Atea Pharmaceuticals Inc (AVIR) 2023 Q4 法說會逐字稿

Good afternoon, everyone, and welcome to the Taro Pharmaceuticals Fourth Quarter 2023 financial results and business update conference call. At this time, all participants are in a listen only mode following the formal remarks, we will open the call up for your questions.

大家下午好，歡迎參加太郎製藥2023年第四季財務表現及業務更新電話會議。目前，在正式發言後，所有參與者都處於只聽模式，我們將開放您的提問。

I would now like to turn the call over to Jonae Barnes, Senior Vice President of Investor Relations and Corporate Communications at ITI. pharmaceuticals. It's Barnes. Please proceed.

我現在想將電話轉給 ITI 投資者關係和企業傳播高級副總裁 Jonae Barnes。藥品。是巴恩斯。請繼續。

Good afternoon, everyone, and welcome to the Taylor Pharmaceuticals Fourth Quarter and Full Year 2023 financial results and business update conference call. Earlier today, we issued a press release which outlines the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by going to the Investors section of our website at ir dot karyopharm.com.

大家下午好，歡迎參加泰勒製藥 2023 年第四季和全年財務業績和業務更新電話會議。今天早些時候，我們發布了一份新聞稿，概述了我們計劃討論的主題。您可以造訪我們網站 ir dot karyopharm.com 的投資者部分，查看我們今天將要審查的新聞稿以及投影片。

With me today from a payer are our Chief Executive Officer and Founder, Dr. Jean-Pierre Summa Doce sector rental HoReCa, Chief Medical Officer, Chief Development Officer, Dr. Janet Hammond, Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran, and our Chief Commercial Officer, John Beaver, Rita. They will all be available for the Q&A portion of today's call.

今天與我一起付款的有我們的首席執行官兼創始人 Jean-Pierre Summa Doce 博士，租賃部門 HoReCa，首席醫療官、首席開發官 Janet Hammond 博士，首席財務官兼法律執行副總裁 Andrea Corcoran和我們的首席商務官約翰·比弗(John Beaver) 麗塔(Rita)。他們都將參加今天電話會議的問答部分。

Before we begin the call and as outlined on slide 2, I would like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risk and uncertainties are outlined in today's press release and in the Company's recent filings with the Securities and Exchange Commission.

在我們開始電話會議之前，如投影片 2 所示，我想提醒您，今天的討論將包含涉及風險和不確定性的前瞻性陳述。今天的新聞稿以及公司最近向美國證券交易委員會提交的文件中概述了這些風險和不確定性。

Which we encourage you to read. Our actual results may differ materially from what is discussed on today's call.

我們鼓勵您閱讀。我們的實際結果可能與今天電話會議中討論的內容有重大差異。

With that, I'll now turn the call over to Jean-Pierre.

現在，我將把電話轉給讓-皮埃爾。

Thank you, gentlemen. And good afternoon, everyone, and thank you for joining us. I will begin on Slide 3. Looking back at our substantial progress throughout 2023. I'm proud of the strong operational execution we achieve across our antiviral programs to 2023.

謝謝你們，先生們。大家下午好，感謝您加入我們。我將從幻燈片 3 開始。回顧2023年我們所取得的長足進展。我對 2023 年我們的抗病毒專案所實現的強大營運執行力感到自豪。

Highlights from our COVID-19 program include the ability to leverage global surges to meaningfully advance our Phase three SUNRISE three study this was made possible by the expansion of the global footprint and the broadening of the eligibility criteria for high-risk patients so far in 2024, we continue to observe encouraging enrollment trends for Sunrise shred, reflecting the continuing unmet medical need. We were granted fast track designation by the FDA for the evaluation of very positive year for COVID-19. We are continuing to demonstrate the benefits. We remain fully active against all variants tested in vitro, including the noise surveillance related to the O Micra profile for Beni fast Viviant is supported by robust clinical data, including favorable efficacy and safety with no drug-drug interactions. We believe that many falls Vivian has the potential to address the key limitations of current COVID-19 for therapies for HCV the 2023 highlights include achieving regulatory approvals of Assure eight-week treatment for the global Phase two trial of the combination of very fast Bolivia and resume for the treatment of HCV, the rapid enrollment of the leading score, which has led to exciting SVR results that we will review today. We demonstrated in vitro synergy of the combination of Beni Class V on the reservoir and the compelling potency profile against major HCV resistance mutations. We are now evaluating several fixed dose combinations, tablets in preparation for the Phase three program and subsequent commercialization and we've presented and published preclinical and clinical data in support of this program. We believe many positive in combination with resist via can significantly improve upon the current standard of care by offering a differentiated short eight weeks protease inhibitor free treatment, which has been well tolerated and has limited potential for drug-drug interactions.

我們的COVID-19 計畫的亮點包括能夠利用全球激增的情況來有意義地推進我們的第三階段SUNRISE 3 研究，這是透過2024 年迄今為止全球足跡的擴大和高風險患者資格標準的擴大而實現的，我們繼續觀察到 Sunrise shred 的令人鼓舞的入學趨勢，反映出持續未被滿足的醫療需求。我們因對 COVID-19 的積極評估而被 FDA 授予快速通道稱號。我們正在繼續展示其好處。我們對體外測試的所有變體保持全面積極的態度，包括與Beni fast Viviant 的O Micra 譜相關的噪音監測，並得到可靠的臨床數據的支持，包括良好的療效和安全性，且無藥物交互作用。我們相信，Vivian 有潛力解決當前 COVID-19 對 HCV 治療的主要限制，2023 年的亮點包括獲得監管部門批准 Assure 進行為期 8 週的治療，用於非常快速的玻利維亞和HCV 治療恢復，領先分數的快速入組，這帶來了令人興奮的SVR 結果，我們今天將回顧。我們在體外證明了 Beni V 類藥物在儲庫上的組合以及針對主要 HCV 抗藥性突變的引人注目的效力特徵的協同作用。我們現在正在評估幾種固定劑量組合、片劑，為第三階段計劃和隨後的商業化做準備，我們已經提交並發表了臨床前和臨床數據來支持該計劃。我們相信，透過提供差異化的短八週無蛋白酶抑制劑治療，許多陽性藥物與抗藥性途徑結合可以顯著改善當前的護理標準，該治療具有良好的耐受性，並且藥物間相互作用的潛力有限。

Moving to Slide 4. Attaining a vision is focused on the discovery and development of antiviral drugs for the treatment and cure for serious viral diseases where there is a significant unmet medical need and where we can make a huge difference. As you know, we believe that COVID is here to stay and the recent winter surge remind us the new dominant variants like GEN-1 strive. And despite the latest vaccine booster and treatments. South CoV two virus is accumulating mutations with amino acid substitutions faster than any other endemic. Irene runs highlighting the desperate need for broader and more diversified arsenal of safe well-tolerated and easy to prescribe oral antiviral therapeutics. Our team continues to efficiently execute our global Phase three trial, and I'm very pleased to announce today that we have achieved another significant clinical milestone and surpass enrollment of 1,400 patients triggering our second interim analysis in the supportive care monotherapy cohort. This is an important milestone allowing for the data review by the independent DSMB for safety and futility for Sunrise Ray, we anticipate several upcoming events, including the first interim analysis in March, the second interim analysis in the second quarter of 2024 and top line results during the second half of 2024.

