All right. Hello, everyone. Thank you for continuing to join us throughout the day here at the Lytham Partners Fall 2024 Investor Conference. My name is Robert Blum, Managing Partner at Lytham Partners. During this presentation, we welcome Jaguar Health, ticker symbol of JAGX on the Nasdaq, and joining us today from the company is this company's CEO, Lisa Conte. Before I turn it over to Lisa, I just want to remind everyone that management is available for one-on-one meetings throughout the conference here. If you've not already scheduled your one-on-one and would like to do so, shoot me an email. That's blum, B-L-U-M, @lythampartners.com, or you can visit the landing page for the conference website. That's lythampartners.com/fall2024. From there, you can click on the Investor Registration button to make your one-on-one selection. So Lisa, once again, thank you very much for your participation in the event, and the floor is all yours. Oh, thank you, Robert, and once again, this is my favorite conference, so thank you for inviting us back here. Good morning, good afternoon, depending on where you are. I am very excited today to be talking about Jaguar Health, because we made a very important clinical announcement this morning. So I'm going to give you just a little bit of background to set the stage for this announcement. Of course, we are a public company, so we have our forward-looking statements. Again, what Jaguar is all about is we do our drug discovery from plants that are used traditionally in tropical areas, and we do have a current FDA-approved product, crofelemer, and it is approved for human use for HIV-related diarrhea under the brand name Mytesi, and crofelemer is approved by the Center for Veterinary Medicine for chemotherapy-induced diarrhea in dogs under the brand name Canalevia. It is plant-based, it's sustainably harvested, it's organic, it's natural, and it is an FDA-approved drug, and the only oral drug approved by the FDA under botanical guidance. And under botanical guidance, there is no practical pathway to bring a generic crofelemer to market. So even though we have a very aggressive IP strategy, we essentially have exclusivity forever. So the most powerful thing about crofelemer, which lays the groundwork for the announcement that we have today, is that it is truly a pipeline within a product, with multiple follow-on indications based on the paradigm-shifting approach of normalizing gut function. We can't do them all, and so two that we have focused on are cancer therapy-related diarrhea, with the recent completion of a phase III clinical trial, and a rare disease business strategy for intestinal failure with short bowel syndrome and congenital diarrheal diseases. So ta-da! Here are the announcements which we were so delighted to make this morning, and so pleased for the benefit in patients. Crofelemer achieved statistical significance in a pre-specified subgroup of adult patients with breast cancer from the prophylactic OnTarget phase III clinical trial that we completed and announced data from a couple of months ago. This was the largest group of participants in the trial, 180 of the 287 patients in the trial. This was based on a responder analysis, and a responder analysis provides the continuity of the analysis of the primary endpoint that led to the approval currently that we have for Mytesi, crofelemer for AIDS-related diarrhea, and also for some phase II studies that we have in other indications. This improvement, this result, has been submitted to an appropriate symposium, and also a full report is being drafted and expected to be submitted to a peer-review journal by the study's primary investigators and our scientific advisory members, which includes also patient advocate membership on our scientific advisory board. The trial is filled with rich data from patient-reported outcomes, ten different tumor types, twenty-four different targeted agents that were studied prophylactically, as I mentioned, patients on or off cytotoxic chemotherapy. So there will continue to be additional analyses, additional reviews, and therefore, as appropriate, additional submissions to symposium and publications as well. So again, statistical significance in the pre-specified subgroup of breast cancer patients on different targeted therapies. This forms the basis of really three categories of robustness in the company that are very powerful right now, and I think rec— Can be recognized in the near-term value creation in the company. First is clinical robustness, clinical and regulatory, the data that we just announced this morning, and separate from that, we have five clinical efforts moving forward in our rare disease program of intestinal failure with short bowel syndrome and a congenital disorder called MVID. Three investigator-initiated efforts and two global phase II clinical trials. We also have two investigator-initiated trials that have been accepted, posters that have been accepted. Again, investigator-initiated by, so by those investigators, one from Harvard, one from Texas, at the upcoming American College of Gastroenterology, and this is for diarrhea-predominant IBS, and again, a continuity of the responder analysis, that same continuity from the data that we announced this morning, and the data that has Mytesi currently approved for HIV-related diarrhea. In our clinical robustness, we also have an IND approved for a second-generation, anti-secretory, paradigm-shifting gastrointestinal agent for the diarrhea and the dehydration associated with cholera and other severe diarrheas, distinct from crofelemer. And we have an early-stage pipeline that is IND-ready for novel psychoactive botanical drugs, three candidates that can be filed as an IND in 2025. Sort of building on the enthusiasm and the interest now to look for new ways to treat and potentially cure mental health disorders with the work that's going on in psychoactive and psychedelics. But a lot of the work that's being done there are the same agents: MDMA, ketamine, psilocybin. What's the next generation of novel agents that can also be paradigm-shifting? So that is our clinical robustness. Commercially robust, we are very proud to announce that our third FDA-sanctioned product is being launched this month, October, October 2024, literally this month, and that is our first commercial foray into cancer-supportive care for oral mucositis. And we'll