Jaguar Health Inc (JAGX) 2023 Q2 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 continued growth prospects for the company, uncertainties regarding market acceptance of products, the impact of competitive products and pricing, industry trends and product initiatives, including products in the development stage, which may not achieve scientific objectives or meet stringent regulatory requirements.

早上好。在我將電話轉交給管理層之前，我想提醒您，管理層可能會就以下事項做出前瞻性陳述：公司的持續增長前景、產品市場接受度的不確定性、競爭產品和定價的影響、行業趨勢和產品舉措，包括處於開發階段的產品，可能無法實現科學目標或滿足嚴格的監管要求。

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 of future events. 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.

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存在重大差異。這些陳述基於當前可獲得的信息以及管理層當前對未來事件的假設、預期和預測。儘管管理層認為，鑑於當前可獲得的信息，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 Forward-Looking Statements and Risk Factors sections of the company's Form 10-K for the year of 2022, which was filed on March 24, 2023, and its other filings with the SEC, which are available on the Investor Relations section of Jaguar's website. 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, future events or otherwise.

由於多種原因，公司的實際結果可能與本次網絡廣播中討論的結果存在重大差異，包括公司於 3 月 24 日提交的 2022 年 10-K 表格的前瞻性陳述和風險因素部分中描述的內容、2023 年以及向SEC 提交的其他文件，可在捷豹網站的投資者關係部分查看。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、未來事件或其他情況的義務。

Additionally, please note that the company supplements its consolidated financial statement presented on a GAAP basis by providing non-GAAP EBITDA and non-GAAP recurring EBITDA. Jaguar believes that the disclosed items of these non-GAAP measures provide investors with additional information that reflects the basis upon which the 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.

此外，請注意，該公司通過提供非 GAAP EBITDA 和非 GAAP 經常性 EBITDA 來補充其按 GAAP 基礎提交的合併財務報表。捷豹相信，這些非公認會計準則衡量標準的披露項目為投資者提供了更多信息，反映了公司管理層評估和經營業務的基礎。這些非公認會計原則財務指標不應被孤立地看待，也不應被視為公認會計原則淨銷售額和公認會計原則淨虧損的替代品，也不能替代或優於符合公認會計原則的財務業績指標。

Today's conference is being recorded. At this time, it is 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 創始人、總裁兼首席執行官 Lisa Conte。麗莎，地板是你的。

Thank you. Thank you all for joining our earnings webcast for the second quarter of 2023, and welcome to all of you. And as you just heard, my name is Lisa Conte. I'd like to begin today's call with a high-level overview of the Jaguar family of companies, and then I will provide updates on our key near-term initiatives and milestones. Following my comments, Carol Lizak, Jaguar's Chief Financial Officer, will provide a detailed recap of the key financial results for the second quarter of 2023, although, spoiler alert, we're very pleased to report that the net revenue increased 36% in Q2 2023 versus the first quarter of this year.

謝謝。感謝大家參加我們 2023 年第二季度的收益網絡廣播，歡迎大家。正如你剛才聽到的，我的名字是麗莎·孔特。我想在今天的電話會議開始時對捷豹公司家族進行高度概述，然後我將提供有關我們近期關鍵舉措和里程碑的最新信息。在我發表評論後，捷豹首席財務官卡羅爾·利扎克(Carol Lizak) 將詳細回顧2023 年第二季度的主要財務業績，不過，劇透警告，我們很高興地報告第二季度淨收入增長了36% 2023 年與今年第一季度相比。

Jaguar, as if you know the company, is a commercial-stage pharmaceuticals company focusing on developing novel proprietary prescription medicines, sustainably derived from plants from rainforest areas for people, primarily, and animals with GI distress, specifically overactive bowel, which is fresh lexicon I'm introducing today. There's a range of interpretations when we use the word diarrhea. With the terminology overactive bowel, we include symptoms such as chronic debilitating loose watery stools or as some will refer to diarrhea, also GI urgency and unpredictability and GI incontinence, all disrupting and disturbing to the patient, their quality of life and their health.

捷豹，就像你認識這家公司一樣，是一家商業階段的製藥公司，專注於開發新型專有處方藥，這些藥物可持續地從雨林地區的植物中提取，主要用於人類和患有胃腸道不適（特別是腸道過度活躍）的動物，這是新鮮詞彙今天我就介紹一下。當我們使用“腹瀉”這個詞時，有多種解釋。在術語“腸道過度活躍”中，我們包括諸如慢性虛弱性稀稀水樣便或有些人所說的腹瀉等症狀，還包括胃腸道緊迫性和不可預測性以及胃腸道失禁，所有這些都會擾亂和困擾患者及其生活質量和健康。

I'll now review also the relationship of the Jaguar family companies. Napo Pharmaceuticals, wholly owned by Jaguar, focuses on developing and commercializing the human prescription pharmaceuticals we develop. Napo Pharmaceuticals' crofelemer drug product candidate is the subject of the OnTarget study, our ongoing pivotal Phase III clinical trial for preventative treatment of chemotherapy-induced overactive bowel, CIOB, and that is the acronym that we're all going to start to get used to, CIOB in adults with cancer on targeted therapy.

