Jaguar Health, Inc.

Good morning. 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 development stage which may not achieve scientific objectives or meet stringent regulatory standards. requirements. 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 made 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 the currently available information, you are cautioned not to place undue reliance on 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 factor sections of the company's Form 10-K for the year 2024, which was filed March 31, 2025, 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 consolidated financial statements presented on a GAAP basis by providing non-GAAP EBITDA and non-GAAP recurring EBITDA. Jaguar believes that the disclosure items of these non-GAAP measures provide investors with additional information that reflect the basis upon which 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 in conformity with GAAP. Today's conference is being recorded. At this time, it's 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 very much. Thank you for those introductory statements. Hello. Excuse me. Thank you for joining our webcast today. As you heard, my name is Lisa Conte. I am 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. So as usual, if you've been on these webcasts before, I may use the words Jaguar and NAPO interchangeably to refer to our company and our company activities. So as announced, this is an earnings webcast. And after I speak, our CFO, Carol Lizak, will provide a recap of the financial highlights for the second quarter of 2025. And as in the past, I am going to steal the thunder of Carol as we're pleased to report that our combined net second quarter 2025 revenue of approximately $3 million for prescription and non-prescription products, including license revenue, increased approximately 35% versus net Q1 2025. And it increased approximately 10% versus net Q2 2025. 2024. We're quite pleased with that. And to move along to the bigger picture for the company, 2025 continues to be the year of convergence of key clinical and regulatory catalysts for Jaguar. Catalysts that we feel will be transformative in terms of the value they bring to all the stakeholders in the company, from patients first and foremost to our shareholders. Simply put, With the recent achievement of these catalysts, our strategy is to seek, and we are seeking, business development partnerships for licensed rights to the development and commercialization of Jaguar's human and animal health products with the goal of generating non-dilutive funding for Jaguar. So important at this time of pullback and hopefully temporary pullback of investor support for innovations in emerging pharma companies well beyond what we're seeing here at Jaguar. These catalysts are the key to those deals. To recap our recent catalysts, and may I comment that these remarkable groundbreaking results are the culmination of years of regulatory and clinical planning activities and implementation, in some cases up to eight years. And it just so happens that we have a convergence of critical catalysts at this time, again, in support of the opportunities for really important business development deals. On April 30th this year, we released initial results from an independent investigator-initiated proof-of-concept study in pediatric patients in Abu Dhabi of a novel liquid formulation of crofilomer, our first-in-class plant-based paradigm-shifting prescription drug for intestinal failure associated with what we call MVID, that's microvelous inclusion disease. I'm going to refer to it as MVID, which is an ultra-rare disease. And also intestinal failure associated with short bowel syndrome, SPS, SBSIS. For both these indications, Profelimer has orphan drug designation in the US and Europe conferring opportunities for expedited development, regulatory approval, which leads to reimbursement. So what is intestinal failure? It's a condition where intestines cannot adequately absorb the nutrients of life, protein, carbs, vitamins, etc. And patients also suffer from devastating diarrhea and therefore dehydration. These are lifelong conditions. and they often require for the patient to survive total parental nutrition, TPN, total parental nutrition, IV nutrition, up to seven days a week for more than 20 hours a day. Obviously, a catastrophic health situation impacting hugely any quality of life of both patients and caregivers, which is usually and often the family, with many, complications, a huge expense to the healthcare system of hundreds of thousands of dollars a year per patient. For MBID patients in particular, TPN, total parenteral nutrition, is necessary from the first day of birth. The patient needs to be diagnosed and put on TPN to survive, otherwise they die. And that need does not change and does not change during what is often their short life. A short life due to the complications from TPN of liver, renal failure, cognitive issues, never get on a full growth curve, IV line complications and others. There are no drugs approved for MVID and we're not aware of any approach even in clinical development. The