Jaguar Health Inc (JAGX) 2024 Q2 法說會逐字稿

Before I turn the call over to the management, I would like to remind you that the management may make forward-looking statements relating to such matters as continued growth prospects for the company, uncertainties regarding market acceptance of products, the impact of competitive products and pricing, industry trends and productive initiatives, including products in the development stage which may not achieve scientific objectives or meet stringent regulatory requirements.

在我將電話轉交給管理層之前，我想提醒您，管理層可能會就以下事項做出前瞻性陳述：公司的持續成長前景、產品市場接受度的不確定性、競爭產品的影響和定價、產業趨勢和生產計劃，包括可能無法實現科學目標或滿足嚴格監管要求的處於開發階段的產品。

Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those contemplated in such forward-looking statements. These statements are based on currently available information and management's current assumptions, expectations, and projections about future events.

前瞻性陳述存在風險和不確定性，可能導致實際結果與此類前瞻性陳述中預期的結果有重大差異。這些陳述是基於目前可獲得的資訊以及管理階層目前對未來事件的假設、預期和預測。

While management believes its assumptions, expectations, and projections are reasonable in view of currently available information, you are cautioned not to place undue reliance on these forward-looking statements.

儘管管理層認為，鑑於當前可用信息，其假設、預期和預測是合理的，但請注意不要過度依賴這些前瞻性陳述。

The company's actual results may differ materially from those discussed during this webcast for a variety of reasons, including those described in the forward-looking statements and risk factors section of the company's Form 10-K for the year 2023, which was filed April 1, 2024 and its other filings with the SEC, which are available on the Investor Relations section of the Jaguar's website.

由於多種原因，本公司的實際結果可能與本次網路廣播中討論的結果有重大差異，包括本公司於4 月1 日提交的2023 年10-K 表格的前瞻性陳述和風險因素部分中所述的內容， 2024 及其向 SEC 提交的其他文件，可在捷豹網站的投資者關係部分找到。

Except as required by the law, Jaguar undertakes no obligation to update or revise any forward-looking statements contained in this presentation to reflect new information, future events, or otherwise. Additionally, please note that the company supplements its condensed consolidated financial statements presented on a GAAP basis by providing non-GAAP EBITDA and non-GAAP recurring EBITDA.

除法律要求外，捷豹不承擔更新或修改本簡報中包含的任何前瞻性陳述以反映新資訊、未來事件或其他情況的義務。此外，請注意，該公司透過提供非 GAAP EBITDA 和非 GAAP 經常性 EBITDA 來補充其按 GAAP 基礎提交的簡明合併財務報表。

Jaguar believes that the disclosure items of these non-GAAP measures provide investors with additional information that reflects the basis upon which company's management assesses and operates the business. These non-GAAP financial measures should not be viewed in isolation or as substitute for GAAP net sales and GAAP net loss and are not substitutes for or superior to measures of financial performance in conformity with GAAP.

捷豹相信，這些非公認會計原則措施的揭露項目為投資者提供了額外的信息，反映了公司管理層評估和經營業務的基礎。這些非 GAAP 財務指標不應被孤立地看待，也不應被視為 GAAP 淨銷售額和 GAAP 淨虧損的替代品，也不能替代或優於符合 GAAP 的財務業績指標。

Today's conference is being recorded. At this time, it is now my pleasure to turn the call over to Lisa Conte, Jaguar Health's Founder, President, and Chief Executive Officer. Lisa, the floor is yours.

今天的會議正在錄製中。此時此刻，我很高興將電話轉給 Jaguar Health 創辦人、總裁兼執行長 Lisa Conte。麗莎，地板是你的。

Thank you. Hello, and thank you all for joining our investor webcast today. My name, as you heard, is Lisa Conte, the Founder, President, and CEO of Jaguar Health and our wholly owned subsidiary, Napo Pharmaceuticals and I'm also the Chairman of our Italian subsidiary, Napo Therapeutics. As usual, I may use the words Jaguar and Napo interchangeably when I'm referring to our company and our activities.

謝謝。大家好，感謝大家今天參加我們的投資人網路廣播。如你所知，我的名字是 Lisa Conte，她是 Jaguar Health 和我們全資子公司 Napo Pharmaceuticals 的創始人、總裁兼首席執行官，我也是我們義大利子公司 Napo Therapeutics 的董事長。像往常一樣，當我提到我們的公司和我們的活動時，我可能會互換使用 Jaguar 和 Napo 這兩個詞。

As announced, this is an earnings webcast for the second quarter of 2024. I'm going to steal the thunder of our CFO, Carol Lizak, who will be speaking at the end of this webcast, as I am pleased to report our combined net second quarter 2024 revenue of approximately $2.72 million for prescription and non-prescription products, increased approximately 16% versus net Q1 2024 revenue, which was $2.35 million. And it increased approximately 2% versus net Q2 2023 revenue of $2.67 million. We're very pleased with that.

正如所宣布的，這是2024 年第二季度的收益網絡廣播。的合併淨利2024 年第二季處方和非處方產品收入約為 272 萬美元，較 2024 年第一季淨收入 235 萬美元成長約 16%。與 2023 年第二季淨收入 267 萬美元相比，成長了約 2%。我們對此非常滿意。

In addition, on this webcast, I will be joined by my colleagues, Dr. Pravin Chaturvedi, our Chief Scientific Officer; and Cathy Collis, our recently appointed Senior Vice President of Growth Strategy to speak to the robustness of our clinical pipeline and commercial activities. Pravin will further review the data and regulatory strategy for the clinically meaningful results we reported on July 23, 2024, clinically meaning results identified in patients in the subgroups of breast and lung cancer.

此外，我的同事、我們的首席科學官 Pravin Chaturvedi 博士也將參加本次網路廣播。我們最近任命的成長策略高級副總裁 Cathy Collis 談到了我們臨床管道和商業活動的穩健性。 Pravin 將進一步審查我們於 2024 年 7 月 23 日報告的具有臨床意義的結果的數據和監管策略，這些結果是在乳癌和肺癌亞組患者中確定的具有臨床意義的結果。

In the initial data from our recently completed pivotal Phase 3 OnTarget trial of crofelemer, for the prophylaxis of diarrhea in adult cancer patients with solid tumors, all solid tumors receiving targeted therapy with or without standard chemotherapy. Again, this signal was seen in the two subgroups of breast and lung cancer.

在我們最近完成的 Crofelemer 關鍵 3 期 OnTarget 試驗的初步數據中，該試驗用於預防患有實體瘤的成年癌症患者的腹瀉，所有實體瘤都接受有或沒有標準化療的標靶治療。同樣，在乳癌和肺癌這兩個亞組中也看到了這個訊號。

Today, Pravin will also discuss Jaguar's other clinical core focus areas for the development of crofelemer for two targeted rare and orphan disease indication, microvillus inclusion disease, we refer to as MVID, which is an ultrarare pediatric congenital diarrheal disorder and also short bowel syndrome with intestinal failure with the acronym SBS-IF or we'll refer to just as SBS.

今天，Pravin 還將討論Jaguar 開發Crofelemer 的其他臨床核心重點領域，用於兩種靶向罕見疾病和孤兒疾病適應症，即微絨毛包涵體病，我們稱為MVID，這是一種極其罕見的小兒先天性腹瀉病，也是一種伴隨短腸症候群的疾病。

As announced with Jaguar leadership and participation from the Jaguar Family company, Napo Therapeutics based in Milan, Italy, we are also supporting independent investigator-initiated proof-of-concept studies of crofelemer for MVID and SBS in the US and the MENA regions, Middle East, North Africa regions.

正如在Jaguar 的領導下以及總部位於義大利米蘭的Jaguar Family 公司Napo Therapeutics 的參與下所宣布的那樣，我們還支持獨立研究者發起的Crofelemer 在美國和中東和北非地區用於MVID 和SBS 的概念驗證研究。

With the results, proof-of-concept results expected by the end of this year 2024 and throughout the beginning of 2025, crofelemer has already received orphan drug designation in both the United States and EU and for both MVID and SBS indications and allows us to pursue that strategy in rare disease business model for these indications.

