CureVac NV (CVAC) 2022 Q4 法說會逐字稿

Greetings, and welcome to the CureVac Fourth Quarter and Full Year 2022 Financial Results Conference Call. (Operator Instructions) This call is being recorded.

您好，歡迎參加 CureVac 2022 年第四季度和全年財務業績電話會議。 （操作員說明）此通話正在錄音。

It is now my pleasure to introduce your host, Sarah Fakih, Vice President, Corporate Communications and Investor Relations. Thank you. You may begin.

現在我很高興向您介紹主持人，企業傳播和投資者關係副總裁 Sarah Fakih。謝謝。你可以開始了。

Thank you. Good morning, good afternoon, and welcome to our conference call. My name is Sarah Fakih, and I'm the Vice President of Corporate Communications and Investor Relations at CureVac.

謝謝。早上好，下午好，歡迎參加我們的電話會議。我叫 Sarah Fakih，是 CureVac 企業傳播和投資者關係副總裁。

Please let me introduce today's speakers. On the call with me from CureVac are Alexander Zehnder, Chief Executive Officer of CureVac; Myriam Mendila, our Chief Development Officer; and Pierre Kemula, Chief Financial Officer of CureVac.

請允許我介紹一下今天的演講嘉賓。 CureVac 首席執行官 Alexander Zehnder 與我通話。 Myriam Mendila，我們的首席開發官；以及 CureVac 首席財務官 Pierre Kemula。

Please note that this call is being webcast live and will be archived on the Events and Presentations section under Investor Relations on our website.

請注意，本次電話會議正在進行網絡直播，並將存檔在我們網站投資者關係下的活動和演示部分。

Before we begin, a few forward-looking statements. The discussion and responses to your questions on this call reflect management's view as of today, Tuesday, April 25, 2023. We will be making statements and providing responses to your questions that state our intentions, beliefs, expectations or predictions of the future. These constitute forward-looking statements for the purpose of the safe harbor provisions. These statements involve risks and uncertainties that could cause actual results to differ materially from those projected. CureVac disclaims any intention or obligation to revise any forward-looking statements. For more information, please refer to our filings with the U.S. Securities and Exchange Commission.

在我們開始之前，先做一些前瞻性陳述。本次電話會議中的討論和對您問題的回答反映了截至今天（2023 年 4 月 25 日星期二）管理層的觀點。我們將發表聲明並回答您的問題，以表明我們的意圖、信念、期望或對未來的預測。這些構成了出於安全港條款目的的前瞻性陳述。這些陳述涉及風險和不確定性，可能導致實際結果與預測存在重大差異。 CureVac 不承擔任何修改任何前瞻性陳述的意圖或義務。欲了解更多信息，請參閱我們向美國證券交易委員會提交的文件。

I will now turn the call over to Alexander.

我現在將把電話轉給亞歷山大。

Thank you, Sarah. Ladies and gentlemen, morning, good afternoon to everybody on the webcast. On April 1 this year, I took over the leadership of CureVac, the pioneer in mRNA technology and the company that is at an inflection point, transforming from a research-oriented biotech to a fully integrated commercial biopharma company.

謝謝你，莎拉。女士們先生們，大家早上好，下午好。今年 4 月 1 日，我接手了 CureVac 的領導權，這是 mRNA 技術的先驅，也是一家正處於拐點的公司，從一家以研究為導向的生物技術公司轉變為一家完全一體化的商業生物製藥公司。

Positive preliminary clinical data in our prophylactic vaccines area reported earlier this year have demonstrated the great potential of our proprietary mRNA platform. This critical milestones opens the door for CureVac to explore new opportunities in the development of effective vaccines and therapeutics, and we are now entering a new chapter of our corporate evolution. So I'm really thrilled to bring my strategic vision and strong operational and commercial experience to CureVac at this pivotal moment for the company.

今年早些時候報告的預防性疫苗領域積極的初步臨床數據證明了我們專有 mRNA 平台的巨大潛力。這一重要的里程碑為 CureVac 探索開發有效疫苗和療法的新機遇打開了大門，我們現在正在進入企業發展的新篇章。因此，我非常高興能在公司的這個關鍵時刻將我的戰略願景以及豐富的運營和商業經驗帶到 CureVac。

Please let me take the opportunity to briefly introduce myself. I'm a medical doctor by training and have worked in the pharmaceutical industry for more than 20 years across different companies, culture, disease areas, in roles of increasing complexity and responsibility. I had the great fortune to learn and grow in positions held at industry stalwarts such as Roche, Genentech and Sanofi in product strategy and commercially focused positions across multiple business units and functional areas.

請允許我藉此機會簡單介紹一下自己。我是一名訓練有素的醫生，在製藥行業工作了 20 多年，跨越不同的公司、文化、疾病領域，擔任的角色越來越複雜，責任也越來越大。我有幸在羅氏、基因泰克和賽諾菲等行業巨頭的多個業務部門和職能領域的產品戰略和商業重點職位中學習和成長。

Most recently, before joining CureVac, I led the global oncology franchise at Sanofi. I was responsible for shaping one of the company's key future growth drivers, rebuilding the product pipeline, launching new medicines, strengthening in the organization and representing the company.

最近，在加入 CureVac 之前，我領導了賽諾菲的全球腫瘤學業務。我負責塑造公司未來的關鍵增長動力之一、重建產品線、推出新藥、加強組織並代表公司。

And I'm convinced that my experience in bringing practice-changing medicines to the market, building pipelines and shaping organization will be of great benefit as we take CureVac to the next level as a relevant commercial player. And I'm really honored to pursue this mission in collaboration with all our RNA people, as well as my colleagues from the CureVac management team, which was strengthened in February this year by the addition of Myriam Mendila as our Chief Development Officer.

我相信，我在將改變實踐的藥物推向市場、建立管道和塑造組織方面的經驗將對我們作為相關商業參與者將 CureVac 提升到一個新的水平大有裨益。我非常榮幸能夠與我們所有 RNA 員工以及 CureVac 管理團隊的同事合作實現這一使命，今年 2 月，Myriam Mendila 擔任我們的首席開發官，這一團隊得到了加強。

So before I go into the quarterly review, I would also like to give Myriam the opportunity to briefly introduce herself.

因此，在進行季度回顧之前，我還想給 Myriam 一個簡單介紹自己的機會。

Thank you, Alexander, and a warm welcome to everyone on the conference call. I'm really excited to have joined the exceptional CureVac team at this decisive moment in the company's corporate development.

謝謝亞歷山大，並熱烈歡迎參加電話會議的所有人。我很高興能在公司發展的這個決定性時刻加入傑出的 CureVac 團隊。

I come to CureVac with more than 20 years of global, regional and local experience and product development. medical affairs, pharmacovigilance and health care compliance, as well as commercial strategy at Roche, Genentech and Novartis.

我加入 CureVac 時擁有 20 多年的全球、區域和本地經驗以及產品開發經驗。羅氏、基因泰克和諾華的醫療事務、藥物警戒和醫療保健合規性以及商業戰略。

Before joining CureVac, I was a Chief Medical Officer and Global Head of Medical Affairs Oncology at Novartis Pharma in Switzerland. In this role, I was accountable for the worldwide oncology medical affairs function and oversaw the development and also execution of the global medical strategy for the entire oncology product portfolio. Furthermore, I ensured high standards in quality and compliance for all related medical activities worldwide.

在加入 CureVac 之前，我曾擔任瑞士諾華製藥公司的首席醫療官兼腫瘤醫學事務全球主管。在此職位上，我負責全球腫瘤學醫療事務職能，並監督整個腫瘤學產品組合的全球醫療戰略的製定和執行。此外，我還確保全球所有相關醫療活動的質量和合規性達到高標準。

As a physician and throughout my entire career, I have been truly committed to making new treatments and therapies available to those who need the most and to do always what is right for the patient. By putting the patient at the center of everything we do, I'm convinced we can make the best decisions and develop the right therapies.

作為一名醫生，在我的整個職業生涯中，我一直致力於為最需要的人提供新的治療方法和療法，並始終為患者做正確的事情。通過將患者置於我們所做的一切的中心，我相信我們可以做出最好的決定並開發正確的療法。

I believe that the mRNA technology is the next function medicine, and I'm really proud that, at CureVac, we have the opportunity to apply this technology and develop innovative therapies to support the fight for human health.

我相信 mRNA 技術是下一個功能醫學，我真的很自豪，在 CureVac，我們有機會應用這項技術並開發創新療法來支持人類健康的鬥爭。

I look forward to putting my operational and strategic product development experience as well as my skills and transformative competency development to work for CureVac as we advance our mRNA product pipeline.

我期待著將我的運營和戰略產品開發經驗以及我的技能和變革能力發展運用到 CureVac 中，以推進我們的 mRNA 產品管線。

Let me now hand it back to Alexander.

現在讓我把它交還給亞歷山大。

Thank you, Myriam. So let's turn to Slide 6 and reflect on the key achievement for 2022. It was indeed a transformational year for CureVac as the company made significant progress on various fronts: Validating our mRNA platform; strengthening our oncology capabilities, namely in antigen discovery; driving the ongoing business transformation; further enhancing our seamless manufacturing capabilities; and importantly, maintaining a strong cash position that should take us well into 2025.

謝謝你，米里亞姆。因此，讓我們轉向幻燈片 6，回顧 2022 年的主要成就。對於 CureVac 來說，這確實是轉型的一年，因為該公司在各個方面都取得了重大進展：驗證我們的 mRNA 平台；加強我們的腫瘤學能力，即抗原發現；推動持續的業務轉型；進一步增強我們的無縫製造能力；重要的是，保持強勁的現金狀況應該能讓我們順利進入 2025 年。

In clinical development, the primary goal for 2022 was achieved with the sort of 4 Phase I clinical trials in COVID-19 and flu, in collaboration with our partner, GSK, which compares modified versus unmodified mRNA in both indications using our advanced second-generation backbone.

在臨床開發方面，2022 年的主要目標是與我們的合作夥伴 GSK 合作，通過針對 COVID-19 和流感的 4 項 I 期臨床試驗實現的，該試驗使用我們先進的第二代技術對這兩種適應症中的修飾與未修飾 mRNA 進行比較骨幹。

In early '23, successful execution of this clinical development program led to a key achievement for CureVac, the validation of our second-generation mRNA technology platform based on positive preliminary data reported for both indications.

23 年初，該臨床開發計劃的成功執行為 CureVac 帶來了一項關鍵成就，即根據針對兩種適應症報告的積極初步數據驗證了我們的第二代 mRNA 技術平台。

The data demonstrated that modified mRNA technology offered better tolerability with a broader applicable dose range. Furthermore, we observed strong antibody induction starting at the lowest tested doses. These clinical insights from our prophylactic vaccine trials will provide an important basis to inform our development programs for oncology, where we significantly expanded our footprint in 2022 by acquiring Frame Cancer Therapeutics and partnering with myNEO. This now gives us access to a state-of-the-art antigen discovery platform which is expected to enable us to build a portfolio of novel cancer vaccine candidates.

數據表明，改良的 mRNA 技術具有更好的耐受性和更廣泛的適用劑量範圍。此外，我們觀察到從最低測試劑量開始強烈的抗體誘導。我們預防性疫苗試驗的這些臨床見解將為我們的腫瘤學開發計劃提供重要基礎，我們通過收購 Frame Cancer Therapeutics 並與 myNEO 合作，在 2022 年顯著擴大了我們的足跡。現在，我們可以使用最先進的抗原發現平台，該平台有望使我們能夠構建一系列新型癌症候選疫苗。

On a corporate level, we further broadened our operational bandwidth with growing the talent base in every area of the company. Two new CureVac sites were inaugurated in 2022, in Amsterdam and Brussels, stepping into the European biotech infrastructure as well as the vaccine-specific talent pools.