biggest impact one can have on a patient with intestinal failure is reduction in the quantity and or time of TPN. It's a remarkably toxic treatment to go through. And as announced and presented on April 26, 2025, at the annual PETA Elite GI Congress, initial proof of concept results from the ongoing trial in Abu Dhabi showed that crofilomer reduced the required TPN and supplementary intravenous fluids in the first participating MVID patient by up to 27%. Huge, 27%. And the first participating SBS patient with intestinal failure by up to 12.5%. And that was... At the end of 12 weeks of treatment, it was an escalation study. In addition, the data showed that profilamer reduced stool volume, output, and or frequency of watery stools and increased the urine output, which is important, an indicator of improved oral absorption of nutrients. These results represent stunning, stunning, groundbreaking disease progression modification benefits from the treatment from profilamer. In addition, at the end of the 12 weeks, these patients, there was as part of the protocol, they were taken off profilamere. And in each case, they relapsed within 10 days and needed to be put back on profilamere, which we're now providing indefinitely to these patients. A third intestinal failure patient completed this IIT protocol with similar results. And we expect patient data from this trial to continue to to be generated throughout the year and the investigator is seeking further publications and presentations as well. While short bowel syndrome affects approximately 40,000 people around the world, MVID is an ultra-rare condition with an estimated prevalence of just a couple of hundred patients globally. Given this situation and nothing approved for these patients, Initial results in even a single-digit number of MVID patients showing benefit-profilamer may support pathways for expedited regulatory approval for this indication, including something called the PRIME program at EMA, European Medicines Agency, the equivalent of the FDA in Europe, for expedited and assisted regulatory approval in the full 27 countries of the EU, And then also FDA's breakthrough therapy program for expedited regulatory approval in the U.S. And we're talking about a single digit number of patients, approval potentially as early as the end of 2026. And I believe at this time we have three additional MVID patients who are in treatment. We are also supporting an investigator-initiated trial in adult patients with short bowel syndrome and intestinal failure at the Cleveland Clinic in the United States with the first patients enrolled in that trial. Beyond these remarkable, really remarkable and important IIT results with prophylactic investigator-initiated trial results, JAGUAR and through NAPO Therapeutics, our subsidiary in Italy, which is important to have a footprint in Europe as we're dealing with the EMA, we're dealing with prime designation. We're currently conducting two placebo-controlled phase two trials for crofilomer, one in the US and in the EU for pediatric MVID patients and one for adults, short bowel syndrome, intestinal failure in the US, EU and the MENA regions. Patient treatment has begun in both of these phase two trials and results are expected in the first half of 2026. And the MVID trial is also occurring in the MENA region. I think I said that backwards. So U.S., E.U. and MENA for MVID, U.S. and E.U. for our short ballast syndrome. And one of the reasons for that in areas where there's consanguineous marriages as part of the culture, there's often an increased incidence and prevalence of congenital disorders, and MBID is a congenital disorder, as well as a certain population of short bowel syndrome patients. Okay, now I'm going to talk about our other core prophylomer development program, cancer therapy-related diarrhea, which I will refer to as CTD, which is a an opportunity for label extension supplemental new drug application for the already approved Mitessi product. Mitessi is approved for HIV-related diarrhea. What we're looking to do is expand the indication, the opportunity to promote the opportunity for reimbursement for cancer therapy-related diarrhea. Same product, same formulation, same dosing, expand the label. For this goal, towards this goal, Last year, Jaguar completed a global phase three study, a prophylactic clinical trial of profilamer for the prophylaxis of diarrhea in cancer patients with all solid tumors. There are about 10 different tumor types on 24 different targeted agents with or without cytotoxic chemotherapy. And this was termed the on target trial. It was a basket trial. It was a big, big hug, big grab to the cancer community since there are close to, or there are many, many dozens, close to 100 different targeted therapies out there now being used in the cancer community. The trial did not meet its primary endpoint for all the tumor types. However, and often nothing is heard after that, however, the trial did meet statistical significance for the pre-specified subgroup of breast cancer patients, which accounted for 64% of the 287 participants in this study. And these results, these