Jaguar Health, Inc. (JAGX) Earnings Call Transcript & Summary

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 the development stage, which may not achieve scientific objectives or meet stringent regulatory 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 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, 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 section 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. 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. Happy to speak with everybody and greet everybody this morning. Thank you, all of you for joining. As you heard, my name is Lisa Conte and 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. And as usual, I may use the word Jaguar and Napo interchangeably when referring to our company. And I am here with Dr. Pravin Chaturvedi, my long-time colleague, Chief Scientific Officer and Chair of our Scientific Advisory Board. He also will quite likely use the words Napo and Jaguar interchangeably. Pravin is a successful developer of 7 new drug applications including his favorite and mine crofelemer. A few moments ago, we released initial results from a proof-of-concept study for intestinal failure associated with MVID, microvillus inclusion disease and ultra-rare disease and intestinal failure associated with SBS, short bowel syndrome another rare disease in pediatric patients. In both situations, intestinal failure requires total parenteral nutrition, which is going to be referred to throughout this webcast as TPN. At least 50% of the time, IV nutrition. For MVID patients, TPN is necessary from day 1 of birth to survive. And that need does not change during their short life, a short life due to complications of liver, renal failure, IV line complications among others. The biggest impact one can have on a patient with intestinal failure is reduction in the quantity and time of TPN. And these results that we have out today show that crofelemer reduced TPN in the MVID patient by up to 27% and 12.5% in the SBS patients. These results in the words of frontline health care professionals, HCPs, health care professionals are groundbreaking medicine that has the opportunity to modify disease progression for a catastrophic patient condition intestinal failure. Why that is important is best expressed by the principal investigator in this proof-of-concept trial and the real-time reaction of this colleague, the key opinion leader a leading investigator in practicing expert health care professional of pediatric patients with intestinal failure. We have an impactful session here today where you will hear directly from them in a fireside chat. I'm going to ask my colleague, Pravin, to introduce the principal investigator, Dr. Mohamad Miqdady and Dr. Tzivinikos and describe the Congress, both Pravin and I attended this past weekend in Abu Dhabi with these 2 experts, building it right to letting the professionals speak to why these results with crofelemer are transformative for patients and all Jaguar stakeholders involved. Pravin and I will then come back and reflect on what this means for Jaguar's business development and drug development strategies and ongoing activities, and we'll take Q&A. [Operator Instructions]. The URL for Jaguar's website is jaguar.health, I'll now hand the discussion over to Pravin. Good morning, Pravin.

Thank you, Lisa. Good morning. And good morning, everybody, to all of you who wake up early to attend this. I am very pleased to discuss the results from the recent presentation of the Elite Pediatric Gastroenterology Congress that we attended, Lisa and I between April 24 and April 26, which is the brainchild of Dr. Mohamad Miqdady, who is the Chief of Pediatric Gastroenterology, Hepatology and Nutrition at Sheikh Khalifa Medical City, SKMC for short in Abu Dhabi in the United Arab Emirates. This is its annual conference. Now it's an 11 year, which brings over 300 leading pediatric gastroenterologists from around the world into one room. Because many pediatric gastroenterology diseases are complications that have a congenital aspect to them, the Middle East, North Africa region, which is called the MENA region, is kind of central to this research because of the prevalence and the incidence of these rare congenital disorders. And the innovation in diagnosing preventing, treating and potentially sometimes even curing some of these disorders. The leaders of that world are in the Middle East, North Africa region. As such, SKMC, Sheikh Khalifa Medical City and other institutions in the United Emirates, such as in Abu Dhabi and Dubai have significant research collaborations also and exchange programs with training centers like Cleveland Clinic, Johns Hopkins, Cincinnati Children's and Boston Children's and many more. It was a 3-day event, had more than 36 sessions, was run flawlessly. And it was the last presentation on the final day, it was a highlight as it was a clinical presentation by the Chair of the conference, Dr. Miqdady. On the initial results that Jaguar reported today on the first 2 pediatric patients with intestinal failure, proof-of-concept results. One had microvillus inclusion disease, short as MVID, and the other had short bowel syndrome with intestinal failure, short is SBS. Dr. Miqdady actually spoke as to why even a single patient result that had a TPN reduction was important and relevant to basically changing the trajectory of disease progression and also very relevant for drug development for new therapies for these intestinal failure patient populations. Right after his presentation, we recorded a fireside chat with Dr. Miqdady and his colleague, Dr. Christos Tzivinikos, and this presentation in the past weekend, which was presented to a full room and many of the attendees subsequently wanted to know how they would have access to our drug, crofelemer. Because the value of this product as well as the value of the Elite Pediatric GI Congress in Abu Dhabi was not lost on any of them. What I will do is, before I say much more, I will have Peter play a recording of the video of the fireside chat between me, Dr. Tzivinikos, and Dr. Miqdady. Just to give you a background on Dr. Tzivinikos, Dr. Christos Tzivinikos is the founder of the Pediatric Gastrointestinal Department at Al Jalila Children's Specialty Hospital in Dubai. And he is an adjunct clinical assistant professor at the Mohamad bin Rashid University of Medicine and Health in Dubai. He's also an investigator and key opinion leader in another trial of ours. So those are the 2 people you will see, Dr. Mohamad Miqdady and Dr. Christos Tzivinikos. Peter, would you mind playing the video for us? Thank you.