轉到投影片 4。實現願景的重點是發現和開發抗病毒藥物，用於治療和治癒嚴重的病毒性疾病，這些疾病的醫療需求尚未得到滿足，而我們可以做出巨大的改變。如你所知，我們相信新冠病毒將持續存在，最近的冬季激增提醒我們像 GEN-1 這樣的新的主導變種正在努力。儘管有最新的疫苗加強劑和治療方法。南冠狀病毒二號病毒累積胺基酸替換突變的速度比其他地方性病毒都要快。艾琳強調迫切需要更廣泛、更多樣化的安全、耐受性良好且易於處方的口服抗病毒療法。我們的團隊繼續有效率地執行我們的全球三期試驗，我今天非常高興地宣布，我們已經實現了另一個重要的臨床里程碑，並超過了1,400 名患者的入組，觸發了我們在支持性護理單一療法隊列中的第二次中期分析。這是一個重要的里程碑，允許獨立DSMB 對Sunrise Ray 的安全性和無效性進行資料審查，我們預計即將發生的幾項事件，包括3 月的第一次中期分析、2024 年第二季的第二次中期分析以及頂線結果2024 年下半年。

Benny first, maybe as a potential to address many of the key limitations of current COVID-19 therapies, including safety tolerability and drug-drug interactions. Our goal is to deliver best-in-class treatment to the millions of patients for whom the current standard of care is suboptimal for insurable as part of a multi-prong approach against COVID-19. We continue to also make progress with our discovery program focused on a highly differentiated second-generation protease inhibitor, and we expect to provide an update midyear for our Phase two HCV program. As stated earlier, we share new results with confirm a 98% SVR4 post treatment in the leading cohort of our Phase two combination eight weeks that Randy will review these results in more details. Our goal for this program is to substantially enhance the current set of care by offering a short eight week for the ACE inhibitor, free treatment that is well tolerated with low potential risk for drug-drug interaction for all HCV patients. Importantly, we are in a strong financial position to execute our strategy with $578.1 million of cash and cash equivalents as of December 31, with a runway anticipation of 2026. And Ray will provide a detailed update on the financial position during today's call. I will now I'll turn the call over to Lorenzo for an update on our HCV program.

Benny 首先，可能是解決當前 COVID-19 療法的許多關鍵限制的潛力，包括安全耐受性和藥物交互作用。我們的目標是作為 COVID-19 的多管齊下方法的一部分，為數百萬目前的護理標準對於可保而言次優的患者提供一流的治療。我們的發現計劃也繼續取得進展，重點是高度差異化的第二代蛋白酶抑制劑，我們預計在年中為我們的第二階段 HCV 計劃提供更新。如前所述，我們分享了新的結果，並確認我們的第二期聯合治療領先隊列治療後 8 週的 SVR4 率為 98%，Randy 將更詳細地審查這些結果。我們該計劃的目標是透過為所有 HCV 患者提供為期 8 週的 ACE 抑制劑免費治療，該治療具有良好的耐受性，藥物間相互作用的潛在風險較低，從而大幅增強當前的護理水平。重要的是，截至 12 月 31 日，我們的財務狀況良好，能夠執行我們的策略，擁有 5.781 億美元的現金和現金等價物，預計到 2026 年。雷將在今天的電話會議上提供有關財務狀況的詳細最新資訊。現在我將把電話轉給 Lorenzo，以了解我們 HCV 計畫的最新情況。

Thank you, Cynthia.

謝謝你，辛西亞。

Turning to slide 6, despite current treatment options. Hcv continues to be a health crisis in the U.S. As Jean-Pierre noted earlier, there are approximately 2.4 million people infected with HCV in the US despite availability of oral treatments. Recent trends indicate they are more new infections and reinfection than peers on a yearly basis. And this statistics highlight the need to improve the HCV treatment landscape of the company, Benny plus from your angle, severe has the potential to substantially improve upon the current standard of care by offering a short eight-week protease inhibitor free treatment with less side effects and a low risk for drug-drug interactions based on our market research with KOLs and high prescribers, these attributes are very critical for a new treatment, as you will see on the next slide.

轉向幻燈片 6，儘管有當前的治療方案。Hcv 在美國仍然是一場健康危機。正如 Jean-Pierre 早些時候指出的，儘管有口服治療，但美國仍有約 240 萬人感染 HCV。最近的趨勢表明，他們每年的新感染和再感染人數都高於同行。這項統計數據強調了改善公司HCV 治療前景的必要性，Benny plus 從您的角度來看，透過提供為期八週且副作用更少的短期無蛋白酶抑制劑治療，重症​​患者有可能大幅改善當前的護理標準根據我們與 KOL 和高處方醫生的市場研究，藥物交互作用的風險較低，這些屬性對於新治療非常重要，正如您將在下一張幻燈片中看到的那樣。

Moving to Slide 7. While the introduction of direct acting antivirals has transformed HCV treatment, significant unmet need still exist in recent quantitative market research conducted by a payer with over 150 used physicians, call it high prescribers of it close on all matters. Only 6% of this physicians reported that they have no unmet needs.

轉到投影片 7。雖然直接作用抗病毒藥物的引入已經改變了HCV 治療，但最近由一家擁有超過150 名使用過的醫生的付款人（稱其為高處方者）進行的定量市場研究表明，仍然存在大量未滿足的需求。只有 6% 的醫生表示他們沒有未滿足的需求。

Regarding HCV treatment key unmet needs. Emerging in this research was shorter length of treatment and higher efficacy, particularly in HIV co-infected patients as well as fewer contraindications As detailed on the right hand of the slide, please note that currently approximately 17% of patients do not complete their treatment regimen mean convenient and shorter treatment durations of particular importance to prescribers.

關於丙肝治療的關鍵未滿足需求。這項研究的特點是治療時間更短、療效更高，特別是在HIV 合併感染患者中，而且禁忌症也更少。如幻燈片右側詳述，請注意，目前大約17% 的患者沒有完成治療方案意味著方便和更短的治療持續時間對處方者尤其重要。

Slide 8 outlines our Phase two open label study of 550 milligrams of the first full year in combination with 180 milligrams of Roche's via once daily for eight weeks, we plan to well up to So 180 DA. nice patients across all genotypes in the initial cohort, sustained biological response or SVR at week four was used as the decision criteria to reinitiate enrollment to complete the Phase two study. The primary endpoint of this study is SVR at week 12, and this will be reported for all patient at study completion.

幻燈片 8 概述了我們的第二階段開放標籤研究，第一年服用 550 毫克，結合 180 毫克羅氏藥物，每天一次，持續八週，我們計劃達到 180 DA。初始隊列中所有基因型的好患者、第四週的持續生物反應或 SVR 被用作重新啟動入組以完成第二階段研究的決策標準。本研究的主要終點是第 12 週時的 SVR，並將在研究完成時報告所有患者的情況。

Slide 9 highlights the patient demographics and baseline characteristics in the lead-in cohort of the Phase two open-label study of any fiscal year in rosacea, patients would be nice with a median age of 47 years old. This cohort was comprised of non-cirrhotic patients only. However, please note that 10 patients had fibrosis stage three or more advanced liver disease stage, which is borderline with cirrhosis. In the second part of the Phase two study conference, periodic patients will also be enrolled.

