Enanta Pharmaceuticals Inc (ENTA) 2024 Q2 法說會逐字稿

Good afternoon and welcome to Enanta Pharmaceuticals fiscal second quarter financial results conference call. (Operator Instructions) Please be advised that this call is being recorded.

下午好，歡迎參加 Enanta Pharmaceuticals 財年第二季財務業績電話會議。（操作員指示）請注意，此通話正在錄音。

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

現在我想將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 financial results was issued this afternoon and is available on our website.

謝謝接線員，也謝謝大家今天下午加入我們。我們第二財季財務業績的新聞稿已於今天下午發布，可在我們的網站上查閱。

Making remarks on today's call are Dr. Jay Luly, President and Chief Executive Officer; and Paul Mellett, our Chief Financial Officer; Dr. Scott Rottinghaus, our Chief Medical Officer; and Dr. Tara Kieffer, our Chief Product Strategy Officer, will be available during the Q&A portion of the call.

在今天的電話會議上發言的有總裁兼執行長 Jay Luly 博士、財務長 Paul Mellett、首席醫療官 Scott Rottinghaus 博士和首席產品策略官 Tara Kieffer 博士，他們將在電話會議的問答環節發言。

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

在我們開始正式發言之前，我們想提醒您，我們將做出前瞻性的陳述。這些聲明可能包括我們有關研發管道和財務預測的計劃和期望。所有這些聲明都涉及我們無法控制的某些假設和風險，可能導致我們的實際發展和結果與這些聲明有重大差異。我們向美國證券交易委員會提交的最新 10-K 表格和其他定期報告中描述了這些風險。Enanta 不承擔更新本次電話會議期間所作任何前瞻性陳述的義務。

I'd now like to turn the call over to Dr. Jay Luly, President and CEO. Jay?

現在我想將電話轉給總裁兼執行長傑伊·盧利博士。傑伊？

Thank you, Jennifer, and good afternoon, everyone. Throughout 2024, Enanta has remained squarely focused on advancing our virology and immunology pipeline to bring important oral therapeutics to market. Our commitment to developing treatments for areas of high unmet need is driven by our mission to transform patients' lives with curative therapies. And we are determined to achieve our milestones to drive near and long-term shareholder value to fulfill this mission. Our focus is critical as we approach meaningful inflection points with the potential to develop the first antiviral treatment for RSV.

謝謝你，詹妮弗，大家下午好。在整個 2024 年，Enanta 始終專注於推進我們的病毒學和免疫學管道，以將重要的口服療法推向市場。我們致力於開發針對未滿足需求領域的治療方法，我們的使命是透過治癒療法改變患者的生活。我們決心實現我們的里程碑，推動近期和長期股東價值，完成這項使命。我們的重點至關重要，因為我們正接近有意義的轉折點，有可能開發出首個針對 RSV 的抗病毒治療方法。

With that, today, I'll begin with an overview of our programs beginning with our respiratory syncytial virus or RSV programs, and then discuss our immunology program for chronic spontaneous urticaria or CSU. As a reminder, RSV is a severe respiratory infection associated with significant morbidity and mortality that can cause serious disease in infants, children and other high-risk populations including the elderly and individuals with congestive heart failure, chronic obstructive pulmonary disease, asthma or other high-risk conditions. Despite the availability of prophylactic options such as vaccines and monoclonal antibodies. There's a clear need for a safe and effective oral RSV antiviral treatments.

今天，我將首先概述我們的項目，從呼吸道合胞病毒或 RSV 項目開始，然後討論我們針對慢性自發性蕁麻疹或 CSU 的免疫學項目。提醒一下，RSV 是一種嚴重的呼吸道感染，具有較高的發病率和死亡率，可導致嬰兒、兒童和其他高風險族群（包括老年人和患有充血性心臟衰竭、慢性阻塞性肺病、氣喘或其他高風險疾病的個人）患上嚴重疾病。儘管有疫苗和單株抗體等預防手段。顯然需要一種安全有效的口服 RSV 抗病毒治療方法。

Adoption of vaccines has been sub-optimal and breakthrough infections still occur. Additionally, pediatric monoclonal antibodies only provide passive immunity for a few months and not long term protection against the infection. With this clear need, we have developed a broad clinical program that has the potential to enable multiple opportunities to treat our RSV. The RSV pipeline includes the most advanced clinicals replication inhibitors, zelicapavir, formerly known as EDP-938, an N-protein inhibitor as well as EDP-323, an L. protein inhibitor.

疫苗的採用情況並不理想，仍會出現突破性感染。此外，兒科單株抗體僅提供幾個月的被動免疫，而無法提供長期的感染保護。鑑於這一明確的需求，我們制定了一項廣泛的臨床計劃，該計劃有可能為治療我們的 RSV 提供多種機會。RSV 管道包括最先進的臨床複製抑制劑、澤利卡帕韋（以前稱為 EDP-938，一種 N 蛋白抑制劑）以及 EDP-323，一種 L 蛋白抑制劑。

Zelicapavir is currently being studied in high-risk patient populations in two Phase 2 studies, RSVPEDS and RSVHR. RAVPEDS is a first in pediatrics, Phase 2 randomized double-blind placebo-controlled study in hospitalized, a non hospitalized RSV patients aged 28 days to 36 months.

目前，正在兩項 2 期研究（RSVPEDS 和 RSVHR）中針對高風險患者群體研究澤利卡帕韋。RAVPEDS 是兒科中首次進行的 2 期隨機雙盲安慰劑對照研究，研究對象為年齡 28 天至 36 個月的住院和非住院 RSV 患者。

The study, which will enroll approximately 90 patients is being conducted in two parts. As this is a first pediatric study, the objective of the first part is to evaluate the safety and pharmacokinetics of zelicapavir in multiple ascending doses to select the optimal dose for each age group. The second part of this study will evaluate the antiviral activity of zelicapavir at the selected dose and virology on symptom scores will be assessed throughout the treatment duration.

研究將招募約 90 名患者，分為兩部分進行。由於這是一項兒科研究，第一部分的目的是評估西利卡帕韋在多個遞增劑量下的安全性和藥物動力學，以選擇每個年齡組的最佳劑量。本研究的第二部分將評估所選劑量的西利卡帕韋的抗病毒活性，並在整個治療期間評估症狀評分的病毒學。

This study was designed as a small proof of concept in pediatric patients to show a trend toward improved virology metrics for zelicapavir compared to placebo and to give confidence to move forward efficiently into larger registrational studies. A key objective of this study is to show improvement in virology endpoints in patients on zelicapvir compared to placebo, sufficient to allow us to advance into Phase 3.

這項研究旨在對兒科患者進行小規模的概念驗證，以顯示與安慰劑相比，西利卡帕韋的病毒學指標呈改善趨勢，並為有效推進更大規模的註冊研究提供信心。本研究的一個主要目標是顯示服用西利卡韋的患者的病毒學終點與服用安慰劑的患者的病毒學終點相比有所改善，足以讓我們進入第 3 階段。

Currently, we have partially enrolled the last age cohort, 20 patients in part two of the study. As this cohort can only enroll patients 28 days to six months of age. The eligible population is narrower, and we will need to continue to recruit in the Southern Hemisphere as we monitor the RSV season in the Southern Hemisphere, we anticipate reporting data from this study in the second half of 2024.

