CureVac NV (CVAC) 2024 Q4 法說會逐字稿

Greetings. Welcome to CureVac fourth-quarter and full year 2024 financial results and business update call. (Operator Instructions) As a reminder, this conference is being recorded. It is now my pleasure to introduce Sarah Fakih, Vice President of Corporate Communications and Investor Relations. Thank you, Sarah, you may begin.

問候。歡迎參加 CureVac 2024 年第四季及全年財務表現及業務更新電話會議。（操作員指示）提醒一下，本次會議正在錄音。現在我很高興介紹企業傳播和投資者關係副總裁 Sarah Fakih。謝謝你，莎拉，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. 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 Scientific Officer; and our Chief Financial Officer, Axel Malkomes. Please note that this call is being webcast live and will be archived on the events and presentations section of the Investor Relations on our website.

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 公司的企業傳播與投資人關係副總裁。請容許我介紹今天的演講者。與我一起通話的還有 CureVac 的執行長 Alexander Zehnder； Myriam Mendila，我們的財務長；以及我們的財務長 Axel Malkomes。請注意，本次電話會議將進行網路直播，並將存檔在我們網站投資者關係的活動和演示部分。

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, Thursday, April 10, 2025. We will be making statements and providing responses to your questions that state our intentions, believes, expectations, or predictions of the future. These constitute forward-looking statements for the purpose of the safe harbor provisions.

在我們開始一些前瞻性陳述之前，本次電話會議的討論和對您問題的回答反映了管理層截至今天（2025 年 4 月 10 日星期四）的觀點。我們將發表聲明並回答您的問題，闡明我們的意圖、信念、期望或對未來的預測。這些構成了安全港條款所規定的前瞻性陳述。

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 US Securities and Exchange Commission. I will now turn the call over to Alexander.

這些聲明涉及風險和不確定性，可能導致實際結果與預測結果有重大差異。CureVac 不承擔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。現在我將把電話轉給亞歷山大。

Thank you, Sarah. Ladies and gentlemen, good morning, good afternoon to everybody on the webcast. The fourth quarter of 2024 completed a transformational year for CureVac, which was marked by significant strategic shifts and positive financial milestones, positioning the company for future growth in oncology and infectious diseases.

謝謝你，莎拉。女士們、先生們，網路直播的各位觀眾大家早安、下午好。2024 年第四季是 CureVac 的轉型之年，這一年標誌著公司實現重大策略轉變和取得積極的財務里程碑，為公司在腫瘤學和傳染病領域未來的成長奠定了基礎。

In July 2024, we took decisive action to streamline and rightsize the company, laying a solid foundation for future success in 2025 and beyond. We have now refocused the company on what we do best: technology, innovation, and R&D and have made substantial progress in expanding and advancing our pipeline of early proprietary clinical development programs. These programs have the potential to address critical unmet medical needs and capitalize on compelling market opportunities.

2024年7月，我們果斷採取行動，精簡公司規模，為2025年及以後的成功奠定堅實的基礎。現在，我們已將公司重點重新放在我們最擅長的領域：技術、創新和研發，並在擴大和推進早期專有臨床開發項目方面取得了實質進展。這些項目有可能解決關鍵的未滿足的醫療需求並利用引人注目的市場機會。

In Oncology, we continue to make progress with our lead program in patient resective glioblastoma. The Phase I study successfully completed enrollment of Part B. The speed of the enrollment underscored the urgent need for new treatment options in this aggressive form of brain cancer and we are encouraged with the rapid progress we are making.

在腫瘤學領域，我們在患者切除性膠質母細胞瘤方面的領先計畫繼續取得進展。I 期研究成功完成 B 部分的招募。招募速度之快凸顯了對這種惡性腦癌新治療方案的迫切需求，我們對所取得的快速進展感到鼓舞。

Our off-the-shelf positioning immunotherapy program in patients with squamous non-small cell lung cancer achieved a significant regulatory milestone with the IND clearance from the US Food and Drug Administration to proceed with Phase 1. We anticipate treating the first patient in the second half of 2025.

我們針對鱗狀非小細胞肺癌患者的現成定位免疫治療方案取得了重要的監管里程碑，獲得了美國食品藥物管理局的 IND 批准，可以進入第一階段。我們預計在 2025 年下半年治療第一位患者。

Transitioning to infectious diseases, our new licensing agreement with GSK prophylactic vaccines continues to progress. In November, GSK initiated a combined Phase 1/2 study for seasonal influenza COVID combination vaccine based on our proprietary second-generation mRNA backbone, which triggered a EUR10 million milestone. The milestone payment was invoiced in the fourth quarter of 2024 and received in the first quarter of 2025.

轉向傳染病領域，我們與葛蘭素史克預防疫苗的新授權協議正在繼續取得進展。11 月，葛蘭素史克啟動了基於我們專有的第二代 mRNA 骨架的季節性流感 COVID 聯合疫苗的 1/2 期聯合研究，該研究創下了 1000 萬歐元的里程碑。里程碑付款於 2024 年第四季開立發票，並於 2025 年第一季收到。

Additionally, in its full-year and fourth-quarter earnings report, GSK confirmed that it's clinical program for a standalone seasonal influenza vaccine is being prepared for Phase 3. Transition to Phase 3 will trigger another significant milestone payment by further validating our technology.

此外，葛蘭素史克在全年和第四季財報中證實，其獨立季節性流感疫苗的臨床計畫正在為第三階段做準備。透過進一步驗證我們的技術，過渡到第三階段將觸發另一個重要的里程碑付款。

On the IP front, as you may have seen recently, the European Patent Office or EPO upheld the validity of our split poly-A tail 668 patent in amended form. This outcome is particularly important as it validates our pioneering role in developing foundational mRNA vaccine technology.

在智慧財產權方面，正如您最近可能看到的，歐洲專利局或 EPO 維持了我們修改後的分裂聚腺苷酸尾 668 專利的有效性。這一結果尤其重要，因為它證實了我們在開發基礎 mRNA 疫苗技術方面的先鋒作用。

And finally, thanks to this steady progress across our portfolio and the successful execution of our restructuring plan. We closed 2024 with a strong cash position of EUR482 million, reaffirming our expected financial run rate into 2028.

最後，感謝我們投資組合的穩定進展和重組計劃的成功執行。截至 2024 年，我們的現金狀況強勁，達到 4.82 億歐元，這再次印證了我們 2028 年的預期財務運行率。

On slide 5, I would like to highlight the key accomplishments in 2024, which has set CureVac on a trajectory for increased performance and innovation. Our previously mentioned licensing agreement with GSK signed in July 2024 and valued up to EUR1.45 billion plus royalties, marked a pivotal moment for CureVac. This agreement provides us with significant capital and leverages GSK's expertise in infectious diseases for successful development and commercialization.

在第 5 張投影片上，我想強調 2024 年的主要成就，這讓 CureVac 走上了提高效能和創新的軌道。我們先前提到的與葛蘭素史克於 2024 年 7 月簽署的授權協議價值高達 14.5 億歐元，另加特許權使用費，這標誌著 CureVac 的關鍵時刻。該協議為我們提供了大量資金，並利用葛蘭素史克在傳染病方面的專業知識實現成功的開發和商業化。

Importantly, we then embarked on a strategic corporate restructuring to streamline the company, including a headcount reduction of approximately 30%, which was completed in 2024. The restructuring has positioned us to achieve higher efficiency and agility in executing our pipeline priorities, allowing us to focus on developing potentially transformational mRNA therapeutics in oncology and infectious diseases.

重要的是，我們隨後開始了一項策略性公司重組，以精簡公司，包括裁員約 30%，該重組於 2024 年完成。此次重組使我們能夠以更高的效率和靈活性執行我們的管道優先事項，使我們能夠專注於開發腫瘤學和傳染病領域具有轉化潛力的 mRNA 療法。

Our quality pipeline of Phase 1 glioblastoma study demonstrated promising dose escalation data last year, confirming acceptable tolerability and antigen-specific T-cell responses in the majority of evaluable patients. We also added a new program for squamous non-small cell lung cancer to our pipeline, featuring a multi-epitope immunotherapy with novel antigens derived from our collaboration with myNEO.

我們第一階段膠質母細胞瘤研究的品質流程去年展示了有希望的劑量遞增數據，證實了大多數可評估患者俱有可接受的耐受性和抗原特異性 T 細胞反應。我們還在我們的產品線中增加了一個針對鱗狀非小細胞肺癌的新項目，該項目採用與 myNEO 合作產生的新型抗原進行多表位免疫療法。

In prophylactic vaccines, we initiated a program against uropathogenic E. coli bacteria or UPEC in urinary tract infections, which is one of the most common bacterial infections with high unmet medical need, supported by promising preclinical data.

在預防性疫苗方面，我們啟動了一項針對泌尿道感染中的泌尿道致病性大腸桿菌或 UPEC 的項目，這是最常見的細菌感染之一，具有很高的未滿足醫療需求，並得到了有希望的臨床前數據的支持。

In the GSK license programs in infectious diseases, positive Phase 2 headline data for seasonal influenza was reported in September 2024, confirming strong antibody titers against both Influenza A strains and the notoriously challenging Influenza B strains. And as I mentioned, starting the Phase 3 trial would trigger another significant milestone payment from GSK.

在葛蘭素史克的傳染病許可項目中，2024 年 9 月報告了季節性流感的第 2 階段陽性標題數據，證實了針對甲型流感病毒株和極具挑戰性的乙型流感病毒株的強抗體滴度。正如我所提到的，啟動第三階段試驗將觸發葛蘭素史克的另一項重要里程碑付款。

On the management side, we welcome two new members to our leadership team, Thaminda Ramanayake, Chief Business Officer; and Axel Malkomes as Chief Financial Officer. Both are seasoned industry experts and bring significant expertise and experience to CureVac.

在管理方面，我們歡迎兩位新成員加入我們的領導團隊，他們是首席商務官 Thaminda Ramanayake；並擔任財務長的 Axel Malkomes。兩位都是經驗豐富的行業專家，為 CureVac 帶來了豐富的專業知識和經驗。

Building on our momentum in oncology, infectious diseases, and senior leadership, we further anticipate key catalysts in 2025 that will further expand our pipeline and reinforce our R&D priorities. Beginning with oncology, we expect to share data from the fully recruited Phase 1 Part B glioblastoma study in the second half of 2025. And pending results, we will take a decision to advance to Phase 2, which is expected in the second half of 2025.

基於我們在腫瘤學、傳染病和高階領導力方面的發展勢頭，我們進一步預測 2025 年的關鍵催化劑將進一步擴大我們的產品線並加強我們的研發重點。從腫瘤學開始，我們預計將在 2025 年下半年分享已全面招募的第 1 期 B 部分膠質母細胞瘤研究的數據。根據結果，我們將決定是否進入第二階段，預計將於 2025 年下半年完成。

Following the IND clearance in the US, the first patient in our program for squamous non-small cell lung cancer is scheduled to be treated in the second half of this year. The clinical development of our new prophylactic vaccine program for UPEC is underway, and we expect to file an IND submission in the second half of this year for a Phase 1 study to commence in the first half of 2026.

隨著美國IND審批通過，我們鱗狀非小細胞肺癌計畫的首位患者預計將於今年下半年接受治療。我們針對 UPEC 的新預防性疫苗計畫的臨床開發正在進行中，我們預計將在今年下半年提交 IND 申請，並於 2026 年上半年開始進行第一階段研究。

Also in the infectious disease area, we expect GSK to announce programs with current candidates based on licensed CureVac technology. And lastly, in 2025, we will continue to defend our broad and innovative IP portfolio and anticipate further key decisions throughout the year in Europe and the US.

