CureVac NV (CVAC) 2024 Q3 法說會逐字稿

Portions of this transcript marked (audio in progress) indicate audio problems. The missing text will be supplied if a replay becomes available.

此文字記錄中標記為（音訊正在進行中）的部分錶示音訊問題。如果可以重播，將提供缺少的文字。

(audio in progress) and our Chief Financial Officer, Axel Malkomes.

（音訊正在進行中）和我們的財務長 Axel Malkomes。

You may have seen the press release last week announcing his joining the CureVac division. Ulrike Vogt, Senior Vice President Finance, will be available for the Q&A session. 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. 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, November 12, 2024.

您可能已經看到上周宣布他加入 CureVac 部門的新聞稿。財務資深副總裁 Ulrike Vogt 將出席問答環節。請注意，本次電話會議正在進行網路直播，並將存檔在我們網站投資者關係下的活動和演示部分。在我們開始一些前瞻性陳述之前。本次電話會議中的討論和您問題的答覆反映了截至今天（2024 年 11 月 12 日星期二）管理層的觀點。

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

我們將發表聲明並回答您的問題，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有重大差異。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。我現在將把電話轉給亞歷山大。

Thank you, Sarah. Ladies and gentlemen, good morning, good afternoon to everyone on the webcast. The first nine months and particularly the third quarter of 2024 marked a turning point for CureVac. We made significant progress on our 2024 priorities, taking decisive steps, rightsizing the company, streamlining our processes and improving our business operations. We have successfully delivered on key milestones, including a new licensing agreement with GSK announced in July.

謝謝你，莎拉。女士們、先生們，網路直播中的大家早安、下午好。2024 年前 9 個月，特別是第三季度，標誌著 CureVac 的轉捩點。我們在 2024 年優先事項上取得了重大進展，採取了果斷措施，調整了公司規模，簡化了流程並改善了業務運作。我們已經成功實現了關鍵的里程碑，包括 7 月宣布與葛蘭素史克 (GSK) 簽署的新授權協議。

This agreement valued at up to EUR1.45 billion includes an upfront payment of EUR400 million, which was fully booked in the third quarter. Additional potential milestones and royalty payments from this agreement are expected to provide significant capital going forward while strongly validating our mRNA technology. Alongside this, we launched a corporate redesign, including a roughly 30% reduction of our workforce, which will be completed by the end of this year. These efforts helped us to reduce costs while maintaining a strong focus on research and development. Looking ahead, we set clear development priorities with a sharpened focus on high-value indications in oncology and infectious diseases.

該協議價值高達14.5億歐元，其中包括4億歐元的預付款，該款項已於第三季全部預訂完畢。該協議的其他潛在里程碑和特許權使用費預計將為未來提供大量資金，同時有力地驗證我們的 mRNA 技術。除此之外，我們也啟動了企業重新設計，包括裁員約 30%，計畫將於今年底完成。這些努力幫助我們降低成本，同時保持對研發的高度關注。展望未來，我們制定了明確的發展重點，重點在於腫瘤學和傳染病領域的高價值適應症。

In oncology, our Phase 1 study in glioblastoma has yielded promising preliminary data showing the potential of our mRNA technology in this highly aggressive cancer. And today, we are disclosing a new cancer vaccine program targeting squamous non-small cell lung cancer, expanding our off-the-shelf cancer vaccine pipeline. In infectious diseases, we launched a new program for urinary tract infections or UTIs, one of the world's most common infections. This program addresses a critical unmet medical need driven by recurring infections and the increase in prevalence of antibiotic resistance against uropathogenic E. coli, the bacteria that primarily causes these infections.

在腫瘤學方面，我們對膠質母細胞瘤的一期研究已經產生了有希望的初步數據，顯示了我們的 mRNA 技術在這種高度侵襲性癌症中的潛力。今天，我們宣布了一項針對鱗狀非小細胞肺癌的新癌症疫苗計劃，擴大了我們現成的癌症疫苗產品線。在傳染病方面，我們針對泌尿道感染或泌尿道感染（世界上最常見的感染之一）啟動了一項新計劃。該計劃解決了因反覆感染和泌尿道致病性大腸桿菌（主要引起這些感染的細菌）抗生素抗藥性普遍增加而導致的未滿足的關鍵醫療需求。

Our UTI program exemplifies our focus on leveraging our technology for areas of high unmet need with significant commercial potential. On slide 5, you can see this achievement in the context of our transformation journey. After I started in April 2023, we conducted a thorough business analysis, identifying key areas to improve our financial discipline, reducing unneeded pandemic era infrastructure and focusing the organization on innovation and R&D. In 2024, we are executing on these insights. We have launched a corporate redesign, which is on track for a roughly 30% workforce reduction by the end of this year without compromising our R&D and manufacturing capabilities.

我們的 UTI 計劃體現了我們專注於利用我們的技術來滿足需求高度未滿足且具有巨大商業潛力的領域。在幻燈片 5 上，您可以在我們的轉型之旅中看到這項成就。我於 2023 年 4 月入職後，我們進行了徹底的業務分析，確定了改善財務紀律的關鍵領域，減少了大流行時期不必要的基礎設施，並將組織重點放在創新和研發上。2024 年，我們將落實這些見解。我們已經啟動了企業重新設計，預計到今年年底將裁員約 30%，而不會影響我們的研發和製造能力。

Operational expenses are expected to decrease by over 30% starting in 2025. The EUR400 million upfront payment from our new licensing agreement with GSK was fully booked in the third quarter, providing us with a strong cash position of EUR551 million at the end of September and resulting in a net profit for the first nine months. As we approach the end of 2024, we are now leaner, more strategically aligned and financially stronger. And from this position of strength, we will double down on research and development activities with a focus on high-value opportunities in oncology and infectious diseases.

從 2025 年開始，營運費用預計將減少 30% 以上。我們與 GSK 簽訂的新許可協議中的 4 億歐元預付款已在第三季度全部入賬，為我們在 9 月底提供了 5.51 億歐元的強勁現金頭寸，並導致前 9 個月實現淨利潤。隨著 2024 年底的臨近，我們現在更加精簡、策略更加一致、財務更加強大。憑藉這一優勢，我們將加倍投入研發活動，並專注於腫瘤學和傳染病領域的高價值機會。

On slide 6, we outlined the pipeline expansion in both oncology and infectious diseases. In oncology, shown on the left, our pipeline expansion spans both off-the-shelf and personalized cancer vaccines. For the off-the-shelf cancer vaccines, we are disclosing a new shared antigen cancer vaccine program in squamous non-small cell lung cancer, which will include novel cancer antigens derived from our proprietary antigen discovery. We are preparing for IND and CTA submissions in the first half of 2025 and expect to start Phase 1 trial shortly thereafter. Discovery activities for additional shared antigen programs continue with a second clinical candidate expected in 2026. Preclinical development of a fully personalized cancer vaccine candidate is also progressing with the first candidate expected to enter the clinic in the second half of 2026.

在投影片 6 上，我們概述了腫瘤學和傳染病領域的產品線擴張。在腫瘤學領域，如左圖所示，我們的產品線擴展涵蓋現成的和個人化的癌症疫苗。對於現成的癌症疫苗，我們正在披露一種針對鱗狀非小細胞肺癌的新的共享抗原癌症疫苗計劃，其中將包括源自我們專有抗原發現的新型癌症抗原。我們正在準備 2025 年上半年的 IND 和 CTA 提交，預計不久後將開始第一階段試驗。其他共享抗原計畫的發現活動仍在繼續，預計將於 2026 年推出第二個臨床候選計畫。完全個人化癌症候選疫苗的臨床前開發也正在取得進展，第一個候選疫苗預計將於 2026 年下半年進入臨床。

In infectious diseases, we are also following a dual strategy, having licensed our most advanced program in respiratory diseases to GSK by focusing our proprietary programs, primarily on non-respiratory diseases with high unmet medical needs. Here, we have launched a new program for urinary tract infections, which are the world's most common infections. And Myriam will present the promising preclinical data for this program later in the presentation. Before I go into the business update, I'm delighted to have our new Chief Financial Officer, Axel Malkomes, who joined CureVac just yesterday on the call with us. On behalf of the whole CureVac team, welcome.