目前，我們已經招募了最後一個年齡組，研究第二部分的 20 名患者。因為該隊列只能招募年齡在 28 天至 6 個月之間的患者。符合條件的人群較窄，我們需要繼續在南半球招募，同時監測南半球的呼吸道合胞病毒季節，我們預計在 2024 年下半年報告這項研究的數據。

Our SVHR. is a Phase 2 randomized double-blind placebo-controlled study of approximately 180 adults with RSV infection who are at high risk of complications, including the elderly those with congestive heart failure, chronic obstructive pulmonary disease or asthma.

我們的 SVHR 是一項 2 期隨機雙盲安慰劑對照研究，研究對象為約 180 名感染 RSV 且併發症風險較高的成年人，包括患有充血性心臟衰竭、慢性阻塞性肺病或氣喘的老年人。

The primary endpoint for RSVHR is time to resolution of RSV, lower respiratory tract disease symptoms as assessed by the respiratory infection intensity and Impact questionnaire symptom scale. Secondary endpoints include additional clinical efficacy measures and antiviral activity compared to placebo, pharmacokinetics and safety of zelicapavir.

RSVHR 的主要終點是 RSV 消退的時間，下呼吸道疾病症狀透過呼吸道感染強度和影響問卷症狀量表進行評估。次要終點包括與安慰劑相比的額外臨床療效測量和抗病毒活性、西利卡帕韋的藥物動力學和安全性。

The primary objective of this study is to show an improvement in time to symptom resolution. Given the study was designed to be a small Phase 2 proof of concept study, it is powered based on a 50% reduction in symptom resolution. However, as there are no data showing a statistically significant effect on symptoms in community acquired RSV adult population with which to benchmark this reduction likely represents a high bar. Therefore, directional efficacy data that is clinically meaningful would provide us with conviction to move directly into Phase 3.

本研究的主要目的是顯示症狀緩解時間的改善。鑑於該研究被設計為一項小型第 2 期概念驗證研究，其依據是症狀緩解率降低 50%。然而，由於沒有數據顯示對社區獲得性呼吸道合胞病毒成年人群的症狀有統計上顯著的影響，因此這種減少可能代表著一個很高的標準。因此，具有臨床意義的定向療效數據將使我們有信心直接進入第 3 階段。

Enrollment is progressing, and we will provide additional guidance on the RSVHR study is the southern hemisphere RSV season evolves. Also ongoing in our RSV portfolio is the Phase 2 challenge study of EDP-323, which is in development as once a daily oral treatment for RSV. In this randomized, double-blind placebo-controlled study up to 114 healthy adult subjects will be infected with RSV and then randomized one to one to one to receive once daily dosing of either 600 milligrams of EDP-323, 200 milligrams of EDP-323 with a loading dose of 600 milligrams on the first day or placebo for five days.

招募工作正在進行中，隨著南半球 RSV 季節的發展，我們將為 RSVHR 研究提供額外指導。我們的 RSV 產品組合中正在進行的還有 EDP-323 的 2 期挑戰研究，該藥物正在開發為 RSV 的每日一次口服治療藥物。在這項隨機、雙盲、安慰劑對照研究中，多達 114 名健康成年受試者將感染 RSV，然後一對一隨機分配接受每日一次劑量的 EDP-323 600 毫克、200 毫克 EDP-323（第一天的負荷劑量為 600 毫克）或安慰劑，持續五天。

Primary and secondary outcome measures include safety changes in viral load measurements and changes in symptoms from baseline. The development of EDP-323 is supported by positive Phase 1 results in which the drug demonstrated favorable safety, tolerability, and pharmacokinetics in healthy volunteers. We anticipate reporting data from this challenge study in the third quarter of 2024. We believe either zelicapavir or EDP. three, two three would be effective as a monotherapy because they do not have cross resistance.

主要和次要結果測量包括病毒量測量的安全性變化和症狀相對於基線的變化。EDP​​-323 的開發得到了第 1 階段積極結果的支持，該藥物在健康志願者中表現出良好的安全性、耐受性和藥物動力學。我們預計將於 2024 年第三季報告此項挑戰研究的數據。我們相信，無論是西利卡帕韋或 EDP.3、2、3，作為單一療法都是有效的，因為它們沒有交叉抗藥性。

We could also potentially use them in combination to broaden the treatment window or expand the eligible patient population to harder to treat patients. Also in respiratory virology data from SPRINT, our Phase 2 study of EDP-235, a 3CL protease inhibitor was presented in April at the ECCMID conference, formerly known as ECCMID. We are pleased to present this comprehensive data package and at scientific forum for the first time as a reminder, we will conduct any future COVID-19 work in the context of the collaboration.

我們也可以將它們結合起來使用，以擴大治療窗口或將符合條件的患者群體擴大到更難治療的患者。此外，在 SPRINT 的呼吸道病毒學數據中，我們對 3CL 蛋白酶抑制劑 EDP-235 的 2 期研究於 4 月在 ECCMID 會議（以前稱為 ECCMID）上進行了展示。我們很高興首次在科學論壇上展示這項綜合資料包，並提醒大家，我們將在合作的背景下進行任何未來的 COVID-19 工作。

I'll now turn to our work in immunology, where we are concentrating on indications with high unmet medical need and a clear clinical development path, including well-defined populations and biomarkers available for early signs of efficacy.

現在我將談談我們在免疫學方面的工作，我們專注於具有高度未滿足醫療需求和明確臨床發展路徑的適應症，包括明確定義的人群和可用於早期療效跡象的生物標記。

Our first immunology indication is CSU, a severely debilitating chronic inflammatory skin disease, which can continue for years before remission. Clinical manifestations include urticaria, commonly called hives, as well as angioedema, which is characterized by pronounced deep tissue swelling. The disease can be severely disabling significantly impair quality of life, and effect performance at work or school as patients with CSU can experience symptoms beyond the skin manifestations, including sleep disturbances, fatigue, irritability, anxiety and depression. CSU is estimated to affect 0.5% to 1% of the global population at any given time.

我們的第一個免疫學適應症是 CSU，這是一種嚴重衰弱的慢性發炎性皮膚病，可持續數年才能緩解。臨床表現包括蕁麻疹（俗稱風疹塊）以及血管性水腫（其特徵是明顯的深層組織腫脹）。這種疾病可能會嚴重致殘，嚴重損害生活品質，並影響工作或學習的表現，因為患有 CSU 的患者可能會出現皮膚表現以外的症狀，包括睡眠障礙、疲勞、煩躁、焦慮和憂鬱。據估計，CSU 在任何時候都會影響全球 0.5% 至 1% 的人口。

The standard of care for CSU antihistamines, but in approximately half patients' symptoms are not alleviated and a minority of patients are treated with one indicated biologic. Consequently, there is a substantial unmet need for a new efficacious drug that can be conveniently dosed as an oral agent. Mast cells are the primary driver for disease in CSU as well as being involved in multiple other allergic disease.