在公司層面，我們通過擴大公司各個領域的人才基礎，進一步拓寬了我們的運營範圍。兩個新的 CureVac 基地於 2022 年在阿姆斯特丹和布魯塞爾落成，進入歐洲生物技術基礎設施以及疫苗專用人才庫。

Company-wide digitization continues to advance with a state-of-the-art ERP system to professionalize our processes, streamline our operations and increase efficiency.

公司範圍內的數字化不斷推進，採用最先進的 ERP 系統，使我們的流程專業化，簡化我們的運營並提高效率。

In manufacturing, the German Pandemic Preparedness Agreement reached in April 22 accelerated the buildup of our commercial grade GMP IV plant as a safeguard against future infectious disease outbreaks. GMP IV is expected to be operational in 2024.

在製造業方面，4 月 22 日達成的德國流行病防範協議加速了我們商業級 GMP IV 工廠的建設，以防範未來傳染病的爆發。 GMP IV 預計將於 2024 年投入運行。

And this really puts us in a unique position to offer seamless, scalable manufacturing capacity from large commercial scale using our GMP IV facility, to small scale using the RNA printer, or highly automated system, for personalized cancer vaccines.

這確實使我們處於獨特的地位，可以提供無縫、可擴展的生產能力，從使用我們的 GMP IV 設施的大規模商業規模，到使用 RNA 打印機或高度自動化系統的小規模個性化癌症疫苗。

Looking at the financials. 2022, closed with a strong cash position of almost EUR 496 million, which benefited from effectively addressing the headwind from first-generation vaccine candidate commitments. In early '23, additional funds were secured to a highly successful capital raise providing us with $250 million in gross proceeds. This extends our cash reach into mid-'25 and support the execution of our strategic goals and priorities in 2023 and beyond.

看看財務狀況。 2022 年，現金狀況強勁，接近 4.96 億歐元，這得益於有效解決第一代候選疫苗承諾帶來的不利影響。 23 年初，我們獲得了額外資金，融資非常成功，總收益達到 2.5 億美元。這將我們的現金儲備延長至 25 年中期，並支持我們在 2023 年及以後執行戰略目標和優先事項。

On Slide 7, we have laid out the CureVac product development pipeline. This pipeline leverages our technology expertise in 3 therapeutic areas: Prophylactic vaccines, oncology and molecular therapies. In our most advanced area, prophylactic vaccines, pipeline expansion is driven by our clinically validated technology platform and our proprietary second-generation mRNA backbone. This backbone forms the basis for the 4 Phase I clinical trials we are currently running in COVID-19 and flu in collaboration with our partner, GSK. It will also be the basis for continued clinical development in these indications. The clinical insights, based on these trials, combined with our antigen-discovering capabilities gained through the acquisition of Frame Cancer Therapeutics, will support the buildup of a differentiated vaccine portfolio in cancer.

在幻燈片 7 上，我們列出了 CureVac 產品開發流程。該產品線利用了我們在 3 個治療領域的技術專業知識：預防性疫苗、腫瘤學和分子療法。在我們最先進的預防性疫苗領域，管道擴張是由我們經過臨床驗證的技術平台和我們專有的第二代 mRNA 骨幹驅動的。這一支柱構成了我們目前與合作夥伴葛蘭素史克 (GSK) 合作針對 COVID-19 和流感進行的 4 項 I 期臨床試驗的基礎。這也將成為這些適應症持續臨床開發的基礎。基於這些試驗的臨床見解，加上我們通過收購 Frame Cancer Therapeutics 獲得的抗原發現能力，將支持建立差異化的癌症疫苗組合。

In the third therapeutic area, molecular therapies, we are developing optimized mRNA therapeutics together with several collaboration partners, which are intended to address therapeutic proteins to treat rare and metabolic diseases. Here, we are currently advancing preclinical studies in the liver (inaudible) as well as working on therapeutic antibodies.

在第三個治療領域，即分子療法，我們正在與多個合作夥伴一起開發優化的 mRNA 療法，旨在解決治療性蛋白質治療罕見和代謝疾病的問題。在這裡，我們目前正在推進肝臟的臨床前研究（聽不清）以及治療性抗體的研究。

In considering the broad spectrum of diseases with high unmet need, it is clear to me that mRNA technology has every potential to deliver practice-changing medicines and to revolutionize treatments in the years to come.

考慮到需求未得到滿足的廣泛疾病，我很清楚 mRNA 技術完全有潛力在未來幾年提供改變實踐的藥物並徹底改變治療方法。

Now let me go on to the key catalysts on Slide 8 that will drive our pipeline and 2023 goals. With the clinical validation of our mRNA technology platform, we have reached an important inflection point, and now our future success will depend on strong execution disciplines of our key catalysts in 2023.

現在讓我繼續討論幻燈片 8 上將推動我們的管道和 2023 年目標的關鍵催化劑。隨著我們的 mRNA 技術平台的臨床驗證，我們已經達到了一個重要的拐點，現在我們未來的成功將取決於我們關鍵催化劑在 2023 年的強有力的執行紀律。

The first priority is to deliver on clinical development programs for prophylactic vaccines in collaboration with GSK. We plan to initiate a Phase I/II study with a multivalent, modified flu construct in the second quarter of this year. And for COVID-19, we expect to start a Phase II trial using both a mono and bivalent modified construct later in 2023.

首要任務是與葛蘭素史克合作實施預防性疫苗的臨床開發計劃。我們計劃在今年第二季度啟動一項針對多價改良流感構建體的 I/II 期研究。對於 COVID-19，我們預計將在 2023 年晚些時候開始使用單價和二價修飾構建體進行 II 期試驗。

In oncology, we previously announced the plan to start 2...

在腫瘤學方面，我們之前宣布了計劃啟動 2...

Ladies and gentlemen, please stand by. Your conference will resume momentarily.

女士們先生們，請稍候。您的會議將立即恢復。

(technical difficulty)

（技術難度）

Sorry for this. So it feels like, even though we are making progress as a company transforming, we still have some work to do with IT.

非常遺憾。因此，儘管我們公司的轉型正在取得進展，但我們在 IT 方面仍有一些工作要做。

So maybe let me go back to Slide 8 and just revisit some of the key catalysts that will drive our pipeline. As mentioned, we plan to initiate a Phase I/II study with a multivalent, modified flu construct in the second quarter of this year. And for COVID-19, we expect to start a Phase II study using both mono and bivalent modified constructs later in '23.

因此，也許讓我回到幻燈片 8，重新審視一些推動我們管道發展的關鍵催化劑。如前所述，我們計劃在今年第二季度啟動一項針對多價改良流感構建體的 I/II 期研究。對於 COVID-19，我們預計將在 23 年晚些時候開始使用單價和二價修飾結構進行 II 期研究。

For oncology, we previously announced the plan to start 2 proof of principle studies in 2023, designed to validate and optimize our second-generation mRNA backbone for tumor-directed immune responses. The first studies in patients with surgically resected glioblastoma is expected to start in the second quarter.

對於腫瘤學，我們之前宣布計劃於 2023 年啟動兩項原理驗證研究，旨在驗證和優化我們的第二代 mRNA 骨幹，以實現腫瘤導向的免疫反應。針對手術切除的膠質母細胞瘤患者的第一項研究預計將於第二季度開始。

Following a recent portfolio review, we decided not to do a second proof-of-concept study using a single antigen approach in melanoma, as previously communicated, but rather focus on fully leveraging our new antigen discovery capabilities with our second-generation mRNA backbone to bring a more differentiated state of the art cancer vaccine candidate addressing multiple novel antigens to the clinic. This study will be conducted in combination with a checkpoint inhibitor and is expected to start in 2024.

在最近的投資組合審查之後，我們決定不像之前所傳達的那樣，在黑色素瘤中使用單一抗原方法進行第二次概念驗證研究，而是專注於充分利用我們的新抗原發現能力和第二代 mRNA 骨幹來將針對多種新型抗原的更加差異化的最先進癌症候選疫苗引入臨床。這項研究將與檢查點抑製劑聯合進行，預計於 2024 年開始。

And in molecular therapies, we generated preclinical data on an undiscussed indication in ocular diseases in collaboration with the Schepens Eye Research Institute in Boston. We expect the scientific publication in the second quarter of this year, followed by the selection of a candidate for further clinical development.

在分子療法方面，我們與波士頓舍彭斯眼科研究所合作，針對眼部疾病中未討論的適應症生成了臨床前數據。我們預計科學發表將在今年第二季度進行，隨後將選擇候選藥物進行進一步的臨床開發。

Last but not least, in manufacturing, we are driving innovation by leveraging the RNA printer, our automated solution for GMP-grade mRNA in oncology. Subject to regulatory approval, we expect the printer to obtain its first drug substance manufacturing license in the first half of 2023.

最後但並非最不重要的一點是，在製造領域，我們利用 RNA 打印機（我們針對腫瘤學 GMP 級 mRNA 的自動化解決方案）推動創新。經監管部門批准，我們預計該打印機將於 2023 年上半年獲得第一個原料藥生產許可證。

With this, let me now hand the call over to Myriam again for a more detailed update on our clinical development programs in prophylactic vaccines and oncology.

現在，讓我再次將電話轉給 Myriam，以獲取有關我們預防性疫苗和腫瘤學臨床開發計劃的更詳細的最新信息。

Thank you, Alexander. So on Slide 9, let me start with an overview of clinical development for our COVID-19 and flu vaccine programs jointly developed with GSK. With the preliminary data reported earlier this year, we identified a modified mRNA as the preferred technology for further clinical development in prophylactic vaccines for both indications.

謝謝你，亞歷山大。在幻燈片 9 上，我首先概述了我們與葛蘭素史克 (GSK) 聯合開發的 COVID-19 和流感疫苗項目的臨床開發情況。根據今年早些時候報告的初步數據，我們確定修飾的 mRNA 作為這兩種適應症預防性疫苗進一步臨床開發的首選技術。

On the left, we summarize the currently ongoing studies, applying modified second-generation backbone construct, the monovalent flu SV mRNA study for flu at the top left, and the monovalent CV0501 study for COVID-19 at the bottom left. The final data readout for both studies are currently being finalized.

在左側，我們總結了當前正在進行的研究，應用了修改後的第二代骨架構建體，左上方針對流感的單價流感 SV mRNA 研究，以及左下方針對 COVID-19 的單價 CV0501 研究。兩項研究的最終數據讀數目前正在敲定中。

On the right side of the slide, you can see the upcoming studies Alexander mentioned in both indications. At the top right, a combined Phase I/II study for flu will be initiated with modified multivalent constructs, addressing all 4 WHO-recommended influenza strains. It will assess the safety, reactogenicity and also immunogenicity of the vaccine construct in healthy, younger and older adults versus a licensed comparator vaccine. The initial Phase I dose escalation part is expected to start shortly and will be conducted in the U.S. and Belgium.

在幻燈片的右側，您可以看到亞歷山大在這兩個跡像中提到的即將進行的研究。在右上角，將使用改良的多價結構啟動針對流感的 I/II 期聯合研究，研究所有 4 種 WHO 推薦的流感病毒株。它將評估疫苗結構與許可的比較疫苗在健康、年輕人和老年人中的安全性、反應原性和免疫原性。最初的第一階段劑量遞增部分預計將很快開始，並將在美國和比利時進行。

For the upcoming COVID-19 study on the bottom right, a Phase II trial is expected to start later in 2023, and with modified mono and bivalent mRNA construct addressing clinically relevant SARS-CoV-2 variants. The study will be conducted in healthy younger and older adults versus a licensed comparator vaccine at clinical sites in the U.S., Germany, Belgium and other countries.