幻燈片 9 強調了任何財政年度紅斑痤瘡第二階段開放標籤研究的導入隊列中的患者人口統計和基線特徵，患者的中位年齡為 47 歲。此隊列僅由非肝硬化患者組成。然而，請注意，有 10 名患者患有纖維化第三期或以上的晚期肝病階段，接近肝硬化。在二期研究會議的第二部分，週期性患者也將被納入。

Moving to Slide 10. We are excited to share with you today that the final results from the Phase two combination study in the lead-in cohort confirm and SVR, four of 98% treatment across all genotypes in January we reinitiated enrollment to complete this study in up to 280 patients with top-line results anticipated in the second half of 2024 and then shows the on-treatment viral kinetics of individual patient data by week four. All 60 patients in this cohort had viral load near or below the lower limit of quantification. Therefore, this very rapid kinetics across all genotypes supports an eight week regimen and compare favorably. It is the only approved eight week treatment for HCV.

轉到投影片 10。今天我們很高興與您分享，導入隊列中的二期聯合研究的最終結果證實了SVR，1 月份所有基因型的98% 治療中的4 項我們重新開始入組，以在多達280 名患者中完成這項研究預計在 2024 年下半年獲得頂線結果，然後在第四週顯示個別患者數據的治療中病毒動力學。該隊列中所有 60 名患者的病毒量均接近或低於定量下限。因此，所有基因型的這種非常快速的動力學支持八週的治療方案並且比較有利。這是唯一被批准的治療丙肝病毒的八週治療方法。

On slide 12, the combination of any force of year-end versus via was generally safe and well tolerated in this cohort of 60 patients. There were no drug-related serious adverse events. No discontinuations and adverse events were mostly mild.

在幻燈片 12 上，年終與 VIA 的任何力量的組合在 60 名患者的隊列中通常是安全的且耐受性良好。沒有發生與藥物相關的嚴重不良事件。沒有停藥，不良事件大多是輕微的。

Turning to Slide 13 to summarize our progress in HCV. Based on the positive lead-in cohort data, we reinitiated enrollment in January for the remainder of the Phase two trial to help advance enrollment and achieve representative genotype distribution. We are increasing this study's footprint to approximately 50 clinical sites in 15 countries. In addition, over the first half of 2024, we are conducting Phase one studies in the U.S. for the selection of them fixed-dose combination tablet, which will be evaluated in the Phase three program and used for subsequent commercialization. We anticipate that the Phase three program will be initiated around the end of this year.

轉向投影片 13 總結我們在 HCV 的進展。基於積極的導入隊列數據，我們於 1 月重新啟動了第二階段試驗剩餘部分的入組，以幫助推進入組並實現代表性基因型分佈。我們正在將這項研究的覆蓋範圍擴大到 15 個國家的約 50 個臨床中心。此外，2024年上半年，我們正在美國進行第一期研究，選擇固定劑量組合片劑，將在三期計畫中進行評估，並用於後續商業化。我們預計第三階段計畫將於今年底啟動。

Slide 14. Next, we will provide an update on our COVID-19 program. I'll turn the call over to Dennis to discuss our St. rice three Phase three trial.

幻燈片 14。接下來，我們將提供有關 COVID-19 計劃的最新資訊。我會將電話轉給丹尼斯，討論我們的聖米三期三期試驗。

Thanks, Art, and good afternoon, everyone. Covid-19 continues to be an established pathogen of concern and according to the World Health Organization, and we believe that COVID-19 will remain an ongoing serious pandemic issue. Alcoa for COVID-19 is to deliver safe and effective treatment for millions of patients for whom the current standard of care is not a surgical option. We believe that the compelling preclinical and clinical profile of any Hospira is differentiated with a low risk for drug-drug interactions, favorable tolerability and a high barrier to resistance and has the potential to become the treatment of choice for COVID-19 for millions of patients.

謝謝阿特，大家下午好。據世界衛生組織稱，Covid-19 仍然是一種已確定的令人關注的病原體，我們相信 COVID-19 仍將是一個持續存在的嚴重流行病問題。美鋁針對 COVID-19 的目標是為數百萬目前標準護理無法進行手術的患者提供安全有效的治療。我們相信，任何 Hospira 的引人注目的臨床前和臨床特徵都具有藥物交互作用風險低、耐受性良好和抗藥性屏障高的特點，有潛力成為數百萬患者的 COVID-19 治療選擇。

Moving to slide 16, supported by our extensive global footprint, we are seeing robust enrollment into SUNRISE three and patient enrollment has current with the latest winter wave. In particular, we've experienced strong enrollment in the US for sites being responsible for approximately 75% of the patients enrolled to date. The majority of patients globally continues to be enrolled in the monotherapy cohort despite the availability of other oral antivirals, which I'd like to share with you today.

前往投影片 16，在我們廣泛的全球足跡的支持下，我們看到 SUNRISE 3 的註冊人數強勁，並且患者註冊人數與最新的冬季浪潮保持同步。特別是，我們在美國的註冊中心經歷了強勁的註冊，迄今為止，這些網站負責約 75% 的註冊患者。儘管有其他口服抗病毒藥物可供使用，但我今天想與大家分享，但全球大多數患者仍繼續接受單一療法隊列。

The Sunrise three surpassed enrollment to 1,400 patients in the monotherapy cohort, triggering the second interim analysis. The DSMB is expected to meet in March for the first interim analysis and we expect the second interim analysis to occur during the second quarter. Just to remind you, the DSMB reviews are primarily geared towards safety and futility. Therefore, this winter, as predicted by the USCDC. respiratory diseases are showing similar high trends to last year. Patients. Most vulnerable to severe COVID infection remain the elderly immunocompromised and those with underlying risk factors for severe infection by oral therapeutics are of critical importance to protect against hospitalization and complications.

Sunrise 3 單一療法組的入組患者人數超過 1,400 名，引發了第二次中期分析。DSMB 預計將在 3 月舉行第一次中期分析會議，我們預計第二次中期分析將在第二季進行。只是提醒您，DSMB 審查主要針對安全性和無用性。因此，今年冬天，正如美國疾病預防控制中心所預測的那樣。呼吸道疾病的發生率與去年相似。患者。最容易受到嚴重新冠病毒感染的仍然是免疫功能低下的老年人，而那些具有潛在嚴重感染危險因素的人，透過口服治療對於預防住院和併發症至關重要。

Turning to Slide 17. I'll now go into detail on our Sunrise three global Phase three trial, discuss our inclusion criteria focused on high risk of patients with mild or moderate COVID-19 regardless of vaccination status. Interim onset is five or less days before randomization. The Phase three study is randomized, double-blind and placebo-controlled study drug either any faster than 550 milligrams BID or placebo. Is it administered concurrently with the locally available standard of care there are two study populations depending on the type of standard of care received. The supportive care monotherapy cohort comprises the primary analysis population. While the combination cohort is part of the secondary analysis and includes patients treated with local standard of care, including other compatible COVID-19 antiviral drugs. The primary endpoint of the study is all cause hospitalization or death through day 29 in the supportive care monotherapy population, which will be approximately 2,200 patients. Secondary endpoints are COVID-19 related hospitalizations and death, medically attended visits and symptom RE/MAX now scare we were granted fast track designation for Benny foster there, reflecting the recognized unmet medical need that remains for COVID-19 patients. Overall, we're seeing strong operational execution for Sunrise three from our clinical team for sure best enrollment trends.

