Arbutus Biopharma Corp (ABUS) 2024 Q3 法說會逐字稿

Good day. And thank you for standing by Welcome to the Arbutus BioPharma 2024 3rd quarter, financial results and corporate update.

再會。感謝您的支持，歡迎來到 Arbutus BioPharma 2024 年第三季財務表現與公司更新。

(Operator Instructions) I would now like to hand the conference over to your first speaker today, Lisa Capparelli, Vice President of Investor Relations. Please go ahead.

（操作員指示）現在，我想將會議交給今天的第一位發言人，投資者關係副總裁 Lisa Capparelli。請繼續。

Thank you, Antoine. Good morning, everyone and thank you for joining arbutus' third quarter, 2024 financial results and corporate update call. Joining me today from the Arbutus executive team are Michael McElhaugh, interim President and Chief Executive Officer David Hastings, Chief Financial Officer, Dr Karen Sims, Chief Medical Officer and Michael Sofia, Chief Scientific Officer, Michael McElhaugh will provide a corporate update including an update on our, on our ongoing clinical programs in HBV. Dave will then provide a review of the company's third quarter, 2024 financial results. After our prepared remarks, we will open the call for Q&A before we begin. I'd like to remind you that some of the statements made during the call today are forward-looking statements which are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our annual report on form 10-K, our quarterly report on form 10-Q which will be filed today and from time to time in our other documents filed with the SEC with that, I'll turn the call over to Michael McElhaugh . Mike.

謝謝你，安托萬。大家早安，感謝您參加 Arbutus 2024 年第三季財務表現和公司更新電話會議。今天與我一起出席 Arbutus 執行團隊會議的還有臨時總裁兼執行長 Michael McElhaugh、財務長 David Hastings、首席醫療官 Karen Sims 博士和首席科學官 Michael Sofia，Michael McElhaugh 將提供公司最新動態，包括我們正在進行的 HBV 臨床項目的最新動態。戴夫隨後將對公司 2024 年第三季的財務表現進行回顧。在我們準備好發言之後，我們將在開始之前開放問答環節。我想提醒大家，今天電話會議上的一些陳述是前瞻性的，這些陳述受多種風險和不確定因素的影響，可能導致我們的實際結果出現重大差異，包括我們10-K表格年度報告、10-Q表格季度報告（將於今天提交）以及我們不時向美國證券交易委員會提交的其他文件中所述的陳述。我將把電話交給麥可麥克爾豪。麥克風。

Thank you Lisa and good morning everyone. I appreciate you joining us today. A few weeks ago, we issued a press release announcing that multiple abstracts highlighting inducer and data were accepted for presentation at the liver meeting 2024 which is the annual meeting held by the American Association for the study of liver diseases.

謝謝麗莎，大家早安。感謝您今天加入我們。幾週前，我們發布了一份新聞稿，宣布多篇強調誘導劑和數據的摘要已被接受在 2024 年肝臟會議上發表，該會議是美國肝病研究協會舉辦的年度會議。

Included in the acceptance are two late breaker poster presentations with inducer and data from our ongoing phase two. A clinical trials improve one and improve two.

接受的內容包括兩份最新海報展示，其中包含我們正在進行的第二階段的誘導劑和數據。臨床試驗改善一、改善二。

Since that meeting kicks off next Friday, November 15th and the data are under embargo. We're not able to provide any updates to those trials at this time.

由於會議將於下週五（11 月 15 日）開始，因此數據處於禁止狀態。我們目前無法提供這些試驗的任何更新資訊。

I will however review at a high level, the data that we presented from those clinical trials earlier this year at the EASL conference before doing so. I want to take a minute to discuss why we are focused on a functional cure for patients with chronic hepatitis B.

不過，在此之前，我將從高層次回顧我們在今年稍早的 EASL 會議上展示的這些臨床試驗的數據。我想花一點時間來討論為什麼我們專注於慢性B型肝炎患者的功能性治療。

Chronic HPV remains a significant global health challenge affecting more than 250 million people worldwide. Despite the availability of preventive vaccines and current treatment options.

慢性 HPV 仍然是全球面臨的重大健康挑戰，影響全球超過 2.5 億人。儘管有預防疫苗和現有治療選擇。

This underscores our mission to address the urgent need to bring innovative combination treatments with a finite duration such as those that could include our RNI therapeutic inducer to patients as quickly as possible. Currently, the primary treatments for chronic HPV include nucleus analogs that suppress HPV DNA and immune modulators like interferon. These agents result in a very low functional cure rate. Therefore, combining new and innovative therapies to reduce surface antigen suppress HPV DNA and boost the immune system with current standard of care is needed to provide a more optimal functional cure rate for patients with HPV.

這強調了我們的使命，即盡快為患者提供有限持續時間的創新聯合治療，例如可能包括我們的 RNI 治療誘導劑的治療。目前，慢性HPV的主要治療方法包括抑制HPV DNA的細胞核類似物和乾擾素等免疫調節劑。這些藥劑導致功能性治癒率非常低。因此，需要將降低表面抗原、抑制 HPV DNA 和增強免疫系統的新型創新療法與目前的標準治療相結合，為 HPV 患者提供更優化的功能性治癒率。

If a functional cure rate were available for patients with chronic HPV, it could potentially significantly reduce the patient's risk of liver cirrhosis and hepatocellular carcinoma, decrease patients stigma and eliminate lifelong treatment and burdensome health care costs.

