最後，我們展示了我們的細胞治療候選產品 BNT211 的數據。我們開發了針對 CLDN6 的高靈敏度第二代 CAR，具有高特異性。癌胚抗原 CLDN6 是細胞治療的理想靶點，因為它在健康組織中不存在，但在許多高醫療需求的癌症中高度表達。

To improve CAR T cell engraftment and persistence, we codeveloped a CAR T cell amplifying RNA vaccine or CARVac for short. The goal is to keep CAR T cells at therapeutically relevant levels. In animal studies, we have shown that the persistence and effector function of CAR T cells can be further enhanced by repeated administration of CARVac, a nanoparticular RNA vaccine that encodes CLDN6. CARVac is based on our uridine nucleotide mRNA (inaudible) vaccine technology and mediates body-wide RNA delivery to lymphoid compartment resident antigen presenting cell.

為了提高 CAR T 細胞的植入和持久性，我們共同開發了 CAR T 細胞擴增 RNA 疫苗或簡稱 CARVac。目標是將 CAR T 細胞保持在治療相關水平。在動物研究中，我們表明，通過重複施用 CARVac（一種編碼 CLDN6 的納米顆粒 RNA 疫苗）可以進一步增強 CAR T 細胞的持久性和效應功能。 CARVac 基於我們的尿苷核苷酸 mRNA（聽不清）疫苗技術，介導全身 RNA 遞送至淋巴室常駐抗原呈遞細胞。

In multiple preclinical models, the display of the translated natively folded CAR target protein on antigen-presenting cells, mediated in vivo stimulation and controlled expansion of CAR T cells, induced a memory T cell phenotype along with higher target sensitivity and enabled tumor control even if subtherapeutic CAR T cells doses were administered.

在多個臨床前模型中，翻譯的天然折疊的CAR 靶蛋白在抗原呈遞細胞上展示，介導CAR T 細胞的體內刺激和受控擴增，誘導記憶T 細胞表型以及更高的靶標敏感性，並能夠控制腫瘤，即使給予亞治療劑量的 CAR T 細胞。

We are testing the safety, tolerability and activity of a combination of CLDN6 CAR T sets and CARVac in a bifurcated dose escalation study with increasing dose levels of CAR T cells and the fixed CARVac schedule in patients with various cancer types that are CLDN6 positives defined as more than 50% of tumor cells with 2 to 3 plus intensity.

我們正在一項分叉劑量遞增研究中測試CLDN6 CAR T 組和CARVac 組合的安全性、耐受性和活性，在CLDN6 陽性的各種癌症類型患者中增加CAR T 細胞的劑量水平和固定的CARVac 方案，定義為超過50%的腫瘤細胞具有2至3+強度。

A dose escalation has been completed for CAR T cells derived from a manual manufacturing process, and we have presented data with highly encouraging signs of clinical activity and manageable safety at various conferences in the past.

來自手動製造過程的 CAR T 細胞的劑量升級已經完成，並且我們在過去的各種會議上提供了具有非常令人鼓舞的臨床活性跡象和可控安全性的數據。

Slide 19. A subsequent cohort of [19] patients have been treated with a CAR T product manufactured with a scalable automated version of the process. No DLTs have been observed so far. And CLDN6 CAR T cell as well as CARVac were well tolerated, reflecting the safety profile detected in the first dose escalation level.

幻燈片 19。隨後的一組 [19] 患者接受了 CAR T 產品的治療，該產品是通過可擴展的自動化版本的流程製造的。迄今為止尚未觀察到 DLT。 CLDN6 CAR T 細胞以及 CARVac 的耐受性良好，反映了在首次劑量遞增水平中檢測到的安全性。

The objective response rate was 41% for all 17 evaluable patients and 75% for 8 patients treated at dose level 2, namely 1 times 10 to the eight CAR T set.

所有 17 名可評估患者的客觀緩解率為 41%，8 名接受 2 級劑量（即 8 個 CAR T 組的 1 倍 10）治療的患者的客觀緩解率為 75%。

Next to germ cell tumors, which dominated the first dose escalation, we observed ovarian cancer patients responding. We are expecting an additional data readout later this year. Once we have determined the recommended Phase II dose for BNT211, we plan to initiate a pivotal trial in germ cell tumors which has already received prime designation by the EMA. Advancing our pipeline remains a key strategic priority for the year. This end next year, we plan to transform our pipeline as we advance multiple programs towards the pivotal stage.

除了在第一次劑量遞增中占主導地位的生殖細胞腫瘤之外，我們觀察到卵巢癌患者的反應。我們預計今年晚些時候會公佈更多數據。一旦我們確定了 BNT211 的推薦 II 期劑量，我們計劃啟動一項針對生殖細胞腫瘤的關鍵試驗，該試驗已獲得 EMA 的主要指定。推進我們的管道仍然是今年的關鍵戰略重點。明年年底，我們計劃轉變我們的管道，將多個項目推進到關鍵階段。

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

我現在將把演示文稿轉交給我們的首席財務官 Jens Holstein。

Thank you, Özlem, and a warm welcome to everyone who dialed into today's call. Before we go into the financial details for the second quarter and the first half of 2023, I'll start with giving you an overview on some key financial figures, which you can find on the next slide.

謝謝您，阿茲萊姆，並熱烈歡迎所有撥打今天電話的人。在我們討論 2023 年第二季度和上半年的財務細節之前，我將首先向您概述一些關鍵財務數據，您可以在下一張幻燈片中找到這些數據。

Our total revenues reached EUR 1.4 billion for the first half of 2023 and are in line with our expectations with Q2 being the expected weakest quarter in the year.

2023 年上半年，我們的總收入達到 14 億歐元，符合我們的預期，第二季度預計將是今年最弱的季度。

Our COVID-19 vaccine revenues, are as stated and expected before, heavily influenced by seasonal effects, especially now as we have summer in our biggest markets in the Northern Hemisphere. As we have outlined in earlier earnings calls, the revenue development for COVID-19 vaccines is expected to mimic a flu-like setting.

正如之前所述和預期的那樣，我們的 COVID-19 疫苗收入受到季節性影響的嚴重影響，尤其是現在北半球最大市場正處於夏季。正如我們在之前的財報電話會議中概述的那樣，COVID-19 疫苗的收入發展預計將模仿流感的情況。

I will go into more details concerning our financial guidance in the course of the call, but I want to emphasize already now that acknowledging the uncertainties related to the seasonal effect we reiterate our 2023 COVID-19 vaccine revenue guidance of around EUR 5 billion for the full 2023 financial year.

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，承認與季節性影響相關的不確定性，我們重申 2023 年 COVID-19 疫苗收入指引約為 50 億歐元整個2023 財年。

With EUR 1.4 billion in revenues, we ended the first 6 months of 2023 with an operating result of EUR 91.1 million and generated earnings per share on a fully diluted basis of EUR 1.28. With respect to the company's financial position, we ended the second quarter of 2023 with EUR 16.8 billion, comprising approximately EUR 14.2 billion cash and cash equivalents as well as approximately EUR 2.7 billion, partly current and partly noncurrent security investments, which are part of our investment strategy.