轉向投影片 17。我現在將詳細介紹我們的 Sunrise 3 全球第三階段試驗，討論我們的納入標準，重點關注患有輕度或中度 COVID-19 的高風險患者，無論疫苗接種狀況如何。中期發作是隨機分組前五天或更短的時間。第三階段研究是隨機、雙盲和安慰劑對照研究藥物，劑量快於 550 毫克 BID 或安慰劑。它是否與當地可用的護理標準同時進行，根據所接受的護理標準的類型，有兩個研究人群。支持性護理單一療法隊列包括主要分析族群。聯合隊列是二次分析的一部分，包括接受當地標準護理（包括其他相容的 COVID-19 抗病毒藥物）治療的患者。研究的主要終點是支持性護理單一療法族群中截至第 29 天的所有原因住院或死亡，該族群約為 2,200 名患者。次要終點是與COVID-19 相關的住院和死亡、就診和症狀RE/MAX 現在擔心我們被授予Benny 福斯特的快速通道指定，這反映了COVID-19 患者仍然存在公認的未滿足的醫療需求。總體而言，我們看到我們的臨床團隊對 Sunrise 3 的強大營運執行力，確保了最佳的入組趨勢。

I'm now going to hand the call over to John to discuss the marketing marketing opportunity for Benny Foster.

我現在將把電話轉給約翰，討論班尼福斯特的行銷機會。

John?

約翰？

Thank you, Jan. Turning to slide 19, we know that the U.S. prescription demand for oral antivirals to treat COVID correlates with the infection rates. The demand for oral antivirals in 2023 was very robust with a total of approximately 7.7 million scripts written last month scripts were approximately 920,000, which reflects the latest winter surge on the next slide, slide 20 late last year, the market for COVID-19 oral antivirals began transitioning to traditional payer markets such as Medicare, Medicaid and private commercial insurance. Oral antiviral therapeutics for COVID-19 are expected to remain a multi-billion dollar opportunity for years to come. Projected annual COVID-19 oral antiviral US demand using IQ, the retail prescriptions suggest an estimated annual global market opportunity of over $4 billion to $5 billion with only two products that each have key limitations. We believe there is still an unmet need with critical gaps, and there is the opportunity to expand this market to patients due to drug-drug interactions and tolerability with Paxil, COVID and safety issues with the Gabriel, I'll now turn the call over to Andrea to discuss the details of financials.

謝謝 Jan。轉向幻燈片 19，我們知道美國治療新冠肺炎的口服抗病毒藥物的處方需求與感染率相關。2023 年口服抗病毒藥物的需求非常強勁，總計約770 萬個腳本，上個月編寫的腳本約為92 萬個，這反映了下一張幻燈片（幻燈片20 去年年底）的最新冬季激增， COVID-19 口服藥物市場抗病毒藥物開始轉向傳統的支付市場，如醫療保險、醫療補助和私人商業保險。COVID-19 的口服抗病毒療法預計在未來幾年仍將是一個價值數十億美元的機會。使用 IQ 預測美國每年的 COVID-19 口服抗病毒藥物需求，零售處方表明，全球每年的市場機會估計超過 40 億至 50 億美元，而其中只有兩種產品，每種產品都有關鍵限制。我們相信，仍然存在未滿足的需求，存在重大差距，並且由於藥物之間的相互作用和 Paxil 的耐受性、COVID 以及 Gabriel 的安全問題，有機會將這個市場擴展到患者，我現在將轉交電話與安德里亞討論財務細節。

Thank you, Dan. As Rene mentioned earlier this afternoon, we issued a press release containing our financial results for the fourth quarter and full year 2023 statement of operations and balance sheet are on slides 22 and 23. There was an increase in R&D expense for the fourth quarter and full year 2023 versus the corresponding periods in 2022 be the primary driver for the higher since with the external expend related to our COVID-19 Phase three SUNRISE three clinical trials in our Phase two clinical trial of the combination of any fast bear interest there for the treatment of hepatitis C, general and administrative expenses remained relatively flat for the fourth quarter and full year versus the corresponding periods in 2022. Interest income increased for the fourth quarter and full year 2023 versus the corresponding periods in 2022. This was the result of investing in higher yield marketable securities and higher interest rates. At the end of the fourth quarter of 2023, our cash cash equivalent and marketable securities balance, as Jean-Pierre mentioned, was $578.1 million. Based on our current plans, we are reiterating our cash guidance with a runway through 2026.

謝謝你，丹。正如 Rene 今天下午早些時候提到的，我們發布了一份新聞稿，其中包含第四季度的財務業績以及 2023 年全年的營運報表和資產負債表，請參閱投影片 22 和 23。與2022 年同期相比，2023 年第四季和全年的研發費用有所增加，這是研發費用增加的主要驅動因素，因為與我們的COVID-19 第三期SUNRISE 第三期臨床試驗相關的外部支出在我們的第二期臨床中由於嘗試將任何快速熊息組合用於治療丙型肝炎，第四季度和全年的一般和管理費用與 2022 年同期相比保持相對平穩。2023 年第四季和全年的利息收入較 2022 年同期增加。這是投資於更高收益的有價證券和更高利率的結果。正如讓-皮埃爾所提到的，截至 2023 年第四季末，我們的現金等價物和有價證券餘額為 5.781 億美元。根據我們目前的計劃，我們重申了 2026 年的現金指引。

I'll now turn the call back over to Jean-Pierre for closing remarks.

現在我將把電話轉回給讓-皮埃爾做總結發言。

Thank you, Andrea and closing. Following up a year of solid operational execution across our two clinical programs, our clinical momentum, server software, a transformational milestone, which 2024 for both our COVID-19 and HCV program for COVID-19, we anticipate meaningful clinical milestones beginning in the first quarter of 2024 was the first interim analysis from our global Phase three trial, followed by a second interim analysis in the second quarter of 2024. Top-line results are expected in the second half of 2024. For HCV, we anticipate completing enrollment of our Phase two study and reporting results during the second half of 2024. We are continuing to target initiation of a Phase three around the end of the year, and we are extremely encouraged by the SVR4 and safety result in the lead-in cohort. We are targeting multibillion-dollar markets, each of which are currently comprised of only two primary products. We believe that our product candidates are very differentiated and have the opportunity if approved, to fill the gap in the current unmet medical needs and become blockbuster product. We are very excited about the opportunities ahead and are confident in our ability to double up and commercialize innovative products and create meaningful shareholder value. In particular, I'm very proud of the team how they work throughout the year. I care is a company with less than 80 employees, which is conducting two global studies in disease with dollar market opportunities with a high degree of efficiency as well as significant financial discipline.

謝謝你，安德里亞，結束了。經過一年的紮實營運執行，我們的兩個臨床計畫、我們的臨床動能、伺服器軟體、一個轉型里程碑，到2024 年，我們的COVID-19 和HCV 計畫將在第一個階段開始實現有意義的臨床里程碑2024 年第四季是我們全球第三階段試驗的第一次中期分析，隨後在 2024 年第二季進行了第二次中期分析。預計 2024 年下半年將公佈頂線結果。對於 HCV，我們預計在 2024 年下半年完成第二階段研究的招募並報告結果。我們的目標是在今年年底左右啟動第三階段，我們對 SVR4 和先導隊列的安全結果感到非常鼓舞。我們的目標是數十億美元的市場，每個市場目前僅由兩種主要產品組成。我們相信，我們的候選產品非常差異化，如果獲得批准，將有機會填補當前未滿足的醫療需求的空白，並成為重磅產品。我們對未來的機會感到非常興奮，並對我們將創新產品加倍和商業化以及創造有意義的股東價值的能力充滿信心。特別是，我對團隊全年的工作方式感到非常自豪。I Care 是一家員工不到 80 名的公司，正在以高效率和嚴格的財務紀律開展兩項針對疾病和美元市場機會的全球研究。

With that, I will turn the call back over to the operator.