此外，在傳染病領域，我們預計葛蘭素史克將宣布基於授權的 CureVac 技術的現有候選藥物項目。最後，2025 年，我們將繼續捍衛我們廣泛而創新的智慧財產權組合，並預計全年在歐洲和美國做出更多重要決策。

Together, this upcoming milestones position CureVac for another year of great momentum and with a sharpened focus and innovative pipeline, we probably remain a leader of innovation within the RNA tech ecosystem.

總之，這些即將到來的里程碑將使 CureVac 在接下來的一年裡保持強勁發展勢頭，憑藉著更專注和創新的管道，我們很可能會繼續成為 RNA 技術生態系統中創新的領導者。

In March 2025, the decision of the European Patent Office or EPO to uphold the validity of our split poly-A tail 668 patent in amended form represents an important step in our ongoing litigation with Pfizer, BioNTech. This decision supports our pioneering role at significant contributions to mRNA vaccine technology, particularly in the space of COVID-19 vaccines.

2025 年 3 月，歐洲專利局 (EPO) 決定維持我們經修訂的分裂 poly-A 尾 668 專利的有效性，這是我們與輝瑞、BioNTech 正在進行的訴訟中的重要一步。這項決定支持了我們在 mRNA 疫苗技術，特別是在 COVID-19 疫苗領域做出重大貢獻的先鋒作用。

Please recall that in Europe, each IP right is handled as a separate case for which validity, infringement, and potential damages will be decided separately. Damages will be assessed only when validity and infringement both have been established.

請記住，在歐洲，每項智慧財產權都作為單獨的案件處理，其有效性、侵權和潛在損害將分別決定。只有當有效性和侵權行為均已確定時，才會評估損害賠償。

On slide 6, you can see a schematic of this bifurcated process. On the left side, the infringement proceedings are displayed. For our IP dispute, infringement is decided by the regional court Dusseldorf as well as potential damages related to all six IP rights at issue.

在第 6 張投影片上，您可以看到這個分叉過程的示意圖。左側展示的是侵權案件的處理過程。對於我們的智慧財產權糾紛，侵權行為以及與所有六項涉案智慧財產權相關的潛在損害均由杜塞爾多夫地區法院裁決。

On the right side, validity proceedings are displayed. Validity for IP rights is served by different authorities depending on the nature of the IP rights. Validity of the split poly-A tail patents is heard by the EPO. Following the EPO's positive position on our first split poly-A 668 patent last month, adhering to rule infringement is scheduled for July 1, 2025. And should validity of the second split poly-A tail patent also be confirmed by the EPO in the hearing, which is scheduled for May 13 to 15, 2025, it would also be included in the July infringement hearing.

右側顯示有效性程序。知識產權的有效性由不同的機構根據其性質來決定。歐洲專利局正在審理分割 poly-A 尾專利的有效性問題。繼上個月歐洲專利局對我們的第一項分割 poly-A 668 專利採取積極立場後，遵守規則侵權的截止日期定於 2025 年 7 月 1 日。如果歐洲專利局在定於 2025 年 5 月 13 日至 15 日舉行的聽證會上確認第二條分裂聚腺苷酸尾專利的有效性，那麼該專利也將被納入 7 月的侵權聽證會。

So we remain confident of our position in the upcoming infringement case and believe that the validated patent is infringed in its amended form. As the earliest pioneered in mRNA technology, we are determined to have our contributions recognized and compensated. And with this, let me now hand over to Myriam for a review of our pipeline development activities.

因此，我們對即將審理的侵權案件中的立場充滿信心，並認為已驗證的專利在其修改形式下受到了侵犯。作為mRNA技術領域的最早先驅，我們決心讓我們的貢獻得到認可和補償。現在，請允許我把時間交給 Myriam，讓她來審查我們的管道開發活動。

Thank you, Alexander. Moving on to slide 7, I would like to provide an overview of our development pipeline, which prioritizes high-value programs where our mRNA technology can make a substantial difference in addressing diseases with significant unmet medical need.

謝謝你，亞歷山大。轉到第 7 張投影片，我想概述我們的開發流程，該流程優先考慮高價值項目，在這些項目中，我們的 mRNA 技術可以在解決具有重大未滿足醫療需求的疾病方面發揮重要作用。

As Alexander already mentioned, our oncology pipeline is led by our Phase 1 glioblastoma study with CVGBM an off-the-shelf precision immunotherapy, encoding eight segments from four known tumor-associated antigens with demonstrated relevance in this indication. The promising initial data we presented from the completed dose escalation Part A of the study at a scientific conference in September and November last year demonstrated successful induction of cancer antigen-specific T cell responses and 77% of 13 evaluable patients.

正如亞歷山大已經提到的，我們的腫瘤學管線由我們的 1 期膠質母細胞瘤研究引領，該研究採用 CVGBM 這種現成的精準免疫療法，對四種已知腫瘤相關抗原的八個片段進行編碼，並證明與該適應症相關。我們在去年 9 月和 11 月的科學會議上展示了已完成劑量遞增研究 A 部分所獲得的有希望的初步數據，表明成功誘導了癌症抗原特異性 T 細胞反應，並且在 13 名可評估患者中佔 77%。

84% of these immune responses are generated de novo, meaning T cell responses are successfully induced in patients with no pre-existing T cell activity against encoded antigens prior to treatment with CVGBM.

84% 的免疫反應是從頭產生的，這意味著在接受 CVGBM 治療之前，患者體內沒有針對編碼抗原的 T 細胞活性，但 T 細胞反應已被成功誘導。

As the recommended 100-microgram dose for the expansion part of the study, the majority of responses were sustainable over a 99-day monitoring period. The treatment was generally well tolerated with no dose-limiting the toxicities reported. The dose expansion Part B of the study is ongoing and has already completed enrollment of 20 additional patients who are treated at the selected dose of 100 micrograms.

作為研究擴展部分建議的 100 微克劑量，大多數反應在 99 天的監測期內是可持續的。該治療通常耐受性良好，且未報告劑量限制毒性。研究的劑量擴展 B 部分正在進行中，並且已經完成了 20 名額外患者的入組，他們接受 100 微克的選定劑量治療。

First data from this part are anticipated to be available in the second half of this year. Our new off-the-shelf multi-epitope precision immunotherapy candidate for patients with squamous non-small cell lung cancer encodes established antigens as well as novel antigens derived from our collaboration with myNEO Therapeutics. I will provide more detail on the study later in this presentation.

該部分的首批數據預計將於今年下半年公佈。我們針對鱗狀非小細胞肺癌患者推出的新型現成多表位精準免疫治療候選藥物編碼了已建立的抗原以及我們與 myNEO Therapeutics 合作衍生的新抗原。我將在本次演講的後面提供有關該研究的更多細節。

In infectious diseases, please recall that we are directing our proprietary research and development efforts towards new nonrespiratory indications. As mentioned, our program targeting respiratory indications are fully licensed to GSK. In our proprietary nonrespiratory infectious disease portfolio, our program for prophylactic vaccine against uropathogenic E. coli bacteria to prevent urinary tract infections is well on track.

在傳染病方面，請記住，我們正將我們的專有研究和開發工作轉向新的非呼吸系統適應症。如上所述，我們針對呼吸系統疾病的計畫已完全授權給葛蘭素史克。在我們專有的非呼吸道傳染病產品組合中，我們針對泌尿道致病性大腸桿菌的預防性疫苗計畫用於預防泌尿道感染的計畫進展順利。

The clinical candidate targets FimH, a highly conserved protein which facilitates adhesion of the bacteria to bladder tissue and biocell formation, thus enabling invasion of the cells in the urinary tract. The candidate mRNA design applies a unique technology resulting in an in vivo self-assembly of a protein nanoparticle with clustering of FimH antigen on its surface, which has shown superior immunogenicity in preclinical studies.

此臨床候選藥物針對的是 FimH，這是一種高度保守的蛋白質，它有助於細菌黏附於膀胱組織和生物細胞形成，使細胞能夠侵入泌尿道。候選 mRNA 設計採用獨特的技術，導致蛋白質奈米顆粒在體內自組裝，其表面聚集有 FimH 抗原，這在臨床前研究中已表現出優異的免疫原性。

In the respiratory infectious disease area, license to GSK programs for seasonal influenza, avian influenza and COVID-19 are currently in Phase 2 development. The newly initiated combined Phase 1/2 study for a seasonal influenza COVID-19 combination vaccine is in Phase 1 development.

在呼吸道傳染病領域，授權葛蘭素史克針對季節性流感、禽流感和COVID-19的計畫目前正處於第二階段開發階段。新啟動的季節性流感 COVID-19 聯合疫苗 1/2 期聯合研究正處於第 1 階段開發階段。

All current candidates of the GSK trials are based on CureVac's proprietary second-generation mRNA backbone. We believe that there's great potential of our growing pipeline and look forward to reporting on its further development in the future.

GSK 試驗的所有目前候選藥物均基於 CureVac 專有的第二代 mRNA 骨架。我們相信，我們不斷增長的產品線具有巨大的潛力，並期待未來報告其進一步的發展。

On slide 8, we'll dive deeper into our oncology strategy. Over the last decade, there has been significant progress in treating solid tumors with immunotherapies either alone or in combination with chemotherapy. However, achieving significantly better patient outcomes remains elusive due to genetic differences in tumors, their ability to develop resistance, the complexity of the tumor microenvironment, and the weakening of the patient's immune system over the course of various therapies.

在第 8 張投影片上，我們將深入探討我們的腫瘤學策略。在過去的十年中，單獨使用免疫療法或與化療聯合使用免疫療法治療實體腫瘤取得了重大進展。然而，由於腫瘤的基因差異、產生抗藥性的能力、腫瘤微環境的複雜性以及患者免疫系統在各種治療過程中的減弱，獲得顯著更好的患者治療結果仍然難以實現。

In this complex landscape, we see tremendous opportunity for our mRNA therapeutics to revolutionize immunotherapy for large patient populations with more precision. We are confident that our mRNA therapeutics could be a game changer based on two factors.

在這種複雜的情況下，我們看到了 mRNA 療法的巨大機遇，它可以更精確地徹底改變大量患者群體的免疫療法。基於兩個因素，我們有信心我們的 mRNA 療法可以改變遊戲規則。

First, our unique mRNA technology, which uses our second-generation mRNA backbone. This backbone is optimized for strong and broad immune responses and most importantly, targets also cellular immune responses and has been clinically validated in Phase 1 and 2 studies in both infection diseases and oncology.

首先，我們獨特的 mRNA 技術，它採用了我們的第二代 mRNA 骨架。該主幹針對強大而廣泛的免疫反應進行了優化，最重要的是，它還針對細胞免疫反應，並已在感染疾病和腫瘤學的 1 期和 2 期研究中得到臨床驗證。

Second, our proprietary and highly differentiated whole genome-based antigen discovery platform. This platform provides access to new classes of tumor antigens, enhancing the precision and effectiveness of our therapies. In our upcoming clinical development, we plan to combine our precision immunotherapies with checkpoint inhibitors. Checkpoint inhibitors release the brakes on the immune system, thereby boosting the ability of our mRNA therapeutics to trigger powerful and precisely targeted immune responses.