如果慢性 HPV 患者的功能性治癒率能夠提高，那麼就有可能顯著降低患者患肝硬化和肝細胞癌的風險，減少患者的恥辱感，並免除終生治療和繁重的醫療保健費用。

As we focus on developing a functional cure for chronic HPV, we believe it is first important to lower viral markers such as hepatitis B surface antigen. Our phase two studies are designed to use inducer to reduce surface antigen as low as possible. Before administering an immune modulator, we are combining our RNA therapeutic inducer with two different immune modulators. In two phase two, a clinical trials, our improved one trial which includes short courses of interferon and our improved two trial which includes a combination of a therapeutic vaccine and an anti PD one monoclonal antibody at the Easel Congress in June. We reported data from our improved one clinical trial showing that the combination of inducer and plus interferon was generally safe and well tolerated.

由於我們專注於開發慢性 HPV 的功能性治療方法，我們認為降低乙肝表面抗原等病毒標記至關重要。我們的第二階段研究旨在使用誘導劑盡可能降低表面抗原。在使用免疫調節劑之前，我們將 RNA 治療誘導劑與兩種不同的免疫調節劑結合。在兩個第二階段臨床試驗中，我們在 6 月的 Easel 大會上進行了改進的一項試驗，其中包括短期幹擾素療程，以及我們改進的兩項試驗，其中包括治療性疫苗和抗 PD 單株抗體的組合。我們報告了改進的一項臨床試驗的數據，表明誘導劑和乾擾素的組合通常是安全的並且耐受性良好。

The cohort that performed the best was cohort A one where HPV patients received six doses of inducer and 24 weeks of interferon. In addition to ongoing nu therapy in cohort, a 1 33% of the patients achieved surface antigen loss at the end of inducer and interferon treatment that was sustained at 24 weeks. Post end of treatment, we also looked at a subset of patients who had surface antigen less than 1,000 international units per mill at baseline in cohort, a 1 67% of the patients who had surface antigen less than 1,000 international units per mill at baseline maintained surface antigen loss 24 weeks after completion of inducer and interfere on treatment. This is one of the highest reported rates of surface antigen loss achieved by patients with baseline surface antigen less than 1,000 international units per mill.

表現最好的隊列是 A 組，其中 HPV 患者接受了六劑誘導劑和 24 週的干擾素治療。除了隊列中持續進行的 nu 療法外，133% 的患者在持續 24 週的誘導劑和乾擾素治療結束時實現了表面抗原的消失。治療結束後，我們也觀察了隊列中基線時表面抗原低於 1,000 國際單位/毫升的患者亞組，其中 167% 的患者在完成誘導劑和乾擾物治療後 24 週仍維持表面抗原流失。這是報告的基線表面抗原低於 1,000 國際單位/毫升的患者的表面抗原流失率最高的比率之一。

This is a relevant population to assess because published studies have shown that patients with surface antigen loss have better long term outcomes. As we think about a phase two B clinical trial and based on these data stratifying the patient population to include those with low surface antigen may best position us for success while still capturing a significant portion of chronic HPV patients.

這是一個需要評估的相關人群，因為已發表的研究表明，表面抗原流失的患者的長期預後較好。當我們考慮第二階段 B 臨床試驗時，根據這些數據對患者群體進行分層，以包括那些具有低表面抗原的患者，這可能使我們獲得成功，同時仍捕獲相當一部分慢性 HPV 患者。

At the time, we reported the data, these four patients in cohort A one with sustained surface antigen loss had discontinued their nucleotide therapy. We've been following these patients to assess them for functional cure as a reminder, functional cure is defined as sustained hepatitis B surface antigen loss and HPV DNA. Less than the lower levels of quantification. 24 weeks off treatment with or without Hepatitis B surface antibodies.

當時，我們報告數據，A組中這四名表面抗原持續流失的患者已經停止了核苷酸治療。我們一直在追蹤這些患者，以評估他們的功能性治癒情況，提醒一下，功能性治癒的定義是持續的乙肝表面抗原消失和 HPV DNA。低於較低的量化水準。 24週內停止治療，不論是否有B肝表面抗體。

We continue to receive positive feedback on these data from key opinion leaders in the HPV field and we are excited to provide additional follow up data from this trial at a SLD next week in June at ESY, we also reported end of treatment data from our improved two clinical trial that is evaluating the safety and immunogenicity of a 24 week lead in with inducer followed by barry biotherapeutics, immunotherapeutic VTP 300 or placebo while continuing new therapy in this trial inducer and lowered surface antigen to levels less than 100 international use per mil prior to dosing with VTP 300 or placebo in 95% of the patients after receiving VTP 300 through 24 weeks. Post end of treatment, more patients maintain surface antigen thresholds of less than 100 or less than 10 international needs per mil versus placebo for patients who reach this time point. A statistically significant difference was achieved in mean surface antigen levels between the treatment arm and placebo recall that we have expanded this improved two clinical trial to evaluate the addition of a low dose of the anti PD one monoclonal antibody neume to the inducer and VTB 300 combination treatment regimen which we believe may further boost the host immune response. We are on track to report preliminary data from this portion of the trial. Next week. At ad the totality of these data support our plans to advance inducer into a phase two B clinical trial as a cornerstone in a potential HPV functional cure treatment regimen.