這樣，我會將電話轉回給接線生。

Certainly as a reminder, to ask a question, please press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star one once again and One moment for our first question. And our first question will come from Eric Joseph of JPMorgan. Your line is open.

當然，提醒一下，要提問，請按電話上的星號一，然後等待宣布您的名字。若要撤回您的問題，請再次按星號 1 並稍等一下我們的第一個問題。我們的第一個問題將來自摩根大通的埃里克約瑟夫。您的線路已開通。

No, thank you and thanks for taking the questions. A couple from us on just on the sizable accrual in patients for Sunrise three, do you have visibility in terms of them? I guess how those are apportioned across the different study arms, monotherapy versus combo gets? What visibility do you have in terms of a percent to enrollment completion of the monotherapy primary analysis population.

不，謝謝您並感謝您提出問題。我們中的一對夫婦剛剛談到了《日出三號》中患者的可觀增長，您對它們有了解嗎？我想這些是如何在不同的研究組中分配的，單一療法與組合療法？在單一療法主要分析人群的註冊完成百分比方面，您的可見性如何。

And on the HCV side, just picking up on a comment you made JP. about potentially being a non protease based inhibitor option. What's the significance of that? Is there sort of a safety advantage that you'd highlight? Or is it more about just being an alternative mechanism compared to the other commercially available week regimen. Thanks.

在 HCV 方面，剛剛注意到您發表的 JP 評論。關於潛在的非蛋白酶抑制劑選項。這有什麼意義呢？您有什麼值得強調的安全優勢嗎？或者與其他市售的周方案相比，它更多的是作為一種替代機制。謝謝。

Thank you. And we've been very, very fruitful for you and the important thing to differentiate your, but let's start with the recovery 19 questions of.

謝謝。我們為您帶來了非常非常有成效的成果，並且讓您脫穎而出的重要事情，但讓我們從恢復 19 個問題開始。

Great question. Janet, you want to give a little bit, but some granularity on two areas.

很好的問題。珍妮特，你想在兩個領域提供一些詳細的資訊。

So thank you for the question. And in regard to how the patients are apportioned to the combination versus monotherapy. I mean, obviously, first of all, just to say that and this is at the discretion of the investigators and prescribers, it sees the patient and they're encouraged to prescribe combination therapy if they believe that is appropriate for the patient and actually educators and quite extensively AHA investigational agents in that regard and important, I think is quite surprising is that the vast majority of patients are actually being assigned to the monotherapy arm. And I think the reasons for this probably are and really the potential extent of potential for drug interactions associated with return of that and in particular with combination treatment, which I think deter people from prescribing combination therapy to patients.

謝謝你的提問。以及如何將患者分配到聯合療法與單一療法。我的意思是，顯然，首先，只是說，這是由研究人員和處方者自行決定的，它會看到患者，如果他們認為這適合患者和實際上的教育者，則鼓勵他們開出聯合療法。在這方面，美國心臟協會（AHA）研究藥物相當廣泛，而且重要的是，我認為相當令人驚訝的是，絕大多數患者實際上被分配到單一療法組。我認為造成這種情況的原因可能是，而且實際上是與藥物交互作用的回歸相關的潛在程度，特別是與聯合治療相關的潛在程度，我認為這阻止了人們向患者開出聯合治療的處方。

And then in regards to your question around when we if we have any visibility as to when we might complete accrual in the monotherapy arm?

然後，關於你的問題，我們是否知道我們何時可以完成單一療法臂的應計？

No, we don't. But I can say that enrollment is proceeding well. But of course, we're very dependent on the fluctuations in COVID cases as they occur. We've seen a very strong winter season pass and frequency, I think at least in the past, we've observed that falling back and some downward trend in the number of cases until we get towards the hotter summer months when people move indoors again. And so we're somewhat dependent on that you're going to have to see, Thank you.

不，我們不。但我可以說招生進展順利。但當然，我們非常依賴新冠病例發生時的波動。我們已經看到了非常強勁的冬季經過和頻率，我認為至少在過去，我們觀察到病例數有所回落和下降趨勢，直到我們進入更炎熱的夏季，人們再次搬到室內。因此，我們在某種程度上依賴您必須看到的內容，謝謝。

So related to the HCV questions are, I think with the Solvay from a third party, I really exemplify the importance of a lack of protease inhibitor in the combination treatment, especially when we are talking about about 40% of HIV infected patients with HCV or you're going to have substantial drug-drug interaction if we are if you have a protease inhibitor. So it is an important differentiation.

與 HCV 問題相關的是，我認為透過第三方的 Solvay，我確實證明了聯合治療中缺乏蛋白酶抑制劑的重要性，特別是當我們談論大約 40% 的 HIV 感染患者患有 HCV 或如果你有蛋白酶抑制劑，你就會發生大量的藥物交互作用。所以這是一個重要的區別。

John, you want to maybe also expand on that. And really, this is not just a gimmick here that we are talking, but really importance from a commercial standpoint and then I will ask around. So from a patient standpoint, John, you want to address that from a commercial standpoint.

約翰，你也許還想對此進行擴充。事實上，這不僅僅是我們在這裡談論的噱頭，而且從商業角度來看確實很重要，然後我會四處詢問。因此，從病人的角度來看，約翰，你想從商業的角度來解決這個問題。

Sure. So Eric, from a commercial standpoint, obviously being pretty three is really important to us for the logo drug in R & DDI. interaction, potential Kong and also it. There's also other advantages such as having a new food effect and also to be able to treat with a shorter treatment duration, particularly important because as Roger mentioned earlier, in the presentation on what conditions are finding is that the shorter time to treat it better. And to highlight this about, you know, maybe we have a obviously a protease inhibitor and when you look at the new Rx market shares, even despite being eight weeks versus 12, and there is a third, there's almost a little bit more than a 10 point share difference in favor of a closer. And so that should you maybe also tell us some things as well.

當然。因此，從商業角度來看，埃里克（Eric）顯然對於我們 R & DDI 的標誌藥物來說，長得漂亮三歲確實很重要。互動，勢崗也。還有其他優點，例如具有新的食物效應，並且能夠以更短的治療持續時間進行治療，這尤其重要，因為正如羅傑之前提到的，在介紹所發現的病症時，治療時間越短越好。為了強調這一點，你知道，也許我們有一個明顯的蛋白酶抑制劑，當你看看新的 Rx 市場份額時，即使是 8 週與 12 週相比，還有第三種，幾乎比10分的分差有利於更接近。因此，您也許也應該告訴我們一些事情。

I'll wrap. So from a Patriot endpoint, after your gas production was down a lot in prescriber growth.

我來包一下因此，從愛國者端點來看，在您的天然氣產量隨著處方者的增長而大幅下降之後。

Yes.