I'm here with Dr. Miqdady and Dr. Tzivinikos at the Elite -- 11th Annual Elite Pediatric GI Congress in Abu Dhabi. Dr. Miqdady is the Chair of the Congress and has been doing that for the last 10-plus years, invites all the leading Pediatric Gastroenterologists in the world. One of them is my favorite, Dr. Tzivinikos who this year had the unique honor of doing 4 talks on different indications. And I'm very grateful to both of them for their support and for their guidance over the years. Dr. Miqdady and I, and Dr. Tzivinikos are all colleagues. And I'm taking this opportunity to interview Dr. Miqdady as he just presented new data, breakthrough data, for first of a kind study in patient who has intestinal failure condition called microvillus inclusion disease, and I'd like Dr. Miqdady explain what is the meaning of that disease. Dr. Miqdady, thank you so much. Could you tell the audience what a patient with microvillus inclusion disease deals with and how you manage that patient and why this study is so important to you?

Thank you very much, and welcome to the 11th ELITE Pediatric GI Congress. microvillus disease in a simple word is a genetic disease that newborn usually within the first few hours of life will develop severe diarrhea and they become severely dehydrated with electrolyte imbalance. And that's really a serious disease that starts from the very beginning. And the only way actually to treat this disease is by giving parenteral nutrition, i.e. to give their feeding before venous route throughout their life. Unfortunately, so far, there's no cure for this disease and we are always concerned about the quality of life they have not being able to eat or drink and to be hooked up to an IV line most of their lives.

Thank you, Dr. Miqdady. Dr. Tzivinikos, do you want to add anymore?

As my colleague, Dr. Miqdady said, this is one of the, I would say, worst concern in neuropathies because the diarrhea is so severe even a few hours of the day 1, if you don't sustain this kid with total parenteral nutrition, they will not survive. They have to stay long life on total parenteral nutrition. And the moment, there -- so far, there's no other treatment or prospect for treatment apart from having total parenteral nutrition. But as we know, this comes with the consequences of having complication with life [indiscernible].

Thank you, Dr. Tzivinikos. So Dr. Miqdady, you've been wanting to do something with the anti-secretory drug of ours called crofelemer and you and I have been talking about it for 7 years. So in that journey, one of the things that we were hearing from the people is that an [indiscernible] approach will not work. So tell us what you told audience today and tell us the meaning of what the reduction of total parenteral nutrition that you and Dr. Tzivinikos are talking about is how it's meaningful to everybody.

Absolutely. As I mentioned earlier, the quality of life of these patients is not as good. They are suffering and they always have to be hooked up to a venous line to get their fluids and electrolytes correct. And any reduction in the dependence of the parenteral nutrition means a lot for these patient. It means they are free from having that intravenous fluids and nutrition that they require. Give them more time to be more active towards their peers and allows them actually to take some oral intake that we help the people to take it as [indiscernible]. So, any reduction will be meaningful. And that's what we are seeing in our patients. This is part of an ongoing trial that we started a few months ago. Hopefully by the end of 2025, we'll be completing that study and we'll share with you and the audience the results of this. So far that initial results are very encouraging. Our patients are doing very well with that. We have no safety concerns, and we have a positive effect that all patients are feeling and their parents are appreciating us.

Thank you, Dr. Miqdady. Dr. Tzivinikos, you saw the data for the first time. And what do you think about this groundbreaking study that Dr. Miqdady started?

I'm quite excited, and this is groundbreaking research data coming up. And I'm looking forward to see -- to start our own double blind randomized placebo trial and hoping we see the same results. I'm pretty optimistic for that. Because really, we need to give a hope for this condition. But further on, I think this will open more horizons for one of the patients for this particular medication.

Thank you, Dr. Tzivinikos. So just for our audience because you talk about the intestinal failure because we have one patient with MVID and the other with short bowel syndrome, and these are pediatric patients and that's a first of a kind patient pediatrics, tell the audience what intestinal failure means.

In simple words intestinal failure, when your intestines fails to do what it should do, that's actually absorbing the fluid and the electrolytes and the nutrients. So intestinal failure is where your intestine is not working so you have to have other route to giving you fluid and nutrition. And that's the only way to stay alive. If your intestine does not work and if you don't get your support, unfortunately, you cannot going to make it.

Dr. Tzivinikos, you probably have a study here too, you're going to start as an investigator randomized double-blind placebo-controlled study. And in that, we have put the requirement that we added Dr. Miqdady's study as well, more than 50% nutrients and calories has to come from nutrition. Tell the audience like in that study, what the meaningfulness of the duration reduction means, like more than 12 hours in a day.