我們繼續從 HPV 領域的關鍵意見領袖那裡收到對這些數據的積極反饋，我們很高興在下週 6 月的 ESY 的 SLD 上提供來自此試驗的更多後續數據，我們還報告了我們改進的兩項臨床試驗的治療結束數據，這兩項試驗正在評估 24 週的安全性和免疫原性，先使用誘導劑，然後使用生物治療、新治療劑的患者接受 VTP 300 治療 24 週後，將表面抗原降低到使用 VTP 300 或安慰劑之前低於 100 國際使用/毫升的水平。治療結束後，與達到此時間點的患者相比，更多患者維持表面抗原閾值低於 100 或低於每毫升 10 國際需求。治療組和安慰劑組之間的平均表面抗原水平存在統計學上的顯著差異，回想一下，我們擴大了這兩項改進的臨床試驗，以評估在誘導劑和VTB 300聯合治療方案中添加低劑量的抗PD單株抗體neume，我們相信這可能會進一步增強宿主的免疫反應。我們正在按計劃報告該部分試驗的初步數據。下週。總之，這些數據支持我們將誘導劑推進到第二階段 B 階段臨床試驗的計劃，作為潛在 HPV 功能性治癒治療方案的基石。

Now, I'd like to move on to ab 101 oral small molecule PD L one checkpoint inhibitor. We believe that the immune checkpoint pathway plays an important role in HPV, specific immune tolerance. And in T cell activation and the addition of a checkpoint inhibitor in combination with inducer could potentially further enhance HPV, specific immune responses.

現在，我想談談 ab 101 口服小分子 PD L 一檢查點抑制劑。我們認為免疫檢查點路徑在HPV、特異性免疫耐受性中扮演重要角色。而在T細胞活化和添加檢查點抑制劑與誘導劑的結合可能會進一步增強HPV特異性免疫反應。

We remain excited about the potential of A B 101 in treating HPV A B 101 is liver centric. And in preclinical studies had typical small molecule pharmacokinetics likely providing a much shorter duration of effect than long acting antibodies. A B 101 was designed with the goal of minimizing systemic exposure and reducing the chance of immune related adverse events that are often seen with checkpoint antibodies.

我們仍然對 A B 101 在治療 HPV 方面的潛力感到興奮 A B 101 以肝臟為中心。並且在臨床前研究中，典型的小分子藥物動力學可能比長效抗體提供更短的作用時間。A B 101 的設計目標是最大限度地減少全身暴露並降低檢查點抗體中常見的免疫相關不良事件的可能性。

Ab 101 is currently in a phase one A one B clinical trial that consists of three parts starting with single and multiple ascending doses in healthy subjects and culminating with multiple doses in patients with chronic HBV. Last quarter, we reported data from the part one single ascending dose portion of the trial showing that ab 101 was generally well tolerated with evidence of dose dependent receptor occupancy.

Ab 101 目前處於第一階段 A 至 B 臨床試驗，該試驗由三部分組成：首先在健康受試者中給予單次和多次遞增劑量，最後在慢性 HBV 患者中給予多次劑量。上個季度，我們報告了試驗第一部分單次遞增劑量部分的數據，顯示 ab 101 通常耐受性良好，並有劑量依賴性受體佔據的證據。

In the 25 mg single dose cohort, all five evaluable subjects showed evidence of PD L one receptor occupancy between 5100% indicating that ab 101 is interacting with its intended target.

在 25 毫克單劑量組中，所有五名可評估受試者均顯示 PD L 一受體佔據率在 5100% 之間，表明 ab 101 正在與其預期目標相互作用。

Today, we reported data from phase two of this trial where part excuse me, part two of this trial where we have so far enrolled two sequential cohorts of 10 healthy subjects. Each cohort received 10 or 25 mg of ab 101 or placebo daily for seven days. Multiple ascending doses of ab 101 were generally well tolerated with evidence of dose dependent receptor occupancy.

今天，我們報告了該試驗第二階段的數據，對不起，這是該試驗的第二部分，到目前為止，我們已經招募了兩組連續的 10 名健康受試者。每組受試者每天接受 10 或 25 毫克 ab 101 或安慰劑，持續七天。ab 101 的多次遞增劑量通常耐受性良好，並有劑量依賴性受體佔據的證據。

In the 25 mg cohort, all subjects showed evidence of receptor occupancy with seven of the eight subjects demonstrating receptor occupancy greater than 70% during the seven day dosing period with a favorable safety profile to date and evidence of receptor occupancy. We have now moved into part three, the global portion of this clinical trial which evaluates 28 days of repeat dosing in a 101 in patients with chronic HPV.