對於右下角即將進行的 COVID-19 研究，II 期試驗預計將於 2023 年晚些時候開始，並採用修改後的單價和二價 mRNA 結構來解決臨床相關的 SARS-CoV-2 變體。該研究將在美國、德國、比利時和其他國家的臨床中心針對健康的年輕人和老年人與獲得許可的比較疫苗進行比較。

While the previously reported positive preliminary data for flu were already quite comprehensive. We would now like to provide an update on data from outstanding dose levels for the COVID-19 Phase I study. On Slide 10, let me walk you through updated preliminary reactogenicity as well as immunogenicity data for CV0501 encoding the Omicron BA.1 variant.

雖然之前報導的流感初步積極數據已經相當全面。我們現在希望提供有關 COVID-19 I 期研究的未完成劑量水平數據的最新信息。在幻燈片 10 上，讓我帶您了解編碼 Omicron BA.1 變體的 CV0501 的最新初步反應原性和免疫原性數據。

The reactogenicity data illustrated on the left represents solicited adverse events within 7 days after the booster vaccination in the younger adult group aged 18 to 64 years and older adult group aged greater or equal to 65 years. In younger adults, the presented data in the upper figure newly featured the previously unavailable dose groups of 3 and 6 micrograms. Both doses are tested only in the younger adults. Here, 1 Grade 3 solicited adverse event occurred at 3 micrograms, which was reported to be fatigue. In older adults, the newly available data in 100 and 200 micrograms in the lower figure showed no Grade 3 solicited adverse events.

左側所示的反應原性數據代表 18 至 64 歲的年輕成人組和 65 歲以上的老年組中加強疫苗接種後 7 天內引起的不良事件。在年輕人中，上圖所示的數據新展示了以前無法獲得的 3 微克和 6 微克劑量組。兩種劑量均僅在年輕人中進行測試。其中，1 例 3 微克劑量下發生 3 級不良事件，據報告為疲勞。在老年人中，下圖中 100 微克和 200 微克的最新數據顯示沒有 3 級不良事件。

Overall, the reactogenicity data of both age groups at the new tested dose levels are consistent with previously reported data and confirmed that CV0501 is generally well tolerated across both age groups and all dose levels.

總體而言，兩個年齡組在新測試劑量水平下的反應原性數據與之前報告的數據一致，並證實 CV0501 在兩個年齡組和所有劑量水平上普遍具有良好的耐受性。

Antibody responses against the BA.1 variant across both age groups are shown as a geometric mean increase of antibody titers, or GMI in short, in the table to the right. The ratio of post to pre-boost tutorizing antibody titers represent a boosting activity of CV0501. Previously reported geometric mean increases of antibody titers at dose levels of 12 to 5 micrograms, ranged between 7 and 9 fold for younger assets and between 13 and 21 fold for older adults, depending on the day when the data were measured. The new preliminary GMI data at 3 and 6 micrograms on day 15 confirm that CV0501 induces meaningful antibody responses even at the lowest tested dose. Data at day 29 is currently being finalized.

兩個年齡組針對 BA.1 變體的抗體反應顯示為抗體滴度的幾何平均增加（簡稱 GMI），如右表所示。加強後與加強前指導抗體滴度的比率代表CV0501的加強活性。先前報導的劑量水平為 12 至 5 微克時，抗體滴度幾何平均增加，對於年輕資產來說在 7 到 9 倍之間，對於老年人來說在 13 到 21 倍之間，具體取決於測量數據的日期。第 15 天 3 微克和 6 微克的新 GMI 初步數據證實，即使在最低測試劑量下，CV0501 也能誘導有意義的抗體反應。第 29 天的數據目前正在最終確定中。

After this data update for the now completed dose range in the CV0501 study, we are not anticipating further updates before the final Phase I data in COVID-19 as well as flu become available.

在 CV0501 研究中現已完成的劑量範圍的數據更新之後，我們預計在 COVID-19 和流感的最終 I 期數據可用之前不會有進一步更新。

With this, let me now shift gears and turn to our oncology area. On Slide 11, I would like to draw your attention once again to the strategy for continued expansion oncology, our next growth driver, which we are rapidly advancing in addition to our progress in prophylactic vaccines. With the key achievements in 2022, we have acquired and assembled all components needed to succeed in oncology. We have a highly potent second-generation mRNA backbone that has clinically shown its ability to raise strong and tolerable immune responses in flu and COVID.

現在讓我換個話題，轉向我們的腫瘤學領域。在幻燈片 11 上，我想再次提請您注意持續擴張腫瘤學的戰略，這是我們的下一個增長動力，除了預防性疫苗方面的進展之外，我們正在迅速推進該戰略。憑藉 2022 年取得的關鍵成就，我們已經獲得併組裝了在腫瘤學領域取得成功所需的所有組件。我們擁有高效的第二代 mRNA 主鏈，臨床證明其能夠在流感和新冠肺炎中引發強烈且可耐受的免疫反應。

We have integrated a cutting-edge genomics and bioinformatics platform for the discovery of differentiated and new tumor antigens. We are rapidly progressing oncology enabling technologies, such as improved and dedicated lipid nanoparticle, or in short LNP, systems that are specifically enhancing T cell immune responses which are most critical in oncology applications. And finally, our scalable manufacturing enables the rapid and flexible availability of cancer vaccines from R&D to commercial scale complemented by the RNA printer, which is expected to open new avenues for providing personalized mRNA-based cancer vaccines.

我們整合了尖端的基因組學和生物信息學平台，用於發現差異化和新的腫瘤抗原。我們正在快速推進腫瘤學支持技術，例如改進的專用脂質納米顆粒（或簡稱 LNP）系統，專門增強 T 細胞免疫反應，這在腫瘤學應用中至關重要。最後，我們的可擴展製造使得癌症疫苗從研發到商業規模的快速、靈活的可用性得以實現，並輔以 RNA 打印機，這有望為提供基於 mRNA 的個性化癌症疫苗開闢新途徑。

Taken together, these elements provide the leverage we need to be successful in oncology. In 2023, a key deliverable will be to bring them together and kick off a broader portfolio of novel cancer vaccine candidates for off the shelf as well as fully personalized therapies.

總而言之，這些要素為我們在腫瘤學領域取得成功提供了所需的槓桿。 2023 年，一個關鍵的成果將是將它們聚集在一起，推出更廣泛的現成新型癌症候選疫苗以及完全個性化的療法。

To this end, and as Alexander has already noted, our anticipated proof-of-principle study in up to 54 patients with surgically resected glioblastoma is well on track to be initiated in the second quarter of 2023. The Phase I dose escalation study will assess the safety and immunogenicity of our second-generation mRNA backbone construct, encoding for 8 epitopes derived from tumor-associated antigens overexpressed in glioblastoma. The trial will be conducted in Germany, Belgium and the Netherlands, and the first data readout is expected in the second half of 2024.

為此，正如 Alexander 已經指出的那樣，我們預計將於 2023 年第二季度啟動對多達 54 名手術切除的膠質母細胞瘤患者進行的原理驗證研究。I 期劑量遞增研究將評估我們的第二代 mRNA 主鏈構建體的安全性和免疫原性，編碼源自膠質母細胞瘤中過度表達的腫瘤相關抗原的 8 個表位。該試驗將在德國、比利時和荷蘭進行，預計首次數據讀出將於 2024 年下半年進行。

With the successful study setup and manufacture of clinical trial material of the complex multi-epitope construct, we have already achieved important milestones to initiate the study.

隨著複雜多表位構建體的研究設置和臨床試驗材料的成功製造，我們已經實現了啟動研究的重要里程碑。

Now the potency of an mRNA vaccine is a combination of the efficacy of the mRNA construct itself, as well as the LNP system that transports the mRNA to the cells. Therefore, our proprietary LNP research is an important enabler for our developments in prophylactic vaccines as well as oncology. We previously reported a new LNP system consisting of a PEG-free lipid composition that showed highly localized distribution in the immune compartment, good cellular and tumoral immune responses in mice, as well as good room temperature stability as a dried presentation.

現在，mRNA 疫苗的效力是 mRNA 構建體本身的效力以及將 mRNA 轉運到細胞的 LNP 系統的效力的組合。因此，我們專有的 LNP 研究是我們預防性疫苗和腫瘤學開發的重要推動力。我們之前報導了一種由不含 PEG 的脂質組合物組成的新 LNP 系統，該系統在免疫室中顯示出高度局部化的分佈，在小鼠中具有良好的細胞和腫瘤免疫反應，以及乾燥後具有良好的室溫穩定性。

Taking this research to the next level, we are now developing effective LNP systems that address specific requirements for efficient mRNA delivery for both prophylactic vaccines as well as cancer vaccines.

我們現在正在開發有效的 LNP 系統，將這項研究提升到一個新的水平，以滿足預防性疫苗和癌症疫苗有效 mRNA 遞送的特定要求。

As implied on Slide 12, the requirements for LNP systems for prophylactic vaccines and cancer vaccines are different, illustrating the need for the development of application-specific LNP systems. By prophylactic vaccines, vaccines should primarily induce tumoral responses, namely strong induction of antibodies. For cancer vaccines, induction of tumor-killing T cells is critical. Prophylactic vaccines need to minimize reactogenicity as we are treating mostly healthy individuals.

正如幻燈片 12 所暗示的，預防性疫苗和癌症疫苗對 LNP 系統的要求是不同的，這說明需要開發特定應用的 LNP 系統。通過預防性疫苗，疫苗應主要誘導腫瘤反應，即強烈誘導抗體。對於癌症疫苗來說，誘導腫瘤殺傷 T 細胞至關重要。預防性疫苗需要盡量減少反應原性，因為我們治療的大多是健康個體。

Cancer vaccines need to activate signaling pathways in the cell for the strong induction of systemic immune responses in seriously ill patients. Activation of certain cytokines and chemokines in those signaling pathways can lead to higher reactogenicity, but is really essential for the induction of a T cell response.

癌症疫苗需要激活細胞中的信號通路，以強烈誘導重病患者的全身免疫反應。這些信號通路中某些細胞因子和趨化因子的激活可能導致更高的反應原性，但對於誘導 T 細胞反應至關重要。

And then lastly, as prophylactic vaccines represent a seasonal standard, they need to be stable enough for longer-term storage at refrigerator or even room temperature. For cancer vaccines, stability can be deprioritized in favor of stronger efficacy.

最後，由於預防性疫苗代表了季節性標準，因此它們需要足夠穩定，以便在冰箱甚至室溫下長期儲存。對於癌症疫苗，為了獲得更強的功效，可以降低穩定性。

The most important finding in our LNP research is that the choice of lipids, their composition and concentration, allows us to tailor distinct immune responses to specific clinical settings. On Slide 13, you can see a data excerpt from comprehensive in vitro studies of selected LNP systems with varying lipid components and concentrations in human immune cells. Full data was presented at the European Molecular Biology Organization workshop in April this year.

我們的 LNP 研究中最重要的發現是，脂質的選擇、其組成和濃度使我們能夠根據特定的臨床環境定制不同的免疫反應。在幻燈片 13 上，您可以看到對人體免疫細胞中具有不同脂質成分和濃度的選定 LNP 系統進行綜合體外研究的數據摘錄。完整數據已在今年四月的歐洲分子生物學組織研討會上公佈。

The figure on the left illustrates the comparison of different LNP systems and their ability to induce inflammatory cytokines, such as interferon [IFN, IL6]. The induction of inflammatory cytokines is an important indicator of a first response by the innate immune system and is absolutely critical in the cancer for the induction of a T cell response. Accordingly, the strong cytokine signals detected with LNP #3 and 4 on the left, are favorable characteristics for developing a cancer vaccine, but are less relevant in a prophylactic vaccine setting.

