Vir Biotechnology Inc (VIR) 2024 Q1 法說會逐字稿

Hello, and welcome to veer biotechnologies First Quarter 2024 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 Sasha Damouni Ellis, Executive Vice President Chief Corporate Affairs Officer.

您好，歡迎參加轉向生物技術 2024 年第一季財務業績和業務更新電話會議。謹此提醒，本次電話會議正在錄音中。（操作員指示）我現在將把電話轉給執行副總裁首席企業事務官 Sasha Damouni Ellis。

You may begin. Sasha Damouni Ellis, thank you and good afternoon. With me today are Dr. Marianne Bakker, Chief Executive Officer, Dr. Carey Blount, Senior Vice President, Clinical Research and interim Chief Medical Officer, and Sung Lee, Executive Vice President and Chief Financial Officer.

你可以開始了。薩莎·達穆尼·埃利斯，謝謝你，下午好。今天與我在一起的有首席執行官 Marianne Bakker 博士、臨床研究高級副總裁兼臨時首席醫療官 Carey Blount 博士以及執行副總裁兼首席財務官 Sung Lee。

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 eight K.

在開始之前，我想提醒大家，我們今天發表的一些聲明屬於證券法規定的前瞻性聲明。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畫、未來結果、績效或成就與此類前瞻性陳述明示或暗示的內容有顯著差異。這些風險和不確定性以及與我們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進行了描述，包括表格 10 K、10 Q 和 8 K。

I will now turn the call over to our CEO, Dr. Marianne de Bakker.

現在我將把電話轉給我們的執行長 Marianne de Bakker 博士。

Thank you, Sasha, and good afternoon to everyone on the webcast, and thank you all for joining us today. During this afternoon's call, I will provide initial remarks before returning to Carey to share an update on our clinical development programs. And pipeline, and then some to summarize our first quarter financial results. We will then open the line for questions.

謝謝薩沙，網路廣播中的每個人下午好，謝謝大家今天加入我們。在今天下午的電話會議中，我將發表初步評論，然後返回凱里分享我們臨床開發計劃的最新情況。和管道，然後總結我們第一季的財務表現。然後我們將開通提問熱線。

Before we proceed, I would like to highlight two recent updates. First our Board of Directors has nominated two new independent directors, Dr. Norbert official Burger and Dr. Randy sorry, for election at our upcoming Annual Stockholders Meeting subdivisions brokers track records of overseeing more than 25 clinical development programs and drug approvals, including in hepatitis during his tenure at Gilead is directly relevant as our own programs progress through mid and late-stage trials.

在我們繼續之前，我想強調最近的兩個更新。首先，我們的董事會提名了兩位新的獨立董事，即Norbert 博士和Randy 博士，抱歉，他們將在我們即將舉行的年度股東大會上進行選舉。審批（包括肝炎）的記錄他在吉利德任職期間的經歷與我們自己的計畫在中期和後期試驗中取得的進展直接相關。

Dr. Sally pioneering work, applying advanced computational methods to drug discovery and choosing our aligns perfectly with our focus on leveraging AI in drug discovery.

Sally 博士的開創性工作是將先進的計算方法應用於藥物發現，並選擇我們的技術與我們在藥物發現中利用人工智慧的重點完美契合。

Two of our long-serving directors, Dr. Phillip sharp and Robert thread want to be standing for reelection as founding board members. They made tremendous contributions, and I want to thank them with a dedicated service.

我們的兩位長期任職的董事 Phillip Sharp 博士和 Robert thread 希望再次當選為創始董事會成員。他們做出了巨大的貢獻，我要以熱忱的服務感謝他們。

Second Sunday, our Chief Financial Officer will be stepping down at the end of this week to pursue another career opportunity. Sales leadership during his time at fear has been instrumental in building a talented financial team and implementing rigorous financial practices and controls. Our finance organization is well positioned for continued success. While we search for a successor, I would like to express my and the company's gratitude for Sun's contributions and wish him all the best in his new opportunities.

第二個星期天，我們的財務長將在本週末辭職，以尋求另一個職業機會。在他的恐懼時期，銷售領導力在建立一支才華橫溢的財務團隊和實施嚴格的財務實踐和控制方面發揮了重要作用。我們的財務組織已做好持續成功的準備。在我們尋找繼任者的同時，我謹向孫先生的貢獻表示我和公司的感謝，並祝他在新的機會中一切順利。

Looking ahead, we expect 2024 to be a transformational year for the year. Our teams are mission driven, and we aim to play an important role in serving patients in areas of high unmet medical need while creating significant value in large potential markets. We continue to make progress on the goals we laid out in January. A key priority is to deliver on our mid-stage clinical pipeline. And I'll begin by discussing our ongoing Phase two Solstice trial in people living with chronic hepatitis delta. Our goal this abrupt provide a lifelong therapy that is impactful and convenient for patients in this area of substantial unmet medical need at least 12 million people globally are estimated to be living with hepatitis delta with most cases remaining undiagnosed. While there are significant challenges with the underdiagnosis and lack of robust epidemiological data for chronic hepatitis delta, we do see positive momentum towards greater awareness and patient screening. For example, in March, the World Health Organization published updated guidelines for the prevention, diagnosis, care and treatment of people with chronic hepatitis B. And this update included recommending hepatitis delta and reflex testing, but everyone with test positive for hepatitis B, this is a major step forward for both patients and researchers within hepatitis delta community, chronic hepatitis delta infection increases the risk of poor outcomes for patients compared to hepatitis B alone, there is approximately a four times greater risk of liver cancer, the two times greater risk of death and more than half of these patients will die from liver disease within 10 years, the need for a safe, efficacious and continuous treatment for these patients is critical. In the first quarter, we completed enrollment of the current cohorts in the Solstice trial, one month ahead of schedule, and our late-breaker Solstice data abstract was accepted for poster presentation at the European Association for the Study of the Liver for April Congress 2024, we plan to host an investor conference call to discuss resources data on June fifth. In the third quarter, we intend to engage with regulatory authorities to discuss the next steps for the development program, shifting our focus to another area of high unmet medical need chronic hepatitis B, where we are making progress in our efforts to achieve a functional cure according to the World Health Organization, global hepatitis reports 2024 for an estimated 253 million people chronically infected and living with hepatitis B. Among this total population, only 13% of HPV-positive patients had been diagnosed and with only 3% specific treatments at the end of 2022. The WHO further estimated that 1.1 million people died from viral hepatitis B in 2022 compared to an estimated 820,000 in 2019. And here, we are committed to addressing this global health crisis, and it's concerning increase in debts, and we believe our two therapeutic candidates to bury Bard and Napster on has the potential to make a meaningful impact to bear. The burden and Epsilon are being studied in our ongoing Phase two March trial in combination with and without that interferon alpha, our aim is that our two therapeutic candidates can help us achieve our goal of a 30% or higher functional cure rate. While this is our stated goal KOLs. We hosted an advisory board last year at AASLD expressed the desire for 25% or better for a regimen that includes interferon and less than that for an interferon-free regimen. We expect to report 48 week end of treatment data for the March 14th trial at a major medical congress in the fourth quarter. Subsequently, we expect to share functional cure data in the second quarter of 2025.