在 25 毫克組別中，所有受試者均顯示出受體佔據的證據，其中八名受試者中有七名在七天的給藥期間表現出受體佔據率大於 70%，迄今為止具有良好的安全性和受體佔據的證據。現在我們已經進入第三部分，即該臨床試驗的全球部分，該部分評估了 101 名慢性 HPV 患者 28 天重複給藥的情況。

We expect to report preliminary data from HPV patients dosed with ab 101 in the first half of next year.

我們預計在明年上半年報告接受 ab 101 治療的 HPV 患者的初步數據。

Finally, I have two brief updates on the litigation progress with Moderna and Pfizer Biontech around our LNP intellectual property in the Moderna case. The trial date is now scheduled for September 24th 2025 which is of course subject to the court's availability in the Pfizer Biontech lawsuit. The date for the claim construction hearing also known as the Markman hearing has been set for December 18th 2024.

最後，我簡單介紹一下我們與 Moderna 和 Pfizer Biontech 在 Moderna 案中圍繞 LNP 智慧財產權的訴訟進展。審判日期現定於 2025 年 9 月 24 日，當然這取決於法院對輝瑞 Biontech 訴訟的可用性。權利要求解釋聽證會（也稱為馬克曼聽證會）的日期已定為 2024 年 12 月 18 日。

I'll now turn the call over to Dave Hastings for a brief financial update. Dave.

現在我將把電話轉給戴夫·黑斯廷斯，讓他簡要報告財務最新情況。戴夫。

Thanks Mike and good morning everybody.

謝謝麥克，大家早安。

We ended the third quarter of 2024 with approximately$131 million of cash, cash equivalents and investments and marketable securities compared to approximately $132 million. As of December 31st 2023.

截至 2024 年第三季度，我們的現金、現金等價物、投資和有價證券約為 1.31 億美元，而去年同期約為 1.32 億美元。截至 2023 年 12 月 31 日。

During the first half of 2024 we received approximately $44 million of net proceeds from the issuance of common shares under our at the market offering program.

2024 年上半年，我們根據市場發行計畫發行普通股獲得了約 4,400 萬美元的淨收益。

These cash inflows were offset by$ 54.5 million of cash used in operations.

這些現金流入被營運中使用的 5,450 萬美元現金所抵消。

We did not issue any common shares under our ATM program in the third quarter of 2024 and we still expect our 2024 cash burn to range from $63million to $67 million.

我們在 2024 年第三季沒有根據 ATM 計劃發行任何普通股，我們仍然預計 2024 年的現金消耗將在 6,300 萬美元至 6,700 萬美元之間。

Importantly, our cash runway is sufficient to fund our operations into the fourth quarter of 2026.

重要的是，我們的現金流足以支持我們到 2026 年第四季的營運。

In closing, we have a strong financial position to advance our mission of developing our HPV assets to provide a functional cure for people with chronic HPV. And with that, I'll turn the call back to Mike.

最後，我們擁有強大的財務實力來推進我們的使命，即開發我們的 HPV 資產，為慢性 HPV 患者提供功能性治療。說完這些，我就把電話轉回給麥克。

Thanks Dave. We look forward to providing an update next week as we intend to report additional data from our improved one clinical trial and preliminary end of treatment data from the volume of arm of the improved two trial at a sld with these planned data announcements and today's reporting of the multiple ascending dose data from healthy subjects in the A B 101 trial, we will have achieved all of our second half milestones operator. We're now ready to open the call for Q&A.

謝謝戴夫。我們期待下週提供最新消息，因為我們打算報告來自改進的一項臨床試驗的更多數據，以及來自改進的兩項試驗的組容量的初步治療結束數據，透過這些計劃中的數據公告和今天報告的來自 A B 101 試驗中健康受試者的多次遞增劑量數據，我們將實現下半年的所有里程碑。我們現在準備開始問答環節。

Thank you at this time. We will conduct a question and answer session as a reminder to ask a question. You need to press star 11 on your telephone and wait for your name to be announced to withdraw your question. Please press star 11 again. Please stand by while I compile the Q&A roster.

這次謝謝你了。我們將進行問答環節，提醒大家提出問題。您需要按下電話上的星號 11，等待播報您的名字後才能撤回您的問題。請再按星號 11。請稍候，我正在整理問答名單。

Your first question comes from Dennis Ding from Jefferies. Please go ahead.

您的第一個問題來自 Jefferies 的 Dennis Ding。請繼續。

Good morning. This is Anthea on for dentists. Thanks for taking our questions. We had a question on functional cure data that's upcoming. I know that you've mentioned the 20% bar but also appreciating that the update will include patients from cohort A two without inducer.

早安.這是為牙醫準備的安西亞 (Anthea)。感謝您回答我們的問題。我們對即將發布的功能性治癒數據有疑問。我知道您提到了 20% 的標準，但也讚賞更新將包括來自 A 組兩名未使用誘導劑的患者。

So do you have any thoughts on what functional cure would look like in this arm? Would you be looking for a 20% incremental benefit on top? When you add inducer? Just imagining if this cohort has 10 15% functional cure, how we should interpret that data is adding him to gets to 20%. Thank you.