在傳染病方面，我們也遵循雙重策略，將我們在呼吸系統疾病方面最先進的項目授權給葛蘭素史克，重點關注我們的專有項目，主要針對醫療需求未滿足的非呼吸系統疾病。在這裡，我們針對泌尿道感染啟動了一項新計劃，泌尿道感染是世界上最常見的感染。Myriam 將在稍後的演示中展示該專案有前景的臨床前數據。在介紹業務更新之前，我很高興有我們新任財務長 Axel Malkomes 參加我們的電話會議，他昨天才剛加入 CureVac。我代表整個 CureVac 團隊表示歡迎。

Axel brings over 30 years of experience across both the corporate and banking sides of our industry. His deep expertise will be crucial for the next chapter of CureVac as we advance our strategic initiatives and strengthen our financial foundation. Axel, would you like to say a few words?

Axel 在我們行業的企業和銀行方面擁有 30 多年的經驗。隨著我們推進策略性舉措並加強我們的財務基礎，他深厚的專業知識對於 CureVac 的下一章至關重要。阿克塞爾，你願意說幾句話嗎？

Thank you, Alex, and good morning, good afternoon to everyone on the webcast and conference call. I'm truly excited to join CureVac during this pivotal moment in the company's evolution. I believe CureVac is poised to make continued remarkable progress in development of innovative mRNA-based medicines. By applying my expertise in financial management and corporate growth, I'm convinced I can help drive CureVac's mission forward and contribute to its future success.

謝謝你，亞歷克斯，網路廣播和電話會議上的每個人都早上好，下午好。我非常高興能在公司發展的這個關鍵時刻加入 CureVac。我相信 CureVac 有望在基於 mRNA 的創新藥物的開發方面繼續取得顯著進展。透過運用我在財務管理和企業發展方面的專業知識，我相信我可以幫助推動 CureVac 的使命向前發展，並為其未來的成功做出貢獻。

Thank you, Axel. As we continue moving forward with our business and pipeline priorities, it's important to highlight what makes CureVac unique. On slide 8, you can see these key strategic and technological differentiators that set CureVac apart in the mRNA field. In terms of strategic differentiators, we have a dual strategy in oncology, working on both off-the-shelf and personalized cancer vaccines to cover a wide range of cancer types. We use a similar dual approach in infectious diseases, where we are focusing on proprietary programs for non-respiratory diseases like viral, bacterial or fungal infections, while we have out-licensed our respiratory disease programs to GSK.

謝謝你，阿克塞爾。隨著我們繼續推進我們的業務和管道優先事項，重要的是要強調 CureVac 的獨特之處。在幻燈片 8 上，您可以看到這些關鍵的策略和技術優勢，使 CureVac 在 mRNA 領域脫穎而出。在策略差異化方面，我們在腫瘤學方面採取雙重策略，致力於開發現成的和個人化的癌症疫苗，以涵蓋廣泛的癌症類型。我們在傳染病方面採用了類似的雙重方法，我們專注於針對病毒、細菌或真菌感染等非呼吸道疾病的專有項目，同時我們將呼吸道疾病項目授權給葛蘭素史克。

Our scalable manufacturing capabilities including the RNA printer, gives us the flexibility to produce preclinical and clinical trial materials efficiently. And our strong intellectual property portfolio further supports our innovation by protecting our technology. In terms of technology differentiators, our precision mRNA backbone is built on 20 years of experience helping us design highly efficient mRNA constructs that improve protein expression and lower dose efficiency. In oncology, we have a unique ability to discover new classes of antigens, which paves the way for innovative cancer treatments. And our work on advanced lipid nanoparticle delivery system tailored for specific indications aims to enhance the effectiveness and stability of our vaccines. Together, these differentiators give us a strong competitive position and drive our mission to develop transformative medicines for patients.

我們的可擴展製造能力（包括 RNA 印表機）使我們能夠靈活且有效率地生產臨床前和臨床試驗材料。我們強大的智慧財產權組合透過保護我們的技術進一步支持我們的創新。就技術差異化而言，我們的精準 mRNA 骨幹建立在 20 年的經驗基礎上，幫助我們設計高效的 mRNA 構建體，從而改善蛋白質表現並降低劑量效率。在腫瘤學領域，我們擁有發現新型抗原的獨特能力，這為創新癌症治療鋪平了道路。我們針對特定適應症量身定制的先進脂質奈米顆粒遞送系統的工作旨在提高我們疫苗的有效性和穩定性。這些優勢共同賦予我們強大的競爭地位，並推動我們實現為患者開發變革性藥物的使命。

Slide 9 shows how our differentiators feed directly into the key focus area of oncology and infectious diseases. Our precise mRNA backbone and proprietary delivery systems are at the heart of our technology platform, which is continuously evolving with the aim to deliver best-in-class products. By focusing our development efforts on high potential areas in oncology and infectious diseases, we are positioning ourselves to deliver impactful health solutions. And with that, I will hand over to Myriam to explain how we're turning these technologies into a strong focused clinical pipeline.

投影片 9 展示了我們的差異化優勢如何直接進入腫瘤學和傳染病的重點領域。我們精確的 mRNA 主幹和專有的遞送系統是我們技術平台的核心，該平台不斷發展，旨在提供一流的產品。透過將我們的開發工作重點放在腫瘤學和傳染病的高潛力領域，我們將自己定位為提供有影響力的健康解決方案。接下來，我將請 Myriam 解釋我們如何將這些技術轉變為強大的重點臨床管道。

Thank you, Alex, and good morning, good afternoon to everyone. Moving on to slide 10. Let me outline our most recent pipeline, which reflects our focused strategic approach to high-value development programs relevant to patients. Both our existing programs and the new programs disclosed today demonstrate our commitment to selecting indications where mRNA technology can make a substantial difference, addressing unmet clinical needs and attractive market opportunities. In oncology, our existing pipeline for off-the-shelf cancer vaccines is led by our Phase 1 study in patients with resected glioblastoma, which has recently provided promising data for the completed dose escalation Part A of the study.

謝謝你，亞歷克斯，大家早安，下午好。繼續看投影片 10。讓我概述一下我們最近的產品線，它反映了我們針對與患者相關的高價值開發專案的重點策略方法。我們現有的項目和今天披露的新項目都表明我們致力於選擇 mRNA 技術可以發揮重大作用的適應症，解決未滿足的臨床需求和有吸引力的市場機會。在腫瘤學方面，我們現有的現成癌症疫苗產品線以針對膠質母細胞瘤切除患者的一期研究為主導，該研究最近為該研究完成的劑量遞增部分提供了有希望的數據。

The study started enrollment for the dose confirmation Part B in August 2024, testing the recommended dose of 100 micrograms and enrollment is progressing well. We also announced a new program with an off-the-shelf cancer vaccine to treat patients with squamous non-small cell lung cancer. The vaccine candidate to be tested and codes for new antigens discovered with our proprietary antigen discovery platform. In the infectious disease area, our most advanced programs cover respiratory indications fully licensed to GSK. Programs for seasonal influenza, avian influenza, and COVID-19 are based on CureVac's proprietary second-generation mRNA backbone and are currently in Phase 2 development.

