Enanta Pharmaceuticals Inc (ENTA) 2023 Q2 法說會逐字稿

Good afternoon, and welcome to Enanta Pharmaceuticals Second Quarter Ended March 31, 2023 Financial Results Conference Call. (Operator Instructions) Please be advised that this call is being recorded.

下午好，歡迎來到 Enanta Pharmaceuticals 截至 2023 年 3 月 31 日的第二季度財務業績電話會議。 （操作員說明）請注意，此通話正在錄音中。

I would now like to turn the call over to Jennifer Viera, Investor Relations. Please go ahead.

我現在想把電話轉給投資者關係部的 Jennifer Viera。請繼續。

Thank you, operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal second quarter 2023 financial results was issued this afternoon and is available on our website. A news release with top line data from our SPRINT clinical trial was also issued this afternoon and can be found on our website as well. Slides from today's webcast will be available on our website after the call ends.

謝謝接線員，也感謝大家今天下午加入我們。包含我們 2023 財年第二季度財務業績的新聞稿於今天下午發布，可在我們的網站上獲取。今天下午還發布了一份新聞稿，其中包含我們 SPRINT 臨床試驗的主要數據，也可以在我們的網站上找到。通話結束後，我們的網站上將提供今天網絡廣播的幻燈片。

On the call today are Dr. Jay Luly, our President and Chief Executive Officer; Dr. Scott Rottinghaus, our Chief Medical Officer; Paul Mellett, our Chief Financial Officer; and Dr. Tara Kieffer, our Senior Vice President of New Product Strategy and Development.

今天接聽電話的是我們的總裁兼首席執行官 Jay Luly 博士；我們的首席醫療官 Scott Rottinghaus 博士；我們的首席財務官 Paul Mellett；以及我們的新產品戰略和開發高級副總裁 Tara Kieffer 博士。

Before we begin with our formal remarks, we do want to remind you that we will be making forward-looking statements, which may include our plans and expectations with respect to our research and development pipeline and financial projections, all of which involve certain assumptions and risks beyond our control that could cause our actual developments and results to differ materially from those statements.

在開始正式發言之前，我們確實想提醒您，我們將做出前瞻性陳述，其中可能包括我們對研發管道和財務預測的計劃和期望，所有這些都涉及某些假設和我們無法控制的風險可能導致我們的實際發展和結果與這些陳述存在重大差異。

A description of these risks is in our most recent Form 10-K and other periodic reports filed with the SEC. Enanta does not undertake any obligation to update any forward-looking statements made during this call.

這些風險的描述在我們最近提交給美國證券交易委員會的 10-K 表格和其他定期報告中。 Enanta 不承擔更新本次電話會議期間所做的任何前瞻性陳述的任何義務。

I'd now like to turn the call over to Dr. Jay Luly. Jay?

我現在想把電話轉給 Jay Luly 博士。傑？

Thank you, Jennifer, and good afternoon, everyone. At Enanta, our goal has always been to develop curative therapies for patients in need. That effort continues today with our announcement of the top line data from our Phase II SPRINT study of EDP-235, our 3CL protease inhibitor in development as an oral once-daily treatment for COVID-19. I'll let Dr. Scott Rottinghaus, our Chief Medical Officer, present the data in a minute, but I will highlight a few key points, which support our belief that EDP-235 could play an important role in the treatment of COVID-19.

謝謝你，詹妮弗，大家下午好。在 Enanta，我們的目標一直是為有需要的患者開發治療方法。這一努力今天繼續進行，我們公佈了 EDP-235 的 II 期 SPRINT 研究的重要數據，EDP-235 是我們正在開發的 3CL 蛋白酶抑製劑，作為 COVID-19 的口服每日一次治療藥物。我將讓我們的首席醫療官 Scott Rottinghaus 博士在一分鐘內展示數據，但我將強調幾個關鍵點，它們支持我們相信 EDP-235 可以在 COVID-19 的治療中發揮重要作用.

First, the trial met its primary endpoint, demonstrating a favorable safety and tolerability profile. In addition, we are excited that the SPRINT data show that EDP-235 had an impact on clinically meaningful endpoints. Scott's presentation will go through this in detail.

首先，該試驗達到了主要終點，顯示出良好的安全性和耐受性。此外，我們很高興 SPRINT 數據顯示 EDP-235 對具有臨床意義的終點產生了影響。 Scott 的演講將對此進行詳細介紹。

With that, I'll turn the call over to Scott. Scott?

有了這個，我會把電話轉給斯科特。斯科特？

Thank you, Jay. As Jay stated, EDP-235 met the primary endpoint and was generally safe and well tolerated. We saw a dose-dependent symptom improvement with EDP-235 treatment compared to placebo. However, we did not see an effect on virologic endpoints likely because of the rapid viral decline in the placebo arm of this immunologically experienced standard risk population.

謝謝你，傑伊。正如 Jay 所說，EDP-235 達到了主要終點，並且通常安全且耐受性良好。與安慰劑相比，我們看到 EDP-235 治療的劑量依賴性症狀改善。然而，我們沒有看到對病毒學終點的影響，這可能是因為在這個具有免疫學經驗的標準風險人群的安慰劑組中病毒迅速下降。

As a reminder, this slide shows the study design of SPRINT, which was a randomized, double-blind, placebo-controlled Phase II clinical trial of EDP-235 in approximately 200 adults with mild or moderate COVID-19, who did not have risk factors for progression to severe disease. Patients were treated with EDP-235 at doses of 200 milligrams, 400 milligrams or placebo, once-daily for 5 days.

提醒一下，這張幻燈片顯示了 SPRINT 的研究設計，這是一項 EDP-235 的隨機、雙盲、安慰劑對照的 II 期臨床試驗，受試者為大約 200 名沒有風險的輕度或中度 COVID-19 成人進展為嚴重疾病的因素。患者接受劑量為 200 毫克、400 毫克或安慰劑的 EDP-235 治療，每天一次，持續 5 天。

We randomized 231 patients in a 1:1:1 fashion. The safety population included all patients randomized. We followed the patients out to day 33. And as you can see, 95% to 97% of the patients completed the study. The ITTc population of 190 patients is a modified intention to treat population that constitutes our primary efficacy analysis population. It includes all patients who are confirmed to have a positive PCR for SARS-CoV-2 at baseline.

我們以 1:1:1 的方式隨機分配了 231 名患者。安全人群包括隨機分配的所有患者。我們跟踪患者到第 33 天。如您所見，95% 到 97% 的患者完成了研究。 190 名患者的 ITTc 人群是構成我們主要療效分析人群的改良意向治療人群。它包括所有在基線時確認 SARS-CoV-2 PCR 呈陽性的患者。

Demographics and baseline characteristics were well balanced between the arms. We had a young patient population with a median age of about 45 years. Most patients were white and Hispanic. Three quarters were enrolled within 3 days of symptom onset. Baseline viral load was about 5 logs across arms. The majority of patients had been vaccinated against COVID and about 95% were seropositive, indicating a high degree of baseline immunity against COVID. This is consistent with recent estimates from the CDC showing a high degree of seropositivity in the U.S. population.

人口統計學和基線特徵在手臂之間得到了很好的平衡。我們有一個年輕的患者群體，中位年齡約為 45 歲。大多數患者是白人和西班牙裔。四分之三的人在症狀出現後 3 天內入組。基線病毒載量約為雙臂的 5 個對數。大多數患者接種了 COVID 疫苗，約 95% 的患者呈血清陽性，表明對 COVID 的基線免疫力很高。這與 CDC 最近的估計一致，顯示美國人口中存在高度的血清陽性。

The next slide summarizes the adverse events that we saw in the study. Among our 231 patients, only 10 adverse events were reported. While there were numerically more adverse events reported on 400 milligrams than on the other arms, the frequency was still low at 6.4% compared to placebo at 2.6%. There were no serious adverse events or discontinuations due to adverse events.

下一張幻燈片總結了我們在研究中看到的不良事件。在我們的 231 名患者中，僅報告了 10 起不良事件。雖然 400 毫克組報告的不良事件在數量上多於其他組，但頻率仍然較低，為 6.4%，而安慰劑組為 2.6%。沒有嚴重的不良事件或因不良事件而停藥。

Most adverse events were mild in severity. The adverse event that was graded as severe in this table was a fall and resulting arthralgia that was judged by the investigator not to be related to study drug.

大多數不良事件的嚴重程度較輕。在該表中分級為嚴重的不良事件是跌倒和由此引起的關節痛，研究者判斷其與研究藥物無關。

This slide shows the specific adverse events. As you can see, no specific pattern of adverse events was identified. The 2 who've had toxicities were asymptomatic, transient elevations of transaminases. The 1 in 200 milligrams with a mild grade 1 elevation and the other in 400 milligrams, I'll discuss more on the next slide.

這張幻燈片顯示了具體的不良事件。如您所見，未發現特定的不良事件模式。出現毒性的 2 人是無症狀的轉氨酶短暫升高。 200 毫克中有 1 毫克具有輕微的 1 級升高，而另一種是 400 毫克，我將在下一張幻燈片中進行更多討論。

Laboratory values were generally unremarkable, but there are 2 specific call-outs. The patient I just mentioned, who is receiving EDP-235 at the 400-milligram dose reported concomitant use of alcohol and acetaminophen. He had ALT at the upper limit of normal at baseline and experienced asymptomatic ALT elevation up to 12x the upper limit of normal on study day 6.

