Jaguar Health Inc (JAGX) 2022 Q4 法說會逐字稿

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

早上好。在我將電話轉交給管理層之前，我想提醒您，管理層可能會就公司的有限增長前景、產品市場接受度的不確定性以及競爭產品和定價的影響等事項做出前瞻性陳述，行業趨勢和產品計劃，包括處於開發階段的項目，可能無法實現科學目標或嚴格的監管要求。

Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially than those contemplating in such forward-looking statements. These statements are based on currently available information and management's current assumptions, expectations and projections about future events. While management believes its assumptions, expectations and projections are reasonable in view of currently available information, your question not to place undue reliance on these forward-looking statements.

前瞻性陳述受到風險和不確定性的影響，這些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存在重大差異。這些陳述基於當前可獲得的信息和管理層對未來事件的當前假設、預期和預測。雖然管理層認為其假設、預期和預測根據當前可用信息是合理的，但您的問題是不要過分依賴這些前瞻性陳述。

The company's actual results may differ materially from those discussed in today's -- during this webcast for a variety of reasons, including those described in forward-looking statements and Risk Factors sections of the company's Form 10-K for the year of 2022, which was filed, March 24, 2023, and its other filings with the SEC, which are available on the Investor Relations section of Jaguar's website.

由於各種原因，公司的實際結果可能與今天在本次網絡廣播中討論的結果存在重大差異，包括公司 2022 年 10-K 表格的前瞻性陳述和風險因素部分中描述的那些，這是於 2023 年 3 月 24 日提交，以及其向美國證券交易委員會提交的其他文件，可在捷豹網站的投資者關係部分查閱。

Except as required by law, Jaguar undertakes no obligation to update or revise any forward-looking statements contained in this presentation to reflect new information and 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演示文稿中包含的任何前瞻性陳述以反映新信息和未來事件或其他情況的義務。此外，請注意，公司通過提供非 GAAP EBITDA 和非 GAAP 經常性 EBITDA 來補充其按 GAAP 編制的簡明合併財務報表。

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

捷豹認為，這些非 GAAP 措施的披露項目為投資者提供了反映公司管理層評估和經營業務的基礎的額外信息。這些非 GAAP 財務措施不應孤立地看待或替代 GAAP 淨銷售額和 GAAP 淨虧損，也不能替代或優於衡量財務業績和符合 GAAP 的措施。今天的會議正在錄製中。

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

此時此刻，我很高興將會議轉交給 Jaguar Health 的創始人、總裁兼首席執行官 Lisa Conte；麗莎，地板是你的。

Thank you very much, and welcome to all. As you just heard, my name is Lisa Conte, and I'm the Founder, President and CEO of Jaguar Health and our wholly owned subsidiary in the United States Napo Pharmaceuticals. Sometimes we use Napo and Jaguar names interchangeably. I'm also a member of the Board of Napo Therapeutics, the corporation we established in 2021 in Milan, Italy, which is focused on expanding access to crofelemer in Europe, in particular for rare disorders.

非常感謝，歡迎大家。正如你們剛剛聽到的，我叫 Lisa Conte，我是 Jaguar Health 的創始人、總裁兼首席執行官，也是我們在美國 Napo Pharmaceuticals 的全資子公司。有時我們會互換使用 Napo 和 Jaguar 名稱。我也是 Napo Therapeutics 的董事會成員，該公司於 2021 年在意大利米蘭成立，專注於在歐洲擴大 crofelemer 的使用範圍，特別是針對罕見疾病。

I'm going to begin today by letting you know we will highlight shortly the key events that we expect in 2023 will be transformative in terms of value generation for all our stakeholders including patients and shareholders. Moving late-stage pipeline opportunities towards revenue-generating reality, this is an important theme that you will hear infused throughout today's call.

今天開始，我要讓您知道，我們將很快強調我們預計 2023 年將在為包括患者和股東在內的所有利益相關者創造價值方面產生變革的關鍵事件。將後期管道機會轉向創收現實，這是您將在今天的電話會議中聽到的一個重要主題。

Right now, I will review the key top line results for the fourth quarter of 2022. Prescription product net revenue was approximately $11.9 million for the year ended December 31, 2022 versus approximately $4.3 million for the previous year ended December 31, 2021, an increase of 178.7%. We are quite pleased with the growth trajectory of our current prescription drug business, which from Mytesi is currently limited to the approved specialty market indication of HIV-related diarrhea and, as I often say, specialty often typically means a relatively small market opportunity.

現在，我將回顧 2022 年第四季度的主要業績。截至 2022 年 12 月 31 日止年度，處方產品淨收入約為 1,190 萬美元，而截至 2021 年 12 月 31 日止年度約為 430 萬美元，增加178.7%。我們對我們當前處方藥業務的增長軌跡感到非常滿意，Mytesi 目前僅限於經批准的 HIV 相關腹瀉的專業市場適應症，正如我經常說的那樣，專業通常意味著相對較小的市場機會。

Regarding the company's cash position, the company had cash of approximately $15.3 million as of March 24, 2023, just a couple of days ago, the filing date of Jaguar's annual report on Form 10-K for the year 2022. I'm going to repeat that. Cash of approximately $15.3 million, as I speak this morning, an important and meaningful subsequent events in our 10-K filing that I'm often asked about.

關於公司的現金狀況，截至 2023 年 3 月 24 日，即幾天前，也就是捷豹 2022 年 10-K 表格年度報告的提交日期，公司擁有大約 1530 萬美元的現金。我打算重複一遍。現金約為 1530 萬美元，正如我今天早上所說，這是我經常被問及的 10-K 文件中重要且有意義的後續事件。

Following my update, Carol Lizak, Jaguar's Chief Financial Officer, will provide a recap of the key financial results for 2022. And then we'll hear from Ian Wendt, Jaguar's Chief Commercial Officer. Ian will speak to updates on Mytesi-related commercial initiatives to continue to educate and serve the HIV community, and about ongoing commercial efforts underway for Canalevia-CA1, our prescription drug for the treatment of chemotherapy-induced diarrhea in dogs.

在我更新後，捷豹首席財務官卡羅爾·利扎克 (Carol Lizak) 將回顧 2022 年的主要財務業績。然後我們將聽取捷豹首席商務官伊恩·溫特 (Ian Wendt) 的講話。 Ian 將介紹與 Mytesi 相關的商業舉措的最新情況，以繼續教育和服務 HIV 社區，以及正在進行的 Canalevia-CA1 的商業活動，Canalevia-CA1 是我們用於治療狗化療引起的腹瀉的處方藥。

As a reminder, our commercialized human drug product is named Mytesi. The generic name is Crofelemer. It's a first-in-class antisecretory agent approved initially in the United States for the specialty indication of HIV-related diarrhea, very specifically the symptomatic relief of noninfectious diarrhea in adult patients with HIV AIDS on anti-retroviral therapy.

提醒一下，我們的商業化人用藥物產品名為 Mytesi。通用名稱是 Crofelemer。它是一流的抗分泌劑，最初在美國批准用於 HIV 相關腹瀉的特殊適應症，特別是在接受抗逆轉錄病毒治療的 HIV AIDS 成年患者中緩解非感染性腹瀉的症狀。

As I mentioned, it's a relatively small market. This indication was fast-tracked by the FDA. And that's why HIV diarrhea is the first approved indication for Crofelemer. As I frequently state, what is really powerful about Crofelemer is that it is a pipeline within a product. And what I'm going to focus on today are our key clinical milestones.

正如我提到的，這是一個相對較小的市場。 FDA 對這一適應症進行了快速跟踪。這就是為什麼 HIV 腹瀉是 Crofelemer 的第一個獲批適應症。正如我經常指出的那樣，Crofelemer 的真正強大之處在於它是產品中的管道。我今天要關注的是我們的關鍵臨床里程碑。

Again, what we believe are potentially transformative events in 2023 in support of the company Crofelemer from pipeline opportunities; two, with the potential of important and significant clinical trial results this year, tangible revenue generating patient benefiting, shareholder, stakeholder benefiting product indications our ongoing pivotal Phase III trial, OnTarget trial, called the OnTarget trial of Crofelemer for cancer therapy-related diarrhea, and I may refer to that as CTD is our flagship development program. This trial is being conducted with the same dose and formulation of our Mytesi product, of course, already commercialized in the United States for HIV-related diarrhea, the same product, same dose, same formulation.