2023 年前 6 個月，我們的收入為 14 億歐元，經營業績為 9110 萬歐元，完全稀釋後每股收益為 1.28 歐元。就公司的財務狀況而言，截至2023 年第二季度，我們的財務狀況為168 億歐元，其中包括約142 億歐元的現金和現金等價物以及約27 億歐元的部分流動和部分非流動證券投資，這些投資是我們的一部分投資策略。

Subsequent to the end of the quarter in July 2023, we received EUR 1.1 billion in cash from our collaboration partner, Pfizer, settling our gross profit share for the first quarter of 2023, alongside with EUR 0.4 million (sic) [EUR 0.4 billion] received until early August in connection with the amended COVID-19 vaccine purchase agreement with the European Commission.

2023 年 7 月季度末後，我們從合作夥伴輝瑞 (Pfizer) 收到了 11 億歐元現金，用於結算 2023 年第一季度的毛利潤份額，以及 40 萬歐元（原文如此）[4 億歐元]截至8月初，已收到與歐盟委員會修訂後的COVID-19 疫苗購買協議有關的信息。

In connection with our acquisition of InstaDeep which closed on July 31, approximately EUR 450 million were invested in form of cash and shares, not including potential future milestones. Overall, with this strong cash position in the background, we are on track to launch our new variant adapted COVID-19 vaccine and intend to start multiple clinical trials across our oncology and infectious disease pipeline such as the ones with OncoC4 and Duality Biologics that Ugur just mentioned earlier.

在我們於 7 月 31 日完成的對 InstaDeep 的收購中，我們以現金和股票的形式投資了約 4.5 億歐元，其中不包括未來潛在的里程碑。總體而言，憑藉強大的現金狀況，我們有望推出新的變異適應的COVID-19 疫苗，並打算在我們的腫瘤學和傳染病管道中啟動多項臨床試驗，例如Ugur 的OncoC4 和Duality Biologics 的臨床試驗剛才提到過。

I'll be moving to our financial results for the second quarter of 2023, as shown on the next slide. Our total revenues reported reached EUR 166.4 million for the second quarter compared to EUR 3.2 billion for the comparative prior year period and decreased with the corresponded lower COVID-19 vaccine market demand. Write-offs by our collaboration partner, Pfizer, significantly reduced our gross profit share in the second quarter and hence negatively influenced our revenues for the 3 months ended June 2023.

我將轉向 2023 年第二季度的財務業績，如下一張幻燈片所示。我們第二季度報告的總收入達到 1.664 億歐元，而去年同期為 32 億歐元，並隨著 COVID-19 疫苗市場需求的相應下降而下降。我們的合作夥伴輝瑞公司的沖銷大大減少了我們第二季度的毛利潤份額，從而對我們截至 2023 年 6 月的三個月的收入產生了負面影響。

Let me move to cost of sales, which amounted to EUR 162.9 million in the second quarter of 2023 compared to EUR 764.6 million for the comparative prior year period. For the first 6 months of 2023, the cost of sales reached EUR 258.9 million compared to EUR 2.1 billion for the comparative prior year period. The change is in line with decreasing COVID-19 vaccine sales.

讓我談談銷售成本，2023 年第二季度的銷售成本為 1.629 億歐元，而去年同期為 7.646 億歐元。 2023 年前 6 個月，銷售成本達到 2.589 億歐元，而去年同期為 21 億歐元。這一變化與 COVID-19 疫苗銷量的下降一致。

Research and development expenses reached EUR 373.4 million for the second quarter of 2023 compared to EUR 399.6 million for the comparative prior year period. For the first 6 months of 2023, research and development expenses amounted to EUR 707.4 million compared to EUR 685.4 million for the comparative prior year period.

2023 年第二季度的研發費用達到 3.734 億歐元，而去年同期為 3.996 億歐元。 2023 年前 6 個月，研發費用為 7.074 億歐元，而去年同期為 6.854 億歐元。

Our R&D expenses are mainly influenced by progressing clinical studies for pipeline candidates, the development of variant adapted as well as next-generation COVID-19 vaccines and the expansion of our R&D headcount.

我們的研發費用主要受到管道候選藥物臨床研究進展、變異適應疫苗和下一代 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 122.7 million for the second quarter of 2023 compared to EUR 130 million for the comparative prior year period. For the first 6 months of 2023, G&A expenses reached EUR 242.1 million compared to EUR 220.8 million for the comparative prior year period. While in Q2, some cost savings have been achieved, G&A expenses for the first 6 months were mainly influenced by increased expenses for IT services as well as expanding the G&A head count.

2023 年第二季度的一般及管理費用為 1.227 億歐元，而去年同期為 1.3 億歐元。 2023 年前 6 個月，一般管理費用達到 2.421 億歐元，而去年同期為 2.208 億歐元。雖然在第二季度實現了一些成本節省，但前 6 個月的 G&A 費用主要受到 IT 服務費用增加以及 G&A 人數增加的影響。

Due to a loss-making second quarter of 2023 and the tax effect of a reorganization of the intellectual property rights within the group, income taxes with an amount of EUR 221.8 million were realized compared to tax expenses of EUR 647.3 million accrued for the comparative prior year period.

由於 2023 年第二季度虧損以及集團內部知識產權重組的稅務影響，實現所得稅金額為 2.218 億歐元，而上年同期應計稅務費用為 6.473 億歐元年期間。

In total, for the first 6 months of 2023, income taxes were realized with an amount of EUR 16.3 million tax income compared to EUR 2 billion tax expenses accrued for the comparative prior year period. The derived effective income tax rate for the first 6 months of 2023 was approximately minus 5.5% which is expected to change over the 2023 financial year to be in line with the updated estimated annual cash effective income tax rate of somewhere around 21% for the BioNTech Group, an improvement that I will elaborate on in a minute.

總體而言，2023 年前 6 個月，所得稅實現了 1,630 萬歐元的稅收收入，而上年同期應計稅收費用為 20 億歐元。 2023 年前 6 個月得出的有效所得稅率約為負 5.5%，預計在 2023 財年將發生變化，與 BioNTech 更新的估計年度現金有效所得稅率約 21% 一致群組，這是一項改進，我將在一分鐘內詳細說明。

As mentioned at the beginning, due to mainly seasonal effect of our COVID business, we recognized a loss during the second quarter of 2023, amounting to EUR 190.4 million compared to EUR 1.7 billion net profit for the comparative prior year period. For the first 6 months of 2023, net profit reached EUR 311.8 million compared to EUR 5.4 billion for the comparative prior year period.

如本文開頭所述，主要由於新冠疫情業務的季節性影響，我們在 2023 年第二季度確認虧損 1.904 億歐元，而去年同期淨利潤為 17 億歐元。 2023 年前 6 個月，淨利潤達到 3.118 億歐元，而去年同期淨利潤為 54 億歐元。

Our loss per share for the second quarter of 2023 amounted to EUR 0.79 compared to a diluted earnings per share of EUR 6.44 for the comparative prior year period. For the first 6 months of 2023, our diluted earnings per share was EUR 1.28 compared to EUR 20.65 for the comparative prior year period.