第二，我們專有的、高度差異化的基於全基因組的抗原發現平台。該平台提供了接觸新類別腫瘤抗原的途徑，提高了我們治療的精確度和有效性。在我們即將進行的臨床開發中，我們計劃將我們的精準免疫療法與檢查點抑制劑結合。檢查點抑制劑釋放了免疫系統的煞車，從而增強了我們的 mRNA 療法觸發強大且精確靶向的免疫反應的能力。

Timing is critical in this approach. Intervening earlier when patients' immune systems are healthier, tumor burden is lower and resistance to therapy is less established, offers the best chance for improved and durable outcomes. Accordingly, we aim to apply mRNA therapeutics at early stages of cancer in the adjuvant of perioperative setting. We believe by intervening early, we have the potential to increase the chances of improved outcomes of patients whose tumors are surgically resected when their immune system is still strong and tumors are easier to control.

在這個方法中，時機至關重要。當患者的免疫系統更健康、腫瘤負擔較低且對治療的抵抗力較弱時進行早期幹預，最有可能獲得改善和持久的治療效果。因此，我們的目標是在癌症早期階段應用 mRNA 療法作為圍手術期的輔助治療。我們相信，透過早期幹預，我們有可能增加患者的治療結果改善的機會，因為當患者的免疫系統仍然強大且腫瘤更容易控制時，透過手術切除腫瘤可以提高患者的治療結果。

Let me show you on the next 2 slides how we intend to make a difference with our physician immunotherapy approach. Specifically, how we expect to deliver strong and precise immune responses in combination with the checkpoint inhibitor in our new program for squamous non-small cell lung cancer.

讓我在接下來的兩張幻燈片中向您展示我們如何利用醫生免疫療法來發揮作用。具體來說，我們希望如何在針對鱗狀非小細胞肺癌的新方案中結合檢查點抑制劑提供強大而精確的免疫反應。

Worldwide, there are more than 2 million patients diagnosed every year with lung cancer. In the United States only, there are approximately 225,000 new cases of lung cancer each year. 87% of which are non-small cell lung cancer or NSCLC according to the American Cancer Society.

全球每年有超過200萬名患者被診斷出患有肺癌。光是在美國，每年就有約 225,000 例新發肺癌病例。根據美國癌症協會的數據，其中 87% 為非小細胞肺癌或 NSCLC。

Squamous non-small cell lung cancer represents approximately 20% to 30% of all NSCLC cases, making it one of the most prevalent cancers worldwide. It's considered a more aggressive form of non-small cell lung cancer with five-year survival rates of patients with advanced disease just around 20%. And even if diagnosed in earlier stages and treated if perioperative immunotherapy, about 30% to 40% of patients relapsed within two years.

鱗狀非小細胞肺癌約佔所有 NSCLC 病例的 20% 至 30%，是全球最常見的癌症之一。它被認為是一種更具侵襲性的非小細胞肺癌，晚期患者的五年存活率僅為 20% 左右。即使在早期階段進行診斷並接受圍手術期免疫治療，也有約 30% 至 40% 的患者在兩年內復發。

Squamous non-small cell lung cancer thereby poses significant challenges in disease control and treatment contributing to the high unmet medical need in the indication. Importantly, squamous non-small cell lung cancer has shown a particularly high prevalence of shared tumor antigens among patients, providing a unique opportunity for developing targeted precision immunotherapies. We aim to leverage this opportunity with an mRNA precision immunotherapy to improve outcomes for a larger patient population.

因此，鱗狀非小細胞肺癌在疾病控制和治療方面提出了重大挑戰，導致該適應症的醫療需求很高且未被滿足。重要的是，鱗狀非小細胞肺癌在患者中表現出特別高的共享腫瘤抗原的盛行率，為開發有針對性的精準免疫療法提供了獨特的機會。我們旨在利用 mRNA 精準免疫療法這一機會來改善更多患者群體的治療效果。

Our selected investigational precision immunotherapy candidate is built on our advanced second-generation mRNA backbone. It features two different mRNA constructs encoding eight tumor-associated antigens with high prevalence across squamous non-small lung cancer patients. Four of these antigens are known with established relevance in solid tumors, providing a strong foundation for efficacy.

我們選定的試驗性精準免疫療法候選藥物是建立在我們先進的第二代 mRNA 骨架之上的。它具有兩種不同的 mRNA 構建體，編碼八種腫瘤相關抗原，在鱗狀非小細胞肺癌患者中患病率很高。其中四種抗原已知與實體腫瘤有關，為其療效提供了堅實的基礎。

The remaining four antigens were discovered within our collaboration with myNEO Therapeutics and are uniquely derived from myNEO Therapeutic's cutting-edge AI power technology platform. All four of these novel antigens were discovered outside the exome and have not been previously tested in cancer immunotherapy trials.

其餘四種抗原是在我們與 myNEO Therapeutics 合作期間發現的，並且源自 myNEO Therapeutic 尖端的 AI 動力技術平台。所有這四種新抗原都是在外顯子組之外發現的，之前從未在癌症免疫療法試驗中進行過測試。

Our patient population coverage calculation for our candidate predict that approximately 95% of patients will express and present epitopes from at least one of the encoded antigens. Approximately 50% of patients are predicted to express and present epitopes from at least four of the encoded antigens.

我們對候選藥物的患者族群覆蓋率計算預測約 95% 的患者將表達並呈現至少一種編碼抗原的抗原決定基。預計約有 50% 的患者會表達並呈現至少四種編碼抗原的抗原決定基。

For our Phase 1 study, this high patient coverage means that we can proceed without the need for specific patient selection beyond the squamous non-small cell lung cancer diagnosis. The general setup of the Phase 1 dose-finding open-label study is illustrated on slide 10. In this study, we will assess the safety and tolerability of our candidate as first-line maintenance treatment in combination with the checkpoint inhibitor pembrolizumab in patients with advanced squamous non-small cell cancer.

對於我們的第一階段研究，這種高患者覆蓋率意味著我們可以繼續進行研究，而無需在鱗狀非小細胞肺癌診斷之外進行特定的患者選擇。第 10 張投影片展示了第 1 階段劑量探索開放標籤研究的整體設定。在這項研究中，我們將評估我們的候選藥物與檢查點抑制劑派姆單抗聯合用於晚期鱗狀非小細胞癌患者的一線維持治療的安全性和耐受性。

In the dose escalation Part A, our candidate will be tested in doses ranging from 100 to 400 micrograms in combination with pembrolizumab maintenance therapy for up to 12 months or until disease progression or undue toxicity occurs. In Part A, we expect to include patients with metastatic stage 4 squamous non-small cell lung cancer who have received at least three cycles of pembrolizumab, either as monotherapy or in combination with chemotherapy.

在劑量遞增 A 部分中，我們的候選藥物將接受 100 至 400 微克劑量範圍的測試，並與 pembrolizumab 維持療法聯合使用，最長 12 個月或直至病情進展或出現不當毒性。在 A 部分中，我們預計納入已接受至少三個週期的 pembrolizumab 治療（單一療法或與化療聯合治療）的轉移性 4 期鱗狀非小細胞肺癌患者。

Following Part A, an optional dose expansion Part B will be conducted. The primary endpoints of the Phase 1 study includes the incidence of dose-limiting toxicities and treatment-related and treatment-emergent adverse events, and secondary endpoints include overall response rate, progression-free survival, duration of response, and disease control rate. A positive outcome from this study would enable us to evaluate this combination in earlier stages of the disease aligned with our goal to apply mRNA precision immunotherapy at early stages of cancer.

在 A 部分之後，將進行可選的劑量擴展 B 部分。1 期研究的主要終點包括劑量限制性毒性以及治療相關和治療出現的不良事件的發生率，次要終點包括總體反應率、無進展生存期、反應持續時間和疾病控制率。這項研究的積極成果將使我們能夠在疾病的早期階段評估這種組合，這與我們的目標一致，即在癌症早期階段應用 mRNA 精準免疫療法。

Moving on to infectious diseases on slide 11, let me provide you with a brief overview of the details of the respiratory disease programs, which were fully licensed to GSK under our new licensing agreement from July last year. The most advanced program for seasonal influenza read out positive Phase 2 headline data last year.

接下來討論第 11 張投影片中的傳染病，讓我向您簡要介紹一下呼吸系統疾病計畫的細節，根據我們去年 7 月簽訂的新授權協議，該計畫已完全授權給葛蘭素史克。最先進的季節性流感計畫去年公佈了積極的第二階段主要數據。

As Alexander already mentioned, GSK confirmed earlier this year that the program is in preparation for a Phase 3 study which will be associated with a significant milestone payment for CureVac. The program for a pre-pandemic vaccine against avian influenza is currently in Phase 2 of the combined Phase 1/2 study initiated in April last year.

正如亞歷山大已經提到的，葛蘭素史克今年稍早證實，該計畫正在為第三階段研究做準備，這將與 CureVac 的重大里程碑付款相關。禽流感大流行前疫苗計畫於去年 4 月啟動了 1/2 期聯合研究，目前正處於第 2 期。

As previously mentioned, a new program for a seasonal influenza COVID-19 combination vaccine entered Phase 1 in November last year. And lastly, Phase 2 of the standalone COVID-19 vaccine program was completed. Please note that disclosure of study timelines and availability of clinical data is at the discretion of GSK.

如前所述，季節性流感 COVID-19 聯合疫苗新計畫於去年 11 月進入第一階段。最後，獨立的 COVID-19 疫苗計劃第二階段已經完成。請注意，研究時間表和臨床數據的可用性的揭露由 GSK 自行決定。

By having licensed these programs to GSK, we leverage their expertise in vaccine development and commercialization to bring innovative vaccine based on our mRNA technology to market. The new licensing agreement strongly validates the potential of our proprietary mRNA platform, while the financial and strategic benefits from the agreement support our continuous innovation and development efforts.

透過將這些項目授權給葛蘭素史克，我們利用他們在疫苗開發和商業化方面的專業知識，將基於我們的 mRNA 技術的創新疫苗推向市場。新的授權協議有力地驗證了我們專有的 mRNA 平台的潛力，同時該協議帶來的財務和策略利益支持我們持續的創新和發展努力。

To further enhance mRNA effectiveness in oncology and infectious diseases, we are advancing our proprietary mRNA delivery technologies with improved proprietary lipid nanoparticles or in short, LNPs. As highlighted on slide 12, specific requirements apply to develop efficacious precision immunotherapies in oncology and prophylactic vaccines in infective diseases.

為了進一步提高 mRNA 在腫瘤學和傳染病中的有效性，我們正在利用改進的專有脂質奈米顆粒（簡稱 LNP）來改進我們專有的 mRNA 遞送技術。如同幻燈片 12 所強調的，開發腫瘤學中有效的精準免疫療法和感染性疾病的預防性疫苗有具體的要求。

LNPs are critical in meeting these specific requirements, underscoring the potential for LNP systems that are tailored to the respective therapeutic area. Prophylactic vaccines for infectious diseases treat healthy individuals, necessitating activation of the immune system with minimal reactogenicity and side effects.

LNP 對於滿足這些特定要求至關重要，凸顯了針對相應治療領域量身定制的 LNP 系統的潛力。預防性傳染病疫苗用於治療健康個體，需要激活免疫系統並儘量減少反應原性和副作用。

In contrast, cancer immunotherapies treat seriously ill patients, requiring robust activation of cellular signaling pathways to induce strong systemic immune responses and allow greater tolerance for reactogenicity.

