Jaguar Health, Inc.

Before I turn the call over to management, I'd 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 make it achieve its scientific objectives or meet stringent regulatory requirements. Forward-looking statements are subject to risks and uncertainties that could cause action results to differ materially from those complicated in such forward-looking statements. These statements are based on current 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, you are cautioned not to place undue reliance on these forward-looking statements. 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 in sections in the company's Form 10-K in the year 2023, which was filed on April 1, 2024, 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. Additionally, please note that the company supplements its condensed consulated financial statements presented in a GAAP basis with provided non-GAAP EBITDA and non-GAAP recurring EBITDA. Jaguar believes that the disclosure items in these 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 conformality with GAAP. As a reminder, today's conference call is being recorded, and 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.

Thank you, Matt. Good morning, everybody. Thank you all for joining our investor webcast today. As you heard, my name is Lisa Conte. I'm the founder, president, and CEO of Jaguar Health and our wholly owned subsidiary, NAPO Pharmaceuticals, and I'm the chairman of our Italian subsidiary, NAPO Therapeutics in Milano. As usual, I may use the words Jaguar and NAPO interchangeably when I'm referring to the company. As announced, this is an earnings webcast. And once again, I'm going to steal the thunder of our CFO, Carol Isaac, as we're pleased to report our net third quarter 2024 revenue of approximately $3.1 million increased approximately 14% versus the net in the second quarter of 2024, which was 2.7 million revenue. And it increased approximately 11%, versus net Q3 2023, last year's revenue, of approximately $2.8 million. So it's an earnings call. Those are the numbers. I couldn't just stop right there, but I'm going to continue. Because as you hear, I'm going to address our ongoing commercial and development efforts. We have multiple near-term catalysts in the fourth quarter of this year, in the next two months, and continuing early into 2025. And we view these as important and value-enhancing catalysts for the recognition of the value in the company. On the topic of key milestones, we are so pleased that we achieved significant results in the recently completed analysis from our recently completed phase three on-target trial in the pre-specified subgroup of breast cancer patients. This result has been accepted for a poster presentation, and it's on December 11th, 2024, so next month, at the very prestigious San Antonio Breast Cancer Symposium, which is the largest international breast cancer symposium and also, I believe, the second largest cancer symposium in the United States after ASCO. Patients with breast cancer accounted for the majority of the participants in the on-target trial. which really was an unprecedented global prophylactic clinical trial for diarrhea in adult patients with all solid tumors receiving 24 different targeted therapies with or without standard chemotherapy. It's what we call a basket trial, attempting to address the treatment-related side effects of chronic diarrhea commonly suffered by all solid tumor patients. This was an ambitious trial, we were putting a big inclusive hug around all patients that could potentially benefit, all solid tumor patients. And while the study did not achieve its primary endpoint for all solid tumor types included in the trial, we did achieve meaningful clinical signals in breast cancer, as you just heard, and also lung cancer patients, two of the most common cancer diagnoses. We are very, very happy, very pleased that this important abstract on breast cancer results has been accepted for San Antonio. And as announced, a second late-breaking abstract related to the OnTarget trial based on data from the placebo arm of the trial has also been accepted for a poster presentation. And that, too, will occur on December 11th. The value of the data in this poster is to shine a light with much greater precision on the rates and impact of cancer therapy-related diarrhea on patients beyond the summary and somewhat unsatisfactory descriptions of side effects, in particular diarrhea, that appear in package inserts for many of the targeted cancer therapies. And the impact in particular that this can have on the ability of patients to remain on their cancer therapy, to not have a reduction, an interruption, or a termination of their cancer therapy based on side effects, and, of course, in particular because of diarrhea. My longtime colleague, Dr. Pravin Chaturvedi, my brother from another mother, our chief scientific officer and chair of our scientific advisory board, he'll speak in a few minutes to discuss the regulatory implications and development plans for profilamer for cancer therapy-related diarrhea, how we can as efficiently as possible get the benefits from profilamer to cancer patients. And also, and separately, and also, are