實驗室值通常不顯著，但有 2 個特定標註。我剛才提到的正在接受 400 毫克劑量的 EDP-235 的患者報告同時使用酒精和對乙酰氨基酚。他在基線時的 ALT 處於正常上限，並且在研究第 6 天出現無症狀的 ALT 升高至正常上限的 12 倍。

His AST was 5x the upper limit of normal. GGT was elevated at baseline and increased further to 4x the upper limit of normal. Bilirubin and alkaline phosphatase were normal. The patient remained asymptomatic, and all labs returned to normal and follow-up, except for GGT, which remained mildly elevated, but consistent with baseline.

他的 AST 是正常上限的 5 倍。 GGT 在基線時升高，並進一步增加至正常上限的 4 倍。膽紅素和鹼性磷酸酶正常。患者保持無症狀，所有實驗室恢復正常並進行隨訪，但 GGT 除外，其仍輕度升高，但與基線一致。

The second laboratory observation is a transient and dose-dependent elevation in total cholesterol and triglycerides with EDP-235. Both total cholesterol and triglycerides then trended toward normal after treatment.

第二個實驗室觀察是 EDP-235 總膽固醇和甘油三酯的短暫和劑量依賴性升高。治療後總膽固醇和甘油三酯均趨於正常。

Wrapping up safety, there was a low frequency of adverse events, and most were mild in severity. There were no serious adverse events or discontinuations due to adverse events. Laboratory values were generally unremarkable apart from the patient with transaminase elevations and the lipid trends that I just discussed.

總結安全性，不良事件的發生頻率很低，而且大多數都是輕微的。沒有嚴重的不良事件或因不良事件而停藥。除了轉氨酶升高的患者和我剛才討論的血脂趨勢外，實驗室值通常沒有什麼特別之處。

Moving to PK. EDP-235 achieved target exposures and the results were consistent with what we saw in Phase I. Plasma drug levels were 7x and 12x higher than the EC90 of Omicron for the 200-milligram and 400-milligram dosing levels. Mean and median predose concentrations of EDP-235 on day 5 are shown in the table.

移動到PK。 EDP-235 實現了目標暴露，結果與我們在第一階段看到的結果一致。對於 200 毫克和 400 毫克的劑量水平，血漿藥物水平比 Omicron 的 EC90 高 7 倍和 12 倍。表中顯示了第 5 天 EDP-235 的平均和中值給藥前濃度。

Now for efficacy. Let's start with the total symptom score in the full efficacy analysis population, the ITTc. As a reminder, the total symptom score comprises all 14 symptoms as defined by the FDA for evaluating drugs to treat COVID. They're listed on the right-hand side of the slide. You can see here that there is a dose-dependent trend favoring EDP-235 with statistical significance being achieved at multiple time points as indicated by the asterisks with a p-value of less than 0.05.

現在為了功效。讓我們從完整療效分析人群 ITTc 的總症狀評分開始。提醒一下，總症狀評分包括 FDA 定義的用於評估 COVID 藥物治療的所有 14 種症狀。它們列在幻燈片的右側。您可以在此處看到，有利於 EDP-235 的劑量依賴性趨勢在多個時間點實現了統計顯著性，如星號所示，p 值小於 0.05。

Statistical significance was observed as early as the first time point evaluated, which was 1 day after the first dose. While the baseline total symptom score of the 400-milligram dose was slightly higher than the others, a rapid, early and sustained improvement in symptoms was observed compared to placebo.

早在第一次評估的第一個時間點，即第一次給藥後 1 天，就觀察到了統計學顯著性。雖然 400 毫克劑量的基線總症狀評分略高於其他劑量，但與安慰劑相比，觀察到症狀迅速、早期和持續改善。

For contextualization, this slide shows our EDP-235 data that I just showed you, next to data from another protease inhibitor Ensitrelvir. We chose Ensitrelvir for contextualization because it's the only antiviral with a sufficiently robust data -- symptom data set in the public domain.

對於背景化，這張幻燈片顯示了我剛剛向您展示的我們的 EDP-235 數據，旁邊是另一種蛋白酶抑製劑 Ensitrelvir 的數據。我們選擇 Ensitrevir 進行情境化，因為它是唯一具有足夠強大數據（公共領域中的症狀數據集）的抗病毒藥物。

Our Phase II study looked at the 14 symptoms I just discussed in 190 patients, and the change from baseline in total symptom score is graphed here out to 10 days. Ensitrelvir's Phase IIb study of 341 patients looked at the same symptoms, except for taste and smell, and these data are grafted out to day 6. As you can see, dose-dependent trends and symptomatic improvement were observed for both antivirals.

我們的 II 期研究考察了我剛剛在 190 名患者中討論的 14 種症狀，總症狀評分相對於基線的變化在此處繪製為 10 天。 Ensitrelvir 對 341 名患者進行的 IIb 期研究觀察了相同的症狀，除了味覺和嗅覺，這些數據移植到第 6 天。如您所見，兩種抗病毒藥物均觀察到劑量依賴趨勢和症狀改善。

As you may remember, the protocol stratified patients at randomization into 2 groups: those with less than 3 days of symptoms and those with greater than 3 days of symptoms. We prespecified an analysis of the patients who were randomized within 3 days of symptom onset. You'll recall from the demographic slide that this population includes about 3/4 of the patients in the study. In this population, EDP-235 at 400 milligrams showed statistically significant reductions in total symptom score compared to baseline at all time points after treatment.

您可能還記得，該方案將隨機分組的患者分為 2 組：症狀出現時間少於 3 天的患者和症狀出現時間超過 3 天的患者。我們預先指定了對在症狀出現後 3 天內隨機分配的患者的分析。您會從人口統計幻燈片中回想起該人群包括研究中大約 3/4 的患者。在該人群中，400 毫克的 EDP-235 在治療後的所有時間點均顯示總症狀評分與基線相比有統計學意義的顯著降低。

We interrogated our data set with the goal of identifying a subset of the FDA-specified 14 symptoms that better reflect the clinical manifestations at the current COVID-19 variants and the treatment effect on these symptoms. Shionogi performed a similar analysis identifying 5 symptoms from their Phase IIb study, which were subsequently used as a primary endpoint in their Phase III.

我們審視了我們的數據集，目的是確定 FDA 指定的 14 種症狀的一個子集，這些症狀可以更好地反映當前 COVID-19 變體的臨床表現以及對這些症狀的治療效果。 Shionogi 進行了類似的分析，從他們的 IIb 期研究中確定了 5 種症狀，這些症狀隨後被用作他們的 III 期研究的主要終點。

As shown here, we identified a subset of 6 symptoms, including shortness of breast, sore throat, stuffy runny nose, chills or shivering, feeling hotter feverish and headache. This figure shows an analysis of these 6 symptoms in the prespecified population of patients enrolled within 3 days of symptom onset. EDP-235 at the 400-milligram dose demonstrated an even greater improvement in symptom score at all time points.

如圖所示，我們確定了 6 種症狀的子集，包括乳房短促、喉嚨痛、鼻塞、發冷或發抖、感覺更熱、發燒和頭痛。該圖顯示了對症狀發作 3 天內入組的預設患者群體中這 6 種症狀的分析。 400 毫克劑量的 EDP-235 在所有時間點都表現出更大的症狀評分改善。

Now let's move to looking at time to symptom improvement. While our prespecified endpoint of time to improvement for all 14 symptoms did not show a difference between the active and placebo arms analysis of the 6 symptoms from the last slide showed a statistically significant difference in the ITT population. Furthermore, as shown on this slide, this difference was even greater among patients who were enrolled within 3 days of symptom onset.

現在讓我們來看看症狀改善的時間。雖然我們預先指定的改善所有 14 種症狀的時間終點並未顯示活性組和安慰劑組之間的差異，但對上一張幻燈片中 6 種症狀的分析顯示 ITT 人群存在統計學上的顯著差異。此外，如這張幻燈片所示，這種差異在症狀出現 3 天內入組的患者中甚至更大。

You can see that the hazard ratio for the difference of EDP-235 at the 400-milligram dose versus placebo is 1.9 with a p-value of 0.006. Median time to improvement for these 6 symptoms was shortened by 2 days. Specifically, patients receiving placebo improved in 5 days while patients receiving 400 milligrams of EDP-235 improved in 3 days.

您可以看到，EDP-235 在 400 毫克劑量下與安慰劑的差異風險比為 1.9，p 值為 0.006。這 6 種症狀改善的中位時間縮短了 2 天。具體來說，接受安慰劑的患者在 5 天內有所改善，而接受 400 毫克 EDP-235 的患者在 3 天內有所改善。

Moving to virologic end points. This graph shows change from baseline in viral RNA as measured by nasopharyngeal swabs. No difference was demonstrated between patients treated with EDP-235 and placebo likely due to the rapid viral decline observed in the placebo arm. The mean baseline viral load in this study population was approximately 5 logs and a precipitous decrease in viral RNA was observed in all study arms, indicating that this highly immune population rapidly cleared virus from the nose.

轉向病毒學終點。該圖顯示了通過鼻咽拭子測量的病毒 RNA 相對於基線的變化。用 EDP-235 和安慰劑治療的患者之間沒有表現出差異，這可能是由於在安慰劑組中觀察到的病毒迅速下降。該研究人群的平均基線病毒載量約為 5 個對數，並且在所有研究組中均觀察到病毒 RNA 急劇減少，表明該高免疫人群迅速從鼻子清除了病毒。

To understand this further, we performed an additional analysis of patients with a baseline viral load greater than 5 logs, and this represented about half of the study population. We saw a viral load decline of 0.4 logs at day 3 in both EDP-235 treatment groups compared to placebo. This 0.4-log decline was sustained at day 5 in the 400-milligram arm.