根據這些結果，預計將於 2024 年底和 2025 年初獲得概念驗證結果，Crofelemer 已在美國和歐盟獲得 MVID 和 SBS 適應症的孤兒藥資格認定，這使我們能夠針對這些適應症在罕見疾病商業模式中推行該策略。

We're very pleased to announce last week that the required import permit for crofelemer has been granted in Abu Dhabi in the UAE, United Arab Emirates, for the planned investigator-initiated proof-of-concept trial in pediatric patients for MVID and SBS, which is an important and critical regulatory event that we worked on for some time and have known the principal investigator there for many years who is excited to treat patients.

我們非常高興地宣布，上週，Crofelemer 所需的進口許可證已在阿拉伯聯合大公國阿聯酋的阿布達比獲得，用於計劃中的研究者發起的針對兒科患者的 MVID 和 SBS 概念驗證試驗，這是一個重要且關鍵的監管事件，我們已經工作了一段時間，並且認識那裡的首席研究員多年，他很高興能夠治療患者。

After Pravin speaks, Cathy will provide a brief overview of our planned October 2024 this year, commercial launch of the FDA-approved oral mucositis prescription product, Gelclair, for the US market. Well, this is our third prescription product launch. Oral mucositis also called the chemo mouth has emerged as the most significant adverse event in oncology according to the National Comprehensive Cancer Network task force.

Pravin 發言後，Cathy 將簡要概述我們計劃於今年 2024 年 10 月在美國市場推出 FDA 批准的口腔黏膜炎處方產品 Gelclair 的商業上市情況。嗯，這是我們第三次推出處方產品。根據國家綜合癌症網絡工作小組的說法，口腔黏膜炎也稱為化療口，已成為腫瘤學中最重要的不良事件。

Cathy was instrumental in executing Jaguar's in-license agreement for Gelclair. She is results-oriented. She's commercial leader with more than 25 years of experience in the biopharmaceutical industry. We're thrilled she has joined Jaguar's team in this important role as Head of Growth Strategy and we're very excited about this important product launch with a side effect that is so devastating to cancer patients.

Cathy 在執行捷豹 Gelclair 的許可協議方面發揮了重要作用。她是一個以結果為導向的人。她是一位商業領袖，在生物製藥行業擁有超過 25 年的經驗。我們很高興她加入捷豹團隊，擔任成長策略主管這一重要角色，我們對這項重要產品的發布感到非常興奮，該產品的副作用對癌症患者來說是毀滅性的。

Towards the end of the webcast, our CFO, finally, Carol Lizak, will provide a recap of the financial highlights for the second quarter of 2024.

在網路廣播即將結束時，我們的財務長卡羅爾·利扎克 (Carol Lizak) 最後將回顧 2024 年第二季的財務亮點。

So before I introduce Pravin, just a reminder that our ambitious Phase 3 OnTarget trial broadly and boldly studied the prophylaxis of diarrhea in adult cancer patients with 10 distinct types of solid tumors, receiving any of 24 different targeted therapy drugs, all of which have a reported rate of diarrhea of more than 50% and with or without standard chemotherapy, so quite a heterogeneous population, quite important that we were looking to understand how we could miniate diarrhea with the broadest potential label.

因此，在介紹Pravin 之前，請提醒一下，我們雄心勃勃的3 期OnTarget 試驗廣泛而大膽地研究了患有10 種不同類型實體瘤的成年癌症患者的腹瀉預防，這些患者接受了24 種不同靶向治療藥物中的任何一種，所有這些藥物都具有報告的腹瀉率超過50%，無論有或沒有標準化療，因此人群相當異質，這一點非常重要，我們希望了解如何透過最廣泛的潛在標籤來減輕腹瀉。

We observed the meaningful clinical signals in breast and lung cancer patients, two of the most common cancer diagnoses.

我們在乳癌和肺癌這兩種最常見的癌症診斷中觀察到了有意義的臨床訊號。

We are collaborating with our clinical and scientific advisers to elevate the significance of these clinical outcomes signals in order to prepare for potential scientific publications as well as submissions to support clinical and regulatory meetings as we seek to explore potential pathways of FDA approval to make crofelemer, which is our novel, oral plant-based prescription medicine, which is already available for people living with HIV/AIDS and diarrhea, available to patient populations of breast and/or lung cancer patients for cancer therapy-related diarrhea, so looking for an opportunity to expand the label.

我們正在與我們的臨床和科學顧問合作，提升這些臨床結果訊號的重要性，以便為潛在的科學出版物以及支持臨床和監管會議的提交做好準備，同時我們尋求探索FDA 批准生產Crofelemer 的潛在途徑，這是我們新型的口服植物處方藥，已經可供愛滋病毒/愛滋病和腹瀉患者使用，也可供乳癌和/或肺癌患者治療與癌症治療相關的腹瀉患者群體使用，因此正在尋找機會來擴展標籤。

It is important to emphasize its standard of care and treatment policy for cancer patients in the OnTarget trial was patient-centric, including, though not limited to the full journey of their treatment, rescue therapies, reductions changes or holidays to the cancer agents causing side effects, many side effects, including diarrhea and other supportive care interventions, which impact gut function at different times in different patient populations.

需要強調的是，OnTarget 試驗中癌症患者的護理標準和治療政策是以患者為中心的，包括但不限於治療的整個過程、搶救治療、減少癌症致病因素的改變或休假。包括腹瀉和其他支持性護理幹預措施，這些幹預措施會在不同時間影響不同患者群體的腸道功能。

Because of this and given the rich and extensive database from OnTarget, there is a great deal of work still ahead to analyze data for numerous prespecified and non-prespecified subgroups from the trial. Complex programming is necessary to address statistical rules for censoring data, for handling missing data points, addressing intercurrent events and data imputations, among others.

因此，考慮到 OnTarget 豐富而廣泛的資料庫，分析試驗中眾多預先指定和非預先指定亞組的資料仍有大量工作要做。複雜的程式設計對於解決審查資料、處理缺失資料點、解決並發事件和資料插補等的統計規則是必要的。

We are absolutely encouraged by the results we've seen thus far, in what are relatively small sample sizes represented by the aforementioned subgroups because they are subgroups of patients with breast and lung cancer and we are energized with anticipation as the analyses continue to reveal important insights and signals to achieve our clinical and regulatory goals. So with that, good morning, Pravin.

我們對迄今為止所看到的結果感到絕對鼓舞，上述亞組代表的樣本量相對較小，因為它們是乳腺癌和肺癌患者的亞組，隨著分析繼續揭示重要的結果，我們充滿期待實現我們的臨床和監管目標的見解和信號。那麼，早上好，普拉文。

Good morning, Lisa, and good morning, all, and thank you for joining today's investor webcast.

早安，麗莎，大家早安，感謝您參加今天的投資者網路廣播。

Okay Pravin, it's been two weeks since we announced the clinically meaningful signals in the subpopulation of breast and lung cancer patients in the OnTarget trial. I know this has been a focus of yours for many years now.

好的，Pravin，自從我們在 OnTarget 試驗中宣布乳癌和肺癌患者亞群中具有臨床意義的信號以來，已經過去兩週了。我知道這一直是您多年來關注的焦點。

Since that time, we also announced significant positive results with crofelemer benefiting subgroups of diarrhea predominant irritable bowel syndrome and that's an acronym IBS-D, irritable bowel syndrome patients with chronic refractory diarrhea.

從那時起，我們也宣布了Crofelemer 對腹瀉為主的腸躁症（IBS-D 的縮寫，即伴有慢性難治性腹瀉的腸躁症患者）亞組的顯著積極結果。

And by the way, each of those studies and results have been accepted for poster presentations at the American College of Gastroenterology Annual Scientific Meeting, ACG which is also in October of this year. Pravin will begin by explaining the relevance of those study results and analyses, which have come out since (technical difficulty) the preliminary results on OnTarget, for the relevance of those study results and analyses to the OnTarget results.

