Vir Biotechnology Inc (VIR) 2025 Q1 法說會逐字稿

Hello. Welcome to Vir Biotechnology's first-quarter 2025 financial results and business update call. As a reminder, this conference call is being recorded. (Operator Instructions) I will now turn the call over to Rich Lepke, Senior Director, Investor Relations. You may begin, Mr. Lepke.

你好。歡迎參加 Vir Biotechnology 2025 年第一季財務表現及業務更新電話會議。提醒一下，本次電話會議正在錄音。（操作員指示）現在我將把電話轉給投資者關係高級總監 Rich Lepke。您可以開始了，萊普克先生。

Thank you, and good afternoon. With me today are Dr. Marianne De Backer, our Chief Executive Officer; Dr. Mark Eisner, our Chief Medical Officer; Jason O'Byrne, our Chief Financial Officer; and Dr. Mika Durink, our Executive Vice President of Oncology, who will be available during the Q&A session.

謝謝，下午好。今天與我一起出席的有我們的執行長 Marianne De Backer 博士、我們的首席醫療官 Mark Eisner 博士、我們的財務長 Jason O'Byrne 以及我們的腫瘤學執行副總裁 Mika Durink 博士，他們將出席問答環節。

Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q and 8-K.

在我們開始之前，我想提醒大家，我們今天所做的一些聲明是證券法下的前瞻性聲明。這些前瞻性陳述涉及重大風險和不確定性，可能導致我們的臨床開發計劃、未來結果、績效或成就與這些前瞻性陳述所表達或暗示的有很大不同。這些風險和不確定性以及與我們的業務相關的風險在公司向美國證券交易委員會提交的報告中有所描述，包括 10-K、10-Q 和 8-K 表格。

I will now turn the call over to our CEO, Dr. Marianne Barker. Please go ahead.

現在我將把電話轉給我們的執行長瑪麗安·巴克博士。請繼續。

Thank you, Rich, and good afternoon, everyone. Thank you for joining us for VIR Biotechnology's first quarter 2025 earnings call. I'm pleased to share our progress and achievements with you today as we continue to execute on our strategic priorities. Before we dive in, I want to express my gratitude for your continued support and interest in our mission of powering the immune system to transform patients' lives. We've had a strong start to 2025 with meaningful progress across our pipeline.

謝謝你，Rich，大家下午好。感謝您參加 VIR Biotechnology 2025 年第一季財報電話會議。今天，我很高興與大家分享我們在繼續執行策略重點的過程中所取得的進展和成就。在我們深入探討之前，我想對您一直以來的支持和對我們增強免疫系統以改變患者生活的使命的關注表示感謝。我們的 2025 年開局強勁，整個管道都取得了有意義的進展。

Our strategic focus on advancing both our infectious disease and oncology programs continues to position us well for future growth and value creation. I'm pleased to share that we successfully initiated our ECLIPSE Phase III registrational program with the first patient enrolled in ECLIPSE-1 during the first quarter. This is a significant milestone in our commitment to develop a potential new standard of care for patients with hepatitis delta virus infection. The ECLIPSE program builds on our SOLSTICE Phase II data, which demonstrated impressive virological responses with our combination therapy. Today, I'd also like to provide our refined assessment of the hepatitis delta market opportunity, which reflects the prelaunch work we have initiated in parallel with our Phase III trials to better characterize the addressable patient population.

我們的策略重點是推進傳染病和腫瘤學項目，這為我們未來的成長和價值創造奠定了良好的基礎。我很高興地告訴大家，我們成功啟動了 ECLIPSE III 期註冊計劃，第一季第一位患者參加了 ECLIPSE-1。這是我們致力於為感染丁型肝炎病毒的患者開發潛在的新護理標準的一個重要里程碑。ECLIPSE 計畫以我們的 SOLSTICE II 期數據為基礎，該數據表明我們的聯合療法具有令人印象深刻的病毒學反應。今天，我還想提供我們對丁型肝炎市場機會的完善評估，這反映了我們與 III 期試驗同時啟動的上市前工作，以更好地描述可針對的患者群體。

Based on our comprehensive market analysis, we estimate that there are approximately 7 million active viremic HDV RNA positive patients globally. In the United States, we estimate approximately 61,000 RNA-positive patients. In the EU member countries plus the UK, we estimate approximately 113,000 RNA-positive patients and additional geographies beyond these could represent long-term opportunities. I want to emphasize that these figures specifically focus on RNA-positive patients with active viremic disease who would be candidates for treatment. This distinction is important because we focus specifically on patients with detectable viral replication who face the highest risk of disease progression.

根據我們全面的市場分析，我們估計全球約有 700 萬名活躍的病毒血症 HDV RNA 陽性患者。在美國，我們估計約有 61,000 名 RNA 陽性患者。我們估計，在歐盟成員國和英國，大約有 113,000 名 RNA 陽性患者，除此之外的其他地區可能代表長期機會。我想強調的是，這些數據特別關注那些患有活動性病毒血症且適合接受治療的 RNA 陽性患者。這種差異很重要，因為我們特別關注面臨疾病進展最高風險的病毒複製可檢測的患者。

We've conducted an extensive evaluation of multiple epidemiological sources and consulted with leading experts in the field to arrive at these estimates. It's important to note that our updated understanding of the market size underscores that hepatitis delta has the characteristics of a rare disease market with significant commercial potential.

我們對多個流行病學來源進行了廣泛的評估，並諮詢了該領域的頂尖專家才得出這些估計。值得注意的是，我們對市場規模的最新理解強調了丁型肝炎具有罕見疾病市場的特徵，具有巨大的商業潛力。

Let me highlight a few key points. First, this is a disease with severe outcomes. More than 50% of hepatitis delta patients succumb to liver-related death within 10 years of diagnosis, and there are no FDA-approved treatments in the United States. Second, treatment is managed by a concentrated group of hepatologists and liver specialists, allowing for a focused commercial engagement.

讓我強調幾個要點。首先，這是一種後果嚴重的疾病。超過50%的丁型肝炎患者在確診後10年內死於肝臟相關疾病，美國目前尚無FDA核准的治療方法。其次，治療由一支由肝病專家和肝病專家組成的專業團隊管理，這使得商業參與更加集中。

Third, the severe clinical outcomes and EMA orphan disease designation support a value-based pricing model, similar to other rare disease therapies. Fourth, the high-cost burden of untreated disease progression, including liver transplantation and end-stage liver disease management provides a compelling economic case for effective treatment. And finally, our market research indicates high physician intent to treat these patients given the lack of effective options. The regulatory designations we've received breakthrough therapy, Fast Track in the United States and prime and orphan drug in the EU underscore the potential impact of our approach and may help accelerate our development timeline.

第三，嚴重的臨床結果和 EMA 孤兒病指定支持基於價值的定價模型，類似於其他罕見疾病療法。第四，未經治療的疾病進展（包括肝臟移植和末期肝病管理）的高成本負擔為有效治療提供了令人信服的經濟理由。最後，我們的市場研究表明，由於缺乏有效的治療選擇，醫生有很高的意願來治療這些患者。我們獲得的突破性療法、美國快速通道以及歐盟主要藥物和孤兒藥的監管認定凸顯了我們的方法的潛在影響，並可能有助於加快我們的開發時間表。

We are focused on driving enrollment in our ECLIPSE-1 trial and preparing for the ECLIPSE 2 and 3 study initiation. As we advance our hepatitis delta program, I'm also pleased to report that during the quarter, we reached an agreement with Alnylam, whereby they elected not to opt into the profit-sharing arrangement for elebsiran, resulting in a continued milestone and royalty-based structure.

我們專注於推動 ECLIPSE-1 試驗的註冊，並為 ECLIPSE 2 和 3 研究的啟動做準備。隨著我們推進丁型肝炎項目，我也很高興地報告，在本季度，我們與 Alnylam 達成了一項協議，他們選擇不加入 elebsiran 的利潤分享安排，從而繼續保持里程碑和基於特許權使用費的結構。

This decision provides clarity for our approach to advance our hepatitis delta program and gives us the flexibility to partner the program in Europe and other international markets. The outcome of this agreement was anticipated and factored into our long-term financial planning and was already included in our projected cash runway extending into mid-2027. Jason will provide additional details on the financial aspects of this agreement later in the call.