同樣，我們認為 2023 年可能會發生變革性事件，以從管道機會中支持 Crofelemer 公司；二，今年有可能取得重要和顯著的臨床試驗結果，產生有形收入，使患者受益，股東，利益相關者受益產品適應症我們正在進行的關鍵 III 期試驗，OnTarget 試驗，稱為 Crofelemer 的 OnTarget 試驗，用於癌症治療相關的腹瀉，我可以將其稱為 CTD 是我們的旗艦開發計劃。該試驗使用我們的 Mytesi 產品的相同劑量和配方進行，當然，已經在美國商業化用於 HIV 相關腹瀉，相同的產品，相同的劑量，相同的配方。

The OnTarget trail is evaluating the effectiveness of Crofelemer's novel mechanism of action, the modulation of two chloride ion channels in the gastrointestinal tract to mitigate or substantially reduce CTD in a prophylactic setting. It is a study that aims to expand the approved indication of Mytesi from the current limited HIV related Diarrhea to the potential blockbuster needs of prophylaxis in patients with cancer therapy-related diarrhea.

OnTarget 試驗正在評估 Crofelemer 的新作用機制的有效性，即在預防環境中調節胃腸道中的兩個氯離子通道以減輕或顯著減少 CTD。這項研究旨在將 Mytesi 的批准適應症從目前有限的 HIV 相關腹瀉擴大到癌症治療相關腹瀉患者預防的潛在重磅炸彈需求。

Our efforts over the past year to expand the OnTarget trial to new U.S. and international sites with trial sites now active in Eastern Europe in both Georgia and the Republic of Serbia as well as in Argentina and Taiwan have significantly accelerated patient enrollment.

在過去的一年裡，我們努力將 OnTarget 試驗擴展到新的美國和國際地點，這些試驗地點目前在東歐的格魯吉亞和塞爾維亞共和國以及阿根廷和台灣都很活躍，這大大加快了患者註冊速度。

Enrollment is now at approximately essentially at over 80%. OnTarget trial enrollment of 256 patients is expected to complete early in the second quarter of 2023, which is literally just around the quarter. We do feel that the OnTarget trial will be transformative for value and value recognition at Jaguar. Diarrhea is the most common side effects associated with cancer therapy. As many as 52 of 100% of patients experienced diarrhea.

現在入學率大約基本超過80%。預計 256 名患者的 OnTarget 試驗註冊將於 2023 年第二季度初完成，也就是該季度左右。我們確實認為 OnTarget 試用將對 Jaguar 的價值和價值認可產生變革。腹瀉是與癌症治療相關的最常見的副作用。 100% 的患者中有多達 52 人出現腹瀉。

In addition to addressing patient comfort and dignity, which is so important, with approximately 40% of patients changing or stopping their life-saving cancer therapy due to diarrhea, there is a clear unmet medical need for a focused paradigm shifting biological approach.

除了解決患者的舒適度和尊嚴這一非常重要的問題外，大約 40% 的患者因腹瀉而改變或停止了挽救生命的癌症治療，顯然還沒有滿足對重點範式轉變生物學方法的醫療需求。

Our expectation is that the placebo-controlled OnTarget trial will provide evidence that diarrhea associated with targeted cancer therapies is chronic, impacts the patient's ability to remain on their targeted cancer therapy regimens, at proven doses for better outcomes in their cancer treatment. And that addressing CTD reduces overall health care costs, such as required hospitalization and rehydration from implications of chronic and/or severe diarrhea. Remember, Crofelemer has providing a potential opportunity for a paradigm shift for both prophylaxis and management of CTD.

我們的期望是，安慰劑對照的 OnTarget 試驗將提供證據表明與靶向癌症治療相關的腹瀉是慢性的，會影響患者在經過驗證的劑量下繼續其靶向癌症治療方案的能力，以獲得更好的癌症治療結果。並且解決 CTD 可以降低整體醫療保健成本，例如因慢性和/或嚴重腹瀉的影響而需要住院和補液。請記住，Crofelemer 為 CTD 的預防和管理模式轉變提供了一個潛在機會。

For which there are no current approved or tested antidiarrheal agents , for which antimotility drugs such as Imodium and loperamide, which are primarily opioids have constipating risks, which is totally inappropriate and, again, untested and unapproved for chronic administration.

對於目前沒有批准或測試的止瀉藥，抗蠕動藥物如 Imodium 和洛哌丁胺（主要是阿片類藥物）具有便秘風險，這完全不合適，並且再次未經測試和批准用於長期給藥。

Crofelemer is not an opioid and does not have that constipating risk associated with opioids. Each year, according to the CDC, more than 1 million cancer patients received chemotherapy or radiation in an outpatient oncology clinic in the United States. Treatment can last for months to years in both the curative and metastatic situations. These targeted therapies, of which there about 70 now, which are used on a chronic basis, often for the rest of the patient's life, work for the most part by mechanism is that induces the type of secretory diarrhea that Crofelemer normalizes.

Crofelemer 不是阿片類藥物，不存在與阿片類藥物相關的便秘風險。據疾病預防控制中心稱，每年有超過 100 萬癌症患者在美國的腫瘤門診接受化療或放療。在治愈和轉移情況下，治療可持續數月至數年。這些靶向療法，現在大約有 70 種，在慢性基礎上使用，通常在患者的餘生中使用，大部分的工作機制是誘導 Crofelemer 正常化的分泌性腹瀉類型。

Again, OnTarget is a prophylactic study which tells you a lot about how important it is to prevent the onset and the impact of diarrhea during cancer treatment with targeted therapy drugs. CTD is not the mile loss of bowel control that we've all invariably experienced with perhaps a mild flu, a bad meal. This is diarrhea that can put patients in the hospital, cause organ shutdown and has even contributed to death in some patients who have been studied in targeted cancer agent manufacturers clinical trials.

同樣，OnTarget 是一項預防性研究，它告訴您很多關於在使用靶向治療藥物進行癌症治療期間預防腹瀉發作和影響的重要性。 CTD 並不是我們在輕度流感、糟糕的一餐中都會經歷的腸道失控。這種腹瀉會使患者住院，導致器官停止運轉，甚至導致一些患者死亡，這些患者已經在靶向癌症藥物製造商的臨床試驗中進行了研究。

To project the potential global market opportunity for CTD, since Crofelemer would be the first drug to be approved for this indication, we're looking at an analogous market. Well, we don't put out financial -- specific financial guidance and forecast, the value of the global chemotherapy-induced nausea and vomiting market, CINV is projected to reach to $3.9 billion by 2029, according to a report published by market research firm, Health Care Analyst. And CINV agents are typically only used for about the first 3 to 5 days in traditional cytotoxic chemotherapy, and many of these agents are generic, which somewhat lowers what the projections -- financial projections can look like for proprietary drugs.

為了預測 CTD 的潛在全球市場機會，因為 Crofelemer 將是第一個被批准用於該適應症的藥物，我們正在尋找一個類似的市場。好吧，我們沒有給出財務——具體的財務指導和預測，根據市場研究公司發布的一份報告，全球化療引起的噁心和嘔吐市場的價值，CINV 預計到 2029 年將達到 39 億美元, 醫療保健分析師。 CINV 藥物通常僅在傳統細胞毒性化療的前 3 至 5 天使用，其中許多藥物都是通用的，這在一定程度上降低了預測——專有藥物的財務預測。

With CTD, we are talking about diarrhea that can persist on a chronic basis for months or years. That's the paradigm shift. We are very excited about our CTD program, the successful completion of patient enrollment in the OnTarget pivotal trial, which, as I mentioned, is targeted for early in the second quarter of 2023. Will -- We expect lead to a primary endpoint readout in Q3 of this year and then to a supplemental new drug application filing for the same formulation of Crofelemer as the currently commercialized drug Mytesi.