研究於 2024 年 8 月開始劑量確認 B 部分的入組，測試了 100 微克的建議劑量，入組進展順利。我們還宣布了一項新計劃，使用現成的癌症疫苗來治療鱗狀非小細胞肺癌患者。待測試的候選疫苗和編碼是透過我們專有的抗原發現平台發現的新抗原。在傳染病領域，我們最先進的項目涵蓋了獲得 GSK 完全許可的呼吸系統適應症。針對季節性流感、禽流感和 COVID-19 的專案是基於 CureVac 專有的第二代 mRNA 主幹，目前正處於第二階段開發。

GSK recently announced positive Phase 2 headline data for seasonal influenza, confirming strong antibody targets against influenza A, strain and most importantly, also against the notoriously challenging influenza B strain compared to the [estimated] standard of care in younger and older adults. The study met all three defined success criteria. And GSK reported that the program is progressing to Phase 3 next year. Based on the validation of our platform in infectious diseases, we launched a new proprietary program to develop a prophylactic vaccine against uropathogenic E. coli, the primary cause of urinary tract infections, which rank amongst the most common infections worldwide.

葛蘭素史克(GSK) 最近宣布了季節性流感的第2 期總體數據，確認了針對甲型流感病毒株的強大抗體靶點，最重要的是，與年輕人和老年人的[估計]護理標準相比，也針對臭名昭著的具有挑戰性的乙型流感病毒株。該研究符合所有三個定義的成功標準。葛蘭素史克報告稱，該計畫將於明年進入第三階段。基於我們在傳染病方面的平台的驗證，我們啟動了一項新的專有計劃，以開發針對尿路致病性大腸桿菌的預防性疫苗，尿路致病性大腸桿菌是尿路感染的主要原因，泌尿道感染是全球最常見的感染之一。

I will go into more detail later in the presentation. In the third therapeutic area, molecular therapies, while the collaboration with the Schepens Eye Research Institute in ocular diseases was recently terminated, we continue to develop and optimize mRNA therapeutics in different areas. We are committed to focus our pipeline on selecting indications where mRNA technology can outperform conventional approaches, guided by our mission to advance innovation in preventive and therapeutic health solutions. On slide 11, we delve deeper into our oncology strategy, where we see tremendous opportunity for mRNA cancer vaccines to bring precision immunotherapy to large patient populations. We have made significant progress in advancing our two-pronged strategy for both off-the-shelf and personalized cancer vaccine development.

我將在稍後的演示中詳細介紹。在第三個治療領域，分子療法，雖然最近終止了與Schepens眼科研究所在眼部疾病的合作，但我們繼續在不同領域開發和優化mRNA療法。在我們推動預防和治療健康解決方案創新的使命的指導下，我們致力於將我們的產品線集中在選擇 mRNA 技術能夠優於傳統方法的適應症上。在幻燈片 11 中，我們深入研究了我們的腫瘤學策略，我們看到 mRNA 癌症疫苗為大量患者群體帶來精準免疫治療的巨大機會。我們在推動現成和個人化癌症疫苗開發的雙管齊下策略方面取得了重大進展。

As a brief reminder, the off-the-shelf assets in our oncology pipeline target tumor antigens that are shared across different patient populations and/or tumor types to induce de novo or amplify pre-existing immune responses in different cancer settings, including advanced stages of cancer. CVGBM, our lead oncology clinical candidate is currently being evaluated in a Phase 1 study in patients with resected glioblastoma and encoding known antigens relevant to this highly aggressive brain cancer. All our next-generation shared antigen cancer vaccines, including the one in squamous non-small cell lung cancer, feature novel antigens discovered through our proprietary antigen discovery platform and will expand our pipeline with new clinical candidates in 2025 and 2026. By identifying novel shared antigen targets, also within our global collaboration with MD Anderson, we aim to make our vaccines even more effective in reducing the risk of tumor recurrence and enhancing outcomes for patients in different cancer settings. For the other part of our oncology strategy, applying personalized cancer vaccines, whole genome sequencing of individual patients' tumor samples, combined with advanced bioinformatics is utilized to identify neo-antigens and/or novel tumor-associated antigens unique to a patient's individual genomic tumor profile.

簡單提醒一下，我們的腫瘤學產品線中的現成資產針對不同患者群體和/或腫瘤類型共享的腫瘤抗原，以從頭誘導或放大不同癌症環境（包括晚期）中預先存在的免疫反應癌症。CVGBM 是我們的主要腫瘤學臨床候選藥物，目前正在一項針對已切除的膠質母細胞瘤患者的一期研究中進行評估，並編碼與這種高度侵襲性腦癌相關的已知抗原。我們所有的下一代共享抗原癌症疫苗，包括鱗狀非小細胞肺癌疫苗，都具有透過我們專有的抗原發現平台發現的新抗原，並將在2025 年和2026 年透過新的臨床候選藥物擴大我們的產品線。透過識別新的共享抗原靶標，以及在與 MD 安德森的全球合作中，我們的目標是使我們的疫苗在降低腫瘤復發風險和改善不同癌症環境下患者的預後方面更加有效。對於我們腫瘤學策略的另一部分，應用個人化癌症疫苗、對個別患者腫瘤樣本進行全基因組定序，並結合先進的生物資訊學來識別患者個體基因組腫瘤特有的新抗原和/或新型腫瘤相關抗原輪廓。

This precision medicine approach increases the likelihood of targeting antigens susceptible to immunotherapy and aims to provide a curative approach, especially in early-stage cancers with lower tumor burden. Our first-line cancer strategy is complemented by the RNA printer, our solution for fast and highly automated manufacturing. We made significant progress with our oncology pipeline and recently presented data from our clinical lead program with the off-the-shelf vaccine candidate, CVGBM, which was tested in a Phase 1 study in patients with resected glioblastoma. You might recall that CVGBM features a uniquely designed single unmodified mRNA construct encoding eight segments derived from four tumor-associated antigens with demonstrated immunogenicity in glioblastoma. It was administered as a monotherapy after surgical resection and completion of radiotherapy with or without chemotherapy.

這種精準醫學方法增加了靶向對免疫療法敏感的抗原的可能性，旨在提供一種治療方法，特別是在腫瘤負荷較低的早期癌症中。RNA 印表機是我們快速、高度自動化製造的解決方案，對我們的第一線癌症策略進行了補充。我們的腫瘤學研發管線取得了重大進展，最近公佈了我們的現成候選疫苗 CVGBM 臨床主導計畫的數據，該疫苗在已切除的膠質母細胞瘤患者中進行了 1 期研究測試。您可能還記得，CVGBM 具有獨特設計的單一未修飾 mRNA 構建體，編碼四種腫瘤相關抗原的八個片段，在膠質母細胞瘤中已證明具有免疫原性。在手術切除和完成放射治療（合併或不合併化療）後，將其作為單一療法進行。

Patients received seven intramuscular vaccinations within 10 weeks and optional maintenance vaccinations in case of non-progression for potential benefit. Preliminary safety and immunogenicity data from the dose escalation Part A of the study were recently presented at ESMO, SITC, and SNO congresses. In this highly challenging and aggressive cancer type, the data confirmed a favorable safety and tolerability profile with no dose-limiting toxicities observed in this part of the trial. Successful induction of antigen-specific T-cell responses was demonstrated in the vast majority of evaluable patients with 77% of patients showing CD8 and/or 31% CD4 T-cell response to at least one of the encoded antigens on the vaccine. Most importantly, within the group of evaluable patients, 84% of immune responses were induced de novo, meaning T-cell responses are successfully induced in patients who had no pre-existing T-cell activity against encoded antigens prior to vaccination with CVGBM.