展望未來，我們預期 2024 年將是轉型的一年。我們的團隊以使命為導向，我們的目標是在為醫療需求未被滿足的地區的患者提供服務方面發揮重要作用，同時在巨大的潛在市場中創造巨大的價值。我們繼續在一月份制定的目標上取得進展。一個關鍵的優先事項是交付我們的中期臨床管道。我將首先討論我們正在進行的針對慢性丁型肝炎患者的第二階段 Solstice 試驗。我們的目標是為這一領域的患者提供一種終生治療，這種治療既有效又方便，醫療需求未得到滿足。確診。儘管慢性丁型肝炎的診斷不足和缺乏可靠的流行病學數據存在重大挑戰，但我們確實看到了提高認識和患者篩檢的積極勢頭。例如，3月份，世界衛生組織發布了慢性乙型肝炎患者預防、診斷、護理和治療的更新指南。這對於三角型肝炎社區內的患者和研究人員來說，這是向前邁出的重要一步，與單獨的乙型肝炎相比，慢性三角型肝炎感染增加了患者不良結果的風險，患有肝癌的風險大約是其四倍，風險是其兩倍死亡人數超過一半，這些患者將在 10 年內死於肝病，因此對這些患者進行安全、有效和持續的治療至關重要。第一季度，我們提前一個月完成了 Solstice 試驗當前隊列的入組，並且我們最新的 Solstice 數據摘要被接受在歐洲肝臟研究協會 2024 年 4 月大會上進行海報展示，我們計劃在6 月5 日舉辦投資者電話會議，討論資源數據。在第三季度，我們打算與監管機構合作，討論開發計劃的後續步驟，將我們的重點轉移到另一個醫療需求未得到滿足的慢性乙型肝炎領域，我們正在努力實現功能性治愈。組織稱，到2024 年全球肝炎報告估計將有2.53 億人慢性感染B型肝炎並患有B型肝炎。在這一總人口中，截至 2022 年底，只有 13% 的 HPV 陽性患者被診斷，只有 3% 的患者得到了特異性治療。世界衛生組織進一步估計，2022 年將有 110 萬人死於B型病毒性肝炎，而 2019 年估計有 82 萬人死於B型病毒性肝炎。在這裡，我們致力於解決這場全球健康危機，這涉及債務的增加，我們相信我們埋葬巴德和納普斯特的兩種治療候選藥物有潛力產生有意義的影響。我們正在進行的3 月第二階段試驗中正在研究Charge 和Epsilon 與乾擾素α 聯合使用和不聯合使用的情況，我們的目標是我們的兩種候選治療藥物可以幫助我們實現30% 或更高的功能性治癒率的目標。雖然這是我們對 KOL 的既定目標。去年，我們在 AASLD 主辦了一個諮詢委員會，表達了對包含幹擾素的治療方案的 25% 或更高的期望，而低於不含幹擾素的治療方案。我們預計將在第四季度的一次重要醫學大會上報告 3 月 14 日試驗的 48 週結束治療數據。隨後，我們預計將在 2025 年第二季分享功能性治癒數據。

Now I will briefly discuss peers 1388 RHRT. and T. cell vaccine candidate currently being evaluated in a Phase one trial. We are looking forward to sharing initial immunologic proof of concept data in the second half of this year. If the data supports the validity of the platform, which could be a springboard to other indications, including period 1949, our preclinical therapeutic vaccine for control, precancerous lesions and cancers caused by each patient in this trial is supported by the National Institute of Allergy and Infectious Diseases, part of the NIH and the Bill & Melinda Gates Foundation in research, we continue to advance multiple investigational antibody therapeutics optimized for increased likelihood of development success, thanks to our proprietary platform powered by AI and machine learning called Daisy safety enables fast and cost-efficient optimization of multiple properties such as binding affinity neutralization, potency and developed ability, and we have applied it to over 10 investigational monoclonal antibodies across multiple projects for our most advanced preclinical programs are prophylactic antibodies for influenza A. and B ROC and or NPV and COVID-19. In addition, we are developing a cocktail of drug neutralizing antibodies for an HIV cure. We look forward to sharing more about these programs during the course of the year, and that's our R&D Day in late November.

現在我簡單討論一下同儕1388 RHRT。目前正在第一階段試驗中評估候選 T 細胞疫苗。我們期待在今年下半年分享初步的免疫學概念驗證數據。如果數據支持該平台的有效性，這可能成為其他適應症的跳板，包括1949 年期間，我們用於控製本次試驗中每位患者引起的癌前病變和癌症的臨床前治療疫苗得到了美國國家過敏研究所的支持，傳染病是NIH 和比爾及梅琳達蓋茲基金會研究的一部分，我們繼續推進多種研究性抗體療法的優化，以提高開發成功的可能性，這要歸功於我們由人工智慧和機器學習驅動的專有平台，稱為Daisy safety，可以快速、安全地實現這一目標。其應用於多個專案中的10 多種研究性單株抗體，我們最先進的臨床前專案是甲型和乙型流感ROC 的預防性抗體和或NPV 和 COVID-19。此外，我們正在開發一種用於治療愛滋病毒的藥物中和抗體混合物。我們期待在這一年中分享更多有關這些項目的信息，也就是 11 月底的研發日。

Now turning to our cash and investments. Our balance sheet enables us to fund our clinical programs through major inflection points, while providing the flexibility to invest in external innovation, we are closely managing our expenses and prudently investing in programs with the greatest opportunity to drive return for our shareholders.

現在轉向我們的現金和投資。我們的資產負債表使我們能夠在重大拐點為我們的臨床項目提供資金，同時提供投資外部創新的靈活性，我們密切管理我們的費用並謹慎投資最有機會為股東帶來回報的項目。

To conclude, I would like to acknowledge and thank our employees, partners, clinical trial participants and shareholders who helped make this all possible. With that, I'll turn the call over to Carey.

最後，我要感謝我們的員工、合作夥伴、臨床試驗參與者和股東，他們幫助這一切成為可能。這樣，我就把電話轉給凱裡。

Thank you, Maria.

謝謝你，瑪麗亞。

I'll begin by reminding you about the initial results from our Phase two psoriasis trial on hepatitis Delta, which was shared at a late-breaker presentation at ASLD. last year and discussed earlier this year. The Solstice trial is evaluating two because of our the commendation of blistering and to build up our alone as a potential chronic treatment for people living with chronic hepatitis delta. Based on initial data reported, we have certain rapid declines in these two. The RNA five out of six participants had undetectable HCV RNA and six other six were below the limit, a lower limit of qualification within 12 weeks of starting combination therapy. Two out of six participants also achieved ALT normalization as Marion mentioned, we completed enrollment for greater than 60 participants across two cohorts one month earlier than anticipated. Physician enthusiasm at AASLD was significant, and this contributed to the rapid rate of enrollment, one group receiving TSR plus Elixir and combination therapy. Every four weeks and a second group is receiving TellApart monotherapy. Every two weeks, approximately 50% of participants have compensated cirrhosis or CPTA. overall, around 40% of patients with hepatitis delta develop cirrhosis with an average of approximately five years to progression. Therefore, it's important to include patients with cirrhosis and trial to understand how our treatment impacts those with more progressive disease. This type of information can help optimize treatment strategies in the future and inform our future trial designs we plan to share updated data on additional posters participants, the late-breaker data abstract that was accepted for poster presentation at the ESMO Congress. Specifically, we will share data on approximately 15 participants per regimen at 12 weeks and approximately 10 participants per regimen at 24 weeks. Additional follow-up for the initial six Solstice trial participants will also be shared at that time complete 24 week treatment data for Solstice participants in these two cohorts is expected in the fourth quarter of 2024. We foresee that the Solstice data update at Easel will be highly informative, who will shed light on several key areas. First, we anticipate gaining greater clarity on the safety profiles that are administered together with the Luxtera second, and we expect to obtain additional insight into virologic response rates and ALT normalization. Third, we aim to evaluate whether there are initial efficacy or safety differences between cirrhotic and non-cirrhotic participants. And finally, we are looking forward to seeing longer follow-up data on durability of viral suppression and safety from the initial six participants previously reported at AASLD. If the data are supportive, we will dialogue with health authorities about the development program later this year. We expect Vera next trial will be designed with deliver tied as a comparator, and we will have greater clarity on potential trial designs following discussions with health authorities.