對於 CTD，我們談論的是可以慢性持續數月或數年的腹瀉。這就是范式轉變。我們對我們的 CTD 計劃感到非常興奮，成功完成了 OnTarget 關鍵試驗的患者登記，正如我提到的，該試驗的目標是在 2023 年第二季度初進行。我們希望在今年第三季度，然後提交了與目前商業化藥物 Mytesi 相同配方的 Crofelemer 的補充新藥申請。

Mytesi is already approved for chronic use in people living with HIV AIDS, and it has a full FDA compliant supply chain in place from the rain forest to our distribution network with specialty pharmacies across the United States. And as a reminder, safety and manufacturing are the 2 most common reasons that new drug applications fail, and these activities are completed for Mytesi from a regulatory perspective. Hence, we spent much care and engage in extensive communication with the FDA in the business line and execution of the final clinical and regulatory steps to support bringing Crofelemer to cancer patients suffering from diarrhea and/or the risk of on a prophylaxis basis from their prescribed therapy.

Mytesi 已獲准長期用於艾滋病病毒感染者，並且它擁有完整的符合 FDA 標準的供應鏈，從雨林到我們在美國各地的專業藥房的分銷網絡。提醒一下，安全和製造是新藥申請失敗的兩個最常見原因，從監管角度來看，這些活動已為 Mytesi 完成。因此，我們非常謹慎地與 FDA 就業務線和最終臨床和監管步驟的執行進行了廣泛的溝通，以支持將 Crofelemer 帶給患有腹瀉和/或有預防風險的癌症患者治療。

In preparation for the expected commercial launch of Crofelemer for CTD, we're increasing our focus on patient advocacy initiatives in the United States. In support of this goal, we're very pleased by Dr. Kelly Shanahan, a former clinician herself and a metastatic breast cancer patient who is now a full-time independent patient advocate, has joined the Jaguar Scientific Advisory Board as both a health care provider in cancer patients, she shares our deep commitment to patient comfort and dignity, especially to the importance of preventing and ameliorating CTD on a chronic basis and in both accurative and metastatic settings. And to supportive care in cancer patients in general. We are so pleased to hear Dr. Shanahan's voice and perspective on how successful supportive care management is a key component to successful cancer treatment outcomes.

為了準備 Crofelemer 用於 CTD 的預期商業發布，我們正在增加對美國患者宣傳計劃的關注。為了支持這一目標，我們非常高興 Kelly Shanahan 博士加入了 Jaguar 科學顧問委員會，她曾是一名臨床醫生，也是一名轉移性乳腺癌患者，現在是一名全職的獨立患者倡導者，她既是一名醫療保健專家作為癌症患者的提供者，她與我們一樣堅定地致力於患者的舒適和尊嚴，尤其是在慢性基礎上以及在準確和轉移環境中預防和改善 CTD 的重要性。以及一般癌症患者的支持性護理。我們很高興聽到 Shanahan 博士關於成功的支持性護理管理如何成為成功的癌症治療結果的關鍵組成部分的聲音和觀點。

She brings a unique and welcome perspective to the community, including industry that will augment our efforts to bring about a paradigm shift to address the very high unmet and neglected comorbidity of CTD as novel targeted agents and approaches are addressing long-term management and potential cures for cancer. We support a full community approach to holistic patient care and comfort to support life and support quality of life.

她為社區帶來了獨特而受歡迎的觀點，包括行業將加強我們的努力，以實現範式轉變，以解決 CTD 非常高的未滿足和被忽視的合併症，因為新的靶向藥物和方法正在解決長期管理和潛在的治療方法對於癌症。我們支持採用完整的社區方法來提供全面的患者護理和舒適度，以支持生命和生活質量。

I'll now discuss our 2 prioritized rare disease target indications for Crofelemer. Short bowel syndrome, which I refer to as SBS with intestinal failure in adults and microvillous inclusion disease, MVID, an ultrarare pediatric congenital diarrheal disorder. This year, Jaguar and the company we established in Europe, Napo Therapeutics, are planning to support third party and we are supporting third-party investigator-initiated proof-of-concept studies of Crofelemer in patients with SBS with intestinal failure or pediatric patients with MVID focused on obtaining proof-of-concept data showing reduction of requirements of parenteral support, including parenteral nutrition and/or IV fluids.

我現在將討論 Crofelemer 的 2 個優先罕見病目標適應症。短腸綜合徵，我稱之為 SBS 伴有成人腸衰竭和微絨毛包涵體病，MVID，一種極其罕見的小兒先天性腹瀉病。今年，Jaguar 和我們在歐洲成立的公司 Napo Therapeutics 計劃支持第三方，我們正在支持第三方研究者發起的 Crofelemer 對伴有腸衰竭的 SBS 患者或伴有腸衰竭的兒科患者的概念驗證研究MVID 專注於獲得概念驗證數據，顯示腸外支持需求減少，包括腸外營養和/或靜脈輸液。

In accordance with the guidelines of specific European Union countries, publications of data from proof-of-concept trials could support early patient access programs to Crofelemer for SBS with intestinal failure or MVID potentially in 2024 through programs in these certain European countries, Italy, France, U.K., perhaps Spain as well.

根據特定歐盟國家的指導方針，概念驗證試驗數據的發布可以通過這些歐洲國家、意大利、法國的項目支持早期患者使用 Crofelemer 治療伴有腸衰竭或 MVID 的 SBS 或 MVID 項目，英國，也許還有西班牙。

Early access programs do not exist in the United States, are revenue generating and reimbursable for participating patients while the indicated product is continuing through clinical development for full approval in the EU.

美國不存在早期訪問計劃，在指定產品繼續通過臨床開發以在歐盟獲得完全批准的同時，為參與的患者創造收入和報銷。

Let me describe for a moment the catastrophic medical situation for people with short bowel syndrome. Normal small intestine is 20 to 25 feet in length. In short bowel syndrome, the patient's small bowel could be less than 5 feet for congenital reasons or as a result of surgery due to cancer inflammation or an accident. As you can imagine, with a very short gut, it's like a [SIV]. What goes in comes right out/. The bottom line is there's not enough intestinal real estate, enough surface area for the SBS patient to absorb the nutrients of life, carbohydrate, protein, fats, vitamins and minerals.

讓我描述一下短腸綜合症患者的災難性醫療狀況。正常的小腸長 20 到 25 英尺。在短腸綜合徵中，患者的小腸可能由於先天性原因或由於癌症炎症或事故而進行手術而小於 5 英尺。您可以想像，腸道非常短，就像 [SIV]。進則出/。底線是沒有足夠的腸道空間，SBS 患者沒有足夠的表面積來吸收生命中的營養素、碳水化合物、蛋白質、脂肪、維生素和礦物質。

So what happens is that such SBS patients that have intestinal failure, often end up on parenteral nutrition, the intravenous feeding of liquid nutrients for up to 20 hours a day, 7 days a week. Obviously, this has a significant negative impact on patients' quality of life, and there are multiple adverse events, infections and other complications associated with parenteral nutrition quite common. And parenteral nutrition is expensive, costing hundreds of thousands to $1 million a year to manage an individual patient including the myriad of associated complications with high morbidity, high mortality.

因此，發生腸衰竭的此類 SBS 患者通常會接受腸外營養，即每週 7 天、每天長達 20 小時的液體營養素靜脈內餵養。顯然，這對患者的生活質量產生了顯著的負面影響，並且與腸外營養相關的多種不良事件、感染和其他並發症相當普遍。腸外營養非常昂貴，每年要花費數十萬到 100 萬美元來管理一名患者，包括無數具有高發病率和高死亡率的相關並發症。

The global SBS market is projected to reach $5 billion by 2027, according to reports from [Vision] Research reports. And this, again, we're an orphan indication of about 40,000 patients around the world, but a classic orphan rare disease business model. Although parental Nutrition is considered the standard of care, there is a drug product approved for SBS call Teduglutide and its GLP-2 analog. It's essentially a growth hormone, intended to grow the real estate of the gut slightly, so there's a little bit more time for absorption of the nutrient of life. It's administered as an injection and is estimated to be utilized in less than 10% of the SBS population. Again, it is not standard care.