左圖展示了不同LNP系統及其誘導炎症細胞因子（如乾擾素[IFN、IL6]）的能力的比較。炎症細胞因子的誘導是先天免疫系統首次反應的重要指標，並且對於癌症中 T 細胞反應的誘導至關重要。因此，左側 LNP #3 和 4 檢測到的強細胞因子信號是開發癌症疫苗的有利特徵，但在預防性疫苗環境中相關性較低。

On the right side of the slide, you can see the corresponding activation of antigen-presenting immune cells quantified via CD8 T as an activation marker. Activation of antigen-presenting immune cells is, again, relevant for the induction of a T cell response as according to published literature, there appears to be a correlation between the amount of activated antigen presenting cells and the abundance of CD8-positive T cells. So the strong induction of cytokine signaling pathways and corresponding activation of antigen-presenting cells in LNP #3 and 4, again, represent essential characteristics needed for the design of a cancer vaccine.

在幻燈片右側，您可以看到通過 CD8 T 作為激活標記來量化的抗原呈遞免疫細胞的相應激活。抗原呈遞免疫細胞的激活再次與 T 細胞應答的誘導有關，根據已發表的文獻，活化的抗原呈遞細胞的數量與 CD8 陽性 T 細胞的豐度之間似乎存在相關性。因此，LNP #3 和 4 中細胞因子信號傳導途徑的強烈誘導以及抗原呈遞細胞的相應激活再次代表了癌症疫苗設計所需的基本特徵。

Our studies also generated comprehensive in vivo data in mice not shown here, which further demonstrate our ability to design specific LNP systems that enable us to endure tailored immune responses for specific applications. We consider our tailored LNP design a critical complementary technology with the potential to further improve the efficacy, safety and stability of our mRNA platform and differentiate our development pipeline.

我們的研究還在小鼠中生成了全面的體內數據（此處未顯示），這進一步證明了我們設計特定 LNP 系統的能力，使我們能夠承受針對特定應用的定制免疫反應。我們認為我們定制的 LNP 設計是一項關鍵的補充技術，有可能進一步提高我們 mRNA 平台的功效、安全性和穩定性，並使我們的開發管道脫穎而出。

With this, let me hand back the call to Alexander.

現在，讓我把電話交回給亞歷山大。

Thank you, Myriam. Looking at manufacturing. Our manufacturing landscape outlined on Slide 14 shows how we can rapidly provide mRNA designs to seamlessly shift across the entire spectrum of large-scale manufacturing for pandemic preparedness as well as innovative small-scale manufacturing for personalized vaccines using our RNA printer. CureVac is one of the few companies in the RNA space that has true end-to-end capabilities from technology development and manufacturing, offering maximum flexibility, speed and scalability.

謝謝你，米里亞姆。再看製造業。幻燈片 14 中概述的我們的製造前景展示了我們如何快速提供 mRNA 設計，以無縫地跨越大流行病防範的大規模製造的整個範圍，以及使用我們的 RNA 打印機進行個性化疫苗的創新小規模製造。 CureVac 是 RNA 領域中少數幾家擁有真正的技術開發和製造端到端能力的公司之一，可提供最大的靈活性、速度和可擴展性。

And with this, let me hand over to Pierre for a review of the financial data.

接下來，讓我將財務數據交給皮埃爾審查。

Thank you, Alexander. Good morning and good afternoon to everyone on the call. 2022 has been a year of transformation as we manage commitments related to a first-generation vaccine candidate and finance in R&D, manufacturing and corporate milestones. We closed 2022 with a solid cash position of EUR 495.8 million. This cash position was strengthened in February by a year -- this year by an additional $250 million in gross proceeds from a successful capital raise.

謝謝你，亞歷山大。各位來電的人早上好，下午好。 2022 年是轉型的一年，我們在研發、製造和企業里程碑方面管理與第一代候選疫苗和財務相關的承諾。 2022 年結束時，我們擁有 4.958 億歐元的穩健現金頭寸。今年 2 月份，這一現金狀況又增強了一年，今年成功的融資籌集了 2.5 億美元的總收益。

With these additional funds based on the issuance of approximately 27 million common shares, we were able to extend our cash runway until mid-2025 and to diversify our investor base with new health care-specialized investors.

憑藉發行約 2700 萬股普通股的額外資金，我們能夠將現金跑道延長至 2025 年中期，並通過新的醫療保健專業投資者來實現投資者基礎的多元化。

We established an aftermarket or ATM facility in September 2021 to provide us with the option to offer shares worth up to a total of $600 million over a period of several years. So far, we have already raised approximately $84 million. In 2023, our solid cash position will allow us to fund the advancement of our mRNA technology platform and further the development of our pipeline.

我們於 2021 年 9 月建立了售後市場或 ATM 設施，以便我們可以選擇在幾年內發行總價值高達 6 億美元的股票。到目前為止，我們已經籌集了約 8400 萬美元。到 2023 年，我們堅實的現金狀況將使我們能夠為 mRNA 技術平台的進步提供資金，並進一步開發我們的產品線。

Looking at the cash position on Slide 16. As already mentioned, we closed 2022 with EUR 495.8 million. Cash used in operations was mainly allocated to capital expenditures for new production in facility GMP IV, purchases for R&D materials and settling of contract as part of the wind-down activities for the first-generation CVnCoV vaccine program. Financial statements reflect CureVac's transition out of its previous exposure to CVnCoV.

查看幻燈片 16 上的現金頭寸。如前所述，我們 2022 年的現金狀況為 4.958 億歐元。運營中使用的現金主要分配給 GMP IV 設施新生產的資本支出、研發材料的採購以及合同結算，作為第一代 CVnCoV 疫苗項目逐步結束活動的一部分。財務報表反映了 CureVac 擺脫了之前接觸 CVnCoV 的局面。

Moving on to the profit and loss statements. Revenues decreased by EUR 29.5 million to EUR 11.7 million for the fourth quarter of 2022 and decreased by EUR 35.6 million to EUR 67.4 million for the full year of 2022 compared to the same period in 2021. The decrease year-on-year was primarily driven by higher 2021 revenues related to the termination of the Boehringer Ingelheim collaboration and the subsequent recognition of EUR 26 million in late 2021.

繼續討論損益表。與 2021 年同期相比，2022 年第四季度收入減少 2950 萬歐元，至 1170 萬歐元，2022 年全年收入減少 3560 萬歐元，至 6740 萬歐元。同比下降的主要原因與勃林格殷格翰合作終止以及隨後在 2021 年底確認的 2600 萬歐元相關的 2021 年收入增加。

Revenue from our 2 GSK collaborations decreased year-on-year by EUR 12 million and amounted to a total of EUR 62.3 million in 2022 compared to EUR 74.3 million in the previous year as the company is focused on the lead programs, flu and COVID.

由於公司專注於流感和新冠肺炎等主導項目，2022 年與葛蘭素史克 (GSK) 的 2 項合作收入同比減少 1,200 萬歐元，總計 6,230 萬歐元，而上一年為 7,430 萬歐元。

In the first quarter of 2022, we received a EUR 10 million milestone payment related to the start of the seasonal influenza clinical trial, of which EUR 6.3 million were recognized as revenues in 2022.

2022年第一季度，我們收到了與季節性流感臨床試驗啟動相關的1000萬歐元里程碑付款，其中630萬歐元確認為2022年收入。

Operating loss was EUR 121.5 million for the fourth quarter of 2022, representing EUR 116 million increase compared to the same quarter of 2021. In the fourth quarter of 2021, we had recognized significant income from the release of governmental contract liabilities related to the upfront payment from the European Commission and the grant from the German Federal Ministry of Education and Research, or BMBF, amounting to a total of EUR 574.5 million. No such income was recognized in 2022.

2022 年第四季度運營虧損為 1.215 億歐元，較 2021 年同季度增加 1.16 億歐元。2021 年第四季度，我們確認了與預付款相關的政府合同負債釋放帶來的大量收入歐盟委員會的資助以及德國聯邦教育和研究部（BMBF）的資助總額為 5.745 億歐元。 2022 年未確認此類收入。

For the full year of 2022, operating loss was EUR 249.5 million, representing EUR 162.8 million decrease year-over-year. The operating results was affected by several key drivers. Cost of sales decreased primarily due to the lower expenses for CMO services. Prior year 2021 was highly impacted by significant expenses for the setup of a European CMO network for CVnCoV, also including recognition of liabilities associated to the wind down of these contracts. This was partially offset in 2022, but increasing write-off raw material, no longer expected to be used following the transfer to another party of reserve production capacity at the CMO.

2022年全年，營業虧損為2.495億歐元，同比減少1.628億歐元。經營業績受到幾個關鍵驅動因素的影響。銷售成本下降主要是由於 CMO 服務費用降低。 2021 年，歐洲 CVnCoV CMO 網絡建設的巨額費用對 2021 年產生了重大影響，其中還包括承認與終止這些合同相關的責任。這在 2022 年被部分抵消，但核銷原材料增加，預計在 CMO 儲備產能轉移給另一方後將不再使用。

R&D expenses decreased year-on-year, primarily due to significantly lower development expenses related to the completion of the large Phase IIb/III clinical trials for CVnCoV. Additionally, 2022 R&D costs were positively impacted by 2 elements amounting to EUR 63.6 million. A, in line with the declining number of continuing study participants and renegotiation of existing contracts both in 2022, our remaining clinical cost estimate decreased, resulting in a reversal of EUR 38.5 million from the provision reported as of December 2021. This decrease was partially offset by the increase in material consumed in R&D. B, R&D costs were positively impacted by a net gain from a change in the estimate of CMO contract termination provisions for EUR 25.1 million following the transfer to another party of reserve production capacity at the CMO.

研發費用同比下降，主要是由於完成 CVnCoV 大型 IIb/III 期臨床試驗相關的開發費用大幅下降。此外，2022 年研發成本受到兩個因素的積極影響，總計 6360 萬歐元。 A，隨著 2022 年繼續研究參與者數量的下降以及現有合同的重新談判，我們的剩餘臨床成本估算有所減少，導致截至 2021 年 12 月報告的準備金沖減 3850 萬歐元。這一減少被部分抵消研發中材料消耗的增加。 B，在 CMO 儲備產能轉移給另一方後，CMO 合同終止條款估計變更帶來的淨收益對研發成本產生了積極影響，淨收益為 2510 萬歐元。

Other income decreased, but was positively impacted by EUR 32.5 million from another party for reimbursement of prepayment and production activity set up at the CMO. In 2021, other income was primarily attributable to amounts recognized from grants from the BMBF.

其他收入有所下降，但受到另一方用於償還 CMO 預付款和生產活動的 3,250 萬歐元的積極影響。 2021 年，其他收入主要來自 BMBF 贈款確認的金額。

Financial results decreased by EUR 8.2 million to a loss of EUR 7.2 million for the fourth quarter of 2022, an increase by EUR 0.5 million to a profit of EUR 0.3 million for the full year 2022 compared to the same period in 2021. They were driven by foreign exchange impacts and interest on investments -- cash investments.

與 2021 年同期相比，2022 年第四季度的財務業績減少了 820 萬歐元，達到虧損 720 萬歐元，2022 年全年的財務業績增加了 50 萬歐元，達到利潤 30 萬歐元。受外匯影響和投資利息（現金投資）影響。

Pretax losses were EUR 128.7 million for the fourth quarter of 2022 and EUR 249.2 million for the 12 months of 2022.