2023 年第二季度的每股虧損為 0.79 歐元，而去年同期的稀釋每股收益為 6.44 歐元。 2023 年前 6 個月，我們的稀釋每股收益為 1.28 歐元，而去年同期為 20.65 歐元。

Now turning to the next slide, I would like to emphasize that we are updating the company's financial outlook for the 2023 financial year with respect to our planned full year R&D and SG&A expenses as well as our planned expenses and growth and maintenance CapEx for operating activities, excluding effects caused by or driven from in-licensing arrangements, collaborations or M&A transactions.

現在轉向下一張幻燈片，我想強調的是，我們正在更新公司2023 財年的財務展望，包括我們計劃的全年研發和銷售、一般行政費用以及我們計劃的運營活動費用以及增長和維護資本支出，不包括由許可安排、合作或併購交易引起或驅動的影響。

Please note that the following numbers reflect current base -- case projections and are calculated based on constant currency rates and do not include further transactions that could occur in the second half of 2023. As stated before, we reiterate our estimated COVID-19 vaccine revenues of around EUR 5 billion for the full 2023 financial year. Our guidance is based on the expectation that the demand in our vaccine will pick up in the year's third and fourth quarter along with our rollout of the adapted COVID-19 vaccine against XBB.1.5.

請注意，以下數字反映了當前的基本病例預測，並根據固定匯率計算，不包括 2023 年下半年可能發生的進一步交易。如前所述，我們重申了我們對 COVID-19 疫苗收入的估計2023 財年的投資額約為50 億歐元。我們的指導基於這樣的預期：隨著我們推出針對 XBB.1.5 的改良版 COVID-19 疫苗，我們的疫苗需求將在今年第三和第四季度回升。

During the second quarter of 2023, the COVID-19 vaccine supply agreement with the European Commission has been amended. The agreed rephasing of deliveries annually through 2026 will play an important role in the future as revenues will be recognized on the expanded term.

2023 年第二季度，與歐盟委員會的 COVID-19 疫苗供應協議進行了修訂。商定的到 2026 年每年重新分階段交付的計劃將在未來發揮重要作用，因為收入將在延長的期限內得到確認。

With the EC contract, giving us a level of clarity in terms of revenue expectations, the demand and vaccination rates in other territories, as for example, the U.S. market remain uncertain regarding these metrics. Our collaboration partner, Pfizer, concerned its plans to achieve its goals for their market. Given their detailed plans to support an increase in vaccination rates in the U.S., we expect to achieve our revenue guidance range as previously mentioned. However, substantial uncertainties underlie the demand for COVID-19 vaccines in general as well as for our vaccine e.g the timing of its approval will have an impact on its demand.

通過 EC 合同，我們在收入預期、其他地區的需求和疫苗接種率方面有了一定程度的明確性，例如美國市場在這些指標方面仍然不確定。我們的合作夥伴輝瑞公司關注其實現其市場目標的計劃。鑑於他們支持提高美國疫苗接種率的詳細計劃，我們預計將實現之前提到的收入指導範圍。然而，總體而言，對 COVID-19 疫苗以及我們的疫苗的需求存在很大的不確定性，例如其批准的時間將對其需求產生影響。

There have been no precedent on how COVID-19 vaccine rates will evolve after years of a pandemic where people have been vaccinated multiple times. We expect to learn from this for future years, but we assume that 2023 will be a very special one, given the mentioned circumstances. It is our aim to move our clinical programs forward as quickly yet cost efficiently as possible towards becoming a multiproduct company.

在人們多次接種疫苗的大流行多年之後，COVID-19 疫苗接種率將如何變化尚無先例。我們希望在未來幾年能從中吸取教訓，但考慮到上述情況，我們認為 2023 年將是非常特殊的一年。我們的目標是盡可能快速且經濟高效地推進我們的臨床項目，成為一家多產品公司。

To do so, we have implemented further measures to increase cost consciousness, which led to a company-wide cost optimization and hence, a reduction of our expected 2023 R&D, SG&A spend and capital expenditures. The increased flexibility at expenditure level will help us navigate for the just described uncertainties while remaining focused on the development of the next wave of innovation in various fields and indications.

為此，我們採取了進一步措施來提高成本意識，從而實現了全公司範圍的成本優化，從而減少了我們預期的 2023 年研發、銷售、行政管理支出和資本支出。支出水平靈活性的增加將幫助我們應對剛才描述的不確定性，同時繼續專注於各個領域和適應症下一波創新的發展。

As summarized for you on this slide, we update our R&D spending for the rest of 2023 from between EUR 2.4 billion and EUR 2.6 billion to between EUR 2 billion and EUR 2.2 billion including the R&D development costs identified from our latest publicly announced M&A activities.

正如本幻燈片為您總結的那樣，我們將2023 年剩餘時間的研發支出從24 億至26 億歐元更新為20 億至22 億歐元，其中包括我們最新公開宣布的併購活動中確定的研發開發成本。

We also updated our SG&A expenses from between EUR 650 million to EUR 750 million now to between EUR 600 million and EUR 700 million and reduce our spending for growth and maintenance CapEx for operating activities from between EUR 500 million to EUR 600 million to between EUR 350 million and EUR 450 million.

我們還將 SG&A 費用從現在的 6.5 億歐元至 7.5 億歐元更新為 6 億至 7 億歐元，並將運營活動的增長和維護資本支出從 5 億歐元至 6 億歐元減少至 350 歐元萬和4.5 億歐元。

As noted before, we have updated our group estimated annual cash effective income tax rate from around 27% to around 21%, excluding potential effects from share-based payment settlements in the course of 2023. Following the reorganization of the intellectual property rights within the group, we recognized deferred tax effects in Germany and the U.S. Previously unrecognized U.S. federal and state deferred tax assets, including unused tax losses and unused tax credits have been reevaluated and now recognized. The recognition of these deferred tax assets lead to a decrease in the effective tax rate for the fiscal year of 2023.

如前所述，我們已將集團預計的年度現金有效所得稅率從約 27% 更新至約 21%，不包括 2023 年股份支付和解的潛在影響。集團中，我們確認了德國和美國的遞延稅項影響。之前未確認的美國聯邦和州遞延稅項資產，包括未使用的稅收損失和未使用的稅收抵免，已重新評估並現已確認。這些遞延所得稅資產的確認導致 2023 財年的實際稅率下降。

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

現在，我想將電話轉給我們的首席戰略官瑞安·理查森 (Ryan Richardson)，請他介紹我們 2023 年戰略展望的最新情況並作總結髮言。謝謝。

Thank you, Jens. I'll now provide a brief summary of the commercial outlook for our updated COVID-19 vaccine launch and provide an update on our acquisition of InstaDeep before concluding with our strategic outlook for the remainder of the year and beyond.