根據 [Vision] Research 的報告，全球 SBS 市場預計到 2027 年將達到 50 億美元。再次，我們是全球約 40,000 名患者的孤兒適應症，但這是一種經典的孤兒罕見病商業模式。儘管腸外營養被認為是護理標準，但有一種藥物產品被批准用於 SBS，稱為替度魯肽及其 GLP-2 類似物。它本質上是一種生長激素，旨在稍微增加腸道的不動產，因此有更多的時間來吸收生命的營養。它作為註射劑給藥，估計只有不到 10% 的 SBS 人群使用。同樣，這不是標準護理。

Teduglutide, which is hard to pronounce, Teduglutide has a range of side effects, including liver disorders, and is not tolerated by many patients on a chronic situation. The primary endpoint in the trial for the approval of teduglutide was the reduction in the time required to be on parenteral nutrition by about 20%. What we're looking to do with Crofelemer is to reduce the time on parenteral nutrition as the primary end point as well that pathway has already been utilized and provide better stool consistency and the quality of life measurement.

Teduglutide，很難發音，Teduglutide 有一系列副作用，包括肝臟疾病，許多慢性病患者不能耐受。批准替度魯肽的試驗的主要終點是將接受腸外營養所需的時間減少約 20%。我們希望用 Crofelemer 做的是減少作為主要終點的腸外營養時間，以及該途徑已經被利用，並提供更好的糞便稠度和生活質量測量。

We are working to design a global Phase II short bowel syndrome study of Crofelemer that harmonizes with the requirements of both the FDA and the European Medicines Agency, EMA, which is the regulatory agency of the EU.

我們正在努力設計 Crofelemer 的全球 II 期短腸綜合徵研究，該研究符合 FDA 和歐洲藥品管理局 (EMA) 的要求，EMA 是歐盟的監管機構。

Jaguar is also planning to submit an investigation of new drug application and IND to the FDA for MVID in the second quarter of 2023. Again, another milestone just around the corner.

捷豹還計劃在 2023 年第二季度向 FDA 提交針對 MVID 的新藥申請和 IND 調查。同樣，另一個里程碑即將到來。

So to recap, early in Q2 2023, literally, just a couple of days away, to get into Q2, we expect to have completion of enrollment in our Phase III trial of prophylaxis of cancer therapy-related diarrhea. That's the OnTarget trial with a primary endpoint readout expected in Q3 of this year, and within the same time frame, we're targeting our first proof-of-concept evidence for patients with either SBS with intestinal failure and/or for MVID in support of potential early access program participation, revenue-generating participation in certain European countries. This pathway could bring in meaningful revenues while Crofelemer continues to go through the process for full approval, not only in the EU on a global basis for these 2 rare disease indications.

因此，回顧一下，2023 年第二季度初，從字面上看，距離第二季度只有幾天的時間，我們預計將完成我們預防癌症治療相關腹瀉的 III 期試驗的註冊。這是 OnTarget 試驗，預計將在今年第三季度公佈主要終點，在同一時間段內，我們的目標是針對 SBS 伴腸衰竭和/或 MVID 患者的第一個概念驗證證據潛在的早期訪問計劃參與，某些歐洲國家的創收參與。這條途徑可以帶來可觀的收入，同時 Crofelemer 繼續通過全面批准的過程，不僅在歐盟在全球範圍內對這兩種罕見疾病適應症進行批准。

I'm now going to discuss our other development stage programs at this time. We are prioritizing for 2023, these 2 late-stage clinical development programs with key near-term milestones with the potential to be transformative in value recognition for Jaguar, particularly with the current financial market conditions for emerging biotech companies, which has not spared Jaguar either.

我現在要討論我們的其他發展階段計劃。我們正在優先考慮 2023 年的這 2 個後期臨床開發計劃，這些計劃具有關鍵的近期里程碑，有可能在 Jaguar 的價值認可方面發生變革，特別是在新興生物技術公司當前的金融市場條件下，Jaguar 也未能倖免.

And a new one to recap, our current cash solution. $15.3 million, relevant to achieving these important clinical milestones. Before I hand the discussion over to our CFO, Carol Lizak, . I want to let you know that anybody participating today that we will have a brief Q&A segment at the end of the webcast to address questions if there are any submitted in writing and that we have time for. Questions can be submitted via the webcast link for today's event that appears on the Events and Presentations page of the Investor Relations section of Jaguar's website. The URL for Jaguar's website is jaguar.health. We will now move along to key financial results for the fourth quarter of 2022 and Carol Lizak, let me hand it over to you.

回顧一下我們目前的現金解決方案。 1530 萬美元，用於實現這些重要的臨床里程碑。在我將討論交給我們的首席財務官 Carol Lizak 之前，......我想讓您知道今天參加的任何人，我們將在網絡廣播結束時有一個簡短的問答環節來解決問題，如果有任何書面提交並且我們有時間。可以通過 Jaguar 網站投資者關係部分的活動和演示頁面上顯示的今天活動的網絡直播鏈接提交問題。 Jaguar 網站的 URL 是 jaguar.health。我們現在將繼續討論 2022 年第四季度的主要財務業績，Carol Lizak，讓我把它交給你。

Well, thank you, Lisa, and thank you all for joining our webcast today. I'll begin our review of our 2022 financials. Prescription product net revenue was approximately $11.9 million for the year ended December 31, 2022 versus approximately $4.3 million for the year ended December 31, 2021, an increase of 178.7%.

好吧，謝謝你，麗莎，感謝大家今天參加我們的網絡廣播。我將開始審查 2022 年的財務狀況。截至 2022 年 12 月 31 日止年度，處方產品淨收入約為 1190 萬美元，而截至 2021 年 12 月 31 日止年度約為 430 萬美元，增長 178.7%。

Prescription product net revenue of approximately $3.3 million in Q4 2022 increased 3.4% over the third quarter in 2022 and increased approximately 57% over Prescription product net revenue in the fourth quarter of 2021.

2022年第四季度處方產品淨收入約為330萬美元，比2022年第三季度增長3.4%，比2021年第四季度處方產品淨收入增長約57%。

Mytesi total prescription volume was approximately 5,947 in the year 2022. Due to the transition to a limited distribution specialty pharmacy model in 2022, the company cannot accurately compare prescription volume from 2021 to 2022, as there are significant differences in reporting methodology from these distribution models. In the future, the company will be able to accurately reflect growth in prescription volume using 2022 as the new baseline.

Mytesi 2022 年總處方量約為 5,947。由於 2022 年向有限分銷專業藥房模式過渡，公司無法準確比較 2021 年至 2022 年的處方量，因為這些分銷模式的報告方法存在顯著差異.未來，公司將能夠以 2022 年為新基線準確反映處方量的增長。

Mytesi total prescription volume decreased slightly by approximately 2% in the fourth quarter of 2022 over the third quarter of 2022. Prescription volume differs from invoiced sales volume, which reflects, among other factors, varying buying patterns among specialty pharmacies in the closed network as they manage their inventory levels.

Mytesi 的總處方量在 2022 年第四季度比 2022 年第三季度略微下降了約 2%。處方量與發票銷售量不同，這反映了封閉網絡中專業藥房的不同購買模式等因素，因為它們管理他們的庫存水平。

The loss from operations decreased by $6.3 million from $40.7 million in the year 2021 to $34.4 million in 2022, largely due to the aggregate improvement in net revenue of $7.6 million, decreased cost of sales and marketing expenses of $400,000 and warrant inducement expenses of $1.6 million in 2021 and none recorded in 2022. These were offset by the aggregate increase in R&D and G&A expenses of $3.3 million.