是的。

So from a medical perspective, I think what we're trying to develop here is really a best-in-class regimen that combines the best of Epclusa and the best of my ability in the sense that it's an eight week regimen and we felt the drug-drug interactions. I actually quite calm on that Maverick and protease inhibitors, a class and these are common drugs we're talking about like contraceptives and the retroviral therapies that beans proton pump inhibitors, which you know, almost everybody over four based on something like that. And so this is this is very important for the patient as the market which research has indicated. But also when we talk to the KOLs on the field than when they were actually trying to reveal our protocol and participate in our clinical trials. All of them were very excited that we could actually develop these best-in-class regimen bringing and the best of both attributes both regimens.

因此，從醫學角度來看，我認為我們在這裡嘗試開發的實際上是一種一流的治療方案，它結合了Epclusa 的優點和我的最佳能力，因為這是一個八週的治療方案，我們感覺藥物與藥物的相互作用。事實上，我對Maverick 和蛋白酶抑制劑這一類藥物非常平靜，這些是我們談論的常見藥物，例如避孕藥和質子幫浦抑制劑的逆轉錄病毒療法，你知道，幾乎所有四歲以上的人都基於類似的藥物。因此，正如研究表明的那樣，這對患者來說非常重要。而且當我們與現場的 KOL 交談時，他們實際上試圖透露我們的方案並參與我們的臨床試驗。他們所有人都非常興奮，因為我們實際上可以開發出這些一流的治療方案，並兼具兩種治療方案的最佳屬性。

Thank you, Lorenzo.

謝謝你，洛倫佐。

One moment for our next question. And our next question will be coming from Maxwell score of Morgan Stanley. Your line is open, Maxwell.

請稍等一下我們的下一個問題。我們的下一個問題將來自摩根士丹利的麥克斯韋評分。你的線路已接通，麥克斯韋。

Great.

偉大的。

Thank you for taking my questions. And given your strong financial position, I was hoping you can elaborate a bit on your capital allocation strategy and how you're preparing for a potential launch in COVID while advancing your global HCV program? Basically, how should we think about spend over the next several quarters? Thank you.

感謝您回答我的問題。鑑於您強大的財務狀況，我希望您能詳細說明您的資本配置策略，以及您在推進全球 HCV 計劃的同時如何準備在新冠病毒中可能推出的產品？基本上，我們應該如何考慮未來幾季的支出？謝謝。

Andre, you want to address that question? Maybe just start I would like to to to indicate that our for the loans we have actually a supply on your far. We are fortunate to have to get an approval in the US but we will not see a substantial investment in manufacturing at risk prior to approval. So we will provide additional information as we get closer to lunch.

安德烈，你想回答這個問題嗎？也許只是開始，我想表明我們的貸款實際上已經向您提供了。我們很幸運能夠在美國獲得批准，但在批准之前我們不會看到對製造業的大量投資面臨風險。因此，當接近午餐時，我們將提供更多資訊。

So with that parenthesis, Andrea, yes.

因此，安德里亞，加上括號，是的。

Thank you, Jean-Pierre, and thanks, Max, for the question. So I think as you've seen or will see when you have the chance to review the financial statements, we continue to exercise really on discipline in our investments for both the COVID-19 program as well as C. and C. program expenses are increasing, but in a very measured way quarter-over-quarter for 2023, we would expect the same type of limited increase in 2024. The Phase three program for COVID will begin to wind down before the Phase three begins for Hep-C and But nonetheless, we will be preparing for commercialization. As you've said, there will be additional activities that we will be funding at that point.

謝謝讓-皮埃爾，也謝謝馬克斯提出的問題。因此，我認為，正如您在有機會審查財務報表時所看到或將會看到的那樣，我們將繼續嚴格遵守 COVID-19 計劃以及 C. 和 C. 計劃支出的投資紀律。增長，但2023年季度環比成長非常謹慎，我們預計2024 年也會出現同樣類型的有限成長。COVID 的第三階段計劃將在 Hep-C 的第三階段開始之前開始結束，但儘管如此，我們仍將為商業化做準備。正如您所說，屆時我們將資助更多活動。

So the expenses for '24 and '25 are expected to increase, but and in a very measured way.

因此，24 年和 25 年的費用預計會增加，但會以非常謹慎的方式增加。

Great.

偉大的。

Thank you.

謝謝。

And one moment for our next question. And our next question will be coming from Jon Miller of Evercore ISI. Your line is open, John.

請稍等一下我們的下一個問題。我們的下一個問題將來自 Evercore ISI 的 Jon Miller。你的線路已接通，約翰。

Hi, this is Jessica on for John Miller. Thanks for taking our questions. I have two questions, if I may. One on COVID one on hep C front, so for COVID. So you said Sunrise top3 line data expected in second half of the year. So how should we think about the various scenarios that can occur, how like how well does the market appreciate that pre-existing immunity from infection and or vaccine vaccination can affect placebo rates possibly making the effect size smaller, it may be a direct comp to exploit the trial data may be limited? And then also worst-case scenario, how should we think about the company direction in the bear case scenario that the primary endpoint is not met.

大家好，我是約翰米勒的潔西卡。感謝您回答我們的問題。如果可以的話，我有兩個問題。一篇關於新冠病毒，一篇關於丙型肝炎，所以對於新冠病毒。所以你說的Sunrise top3線數據預計在下半年。因此，我們應該如何考慮可能發生的各種情況，市場對預先存在的感染免疫力和/或疫苗接種可能會影響安慰劑率的認識程度如何，可能會使效應規模更小，這可能是一個直接的補償漏洞利用試驗數據可能有限？然後也是最壞的情況，在主要終點未達到的熊市情況下，我們應該如何考慮公司的方向。

And then a follow-up question. Thank you.

然後是後續問題。謝謝。

Jeff, if you'd like to address the question, please?

傑夫，你願意回答這個問題嗎？

Thank you, Jessica. And yes, I think and I think everybody realizes that and with vaccination and prior exposure to COVID-19. And this diversity will frequency unless that fortunately right was how we were going through in particular, I think the Delta wave and hospitalizations are an all-time high for us that is designed to show a delta in efficacy comparable. So I think and what Pfizer most recently reported in their outpatient study where there was about a 50% or in the 50s, a difference between the active and the placebo groups into that. That's what we're expecting to see. I think particularly when you're talking about high-risk patients and hospitalizations, that is still an important and meaningful difference and of course, hospitalization and death of the worst outcomes. And so if one can prevent boost and reduce the severity of disease. I think that's going to be really important.

謝謝你，潔西卡。是的，我認為每個人都意識到這一點，並且透過疫苗接種和之前接觸過 COVID-19。這種多樣性將會頻繁出現，除非幸運的是，我們正在經歷特別的情況，我認為德爾塔波和住院治療對我們來說是歷史最高水平，旨在顯示可比的療效德爾塔。所以我認為輝瑞最近在門診研究中報告的情況是，活性藥物組和安慰劑組之間存在大約 50% 或 50 多歲的差異。這就是我們期待看到的。我認為特別是當你談論高風險患者和住院治療時，這仍然是一個重要且有意義的差異，當然，住院和死亡是最糟糕的結果。因此，如果能夠預防疾病的惡化並減輕疾病的嚴重程度。我認為這非常重要。

I'd just like to add anything on. Oh, go ahead, Jim. Sorry.