患者在 10 週內接受了 7 次肌肉注射疫苗接種，並在病情未進展時可選擇維持疫苗接種以獲得潛在益處。研究的劑量遞增部分 A 的初步安全性和免疫原性數據最近在 ESMO、SITC 和 SNO 大會上公佈。在這種極具挑戰性和侵襲性的癌症類型中，數據證實了良好的安全性和耐受性，在這部分試驗中沒有觀察到劑量限制性毒性。在絕大多數可評估的患者中，成功誘導了抗原特異性 T 細胞應答，其中 77% 的患者對疫苗上至少一種編碼抗原表現出 CD8 和/或 31% CD4 T 細胞應答。最重要的是，在可評估的患者群體中，84% 的免疫反應是從頭誘導的，這意味著在接種 CVGBM 疫苗之前不存在針對編碼抗原的 T 細胞活性的患者成功誘導了 T 細胞反應。

Additionally, 67% of responding patients had T-cell responses against multiple encoded cancer antigens, supporting our antigen selection and successful mRNA design. At the highest tested dose of 100 micrograms, ongoing monitoring of T-cell durability showed that responses were sustained over a period of 99 days. The 100-microgram dose was also selected for the dose confirmation Part B of the study, which began enrollment in August this year. The first data readout of Part C is expected in the second half of 2025.

此外，67% 的應答患者對多種編碼的癌症抗原產生 T 細胞應答，支持我們的抗原選擇和成功的 mRNA 設計。在 100 微克的最高測試劑量下，對 T 細胞耐久性的持續監測表明，反應持續了 99 天。100微克劑量也被選用於研究的劑量確認B部分，該研究於今年8月開始入組。C 部分的首次數據預計將於 2025 年下半年讀出。

We continue to advance our oncology pipeline. And on slide 13, we have summarized our upcoming oncology catalyst, which provides a strong development path over the next 24 months. That is our most advanced Phase 1 off-the-shelf program in resected glioblastoma as already mentioned. And enrollment of the dose confirmation Part B of the study is progressing well. We expect enrollment to be completed the latest in the first half of 2025, allowing for Part B data readout in the second half of 2025. Data from an additional up to 20 patients dosed at 100 micrograms will provide the basis for potentially continuing to a Phase 2 study, which could start in the second half of '26.

我們繼續推進我們的腫瘤學產品線。在投影片 13 上，我們總結了即將推出的腫瘤學催化劑，它為未來 24 個月提供了強有力的發展道路。正如已經提到的，這是我們在切除膠質母細胞瘤方面最先進的一期現成計畫。該研究 B 部分的劑量確認入組進展順利。我們預計註冊最遲將於 2025 年上半年完成，以便在 2025 年下半年讀出 B 部分資料。另外 20 名服用 100 微克劑量的患者的數據將為可能繼續進行 2 期研究提供基礎，該研究可能會在 26 年下半年開始。

The newly announced off-the-shelf program in squamous non-small cell lung cancer is expected to enter Phase 1 clinical development in the second half of 2025. With our proprietary antigen discovery work continuing, we intend to disclose additional off-the-shelf programs with new clinical candidates in different indications in 2026. Lastly, the first clinical Phase 1 study with a personalized cancer vaccine candidate is expected to start in the second half of 2026. These strong catalysts highlight our strategic focus on opportunities in oncology, leveraging our mRNA technology designed to ensure continued progress and innovation in our oncology pipeline. Let me now shift gears and turn to our infectious disease area.

新宣布的鱗狀非小細胞肺癌現成計畫預計將於2025年下半年進入第一期臨床開發。隨著我們專有抗原發現工作的繼續，我們計劃在 2026 年披露更多具有不同適應症的新臨床候選藥物的現成項目。最後，第一個針對個人化癌症候選疫苗的臨床 1 期研究預計將於 2026 年下半年開始。這些強大的催化劑凸顯了我們對腫瘤學機會的戰略重點，利用我們旨在確保我們的腫瘤學管道持續進步和創新的 mRNA 技術。現在讓我轉向我們的傳染病領域。

In infectious diseases, we are directing our current proprietary research and development efforts towards new non-respiratory indications while benefiting from the ongoing clinical development of respiratory indications with current programs licensed to GSK. Targeting non-respiratory infections caused by bacteria, viruses, and fungi, we aim to deliver safe and cost-effective vaccines for high unmet medical need areas with compelling market potential where our mRNA technology offers an advantage over conventional vaccine technologies. In this area, we are excited to introduce a new fully owned infectious disease program targeting uropathogenic E. coli bacteria in short UPEC. UPEC is the primary cause of urinary tract infections, which rank amongst the most common infections worldwide.

在傳染病方面，我們將目前的專有研發工作轉向新的非呼吸系統適應症，同時受益於葛蘭素史克 (GSK) 許可的當前項目正在進行的呼吸系統適應症臨床開發。針對細菌、病毒和真菌引起的非呼吸道感染，我們的目標是為未滿足的醫療需求高的領域提供安全且具有成本效益的疫苗，這些領域具有巨大的市場潛力，其中我們的mRNA 技術比傳統疫苗技術具有優勢。在這一領域，我們很高興推出一項針對泌尿道致病性大腸桿菌（簡稱 UPEC）的全新全資傳染病計畫。UPEC 是尿路感染的主要原因，泌尿道感染是全世界最常見的感染之一。

The statistics presented on slide 15 highlights the significant incidence and disease burden associated with UPEC in the US. The high prevalence of UTIs with more than 50% of patients requiring antibiotic therapy, leading to increased antibiotic resistance and high rates of recurrence presents a substantial challenge in current medical practice. This results in direct medical costs reaching billions of dollars annually in the US alone. Currently, there are very limited treatment options to prevent recurrent UTIs.

第 15 張幻燈片中的統計數據強調了美國與 UPEC 相關的重大發病率和疾病負擔。泌尿道感染的高盛行率超過 50% 的患者需要抗生素治療，導致抗生素抗藥性增加和高復發率，這對目前的醫療實踐提出了巨大的挑戰。光是在美國，每年的直接醫療費用就達到數十億美元。目前，預防復發性泌尿道感染的治療選擇非常有限。

Our mRNA technology has a potential to deliver a best-in-class solution, including function inducing functional antibodies as well as T-cell responses against UPEC. To tackle this infection, we developed mRNA vaccine candidates, that encode FimH, a bacterial protein considered crucial for adhesion of the bacteria to bladder tissue and bias the formation. FimH is highly observed in UPEC's strain and therefore, represents an excellent vaccine target for the vast majority of patients. For our vaccine candidates tested in preclinical studies, we have applied rational antigen designs to optimize immunogenicity. In addition, we have applied a unique technology to design candidates that lead to the in vivo cell assembly of a SIH nanoparticle.

我們的 mRNA 技術有潛力提供一流的解決方案，包括功能性誘導功能性抗體以及針對 UPEC 的 T 細胞反應。為了應對這種感染，我們開發了 mRNA 候選疫苗，它編碼 FimH，一種細菌蛋白，被認為對於細菌黏附到膀胱組織並偏向其形成至關重要。FimH 在 UPEC 菌株中被高度觀察到，因此對於絕大多數患者來說是一個極好的疫苗標靶。對於在臨床前研究中測試的候選疫苗，我們應用了合理的抗原設計來優化免疫原性。此外，我們還應用了獨特的技術來設計候選物，從而實現 SIH 奈米顆粒的體內細胞組裝。

This innovative design is expected to lead to even higher immunogenicity. Let me show you the very promising preclinical data we created with two of our candidates. On slide 16, you can see the first preclinical data, which are currently being presented at the 12th mRNA Health Conference taking place this week in Boston. We tested our vaccine candidates in two preclinical models, Wistar Rat and BALB/c mice in comparison to non-licensed recombinant protein vaccines. Trying of binding and functional antibodies, meaning antibodies inhibiting halogenation and/or bacterial adhesion were measured in both models in serum and urine candidates.