CSU 抗組織胺的治療標準，但大約一半患者的症狀沒有得到緩解，少數患者接受一種適應症生物製劑治療。因此，對於可以方便地以口服劑型服用的新型有效藥物存在著巨大的未滿足需求。肥大細胞是 CSU 疾病的主要驅動因素，同時也與多種其他過敏性疾病有關。

In our first immunology program, we are seeking to develop a best in disease oral KIT inhibitor treatment that reduces the number of mast cells available to drive pathology in patients suffering from CSU. We are also encouraged by the potential to study KIT inhibition and additional indications. Currently our prototype KIT inhibitors in preclinical development demonstrate potent inhibition and are highly selective for KIT.

在我們的第一個免疫學計畫中，我們正在尋求開發一種最佳的口服 KIT 抑制劑治療方法，以減少 CSU 患者中可驅動病理的肥大細胞數量。我們也對研究 KIT 抑制和其他適應症的潛力感到鼓舞。目前，我們處於臨床前開發階段的原型 KIT 抑制劑表現出強大的抑製作用，並且對 KIT 具有高度選擇性。

We continue to optimize these leads around potency, selectivity and DMPK properties. And we are on track to select a development candidate in the fourth quarter of 2024 and plan to move into the clinic shortly thereafter. We are excited about our pipeline growth into immunology and are confident in the team's ability to translate the learnings from our previous success with small molecule drugs to enable our development of a best-in-disease therapeutic for CSU.

我們將繼續圍繞效力、選擇性和 DMPK 特性優化這些線索。我們預計將於 2024 年第四季選定一名開發候選人，並計劃隨後不久進入臨床階段。我們對我們在免疫學領域的管道成長感到興奮，並相信團隊有能力將我們先前在小分子藥物方面取得的成功經驗轉化為針對 CSU 的最佳疾病治療方法。

We are also pursuing additional immunology targets and look forward to introducing a second program this year. Beyond our pipeline, I would also like to take a moment to welcome Matthew Koraleski as our Chief Legal Officer, who joined last week. Matt is a strong addition to our team as he brings more than 20 years of experience in the life sciences industry handling, corporate governance, public company reporting, intellectual property, financing, business development, and M&A activities. At Enanta, he will lead all legal and compliance activities for the company and provide strategic guidance and corporate governance oversight.

我們也正在追求更多的免疫學目標，並期待今年推出第二個計畫。除了我們的人才儲備之外，我還想花點時間歡迎上週加入的 Matthew Koraleski 擔任我們的首席法律長。馬特是我們團隊的強大補充，他在生命科學產業處理、公司治理、上市公司報告、智慧財產權、融資、業務發展和併購活動方面擁有 20 多年的經驗。在 Enanta，他將領導公司的所有法律和合規活動，並提供策略指導和公司治理監督。

With that, I'd like to conclude by highlighting our upcoming milestones. We anticipate reporting data from the Phase 2a challenge study of EDP-323 in the third quarter and reporting data from the Phase 2 pediatric study of zelicapavir in the second half of this year. Further, we plan to identify a clinical candidate for our CSU program in the fourth quarter. And finally, we also plan to announce a second immunology program this year.

最後，我想強調一下我們即將實現的里程碑。我們預計今年第三季報告 EDP-323 第 2a 階段挑戰研究的數據，並於今年下半年報告澤利卡帕韋第 2 階段兒科研究的數據。此外，我們計劃在第四季度為我們的 CSU 計畫確定一名臨床候選人。最後，我們也計劃今年宣布第二個免疫學計畫。

Now I'll turn the call over to Paul to discuss our financials. Paul?

現在我將把電話轉給保羅來討論我們的財務狀況。保羅？

Thank you, Jay. I would like to remind everyone that Enanta reports on a September 30, fiscal year schedule. Today, we are reporting results for our fiscal second quarter ended March 31, 2024. For the quarter, total revenue was $17.1 million and consisted of royalty revenue earned on AbbVie's global MAVYRET net product sales. This compares to total revenue of $17.8 million for the same period of 2023.

謝謝你，傑伊。我想提醒大家，Enanta 的報告是按照 9 月 30 日的財政年度時間表進行的。今天，我們將報告截至 2024 年 3 月 31 日的第二財季業績。本季總收入為 1,710 萬美元，包括 AbbVie 全球 MAVYRET 淨產品銷售額所獲得的特許權使用費收入。相較之下，2023 年同期的總收入為 1,780 萬美元。

As a reminder, our royalties are calculated on a calendar year basis. Therefore, royalties for our fiscal first quarter ending December 31, were calculated at 12%, the highest royalty rate for the year and royalties for our fiscal quarter ending March 31, are calculated at 10%, our lowest royalty tier.

提醒一下，我們的版稅是按日曆年計算的。因此，我們截至 12 月 31 日的第一財季的特許權使用費以 12% 計算，即年度最高特許權使用費率，而我們截至 3 月 31 日的第一財季的特許權使用費按 10% 計算，即我們的最低特許權使用費率等級。

Of note, 54.5% of Enanta's ongoing royalties from AbbVie's net sales of MAVRET that are included in our revenue are being paid to OMERS. The royalty buyer in our April 2023 royalty sale transaction for financial reporting purposes the sale transaction was treated as debt with the upfront purchase payment to us of $200 million reported as a liability.

值得注意的是，Enanta 從 AbbVie 的 MAVRET 淨銷售額中獲得的持續特許權使用費中有 54.5% 已計入我們的收入，並支付給了 OMERS。我們 2023 年 4 月特許權使用費銷售交易中的特許權使用費買家出於財務報告目的，該銷售交易被視為債務，向我們支付的 2 億美元預付購買款被報告為負債。

As such, we continue to record 100% of the royalties earned as revenue, and we'll then amortize the debt liability at 54.5% of the cash royalty payments are paid to owners through June 30, 2032, subject to a cap of 1.42 times the purchase statement, after which point 100% of the cash royalty payments will be retained by Enanta. Interest expense from the debt will be recorded in and Enanta's consolidated statement of operations based on an imputed interest rate. Interest expense was $2.6 million for the three months ended March 31, 2024.

因此，我們繼續將 100% 的特許權使用費記錄為收入，然後我們將以 54.5% 的現金特許權使用費攤銷債務負債，截至 2032 年 6 月 30 日支付給所有者，但上限為購買報表的 1.42 倍，此後 100% 的現金特許權使用費將由 Enanta Enanta 保留。債務利息支出將根據估算利率記錄在 Enanta 的合併經營報表中。截至 2024 年 3 月 31 日的三個月，利息支出為 260 萬美元。

Moving on to other expenses for the three months ended March 31, 2024, research and development expenses totaled $35.6 million compared to $43.5 million for the same period in 2023. The decrease was primarily due to a decrease in costs associated with our COVID-19 program, as we previously announced, the plans to pursue any future COVID-19 efforts would be in the context of a collaboration. This was partially offset by increased costs associated with our RSV program and our recently announced immunology programs.

截至 2024 年 3 月 31 日的三個月的其他費用方面，研發費用總計 3,560 萬美元，而 2023 年同期為 4,350 萬美元。下降的主要原因是與我們的 COVID-19 計劃相關的成本下降，正如我們之前宣布的那樣，未來任何 COVID-19 工作的計劃都將在合作的背景下進行。這部分被與我們 RSV 計畫和最近宣布的免疫學計畫相關的成本增加所抵消。

General and administrative expense for the quarter was $14.2 million compared to $13.8 million for the same period in 2023. This increase was primarily due to an increase in legal expenses related to a patent infringement lawsuit against Pfizer. Enanta recorded an income tax benefit of $0.4 million for the three months ended March 31, 2024.