這項決定明確了我們推進丁型肝炎計畫的方針，並使我們能夠靈活地與歐洲和其他國際市場合作開展該計劃。該協議的結果已在我們的預期之內，並已納入我們的長期財務規劃中，並已納入我們預計到 2027 年中期的現金流中。傑森將在稍後的電話會議中提供有關該協議財務方面的更多細節。

Turning briefly to our hepatitis B program. We are presenting 24-week post-treatment follow-up data from our MARCH Phase II study at the upcoming EASL Congress on May 9. Specifically, we will be sharing functional cure data from participants who have completed 24 weeks of follow-up after treatment discontinuation. Shifting gears to our oncology portfolio. We continue to make steady progress with the PRO-XTEN Dual Masked T-Cell Engager program.

簡單談談我們的乙肝計畫。我們將在 5 月 9 日即將召開的 EASL 大會上展示 MARCH II 期研究的 24 週治療後追蹤資料。具體來說，我們將分享治療停止後完成 24 週追蹤的參與者的功能性治癒數據。轉向我們的腫瘤學產品組合。我們在 PRO-XTEN 雙掩蔽 T 細胞接合器計劃上繼續取得穩步進展。

As a reminder, we have worldwide rights to the PRO-XTEN platform in infectious disease and oncology. For VIR-5818, our dual mask to HER2 targeted T-cell engager, we are continuing to dose escalate as monotherapy and in combination with pembrolizumab. Our data presented in January showed a 33% confirmed partial response rate in HER2-positive colorectal cancer patients at doses of 400 micrograms per kilogram and above with 1 response lasting over 18 months.

提醒一下，我們擁有 PRO-XTEN 平台在傳染病和腫瘤學領域的全球權利。對於 VIR-5818（我們的 HER2 標靶 T 細胞接合劑的雙重掩蔽），我們將繼續以單一療法和與 pembrolizumab 聯合療法增加劑量。我們在一月份公佈的數據顯示，在劑量為每公斤 400 微克及以上的 HER2 陽性結直腸癌患者中，確認的部分緩解率為 33%，其中 1 次緩解持續超過 18 個月。

We are particularly encouraged by these results in colorectal cancer, where there remains a significant unmet need for effective therapies. These responses were observed in microsatellite stable tumors, which are typically resistant to immunotherapy, suggesting VIR-5818 could potentially address an important treatment gap for these patients.

我們對大腸直腸癌的這些結果感到特別鼓舞，因為該領域對有效治療方法的需求仍有很大差距。這些反應是在通常對免疫療法有抗性的微衛星穩定腫瘤中觀察到的，這表明 VIR-5818 可能能夠解決這些患者的一個重要的治療空白。

For VIR-5500, our dual masked PSMA targeted T-cell engager, we continue to dose escalate given our favorable safety profile and the learnings from VIR-5818. We've evaluated multiple additional dose levels since our last update. Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA declines with 58% achieving a PSA50 response, all without prophylactic steroids and with minimal cytokine release syndrome. We continue to see strong investigator enthusiasm for this program based on the early signals we've observed. We're also on track to initiate our Phase I study for VIR-5525, our dual masked EGFR targeted T-cell engager this quarter.

對於我們的雙掩蔽 PSMA 靶向 T 細胞接合劑 VIR-5500，鑑於我們良好的安全性和從 VIR-5818 中吸取的經驗教訓，我們將繼續增加劑量。自上次更新以來，我們已評估了多個額外的劑量水平。我們一月份的數據顯示，接受劑量超過 120 微克/公斤的患者中 100% 都出現了 PSA 下降，其中 58% 達到了 PSA50 反應，所有患者均未使用預防性類固醇，且細胞激素釋放綜合徵的發生率極低。根據我們觀察到的早期信號，我們繼續看到研究人員對該計劃的強烈熱情。我們也計劃於本季啟動針對 VIR-5525（我們的雙掩蔽 EGFR 標靶 T 細胞接合劑）的 I 期研究。

This program has the potential to address multiple high-value indications, including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma and other EGFR-expressing tumors. The PRO-XTEN universal dual masking approach continues to demonstrate potential advantages in terms of safety profile and dosing flexibility.

此計畫有可能解決多種高價值適應症，包括非小細胞肺癌、大腸直腸癌、頭頸部鱗狀細胞癌和其他表達 EGFR 的腫瘤。PRO-XTEN 通用雙重遮蔽方法在安全性和劑量靈活性方面繼續展現出潛在優勢。

Beyond our clinical stage programs, we are rapidly advancing several next-generation targets in areas of high unmet medical need. Our antibody discovery and protein engineering capabilities are key to the discovery of new tumor-associated antigen binders to quickly advance new TCE programs. And the universal nature of the PRO-XTEN platform allows us to efficiently apply our dual masking approach.

除了臨床階段項目外，我們還在醫療需求尚未滿足的領域迅速推進幾個下一代目標。我們的抗體發現和蛋白質工程能力對於發現新的腫瘤相關抗原結合劑以快速推進新的 TCE 計畫至關重要。PRO-XTEN 平台的通用特性使我們能夠有效地應用雙重掩蔽方法。

The synergies between antibody discovery capabilities and the PRO-XTEN platform have begun to translate into meaningful progress with seven targets progressing in preclinical development across a number of solid tumor indications with high unmet need. These research efforts represent important long-term value drivers for our oncology portfolio.

抗體發現能力與 PRO-XTEN 平台之間的協同作用已開始轉化為有意義的進展，七個目標在多種具有高度未滿足需求的實體瘤適應症的臨床前開發中取得進展。這些研究工作對於我們的腫瘤學產品組合而言是重要的長期價值驅動力。

We're also exploring potential collaborations that could further unlock and maximize value from the PRO-XTEN platform. Additionally, leveraging our expertise in infectious disease immunology, we have advanced a broadly neutralizing antibody to development candidate status in our HIV cure program. Looking ahead, our financial position remains strong with approximately $1 billion in cash, cash equivalents and investments at the end of the first quarter.

我們也正在探索潛在的合作，以進一步釋放和最大化 PRO-XTEN 平台的價值。此外，利用我們在傳染病免疫學方面的專業知識，我們在愛滋病毒治療計劃中將廣譜中和抗體提升為候選抗體。展望未來，我們的財務狀況依然強勁，第一季末的現金、現金等價物和投資約為 10 億美元。

This provides us with cash runway extending into mid-2027, giving us the resources to advance our key programs through critical value inflection points. We're maintaining a disciplined approach to capital allocation, focusing our resources on our most promising programs. As we continue to execute on our strategic priorities, we recognize the challenging market environment facing the biotechnology sector as a whole. In times like these, we believe the most important thing we can do for our shareholders is to remain focused on operational excellence and advancing our pipeline with discipline and purpose. Our strong cash position allows us to weather market volatility.

這為我們提供了延伸至 2027 年中期的現金流，使我們有資源透過關鍵價值轉折點來推進我們的關鍵項目。我們保持嚴謹的資本配置方式，將資源集中在最有前景的項目上。在我們繼續執行策略重點的同時，我們認識到整個生物技術領域面臨著充滿挑戰的市場環境。在這樣的時刻，我們相信，我們能為股東做的最重要的事情就是繼續專注於卓越運營，並有紀律、有目的地推進我們的產品線。我們強大的現金狀況使我們能夠抵禦市場波動。

I'm confident that our focused approach to developing potentially transformative medicines for patients with significant unmet needs will make a difference in the lives of patients while driving value creation for our shareholders. With that, I'll now turn the call over to Mark to provide a more detailed update on our clinical development programs.

我相信，我們專注於為具有重大未滿足需求的患者開發具有變革性潛力的藥物，這將改變患者的生活，同時為我們的股東創造價值。說完這些，我現在將電話轉給馬克，讓他提供有關我們的臨床開發計劃的更詳細的更新。

Thank you, Marianne. I'm pleased to provide an update on our clinical development programs. We've made significant progress across both our infectious disease and oncology portfolios during the first quarter, and I'll walk you through the key developments. Let me start with our hepatitis delta program, where we've achieved an important milestone with the initiation of our registrational ECLIPSE Phase III program. I'm pleased to report that we enrolled the first patient in ECLIPSE-1 during the first quarter, keeping us on track with our development timeline.