這種創新設計預計將帶來更高的免疫原性。讓我向您展示我們與兩位候選人創建的非常有希望的臨床前數據。在投影片 16 上，您可以看到第一個臨床前數據，這些數據目前正在本週於波士頓舉行的第 12 屆 mRNA 健康會議上公佈。我們在兩種臨床前模型（Wistar 大鼠和 BALB/c 小鼠）中測試了我們的候選疫苗，並與未經許可的重組蛋白疫苗進行了比較。嘗試結合和功能性抗體，這意味著在血清和尿液候選物的兩個模型中測量了抑制鹵化和/或細菌黏附的抗體。

Additionally, CD8 and CD4 T-cell responses were determined in mice. Both mRNA vaccine candidates induced high levels of binding antibody titers in blood and urine in both models that also correlated with highly functional antibody titers in serum. Importantly, functional serum antibodies were higher with both mRNA vaccine candidates compared to the protein-based comparator vaccines. Our nanoparticle candidate demonstrated the highest overall levels of FIMH specific binding and functional antibody responses in serum enduring of the animals, outperforming all other tested candidates. Additionally, both mRNA vaccine candidates induced higher T-cell responses than the comparator protein-based vaccines with a nanoparticle candidate again strongly outperforming all other candidates.

此外，也測定了小鼠的 CD8 和 CD4 T 細胞反應。兩種 mRNA 候選疫苗在兩種模型中均誘導血液和尿液中高水平的結合抗體滴度，這也與血清中的高功能抗體滴度有關。重要的是，與基於蛋白質的比較疫苗相比，兩種 mRNA 候選疫苗的功能性血清抗體均較高。我們的奈米顆粒候選物在動物血清中表現出最高的 FIMH 特異性結合和功能性抗體反應總體水平，優於所有其他測試的候選物。此外，兩種 mRNA 候選疫苗比基於蛋白質的比較疫苗（奈米顆粒候選疫苗）誘導了更高的 T 細胞反應，再次明顯優於所有其他候選疫苗。

Overall, our infectious disease programs show promising progress with both non-respiratory and respiratory areas advancing based on solid development catalysts outlined on slide 17. For our newly launched UPEC program, we expect to select a clinical candidate in the first half of 2025, enabling us to file for IND submission in the second half of 2025. This is anticipated to allow Phase 1 clinical development to start in the first half of 2026. Additional discovery work in other non-respiratory diseases is also progressing. And we anticipate strengthening our pipeline in this area with additional programs in 2025 for which clinical candidates could be selected in the second half of 2026.

總體而言，我們的傳染病計畫顯示出有希望的進展，非呼吸系統和呼吸系統領域都在幻燈片 17 概述的堅實發展催化劑的基礎上取得了進展。對於我們新推出的 UPEC 項目，我們預計在 2025 年上半年選擇臨床候選藥物，使我們能夠在 2025 年下半年提交 IND 申請。預計一期臨床開發將於 2026 年上半年啟動。其他非呼吸系統疾病的其他發現工作也在取得進展。我們預計 2025 年將透過其他項目加強我們在這一領域的管道，並可在 2026 年下半年選出臨床候選人。

For the respiratory program licensed to GSK, please note that the disclosure of the timelines remains at the discretion of GSK. As recently confirmed by GSK, the seasonal influenza program is expected to progress to Phase 3 in 2025. Further available timelines for the license program include anticipated data readout for the avian influenza study in the first half of 2025. GSK is also about to initiate a new combined Phase 1 study for an influenza COVID-19 combination vaccine. Corresponding information can be found on clinicaltrials.gov. Data is expected in the first half of 2025.

對於授權給葛蘭素史克的呼吸項目，請注意，葛蘭素史克仍可自行決定是否揭露時間表。葛蘭素史克最近證實，季節性流感計畫預計將在 2025 年進入第三階段。許可計劃的進一步可用時間表包括 2025 年上半年禽流感研究的預期數據讀出。GSK 也即將啟動一項新的流感 COVID-19 聯合疫苗聯合 1 期研究。相關資訊可在 ClinicalTrials.gov 上找到。預計數據將於 2025 年上半年公佈。

With this, I would like to conclude the portfolio update and hand over to Axel for a review of the financial data.

至此，我想完成投資組合的更新，交給阿克塞爾審查財務數據。

Thank you, Myriam. Looking at the significant progress we've made in streamlining our operations and focusing on strategic priorities. I would like to provide context to key financial metrics on slide 18, demonstrating our financial health and enabling us to reinvest in key areas of growth and innovation. Today, we report a strong cash position of EUR550.9 million at the end of the third quarter 2025 and reaffirm our cash runway into 2028. Our quarterly results are driven by the new licensing agreement with GSK, which positively impacted our cash position as well as revenues.

謝謝你，米里亞姆。看看我們在簡化營運和關注策略重點方面取得的重大進展。我想提供幻燈片 18 中關鍵財務指標的背景信息，展示我們的財務健康狀況，並使我們能夠在增長和創新的關鍵領域進行再投資。今天，我們報告稱，截至 2025 年第三季末，我們擁有 5.509 億歐元的強勁現金頭寸，並重申我們到 2028 年的現金跑道。我們的季度業績是由與 GSK 簽訂的新授權協議推動的，這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 non-refundable payment for granting licenses to GSK and the right to use CureVac's intellectual property with no further R&D work obligation on our side. As such, it was fully recognized as revenue in the third quarter of 2024. 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 EUR18.4 million were also recognized as revenue in the third quarter of 2024. Setting the course for increased future financial stability, our strategic redesign is a key to enhancing our operational efficiency to further reduce costs. The efficient execution of the 30% workforce reduction is on track to be complete by the end of 2024 incurred costs approximately 40% below the allocated budget.

該協議中的 4 億歐元預付款是一筆不可退還的款項，用於向葛蘭素史克授予許可以及使用 CureVac 知識產權的權利，而我們這邊沒有進一步的研發工作義務。因此，它在 2024 年第三季完全確認為收入。鑑於根據新授權協議的條款，先前合作中與研發服務相關的所有義務均已到期，剩餘合約負債1,840萬歐元也被確認為2024年第三季的收入。我們的策略重新設計為提高未來財務穩定性奠定了基礎，是提高營運效率以進一步降低成本的關鍵。裁員 30% 的工作預計在 2024 年底前完成，所產生的成本比分配的預算低約 40%。

From 2024 onwards, we anticipate a substantial increase 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 had also eliminated the need for commercial build-up and large-scale manufacturing activities. Streamlining of our in-house manufacturing capacity to provide a new manufacturing footprint better suited to our needs was accompanied by a partial impairment of a large-scale GMP IV 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 in the third quarter, ensuring no further related payments.

從 2024 年起，我們預計營運費用將大幅增加 30% 以上，其中人員成本將大幅減少 2,500 萬歐元。我們與 GSK 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。精簡我們的內部製造能力以提供更適合我們需求的新製造足跡，同時大型 GMP IV 生產設施也受到部分損害。最後，我們已在第三季度成功終止了所有剩餘的原材料承諾，並結束了第一代 COVID-19 疫苗的所有合約製造組織 (CMO) 相關仲裁，確保不再發生任何相關付款。

Moving on to our condensed financial statement on slide 19. You can see that our cash position of EUR550.9 million increased from EUR402.5 million at the end of '23 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 lapse payments related to our first-generation COVID-19 vaccine. As already discussed, revenues strongly increased by EUR477.4 million to EUR493.9 million for the third quarter and by EUR489.5 million to EUR520.7 million for the nine months end of 2024 compared to the same period in 2023. As the year-on-year increase was primarily driven by the license agreement with GSK, this must be seen as a positive onetime events. Operating profit was EUR368.4 million for the third quarter of 2024 compared to an operating loss of EUR54 million for the same quarter in 2023.