本季的一般及行政開支為 1,420 萬美元，而 2023 年同期為 1,380 萬美元。這一增長主要是由於針對輝瑞的專利侵權訴訟相關的法律費用增加。截至 2024 年 3 月 31 日的三個月，Enanta 的所得稅收益為 40 萬美元。

For interest earned and pending $28 million of federal income tax refunds compared to an income tax expense of less than $0.1 million for the three months ended March 31, 2023. Net loss for the three months ended March 31, 2024, was $31.2 million or a loss of $1.47 per diluted common share compared to a net loss of $37.7 million or a loss of $1.79 per diluted common share for the corresponding period in 2023.

利息收入和待付的聯邦所得稅退稅為 2,800 萬美元，而截至 2023 年 3 月 31 日的三個月的所得稅支出不到 10 萬美元。截至 2024 年 3 月 31 日的三個月的淨虧損為 3,120 萬美元，即每股稀釋普通股虧損 1.47 美元，而 2023 年同期的淨虧損為 3,770 萬美元，即每股稀釋普通股虧損 1.79 美元。

At this fiscal year midpoint, we are updating our expense guidance. We now expect our research and development expense to be between $125 million and $145 million. And our general and administrative expense to be between $50 million and $60 million.

在本財政年度中期，我們正在更新我們的費用指引。我們現在預計我們的研發費用將在 1.25 億美元至 1.45 億美元之間。我們的一般和行政費用在 5000 萬美元到 6000 萬美元之間。

The research and development expense increase reflects the impact of our new immunology program as well as additional efforts to accelerate our RSV clinical studies. The general and administrative expense increase is due to additional stock compensation expense and costs associated with pursuing our patent infringement lawsuit. Enanta ended of the quarter with approximately $300 million of cash and marketable securities.

研發費用的增加反映了我們新的免疫學計畫的影響以及加速我們的 RSV 臨床研究的額外努力。一般和行政費用的增加是由於額外的股票薪酬費用和與追究我們的專利侵權訴訟相關的費用。本季結束時，Enanta 擁有約 3 億美元的現金和有價證券。

We expect that our current cash, cash equivalents and short-term marketable securities, as well as our retained portion of ongoing royalties, will continue to be sufficient to meet the anticipated cash requirements of our existing business and development programs through the third quarter of fiscal 2027. Further financial details are included in our press release and will be available in our report on Form 10-Q when filed.

我們預計，到 2027 財年第三季度，我們目前的現金、現金等價物和短期有價證券以及我們保留的持續特許權使用費部分將繼續足以滿足我們現有業務和發展計劃的預期現金需求。更多財務細節包含在我們的新聞稿中，並將在提交的 10-Q 表格報告中提供。

I'd now like to turn the call back to the operator and open up the lines for questions. Operator?

現在我想將電話轉回給接線員並開放問答熱線。操作員？

(Operator Instructions) Akash Tewari, Jefferies.

（操作員指示）Akash Tewari，Jefferies。

Hi, this is Kathy on for Akash. So I had a question for RCVs, since RCVs isn't explicitly powered to hit on viral loads or symptoms, what will you be looking at in terms of the data to inform your design for Phase 3? And as such, how should we think about gauging efficacy or safety and then how much of a read-across do you believe the data will have for our RSVHR? And then are you expecting a symptom benefit of like one or two days. Thank you.

大家好，我是 Akash 的 Kathy。因此，我對 RCV 有一個疑問，由於 RCV 並沒有明確地針對病毒量或症狀提供動力，那麼您將根據哪些數據來為第 3 階段的設計提供資訊？那麼，我們應該如何衡量功效或安全性，然後您認為這些數據對我們的 RSVHR 有多大的影響？那麼您是否期望症狀在一兩天內得到緩解？謝謝。

Thank for the question. This is Jay. I think I'll hand it over to Tara Keefer to talk about how we were going to be viewing the data set coming out of PEDs. Tara?

謝謝你的提問。這是傑伊。我想我會把它交給塔拉·基弗 (Tara Keefer) 來談論我們將如何查看來自 PED 的資料集。塔拉？

Sure. Yeah. RSVPEDs study is our proof of concept Phase 2 study in pediatrics. We have to think about it a little bit differently than our adult study in Phase 2 because it's the first time that we're dosing children in this young age range of 28 days to three years. So we have to first confirm the safety profile and the dose. So the study has been done in two parts.

當然。是的。RSVPEDs 研究是我們在兒科領域進行的概念驗證第 2 期研究。我們必須以與第二階段成人研究略有不同的方式來考慮這個問題，因為這是我們第一次對 28 天至 3 歲年齡層的兒童進行給藥。因此我們必須先確認安全性和劑量。因此，這項研究分為兩部分進行。

Part one, the primary endpoint is safety and PK and done in a dose and dose ascending fashion. And we select the optimal dose from that part, which has been studied in part two and in that part, the primary objective is to look at the virology endpoints. So we're primarily, again looking for improvements in virology endpoints between the patients on 938 or zelicapavir and placebo, with directional data that would give us the confidence to move into a Phase 3 study. So we'll look at a number of different virology endpoints.

第一部分，主要終點是安全性和 PK，以劑量和劑量遞增的方式進行。我們從該部分中選擇最佳劑量，該部分已在第二部分進行了研究，在該部分中，主要目標是觀察病毒學終點。因此，我們主要再次尋找 938 或澤利卡帕韋與安慰劑患者之間的病毒學終點的改善，並提供方向性數據，讓我們有信心進入第 3 階段研究。因此，我們將研究許多不同的病毒學終點。

We'll also look at the clinical endpoints as well but primarily we'll be looking at virology, it's hard to give a specific threshold or bar in terms of what we're looking at because there's not a lot of data out there in RSV naturally acquired RSV in children. But there's one study that we can point to from a company called Arc Bio that did a Phase 3 study in pediatrics in China. They did show a 0.6 log drop at day four, a statistically significant effect in virology.

我們也將研究臨床終點，但主要研究病毒學，很難給出我們所研究的具體閾值或標準，因為關於兒童自然感染 RSV 的數據並不多。但我們可以指出一家名為 Arc Bio 的公司在中國進行的兒科 3 期研究。它們在第四天確實顯示出 0.6 對數下降，這在病毒學上具有統計上的顯著影響。

And they also in that same study demonstrated an improvement in symptoms. So we're not able to really give any a bar that we're looking for. But we're really interested in the totality of the data and so showing those trends and directional data that would give us the confidence to move into a larger, more well-powered study to be able to tease out these effects.

在同一項研究中，他們也表現出症狀的改善。所以我們無法真正給出我們想要的標準。但我們真正感興趣的是數據的整體性，因此展示這些趨勢和方向數據將使我們有信心進行更大、更有力的研究，以梳理出這些影響。

Eric Joseph, JP Morgan.