首先，我要提醒您有關 Delta 型牛皮癬第二階段試驗的初步結果，該結果是在 ASLD 的一次最新報告中分享的。去年並於今年早些時候討論過。Solstice 試驗正在評估兩項試驗，因為我們對起泡療法的認可，並希望將我們的試驗作為慢性丁型肝炎患者的潛在慢性治療方法。根據初步報告的數據，我們發現這兩者都在快速下降。六名參與者中有五名的 HCV RNA 檢測不到，另外六名六名受試者的 RNA 低於限制，即開始聯合治療 12 週內的資格下限。正如 Marion 所提到的，六分之二的參與者也實現了 ALT 正常化，我們比預期提前一個月完成了兩個隊列中超過 60 名參與者的註冊。AASLD 的醫生熱情很高，這促進了入組率的快速增長，其中一組接受 TSR 加 Elixir 和聯合治療。每四個星期，第二組接受 TellApart 單一療法。每兩週，大約 50% 的參與者出現代償性肝硬化或 CPTA。整體而言，約 40% 的丁型肝炎患者會發展為肝硬化，平均約五年才會出現進展。因此，將肝硬化患者納入試驗以了解我們的治療如何影響那些病情進展較嚴重的患者非常重要。此類資訊可以幫助優化未來的治療策略，並為我們未來的試驗設計提供信息，我們計劃分享其他海報參與者的最新數據，這些最新數據摘要已被接受在 ESMO 大會上進行海報展示。具體來說，我們將分享每個方案約 15 名參與者在 12 週時的數據以及每個方案在 24 週時約 10 名參與者的數據。最初 6 名 Solstice 試驗參與者的額外後續行動也將在屆時分享，這兩個隊列中 Solstice 參與者的完整 24 週治療數據預計在 2024 年第四季度公佈。我們預計 Easel 的 Solstice 數據更新將提供大量信息，將闡明幾個關鍵領域。首先，我們期望對與 Luxtera 一起使用的安全性有更清晰的了解，其次我們期望獲得對病毒學反應率和 ALT 正常化的更多了解。第三，我們的目的是評估肝硬化和非肝硬化參與者之間是否存在初始療效或安全性差異。最後，我們期待看到先前在 AASLD 報告的最初六名參與者提供的關於病毒抑制持久性和安全性的更長期的後續數據。如果數據支持，我們將在今年稍後與衛生當局就發展計畫進行對話。我們預計 Vera 的下一個試驗將設計為將交付作為比較器，並且在與衛生當局討論後，我們將更清楚地了解潛在的試驗設計。

Switching gears to our Phase two program for chronic hepatitis B, our preliminary data suggests that on the left, Søren was administered with peginterferon alfa for up to 40 weeks, about 26% of participants achieved hepatitis B surface antigen loss at the end of treatment and 16% achieve functional cure, meaning they maintain hepatitis B surface antigen loss 24 weeks after the end of treatment. Current therapies such as NRTI.s require lifelong therapy, but rarely achieve functional cure. The only other therapy approved for hepatitis B is peg interferon alpha, which has a low functional cure rate of 3% to 7% with poor tolerability in the March trial. When added to this apart to a regimen of a lesser and alone or less around plus peginterferon alfa, we observed an almost threefold increase in the treatment response rates at 24 weeks of treatment These data were the first indication of the potentially important role of an HBV directed antibody and hepatitis B functional cure. We look forward to sharing end of treatment data from the March Part B trial, which is evaluating 48 weeks of the doublet and triplet regimens in the fourth quarter. This readout will be followed by post-treatment data in the second quarter of 2025, which will allow us to assess functional cure rates.

切換到我們針對慢性乙型肝炎的第二階段計劃，我們的初步數據表明，在左側，Sären 服用聚乙二醇幹擾素α長達40 週，約26% 的參與者在治療結束時實現了乙型肝炎表面抗原喪失。目前的治療方法，例如 NRTI.s，需要終生治療，但很少能實現功能性治癒。唯一被批准用於治療乙型肝炎的其他療法是聚乙二醇幹擾素α，其功能治癒率較低，為 3% 至 7%，並且在 3 月的試驗中耐受性較差。當將其添加到較少、單獨或較少加聚乙二醇幹擾素α的治療方案中時，我們觀察到治療24 週時治療反應率幾乎增加了三倍。重要作用定向抗體和乙型肝炎功能性治癒。我們期待分享 3 月 B 部分試驗的治療結束數據，該試驗正在第四季度評估 48 週的雙聯和三聯療法。此讀數之後將在 2025 年第二季度提供治療後數據，這將使我們能夠評估功能性治癒率。

Finally, we recently published a full year of 24 82 Peninsula trial data manuscript and met archives we are applying key learnings from the political trials, our next-generation prophylactic flu antibody beyond 29 81.

最後，我們最近發布了全年 24 82 半島試驗數據手稿和會議檔案，我們正在應用從政治試驗中獲得的重要經驗，我們的下一代預防性流感抗體超越 29 81。

Now turning to our early stage pipeline beyond 1949 is an investigational therapeutic T cell vaccine based on our HCLD. vector platform and is designed to treat precancerous lesion caused by the Human Papilloma Virus Despite advances in vaccination and scream HPV-associated cancers and conditions such as high grade squamous interest affiliate lesions. We made significant global health concerns. We look forward to sharing more later this year of this program and the timing of a potential IND submission. We are seven to nine is a next-generation COVID-19 monoclonal antibody candidate with increased potency, breadth and resistance to viral escape. Thanks to AI engineering and optimization. The development of your sum of two to nine to the end of Phase one is supported by Barta. We look forward to continuing to share our progress over the coming quarters and during a virtual R&D Day planned for late November.

現在我們轉向 1949 年後的早期研發管線，這是一種基於 HCLD 的研究性治療性 T 細胞疫苗。載體平台，旨在治療由人類乳突病毒引起的癌前病變，儘管疫苗接種和尖叫 HPV 相關癌症和病症（例如高級鱗狀興趣附屬病變）取得了進展。我們提出了重大的全球健康問題。我們期待在今年稍後分享該計劃的更多資訊以及潛在 IND 提交的時間。We are Seven to Nine 是下一代 COVID-19 單株抗體候選藥物，具有更強的效力、廣度和對病毒逃脫的抵抗力。感謝人工智慧工程和優化。從二到九的總和到第一階段結束的發展得到了巴塔的支持。我們期待在未來幾季以及計劃於 11 月底舉行的虛擬研發日期間繼續分享我們的進展。

I will now turn the call over to Sung.

我現在將電話轉給宋。

Thank you, Karri. Before I came to the financial results, I would like to take this moment to thank Marianne and the Board for the opportunity to make an impact there. I've truly enjoyed my time as CFO, and I'm proud of what we have accomplished, I'm confident that the company and the finance organization are well positioned for continued success.