orphan-designated indications for profilamer of microvirus inclusion disease, which is a congenital diarrheal disorder in pediatric patients when they're born, and short bowel syndrome for intestinal failure. This is But it is a different product than Mitessi, which is the commercial, the brand name for the product that's currently on the market and the product for cancer therapy-related diarrhea. This is a different formulation that is clinically, medically, administration-appropriate for these patients with intestinal failure. And then after Provence speaks, our CFO, Carol Isaac, she'll provide a recap. in more detail of the financial highlights for the third quarter of 2024. On our expanding commercialization front, which is very exciting, Jaguar launched the FDA-approved oral mucositis prescription product, GelClear, our third commercialized prescription product. We launched it in the United States about a month ago, a little less than a month ago, and it's another important milestone in support of our deep, deep commitment to supportive care and needs of people, and in particular, undergoing cancer treatment. Oral mucositis is among the most common, painful, and debilitating cancer treatment-related side effects. And for those who don't specifically know what mucositis is, I can give you actually a firsthand assessment. I had an odd reaction two years ago to a COVID treatment, and I ended up with grade four oral mucositis, it feels like broken glass in your mouth all day long and with a habanero pepper on top of it. It is remarkably painful. And what GelClear does, it's a gel. It has a mechanical action and it's indicated for the management and relief of pain, the soothing of the pain by adhering to the mucosal surface of the mouth. It coats and protects which soothes and supports healing. Oral mucositis, which commonly sometimes is called chemo mouth, it has emerged as the most significant adverse event in oncology according to National Comprehensive Cancer Network. Up to 40% of all patients treated with chemo develop oral mucositis. And the same thing that I was mentioning about with our placebo results, it can impact the ability of the patient to stay on their cancer therapy, their life-saving therapy. When we talk about patients with head and neck cancers treated with chemotherapy and or radiation experiencing severe oral mucositis, this impacts a patient's ability to swallow, to speak, to eat, to drink, and of course, again, can lead to their cancer treatment disruption and discontinuation. And it essentially hits about 100%, almost every single patient that is dealing with head and neck radiation and bone marrow transplant. So as we have launched, our core target audience are, in fact, the patients with head and neck cancer and the team that supports them, the oncology radiologists, nurses, nurse practitioners, dieticians, all the support groups. The National Cancer Institute estimates that about 71,000, more than 71,000 cases of cancer in the oral cavity, pharynx, and larynx will occur in the United States each year and in this year, 2024. One subset of the prescribers that has been quick to adopt and repeat gel clear prescriptions are nurse practitioners. Recognizing the importance that nurses play in the management of cancer patients' overall treatment, we had the opportunity to meet with many of these providers at the American Academy of Nurse and Patient Navigators Conference just last week. Many of the nurses that we spoke with were familiar with Gell-Claire and recognized the lasting and soothing benefits it provides to oral mucositis patients versus other treatments which don't last long, can sting, can burn, can cause numbing, and really are not satisfactory when put in the mouth. This is a wide open space for us to open with the benefits from Gelclair. We also met with many providers for this patient population at the American Society of Radiation Oncology Conference earlier in October and heard strong, strong support for the availability of this as an alternative treatment, as an option for their patients with oral mucositis. Again, to relieve the patient, the pain, the quality of life, and allow the patient to stay on their cancer therapy. Our other key area for near-term catalysts on the clinical development front, so now going back to the clinical development front, is profilamer, as I mentioned, for rare and orphan diseases. MVID, microvirus inclusion disease, is this congenital diarrheal disorder, which is an ultra-rare pediatric congenital diarrheal disorder and short bowel syndrome with intestinal failure, which we'll refer to here shorthand SBSIF. We have two Phase II trials in the fourth quarter of this year, the next two months, and we are supporting multiple investigator-initiated proof-of-concept studies for these two indications, including territories in the United States, Europe, and the MENA regions, the UAE in particular, with results from the proof of concept studies expected potentially by the end of this year, over the next two months, and throughout the beginning of 2025. These are five different clinical efforts that I just mentioned initiating essentially now, real time, that have been in the development for almost two years