接下來是投影片 19 上的簡明財務報表。您可以看到，基於 2024 年 8 月葛蘭素史克預付款 4 億歐元，我們的現金部位從 23 年底的 4.025 億歐元增加到 5.509 億歐元。這一增長被我們正在進行的研發活動以及與第一代 COVID-19 疫苗相關的逾期付款所部分抵消。如前所述，與 2023 年同期相比，第三季營收強勁成長 4.774 億歐元，達到 4.939 億歐元，2024 年底九個月營收成長 4.895 億歐元，達到 5.207 億歐元。由於同比增長主要是由與 GSK 的許可協議推動的，因此這必須被視為一次性的積極事件。2024 年第三季的營業利潤為 3.684 億歐元，而 2023 年第三季的營業虧損為 5,400 萬歐元。

For the first nine months of 2024, operating profit was EUR221.4 million compared to an operating loss of EUR186.2 million for the same period in 2023. The operating result was affected by several key drivers. First, cost of sales increased year-on-year, mainly due to higher arbitration costs for CMO activities related to the first-generation COVID-19 vaccine as well as due to higher personnel expenses related to the redesign of the organization. Second, R&D expenses increased with higher investments in oncology development programs as well as increased expenses related to the litigation to enforce intellectual property rights. Third, general and administrative expenses decreased compared to the prior year period, mainly driven by lower personnel expenses.

2024 年前 9 個月，營業利潤為 2.214 億歐元，而 2023 年同期營業虧損為 1.862 億歐元。經營業績受到幾個關鍵驅動因素的影響。首先，銷售成本較去年增加，主要是因為與第一代COVID-19疫苗相關的CMO活動的仲裁費用增加，以及與組織重新設計相關的人員費用增加。其次，隨著腫瘤學開發案投資的增加以及與執行智慧財產權訴訟相關的費用的增加，研發費用也隨之增加。第三，一般及管理費用較上年同期下降，主要是因為人員費用減少所致。

Lastly, other operating expenses increased due to the discussed partial impairment of CureVac's GMP IV production facility. Financial results decreased by EUR3.1 million to EUR2.2 million in the third quarter of 2024 and decreased by EUR4.7 million to EUR8 million for the first nine months of 2024 compared to the same periods in 2023. The decrease was mainly driven by lower interest income on cash investments. Pretax profit was EUR370.6 million for the third quarter and EUR229.4 million for the first nine months of 2024 compared to a pretax loss in the same period of 2023. And with this, I'd like to hand back the call over to Alexander for today's key messages.

最後，由於所討論的 CureVac GMP IV 生產設施的部分減值，其他營運費用有所增加。與 2023 年同期相比，2024 年第三季的財務表現減少了 310 萬歐元，至 220 萬歐元，2024 年前 9 個月的財務表現減少了 470 萬歐元，至 800 萬歐元。下降的主要原因是現金投資利息收入下降。2024 年第三季稅前利潤為 3.706 億歐元，2024 年前 9 個月稅前利潤為 2.294 億歐元，而 2023 年同期為稅前虧損。在此，我想將電話轉交給亞歷山大，以傳達今天的關鍵訊息。

Thank you, Axel. Now let's summarize the key highlights for Q3 2024. We closed the third quarter of 2024 with a cash balance of EUR550.9 million, providing us with a solid financial runway into 2028. This strengthens our ability to continue driving innovation and growth. In addition, we are making significant progress on our strategic transformation, including a 30% reduction by the end of 2024.

謝謝你，阿克塞爾。現在讓我們總結一下 2024 年第三季的主要亮點。截至 2024 年第三季度，我們的現金餘額為 5.509 億歐元，為我們進入 2028 年提供了堅實的財務跑道。這增強了我們繼續推動創新和成長的能力。此外，我們的策略轉型正在取得重大進展，包括到 2024 年底減少 30%。

This will contribute to substantial cost savings starting in 2025 and enhancing our operational efficiencies. In oncology, we are advancing our off-the-shelf and personalized cancer vaccines. Our glioblastoma trial has shown promising early results. And we are planning new trials in 2025 and 2026. And in infectious diseases, we are moving forward with the UPEC vaccine for UTIs.

這將有助於從 2025 年開始大幅節省成本並提高我們的營運效率。在腫瘤學方面，我們正在開發現成的個人化癌症疫苗。我們的膠質母細胞瘤試驗顯示出有希望的早期結果。我們計劃在 2025 年和 2026 年進行新的試驗。在傳染病方面，我們正在推進針對泌尿道感染的 UPEC 疫苗的研發。

Additionally, our partner, GSK, is advancing a seasonal influenza vaccine into Phase 3 next year and is about to initiate a combined Phase 1/2 study for COVID influenza combination vaccine, both leveraging our platform. And as we enter 2025, we are well positioned, well financed, focused on high-value opportunities and supported by strategic partnerships and a robust IP portfolio. These elements position us well for ongoing growth and success in tackling major health challenges. And with that, I would like to conclude our presentation and open the floor for your questions.

此外，我們的合作夥伴葛蘭素史克 (GSK) 將於明年將季節性流感疫苗推進到 3 期，並即將啟動針對新冠肺炎聯合疫苗的 1/2 期聯合研究，兩者均利用我們的平台。進入 2025 年，我們處於有利位置，資金充足，專注於高價值機會，並得到策略合作夥伴關係和強大智慧財產權組合的支持。這些要素使我們能夠持續成長並成功應對重大健康挑戰。至此，我想結束我們的演講並開始提問。

(Operator Instructions) Charlie Yang, Bank of America.

（操作員指示）Charlie Yang，美國銀行。

Great. Thanks for taking the question. I have two, please. I think one; can you discuss perhaps kind of your thoughts about business opportunity, licensing opportunity outside of the mRNA kind of your core expertise. Whether that is an area of kind of potential interest just given your cash position? And then second of all, can you discuss about the kind of the litigation update and kind of what should we expect on that front? Thank you.

偉大的。感謝您提出問題。我有兩個，拜託。我認為有一個；您能否談談您對 mRNA 核心專業知識以外的商業機會、授權機會的看法。考慮到您的現金狀況，這是否是一個潛在的興趣領域？其次，您能否討論一下訴訟更新的類型以及我們在這方面應該期待什麼？謝謝。

Okay. Thank you. So on your first question on business opportunities. At the moment, we stay very focused on the two areas that we described during the presentation, which is oncology on one hand and infectious diseases on the other hand. And within these two areas, we already do have collaboration with GSK on one hand and the MD Anderson on the other hand.

好的。謝謝。關於你的第一個問題，關於商業機會。目前，我們非常關注我們在演示中描述的兩個領域，一方面是腫瘤學，另一方面是傳染病。在這兩個領域，我們已經一方面與葛蘭素史克（GSK）合作，另一方面與 MD 安德森癌症中心（MD Anderson）合作。

But of course, we are always open to look at new opportunities within these two areas that will help us to strengthen our portfolio and especially accelerate our path to the clinic. With regards to litigation, so these are ongoing. I think the next time point for you to keep in mind is the US court case, which has been scheduled for March '25, so March next year. So work is ongoing for us to prepare as best as we can for these events. So other than that, we don't have much to update you on just now.

當然，我們始終樂於尋找這兩個領域的新機會，這將有助於我們加強我們的產品組合，特別是加速我們走向臨床的道路。關於訴訟，這些正在進行中。我認為您要記住的下一個時間點是美國法庭案件，原定於 25 月 25 日舉行，所以是明年 3 月。因此，我們正在努力為這些活動盡最大努力做好準備。除此之外，我們目前沒有太多更新資訊。

Thank you.

謝謝。

Mani Foroohar, Leerink Partners.

Mani Foroohar，Leerink 合夥人。

Hi, there. Thanks for taking our question. This is CJ on Mani. Following your encouraging flu data, I was wondering if you could share any commentary and plans for developing a combo vaccine for flu COVID? Thank you.

你好呀。感謝您提出我們的問題。這是 CJ 在 Mani 上的報道。根據您令人鼓舞的流感數據，我想知道您是否可以分享有關開發流感新冠聯合疫苗的任何評論和計劃？謝謝。

Question on flu, flu combo, flu COVID combo, Myriam?

關於流感、流感組合、流感新冠組合、Myriam 的問題嗎？

Yeah. I mean this question should ideally be addressed by GSK. But of course, we all believe that given the epidemiology and the occurrence of infections, that combination for patients of the flu vaccine and COVID vaccine would be the most convenient approach, right, and most promising. That's why all of the development efforts in the past when we were still in collaboration. We are focused on this.