相較之下，癌症免疫療法治療重症患者，需要強力活化細胞訊號通路以誘導強烈的全身性免疫反應並提高對反應原性的耐受性。

Prophylactic vaccines often target induction of high antibody titers and T cell responses only were relevant. For cancer immunotherapies, activation of tumor killing T cells is critical even if this is associated with increased reactogenicity.

預防性疫苗通常以誘導高抗體滴度為目標，並且僅與 T 細胞反應有關。對於癌症免疫療法，活化殺死腫瘤的 T 細胞至關重要，即使這會增加反應原性。

Additionally, prophylactic vaccines need to be stable for longer periods at refrigerator or room temperature given their seasonal use. For precision cancer immunotherapy applications, maximized efficacy is key with stability being the secondary goals.

此外，由於預防性疫苗的季節性使用，其需要在冰箱或室溫下保存更長時間。對於精準的癌症免疫治療應用，最大化療效是關鍵，穩定性是次要目標。

We previously reported a proprietary LNP system for infectious diseases, featuring a PEG-free lipid composition that demonstrated strong humoral and cellular immune responses in preclinical models, and highly localized biodistribution in the immune compartment, showing no or very low expression in distant organs such as the liver, spleen, and lung, avoiding potential side effects by maximizing immunogenicity.

我們先前報告了一種用於治療傳染病的專有 LNP 系統，其特點是不含 PEG 的脂質組成，在臨床前模型中表現出強大的體液和細胞免疫反應，並在免疫區內高度局部化生物分佈，在肝臟、脾臟和肺等遠處器官中沒有或幾乎沒有表達，通過最大限度地提高免疫原性避免了潛在的副作用。

Focusing on the additional need for stability in prophylactic vaccines, we have now advanced our infectious disease LNP system to achieve promising thermal stability as well. On slide 13, you can see data from our ongoing STABILITY study with a bespoke infectors disease LNP system over a period of 12 months.

考慮到預防性疫苗對穩定性的額外需求，我們現在已經改進了傳染病 LNP 系統，以實現良好的熱穩定性。在第 13 張投影片上，您可以看到我們正在進行的 STABILITY 研究的數據，該研究使用客製化的感染者疾病 LNP 系統進行了為期 12 個月的調查。

mRNA encoding a rabies antigen was formulated within the new LNP system and stored either as a freeze-dried powder at room temperature of 25-degree Celsius equivalent to 77-degree Fahrenheit or under refrigeration at 2 to 8-degree Celsius, which equates to 36 to 46 degrees Fahrenheit. The formulated mRNA was also stored as a frozen liquid at minus 80 degrees Celsius or minus 112 degrees Fahrenheit as a control.

編碼狂犬病抗原的 mRNA 在新的 LNP 系統中配製，並以凍乾粉的形式儲存在室溫 25 攝氏度（相當於 77 華氏度）下，或冷藏在 2 至 8 攝氏度（相當於 36 至 46 華氏度）下。作為對照，配製的 mRNA 也以冷凍液體的形式儲存在攝氏零下 80 度或零下 112 度。

The data on the left shows that with the new LNP system, mRNA integrity remains stable with the mRNA being intact and securely formulated for at least 12 months under all three storage conditions. As shown in the middle, LNP size also remained stable over time and under different storage conditions.

左側數據顯示，採用新的 LNP 系統，mRNA 完整性保持穩定，在三種儲存條件下，mRNA 保持完整且安全至少 12 個月。如中間所示，LNP 尺寸在不同的儲存條件下也隨時間保持穩定。

In vivo experiments in mice, confirm that throughout the test period, the vaccines start under the different conditions maintain their ability to induce strong neutralizing antibodies. These findings provide a competitive advantage in addressable patients as our vaccines can be utilized globally without the need for complex cold stain storage requirements.

小鼠體內實驗證實，在整個測試期間，疫苗在不同條件下啟動均保持誘導強效中和抗體的能力。這些發現為可尋址患者提供了競爭優勢，因為我們的疫苗可以在全球範圍內使用，而無需複雜的冷染色儲存要求。

On slide 14, let me now summarize our upcoming pipeline catalysts, which provides a strong development path through the end of 2026. On the oncology front, starting with our most advanced Phase 1 off-the-shelf program in glioblastoma. As already mentioned, Part B of the study is fully enrolled, and first data is expected in the second half of 2025. This data will provide the basis for potentially continuing to a Phase 2 study, which could start in the second half of 2026.

在第 14 張投影片上，現在讓我總結我們即將推出的管道催化劑，它為 2026 年底提供了一條強勁的發展道路。在腫瘤學方面，我們首先進行的是最先進的膠質母細胞瘤第一階段現成計畫。如前所述，研究的 B 部分已全部招募完畢，預計將於 2025 年下半年獲得第一批數據。這些數據將為可能在 2026 年下半年開始的第二階段研究提供基礎。

Following FDA clearance of the IND submission, the Phase 1 study of our off-the-shelf program in squamous non-small cell lung cancer is expected to start dosing patients in the second half of 2025. With our antigen discovery were continuing, we intend to disclose additional off-the-shelf programs and select new clinical candidates in different indications in 2026.

在 FDA 批准 IND 提交後，我們針對鱗狀非小細胞肺癌的現成方案的 1 期研究預計將於 2025 年下半年開始對患者給藥。隨著我們抗原發現的持續進行，我們打算在 2026 年披露更多現成的方案並選擇針對不同適應症的新臨床候選藥物。

Lastly, the first clinical Phase 1 study with a personalized cancer vaccine candidate is expected to start in the second half of 2026. In infectious diseases, for our proprietary UPEC program, we expect to file an IND application in the second half of 2025 and to start Phase 1 clinical development in the first half of 2026. Additional discovery work in other nonrespiratory diseases is ongoing, and we anticipate expanding our pipeline in this area with additional programs in 2025 from which clinical candidates could be selected in the second half of 2026.

最後，針對個人化癌症疫苗候選物的首個臨床 1 期研究預計將於 2026 年下半年開始。在傳染病領域，對於我們專有的 UPEC 項目，我們預計將在 2025 年下半年提交 IND 申請，並在 2026 年上半年開始第 1 階段臨床開發。其他非呼吸系統疾病的進一步研發工作正在進行中，我們預計在 2025 年推出更多計畫來擴大該領域的研發線，並可在 2026 年下半年從中選出臨床候選藥物。

For the respiratory program, licensed to GSK, as stated in GSK's fourth-quarter and full-year earnings report in February this year, the seasonal Influenza program is in preparation to progress to Phase 3. Taken as a whole, this slide illustrates that we have before us a strong path of pipeline catalysts in both oncology and infectious diseases.

對於授權給葛蘭素史克的呼吸系統項目，正如葛蘭素史克今年2月發布的第四季度及全年財報中所述，季節性流感項目正在準備進入第3階段。總的來說，這張幻燈片表明，我們在腫瘤學和傳染病領域都擁有強大的管道催化劑路徑。

With a substantial set of anticipated upcoming milestones, we are in a strong position to make lasting impact on the future of mRNA medicines. I would now like to conclude the portfolio update and hand over to Axel for a review of the financial data.

隨著一系列預期即將到來的里程碑，我們有能力對 mRNA 藥物的未來產生持久影響。我現在想結束投資組合更新，交給 Axel 審查財務數據。

Thank you, Myriam. Looking at the significant progress we have made in streamlining our operations and focusing on strategic priorities on slide 15, I would like to provide context to key financial metrics in 2024, demonstrating our financial health and enabling us to reinvest in key areas of growth and innovation.

謝謝你，米里亞姆。回顧我們在精簡營運和關注第 15 張投影片上的策略重點方面取得的重大進展，我想提供 2024 年關鍵財務指標的背景，展示我們的財務健康狀況，並使我們能夠在關鍵成長和創新領域進行再投資。

Today, we report a strong cash position of EUR481.7 million at the end of 2024 and reaffirm our expected cash runway into 2028. Our results are driven by the new licensing agreement with GSK, which positively impacted our cash position as well as revenues.

今天，我們報告稱，2024 年底我們的現金狀況強勁，達到 4.817 億歐元，並重申了我們預計到 2028 年的現金流。我們的業績受到與葛蘭素史克簽訂的新授權協議的推動，該協議對我們的現金狀況和收入產生了積極影響。

The EUR400 million upfront from the agreement was received as a nonrefundable payment for granting licenses to GSK and the exclusive right to use CureVac's intellectual property relating to applicable vaccine programs with no further R&D work obligation on our side. As such, it was fully recognized as revenue in 2024.

該協議中的 4 億歐元預付款是作為授予葛蘭素史克許可的不可退還款項以及使用 CureVac 與適用疫苗計劃相關的知識產權的獨家權利而收到的，我們無需承擔進一步的研發工作義務。因此，該金額​​於 2024 年全額確認為收入。

Given that under the terms of the new licensing agreement all obligations from prior collaborations relating to R&D services had expired, remaining contract liabilities amounting to EUR80.4 million were also recognized as revenue in 2024. Additionally, in 2024, a development milestone of EUR10 million was reached under the new license agreement for the initiation of a Phase 1 for the combo vaccine, which was also fully recognized as revenue.

鑑於根據新授權協議的條款，與研發服務相關的所有先前合作的義務均已到期，剩餘的合約負債 8,040 萬歐元也將在 2024 年確認為收入。此外，2024年，根據新的許可協議，該組合疫苗第一階段的啟動達到了1000萬歐元的開發里程碑，這也被全部確認為收入。

Setting the course for increased future financial stability, our strategic redesign is key to enhancing our operational efficiency to further reduce costs. The 30% workforce reduction was completed by end of 2024, with incurred costs 70% below the allocated budget.

我們的策略重新設計為提高未來財務穩定性設定了方向，是提高營運效率以進一步降低成本的關鍵。30% 的裁員計畫已於 2024 年底完成，發生的成本比分配的預算低 70%。

From 2025 onwards, we anticipate a substantial decrease in operating expenses by over 30%, including a notable EUR25 million reduction in personnel costs. Our licensing agreement with GSK and renewed focus on innovation and R&D activities have also eliminated the need for commercial buildup and large-scale manufacturing activities.

從 2025 年起，我們預計營運費用將大幅下降 30% 以上，其中人員成本將大幅減少 2,500 萬歐元。我們與葛蘭素史克簽訂的授權協議以及對創新和研發活動的重新關注也消除了商業建設和大規模製造活動的需求。

Streamlining of our in-house manufacturing capacities to provide a new manufacturing footprint better suited to our needs was accompanied by impairment of our large-scale production facility. Lastly, we have successfully terminated all remaining raw material commitments and closed all contract manufacturing organization, or CMO, related arbitrations for our first-generation COVID-19 vaccine, ensuring no further related payments for CVnCoV going forward.

我們精簡內部製造能力，以提供更適合我們需求的新製造足跡，但同時也損害了我們的大型生產設施。最後，我們已成功終止所有剩餘的原材料承諾，並結束了與第一代 COVID-19 疫苗相關的所有合約製造組織 (CMO) 仲裁，確保今後不再為 CVnCoV 支付相關費用。

Taken together, in 2024, extraordinary payments related to CVnCoV, our strategic redesign and ongoing patent litigation amount to a total of EUR137 million. Moving on to our condensed financial statement on slide 16, you can see that our cash position of EUR481.7 million increased from EUR402.5 million at the end of 2023 based on the EUR400 million upfront payment from GSK in August 2024. The increase is partially offset by our ongoing R&D activities as well as a total of EUR137 million one-off payments related to our first-generation COVID-19 vaccine as already discussed.