謝謝你，延斯。現在，我將簡要概述我們更新的 COVID-19 疫苗推出的商業前景，並提供我們收購 InstaDeep 的最新情況，然後再總結我們今年剩餘時間及以後的戰略前景。

I would like to touch on our key readiness activities that have put us in a strong position to execute on our planned launch this fall. On the back of the regulatory recommendation for an XBB.1.5-adaptive monovalent vaccine, we and Pfizer have made more than 40 regulatory submissions in key geographies around the world. We are on track to begin vaccine distribution once regulatory approval is received with first shipments expected from September onwards.

我想談談我們的關鍵準備活動，這些活動使我們處於有利地位來執行我們計劃於今年秋天推出的產品。在針對 XBB.1.5 適應性單價疫苗的監管建議的支持下，我們和輝瑞已在全球主要地區提交了 40 多項監管申請。一旦收到監管部門的批准，我們將開始分發疫苗，預計從 9 月份開始發貨。

We believe Comirnaty is positioned to maintain its leading position in multiple key geographies. Most of the world will continue to be supplied under existing pandemic booster contracts. This includes our contract with the European Union, our largest contract, which was recently renegotiated to extend to a period over 4 years. In the United States, we expect our first major commercial market opening, where we will leverage Pfizer's commercial capabilities.

我們相信 Comirnaty 有能力在多個關鍵地區保持領先地位。世界大部分地區將繼續根據現有的大流行加強合同獲得供應。這包括我們與歐盟的合同，這是我們最大的合同，最近經過重新談判，期限延長至 4 年以上。在美國，我們預計將開放第一個主要商業市場，我們將利用輝瑞的商業能力。

Turning to the next slide. This week, we announced that our acquisition of InstaDeep has closed following receipt of all required approvals. With the acquisition, we add world-class AI and machine learning technologies and research capabilities to accelerate and enhance our broader strategic vision. The acquisition will bring over 290 data scientists, ML engineers and tech professionals to our team, positioning us to lead in this disruptive new field.

轉到下一張幻燈片。本週，我們宣佈在收到所有必要的批准後，我們​​對 InstaDeep 的收購已結束。通過此次收購，我們增加了世界一流的人工智能和機器學習技術和研究能力，以加速和增強我們更廣泛的戰略願景。此次收購將為我們的團隊帶來 290 多名數據科學家、機器學習工程師和技術專業人員，使我們能夠在這個顛覆性的新領域處於領先地位。

In combining InstaDeep's AI and ML expertise with our own research and development capabilities, we aim to develop novel therapeutic and vaccine product candidates with increased speed and efficiency. We also see opportunities to leverage these AI and ML capabilities outside of R&D across other functions of BioNTech. This makes this a highly strategic acquisition with significant long-term transformational potential across our firm. We will operate InstaDeep as an independent technology subsidiary of BioNTech.

通過將 InstaDeep 的人工智能和機器學習專業知識與我們自己的研發能力相結合，我們的目標是更快、更高效地開發新型治療和疫苗候選產品。我們還看到了在 BioNTech 的其他職能領域在研發之外利用這些人工智能和機器學習能力的機會。這使得這是一次高度戰略性的收購，在我們公司具有巨大的長期轉型潛力。我們將作為 BioNTech 的獨立技術子公司運營 InstaDeep。

On the next slide, we show the 3 pillars of value creation that we expect from this transaction. The first is to apply cutting-edge AI and machine-learning technologies across our therapeutic and vaccine platforms. We plan to connect these AI-enabled discovery capabilities with automated lab infrastructure to enable high throughput drug discovery. While we do expect our overall AI investments to increase in the coming years, we do expect some midterm cost efficiencies from the acquisition by internalizing our largest AI technology and services provider.

在下一張幻燈片中，我們展示了我們期望從這次交易中創造價值的三大支柱。首先是在我們的治療和疫苗平台上應用尖端的人工智能和機器學習技術。我們計劃將這些人工智能支持的發現能力與自動化實驗室基礎設施連接起來，以實現高通量藥物發現。雖然我們確實預計未來幾年我們的整體人工智能投資將會增加，但我們確實預計通過內部化我們最大的人工智能技術和服務提供商的收購可以帶來一些中期成本效率。

Finally, we will continue to operate InstaDeep's third-party business, which delivers technology solutions and services to external customers in the technology sector and other industries. We are excited to kick off the next phase of our collaboration with the leadership and bright minds at InstaDeep and believe that together, we can become a global leader in applying cutting-edge artificial intelligence and machine-learning technologies to discover, design and develop next-generation immunotherapies at scale.

最後，我們將繼續運營InstaDeep的第三方業務，為科技領域和其他行業的外部客戶提供技術解決方案和服務。我們很高興與 InstaDeep 的領導層和聰明才智開始下一階段的合作，並相信我們可以共同成為應用尖端人工智能和機器學習技術來發現、設計和開發下一代產品的全球領導者。大規模的一代免疫療法。

The next slide provides an overview of our expected pipeline news flow for 2023 and 2024. Some of these points have been covered, so I won't go through them all in detail here. With the collective efforts and dedication from our teams, we have achieved remarkable progress for several of our product candidates. At this year's ASCO Congress, we presented data for 3 of our pipeline candidates. We're on track to share additional data updates across a range of technologies later this year.

下一張幻燈片概述了我們預計 2023 年和 2024 年的管道新聞流。其中一些要點已經涵蓋，因此我不會在這裡詳細介紹它們。在我們團隊的集體努力和奉獻下，我們的多個候選產品取得了顯著的進展。在今年的 ASCO 大會上，我們展示了 3 個候選產品的數據。我們有望在今年晚些時候分享一系列技術的更多數據更新。

In June, we initiated our first Phase III trial in oncology. Additionally, we started a Phase II trial for one of our FixVac candidates in collaboration with Regeneron, focusing on first-line NSCLC. As Özlem has elaborated, we anticipate initiating several further trials in the near future.

六月，我們啟動了第一個腫瘤學 III 期試驗。此外，我們與 Regeneron 合作，針對其中一款 FixVac 候選藥物啟動了 II 期試驗，重點關註一線 NSCLC。正如阿茲萊姆所闡述的那樣，我們預計在不久的將來啟動幾項進一步的試驗。

On the next slide, I'll summarize the strategic outlook for the remainder of the year. We are on track to roll out our new variant-adapted COVID-19 vaccine in the coming month. We also plan to initiate multiple registrational oncology clinical trials while expanding our infectious disease pipeline.

在下一張幻燈片中，我將總結今年剩餘時間的戰略前景。我們有望在下個月推出新的針對變體的 COVID-19 疫苗。我們還計劃啟動多項註冊腫瘤學臨床試驗，同時擴大我們的傳染病管道。

With the InstaDeep acquisition now closed, we intend to rapidly scale up our activity in AI-enabled drug discovery, and we'll continue to execute transactions to expand our innovation ecosystem and execute on our corporate development strategy to in-license complementary assets.