是的。我的意思是這個問題最好由葛蘭素史克來解決。當然，我們都相信，考慮到流行病學和感染的發生情況，對於患者來說，流感疫苗和新冠疫苗的組合將是最方便、正確、最有希望的方法。這就是為什麼過去我們還在合作時的所有開發工作。我們專注於此。

The Phase 1 study starts now as we also shared. And we expect the data readout next year for decision-making for progress to Phase 2. I'm not sure I addressed your question. But I think the program is progressing, especially because of the very positive Phase 2 data in influenza. And we are optimistic that this is going to be a continued and successful program.

正如我們所分享的，第一階段研究現已開始。我們預計明年將公佈數據，以便為第二階段的進展做出決策。我不確定我是否回答了你的問題。但我認為該計劃正在取得進展，特別是因為流感的第二階段數據非常積極。我們樂觀地認為這將是一個持續且成功的計劃。

Great. Thank you so much.

偉大的。太感謝了。

[Chira Mantoori, CureVac].

[Chira Mantoori，CureVac]。

Hello, team, congrats with the update. This is Sarah from Van Lanschot Kempen. And I'm on behalf of Suzanne. So I was wondering any color or reasoning you can provide on selecting lung cancer as the new indication? And then following up the previous question, can you say something regarding patent litigation on the EU front, on the Europe front. Thanks.

你好，團隊，恭喜更新。我是 Van Lanschot Kempen 的莎拉。我代表蘇珊娜。所以我想知道您可以提供關於選擇肺癌作為新適應症的任何顏色或推理嗎？然後繼續上一個問題，您能談談歐盟方面、歐洲方面的專利訴訟嗎？謝謝。

Okay. I think, Myriam, maybe one question for you. I think it was a question, if I understood correctly on indication selection or vice claimants.

好的。我想，米里亞姆，也許有個問題想問你。我認為這是一個問題，我是否正確理解適應症選擇或副索賠人。

Exactly. That's what I also understand. And sorry, because the acoustics were not great. Yeah. So we have to, of course, when we select the candidate, we have to follow the science, right? And basically, in our approach, just covered antigens, shared antigens that are shared from different cancer indications.

確切地。我也是這麼理解的。抱歉，因為音響效果不太好。是的。當然，當我們選擇候選人時，我們必須遵循科學，對嗎？基本上，在我們的方法中，只涵蓋了抗原，不同癌症適應症所共有的抗原。

And one also wanted to include novel classes of antigens. And so in our research, again, we found appropriate coverage of novel antigens in squamous non-small cell lung cancer. So following the sign that the indication we selected for our -- what we think very innovative next antigen cancer vaccine to address the high unmet need in this population. So the indication is basically based on the science of the data and the readout of our antigen discovery work. Does that address your question, again, because it wasn't super easy to understand it?

人們也希望包括一類新的抗原。因此，在我們的研究中，我們再次發現鱗狀非小細胞肺癌中新抗原的適當覆蓋。因此，根據我們為我們選擇的適應症——我們認為非常創新的下一個抗原癌症疫苗來解決這一人群中未滿足的高度需求。因此，該適應症基本上是基於數據科學和我們抗原發現工作的結果。這是否再次解決了您的問題，因為它不太容易理解？

Yes, perfectly. I hope my sound is now better, but it was perfectly (technical difficulty). And regarding the recent litigation on the European front?

是的，完美。我希望我的聲音現在更好了，但它已經很完美了（技術難度）。關於最近歐洲方面的訴訟？

Yeah. So in Europe, it's a bit more complex, whereas in the US, all the different cases are bundled in one case. And we have one court case on validity infringement and damages. In Europe, it's really on a case-by-case basis, right? So this is something that will continue throughout the next years.

是的。因此，在歐洲，情況要複雜一些，而在美國，所有不同的案例都捆綁在一個案例中。我們有一件關於有效性侵權和損害賠償的法庭案件。在歐洲，這確實是根據具體情況而定，對嗎？因此，這將在未來幾年持續下去。

We do expect further rulings from the European patent office on our patents in the second quarter of next year as well as from the regional court in Dusseldorf more in the second or third quarter. But in Europe, it's going to be an ongoing process throughout '25 and maybe leading into '26 on a patent per patent basis, right? But I think the key visibility, the key event from -- at least for the first half will be the US case in March.

我們確實預計歐洲專利局將在明年第二季對我們的專利做出進一步裁決，杜塞爾多夫地區法院將在第二或第三季對我們的專利做出更多裁決。但在歐洲，這將是整個 25 年持續的過程，並且可能會以每個專利為基礎進入 26 年，對吧？但我認為至少上半年的關鍵能見度和關鍵事件將是美國三月的情況。

Okay. Thank you so much.

好的。太感謝了。

Roy Buchanan, Citizens.

羅伊·布坎南，公民。

Hey. Thanks for taking the questions. Just a couple of FimH questions. I think there was a prior protein-based program that didn't move forward. Can you just maybe comment on if your engineering approaches address maybe why that program didn't move forward? And then any thoughts on how you -- I think there's a glyco conjugate program in Phase 3. Any thoughts on how your approach could be better than that? Thanks.

嘿。感謝您提出問題。只是幾個 FimH 問題。我認為之前有一個基於蛋白質的計劃沒有進展。您能否評論一下您的工程方法是否解決了該計劃未能取得進展的原因？然後關於你如何的任何想法 - 我認為第三階段有一個糖結合物計劃。你有什麼想法可以讓你的方法變得比這更好嗎？謝謝。

So again, I'm sorry, the audio is a little bit difficult. So I heard the first question why FimH, right, if I understand correctly. And FimH is easy to address. It's a highly conserved antigen in UPEC bacteria. And by seating and targeting this antigen, we basically are able to cover about 95% of the population affected by UPEC.

再次抱歉，音頻有點困難。所以我聽到第一個問題為什麼是FimH，對吧，如果我理解正確的話。FimH 很容易解決。它是 UPEC 細菌中高度保守的抗原。透過定位和靶向這種抗原，我們基本上能夠涵蓋約 95% 的受 UPEC 影響的人群。

That's the first one. The second one is this basically antigen target has been kind of validated in preclinical trials. And even if you want to go there in a Phase 1/2 study by another sort of company who is testing a peptide-based vaccine. So FimH is validated. I think, as a target to address UPEC bacteria and this is a promising antigen.

這是第一個。第二個是這個基本的抗原標靶已經在臨床前試驗中得到了驗證。即使您想參加另一家正在測試勝肽疫苗的公司進行的 1/2 期研究。因此 FimH 得到驗證。我認為，作為解決 UPEC 細菌的標靶，這是一種很有前途的抗原。

If your second part of the question is about the antigen design, again, we applied something very innovative, right, in the way how we selected to target FimH. And I don't want to get too much into the detail, but in a pre-binding confirmation so that we really can get the bacteria before it has attached to the endothelial cells in the bladder. And then we have, for the first time, applied a design where, again, the encoded protein forms a nanoparticle with fin in the core and then basically a lot of FimH proteins expressed on the surface to really induce a stronger immune response. And that is design, again, in our preclinical studies translated to a really beautiful immunogenicity, showing very high titers of binding and what is even more important functional antibodies. And when we compare it to a protein-based design targeting FimH, it shows basically superior immunogenicity, both for humoral antibody responses and T-cell responses.