運營虧損從 2021 年的 4070 萬美元減少 630 萬美元至 2022 年的 3440 萬美元，這主要是由於淨收入總計增加 760 萬美元、銷售成本和營銷費用減少 400,000 美元以及認股權證誘導費用減少 160 萬美元2021 年沒有記錄，2022 年沒有記錄。這些被研發和 G&A 費用總計增加 330 萬美元所抵消。

Non-GAAP EBITDA for the year 2022 and the year 2021 were a net loss of $28.1 million and net loss of $37.5 million, respectively. Net loss attributable to common shareholders decreased by approximately $5.1 million from $52.6 million in the year 2021 to $47.5 million in 2022.

2022 年和 2021 年的非美國通用會計準則 EBITDA 分別為淨虧損 2810 萬美元和 3750 萬美元。歸屬於普通股股東的淨虧損從 2021 年的 5260 萬美元減少約 510 萬美元至 2022 年的 4750 萬美元。

In addition to the loss from operations, interest expense increased by $4.3 million from $8.4 million in the year 2021 to $12.7 million in 2022, primarily due to the additional interest expense incurred on royalty interest agreements as a result of the change in the timing of payments due to exchanges in the new royalty interest purchase agreement.

除運營虧損外，利息支出增加了 430 萬美元，從 2021 年的 840 萬美元增加到 2022 年的 1270 萬美元，這主要是由於付款時間的變化導致特許權使用費利息協議產生的額外利息支出由於交換了新的特許權使用費權益購買協議。

The loss on the extinguishment of debt increased by $1.4 million from $800,000 for the year 2021 to $2.2 million in 2022 due to the extinguishment loss from the exchange of the outstanding balance of a royalty agreement for shares of the company's common stock. Change in fair value of financial instruments and hybrid instruments designated at fair value option or FVO, decreased by $1.9 million from a loss of approximately $2 million in the year 2021 to a loss of about $21,000 for the year 2022 primarily due to fair value adjustments in liability classified warrants and notes payable designated as FVO.

債務清償損失增加 140 萬美元，從 2021 年的 800,000 美元增加到 2022 年的 220 萬美元，原因是將特許權使用費協議的未償餘額交換為公司普通股的股份而產生的清償損失。指定為公允價值期權或 FVO 的金融工具和混合工具的公允價值變動減少了 190 萬美元，從 2021 年的虧損約 200 萬美元減少到 2022 年的虧損約 21,000 美元，主要原因是公允價值調整責任分類認股權證和指定為 FVO 的應付票據。

Other income or expenses increased $1.7 million from approximately $800,000 and other expenses for the year 2021 to approximately $1 million and other income in 2022 due to write-off of extinguished liabilities as a result of legal release and reversal of long outstanding accruals with reasonable uncertainty to not be incurred.

其他收入或支出增加了 170 萬美元，從 2021 年的約 800,000 美元和其他支出增加到 2022 年的約 100 萬美元和其他收入，原因是由於合法釋放和長期未結應計費用的逆轉而註銷了已消除的負債，具有合理的不確定性不會招致。

Well, that concludes my recap of high-level financials for the fourth quarter and the full year of 2022. I will now hand the discussion over to Ian Wendt, Jaguar's Chief Commercial Officer.

好吧，我對第四季度和 2022 年全年的高級財務回顧到此結束。我現在將討論交給捷豹首席商務官 Ian Wendt。

Thank you, Carol, and good morning to all. Q4 2022 is the sixth consecutive quarter of growth in Mytesi net revenue, which we're quite pleased about. As previously announced, the transition we completed in January 2022 to a limited distribution network of specialty pharmacies resulted in a meaningful reduction in Mytesi distribution costs as well as a higher average net price.

謝謝卡羅爾，大家早上好。 2022 年第四季度是 Mytesi 淨收入連續第六個季度增長，我們對此感到非常高興。正如之前宣布的那樣，我們在 2022 年 1 月完成了向有限的專業藥店分銷網絡的過渡，從而顯著降低了 Mytesi 分銷成本並提高了平均淨價。

I'm very pleased to report that we significantly outperformed the industry gross to net average in the fourth quarter of 2022 as we did in the 4 previous quarters for sales of our human prescription product. For comparison, according to prescription drug data and analytics firm SSR Health, the rolling 4-quarter average gross to net discount rate in Q3 2022 was 48.9% for all U.S. prescription branded products.

我很高興地報告，我們在 2022 年第四季度的人用處方產品銷售業績明顯優於行業平均水平，就像我們在前四個季度所做的那樣。相比之下，根據處方藥數據和分析公司 SSR Health 的數據，2022 年第三季度所有美國處方品牌產品的滾動 4 季度平均毛淨折扣率為 48.9%。

In 2022, the total gross to net discount for Mytesi was approximately 20%. The transition to specialty pharmacy distribution also assists in the preparation of the company's U.S. commercial distribution network for a potential future indication expansion of Crofelemer to other populations of patients with complex medical needs, such as CTD, inflammatory bowel disease and SBS.

2022 年，Mytesi 的毛淨折扣總額約為 20%。向專業藥房分銷的過渡還有助於準備公司的美國商業分銷網絡，以便未來將 Crofelemer 的適應症擴展到其他有復雜醫療需求的患者群體，如 CTD 、炎症性腸病和 SBS 。

I'm also pleased to report that our innovative recently launched programs that further support patients' connection to care and medication and access services are continuing as planned. Our telehealth initiative, which went live in May 2022, enables patients seeking help with their HIV-related diarrhea to be linked immediately to a provider for assistance with their medical needs. This capability prevents patients from having to wait until their next scheduled doctor visit to get help with what is an urgent problem.

我也很高興地報告，我們最近啟動的創新項目正在按計劃繼續進行，這些項目進一步支持患者與護理和藥物的聯繫以及獲得服務。我們的遠程醫療計劃於 2022 年 5 月上線，使尋求 HIV 相關腹瀉幫助的患者能夠立即與提供者聯繫，以幫助滿足他們的醫療需求。這種能力使患者不必等到下一次預定的醫生就診時才能獲得緊急問題的幫助。

Additionally, as announced on March 13, we are excited to be developing an artificial intelligence-powered web portal for U.S. health care professionals to support patient access to Mytesi. We remain committed to reducing access and reimbursement barriers for Mytesi patients and one key challenge we often hear from patients and their health care providers is that payers and insurance companies frequently require prior authorization to approve medication reimbursement. Artificial intelligence, AI, technology, like open AI's, generative AI platform model ChatGPT is an innovative and powerful tool that allows providers to expeditiously communicate the professional judgment by significantly reducing the time and complexity of drafting letters of medical necessity.

此外，正如 3 月 13 日宣布的那樣，我們很高興為美國醫療保健專業人員開發一個人工智能驅動的門戶網站，以支持患者訪問 Mytesi。我們仍然致力於減少 Mytesi 患者的獲取和報銷障礙，我們經常從患者及其醫療保健提供者那裡聽到的一個主要挑戰是付款人和保險公司經常需要事先授權才能批准藥物報銷。人工智能、AI、技術，如開放式 AI 的生成式 AI 平台模型 ChatGPT 是一種創新且功能強大的工具，它允許提供者通過顯著減少起草醫療必要性信件的時間和復雜性來迅速傳達專業判斷。

We are working to create a user-friendly ChatGPT-enabled interface to help make this otherwise burdensome process easier and faster for health care providers to navigate in a compliant way.

我們正在努力創建一個用戶友好的支持 ChatGPT 的界面，以幫助醫療保健提供者以合規的方式更輕鬆、更快速地完成這個繁瑣的過程。

Leveraging AI technology in support of the prior authorization process is expected to help a significant number of Mytesi patients start on their medically appropriate and necessary medication quicker and be able to stay on their prescribed regimen helping ensure they spend fewer days suffering needlessly from HIV-related diarrhea.

利用 AI 技術支持事先授權流程，預計將幫助大量 Mytesi 患者更快地開始他們的醫學上適當和必要的藥物治療，並能夠堅持他們的處方方案，幫助確保他們減少不必要地遭受 HIV 相關痛苦的天數腹瀉。

Turning to the Animal Health side of our business, Canalevia-CA1, our FDA initially approved drug for the treatment of chemotherapy-induced diarrhea or CID in dogs became commercially available to veterinarians across the United States at the end of April 2022. Since that time, we have succeeded in pushing Canalevia-CA1 into broad distribution with the leading veterinary distribution centers. Canalevia-CA1 net revenue was approximately $24,000 in the fourth quarter of 2022 representing an increase of 100% over Canalevia-CA1 net revenue in the third quarter of 2022, which totaled approximately $12,000.