2022 年第四季度的稅前虧損為 1.287 億歐元，2022 年 12 個月的稅前虧損為 2.492 億歐元。

With this, I would like to hand back the call to Alexander for the summary of any key messages.

至此，我想將電話交還給亞歷山大，以獲取任何關鍵信息的摘要。

Thank you, Pierre. As the pioneer of mRNA technology, CureVac has entered next chapter in its transformation from a research-oriented biotech company to a fully integrated commercial biopharma company. In 2022, we significantly accelerated the pace of our development and achieved key milestones with the initiation of comprehensive clinical programs in COVID and flu and the integration of a highly differentiated antigen discovery platform.

謝謝你，皮埃爾。作為 mRNA 技術的先驅，CureVac 已進入從研究型生物技術公司向完全整合的商業生物製藥公司轉型的新篇章。 2022年，我們顯著加快了發展步伐，並通過啟動新冠病毒和流感綜合臨床項目以及整合高度差異化的抗原發現平台，實現了關鍵里程碑。

In 2023, we are taking the next critical steps. Together with our partner, GSK, we are committed to advance and execute our clinical programs with the highest level of rigor and efficiency to bring safe and efficacious vaccines to people. The next clinical studies in COVID and flu are well on track to be initiated this year. We're also well on track to initiate the first proof-of-principle study in oncology in the second quarter, leveraging our second-generation mRNA backbone.

2023 年，我們將採取接下來的關鍵步驟。我們與我們的合作夥伴葛蘭素史克 (GSK) 一起，致力於以最高的嚴謹性和效率推進和執行我們的臨床項目，為人們帶來安全有效的疫苗。新冠病毒和流感的下一項臨床研究有望於今年啟動。我們也有望利用我們的第二代 mRNA 主幹，在第二季度啟動第一個腫瘤學原理驗證研究。

Our strong cash position of EUR 495.8 million at the end of 2022 was reinforced by a successful financing round earlier this year. It confirmed the broad confidence in the potential of our unique end-to-end mRNA capabilities, supported by a strong IP position, and it extends our cash reach into mid-2025 and supports the execution of our 2023 priorities and beyond.

今年早些時候的一輪成功融資進一步鞏固了我們截至 2022 年底 4.958 億歐元的強勁現金狀況。它證實了人們對我們獨特的端到端 mRNA 能力潛力的廣泛信心，並得到了強大知識產權地位的支持，並將我們的現金覆蓋範圍延長至 2025 年中期，並支持我們 2023 年及以後優先事項的執行。

And with this, I would like to conclude our presentation, and we'll now open the webcast to your questions.

至此，我想結束我們的演示，現在我們將通過網絡廣播回答大家的問題。

(Operator Instructions) Our first question comes from the line of Jonathan Miller with Evercore.

（操作員說明）我們的第一個問題來自 Evercore 的 Jonathan Miller。

When do you expect to release data on the new flu and COVID programs that you're initiating. I ask because it seems like you're starting with new constructs again, when we haven't seen a fulsome publication of the prior data, and I guess the corollary to that question is what sort of venue would you publish those results in? Should we expect more press releases and company presentations? Or would you aim to publish those results in a peer-reviewed setting?

您預計什麼時候發布您正在啟動的新流感和新冠病毒計劃的數據。我問這個問題是因為，當我們還沒有看到之前數據的完整髮佈時，您似乎又開始使用新的構造，我想這個問題的必然結果是您會在什麼樣的場所發布這些結果？我們是否應該期待更多的新聞稿和公司演示？或者您的目標是在同行評審的環境中發布這些結果？

Thank you, John. So the question on when we will release new data and what the venue for that be, Myriam, do you want to take that one?

謝謝你，約翰。那麼問題是我們何時發布新數據以及發布地點是什麼，Myriam，你想接受那個嗎？

Yes. Thanks, John. It's a great question. We are about to initiate the trials. And so at this point in time, it's always hard to predict when the data will come in because we have to set up the centers and have to recruit the patients. And hence, at this point in time, it's difficult to project time lines maybe in the most optimistic case towards end of the year, beginning of next year.

是的。謝謝，約翰。這是一個很好的問題。我們即將開始試驗。因此，在這個時候，總是很難預測數據何時會到來，因為我們必須建立中心並招募患者。因此，在這個時間點上，很難預測時間線，也許在最樂觀的情況下，到今年年底、明年年初。

And regarding the publication of the data from the current Phase I studies. For the COVID Phase I trial, the trial is ongoing, and so we have to finalize data collection, and then we'll publish at 1 point, probably also end of the year, beginning of next year. But we have to confirm that, so please don't quote me on this.

以及關於當前第一階段研究數據的發布。對於新冠病毒一期試驗，試驗正在進行中，所以我們必須完成數據收集，然後我們會在某個時間發布，可能也是今年年底、明年年初。但我們必須確認這一點，所以請不要引用我的話。

And for the flu Phase I study, that trial is also ongoing and we are currently discussing whether we are adding additional dose cohorts. And since -- as I said in the beginning, we do not or will not conduct additional preliminary exploratory analysis. Again, here, we also have to wait for the final data expected maybe towards the end of the year, beginning of next year.

對於流感 I 期研究，該試驗也在進行中，我們目前正在討論是否增加額外的劑量組。正如我一開始所說，我們不會也不會進行額外的初步探索性分析。同樣，在這裡，我們還必須等待預計可能在今年年底、明年年初公佈的最終數據。

Okay. Makes sense. And then a follow-up, I guess, on the oncology side of the business. We've seen relatively little data from the platform so far. So will there be any publications on the technology or on preclinical data or is tough for us to look at before GBM data, second half of next year? And I just want to confirm that both GBM -- the GBM is a fixed vac. It's not a personalized cancer vaccine? It's a shared antigens?

好的。說得通。我想，然後是腫瘤學方面的後續行動。到目前為止，我們從該平台看到的數據相對較少。那麼，在明年下半年 GBM 數據之前，是否會有任何關於該技術或臨床前數據的出版物，或者我們很難看到？我只是想確認 GBM——GBM 是一個固定的真空。這不是個性化癌症疫苗嗎？這是共享抗原嗎？

Can you say -- repeat the second question, John, sorry, I got the -- maybe let me ask or address the first one.

你能說——重複第二個問題，約翰，抱歉，我明白了——也許讓我問或解決第一個問題。

The publications on the platform, we basically happened at the end of '21 in nature, where we basically published on our new backbone compared to the old backbone. But we haven't published -- and we have generated a lot of preclinical data with our oncology construct, but those have not been published, and we're working with the team on this to see how we can quickly release those data.

我們在平台上的發布基本上發生在 21 世紀末，與舊主幹相比，我們基本上在新主幹上發布。但我們還沒有發布——我們已經用我們的腫瘤學構建生成了大量臨床前數據，但這些數據還沒有發布，我們正在與團隊合作解決這個問題，看看如何快速發布這些數據。

Can you repeat the second question, please? Because I didn't get that one.

請您重複一下第二個問題好嗎？因為我沒有拿到那個。

Yes. I think it was around the construct we're using for GBM. Shared antigen. And maybe you can -- I think you mentioned in your presentation, but maybe you can just repeat it.

是的。我認為這與我們用於 GBM 的構造有關。共享抗原。也許你可以——我想你在演講中提到過，但也許你可以重複一遍。

Yes, exactly. So the Phase I trial in GBM is a proof of principle trial. So our goal is really to show that the mRNA backbone we are using works in the cancer setting. This is why we decided to basically load our mRNA construct with known epitopes or epitopes known to be immunogenic. And so these are shared antigens, again, derived from proteins that are overexpressed in glioblastoma patients and were also recently published.

對，就是這樣。因此，GBM 的第一階段試驗是原則性試驗的證明。因此，我們的目標實際上是證明我們正在使用的 mRNA 主幹在癌症環境中有效。這就是為什麼我們決定基本上用已知表位或已知具有免疫原性的表位加載我們的 mRNA 構建體。因此，這些都是共享抗原，源自膠質母細胞瘤患者中過度表達的蛋白質，並且最近也已發表。

Our next question comes from the line of Eli Merle with UBS.

我們的下一個問題來自瑞銀集團的 Eli Merle。

Just a follow-up on oncology. I guess, in terms of the time lines we're starting other studies, are you going to wait for the proof of principle or initial data from the GBM study before you would start other trials in oncology, such as with your personalized neoantigen studies? Or could those perhaps start in parallel?

只是腫瘤學的後續行動。我想，就我們開始其他研究的時間線而言，您是否會等待 GBM 研究的原理證明或初始數據，然後再開始其他腫瘤學試驗，例如個性化新抗原研究？或者這些可能會同時開始嗎？

And just in terms of your neoantigen approach with your acquisition of Frame, maybe if you could elaborate a little bit more on how you're neoantigen selection approach might be differentiated from other players in the space in light of some of the recent data that we're seeing from Moderna.

就您收購 Frame 時的新抗原方法而言，也許您可以根據我們最近的一些數據詳細說明您的新抗原選擇方法如何與該領域的其他參與者區分開來。從 Moderna 看到的。

Yes. Thank you, Eli. So 2 questions. One, whether we would do a sequential versus parallel approach for the first GBM study and then the next generation of studies. And then I guess we can expand a little bit on our approach to neoantigens for the interfering cancer therapeutics acquisition and the partnership with myNEO.

是的。謝謝你，伊萊。所以有2個問題。第一，我們是否會在第一個 GBM 研究和下一代研究中採用順序方法還是並行方法。然後我想我們可以稍微擴展一下我們的新抗原方法，以獲取乾擾性癌症療法以及與 myNEO 的合作。

Yes, so let me start with the first question. We will start the Phase I in glioblastoma in the second quarter. And in parallel, we are already planning for the next Phase I trials targeting other antigens. So the plan is really to move forward.

是的，所以讓我從第一個問題開始。我們將在第二季度開始膠質母細胞瘤的第一階段。與此同時，我們已經在計劃針對其他抗原的下一期試驗。所以這個計劃確實是向前推進的。

The time lines around this sort of like next set of trials are probably later in 2024. But again, we need to confirm and work this out. But the key message is we're working and we want to initiate additional oncology trials.

類似下一組試驗的時間線可能會在 2024 年晚些時候。但同樣，我們需要確認並解決這個問題。但關鍵信息是我們正在努力，我們希望啟動更多的腫瘤學試驗。

Regarding the neoantigen approach, that's really a great question. And that's where actually we believe that our CureVac approach is very differentiated compared to what our industry peers are doing. When you look at some of the data or the trials published, the way how antigens are usually discovered is by using whole exome sequencing. So most of the, again, industry peers sequence for only like the 2% of our DNA that code for proteins. What we do with our Frame approach is, actually, we go for whole genome sequencing, because then, we get really all genomic variations, including structural variations of the entire genome. And with that, you have a much, much larger repertoire of antigens to select from. And we also know from published literature that some of these antigens are large molecules considered to be not like cells antigens and also shown to be more immunogenic.

關於新抗原方法，這確實是一個很好的問題。事實上，我們相信我們的 CureVac 方法與業內同行的做法非常不同。當您查看一些已發表的數據或試驗時，發現抗原的方法通常是使用全外顯子組測序。因此，大多數業界同行僅對我們編碼蛋白質的 DNA 的 2% 進行測序。實際上，我們使用 Frame 方法所做的是進行全基因組測序，因為這樣我們就可以獲得真正的所有基因組變異，包括整個基因組的結構變異。有了這個，你就有了一個非常非常多的抗原庫可供選擇。我們還從已發表的文獻中得知，其中一些抗原是大分子，被認為與細胞抗原不同，並且也顯示出更具免疫原性。

And with this approach, again, and then complemented by a very, very unique bioinformatics platform, we believe we have a different approach on how we select and prioritize the antigens and then load them on our construct. So that's the first one.