那麼，您對這手臂的功能性治療有何看法？您是否希望獲得 20% 的增量收益？什麼時候添加誘導劑？試想一下，如果這個群體有 10 15% 的功能性治愈，我們應該如何解釋該數據，將他添加到達到 20% 的水平。謝謝。

Good morning Atea. This is, this is Mike. So let me, let me try to try to understand where you're headed with this question. So, first of all, we have not presented any functional cure data related to inducer. And to date, we've only presented end of treatment and post nucleus site consolidation. The 20% functional curate that you've mentioned is sort of a stick in the mud for us. Sort of a baseline of what we think is a meaningful functional curate. As you know, the current therapies don't do very well, less than 10% somewhere around 5% and less for nucleus size.

早上好，Atea。這是，這是麥克。那麼，讓我試著去理解一下您提出這個問題的真正目的。因此，首先，我們沒有提供任何與誘導劑相關的功能性治療數據。到目前為止，我們僅介紹了治療結束和核部位鞏固後的情況。您提到的 20% 功能性措施對我們來說有點難以接受。我們認為這是有意義的功能性策展的基線。如您所知，目前的治療方法效果不太好，細胞核大小的治療效果不到 10%，約 5%，甚至更低。

So we, as a company have sort of set a goal for, for our programs that if we can hit a functional cure of 20% as a goal as an aspirational goal that that would be meaningful and and beneficial to patients going forward. So, you know, whether we're talking about cohort A one or a two, or B one or B two. You know, we should, we should see sort of how that, how that continues at a sld next week. And Karen, do you want, if you want to add anything to that, please?

因此，作為一家公司，我們為我們的專案設定了一個目標，如果我們能夠達到 20% 的功能性治癒率，作為一個理想目標，那麼這將是有意義的，並且對患者的未來有益。所以，您知道，我們談論的是 A 組一還是 A 組二，還是 B 組一還是 B 組二。你知道，我們應該看看下週的 sld 會如何繼續。凱倫，您還有什麼要補充的嗎？

And I would like to clarify how the study is designed just to avoid any misinterpretation. So all of the subjects in the improved one study received at least four doses of induced around so 60 mg every eight weeks for a period of 24 weeks. And then they were randomized to the different interferon containing cohort. The two group did in fact receive four doses of induced before they were randomized to receive the 24 weeks of interferon.

我想澄清一下這項研究的設計方式，以避免任何誤解。因此，改進的一項研究中的所有受試者每八週接受至少四劑誘導劑量，每次約 60 毫克，為期 24 週。然後將他們隨機分配到含有不同幹擾素的組別。這兩組患者在隨機接受 24 週幹擾素治療之前確實接受了四劑誘導治療。

The difference between the A one and the A two cohort is the A one cohort continued to receive induced during the interferon treatment period. Whereas the A two cohort just received the initial four doses and then received interferon only. So I just want to clarify that point in case there's a misunderstanding about the trial design.

A一隊列與A二隊列的差異在於A一隊列在幹擾素治療期間繼續接受誘導。而 A2 組僅接受了最初四劑疫苗，之後僅接受了乾擾素治療。因此，我只是想澄清這一點，以防對試驗設計產生誤解。

Okay. Got it. And so the bar would be 20% in either cohort.

好的。知道了。因此，任一群體的標準都是 20%。

Because they're both interference or induced grant and interferon containers.

因為它們都是乾擾或誘導授予和乾擾素容器。

Yes, got it. Thank you.

是的，明白了。謝謝。

Thank you one moment for our next question.

感謝您的提問。

Our next question comes from Roy Buchanan from J MP Securities . Please go ahead.

我們的下一個問題來自 J MP Securities 的 Roy Buchanan。請繼續。

Hey, great. Thanks for taking the questions. I guess to follow up on that, that last question that how, what should we consider as a denominator? So if we just take cohort a one, for example, is the denominator for functional cure going to be 12 patients or are you thinking about the four patients who achieved and loss and then kind of along the same lines. How are you thinking about the inducer and lead in for subsequent studies? You can get Pati a lot of patients below 1,000 with induce itself. So you may be thinking to screen after inducer and lead in or at the very beginning. Thanks.

嘿，太棒了。感謝您回答這些問題。我想繼續討論這個問題，最後一個問題是，我們應該將什麼視為分母？因此，如果我們僅以隊列 A 為例，那麼功能性治癒的分母是否是 12 名患者，或者您是否考慮過 4 名成功治癒和失敗的患者，然後沿著相同的思路。您如何考慮後續研究的誘導劑和引導劑？您可以透過誘導來獲得許多低於 1,000 的 Pati 患者。因此，您可能正在考慮在誘導劑和引導劑之後或一開始就進行篩選。謝謝。

Yeah. So getting back to your first question about the the denominator. So, you know, each cohort, as you noted, had a denominator of around 12 or 13 subjects for the 24 week cohort. So certainly we'd be looking, you know, at functional care across the entire population of that cohort. And we've already presented some an and loss data as Mike said, at end of treatment, four weeks, post end of treatment after the new consolidation period, looking at that denominator of 12 where we get 33%. If we then look at the population a little differently and look at subjects who entered the study with baseline surface antigen less than 1,000, we see that percentage of surface antigen loss go up to 67% and this is consistent with what a lot of sponsors have seen across clinical trials recently in the Hepatitis B area that subjects with lower surface antigen tend to respond better to these therapies.