艾瑞克‧約瑟夫，摩根大通。

Great. Thank you. Just a couple of questions related to the immunology program, I guess, for the KIT development candidate. Can you talk a little bit about your strategic plans with respect to clinical development there? I guess to the extent you might be seeking out a strategic partner at some point along the way, there is a certain thing hurdles milestones you'd want to see clear first.

偉大的。謝謝。我想，針對 KIT 開發候選人，我只想問幾個與免疫學計畫相關的問題。您能談談那裡臨床發展的策略計畫嗎？我想，在某種程度上，你可能會在某個時候尋找策略夥伴，你會希望先弄清楚某些障礙和里程碑。

And then secondly, just to expand into or expand with the immunology program. Can you give us a bit of a preview there in terms of either target you may be pursuing? Are you perhaps doubling down on KIT? Thanks very much.

其次，只是擴大或擴展免疫學計劃。您能否就您可能追求的目標向我們稍微透露一下？您是否正在加倍投入 KIT？非常感謝。

Thanks, Eric. This is Jay. So we're working up a few different approaches in parallel to figure out which we might prioritize going forward. It's a little early to be discussing that. I think you asked where we doubling down on a KIT. We have one major KIT program now. I think we're looking to broaden beyond that, and so we'll provide more details as the year progresses and after we've generated more data in house, made more molecules in-house filed intellectual property and so forth. So stay tuned on that front.

謝謝，埃里克。這是傑伊。因此，我們正在同時研究幾種不同的方法，以確定未來可以優先考慮哪種方法。現在討論這個還為時過早。我想您問過我們在哪裡加倍投入 KIT。我們現在有一個主要的 KIT 專案。我認為我們正在尋求拓寬這一領域，因此隨著時間的推移，在我們內部產生更多數據、內部製造更多分子、提交智慧財產權等後，我們將提供更多細節。因此請繼續關注此事。

With regards to, I wasn't quite sure on your the first part of your question, you were talking about strategic partnering. I mean, our plan just in a nutshell, initially at least is to, again identify the candidate in the fourth quarter. We're going to be aiming to get it into the clinic, hopefully rapidly thereafter. And then Phase 1, I think should be fairly straightforward and healthy. The nice thing is with this mechanism, you can get surrogate readouts of target engagement by looking at tryptase changes that'll help a lot having the biomarker available to us.

關於您問題的第一部分，我不太確定，您談論的是策略夥伴關係。我的意思是，我們的計劃簡而言之，至少最初是在第四季度再次確定候選人。我們的目標是將其投入臨床，希望能夠盡快實現。然後，我認為第一階段應該相當簡單和健康。好處是，透過這種機制，您可以透過觀察類胰蛋白酶的變化來獲得目標參與的替代讀數，這將對我們獲得生物標記有很大幫助。

And then from the clinical development in CSU. I think is actually pretty straightforward. So we would be thinking about progressing to a fairly straightforward proof of concept study. It's a defined accessible in large patient populations. So we hopefully won't have the seasonal trends that we experienced in our RSV. and are looking very much forward to progressing that first program in immunology and then again bringing on additional our targets and mechanisms as time goes on.

然後從 CSU 的臨床發展來看。我認為實際上非常簡單。因此，我們會考慮進行一項相當簡單的概念驗證研究。它被定義為在大量患者群體中可獲得的。因此，我們希望不會出現 RSV 所經歷的季節性趨勢。我們非常期待推進免疫學領域的第一個項目，然後隨著時間的推移再次提出更多的目標和機制。

Can I just add one thing to that? Jay is, the biomarker that Jay mentioned, we can monitor and Phase 1 in healthy volunteers is serum tryptase. There's a lot of data out there generated from some of the monoclonal antibodies against KIT from CellDex that have we have nicely been able to show a tight correlation with impacts on that biomarker and ultimate clinical outcomes. So I think it's something that really can derisk program early on in those Phase 1 studies.

我可以補充一點嗎？Jay 是 Jay 提到的生物標記物，我們可以監測，健康志願者的第一階段是血清類胰蛋白酶。我們已經能夠很好地證明，CellDex 的一些針對 KIT 的單株抗體所產生的大量數據與生物標記和最終臨床結果的影響之間存在緊密的相關性。因此，我認為這確實可以在第一階段研究的早期階段降低專案風險。

Patrick, thanks for taking the questions.

派崔克，感謝您回答這些問題。

Ed Arce, H.C. Wainwright.

艾德·阿爾斯、H.C. 溫賴特。

Good afternoon, everyone. This is Thomas asking a couple of questions for Ed. So thank you for taking our questions. So first, can you outline what's your estimate of the patient population break down between the Northern and Southern Hemisphere to date, both for the RSVPED study and also for the REVHR study as well.

大家下午好。我是湯瑪斯，想問艾德幾個問題。感謝您回答我們的問題。那麼首先，您能否概述迄今為止您對北半球和南半球患者人口分佈的估計，包括 RSVPED 研究和 REVHR 研究。

Are you making reference to numbers of sites, you say patient population, but are you talking about markets? Are you talking about clinical trial conduct?

您指的是站點數量，您說的是患者人數，但您談論的是市場嗎？您是在談論臨床試驗的實施嗎？

More on the clinical trial conduct, so perhaps the number of sites. So both the number of sites or the number of patients enrolled, just a ballpark sandwich?

更多關於臨床試驗實施的信息，因此可能是試驗地點的數量。那麼站點數量和入組患者數量只是一個大概的數字嗎？

Yeah, I don't have the exact figures in front of me. We have I mean, maybe, Scott, maybe I'll just let you amplify on that.

是的，我面前沒有確切的數字。我的意思是，也許，斯科特，也許我只是讓你進一步闡述這一點。

Yeah, sure. Thanks, Jay. We've enrolled patients in both Northern and Southern hemispheres in both the pediatric and the high-risk studies, including in the current season ongoing in the South. So I don't have the exact numbers in front of me either, but we are continuing to enroll actively in both of those studies. And as Jay mentioned on the call, in the pediatric study, in particular, we're down to the last cohort and enrolling in the South.

是的，當然。謝謝，傑伊。我們在兒科和高風險研究中招募了北半球和南半球的患者，包括目前在南半球進行的研究。所以我面前也沒有確切的數字，但我們正在繼續積極參與這兩項研究。正如傑伊在電話中提到的那樣，特別是在兒科研究中，我們已經到了最後一批患者，並且正在南方招募。

Yeah, I think directionally, maybe the Northern Hemisphere beyond question is more highly represented in terms of clinical trial sites than the Southern Hemisphere. And we're in many different European countries, many different North American countries. We're in Asia. In the southern hemisphere, we're in South Africa, we're in Brazil, we're in Argentina, New Zealand, Australia, not as large a footprint in the Southern Hemisphere, but nonetheless, we're hoping to make good progress on enrollment and wrap this up as soon as possible.

是的，我認為從方向來看，北半球在臨床試驗地點的代表性無疑比南半球更高。我們的業務範圍遍及許多不同的歐洲國家和許多不同的北美國家。我們在亞洲。在南半球，我們在南非、巴西、阿根廷、紐西蘭、澳大利亞，我們在南半球的足跡沒有那麼大，但儘管如此，我們希望在招生方面取得良好進展，並儘快完成這項工作。

And then just follow-up on that, can you please remind us how much overlap are there between the Southern Hemisphere RSV season and flu season? And also, do you expect at that point for the HR study, do you expect the study to complete enrollment in line with the conclusion of the Southern Hemisphere RSV season.