我現在還要回顧一下捷豹家族公司的關係。 Napo Pharmaceuticals 由 Jaguar 全資擁有，專注於我們開發的人類處方藥的開發和商業化。 Napo Pharmaceuticals 的Crofelemer 候選藥物是OnTarget 研究的主題，該研究是我們正在進行的關鍵III 期臨床試驗，用於預防性治療化療引起的腸道過度活動症(CIOB)，這是我們都將開始使用的縮寫詞到，CIOB 對成人癌症患者進行靶向治療。

Jaguar family company Napo Therapeutics, as opposed to Napo Pharmaceuticals, Napo Therapeutics is an Italian corporation Jaguar established in Milan, Italy in 2021, focused on expanding crofelemer access in Europe, specifically for rare diseases. Jaguar Health is doing business as animal -- Jaguar Animal Health focuses on developing and commercializing animal prescription pharmaceuticals and nonprescription products, a small portion of our business. And then Magdalena Biosciences is a joint venture recently formed by Jaguar and Filament Health and is focused on earlier stage developing novel prescription medicines derived from plants for mental health indications, non-crofelemer-related.

Jaguar 家族公司 Napo Therapeutics 與 Napo Pharmaceuticals 不同，Napo Therapeutics 是 Jaguar 於 2021 年在意大利米蘭成立的一家意大利公司，專注於擴大 Crofelemer 在歐洲的使用，特別是針對罕見疾病。 Jaguar Health 作為動物開展業務 -- Jaguar Animal Health 專注於動物處方藥和非處方產品的開發和商業化，這僅占我們業務的一小部分。 Magdalena Biosciences 是 Jaguar 和 Filament Health 最近成立的一家合資企業，專注於早期開發源自植物的新型處方藥，用於精神健康適應症，與 Crofelemer 無關。

As a reminder, our commercialized human prescription drug product, crofelemer, is brand-named Mytesi. The generic name is crofelemer; brand name, Mytesi. It's a first-in-class, antisecretory chloride ion channel modulator approved initially in the U.S. for the specialty indication of symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. That is the label. As the term specialty market implies, this is a relatively small market in the United States. Indication was fast-tracked by the FDA, and that's primarily the reason why it's the first FDA-approved indication for crofelemer.

提醒一下，我們商業化的人類處方藥產品 Crofelemer 的品牌名稱是 Mytesi。通用名是Crofelemer；品牌名稱：邁特西。它是一種一流的抗分泌氯離子通道調節劑，最初在美國獲得批准，用於緩解接受抗逆轉錄病毒治療的成年艾滋病毒/艾滋病患者的非感染性腹瀉症狀。這就是標籤。正如專業市場一詞所暗示的那樣，這是美國一個相對較小的市場。 FDA 對適應症進行了快速跟踪，這也是它成為 FDA 批准的第一個 Crofelemer 適應症的主要原因。

Crofelemer Mytesi is plant-based, it's organic, it's natural, it's sustainably harvested, it's fair trade. And it is the only oral prescription drug approved by the FDA under botanical guidance. There is no practical pathway to bring a generic version of crofelemer to the market under botanical guidance. So in addition to all the patents we filed, just like any other pharmaceutical company does and all the expense associated with that, we essentially have an exclusivity position forever.

Crofelemer Mytesi 以植物為基礎，是有機的、天然的、可持續收穫的、公平貿易的。它是唯一在植物學指導下獲得 FDA 批准的口服處方藥。在植物學指導下，沒有可行的途徑將 Crofelemer 的通用版本推向市場。因此，除了我們申請的所有專利之外，就像任何其他製藥公司一樣以及與之相關的所有費用，我們基本上永遠擁有排他性地位。

And that's a very powerful factor when we're in discussions, for example, corporate partnerships, and we're talking about terminal value and net present value and potential license fees, non-dilutive funds to come into the company. We have global unencumbered rights to crofelemer, so there are always business development activities and discussions going on. And you never know when these are actually going to occur and come to the public consciousness.

當我們討論企業合作夥伴關係時，這是一個非常重要的因素，我們談論的是終值、淨現值、潛在的許可費、進入公司的非稀釋資金。我們對 Crofelemer 擁有全球不受阻礙的權利，因此業務開發活動和討論始終在進行。你永遠不知道這些事情什麼時候會真正發生並進入公眾意識。

Well, the market for small-cap biotechs is undeniably in a horrible state at present. We, at Jaguar, are fortunate this year that we have 2 major and what we feel are transformative clinical events coming up in the next couple of months, literally around the corner, that take pipeline opportunities to major blockbuster opportunities. And this is the most important takeaway message from today, and I'll say it again, 2 major late-stage clinical events, which we feel will be transformative for company value, recognition and patient assistance.