順便說一句，這些研究和結果均已在今年 10 月舉行的美國胃腸病學會年度科學會議 (ACG) 上進行海報展示。 Pravin 將首先解釋這些研究結果和分析的相關性，這些研究結果和分析是自 OnTarget 初步結果（技術難度）以來得出的，這些研究結果和分析與 OnTarget 結果的相關性。

Thank you, Lisa. I think I'll go into some specific details. As you stated last week, we were very excited about the fact that crofelemer continues to demonstrate clinical robustness in the responder analysis for multiple gastroenterology conditions, including functional diarrhea and chronic idiopathic diarrhea in the subgroups of diarrhea predominant irritable bowel syndrome patients. These analyses are done by what is called responder analysis and that's the keyword.

謝謝你，麗莎。我想我會討論一些具體細節。正如您上週所說，我們感到非常興奮的是，Crofelemer 在多種胃腸病的反應者分析中繼續證明了臨床穩健性，包括腹瀉為主的腸躁症患者亞群的功能性腹瀉和慢性特發性腹瀉。這些分析是透過所謂的響應者分析來完成的，這就是關鍵字。

Simply put, a responder analysis is a preponderance of weeks of improvement in lose watery stool frequency, lose watery stool consistency and other bowel end points, depending on the indication within a chronic multi-month study. That's what these two recent diarrhea predominant IBS study showed.

簡而言之，反應者分析是指水樣便頻率、水樣便稠度和其他腸道終點改善數週的優勢，取決於一項長期的多月研究中的指示。這就是最近兩項以腹瀉為主的腸躁症研究所顯示的結果。

Just to remind, similarly, we analyzed the pivotal trial for the currently approved indication of crofelemer for HIV-related diarrhea, which was based on the proportion of patients with an acceptable number of lose watery stools per week for 50% of the time.

提醒一下，同樣，我們分析了目前批准的 Crofelemer 治療 HIV 相關腹瀉適應症的關鍵試驗，該試驗基於每週 50% 的時間內排便次數可接受的患者比例。

Our responder analysis is where we saw the initially clinically important signals in patients with breast and lung cancer. And although it is not a prespecified primary endpoint in the OnTarget study, it's clinically important.

我們的反應者分析是我們在乳癌和肺癌患者中看到最初臨床重要訊號的地方。儘管它不是 OnTarget 研究中預先指定的主要終點，但它在臨床上很重要。

Clinical importance is defined as a greater than 10 percentage point difference in the proportion of subjects with less than or equal to less than seven watery stools per week compared to placebo, that was seen in the breast and lung cancer patients in months two and three, of the three-month treatment period of the OnTarget study.

臨床重要性定義為與安慰劑相比，每週水樣便少於或等於七次的受試者比例差異大於10 個百分點，這在乳癌和肺癌患者的第二個月和第三個月中觀察到。

Clinical relevance for this analysis has been informed by a cancer patient survey that we conducted prior to the start of the OnTarget study that indicated that the patients wanted to get to less than or equal to two watery stools per day, i.e., less than or equal to 14 watery stools per week, which would be clinically meaningful to the patients, which would reflect an improvement in their bowel control habits, presumably leading to more comfort and improve quality of life.

我們在 OnTarget 研究開始之前進行的一項癌症患者調查表明了該分析的臨床相關性，該調查表明患者希望每天的水樣便少於或等於兩次，即少於或等於每週排便次數達到14次，這對患者俱有臨床意義，這反映了他們排便控制習慣的改善，可能會帶來更多舒適感並提高生活品質。

And I'll provide some more technical details about the responder analysis in the OnTarget trial subgroups. Since these are exploratory analyses and subgroups of breast and lung cancer patients receiving targeted therapies, the sample size for each of these subgroups is smaller.

我將提供一些有關 OnTarget 試驗亞組中應答者分析的更多技術細節。由於這些是探索性分析以及接受標靶治療的乳癌和肺癌患者的亞組，因此每個亞組的樣本量較小。

As we had designed the trial to be all inclusive for adult solid tumor patients that were eligible to receive diarrheagenic targeted therapies in at least 50% of the patients receiving those therapies. And it was a multi-center, double-blind, placebo-controlled study that included US and ex-US sites and it used patient-reported outcomes, PROs, as the primary determinant of the clinical responses.

因為我們設計的試驗涵蓋了成年實體瘤患者，其中至少 50% 的患者有資格接受致瀉性標靶治療。這是一項多中心、雙盲、安慰劑對照研究，包括美國和美國以外的地點，並使用患者報告的結果（PRO）作為臨床反應的主要決定因素。

When we combined all the breast and lung cancer patients receiving different targeted therapies that achieved the monthly responder status in months two and three, defined as those patients having less than or equal to seven watery stools per week, at least 50% of the time, it showed that 79% of the patients in crofelemer group had achieved this threshold compared to 68% in the placebo group patients.

當我們將所有接受不同標靶治療的乳癌和肺癌患者合併起來時，這些患者在第二個月和第三個月內達到了每月反應者狀態，定義為每周至少有50% 的時間少於或等於7 次水樣大便的患者，研究表明，Crofelemer 組中有 79% 的患者達到了這一閾值，而安慰劑組中這一比例為 68%。

As a reminder for our audience, it was a prophylactic trial, which means the patients not come in with diarrhea. The one-sided p-value was 0.027, which is nearly statistically significant as a hurdle for OnTarget study design is less than 0.025, and the difference was clinically important.

提醒我們的觀眾，這是一項預防性試驗，這意味著患者不會腹瀉。單邊 p 值為 0.027，幾乎具有統計顯著性，因為 OnTarget 研究設計的障礙小於 0.025，且差異具有臨床重要性。

As the subgroup sample size gets smaller, the p-value is further impaired as the study was not powered to detect these signals at a statistically significant value. We are also looking at odds or hazard ratios. For sake of clarity and odds ratio analysis, it's similar to a hazard ratio assessment which measures the frequency of an event in two groups over time and a ratio being greater than 1 is deemed favorable for crofelemer.

隨著子組樣本量變小，p 值進一步受損，因為研究無法以統計顯著值檢測這些訊號。我們也在研究賠率或風險比。為了清楚起見和優勢比分析，它類似於風險比評估，測量兩組中事件隨時間變化的頻率，大於 1 的比率被認為對 Crofelemer 有利。

When we evaluated all the breast cancer patients receiving three different types of targeted therapies, the proportion of monthly responders for months two and three that achieved less than seven watery stools per week, at least 50% of the time, crofelemer group had 78% responders compared to 68% in the placebo group.

當我們評估接受三種不同類型標靶治療的所有乳癌患者時，第二個月和第三個月的每月有反應者每週排便次數少於7 次的比例（至少50% 的時間） ，Crofelemer 組有78% 的反應者相比之下，安慰劑組的比例為 68%。

For breast cancer patients receiving abemaciclib, the monthly responder rate was for having less than seven watery stools for months two and three was 69% for the crofelemer group versus 58% of the placebo group. And the odds ratio for this group, the subgroup was 1.796 over the three-month period.

對於接受 abemaciclib 的乳癌患者，Crofelemer 組第二個月和第三個月水樣便次數少於 7 次的每月反應率為 69%，而安慰劑組為 58%。該組（子組）在三個月內的優勢比為 1.796。

Continuing with breast cancer patients, those patients that received pertuzumab, that were monthly responders in months two and three having at least less than seven water stools per week for 50% of the time. It was 87% of patients in the crofelemer arm compared to 75% in the placebo arm and the odds ratio was 1.44.

繼續針對乳癌患者，那些接受帕妥珠單抗治療的患者在第二個月和第三個月內每月有反應，其中 50% 的時間每周至少少於 7 次水便。 Crofelemer 組的患者比例為 87%，而安慰劑組的患者比例為 75%，比值比為 1.44。

Similarly, lung cancer patients receiving kinase inhibitors, achieving a monthly responder status for months two and three with less than seven watery stools per week was 81% in the crofelemer arm compared to 64% in the placebo group.

同樣，在接受激酶抑制劑治療的肺癌患者中，Crofelemer 組的81% 患者在第二個月和第三個月內達到每月緩解狀態且每週水樣便少於7 次，而安慰劑組中這一比例為64%。

Had the sample sizes being larger in these subgroups, these same differences that we observed would have reached statistical significance. This exploratory odds ratio analysis for each sub group are also being evaluated using nonparametric rank sum tests due to the skewness of the data in both groups but especially in the placebo group.