謝謝你，瑪麗安。我很高興提供有關我們的臨床開發計劃的最新進展。我們在第一季的傳染病和腫瘤學領域都取得了重大進展，我將向您介紹主要進展。首先介紹我們的丁型肝炎項目，隨著註冊 ECLIPSE 第三階段項目的啟動，我們取得了一個重要的里程碑。我很高興地報告，我們在第一季招募了第一位 ECLIPSE-1 患者，讓我們的開發時間表保持在正軌上。

ECLIPSE-1 is designed to evaluate our combination therapy in regions where bulevirtide is not available or has limited use, including the United States. The study will enroll 120 participants randomized 2-to-1 to receive either our combination therapy or deferred treatment. The primary endpoint is a composite endpoint of HDV RNA target not detected, meaning that there was no measurable presence of the virus in the blood and ALT normalization at week 48. The key secondary endpoint is HDV RNA target not detected. We're also preparing for the initiation of ECLIPSE-2, which will evaluate switching to our combination therapy in patients who have not adequately responded to bulevirtide.

ECLIPSE-1 旨在評估我們在布洛韋肽無法使用或使用有限的地區（包括美國）的聯合療法。研究將招募 120 名參與者，以 2 比 1 的比例隨機接受我們的聯合療法或延遲治療。主要終點是未檢測到 HDV RNA 標靶的複合終點，這意味著在第 48 週時血液中沒有可測量的病毒存在和 ALT 正常化。關鍵次要終點是未檢測到 HDV RNA 標靶。我們也正在為啟動 ECLIPSE-2 做準備，該試驗將評估對布洛韋肽反應不佳的患者改用我們的聯合療法。

ECLIPSE-2 will have a 24-week primary endpoint of HDV target not detected. Together, ECLIPSE 1 and 2 are designed to form the backbone of our regulatory submissions in the United States and Europe. This comprehensive approach addresses different patient populations and treatment scenarios, providing a robust evidence package for regulatory review. These studies will include both non-cirrhotic participants and those with compensated cirrhosis. This broad eligibility is important as it reflects the real-world patient population and will provide valuable insights into the treatment effects across different stages of disease.

ECLIPSE-2 的 24 週主要終點為未偵測到 HDV 目標。ECLIPSE 1 和 2 共同構成了我們在美國和歐洲監管提交的支柱。這種綜合方法針對不同的患者群體和治療情況，為監管審查提供了強有力的證據包。這些研究將包括非肝硬化參與者和代償性肝硬化參與者。這種廣泛的資格非常重要，因為它反映了現實世界的患者群體，並將為不同疾病階段的治療效果提供寶貴的見解。

The regulatory designations we've received, breakthrough therapy and Fast Track in the United States and prime and orphan drug in the EU, reflect the significant unmet need and the potential of our approach to address it. These designations may help accelerate our development and review timelines, potentially bringing this important therapy to patients sooner.

我們獲得的監管認定，在美國被認定為突破性療法和快速通道，在歐盟被認定為主要療法和孤兒藥，反映了巨大的未滿足需求以及我們解決這一問題的方法的潛力。這些指定可能有助於加快我們的開發和審查時間表，並有可能更快地為患者帶來這種重要的治療方法。

At the upcoming EASL Congress, we'll be presenting a poster showcasing data from a 24-week subgroup analysis of our SOLSTICE trial, examining the impact of baseline viral parameters and cirrhosis status on responses to our combination therapy. For our hepatitis B program, we'll be presenting 24-week post-treatment follow-up data from our MARCH Phase II study at EASL on May 9. This presentation will provide insights into functional cure after treatment discontinuation.

在即將舉行的 EASL 大會上，我們將展示一張海報，展示我們 SOLSTICE 試驗的 24 週亞組分析數據，研究基線病毒參數和肝硬化狀態對我們的聯合療法反應的影響。對於我們的乙肝項目，我們將於 5 月 9 日在 EASL 上展示 MARCH II 期研究的 24 週治療後追蹤數據。本演講將提供關於停止治療後功能性治癒的見解。

As a reminder, advancement of this program into further clinical development is contingent on securing a partner. Now I'd like to turn to our oncology portfolio, where we continue to make progress with the PRO-XTEN masked T-cell engager programs. Our dual masked approach is designed to selectively activate T-cell engagers in the tumor microenvironment, potentially providing a wider therapeutic window than traditional unmasked approaches. Our PRO-XTEN masked TCEs achieved this through the addition of long hydrophilic polypeptide XTEN masks that shield both the CD3 and tumor-associated antigen binding domains by a steric hindrance. Importantly, these universal masks are cleaved by proteases found within the tumor microenvironment, enabling selective activation where it's needed most.

提醒一下，該計畫的進一步臨床開發取決於能否找到合作夥伴。現在我想談談我們的腫瘤學產品組合，我們在 PRO-XTEN 掩蔽 T 細胞接合器計畫方面繼續取得進展。我們的雙重掩蔽方法旨在選擇性地激活腫瘤微環境中的 T 細胞接合劑，從而可能提供比傳統未掩蔽方法更廣泛的治療窗口。我們的 PRO-XTEN 掩蔽 TCE 透過添加長親水性多肽 XTEN 掩蔽物實現了這一點，該掩蔽物透過空間位阻屏蔽了 CD3 和腫瘤相關抗原結合域。重要的是，這些通用掩模被腫瘤微環境中的蛋白酶裂解，從而能夠在最需要的地方進行選擇性活化。

This technology allows for higher dosing with reduced systemic toxicity, which we believe could translate to improved efficacy and safety profiles. The selective activation in the tumor microenvironment is key to minimizing off-target effects while maximizing antitumor activity. For VIR-5818, our HER2-targeted T-cell engager, we're continuing dose escalation in both monotherapy and in combination with pembrolizumab. As a reminder, our data presented in January showed a 33% confirmed partial response rate in HER2-positive colorectal cancer at doses of 400 micrograms per kilogram and above with response lasting over 18 months. This durability is particularly encouraging in this heavily pretreated population.

該技術可以實現更高的劑量並降低全身毒性，我們相信這可以轉化為提高療效和安全性。腫瘤微環境中的選擇性活化是最大限度地減少脫靶效應同時最大限度地提高抗腫瘤活性的關鍵。對於我們的 HER2 標靶 T 細胞接合劑 VIR-5818，我們正在單一療法和與 pembrolizumab 聯合療法中持續增加劑量。提醒一下，我們在一月份公佈的數據顯示，在劑量為每公斤 400 微克及以上的情況下，HER2 陽性結直腸癌的確認部分緩解率為 33%，且緩解持續時間超過 18 個月。對於經過大量預處理的人群來說，這種耐久性尤其令人鼓舞。

Importantly, as Marianne mentioned, the responses we observed in microsatellite stable colorectal cancer are noteworthy from a mechanistic perspective. These tumors typically have low tumor mutational burden and limited T-cell infiltration, creating significant challenges for immunotherapy approaches. Our data suggests that VIR-5818's ability to redirect T-cells to HER2-expressing tumor cells may provide a way to overcome these immunological barriers.

重要的是，正如瑪麗安所提到的，從機制角度來看，我們在微衛星穩定性大腸癌中觀察到的反應是值得注意的。這些腫瘤通常具有較低的腫瘤突變負擔和有限的 T 細胞浸潤，這對免疫治療方法帶來了重大挑戰。我們的數據表明，VIR-5818 將 T 細胞重定向至表達 HER2 的腫瘤細胞的能力可能提供一種克服這些免疫障礙的方法。

The durability of response we've seen further supports the potential of this approach in a setting where patients typically experience rapid progression after exhausting standard treatment options. We remain focused on evaluating the potential of this program across multiple HER2-expressing tumor types as we believe our approach could address significant unmet needs in various solid tumors where HER2 expression plays a role.

我們所看到的反應的持久性進一步支持了這種方法的潛力，因為患者在用盡標準治療方案後通常會經歷快速進展。我們仍然專注於評估該計劃在多種 HER2 表達腫瘤類型中的潛力，因為我們相信我們的方法可以滿足 HER2 表達發揮作用的各種實體腫瘤中尚未滿足的重大需求。

For VIR-5500, our PSMA-targeted T-cell engager, we're advancing our dose escalation strategy in both weekly and Q3-week dosing regimens. Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA declines with 58% achieving a PSA50 response, all without prophylactic steroids and with minimal cytokine release syndrome. This favorable safety profile differentiates our approach from other PSMA-targeted therapies in development. The program continues to evaluate the potential of our PRO-XTEN dual masked approach in metastatic castration-resistant prostate cancer, a setting with significant unmet need despite recent therapeutic advances. We are particularly encouraged by the potential for Q3-week dosing.