無可否認，小型生物技術公司的市場目前正處於可怕的狀態。捷豹今年很幸運，我們有 2 個重大的、我們認為是變革性的臨床事件將在接下來的幾個月內發生，幾乎即將到來，這些事件將管道機會轉變為重大的重磅機會。這是今天最重要的信息，我會再說一遍，兩個主要的後期臨床事件，我們認為這將對公司價值、認可和患者幫助產生變革。

First and foremost, these late-stage clinical events are major opportunities to help address neglected medical needs for patients. And what follows from a focus on patients are the benefits to all the stakeholders in the company, financial and otherwise. As I frequently say, what's really powerful about crofelemer is that it is a pipeline within a product. Crofelemer has the potential to be expanded to multiple follow-on indications beyond the HIV indication.

首先也是最重要的是，這些後期臨床事件是幫助解決患者被忽視的醫療需求的重要機會。對患者的關注將為公司的所有利益相關者（包括財務利益相關者和其他利益相關者）帶來好處。正如我經常說的，Crofelemer 的真正強大之處在於它是產品中的一條管道。 Crofelemer 有潛力擴展到 HIV 適應症以外的多種後續適應症。

We can focus on all potential indications at the same time. So the ones that we have prioritized and are focusing on now are chemotherapy-induced overactive bowel, CIOB, an acronym which we're going to get used to, CIOB, which previously we have been referring to as cancer therapy-related diarrhea. So let me make that link for our long-term followers. CTD, cancer therapy-related diarrhea now referred to as a more inclusive CIOB.

我們可以同時關注所有潛在的跡象。因此，我們現在優先考慮並關注的是化療引起的腸道過度活躍，CIOB，我們將要習慣的縮寫詞，CIOB，之前我們一直將其稱為癌症治療相關性腹瀉。因此，讓我為我們的長期關注者建立這個鏈接。 CTD，癌症治療相關腹瀉現在被稱為更具包容性的 CIOB。

And 2 rare disease indications, short bowel syndrome and microvillus inclusion disease, MVID, with intestinal failure. SBS, short bowel syndrome, and MVID with intestinal failure are catastrophic medical situations for patients where they end up on total parenteral nutrition for up to 20 hours a day, 7 days a week. There are currently no approved drug treatments for MVID. As we were thrilled to announce last week, the FDA activated our Investigational New Drug Application for crofelemer for the treatment of MVID, and the FDA approved a physician IND for an SBS patient with a distressful and severe diarrhea situation.

還有2個罕見疾病適應症，短腸綜合徵和微絨毛包涵體病，MVID，伴有腸衰竭。 SBS、短腸綜合徵和伴有腸道衰竭的 MVID 對於患者來說是災難性的醫療狀況，他們最終需要每週 7 天、每天 20 小時的全腸外營養。目前尚無批准的 MVID 藥物治療方法。正如我們上週很高興地宣布的那樣，FDA 啟動了用於治療 MVID 的 Crofelemer 的研究性新藥申請，並且 FDA 批准了一名醫生針對一名患有嚴重腹瀉的 SBS 患者的 IND。

We are so grateful that crofelemer has an opportunity to benefit these patients who are not only managing really difficult health situations, so also the dramatic impact on their quality of life. Our paramount near-term completion of our clinical activity for our Phase III pivotal OnTarget trial of Mytesi, this is literally the same formulation as Mytesi currently in the market, for the follow-on indication of the preventative treatment of chemotherapy-induced overactive bowel.

我們非常感激 Crofelemer 有機會造福這些患者，他們不僅面臨著非常困難的健康狀況，而且還對他們的生活質量產生了巨大影響。我們近期最重要的是完成了 Mytesi III 期關鍵 OnTarget 試驗的臨床活動，這實際上與目前市場上的 Mytesi 的配方相同，用於預防性治療化療引起的腸道過度活躍的後續適應症。

We've completed patient enrollment for OnTarget, an important milestone on our journey to making crofelemer available to treat the neglected comorbidity of CIOB. And top line results from this pivotal trial are expected in late October of this year, 2023. Again, one of the most important takeaway messages from this call, top line results in late October of this year to potentially expand the indication Mytesi to CIOB.

我們已經完成了 OnTarget 的患者入組，這是我們使 Crofelemer 可用於治療被忽視的 CIOB 合併症的旅程中的一個重要里程碑。這項關鍵試驗的頂線結果預計將於今年2023 年10 月下旬得出。同樣，本次電話會議最重要的信息之一是，今年10 月下旬的頂線結果可能會將Mytesi 適應症擴展到CIOB。

In support of our goal of obtaining FDA approval for a paradigm-shifting first oral drug for the preventative treatment and management of CIOB, OnTarget is the first trial of its kind. The trial includes participation of adult cancer patients with a diversity of solid tumor types. We call that a basket trial. It is the first clinical trial to include multiple targeted therapies that have greater than 50% all-grade diarrhea on their label and, which by the way, decided because typically it works in a real-world situation than the label; includes targeted therapy with or without standard cytotoxic chemotherapy being administered to the patient; and it is the first trial for prophylactic use, the preventative treatment, which with targeted therapy is a situation where you're treating the patient potentially for months and years, often essentially for the rest of their lives in both the curative and metastatic situation.