breast cancer results, were the subject of a presentation on December 11, 2024 at the acclaimed San Antonio Breast Cancer Symposium and additional significant results in adult breast cancer patients from this study were the subject of an abstract presented at MASC, which is the Multinational Association of Supportive Care in Cancer. And that meeting was in Seattle just this past June. So let's talk about the diarrhea in targeted therapy. Diarrhea is a very common side effect of targeted cancer therapies, specifically a type of diarrhea that is mediated by chloride ion secretion, which is the target of the mechanism, the groundbreaking paradigm shifting mechanism that crofilomer is able to normalize. And the effect of this diarrhea is that it can lead to dose changes, treatment delays, or even cessation, termination of the cancer treatment altogether. And now you're talking about an impact on the outcome of the cancer treatment of these patients. So in this analysis, which was called a responder analysis of the on-target patients with breast cancer and on-target therapies. Cofelomer resulted in a greater proportion of the monthly responders of diarrhea improvement compared to the placebo-controlled trial. Overall, cofelomer was significantly more effective than placebo in providing sustained response in breast cancer patients. The important regulatory catalyst for this program occurred on May 28, 2025, when JAGUAR participated in an in-person Type C meeting with the FDA to discuss these results. The meeting kicked off with patient advocates who are formal members of our scientific advisory board in discussing the impact of diarrhea on their ability and the entire community, the cancer community, the ability to stay on life-saving therapy, as well as the devastating impact on quality of life and comfort. One advocate had received an off-label prescription for Crofilmer and targeted agents, and these are categories that you may have heard of. We all seem to have been touched somewhere in our relationships and our networks by cancer. So agents that are TKIs, CDK4-6s, epidermal growth factor receptor antibodies, they can have rates of diarrhea and they all have diarrhea, secretory chloride ion mediated diarrhea, but some of them has rates as high as 80 to 90%. There's four grades of diarrhea. Even grade two is four to six loose watery stools a day. with the uncertainty, the size surprise factor, the incontinence. As one of our patient advocates mentioned in the FDA meeting and looked at all the FDA regulators, where do you have time in your day to deal with that? Every single day. Targeted agents are taken in a metastatic situation for the rest of the patient's life and wonderfully metastatic patients now are living 5, 10, 15 years. And even in a curative situation, for nine months with some recommendations for years for targeted therapy. With those powerful messages kicking off the meeting, Jaguar, the company, we then proposed two simultaneous pathways for making crofilomer available in particular to the metastatic breast cancer patients with the significant unmet medical need of cancer therapy related diarrhea. So the two pathways, number one, conducting a pivotal treatment trial. On target trial was prophylaxis. So to expand to a treatment trial to facilitate the approval of crofilomer for CTD in this focused metastatic breast cancer patient population and initiating with promptly pursuit of authorization for an expanded access program immediately for breast cancer patients with CTD who may not be eligible for this study, and that could include breast cancer patients in both the adjuvant and neoadjuvant settings. The FDA formally acknowledged both of these key discussion points in correspondence, written correspondence to NAPO, and acknowledging the supportive data for prophylaxis from the on-target trial. So what we're doing now is we are preparing to submit a protocol to the FDA for a pivotal treatment trial for a smaller trial, smaller number, and this would be metastatic breast cancer patients using profilamer. Complete the trial in 2026 in support of our goal of expanding the label for a product that's already on the market, expanding the label and the approval of Mitessi to include metastatic breast cancer patients, give us the opportunity to promote and sell to that community and for them to gain reimbursement. based on the label expansion. We believe the current estimated US metastatic breast cancer population, which is growing, which is wonderful because of these treatments, is approximately 150,000-160,000 people. And this potentially qualifies as an orphan population in alignment with the company's core focus on orphan diseases and different expedited pathways that that provides in regulatory flexibility. We therefore intend to request orphan drug designation from the FDA for profilamer for CTD indication in this population, and you can look forward to us announcing that when we complete that application. Now I'm going to talk about the animal health side of our business, which is a small piece of our business, but a remarkably important piece of our business. And our primary