然後繼續問這個問題，您能否提醒我們南半球呼吸道合胞病毒季節和流感季節有多少重疊？此外，您是否預期 HR 研究將在南半球 RSV 季節結束時完成招募？

Was the first question about overlap with the flu season?

第一個問題是否與流感季節重疊？

Yeah. How much overlap are there between the RSV season and flu season?

是的。呼吸道合胞病毒感染季節與流感季節有多少重疊？

I mean, generally they're somewhat correlated, but even in any given year, they can deviate a little bit one way or the other. Flu could come on a little earlier or a little later, come on twice. RSV has been and flu, but especially RSV have been substantially on impacted by the pandemic years in terms of just only more recently starting to settle down into what we would call more normal seasonality. So I think again, we follow We track RSV season much more closely than flu.

我的意思是，一般來說，它們有一定的相關性，但即使在任何一年，它們也可能會以某種方式出現一點偏差。流感可能來得早一點，也可能來得晚一點，甚至可能來兩次。RSV 和流感，尤其是 RSV，在大流行時期受到了很大的影響，直到最近才開始穩定下來，進入我們所說的更正常的季節性。所以我再次認為，我們追蹤呼吸道合胞病毒季節比追蹤流感季節更為密切。

As it relates to HR, my guess is we'll need to come back to the Northern Hemisphere, given that we again have just much stronger footprint there. We made excellent strides in the Northern Hemisphere this year. That's why, especially a very nice season for us. So we may need some of that as well. Again, we'll be tracking this and reporting progress later this summer when we're well into the Southern Hemisphere season, and we'll be able to forecast a little bit better based on more current data. But that's my expectation.

就人力資源而言，我猜我們需要回到北半球，因為我們在那裡再次擁有更強大的影響力。今年我們在北半球取得了長足的進步。這就是為什麼，這對我們來說是一個非常好的賽季。所以我們可能也需要一些。再次，我們將在今年夏天晚些時候進入南半球季節時跟踪這一情況並報告進展情況，並且我們將能夠根據更多當前數據做出更好的預測。但這是我的期望。

Okay, understood. Thank you again for taking my questions, and we look forward to the progress in the second half of this year.

好的，明白了。再次感謝您回答我的問題，我們期待今年下半年取得進展。

You're welcome.

不客氣。

Roy Buchanan, Citizens GMP.

羅伊·布坎南 (Roy Buchanan)，公民 GMP。

Thanks for taking my question. Just a couple on RSV. Jay, for the RSVHR, I think I heard you say that, it was powered for a 50% reduction in symptoms and it's probably a high bar. Just wondering where that conclusion about it being a high bar come from, I think the challenge trial, you had a 75% reduction in symptoms. Are you just interpolating between that and RSVP is there something you're seeing in the trial?

感謝您回答我的問題。RSV 上只有幾個。傑伊，對於 RSVHR，我想我聽到你說過，它能夠將症狀減少 50%，這可能是一個很高的標準。我只是想知道關於它的標準很高的結論是從哪裡來的，我認為在挑戰試驗中，症狀減少了 75%。您只是在它和 RSVP 之間進行插值嗎？您在試用中看到了什麼嗎？

Yeah. So to be clear, we're talking about time to resolution of symptoms. So it's different than any challenge. We're looking at the number of days improvement in time to resolution of symptoms versus placebo. I can give a little color on that. I think, for example, with flu a placebo study, Tara, correct me if I'm wrong, there's about a four day time period for time to resolution and Tamiflu, we'll shorten that by day. So it's a three day time resolution. So it's a one-day shortening out of four days, that's a 25% improvement in time to resolution.

是的。因此，明確地說，我們討論的是症狀消退的時間。所以它與任何挑戰都不同。我們正在觀察與安慰劑相比症狀緩解時間的改善天數。我可以對此稍加說明。例如，我認為，對於流感安慰劑研究，塔拉，如果我錯了請糾正我，解決時間大約需要四天，而達菲，我們會將其縮短一天。所以這是一個三天的時間決議。因此，問題解決時間從四天縮短為一天，即解決時間提高了 25%。

And so the way this was powered with HR and in order to keep it a relatively small study of only just under 200 patients, it was powered on a 50% effect. Had we powered it on a 25% effective rate, the study would be even much larger. So it's that fine balance of running a Phase 2 study that is enabling of a pivotal trial keeping it at a manageable size. And we felt with a couple of hundred patients, even though it's a high bar to reach stat segment on the way it was powered, we should be able to make good decisions based on clinicaly meaningful improvements. And again, shortening the time to resolution of sometimes by one or more days would be clinically meaningful.

因此，這項研究採用 HR 進行驅動，為了使其成為一項相對較小的研究，僅涉及不到 200 名患者，其驅動效果為 50%。如果我們以 25% 的有效率進行研究，那麼研究規模將會更大。因此，進行第二階段研究需要微妙的平衡，以便將關鍵試驗保持在可控的規模。我們認為，對於數百名患者來說，儘管以目前的技術水平達到統計部分的標準很高，但我們應該能夠根據臨床上有意義的改善做出正確的決定。再次，將解決時間縮短一天或幾天具有臨床意義。

Okay. Makes sense. And then that for the 323 challenge, what are you hoping to see there? We've said many times zelicapavir data is probably best in class, are you expecting to see something similar or do you need to see something similar? Just help us think about that? Thanks.

好的。有道理。那麼對於 323 挑戰，您希望看到什麼？我們已經多次說過，澤利卡帕韋的數據可能是同類中最好的，您是否期望看到類似的結果或您是否需要看到類似的結果？只是幫我們想想嗎？謝謝。

Yeah, zelicapavir sets a high bar. The mechanism is an in-protein inhibitor, it is about the best challenge study data and any book companies that are put on the boards. So it does represent a high bar that said, 323 is another mechanism. It's a polymerase inhibitor. It's a picomolar polymerase inhibitor. So it's super potent. Can we replicate the same best-in-class data that we saw with zelicapavir? We'll see.

是的，西利卡帕韋設定了很高的標準。該機制是一種蛋白質抑制劑，它涉及最佳挑戰研究數據和任何放在板上的圖書公司。所以它確實代表了一個很高的標準，也就是說，323 是另一種機制。它是一種聚合酶抑制劑。它是一種皮摩爾聚合酶抑制劑。所以它非常有效。我們能否複製我們在西利卡帕韋中看到的相同最佳數據？我們拭目以待。

Hopefully, yeah, it's hard to do much better. I think we want to be in the same range to declare it as a strong, player in the field. But based on every bit of data that we have preclinically in our Phase 1 data, which showed good safety, tolerability, wonderful exposures after QD dosing. And again, very, very strong virology. We've set it up about as best as we can. We're running at at the same clinical site as we ran the zelicapavir trial. So we should have data for that in Q3 next quarter.