為了支持我們獲得 FDA 批准第一種用於 CIOB 預防性治療和管理的範式轉變口服藥物的目標，OnTarget 是此類試驗中的第一個。該試驗包括患有多種實體瘤類型的成年癌症患者的參與。我們稱之為籃子試驗。這是第一個包含多種靶向療法的臨床試驗，這些療法的標籤上有超過50% 的全級別腹瀉，順便說一下，之所以做出這樣的決定是因為它通常在現實世界中比標籤上更有效；包括對患者進行或不進行標準細胞毒性化療的靶向治療；這是預防性使用、預防性治療的首次試驗，通過靶向治療，您可以在治療和轉移情況下對患者進行數月甚至數年的治療，通常基本上是在他們的餘生中進行治療。

If we compare this to, for example, the established chemotherapy-induced nausea and vomiting protocols, and by the way, that is referred to as CINV, treatment typically occurs for the first 3 days with CINV in a limited cytotoxic chemotherapy treatment protocol. So CIOB, chemotherapy-induced overactive bowel, is a dramatically different from the nausea CINV in terms of the length of treatment.

例如，如果我們將其與已建立的化療引起的噁心和嘔吐方案進行比較，順便說一下，這被稱為 CINV，則通常在有限的細胞毒性化療治療方案中使用 CINV 進行前 3 天的治療。因此，CIOB（化療引起的腸過度活躍）在治療時間上與噁心 CINV 顯著不同。

There's an estimated 1.9 million new cancer cases projected in the U.S. for this year, 2023. The global market for the comparable CINV prophylactic indication is projected to reach a value of approximately $3.9 billion by 2029, and that's according to market research from an outside firm, iHealthcareAnalyst. Again, those products are taken for approximately 3 days for the 6 months or so of the duration of cytotoxic chemo.

據估計，到 2023 年，美國將新增 190 萬癌症病例。根據一家外部公司的市場研究，預計到 2029 年，類似 CINV 預防適應症的全球市場價值將達到約 39 億美元，iHealthcare 分析師。同樣，在細胞毒性化療的 6 個月左右的時間內，這些產品需要服用大約 3 天。

The OnTarget study design is studying preventative treatment of CIOB from chronically administered targeted therapy, essentially every day for months and years and sometimes for the rest of the patients' hopefully extended and quality of life. Another important similarity is the preventative treatment to address and assist the opportunity for the patient to stay compliant with their anticancer therapy, potentially affecting the outcome of the patient's cancer care in a positive way.

OnTarget 研究設計正在研究通過長期給予靶向治療對 CIOB 進行預防性治療，基本上每天進行數月甚至數年，有時是為了延長其餘患者的生活質量並提高其生活質量。另一個重要的相似之處是預防性治療，旨在解決並幫助患者有機會保持抗癌治療的依從性，從而可能以積極的方式影響患者的癌症護理結果。

I'm going to refer back to the lexicon shift of CIOB, which as you've heard is similar to the terminology for CINV, also CINP, chemotherapy-induced neuropathic pain. A preventative labeling benefits the patient who could be dealing with severe watery stools daily, essentially chaining the patient to their home; as well as the patient who deals with the unsettling, unpredictable and disrupting surprise diarrhea, which might happen once a week, once a month, but unpredictable. Both circumstances can be isolating, embarrassing and impact the dignity and well-being of the person with the cancer diagnosis as well as the health and compliance to other therapy implications, the anticancer therapies.

我將回顧一下 CIOB 的詞彙轉變，正如您所聽到的，它與 CINV 以及 CINP（化療引起的神經性疼痛）的術語相似。預防性標籤對每天可能要處理嚴重水樣大便的患者有益，本質上是將患者束縛在家裡；以及處理令人不安、不可預測和破壞性意外腹瀉的患者，這種腹瀉可能每週一次、每月一次，但不可預測。這兩種情況都可能會造成孤立、尷尬，並影響癌症診斷患者的尊嚴和福祉，以及其他治療方法（抗癌療法）的健康和依從性。

As an analogy, think of preventative treatment for epilepsy. You don't want to wait until the seizure occurs to treat you on therapy on board to prevent and/or mitigate the impact of the seizure. That's how we think about the preventative treatment of the full range of episodes of CIOB. The cancer treatment landscape has wonderfully radically changed. We're in the age of targeted therapies. You're seeing advertisements for new targeted therapies. Wherever pharmaceutical companies advertise direct to consumers, there are now dozens of approved targeted therapies, most, if not all, of which cause diarrhea by the exact secretory mechanism that crofelemer normalizes.