是的。所以回到你關於分母的第一個問題。因此，正如您所說，每個隊列在 24 週隊列中的分母約為 12 或 13 個受試者。因此，我們肯定會關注整個群體的功能性護理。正如 Mike 所說，我們已經提供了一些治療結束時、治療結束後四周、新的鞏固期後的數據，以分母 12 計算，我們得到了 33% 的結果。如果我們稍微改變一下人群，看看那些進入研究時基線表面抗原低於 1,000 的受試者，我們會發現表面抗原丟失的百分比上升到 67%，這與許多申辦方最近在乙肝領域的臨床試驗中看到的情況一致，即表面抗原較低的受試者往往對這些療法反應更好。

But I think in either situation, you know, if, if our surface antigen loss data transfers to functional cure data, we're above that 20% bar regardless of whether we look at the entire cohort or whether we look at the subjects with surface antigen less than 1,000. So, you know, I think we'll be looking, you know, as the data merges and looking forward to updated a slg about how the the functional cure data will appear, looking at both of those denominators. In regards to your second question about the inducer and lead in period. So, you know, obviously, we're continuing to look at all different possibilities of study designs moving forward. I think what has been a little differentiating about this particular trial with improved one, for example, is we're using this lead in period to drive surface antigen as low as possible.

但我認為，無論哪種情況，如果我們的表面抗原損失數據轉移到功能性治癒數據，那麼無論我們看整個隊列還是看表面抗原少於 1,000 的受試者，我們都高於 20% 的標準。所以，你知道，我認為我們會觀察數據合併的情況，並期待更新 slg，了解功能性治癒數據將如何出現，並觀察這兩個分母。關於您關於誘導劑和引導期的第二個問題。所以，您知道，顯然，我們正在繼續研究未來研究設計的所有不同可能性。我認為這次試驗與改進試驗的一點不同之處在於，我們利用這個引導期來盡可能降低表面抗原。

And when we do that and then come with the im you know, modulator after lowering surface antigen, we're seeing these very high rates of surface antigen loss. So I think, you know that so far has that been I think a good study design for us in terms of our goals of lowering surface antigen and then boosting the host immune response with an immunomodulator. So certainly, as I mentioned, as we go forward, we're looking at all different types of, study design options. And you know, we'll see where the data lead us with these face to a studies.

當我們這樣做，然後在降低表面抗原後使用調節劑時，我們會看到表面抗原流失率非常高。所以我認為，就我們降低表面抗原然後用免疫調節劑增強宿主免疫反應的目標而言，到目前為止，我認為這對我們來說是一個很好的研究設計。因此，正如我所提到的，隨著我們不斷前進，我們正在研究各種不同類型的研究設計方案。你知道，我們將透過這些面對面的研究看到數據將引導我們走向何方。

Okay, great. That's helpful. Thank you and a couple on a 101.

好的，太好了。這很有幫助。謝謝你和 101 號上的一對夫婦。

The, so the results in the first half of next year is that likely just going to be cohort A and is that so 12 subjects from that? And then do you have any plans to present the the part one or, or two results? Thanks.

那麼，明年上半年的結果很可能只是 A 組，那麼是其中的 12 個科目嗎？那麼，您有什麼計劃來展示第一部分或第二部分的結果嗎？謝謝。

Yeah. So Roy, we're still, l working through that. We will, we can't, I can't give you any additional detail on what specifically that, what specific data set will be presented in the first half, but there will be HPV patient data in the first half with regards to the, the M ad portion of the data. We will, we'll figure out the right forum to get that out. But of course, you know, we're, pretty, open with the data that we, that we have and we like to get that in the hands of a, you know, in the hands of the likes of you. know, as quickly as we typically can. So stay tuned.

是的。所以羅伊，我們仍在努力解決這個問題。我們無法為您提供任何關於具體內容的額外細節，無法提供關於上半部將呈現哪些具體資料集，但關於資料的 M 廣告部分，上半部將有 HPV 患者資料。我們會的，我們會找到合適的論壇來解決這個問題。但是，當然，你知道，我們對我們擁有的數據非常開放，我們希望盡快將這些數據交到像你這樣的人手中。敬請關注。

All good. Thank you.

一切都好。謝謝。

Thank you one moment for our next question.

感謝您的提問。

Our next question comes from Keay, Nakae from Chardan Capital Markets. Please go ahead.

我們的下一個問題來自 Chardan Capital Markets 的 Keay, Nakae。請繼續。

Yes, thank you. So I'm wondering if you can give us any further clarity on how you're thinking about timing for face to B.

是的，謝謝。所以我想知道您是否可以進一步向我們解釋一下您對 Face to B 時間安排的看法。

Yeah, so, good morning Kay. Good to hear from you. I, I, at this point, I can't really give you any additional timing related to the phase two B. Other than to say that we're working through it as diligently as we can. We are, you know, we're looking at the data that we have on hand and what's going to be coming up. And obviously, we need to, we need to have internal discussions, talk to regulators and figure out what the right, the right path is for inducer and to get it to market as quickly as we can. So, you know, all I can say at this point is we're being diligent and we will continue to do so. And we'll get there just as quickly as we can.