謝謝你，卡里。在公佈財務業績之前，我想藉此機會感謝瑪麗安和董事會給我機會發揮影響力。我真的很享受擔任財務長的時光，我為我們所取得的成就感到自豪，我相信公司和財務組織已做好準備，能夠持續取得成功。

With that, I'll now share the financial results for the first quarter of 2024. Total revenues in the first quarter of 2024 were $56.4 million compared to 63 million for the same period in 2023 as anticipated, we saw year-over-year declines in collaboration and grant revenues. These declines were partially offset by higher contract revenue in the first quarter of 2024, driven primarily by the recognition of deferred revenue related to our 2021 agreement with GSK.

接下來，我將分享 2024 年第一季的財務表現。2024 年第一季的總收入為 5,640 萬美元，而 2023 年同期的總收入為 6,300 萬美元，正如預期的那樣，我們看到合作和資助收入同比下降。這些下降被 2024 年第一季合約收入的增加部分抵消，這主要是由於我們與 GSK 的 2021 年協議相關的遞延收入的確認所致。

Turning to operating expenses, cost of revenue for the first quarter of 2024 was nominal compared to 1.9 million for the same period in 2023. R&d expenses in the first quarter of 2024 were 100.1 million compared to 157.6 million in the same periods in 2023. The decrease was primarily driven by lower clinical development and manufacturing costs related severe 24 82. Sg&a expenses in the first quarter of 2024 were 36.3 million compared to 46.8 million in the same period in 2020. Three. The decrease was primarily driven by disciplined expense management, which resulted in a significant reduction in external expenses.

至於營運費用，2024 年第一季的收入成本僅為名義收入，而 2023 年同期為 190 萬美元。2024年第一季的研發費用為1.001億美元，而2023年同期為1.576億美元。這一下降主要是由於嚴重 24 82 相關的臨床開發和製造成本降低。2024 年第一季的銷售、管理及行政費用為 3,630 萬美元，而 2020 年同期為 4,680 萬美元。三。這一下降主要是由於嚴格的費用管理導致外部費用大幅減少。

Moving to the balance sheet, we ended the first quarter of 2024 with cash, cash equivalents and investments of 1.51 billion compared to $1.63 billion at the end of 2023, representing a 118 million decline quarter over quarter.

轉向資產負債表，截至 2024 年第一季末，我們的現金、現金等價物和投資為 15.1 億美元，而 2023 年底為 16.3 億美元，環比減少 1.18 億美元。

Turning to our financial guidance for 2020 for the year is progressing as expected, and we are reiterating all aspects of our guidance, which can be found on slide 28 of our corporate presentation. We will continue to be disciplined in managing our expenses and focus our investments on programs with the greatest opportunity to drive return for shareholders.

談到我們 2020 年的財務指引，今年的進展符合預期，我們重申了我們指引的各個方面，這些可以在我們公司簡報的幻燈片 28 中找到。我們將繼續嚴格管理開支，並將投資重點放在最有機會為股東帶來回報的項目上。

I will now turn the call back to Sasha.

我現在將電話轉回給薩莎。

Thank you, John. We will now start the Q&A section. Please limit your questions to two per person. So that we are able to get to all of our covering analysts. Operator, please open up the line for questions.

謝謝你，約翰。我們現在開始問答部分。請將您的問題限制為每人兩個。這樣我們就能夠聯繫到所有覆蓋分析師。接線員，請開通提問線。

(Operator Instructions) Gena Wang, Barclays.

（操作員指示）Gena Wang，巴克萊銀行。

Thank you for taking my questions. So my best wishes to your next journey. And I have a two questions regarding HDV, our first question is and regarding patients with baseline cirrhosis, any restriction or exclusion criteria for cirrhotic condition? And my second question is of which measurement will be more meaningful in your view regarding the lower limit of quantification and the limit of detection? And is the Phase two efficacy data setting a bar for Easel?

感謝您回答我的問題。所以我對你的下一次旅程致以最良好的祝愿。我有兩個關於 HDV 的問題，我們的第一個問題是關於基線肝硬化的患者，肝硬化有什麼限製或排除標準嗎？我的第二個問題是，在您看來，關於定量下限和檢測極限，哪一種測量比較有意義？二期療效數據是否為 Erasel 設定了標準？

Yes. Thank you very much for that question for those questions, Gena, which are very, very relevant. I will ask Carey to address them.

是的。非常感謝你提出這些問題，Gena，這些問題非常非常相關。我會請凱裡向他們講話。

Thank you, Gena. So for your first question around baseline cirrhosis and restrictions in our trials. So as I mentioned, the two new cohorts that we enrolled in Solstice, we included CPTA., how patients so they have compensated cirrhosis. And so we have about 50% of those participants in those two new cohorts. And so this will help us for going forward the safety and efficacy of our regimen in those populations. So we look forward to looking at that, any if there are any differences between cirrhotics and U.S. robotics in that population?

謝謝你，吉娜。關於你的第一個問題，關於基線肝硬化和我們試驗中的限制。正如我所提到的，我們在 Solstice 中招募的兩個新隊列包括 CPTA，研究患者如何補償肝硬化。因此，我們有大約 50% 的參與者屬於這兩個新群體。因此，這將有助於我們在這些人群中提高我們的治療方案的安全性和有效性。因此，我們期待研究這個問題，看看肝硬化和美國機器人在該族群中是否有任何差異？

In regards to your second question around which measurement lower than the quantification or limit of detection at different assets have different cutoff for the for those parameters. And so these will be discussed with regulatory authorities in terms of which of these parameters would be acceptable from an endpoint perspective. So I can't answer that right now, but that was something that will be something that we will have to.

關於第二個問題，低於不同資產的量化或檢測極限的測量對這些參數有不同的截止值。因此，我們將與監管機構討論從端點角度來看哪些參數是可以接受的。所以我現在無法回答這個問題，但這是我們必須回答的問題。

We will clarify with regulators and the bar for Eagle update.

我們將向監管機構和 Eagle 更新的標準進行澄清。

Right.

正確的。

And then the last question is whether that people thought that data would be setting a new efficacy bar that you're familiar with from our AFLD. presentation from our six purchased first six participants were able to achieve a six out of six that achieved HCV RNA less than a minimum of complications and five out of six that were undetectable or less on the detection. I think if we are able to demonstrate these results in a larger population than I think that it could set a new efficacy bar because as with any chronic viral disease, the goal is always to suppress viral replication to undetectable levels such as in HIV. And so if we're able to do that. I think that would set that benchmark.

最後一個問題是，人們是否認為這些數據會設定一個新的療效標準​​，正如您在我們的 AFLD 中所熟悉的那樣。在我們購買的六名前六名參與者的演示中，六分之六的 HCV RNA 併發症低於最低限度，六分之五的人在檢測中無法檢測到或更少。我認為，如果我們能夠在比我想像的更多的人群中證明這些結果，那麼它可能會設定一個新的療效標準​​，因為與任何慢性病毒性疾病一樣，我們的目標始終是將病毒複製抑製到不可檢測的水平，例如愛滋病毒。如果我們能夠做到的話。我認為這將設定基準。

Paul Choi, Goldman Sachs.

保羅‧崔，高盛。

I thank you.

我謝謝你。

Good afternoon and thank you for taking our questions. I want to follow up on Julian's question regarding on the compensated cirrhosis population in Mount and Solstice. And could you maybe just clarify for us, particularly among the patients for which we'll have the 12 week additional public update versus those who have had the 24 week treatment update on just how you're thinking that baseline of asthma patients having cirrhosis might affect those particular updates? And then my second question is in terms of the earlier stage pipeline, just given the success that we've seen with the various RSV drugs from both GSK and Pfizer.