of regulatory filings, meeting with key opinion leaders, assessing the needs that are relevant to patients and providers, designing protocols, and they're all coming to fruition now and providing this opportunity for, again, what we feel will be value-enhancing catalysts starting right now. We do have orphan drug designation for profilamer in both the United States and Europe for both MVID and the SPS indications. In accordance with the guidelines of specific European countries, published data from clinical investigations, proof of concept studies, could, for both of these indications, could support reimbursed early patient access to crofilomer for these debilitating conditions before there is full regulatory approval. Early patient access programs that don't exist in the United States, and it's part of the reason why we have our subsidiary, NAPO Therapeutics, in Europe with a team that has the capability and the experience to move on this important strategy to get products to patients that need them. Rare diseases are really a very important business model. And there are many companies that are built around only focusing on rare diseases. It's a program within Jaguar. But it's important to recognize that Profelemer for these indications relatively small population, high morbidity, high mortality, high expense taking care of these patients, highly activated patient support groups. And it's a different business model, different pricing. And as I mentioned, it is Crofilamer, yet it is a different product because of the different formulation. Before I hand the discussion over to Praveen, I'd like to let you all know that we will have a brief Q&A. at the end of the webcast, and if there are any questions, we won't be able to, hopefully there are questions, and if there are questions, we may not be able to get to them all. They can be submitted in writing, and they can be submitted via the webcast link for the event right now that's on the events and presentations page of the investor relations section of Jaguar's website. The URL for the website is jaguar.health. Praveen, I'm now going to hand this over to you. Good morning, and we look forward to your update.

Good morning, Lisa, and good morning, all. Thank you for taking part in today's investor webcast. As Lisa stated, we are thrilled with the abstract of the results of the breast cancer subgroup responder analysis from the OnTarget Phase 3 trial have been accepted for presentation at the San Antonio Breast Cancer Symposium. Additional analyses of the on-target data are ongoing, and these additional analysis may result in future submissions to other appropriate scientific forums. We plan to submit the breast cancer subgroup responder analysis to a peer reviewed journal for publication in the future. Furthermore, the content of the breast cancer subgroup responder analysis will serve as the basis for preparing a briefing document that we plan to submit to the FDA for further discussion. We plan to request a meeting with the GI division of the FDA in the first half of 2025 to discuss potential regulatory pathways for proforma approval for the subgroup of, say, breast cancer patients. As a reminder, proforma formulation that was studied in the on-target study is Mitessi formulation, which is currently approved by the FDA for the HIV indication. Hence, the safety and manufacturing sections of the new drug application have already been reviewed and approved by the GI Division of the FDA for Profilma delayed release tablets. The breast cancer subgroup results from the on-target study that are being presented at the San Antonio Breast Cancer Symposium or our responder analysis, which is also the analysis for the primary endpoint in the pivotal phase 3 advent trial that led to the FDA approval of Profilma for its current indication of symptomatic relief of non-infectious diarrhea. in adult patients with HIV AIDS on antiretroviral therapy. Crofilmer has consistently shown clinical benefit in other clinical studies based on responder analysis of gastrointestinal function. The results from two independent investigator-initiated trials for Crofilmer in functional diarrhea and chronic idiopathic diarrhea in irritable bowel syndrome patients based on responder analysis were recently presented last month. at the American College of Gastroenterology Annual Scientific Meeting in Philadelphia. We continue to evaluate profilma in patients with gastrointestinal unmet needs and have observed profilma shows benefit in various patient populations that have secretory diarrhea. As Lisa mentioned, development of profilma has also been initiated for the orphan and rare disease indications of microvillous inclusion disease, MBID, and short bowel syndrome with intestinal failure, SPSIF. which are a key focus for the company. We have focused on developing appropriate clinical study design, clinical endpoints that would meet regulatory requirements and also support clinical outcomes. By the end of 2024 in the EU, we expect to activate the phase two trial in adult SPS-IF patient requiring total parental support, which includes total parental nutrition, TPN, with additional supplementary intravenous IV fluids if needed. Our Italian