如果這些亞組中的樣本量較大，我們觀察到的這些相同差異將達到統計顯著性。由於兩組（尤其是安慰劑組）資料的偏度，也使用非參數秩和檢定來評估每個子組的探索性比值比分析。

To be more specific, the range of average number of weekly lose watery stools for the crofelemer group was 0 to 30, compared 0 to 42 for the placebo group across all tumor types and targeted therapies in the OnTarget study.

更具體地說，在 OnTarget 研究中，在所有腫瘤類型和標靶治療中，Crofelemer 組每周平均排便次數為 0 至 30 次，而安慰劑組為 0 至 42 次。

The wide variation in the average number of weekly loose watery stools contributes to the skewness of the data. But we are very encouraged by the signals we are seeing in these small subgroups, while different tumor types, different treatment regimens and complex handling of data for various intercurrent events in each individual patient's journey have limited the subgroup patient sizes.

每週稀稀水樣便的平均次數的巨大差異導致了數據的偏差。但我們對這些小亞組中看到的訊號感到非常鼓舞，而不同的腫瘤類型、不同的治療方案以及每個患者旅程中各種併發事件的複雜數據處理限制了亞組患者的規模。

We are grateful for the consistency of the signals and the benefit we're able to discern in breast and lung cancer patients. We have seen crofelemer benefit patients in multiple studies and in multiple patient populations. I will underscore your comment, Lisa.

我們對訊號的一致性以及我們能夠在乳癌和肺癌患者中發現的益處表示感謝。我們在多項研究和多個患者群體中看到 Crofelemer 使患者受益。我會強調你的評論，麗莎。

We are energized and helpful as we undertake more analyses and potentially further reveal important and potentially statistically significant results in these complex data sets. As an important example, we have not yet evaluated the responder analysis for patients who continued into the extension phase of the OnTarget study called Stage 2, which is for the whole study, we know about two-thirds of the patients continued to receive the treatment for another three months and we plan to analyze those as well.

當我們進行更多分析並可能進一步揭示這些複雜數據集中的重要且可能具有統計意義的結果時，我們充滿活力且樂於助人。舉一個重要的例子，我們尚未評估繼續進入 OnTarget 研究擴展階段（稱為第 2 階段）的患者的反應者分析，對於整個研究，我們知道大約三分之二的患者繼續接受治療再過三個月，我們也計劃對其進行分析。

In addition to these clinically important signals in breast and lung cancer patients receiving targeted therapies, I'd like to add that crofelemer continues to show improvement in various gastrointestinal indications due to its novel paradigm shifting mechanism of action, physiologic mechanism of action.

除了接受標靶治療的乳癌和肺癌患者的這些臨床重要訊號之外，我想補充一點，由於其新穎的範式轉換作用機制、生理作用機制，Crofelemer 在各種胃腸道適應症方面繼續顯示出改善。

We had previously conducted two diarrhea predominant IBS-D clinical trials and crofelemer showed improvement in abdominal pain and discomfort and stool consistency in those studies. The change in stool consistency together with improvement in abdominal pain and discomfort are now regulatory and clinically specified primary endpoints for drugs being developed for diarrhea predominant irritable bowel syndrome patients.

我們先前進行了兩項以腹瀉為主的 IBS-D 臨床試驗，Crofelemer 在這些研究中顯示出腹痛和不適以及大便稠度的改善。大便稠度的變化以及腹痛和不適的改善現在是針對腹瀉為主的腸躁症患者開發的藥物的監管和臨床指定的主要終點。

Two independent scientific and clinical thought leaders in gastroenterology at the Beth Israel Deaconess Hospital at Harvard Medical School and at the University of Texas and Houston, studied crofelemer in refractory diarrhea subgroups or diarrhea predominant IBS patients with functional and chronic idiopathic diarrhea, respectively. And they submitted their abstracts that were accepted for poster presentations, at the American College of Gastroenterology meeting later this year. Any questions now, Lisa?

哈佛醫學院貝斯以色列女執事醫院以及德州大學和休士頓分校的兩位胃腸病學獨立科學和臨床思想領袖分別在難治性腹瀉亞群或腹瀉為主的功能性和慢性特發性腹瀉IBS 患者中研究了Crofelemer。他們提交的摘要被接受在今年稍後的美國胃腸病學會會議上進行海報展示。現在還有什麼問題嗎，麗莎？

Well, thank you for that detailed response Pravin, it's a snapshot of just how rich this database is and how complex this trial was, the OnTarget trial. But I know Pravin that you have personally designed many of the successful trials with crofelemer in different patient populations. So definitely appreciate that detailed explanation.

嗯，謝謝 Pravin 的詳細回复，它只是一個快照，說明了這個資料庫有多豐富，以及這個 OnTarget 試驗有多複雜。但我知道 Pravin，您親自設計了許多針對不同患者群體的 Crofelemer 成功試驗。所以絕對感謝這個詳細的解釋。

Pravin, I'd like you please now explain the plan with the responder analysis in the OnTarget trial and the plan specifically related to our goal of meeting with the FDA which is the gating item to get crofelemer, Mytesi to people living with cancer therapy-related diarrhea.

Pravin，我希望您現在透過 OnTarget 試驗中的反應者分析來解釋該計劃，該計劃特別與我們與 FDA 會面的目標相關，FDA 是向癌症治療患者提供 Crofelemer、Mytesi 的門控項目 -相關腹瀉。

Thanks, Lisa. That's a good question. The plan is to continue with the responder analysis and detect -- show the robustness of our findings, particularly in the subgroups of breast and lung cancer patients in the OnTarget trial.

謝謝，麗莎。這是個好問題。該計劃是繼續對應答者進行分析和檢測——展示我們研究結果的穩健性，特別是在 OnTarget 試驗中的乳癌和肺癌患者亞群中。

We will discuss the findings of our exploratory analyses with our clinical and regulatory key opinion leaders and evaluate other gastrointestinal endpoints now a very rich and extensive patient-reported outcomes database which will better inform us about the preponderance of evidence for the clinical meaningfulness of what we are seeing, with crofelemer.

我們將與我們的臨床和監管關鍵意見領袖討論我們探索性分析的結果，並評估其他胃腸道終點，現在這是一個非常豐富和廣泛的患者報告結果資料庫，這將更好地讓我們了解我們研究的臨床意義的優勢證據。

Since OnTarget is a pivotal Phase 3 trial, we will prepare a briefing document for the FDA after our meetings with our internal KOLs on the obligatory pre-specified statistical analysis. We will also prepare a report on the additional exploratory responder analysis and provide the FDA the findings and the results of our findings in these subgroups of breast and lung cancer.

由於 OnTarget 是一項關鍵的 3 期試驗，因此我們將在與內部 KOL 就強制性預先指定的統計分析進行會議後，為 FDA 準備一份簡報文件。我們還將準備一份關於額外探索性反應者分析的報告，並向 FDA 提供我們在乳癌和肺癌這些亞組中的發現和結果。

By providing more information on the incident, severity, and duration of diarrhea from the OnTarget trial, which we'll particularly see in the placebo group, we will also have more informed discussion with the FDA about patient impact.

透過提供 OnTarget 試驗中腹瀉事件、嚴重程度和持續時間的更多資訊（我們將特別在安慰劑組中看到），我們​​也將與 FDA 就患者影響進行更明智的討論。

And the appropriate clinical endpoints and analyses to be able to provide them with an assessment of the benefit/risk ratio of crofelemer since crofelemer delayed release tablets are already approved by the FDA under the brand name Mytesi for HIV-related diarrhea. And the drug acts locally in the gut without any food or drug interactions and we have seen no crofelemer related serious adverse events in the 10-plus year of commercialization history.

適當的臨床終點和分析能夠為他們提供 Crofelemer 的益處/風險比評估，因為 Crofelemer 緩釋片劑已獲得 FDA 批准，商品名為 Mytesi，用於治療 HIV 相關腹瀉。該藥物在腸道局部發揮作用，沒有任何食物或藥物相互作用，在十多年的商業化歷史中，我們沒有看到與 Crofelemer 相關的嚴重不良事件。

The assessment of benefit risk ratio adds to the totality of evidence to support crofelemer's value for the cancer therapy-related diarrhea, CTD indication, in at least the subgroups of breast and lung cancer patients.