是的，早上好，凱。很高興收到你的來信。我，我，在這一點上，我真的無法給你任何與第二階段 B 相關的額外時間。除了說我們正在盡可能努力地完成它。你知道，我們正在查看手頭上的數據以及即將出現的情況。顯然，我們需要進行內部討論，與監管機構溝通，找出誘導劑的正確途徑，並儘快將其推向市場。所以，你知道，我現在只能說我們正在努力，我們將繼續這樣做。我們會盡快到達那裡。

Okay. Thanks.

好的。謝謝。

Thank you one moment for our next question.

感謝您的提問。

Our next question comes from Brian Skorney from Baird. Please go ahead.

我們的下一個問題來自貝爾德公司的 Brian Skorney。請繼續。

Hey, good morning everyone. Thanks for taking the question. I actually I went on ad 101 going into part three of the study. Just wondering if, if you had any insight into prior looks at PD one or PDL 11 date in HBV. Is there any HPV specific biomarker that would be expected to move here? Not sure if you're enrolling just a mix of the antigen positives or negatives, but just trying to level set expectations on, on what a 28 8 day result could show in HPV patients with the anti PD L one. Thanks.

嘿，大家早安。感謝您回答這個問題。實際上，我進入了廣告 101 研究的第三部分。我只是想知道，您是否對 HBV 中的 PD 1 或 PDL 11 日期的先前觀察有任何見解。是否有任何 HPV 特異性生物標記預計會轉移到這裡？不確定您是否只招募抗原陽性或陰性的混合體，但只是想設定一個期望值，即 28 8 天的結果對於具有抗 PD L 抗體的 HPV 患者會有什麼影響。謝謝。

Sure, good morning, Brian. Thanks for the call. Maybe I'll ask Karen or Mike to handle, to handle that one.

當然，早上好，布萊恩。謝謝您的來電。也許我會請凱倫 (Karen) 或麥克 (Mike) 來處理這個問題。

Yeah, I can start. I mean, you know, as you probably know from following, you know, our company over the years, we tend to be very biomarker heavy. So we always like to explore you know, biomarkers to the extent we can in any of our trials including phase one trial. So we are doing a robust biomarker collection to you know, look as we've already reported receptor occupancy and other markers. So that continues into the, the part three of the study, the hepatitis B portion of the study.

是的，我可以開始了。我的意思是，您可能知道，透過多年來對我們公司的關注，我們傾向於非常重視生物標記。因此，我們總是喜歡在任何試驗（包括第一階段試驗）中盡可能地探索生物標記。因此，我們正在進行強大的生物標記收集，正如我們已經報告的受體佔有率和其他標記一樣。因此，這將持續到研究的第三部分，即研究的乙肝部分。

You know, I will remind everyone that it is just a 28 day treatment period and 81 on one is not a direct acting antiviral, right? It's an immune modulator. So we're not, we don't have clear expectations yet on what we might see in terms of actual effects on Hepatitis B on the anti hepatitis B immune response in these subjects with a 28 day treatment period. So we'll have to, you know, see that data as it evolves and as we dose escalate through that portion of the trial, but had any other, you know, I mean, I know obviously fair, fair made it clear what the expectations.

你知道，我要提醒大家，這只是一個 28 天的治療期，而且 81 對一療法並不是直接起抗病毒作用的藥物，對嗎？它是一種免疫調節劑。因此，我們還沒有明確的預期，對於在 28 天的治療期內對這些受試者的抗乙肝免疫反應產生的實際效果，我們可能會看到什麼。因此，我們必須觀察數據的發展，並觀察在試驗的這一部分中劑量的增加，但還有其他什麼，你知道，我的意思是，我知道顯然是公平的，公平地明確了期望。

So.

所以。

The goal, the goal with 101, obviously, Brian is to get it in combination with inducer as quickly as we can. Our strategy has always been to lower surface first, then add an immune booster. So, you know, unfortunately, our, I guess it's just the reality of drug development. You have to take it as monotherapy first and see how it performs and then we can get it into combo as quick as we can. So.

顯然，Brian 的目標，101 的目標，是盡快將其與誘導劑結合。我們的策略一直是先降低表面，然後再添加免疫增強劑。所以，你知道，不幸的是，我想這只是藥物開發的現實。您必須先將其作為單一療法，看看它的效果如何，然後我們才能盡快將其納入組合療法。所以。

Great.

偉大的。

Thanks.

謝謝。

Thank you.

謝謝。

One moment for our next question.

請稍等片刻，回答我們的下一個問題。

Our next question comes from Ed Arce from HC Wainwright. Please go ahead.

我們的下一個問題來自 HC Wainwright 的 Ed Arce。請繼續。

Hi, good morning, everyone. This is Thomas asking a couple of questions for Ed. Thank you for taking our questions. So, so first question first to clarify the A S LP lead breaking presentation with the improved to study. So, are we expecting data only from the expansion cohort or can we expect the updated data from the main study as well?