為進一步了解這一點，我們對基線病毒載量大於 5 個對數的患者進行了額外分析，這約佔研究人群的一半。與安慰劑組相比，我們在第 3 天看到兩個 EDP-235 治療組的病毒載量下降了 0.4 個對數。 400 毫克組在第 5 天持續下降 0.4 個對數。

For more contextualization, this slide compares the viral RNA change from baseline in the placebo arms of other direct-acting antiviral COVID studies. You can see here that the decline seen in the placebo arm of the SPRINT study was more rapid than in any other study. This may not be surprising given the highly immune population in which this study was conducted, as evidenced by recent CDC data from a nationwide seroprevalence study showing the high prevalence of natural and hybrid immunity, which continues to grow over time. Details of these data can be found in the appendix of the slides posted to our website.

為了獲得更多背景信息，這張幻燈片比較了其他直接抗病毒 COVID 研究的安慰劑組中病毒 RNA 相對於基線的變化。您可以在這裡看到，SPRINT 研究安慰劑組的下降速度比任何其他研究都快。考慮到進行這項研究的高免疫人群，這可能並不令人驚訝，正如美國疾病控制與預防中心最近的一項全國血清陽性率研究數據所證明的那樣，該數據顯示自然和混合免疫的高流行率，並隨著時間的推移繼續增長。這些數據的詳細信息可以在發佈到我們網站的幻燈片的附錄中找到。

In summary, EDP-235 was generally safe and well tolerated. There was a low frequency of adverse events, and most were mild in severity. There were no serious adverse events or discontinuations due to adverse events. EDP-235 showed a dose-dependent improvement in total symptom score. Among patients enrolled within 3 days of symptom onset, there was a statistically significant improvement in the total symptom score for EDP-235 at 400 milligrams at all time points, starting at 1 day after dosing.

總之，EDP-235 總體上是安全且耐受性良好的。不良事件的發生頻率很低，而且大多數都是輕微的。沒有嚴重的不良事件或因不良事件而停藥。 EDP-235 顯示總症狀評分呈劑量依賴性改善。在症狀發作 3 天內入組的患者中，從給藥後 1 天開始，EDP-235 在所有時間點 400 毫克的總症狀評分均有統計學顯著改善。

There was no difference between treatment arms and placebo for viral RNA decline in this highly immune population that was able to rapidly clear SARS-CoV-2 from the nose. However, an additional analysis of patients with a baseline viral load greater than 5 logs showed a viral RNA decline of 0.4 logs at day 3 in both EDP-235 treatment groups compared to placebo.

在這個能夠從鼻子中快速清除 SARS-CoV-2 的高免疫人群中，治療組和安慰劑之間的病毒 RNA 下降沒有差異。然而，對基線病毒載量大於 5 個對數的患者進行的額外分析顯示，與安慰劑相比，兩個 EDP-235 治療組在第 3 天的病毒 RNA 下降了 0.4 個對數。

In conclusion, we're excited to see the EDP-235 at the 400-milligram dose had a significant effect on symptoms in the SPRINT study, suggesting that we have the potential to affect clinically meaningful endpoints moving forward in development.

總之，我們很高興看到 400 毫克劑量的 EDP-235 對 SPRINT 研究中的症狀產生了顯著影響，這表明我們有可能在開發過程中影響具有臨床意義的終點。

That concludes my presentation of the data. With that, I'll turn the call back to Jay. Jay?

我對數據的介紹到此結束。有了這個，我會把電話轉回傑伊。傑？

Based on the positive SPRINT data, we are focusing on partnership opportunities for Phase III and on the potential for a Phase II study in acute or long COVID that could further demonstrate the efficacy of EDP-235. We look forward to providing an update on our plans in the coming months.

基於積極的 SPRINT 數據，我們正在關注 III 期的合作機會，以及對急性或長期 COVID 進行 II 期研究的潛力，這可以進一步證明 EDP-235 的功效。我們期待在未來幾個月內提供有關我們計劃的最新信息。

I also want to note, we continue to progress our research program to develop SARS-CoV-2 papain-like protease or PLpro inhibitors. Beyond COVID-19, our patient-centric approach continues with our industry-leading respiratory virology treatment portfolio. With RSV specifically, we are advancing a broad program, which includes EDP-938, the most advanced and protein inhibitor in clinical development as well as EDP-323, our novel oral therapeutic targeting RSV L-protein RNA polymerase.

我還想指出，我們繼續推進我們的研究計劃，以開發 SARS-CoV-2 木瓜蛋白酶樣蛋白酶或 PLpro 抑製劑。除了 COVID-19，我們以患者為中心的方法繼續使用我們行業領先的呼吸道病毒學治療產品組合。具體到 RSV，我們正在推進一個廣泛的項目，其中包括臨床開發中最先進的蛋白質抑製劑 EDP-938 以及我們針對 RSV L 蛋白 RNA 聚合酶的新型口服治療藥物 EDP-323。

We are monitoring RSV epidemiology to evaluate the impact on trial enrollment and timing for data readouts and our ongoing Phase II studies of EDP-938, and we expect enrollment to continue throughout 2023.

我們正在監測 RSV 流行病學，以評估對試驗註冊和數據讀出時間的影響以及我們正在進行的 EDP-938 的 II 期研究，我們預計註冊將在整個 2023 年繼續進行。

Meanwhile, we are wrapping up our ongoing Phase I study of EDP-323. We look forward to reporting top line data for EDP-323 next month. This quarter, we also announced that the FDA granted Fast Track designation to EDP-323, underscoring its potential as a once-daily oral therapeutic for the treatment of RSV. As a reminder, the Phase I study is a double-blind, placebo-controlled, first-in-human study that will enroll approximately 80 healthy subjects and is evaluating the safety, tolerability and pharmacokinetics of orally administered single and multiple doses of EDP-323.

與此同時，我們正在結束正在進行的 EDP-323 的第一階段研究。我們期待下個月報告 EDP-323 的頂級數據。本季度，我們還宣布 FDA 授予 EDP-323 快速通道稱號，強調其作為每日一次口服治療 RSV 的潛力。提醒一下，I 期研究是一項雙盲、安慰劑對照、首次人體研究，將招募大約 80 名健康受試者，並評估口服單劑量和多劑量 EDP-的安全性、耐受性和藥代動力學。 323.

Beyond our clinical RSV programs, we are particularly excited by the potential of our novel broader spectrum antiviral research program targeting both RSV and human metapneumovirus, or hMPV, with a single agent. Both of these viruses have a severe impact on several vulnerable patient populations, such as children, the elderly adults within cardiopulmonary disease and those who are immune compromised.

除了我們的臨床 RSV 項目外，我們對我們的新型廣譜抗病毒研究項目的潛力感到特別興奮，該項目使用單一藥物同時針對 RSV 和人偏肺病毒 (hMPV)。這兩種病毒都對一些脆弱的患者群體產生嚴重影響，例如兒童、患有心肺疾病的老年人和免疫力低下的人。

Our preclinical data in support of this program showed that our prototype dual inhibitor demonstrated potent nanomolar activity against multiple genotypes and strains of both viruses in a range of cell types. We're making progress in the optimization of our potent dual inhibitors and aim to select a clinical candidate in the fourth quarter of 2023.

我們支持該計劃的臨床前數據表明，我們的原型雙重抑製劑在一系列細胞類型中對兩種病毒的多種基因型和毒株表現出強大的納摩爾活性。我們正在優化我們的強效雙抑製劑方面取得進展，目標是在 2023 年第四季度選擇臨床候選藥物。

Before I turn the call over to Paul to provide an update on our financials, I want to comment on the $200 million royalty sale transaction we closed 2 weeks ago. The additional nondilutive funding has increased our financial flexibility and extended our cash runway.

在我將電話轉給 Paul 以提供我們財務狀況的最新信息之前，我想對我們 2 週前完成的 2 億美元特許權使用費銷售交易發表評論。額外的非稀釋資金增加了我們的財務靈活性並擴大了我們的現金跑道。

With that, I'll turn the call over to Paul.

有了這個，我會把電話轉給保羅。

Thank you, Jay. Before I provide details on our second quarter financial results, I also want to take a moment to comment on our royalty sales transaction, which we announced in April. This transaction involved the sale of 54.5% of our future global royalties we earned on net sales of MAVYRET beginning in July 2023 through June 2032, with total payments capped at 1.42x the purchase price.

謝謝你，傑伊。在我提供有關我們第二季度財務業績的詳細信息之前，我還想花點時間談談我們在 4 月份宣布的特許權使用費銷售交易。該交易涉及出售我們從 2023 年 7 月至 2032 年 6 月期間從 MAVYRET 淨銷售額中獲得的未來全球特許權使用費的 54.5%，總付款上限為購買價格的 1.42 倍。

In exchange, the purchaser OMERS paid us $200 million upfront. We are excited to partner with OMERS, which is 1 of the Canada's largest defined benefit pension plans. This sale not only secures us additional nondilutive funding but also gives us increased financial flexibility and retained economics. Please note that Enanta retains 45.5% of all royalties until the cap is hit, at which point, 100% of all further royalties revert to Enanta.

作為交換，買方 OMERS 預付了 2 億美元。我們很高興與 OMERS 合作，這是加拿大最大的固定收益養老金計劃之一。此次出售不僅為我們提供了額外的非稀釋性資金，還為我們提供了更高的財務靈活性和保留的經濟效益。請注意，在達到上限之前，Enanta 保留所有特許權使用費的 45.5%，屆時，所有其他特許權使用費的 100%將歸還給 Enanta。

Now let's turn to our quarterly results. For the quarter, total revenue was $17.8 million and consisted of royalty revenue earned on AbbVie's global MAVYRET net product sales. This compares to total revenue of $18.7 million for the same period in 2022. The decrease was due to lower patient volumes in 2023 compared to 2022.