隨著 InstaDeep 收購現已完成，我們打算迅速擴大我們在人工智能藥物發現方面的活動，我們將繼續執行交易以擴大我們的創新生態系統，並執行我們的企業發展戰略，以許可補充資產。

Before concluding and opening up the floor for questions, I'd like to reiterate that we will hold our Innovation Series event on November 7. We'll provide further details on the event in the coming weeks.

在結束髮言並開始提問之前，我想重申一下，我們將於 11 月 7 日舉行創新系列活動。我們將在未來幾週內提供有關該活動的更多詳細信息。

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

在此，我要感謝我們的股東一直以來的支持，我將結束我們準備好的發言並開始提問。

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

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

Yes. I have one ONC-392. The Phase III that you have started, I forget the name of it, is different in design from the Phase II and some of the inclusion/exclusion criteria. And I wonder if you could talk about why the difference is? And why you decided to go forward now in a Phase III with single-agent CTLA-4 rather than gathering more data and doing a combination study with PD-1 or any other agents in this pretty hard-to-treat and difficult-to-do trial setting?

是的。我有一台 ONC-392。你們已經啟動的第三階段，我忘記了它的名字，在設計上與第二階段不同，並且一些納入/排除標準也不同。我想知道你能否談談為什麼會有這樣的差異？以及為什麼您現在決定繼續使用單藥 CTLA-4 進行 III 期臨床試驗，而不是收集更多數據並與 PD-1 或​​任何其他藥物在這個相當難以治療和難以治療的疾病中進行聯合研究進行試用設置？

Daina, Hi. This is Ugur. Thank you for the question. So as you know, in the Phase I/II study collected data in different combinations and we have seen single compound activity in non-small cell lung cancer in patients who have received and progressed under first-line checkpoint blockade treatment. These were encouraging objective response rate around 35%. We do not see an added benefit in combining that with the current status quo, which is chemotherapy and therefore, decided in also with favoring clean safety profile to go with a single compound alone. And patient population that have been selected for the study reflects historical patient populations with regard to the inclusion and exclusion criteria.

戴娜，嗨。這是烏吾爾族。感謝你的提問。如您所知，在 I/II 期研究中收集了不同組合的數據，我們已經在接受一線檢查點阻斷治療並進展的患者中觀察到單一化合物對非小細胞肺癌的活性。這些客觀反應率令人鼓舞，約為 35%。我們認為將其與目前的化療現狀相結合併沒有帶來額外的好處，因此，我們還決定單獨使用單一化合物，以保證清潔的安全性。為研究選擇的患者群體反映了納入和排除標準方面的歷史患者群體。

Okay. Perhaps a follow-up. I think the difference, and tell me if I'm wrong, was the length for which the patients could have received a prior checkpoint that it's a lot -- you're requiring a longer prior checkpoint than you in Phase III than you did in the Phase II. So some Phase II patients, wouldn't be eligible for Phase III, do you expect any negative impact from?

好的。也許是後續行動。我認為區別在於，如果我錯了，請告訴我，患者可以接受先前檢查點的時間長度，這是很多——你需要比第三階段更長的先前檢查點。第二階段。那麼一些 II 期患者，不符合 III 期資格，您預計會產生什麼負面影響嗎？

Yes. Daina -- and the protocol has also emerged based on discussions with the FDA and FDA request.

是的。 Daina——該協議也是根據與 FDA 的討論和 FDA 的要求而製定的。

And your next question comes from the line of Tazeen Ahmad from Bank of America.

您的下一個問題來自美國銀行的 Tazeen Ahmad。

Just a point of clarification. As you think about the rest of the year for COVID vaccine sales, I know you talked about the difficulties involved in really getting a sense for the trends. But when you decided to maintain guidance at least for now, what key factors are you taking into account that gives you confidence that sales will be -- or revenues rather will be at least close to, if not at the EUR 5 billion mark? And I think that's probably the best question for Ryan to answer.

只是澄清一點。當您思考今年剩餘時間的新冠疫苗銷售情況時，我知道您談到了真正了解趨勢所涉及的困難。但是，當您決定至少暫時維持指導時，您會考慮哪些關鍵因素，讓您相信銷售額（或者收入）即使不是達到 50 億歐元大關，也至少會接近 50 億歐元？我認為這可能是瑞安要回答的最佳問題。

Yes, I'll start, Tazeen, and Jens should also chime in here. So I think the starting point here was that we are expecting the total volume of COVID vaccines in the fall to be down. You may remember that last year, we had distributed more than 500 million doses of our B4/B5 variance-adaptive vaccine globally. And for the full year last year, we had -- the market in the United States was about 144 million doses. We are expecting those numbers to come down, both in the United States and globally.

是的，我要開始了，Tazeen，Jens 也應該插話一下。所以我認為這裡的出發點是我們預計秋季新冠疫苗的總量將會下降。您可能還記得，去年我們在全球分發了超過 5 億劑 B4/B5 變異適應性疫苗。去年全年，美國市場的疫苗數量約為 1.44 億劑。我們預計美國和全球的這些數字都會下降。

So we factor that in. However, we also expect that -- in the United States that we're going to see a commercial market opening, so a higher price pool. We along With Pfizer, have talked about a gross price in the $110 to $130 range. That's our expectation. And so a higher price point in the U.S. and much of the rest of the world, we're still expecting contracts that have already been signed to be the primary sort of contractual mode governing the second half deliveries, but demand will still matter. So in the rest of the world, we're still expecting effectively a continuation of the booster contracts, and that's factored in as well.

因此，我們將這一點考慮在內。但是，我們也預計，在美國，我們將看到商業市場開放，因此價格會更高。我們與輝瑞一起討論了 110 至 130 美元範圍內的總價格。這是我們的期望。因此，由於美國和世界其他大部分地區的價格較高，我們仍然預計已簽署的合同將成為管理下半年交付的主要合同模式，但需求仍然很重要。因此，在世界其他地區，我們仍然預計有效的助推器合同會繼續存在，這也已考慮在內。

Yes. Maybe Tazeen, just to add, I mean, Ryan basically described the situation. And I think we made some statements in our speeches as well in that respect. But of course, a situation like we currently see hasn't been seen before for any product so far. Patients have received and people have received multiple vaccinations in the last 2 years. And of course, there is some level of tiredness, so to say, on getting vaccinated.

是的。也許塔澤恩，只是補充一下，我的意思是，瑞安基本上描述了這種情況。我認為我們在演講中也在這方面發表了一些聲明。當然，到目前為止，任何產品都還沒有遇到過像我們現在看到的情況。在過去 2 年裡，患者和人們都接受了多次疫苗接種。當然，可以說，接種疫苗時會產生一定程度的疲勞。

And -- but we see the need for further vaccinations. And I think specifically for the U.S., you've heard probably some of the clients that Pfizer and as well as our competitor, Moderna has announced them, how the expectations will be going up for the rest of the year to pick up with the vaccination rates.