下午好，感謝您回答我們的問題。我想跟進朱利安關於芒特和至日地區補償性肝硬化人口的問題。您能否為我們澄清一下，特別是對於那些我們將獲得 12 週額外公開更新的患者以及那些接受了 24 週治療更新的患者，您認為患有肝硬化的哮喘患者的基線可能會如何？特定的更新？然後我的第二個問題是關於早期管道，考慮到我們在葛蘭素史克和輝瑞的各種 RSV 藥物上所取得的成功。

In terms of mark recent market success on, can you maybe elaborate on sort of what the criteria that you and your partner, GSK are looking at for sort of a go or no-go decision in terms of advancing of 81 90. Thank you.

就近期市場成功而言，您能否詳細說明您和您的合作夥伴葛蘭素史克在推進 81 90 方面正在考慮採取或不採取決定的標準是什麼。謝謝。

Yes.

是的。

So thank you, Paul, for the question. So in terms of how we think cirrhosis might affect safety or efficacy, and we have done initial hepatic impairment study and CPTA. participants, and we have not seen any safety signals or any clinically significant changes in a PK. that would cause us any concern. And so our expectation is that and this compensated for raw fibrotic population we should not see any significant differences in terms of the safety or efficacy profile of between those two populations. And we will have that data for the coming out relatively soon.

謝謝保羅提出這個問題。因此，就我們認為肝硬化可能如何影響安全性或有效性而言，我們已經進行了初步肝損傷研究和 CPTA。參與者，我們沒有看到任何安全訊號或 PK 的任何臨床顯著變化。這會引起我們的任何擔憂。因此，我們的期望是，這補償了原始纖維化人群，我們不應該看到這兩個人群之間的安全性或有效性概況有任何顯著差異。我們很快就會得到這些數據。

In terms of RSV and given the success of those vaccines from Pfizer and GSK, I think these are ongoing discussions that we have with our partner in terms of looking at the profile of the beer 80 or 90 or other potential monoclonal antibodies. And so we've certainly only want to present or kind of progress antibodies that fill an unmet need in the space. And so those are ongoing discussions that will help our partners that make those decisions.

就 RSV 而言，鑑於輝瑞和葛蘭素史克的疫苗取得了成功，我認為我們正在與合作夥伴就啤酒 80 或 90 或其他潛在單株抗體的概況進行持續討論。因此，我們當然只想提供或改進抗體來滿足該領域未滿足的需求。因此，這些正在進行的討論將有助於我們的合作夥伴做出這些決定。

Great.

偉大的。

Thank you.

謝謝。

[Alex China], Bank of America.

[Alex China]，美國銀行。

You guys.

你們。

Thanks for taking our questions.

感謝您回答我們的問題。

And just a couple from us as well. I guess first, how should we be thinking about the Easel update in the context of the more advanced update expected in 4Q?

我們也只有幾個人。我想首先，我們應該如何在第四季度預期的更高級更新的背景下考慮 Easel 更新？

I guess in terms of which questions you think will we'll have answered, I think, diesel versus what will be so outstanding for the four Q data.

我想就您認為我們會回答哪些問題而言，我認為柴油引擎與四個 Q 數據的表現將如此突出。

And as a follow-up, what would inform a go no-go on a Phase three and in this setting sounds like you'll likely wait until the additional 24-week data becomes available, even though you may I've already aligned with regulators on that on next steps in 3Q?

作為後續行動，什麼會告知第三階段的繼續和不繼續，在這種情況下，聽起來您可能會等到額外的 24 週數據可用，即使您可能已經與監管機構對第三季度的下一步行動有何看法？

Yes.

是的。

Well, yes.

嗯，是。

Thank you, Alex. So in terms of how we would think about the data that we will have at Easel. So we will have about 15 participants in each of the cohorts at week 12 and about 10 of participants in each cohort at week 24. So we have four things that we would be looking at at this time point.

謝謝你，亞歷克斯。因此，就我們如何看待 Easel 所擁有的數據而言。因此，在第 12 週，每個隊列將有大約 15 名參與者，在第 24 週，每個隊列將有大約 10 名參與者。所以我們現在要考慮四件事。

Number one, the safety profile of a bar and a lot of store explanation number two, but the virologic response rates and ALT normalization rates, our third, the potential efficacy and safety differences between cirrhotic and non-cirrhotic patient participants.

第一，酒吧的安全性和大量的解釋；第二，病毒學反應率和 ALT 正常化率；第三，肝硬化和非肝硬化患者參與者之間的潛在療效和安全性差異。

And then finally, the longer-term follow-up data on the initial six participants that we reported SLV. to see if we have durability of response over time. So I think we are the Eagle Sadara will further, hopefully further expand the dataset that we have from the initial six for and confirm the directionality of what we're seeing in terms of efficacy and safety. And then obviously, the 24-week data will be a complete data set across those two populations.

最後是我們報告的 SLV 最初六名參與者的長期追蹤數據。看看我們的反應是否能隨著時間的推移而持久。因此，我認為我們 Eagle Sadara 將進一步、希望進一步擴展我們從最初的六個資料集獲得的資料集，並確認我們在功效和安全性方面所看到的方向性。顯然，24 週的數據將是這兩個人群的完整數據集。

So in terms of your second question around what would inform a go no go on a Phase three of our Delta.

那麼，就你的第二個問題而言，是什麼決定了我們在三角洲第三階段的進展。

So I think, yes, it depends on the strength of the data.

所以我認為，是的，這取決於數據的強度。

I think if our data with the equal data cutoff, we believe that is strong enough I think that would be a possibility of taking that path forward for conversations. But it all depends on the strength of that data going forward. Obviously, the 24 weeks would be the complete dataset. But if we have a very strong indication of efficacy, then I think we can go earlier group recruit.

我認為，如果我們的數據具有相同的數據截止值，我們相信這足夠強大，我認為這將有可能沿著這條道路進行對話。但這一切都取決於未來數據的強度。顯然，24 週就是完整的資料集。但如果我們有非常強烈的療效跡象，那麼我認為我們可以更早進行團體招募。

Thanks a lot.

多謝。

Phil Nadeau, TD Cowen.

菲爾·納多，TD·考恩。

Good afternoon and thanks for taking our questions and let us add our best wishes to Song as he moves on to from us. First on, as you just highlighted, durability response as a key question that's going to be answered by what you saw in Q4 updates. Is there any reason to worry that the effect could be lost for the combination regimen or monotherapy regimen over time. Any preclinical signs that and resistance could develop in hepatitis delta?

下午好，感謝您提出我們的問題，讓我們向宋先生致以最美好的祝愿，因為他即將離我們而去。首先，正如您剛才強調的那樣，耐久性回應是一個關鍵問題，您在第四季度的更新中看到的內容將回答這個問題。有沒有理由擔心隨著時間的推移，聯合療法或單一療法的效果可能會消失？有任何臨床前跡象顯示丁型肝炎可能產生抗藥性嗎？

And then second, totally unrelated on business development with $1.5 billion in cash. Can you talk a bit about the environment you're seeing in business development and what your most recent thoughts are on some priorities for investing externally?

其次，與 15 億美元現金的業務發展完全無關。您能否談談您在業務發展中看到的環境以及您最近對外部投資的一些優先事項的想法是什麼？

Thank you for those questions, Phil, and maybe we'll get to your second question first.