對於我們的 PSMA 標靶 T 細胞接合劑 VIR-5500，我們正在每周和每三季的給藥方案中推進劑量遞增策略。我們一月份的數據顯示，接受劑量超過 120 微克/公斤的患者中 100% 都出現了 PSA 下降，其中 58% 達到了 PSA50 反應，所有患者均未使用預防性類固醇，且細胞激素釋放綜合徵的發生率極低。這種良好的安全性使我們的方法有別於其他正在開發中的針對 PSMA 的療法。該計畫繼續評估我們的 PRO-XTEN 雙掩蔽方法在轉移性去勢抵抗性前列腺癌中的潛力，儘管最近治療取得了進展，但該領域仍存在大量未滿足的需求。我們對第三季劑量的潛力感到特別鼓舞。

With a half-life of 8 to 10 days for VIR-5500, we believe we can offer a much more convenient dosing schedule. This would be especially important for patients in earlier lines of treatment where quality of life considerations become increasingly significant. We've successfully evaluated multiple dose levels since the data we shared in our January 8 event and are continuing with dose escalation.

VIR-5500 的半衰期為 8 至 10 天，我們相信我們可以提供更方便的給藥時間表。這對於早期治療的患者尤其重要，因為他們的生活品質變得越來越重要。自 1 月 8 日的活動中分享數據以來，我們已成功評估了多種劑量水平，並且正在繼續增加劑量。

This ongoing dose optimization is critical to identifying a regimen that provides the optimal balance of efficacy and safety. We believe VIR-5500 has the potential to be a best-in-class treatment option in this area of significant unmet medical need, offering a combination of efficacy, safety and convenience that could meaningfully improve outcomes for patients with prostate cancer.

持續的劑量優化對於確定提供療效和安全性最佳平衡的方案至關重要。我們相信 VIR-5500 有潛力成為這一重大未滿足醫療需求領域的最佳治療選擇，它兼具療效、安全性和便利性，可以顯著改善前列腺癌患者的治療效果。

Building on our progress with our first 2 TCE programs, we're now expanding our portfolio with our third clinical candidate. We're on track to initiate our Phase I study for VIR-5525, our EGFR-targeted T-cell engager during this quarter. This program has the potential to address multiple high unmet need and high-value indications with EGFR expression, including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma and other EGFR-expressing tumors.

在我們前兩個 TCE 項目取得進展的基礎上，我們現在正在透過第三個臨床候選項目擴展我們的產品組合。我們將在本季啟動針對 EGFR 標靶 T 細胞抑制劑 VIR-5525 的 I 期研究。此計畫有可能解決多種EGFR表現的未滿足需求和高價值適應症，包括非小細胞肺癌、大腸直腸癌、頭頸部鱗狀細胞癌和其他表達EGFR的腫瘤。

The unmet need in these indications remain substantial despite recent advances with hundreds of thousands of patients diagnosed annually with EGFR-expressing tumors across these indications. VIR-5525 has the potential to address a substantial unmet need through a novel modality that harnesses the patient's T-cells to kill EGFR-expressing cancer cells.

儘管近年來取得了一些進展，每年有數十萬名患者被診斷出患有 EGFR 表達腫瘤，但這些適應症中未滿足的需求仍然很大。VIR-5525 有可能透過一種利用患者 T 細胞殺死表達 EGFR 的癌細胞的新方式來解決大量未滿足的需求。

Our PRO-XTEN dual masked approach could offer a differentiated safety profile, potentially allowing for more aggressive targeting of EGFR-expressing tumors compared to traditional approaches. The universal nature of the PRO-XTEN platform enables us to leverage our learnings from our earlier T-cell engager programs to optimize study design and dose escalation for VIR-5525. In conclusion, I'm very pleased with the progress we're making across our entire portfolio. The initiation of our ECLIPSE Phase III program and continued advancement of our T-cell engager programs demonstrates our commitment to addressing significant unmet medical needs. We remain focused on executing our clinical development plans with scientific rigor and operational excellence, always keeping in mind the patients who could benefit from these potential therapies.

我們的 PRO-XTEN 雙重掩蔽方法可以提供差異化的安全性，與傳統方法相比，可能允許更積極地針對 EGFR 表達腫瘤。PRO-XTEN 平台的通用性使我們能夠利用從早期 T 細胞接合器計劃中獲得的經驗來優化 VIR-5525 的研究設計和劑量遞增。總而言之，我對我們整個投資組合所取得的進展感到非常滿意。我們的 ECLIPSE 第三階段計劃的啟動和 T 細胞接合器計劃的持續推進表明了我們致力於解決重大未滿足的醫療需求的承諾。我們始終專注於以科學嚴謹性和卓越營運執行我們的臨床開發計劃，並始終牢記那些可以從這些潛在療法中受益的患者。

With that, I'll now hand over the call to Jason.

說完這些，我現在將電話交給傑森。

Thank you, Mark. I'm pleased to share our first quarter financial performance and overall financial position. We continue to maintain a strong financial foundation while advancing our key programs, and I'll start with several key financial metrics for this past quarter. R&D expenses for the first quarter of 2025 were $118.6 million, which included $7 million of noncash stock-based compensation expense compared to $100.1 million for the same period in 2024, which included $13.6 million of stock-based compensation expense. The increase in R&D expenses was primarily driven by a $30 million payment to Alnylam and expenses related to the initiation of the ECLIPSE registrational program.

謝謝你，馬克。我很高興分享我們第一季的財務表現和整體財務狀況。我們在推進關鍵項目的同時繼續保持強勁的財務基礎，我將首先介紹上個季度的幾個關鍵財務指標。2025 年第一季的研發費用為 1.186 億美元，其中包括 700 萬美元的非現金股票薪酬費用，而 2024 年同期的研發費用為 1.001 億美元，其中包括 1,360 萬美元的股票薪酬費用。研發費用的增加主要由於向 Alnylam 支付的 3000 萬美元以及啟動 ECLIPSE 註冊計劃的相關費用。

These increases were partially offset by lower R&D expenses associated with past headcount reductions, deprioritized programs and the closing of our St. Louis, Missouri and Portland, Oregon sites. SG&A expenses for the first quarter of 2025 were $23.9 million, which included $7.1 million of stock-based compensation expense. compared to $36.3 million for the same period in 2024, which included $10.2 million of stock-based compensation expense. The decrease was largely due to ongoing cost savings realized through headcount reductions and other initiatives.

這些增長被過去裁員、降低優先項目以及關閉位於密蘇裡州聖路易斯和俄勒岡州波特蘭的工廠所導致的研發費用降低部分抵消。2025 年第一季的銷售、一般及行政費用為 2,390 萬美元，其中包括 710 萬美元的股票薪酬費用。而 2024 年同期為 3,630 萬美元，其中包括 1,020 萬美元的股票薪酬費用。下降的主要原因是透過裁員和其他措施實現的持續成本節約。

Combined, our first quarter operating expense of $142.6 million increased modestly by approximately $6 million year-over-year. Net loss for the first quarter of 2025 was $121 million compared to a net loss of $65.3 million for the same period in 2024. The higher net loss was largely driven by $52 million of revenue in the first quarter of 2024 compared to approximately $3 million of revenue in the first quarter of 2025. Turning to cash. Our net cash consumed in the first quarter was $75.6 million, which is in line with our expectations.

總體而言，我們第一季的營運費用為 1.426 億美元，年比小幅增加約 600 萬美元。2025 年第一季淨虧損為 1.21 億美元，而 2024 年同期淨虧損為 6,530 萬美元。淨虧損增加的主要原因是 2024 年第一季的營收為 5,200 萬美元，而 2025 年第一季的營收約為 300 萬美元。轉向現金。我們第一季的淨現金消耗為7560萬美元，符合我們的預期。

We ended the quarter with approximately $1 billion in cash, cash equivalents and investments. Based on our current operating plan, we continue to project our cash runway extending into mid-2027. This provides us with the resources to advance key programs through planned value inflection points. As Marianne mentioned earlier, Alnylam has elected not to opt into the profit-sharing arrangement for elebsiran. As a result, we recognized $3 million as R&D expense in the first quarter, which was paid in cash to Alnylam in April of this year.