總的來說，2024 年與 CVnCoV、我們的策略重新設計和正在進行的專利訴訟相關的額外支出總額達到 1.37 億歐元。請繼續查看投影片 16 上的簡明財務報表，您可以看到，基於葛蘭素史克在 2024 年 8 月支付的 4 億歐元預付款，我們的現金狀況從 2023 年底的 4.025 億歐元增加到 4.817 億歐元。這一成長部分被我們正在進行的研發活動以及與我們第一代 COVID-19 疫苗相關的總計 1.37 億歐元的一次性付款所抵消（如前所述）。

Revenues decreased by EUR8.1 million to EUR14.5 million for the fourth quarter and strongly increased by EUR481.4 million to EUR535.2 million for the 12 months of 2024 compared to the same periods in 2023. As the year-on-year increase was primarily driven by the new licensing agreement with GSK, such increase must be considered to be a positive onetime event.

第四季營收減少 810 萬歐元至 1,450 萬歐元，2024 年 12 個月營收與 2023 年同期相比強勁成長 4.814 億歐元至 5.352 億歐元。由於年成長主要得益於與葛蘭素史克簽訂的新授權協議，因此這種成長必須被視為一次性的正面事件。

Operating loss was EUR43.8 million for the fourth quarter of 2024 compared to an operating loss of EUR88 million for the same quarter of 2023. For the full year 2024, operating profit was EUR177.7 million compared to an operating loss of EUR274.2 million for the same period in 2023. The operating result was affected by several key drivers.

2024 年第四季營業虧損為 4,380 萬歐元，而 2023 年同期營業虧損為 8,800 萬歐元。2024 年全年營業利潤為 1.777 億歐元，而 2023 年同期營業虧損為 2.742 億歐元。經營業績受到幾個關鍵因素的影響。

First, cost of sales decreased year on year, mainly due to the change in strategy associated with the new license agreement with GSK, resulting in adapted R&D activities. The cost of CureVac's manufacturing organization are no longer supporting revenue-generating activities and are thus no longer classified as cost of sales.

首先，銷售成本較去年同期下降，主要由於與GSK簽訂的新授權協議相關的策略變化，導致研發活動調整。CureVac 製造組織的成本不再支援創收活動，因此不再歸類為銷售成本。

Additionally, high material costs appeared in the prior year, which were driven by write-offs of raw materials, originally purchased with stockpiling of the terminated pandemic preparedness agreement. Second, R&D expenses increased due to the strategic change mentioned, classifying CureVac's manufacturing organization, R&D rather than in cost of sales, with higher investments in oncology development programs as well as increased expenses related to the litigation to enforce intellectual property rights and higher personnel expenses related to the redesign of the organization.

此外，上一年材料成本較高，這是由於註銷了最初為儲存已終止的大流行病防備協議而購買的原材料所致。其次，由於上述策略變化，研發費用增加，將 CureVac 的製造組織歸類為研發而不是銷售成本，對腫瘤學開發項目的投資增加，以及與執行知識產權訴訟相關的費用增加，以及與組織重新設計相關的人員費用增加。

Third, general and administrative expenses decreased compared to the prior year period, mainly driven by lower personnel expenses. Lastly, other operating expenses increased year on year due to the impairment of one production line within our GMP IV production facility, which was initially planned and set up for commercial large-scale production and cannot be scaled down to provide products for clinic production in alignment with CureVac's refocus on R&D.

第三，一般及行政開支較去年同期下降，主要由於人員開支減少。最後，其他營運費用同比增長是由於我們 GMP IV 生產設施內一條生產線的減值，該生產線最初是為商業化大規模生產而規劃和設立的，無法縮小規模來為臨床生產提供產品，以配合 CureVac 重新關注研發。

Financial results increased by EUR3.7 million to EUR5.2 million in the fourth quarter of 2024, and decreased by EUR1 million to EUR13.2 million for the 12 months of 2024 compared to the same periods in 2023. The decrease was mainly driven by lower interest income on cash investments. For the fourth quarter, pretax loss was EUR38.6 million. For the full year, pretax profit was EUR190.9 million. This compares to pretax losses in the same periods of 2023.

2024 年第四季財務業績增加 370 萬歐元至 520 萬歐元，2024 年 12 個月財務業績與 2023 年同期相比減少 100 萬歐元至 1,320 萬歐元。下降的主要原因是現金投資利息收入減少。第四季稅前虧損為3,860萬歐元。全年稅前利潤為1.909億歐元。相較之下，2023 年同期的稅前虧損則有所增加。

With this, I'd like to reinforce those key strategic decisions made to conserve resources throughout 2024 has had positive impact, moving us into a position of strength as we work towards key milestones and continue to reshape what's possible in medicine. I'll now hand the call back to Alexander for today's key messages.

在此，我想強調，2024 年為節約資源而做出的關鍵策略決策產生了積極影響，使我們在努力實現關鍵里程碑和繼續重塑醫學領域的可能性時處於強勢地位。現在我將把電話轉回給亞歷山大，讓他傳達今天的關鍵訊息。

Thank you, Axel, and thank you all for your attention. the fourth quarter of 2024 closed out a year of remarkable change for CureVac. The potential of MRNA to transform medicines is enormous, and our agility as an organization and ability to pivot has enabled us to further build upon that potential and unlock new areas in which mRNA technology can make a meaningful impact for patients.

謝謝你，阿克塞爾，也謝謝大家的關注。 2024 年第四季結束了 CureVac 發生顯著變化的一年。MRNA 改變藥物的潛力是巨大的，我們作為一個組織的敏捷性和轉變能力使我們能夠進一步發揮這一潛力並開拓 mRNA 技術可以為患者帶來有意義影響的新領域。

Financially, we closed the fourth quarter 2024 with a cash position of EUR482 million, providing us with a solid expected financial runway into 2028. This gives us the stability needed to continue to drive innovation. We are making great progress in oncology or off-the-shelf and personalized precision immunotherapies and with encouraging results for our lead candidate in glioblastoma, we are eager to show continued progress with an anticipated Part B readout as well as advancements of our off-the-shelf program in squamous and non-small cell lung cancers.

財務方面，截至 2024 年第四季度，我們的現金狀況為 4.82 億歐元，為我們到 2028 年的穩健預期財務狀況提供了保障。這為我們提供了繼續推動創新所需的穩定性。我們在腫瘤學或現成的和個性化精準免疫療法方面取得了巨大進展，並且我們在膠質母細胞瘤方面的主要候選藥物取得了令人鼓舞的結果，我們渴望透過預期的 B 部分讀數展示持續的進展以及我們在鱗狀細胞癌和非小細胞肺癌方面的現成計劃的進展。

In infectious diseases, we are quickly moving forward with the UPEC vaccine in urinary tract infections, eager to make a new medical breakthrough in an indication where great unmet [medical needs]. We continue in 2025 with our focus on high-value mRNA opportunities from a well-financed position and supported by strong strategic partnerships and a broad IP portfolio. With that, I conclude our presentation and open the floor for your questions.

在傳染病領域，我們正快速推進泌尿道感染的UPEC疫苗研發，渴望在尚未滿足的領域取得新的醫學突破。[醫療需求]。2025 年，我們將繼續專注於高價值 mRNA 機會，以充足的資金、強大的策略合作夥伴關係和廣泛的智慧財產權組合為後盾。我們的演講到此結束，現在開始回答大家的提問。

(Operator Instructions) Alec Stranahan, Bank of America.

（操作員指示）美國銀行 Alec Stranahan。

Hey guys, thanks for taking our questions and congrats on the progress to close '24. Two questions from us. Maybe first -- actually, both are on the squamous program. The use of the antigens outside of the exome is pretty unique to this program. What would you say maybe the early signs you point folks to in the first-in-human clinical readout as evidence that including these antigens is maybe having a preferential effect on activity?

嘿，大家好，感謝你們回答我們的問題，並祝賀你們在 24 年取得的進展。我們有兩個問題。也許首先——實際上，兩者都屬於鱗狀細胞癌計畫。外顯子組之外的抗原的使用對於這個程序來說非常獨特。您認為在首次人體臨床讀數中您指出的早期跡像是否能證明這些抗原可能對活性產生優先影響？

And is it safe to say that the first patient dose in the second half of this year would set you up to maybe a mid or second half '26 readout from the Phase 1. Didn't see this on your catalyst slide in your prepared remarks. Thank you.

是否可以肯定地說，今年下半年的首劑患者劑量可能會讓您在 2026 年中期或下半年獲得第一階段的讀數。在您準備好的發言中的催化劑幻燈片上沒有看到這一點。謝謝。

So I didn't quite get the last part of the question, but I'll start with the first part. So in -- with our antigen discovery platform, especially for off-the-shelf antigens, they usually run them through an extensive set of validation assays, where we basically look whether the antigens is selected, especially the novel ones outside the exomes, whether they are expressed on the tumor, whether they are not expressed on healthy tissue, whether human T cells or immune cells can recognize them, and whether basically they are presented via MHC complexes, and whether they basically lead to tumor cell killings.

所以我不太明白問題的最後一部分，但我將從第一部分開始。因此，在我們的抗原發現平台上，特別是對於現成的抗原，他們通常會對其進行一系列廣泛的驗證分析，我們主要查看抗原是否被選中，特別是外顯子組之外的新抗原，它們是否在腫瘤上表達，它們是否不在健康組織上表達，人類 T 細胞或免疫細胞是否基本上能夠識別它們，以及它們是否基本上通過 MHC 複合物呈現，以及它們是否導致腫瘤。

And we have internally company-defined algorithm with very clearly set criteria to when we say an antigen passes the selection criteria or not. And based on all of the preclinical experiments we have done with these novel antigens, we remain optimistic that we would see basically strong immune responses to this quite novel and again, also very foreign proteins to the -- in cancer patients.

我們有公司內部定義的演算法，其中設定了非常明確的標準來判斷抗原是否透過選擇標準。根據我們對這些新型抗原進行的所有臨床前實驗，我們仍然樂觀地認為，我們會看到癌症患者對這種相當新穎且非常外來的蛋白質產生強烈的免疫反應。

There is right now no clinical evidence, right, because we said this is the first time we ever testing for this novel antigens in cancer patients. But there is also preclinical evidence from other groups in cancer animal models showing that when you vaccinate animals -- this was a colon cancer model when you vaccinate animals who have a colorectal cancer with the vaccine against these novel antigens that you see cancer regressions.

目前還沒有臨床證據，因為我們說這是我們第一次在癌症患者身上檢測這種新型抗原。但是，其他癌症動物模型研究小組也有臨床前證據表明，當你給動物接種疫苗時——這是一個結腸癌模型，當你給患有結腸直腸癌的動物接種針對這些新抗原的疫苗時，你會看到癌症消退。

So that's preclinical evidence from others that are supporting is our own, again, experiments have suggested that these antigens are immunogenic and that's why we are taking them into the clinic. Would you mind repeating the second part of the question? I'm sorry, I didn't quite understand it because you said something about the dosing of the first patient and what that mean of what indication that would give?

因此，這是來自其他人的臨床前證據，支持我們自己的觀點，再次，實驗表明這些抗原具有免疫原性，這就是我們將它們帶入臨床的原因。您介意重複一下問題的第二部分嗎？對不起，我不太明白，因為您提到了第一位患者的劑量以及這意味著什麼或會給出什麼指示？

Yeah. No, just more in terms of data readout time. Obviously, pace of enrollment is probably the biggest swing factor here, but I just didn't see a data catalyst on, I think, of a slide 14, if you prepared that?