獲益風險比的評估增加了支持 Crofelemer 對癌症治療相關腹瀉、CTD 適應症（至少在乳癌和肺癌患者亞群中）的價值的全部證據。

A very important point that benefit/risk ratio. And it's interesting to see if there's any analogous situations out there with a drug that has been on the market for such a long period of time. with this safety record.

非常重要的一點就是收益/風險比。有趣的是，看看已經上市這麼長時間的藥物是否有類似的情況。有了這個安全記錄。

Pravin, let's also just remind everybody of the previous work that has been done in cancer patients, in particular, in breast cancer patients, the OnTarget trial added more clinical evidence or did they, in fact, add more clinical evidence than the previous Phase 2 study that was conducted in breast cancer patients?

Pravin，我們也提醒大家，之前在癌症患者中所做的工作，特別是在乳癌患者中，OnTarget 試驗添加了更多的臨床證據，或者說他們實際上比之前的2 期試驗添加了更多的臨床證據在乳癌患者中進行的研究？

Thanks for bringing that up, Lisa. I think you're referring to the HALT-D Phase 2 trial that was conducted in breast cancer patients receiving pertuzumab with standard chemotherapy. The HALT-D study which was a prophylactic study, helped inform us about conducting a longer-duration study. And hence, the OnTarget study was designed to have an overall period of treatment of 24 weeks, with the initial analysis being conducted at 12 weeks.

謝謝你提出這個問題，麗莎。我認為您指的是 HALT-D 2 期試驗，該試驗是在接受帕妥珠單抗和標準化療的乳癌患者中進行的。 HALT-D 研究是一項預防性研究，可幫助我們了解如何進行更長時間的研究。因此，OnTarget 研究的總治療期為 24 週，初步分析在第 12 週時進行。

The OnTarget study also identified that crofelemer in addition to its effects in breast cancer patients receiving targeted therapies, is also beneficial to lung cancer patients receiving targeted therapy with kinase inhibitor. That's a feature of having this all-inclusive solid tumor trial, the OnTarget study. So it was useful.

OnTarget研究也發現，Crofelemer除了對接受標靶治療的乳癌患者有作用外，對接受激酶抑制劑標靶治療的肺癌患者也有益。這是 OnTarget 研究這項包羅萬象的實體瘤試驗的一個特點。所以它很有用。

Yeah which I agree is the gift of this trial design that we were able to find this benefit in lung cancer patients as well. I know a lot of work has to be done to understand the significance of the rich and extensive database from OnTarget and I hope everybody got a feeling for that from your presentation here.

是的，我同意這是這個試驗設計的禮物，我們也能夠在肺癌患者中發現這種益處。我知道需要做很多工作才能理解 OnTarget 豐富而廣泛的資料庫的重要性，我希望每個人都能從您在這裡的演示中感受到這一點。

And I know this work will take some time. I'd like to call it, leaving no statistical analysis stone unturned here and it's likely going to go into 2025. So we have the most comprehensive briefing package prepared for the FDA. I'd like to just address the robustness of the crofelemer mechanism of action you called the paradigm shifting and other near-term pipeline opportunities for data reveal.

我知道這項工作需要一些時間。我想不遺餘力地進行統計分析，很可能會持續到 2025 年。我只想談談 Crofelemer 作用機制的穩健性，您稱之為範式轉移和其他近期數據揭示的管道機會。

With this in mind, Pravin, please now tell us about the targeted rare disease indications for crofelemer of SBS or bowel syndrome and MVID for crofelemer which have both received, of course, as I mentioned, orphan drug designation in the US and Europe. And describe how we expect crofelemer to work in these patient populations, what is the disease progression like for these patients and their standard of care?

考慮到這一點，Pravin，現在請告訴我們Crofelemer 的SBS 或腸綜合徵和MVID 的靶向罕見疾病適應症，當然，正如我提到的，這兩種藥物都在美國和歐洲獲得了孤兒藥資格。並描述我們期望 Crofelemer 如何在這些患者群體中發揮作用，這些患者的疾病進展及其護理標準如何？

Thanks, Lisa. Continuing this discussion into the orphan and rare disease indication for crofelemer is very important to me. We have made significant progress in achieving clinical and regulatory milestones, for the rare and orphan disease indications of short bowel syndrome with intestinal failure, SBS-IF as well as microvillus inclusion disease, MVID or crofelemer.

謝謝，麗莎。繼續討論 Crofelemer 的孤兒和罕見疾病適應症對我來說非常重要。我們在實現臨床和監管里程碑方面取得了重大進展，針對短腸症候群伴隨腸衰竭、SBS-IF 以及微絨毛包涵體病、MVID 或 Crofelemer 等罕見疾病和孤兒疾病適應症。

As I mentioned earlier, crofelemer shows a consistency in symptomatic management of diarrhea and other gastrointestinal symptoms in various clinical indications. Adult or pediatric patients which showed bowel syndrome with intestinal failure, are unable to absorb adequate calories from their oral intake due to intestinal failure, which can be due to either anatomic or functional reasons for their intestinal failure, which basically means that they have lost a part of their intestinal tract.

正如我之前提到的，Crofelemer 在各種臨床適應症中對腹瀉和其他胃腸道症狀的症狀管理表現出一致性。表現出腸症候群伴隨腸衰竭的成人或兒童患者，由於腸衰竭而無法從口服攝取中吸收足夠的熱量，這可能是由於腸衰竭的解剖或功能原因，這基本上意味著他們失去了他們腸道的一部分。

Hence, these patients require their daily caloric and nutritional requirements to be supplemented, to using total parenteral nutrition potentially up to 20 hours a day and up to seven days a week in some cases. Obviously, this is a catastrophic situation for the patients and their families.

因此，這些患者需要補充其每日熱量和營養需求，每天可能使用全腸外營養長達 20 小時，在某些情況下每週長達 7 天。顯然，這對病人及其家屬來說是一場災難。

In addition, some patients require TPN, total parenteral nutrition with more supplemental IV fluid, intravenous fluids as they are at risk for dehydration due to severe diarrhea. We are initiating a clinical trial in 2024 in the European Union. In adult, SBS-IF, short bowel syndrome with intestinal failure patients requiring TPN, with regulatory clearance from the European Medicines Agency, EMA which is the European counterpart of the US FDA.

此外，有些患者需要 TPN、全腸外營養以及更多補充靜脈輸液、靜脈輸液，因為他們有因嚴重腹瀉而脫水的風險。我們將於 2024 年在歐盟啟動一項臨床試驗。對於需要 TPN 的成人 SBS-IF 短腸症候群伴隨腸衰竭患者，已獲得歐洲藥品管理局 EMA（相當於美國 FDA 的歐洲同行）的監管許可。

In addition, we are supporting a couple of investigator-initiated exploratory studies in adult and pediatric SBS-IF patients, adult being at Cleveland Clinic and pediatric being at the Sheikh Khalifa Medical City in Abu Dhabi, for evaluating crofelemer's benefits in SBS-IF patients.

此外，我們也支持幾項由研究者發起的針對成人和兒童SBS-IF 患者的探索性研究，成人在克利夫蘭診所進行，兒童在阿布扎比謝赫哈利法醫療城進行，以評估Crofelemer 對SBS -IF 患者的益處。

It is important for everyone to understand that these SBS-IF patients are monitored very closely. And due to the shortened length of the intestinal tract and oral delayed-release tablet formulation of crofelemer currently on the market here in the US is not viable for these patients.

每個人都必須了解這些 SBS-IF 患者受到非常密切的監測，這一點很重要。由於腸道長度縮短，目前在美國市場上銷售的 Crofelemer 口服緩釋片配方對這些患者不可行。

Our team developed a novel, proprietary, highly concentrated like-for-like part of oral solution, which can be administered orally to these patients in very small volumes to evaluate the effects of crofelemer on various clinical symptoms of SBS-IF patients, including reductions in the stool volume output and the need for reduced parenteral support as a result of crofelemer's effects.