打個比方，想想癲癇的預防性治療。您不想等到癲癇發作才在船上接受治療以預防和/或減輕癲癇發作的影響。這就是我們對各種 CIOB 發作的預防性治療的看法。癌症治療領域已經發生了翻天覆地的變化。我們正處於靶向治療的時代。您正在看到新的靶向療法的廣告。無論製藥公司直接向消費​​者做廣告，現在都有數十種批准的靶向療法，其中大多數（如果不是全部）都是通過 Crofelemer 正常化的確切分泌機制引起腹瀉。

Crofelemer is a novel, first-in-class, antisecretory gastrointestinal chloride channel modulator. It is -- the disruption to the gut is caused by oversecretion of fluids into the intestines following the active secretion of chloride ions into gut. So the osmosis that occurs from the active secretion of excess chloride ions into the gut and the water, therefore, that follows and then the watery diarrhea that occurs. By normalizing ion flow, crofelemer's unique mechanism of action normalizes the flow of fluids into the intestine and normalize intestinal behavior.

Crofelemer 是一種新型、一流的抗分泌胃腸道氯離子通道調節劑。它是——對腸道的破壞是由於氯離子主動分泌到腸道後，液體過度分泌到腸道造成的。因此，過量氯離子主動分泌到腸道和水中而發生滲透，隨後發生水樣腹瀉。通過使離子流正常化，Crofelemer 獨特的作用機制使進入腸道的液體流動正常化，並使腸道行為正常化。

Crofelemer is taken orally and it acts locally in the gut, meaning it goes into the intestine and it normalizes that over-activation, as I just described. It doesn't block it up or clog it up. It normalizes that over-activation, which normalizes the flow of water into the intestines and brings the fluid situation back to normalcy. When you think of antidiarrheals historically, you think of products such as Imodium and loperamide, which are taken typically after a diarrhea episode occurs.

Crofelemer 是口服的，它在腸道局部起作用，這意味著它進入腸道，使過度激活正常化，正如我剛才所描述的。它不會堵塞它或堵塞它。它使過度激活正常化，從而使進入腸道的水流正常化，並使液體狀況恢復正常。當您想到歷史上的止瀉藥時，您會想到易蒙停和洛哌丁胺等產品，這些產品通常在腹瀉發作後服用。

These products are opioids, and they essentially work by the mechanism of constipation. And obviously, you can't stay constipated chronically. Crofelemer is not an opioid and, therefore, does not have that risk of constipation because crofelemer is acting locally in the gut, it doesn't have any known drug-drug interactions. Crofelemer doesn't have secondary metabolites causing problems later on. You don't have a first pass effect in the liver. And it's not an antibiotic, so you don't have the resistance that antibiotics can generate. And the safety profile is part of why we focus on complicated patient situations where you don't want to interfere with their life-saving therapies, and you do want to address the quality of life and the health care -- health benefit implications that can come from managing CIOB.

這些產品是阿片類藥物，它們本質上是通過便秘機制起作用的。顯然，你不能長期保持便秘。 Crofelemer 不是阿片類藥物，因此不存在便秘的風險，因為 Crofelemer 在腸道局部起作用，它沒有任何已知的藥物間相互作用。 Crofelemer 不含有會導致後續問題的次生代謝物。肝臟沒有首過效應。而且它不是抗生素，因此不會產生抗生素產生的耐藥性。安全性是我們專注於復雜患者情況的部分原因，在這些情況下，您不想干擾他們的救生療法，並且您確實希望解決生活質量和醫療保健問題，這些問題可能會對健康益處產生影響。來自管理CIOB。

The 2 most common reasons why new drug applications fail are safety and manufacturing. Mytesi is already on the market for an approved chronic indication. So we've already completed, for example, 2-year carcinogenicity. Safety is a huge hallmark of the product. We have never seen a side-effect profile different than placebo, and we have no serious adverse events that have been reported for a product that's been in the market for many years now and in thousands of patients living with HIV/AIDS on label.

新藥申請失敗的兩個最常見原因是安全性和製造。 Mytesi 已上市用於批准的慢性適應症。例如，我們已經完成了 2 年致癌性測試。安全是該產品的一大標誌。我們從未見過與安慰劑不同的副作用，而且我們還沒有報告過該產品已上市多年並在標籤上的數千名艾滋病毒/艾滋病患者身上發生的嚴重不良事件。

So in October, when we release top line data, it's a matter of what is the statistical significance on the primary endpoint for the OnTarget trial in people undergoing cancer treatment. That's the key transformative event for the cancer indication CIOB. Again, top line data, last week of October. And then the rest of the data is -- there's a beautiful collection of secondary endpoints and a rich database that will come from the completion of this trial.