是的。不，只是資料讀取時間更長。顯然，入學速度可能是這裡最大的決定因素，但我認為在第 14 張投影片上沒有看到數據催化劑，如果您準備好了的話？

We want to be a bit cautious here, right, because it's a first-in-human study. And we have to do the dose escalation, of course, with a quite broad dose-limiting toxicity window. And that's why we sort of like have our internal projections, but right now, do not feel comfortable to share them because you never know.

在這裡我們要謹慎一點，因為這是一項首次人體研究。當然，我們必須在相當寬的劑量限制毒性窗口內增加劑量。這就是為什麼我們有自己的內部預測，但現在，我們不太願意分享它們，因為你永遠不知道。

We want to see -- like you said, we want to see how recruitment goes in the first cohort and then maybe at the next update, we can give better projections when you will see the first data next year. But you probably can know that we will do everything to speed up, get recruitment on track or even faster, and then, of course, analyze the data as quickly as possible.

我們希望看到——就像您說的，我們希望看到第一批學生的招募情況，然後也許在下一次更新時，當您明年看到第一批數據時，我們可以給出更好的預測。但您可能知道，我們將盡一切努力加快速度，讓招募步入正軌甚至更快，然後當然，盡快分析數據。

Got it. Thank you.

知道了。謝謝。

Mani Foroohar, Leerink Partners

Leerink Partners 的 Mani Foroohar

Hey guys, you have Ryan on for Mani. Thanks for taking our question. Just hoping you could provide a bit more detail on what you see as the regulatory path for the CVGBM asset. Have you had conversations with regulators at this point on steps to approval and what that would look like? And then I guess just to pivot off of that, do you see the recent changes that the FDA influencing any prior conversations that you guys have had? Thanks.

嘿夥計們，Ryan 代替 Mani。感謝您回答我們的問題。只是希望您能提供更多有關您所看到的 CVGBM 資產監管路徑的細節。目前您是否與監管機構討論過審批步驟以及審批的具體內容？然後我想從這個角度來看，您是否認為 FDA 最近的變化會影響您之前的對話？謝謝。

Maybe I'll start with the second one and then, Myriam, you can comment on the regulatory path. On your question on whether we've seen any impact yet with the FDA so far, not for our program. We have the IND cleared for our squamous program on time and without any major surprises. So no negative impact on that so far. But we all understand it's quite a fluid situation with everything that's going on.

也許我會從第二個開始，然後，Myriam，你可以對監管路徑發表評論。關於您的問題，到目前為止我們是否已經看到 FDA 的任何影響，但對我們的計劃沒有影響。我們的鱗狀細胞癌計畫的 IND 按時獲得批准，且沒有任何重大意外。因此到目前為止還沒有任何負面影響。但我們都知道，目前發生的一切情況都很不穩定。

But so far, at least in our own programs, we have not seen any negative impact. Myriam, if you want to comment on GBM potential regulatory path and how to move forward with the (multiple speakers).

但到目前為止，至少在我們自己的專案中，我們還沒有看到任何負面影響。Myriam，如果你想評論一下膠質母細胞瘤（GBM）的潛在監管路徑以及如何推進（多位發言者）

Maybe one point to add. We also interacted with FDA on our UPEC program, and it was the same, right? We don't see any impact. We get responses quickly. Same quality unbiased, absolutely no changes compared to the past.

也許需要補充一點。我們也就 UPEC 計劃與 FDA 進行了互動，情況是一樣的，對嗎？我們沒有看到任何影響。我們很快就得到回應。品質不變，與過去相比絕對沒有任何變化。

For CVGBM, right, I said, if the data from Phase 1 and the expansion cohort show meaningful clinical activity, then -- and we would go for Phase 2, of course, we would do as a next step, I'm discussing. Again, this is all just under discussion, a randomized Phase 2 with an appropriate comparator arm and an appropriate endpoint.

對於 CVGBM，對的，我說，如果第 1 階段和擴展隊列的數據顯示出有意義的臨床活動，那麼 - 我們將進入第 2 階段，當然，我們將作為下一步進行，我正在討論。再次強調，這一切都還在討論中，這是一個隨機的第二階段，有適當的比較組和適當的終點。

And we haven't yet had any discussions with regulatory authorities so far because we wanted to await more data from Phase 1 knowing that this is a high-risk population. And we sort of like wanted to have more confidence that we will have indications as we go forward.

到目前為止，我們還沒有與監管機構進行任何討論，因為我們希望等待第一階段的更多數據，因為我們知道這是一個高風險族群。我們希望能夠更有信心，相信隨著我們不斷前進，我們會獲得一些跡象。

Great. Thank you.

偉大的。謝謝。

Roger Song, Jefferies.

傑富瑞 (Jefferies) 的羅傑宋 (Roger Song)。

Thanks for that day. And then taking on question, a couple of questions maybe the first one related to GBM given the Part B data can be second half and then you will have -- you will make go-forward decisions. So just curious what is the criteria to make that decision?

感謝那一天。然後回答問題，有幾個問題，也許第一個問題與 GBM 有關，因為 B 部分的數據可能是下半部分，然後您將 - 您將做出前進的決定。所以只是好奇做出這個決定的標準是什麼？

And then on the squamous small cell lung cancer, this multi-complex antigen selection is very interesting. Just curious, given you say 95% of the patient, they have a one-plus antigen, 50% have four-plus. Just curious in your preclinical model, do you see the difference when you -- the model only have for one versus four plus? You see the difference on the activity anti-tumor activity.

然後對於鱗狀小細胞肺癌，這種多複雜抗原選擇非常有趣。只是好奇，鑑於您說 95％ 的患者有一個加抗原，50％ 的患者有四個加抗原。只是好奇您的臨床前模型，您是否看到了差異——模型只有一個與四個以上？您可以看到抗腫瘤活性的差異。

The last part of the question is regarding your cash runway guidance into 2028. Just -- can you give us some color around how much operation is included in this cash runway guidance given you have a couple of ongoing pipeline and then new pipeline coming like GBM, squamous lung, and UTI? And then this cash will incur the Phase 1, Phase 2 implant? Thank you.

問題的最後一部分是關於您對 2028 年現金流的指導。只是——考慮到您有幾個正在進行的管道，然後還有新的管道即將推出，例如 GBM、鱗狀肺和 UTI，您能否向我們透露一下這個現金跑道指南中包含了多少操作？那麼這些現金將用於第一階段、第二階段的植入嗎？謝謝。

Okay. So Myriam three questions. One on GBM, I guess where the bar is or how we would assess go, no-go decisions? And the one on squamous on the number of antigens? And when do we see differences? And then maybe one for Axel on the cash runway.

好的。所以 Myriam 有三個問題。關於 GBM，我猜標準在哪裡或我們如何評估可以或不可以的決定？那麼鱗狀細胞癌的抗原數量是多少呢？我們什麼時候會看到差異？然後也許還有一條適合 Axel 的現金走道。

Okay. I'll start with the GBM question. And so yes, we have set basically high threshold for GBM. And basically, I would expect to see in our population immediate overall survival of 50 months or longer to say if it go or and/or also an overall response rate of about 20%. If we would see that in our population that would give us confidence to say, look, this could look promising and potentially warrant an investment into a Phase 2.

好的。我將從 GBM 問題開始。是的，我們為 GBM 設定了相當高的門檻。基本上，我希望看到我們人群的即時總體生存期達到 50 個月或更長時間，或者說總體反應率達到 20% 左右。如果我們在我們的人口中看到這一點，我們就會有信心說，看，這看起來很有希望，並且可能值得對第二階段進行投資。

Regarding your question on coverage for squamous program, which is I think it's a really interesting question. But I have to tell you that the animal models do not allow us to actually investigate how clinical efficacy in those animals would look like if they have a response to two antigens or four antigens. The animal model is actually -- or in our animal models, we cannot vaccinate against the targets we use to vaccinate human beings, right, because we have to vaccinate for murine antigens. And that's why no animal model would give you the answer to this.

關於您關於鱗狀細胞癌項目覆蓋範圍的問題，我認為這是一個非常有趣的問題。但我必須告訴你，動物模型不允許我們真正研究如果這些動物對兩種抗原或四種抗原有反應，它們的臨床療效會如何。動物模型實際上是 - 或者在我們的動物模型中，我們不能針對我們用於給人類接種疫苗的目標進行接種，對的，因為我們必須針對鼠類抗原進行接種。這就是為什麼沒有動物模型可以給你答案。

And the question you asked is the sort of like a million-dollar question, right? Do you -- do we need to have a broad immune response against multiple antigens to achieve maximum clinical efficacy or a deep and strong responses to few antigens that are the right ones enough to give you clinical efficacy?

您問的問題就像是一個價值百萬美元的問題，對嗎？我們是否需要對多種抗原產生廣泛的免疫反應才能獲得最大的臨床療效，或對少數抗原產生深度且強烈的免疫反應才能獲得臨床療效？

And based on the data from other not our own, we have seen some promising data. We are basically -- immune responses against on average four antigens showed a difference. And other trials suggested that two antigens are enough. So we don't really know the answer, but we would say based on all of our knowledge that some kind of diversity in terms of immune response would be good.

並且根據其他人提供的數據（不是我們自己的數據），我們看到了一些有希望的數據。我們基本上——針對平均四種抗原的免疫反應表現出差異。其他試驗顯示兩種抗原就足夠了。所以我們真的不知道答案，但根據我們所有的知識，我們可以說，免疫反應的某種多樣性是有益的。

And so hopefully, again, we would see responses to two more or more of those antigens that would then translate into clinical efficacy. So I cannot really give you an answer to the question because that's a one million question that we have to address in our clinical trials in the future.

因此，我們希望能夠再次看到對兩種或更多抗原的反應，然後將其轉化為臨床療效。所以我無法真正回答你這個問題，因為這是我們必須在未來的臨床試驗中解決的百萬個問題。

Yeah. In terms of the cash runway into 2028, so what I can tell you is that -- and we also want to be a little bit cautious here, but what I can tell you is that the current -- for the current core program, meaning our IND portfolio preparing for clinical start in 2026 as well as our oncology programs, GBM and squamous non-small cell lung cancer as well as our personalized cancer vaccine, the clinical phases are included.

是的。就 2028 年的現金流而言，我可以告訴您的是 - 我們也想在這裡保持謹慎，但我可以告訴您的是，當前 - 對於當前的核心計劃，即我們的 IND 產品組合準備在 2026 年開始臨床研究，以及我們的腫瘤學計劃、GBM 和鱗狀非小細胞肺癌以及我們的個性化癌症疫苗，都包括臨床階段。

But always, please remember that some of these clinical phases are also after the cash out. So everything, of course, is planned as the clinical pipeline is developed and planned for, but not all Phase 1 and Phase 2s are prior to the potential cash out. Hope that answers your question.

但請始終記住，其中一些臨床階段也是在兌現之後。因此，當然，一切都是在臨床管道開發和規劃時計劃好的，但並非所有第 1 階段和第 2 階段都在潛在的現金流之前。希望這能回答你的問題。

Thank you.

謝謝。

Eliana Merle, UBS.

瑞銀的 Eliana Merle。

Hi. This is Jasmine on for Ellie. Thanks so much for taking our question. Wanted to ask about your latest strategy on collaboration. So across oncology and the nonrespiratory infectious disease programs, what's your latest thinking about where you would want to potentially partner versus keep developing yourselves? Thanks.