謝謝你提出這些問題，菲爾，也許我們會先回答你的第二個問題。

Yes, we have shared we are in a great position that we can really use our strong balance sheet to fund our priorities. And of course, that is hepatitis delta and hepatitis B in our pipeline. However, we also have the opportunity to look for external innovation and especially in our early clinical programs would be of interest there. And we continue to be very thoughtful and strategic in looking at those opportunities and discerning whether dose would be a great fit for us and creating value for the Company and our shareholders.

是的，我們已經分享過，我們處於有利地位，我們可以真正利用我們強大的資產負債表來為我們的優先事項提供資金。當然，我們正在研發的產品包括丁型肝炎和B型肝炎。然而，我們也有機會尋找外部創新，特別是在我們的早期臨床計畫中，我們對此感興趣。我們將繼續以非常深思熟慮和策略性的方式尋找這些機會，並判斷劑量是否非常適合我們並為公司和股東創造價值。

And I will ask Gary to answer your question related to durability of response Thank you, Matt, and thank you, Phil, for the question.

我將請加里回答您有關響應持久性的問題，謝謝馬特，謝謝菲爾提出的問題。

So your question around durability of response, would we expect to see any resistance or loss of zero durability with our client hepatitis delta regimen. So I mean, based on what we've seen to date, we have from vitro data. We haven't seen any resistance to date, and we have a lot of hepatitis B data looking at surface antigen. And we haven't seen a rebalance and hepatitis surface antigen over time with a combination of a lot sort of argument together. And I think as with other chronic infectious diseases on the left or end of our work through two different mechanisms. And because we're working through two different mechanisms in terms of inhibiting levels of surface antigen and then HDV RNA. But the likelihood of developing resistance is much less compared to if you were going forward with the monotherapy. So time will tell. But based on what we know so far from hepatitis B from our in vitro work and what the expectations are with having two different independent mechanisms against the virus. And my my guess is that a rebalance and resistance would be rare.

因此，您關於反應持久性的問題，我們是否期望在我們的客戶三角洲治療方案中看到任何抗藥性或零持久性的喪失。所以我的意思是，根據我們迄今為止所看到的情況，我們得到了體外數據。到目前為止，我們還沒有發現任何抗藥性，而且我們有大量關於表面抗原的乙型肝炎數據。隨著時間的推移，我們還沒有看到重新平衡和肝炎表面抗原與許多爭論的結合。我認為，與其他慢性傳染病一樣，我們工作的左側或末端透過兩種不同的機制。因為我們正在透過兩種不同的機制來抑製表面抗原和 HDV RNA 的水平。但與繼續單一療法相比，產生抗藥性的可能性要小得多。所以時間會證明一切。但根據我們迄今為止從體外工作中對乙型肝炎的了解，以及對兩種不同的獨立機制對抗病毒的期望。我的猜測是，重新平衡和阻力將是罕見的。

That's very helpful.

這非常有幫助。

Thank you.

謝謝。

Your next question comes from the line of Patrick Trucchio of H.C. Wainwright. Your line is now open.

您的下一個問題來自 H.C. 的 Patrick Trucchio。溫賴特。您的線路現已開通。

Thanks, good afternoon. Just a couple of questions from me. The first is just on the Delta program, given the lack of treatments available. I'm wondering if you can talk about if there's a possibility for an accelerated pathway to approval depending on the outcome from Solstice and what that might look like in terms of potential Phase three and pathway to approval.

謝謝，下午好。我只想問幾個問題。第一個是達美計劃，因為缺乏可用的治療方法。我想知道您是否可以談談是否有可能根據 Solstice 的結果以及潛在的第三階段和批准途徑的結果來加速批准途徑。

And then just on the HPV. program. I'm wondering if you can talk about whether you expect to have data segmented based on surface antigen levels at baseline? And if so, at what levels of baseline. Would you expect to report this data? And related to this, how important is it to demonstrate loss of surface antigen in all comers relative to patient cohort with relative lower baseline surface antigen, especially as you consider potential advancements to the program of the program to Phase three.

然後就是 HPV。程式.我想知道您是否可以談談您是否希望根據基線的表面抗原水平對數據進行分段？如果是這樣，基線水平是多少？您希望報告這些數據嗎？與此相關的是，證明所有參與者相對於基線表面抗原相對較低的患者群體的表面抗原損失是多麼重要，特別是當您考慮到第三階段計劃的潛在進展時。

Thank you, Patrick, for the questions. So in terms of hepatitis delta, and possibilities for accelerated pathways. As you know, there's no therapy that's currently approved in the United States at this time. And so based on the strength of our data, we will look for any of those mechanisms that we can accelerate our path to approval, such as Fast Track breakthrough prime. And then these other matters that are available to us from regulatory agencies. So we will be looking at those pathways to move forward and to facilitate discussions with regulators as we get the ballpark and get alignment on our registrational pathway going forward.

謝謝帕特里克提出的問題。因此，就丁型肝炎以及加速途徑的可能性而言。如您所知，目前美國尚無核准的治療方法。因此，根據我們的數據強度，我們將尋找任何可以加速我們獲得批准的機制，例如快速通道突破性優勢。然後我們可以從監管機構獲得這些其他事項。因此，當我們掌握大致情況並就未來的註冊途徑取得一致時，我們將研究這些前進的途徑，並促進與監管機構的討論。

And then in terms of your second question around hepatitis B with the segment, looking at the segment data by surface antigen levels, so you have some large files actually to date in our hepatitis B trials, we have taken all comers and we are not just enrolling participants with surface antigen less than 3,000 or 1,000. We're taking a broader view but we will be able to look at subgroups within our data sets to see whether certain cutoff. So we'd increase serum clearance rates in surface antigen. So those will be areas that we will be evaluating and working out our data set.

然後，就您關於乙型肝炎片段的第二個問題而言，透過表面抗原水平查看片段數據，因此，迄今為止，在我們的乙型肝炎試驗中，您實際上有一些大文件，我們已經採取了所有來者，我們不僅僅是招募表面抗原少於 3,000 或 1,000 的參與者。我們正在採取更廣泛的視角，但我們將能夠查看資料集中的子組，以查看是否存在特定的截止點。因此，我們會提高表面抗原的血清清除率。因此，這些將是我們將評估和製定資料集的領域。

Your next question comes from the line of Erwan Reeves, Leerink Partners.

您的下一個問題來自 Leerink Partners 的 Erwan Reeves。

Your line is open sciences research in Ontario, honorees at Leerink Partners.

您所在的行業是安大略省的開放科學研究，Leerink Partners 的獲獎者。

Thanks so much for taking your question on first a couple on HDV. So first Solstice, what level of ALT normalization Are you expecting to see in the upcoming data at Easel, given that we didn't really see meaningful normalization in the early data that you presented last?

非常感謝您就 HDV 上的前幾個問題提出問題。首先，Solstice，考慮到我們在您上次提供的早期數據中並沒有真正看到有意義的標準化，您希望在 Easel 即將發布的數據中看到什麼水平的 ALT 標準化？

Yes, Greg, thank you, Rossa, for the question.

是的，格雷格，謝謝你，羅莎，提出這個問題。

So I think that the data set from our ASLD. said it was small numbers. We only have six participants. We have two out of six that achieved ALT normalization, but other participants who did not achieve ALT normalization. A majority of those were tests around that upper limit of normal. And so I think with potential longer treatment, we may see more call normalization, but the data set coming out at E. So we will have a more robust data set. And so that will help inform us further in terms of what we would expect to see in terms of ALT normalization with this regimen going forward.