I mean every reduction counts. But, If you -- the more you manage to [indiscernible], meaning cycling that we're not having all the time, it has a huge impact as we know now for many studies on the liver in the patients, even in this particular patient is renal implications. Well, because in this type of failure, most of the medical colleagues, they know about the liver impact. But in this particular condition, it's also the renal impact. The more you reduce the time of PN, the better for this patient, not only the amount, but also the time, plus the quality of life, plus having more normal life as kids, going to school and so on.

Thank you. When I have first met you, Dr. Tzivinikos, you told me, none of my patients will ever get intestinal transplant. Because these patients many times are candidates for intestinal transplant. Neither you nor Dr. Miqdady like that option. Can you just tell the audience why?

I mean there are certain criteria for multiple [indiscernible]. Someone can see the publication in 2020. If you go 20 years back, microvillus inclusion disease, actually per se was the indication for intestinal transplant. This is not anymore the case. Of course, at some point, they may reach this level either because they will lose the central line or they will have a problem with the liver, but the parenteral nutrition care has improved so much and if we have now an agent which can ameliorate the impact of the parenteral nutrition by reducing the need for that, we buy years and who knows how much benefits, we'll get from that.

If I may add to that, the quality of life is the main concern we have, and multivisceral transplant, i.e. intestinal transplant and liver transplant, the quality of life might be significantly compromised post transplant and that's not the cure...

It's another disease. Yes, it may save your life at that particular point it it's indicated. I'm not against that because it's indicated but it's another disease. There are a lot of complication that happened from the immunosuppression.

Thank you for teaching us that when we started working together. So one of the things that today you saw in MVID patients is that in 12 weeks, you have seen 25% reduction in parenteral support, both TPN and supplemental fluids. You have seen reduction in stool output, you've seen some increased urine output, and you've seen reduction of the duration of TPN.

Yes, that's the most important. Again, it's the quality of life. So that's where we aim for, improving their quality of life so they can enjoy life and reach their potential, physically and mentally as well.

All the studies have shown, particularly for intestinal failure associated liver disease, the best strategy to prevent that is to [indiscernible]. One of the common, or the most important factor [indiscernible].

And one of the things that our audience sometimes misconstrued is they think that because of the availability of GLP-2 analogue, teduglutide [indiscernible] that this is not an unmet need that needs to be addressed. But I think that...

Microvillus inclusion disease does not apply that, GLP-2 or short gut syndrome, [indiscernible]. Maybe if we can have a discussion about it, the pediatric patients may have a potential, but why not combining them.

Thank you. So we will do that. Absolutely. So you have plans for having at least 1 or 2 more microvillus inclusion...

Well, hopefully, a total of 6 patients, although the number 6 might sound small, but actually it's a large number, given how rare this disorder is.

So tell the audience how rare it is in all the countries in the world.

It's -- this is an ultra-rare disease, and when we talk with colleagues and experts around the world. And nobody has more than -- will probably had a number of patients at the most and in big symptoms. So 6 is a very large number. And again, this disease has no cure or treatment so far. So hopefully crofelemer will add to that and at least will give them a better quality of life and let them enjoy their youth as we want our children to be.

And you both know this, but our audience may or may not understand this. The European Medicines Agency has this initiative called PRIME, which is Priority Medicines. And they have basically identified us to come talk to them, and your data is basically something that people talk about, [indiscernible] and I think that's very important for -- and it will affect both -- all intestinal failure patients because it's not just...

That's something the most important thing because we have now microvillus inclusion disease as a disease model to do the trial, but the proof of concept, our quality of life for proof of concept can apply to other diseases with a similar pathology.

Well, I know you're both short on time, and I really, really appreciate both of you taking the 10 minutes with me. Tell our audience -- and can you elaborate on the urine as well?

Well, it's very interesting because when we follow these patients, I -- we ask them about what are the side effects and the only complain they have that kid is urinating more. I was excited to hear that, because when you urinate more means you are very well hydrated and you are responding to the medications so that's actually an effect rather than a side effect of the medication and an indications to decrease the parenteral support.

The kidneys are working.

Exactly.

All right. Well, many, many thanks.

Thank you for the opportunity. Thank you.