現在讓我們來看看我們的季度業績。本季度總收入為 1780 萬美元，其中包括艾伯維全球 MAVYRET 產品淨銷售額所賺取的特許權使用費收入。相比之下，2022 年同期的總收入為 1870 萬美元。減少的原因是 2023 年的患者數量低於 2022 年。

Moving on to our expenses. For the 3 months ended March 31, 2023, research and development expenses totaled $43.5 million compared to $42.1 million for the same period in 2022. The slight increase was primarily due to the timing of clinical trial expenses in our virology programs.

繼續我們的開支。截至 2023 年 3 月 31 日的三個月，研發費用總計 4350 萬美元，而 2022 年同期為 4210 萬美元。略有增加的主要原因是我們病毒學項目的臨床試驗費用的時間安排。

General and administrative expense for the quarter was $13.8 million compared to $10.5 million for the same period in 2022. The increase was due to increased stock-related compensation expense and legal fees associated with our patent infringement suit against Pfizer.

本季度的一般和行政費用為 1,380 萬美元，而 2022 年同期為 1,050 萬美元。增加的原因是與股票相關的補償費用以及與我們針對輝瑞公司提起的專利侵權訴訟相關的法律費用增加。

Net loss for the 3 months ended March 31, 2023, was $37.7 million or a loss of $1.79 per diluted common share compared to a net loss of $33.6 million or a loss of $1.63 per diluted common share for the corresponding period in 2022.

截至 2023 年 3 月 31 日止三個月的淨虧損為 3770 萬美元或每股稀釋普通股虧損 1.79 美元，而 2022 年同期為淨虧損 3360 萬美元或每股稀釋普通股虧損 1.63 美元。

Enanta ended the quarter with approximately $225 million in cash and marketable securities before giving effect of the royalty sale transaction. We expect that our current cash, cash equivalents and short-term and long-term marketable securities, along with the $200 million in cash we received on the sale of our portion of MAVYRET royalties as well as our retained portion of royalty revenue will continue to be sufficient to meet the anticipated cash requirements of our existing business and development programs into calendar 2026.

在特許權使用費銷售交易生效之前，Enanta 在本季度結束時擁有約 2.25 億美元的現金和有價證券。我們預計我們目前的現金、現金等價物和短期和長期有價證券，以及我們在出售我們的 MAVYRET 特許權使用費部分以及我們保留的特許權使用費收入部分時收到的 2 億美元現金將繼續足以滿足我們現有業務和發展計劃到 2026 年的預期現金需求。

Further financial details are available in our press release and will be available in our report on Form 10-Q when filed. I'd now like to turn the call back to the operator and we'll open up the lines for questions. Operator?

更多財務細節可在我們的新聞稿中找到，並將在提交時在我們的 10-Q 表格報告中找到。我現在想把電話轉回給接線員，我們將開通問題熱線。操作員？

(Operator Instructions) That comes from Yasmeen Rahimi with Piper Sandler.

（操作員說明）來自 Yasmeen Rahimi 和 Piper Sandler。

Thank you so much for all the details from SPRINT. I guess maybe now with this data on hand, like what are the next steps, right? Like how soon can you meet with the agency and get insight in regards to the Phase III design? And maybe given that there was quite a bit of variability in the viral load and maybe not differences were depicted in the total symptom score.

非常感謝您提供 SPRINT 的所有詳細信息。我想也許現在有了這些數據，接下來的步驟是什麼，對吧？比如您多久可以與該機構會面並了解有關 III 期設計的見解？也許考慮到病毒載量存在相當大的變異性，並且可能在總症狀評分中沒有描述差異。

Like do you think those data points could impact or may or may not impact the discussions with potential partners? So if you could maybe highlight whether they have a deep appreciation to those variabilities and nuances and then I'll jump back in the queue. And thank you for allowing me to ask my questions.

比如您認為這些數據點會影響或可能會或不會影響與潛在合作夥伴的討論嗎？所以，如果你能強調他們是否對這些變化和細微差別有深刻的理解，那麼我會跳回隊列。感謝您允許我提出問題。

This is Jay. So maybe I'll let Scott fill in some of the -- a little bit of the details. But I think we'll be progressing our data set, taking it to the agency as a matter of course, of finishing up the study. We'll be also in the context of the data, the viral load bid, which we can talk a lot more about. But at the end of the day, the agency doesn't approve any of the COVID drugs based on viral load. It's based on some other endpoints.

這是傑。所以也許我會讓斯科特填寫一些——一些細節。但我認為我們會改進我們的數據集，理所當然地把它交給該機構，以完成研究。我們也會在數據的背景下，病毒載量出價，我們可以談論更多。但歸根結底，該機構不會根據病毒載量批准任何 COVID 藥物。它基於其他一些端點。

So if you're looking at a standard risk patient population, it's going to be based on symptoms. If you're going to be looking at a high-risk patient population, it's going to be on hospitalization and death. And so I think, in particular, that's why we were really pleased to see the statistically significant improvements in the total symptom score and on the time to improvement. So those are both really important metrics that could be viewed as clinically -- highly clinically relevant. So Scott, anything to add on that? Or...

因此，如果您正在查看標準風險患者群體，它將基於症狀。如果你要研究高危患者群體，他們會住院和死亡。所以我認為，特別是，這就是為什麼我們真的很高興看到總症狀評分和改善時間在統計上有顯著改善。所以這些都是非常重要的指標，可以被視為臨床 - 高度臨床相關。 Scott，還有什麼要補充的嗎？或者...

Yes, Yasmeen, thanks for that question. I mean, just to reiterate, we're so excited about the strong data in symptoms, and we do expect that to form the basis of a discussion with regulators to look at next steps in terms of Phase III design. While the virology data are mixed, as you say, I do think we have an opportunity here given the symptom data. So we are very excited and looking forward to moving this to next steps.

是的，Yasmeen，謝謝你提出這個問題。我的意思是，重申一下，我們對症狀方面的強大數據感到非常興奮，我們確實希望這能成為與監管機構討論的基礎，以研究 III 期設計的後續步驟。正如你所說，雖然病毒學數據是混合的，但我確實認為，鑑於症狀數據，我們在這裡有機會。因此，我們非常興奮並期待著將其推進到下一步。

I think one of the other things that's clear is that the patient population over time since the beginning of the pandemic has changed dramatically as has the virus. And so good for the humans, the seropositivity that we're building up over time, either through vaccination or through natural infection or both giving you hybrid immunity. This is only built and built and built over time, and in every sort of consecutive study population that people are looking at. And for that reason, and as you saw the data, just even looking at the placebo curves in the slide deck, and again, this slide deck will be posted at the end of the call.

我認為另一件明確的事情是，自大流行開始以來，患者人數隨著時間的推移發生了巨大變化，病毒也是如此。對人類非常有益，隨著時間的推移，我們正在建立的血清陽性，無論是通過疫苗接種還是通過自然感染，或者兩者都給你混合免疫。這只會隨著時間的推移，在人們正在觀察的各種連續研究人群中不斷建立和建立。出於這個原因，正如你看到的數據，甚至只是看一下幻燈片中的安慰劑曲線，再一次，這個幻燈片將在電話會議結束時發布。

But when you look at all those placebos from all the various studies, it becomes clear that over time, the viral load drops have happened more quickly and more dramatically as time has gone on. At least as you can measure viral loads in the nose, which is obviously the compartment that can easily be interrogated.

但是，當您查看所有各種研究中的所有這些安慰劑時，很明顯隨著時間的推移，隨著時間的推移，病毒載量下降的速度越來越快，也越來越顯著。至少你可以測量鼻子中的病毒載量，這顯然是很容易被詢問的隔間。

What's happening in the rest of the body and the rest of the tissues from a virologic standpoint, much more difficult to assess. But we know that our drug has great tissue penetration, high potency, good exposures, high multiples of EC90s and has had a very significant effect on symptoms, which, again, we think compares very well to any other study that's been done in this patient population.

從病毒學的角度來看，身體的其他部分和組織的其他部分發生了什麼，更難評估。但我們知道我們的藥物具有很好的組織滲透性、高效力、良好的暴露、EC90 的高倍數並且對症狀有非常顯著的影響，我們認為這與對該患者進行的任何其他研究相比非常好人口。

So I think that's an interesting next study. I think the question I think you asked, Yas, was next plans. I mean we'll be thinking about other kinds of studies. There's things you could think about, and I'm talking about Phase IIs now, either you could conduct in long COVID or in another patient population. I think we want to think about what any such study might look like. And at the same time, obviously, it's thinking about the future with Phase III.

所以我認為這是一項有趣的下一項研究。 Yas，我想你問的問題是下一步計劃。我的意思是我們會考慮其他類型的研究。有些事情你可以考慮，我現在談論的是 II 期，你可以在長期 COVID 或其他患者群體中進行。我想我們想考慮一下這樣的研究會是什麼樣子。同時，很明顯，它正在考慮 Phase III 的未來。

Our plan's always been to engage a partner for late-stage development, the commercialization strategy and ultimately, the launch. I think with this positive SPRINT data, we see a broad opportunity for 235 in multiple different treatment paradigms for COVID. You can think of standard risk, high-risk, prophylaxis, long COVID.