談到我們業務的動物健康方面，我們的 FDA 最初批准用於治療狗化療引起的腹瀉或 CID 的藥物 Canalevia-CA1 於 2022 年 4 月底在美國各地的獸醫市場上銷售。從那時起，我們已經成功地將 Canalevia-CA1 推向領先的獸醫配送中心的廣泛分銷。 Canalevia-CA1 2022 年第四季度的淨收入約為 24,000 美元，比 Canalevia-CA1 2022 年第三季度的總收入約為 12,000 美元增長了 100%。

Commercial activities for the drug remain underway and reception of Canalevia-CA1 among general practice vets and veterinary oncologists continues to be extremely positive. That concludes my comments. Thank you all for your time today. I'll pass the conversation back to Lisa.

該藥物的商業活動仍在進行中，全科獸醫和獸醫腫瘤學家對 Canalevia-CA1 的接受度仍然非常高。我的評論到此結束。謝謝大家今天的時間。我會把談話轉回給麗莎。

Thank you, Ian. Okay -- and Carol, thank you, Ian and Carol. So we at Jaguar, Napo and Napo Therapeutics, we're energized about all of our important activities underway in 2023 and beyond with a very, very sharp strategic focus on these key clinical milestones in 2023, which I just cannot say enough, which we feel will be transformative for some value recognition for a company whose value and this industry has been hit hard in the past months and year.

謝謝你，伊恩。好的——卡羅爾，謝謝你們，伊恩和卡羅爾。因此，在 Jaguar、Napo 和 Napo Therapeutics，我們對 2023 年及以後正在進行的所有重要活動充滿活力，並將非常、非常敏銳的戰略重點放在 2023 年的這些關鍵臨床里程碑上，我說得不夠多，我們對於一家價值和該行業在過去幾個月和一年中受到重創的公司而言，這種感覺將對某些價值認可產生變革。

I do want to say in closing, uniquely about Jaguar, this past Tuesday was International Day of Ours and I want to take a moment to express how proud we are to be collaborating and interdependent with the people and tropical forest ecosystems of Peru from where we sustainably source the Latex and Dragon's Blood Tree, the plant also known as Croton lechleri from which Crofelemer is isolated and purified. It is clear that the cultural and ecological health of people and forests are intertwined at multiple levels, and we wish to express our gratitude to our partners and communities in the rain forest who have been working with us and teaching us for several decades, how to sustainably manage this valuable medicinal plant within their ecosystem in support of our mission to expand Crofelemer access to all patient populations in need around the globe.

最後，關於捷豹，我確實想說一下，上週二是我們的國際日，我想花點時間表達我們是多麼自豪能夠與秘魯的人民和熱帶森林生態系統合作和相互依存，我們來自那裡以可持續方式採購乳膠和龍血樹，這種植物也被稱為巴豆，Crofelemer 就是從中分離和純化的。很明顯，人與森林的文化和生態健康在多個層面交織在一起，我們希望向雨林中的合作夥伴和社區表示感謝，他們幾十年來一直與我們合作並教導我們，如何在其生態系統中可持續地管理這種有價值的藥用植物，以支持我們的使命，即擴大 Crofelemer 對全球所有有需要的患者群體的訪問。

And I do also want to remind everybody that Crofelemer, Mytesi is a natural product. It's organic, as I mentioned, sustainably harvested fair trade, and it is the only oral drug approved by the FDA under botanical guidance. And under botanical guidance, there's no practical pathway to bring a generic to market. And so while we have well over 100 patents issued and many more that are being filed on a regular basis as you do in the pharmaceutical industry. We essentially have exclusivity forever, which is a valuable and additional valuable asset and characteristic of this product as we go into business development discussions and conversations and negotiations.

我也想提醒大家，Crofelemer、Mytesi 是一種天然產品。它是有機的，正如我提到的，可持續收穫的公平貿易，它是 FDA 在植物學指導下批准的唯一口服藥物。在植物學指導下，沒有實用的途徑將仿製藥推向市場。因此，雖然我們已經發布了 100 多項專利，而且還有更多專利正在定期提交，就像您在製藥行業所做的那樣。我們基本上永遠擁有排他性，這是一項寶貴的和額外的寶貴資產，也是我們進行業務發展討論、對話和談判時該產品的特徵。

So this concludes our formal webcast for today, and I'm going to now look at some of the questions, and we will do a few Q&A as we have a little bit of time left. So give me a moment here to pull those up.

我們今天的正式網絡廣播到此結束，我現在要看一些問題，我們會做一些問答，因為我們還有一點時間。所以給我一點時間把它們拉起來。

It looks like there are a few questions in there. Okay. Is the primary completion date still this month, March 2023 for chemotherapy-induced diarrhea.

裡面好像有幾個問題。好的。化療引起的腹瀉的主要完成日期是否仍為本月，即 2023 年 3 月。

So as I mentioned, I'm just going to recap timing here. We expect to complete enrollment early in the second quarter. So early in the second quarter is April, beginning of May. We are standing behind that. And then that's completion of enrollment. The primary endpoint is after 3 months of treatment. So you can count forward, let's say, April, May, June, July, so the end of July, beginning of August. And then typically, in the industry, you would have about 8 weeks, plus or minus, to freeze the database upon which you get the primary endpoint released. And so that's the time frame that you can look at and give us -- the -- what we mentioned that we expect to and are targeting the primary endpoint in the third quarter of this year. So you can see the cascade of events from completing patient enrollment.

所以正如我提到的，我只是想在這裡回顧一下時間安排。我們預計將在第二季度初完成註冊。所以第二季度初是四月，五月初。我們支持它。然後就是完成註冊。主要終點是治療 3 個月後。所以你可以往前數，比方說，四月、五月、六月、七月，所以七月底、八月初。然後通常，在行業中，您將有大約 8 週的時間（或多或少）來凍結您發布主要端點的數據庫。因此，這就是您可以查看並給我們的時間框架 - 我們提到的我們期望並針對今年第三季度的主要終點。因此，您可以看到完成患者登記後的一系列事件。

Again, what we're looking for here is the statistical significance as negotiated with the FDA, and there was a lot of discussion with the FDA on this trial in a positive sense. On that primary end point, because we are talking about the expansion of the indication for supplemental NDA for Mytesi already on the market, same dose, same formulation, literally the same bottle. Mytesi already on the market, already approved for chronic indications. So for example, chronic safety studies, carcinogenicity studies have already been completed and supported that chronic indication. And obviously, we have a full supply chain regulatory compliant in place to take the product from Peru to a bottle and essentially any specialty pharmacy that we're working with in the United States. So manufacturing is completed as well.

同樣，我們在這裡尋找的是與 FDA 協商的統計顯著性，並且在積極意義上與 FDA 就該試驗進行了很多討論。在這個主要終點上，因為我們正在談論擴大市場上已經上市的 Mytesi 的補充 NDA 的適應症，相同的劑量，相同的配方，實際上是同一瓶。 Mytesi 已經上市，已獲准用於慢性適應症。因此，例如，慢性安全性研究、致癌性研究已經完成並支持該慢性適應症。顯然，我們有一個完整的供應鏈監管合規性，可以將產品從秘魯帶到瓶子裡，基本上是我們在美國合作的任何專業藥房。所以製造也完成了。

To most common reasons why new drug applications get pushed back, safety manufacturing completed at Jaguar. And then there was another question about the primary endpoint. So I've just answered that as well.

對於新藥申請被推遲的最常見原因，捷豹完成了安全生產。然後還有另一個關於主要終點的問題。所以我也剛剛回答了這個問題。

Are you planning any cash raises to support your trials this year?