Wonderful. I hope everyone can hear me again, and I hope you all enjoyed watching the fireside chat. I was there. And every time I watch it, I learned something new. I love the passion, the commitment, the promise for changing medical outcomes in such a meaningful way for intestinal failure patients and their families. As you heard, any reduction in TPN would have been important. 27% and 12.5% reduction in TPN is huge. I met Dr. Miqdady, 8 years ago, when I was dropping my daughter at NYU Abu Dhabi, and walked into this conference that was going on just around the corner. It's been nothing less than inspiring as we have spent the past 8 years developing close working relationships with key opinion leaders and principal investigators around the world regulatory interactions and protocols, endpoint definition and formulation development. These patients are the true personification of a phrase, which sometimes is overused. But the true personification of the phrase unmet medical need, and their HCPs and caregivers, the personification of nurture, of being there every day, every hour. These patients are quite fragile and it's a family disease. Jaguar through Napo Pharmaceuticals and Napo Therapeutics in Italy is currently supporting 2 ongoing proof-of-concept investigator-initiated trials and conducting 2 placebo-controlled Phase II trials for crofelemer, for MVID and adult short bowel syndrome intestinal failure patients in the United States, European Union and the MENA region. In addition to Dr. Miqdady's ongoing study, an investigator-initiated trial in adult patients with short bowel syndrome intestinal failure has been initiated at Cleveland Clinic. We expect to have proof-of-concept results from these investigator-initiated trials throughout 2025. And the 2 placebo-controlled Phase II trials are expected to conclude and have results in the first half of 2026. Pravin, as you can see, has established a fabulous collaborative and productive relationship with our KOLs and clinical investigators. As I think you can glean from the general -- genuine report in the fireside chat, Dr. Miqdady even got Pravin to put on a suit. Genuinely, there is a lot of patient passion there. Pravin, I'm going to ask you, please mention the names here of a few heroes in the community of intestinal failure, and then speak a bit more to PRIME, which you mentioned at the end of the fireside chat.

Thank you, Lisa. And indeed, it's a pleasure to watch the video because we did it really live and extempore. So none of that was a cookie-cutter question. Everything was extempore. So in addition to Dr. Miqdady and Dr. Tzivinikos, who are both pediatric gastroenterologists and our participants in our microvillus inclusion disease campaign. We have -- in Italy, we have Dr. Antonella Diamanti and she is a leading gastroenterologists -- pediatric gastroenterologists and at Bambino Gesu, which is the Children's Hospital in Vatican City. And of course, the national and international principal investigator for the MVID campaign that we have, he's here at Boston Children's. Her name is Dr. Lisette Jimenez, and she will be joining me next week at an investigator's meeting. These are for microvillus inclusion disease campaigns that we are doing. In addition, for adults, including SBS, Lisa mentioned, Cleveland Clinic, which is the largest adult gastroenterology clinic for a short bowel syndrome with intestinal failure in the world. And the person we are working there is Dr. Lindsey Russell, and she is going to do a small proof-of-concept study in addition to a Phase II study that we're going to initiate in European Union first in Italy and Germany. And the Italy and Germany Adult gastroenterologists who treat intestinal failure patients who are on home parenteral nutrition are the who's, who list of intestinal failures. So in Italy, we have sites in Naples, in -- and we have Dr. Pasanisi there. We have Dr. Morabito, who's still thinking about doing a pediatric study. We have Dr. Berberio and [indiscernible] and we have Dr. Lamprecht in Rostock in Germany. Dr. Von Websky in Essen, we have 3 others in Germany, including Dr. Ulrik Pape, who's a world leader in this section. We have visited all of them, met them in person. And they are truly interested in the use of crofelemer. Because crofelemer, as Dr. Tzivinikos mentioned in the video, is ambivalent and agnostic to what other treatments the patients are on because it is actually an antisecretory. And it works on the other side of reducing secretory diarrhea rather than changing any of the bowel adaptation, which is what all of the GLP-2 analogs need, as Dr. Miqdady and Dr. Tzivinikos were talking about. So what Lisa had asked me also just now is to say, hey, let's talk about why PRIME, the priority medicines initiative has been of interest to us. In fact, we did not know that because through our Italian subsidiary, Napo Therapeutics, we had preliminary communications with European Medicines Agency regulatory members that focus on PRIME. PRIME stands for Priority Medicines, which is a program that provides enhanced interactions and early dialogue for the development of novel medicines targeting unmet medical needs. With these initial results are in pediatric patients with MVID and SBS with intestinal failure, and given the ultra rare nature of MVID, there are only 50 to 100 cases in the U.S. that are known because incidence and prevalence are just about equal, these patients don't live very long. If they live longer, we want to help them have good quality of life as Dr. Miqdady was talking about. And even with a small number of patients, we can actually get an expedited review and approval. So the discussion we want to have with them is to explore pathways for expedited regulatory approval in Europe. If crofelemer -- it might qualify for PRIME in European Union and the PRIME designation in European Union may actually help us to get breakthrough designation with the U.S. FDA, which is also an expedited regulatory pathway. Now just for those of you who may not know this, crofelemer is being evaluated in a novel liquid formulation for pediatric patients and adult patients with intestinal failure, because there are volumes of nutrition and electrolyte supplementing is very tightly controlled. So we have made a highly concentrated like-for-like product. And it is called a Type 3 NDA in the U.S., which means it's a new product, so it is not the same tablets. It's different from Mytesi. That's why it doesn't have a name yet. And this is very important for us to understand that this liquid formulation is literally given at 0.1 milliliters per kilogram body weight. And so there was no big change in the volume for these patients who are receiving more than 50% of their nutrient and electrolyte requirements through parenteral nutrition. And if we get the PRIME designation, which is the pediatric MVID indication, SBS obviously has a longer duration for the Phase II to be finished, which has about 40,000 patients worldwide to our estimate, at least between the EU and the United States. The market size for just SBS has been estimated in the U.S. to be exceeding 5 billion based on what we know with teduglutide and other biosimilars for that. So this is an opportunity to make a very meaningful impact for intestinal failure patients as well as actually do something, which is completely novel, has never been done before, which is to reduce the need for parenteral support. One of my KOLs for adult SBS is the Chair, Director of the inflammatory Bowel Disease Center Dartmouth. And Dr. Siegel has taught me that the 2 most toxic treatments in medicine are total parenteral nutrition and chemotherapy. So anything we can do to reduce that is extremely meaningful in good outcomes. So I will actually turn it back to Lisa now so that we can continue our discussion. Lisa, I hope that was helpful.