因此，當我們在 10 月份發布頂線數據時，問題在於 OnTarget 試驗在接受癌症治療的患者中的主要終點的統計顯著性如何。這是癌症適應症 CIOB 的關鍵變革事件。再次強調十月最後一周的重要數據。然後剩下的數據是——這次試驗完成後將獲得一系列漂亮的次要終點和豐富的數據庫。

The rest of that data will come out in conferences and presentations that we'll make throughout the next year as we prepare for the potential approval of Mytesi, a product that's already in full supply chain from the rainforest to essentially any specialty pharmacy in the United States for this important new indication and for this much larger neglected market opportunity with a much larger number of patients potentially benefiting.

其餘數據將在明年全年舉行的會議和演示中公佈，我們正在為 Mytesi 的潛在批准做準備，該產品已經進入從雨林到美國幾乎所有專業藥房的完整供應鏈。國家對這個重要的新適應症和這個更大的被忽視的市場機會有更多的患者可能受益。

We believe the OnTarget trial will successfully demonstrate the normalization crofelemer provides to the over-activation from targeted cancer therapies and that crofelemer should be taken as a companion drug every single day and should be part of the standard targeted therapy protocols while patients are remaining on their targeted cancer therapy, again, either in a curative situation or to maintain cancer as a chronic situation that patients can live with. And the keyword here is live with, not just exist, but live life fully, addressing the quality of life of patients undergoing cancer treatment, focusing on control and dignity and a common voice in the choice of how to live.

我們相信 OnTarget 試驗將成功證明 Crofelemer 可以使靶向癌症治療的過度激活正常化，並且 Crofelemer 應作為伴隨藥物每天服用，並且應成為標準靶向治療方案的一部分，同時患者仍繼續接受治療再次，有針對性的癌症治療，要么是在治癒的情況下，要么是將癌症維持為患者可以忍受的慢性病。這裡的關鍵詞是“共存”，不僅僅是存在，而是充分地生活，解決接受癌症治療的患者的生活質量，注重控制和尊嚴，以及在選擇如何生活時的共同聲音。

This is the power of patient voice, which importantly is infused throughout our development and educational planning. And there are potential important health benefits to highlight as well, which is very important not only for the patients, and of course, the health care providers, the prescribing providers, also for payers. Publications show that about 40% of the time, people living with cancer on targeted therapies will go to a subtherapeutic dose or go off their life-saving targeted therapy because of the side effect of diarrhea, loose watery stools, overactive bowel.

這就是患者聲音的力量，重要的是，它貫穿於我們的發展和教育規劃中。還需要強調潛在的重要健康益處，這不僅對患者非常重要，當然對醫療保健提供者、處方提供者以及付款人也非常重要。出版物顯示，大約 40% 的情況下，接受靶向治療的癌症患者會因為腹瀉、稀稀水樣便、腸道過度活躍等副作用而服用亞治療劑量或放棄挽救生命的靶向治療。

So preventing this type of diarrhea, otherwise known as chemotherapy-induced overactive bowel, as we are introducing today, can support better adherence to cancer treatment for patients and better treatment outcomes. And it's been shown that it costs about 3x as much to take care of people living with cancer in targeted therapies when they suffer from loose watery stools, diarrhea as well.

因此，正如我們今天所介紹的，預防這種類型的腹瀉（也稱為化療引起的腸道過度活躍）可以支持患者更好地堅持癌症治療並獲得更好的治療結果。研究表明，當患有稀稀水樣便和腹瀉的癌症患者接受靶向治療時，其費用大約是原來的三倍。

I'll now discuss Jaguar's 2 prioritized rare disease investigative indications for a novel crofelemer powder and a highly concentrated oral formulation. So crofelemer yet a different product than Mytesi. MVID is life-threatening in ultra-rare autosomal recessive disease estimated to affect a couple of hundred newborns and children globally, leading to intestinal failure, significant morbidity and even death from severe secretory diarrhea.

我現在將討論 Jaguar 針對新型 Crofelemer 粉末和高濃縮口服製劑的 2 個優先罕見病研究適應症。所以 Crofelemer 是一個與 Mytesi 不同的產品。 MVID 是一種極其罕見的常染色體隱性遺傳病，可危及生命，估計影響全球數百名新生兒和兒童，導致腸道衰竭、嚴重發病甚至因嚴重分泌性腹瀉而死亡。

While there are currently no approved therapeutic treatments for MVID, total parenteral nutrition, the delivery of nutrition of life, the NIV, which is the standard of care for the management of MVID, can cost around $150,000 a year or multiples of that with complications. MVID patients suffer from severe cholera-like diarrhea daily. And symptomatic management of diarrhea and MVID may reduce their dependence on parenteral nutrition. We plan to host an investor-facing webinar in the near future with leading pediatric gastroenterologists to further elaborate the value of managing diarrhea and MVID patients with intestinal failure and bring a greater understanding to this ultra-rare disease.