而且——但我們認為需要進一步接種疫苗。我認為，特別是在美國，您可能已經聽說輝瑞和我們的競爭對手 Moderna 已經宣布了一些客戶的消息，他們對今年剩餘時間的疫苗接種預期將如何上升費率。

So in that respect, the next couple of months, the next 2, 3 months will give us a good sign, how the year will end. There is some uncertainty. We just wanted to make that clear. And we see 2023 as a very special year, though, too, I have to say. So from our perspective, that situation that people have received multiple vaccinations and now are maybe a little bit tired, have to grow into a market where you have annual vaccinations. And I think it gives -- '23 gives us some indication, but we also believe there will be a further increased potential from our perspective for '24 and the outer years just given the specific situation that we now have in this year with 2 years of multiple vaccinations for people.

因此，從這方面來說，接下來的幾個月、接下來的兩三個月將會給我們一個好的跡象，即今年將如何結束。存在一些不確定性。我們只是想澄清這一點。但我也不得不說，我們認為 2023 年是非常特殊的一年。所以從我們的角度來看，人們已經接種了多次疫苗，現在可能有點累了，必鬚髮展成為每年接種疫苗的市場。我認為它給了 - '23 給了我們一些指示，但我們也相信，從我們的角度來看，'24 和外部年份將進一步增加潛力，只是考慮到我們今年在 2 年中所面臨的具體情況為人們接種多種疫苗。

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

您的下一個問題來自 Jefferies 的 Akash Tewari。

This is Amy on for Akash. So Pfizer has alluded to an enterprise-wide cost-cutting program, particularly around COVID is long-term vaccine demand ends up being modest. How would Pfizer's cost cut change your long-term OpEx on your COVID programs and spend more broadly? And on a related note, can you go over what's changed in your new 2023 OpEx and CapEx guide? We're seeing that BNT141 isn't on your pipeline slide this quarter. Are there any other components that may be driving these cost cuts?

這是艾米為阿卡什主持的節目。因此，輝瑞提到了一項全企業範圍的成本削減計劃，特別是在新冠疫情期間，長期疫苗需求最終不大。輝瑞的成本削減將如何改變您在新冠肺炎項目上的長期運營支出以及更廣泛的支出？與此相關的是，您能否回顧一下新的 2023 年運營支出和資本支出指南中發生的變化？我們發現 BNT141 不在本季度的管道幻燈片上。是否還有其他因素可以推動成本削減？

Yes. Thank you for the question. So I'll speak to the OpEx point and then I'll ask Jens to opine on what's driving the cost lines in our guidance. But on the OpEx side, the short answer is no. And actually, one of the unique features of our -- of our economic model for COVID-19 is that our OpEx is very lean. So as you may recall, we get a gross profit share on every COVID vaccine dose produced and delivered through the Pfizer partnership.

是的。感謝你的提問。因此，我將討論運營支出問題，然後請 Jens 就我們指南中成本線的推動因素發表意見。但在運營支出方面，簡單的回答是否定的。實際上，我們針對 COVID-19 的經濟模型的獨特之處之一是我們的運營支出非常精簡。您可能還記得，通過輝瑞合作夥伴關係生產和交付的每一劑新冠疫苗，我們都會獲得毛利潤分成。

And only in Germany and Turkey, do we book top line product sales and actually have a significant OpEx only in those 2 countries. So that does translate into a very differentiated profile across our P&L. And I think you see some of that leanness reflected in the numbers that we've disclosed today. Jens, do you want to speak to the drivers of the cost that you expect?

僅在德國和土耳其，我們實現了頂級產品銷售，並且實際上僅在這兩個國家/地區擁有可觀的運營支出。因此，這確實轉化為我們損益表中非常差異化的概況。我認為您會在我們今天披露的數字中看到一些精簡的內容。 Jens，您想與司機談談您預期的成本嗎？

Yes. I mean from -- for us, we, of course, can only talk for us, yes, and we cannot talk about Pfizer and their cost-cutting plans that they have announced in their earnings call. So from our perspective, we see a little bit less spend for the collaboration with Pfizer in the course of 2023. But we also have a close look on our own spending in the areas of oncology, for example, or in building up production capacities. So those have been specific areas where we just look at controlling our costs going forward to have more flexibility.

是的。我的意思是，對於我們來說，我們當然只能為我們說話，是的，我們不能談論輝瑞及其在財報電話會議中宣布的成本削減計劃。因此，從我們的角度來看，我們認為 2023 年與輝瑞合作的支出會有所減少。但我們也仔細審視了我們自己在腫瘤學領域的支出，例如，或在建設生產能力方面的支出。因此，在這些特定領域，我們只是著眼於控製成本，從而獲得更大的靈活性。

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

這個問題來自高盛的 Chris Shibutani。

Yes. Two questions, if I can. One on the pipeline and the other more financially related. On the pipeline, BNT122 first-line metastatic melanoma seemed a bit conspicuous in terms of the absence of mentioned in the press release and in prepared comments. I do see it in the pipeline table. Have your expectations for this trial changed? I believe we should still be expecting updates in the balance of this year. And then I'll have a follow-up on financial.

是的。有兩個問題，如果可以的話。一項正在籌備中，另一項則與財務相關。在管道上，BNT122一線轉移性黑色素瘤似乎有點引人注目，因為在新聞稿和準備好的評論中沒有提及。我確實在管道表中看到了它。您對這次試驗的期望有變化嗎？我相信我們仍然應該期待今年的更新。然後我將對財務進行跟進。

Yes. Thanks, Chris. Let me start on the BNT122 and Ugur and Özlem can also chime in here. So we've reiterated our guidance for an update later this year. We still intend to provide that. I think on a previous call, we had also mentioned that the full -- the PFS analysis would be triggered on an event basis. And the fact is we still haven't met that event trigger -- reached that event trigger, which does mean that we're not in a position right now to be specific about the full -- the data that we're likely to bring out later this year. So we do intend to provide an update before year-end, but I think it's likely that there won't be a full data update. So more to come on that.

是的。謝謝，克里斯。讓我從 BNT122 開始，Ugur 和 äzlem 也可以在這裡插話。因此，我們重申了今年晚些時候的更新指導。我們仍然打算提供這一點。我想在之前的電話會議中，我們還提到了完整的 PFS 分析將根據事件觸發。事實上，我們仍然沒有達到該事件觸發點——達到該事件觸發點，這確實意味著我們現在無法具體說明我們可能帶來的完整數據今年晚些時候出來。所以我們確實打算在年底前提供更新，但我認為很可能不會有完整的數據更新。所以還有更多的事情要做。

Yes. I can just echo what Ryan said. Gathering these events is not entirely under our control. And therefore, we, at this point, cannot forecast when we will be able to report the data -- interim analysis data point.

是的。我只能重複瑞安所說的。收集這些事件並不完全在我們的控制之下。因此，我們目前無法預測何時能夠報告數據——中期分析數據點。

Got it. And then on the financial follow-up. Very healthy cash balance, obviously, post COVID, and we are watching the decisions you're making on the capital allocation front. The InstaDeep is an example of that. And Ryan, you mentioned during the call, you look to intend to continue to in-license assets.