我只是想補充點什麼。哦，繼續吧，吉姆。對不起。

Yes, it's just going to ask you if you wanted to follow on with Jessica's other question, Randy scenario clearly fails to achieve the primary endpoint.

是的，它只是問您是否想繼續回答傑西卡的另一個問題，蘭迪場景顯然無法達到主要終點。

Yes, correct.

是，對的。

Okay.

好的。

So I think I mean, certainly I mean, it's one of the things that is that is under consideration is, you know if we're unable to do that and other sort of avenues to pursue in terms of looking for trends and we have a fast track designation with FDA to assess how how to proceed. And we also have, as I think, has been mentioned, two interim analyses and gravity S and B will help us to make the decision not to proceed, should we and see that data and no number of patients in what we are projecting would allow us to be successful so I think those are the scenarios that we're certainly aware of and thinking about and that at the moment and things are moving forward well. And and we look forward to presenting results unless you need to update as we move forward.

所以我想我的意思是，當然我的意思是，正在考慮的事情之一是，你知道我們是否無法做到這一點以及在尋找趨勢方面追求其他途徑，我們有一個FDA 的快速通道指定以評估如何進行。正如我所認為的，我們也已經提到過，兩項中期分析和重力 S 和 B 將幫助我們做出不繼續進行的決定，如果我們看到數據和我們預測的患者數量不允許的話我們要取得成功，所以我認為這些是我們當然意識到和思考的場景，而且目前事情進展順利。我們期待著公佈結果，除非您需要在我們前進的過程中進行更新。

Thank you, John. And just what I wanted to add to the first question is I think he was very telling that the NIH actually recently reported that only 15% of high risk actually had taken impacts love it and actually saw 85% of aiWARE school should get an old therapeutic done, we'll very likely many of the reason of the limitation of banks love it. So you can see that there is a huge opportunity for a best-in-class pilot and including even with the challenging that the challenges that we face as Janet and Jessica, you recognize in term of number of low event. But we believe that the way this study has been built, it will maximize the results for the efficacy and safety of this drug.

謝謝你，約翰。我想對第一個問題補充的是，我認為他非常有說服力地指出，美國國立衛生研究院最近實際上報告說，只有15% 的高風險患者實際上受到了影響，並且實際上看到85% 的aiWARE 學校應該接受舊的治療方法完成後，我們很可能會因為銀行的限製而喜歡它。因此，您可以看到，對於一流的飛行員來說，存在著巨大的機會，即使我們面臨著珍妮特和傑西卡所面臨的挑戰，您也可以從低事件數量方面認識到這一點。但我們相信，這項研究的建立方式將最大限度地提高該藥物的功效和安全性。

So I understand you may have another question on HCV as well.

我知道您可能還有關於C肝病毒的另一個問題。

Yes.

是的。

Thank you.

謝謝。

So I'm on the hep C program, given the context that compliance with existing therapies is lacking with existing regimen. So there's an unmet need here and the patients you're presumably going after are the ones that we know already are better compliance or else they procured.

因此，鑑於現有療法缺乏對現有療法的依從性，我參加了丙型肝炎計畫。因此，這裡存在著未滿足的需求，而您要尋找的患者可能是我們已經知道具有更好依從性的患者，或是他們購買的患者。

All right.

好的。

How do you guys plan to ensure for the Phase three that the protocol and clinical sites can optimize good drug adherence, especially since. But we've already seen that one patient in Phase two part here at Road was thus unable to achieve SVR four.

你們計劃如何確保第三階段的方案和臨床場所能夠優化良好的藥物依從性，特別是從那時起。但我們已經看到，Road 的第二階段中的一名患者無法達到 SVR 4。

It's a great question Jessica, I'll answer and we spend quite some time on that. So answer you like to address two questions.

這是一個很好的問題，傑西卡，我會回答，我們花了很多時間在這個問題上。所以回答你想解決兩個問題。

Yes, it is a great question. I think a nice bar and the compliance issues are just part of the nature of doing trials right now in hepatitis C, the population that we have that is in high unmet need right now is a bit of a mix of the patients who are not taking drugs and they are just generalizations, but also does have a large population of patients that are ex IV drug users or producers and those really benefit from short treatment durations. As so I think by all financial remuneration, you're already addressing some of the compliance issues because, you know, patients in general are very excited to take dress at the beginning of it. Then, you know, sometimes they forget towards the end of the treatment. I think we have all experienced that. So the eight-week duration already held. And we, of course, have, you know, the level of measurements of checking with the patients calling them being in the mean and very important in Phase three is that we're going to have a comparator. So the issues with compliance will affect both arms equally because the patients are randomized and there, you're really going to see how the virus is behaving into a kind of population, which includes these patients that are noncompliant in general.

是的，這是一個很好的問題。我認為一個不錯的酒吧和合規問題只是目前在丙型肝炎方面進行試驗的性質的一部分，我們目前需求未得到滿足的人群是一些不接受治療的患者的混合體藥物，它們只是概括，但也確實有大量患者是前靜脈注射藥物使用者或生產者，這些患者真正受益於短期治療時間。因此，我認為透過所有財務報酬，您已經解決了一些合規問題，因為您知道，患者通常都非常高興在開始時穿好衣服。然後，你知道，有時他們會在治療結束時忘記。我想我們都經歷過這一點。所以八週的期限已經成立了。當然，我們有，你知道，與患者進行檢查的測量水平，稱他們處於平均值，並且在第三階段非常重要的是我們將有一個比較器。因此，依從性問題將同樣影響雙臂，因為患者是隨機的，在那裡，你真的會看到病毒如何在某種人群中表現，其中包括這些總體上不依從的患者。

And obviously, we will we will finalize any protocol with the regulatory authorities. So but but based on our initial interaction, it's clear that a a comparator is required for our Phase three program seeking them.

顯然，我們將與監管機構敲定任何協議。但是，根據我們最初的互動，很明顯，我們的第三階段計劃需要一個比較器來尋找它們。

Thank you, very much.

非常感謝。

And one moment for our next question.

請稍等一下我們的下一個問題。

And our next question will be coming from Roanno Ruiz with Leerink Partners. Your line is open.

我們的下一個問題將來自 Leerink Partners 的 Roanno Ruiz。您的線路已開通。

And here this is Joseph Chan on for honorees at Leerink Partners. Just a couple from us. First on COVID, so thinking of all the various high-risk patients you're enrolling and site three, which the population do you think that the software can offer the most differentiated profile from currently available antivirals and any thoughts on how you could leverage the data from the combination therapy arm?

這是 Joseph Chan 為 Leerink Partners 的得獎者所做的演講。只有我們幾個人。首先是關於新冠病毒，所以考慮一下您正在招募的所有各種高風險患者和站點三，您認為該軟體可以提供與目前可用的抗病毒藥物相比最具差異化的特徵的人群，以及關於如何利用該軟體的任何想法來自聯合治療組的數據？

Do you like to address the question first?