本季末，我們擁有約 10 億美元的現金、現金等價物和投資。根據我們目前的營運計劃，我們預計現金流將持續到 2027 年中期。這為我們提供了透過計劃價值拐點來推進關鍵項目的資源。正如 Marianne 之前提到的，Alnylam 選擇不加入 elebsiran 的利潤分享協議。因此，我們在第一季確認了 300 萬美元的研發費用，並於今年 4 月以現金支付給了 Alnylam。

This payment reduced potential future development and regulatory milestones that were described in our most recent 10-K from $175 million to $145 million. The amended terms are further described in our first quarter 10-Q. The agreement with Alnylam remains a milestone and royalty-based arrangement. This was our base case outcome and was assumed in our current runway guidance. Our capital deployment strategy remains focused on our most promising programs, advancing our hepatitis delta ECLIPSE registrational studies with ECLIPSE-1 continuing to enroll and preparations underway for ECLIPSE-2 and ECLIPSE-3; continuing dose escalation for our T-cell engager programs, VIR-5818 and VIR-5500; and finally, initiating and advancing the Phase I study for 5525.

這筆款項將我們最近的 10-K 報告中描述的潛在未來開發和監管里程碑從 1.75 億美元減少到 1.45 億美元。修改後的條款在我們的第一季 10-Q 中有進一步描述。與 Alnylam 達成的協議仍然是一個里程碑和基於特許權使用的安排。這是我們的基本情況結果，也是我們目前跑道指導中的假設。我們的資本部署策略仍然專注於我們最有前景的項目，推進我們的丁型肝炎 ECLIPSE 註冊研究，其中 ECLIPSE-1 繼續招募患者，ECLIPSE-2 和 ECLIPSE-3 的準備工作正在進行中；繼續提高我們的 T 細胞接合器項目 VIR-5818 和 VIR-5500 的 55 期啟動和 525 期啟動和研究的 525 期啟動和研究。

For our hepatitis B program, any further development will be contingent upon securing a development and commercialization partner. We continue to apply financial discipline as we deploy resources toward advancing these key programs to create value and benefit for patients. With that, I'll hand it back to Rich to initiate the Q&A session.

對於我們的B型肝炎項目，任何進一步的發展都將取決於是否能找到開發和商業化合作夥伴。我們在部署資源推進這些關鍵項目、為患者創造價值和利益的同時，將繼續嚴格遵守財務紀律。說完這些，我會把話題交還給 Rich，開始問答環節。

Thank you, Jason. This concludes our prepared remarks, and we will now start the Q&A session. Please limit your question to two per person so we can get to all of our covering analysts. I'll turn it over to you, operator.

謝謝你，傑森。我們的準備好的演講到此結束，現在我們將開始問答環節。請將每個人的問題限制為兩個，以便我們能夠聯繫到所有相關分析師。我將把它交給你，接線員。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

I have two questions. So maybe the first one regarding the Alnylam decision. Did they see most up-to-date data for both HBV and HDV? And what was the reason they provided for not opting? And the second question is thinking about you have so many programs progress so rapidly in the oncology space. So when should we see the next update from the programs, and which will be likely the venue when we'll see those data update?

我有兩個問題。所以這可能是第一個關於 Alnylam 決定的問題。他們是否看到了 HBV 和 HDV 的最新數據？他們沒有選擇的理由是什麼？第二個問題是，考慮到腫瘤學領域有這麼多計畫進展如此迅速，我們應該在什麼時候看到這些計畫的下一次更新？這些數據更新最有可能在哪個平台發布？

Yes. Thank you, Gena, for those questions. Maybe I'll start with the last one first. So when the next oncology data update will be coming. So the way we think about it for any next data update, what we would be anticipating to share is, first of all, obviously, more mature data at higher dose levels beyond what we presented just a couple of months ago in January.

是的。謝謝吉娜提出這些問題。也許我應該先從最後一個開始。那麼下一次腫瘤學數據更新什麼時候會到來呢？因此，對於任何下一次數據更新，我們考慮的方式是，我們期望分享的首先顯然是更高劑量水平的更成熟的數據，而不是我們在幾個月前一月份提供的數據。

We would also want to share comparative data between weekly and every three-week dosing. We think the latter is especially relevant for our ambition to go into earlier lines. Also, a clearer picture, obviously, on dose response relationships, additional insights into the safety profile at higher doses and, of course, also PSA responses. So once we have all that for 500 and for 5818, we will be sharing it, of course, either through a medical congress or through a more focused investor event. So as soon as we are ready, we will do so.

我們也希望分享每周和每三週劑量之間的比較數據。我們認為後者對於我們進軍早期領域的野心尤其重要。此外，顯然，劑量反應關係可以更清楚地展現，對較高劑量下的安全性有更多了解，當然還有 PSA 反應。因此，一旦我們掌握了 500 和 5818 的全部信息，我們就會透過醫學大會或更有針對性的投資者活動來分享。因此，一旦我們準備好了，我們就會這樣做。

Your second question, Gena, related to Alnylam. So Alnylam made their decision to opt out of the profit-sharing arrangement before our most recent HBV functional cure data was available. As you know, that data is only going to be presented for the first time on Friday at EASL on May 9. So this decision was really based on their own strategic portfolio prioritization.

吉娜，你的第二個問題與 Alnylam 有關。因此，在我們最新的 HBV 功能性治癒數據公佈之前，Alnylam 決定退出利潤分享協議。如您所知，該數據將於 5 月 9 日星期五在 EASL 上首次公佈。因此，這個決定實際上是基於他們自己的策略性投資組合優先順序。

Paul Choi, Goldman Sachs.

高盛的保羅·崔（Paul Choi）。

I want to ask about -- first about EASL, and it looks like you have a late breaker of the doublet in combination with the Virion 200 asset. Just curious, I think that's the first look we'll get at that program. And so just curious sort of what the rationale is behind that new triplet combination strategy there and just sort of how you think about the development plans for that versus your other combinations?

我想問一下——首先是關於 EASL 的問題，看起來你們與 Virion 200 資產的結合帶來了雙重突破。只是好奇，我想這是我們第一次看到這個程式。所以我很好奇這種新的三重組合策略背後的原理是什麼，以及您如何看待這種組合與其他組合相比的發展計劃？

And my second question is, can you comment maybe in broad strokes on how you're thinking about completing enrollment or completing either the ECLIPSE1 or ECLIPSE-2 studies. This will be helpful to understand in the context of your cash guidance runway to 2027 since you're just putting in first patient in the first quarter here? Just some context on that timing would be helpful.

我的第二個問題是，您能否大致評論一下您對完成入學或完成 ECLIPSE1 或 ECLIPSE-2 研究的想法。由於您在第一季才接收了第一位患者，所以這將有助於理解您2027年的現金指導路線。請提供一些關於這個時間點的背景資訊。

Thank you, Paul. So maybe the first question on the Virion combination. Mark, do you want to answer that?

謝謝你，保羅。所以第一個問題可能與病毒體組合有關。馬克，你想回答這個問題嗎？

Yes. So thanks, Paul, for the questions. I mean, first of all, that's a study conducted by Virion, and we did provide access to tobevibart and elebsiran for that study. But we're not -- it's being run by Virion, and it's in their portfolio and not ours. So I think the data are interesting in terms of some of the early responses in terms of surface antigen decline, but that's really in their portfolio rather than ours.

是的。所以，保羅，謝謝你的提問。我的意思是，首先，這是 Virion 進行的一項研究，我們確實為該研究提供了 tobevibart 和 elebsiran 的訪問權限。但我們不是——它是由 Virion 經營的，它屬於他們的投資組合，而不是我們的。因此，我認為就表面抗原下降方面的一些早期反應而言，數據很有趣，但這實際上是他們的業務範圍，而不是我們的業務範圍。

You're asking a really good question about HDV and our timelines. We did announce first patient dosed for ECLIPSE-1, and we have a study estimated completion date of the end of 2026. So that means we would be aiming to complete enrollment in that study by the end of this year. I mean that's an aggressive target, but we are putting all of our resources behind getting these ECLIPSE trials up and running. For ECLIPSE-2, we haven't provided guidance yet, but I can assure you that we are laser-focused on getting that study up and running.