雖然目前尚無針對 MVID、全腸外營養、生命營養輸送的批准治療方法，但作為 MVID 管理標準護理的 NIV 每年的費用約為 150,000 美元，是並發症費用的數倍。 MVID 患者每天都會遭受嚴重的霍亂樣腹瀉。對腹瀉和 MVID 進行對症治療可能會減少他們對腸外營養的依賴。我們計劃在不久的將來與領先的兒科胃腸病學家一起舉辦面向投資者的網絡研討會，進一步闡述治療腹瀉和腸道衰竭 MVID 患者的價值，並加深對這種極其罕見疾病的了解。

Crofelemer has been granted Orphan Drug Designation by the FDA and the European Medicines Agency, EMA, for MVID; and crofelemer has also been granted Orphan Drug Designation by the FDA and the EMA for short bowel syndrome, which is referred to as SBS. SBS patients with intestinal failure are also treated with parenteral nutrition. Jaguar is supporting investigator-initiated proof-of-concept studies of crofelemer for SBS and MVID with intestinal failure in the EU and MENA regions with the goal of reducing dependence on parenteral nutrition by about 15% to 20%, a known and accepted regulatory endpoint.

Crofelemer 已被 FDA 和歐洲藥品管理局 (EMA) 授予 MVID 孤兒藥資格； Crofelemer 還被 FDA 和 EMA 授予治療短腸綜合徵（簡稱 SBS）的孤兒藥資格。患有腸衰竭的 SBS 患者也接受腸外營養治療。 Jaguar 正在支持研究人員發起的Crofelemer 在歐盟和中東和北非地區治療SBS 和MVID 腸道衰竭的概念驗證研究，目標是將對腸外營養的依賴減少約15% 至20%，這是一個已知且公認的監管終點。

We're also providing product for an FDA-approved physician IND for an SBS patient here in the United States. We'll be looking at improved stool volume and stool formation and other metabolic measures. In accordance with the guidelines of specific EU countries, published data from such clinical investigations could support reimbursed early patient access to crofelemer for short bowel syndrome or MVID or both potentially in 2024 for these debilitating conditions.

我們還為美國 SBS 患者的 FDA 批准醫師 IND 提供產品。我們將關注糞便量和糞便形成以及其他代謝指標的改善。根據特定歐盟國家的指導方針，此類臨床研究公佈的數據可以支持患者在 2024 年早期獲得 Crofelemer 治療短腸綜合徵或 MVID 或兩者兼而有之的報銷，以治療這些使人衰弱的疾病。

And early access programs, which do not exist in the United States, provide an opportunity for reimbursement while impacting the morbidity and high cost of care of these chronic neglected needs and was a major catalyst and impetus for us establishing Napo Therapeutics in Europe to be able to have feet on the ground to be able to access these early patient access opportunities for both patients and the benefit for all our stakeholders.

美國不存在的早期獲取計劃提供了報銷的機會，同時影響了這些長期被忽視的需求的發病率和高昂的護理費用，並且是我們在歐洲建立 Napo Therapeutics 的主要催化劑和推動力，以便能夠腳踏實地，能夠為患者提供這些早期患者就診的機會，並為我們所有利益相關者帶來利益。

And again, that is the second major what we feel is a transformative clinical event, late-stage clinical event in 2023, around the corner, for these rare diseases to effect the opportunity for patients to access these products in 2024. An estimated 40,000 short bowel syndrome patients around the world, so it's a typical rare disease business model. SBS patients have high morbidity, high mortality, high expense, active patient advocacy group and the patients require very expensive and toxic, in some cases, very toxic parenteral nutrition essentially every single day, 20 hours a day for the rest of their lives.

再說一遍，這是我們認為的第二個重大臨床事件，即 2023 年的後期臨床事件，即將到來，這些罕見疾病將影響患者在 2024 年獲得這些產品的機會。估計短缺 40,000全世界都有腸道綜合症患者，所以這是一種典型的罕見病商業模式。 SBS患者發病率高、死亡率高、費用高、患者倡導團體活躍，患者在餘生中基本上每天需要非常昂貴且有毒的、在某些情況下甚至是劇毒的腸外營養，每天20小時。

The goal -- the global SBS market is projected -- again, these are rare disease business models, it's projected to grow to, by third parties, to $4.6 billion in 2027. This is the market research firm, Vision Research Reports. Other studies put the growth to approximately $12 billion. And the standard of care at this time for the population of SBS patients is, in fact, parenteral nutrition.

我們的目標——全球 SBS 市場預計——同樣，這些都是罕見疾病商業模式，第三方預計到 2027 年將增長到 46 億美元。這是市場研究公司 Vision Research Reports。其他研究表明這一增長量約為 120 億美元。事實上，目前 SBS 患者群體的護理標準是腸外營養。

So to recap here, we expect to have top line results from our Phase III trial crofelemer for the prophylaxis of chemotherapy-induced overactive bowel, CIOB, in the last week of October this year. And we expect initial proof-of-concept evidence before the end of the year for patients with either SBS and/or MVID with intestinal failure in support of early patient access participation in certain European countries. So both potentially important revenue generations in 2024 based on these late-stage clinical results in 2023.

