Jaguar Health, Inc. Investor update

Oh, thank you very much, Paul. Hello, and thank you all for joining our investor webcast today. My name is Lisa Conte, as you heard. I am the founder, President, and CEO of Jaguar Health and our wholly-owned subsidiary, Napo Pharmaceuticals. I am also the Chairman of our Italian subsidiary, Napo Therapeutics. As usual, I may use the words Jaguar and Napo interchangeably when I am referring to our company. After I speak, our CFO, Carol Lizak, will provide a recap of the financial highlights for the second quarter of 2026. The theme of today's webcast is transformation, near-term catalysts, and sharp strategic focus.

As many of you who have followed this company may recall, this past January 2026, we completed a transformative transaction, the signing of a U.S. commercial out-license agreement with Future Pak for Mytesi, the brand name of our FDA-approved tablet formulation of crofelemer for adults living with HIV, AIDS, and diarrhea. For the brand name Canalevia-CA1, our conditionally approved formulation of crofelemer for dogs with chemotherapy-induced diarrhea. We made the strategic decision to out-license Mytesi to Future Pak, first, because they had recently acquired Theratechnologies, an HIV-focused commercial company with more than four times the commercial effort of Jaguar in the U.S., including two other HIV-related and relevant products. Secondly, to fulfill our strategic plan to bring in meaningful non-dilutive dollars to help fund our sharp development focus on our pivotal stage program for our novel proprietary powder for oral solution formulation of crofelemer.

A different product of crofelemer. Same active ingredient, a different product, different formulation for rare intestinal failure indications. Rare meaning we have orphan drug designation for the intestinal failure indications in the United States and Europe. We are now fully a rare disease GI company with 100% of our human development efforts sharply and strategically focused on our rare disease program. Our ultimate strategy continues to involve identifying a development and commercialization partner for this program. Just to put this in perspective, the out-license to Future Pak was $18 million upfront, primarily for the U.S. HIV market, a market with peak annual market opportunity of maybe $50 million to $70 million annually. Intestinal failure has an annual peak market opportunity assessed by third parties of approximately $8 billion. To comment for a moment on two recent third-party transactions of interest.

In June of 2026, Eli Lilly licensed Hanmi Pharm's phase II GLP-2 antagonist. Not GLP-1, not the weight loss thing. GLP-2, which is for an intestinal failure, short bowel syndrome. In fact, for the rare disease of short bowel syndrome in a deal worth up to $1.26 billion, including $75 million upfront and up to $1.185 billion in milestones plus royalties. In August of 2026, just a week ago Jazz Pharmaceuticals agreed to acquire Actio Biosciences for $820 million upfront, plus up to $500 million in milestones. A potential $1.32 billion deal centered on a proof of concept clinical stage, it is called a KCNT1 inhibitor for an ultra-rare genetic epilepsy. Remarkably analogous to the program we have going on in intestinal failure.

We are now focused on identifying a potential partner for rare disease indications that have a global market estimated to be in the multi-billions with analogous deals that have proof of concept that is earlier stage than what we have in hand. The near-term value driver in our intestinal failure development program is our lead target indication, pediatric microvillous inclusion disease. I am going to refer to that as MVID, an ultra-rare disorder. Ultra-rare, with no approved therapies and a lethal natural history. We have embarked on an ongoing clinical path toward a potential clinical package to be finalized by the end of 2026, so we are talking just a couple of months away, and an NDA submission in mid next year, 2027.

Short bowel syndrome, which you will hear me refer to as SBS with intestinal failure, SBS-IF, represents a larger follow-on indication using the same dosage form and physiological mechanism as intestinal failure with MVID patients. Still, a rare orphaned indication. Our intestinal failure program represents a blockbuster global market opportunity in terms of addressing this catastrophic unmet medical need in patients, and blockbuster in terms of beneficial impact to morbidity, mortality, and the cost to the healthcare system. In the financial return opportunity for all stakeholders, including, of course, shareholders. This return opportunity is especially important to a potential corporate partner. The global market for short bowel syndrome with intestinal failure, as I mentioned, is estimated to reach approximately $8 billion in 2033, and this is according to a third-party market research.

A different third party, but a third party, estimates the value of the global MVID marketplace, which is an ultra-rare indication, at over $1 billion in 2033, for which there are no treatments and nothing in clinical development other than crofelemer. I want to take a moment to describe the catastrophic impact of intestinal failure on patients and what this means for their caregiving community, which includes the healthcare professionals, the family members, and others. Intestinal failure, it is a debilitating condition that often requires patients to receive life-sustaining fluids, electrolytes, nutritions through IV administration. IV administration for the nutrients in life, which is all encompassed in something called TPN, total parenteral nutrition, with supplemental intravenous fluids, and overall TPN with fluids is called PN, parenteral support. IV support for your nutrients of life.

Many intestinal failure patients require parenteral support, IV nutrition, up to 7 days a week and sometimes for 20 hours a day or more. Obviously, this is a catastrophic situation for the patient, healthcare, quality of life. While it is supportive, it is palliative, and it is necessary for life sustenance, it is also associated with serious complications, including liver and kidney toxicities, compromised cognitive function, can have negative impact on growth and survival. The cost is meaningful. It is estimated about $500,000 a year in the United States per patient, but the cost to the healthcare system with the inevitable complications, if you can imagine being on IV nutrition every single day. The complications of infections and keeping that balance of the nutrients of life correct can top over $1 million per year per patient. In addition, the mortality risk. MVID is a congenital disease.

The patient is born and has massive diarrhea and unable to absorb nutrients of life. Often, these patients just die right away. If the patient is not diagnosed immediately, that is what happens. If the patient is diagnosed, they will be on parenteral support for the rest of their life, again, 7 days a week, 20 hours a day. The key of what we are looking for in providing adjunctive therapy to these patients is a reduction in the amount of time that they are on parenteral support. Reducing that parenteral support can have a significant impact on the massive toxicities and comorbidities that are life-shortening for these patients. Life-sustaining parenteral support that is life-shortening because of the toxicities associated with them. The endpoint in the clinical development is the possibility to reduce parental support by even 10%-15%.

That, from a quality of life perspective, would allow the patient to receive most of their parenteral support at night while sleeping, preserving some quality of life, the ability to go to school during waking hours, and the patient would not need to be attached to an IV to go through some of the normal daily living activities. Remember that number, 10%-15%. This past June, we presented groundbreaking results at the 58th Annual, it is called the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition meeting, ESPGHAN, and it was in Lille, France. We presented at ESPGHAN the results of the liquid oral crofelemer, the formulation specifically for intestinal failure.

It demonstrates substantial reductions in PS, and PS in particular because these are children who are growing, normalized to body weight in pediatric intestinal failure patients that were dosed orally for more than one year with no significant clinical or laboratory abnormalities. Basically clean safety. In one MVID patient, the weekly parenteral support requirements normalized to body weight were reduced by up to 48%. Remember the 10%-15% I mentioned. We are talking about up to 48% following more than 12 months of crofelemer therapy. In the two SBS-IF patients, the PS requirements normalized to body weight were reduced by up to 40%, again, for over a year of treatment. This is a stunning result. It is hard to express how clinically relevant this is. As I mentioned, even a 10% reduction would have been considered clinically relevant.