subsidiary, Napo Therapeutics SBA, has received the initial regulatory clearance for conducting the adult SPS-IF trial from the European Medicines Agency. For the pediatric MVID trial, we are initiating a phase two trial in the United States and at additional clinical sites in Europe and the Middle East, North Africa, MENA regions. The pediatric MVID clinical protocol has received regulatory clearances from the FDA and European Medicines Agency. Additionally, we are supporting some investigator-initiated proof-of-concept studies in adult and pediatric SPS-IF patient populations at Cleveland Clinic in the U.S. and at Sheikh Khalifa Medical City in Abu Dhabi, UAE to evaluate Profirma's benefits in patients requiring total parental support to meet their requisite daily needs for nutrition, electrolytes, and fluids from total parental support. Upon obtaining some initial results in these investigator-initiated studies and with published proof of concept data, we also have the potential to move towards reimbursed early patient access in certain European markets prior to full product approval in Europe, a program which does not exist in the United States. This is also an important strategic advantage for an apotherapeutic subsidiary. Adult or pediatric patients with SPSIF are unable to absorb adequate calories for their oral intake due to the anatomic or functional reasons of their intestinal failure, which means they have lost a part of their intestine, either anatomically or functionally or both. And in some cases, These are provided, their caloric requirements are provided predominantly through total parenteral nutrition, potentially up to 20 hours in a day, sometimes for all seven days of the week. Obviously, this is a catastrophic situation for these patients and their families. In addition, some patients require TPN along with more supplemental intravenous fluids as they risk dehydration due to severe diarrhea. As a reminder, Profelma is a novel inhibitory intestinal chloride ion channel modulator, which decreases the intestinal secretion of chloride ions and the accompanying fluid in the gut. This anti-secretory mechanism of action of grofilma reduces fluid and electrolyte accumulation in the GI tract and improves stool consistency. Importantly, due to the shortened length of the intestinal tract in SPS-IF patients, The oral formulation of Profilmo was not suitable and not viable. Our team has developed a novel proprietary, highly concentrated lyophilized Profilmo powder for oral solution formulation, which will be administered orally to these patients in very small volumes to evaluate the effects of Profilmo on various clinical symptoms, including reduction in stool volume output and the requirements for total parenteral support. As you may know, both the FDA and EMA, European Medicines Agency, have approved a growth hormone for the management of adult and pediatric SPS-IF patients, but not for MVID. The approved growth hormone is a GLP-2 analog, and it functions by promoting growth of villi in the intestinal mucosa, which means it helps increase the length of the villi after surgery or other interventions to help SPS patients or bowel syndrome patients increase their fluid and or nutrient absorption from their intestine, thus allowing for the reduction of TPN by about 20% over a 24-week period. There are some biosimilars under clinical development by other companies, and their clinical effects are similar to those previously reported for the approved GLP-2 analog. It should be noted that this growth hormone mechanism is not considered standard of care for SPSIF, standard of care remains total parental nutrition. A key limitation of the mechanism of action of growth hormones is that they cannot be used in cancer patients and in patients with abnormal hyperproliferative medical conditions. As I said earlier, GLP-2 growth hormone or any other therapies are not approved for pediatric MVID patients and cannot be expected to provide any benefit because these patients, although they have a full intact gut, They do not have any villi. They have no brush border membrane, and hence the name microvillous inclusion disease. And there are needs for new approaches that are potentially provided by Profelma to reduce their stool volume output and some reduction in their total parental support requirements. Since Profelma is also not a growth hormone, it does not have any of the limitations of the GLP-2 analog. Crofilma is a locally acting drug in the gastrointestinal tract without significant oral absorption, and it provides the ability to reduce chloride secretion into the gut and accompanying fluid accumulation, which will then result in reduction of stool volume output and potentially reduction of total parental support requirements. Nevertheless, with the approval of GLP analogs, the regulatory endpoint for reduction of total parental nutrition has been established. The GLP-2 analogs cost approximately $500,000 per year per patient in the U.S., and the cost of TPM with or without supplementary fluids is not included in that. It is in addition to the cost of the GLP-2 analog. Lisa, that's the overall summary, and I'll hand it back to you for continuing the discussion. Thank you.