知道了。然後是財務跟進。顯然，在新冠疫情之後，現金餘額非常健康，我們正在關注你們在資本配置方面做出的決定。 InstaDeep 就是一個例子。 Ryan，您在電話會議中提到，您打算繼續許可資產。

Can you give us a sense for potentially any areas that you feel either disease area, modality size. A lot of these have been smaller and InstaDeep was a little bit more kind of adjacent as opposed to immediately obvious. Just be helpful to get a sense for what this mosaic is that you're creating given your capacity?

您能否讓我們了解您可能感覺到的任何區域，無論是疾病區域還是模態大小。其中很多都較小，InstaDeep 更接近，而不是立即顯而易見。是否有助於了解您根據自己的能力正在創建的馬賽克是什麼？

Yes, absolutely. Absolutely, Chris. So as you see from the deals we've announced so far this year that we've allocated a little bit less than $1 billion in terms of upfront payments across the InstaDeep transaction and then several in-licensing deals for several assets that we talked about today. So I think in that sense, InstaDeep was a sort of strategic exception. We thought that was a very unique opportunity.

是的，一點沒錯。當然，克里斯。正如你從我們今年迄今為止宣布的交易中看到的那樣，我們在 InstaDeep 交易中分配了不到 10 億美元的預付款，然後就我們談到的幾項資產進行了幾項許可交易今天。所以我認為從這個意義上說，InstaDeep 是一種戰略例外。我們認為這是一個非常獨特的機會。

I wouldn't expect that, that would be one that would be replicated as such, but I think the licensing deals and small-scale M&A, I think you can expect us to continue to operate along the same lines as what you've seen so far in the first half of the year. So relatively small deals, those are at our sweet spot, under $1 billion is our sweet spot. We will look at and consider larger deals, but that's I think it has to be a very, very good strategic fit for us to make a larger move. We do see opportunities in that sub-$1 billion range to further bolster the pipeline. And in terms of focus areas, as you've seen so far in the first half, IO -- differentiated I/O assets are going to continue to be an area of focus.

我沒想到，這會被複製，但我認為許可交易和小規模併購，我認為你可以期望我們繼續按照你所看到的方式運營上半年到目前為止。因此，相對較小的交易是我們的最佳選擇，10 億美元以下是我們的最佳選擇。我們將考慮並考慮更大的交易，但我認為這必須是非常非常適合我們採取更大行動的戰略。我們確實看到了 10 億美元以下範圍內進一步加強管道的機會。就重點領域而言，正如您在上半年所看到的那樣，IO——差異化 I/O 資產將繼續成為重點領域。

Great. Will look for more insights on your innovation day.

偉大的。將在您的創新日尋找更多見解。

Thank you.

謝謝。

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

您的下一個問題來自 TD Cowen 的 Yaron Werber。

This is Brendan on for Yaron. Just really quickly, I wanted to also ask maybe about the potential flu-COVID combo approach here. First, I guess, when you think we might see data from that study, but also maybe a little bit more broadly, kind of what the path forward is for this combo. And really, I guess, trying to understand with each updated booster, how this would kind of play out here. Just kind of trying to get at Sanofi kind of cast some doubt a little bit on the whole mRNA approach, obviously, from their own perspective, but really how you're kind of thinking about mRNA fitting into whole COVID-flu combo space from what you're seeing at this point?

這是布倫丹 (Brendan) 替補亞龍 (Yaron)。很快，我還想問一下這裡潛在的流感-新冠肺炎聯合治療方法。首先，我想，當你認為我們可能會看到該研究的數據時，但也可能更廣泛一點，這個組合的前進道路是什麼。事實上，我想，嘗試了解每個更新的助推器，這將如何在這裡發揮作用。顯然，從他們自己的角度來看，只是試圖了解賽諾菲對整個 mRNA 方法產生了一些懷疑，但實際上你是如何考慮 mRNA 融入整個新冠病毒組合空間的？你現在看到了嗎？

Yes, sure. I'll start. So as you know, Pfizer currently has an ongoing Phase I study of a flu-COVID combo vaccine, and they also have a Phase III study ongoing of their mRNA-flu vaccine, which we've licensed the technology to them. We still retain some economics on the program, but they're in control in driving that program forward, the mono program.

是的，當然。我開始吧。如您所知，輝瑞目前正在進行流感-新冠聯合疫苗的 I 期研究，他們的 mRNA-流感疫苗也正在進行 III 期研究，我們已將該技術授權給他們。我們仍然保留了該計劃的一些經濟因素，但他們在推動該計劃（單一計劃）方面擁有控制權。

So we do see opportunity for a combination vaccine. I think in terms of timeline, Pfizer has guided to a potential Phase I data update this year for the combination. And they've also guided to near-term Phase III data on the flu mono, both of which I think will be relevant data points here to help inform the next stage of development.

因此，我們確實看到了聯合疫苗的機會。我認為就時間表而言，輝瑞已指導今年對該組合進行潛在的第一階段數據更新。他們還提供了有關流感單藥的近期第三階段數據，我認為這兩個數據都將是相關數據點，以幫助為下一階段的開發提供信息。

The last point I would add is just that Pfizer has indicated, I think, just the last couple of days that -- or they've reiterated that they see a flu -- both a flu mono and also flu-COVID combo being -- starting to become relevant from 2024 onwards. So not something to look at this year, although I think positive data could obviously be a helpful catalyst for us as well.

我要補充的最後一點是，我認為輝瑞公司在過去幾天已經表示——或者他們重申他們看到了流感——既是流感單藥，也是流感-新冠組合——從 2024 年起開始變得重要。因此，今年不值得關注，儘管我認為積極的數據顯然也對我們有幫助。

And your next question comes from the line of Terence Flynn from Morgan Stanley.

你的下一個問題來自摩根士丹利的特倫斯·弗林。

Just was wondering if you could elaborate more on the rationale to advance BNT116 into the metastatic setting well in iNeST, I know you've talked more about the potential there in the adjuvant setting. So just wondering if you could kind of compare and contrast those 2 approaches?

只是想知道您是否可以在 iNeST 中詳細說明將 BNT116 推進轉移設置的基本原理，我知道您已經更多地談論了輔助設置中的潛力。所以只是想知道您是否可以比較和對比這兩種方法？

Yes. Thank you. The question is highly relevant. It's a six pack approach -- is based on the off-the-shelve availability of the vaccines. That means in the metastatic setting the disease is rapidly progressing, we would like to get as quickly as possible an immune response initiated and personalized vaccine, [in 116] approach requires around 4 to 6 weeks for a preparation of the vaccine and is particularly suited for the adjuvant setting. And because in the adjuvant setting, there is a longer time frame before patients progress. So that gives us the opportunity to build an immune response that can counteract potential progression of the disease.