如果問題的第二部分是關於抗原設計，那麼我們再次應用了一些非常創新的東西，對吧，就是我們選擇靶向 FimH 的方式。我不想透露太多細節，但在預結合確認中，這樣我們就能在細菌附著到膀胱內皮細胞之前真正獲得細菌。然後，我們首次應用了一種設計，其中編碼的蛋白質再次形成核心帶有鰭的奈米顆粒，然後基本上在表面上表達大量 FimH 蛋白質，以真正誘導更強的免疫反應。這也是設計，在我們的臨床前研究中轉化為非常好的免疫原性，顯示出非常高的結合滴度以及更重要的功能性抗體。當我們將其與針對 FimH 的基於蛋白質的設計進行比較時，它顯示出基本上優越的免疫原性，無論是體液抗體反應還是 T 細胞反應。

I know you had a part of the question about another program, but I didn't hear that very clearly.

我知道您的問題中有一部分是關於另一個程序的，但我聽得不太清楚。

I think it was more a question around differentiation with our more advanced program. Why do we believe an approach with an mRNA, or our vaccine could be differentiated or different?

我認為這更多是一個關於我們更先進的程序的差異化問題。為什麼我們相信 mRNA 方法或我們的疫苗可以有所差異或不同？

Well, I think especially in this setting, again, mRNA per se is differentiated in that we can show clearly induction of tumor and cellular immune responses as shared in our preclinical data, because we believe you have to address through, again, targeting targeted antibodies as well as cellular responses because the bacteria rest on the cells in the bladder. So that's the first part why it is differentiated. And then the other part is, of course, because of the way how we designed our vaccine and the target that we have selected.

嗯，我認為特別是在這種情況下，mRNA 本身是有區別的，因為我們可以清楚地顯示腫瘤和細胞免疫反應的誘導，正如我們在臨床前數據中所共享的那樣，因為我們相信您必須再次透過靶向靶向抗體來解決這個問題以及細胞反應，因為細菌停留在膀胱的細胞上。這就是它與眾不同的第一部分。當然，另一部分是因為我們設計疫苗的方式和我們選擇的目標。

Okay, great. And the design was all in house or did you in-license any technology? Thanks. That's it.

好的，太好了。設計全部是在內部完成的，還是您授權了任何技術？謝謝。就是這樣。

This is the proprietary technology that it is all or a section of it.

這是全部或部分專有技術。

Got it. Thank you.

知道了。謝謝。

Jon Miller, Evercore.

喬恩‧米勒，《Evercore》。

Hi. It's (inaudible) on for Jon. Thanks for taking our question. I guess on the GBM program, apparently, very good response from T-cells. But how should we think about the translation towards tumor response based off the data? And also for the overall off-the-shelf program, what are the indications that of most interest? Thank you.

你好。喬恩（聽不清楚）已經開始了。感謝您提出我們的問題。我猜想，對於 GBM 計劃，T 細胞顯然反應非常好。但我們該如何考慮基於數據的腫瘤反應轉化？對於整個現成程序來說，最感興趣的跡像是什麼？謝謝。

Yeah, thanks a lot. So maybe for GBM, this is a super important question, right, that nobody can answer at this point. How does the immunologic response translate into clinical benefit? And there, again, we need to wait for more data coming from our expansion cohort. We have presented at ESMO very early preliminary clinical readouts from our Phase 1 dose escalation cohort.

是的，非常感謝。所以也許對於 GBM 來說，這是一個非常重要的問題，對吧，目前沒有人可以回答。免疫反應如何轉化為臨床益處？在這裡，我們再次需要等待來自我們的擴展隊列的更多數據。我們在 ESMO 上展示了我們 1 期劑量遞增隊列的早期初步臨床數據。

In those data, we shared that we had one partial response in a patient who entered the trial with only a partial tumor reduction. And again, under monotherapy with our vaccine, that patient developed a partial response. Unfortunately, the immunogenicity readout did fail in this patient, because they couldn't collect enough cell samples. But at least one partial response was observed in our Phase 1 dose escalation part. And then the other parameters you could look at, again, all under the caveat with early data at 16 patients.

在這些數據中，我們分享了一位進入試驗的患者僅獲得部分腫瘤縮小的結果，我們獲得了部分緩解。同樣，在我們的疫苗單一治療下，該患者出現了部分反應。不幸的是，該患者的免疫原性讀數確實失敗了，因為他們無法收集足夠的細胞樣本。但在我們的第一階段劑量遞增部分中至少觀察到了部分反應。然後您可以再次查看其他參數，這些參數均在 16 名患者的早期數據的警告下。

But we also looked at the PFS at six months in this bad prognosis population where we saw in our trial a PFS at six months of about 34%. And then you compare this to data shared at ASCO this year from basically a trial conducted by similar investigators that participated in our trial (inaudible). And they shared that patients with un-methylated GBMs treated just with radiotherapy plus/minus temozolomide had a PFS at six months of only 18%. So again, I have to caveat this is early data. It's a handful of patients.

但我們也觀察了這個預後不良族群的 6 個月 PFS，在我們的試驗中發現 6 個月時的 PFS 約為 34%。然後你將其與今年在 ASCO 共享的數據進行比較，該數據基本上來自參與我們試驗的類似研究人員進行的試驗（聽不清楚）。他們也表示，僅接受放射治療加/減替莫唑胺治療的未甲基化 GBM 患者在 6 個月時的 PFS 僅為 18%。因此，我必須再次警告這是早期數據。這是少數病人。

But we do see some promising even clinical signals. Now what we are doing in the dose expansion part, again, we collect more information on more patients. We collect more and also deeper immunogenicity data. And we will collect, of course, the clinical data. So that at the end, we can hopefully correlate the two and then make a robust decision whether we go into Phase 2 or not.

但我們確實看到了一些有希望的臨床訊號。現在我們在劑量擴展部分所做的事情，我們再次收集更多患者的更多資訊。我們收集更多、更深入的免疫原性數據。當然，我們會收集臨床數據。因此，最後，我們有望將兩者聯繫起來，然後做出是否進入第二階段的穩健決定。

I guess the second question was around indication selection for the rest of the off-the-shelf vaccine. So I think we already communicated candidate squamous non-small cell lung cancer, right? And I think work on the indication selection for the next CRAC program potentially out of the MD Anderson collaboration is still ongoing.

我想第二個問題是關於其餘現成疫苗的適應症選擇。所以我認為我們已經傳達了候選鱗狀非小細胞肺癌，對吧？我認為與 MD 安德森合作的下一個 CRAC 項目的適應症選擇工作仍在進行中。

Got it. And maybe just to build on this, we have conducted end of last year, beginning of this year, an extensive oncology strategy exercise where we looked at all different kinds of indications which could be targeted by a cancer vaccine. And we considered criteria such as likelihood of scientific success, unmet medical need, competitive environment, commercial opportunities, and have prioritized a few cancer indications that where we will go deeper into the discovery for cancer antigens. So it's selection of next indications is really following a strategic approach that has been also translated into our collaboration with MD Anderson, where we focused together on, again, promising scientifically but also commercially promising areas in oncology.

知道了。也許只是為了在此基礎上，我們在去年底、今年年初進行了一項廣泛的腫瘤學策略演習，我們研究了癌症疫苗可能針對的所有不同類型的適應症。我們考慮了科學成功的可能性、未滿足的醫療需求、競爭環境、商業機會等標準，並優先考慮了一些癌症跡象，我們將在這些跡像中更深入地發現癌症抗原。因此，它對下一個適應症的選擇實際上遵循了一種戰略方法，該方法也轉化為我們與 MD 安德森的合作，我們再次共同關注在腫瘤學領域具有科學前景和商業前景的領域。

Thank you very much.

非常感謝。

(Operator Instructions) There are no further questions. I'd like to turn the floor back to management for any closing comments.

（操作員說明）沒有其他問題。我想請管理階層發表最後評論。

With this, we would like to conclude our 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，我們的電話會議就結束了。非常感謝您的參與。請確保安全，如果您有任何其他問題，請隨時與我們聯繫。謝謝你，再見。

This concludes today's teleconference. You may disconnect your lines at this time. Thank you again for your participation.

今天的電話會議到此結束。此時您可以斷開線路。再次感謝您的參與。