您問了一個關於 HDV 和我們的時間表的非常好的問題。我們確實宣布了第一位接受 ECLIPSE-1 治療的患者，我們預計研究將於 2026 年底完成。這意味著我們的目標是在今年年底前完成該研究的招募。我的意思是，這是一個積極的目標，但我們正在投入所有資源來啟動和運行這些 ECLIPSE 試驗。對於 ECLIPSE-2，我們尚未提供指導，但我可以向你保證，我們專注於啟動和運行這項研究。

It's important to note that the ECLIPSE-2 actually has a 24-week endpoint. So even though it's starting dosing a little bit later, it will have a 24 versus 48-week readout. So the timing will provide some more guidance when we're able to do that, but that's an important point to consider.

值得注意的是，ECLIPSE-2 實際上有 24 週的終點。因此，儘管開始給藥的時間稍晚一些，但也會有一個 24 週而不是 48 週的讀數。因此，當我們能夠做到這一點時，時機將提供更多指導，但這是需要考慮的重要一點。

Mike Ulz, Morgan Stanley.

摩根士丹利的麥克烏爾茲。

This is Avi Novick on the line for Mike. So a competitor of yours recently shared updated data from its TCE PSMA targeting program in metastatic CRPC. So I was wondering if you had any updated thoughts on your -- on the competitive positioning of AR-5500? And do you see a median PFS of around 7.5 months as, I guess, a fair and achievable benchmark for your program?

我是 Avi Novick，接聽 Mike 的電話。因此，您的競爭對手最近分享了其轉移性 CRPC 中的 TCE PSMA 標靶計劃的最新數據。所以我想知道您對 AR-5500 的競爭定位有什麼最新的想法嗎？您是否認為大約 7.5 個月的中位 PFS 是您的計劃公平且可實現的基準？

So yes, I can take that question. First of all, we're actually very encouraged about the continued progress for T-cell engagers in general, including the fact that JANX continues to prove proof-of-concept that masking technology actually extends the therapeutic index. And while I can't comment directly on how we would be compared, because we are relatively earlier in our dose escalation compared to where they are, we do think that we are quite differentiated in that our PRO-XTEN is a dual mask technology. It's quite a different masking technology than the other masks that are out there. It's a universal mask.

是的，我可以回答這個問題。首先，我們實際上對 T 細胞接合劑整體上的持續進展感到非常鼓舞，包括 JANX 繼續證明掩蔽技術實際上延長了治療指數的概念驗證。雖然我無法直接評論我們之間的比較，因為我們的劑量增加相對較早，但我們確實認為我們之間的差異很大，因為我們的 PRO-XTEN 是一種雙面罩技術。這是一種與現有的其他面罩截然不同的面罩技術。這是一個通用面具。

It's the only clinically validated mask in terms of having clinical validation in other platforms such as the drug Altuvia, a hemophilia drug. And we do think that we have a really very favorable safety profile. We demonstrated in our January update that we have a very low rate of CRS. We do not use any prophylactic steroids. We know that every other T-cell engager program needs some form of prophylaxis.

它是唯一在其他平台（例如血友病藥物 Altuvia）上經過臨床驗證的口罩。我們確實認為我們的安全狀況非常良好。我們在一月份的更新中表明我們的 CRS 率非常低。我們不使用任何預防性類固醇。我們知道，每個 T 細胞接合程序都需要某種形式的預防措施。

And despite the lack of use of corticosteroids, we have this very low-grade CRS and also no evidence of significant IL-6 elevations. And despite that, we are seeing some nice really early activity. The other big differentiator, which I think is important, both for safety and is in the front line is that we have a longer half-life of 8 to 10 days, which enables our Q3 week dosing schedule. We know that for convenience and quality of life in the frontline setting for prostate cancer, in particular, these types of differentiation is going to be critically important for overall tolerability, a huge unmet need where we think these drugs could potentially offer significant convenience for that.

儘管沒有使用皮質類固醇，但我們的 CRS 等級非常低，也沒有 IL-6 明顯升高的證據。儘管如此，我們還是看到了一些非常好的早期活動。另一個我認為很重要的重大區別是，無論是對於安全性還是在前線，我們的半衰期都更長，為 8 到 10 天，這使得我們能夠按照 Q3 週的給藥計劃進行。我們知道，為了前列腺癌一線治療的便利性和生活質量，這些類型的分化對於整體耐受性至關重要，這是一個巨大的未滿足的需求，我們認為這些藥物可能會為此提供很大的便利。

Eric Joseph, JPMorgan.

摩根大通的艾瑞克‧約瑟夫。

This is Ron on for Eric. I wanted to ask how does the recent bulevirtide update impact you're thinking around the potential finite versus long-term chronic treatment with the combination for HDV?

這是羅恩 (Ron) 代替埃里克 (Eric) 上場。我想問一下，最近關於布列衛肽的更新對您對 HDV 聯合治療的潛在有限治療和長期慢性治療有何影響？

Sure. Mark, do you want to take for the question?

當然。馬克，你想回答這個問題嗎？

So I think your question is about bulevirtide and their long-term outcome data and their ability to achieve finite treatment, how does that affect our program? So just to remind everybody, I mean, we achieved in our SOLSTICE study very high rates of target not detected or complete viral suppression. We're achieving it in the majority of patients by week 24 and week 36. And we're getting to 64% at week 36. So that compares to bulevirtide in week 48 of only 12%.

所以我認為您的問題是關於布列衛肽及其長期結果數據以及其實現有限治療的能力，這對我們的計劃有何影響？所以只是為了提醒大家，我的意思是，我們在 SOLSTICE 研究中實現了非常高的目標未偵測到率或完全病毒抑制率。我們將在第 24 週和第 36 週對大多數患者實現這一目標。到第 36 週時，我們已達到 64%。相較之下，第 48 週的布洛韋肽僅為 12%。

So we think we can achieve very high rates of viral suppression in terms of long-term suppression. Gilead, the bulevirtide data that are related to finite treatment are with their higher dose. So that's one thing to consider. And it's not really something that's in their label right now. So we are aiming for a chronic viral suppressive regimen.

因此我們認為，就長期抑製而言，我們可以實現非常高的病毒抑制率。吉利德（Gilead），與有限治療相關的布洛韋肽數據與其較高的劑量有關。這是需要考慮的一件事。而這其實並不是他們現在的標籤上的東西。因此，我們的目標是採取慢性病毒抑制療法。

We think we can suppress the virus in the vast majority of patients. We're also achieving three log declines in hepatitis B surface antigen, again, just pointing to the potency and the depth and breadth of our viral suppression for delta. So we're really excited to be moving into the Phase III program.

我們認為我們可以抑制絕大多數患者的病毒。我們也實現了乙肝表面抗原的三次對數下降，這再次顯示了我們對病毒抑制的效力和深度和廣度。因此，我們非常高興能夠進入第三階段計劃。

Roanna Ruiz, Leerink Partners.

Roanna Ruiz，Leerink Partners。

This is Nick Gasic on for Roanna. Maybe first on HBV. How should we think about your expectations heading into the 24-week off-treatment data for March at EASL? What are you hoping to see from a functional cure standpoint relative to the end of treatment data we got at AASLD? And maybe what implications could this new data have for potential partnership discussions in HBV?

這是尼克·加西克 (Nick Gasic)，代表羅安娜 (Roanna) 出場。也許首先針對的是 HBV。我們該如何看待您對 EASL 三月 24 週停藥資料的期望？相對於我們在 AASLD 獲得的治療結束數據，您希望從功能性治癒的角度看到什麼？這些新數據對於 HBV 領域的潛在合作討論有何影響？

Go ahead, Mark. No, go ahead.

繼續吧，馬克。不，繼續吧。

So I was just going to say we are looking forward to presentation of our March data, 24-week off-treatment data this Friday at EASL. This will be the look at our functional cure rate. As you might imagine, we are going into a quiet period because it is just a very short period between now and then. So we don't want to comment extensively except to say that we have been signaled in the past that we're looking for 20% in the doublet and a 30% functional cure rate in the triplet. But I think stay tuned, and you'll see the full data at EASL in just a couple of days.