我們的團隊開發了一種新型、專有的、高度濃縮的口服溶液，可以以非常小的劑量口服給這些患者，以評估 Crofelemer 對 SBS-IF 患者各種臨床症狀的影響，包括減少由於Crofelemer 的作用，糞便量減少，並且需要減少腸外支持。

The collateral benefits of the novel lyophilized oral powder resolution, crofelemer formulation is that we can also administer that orally to pediatric patients that have the ultra-rare congenital diarrheal disorders called microvillus inclusion disease.

新型凍乾口服粉末解決方案 Crofelemer 製劑的附帶好處是，我們還可以給患有極其罕見的先天性腹瀉病（稱為微絨毛包涵體病）的兒科患者口服該製劑。

MVID patients do have a full length gut, but they do not have what is called a brush border membrane in their intestines. And therefore, they cannot absorb their required daily intake of nutrients or electrolytes. Hence, these patients also require lifelong total parenteral nutrition support to support their nutrition and caloric needs.

MVID 患者確實有完整的腸道，但他們的腸道中沒有所謂的刷狀緣膜。因此，他們無法吸收每日所需的營養或電解質攝取量。因此，這些患者也需要終生全腸外營養支持來滿足他們的營養和熱量需求。

And these patients fail to thrive. which means they don't grow as a normal child would. Thus, MVID is associated with significant morbidity and mortality. We've an active US IND for MVID and we're initiating a pioneer in clinical study to evaluate the benefit of crofelemer in pediatric MVID patients receiving TPN with or without supplemental IV fluids in 2024.

這些患者無法茁壯成長。這意味著他們不會像正常孩子一樣成長。因此，MVID 與顯著的發病率和死亡率有關。我們在美國有一項針對 MVID 的活躍 IND，並且正在啟動一項先鋒臨床研究，以評估 Crofelemer 對 2024 年接受 TPN（有或沒有補充靜脈輸液）的兒科 MVID 患者的益處。

We are also adding clinical sites in the European Union and in the Middle East, North Africa, MENA region as the incidence of MVID in those geographies is higher than the United States due to consanguineous marriages.

我們也在歐盟以及中東、北非、中東和北非地區增加臨床中心，因為這些地區由於近親結婚，MVID 的發生率高於美國。

An important near-term milestone for us will be the support we are providing for an investigator-initiated trial with one of our key opinion leaders and a member of my Scientific Advisory Board in the MENA region, Dr. Mohamad Miqdady, who was evaluating the effects of crofelemer in his pediatric patients with either microvillus inclusion disease or short-bowel syndrome with intestinal failure.

對我們來說，近期的一個重要里程碑將是我們為一項由研究者發起的試驗提供支持，該試驗由我們的一位關鍵意見領袖和我在中東和北非地區的科學顧問委員會成員Mohamad Miqdady 博士負責，他正在評估Crofelemer 對患有微絨毛包涵體病或伴有腸衰竭的短腸綜合徵的兒科患者的影響。

As you mentioned at the beginning of this webcast, we just received clearance for an import permit for shipping crofelemer to our SAB member in Abu Dhabi. And we are looking forward to his first patient being dosed there and proof-of-concept results as early as potentially in Q4 of this year.

正如您在本次網路廣播開始時所提到的，我們剛剛收到了向阿布達比的 SAB 成員運送 Crofelemer 的進口許可證。我們期待他的第一位患者在那裡接受給藥，並最早在今年第四季獲得概念驗證結果。

Thank you, Pravin for that. I do want to mention I've known Dr. Miqdady for about six years and I met him several times in Abu Dhabi. And the fortitude and the persistence he showed in going through all the regulatory paperwork to bring the product to his patients and the care that he has for these patients and the lack of alternative treatments, again, with pediatric MVID congenital diarrheal disorders, nothing else other than TPN.

謝謝你，普拉文。我確實想提一下，我認識 Miqdady 博士大約六年了，我在阿布達比見過他幾次。他在辦理所有監管文件以將產品帶給患者時所表現出的毅力和毅力，以及他對這些患者的護理，以及缺乏替代療法，再次強調，對於兒科 MVID 先天性腹瀉病，僅此而已比TPN 。

And key members of the Jaguar Napo team including myself and Pravin have visited many KOLs on three different continents. And what we hear is two of the most devastating toxic things that you administer to patients for their situation in both cancer and intestinal failure are chemotherapy and TPN, respectively.

Jaguar Napo 團隊的主要成員包括我和 Pravin 都拜訪過三個不同大陸的許多 KOL。我們聽到的是，針對癌症和腸道衰竭患者的情況，您給予的兩種最具破壞性的有毒物質分別是化療和 TPN。

So it is remarkable the commitment and the care that these physicians have to not only treating the patient's disorders, but also the focus on supportive care, quality of life, patient comfort, patient dignity.

因此，這些醫生不僅要治療患者的疾病，還要關注支持性照護、生活品質、病人舒適度和病人尊嚴，他們的承諾和照護是值得注意的。

So also, Pravin, I have asked you to describe some of the key learnings from these meetings that inform the protocol development.

Pravin，我也請你描述從這些會議中學到的一些重要知識，這些知識為協議的發展提供了資訊。

Thanks, Lisa. As you know, both MVID and SBS-IF are malabsorptive syndromes and much of the focus of clinicians have been on improving absorption of nutritional and caloric intake in these patients. Both FDA and EMA have approved a drug called teduglutide which is a growth hormone of GLP-2 for the management of adult and pediatric SBS-IF patients, it's given parenterally by injection.

謝謝，麗莎。如您所知，MVID 和 SBS-IF 都是吸收不良綜合徵，臨床醫生的主要關注點是改善這些患者的營養和熱量攝取吸收。 FDA 和 EMA 都批准了一種名為替度魯肽的藥物，該藥物是 GLP-2 的生長激素，用於治療成人和兒童 SBS-IF 患者，透過腸外注射給藥。

Since the approval of teduglutide, several additional biosimilars are also under the clinical development. And their clinical effects are very similar to teduglutide and their only differentiating feature relies on ease or convenience of administration to these patients, such as instead of giving daily, you give it once or twice a week.

自替度魯肽核准以來，其他幾種生物相似藥也正在臨床開發中。它們的臨床效果與替度魯肽非常相似，它們唯一的區別特徵依賴於這些患者給藥的簡易性或便利性，例如不是每天給藥，而是每週給藥一次或兩次。

It is important for the audience to understand that a standard of care for short bowel syndrome intestinal failure patient, is total parenteral nutrition, TPN. And teduglutide or any of the biosimilars and other growth hormones cannot be used in cancer patients that have showed bowel syndrome because it's a growth hormone. And teduglutide is not approved for pediatric MVID patients.

觀眾必須了解，短腸症候群腸衰竭患者的照護標準是全腸外營養 (TPN)。替度魯肽或任何生物相似藥和其他生長激素不能用於患有腸道綜合症的癌症患者，因為它是一種生長激素。替度魯肽未獲核准用於兒童 MVID 患者。

And it cannot be expected to provide benefit in these patients -- in MVID patients, that is, because they don't even have a brush problem membrane and they have limited ability to grow any absorbed through villi in the intestine with a growth hormone mechanism of action.

不能指望它會對這些患者（MVID 患者）帶來益處，也就是說，因為他們甚至沒有刷子問題膜，而且透過生長激素機制，他們透過腸道絨毛吸收的物質生長的能力有限。

So in our travels and discussions with KOLs, crofelemer not having any such limitations of a growth hormone because it acts locally in the gut lumen without significant oral absorption and provides the ability to reduce chloride secretion in the gut, along with the accompanying gut fluid accumulation that's reducing diarrhea.

因此，在我們的旅行和與KOL 的討論中，Crofelemer 沒有任何生長激素的局限性，因為它在腸腔中局部作用，沒有顯著的口服吸收，並且能夠減少腸道中氯化物的分泌，以及伴隨的腸液累積這就是減少腹瀉。

All clinical investigators across the US, the EU, and the MENA region, we welcome the opportunity to evaluate crofelemer because of its truly novel and well-tolerated therapy for their adult SBS-IF and pediatric MVID patients. I couldn't be more grateful to all these clinical investigators who are willing to study the patients because they are looking forward to giving a new therapy to their patients with crofelemer. Thank you.