您是否計劃籌集任何現金來支持您今年的試驗？

So I can tell you that we -- what -- I think the most important thing that I can tell you is what I did tell you already that are -- and what's in the public domain here, $15.3 million in the bank right now with those key clinical activities that we're looking for, which we feel can be transformative in value in targeted for the third quarter of this year. So I think that addresses the sentiment behind that question. Okay.

所以我可以告訴你我們 - 我認為我能告訴你的最重要的事情是我已經告訴過你的 - 以及這裡的公共領域，現在銀行有 1530 萬美元我們正在尋找的那些關鍵臨床活動，我們認為這些活動可以在今年第三季度的目標中產生變革性的價值。所以我認為這解決了這個問題背後的情緒。好的。

Let's see. The question is with Phase III enrollment largely complete in the second quarter and the switch to specialty pharmacy for Mytesi complete. Should investors expect expenses to significantly decrease going forward?

讓我們來看看。問題是第三階段的註冊在第二季度基本完成，而 Mytesi 的專業藥房也已完成。投資者是否應該預期未來費用會大幅減少？

And Carol, why don't you make any comments that would you like on that. But let me point out that the significant expenses in the company right now are associated with the clinical work to expand the indications and to get to new populations for Crofelemer. And those clinical trials are still ongoing. And in fact, as you come towards the end of clinical trials, you have additional activity from statisticians, quality operations to make sure that you clean up and you freeze those databases in an accurate way. But Carol, did you want to make any additional commentary?

Carol，你為什麼不發表任何你喜歡的評論呢？但我要指出，公司目前的大量開支與擴大 Crofelemer 適應症和接觸新人群的臨床工作有關。這些臨床試驗仍在進行中。事實上，當你接近臨床試驗的尾聲時，你會有來自統計學家的額外活動，質量操作以確保你清理並以準確的方式凍結這些數據庫。但是卡羅爾，你想發表任何額外的評論嗎？

Sure. We did save around the distribution costs compared to 2021 and 2022. So those were the big cost savings right there. And of course, the net revenue significantly increased.

當然。與 2021 年和 2022 年相比，我們確實節省了分銷成本。因此，這些是在那裡節省的大量成本。當然，淨收入顯著增加。

For R&D, yes, there will be some increases there because of the clinical trials surrounding our main indications focus, which is CTD and the SBS group. So I think those are the key savings that we had for 2022 and 2021.

對於研發，是的，由於圍繞我們主要適應症的臨床試驗，即 CTD 和 SBS 組，那裡會有一些增加。因此，我認為這些是我們在 2022 年和 2021 年節省的主要資金。

Thanks, Carol. So here's a question that I appreciate to bring up this topic. Someone was wondering, if there still future plans of attaining fast-track voucher for Cholera .

謝謝，卡羅爾。所以這裡有一個問題，我很高興提出這個話題。有人在想，未來是否還有獲得霍亂快速通道憑證的計劃。

so the Cholera program, it's very important and exciting program and it's Cholera mechanism of diarrhea is the pure clinical manifestation of the mechanism by which Crofelemer works and our second antisecretory agent known affectionately right now is NP-300. So we do have an approved IND for NP-300. And that -- so what this is referring to is that product is being developed with the financial return that is being targeted by us of a tropical disease priority review voucher.

所以霍亂計劃，這是一個非常重要和令人興奮的計劃，它的霍亂腹瀉機制是 Crofelemer 工作機制的純粹臨床表現，我們現在親切地知道的第二種抗分泌劑是 NP-300。所以我們確實有 NP-300 的批准 IND。而且 - 所以這是指正在開發的產品具有財務回報，這是我們針對熱帶病優先審查憑證的目標。

And what that is, is sort of a price that you get from the FDA that provides incentive to develop products for certain tropical diseases, certain rare diseases and Cholera is on that list. And so you get this prize, this voucher when you have a successfully approved new drug application, and that voucher is a voucher that if you can put it to any product, and it requires the FDA to review that new drug application for another product that you put it towards in 6 months or less.

那就是你從 FDA 獲得的某種價格，它為開發針對某些熱帶疾病、某些罕見疾病和霍亂的產品提供了激勵。所以當你有一個成功批准的新藥申請時，你會得到這個獎品，這張憑證，如果你可以把它放在任何產品上，它就需要 FDA 審查另一個產品的新藥申請你把它放在 6 個月或更短的時間內。

So it provides certainty and in some sense, greater efficiency and speed in reviewing a new drug application. And that voucher is transferable in sales, and you can sell them and there is a market for them. And they sell anywhere from the lowest ever was something like $67 million. I think the highest ever was $300-and-something million. Recently, they've sold for about over $100 million. It depends on who has the voucher and who needs the voucher at the time that you want to sell it.

因此，它提供了確定性，並在某種意義上提高了審查新藥申請的效率和速度。並且該優惠券可以在銷售中轉讓，您可以出售它們並且它們有市場。他們的銷售額從最低的 6700 萬美元開始。我認為有史以來最高的是 300 萬美元。最近，它們的售價已超過 1 億美元。這取決於您要出售憑證時誰擁有憑證以及誰需要憑證。

So they're not they are somewhat rare to come across, although you've seen more in recent years. So we're pursuing -- the key is that, that voucher is only available for the first indication for which a product is approved.

所以他們不是他們很少遇到，儘管你近年來看到的更多。所以我們正在追求 - 關鍵是，該優惠券僅適用於產品獲得批准的第一個跡象。

Crofelemer is already approved. But our second-generation antisecretory NP-300 is also an antisecretory agent. We feel as a distinct product under botanical guidance and comes from the same planned Croton lechleri, Dragon's blood and works by the same mechanism of action.

Crofelemer 已經獲得批准。但我們的第二代抗分泌劑 NP-300 也是一種抗分泌劑。我們感覺自己是植物學指導下的獨特產品，來自相同計劃的巴豆、龍血，並通過相同的作用機制發揮作用。

In the earlier years, we had done clinical work in Cholera with Crofelemer that is published posters are published that showed statistical significance in a key endpoint for the reduction of dehydration. And what kills a cholera patient does not the Cholera infection. It's the dehydration that typically occurs between 6 and 18 hours after infection, so often consider the death zone. And that's where we saw the significant reduction in the dehydration.

在早些年，我們使用 Crofelemer 在霍亂中進行了臨床研究，發表的海報顯示減少脫水的關鍵終點具有統計學意義。殺死霍亂患者的不是霍亂感染。脫水通常發生在感染後 6 到 18 小時之間，因此通常考慮死亡區。這就是我們看到脫水顯著減少的地方。

So we'll be following the same clinical pathway, in fact, the same principal investigator, the same clinical trial site with NP-300. Why did I not talk about it because again, with the industry and the valuation of Jaguar and other companies in the industry hit so hard this year, we are focusing on what I talked about those key what we feel are transformative clinical events that move us from pipeline to revenue generation. And the Cholera program wouldn't do that in 2023.

所以我們將遵循相同的臨床路徑，事實上，相同的主要研究者，與 NP-300 相同的臨床試驗站點。為什麼我不談論它，因為今年行業和 Jaguar 及業內其他公司的估值受到如此嚴重的打擊，我們正在關注我所說的那些我們認為是推動我們的變革性臨床事件的關鍵從管道到創收。霍亂計劃不會在 2023 年這樣做。

So it's longer term before we get to that revenue-generating or voucher generating situation. So it is on hold just for 2023. And as we get through these milestones and get some value recognition in this company, God bless, we will be able to turn that very, very important program on. And it's not as long the program as CTD or even HIV was because these are acute clinical trials. So they are 2 to 3 days of drug administration. So the trials move much faster. So thank you for that question.

因此，在我們達到創收或代金券生成情況之前，需要更長的時間。所以它只在 2023 年被擱置。當我們完成這些里程碑並在這家公司獲得一些價值認可時，上帝保佑，我們將能夠啟動這個非常非常重要的項目。而且它不像 CTD 甚至 HIV 那樣長，因為這些都是急性臨床試驗。所以他們是2到3天的給藥時間。所以試驗進行得更快。謝謝你提出這個問題。

Okay. Somebody asked about Canalevia for exercise-induced diarrhea in dogs.