That was terrific. And that's how drug development is done. It is quite a process for those who are not in this industry to understand and the long-term nature and the relationships and all the thought leaders and thought process that goes into it. So thank you, Pravin, for your leadership here on the scientific side. And what we've discussed today is the first catalyst in one of our major 2 programs, our rare disease intestinal failure program. Now as you heard, we're currently supporting 4 clinical efforts in this rare disease intestinal failure program. The first proof-of-concept results are also catalyst to enhanced potential business development plans for partnering and receiving non-dilutive dollars. We own the global rights to crofelemer. There has been a strategic shift in the pharmaceutical industry towards rare and orphan indications. Smaller populations, therefore, potentially less expensive clinical development programs, opportunities for expedited regulatory pathways as you've heard, such as PRIME and breakthrough designation, business models that support the relevant pricing necessary for these small populations and reimbursement for these diseases, which typically have high morbidity, high mortality, and high expense. For example, a typical patient on lifelong TPN caused the system approximately $500,000 a year to treat without patients. And they all end up with complications, with double or more with the complications as Dr. Tzivinikos mentioned. These initial results that you heard today catalyze the value proposition of crofelemer in treating and managing intestinal failure patients. There are many precedents for major highly valued rare disease collaborations in the pharmaceutical industry. Tens to hundreds of millions of dollars based on initial proof-of-concept data in rare diseases. We're actively pursuing in discussions for collaborations to cover our development costs and more until crofelemer reaches these patients through commercial success. Finally, while I have Pravin here, I will mention another near-term catalyst in our second major drug development programs that Pravin is also leading. Crofelemer in the same delayed release pill formula of Mytesi, which is our commercialized formulation, distinct from the rare disease program, as Pravin mentioned, a distinct formulation, a distinct product, Mytesi is approved for HIV-related diarrhea. And Crofelemer in this formulation will be the subject of an FDA Type C meeting in the second quarter of 2025. Now -- right now regarding the potential pathway to bring the product to a supplemental new drug application for crofelemer, for prophylaxis of cancer therapy-related diarrhea, in breast cancer patients on targeted therapy with or without cytotoxic chemotherapy. Results which have been presented with statistical significance and a responder analysis based on a prospectively described subgroup from our Phase III clinical trial called OnTarget. And these results were just presented this past December 2024 at the [indiscernible] San Antonio Breast Cancer Symposium. And I'm sure Pravin would be pleased if there are any questions that should refer to that program as well. But now back to the intestinal failure results that we presented today. They are groundbreaking. They do humble us and we are quite proud of what we've put together to allow Crofelemer to show its benefits preliminarily in these patients. So I'm going to go look to questions now, which have come in written, some Pravin are going to be for you.

Here's an easy one. What is the current number of patients in the proof-of-concept trial how many further will be enrolled? And I think there is a related second question, similarly about the Phase II trials, the number of patients in the Phase II trials and the timing for that. So basically Pravin, the 4 trials, the 2 investigator initiated and the 2 placebo-controlled trials. If you could speak to the number of patients and timing, please.

Okay. Can you hear me?

Yes, we can.

Okay. Good. All right. So in this proof-of-concept study that Dr. Miqdady was discussing, which is an open-label study, he plans to enroll, as he mentioned, up to six patients with intestinal failure, he's got, to my knowledge, the third patient enrolled out of the 6 just recently, and that's also a short bowel syndrome patient. So he has got a plethora of patients in the region, and he's expecting maybe 1 or 2 more MVID patients and maybe 2 to 4 SBS patients and they're all pediatric, his study is only for the age groups of 1 to 18. Then total number of patients in the other investigator study that Lisa would have mentioned, which is for the adult SBS, intestinal failure patients in Cleveland Clinic also intends to have 6 adult patients, and that's about to start this quarter and so that will go on. For the Phase II studies that are Napo sponsored, so remember, these studies are investigator-sponsored. So Napo is just providing support through formulation and drug, doesn't have any oversight or accountability for data management for the 2 Phase II studies that are under our sponsorship. The first one is pediatric microvillus inclusion disease study. This study was initiated first in the United States under the IND with the FDA with Boston Children's having 2 patients. Subsequently, we got interest from the European Union from Italy, in particular, from Dr. Diamanti which is a center of excellence for intestinal failure patients in Europe. And then we also got interest from Dr. Tzivinikos in the UAE. So we had to basically make it into a global trial from a U.S. trial, keep the same protocol and then basically get regulatory approvals or clearance, from all 3 geographies. So now the FDIT trial has become a global trial. We expect up to 8 patients with MVID, pediatric, obviously, to be enrolled and randomized and treated in our Napo-sponsored study, which may seem like a small number to some of you, but with the prevalence of being 50 to 100 cases, 8 patients represents almost 5% of the living population of these pediatric children. The second -- Phase II study that Lisa mentioned, is an adult SBS study, which we are only doing it under the hospices of EMA, European Medicines Agency, and we are doing it in 2 countries, Italy and Germany. And we have 8 centers there, and we intend to enroll up to 18 patients. It's randomized double-blind, placebo-controlled and 6 months of treatment. So again, in that Phase II study, we expect some results in the first half of 2026 and MVID, we'll have some of that data in the first half of 2026. I hope I answered the question, Lisa.