希望如此，是的，做得更好很難。我認為我們希望處於同一範圍內，以宣布它是該領域的強大參與者。但根據我們在第一階段臨床前獲得的每一點數據，都顯示出良好的安全性、耐受性以及 QD 給藥後的極佳暴露效果。再次強調，病毒學非常非常強大。我們已經盡力做好了一切準備。我們在進行西利卡帕韋試驗的同一臨床地點進行試驗。因此我們應該在下個季度的第三季獲得相關數據。

Roanna Ruiz, Leerink Partners.

Roanna Ruiz，Leerink Partners。

This is [Nick Asic] on Toronto. Thanks for taking our questions. Maybe first on RSVPEDs, could you give us a sense of how close you are to completing enrollment at a younger age cohort of RSVPEDs? Maybe how long do you think it could take to analyze and ultimately share the data accurate?

我是多倫多的 [Nick Asic]。感謝您回答我們的問題。首先，關於 RSVPED，您能否告訴我們，您距離完成 RSVPED 較年輕年齡層的招生還有多遠？您認為分析並最終共享準確數據需要多長時間？

Yeah, again. So there are two parts to this study part 1 is completed in all age cohorts. Part 2 of this study is done in the older age cohorts. We're down to the final cohort of 20 patients. It's the youngest children from age of 28 days to six months, and we've been actively recruiting that cohort. So we're in the homestretch and we just -- unfortunately our pool of patients is now only one-sixth of what it was based on age groups.

是的，又一次。因此，本研究分為兩部分，第一部分針對所有年齡層完成。本研究的第二部分是在老年族群中進行的。我們最後一批病人只剩下 20 名了。這是年齡最小的 28 天到 6 個月大的兒童，我們一直在積極招募這個群體。因此，我們已進入最後階段，但不幸的是，我們的患者數量現在僅為按年齡組劃分的患者數量的六分之一。

So it's a narrower pool and any older children. We really have to -- we can't enroll on the study anymore. So we're just really zeroed in and focused on getting the remaining young children to fill out this cohort.

因此，游泳池較窄，不適合年齡較大的孩子。我們確實必須——我們不能再參加這項研究了。因此，我們真正集中精力並致力於讓剩下的孩子填補這個群體。

Got it. Thanks, Jay. And then maybe on CSU curious, what are you hoping to see in a future Phase 1 for your oral KIT inhibitor in terms of safety, maybe how should we think about frequency administration for this asset? Is it once daily twice daily, how should we think about that?

知道了。謝謝，傑伊。然後也許對 CSU 感到好奇，您希望在未來的第一階段看到口服 KIT 抑制劑在安全性方面取得什麼進展，也許我們應該如何考慮該資產的頻率管理？是每天一次還是每天兩次，我們該如何考慮呢？

We're still on finalizing the candidate, again, we are targeting to have the finalists in Q4. But suffice it to say, we're very much zeroed in on QD dosing. We've made molecules that are very potent that are very selective. We're optimizing DMPK profiles, tissue distribution, a number of other parameters like that to make it the candidate that we typically bring forward.

我們仍在最終確定候選人，我們的目標是在第四季度確定最終候選人。但可以說，我們非常專注於 QD 劑量。我們已經製造出非常有效且具有選擇性的分子。我們正在優化 DMPK 概況、組織分佈以及許多其他類似的參數，以使其成為我們通常提出的候選藥物。

So we've already shown data on a strong prototype, and we continue to -- the chemists are very busy well, not just chemist but the chemist and all the of the biology people who are doing the characterization and our DMPK and safety team are working very, very diligently on this. So we would be aiming for QD candidate that would be and the best safety profile we can provide as well as good potency and selectivity.

因此，我們已經展示了強大原型的數據，並且我們將繼續——化學家們非常忙碌，不僅是化學家，而且化學家和所有進行表徵的生物學家以及我們的 DMPK 和安全團隊都在非常非常努力地開展這項工作。因此，我們的目標是 QD 候選藥物具有最佳的安全性以及良好的效力和選擇性。

That's helpful. Thank you.

這很有幫助。謝謝。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

Hi, this is Luke on for Brian. For EDP323, can you remind us of your current thoughts on potentially entering a Phase 2b in otherwise healthy adults as opposed to starting with the higher risk in pediatric populations like you've done with zelicapavir? And would you wait for our RSVPED or RSVHR data to make this decision?

大家好，我是盧克，為布萊恩報道。對於 EDP323，您能否提醒我們您目前的想法，即在其他健康成年人中進入 2b 期試驗，而不是像您對西利卡帕韋所做的那樣從兒科人群中的高風險開始？您會等待我們的 RSVPED 或 RSVHR 數據來​​做出此決定嗎？

Yeah, that's a good question. I mean, the short answer is we won't do another RSV study in otherwise healthy adults. We found out from our RSVP trial from that otherwise healthy folks just resolve the self resolve the infection. So quickly on their own. So they're really not in need of other therapy. We would only focus on high-risk patient populations, and we're hoping to have an abundance of data here, in the second half. We'll have 323 data, we'll have PED's data. We'll be able to look at the totality of the information and figure out how best to position 323.

是的，這是個好問題。我的意思是，簡而言之，我們不會對健康的成年人進行另一項 RSV 研究。我們從 RSVP 試驗中發現，原本健康的人只需自行解決感染即可。這麼快就自己了。所以他們其實不需要其他治療。我們只關注高風險患者群體，我們希望在下半年獲得大量數據。我們將有 323 個數據，我們將有 PED 的數據。我們將能夠查看全部資訊並找出最佳定位 323 的方法。

So for us, it's been about bringing another strong mechanism forward. We've been working on this from the beginning, and I guess we've been working on it for a few years now to bring forward another differentiated asset in RSV. And that could give us the potential for doing combination therapy down the road in particularly hard to treat patient populations.

因此對我們來說，這是為了推動另一個強而有力的機制。我們從一開始就致力於此，我想我們已經為此努力了幾年，以在 RSV 中推出另一項差異化資產。這可能使我們在未來針對特別難治療的患者群體進行聯合治療。

Potentially could help widen the treatment window where we to go after a patient with two drugs rather than one. So it's just part of our strategy overall to trying to build a leadership position in RSV as a therapeutics company and the more cards we have to play, I think we can come up with ways to leverage another asset over time. So the key is getting it up to a strong threshold on the challenge study data first.

這可能有助於擴大治療窗口，讓我們能夠用兩種藥物而不是一種藥物來治療患者。因此，這只是我們整體策略的一部分，即作為一家治療公司試圖在 RSV 領域建立領導地位，而且我們能打出的牌越多，我認為我們就能想出辦法隨著時間的推移利用另一項資產。因此，關鍵是先讓它達到挑戰研究數據的強大閾值。

Great. Thank you.

偉大的。謝謝。

Liisa Bayko, EVR.

Liisa Bayko，EVR。

Hi, this is Zima on for Lisa. I have a question on the 323 program. What doses of 323 are you testing in Phase 2a human challenge study?

大家好，我是 Zima，為 Lisa 服務。我對 323 計劃有一個疑問。您在第 2a 階段人體挑戰研究中測試了多少劑量的 323？

Yeah. We're looking at a couple of different dose regimens. So the first it's 600 milligrams straight across for five days. The other is 600 milligram loading dose on day one, followed by 200 milligrams on each subsequent day. It's like a in antibiotics, they do that sometimes to give you a loading dose on day one and then a lower maintenance dose for a few days and thereafter.