是的。謝謝。這個問題非常相關。這是一種六包方法——基於疫苗的現成可用性。這意味著在轉移性環境中，疾病正在迅速進展，我們希望盡快啟動免疫反應和個性化疫苗，[116]方法需要大約 4 至 6 週的時間來準備疫苗，並且特別適合用於輔助設置。因為在輔助治療中，患者病情進展需要更長的時間。因此，這使我們有機會建立免疫反應，以抵消疾病的潛在進展。

Therefore, all these adjuvant types will have as an end point relapse-free survival as an endpoint, whereas in the metastatic setting, endpoints will be, for example, progression-free survival or OS.

因此，所有這些輔助劑類型都將以無復發生存作為終點，而在轉移情況下，終點將是例如無進展生存或 OS。

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

您的下一個問題來自 Canaccord 的 Bill Maughan。

So I have a question on self-amplifying RNA. I know that you had been developing a few programs with yourself implying RNA, and it's kind of not center stage anymore with several other companies that are earlier in their cancer vaccine development are using self-amplifying RNA and kind of singing its praises. So I was just wondering if we could expect self-amplifying RNA to occupy more of the spotlight and maybe be advanced in some programs coming up in the future?

我有一個關於自擴增RNA的問題。我知道您自己一直在開發一些涉及 RNA 的項目，但它不再是中心舞台，因為其他幾家早期開發癌症疫苗的公司正在使用自擴增 RNA 並對其大加讚揚。所以我只是想知道我們是否可以期待自擴增 RNA 佔據更多的關注，並可能在未來的一些項目中取得進展？

Yes. Thank you for the question. As you know, we have 2 mRNA amplification program, it's a self-amplifying mRNA program as well as the trans-Amplification program. We have observed and if you look closer into the data -- into publish data of (inaudible) we have observed that the self-amplifying mRNA in humans are limited in the full response on innate, quick initiation of innate response and hindering the full capacity of self-amplifying mRNA.

是的。感謝你的提問。如您所知，我們有2種mRNA擴增程序，即自擴增mRNA程序以及反式擴增程序。我們觀察到，如果你仔細觀察數據——進入（聽不清）的發布數據，我們觀察到人類的自我放大 mRNA 在先天反應的全面反應中受到限制，先天反應的快速啟動並阻礙了充分的能力自我擴增mRNA。

And we are working on an improved approach of overcoming this innate immune response limitation on a trans-amplifying mRNA platform, which comes -- which combines 2 advantages, the advantage of safety.

我們正在研究一種改進的方法來克服反式放大 mRNA 平台上的先天免疫反應限制，該方法結合了兩個優點，即安全性優勢。

So the replicate itself is not amplified. It provides only trans-mRNA activity and the target mRNAs are amplified. We thereby separate the target mRNA and the replicate mRNA and have the opportunity to combine multiple targets. And this is something where we made a lot of progress in the preclinical setting, and we will report end of this year here on this platform, particularly we see their suitability in the impacted disease setting, particularly in the setting of combination vaccine.

所以復製本身並沒有被放大。它僅提供反式 mRNA 活性，並且目標 mRNA 會被擴增。因此，我們將目標 mRNA 和復制 mRNA 分開，並有機會組合多個目標。這是我們在臨床前環境中取得很大進展的地方，我們將在今年年底在此平台上報告，特別是我們看到它們在受影響的疾病環境中的適用性，特別是在聯合疫苗的環境中。

And your next question comes from the line of Ellie Merle from UBS.

您的下一個問題來自瑞銀集團的埃莉·梅爾 (Ellie Merle)。

This is Sarah on for Ellie. I guess a quick one on 211 and the data update later this year. What are the expectations for data there? And what are you guys hoping to see?

這是莎拉為艾莉配音。我想 211 和今年晚些時候的數據更新會很快。對那裡的數據有什麼期望？你們希望看到什麼？

Thank you for the question. So we have an ongoing Phase I/II trial, and we have had a couple of data updates this year, the year before. And the trial is ongoing. What we expect report end of this year is additional data on the 1 hand, on safety of different doses and in combination with our CARVac vaccine, also data on clinical activity in additional clinical indications. We have been very focused on testicular cancer in the previous updates.

感謝你的提問。因此，我們正在進行 I/II 期試驗，並且今年和前年我們進行了幾次數據更新。審判正在進行中。我們預計今年年底的報告一方面是關於不同劑量以及與我們的 CARVac 疫苗聯合使用的安全性的更多數據，還有關於其他臨床適應症的臨床活動的數據。在之前的更新中，我們一直非常關注睾丸癌。

Further, we will report on durability of these responses. We have been focused on objective response rates. Now that the data is maturing, we will provide more insights into durability of those responses and how use of a vaccine impacts that.

此外，我們將報告這些響應的持久性。我們一直關注客觀回复率。現在數據正在成熟，我們將提供更多有關這些反應的持久性以及疫苗的使用如何影響的見解。

We will now take our last question for today. And your last question comes from the line of Simon Baker from Redburn.

現在我們將回答今天的最後一個問題。你的最後一個問題來自 Redburn 的 Simon Baker。

It relates to the PRESERVE-003 study. It's a 2-stage Phase III study. So I just wanted to get some idea of what data you will be presenting at the conclusion of Stage 1 and any timing that is indicated based on your expectations for (inaudible) and treatment? And I see the clinical trials is showing a primary completion in mid-2026. Is that a reasonable estimate at this stage for the final data of Stage 2?

它與 PRESERVE-003 研究有關。這是一項 2 階段的 III 期研究。所以我只是想了解一下您將在第一階段結束時提供哪些數據以及根據您對（聽不清）和治療的期望指示的任何時間？我看到臨床試驗將於 2026 年中期初步完成。現階段對於第二階段的最終數據來說，這是一個合理的估計嗎？

I didn't fully get that, Simon. Was this about data expectations for the ongoing ONC392 trial?

我沒有完全明白這一點，西蒙。這是關於正在進行的 ONC392 試驗的數據預期嗎？

Yes, it was because it's a 2-stage study. So I wondered what data you will disclose when Stage I is completed and the dose is selected?

是的，這是因為這是一項兩階段研究。所以我想知道當第一階段完成並選擇劑量時，您會透露哪些數據？

So it will be safety data and clinical activity data in different tumor indications.

因此，這將是不同腫瘤適應症的安全性數據和臨床活性數據。

No, no, this is -- I think it's a lung cancer trial...

不，不，這是——我認為這是一項肺癌試驗……

Sorry, I didn't get that.

抱歉，我沒聽懂。

So we expect around 2025 [ORR] data and safety data. Now we have started the clinical trial with 2 different doses. We will select one dose to continue. And it's a stage approach based on the OR data, initial assessment of the PFS that clinical trial will continue for full maturation.

因此，我們預計 2025 年左右會出現 [ORR] 數據和安全數據。現在我們已經開始了2種不同劑量的臨床試驗。我們將選擇一劑繼續。這是一種基於 OR 數據的階段方法，是對 PFS 的初步評估，臨床試驗將繼續進行直至完全成熟。

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

謝謝。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。