objective for our commercial product called Canalivia, this is profilamer, chemotherapy-induced diarrhea in doggies. This is a prescription drug by the Center of Veterinary Medicine of the FDA. And it's called something called Conditional Approval under the name Canalevia DA1. And our goal here is to identify a partner, a corporate partner from one of the large animal health companies or medium-sized animal health companies with which to collaborate to achieve three parallel goals for this drug. Obtain approval in the European Union for Canalevia for the treatment of general diarrhea, not just chemotherapy and juice diarrhea. General diarrhea, which includes chemotherapy and juice diarrhea in dogs. And this is based on the existing studies that we have in hand. Goal number two, maintain, of course, the continuity of the availability in the United States of canolevia for chemotherapy-induced diarrhea in dogs, of course. We get a remarkable response there. And then also to expand the indication in the United States from just chemotherapy-induced diarrhea to treatment of general diarrhea in doggies and other companion animals. The mechanism by which profilamer works The channels on which it works are highly conserved in mammals and so the opportunity to expand to companion animals is there for a company that is focused in the veterinary marketplace. We are currently in discussions with multiple potential animal health potential partners. As, by the way, we are on the human side as well. I want to point that out, major goal of the company. and to collaborate on the animal health side to bring canolevia to regulatory approval and commercialization for the general diarrhea population globally. For dogs in particular, diarrhea is one of the most common reasons owners bring their dogs to the vet, and it's the second most common reason for visits to the veterinary emergency hospital. And there's no FDA-approved drugs to treat general diarrhea in doggies. So I find this remarkable. A cancer patient in the United States experiencing diarrhea can have profilamer promoted and prescribed, promoted by the company, prescribed by their health care provider, if that patient is a dog but not a human, but not yet. I'm now going to hand the discussion over to Carol. We'll go back to the financial reporting for today. And Carol, you can recap the financial highlights for the second quarter of 2025, please.

Good morning, Lisa, and thank you to all of you who have joined our webcast today. I'll begin my review of our financials for the second quarter of 2025. The combined net second quarter 2025 revenues of approximately 3 million for prescription and non-prescription products, including license revenue, increased approximately 35% versus the net first quarter 2025 revenue of approximately $2.2 million and increased approximately 10% versus net second quarter of 2024 revenue of approximately $2.7 million. My TESI prescription volume increased by approximately 6.5% in the second quarter of 2025 over the first quarter of 2025. And my TESI prescription volume in the second quarter of 2025 was equal to the volume in the second quarter of last year. Prescription volume differs from invoice sales volume, which reflects, among other factors, varying buying patterns amongst specialty pharmacies in the closed network as they manage their inventory levels. Loss from operations increased by 800,000 from 7.2 million in the quarter ended June 30, 2024, to 8 million during the same period this year. Non-GAAP recurring EBITDA for the second quarters of 2025 and 2024 were a net loss of 7.9 million and 8.8 million, respectively. Net loss attributable to common shareholders increased by approximately $900,000 from 9.5 million and the quarter ended June 30, 2024, to $10.4 million in the same period in 2025. And that concludes my recap of high-level financials for the second quarter of 2025. I will now hand the discussion back to you, Lisa.

Thank you very much, Carol. It's very exciting financial results. And let me conclude with all the members of Jaguar and NAPO, NAPO Therapeutics, we're energized and we are excited about the multiple near-term as well as upcoming expected catalysts for Cofellum and the company, all of which we view as value-enhancing and potentially transformative for patients, all our stakeholders, including our shareholders. These catalysts, as I mentioned, it's the year of catalysts, represent the convergence of key potential inflection points in our major programs, And we are working and expect that these catalysts will bring in significant non-diluted dollars from business collaborations, licensing deals. This is a major focus of our activities right now based on these late stage products and programs on the clinical and the regulatory side. So this concludes our webcast for today. Thank you very much for joining. Enjoy the rest of the summer. We will be furthering our business development and other company objectives based on these clinical and regulatory catalysts that we reviewed today and continuing to work for all our stakeholders. Thank you.

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