您想先解決這個問題嗎？

And I think with regard to the high-risk patient population mean it's quite interesting. But I think in the last few months, there have been a couple of publications really sharing best and from the most high responses to the elderly particularly, I think there's 75 and above and those that are highly immunocompromised. And I think in that regard, particularly solid organ transplant patients and how many times they get vaccinated it doesn't really seem to reduce their risk of getting severely ill when they and do become infected with COVID. So I think and these are the patient populations, which are probably the ones where there's likely to be the greatest benefit. And I think another reason why ultimately and I think Pammi foster there would be an ideal drug for patients such as these is that these are patient populations that are on multiple concomitant medications. And as Jean-Pierre mentioned, and as we've alluded to, I think the potential for drug interactions, particularly with protease inhibitors is much higher than with nucleoside antagonist. And so I think these are the patient populations flare and frequently that actually in eligible to receive a drug such as Paxil and I have been in the past fortunate enough to have been able to receive monoclonal antibodies. But as you know, the monoclonal antibodies haven't been able to keep pace with the evolution of the virus. And then with regard to the combination, the combination group and what really drove them to educate ourselves, it's ready. And most important, I think because we have as Jean-Pierre mentioned in her remarks and a protease inhibitor, which is being developed and which we hope to share more information later in the year. And so I think and being able to see how combination therapy and in particular, appreciate instances having combinations and Hospira is able to provide synergy and potentially reduced versus the teams and allow patients to improve better and also we're going to be looking at such things as on drug interactions and follow kinetics on safety and tolerability. I think all of that information is important in understanding how best we use these drugs and maximize them just as we do as we move further down the line.

我認為對於高風險患者群體意味著這非常有趣。但我認為在過去的幾個月裡，有幾篇出版物真正分享了最好的成果，尤其是對老年人的最高反應，我認為有 75 歲及以上以及那些免疫功能嚴重低下的人。我認為在這方面，特別是實體器官移植患者，以及他們接種疫苗的次數，似乎並沒有真正降低他們感染新冠病毒後罹患重病的風險。所以我認為這些是患者群體，他們可能是受益最大的群體。我認為帕米最終會培育出一種適合此類患者的理想藥物的另一個原因是，這些患者群體同時服用多種藥物。正如讓-皮埃爾提到的，以及我們已經提到的，我認為藥物相互作用的可能性，特別是與蛋白酶抑製劑的相互作用，比與核苷拮抗劑的相互作用要高得多。因此，我認為這些患者群體通常沒有資格接受 Paxil 等藥物，而我過去很幸運能夠接受單株抗體。但如您所知，單株抗體無法跟上病毒的演化步伐。然後關於組合、組合小組以及真正促使他們自我教育的因素，它已經準備好了。最重要的是，我認為因為正如讓-皮埃爾在她的演講中提到的那樣，我們有一種正在開發的蛋白酶抑制劑，我們希望在今年晚些時候分享更多資訊。因此，我認為，能夠看到聯合治療，特別是欣賞聯合治療和 Hospira 的實例如何能夠提供協同作用，並可能減少與團隊的比較，並讓患者更好地改善，而且我們將研究這樣的情況藥物相互作用等問題，並遵循安全性和耐受性動力學。我認為所有這些資訊對於理解我們如何最好地使用這些藥物並最大限度地發揮它們的作用非常重要，就像我們進一步前進一樣。

Thank you.

謝謝。

Thanks so much. And then on HCB., how should we think about the PK and efficacy of semi-soft there, Andrew, is that fair in the patient population that actually have compensated cirrhosis compared to those without cirrhosis in your lead-in cohort? And then are you considering including patients with decompensated cirrhosis and Alta HIV co-infection and your Phase three U.S.?

非常感謝。然後關於 HCB，我們應該如何考慮半軟治療的 PK 和功效，Andrew，與您的導入組中沒有肝硬化的患者群體相比，在實際代償性肝硬化患者群體中這是否公平？那麼您是否正在考慮將失代償性肝硬化和 Alta HIV 合併感染患者以及您在美國的第三階段納入其中？

So it's a similar. It was to pursue a similar label as Epclusa And then separately, who are these low hanging fruit patients that you could target if it's approved?

所以這是一個相似的。它是為了追求與 Epclusa 類似的標籤。然後分別來說，如果它獲得批准，您可以針對哪些容易實現目標的患者？

So I'll answer. Maybe you want to I'll start to address the question and then I have maybe a comment as well, so I'll answer.

那我來回答一下。也許你想要我開始解決這個問題，然後我可能也會發表評論，所以我會回答。

Yes.

是的。

Well, I think the PK, we don't anticipate major changes in PK. or even PKPV. and viral kinetics and as you saw in the in the data and a lot of change, the kinetics were very fast even in the S. threes, which are really borderline compensated cirrhotics. So we think that and we've seen also in previous trials that the PK should be the same.

嗯，我認為PK，我們預計PK不會有重大變化。甚至 PKPV。和病毒動力學，正如您在數據和大量變化中看到的那樣，即使在三歲以內，動力學也非常快，這實際上是邊緣代償性肝硬化。所以我們認為，而且我們在先前的試驗中也看到，PK 應該是相同的。

And that is for the compensated cirrhotics for the compensation metrics. It's a great population.

這是補償指標的代償性肝硬化。這是一個龐大的人口。

I think that we are going to have targeted is probably a probably a little bit later for the HIV. Certainly we are considering inclusion in Phase three trial. It is like you said and great unmet need population.

我認為我們可能要晚一點才能針對愛滋病毒。當然，我們正在考慮納入第三階段試驗。就像你說的，還有大量未滿足的需求人口。

Yes, no, actually, just one comments are for the decompensated patient. Obviously, that will be a we believe, a major advance because we foresee at least we see the potential to eliminate the rebannering, which right now you have only one approved treatment, which is a combination of a crews and rebalance in those patients.

是的，不，實際上，只有一則評論是針對失代償患者的。顯然，我們相信這將是一個重大進步，因為我們至少預見到我們看到了消除重新標誌的潛力，目前只有一種批准的治療方法，即工作人員和患者重新平衡的結合。

Now let's not forget that this is it patient population that is very difficult, very likely in trial. You have interest from the U.S. So obviously, we foresee that this population will be very likely not part of the Phase three program unless the regulatory authorities will request that, but more as a first NDA commitment. But definitely we definitely want to go there, maybe not with a eight week, probably a 12 week would be already highly differentiated with the elimination of free Bhavin. And obviously, these patients do we acquire are they the best chance of success and that the length of treatment are less of an importance than what we have with a patient population that I will answer just share with you before.

現在我們不要忘記，這是非常困難的患者群體，很可能正在接受試驗。美國對此很感興趣。很明顯，我們預計這一人群很可能不會成為第三階段計劃的一部分，除非監管機構提出要求，但更多的是作為第一個 NDA 承諾。但我們絕對想去那裡，也許不是八週，可能是 12 週，隨著自由巴文的消除，情況已經非常不同了。顯然，我們獲得的這些患者是他們獲得成功的最佳機會，並且治療時間的長短不如我們對患者群體的治療時間重要，我將在之前與您分享。

Got it. Thanks, so much for taking our question.

知道了。非常感謝您提出我們的問題。

You're welcome.

不客氣。

I would now like to turn the conference back to Jean-Pierre for closing remarks.

現在我想請讓-皮埃爾致閉幕詞。

And thank you all for joining our fourth quarter and full year of 2023 Earnings Conference Call, and thank you as well for. We'll continue to support.

感謝大家參加我們的 2023 年第四季和全年財報電話會議，也謝謝你們。我們將繼續支持。

Ladies and gentlemen, this concludes today's conference. You may now disconnect.

女士們、先生們，今天的會議到此結束。您現在可以斷開連線。