再次通過這種方法，然後輔以一個非常非常獨特的生物信息學平台，我們相信我們在如何選擇和優先考慮抗原然後將它們加載到我們的構建體上有不同的方法。這是第一個。

The second is, again, our backbone is differentiated and improved. And as I alluded to in the slides, we are also working on oncology-specific LNP systems to deliver the RNA to the immune cells, enhance the intracellular signaling pathways, and with that the immune response.

二是我們的骨幹力量再次得到差異化和提升。正如我在幻燈片中提到的，我們還在研究腫瘤特異性 LNP 系統，將 RNA 傳遞到免疫細胞，增強細胞內信號傳導途徑，從而增強免疫反應。

And then last but not least, we also have the RNA printer platform, which will enable us to really quickly deliver, especially in the setting of personalized cancer vaccines.

最後但並非最不重要的一點是，我們還有 RNA 打印機平台，這將使我們能夠真正快速地交付，特別是在個性化癌症疫苗方面。

Our next question comes from the line of Eun Yang with Jefferies.

我們的下一個問題來自 Eun Yang 和 Jefferies 的對話。

So Alexander and Myriam, you have a very extensive oncology experience over the years. So my first question to you is that, in your oncology program, currently, you are planning for glioblastoma and melanoma. But with the messenger RNA vaccine approaches, what other solid tumor types do you think would be quite applicable? As well as do you think there is a potential for liquid tumor opportunities?

Alexander 和 Myriam，多年來你們擁有非常豐富的腫瘤學經驗。所以我向您提出的第一個問題是，在您的腫瘤學計劃中，目前您正在計劃治療膠質母細胞瘤和黑色素瘤。但是，對於信使 RNA 疫苗方法，您認為還有哪些其他實體瘤類型非常適用？您認為液體腫瘤有潛力嗎？

And the second question is on the prophylactic vaccines. So for the COVID vaccine, you're going to be testing mono as well as bivalent cancer -- the vaccine candidate. So this monovalent, is this same as the CV0501, or would that be a new construct?

第二個問題是關於預防性疫苗。因此，對於新冠疫苗，您將測試單價和二價癌症（候選疫苗）。那麼這個單價是否與 CV0501 相同，還是一個新的構建體？

Okay. So 2 questions. One on our thinking around indications in oncology and then on prophylactic vaccines. Maybe I can start with the oncology one.

好的。所以有2個問題。一是我們對腫瘤學適應症的思考，然後是預防性疫苗。也許我可以從腫瘤學開始。

Obviously, there are a lot of learnings from our experience with checkpoint inhibitors that will guide as well how we develop both shared antigen and personalized cancer vaccines. So I think it's no surprise that some of the data that you're seeing into the clinic is in melanoma, maybe head a neck and lung. And I would say our focus initially while we're still looking at which antigens to which tumor types, and to have a perfect match, most likely would be in kind of the indication that you would expect, i.e., skin, maybe head and neck, maybe lung, but maybe patients with MSI high. But we will follow the signs, but I think that's what you can expect.

顯然，我們從檢查點抑製劑的經驗中學到了很多東西，這些經驗也將指導我們如何開發共享抗原和個性化癌症疫苗。因此，我認為您在診所看到的一些數據是關於黑色素瘤的，也許是頭部、頸部和肺部的數據，這並不奇怪。我想說的是，當我們仍在研究哪種抗原與哪種腫瘤類型並進行完美匹配時，我們最初的重點很可能是您所期望的指示，即皮膚，也許是頭部和頸部，可能是肺，但也可能是 MSI 高的患者。但我們會遵循標誌，但我認為這就是你所期望的。

I think probably focused on solid tumors first. I think in liquid tumors, that's a whole other ball game. And Myriam has a lot of experience in liquid tumors, so maybe she can share thoughts as well. Maybe let's finish the oncology question first, and then we can go back to the prophylactic vaccines.

我認為可能首先關注實體瘤。我認為在液體腫瘤中，這完全是另一回事。 Myriam 在液體腫瘤方面擁有豐富的經驗，所以也許她也可以分享一些想法。也許我們先解決腫瘤學問題，然後我們可以回到預防性疫苗。

No, I think you said it well, right? For oncology, our antigen discovery work has just begun. And again, we cannot look at all the possible tumor types at the same time and do that subsequently. And so as, again, the data evolving, as we discover shared antigens across different tumor types, we will be setting up additional Phase I trials. And that work is ongoing. And hopefully, we can communicate more at the end of the year and the beginning of 2024.

不，我覺得你說得很好，對吧？對於腫瘤學來說，我們的抗原發現工作才剛剛開始。再說一次，我們不能同時觀察所有可能的腫瘤類型並隨後進行。因此，隨著數據的不斷發展，當我們發現不同腫瘤類型的共享抗原時，我們將建立額外的一期試驗。這項工作正在進行中。希望我們能夠在年底和 2024 年初有更多的溝通。

For personalized cancer vaccines, I think basically we can go into every tumor that we want, right, and where we expect to see genetic alterations. And here again, we will look where will be the highest unmet needs not yet addressed in other programs and then sort of like decide in which indications we will start our clinical trial first.

對於個性化癌症疫苗，我認為基本上我們可以研究我們想要的每一種腫瘤，以及我們期望看到基因改變的地方。在這裡，我們將再次關注其他計劃中尚未解決的最高未滿足需求，然後決定我們將首先開始臨床試驗的適應症。

For liquid tumors, as you ask, I think that's actually a field where cancer vaccines, or not so much activity with cancer vaccines has been initiated so far. And it's also an area where we will sort of like focus our antigen discovery work on in the coming months.

對於液體腫瘤，正如你所問的，我認為這實際上是一個癌症疫苗的領域，或者說到目前為止還沒有啟動太多的癌症疫苗活動。這也是我們在未來幾個月內重點關注抗原發現工作的領域。

Yes. Maybe my own thought on cancer vaccines, more broadly, I think we have tried this for many, many years. And I think the path of cancer vaccine has been mostly failures over many, many years. But I do believe, as we are kind of at an inflection point with mRNA, COVID and flu, I think the same is true for oncology as well, with now a better understanding on antigen, how to select them, ability to build more advanced constructs with platforms as well as the LNPs, I do believe we are at an inflection point potentially for cancer vaccines as well. A very broad field, and we see definitely a lot of potential here.

是的。也許是我自己對癌症疫苗的看法，更廣泛地說，我認為我們已經嘗試了很多很多年。我認為多年來癌症疫苗的發展道路大多以失敗告終。但我確實相信，由於我們正處於 mRNA、新冠病毒和流感的拐點，我認為腫瘤學也是如此，現在對抗原、如何選擇它們、建立更先進的能力有了更好的了解。隨著平台和 LNP 的構建，我確實相信我們也正處於癌症疫苗潛在的拐點。這是一個非常廣闊的領域，我們在這裡絕對看到了很大的潛力。

And maybe we can move on to your second question, right? You asked whether the sort of like a monovalent also bivalent construct in our, to start, Phase II COVID-19 trial is the same as CV0501. And the answer is no, it's not the same. In CV0501, we targeted BA.1 as a relevant SARS-CoV-2 variant. And for our Phase II trial, we are targeting BA.5 as a variant in the monovalent as well as in the bivalent construct.

也許我們可以繼續討論你的第二個問題，對吧？您詢問我們的第二階段 COVID-19 試驗中的單價和二價結構是否與 CV0501 相同。答案是否定的，這是不一樣的。在 CV0501 中，我們將 BA.1 作為相關的 SARS-CoV-2 變體。對於我們的 II 期試驗，我們將 BA.5 作為單價和二價構建體的變體。

That -- but of course, we -- no, just to compete on this, we have to be agile, right, because we know the field is evolving. There may be other variants emerging over the summer and autumn. And so we, again, will need to stay flexible for future programs. But for the Phase II, this is basically our starting point.

那 - 但當然，我們 - 不，只是為了在這方面競爭，我們必須保持敏捷，對吧，因為我們知道這個領域正在不斷發展。夏季和秋季可能會出現其他變種。因此，我們再次需要對未來的計劃保持靈活性。但對於第二階段來說，這基本上是我們的起點。

Our next question comes from the line of Roy Buchanan with JMP Securities.

我們的下一個問題來自 JMP 證券公司的羅伊·布坎南 (Roy Buchanan)。

Just to follow up, make sure I'm clear on the multi-epitope Phase I and starting in '24. Is that personalized or shared antigen? And if it's personalized, is it going to use the printer? And then the follow-up is, does the trial have a monotherapy arm of vaccine-only and/or PD-1-only?

只是為了跟進，請確保我清楚多表位第一階段並從 24 年開始。該抗原是個性化的還是共享的？如果是個性化的，是否會使用打印機？接下來的問題是，該試驗是否有僅疫苗和/或僅 PD-1 的單一療法？

Yes, maybe I can start. So the trial you mentioned starting in '24, it's going to be shared antigen, one. And it's going to be done in combination with the checkpoint inhibitor, right? and...

是的，也許我可以開始。所以你提到的從 24 年開始的試驗將是共享抗原，其中之一。它將與檢查點抑製劑結合使用，對嗎？和...

No monotherapy?

沒有單一療法嗎？

No. No. Not at this point in time.

不，不，目前還不行。

Our next question comes from the line of Evan Wang with Guggenheim.

我們的下一個問題來自Evan Wang 與古根海姆的對話。

So Alex, congrats on the CEO appointment. I just wanted to get a sense of your thoughts on -- in terms of CureVac moving forward. Probably how do you view the evolution of CureVac relative to other mRNA companies? What do you think the company needs to do to succeed competitively?

亞歷克斯，恭喜你被任命為首席執行官。我只是想了解一下您對 CureVac 未來發展的想法。您如何看待 CureVac 相對於其他 mRNA 公司的發展？您認為公司需要做什麼才能在競爭中取得成功？

And from a strategic perspective, can you give us your thoughts on how you plan to shape the strategy going forward?

從戰略角度來看，您能否告訴我們您計劃如何制定未來戰略的想法？

Thanks, Evan. Great question. So I've been in the role now for a bit less than a month. What I can tell you is this is a very, very special company. There is 20 years of experience, so it's a real pioneer. And I'm really impressed by the deep science, the deep expertise, really understanding, constructing mRNA. So there's a real deep science here.

謝謝，埃文。很好的問題。我擔任這個職位到現在還不到一個月。我可以告訴你的是，這是一家非常非常特別的公司。有20年的經驗，所以它是真正的先驅。深刻的科學、深厚的專業知識、真正理解、構建 mRNA 給我留下了深刻的印象。所以這裡有一個真正深奧的科學。

I think we now have an excellent platform. So that's why I do believe we need to transition now from a company that has been focused mostly on research and technology, and now we really need to shift gears and bring products to the clinic. So that's going to be a key focus for us, together with the whole team and under Myriam's leadership as well.

我認為我們現在擁有一個非常好的平台。所以這就是為什麼我確實相信我們現在需要從一家主要專注於研究和技術的公司轉型，現在我們確實需要轉變方向並將產品帶入臨床。因此，這將成為我們以及整個團隊以及 Myriam 領導下的重點關注點。

I do believe it's a special company as well because it can really do mRNA end-to-end. And there are very few companies that really have the platform we have, can build products to the clinic, can manufacture them as well and has a strong IP position to defend it then on top of it. And last but not least, there are really great people here. So I mean, I'm really excited to be here. I think there's a lot of potential, a lot of work that we will need to do.