Well done, Pravin, and I'm going to continue with the questions for you before I move on to the questions that I should answer. So another question has come in is, how confident is the team that PRIME designation will be granted leading to early access a potentially expedited review for the patients in the 27 EU countries?

Well, we are cautiously optimistic that we will have a good dialogue with European Medicines Agency for the PRIME designation. Obviously, this is not something that we can predict because it's a review issue and we intend to have a submission to them later in about 4 weeks from now, and we'll hear from them in mid-July if they want to invoke a meeting. But the fact that they invited us to speak with us, speaks to the burden of the unmet need in this pediatric patient population and the rarity and the desire to give some treatments other than TPN which is all that these MVID patients get. And so I'm cautiously optimistic, but I cannot put a percentage on that.

Perfect. And here's a question that's probably more sort of understanding how clinical trials work on a global basis. Are the treatments that are happening in Germany and Italy during the clinical trials, are they reimbursed by these countries, how does that happen? How do these patients in European countries participate in our clinical trials.

So are you asking if the TPN is considered a standard of care? Is that the question?

No, I think the question is asking about does crofelemer get reimbursed during the clinical trial. So it's sort of understanding how the clinical trial process works in the pharmaceutical industry sort of gets to why it's so expensive to develop new drugs.

I see. Okay, sorry. So in the Napo sponsored studies, we are paying the investigators and the sites a per patient cost because TPN is standard of care, so that is reimbursed by their government. But we pay for all of the testing and everything else. So it is not something that is normally reimbursed by insurance in their country. If we get good results and we are the subject of approval by EMA, we still have to negotiate with the HTAs, the health technology assessment groups, which are the payers. In Europe, one by one. We have a market access lead person for our Italian subsidiary, Napo Therapeutics. She is already engaging with them, along with our medical affairs head over there with some of these HTAs. Our anticipation is that upon approval in Europe, the first country that is likely to allow us within 6 months after approval to launch and get reimbursed will be Germany. Because the Germans are the fastest. And after that, we expect Italy to come second and France to come third. So I think it's -- that's the way it's going to work. But at this point in time, under clinical trials, TPN is standard of care, so we don't have to pay for that. But other than that, any other testing and the use of any of our materials and home nurse or anything else is all covered by Napo in our Napo sponsored trial.

Terrific. And then don't go away Pravin, there is another question coming up for you. But there is a question that I think I'll answer. Which is talking about -- we are a business here, what is the market size? What are we talking about? And rare diseases are really remarkable, the incentives that are in place, the reimbursement opportunities for small populations. But as you can hear, the activities, the time, the expense involved in coming up with breakthrough medicines and breakthrough interventions. So let's talk about MVID first. The support -- well, actually, let's talk about SBS. There is a product that's approved an approach that you heard Dr. Tzivinikos talk about, and Pravin mentioned, a GLP-2 which is essentially a growth hormone. So it does have some utility in a small number of patients, literally single-digit number of patients with SBS not standard of care, lots of limitations in how a growth hormone can be used. For example, you can't use it in an abnormal hyperprolifetive disease situation. You can't use it in the cancer patient. But nevertheless, the product is reimbursed in the United States at about $500,000 a year and a couple of hundred thousand dollars a year in Europe. So if you use that as a bench mark for annual reimbursement, with MVID, which is ultra rare, you're talking about the market opportunity of a couple of hundred million dollars, about 200 patients, $500,000 a year total market opportunity. that same formulation, that same product then in the short bowel syndrome market, which is about 40,000 patients around the world, that's where you're getting into blockbuster territory. And as I mentioned, third party analysts have put that market. We've seen estimates from about $5 billion up to about $12 billion a year, which was not even taking into account the opportunity of something like the crofelemer, with the safety, the broad use opportunity without limitations, for example, in cancer patients or patients after surgery having to have bowel adaptation. So this is quite impactful for the financial stakeholders in the company. Of course, we've talked what's driving force here is the need for patients as well. And the strategy here, the clinical results are playing into a very important business strategy because MVID has nothing -- MVID patients, their gut is fully intact. It's not short. It's just not functioning. So there's no growth hormone approach. Again, as you heard from Dr. Tzivinikos, there's nothing. There's nothing in development. There's nothing for these patients. Nothing was ever expected to have an opportunity to reduce TPN in these patients. That's the driving force behind PRIME, which is potential accelerated approval, potentially gets us breakthrough designation get that product out there as quickly as possible, get the reimbursement challenges and all that done, and it's the same product, the same formulation that will go into the short bowel syndrome market as well. Which is, I think, a good lead into what I believe is the last question here. And Pravin, I'm going to send this one to you. And the question is, why do you think in these 2 patients, there was 1 patient with 25% reduction in TPN and another with 12.5%.