所以我認為數據集來自我們的 ASLD。說是小數字。我們只有六名參與者。我們有六分之二的參與者實現了 ALT 正常化，但其他參與者沒有 ALT 正常化。其中大部分都是在正常上限附近進行的測試。因此，我認為，隨著治療時間的延長，我們可能會看到更多的呼叫標準化，但數據集來自 E.所以我們將擁有更強大的數據集。因此，這將有助於進一步告知我們，隨著該方案的推進，我們預期 ALT 正常化會發生什麼情況。

Okay, got it. Thanks. And then another one on HDV. two. We haven't heard too much recently about of Corixa's resubmission in the US. So can you share how you guys are thinking about maybe the competitive positioning of your regimen versus therapeutics? And how are you thinking about maybe the patients who could be more responsive to your regimen versus accrued X if both are available?

好，知道了。謝謝。然後是 HDV 上的另一篇。二。最近我們沒有聽到太多關於 Corixa 在美國重新提交的消息。那麼您能否分享一下您們如何看待你的治療方案與治療方法的競爭定位？如果兩者都可用，您如何考慮可能對您的治療方案比累積 X 更敏感的患者？

Yes.

是的。

Thanks for that question. So I think as you said, Bill is not approved in the US, but as I mentioned in my prepared remarks, that we would plan to have delivered side of our comparator in our trials going forward. And based on the at least what we see from the first six participants and our ability to really get to undetectable levels very quickly only after 12 weeks of combination therapy. I think that as a potential differentiator for us going forward. As I mentioned, the goal is always to achieve a biologic suppression for any therapy in chronic viral diseases. And if we're able to demonstrate that in a larger data set than that that gives us further confidence in moving forward. In addition, I think the regimen that we are developing is also being administered subcu once monthly, which is also a potential differentiator there as well.

謝謝你提出這個問題。所以我認為正如你所說，比爾在美國沒有獲得批准，但正如我在準備好的發言中提到的，我們計劃在未來的試驗中提供我們的比較器的一側。至少基於我們從前 6 名參與者身上看到的情況，以及我們僅在 12 週的聯合治療後才真正快速達到不可檢測水平的能力。我認為這是我們前進的一個潛在的差異化因素。正如我所提到的，目標始終是對慢性病毒性疾病的任何療法實現生物抑制。如果我們能夠在更大的資料集中證明這一點，那麼我們就會更有信心繼續前進。此外，我認為我們正在開發的方案也每月進行一次 subcu，這也是一個潛在的差異化因素。

I think also because as I mentioned previously in a previous answer, we are attacking the delta virus through two different mechanisms there's less of a concern was with resistance or nonresponse a different patient population.

我認為也是因為正如我在先前的回答中提到的，我們透過兩種不同的機制攻擊δ病毒，因此不太擔心不同患者群體的抗藥性或無反應。

Super helpful.

超有幫助。

If I could squeeze one for HBV. So as it relates to the thrive and survive trial. Can you give us a sense of the real-world prevalence of these immune active chronic HBV patients versus the inactive carriers? And how we should think about the data in these populations?

如果我能擠一粒乙肝病毒就好了。因此，因為它涉及茁壯成長和生存考驗。您能否讓我們了解這些免疫活躍的慢性B型肝炎患者與非活躍帶原者的真實盛行率？我們該如何看待這些人群的數據？

Yes, the rate the reason we are studying these populations is because these populations have kind of the strongest immune response to be able to be in that stage of hepatitis B. However, in these populations, they're about normally as guidelines indicated for treatment. And so these patient populations are a little bit more difficult to find. So in terms of kind of overall prevalence of these subpopulations overall, and it is a little bit unclear. But this is something that we are looking at specifically in these populations trying to recruit and find to be able to determine whether we can achieve functional cure at higher rates in these populations compared to your on a chronic suppression population.

是的，我們研究這些族群的原因是因為這些族群具有最強的免疫反應，能夠處於B型肝炎的這個階段。然而，在這些人群中，它們與治療指南所示的情況大致相同。因此，這些患者群體更難找到。因此，就這些亞人群的總體盛行率而言，目前還不清楚。但這是我們專門在這些人群中研究的，試圖招募並發現能夠確定與慢性抑制人群相比，我們是否可以在這些人群中以更高的比率實現功能性治癒。

But thanks so much for the Clarix.

但非常感謝 Clarix。

That's it for me.

對我來說就是這樣。

Your next question comes from the line of Joseph Turner of Needham. Your line is open.

你的下一個問題來自李約瑟的約瑟夫‧特納。您的線路已開通。

I thank you for taking our question.

我感謝您提出我們的問題。

I just wanted to get your updated thoughts on functional cure rates for HBV. You mentioned based on some recent KOL feedback that you believe that 25 plus percent for interferon containing regimen and perhaps less than that for a non interferon containing regimen would be considered acceptable.

我只是想了解您對乙型肝炎功能治癒率的最新想法。您提到，根據最近的一些 KOL 回饋，您認為含幹擾素治療方案的 25% 以上（可能低於不含幹擾素的治療方案）被認為是可以接受的。

Just curious if that's sort of a minimum bar for success amongst treating physicians, or is there a functional cure rate where say a certain percentage of docs would use the treatment?

只是好奇這是否是治療醫生成功的最低門檻，或者是否存在功能性治癒率，即一定比例的醫生會使用這種治療方法？

And would that be higher than sort of the numbers that you're providing?

這會比您提供的數字更高嗎？

Any additional color on that would be?

還有什麼額外的顏色嗎？

Yes, instruments.

是的，樂器。

Thank you for the question, Joe. We yes, we had a advisory board with many of the leading key opinion leaders within hepatitis back in November. And we did post a question to them for them, at least the best tier between 20% and 30% of like a functional cure rate would be highly meaningful for them. I think the other piece of component to think about in these regimens is whether a regimen containing interferon or not interferon sparing regimens. We are certainly much more tolerable easier to for patients to take easier for physicians to monitor so they would likely tolerate a lower functional cure rate to use interferon sparing regimens, fillers like interferon containing regimen, the bars a little bit higher in terms of what they would like to see in terms of functional cure rates. So it's hard to really kind of pin pin down exactly customer sliding scales for different factors to consider.

謝謝你的提問，喬。是的，早在 11 月份，我們就有了一個由許多肝炎領域主要意見領袖組成的諮詢委員會。我們確實向他們提出了一個問題，至少 20% 到 30% 之間的最佳等級（例如功能性治癒率）對他們來說非常有意義。我認為這些治療方案中需要考慮的另一個因素是治療方案是否含有乾擾素或不含幹擾素。我們當然更容易讓患者更容易接受醫生的監測，因此他們可能會容忍較低的功能性治癒率，以使用乾擾素保留方案，填充劑（如含幹擾素的方案），就其治療效果而言，標準要高一些。因此，很難真正確定要考慮的不同因素的客戶滑動比例。

Your next question comes from the line of Eric Joseph of JPMorgan. Your line is open.

你的下一個問題來自摩根大通的艾瑞克約瑟夫。您的線路已開通。

Hi.

你好。

Thanks for taking the questions. And you've noted carry that potential Phase three trial in HCV was the consequence using both retired as a comparator arm. Can you maybe just talk about sort of the investigator or regulatory feedback that informs that? And if you do move forward with that plan operationally, would you intend to include US sites given the fact that it's not approved here? And then as a follow-up, I'll give the question then I had a follow-up to that.