我確實相信它也是一家特殊的公司，因為它確實可以端到端地進行 mRNA 生產。很少有公司真正擁有我們所擁有的平台，可以為臨床生產產品，也可以製造產品，並擁有強大的知識產權地位來捍衛它。最後但並非最不重要的一點是，這裡有很多很棒的人。所以我的意思是，我很高興來到這裡。我認為有很大的潛力，我們需要做很多工作。

In terms of strategy moving forward. So this is kind of ongoing, so please give me some time. And I will sure I will come back to all of you to -- with my analysis a bit later on. But what is clear is the priorities are, we need to really execute on our COVID and flu programs in collaboration with GSK. We need to expand beyond infectious diseases with the work that we're doing in oncology.

從戰略上看，是在推進。所以這是一個持續的過程，所以請給我一些時間。我確信稍後我會回到你們所有人那裡進行我的分析。但顯而易見的是，我們的首要任務是，我們需要與葛蘭素史克合作，真正執行我們的新冠肺炎和流感項目。我們需要將腫瘤學領域的工作擴展到傳染病以外的領域。

And I think beyond that, if I look at molecular therapies or rare diseases, we're going to be opportunistic. We have a cool few collaboration with academic institution ongoing. And if you see something that is great science, we will jump on it as well. So that's kind of my 3 big view on CureVac, Evan.

我認為除此之外，如果我關注分子療法或罕見疾病，我們將是機會主義的。我們與學術機構正在進行一些很酷的合作。如果您看到一些偉大的科學成果，我們也會加入其中。這就是我對 CureVac 的三大看法，Evan。

One follow-up. I saw that new study for flu was posted on clinicaltrials.gov. Just it's evaluating a number of different formulations. Just wondering, as we're kind of seeing some competitor readouts here. I guess what is the intended product profile that you plan to take forward to Phase III trial? Do you expect to show superiority or noninferiority with this first gen for Frame flu?

一項後續行動。我看到臨床試驗網站上發布了一項針對流感的新研究。只是它正在評估許多不同的配方。只是想知道，因為我們在這裡看到了一些競爭對手的讀數。我猜你們計劃進行第三階段試驗的預期產品概況是什麼？您希望第一代 Frame Flu 表現出優越性還是非劣勢？

So the first -- the Phase I trial in glioblastoma is a proof of principle trial, right? So our main goal is really to show that the mRNA backbone works in the cancer setting and really our first trial to go into, again, an oncology setting.

所以第一個——膠質母細胞瘤的第一階段試驗是原則性試驗的證明，對嗎？因此，我們的主要目標實際上是證明 mRNA 主幹在癌症環境中發揮作用，這也是我們首次在腫瘤學環境中進行的試驗。

We have to really wait and see for the data, right? And then once the data are evolving, then we will decide how and if we take this program forward. I do believe, with the data published at the end of last year in glioblastoma, if that's what you were referring to, while they look promising, there's still a lot of room for improvement and a lot that can be done for the glioblastoma patients. And if our study, basically, results in the future indicate that we can contribute here again, then we will sort of like take it -- take this program further for patients.

我們必須真正等待並觀察數據，對吧？一旦數據不斷發展，我們將決定如何以及是否推進該計劃。我確實相信，根據去年年底公佈的膠質母細胞瘤數據，如果這就是您所指的，雖然它們看起來很有希望，但仍有很大的改進空間，並且可以為膠質母細胞瘤患者做很多事情。如果我們的研究，基本上，未來的結果表明我們可以再次在這裡做出貢獻，那麼我們會有點喜歡接受它——為患者進一步推進這個項目。

Well, I was referring to the flu Phase I/II study that was posted.

嗯，我指的是已發布的流感 I/II 期研究。

The flu -- or sorry, I misunderstood it. I thought I heard you say glioblastoma.

流感——或者抱歉，我誤解了。我想我聽到你說膠質母細胞瘤。

The question on flu was what is the comparator we're using in (inaudible) compares, I guess, is what I understood.

關於流感的問題是我們在（聽不清）比較中使用的比較器是什麼，我想，這就是我所理解的。

Yes. So this study is currently still in sort of like design phase and in discussion with the health authorities. And we will disclose more details when we sort of like have finalized the design and we'll communicate when we will start. I hope that's okay for you.

是的。因此，這項研究目前仍處於設計階段，並正在與衛生當局進行討論。當我們完成設計時，我們將披露更多細節，並且我們將在開始時進行溝通。我希望你沒問題。

Our next question comes from the line of Andy Chan with Berenberg.

我們的下一個問題來自 Andy Chan 和 Berenberg 的對話。

So both of my questions are around the cancer vaccines. So regarding the melanoma vaccine starting in 2024, I'm just wondering if you can provide more color around the multi-epitope design. I think the slide mentions that it's an innovative design. How is it different from the GBM design? If you can provide more color, that would be great.

所以我的兩個問題都與癌症疫苗有關。因此，關於 2024 年開始的黑色素瘤疫苗，我只是想知道您是否可以圍繞多表位設計提供更多顏色。我認為幻燈片提到這是一個創新的設計。它與 GBM 設計有何不同？如果你能提供更多的顏色，那就太好了。

The other question is, so with emerging data from other companies around cancer vaccines in the past few days, how does that inform your decision going forward, both in melanoma and GBM and maybe in the future in head and neck and lung.

另一個問題是，隨著過去幾天其他公司關於癌症疫苗的不斷湧現的數據，這對您未來的決策有何影響，無論是黑色素瘤和 GBM，還是未來的頭頸和肺部。

Maybe I can start and Myriam you can add to this. Maybe I'll start with the second question on the recent data on personalized cancer vaccines that were updated just recently at the AACR as well. I guess that's the data set you're referring to.

也許我可以開始，Myriam 你可以補充一下。也許我會從第二個問題開始，關於個性化癌症疫苗的最新數據，這些數據最近也在 AACR 上更新。我想這就是你所指的數據集。

For me, it's positive. It's good for patients. It's a proof of concept, right? It shows that personal cancer vaccines, in addition to a checkpoint inhibitor, can bring meaningful benefit to patients. So it's Phase II data. So we still need to be confirmed in a Phase III trial, of course. But I think it shows a path forward for personalized cancer vaccines.

對我來說，這是積極的。這對病人有好處。這是一個概念證明，對吧？它表明，除了檢查點抑製劑之外，個人癌症疫苗還可以為患者帶來有意義的益處。這是第二階段的數據。當然，我們仍然需要在第三階段試驗中得到證實。但我認為它為個性化癌症疫苗指明了一條前進的道路。

I also believe there's still room for improvement. As Myriam has outlined, we are taking, I would say, a more comprehensive approach when we design our personalized cancer vaccines, really trying to cover as many variations as possible, looking at neoantigens as well as tumor-associated antigens, but I see it positive, but I think we can improve on this, and that's certainly what we're trying to do. We want to bring in differentiated medicines to patients. So that's what we want to do.

我也相信仍有改進的空間。正如 Myriam 所概述的那樣，我想說，當我們設計個性化癌症疫苗時，我們正在採取一種更全面的方法，真正嘗試涵蓋盡可能多的變異，著眼於新抗原以及腫瘤相關抗原，但我認為積極的，但我認為我們可以改進這一點，這當然是我們正在努力做的。我們希望為患者提供差異化藥物。這就是我們想做的。

And I guess the second question was -- maybe Myriam, I'll let you comment on personalized cancer vaccines first.

我想第二個問題是——也許 Myriam，我首先讓你評論一下個性化癌症疫苗。

Yes. Thank you. And I agree with you. The data on personalized vaccines look promising, right? And today, right now, we do not know if the future will be sort of like setting up or will be successful for personalized cancer vaccines or for off-the-shelf vaccines with shared antigens loaded on the RNA construct offer both, and then in which indications.

是的。謝謝。我同意你的觀點。關於個性化疫苗的數據看起來很有希望，對嗎？今天，現在，我們不知道未來是否會像個性化癌症疫苗或在 RNA 構建體上加載共享抗原的現成疫苗一樣建立或會成功，然後在哪些指示。

So this is what we have to sort of like where we have to wait for more data evolving. And that's why we are basically pursuing, with our oncology strategy with both settings, right? Developing off-the-shelf antigen vaccines and then also a platform for personalized cancer vaccine.

所以這就是我們必須等待更多數據發展的情況。這就是為什麼我們基本上追求兩種環境下的腫瘤學策略，對吧？開發現成的抗原疫苗，然後開發個性化癌症疫苗的平台。

Regarding to your question, the sort of like newly to be designed trial in melanoma and other indications. So as we said, this will be a trial with an mRNA construct with sort of shared antigens and the approach we are taking right now is really looking at specific and different tumor types. And the sequencing data and then analyzing which antigens are shared and how we can -- and then sort of like taking those antigens through a validation step to show that they are not just shared, but also immunogenic that they are presenting -- presented on the MHC on the surface of the sales and then also recognized by the T cells.

關於你的問題，類似於新設計的針對黑色素瘤和其他適應症的試驗。正如我們所說，這將是一項具有某種共享抗原的 mRNA 構建體的試驗，我們現在採取的方法實際上是在研究特定的和不同的腫瘤類型。測序數據，然後分析哪些抗原是共享的，以及我們如何共享這些抗原，然後有點像通過驗證步驟來顯示這些抗原，以表明它們不僅是共享的，而且還具有它們所呈現的免疫原性。 MHC在表面銷售然後也被T細胞識別。

So this is happening right now. And depending then on the outcome, we will select the antigens that are the most promising and load them to the construct. And then decide, based on the results of this effort, which trials we will initiate and which indications.

所以這件事現在正在發生。然後根據結果，我們將選擇最有希望的抗原並將其加載到構建體中。然後根據這項工作的結果決定我們將啟動哪些試驗以及哪些適應症。

Our next question comes from the line of Luisa Morgado with Kempen.

我們的下一個問題來自 Luisa Morgado 和 Kempen 的對話。

This is Luisa dialing in for Suzano from Kempen. I wanted to ask you guys if you could elaborate a bit more on your projection for distribution of operating expenses. So across the clinical development plans that you have now for the remainder of the year. And just overall on your cash burn that you are expecting more or less for this year.

我是路易莎從肯彭撥通蘇扎諾的電話。我想問你們是否可以詳細說明一下運營費用分配的預測。因此，您現在已經制定了今年剩餘時間的臨床開發計劃。總體而言，您預計今年或多或少都會消耗現金。

So happy to jump in. So we didn't break out, right, the P&L line by line in terms of spend. But what we try to provide is with the cash balance that we had at the end of last year, plus the cash that we raised earlier in this year, that this would -- according to our plan that as of today, bring us through to, say, May 2025. I think that's the disclosure that we wanted to put forward.

很高興加入。所以我們沒有逐行列出支出方面的損益表，對吧。但我們試圖提供的是去年年底的現金餘額，加上今年早些時候籌集的現金，根據我們截至今天的計劃，這將使我們能夠實現，比如說 2025 年 5 月。我認為這就是我們想要提出的披露。

Okay. And -- just another, second question. Could you also elaborate a bit more on how has it been, the integration of technology from the -- your recent acquisition of Frame Cancer Therapeutics?

好的。還有——還有第二個問題。您能否詳細說明一下您最近收購的 Frame Cancer Therapeutics 的技術整合情況如何？

Maybe I can comment on this. It has been relatively seamless, right? So we integrate Frame Therapeutics starting last year. We established a site in Amsterdam as well, where Frame Therapeutics was located originally. And we're now incorporating this in our overall organization as well. This allows us also to recruit talent in the Amsterdam side. So it has been really seamless, working well across the different sites.