Yes. It's a good question. So I see the question in the chat box here. So I think what -- this is guesswork on my part. There are 2 possibilities that I can speculate upon. In MVID patients, nobody had quite understood the possibility that if we were able to reduce the amount of secretion, which we had done in an [indiscernible] organoid model at Boston Children's and publish that, that, that would have an indirect benefit in oral absorption, oral intake. In an indirect benefit of that, what is -- what Dr. Miqdady spoke about in the fireside chat with us, which is that while the mom was complaining that the child was peeing more, that is actually a direct effect of more oral absorption. So I think in the MVID person, over time, we see sort of a gradual reduction in stool volume output and a little bit of a bounce, but more urine output over time and we could see that. In the SBS child, we do not know the gastro surgeons when they cut the bowel, they don't record the remnant bowel's length. And so these patients, it is likely, let's say, this child is a type 1 patient. That's my guess, which means that the patient does not have a colon in continuity. And the reason for saying that is that the volume of TPN that this child needed every day, and I saw that number from Dr. Miqdady's presentation, on a weekly basis, the child was getting more than 18 -- 20 liters, 21 liters in TPN. And so I think because they don't have much capacity to absorb, that might take a little bit longer. So it is not that the reduction is different as it may be more a temporal effect. So maybe it will take a little bit longer, this was only the -- Dr. Miqdady was doing only a 12-week study in which he dose escalated. So I think in MVID, we saw it more because the child had a full length cut. And so maybe that helped with the absorption and then the benefit of crofelemer in its antisecretory mechanism actually played a good role in that. So that's my guess. It's not precise, but I think over time, all our other trials are 24 weeks or longer. And we are continuing Dr. Miqdady's exploratory open-label study. And if the child continues to benefit, we'll get long-term data, both in SBS as well as in MVID. So we'll be able to answer that question more accurately in the coming weeks. This is -- we just had the first 12 weeks of data right now. I hope that answers the question, Lisa, on that one.

Yes, I think that's well put. In summary, one word, yes, right? That's how much so far. Another thing that I think would be is important to actually highlight here is the MVID patient according to the protocol after 12 weeks, which as you just described, is limited. But then the protocol called for the patient to go off crofelemer for 2 months. And why don't you talk about what happened in that situation?

And I see that another question has come in on MVID on the patient's appetite. So sorry, I'll try to take that as well later. Yes, so one of the things that we have done is these are called NF-1 trials regulatorily because the FDA had put out guidance is about 10, 12 years ago on what is called substantial evidence of effectiveness. And in that, they had for rare diseases and orphan diseases created a paradigm wherein you show NF-1 trials where you basically treat a patient and then -- with whole treatment, and then if the condition worsens, then you restart and you show if there is benefit again. Pretty much is exactly what we did in the open-label study that Dr. Miqdady described, where the patients were supposed to get the drug for 12 weeks and to the maximum dose that Dr. Miqdady determined based on safety. And then at the end of 12 weeks, TPN continues, but crofelemer as an investigational product is stopped. And in the protocol that Dr. Miqdady had submitted to the authorities, he had asked for a 30-day withholding period. But he amended that with his IRB to say if the symptoms start to worsen he would like to reinitiate crofelemer treatment in addition to the TPN and other therapies. Good thing he did that because after stopping in the MVID patient, 8 days later, the mother called Dr. Miqdady and said, my child's stool volume output is going up. Urine output is going down. Please, please, can we reinitiate the treatment with crofelemer. So he restarted 8 days later itself. And this was something that another regulatory clinician had warned me about and said that don't have and don't wait for the entire protocol specified 30 days because sometimes the worsening does more harm. And so reinitiate at the first signs that in the clinical judgment are necessary, which is what Dr. Miqdady said. And now that's also evidence of the NF-1 trial that the patient was truly benefiting from the crofelemer therapy because that was the only other additional variable that was taken away. So I think that was -- Dr. Miqdady was quite pleased to be able to reinitiate after 8 days rather than having to wait for 30 days. Yes, there's another question related to the oral intake, Lisa, in there.

Go ahead. Take that question.