你好。這是 Jasmine 為 Ellie 演唱的。非常感謝您回答我們的問題。想詢問一下你們最新的合作策略。那麼，在腫瘤學和非呼吸道傳染病計畫方面，您最近想在哪些方面進行潛在的合作，而不是繼續自行發展？謝謝。

That's a good question. I think in general, what we tried to do this year is really focus CureVac on what we are really good at, which is mostly technology innovation, research and I would say, early development. Of course, we have a few collaborations already in place. That's the one with GSK for the respiratory infectious disease program. We have a collaboration in place as well with MD Anderson Cancer Center or next generation shared off-the-shelf cancer vaccines.

這是個好問題。我認為總的來說，我們今年嘗試做的是真正將 CureVac 的重點放在我們真正擅長的領域，主要是技術創新、研究以及早期開發。當然，我們已經有一些合作。這是與葛蘭素史克合作的呼吸道傳染病計畫。我們也與 MD 安德森癌症中心合作，共同研發下一代現成的癌症疫苗。

And I think in general, as Axel just outlined, I feel we are in a position from a financial perspective, but also from a capability and manufacturing perspective to run the early clinical trials. Phase 1s and maybe depending on the indication also in Phase 2.

我認為總的來說，正如 Axel 剛才概述的那樣，我認為我們從財務角度，以及從能力和製造角度都能夠開展早期臨床試驗。第 1 階段，也可能取決於第 2 階段的指示。

But I think the goal, especially for the large PAs such as oncology would be clearly to partner than the late-stage development program with somebody that has real muscle in the field that really has the need to develop it more broadly and then eventually also commercialize worldwide.

但我認為，目標，特別是對於腫瘤學等大型 PA 來說，顯然是與後期開發計劃中的合作夥伴合作，與該領域真正有實力、真正需要更廣泛開發並最終在全球範圍內實現商業化的公司合作。

Great. Thank you.

偉大的。謝謝。

Roy Buchanan, Citizens.

羅伊·布坎南，公民。

Thanks for taking the questions. I had a few on the European patent proceedings. I guess can you give us a sense of the timelines for the infringement hearing and possibly that assuming that's positive, the damage proceedings for the 668 and 755, that was just upheld and solid.

感謝您回答這些問題。我有一些關於歐洲專利程序的事情。我想您能否給我們介紹一下侵權聽證會的時間表，並假設這是積極的，那麼針對 668 和 755 的損害訴訟，剛剛得到支持和堅定。

And then does Pfizer and BioNTech, do they have a chance to appeal the validity decision for 668? And then can you give a little bit of more detail on the subject to amendments comment in the slide 14, I think, or 6? Thanks.

那麼輝瑞和 BioNTech 是否有機會對 668 的有效性決定提出上訴？然後，您能否就幻燈片 14（我想是 6）中的修正案評論主題提供更多細節？謝謝。

Sure. I mean, the highlight kind of the key overarching timelines on slide 6, after financial presentation, right? So the kind of next milestones is we have a further European Patent Office hearing for our second poly-A patent, the 775 patent, which takes place on May 13 to 15. And then as it's a bifurcated process, should that validity be confirmed as well. It goes back to the infringement court.

當然。我的意思是，在財務簡報之後，第 6 張投影片上重點介紹了關鍵的整體時間表，對嗎？因此，下一個里程碑是，我們將於 5 月 13 日至 15 日舉行第二項 Poly-A 專利（775 專利）的進一步歐洲專利局聽證會。然後，由於這是一個分叉過程，其有效性也應該得到確認。它將返回侵權法庭。

In this case, it's the infringement court in Dusseldorf where the hearing is scheduled for July 1. And as I mentioned, it includes the 668 and if the validity is confirmed as well the 775 poly-A patent, then yes, there is no opportunity for the opposing partner to appeal.

該案將在杜塞爾多夫侵權法庭審理，審理時間定於 7 月 1 日。正如我所提到的，它包括 668 項專利，如果有效性得到確認，那麼 775 項 poly-A 專利也同樣如此，那麼是的，對方合作夥伴沒有機會上訴。

But if infringement is confirmed, that validity has been converted prior, that would nevertheless start at least the damages process in Europe, which -- don't call me exactly this, but my understanding is it can take up to one year to be completed. In the US, of course, it's different in the US you have one legal case, which will start in September 8 this year. And in the US, you have 1 process that covers validity, infringement as well as damages at the same time.

但如果侵權被確認，有效性已經提前轉換，那麼至少會啟動歐洲的損害賠償程序，雖然我不是很清楚這個程序，但我的理解是，它可能需要長達一年的時間才能完成。當然，在美國情況有所不同，在美國祇有一個法律案件，將於今年 9 月 8 日開始審理。而在美國，有一個流程同時涵蓋有效性、侵權行為以及損害賠償。

Yeah, I'm just curious to subject to amendment comment on the --

是的，我只是好奇關於修改意見--

Yeah. So the amendment was mostly related to the length of the poly-A tail, i.e., the number of adenine nucleotides that were included. It's quite technical, but I think we don't believe that this amendment will weaken our infringement position. I think that's the key point.

是的。因此，修正主要與 poly-A 尾的長度有關，即所包含的腺嘌呤核苷酸的數量。這是相當技術性的，但我認為我們不相信這項修正案會削弱我們的侵權地位。我認為這是關鍵點。

Okay. Great. And then maybe just throwing one on the Genmab collaboration that was terminated. Can you just give us the crux of why that was terminated and what stage it got to? Thanks.

好的。偉大的。然後也許只是將其中一個放在已終止的 Genmab 合作上。您能否告訴我們終止計劃的關鍵原因以及目前進展到什麼階段？謝謝。

Well, I think it's -- the question was with the Genmab and Genmab collaboration. So I think it was dormant for quite some time. It didn't really lead do anything -- so also in our interest to really focus on the most promising programs, I think we terminated the program in kind of mutual agreement.

嗯，我認為——問題在於 Genmab 和 Genmab 合作。所以我認為它已經休眠了相當長一段時間了。它實際上並沒有起到什麼作用——因此，為了真正專注於最有前途的項目，我認為我們以雙方同意的方式終止了該項目。

Okay. Thank you.

好的。謝謝。

Jonathan Miller, Evercore ISI.

喬納森·米勒（Jonathan Miller），Evercore ISI。

Hi guys, thanks for taking the question and congrats on the recent progress. Maybe i'll start with one on the non-small cell program. Obviously, you like others are trying to develop this primarily in early-stage setting. But of course, the Phase 1 is in later-stage patients and metastatic patients. So I'd just love to get a sense for what you're hoping to see in that Phase 1 data that would move you to early-stage setting?

大家好，感謝您的提問，並祝賀您最近的進展。也許我會從非小型蜂窩計劃開始。顯然，您和其他人一樣，主要嘗試在早期階段開發此功能。但當然，第一階段是針對晚期患者和轉移性患者。所以我很想了解您希望在第一階段的資料中看到什麼，以便進入早期階段？

Do you need to see efficacy signs of early efficacy in metastatic setting beyond maybe immune engagement or T cell induction for instance? Do you need to see increases in ORR, increases in PFS to drive early stage or would safety and immune engagement be sufficient to make that decision? And then secondly, maybe on the IP case. But I'll let you answer cancer first, please.

除了免疫參與或 T 細胞誘導之外，您是否需要觀察轉移環境中早期療效的療效跡象？您是否需要看到 ORR 的增加、PFS 的增加來推動早期階段，或者安全性和免疫參與是否足以做出該決定？其次，也許是關於智慧財產權案件。但請你先回答癌症的問題。

Okay. No, it's a great question. So as we said, right, we do believe that the precision immunotherapies will work in earlier cancer settings because the immune system is functioning, and you have less tumor burden to control. And so with that, basically, our criteria and primary objectives for the Phase 1 trial in squamous non-small cell lung cancer would be to see immune responses against the encoded antigens. So that would be sort of like the primary hurdle.

好的。不，這是一個很好的問題。所以正如我們所說的，我們確實相信精準免疫療法將在早期癌症環境中發揮作用，因為免疫系統正在發揮作用，並且需要控制的腫瘤負擔較少。因此，基本上，我們對鱗狀非小細胞肺癌進行第一階段試驗的標準和主要目標是觀察針對編碼抗原的免疫反應。所以這可以說是主要的障礙。

If we see then, of course, clinical activity, that would be most encouraging. But we also basically really want to test this treatment in earlier stages of cancer because we have seen with other programs, sort of like similar platform that in advanced metastatic stages of cancer, these immunotherapies do not work that well.

當然，如果我們看到臨床活動，那將是最令人鼓舞的。但我們也確實想在癌症早期階段測試這種治療方法，因為我們已經看到其他項目，類似平台，在癌症晚期轉移階段，這些免疫療法效果並不好。

So immune response is our primary target to see that we see strong immune responses against the encoded antigens. And that would be encouraging and all we want to see because we would then sort of like to do an expansion cohort in earlier settings and from there, then look for clinical activity signals in the earlier cancer settings that would then determine whether we go for Phase 2 and beyond in that setting. Does it answer your question?

因此，免疫反應是我們的主要目標，即觀察對編碼抗原的強烈免疫反應。這將是令人鼓舞的，也是我們希望看到的，因為我們想在早期環境中進行擴展隊列研究，然後從那裡尋找早期癌症環境中的臨床活動信號，從而決定我們是否在該環境中進入第 2 階段及以後的階段。它回答了你的問題嗎？

Yeah, absolutely. I guess one more then on that. On the novel X-exome antigens, I'd be really curious to see more of that preclinical data, more that antigen development data. Do you have plans in the near term to discuss that antigen selection process more to get deeper into the contribution of those X-exome novel antigens to immune engagement and efficacy?

是的，絕對是如此。我想，那還得再說一次。對於新型 X-exome 抗原，我非常想了解更多臨床前數據和抗原開發數據。您是否計劃在近期進一步討論抗原選擇過程，以更深入地了解這些 X-exome 新抗原對免疫參與和功效的貢獻？

So we are discussing that we would like to discuss and disclose more. We have to see when is what's possible. It's too exciting, and I know everybody is interested right? There are some, let's say, internal checks we have to take before we can go public and share all the data around that.

因此我們正在討論我們想要討論和披露的更多資訊。我們必須看看什麼時候才有可能。這太令人興奮了，我知道大家都很感興趣，對吧？在我們公開並分享所有相關數據之前，我們必須進行一些內部檢查。

Okay, makes sense. On the IP front, the poly-A patent that was just held up in the EPO, is this the same set of IP that was struck down in the UK court last year, I believe it was in the last year? And if so, can you discuss maybe some of the differences between those two cases and whether we should be reading through from some prior that they brought into the potential for the patents in the US court?

好的，有道理。在智慧財產權方面，剛在歐洲專利局被擱置的 Poly-A 專利，是否與去年在英國法院被駁回的智慧財產權是同一套呢？我相信是去年？如果是的話，您能否討論一下這兩個案例之間的一些差異，以及我們是否應該從一些先前的案例中了解它們在美國法院提起專利訴訟的可能性？

John, this is quite a complex question, and maybe we can do a follow-up call on this. But I mean, the UK, the situation is different. The assessment is different. I mean -- and just the fact that the German Validity Court came to a different conclusion, I think, highlights some of these differently. But Jon, very happy to set up a follow-on call with our IT team to go more into the details.