好的。有人詢問 Canalevia 是否用於治療狗運動引起的腹瀉。

So Canalevia-CA1 is a conditionally approved product. And in the second, Ian, I'm going to let you talk about what that means specifically and how that affects our ability to educate and promote that product. But a second conditional approval exercise-induced diarrhea. I think like I did [a rod Dogs] is in discussions with the Center Of Veterinary Medicine at the FDA right now. So what's being discussed and negotiated is their desire for us to do some clinical work specifically in that patient population, though it is for a conditional approval, which often gives you a lot lower bar for clinical work.

所以Canalevia-CA1是有條件批准的產品。第二，伊恩，我要讓你談談這具體意味著什麼，以及這如何影響我們教育和推廣該產品的能力。但有條件批准運動引起的第二次腹瀉。我想就像我所做的那樣 [a rod Dogs] 正在與 FDA 的獸醫中心進行討論。因此，正在討論和協商的是他們希望我們專門針對該患者群體進行一些臨床工作，儘管這是有條件的批准，這通常會給您降低臨床工作的門檻。

And again, it falls in the same category as Cholera, where are we going to put our dollars and resources in 2023 to make a revenue-generating difference in the near term? So that's still under discussion with the Center of Veterinary Medicine.

再一次，它與霍亂屬於同一類別，我們將在 2023 年將我們的美元和資源投入何處以在短期內產生創收差異？所以這仍在與獸醫中心進行討論。

Ian, do you want to talk about some of the limitations of a conditionally approved product, but the excitement of what we're seeing with chemotherapy-induced diarrhea in dogs. And by the way, chemotherapy-induced diarrhea in dogs is highly predictive and analogous to the situation in humans. So it gives us, again, another reason to be highly confident about our OnTarget trial in humans the heading.

伊恩，你想談談有條件批准的產品的一些局限性，但我們看到化療引起的狗腹瀉的令人興奮。順便說一句，狗因化療引起的腹瀉具有很高的預測性，類似於人類的情況。因此，這再次給了我們另一個對我們在人類身上進行的 OnTarget 試驗充滿信心的理由。

Yes. The CA1 or conditional approval designation that you see for Canalevia right now is an easier pathway to approval. You have to show a reasonable expectation of effectiveness and doesn't require necessarily a full effect of this trial that you might -- in the designated population that you might see for traditional approval. So it allows you to get to market faster and for less cost, but it does come with some limitations. And a couple of them, just so you understand what those might be. are that it cannot be used off label. So there's a federal law in place that for CA1 designated medications, prescription medications, they have to strictly adhere to the label as indicated. And you might be aware that the veterinary community, they write off-label medications all the time and human health physicians do as well. But in this case, for CA1, there is that limitation. There's also a limitation in the size of the market. So right now, you can only seek this for -- in the canine arena for indications that would dose no more than 70,000 dogs. So there are some limitations there.

是的。您現在看到的 Canalevia 的 CA1 或有條件批准指定是更容易獲得批准的途徑。你必須表現出對有效性的合理預期，並且不一定需要你可能會在指定人群中看到你可能會看到的傳統批准的全部效果。因此，它可以讓您以更低的成本更快地進入市場，但它也有一些局限性。還有幾個，只是為了讓您了解它們可能是什麼。是它不能在標籤外使用。因此，聯邦法律規定，對於 CA1 指定的藥物、處方藥，它們必須嚴格遵守所指示的標籤。你可能知道獸醫界，他們一直在寫標籤外的藥物，人類健康醫生也是如此。但在這種情況下，對於 CA1，存在該限制。市場規模也有限制。所以現在，你只能在犬類領域尋找這種藥物，以獲得不超過 70,000 隻狗的適應症。所以那裡有一些限制。

And then it comes to some requirements to complete the full effectiveness trial for traditional approval within a 5-year time frame of your initial approval. So we're working on that. And ultimately, we will end up -- we anticipate having full approval in the future. We're working with the CVM on that clinical development program. But we are seeing great uptake of Canalevia-CA1 especially among better oncologists, which are our primary target audiences. We engage with them in a variety of ways. In fact, I'm of in a couple of weeks at the Veterinary Cancer Society Meeting. We will have a chance to further educate an important customer group on the benefits of Canalevia-CA1.

然後涉及到一些要求，即在初始批准後的 5 年時間範圍內完成傳統批准的全面有效性試驗。所以我們正在努力。最終，我們將結束——我們預計在未來會獲得完全批准。我們正在與 CVM 合作開展該臨床開發計劃。但我們看到 Canalevia-CA1 的使用率很高，尤其是在更好的腫瘤學家中，他們是我們的主要目標受眾。我們以多種方式與他們互動。事實上，幾週後我將參加獸醫癌症協會會議。我們將有機會就 Canalevia-CA1 的好處進一步教育一個重要的客戶群。

Thanks, Ian. Okay. We have time for one more question here. We're coming up on the which we're trying to keep this to an hour. Does it, which I assume is talking about Crofelemer, also work on IBS?

謝謝，伊恩。好的。我們有時間再問一個問題。我們正在努力將這個時間限制在一個小時內。它，我認為是在談論 Crofelemer，是否也適用於 IBS？

So there are so many potential indications that reference to a pipeline within a product. There is published Phase II data for IBS, irritable bowel syndrome, with Crofelemer and we couldn't do everything. So there are target pipeline indications of Crohn's disease, inflammatory bowel disease. There are investigator-initiated trials going on right now in functional diarrhea in IBS as well. Of course, we have short bowel syndrome in CDD. So there are other indications, other important patient populations to go after in the future, which is a very risk-mitigated future drug development strategy for this company because, again, it would be indications if it's Mytesi where we already have the safety, we have the chronic safety, we have the manufacturing, how can we continue to expand the label, how can we continue to expand the population that in the health care providers that Ian can educate and promote to and grow the revenue even further. And of course, the patients that can benefit even further. But right now, we are very focused can't say it enough on cancer therapy-related diarrhea, short bowel syndrome and MVID and other indications and other territories in the future.

所以有很多潛在的跡象表明產品中的管道。 IBS、腸易激綜合症和 Crofelemer 的 II 期數據已發布，但我們無法做到一切。所以有克羅恩病、炎症性腸病的靶標管線適應症。現在也有研究者發起的針對 IBS 功能性腹瀉的試驗正在進行。當然，我們在 CDD 中有短腸綜合症。因此，還有其他適應症，未來還有其他重要的患者群體需要關注，這對這家公司來說是一個非常降低風險的未來藥物開發戰略，因為，如果是 Mytesi，我們已經擁有安全性，這將是適應症，我們有長期的安全性，我們有製造，我們如何繼續擴大標籤，我們如何繼續擴大伊恩可以教育和促進的醫療保健提供者的人口，並進一步增加收入。當然，可以進一步受益的患者。但現在，我們非常關注與癌症治療相關的腹瀉、短腸綜合徵和 MVID 以及其他適應症和未來的其他領域。

So with that, I know there's some other questions there. I can't get to all of them and some of them we've already referred to, again, the sentiment behind the question and the comments that we've made. Thank you all very much for listening. Thank you very much for your support for Crofelemer, Mytesi, Jaguar, Napo, Napo Therapeutics, we're going to get back to work here. It's going to be a very, very important year for all the stakeholders, and we're really looking forward to what will be uncovered in the next 6, 7, 8, 9 months of this company. Thank you. I'll conclude now.

因此，我知道那裡還有其他一些問題。我沒法說到所有這些問題，其中一些我們已經提到過，再一次，問題背後的情緒和我們所做的評論。非常感謝大家的聆聽。非常感謝您對 Crofelemer、Mytesi、Jaguar、Napo、Napo Therapeutics 的支持，我們將重新回到這里工作。對於所有利益相關者來說，這將是非常非常重要的一年，我們真的很期待在接下來的 6、7、8、9 個月內，這家公司會發現什麼。謝謝。我現在就結束吧。

Thank you. This will conclude today's webcast. You may disconnect at this time, and thank you for your participation.

謝謝。今天的網絡廣播到此結束。此時您可以斷開連接，感謝您的參與。