是的。我們正在研究幾種不同的劑量方案。因此，首先連續服用 600 毫克，持續五天。另一種是第一天服用 600 毫克負荷劑量，然後每天服用 200 毫克。這就像抗生素一樣，他們有時會在第一天給你負荷劑量，然後在接下來的幾天內給你較低的維持劑量。

So we just put both of them in and I think in theory, either at least based on calculations and modeling either has a good chance of demonstrating the activity we want. One, obviously is a lower dose and has different cost of goods ramifications, et cetera, et cetera. We're just -- the challenge study is just such a wonderful way to tease all those questions out because you don't have to wait for the disease. You can just in fact, human volunteers, line cohorts up every few weeks and dose them. Does that answer your question?

所以我們把它們都放進去，我認為從理論上講，至少基於計算和建模，它們都很有可能展示我們想要的活動。一是顯然劑量較低，對商品成本的影響也不同，以此類推。我們只是——挑戰研究是解決所有這些問題的絕妙方法，因為你不必等待疾病的發生。事實上，你可以讓人類志工每隔幾週排隊一次，並給他們服藥。這回答了你的問題嗎？

Yeah, that's helpful. Thank you. I had second question on the patent against Pfizer because last year, Pfizer said that PAXLOVID doesn't infringe the patent because PAXLOVID has chi-floral group, which is not described in your patent. If you can comment on that?

是的，這很有幫助。謝謝。我對針對輝瑞的專利有第二個疑問，因為去年輝瑞表示 PAXLOVID 不侵犯該專利，因為 PAXLOVID 具有 chi-floral 基團，而這在您的專利中沒有描述。您能對此發表評論嗎？

Yeah. I really can't get into the discussion on our ongoing patent litigation. The only thing I can say is that I'm assuming it were to go to trial, we would expect to trial around the end of the year.

是的。我真的無法參與我們正在進行的專利訴訟的討論。我唯一能說的是，我假設它會進入審判階段，我們預計在年底左右進行審判。

Okay. Thank you. That's helpful.

好的。謝謝。這很有幫助。

(Operator Instructions) Jay Olson, Oppenheimer.

（操作員指示）傑伊·奧爾森，奧本海默。

Hi, Jay. Thanks for providing the update and taking the questions. On the immunology program, what are the most important differentiators you are looking for with your oral KIT inhibitor candidate versus other oral KIT inhibitors in development? And how are you thinking about positioning oral KIT inhibitors versus other oral therapies for CSU, such as BTK inhibitors?

你好，傑伊。感謝您提供最新消息並回答問題。在免疫學計畫中，與其他正在開發的口服 KIT 抑制劑相比，您最希望找到的口服 KIT 抑制劑候選藥物之間最重要的差異是什麼？您如何看待口服 KIT 抑制劑與其他 CSU 口服療法（如 BTK 抑制劑）的定位？

Thanks for the question, Jay. I'll let Tara speak that.

謝謝你的提問，傑伊。我讓塔拉來說這個。

Sure. Hi, Jay. So I think some of the data that's been generated from the monoclonal antibodies against kit that would be from Celldex. And then an earlier program with Jasper had indicated that inhibiting this target has some of the best-in-disease efficacy, at least from the Phase 2 trials that have been run. It gives us confidence in the target and what we're really hoping for our program is to match or even exceed potentially that efficacy with a good safety profile just with an oral route of administration.

當然。你好，傑伊。因此我認為一些數據是從 Celldex 的單株抗體試劑盒中產生的。然後，Jasper 早期的一個項目表明，抑制該目標具有最佳的疾病療效，至少從已經進行的第 2 階段試驗來看是如此。它讓我們對目標充滿信心，我們真正希望的是，我們的計畫僅透過口服給藥途徑就能達到甚至超過該療效，同時具有良好的安全性。

So that's the goal of our program, you mentioned there's other companies working on this as well. They're all early. They're all preclinical at the moment. There's really only preclinical data at the moment. So it's hard to say what would be differentiated, but I can tell you what our program is looking to achieve and that would be something that is able to be dosed QD orally, something that is very potent against KIT, but selective. And so leading to a good safety profile and just balancing that potency and selectivity so that the efficacy and safety profile could potentially be something that you would have as best-in-class.

這就是我們計劃的目標，您提到還有其他公司也在致力於此。他們都來得很早。目前它們都處於臨床前階段。目前確實只有臨床前數據。因此很難說什麼會有所不同，但我可以告訴你我們的計劃想要實現什麼，那就是能夠每天口服 QD 的藥物，對 KIT 非常有效，但有選擇性的藥物。這樣就形成了良好的安全性，並平衡了效力和選擇性，從而使功效和安全性有可能成為同類產品中最好的。

And then I would just say that the oral inhibitors may be more tunable. I think this is something that remains to be proven in the clinic. But whether they're able to be dosed and tune more finely than a monoclonal antibody, you can certainly have a little bit more some flexibility over that. So I think remains to be determined, but one potential strategy as well.

然後我只想說口服抑制劑可能更具可調性。我認為這還有待臨床驗證。但無論它們是否能夠比單株抗體進行更精細的劑量調整和調節，你肯定可以在這方面擁有更多的靈活性。所以我認為這還有待確定，但這也是一種潛在的策略。

Okay, great. Thank you. And then can you just talk about how you're thinking about additional indications in your development plan beyond CSU?

好的，太好了。謝謝。然後您能否談談您如何考慮在 CSU 之外的發展計劃中添加其他指示？

Sure. You mean for the KIT inhibitor?

當然。你是指 KIT 抑制劑嗎？

Yes.

是的。

Yeah. So the reason that we're interested in KIT is it obviously is a key driver for mass cells. And we know that mast cells have been implicated in a number of different indications. So certainly chronic inducible urticaria or CIndU is something that's also been studied with this target. There's some good data from the monoclonal antibody here. EoE or eosinophilic esophagitis is also another indication we'd be interested in. As well and even potentially asthma is something that one could think about with these types of inhibitors.

是的。因此，我們對 KIT 感興趣的原因是它顯然是大量細胞的關鍵驅動因素。我們知道肥大細胞與多種不同的疾病有關。因此，慢性誘發性蕁麻疹或 CIndU 肯定也是以此為目標進行研究的。這裡有一些來自單株抗體的良好數據。EoE 或嗜酸性食道炎也是我們感興趣的另一個跡象。人們也可以考慮使用這些類型的抑制劑來治療氣喘。

Thank you. And I'm showing no further questions. I would now like to turn the call back over to Jennifer Viera for closing remarks.

謝謝。我沒有其他問題。現在我想將電話轉回給詹妮弗·維埃拉 (Jennifer Viera) 做結束語。

Thank you, operator, and thanks to everyone for joining us today. If you have additional questions, please feel free to contact us by e-mail or call the office. Have a great night.

謝謝接線員，也謝謝大家今天的加入我們。如果您還有其他問題，請隨時透過電子郵件與我們聯繫或致電辦公室。祝您有個愉快的夜晚。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。