我們的計劃一直是聘請合作夥伴進行後期開發、商業化戰略以及最終的發布。我認為，有了這個積極的 SPRINT 數據，我們看到了 235 在 COVID 的多種不同治療範例中的廣泛機會。你可以想到標準風險、高風險、預防、長期 COVID。

So really in order to realize this vision, we feel a pharma partnership would better enable us to get the best registration program and to achieve that optimal label. So that's going to be our focus in terms of Phase III. I don't know if you -- I think you dropped off the call but...

因此，為了真正實現這一願景，我們認為與製藥公司建立合作夥伴關係可以更好地幫助我們獲得最佳註冊計劃並獲得最佳標籤。所以這將是我們在第三階段的重點。我不知道你是否——我想你掛斷了電話但是……

No, that was great.

不，那太好了。

It comes from the line of Brian Abrahams with RBC Capital Markets.

它來自 RBC Capital Markets 的 Brian Abrahams 系列。

And thanks, too, for all the detailed SPRINT data, really, really helpful. I guess my first question is, when you think about a potential go-forward dose here, I guess, how confident are you that some of the symptomatic benefits that you're seeing are indeed dose-dependent versus maybe related to a slightly higher baseline for the 400-milligram arm. I guess I'm curious sort of at the end of day 5, how 400- and 200-milligram patients compared in terms of where they got to on an absolute basis on symptom score and how you're thinking about the go-forward dose?

還要感謝所有詳細的 SPRINT 數據，真的非常有用。我想我的第一個問題是，當你在這裡考慮潛在的前進劑量時，我想，你對你看到的一些症狀益處確實是劑量依賴性而不是可能與略高的基線有關有多大信心對於 400 毫克的手臂。我想我很好奇在第 5 天結束時，400 毫克和 200 毫克的患者在症狀評分的絕對基礎上如何比較他們到達的位置以及您如何考慮前進劑量？

I think the go-forward dose is going to be 400. I mean that stood out in so many ways. There were slight differences in the baseline. But what that -- what happened there is that within the first -- really in the first 24 hours, the 400-milligram dose brought things down very quickly and basically lined up with the other patient population. So there's clear evidence that, that 400-milligram moved very quickly and efficaciously in the right direction.

我認為前進劑量將是 400。我的意思是這在很多方面都很突出。基線略有不同。但是那是什麼 - 在那裡發生的事情是在第一個 - 真的是在第一個 24 小時內，400 毫克的劑量很快使事情下降並且基本上與其他患者群體保持一致。所以有明確的證據表明，這 400 毫克在正確的方向上非常快速有效地移動。

And I would point out that -- sorry, Brian, I was just going to point out also that in addition to the decrease in total symptom score, if you look at those specific symptoms, you see an improvement in time to improvement. And so we have multiple different avenues of evidence that point to the fact that this is really a real dose-dependent improvement in efficacy. And yes, we feel quite confident in it.

我要指出的是——對不起，布賴恩，我只想指出，除了總症狀評分下降之外，如果您查看這些特定症狀，您會發現改善時間有所改善。因此，我們有多種不同的證據途徑表明，這確實是一種真正的劑量依賴性療效改善。是的，我們對此很有信心。

Got it. And -- so what do you attribute the TSS symptom signals that you're seeing here, given that there isn't a measurable antiviral effect? Is this related to maybe sort of like an unmeasurable effect that's going on in terms of viral clearance in a different reservoir or some sort of additional benefit on anti-inflammatory benefit?

知道了。並且 - 鑑於沒有可測量的抗病毒作用，您如何看待您在這裡看到的 TSS 症狀信號？這是否與在不同儲庫中的病毒清除方面正在發生的某種不可測量的影響有關，或者與抗炎益處的某種額外益處有關？

Yes. Key question, Brian. So we think it's the compartment that we're measuring, right? Everybody looks at the nose that's where we can easily access and check, but we know that these patients have 95% seropositivity. You can look at some of the background information that we put in our decks as well. The whole population is becoming really strong in terms of hybrid immunity and ability to clear this virus.

是的。關鍵問題，布賴恩。所以我們認為這是我們正在測量的隔間，對嗎？每個人都看鼻子，我們可以很容易地接近和檢查，但我們知道這些患者有 95% 的血清陽性。您也可以查看我們放在套牌中的一些背景信息。就混合免疫和清除這種病毒的能力而言，整個人群都變得非常強大。

Now that having been said, we do believe when you see these systemic symptoms, in particular, there are clearly other reservoirs of virus throughout the body that we can't necessarily access to measure efficiently. But we do know that our drug has excellent tissue distribution, excellent tissue penetration. And we believe that, that's what potentially sets it apart. And that's what's allowing us to get a therapeutic effect on symptoms, whereas we don't see so much on virus in the nasal flarings.

話雖如此，我們確實相信，當你看到這些全身症狀時，尤其是，全身顯然還有其他病毒庫，我們不一定能有效地進行測量。但我們確實知道我們的藥物具有出色的組織分佈，出色的組織滲透性。我們相信，這可能使它與眾不同。這就是使我們能夠對症狀產生治療效果的原因，而我們在鼻翼燃燒中看不到太多病毒。

That makes sense. And if I could squeeze one more quick one in. Wondering if you could maybe talk a little bit more about the triglyceride and total cholesterol effects that you're seeing in terms of, I guess, how long you follow those patients and how close to their baselines, did they return. Does that imply anything in terms of how you might think about future studies in higher risk patients who may have concurrent hyperlipidemia baseline?

這就說得通了。如果我能再擠一個快一點。想知道你是否可以多談談你所看到的甘油三酯和總膽固醇的影響，我猜，你跟踪這些患者多長時間以及接近多長時間他們的基線，他們回來了嗎？這是否意味著您如何看待未來可能同時患有高脂血症基線的高風險患者的研究？

Yes, absolutely. So obviously, we'll follow patients very closely in terms of lipids going forward. But we saw within 14 days, the triglycerides had returned entirely to normal. And within 14 days, the total cholesterol was well on its way. It's a little bit delayed from the metabolic perspective, of course. So we have every reason to believe that these cholesterol changes are mild and very manageable. So yes, we think that we can monitor them and manage them pretty effectively, particularly given that this drug is for acute and not chronic use.

是的，一點沒錯。很明顯，我們將在未來的血脂方面非常密切地關注患者。但我們看到，在 14 天內，甘油三酯已完全恢復正常。並且在 14 天內，總膽固醇就在變化中。當然，從新陳代謝的角度來看，它有點延遲。所以我們有充分的理由相信這些膽固醇的變化是溫和的並且非常容易控制的。所以是的，我們認為我們可以非常有效地監測和管理它們，特別是考慮到這種藥物是用於急性而不是慢性使用。

I think the other thing that's interesting on that front is Shionogi saw some of these findings as well. And so I guess it [bakes] in with a very sort of a different chemical class. And so you could make the question is that some exposure is something that you will see with protease inhibitors, and that's an outstanding question. But I think we're all finding the stuff out as more and more protease inhibitors gather clinical information.

我認為這方面的另一件有趣的事情是 Shionogi 也看到了其中的一些發現。所以我猜它 [bakes] 與一種非常不同的化學類別。所以你可能會問，一些暴露是你會看到的蛋白酶抑製劑，這是一個懸而未決的問題。但我認為隨著越來越多的蛋白酶抑製劑收集臨床信息，我們都在尋找答案。

Also remind the folks that looking at other mechanisms, even that measuring viral load changes in the nose has not always yielded findings. I mean earlier in the pandemic, a Gilead's drug, remdesivir, failed to demonstrate viral load changes in the nose. Other people have demonstrated viral changes in the nose, but not something else, other.

還要提醒人們注意其他機制，即使測量鼻子中的病毒載量變化也不一定總能得出結果。我的意思是在大流行早期，吉利德的一種藥物瑞德西韋未能證明鼻子中的病毒載量發生了變化。其他人已經證明了鼻子的病毒變化，但不是別的，其他的。

So this is why the FDA doesn't want to use viral loads as an approvable end point. When we did look at a sub-patient population that had viral loads higher than the, I mean, 5, we did see about 0.5 log change in this still experienced patient population. So it's just getting -- I think it's just getting harder and harder to find that in this otherwise healthy standard risk patient population with the current variants in the current state of immune education that patients have.

所以這就是為什麼 FDA 不想使用病毒載量作為可批准的終點。當我們確實觀察了一個病毒載量高於 5 的亞患者群體時，我們確實看到在這個仍然有經驗的患者群體中有大約 0.5 個對數變化。所以它只是越來越 - 我認為越來越難在這個健康的標準風險患者群體中發現患者當前免疫教育狀態下的當前變異。

And it comes from the line of Roy Buchanan with JMP Securities.

它來自 JMP Securities 的 Roy Buchanan 系列。

Most have been answered. A couple of quick ones. Just I noticed that drug-drug interaction studies had completed. I know they're not the most exciting, but anything you can tell us about the drug-drug interaction profile of 235? And then just any potential alternative explanations for the lack of viral load effect. I guess maybe you guys have gone through it already, the tissue, distribution of the virus, et cetera. Does anything else you guys can think of? And then just really quickly, EDP-514, just what's the status of...

大部分都已經回答了。幾個快速的。只是我注意到藥物相互作用研究已經完成。我知道它們不是最令人興奮的，但是您能告訴我們有關 235 的藥物相互作用概況的任何信息嗎？然後是對缺乏病毒載量效應的任何潛在替代解釋。我想你們可能已經經歷過了，組織、病毒的分佈等等。大家還有什麼能想到的嗎？然後很快，EDP-514，它的狀態是什麼……

Maybe we will just focus on the first question first. So I think in relation to -- well, first of all, there's -- I think we've kind of explained what we can really tell you about viral load in the nose today. I think we've addressed that a couple of different times. No further thoughts right now certainly. And then with regards to the DDI studies that are ongoing, ritonavir has a very substantial load of baggage with it in terms of hitting all kinds of P450s and transporters and all kinds of stuff.