Yes. So the question is, in the proof-of-concept study, did you observe any changes in patient's appetite or oral intake in the 12 months overall treatment period. So I can't answer that question because that's Dr. Miqdady patient, it's an investigator sponsored. But I can indirectly answer that question that the urine output going up and the TPN duration going down. So you heard from the video from Dr. Tzivinikos and Dr. Miqdady, that this child was getting 16 hours of parenteral support every day, and it was down to 11 hours by the end of the study and his urine output was going up. So that's indirect evidence that the oral intake did go up. And this has been sort of postulated at least in the U.S. with my colleagues at Boston Children's. That MVID patients may benefit and they might be able to improve their oral intake, if we are able to basically reduce some of these needs for parenteral support. So I think it's our first evidence. It's early days, but I'm cautiously optimistic that the oral intake is improving. I hope that answers that question for your MVID question.

Yes. I love this dialogue. We could go on forever, but just a comment about that one is things you learn as you start to interact in this community is that very important early on, even though the patients can absorb anything from what they're taking any nutrition or orally if you don't get them in the habit of taking things orally and eating, they will never eat. They just have no interest, no desire, it's almost garbagy in their mouth to have the meat. So that's very -- it's something that they learned and they try to start as soon as a child can put something in their mouth even though it doesn't get absorbed. There is a question here about potential cognitive benefits. This was very interesting when I was sitting in the conference in Abu Dhabi unrelated to this presentation, which was the last presentation, there are many presentations on cognitive disorders and parenteral nutrition and a whole bunch of disorders that have intestinal failure, well beyond the MVID and the SBS that we're talking about where we expect and hope crofelemer will eventually be able to have impacts as well. And the number one thing that the investigator -- I actually happened to be sitting next to him, his name is Dr. Cole from John Hopkins a new facility that they opened in Gainesville, again, another collaboration with the renowned centers here in the Mid East. The number one issue for him was the cognitive impact and deficits in these patients because they're young, they're pediatric patients, often, it's from day 1 when they're born and they're not getting adequate nutrition on a regular basis. These patients are fragile. TPN is not an easy thing to monitor. These patients are monitored, for example, by Dr. Miqdady every single week. There were some patients in the Children's Hospital in Rome, who've never even left the hospital. And so when -- with that variability, there's variability in their nutrition and obviously in their cognitive development. So that's what he finds is the one impact to these patients. Okay. Here's a question, a business question. With these rare patient populations, do you plan on marketing the product you're own or partner regionally. What is your strategy here? Okay. So right now, commercially, we do have a commercial product for Jaguar and that is Mytesi for HIV-related diarrhea, we do commercialize ourselves in the United States. The strategy we have global unencumbered rights to our technology. We have some partnerships. For example, we have a partnership in place in Turkey, in some Eastern European countries. Our intention is to bring on partners and collaborations, as I mentioned, with this proof-of-concept data, and by the way, separately in our cancer program as we get clarity from our FDA meeting to bring in nondilutive dollars from these transformative catalysts that will help fund the company and these programs until these products come through for commercial access. In the United States, we would like to continue to commercialize ourselves, perhaps in some of the bigger areas like cancer, we would have co-promotion. So we have an opportunity to bring additional feet on the ground. But for rare diseases, these are really very focused centers of excellence, the leaders that we've already identified that are working in our clinical trials, patient advocacy organizations, patient advocacy is near and dear to our heart. The patient voice is so important, for example, we've done a very strong role on the cancer side with make cancer less s***** and the patient advocacy and opportunities for the entire community and rare diseases is very strong. So that, in general, is the plan. Rights outside the United States, bringing nondilutive dollars based on these catalysts and these very near-term happening right now, transforming the events and hang on to the U.S. rights or at the very least co-promotion in the United States.

So Lisa, there are 2 more clinical questions. Let me just handle them so that we can answer. I know we are running out of time here. So the first one is whether we are going to do every MVID patient mutation one at a time. The short answer is no, because genetic mutations do not dictate the phenotype. The diagnosis of MVID is basically done with clinical symptoms and genetic mutations, all 4 of them are included. We already have the [indiscernible] study we have done with 2 different mutations. They present with the same phenotype regardless of the underlying genetic mutation, and genetic testing results come forward 6 months afterwards. So our KOLs have told us not to worry about what the underlying mutation is. That's the answer. And the other question is about cognitive benefits that we expect to augment your answer, Lisa, from Dr. Cole. This is something that every pediatric gastroenterologist always wonders that as tightly as they regulate the TPN growth is stunted and neurodevelopment is slow. So if we can improve oral absorption, the question is basically reverse, yes, I'll basically say, yes, our hypothesis is that the more the patients can absorb orally, these MVID patients, their neuro and cognitive development will be better. That is the working hypothesis we will see that. So we are not including that as a trial endpoint, but we are definitely going to assess that over time. Those are the 2 questions which are clinical. Lisa back to you. Sorry.

Okay. I think we are done here with the questions, and we've run a little over. I want to thank everybody for participating. I'll leave you -- I so enjoyed this session, I enjoyed the dialogue. And let me just leave you with a few words here, which is catalyst, transformative, groundbreaking, hope for these patients and for all the stakeholders involved in this endeavor of drug development. Thank you, Pravin, for your leadership and your participation. Thank you all for listening this morning and more to come. Here we go.

Thank you all. Goodbye.