美國、歐盟和中東和北非地區的所有臨床研究人員，我們歡迎有機會評估 Crofelemer，因為它對於成人 SBS-IF 和兒科 MVID 患者來說是一種真正新穎且耐受性良好的療法。我非常感謝所有這些願意研究患者的臨床研究人員，因為他們期待為 Crofelemer 患者提供新的治療方法。謝謝。

Thank you, Pravin. And I could not be more grateful to the Jaguar Napo team. This is truly a pipeline within a product with crofelemer and no other mechanism of action out there like that and it's a lot going on in a small company and you've got a snapshot here of just how complex clinical trial planning, execution, implementation, and analysis is, and we are committed to get crofelemer to all the patient populations that can benefit in the most efficient way possible. So Pravin, I think we should let you get back to work now, because clearly, you have a lot to do.

謝謝你，普拉文。我非常感謝 Jaguar Napo 團隊。這確實是 Crofelemer 產品中的一條管道，沒有其他類似的作用機制，這在一家小公司中發生了很多事情，您可以在這裡了解臨床試驗計劃、執行、實施是多麼複雜。將Crofelemer 帶給所有能夠以最有效的方式受益的患者群體。所以普拉文，我認為我們現在應該讓你回去工作，因為顯然，你有很多事情要做。

And we are now going to move the discussion over to the expansion of our commercial pipeline with a discussion Cathy Collis is going to leave and talk about our planned October 2024 commercial launch of Gelclair, which is FDA approved for mucositis.

我們現在將把討論轉移到擴大我們的商業管道上，Cathy Collis 將離開討論，討論我們計劃於 2024 年 10 月商業推出 Gelclair，該藥物已被 FDA 批准用於治療粘膜炎。

And I will just bring on a personal point. We had a mucositis experience in our family. And I can tell you, when that side effect occurs, all the focus is on eliminating the side effect and not on the treatment of the cancer or the underlying cause because it is so devastating.

我只想談談個人觀點。我們家有過黏膜炎的經驗。我可以告訴你，當副作用發生時，所有的重點都是消除副作用，而不是治療癌症或根本原因，因為它具有毀滅性。

But I'm so pleased that we have a commercial launch and a product opportunity in this area to again address patient comfort, their ability to stay on their cancer care which affects the outcome and also the dignity of the patient. So Cathy, over to you.

但我很高興我們在這一領域有一個商業發布和產品機會，再次解決患者的舒適度、他們繼續接受癌症護理的能力，這會影響結果和患者的尊嚴。那麼凱茜，交給你了。

Good morning, Lisa, and good morning to all of you joining us today. As Lisa has alluded and many of you are aware, oral mucositis is among the most common, painful and debilitating cancer treatment-related side effects. Gelclair is a protective gel with a mechanical action indicated for the management of pain and relief of pain by adhering to the mucosal surface of the mouth soothing oral lesions of various etiologies, including oral mucositis/stomatitis.

早安，麗莎，今天加入我們的所有人早安。正如麗莎所提到的，並且你們中的許多人都知道，口腔黏膜炎是與癌症治療相關的最常見、痛苦和衰弱的副作用之一。 Gelclair 是一種具有機械作用的保護性凝膠，透過黏附在口腔黏膜表面來控制疼痛和緩解疼痛，舒緩各種病因的口腔病變，包括口腔黏膜炎/口腔炎。

It is a clinically proven FDA-approved convenient and easy-to-use product that provides rapid and long-lasting pain relief and approves the ability of oral mucositis patients to eat, drink, swallow, speak, and sleep. Unlike other products for oral mucositis, it is not a numbing agent and does not sting the mouth. We all know cancer is chaotic because relations feel a loss of control over their life, their treatment, and their supportive care needs.

它是一種經臨床證明、經 FDA 批准的方便易用的產品，可提供快速、持久的疼痛緩解，並批准口腔黏膜炎患者進食、飲水、吞嚥、說話和睡眠的能力。與其他治療口腔黏膜炎的產品不同，它不是麻木劑，也不會刺痛口腔。我們都知道癌症是混亂的，因為親屬覺得對自己的生活、治療和支持性照護需求失去了控制。

Jaguar's mission is to change patients' lives for the better, especially in the area of supportive care for complex disease states like cancer. We are excited about our planned commercial launch of Gelclair in October 2024 because we believe we can help cancer patients by giving them a supportive care product for oral mucositis that provides soothing, pain relief without numbing and which is effective and safe.

捷豹的使命是改善患者的生活，特別是在癌症等複雜疾病狀態的支持性護理領域。我們對計劃於2024 年10 月商業推出Gelclair 感到興奮，因為我們相信我們可以透過為癌症患者提供一種治療口腔黏膜炎的支持性護理產品來幫助他們，該產品可以舒緩、緩解疼痛，且不會麻木，且有效且安全。

Our focus for the Gelclair launch will be patients with head and neck cancer. Head and neck cancers account for nearly 4% of all cancers in the United States according to the National Cancer Institute. Counting cancers of the oral cavity, pharynx, and larynx, the NCI, National Cancer Institute estimates that about 71,110 cases will occur in the United States this year. While up to 40% of all patients treated with chemotherapy develop oral mucositis, this percentage rises to approximately 90% for patients with head and neck cancers treated with chemotherapy and radiotherapy.

我們推出 Gelclair 的重點將是頭頸癌患者。根據美國國家癌症研究所的數據，頭頸癌占美國所有癌症的近 4%。根據NCI、美國國家癌症研究所的統計，美國今年將發生約71,110例口腔癌、咽癌和喉癌。在所有接受化療的患者中，高達 40% 的患者會出現口腔黏膜炎，而對於接受化療和放療的頭頸癌患者，這一比例上升至約 90%。

Of the latter, 19% may end up being hospitalized, experiencing a delay in their cancer treatment for high-grade mucositis management resulting in a reduction of the quality of life, a worse prognosis and an increase in patient management costs.

在後者中，19% 可能最終需要住院治療，因重度黏膜炎管理而延遲癌症治療，導致生活品質下降、預後更差以及患者管理成本增加。

Those of us working in the oncology field know the impact that side effect related delays or cessation of cancer treatment can have on the overall survival and the efficacy of treatment of patients with head and neck cancers treated with chemotherapy and radiotherapy, who develop oral mucositis, half the cases are typically considered severe, meaning oral mucositis of Grade 3 or 4 which typically puts a patient in the hospital, requiring parenteral nutrition and IV hydration, and, of course, the morbidity and expense associated with those treatments.

我們在腫瘤學領域工作的人都知道，與副作用相關的癌症治療延遲或停止可能會對接受化療和放療、出現口腔粘膜炎的頭頸癌患者的總體生存率和治療效果產生影響，一半的病例通常被認為是嚴重的，即3 級或4 級口腔黏膜炎，通常會使患者住院，需要腸外營養和靜脈補液，當然還有與這些治療相關的發病率和費用。

We're dedicating a great deal of effort to ensuring that our commercial launch plan for Gelclair is executed with sharp strategic focus. We're enhancing our educational, promotional, and sales representative team to cover cancer-related supportive care specialists. This positions us well as we anticipate future commitments in the cancer supportive care space.

我們正在付出巨大的努力來確保我們的 Gelclair 商業發布計劃能夠以明確的策略重點執行。我們正在加強我們的教育、促銷和銷售代表團隊，以涵蓋與癌症相關的支援護理專家。這使我們處於有利地位，因為我們預計未來在癌症支持護理領域的承諾。

To kick off the Gelclair launch, we plan to exhibit at several key oncology conferences in Q4 of this year. There will also be a strong digital component to our launch, providing information and education for patients to self-advocate. With that, I'll hand the conversation back to Lisa.

為了啟動 Gelclair 的推出，我們計劃在今年第四季的幾個重要腫瘤學會議上進行展示。我們的推出還將有一個強大的數位組成部分，為患者提供自我倡導的資訊和教育。說到這裡，我會把話題交回給麗莎。

Thank you so much, Cathy. And I'm so pleased about that last point of the opportunity to educate, inform patients for their ability to self-advocate. Jaguar's mission clearly is to change patients' lives for the better, especially in the area of supportive care for complex disease states like cancer.