也許我們先關注第一個問題。所以我認為關於 - 嗯，首先，有 - 我認為我們已經解釋了我們今天真正可以告訴你的關於鼻子病毒載量的內容。我認為我們已經在不同的時間解決了這個問題。現在當然沒有進一步的想法。然後關於正在進行的 DDI 研究，利托那韋在打擊各種 P450 和轉運蛋白以及各種東西方面有很大的負擔。

So it's fair to assume that we don't -- we have nothing close to a ritonavir like profile when it comes to DDIs. So we think it will be a competitive profile going forward.

因此，可以公平地假設我們沒有——當涉及到 DDI 時，我們沒有任何類似利托那韋的資料。因此，我們認為這將是一個具有競爭力的形象。

I'm sorry, you can go on to the next question, if you have one, a brief one. I think you said 514, if you're still on, Roy? If not, maybe you'll come back in the queue.

抱歉，您可以繼續下一個問題，如果有的話，一個簡短的問題。我想你說 514，如果你還在，羅伊？如果沒有，也許您會回到隊列中。

Yes, sorry, 514. Just the status of searching for additional candidates to combine with that. Have you considered out-licensing 514 in addition to in-licensing something else?

是的，抱歉，514。只是正在尋找其他候選人以與之結合的狀態。除了向內授權其他東西外，您是否考慮過向外授權 514？

I think we'd be open-minded in any way to bring together a marriage of the right combination. And to that end, I think there's more data readouts that are going to come out in the area of hep B. It's still a little tricky to know exactly what that right combination might be for us or anybody else.

我認為我們會以任何方式開明地組建正確組合的婚姻。為此，我認為在乙肝領域將會有更多的數據讀出。要確切地知道對我們或其他任何人來說正確的組合是什麼仍然有點棘手。

So our plan is to continue to watch other data sets, think about other mechanisms, follow the literature closely and looking at external assets that could be combined, and we're agnostic as to whether we export our asset or import another. But we just want to make sure it's the right combination.

所以我們的計劃是繼續觀察其他數據集，考慮其他機制，密切關注文獻並查看可以組合的外部資產，我們不知道我們是輸出我們的資產還是輸入另一個資產。但我們只是想確保它是正確的組合。

Again, it comes from the line of Akash Tewari with Jefferies.

同樣，它來自 Jefferies 的 Akash Tewari 系列。

This is Amy on for Akash. So Shionogi also had a high prior vaccinated plus seropositive patients in their Phase II trials in the range of mid- to high-80% range and believe they showed 0.5 log to 1 log benefit over on viral load over placebo. What are the major differences between your Phase II and prior COVID antivirals that would attribute to a potentially more aggressive placebo?

這是阿卡什的艾米。因此，Shionogi 在他們的 II 期試驗中也有較高的先前接種疫苗和血清反應陽性的患者，範圍在 80% 的中高範圍內，並且相信他們在病毒載量方面比安慰劑顯示出 0.5 log 到 1 log 的益處。您的 II 期和之前的 COVID 抗病毒藥物之間的主要差異是什麼，這些差異可能歸因於可能更具攻擊性的安慰劑？

I was going to say either 1 of us can take that. The Shionogi study was run in Japanese patients, Asian patients, clearly, with -- at a time that they had less exposure to natural infection. So we would expect a much -- and I don't have these data for either population yet, but we'd expect a much lower rates of nucleocapsid positivity among that population than among our population.

我想說我們中的任何一個都可以接受。 Shionogi 研究是在日本患者、亞洲患者中進行的，很明顯，在他們接觸自然感染的時間較少。所以我們期望很多——我還沒有這兩個人群的這些數據，但我們預計該人群的核衣殼陽性率比我們的人群低得多。

So we can see here in the year 2023 again, that populations have very high hybrid immunity. So it's challenging to find any patients much less a population that has a baseline viral load of 7 logs like Shionogi did in order to show that they dropped in viral load. I don't know if, Tara, you had anything to add to that?

所以我們可以在 2023 年再次看到，人群具有非常高的混合免疫力。因此，很難找到像 Shionogi 那樣基線病毒載量為 7 個對數的患者，以證明他們的病毒載量下降了。塔拉，我不知道你有什麼要補充的嗎？

Yes. I think the terminology of seropositivity is somewhat heterogeneous in terms of what provides that seropositivity whether it's through vacation or natural infection. And we're seeing data coming out of the CDC now that in the U.S., the percentage of people with hybrid immunity, meaning they have had it through both vaccination and/or natural infection is increasing, probably provides somewhat better immunity, and that's probably borne out in the difference in baseline viral load between the 2 studies. We know that, that is a major factor in seeing these viral load declines. So yes, the Shionogi study had a baseline viral load of 7, which was 2 logs higher than what we had in SPRINT.

是的。我認為血清陽性的術語在提供血清陽性（無論是通過假期還是自然感染）方面有些不同。我們現在看到 CDC 的數據表明，在美國，具有混合免疫力的人的百分比，這意味著他們通過疫苗接種和/或自然感染獲得混合免疫力的人正在增加，可能提供更好的免疫力，這可能是證實了兩項研究之間基線病毒載量的差異。我們知道，這是病毒載量下降的一個主要因素。所以是的，Shionogi 研究的基線病毒載量為 7，比我們在 SPRINT 中的高 2 個對數。

And with that just as an appendix to the slide deck that we presented today, which again should be on our website soon if it's not already there, has a little bit of supplemental information about seropositivity and also percent of patients or percent of the population that have been previously infected as measured by nucleocapsid antibodies. So I think those trends are pretty interesting. So if you extrapolate them backward into Japan at that time in place, I think you would get a sense that it likely was a bit of a different patient population.

就像我們今天展示的幻燈片的附錄一樣，它應該很快再次出現在我們的網站上，如果它還沒有的話，它有一些關於血清陽性的補充信息，以及患者的百分比或人口的百分比根據核衣殼抗體的測量，先前已被感染。所以我認為這些趨勢非常有趣。因此，如果你將它們逆推到當時的日本，我想你會感覺到這可能是一個不同的患者群體。

It comes from the line of Liisa Bayko with Evercore ISI.

它來自 Evercore ISI 的 Liisa Bayko 系列。

I guess first question, do you think showing an RNA change is important in terms of partnering discussions, like how important is that? I know you've got symptoms, and that's going to be important for Phase III, but just wondering how much of a -- how important that would be to potential partnering discussions?

我想第一個問題，你認為在合作討論方面顯示 RNA 變化是否重要，比如這有多重要？我知道你有症狀，這對第三階段很重要，但只是想知道這對潛在的合作討論有多重要？

Well, I mean, again, you have to look at the totality of any data set. I think at the end of the day, people want to make sure you have sort of signs of a registration path forward and symptoms certainly help to provide that. The viral load data, I mean, again, it's the -- again, it was never powered on virology.

好吧，我的意思是，你必須再次查看任何數據集的整體。我認為歸根結底，人們希望確保您有某種跡象表明可以前進，而症狀肯定有助於提供這種跡象。病毒載量數據，我的意思是，再一次，它從未在病毒學上得到支持。

And it was surprising to us when we saw the placebo, especially when we laid our placebo against every other placebo that's been done in a comparable study, just how disadvantaged our patient population treatment arm was in terms of demonstrating that. But it's -- I think it's a sign of the times in terms of, again, sort of immune training of patients as well as the evolution of the virus.

當我們看到安慰劑時，特別是當我們將安慰劑與在一項可比研究中進行的所有其他安慰劑進行對比時，我們感到很驚訝，我們的患者群體治療組在證明這一點方面處於多麼不利的地位。但它——我認為這是時代的標誌，再一次，在某種程度上對患者進行免疫訓練以及病毒的進化。

Okay. And so do you think if you were able to tap into some of these other viral reservoirs and I know that's not possible to do, but just theoretically, you would see the change? Or I guess I was trying to make the linkage between like a change in symptoms and actual viral reduction, whether or not you can see it as a different -- detects -- I understand it's a different question.

好的。所以你認為如果你能夠利用這些其他病毒庫中的一些，我知道這是不可能的，但只是理論上，你會看到變化嗎？或者我想我是想在症狀的變化和實際的病毒減少之間建立聯繫，無論你是否可以將其視為不同的——檢測——我知道這是一個不同的問題。

Yes. No. I mean I suspect you would, but again, accessing those compartments, whether it's the heart, the liver, lungs, other tissues. These are reservoirs. I mean the virus has been found in the brain, right? So I mean, there's all kinds of places you could go and look but I think that, that's a -- it becomes a challenge. Obviously, sort of in the long COVID, for example, I mean, long COVID, that's probably a subset, maybe even a good subset of patients out there that still have virus fermenting in various other tissues.

是的。不，我的意思是我懷疑你會再次進入那些隔間，無論是心臟、肝臟、肺還是其他組織。這些是水庫。我的意思是在大腦中發現了病毒，對嗎？所以我的意思是，有各種各樣的地方你可以去看看，但我認為，這是一個 - 它成為一個挑戰。顯然，在長 COVID 中，例如，我的意思是，長 COVID，這可能是一個子集，甚至可能是仍然有病毒在各種其他組織中發酵的患者的一個很好的子集。

It might not be the nose. The folks continue to swab negatively. But when you look at some of the symptoms and the drivers of some of the symptoms that are exhibited in long COVID, there are very likely patient populations that could have reservoirs of that. And that's something we're thinking hard about, are there interesting ways to go interrogate that and sort that out. But too early to call whether or not we would do sort of a smaller Phase II study to explore and exploit some of those kinds of reservoirs of virus with 235.