所以我只是想說，我們期待本週五在 EASL 上展示我們的 3 月數據和 24 週停藥數據。這就是我們對功能性治癒率的觀察。正如你可能想像的那樣，我們正進入一個平靜期，因為從現在到那時只是一段很短的時期。因此，我們不想發表過多的評論，只想說，我們過去曾得到信號，我們期望雙聯療法的功能性治癒率為 20%，三聯療法的功能性治癒率為 30%。但我認為請繼續關注，您將在幾天后在 EASL 上看到完整的數據。

Yes. The only thing I would add is that, as we have already mentioned, in January, any further development on the HBV program is contingent on securing a worldwide development and commercialization partner.

是的。我唯一想補充的是，正如我們在一月份已經提到的，HBV 計劃的任何進一步發展都取決於能否找到一個全球性的開發和商業化合作夥伴。

Phil Nadeau, TD Cowen.

菲爾·納多 (Phil Nadeau)，TD Cowen。

Two from us. First, on 5500, you mentioned that there have been multiple doses tested since the data in January. We're wondering if you would care to comment on whether those additional doses have continued to suggest a dose response in efficacy in terms of PSA response rate and durability. That's the first question. And then second, on HDV, the RNA positive figures that you gave for the prevalence of the condition, can you clarify, are those overall prevalence or patients diagnosed having positive RNA?

我們有兩個。首先，關於 5500，您提到自 1 月的數據以來已經進行了多劑測試。我們想知道您是否願意評論一下這些額外劑量是否繼續表明 PSA 反應率和持久性方面的劑量反應。這是第一個問題。其次，關於 HDV，您給出的 RNA 陽性數字代表了疾病的盛行率，您能否澄清一下，這些是總體盛行率還是被診斷為 RNA 陽性的患者？

And if it's not diagnosed, do you have a sense of what the diagnosis rate is? Yes. Thank you, Phil. Maybe I'll start with your last question on delta prevalence. So what we did is we really looked across all available studies, all available reports on delta prevalence.

如果沒有診斷，您是否知道診斷率是多少？是的。謝謝你，菲爾。也許我應該從你關於增量流行率的最後一個問題開始。因此，我們所做的就是認真研究所有可用的研究，所有有關患病率差異的可用報告。

And we sort of started out with determining that based on all the numbers we could get our hands on, that there are about 2 million patients in US that are HPV positive. And again, through a very extensive literature search talking to KOLs, different sources, we found that on average, about 4.7% of those B patients are delta antibody positive. And again, then further drilling down, so that gives you about 92,000 patients actually in the United States. But if you then think about the patients that are actually going to get treated, those are the patients that are RNA positive that are actively viremic.

我們首先根據所能獲得的所有數據確定，美國約有 200 萬 HPV 陽性患者。再次，透過與 KOL 和不同來源進行非常廣泛的文獻檢索，我們發現平均而言，約有 4.7% 的 B 類患者為 delta 抗體陽性。再進一步深入研究，就會發現美國其實有大約 92,000 名患者。但如果你再想想那些真正需要治療的患者，你會發現那些是 RNA 陽性且處於活躍病毒血症狀態的患者。

And so again, based on a lot of sources, we came to the conclusion, as we shared that about 61,000 patients in the United States would be RNA positive and eligible for treatment for our regimen. So that's sort of the breakdown of how we got to the numbers. And then your first question related to 5,500 dosing, maybe, Mika, you can comment.

因此，再次基於大量資料，我們得出結論，正如我們所分享的，美國約有 61,000 名患者的 RNA 呈陽性，有資格接受我們的方案治療。這就是我們得到這些數字的詳細分析。然後，您的第一個問題與 5,500 次劑量有關，也許，Mika，您可以發表評論。

Yes. We have continued the dose escalation, both at the Q week and the Q3 week dosing. But really, we are not prepared to make any comments. We are encouraged with the 5818 data that also showed a nice dose response. We have that one patient who clearly had a dose response within that -- while he intra-patient dose escalated, a colorectal cancer patient who went from 60 micrograms per kg up to 600 micrograms per kg and continue to have a long durability of response lasting over 18 months. But just sit tight and hopefully, we'll be able to say something soon.

是的。我們繼續增加劑量，包括 Q 週和 Q3 週的給藥。但實際上，我們不准備發表任何評論。5818 的數據令我們感到鼓舞，它也顯示出良好的劑量反應。我們有一個病人，他明顯出現了劑量反應——雖然他每次劑量遞增，但這位結直腸癌患者的劑量從每公斤60微克增加到每公斤600微克，並且持續了超過18個月的長期反應。請耐心等待，希望我們很快就能有結果。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

This is Matthew on for Alec here. Maybe a couple from us on 5525. We saw recently that the trial design on clin trials for 5525 includes 4 parts: monotherapy escalation/expansion and then combos with pembro escalation/expansion. Would be helpful to have any color on why you chose this design, maybe the ordering of the parts and whether you would still explore combination options if initial monotherapy data looks good.

這是馬修，代替亞歷克。也許我們 5525 上有幾個這樣的人。我們最近看到，5525 的臨床試驗設計包括 4 個部分：單一療法升級/擴展，然後與 pembro 升級/擴展相結合。解釋一下您選擇這種設計的原因，也許是各部分的順序，以及如果初始單一療法數據看起來不錯，您是否仍會探索組合選項，這將會很有幫助。

So yes, I'm happy to answer that. Thank you for the question. Yes, we're very excited about having our third PRO-XTEN T-cell engager program go into the clinic. We believe we've shown some nice early proof of concept with the prior two molecules. And in terms of the trial design, we do know that there's good scientific rationale for combining with a checkpoint inhibitor.

是的，我很樂意回答這個問題。謝謝你的提問。是的，我們非常高興我們的第三個 PRO-XTEN T 細胞接合器計畫進入臨床。我們相信，我們已經透過前兩種分子展示了一些很好的早期概念證明。就試驗設計而言，我們確實知道與檢查點抑制劑結合具有良好的科學原理。

What we've seen with prior T-cell engagers is that you can see upregulation of PD-L1 upon treatment with the T-cell engager. And so it really makes sense in terms of combining with a checkpoint inhibitor as well with combinations, again, in the context of other T-cell engagers, is that we've seen deeper responses and more durable responses with the combination. Hence, we are considering the combination for the 5525 program as well. And as you mentioned, there are 4 parts. The first part is dose escalation as monotherapy.

我們在先前的 T 細胞接合器中看到，在使用 T 細胞接合器治療後，可以看到 PD-L1 的上調。因此，就與檢查點抑制劑以及其他 T 細胞抑制劑的結合而言，這確實有意義，因為我們已經看到了這種結合產生更深層的反應和更持久的反應。因此，我們也在考慮 5525 計劃的組合。正如您所說，共有 4 個部分。第一部分是單一療法的劑量遞增。

The second part is to look at specific indications in expansion cohorts as monotherapy and then Parts 3 and 4 is similar except in combination, a dose escalation component with pembrolizumab followed by an expansion cohort with combination at, again, a data-driven decision on which combination -- which indications that we would pursue.

第二部分是將擴展隊列中的特定適應症視為單一療法，然後第 3 部分和第 4 部分類似，但組合療法除外，即使用 pembrolizumab 的劑量遞增部分，然後是組合療法的擴展隊列，同樣，由數據驅動決定採用哪種組合 — — 我們將追求哪些適應症。

Patrick Trucchio, H.C. Wainwright.

派崔克‧特魯基奧、H.C. 溫賴特。

Patrick, we cannot hear you.

派崔克，我們聽不到你說話。

Just the first question is on the CHB program. I'm wondering if you can tell us in terms of the functional cure rates that you're looking for, would you be looking for those rates in kind of certain levels of HB surface antigen at baseline? And separately, I'm wondering on the HDV program, do you need data from all the ECLIPSE trials in order to submit for regulatory approval? Or how should we think about potential for accelerated approval? Is that a possibility?

第一個問題是關於 CHB 計劃的。我想知道您是否可以告訴我們您所尋求的功能性治癒率，您是否會尋求基線時某些 HB 表面抗原水平的治癒率？另外，我想知道關於 HDV 計劃，您是否需要所有 ECLIPSE 試驗的數據才能提交給監管部門批准？或者我們應該如何考慮加速批准的可能性？有可能嗎？

And then just the last question is just in terms of partnering or collaborations, how should we think about both the CHB program, but as well any of the PRO-XTEN programs? And in particular, is there seven additional programs in preclinical development.