因此，回顧一下，我們預計將在今年 10 月的最後一周獲得用於預防化療引起的腸道過度活躍 (CIOB) 的 III 期試驗 Crofelemer 的主要結果。我們預計在今年年底之前將獲得針對伴有腸道衰竭的 SBS 和/或 MVID 患者的初步概念驗證證據，以支持某些歐洲國家的早期患者參與。因此，基於 2023 年的這些後期臨床結果，這兩個項目在 2024 年都可能產生重要的收入。

Before I hand the discussion over to our CFO, Carol, I'd like to let all of you participating today know that we will have a brief Q&A segment at the end of the webcast to address any questions submitted in writing. They can be submitted via the webcast link for today's event that appears on the Events & Presentations page of the Investor Relations section of Jaguar's website, and the URL for our website is jaguar.health.

在將討論交給我們的首席財務官卡羅爾之前，我想讓今天參與的所有人知道，我們將在網絡廣播結束時有一個簡短的問答環節，以解決以書面形式提交的任何問題。它們可以通過捷豹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廣播鏈接提交，我們網站的 URL 是 jaguar.health。

And we'll now move along to the key financial results for the second quarter of 2023. Carol, I'll turn it over to you.

現在我們將討論 2023 年第二季度的主要財務業績。卡羅爾，我將把它交給你。

Well, thank you, Lisa, and thank you all for joining our webcast today.

好的，謝謝你，麗莎，也感謝大家今天參加我們的網絡廣播。

I'll begin my review of our financials for the second quarter of 2023. Prescription product net revenue was approximately $2.7 million in the second quarter of 2023, representing an increase of 36% compared to prescription product net revenue in the first quarter of 2023, which totaled approximately $2 million, and a decrease of approximately 8% over prescription product net revenue in the second quarter of 2022, which totaled approximately $2.9 million.

我將開始審查我們 2023 年第二季度的財務狀況。2023 年第二季度處方產品淨收入約為 270 萬美元，與 2023 年第一季度處方產品淨收入相比增長了 36%，總計約200 萬美元，比2022 年第二季度處方產品淨收入（總計約290 萬美元）減少約8%。

Mytesi prescription volume increased approximately 4% in the second quarter of 2023 compared to the first quarter of 2023 and decreased approximately 4.5% in the second quarter of '23 compared to the second quarter of 2022. 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2023 年第一季度相比，Mytesi 處方量在2023 年第二季度增長了約4%，在2023 年第二季度與2022 年第二季度相比下降了約4.5%。處方量與發票銷量不同，這反映了除其他因素外，封閉網絡中的專業藥房在管理庫存水平時的購買模式也有所不同。

Loss from operations increased by $1.6 million from $6.5 million in the quarter ended June 30, 2022, to $8.1 million during the same period in 2023, largely from increased research and development expenses related to the clinical trials for CIOB and other indications.

運營虧損從截至 2022 年 6 月 30 日的季度的 650 萬美元增加到 2023 年同期的 810 萬美元，增加了 160 萬美元，主要是由於與 CIOB 和其他適應症的臨床試驗相關的研發費用增加。

Non-GAAP recurring EBITDA for the second quarter of 2023 and the second quarter of 2022 were a net loss of $7.8 million and $5.3 million, respectively. Net loss attributable to common shareholders increased by approximately $2.8 million from $9.4 million in the quarter ended June 30, 2022, to $12.2 million in the same period in 2023.

2023 年第二季度和 2022 年第二季度的非 GAAP 經常性 EBITDA 分別為淨虧損 780 萬美元和 530 萬美元。歸屬於普通股股東的淨虧損從截至2022年6月30日的季度的940萬美元增加約280萬美元，至2023年同期的1220萬美元。

That concludes my recap of high-level financials for the second quarter of 2023. And I will now hand the discussion back to Lisa Conte.

我對 2023 年第二季度高層財務狀況的回顧到此結束。現在我將把討論交還給麗莎·孔特 (Lisa Conte)。

Thank you, Carol. We, at Jaguar, and our family companies are highly, highly energized about all our important initiatives underway in 2023 and the culmination of these late-stage clinical events and what this can mean for patients and all that follows from that.

謝謝你，卡羅爾。我們捷豹和我們的家族企業對 2023 年正在進行的所有重要舉措以及這些後期臨床事件的高潮以及這對患者意味著什麼以及隨之而來的一切感到非常非常興奮。

We have no questions that have come in, unless I have screwed up my access to them, but I believe we have no questions. So with that, we'll conclude our call for today. Thank you all who have listened and participated and support Jaguar. Have a good day.

我們沒有收到任何問題，除非我搞砸了對它們的訪問，但我相信我們沒有任何問題。我們就這樣結束今天的電話會議。感謝所有傾聽、參與和支持捷豹的人。祝你有美好的一天。

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

謝謝。今天的會議到此結束。此時您可以斷開連接，感謝您的參與。