約翰，這是一個相當複雜的問題，也許我們可以就此進行後續討論。但我的意思是，英國的情況有所不同。評價不同。我的意思是——我認為，德國有效性法院得出了不同的結論，這一事實從不同角度凸顯了其中的一些問題。但 Jon 非常高興與我們的 IT 團隊進行後續通話，以便更詳細地討論。

All right. Fair enough. I look forward to that.

好的。很公平。我對此充滿期待。

[Kiara Manitroni, Kempen].

[Kiara Manitroni，肯彭]。

Hello team. Thanks a lot for taking my question. This is Kiara. I am on for Suzanne van Voorthuizen. Congratulations with the progress. I was wondering on the glioblastoma program. How should we think about the translation of immunogenicity data to tumor responses? And then I was curious to know for the next indication for the shared antigen vaccine, how do you usually go about selecting indication besides, let's say, having a common expression of the antigen on these tumors?

大家好，團隊。非常感謝您回答我的問題。這是 Kiara。我代表蘇珊娜‧範‧福爾修仁 (Suzanne van Voorthuizen)。恭喜取得進展。我對膠質母細胞瘤計畫感到好奇。我們該如何看待免疫原性數據對腫瘤反應的轉換？然後我很好奇，對於共享抗原疫苗的下一個適應症，除了在這些腫瘤上具有抗原的共同表達之外，您通常如何選擇適應症？

Okay. So I'll start with the GBM question. So we have shared at the congresses that in that first Part A of the trial, a dose escalation part of the trial where we were able to analyze 13 patients. We also saw in 7 patients who entered the trial with a residual tumor mass, we saw one partial response. Unfortunately, we couldn't -- unfortunately, this passion didn't have enough material to do the immune -- immuno-assessment. And that's why it's hard to correlate.

好的。因此我將從 GBM 問題開始。因此，我們在大會上分享了在試驗的第一部分 A 中，即試驗的劑量遞增部分，我們能夠分析 13 名患者。我們也發現，在參加試驗的 7 名有殘留腫瘤的患者中，有一名出現了部分反應。不幸的是，我們不能——不幸的是，這種激情沒有足夠的材料來進行免疫——免疫評估。這就是為什麼很難關聯。

But normally coming to your question, if we see new responses, we would like to, of course, see a translation into a growth control or clinical overall response. But it's not happening in all cases, right, because we know that sometimes immunotherapy just controls the tumor growth and can keep the tumor stable and -- but still by doing so can prolong overall survival.

但通常回答你的問題，如果我們看到新的反應，我們當然希望看到其轉化為生長控製或臨床整體反應。但這並非在所有情況下都會發生，因為我們知道有時免疫療法只是控制腫瘤生長並能保持腫瘤穩定 - 但這樣做仍然可以延長整體生存期。

So why, again, it would be highly encouraging with any of our precision immunotherapy treatments, if we see more clinical responses, the real benchmark to make a decision go, no-go is based on overall survival because if you don't have too much shrinkage, you can still have tumor more growth control and with that prolonged overall survival. Does that answer your question?

那麼，如果我們看到更多的臨床反應，我們的任何精準免疫療法都會令人鼓舞，而決定是否繼續治療的真正基準是基於總體生存率，因為如果沒有太多的收縮，你仍然可以更好地控制腫瘤的生長，從而延長總體生存率。這回答了你的問題嗎？

Yes, very clear. Thank you.

是的，非常清楚。謝謝。

Okay, on GBM. And then the selecting indications. So in our antigen discovery approach, we sort of like screen antigens and then run them through our algorithms using like everybody else, but our unique proprietary sort of like selection and ranking criteria. And only for antigens when they sort of like has, we would basically pick them and consider them to be encoded on one of our candidates.

好的，在 GBM 上。然後選擇指示。因此，在我們的抗原發現方法中，我們有點像篩選抗原，然後像其他人一樣使用我們的演算法來運行它們，但我們使用獨特的專有選擇和排名標準。只有當抗原有某種相似之處時，我們才會選擇它們並考慮將它們編碼在我們的候選物之一上。

What we usually do is then, in oncology, we have designed one year or so ago, a strategic therapeutic area strategy where we looked across different cancer types. A ton of cancer types had a certain criteria in terms of are these cancers responding to immunotherapy, is there a high unmet medical need, competitive landscape, commercial case and so on and sort of like prioritize the cancer cases.

在腫瘤學領域，我們通常的做法是，大約在一年前，我們就設計了一個策略性治療領域策略，研究不同類型的癌症。許多癌症類型都有一定的標準，例如這些癌症是否對免疫療法有反應、是否存在大量未滿足的醫療需求、競爭格局、商業案例等，並優先考慮癌症病例。

And then in those highly prioritized or higher ranked cancer indications, we drove antigen discovery activities that then led to the identification of potential antigens that we ran through our algorithm and then came up with the antigens.

然後，在那些優先考慮或排名較高的癌症適應症中，我們推動了抗原發現活動，從而識別出潛在的抗原，並透過我們的演算法運行這些抗原，然後得出這些抗原。

And of course, as you can imagine, when you look at all cancer types, lung cancer comes up as the number one priority often highly responding to immunotherapy. And that's where basically some of our antigens discovery efforts initially focused on lung cancer, but also in others. But we prioritize this program for the reasons I mentioned. So I hope this answer your question.

當然，正如您所想像的，當您查看所有癌症類型時，肺癌是首要考慮因素，並且通常對免疫療法反應良好。這就是我們的一些抗原發現工作最初集中於肺癌的地方，但也關注其他癌症。但出於我提到的原因，我們優先考慮這個項目。我希望這能回答你的問題。

Yes, absolutely. Thank you.

是的，絕對是。謝謝。

Max Star, Goldman Sachs.

高盛的馬克斯·斯塔爾 (Max Star)。

This is Max on behalf of Rajan Sharma. The first one is about R&D. How do you expect cost to progress through 2025 given your clinical development plans? And the second question is about the lung cancer trial. Do you plan to check how the response rate could change after patients receive the vaccine because I believe the first treatment is supposed to be pembro or pembro combined with chemo. Then you inject patients with a vaccine. Just curious how the clinical trial design is for that part?

我是 Rajan Sharma 的 Max。第一個是關於研發。根據您的臨床開發計劃，您預計到 2025 年成本將如何變化？第二個問題是關於肺癌試驗的。您是否計劃檢查患者接種疫苗後反應率如何變化，因為我相信第一種治療方法應該是 pembro 或 pembro 與化療相結合。然後給病人注射疫苗。只是好奇那部分的臨床試驗設計是怎麼樣的？

Okay. So maybe I'll start with the second question because I have a question or clarifying questions for your first one. So in our Phase 1 trial, again, we select patients with metastatic disease who are on pembro9 maintenance. These patients, usually with lung cancer, very few will have a complete response, so they will have some sort of like residual tumor that is stable under pembrolizumab monotherapy, and we are adding the vaccine.

好的。因此，也許我會從第二個問題開始，因為我對你的第一個問題有一個疑問或澄清問題。因此，在我們的第 1 期試驗中，我們再次選擇了接受 pembro9 維持治療的轉移性疾病患者。這些患者通常患有肺癌，很少有人會完全緩解，因此他們會留下某種殘留腫瘤，在接受派姆單抗單藥治療後會保持穩定，而我們正在添加疫苗。

And again, what we would look at is immune responses. And we will also monitor clinical efficacy. So if we do see a partial response or tumor shrinkage by adding the vaccine, we will definitely measure that and also report that. We look at progression-free survival, duration of response, and other sort of like endpoint-driven parameters in that setting.

再次強調，我們要關注的是免疫反應。我們也將監測臨床療效。因此，如果我們確實透過添加疫苗看到部分反應或腫瘤縮小，我們肯定會測量並報告。我們在該環境中觀察無惡化存活期、反應持續時間和其他類似的終點驅動參數。

But basically, patients come in are stable under pembrolizumab. And we are adding the vaccine. And from that moment on, we will measure -- we'll have regular tumor measurements to see the impact of adding the vaccine. And then for your first question, R&D cost, can you please repeat because I wasn't sure what you were asking.

但基本上，患者在接受派姆單抗治療後，情況都很穩定。我們正在添加疫苗。從那一刻起，我們將進行測量——我們將定期進行腫瘤測量，以觀察添加疫苗的影響。然後對於您的第一個問題，研發成本，您能否重複一遍，因為我不確定您在問什麼。

The question was on R&D spend '25 moving forward. I don't know if you want to comment if you want to comment in detail, Axel?

問題是關於 25 年以後的研發支出。我不知道您是否想詳細評論，阿克塞爾？

I think there is -- as I said earlier, there are two things maybe to this equation. As I said earlier to another analysts that we included our core pipeline into also the early clinical phases into the cash runway. Of course, very important to recognize is that as you know, we came from a transformation in 2024, and we continue to try to have more efficiency -- more cost efficiency and reduce our overall expenses.

我認為——正如我之前所說，這個等式可能包含兩點。正如我之前對其他分析師所說的那樣，我們將核心產品線也納入了早期臨床階段的現金流中。當然，非常重要的是要認識到，正如你所知，我們在 2024 年經歷了轉型，我們將繼續努力提高效率、提高成本效率並降低整體開支。

And that, of course, applied. And on the other side, as you know, we move this company being more of a biotech pipeline company, meaning that we focus very much on our -- from a cost -- R&D cost perspective on our pipeline programs. So there, of course, we try to be as efficient and focused as possible. I don't know if that answers your question.

這當然適用。另一方面，正如您所知，我們將這家公司定位為生物技術管道公司，這意味著我們非常關注我們的管道項目——從成本角度來看——研發成本。因此，我們當然會盡力做到有效率和專注。我不知道這是否回答了你的問題。

Got it. Can I slip in another question. I noticed that one of your charts still declining mRNA integrity at 25 degrees Celsius. Could you talk about that? I think it's slide 13.

知道了。我可以再問一個問題嗎？我注意到您的一張圖表顯示，在 25 攝氏度時 mRNA 完整性仍在下降。你能談談這個嗎？我認為是第 13 張投影片。

Yes. Okay. So you're talking about our proprietary LNP where I introduce the data on slide 13, right? where I showed RNA integrity and on the left side, right, where basically the data there -- I guess your question is about the blue line where free strike and RNA integrity decreased to something around 58%, 60%. Is that the question?

是的。好的。所以您說的是我們的專有 LNP，我在第 13 張投影片上介紹了數據，對嗎？我展示了 RNA 完整性，在左側和右側，基本上那裡的數據——我猜你的問題是關於藍線的，其中自由打擊和 RNA 完整性下降到大約 58%、60%。這是問題嗎？

Yeah.

是的。

This is still with specifications. Right? This is still with a specification. If you look at integrity and where the specifications are with regulators. And so that's why this is encouraging because remember, this is at room temperature. Our mRNA at room temperature. And after one year at room temperature, it's still in terms of integrity within the specifications agreed with regulators today.

這還是有規格的。正確的？這還是有規範的。如果您看一下完整性以及監管機構的規範。這就是為什麼這是令人鼓舞的，因為請記住，這是在室溫下。我們的 mRNA 處於室溫下。在室溫下放置一年後，其完整性仍然符合當今監管機構商定的規格。

Got it. All right. Thank you.

知道了。好的。謝謝。

We have reached the end of our question-and-answer session. I would like to turn the conference back over to Sarah for closing remarks.

我們的問答環節已經結束。我想將會議交還給莎拉，請她做最後發言。

Thank you. 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.

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