最後一個問題是，就合作或協作而言，我們應該如何看待 CHB 計劃以及 PRO-XTEN 計劃？特別是，臨床前開發還有七個附加項目。

Yes. Thank you, Patrick, for that question. Maybe I'll ask Mark first to address your questions on the hepatitis B and delta programs.

是的。謝謝帕特里克提出這個問題。也許我會先請馬克回答你關於B型肝炎和三角洲計畫的問題。

Sure. Thanks for the question. So for the MARCH Phase II study in chronic hepatitis B, as we presented at AASLD, we saw the best responses at end of treatment in those patients with surface antigen levels at baseline of less than 1,000. This is very consistent with what others are seeing with different mechanisms of action in the field that patients with low surface antigen at baseline are responding better than patients who have surface antigens that are very elevated at baseline. So we will present the data, both all comers and divided by surface antigen as we did for the end of treatment data for the functional cure data in 2 days.

當然。謝謝你的提問。因此，對於慢性乙型肝炎的 MARCH II 期研究，正如我們在 AASLD 上所展示的那樣，我們在治療結束時發現，基線時表面抗原水平低於 1,000 的患者的反應最佳。這與其他人在本領域中觀察到的不同作用機制的結果非常一致，即基線時表面抗原較低的患者的反應比基線時表面抗原非常高的患者更好。因此，我們將呈現所有角點的數據，並除以表面抗原，就像我們對 2 天內功能性治癒數據的治療結束數據所做的那樣。

So look forward to that. For your HDV question, your question was, do we need all 3 ECLIPSE studies for approval. I do not believe so. I believe we need ECLIPSE-1 and ECLIPSE-2 as our base case for a filing package that should be sufficient for approval. We would be looking for an accelerated approval based on in ECLIPSE-1, the composite of target not detected in ALT normalization and for ECLIPSE-2, target not detected at virologic end point.

所以，請期待這一點。對於您的 HDV 問題，您的問題是，我們是否需要所有 3 項 ECLIPSE 研究來獲得批准。我不這麼認為。我認為我們需要 ECLIPSE-1 和 ECLIPSE-2 作為足以獲得批准的備案包的基本案例。我們希望獲得基於 ECLIPSE-1 的加速批准，即在 ALT 正常化時未檢測到目標的複合體，以及 ECLIPSE-2 的加速批准，即在病毒學終點時未檢測到目標的複合體。

Of course, we have breakthrough therapy designation in the US, and we have Prime in Europe as well as orphan in Europe. So we are in active dialogue with regulators globally about the program, how to accelerate the program and how to get this drug combination to patients as quickly as possible because the unmet need is so high. Just one other comment about partnering, and I'll turn it back to Marianne is for hepatitis B, as we've said, that we are only going to be able to move hepatitis B forward if we have a global development and commercialization partner, whereas for hepatitis delta, we are in full study start-up mode for all 3 ECLIPSE studies, and we are running those studies as Vir Biotechnology on our own.

當然，我們在美國擁有突破性療法認定，在歐洲擁有 Prime 認定以及孤兒藥認定。因此，我們正在與全球監管機構就該計劃進行積極對話，討論如何加速該計劃以及如何盡快將這種藥物組合提供給患者，因為未滿足的需求非常高。關於合作的另一條評論，我將把它交還給瑪麗安，關於乙肝，正如我們所說的那樣，如果我們有一個全球開發和商業化合作夥伴，我們只有能夠推動乙肝的發展，而對於丁肝，我們正處於所有 3 項 ECLIPSE 研究的全面啟動模式，並且我們正在以 Vir Biotechnology 的名義自行開展這些研究。

Thank you, Mark. And I would just add related to your question on partnering of the preclinical programs, Patrick. I mean what is really unique is that the universal nature of the PRO-XTEN platform allows us to come up very efficiently with new potential therapeutic molecules, right, which are going to be, from a T-cell engager perspective, very well engineered because that's a capability we've had here at Vir for a very long time, and we can now combine it really with that masking capability.

謝謝你，馬克。派崔克，我只想補充一下關於臨床前計畫合作的問題。我的意思是，真正獨特的是，PRO-XTEN 平台的通用性使我們能夠非常有效地提出新的潛在治療分子，從 T 細胞接合器的角度來看，這些分子將被精心設計，因為這是我們在 Vir 公司已經擁有很長時間的能力，現在我們可以將它與掩蔽能力結合起來。

So the seven preclinical programs that we have started, it will be -- we envision a mix of approaches. Some of them will be kept for internal development on a number of select really high-priority targets that align well with our strategic focus. And some are open to partnerships and especially those where we think there could be complementary expertise elsewhere. So it's going to be really a mix of both strategies.

因此，我們已經啟動了七個臨床前項目，我們設想採用多種方法。其中一些項目將保留用於內部開發，用於一些與我們戰略重點高度契合的、真正優先的目標。還有一些專案則對合作夥伴持開放態度，特別是那些我們認為可以與其他公司互補專業知識的專案。所以這實際上將是兩種策略的結合。

Joseph Stringer, Needham & Company.

約瑟夫·斯特林格，Needham & Company。

Just given some of your recent work updating your HDV patient estimates, I had a question on HDV diagnosis. Have there been any changes to US guidelines? And I suppose, do you anticipate any updates to this in the near term? And how big of an impact could this be to the potentially addressable patient population in the US?

鑑於您最近更新了 HDV 患者估計值的一些工作，我對 HDV 診斷有一個疑問。美國指導方針有任何變化嗎？我想，您預計近期會對此做出任何更新嗎？這對美國潛在的患者群體會產生多大的影響？

Thank you for that question. No changes yet to the guidelines for delta diagnosis or reflex testing here in the United States. We do believe that there is a heightened awareness also in the context of the American Association of Liver Diseases. So we are hopeful that we will continue to have that conversation, obviously, and that when we have AASLD coming up later in the year that there might be some announcements in that regard. But thus far, no changes on reflex testing.

謝謝你的提問。美國的 delta 診斷或反射測試指南尚未改變。我們確實相信，在美國肝病協會的背景下，人們的認識也有所提升。因此，我們顯然希望能夠繼續進行這樣的對話，並且在今年稍後召開 AASLD 會議時可能會發布一些這方面的公告。但到目前為止，反射測試沒有任何變化。

That is, however, very effectively already deployed in Europe. And they are really seeing that if you just base diagnosis based on risk factors, et cetera, you're really not finding the patients. It's really only when patients are tested for hepatitis B and when they are found to be positive, they're automatically tested for delta that you end up identifying many more patients. Mark, anything to add there from your perspective?

然而，這項措施已在歐洲得到非常有效的實施。他們確實發現，如果僅根據風險因素等進行診斷，那麼就無法找到患者。實際上，只有當患者接受乙肝檢測並發現其呈陽性時，才會自動進行 delta 檢測，最終才能識別出更多的患者。馬克，從你的角度來看，還有什麼要補充的嗎？

No, I think you captured it very well, Marianne. Just to state that we do believe that the prevalence of diagnosed HDV or delta is underestimated because of the lack of reflex testing in the United States. I think once we have our therapy approved and on the market, assuming success that we would expect with such an effective product that this will drive more diagnosis and more disease prevalence. I think there's other examples of similar cases like this in medicine. But to your point, we're still not seeing the reflex testing deployed in the United States at this time.

不，我認為你捕捉到了這一點，瑪麗安。只是說明一下，我們確實認為由於美國缺乏反射測試，確診的 HDV 或 delta 的盛行率被低估了。我認為，一旦我們的療法獲得批准並進入市場，假設成功，我們就會期望這種有效的產品能推動更多的診斷和更多的疾病流行。我認為醫學上還有其他類似的案例。但正如您所說，我們目前仍然沒有看到美國部署反射測試。

This concludes the Q&A session of the call. Thank you for participating. And I'll turn the call back over to Rich.

本次電話會議的問答環節到此結束。感謝您的參與。我會把電話轉回給里奇。

Thank you, Eric, and thank you all for your continued support for joining us today. We look forward to updating you on our progress in the coming months. Operator, you may now end the call.

謝謝你，艾瑞克，也謝謝大家今天加入我們，給予我們持續的支持。我們期待在未來幾個月向您通報我們的進展。接線員，您現在可以結束通話了。