可能不是鼻子。人們繼續消極地擦拭。但是，當您查看長 COVID 中表現出的某些症狀和某些症狀的驅動因素時，很可能患者群體中可能存在這種症狀。這是我們正在認真思考的事情，是否有有趣的方法來審問並解決這個問題。但現在就斷言我們是否會進行某種規模較小的 II 期研究來探索和利用 235 的某些病毒庫還為時過早。

Okay. And does, I guess, natural immunity or vaccination disproportionately reduced virus in the nasal passage? Or why would it be different, I guess, than other reservoirs?

好的。我猜想，自然免疫或疫苗接種是否會不成比例地減少鼻道中的病毒？或者我猜為什麼它會與其他水庫不同？

Liisa, I think that's a good question. Certainly, hybrid immunity, we think from at least some of the data that's out there provides better -- could provide additional protection. The nose is where the virus first enters and then continues to spread and replicate in other parts of the body, and that just appears to be where it's being cleared. And patients have mucosal immunity built up that can contribute to the clearance at least in the nasal compartment.

麗莎，我認為這是個好問題。當然，混合免疫，我們認為至少從現有的一些數據來看可以提供更好的保護——可以提供額外的保護。鼻子是病毒首先進入的地方，然後繼續在身體的其他部位傳播和復制，而這似乎正是病毒被清除的地方。患者的粘膜免疫力得到增強，至少可以促進鼻腔的清除。

And particularly -- yes, I was just going to say, Liisa, particularly associated with natural infection. You get the mucosal immunity that you wouldn't not necessarily get to the same degree with vaccination.

特別是 - 是的，我只是想說，Liisa，特別是與自然感染有關。您獲得的粘膜免疫力不一定能達到與接種疫苗相同的程度。

Okay. That makes sense. Yes, I get that. And then -- my associate, Schimmer, who's sitting with me here raised a good point about rebounds. I think that was something that you were going to be exploring. Could you comment at all on if you've seen any difference in rebounds, if you check for that or if you will be checking or what's the plan there?

好的。這就說得通了。是的，我明白了。然後——我的同事 Schimmer，他和我坐在一起，就籃板提出了一個很好的觀點。我認為那是你要探索的東西。你能不能評論一下你是否看到籃板有什麼不同，你是否會檢查，或者你是否會檢查，或者那裡有什麼計劃？

Yes, nothing yet, Liisa. We have looked grossly and haven't seen differences between arms and we're working on getting those analyses done properly.

是的，還沒有，麗莎。我們粗略地觀察了一下，沒有看到武器之間的差異，我們正在努力正確地完成這些分析。

Okay. And then just as we think about kind of next steps, are those predicated on finding a partnership? Or is that something you'd be willing to take on yourself, like how are we thinking about the gating factors for developing...

好的。然後就在我們考慮下一步的時候，這些是否以尋找合作夥伴為前提？或者是您願意自己承擔的事情，例如我們如何考慮發展的門控因素......

I don't think any Phase II study would be gating in a different population like long COVID or something like that, that's not gated. And in fact, it's built into the financial guidance that Paul talked about. We would be able to do that and still have cash into calendar '26. But I do believe that as it relates to Phase III, these are bigger, much more expensive trials that ultimately, I think you do want to have a partner engaging on the trial design, how you would set those up and then push them forward with dispatch and importantly, gaining a launch partner.

我認為任何 II 期研究都不會在不同的人群中進行門控，比如長 COVID 或類似的東西，沒有門控。事實上，它已內置於 Paul 談到的財務指南中。我們將能夠做到這一點，並且仍然有現金進入 26 年日曆。但我確實相信，由於它與 III 期相關，這些是更大、更昂貴的試驗，最終，我認為你確實希望有一個合作夥伴參與試驗設計，你將如何設置這些，然後推動它們向前發展派遣，重要的是，獲得發射合作夥伴。

We're not -- we've never planned on commercializing in COVID, but rather to do -- we've said this since the beginning of the time, our plan has always been to find a late stage partner and commercialization launch partner for this. So I think that is going to be our current plan for progressing Phase III.

我們不是——我們從未計劃將 COVID 商業化，而是打算——我們從一開始就說過，我們的計劃一直是為尋找後期合作夥伴和商業化啟動合作夥伴這。所以我認為這將是我們目前推進第三階段的計劃。

And it comes from the line of Brian Skorney with Baird.

它來自 Brian Skorney 和 Baird 的血系。

Question on -- I'm just wording in the press release as it relates to sort of the prespecified protocol. You talked about total symptoms score and then you talked about 14 targeted COVID-19 symptoms. Can you just help me understand, are these different arrays of symptoms that you're evaluating here? And when I pull up the protocol that's posted on clinicaltrials.com #3 and 4, the ones that relate to symptoms, let me say, proportion of COVID-19 symptoms and change from baseline in COVID-19 symptoms. Is that the TSS? Or is that the 14 targeted COVID-19 symptoms?

問題——我只是在新聞稿中措辭，因為它與某種預先指定的協議有關。你談到了總症狀評分，然後談到了 14 種有針對性的 COVID-19 症狀。你能幫我理解一下，你在這裡評估的是這些不同的症狀嗎？當我提取在 clinicaltrials.com #3 和 4 上發布的協議時，與症狀相關的協議，讓我說，COVID-19 症狀的比例以及 COVID-19 症狀相對於基線的變化。是TSS嗎？還是這 14 種針對 COVID-19 的症狀？

It's the same. Yes. So the way we get it is we have the 14 symptoms and each 1 is graded by the patient on a scale of 0, 1, 2 or 3 and then add up the score, and that's the score. So total symptom score and all 14 symptoms, we mean to be the same thing. Does that help?

一樣的。是的。所以我們得到它的方法是我們有 14 種症狀，每 1 種症狀由患者按照 0、1、2 或 3 的等級進行評分，然後將分數相加，這就是分數。所以總症狀評分和所有 14 種症狀，我們的意思是一樣的。這有幫助嗎？

I guess I'm having trouble understanding the line where you say, well, no differences observed in time to improvement of 14 targeted COVID-19 symptoms. Is that basically there's no difference in observed time to improvement in the TSS? I don't really understand the distinction which we look at.

我想我很難理解你說的那句話，好吧，在改善 14 種目標 COVID-19 症狀的時間上沒有觀察到差異。基本上觀察到的 TSS 改進時間沒有差異嗎？我真的不明白我們所看到的區別。

Oh, I see what you mean. So we have a different evaluation for the time to improvement. So for the time to improvement, you have to have all of your symptoms either absent or mild. And anything that was present or anything that was absent at baseline needs to still be absent, and that has to be the case for 2 days.

哦，我明白你的意思了。所以我們對改進的時間有不同的評估。因此，為了改善時間，您必須讓所有症狀都消失或輕微。任何在基線存在或不存在的東西都需要仍然不存在，並且必須持續 2 天。

And that has to be the case with all 14 symptoms, right? So that's what I mean by time to improvement of all 14 symptoms. And then when I say to take a selected group of those symptoms, then that's looking at just those symptoms specifically. And the selected symptoms have given us a greater degree of power to detect the difference with placebo because those symptoms seem to persist more in placebo and go away more quickly with EDP-235.

所有 14 種症狀都必須如此，對嗎？所以這就是我所說的改善所有 14 種症狀的時間。然後當我說要選擇一組這些症狀時，那就是專門研究這些症狀。選定的症狀使我們能夠更大程度地檢測與安慰劑的差異，因為這些症狀似乎在安慰劑中持續時間更長，而在 EDP-235 中消失得更快。

And it comes from the line of Ed Arce with H.C. Wainwright.

它來自 Ed Arce 和 H.C.溫賴特。

It's Thomas Yip asking a couple of questions for Ed. So just trying to figure with COVID-19 entering endemic phase, what the estimate could be the market opportunity, both in U.S. and ex-U.S. markets and especially given how Pfizer and Moderna latest performance with the inventory write-down that they just reported.

我是 Thomas Yip 向 Ed 問了幾個問題。因此，只是想弄清楚 COVID-19 進入流行階段，估計可能是美國和美國以外的市場機會。市場，特別是考慮到輝瑞和 Moderna 的最新表現以及他們剛剛報告的庫存減記。

Sorry, could you repeat? I mean, you're asking what the market opportunity is for COVID therapeutics?

抱歉，你能重複一遍嗎？我的意思是，您是在問 COVID 療法的市場機會是什麼？

Yes, because as COVID-19 has transitioned from a pandemic and to an endemic phase and also demand for treatment as well. How do you look at the COVID-19 treatment market going forward?

是的，因為隨著 COVID-19 已經從大流行過渡到流行階段，也需要治療。您如何看待未來的 COVID-19 治療市場？

Sure. So, I think what we can look at is what the guidance has been provided in terms of revenue from the drugs that are currently available, looking at remdesivir, molnupiravir and Paxlovid, I think combined, it's around $10 billion market size.

當然。所以，我認為我們可以看看就目前可用藥物的收入方面提供的指導，看看 remdesivir、molnupiravir 和 Paxlovid，我認為加起來，它的市場規模約為 100 億美元。

And so if you look at Pfizer's information that they just released on their quarterly revenue, they were guiding to $8 billion in revenue to 2023, and they actually reported $4 billion just in Q1. So we do believe that there is a good market and still a lot of use for antivirals in this indication.