大家好，早安。我是湯瑪斯，想問艾德幾個問題。感謝您回答我們的提問。因此，第一個問題首先要澄清的是 A S LP 領先突破的演示以及需要研究的改進之處。那麼，我們是否只期望從擴展隊列中獲得數據，還是也可以從主要研究中獲得更新的數據？

Hi, Thomas. Yes. So the, the presentation will be focused on group C of the improved two studies. So that was the cohort with the addition of low dose evol ofab. We did present the update on the, the A&D groups back at easel in the June.

你好，托馬斯。是的。因此，本次演講將集中討論改進的兩項研究的 C 組。這就是添加了低劑量 evol ofab 的隊列。我們確實在 6 月在畫架上介紹了 A&D 小組的最新進展。

Got it. Okay. Yeah, that, makes sense and, and then perhaps moving, moving a little bit on the legal side. Just, wonder what, can we expect after declaring construction hearing, following the lawsuit, you know, and, your lawsuit against Pfizer.

知道了。好的。是的，這是有道理的，然後也許在法律方面有所轉變。只是，想知道在宣布施工聽證會之後，在訴訟之後，以及對輝瑞的訴訟之後，我們能期待什麼。

Thomas, I just want to make sure I caught that question correctly. It was the question is what can we expect after the, the claim construction, the Markman hearing for Pfizer. Is that correct?

湯瑪斯，我只是想確保我正確理解了這個問題。問題是，在輝瑞的索賠解釋和馬克曼聽證會之後，我們能期待什麼。對嗎？

Yes. Both, the, you know, what, what kind of, results can we expect from that hearing? And, and also what's, what's the next step in the process?

是的。您知道，我們可以從這次聽證會中期待什麼樣的結果嗎？還有，這個過程的下一步是什麼？

Sure. So as you know, as is always the case, I can say very little about the litigation. So as far as what to expect, we'll, we can, we can, you know, wait until the, until the hearing happens and we'll, we'll learn at the same time, you do sort of what, what we can expect coming out of that. The process as far as, as far as, you know, feedback is concerned is, is sort of similar to what we saw in the past. It's going to take some time after that hearing before we get some kind of report.

當然。所以，正如你所知，和往常一樣，我對訴訟的情況知之甚少。因此，至於預期結果，我們可以等到聽證會舉行，同時，我們也會了解，我們可以期待什麼結果。就回饋而言，這個過程與我們過去看到的有點類似。聽證會結束後我們還需要一段時間才能得到某種報告。

What we are, what we are looking forward to is sort of a court schedule, right? Which after the, after the results of the Markman hearing, get made available, we will also have a court schedule available to us which will give us a little more insight into when we may move forward with the trial and when, you know, when the trial date may come and when all the goodies that happened in between there, could take place. So, you know, stay tuned. We're, not that far away from December 18th now and then it'll be likely a couple of months before we have the, the outcome of that meeting in writing. But, we're, we're anxiously awaiting the results just like you.

我們所期待的是某種法庭日程安排，對嗎？在馬克曼聽證會的結果公佈之後，我們還將獲得一份法庭日程安排，這將使我們更深入地了解何時可以推進審判，何時可以確定審判日期，以及其間發生的所有好事何時可以發生。所以，請繼續關注。現在距離 12 月 18 日已經不遠了，可能還需要幾個月的時間我們才能拿到書面的會議結果。但是，我們和您一樣焦急地等待結果。

Understood. Perhaps one more question from us. This was regarding cash runway about 24 months from now. So, I wonder if that includes any expected receipts from the ATM program?

明白了。也許我們還有一個問題。這是關於從現在起大約 24 個月後的現金流。那麼，我想知道這是否包括來自 ATM 程式的任何預期收入？

I'm I'm sorry, you tailed off the end there.

我很抱歉，你講到這裡就結束了。

Does it include any expected proceeds from the ATM program?

它是否包括 ATM 計劃的預期收益？

Oh, no, no, no. It does not. It assumes no financing. Sorry about that.

噢，不，不，不。但事實並非如此。它不承擔任何融資。很抱歉。

Yeah.

是的。

Okay. Thank you.

好的。謝謝。

Thank you.

謝謝。

Okay, got it. Yeah, so straight talk. So thank you. Bye bye.

好的，明白了。是啊，說話很直白。所以謝謝你。再見。

Thank you.

謝謝。

I'm showing no further questions. I will now turn it back over to management for close remarks.

我沒有其他問題。現在我將把會議交還給管理階層，請他們發表最後的評論。

Thank you everyone for joining us this morning. We remain committed to transforming the HPV treatment landscape and providing hope to millions of patients worldwide. As always, we appreciate your continued support and confidence in our vision. We look forward to providing updates next week at a sld on the clinical development of inducer and operator that concludes our call.

感謝大家今天上午加入我們。我們始終致力於改變 HPV 治療格局，為全球數百萬名患者帶來希望。一如既往，我們感謝您對我們願景的持續支持和信任。我們期待在下週的電話會議上提供有關誘導劑和操作劑臨床開發的最新消息。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

感謝大家參加今天的會議。該計劃確實就此結束。您現在可以斷開連線。