也許我可以對此發表評論。一切都比較順利，對吧？因此，我們從去年開始整合 Frame Therapeutics。我們還在阿姆斯特丹建立了一個站點，即 Frame Therapeutics 最初的所在地。我們現在也將其納入我們的整個組織中。這使我們還可以在阿姆斯特丹方面招募人才。所以它確實是無縫的，在不同的站點上運行良好。

And I think you will see soon, hopefully, that it also shows the results, that we're going to be able to really use these capabilities that we got with Frame. Not just the genetics, but also the bioinformatics capabilities, and that it will start to show and help us to really develop the next generation of cancer vaccines. So Luisa, to your question, very, very smooth, already producing great results.

我想您很快就會看到，希望它也顯示結果，我們將能夠真正使用通過 Frame 獲得的這些功能。不僅僅是遺傳學，還有生物信息學能力，它將開始展示並幫助我們真正開發下一代癌症疫苗。路易莎，對於你的問題，非常非常順利，已經產生了很好的結果。

Our next question comes from the line of Charlie Yang with Bank of America.

我們的下一個問題來自查理·楊與美國銀行的對話。

This is Charlie Yang for Jeff Meacham. So I guess regarding the oncology vaccine, I'm wondering like what's the rationale for choosing the glioblastoma as sort of first proof of principle indication versus melanoma?

我是傑夫·米查姆的查理·楊。所以我想關於腫瘤疫苗，我想知道選擇膠質母細胞瘤作為與黑色素瘤相比的第一個原理適應證的理由是什麼？

And I guess, in terms of like what would be the data less needed for you to make the, I guess, go/no-go decision to move to a next stage of development?

我想，就您而言，做出前進/不前進的決定以進入下一開發階段時，需要哪些數據？

And secondly, I guess, regarding the melanoma trial, is this going to be in the adjuvant setting or metastatic settings? And then I have just one follow-up after that.

其次，我想，關於黑色素瘤試驗，這將是在輔助治療還是轉移治療中進行？此後我只有一次跟進。

Thanks, John. Maybe Myriam, a question on why GBM?

謝謝，約翰。也許是 Myriam，關於為什麼是 GBM 的問題？

Yes. So Charlie, you may know, GBM is still a tumor or cancer indication with a really high unmet need. And there, we have recently published some promising or encouraging data showing that a cancer vaccine in glioblastoma can not only induce immune responses, but also clinical responses and then clinical benefit.

是的。所以查理，你可能知道，GBM 仍然是一種腫瘤或癌症適應症，具有非常高的未滿足需求。在那裡，我們最近發表了一些有希望或令人鼓舞的數據，表明膠質母細胞瘤的癌症疫苗不僅可以誘導免疫反應，還可以誘導臨床反應，然後產生臨床效益。

And so we -- and then with the sort of application of data showing that specific epitopes can induce immune responses in glioblastoma. And then with our sort of like goal to really show proof of principle that our backbone works in this kind of a setting. We thought it's a reasonable approach to take known epitopes or antigens, load them on our construct, and then start the Phase I trial to really show that our mRNA backbone works.

所以我們——然後通過一些數據的應用表明特定的表位可以誘導膠質母細胞瘤的免疫反應。然後我們的目標是真正證明我們的骨幹在這種環境下工作的原則。我們認為這是一種合理的方法，採用已知的表位或抗原，將它們加載到我們的構建體上，然後開始第一階段試驗，以真正證明我們的 mRNA 主幹有效。

Regarding the data to make a go/no-go decision. I guess this is a composition of safety, efficacy and immunological data that will sort of like inform the decision to go or not go for further Phase II.

根據數據做出繼續/不繼續的決定。我想這是安全性、有效性和免疫學數據的組合，這些數據將有點像告知是否繼續進行第二階段的決定。

And then for melanoma, I think the answer is very easy. Right now, we are in the design phase. So we can't tell you is this adjuvant, will it be metastatic first line, second line, low tumor burden, all in. And so these are the conversations ongoing, and we'll come back once we have a final study design and also more fine-tuned time lines.

對於黑色素瘤，我認為答案很簡單。目前，我們正處於設計階段。所以我們不能告訴你這個佐劑是不是轉移性一線、二線、低腫瘤負荷等等。所以這些都是正在進行的對話，一旦我們有了最終的研究設計，我們就會回來還有更微調的時間線。

Just I guess on my follow-up question, in terms of your LNP design, can you just compare and contrast that with the competitors LNP? And is this design going to be used in your vaccines for glioblastoma? Or is that more of the design that will be used for the next stage of development?

我想就我的後續問題而言，就你們的 LNP 設計而言，你們能否將其與競爭對手的 LNP 進行比較和對比？這種設計會用於你們的膠質母細胞瘤疫苗嗎？或者更多的設計將用於下一階段的開發？

So we can't compare our LNP with that of industry peers, right?

所以我們不能將我們的 LNP 與業界同行進行比較，對嗎？

And regarding your question, what are we using for the glioblastoma trial. So we are using the -- for this, because it's a proof of principle trial and we wanted to go fast, we're using the (inaudible) LNP-315 and basically are getting ready for our next trial with off-the-shelf or personalized cancer vaccines to test our proprietary oncology LNPs. That's the plan.

關於你的問題，我們在膠質母細胞瘤試驗中使用什麼。因此，我們正在使用 - 為此，因為這是原則性試驗的證明，我們想要快速進行，我們正在使用（聽不清）LNP-315，基本上正在為我們的下一個現成試驗做好準備或個性化癌症疫苗來測試我們專有的腫瘤學 LNP。這就是計劃。

Our next question is a follow-up question from Eun Yang with Jefferies.

我們的下一個問題是 Eun Yang 和 Jefferies 提出的後續問題。

So I have a couple of questions for the prophylactic vaccines. So for the flu and COVID, the planned clinical trials for the new construct, are they going to be run by you or GSK? If not, when do you think the GSK will take over for the development?

我對預防性疫苗有幾個問題。那麼，對於流感和新冠病毒，計劃中的新結構臨床試驗將由您還是葛蘭素史克進行？如果不是，您認為葛蘭素史克什麼時候會接手開發？

And the second question is, with the GSK, you have additional 4 undisclosed target. So when do you think we may expect a new target or targets from the collaboration?

第二個問題是，對於葛蘭素史克來說，還有另外 4 個未公開的目標。那麼您認為我們什麼時候可以從合作中期待一個或多個新目標？

Okay. So flu, COVID, who will run the trials? So GSK.

好的。那麼流感、新冠病毒，誰來進行試驗呢？所以葛蘭素史克。

It's GSK, yes. So it's done in partnership, but GSK is a sponsor for the Phase I/II flu and also for the Phase II COVID trial.

是的，是葛蘭素史克。所以這是合作完成的，但葛蘭素史克是 I/II 期流感以及 II 期新冠試驗的讚助商。

Maybe I can take the other question. So as part of CLA 1, we have 5 basically, the right targets, right? One has been disclosed, and that is flu, right? The other 1 is outside of this collaboration in CLA 2, and that's COVID. So the other 4 are part of the first agreement have not been disclosed at this stage. And so we cannot comment.

也許我可以回答另一個問題。那麼作為 CLA 1 的一部分，我們基本上有 5 個正確的目標，對吧？已經披露了一個，那就是流感，對吧？另外 1 個不屬於 CLA 2 中的合作範圍，那就是 COVID。因此，其他 4 項屬於第一份協議的一部分，現階段尚未披露。所以我們無法發表評論。

Our next question is a follow-up question from Roy Buchanan with JMP Securities.

我們的下一個問題是 JMP 證券公司 Roy Buchanan 提出的後續問題。

I'm going to follow right up on that last one, Pierre just answered the next target. Can you say if that's -- if it's in your hands or their hands? What state of development it's at?

我將繼續最後一個目標，皮埃爾剛剛回答了下一個目標。你能說這是在你手裡還是在他們手裡？目前處於什麼發展狀態？

Sure, I can comment. So basically, they can choose and not for any target they want, right? So outside of certain targets, which are booked saved by BMGF or stuff like that or other targets that we have kept to ourselves. But typically, they can opt -- within that restriction, they can opt to any target until the very last moment of collaboration.

當然，我可以評論。所以基本上，他們可以選擇而不是為了他們想要的任何目標，對嗎？因此，除了由 BMGF 預訂保存的某些目標或類似的目標或我們保留的其他目標之外。但通常情況下，他們可以選擇——在限制範圍內，他們可以選擇任何目標，直到合作的最後一刻。

Okay. Great. But any sense of the stages of development you can give us? Probably not.

好的。偉大的。但您能給我們介紹一下發展的各個階段嗎？可能不是。

No, sorry. It need to be on disclosure.

不，抱歉。它需要披露。

Okay. All right. I guess, just long term, can you give us the best guess on when you think you can be on market for flu and COVID? And again, I realize you have a partner in this.

好的。好的。我想，從長遠來看，您能否給我們最好的猜測，您認為您何時可以進入流感和新冠病毒市場？再說一次，我意識到你在這方面有一個合作夥伴。

And then the last question, just the Bill & Melinda Gates candidates, rotavirus, malaria, universal flu. Just any idea when those might be in the clinic?

最後一個問題是比爾和梅琳達·蓋茨的候選人，輪狀病毒，瘧疾，通用流感。知道這些什麼時候可以進入診所嗎？

Okay. So 2 questions, 1 on time lines for potential approvals for flu and COVID, and a question -- follow-up question on the programs within Bill and Melinda Gates.

好的。所以有兩個問題，一個是關於流感和新冠病毒潛在批准的時間表，還有一個問題——關於比爾和梅琳達·蓋茨內部項目的後續問題。

I can take the BMGF question, if you want to. So right -- you're right, Roy, there is a set of indications, which are -- we're working on with the Gates Foundation. Today, I guess the work is actually pretty early in preclinical, so difficult for me to give any guidance in terms of clinical timeline. There's a lot of science being worked on quite cutting-edge science, but that's not quite yet ready for the clinic.

如果你願意的話，我可以回答 BMGF 的問題。所以，你是對的，羅伊，有一系列跡象，我們正在與蓋茨基金會合作。今天，我想這項工作實際上還處於臨床前階段，所以我很難在臨床時間表方面提供任何指導。有很多科學研究正在研究非常前沿的科學，但還沒有為臨床做好準備。

Right. And regarding the question on -- I think it was about when it could be launch or with the flu and/or COVID vaccines come to the market again. We -- hard to comment right now because the Phase I and II trials are basically about to start. And so we will sort of like give better projections as the trials are progressing and again, don't want to disclose right now.

正確的。關於這個問題——我認為這是關於何時推出或流感和/或新冠疫苗再次上市的問題。我們現在很難發表評論，因為第一階段和第二階段試驗基本上即將開始。因此，隨著試驗的進展，我們會給出更好的預測，但現在不想透露。

We have no further questions at this time. I would now like to turn the floor back over to management for closing comments.

目前我們沒有進一步的問題。我現在想將發言權交還給管理層以徵求結束意見。

With this, we would like to conclude this conference call. Thank you very much for your participation. Stay safe, and please don't hesitate to contact us should you have any further questions. Thank you, and goodbye.

至此，我們結束本次電話會議。非常感謝您的參與。請注意安全，如果您有任何其他問題，請隨時與我們聯繫。謝謝，再見。

Ladies and gentlemen, this does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation, and have a wonderful day.

女士們、先生們，今天的電話會議到此結束。此時您可以斷開線路。感謝您的參與，祝您度過美好的一天。