因此，如果你看一下輝瑞公司剛剛發布的季度收入信息，他們預計到 2023 年的收入將達到 80 億美元，而他們實際上僅在第一季度就報告了 40 億美元。因此，我們確實相信抗病毒藥物在這個適應症中有一個很好的市場並且仍然有很多用途。

Thank you for the essential information. Perhaps 2 more questions from us. You mentioned in the press release that a long COVID will be a possibility. How does that ultimately compare to COVID? And are there any endpoints in the Phase II study that you grant that could suggest potential in the long COVID?

感謝您提供重要信息。也許我們還有 2 個問題。您在新聞稿中提到，有可能出現較長的 COVID。這最終與 COVID 相比如何？您授予的 II 期研究中是否有任何終點可以表明長期 COVID 的潛力？

Yes. Well, long COVID is very different than acute COVID. It has different clinical manifestations and a diverse patient population. That said, there are maybe common elements in a subset that could be a patient population that could benefit from an antiviral.

是的。好吧，長 COVID 與急性 COVID 有很大不同。它具有不同的臨床表現和多樣化的患者人群。也就是說，子集中可能存在共同元素，這些元素可能是可以從抗病毒藥物中受益的患者群體。

And so again, as I mentioned a minute ago, we're going to look and think about that and any plans for any next study where we to do 1 in long COVID, we'll design or give further details around the design at that point. So it's premature for us to comment on it today.

因此，正如我一分鐘前提到的，我們將再次研究並考慮這一點，以及我們在長 COVID 中進行 1 的任何下一項研究的任何計劃，我們將設計或提供有關該設計的更多細節觀點。因此，我們今天對此發表評論還為時過早。

Got it. Just one last one from us with the 323 -- switching gears to 323 with the Phase I data expected next month. Can you remind us what is -- what will be the next step as to the challenge study? And if so, can you give us some preliminary thoughts on what that study will look like?

知道了。我們的 323 只是最後一個——切換到 323，預計下個月將獲得第一階段數據。您能否提醒我們挑戰研究的下一步是什麼？如果是這樣，你能給我們一些關於這項研究的初步想法嗎？

Yes. So 323 again, our polymerase inhibitor, super potent, great clinical PK and safety, took it into Phase I study in healthy, MAD, SAD study. That's the data that we'll report out next month. Top line would have safety, tolerability and PK. From that, it will allow us to derive what sorts of multiples we have of protein adjusted EC90, which are the hallmarks of efficacy surrogates that you can measure in a Phase I study even in healthy patient population.

是的。所以 323 再次，我們的聚合酶抑製劑，超強效，出色的臨床 PK 和安全性，將其納入健康、MAD、SAD 研究的 I 期研究。這是我們將在下個月報告的數據。頂線將具有安全性、耐受性和 PK。由此，我們可以推導出蛋白質調整後的 EC90 的倍數類型，這是您可以在 I 期研究中甚至在健康患者群體中測量的療效替代指標的標誌。

So I think the logical next step, assuming positive data there would be a challenge study. And from that standpoint, we've had a very successful challenge study for EDP-938 in the past. Again, one could look at that to get insights as to how we might be thinking about progressing 323, assuming positive data. And we'll have more details on data and next steps when we release it next month.

所以我認為下一步是合乎邏輯的，假設數據是積極的，那將是一項挑戰研究。從這個角度來看，我們過去對 EDP-938 進行了非常成功的挑戰研究。同樣，人們可以看看它，以了解我們如何考慮推進 323，假設數據是積極的。下個月發佈時，我們將提供有關數據和後續步驟的更多詳細信息。

And it comes from the line of Roanna Ruiz with SVB Securities.

它來自 Roanna Ruiz 與 SVB Securities 的關係。

Some of my questions were already asked, but maybe a quick one on 235. I was curious if your outlook on time to possible approval for that asset has changed at all? Especially considering the Phase III and possibly an addition Phase II that you might run?

我的一些問題已經被問到，但可能是 235 上的一個快速問題。我很好奇你對可能批准該資產的時間的看法是否完全改變了？特別是考慮到第三階段和可能運行的第二階段？

Well, again, a Phase II would be supportive perhaps of a different indication. I think the wildcard there is in the context of a partner. I mean, obviously, one of the reasons we're seeking a partner would be the potentially the time to approval could be accelerated by the strength and resources of a global pharma partner helping us to execute. So yes, I think right now, I would assume that it's going to be a lot driven by a partner in terms of moving that time either forward or backward, let's see.

好吧，第二階段可能會支持不同的適應症。我認為通配符存在於合作夥伴的背景下。我的意思是，很明顯，我們正在尋找合作夥伴的原因之一是，通過幫助我們執行的全球製藥合作夥伴的實力和資源，可能會加快批准時間。所以是的，我認為現在，我認為在向前或向後移動時間方面，合作夥伴將在很大程度上推動它，讓我們看看。

Understood. And then last one from me. I was curious, in the individuals where you saw elevated cholesterol or triglycerides, was there any trends or commonalities among them that could help you identify them proactively in some of the data that you've seen so far?

明白了。然後是我的最後一個。我很好奇，在你看到膽固醇或甘油三酯升高的個體中，他們之間是否有任何趨勢或共性可以幫助你在你目前看到的一些數據中主動識別它們？

Thanks, Roanna. So nothing specifically. We've gone through it at a population basis. There weren't any substantial outliers who didn't already have really high lipids at baseline. So we haven't detected anything specific or any patterns in terms of outliers. It was just kind of a general population trend.

謝謝，羅安娜。所以沒什麼特別的。我們已經在人口基礎上完成了它。沒有任何實質性的異常值在基線時不具有非常高的脂質。所以我們沒有檢測到異常值方面的任何特定或任何模式。這只是一種普遍的人口趨勢。

And it comes from the line of Hannah Adeoye with JPMorgan.

它來自摩根大通的 Hannah Adeoye。

This is Hannah on for Eric Joseph. So just acknowledging that there are a number of details left to be finalized as it relates to a pivotal study design, given the fact that you have observed treatment benefit in non-high-risk mild to moderate COVID patients. How are you thinking about the target patient population for the therapy?

這是埃里克約瑟夫的漢娜。因此，鑑於您已經觀察到非高危輕度至中度 COVID 患者的治療獲益，因此僅承認還有許多細節有待最終確定，因為它與關鍵研究設計有關。您如何考慮治療的目標患者人群？

And then just secondly, with Pfizer announcing plans to develop a next-gen COVID antiviral to Paxlovid that won't be using ritonavir boosting. Just wanted to get your sense of how you're thinking about the impact that might have and it might have on bearing potential partnership discussions for EDP-235?

其次，輝瑞公司宣布計劃開發下一代 COVID 抗病毒藥物來對抗 Paxlovid，該藥物將不使用利托那韋促進劑。只是想了解您如何考慮可能產生的影響以及它可能對 EDP-235 的潛在合作夥伴關係討論產生的影響？

Yes. No, I mean, we've always assumed there are going to be multiple players in the COVID space. I mean that's not different than. So I think with regards to Pfizer's next molecule, we'll see what data they can achieve with that one. I mean we know what they have with Paxlovid. I think we know what Shionogi has.

是的。不，我的意思是，我們一直假設 COVID 領域會有多個參與者。我的意思是那和沒有什麼不同。所以我認為關于輝瑞的下一個分子，我們將看看他們可以用那個分子獲得什麼數據。我的意思是我們知道他們對 Paxlovid 有什麼看法。我想我們知道 Shionogi 有什麼。

And apart from Pfizer and Shionogi, I would say, we've got the other one. So at least right now, the space, I think, is still favorable given the size of the market and what a protease can add to the overall treatment landscape in COVID. So -- I'm sorry, what was the other part of your question?

除了輝瑞和 Shionogi，我想說，我們還有另一個。所以至少現在，我認為，考慮到市場規模以及蛋白酶可以為 COVID 的整體治療前景增加什麼，這個空間仍然是有利的。那麼 - 抱歉，您問題的另一部分是什麼？

Just your thoughts on targeted patient population for the therapy since the Phase I study most on high risk.

自第一階段研究以來，您對治療的目標患者人群的想法是高風險的。

Yes. No, the patient population. I mean, again, I think we're thinking broadly about it, standard risk, the high-risk patient population, which fits sort of a different risk profile. Prophylaxis long COVID, I mean there's nothing that I would see that would necessarily be not to be considered in a broad development program.

是的。不，是患者群體。我的意思是，我認為我們正在廣泛考慮它，標準風險，高風險患者群體，它適合不同的風險狀況。預防性長期 COVID，我的意思是，在廣泛的開發計劃中，我認為沒有什麼是必然不被考慮的。

And with that, I'll turn the call back to Jennifer Viera for final comments.

然後，我將把電話轉回 Jennifer Viera 以徵求最終意見。

Thank you, everyone, for joining us today. Please note that we will have these slides on our website as well as our updated corporate presentation. If you have any additional questions, feel free to contact us by e-mail or call the office. Thanks, and have a great night.

謝謝大家今天加入我們。請注意，我們將在我們的網站上提供這些幻燈片以及更新的公司介紹。如果您有任何其他問題，請隨時通過電子郵件與我們聯繫或致電辦公室。謝謝，祝你有個愉快的夜晚。

Thank you, ladies and gentlemen, for participating in today's conference. You may now disconnect.

女士們，先生們，感謝你們參加今天的會議。您現在可以斷開連接。