感謝您提出問題。您已經注意到，丙肝病毒的潛在第三階段試驗是使用兩者作為比較臂的結果。您能否談談調查人員或監管機構的回饋？如果您確實在操作上推進該計劃，鑑於該計劃未在美國獲得批准，您是否打算將美國站點納入？然後作為後續行動，我將提出這個問題，然後我對此進行了後續行動。

Yes.

是的。

Thank you, Eric, for the question. So we are, as I mentioned, we would include delivery side as a comparator, even though it's currently not approved yet in the United States. They'll be there, I guess and obviously be with our discussions with regulators moving forward in terms of what would be included in the study design and what that would look like. But I think also from because we are looking globally for this therapy and a lot of payers now want you to be compared against the standard of care, especially in Europe. So that's another reason that we would want to be including deliberate, highest comparator because we have a global footprint in this trial. We have we've done these trials before and even though delivered high is not or may not be approved yet by the time we start a trial, there are mechanisms in which we will be able to conduct the trial in the U.S. with delivered high even if it's not approved. So that would be the plan.

謝謝埃里克提出的問題。因此，正如我所提到的，我們將把交付方作為比較對象，儘管它目前尚未在美國獲得批准。我猜他們會在那裡，並且顯然會參與我們與監管機構的討論，討論研究設計中將包含的內容以及研究設計的內容。但我認為也是因為我們正在全球範圍內尋找這種療法，現在許多付款人希望將您與護理標準進行比較，尤其是在歐洲。因此，這是我們希望納入故意的、最高的比較者的另一個原因，因為我們在這項試驗中擁有全球足跡。我們之前已經做過這些試驗，即使在我們開始試驗時，高交付尚未或可能尚未獲得批准，但我們有一些機制可以在美國進行試驗，即使高交付如果未獲批准。這就是計劃。

Okay.

好的。

Rich, maybe just a follow-up. Coming back to the topic of <unk> ALTLT. normalization in HCV-infected patients is the is the prospect of normalization in cirrhotic patients. Any more challenging than it is on non cirrhotics and I guess is there sort of a difference in them sort of baseline LFT?

豐富，也許只是後續。回到altlt的主題。 HCV 感染患者的正常化是肝硬化患者正常化的前景。比非肝硬化患者更具挑戰性，我猜他們的基線 LFT 是否有某種差異？

Yes, presence, I guess that we should be thinking about here between the non-cirrhotic and sort of patient population?

是的，我想我們應該在這裡考慮非肝硬化患者群體和某種患者群體之間的情況？

Thank you.

謝謝。

Yes. Thank you for the question. Yes, and I think it's a very good question, and that's something that we will be able to show with our data in terms of looking at iStar, if there are baseline differences in ALT levels, if there are no public or higher or lower in SaRonix versus non SaRonix and then also looking at the rate of normalization. So yes, so we outsource our data set will be able to help answer us answer that question for us moving forward. But I think as I mentioned earlier in terms of the antiviral efficacy and then potential impact on ALT.?

是的。感謝你的提問。是的，我認為這是一個非常好的問題，如果 ALT 水平存在基線差異，如果沒有公開的或更高或更低的指標，我們將能夠透過 iStar 的數據來展示這一點。比較，然後也查看標準化率。所以是的，所以我們外包我們的資料集將能夠幫助我們回答這個問題，讓我們繼續前進。但我認為正如我之前提到的抗病毒功效以及對 ALT 的潛在影響。

Yes, we don't really we don't expect to see significant differences between SaRonix and on SurModics on these in the CPTA. population.

是的，我們確實不希望在 CPTA 中看到 SaRonix 和 SurModics 之間的顯著差異。人口。

But obviously the data set will inform us on that figure.

但顯然數據集會告訴我們這個數字。

Excellent. Thanks for taking the questions.

出色的。感謝您提出問題。

Your next question comes from the line of Mike, all of Morgan Stanley.

你們的下一個問題來自麥克，摩根士丹利的全體員工。

Your line is now open, but Good afternoon and thanks for taking the question.

您的熱線現已開通，下午好，感謝您提出問題。

Maybe just a quick one on the Phase one HIV program.

也許只是第一階段愛滋病毒計畫的快速介紹。

I think you'll have data in the second half of this year.

我想今年下半年你就會得到數據。

Maybe you can just talk about some of the key points and the key endpoints in that early study and what we should be looking for?

也許您可以談談早期研究中的一些關鍵點和關鍵終點以及我們應該尋找什麼？

And and maybe what would be would be positive in your view to sort of keep that program moving forward? Thanks.

也許您認為什麼對保持該計劃向前推進有積極作用？謝謝。

Thank you for the question. So we do have this ongoing trial with fear 1388, which is our HCMV. vector of both potential HIV vaccine. And this is in partnership with the HBTM., who is helping us conduct the trial. And we have completed enrollment of Part A. of that trial. And as we've guided to, we expect to see initial immunologic data from that trial second half of this year. And so far, we are really looking for is these immunologic endpoints, specifically looking at T cell markers and we see restricted CAR T cell responses and kind of seeing what we would we at least see similar types of immune responses that were observed in them attacks that were protective from SIP in those animals. And so so if we're able to see the proof of immunology, then we have this opens up this platform to other areas, potential areas of exploration such as in human papilloma virus that with our beer 1949 vector.

感謝你的提問。所以我們確實正在進行這項針對恐懼 1388 的試驗，而這就是我們的 HCMV。兩種潛在的愛滋病毒疫苗的載體。這是與 HBTM 合作的，HBTM 正在幫助我們進行試驗。我們已經完成了該試驗 A 部分的註冊。正如我們所指導的那樣，我們預計將在今年下半年看到該試驗的初步免疫學數據。到目前為止，我們真正在尋找的是這些免疫學終點，特別是關注 T 細胞標記，我們看到了有限的 CAR T 細胞反應，並且看到了我們至少會看到在攻擊中觀察到的類似類型的免疫反應對這些動物具有保護作用，使其免受SIP 的侵害。因此，如果我們能夠看到免疫學的證據，那麼我們就可以為其他領域、潛在的探索領域打開這個平台，例如使用我們的啤酒 1949 載體來研究人類乳頭瘤病毒。

Yes.

是的。

Great. Thank you.

偉大的。謝謝。

There are no further questions at this time. I will now turn the conference back over to Marianne for the closing remarks.

目前沒有其他問題。現在我將把會議轉回瑪麗安致閉幕詞。

Thank you, operator. To concludes our companies beginning to realize benefits from the cost savings initiatives we implemented in 2023, and we look forward to sharing important data from our Solstice trial at Easel. This is a milestone that brings us closer to addressing the significant unmet medical need for millions of people that are living with hepatitis delta. Looking ahead, we also anticipate additional data readouts in the fourth quarter that could serve as important catalysts for the company. Thank you. And operator, you may conclude the call.

謝謝你，接線生。總而言之，我們的公司開始從我們在 2023 年實施的成本節約計畫中獲益，我們期待分享 Easel 的 Solstice 試驗的重要數據。這是一個里程碑，使我們更接近解決數百萬丁型肝炎患者未滿足的重大醫療需求。展望未來，我們也預計第四季將有更多數據公佈，這可能成為該公司的重要催化劑。謝謝。接線員，您可以結束通話了。

Thank you. That concludes today's call and thank you all for joining. You may now disconnect.

謝謝。今天的電話會議到此結束，感謝大家的加入。您現在可以斷開連線。