非常感謝你，凱西。我很高興有機會教育和告知患者自我倡導的能力。捷豹的使命顯然是讓患者的生活變得更好，特別是在癌症等複雜疾病狀態的支持性護理領域。

We do not believe that any cancer therapy-related side effects whether it's oral mucositis, debilitating diarrhea, extreme fatigue, neuropathy, chronic pain, I mean the list goes on and on and on, should ever, ever be viewed as acceptable or tolerable.

我們不認為任何與癌症治療相關的副作用，無論是口腔黏膜炎、衰弱性腹瀉、極度疲勞、神經病變、慢性疼痛，我的意思是這樣的例子不勝枚舉，不應該被視為可以接受或可以忍受。

This belief is a core message of our ongoing Make Cancer Less Shitty campaign, which seeks to broadly acknowledge the rigors of both short-term and perpetual treatment cancer treatments for the metastatic patients, which are remarkable, allowing patients to live 5, 10, 15, 20 years with cancer as a chronically managed state.

這一信念是我們正在進行的「讓癌症不再那麼糟糕」運動的核心訊息，該運動旨在廣泛認可對轉移性患者進行短期和永久癌症治療的嚴格性，這是非常了不起的，可以讓患者活5 年、10 年、15 年, 20 年患有癌症作為長期管理狀態。

And with the Make Cancer Less Shitty campaign, allowing patients to share the voices and the stories with a lived experience, we launched the Make Cancer Less Shitty campaign with three remarkable patient ambassadors and you can find their stories and our commitment on the campaign website which is www.makecancerlessshitty.com. The primary social media channel for the Make Cancer Less Shitty Campaign is X, Twitter under the handle CancerSuckLess.

透過「讓癌症不再那麼糟糕」運動，讓患者透過生活體驗分享聲音和故事，我們與三位傑出的患者大使一起發起了「讓癌症不再那麼糟糕」運動，您可以在該運動網站上找到他們的故事和我們的承諾，是 www.makecancerlessshitty.com。 「讓癌症不再那麼糟糕」運動的主要社群媒體管道是 X、Twitter，其帳號為 CancerSuckLess。

We'll now hear from our CFO, Carol Lizak, regarding the financial highlights from the second quarter of 2024 and then I will be back. Good morning, Carol.

現在我們將聽取財務長 Carol Lizak 介紹 2024 年第二季的財務亮點，然後我會回來。早上好，卡羅爾。

Good morning, Lisa and thank you to all of you who have joined our webcast today. I'll begin my review of our financials for the second quarter of 2024. The combined second quarter 2024 revenue of approximately $2.72 million for prescription and non-prescription products, increased approximately 16% versus net first quarter 2024 revenue of $2.35 million and 2% versus net second quarter 2023 revenue of $2.67 million.

早安，麗莎，感謝今天參加我們網路廣播的所有人。我將開始審查我們2024 年第二季的財務狀況。成長約16%相比之下，2023 年第二季淨收入為 267 萬美元。

Mytesi prescription volume increased in the second quarter of 2024 compared to the first quarter of 2024 by 5.2%. Prescriptions decreased slightly by 0.4% in the second quarter of 2024, compared to the same period in 2023. Prescription volume differs from invoice sales volume, which reflects, among other factors, varying buying patterns among specialty pharmacies in the closed network as they manage their inventory levels.

與 2024 年第一季相比，2024 年第二季 Mytesi 處方量增加了 5.2%。與 2023 年同期相比，2024 年第二季度的處方藥數量略有下降 0.4%。處方藥量與發票銷量不同，這反映出封閉網絡中的專科藥房在管理其藥品時不同的購買模式等因素。水平。

Loss from our operations decreased by $0.9 million from $8.1 million in the quarter ended June 30, 2023, to $7.2 million during the same period in 2024. Non-GAAP recurring EBITDA for the second quarter of 2024 and the second quarter of 2023 were a net loss of $8.8 million and $7.7 million, respectively.

我們的營運虧損從截至2023 年6 月30 日的季度的810 萬美元減少了90 萬美元，至2024 年同期的720 萬美元。為淨額分別損失 880 萬美元和 770 萬美元。

Net loss attributable to common shareholders decreased by approximately $2.6 million from $12.1 million in the quarter ended June 30, 2023, to $9.5 million in the same period in 2024. Well, that concludes my recap of high-level financials for the second quarter of 2024. And I will now hand the discussion back to Lisa Conte.

普通股股東應佔淨虧損從截至2023 年6 月30 日的季度的1210 萬美元減少約260 萬美元，至2024 年同期的950 萬美元。回顧到此結束現在我將把討論交還給麗莎·孔特。

Thank you, Carol. Thank you, Cathy. Thank you, Pravin. Thanks to all of you who joined this webcast and are interested in support of Jaguar Health. And I also would like to thank Peter Hodge, who handles our Investor Relations.

謝謝你，卡羅爾。謝謝你，凱西。謝謝你，普拉文。感謝所有參加本次網路廣播並有興趣支持 Jaguar Health 的人。我還要感謝負責我們投資人關係的 Peter Hodge。

Again, our mission at Jaguar and the family of Napo Companies is to change patients' lives, of course, for the better. Our mission is unwavering and we're inspired by the potential of a crofelemer's novel and paradigm shifting mechanism of action may have to impact outcomes for certain complex diseases by providing that supportive care.

再說一遍，捷豹和 Napo Companies 家族的使命是改變患者的生活，當然，是為了讓他們的生活變得更好。我們的使命是堅定不移的，我們受到 Crofelemer 新穎且範式轉移的作用機制的潛力的啟發，該機制可能會透過提供支持性護理來影響某些複雜疾病的結果。

We're also very excited about our upcoming Gelclair launch, October just around the corner of this year. Patients are and always remain at the heart of our mission.

我們也對即將於今年 10 月推出的 Gelclair 感到非常興奮。患者始終是我們使命的核心。

Through the process of sustainably bringing crofelemer from a tree in the rainforest, to an FDA-approved prescription product and that is, of course, the trade name Mytesi, in pharmacies across the United States for supportive care indication or the indication currently approved is adults living with HIV/AIDS, who have non-infectious diarrhea, we have gained a great deal of experience about educating healthcare professionals and patients and payers about the novel paradigm shifting mechanism.

透過可持續地將來自熱帶雨林中的 Crofelemer 製成 FDA 批准的處方產品（當然是商品名 Mytesi）的過程，在美國各地的藥房中用於支持性護理適應症或目前批准的適應症是成人對於患有非感染性腹瀉的愛滋病毒/愛滋病患者，我們在向醫療保健專業人員、患者和付款人宣傳新型範式轉變機制方面獲得了大量經驗。

We've learned also from the veterinary and pet parent response to our crofelemer prescription product, Canalevia-CA1, which is conditionally approved by the FDA, interestingly, for the treatment of chemotherapy-induced diarrhea in dogs. Yes, our dog in the United States with cancer on chemotherapy and diarrhea, you can receive a prescription for crofelemer.

我們也從獸醫和寵物家長對我們的 Crofelemer 處方產品 Canalevia-CA1 的反應中了解到，該產品已獲得 FDA 有條件批准，有趣的是，用於治療狗化療引起的腹瀉。是的，我們在美國的狗因化療和腹瀉而患有癌症，您可以獲得 Crofelemer 處方。

We thank you, our shareholders, for your support and your dedication to our mission to bring innovative and novel prescription products to patients in need around the world. plant-based products from our basic enabling discovery technology. We thank you for your persistence and your patience as drug development is a long process and we thank you once again for joining today's webcast. All please be well.

我們感謝您，我們的股東，感謝您對我們使命的支持和奉獻，為世界各地有需要的患者提供創新和新穎的處方產品。來自我們基本上支持發現技術的植物產品。我們感謝您的堅持和耐心，因為藥物開發是一個漫長的過程，我們再次感謝您加入今天的網路廣播。一切請一切安好。

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

謝謝。今天的電話會議到此結束。此時您可以斷開線路。感謝您的參與。