talk more about that in a moment, and that product is called GelClair. And then, our financial robustness with our current sales that we have for the current approved indications of crofelemer, we had a nice increase of Q2 over Q1 of 16% in our net revenue, and would expect that to accelerate even further as we are bringing GelClair to market and GelClair revenues into the financial picture currently at Jaguar. We don't put out specific guides, but to give some idea of how a paradigm-shifting approach can benefit all the stakeholders in the company. Of course, this is blockbuster for the patients who have no alternative treatments and unmet medical needs, but for all the stakeholders, if we can talk about some of the third-party analysis of how big these markets can be. If we look at prophylaxis in cancer treatments for chemotherapy-induced nausea and vomiting, that's expected to be a $3 billion market, and about $1.5 billion of that market is valued as a generic. And those agents are typically taken for the first three days in cytotoxic chemotherapy. With cancer therapy-related diarrhea, prophylactic for targeted therapy, we're talking about targeted therapy in a metastatic setting that is taken essentially indefinitely for the rest of the patient's life, in a curative situation, often for nine, 12, 15 months. A much different impact on how big this can be and how beneficial to all the stakeholders in the company, first and foremost, the patients. And then, as we look at short bowel syndrome, third parties put that analysis at about a $5 billion market opportunity, and this was an analysis that was looking really at entries into an approach of a growth hormone approach, which we'll talk about more in a moment. Crofelemer is an anti-secretory agent, which wasn't publicly in clinical development at the time and wasn't even considered in that analysis. Again, this is something where we're looking to provide a standard of care and a really paradigm-shifting approach to supporting these patients. Crofelemer, as I've mentioned, is paradigm shifting and important not only for what it does do, but what it doesn't do. So what it does do is it normalizes gut function, it normalizes ion flow, it normalizes water flow, and specifically mitigates the dehydration and the downstream ill effects associated with that. What it doesn't do is get systemically absorbed. So it's a product you take orally, it goes to the intestine and acts locally in the gut, and then out it goes. So you don't have drug-drug interactions, you don't have first- pass effects, you don't have systemic exposure to the product. Very, very important, and the differential is highly recognized and valued in complicated patients like AIDS patients, cancer patients, short bowel syndrome patients, IBD patients, Crohn's patients, where you don't want to interfere with their other life-saving or disease-modifying medications. Also, crofelemer is not an antibiotic, so we don't have the risk of resistance. It's not an opioid, like Imodium or loperamide, antimotility agents, and therefore does not have the risk of constipation associated with those agents. Doesn't have a tolerance build-up, so safety is a huge, huge hallmark of this product. In dozens of published clinical trials, we've never seen a side effect profile different than placebo and never have seen a serious adverse event with dozens of years and thousands of patients on the market commercially at this point. So to go back to the trial, where we released the subgroup analysis data today, and we released the data, a couple of months ago, this was called the OnTarget study, a very ambitious study looking to, you know, put our arms around and a big hug around as many patients as we could: 10 different solid tumor types, 24 different targeted agents, prophylaxis on or off cytotoxic chemotherapy. We did not meet the primary endpoint in that trial. However, clinically meaningful results in the subpopulations of breast cancer patients, subpopulation of lung cancer patients, and we have done the responder analysis at this point, suitable for submission for the breast cancer patients. Some of the power here is, you have about 40% of patients on cancer therapy go off their therapy or go to a subtherapeutic dose, specifically because of the side effect of diarrhea. That's a poster that was presented a couple of years ago that was just accepted for presentation as well. Now you're not only talking about the quality of life, the dignity, the comfort of the patient, which is very important, but you're also talking about an impact on the outcome of the cancer and the ability of the patient to stay on their cancer therapy. And who could ever argue with the opportunity for a patient to stay on the protocol-defined dose of their life-saving therapy? There also is a poster from a couple of years ago that showed that it costs almost 3x as much to take care of a cancer patient who's managing diarrhea. So we all have experienced diarrhea. We've all had a bad meal or something's happened. This is a different level. Grade 3 diarrhea is more than 10 watery stools a day, often have to go into hospital for rehydration. That's where the cost comes in. There have even been patients in the targeted therapy trials who have died from the side effects of the dehydration. So we have comfort, we have cost, we have outcome of the cancer care, all important, of different level importance, depending on who the audience is. One of the most important audiences, probably the most important, of course, is the patient. And patient advocacy, and particularly in breast cancer, is becoming very, very appropriately loud, particularly for the metastatic patient. Metastatic patient, you know, used to not survive very long, but now there are many metastatic patient advocacy organizations, and they're gonna be on therapy, you know, for the rest of their life. And that's exactly the point. They want to live. They don't just want to exist. There's 21 different documented side effects associated with cancer therapy. There's a huge world of unmet medical need there. That is a commitment and a focus of Jaguar. Now, with the launch that we have of GelClair this month, with the results that we're seeing with Mytesi and with crofelemer in the cancer therapy-related diarrhea trial, and our pathway to hopefully bring that to market and start picking off those side effects one by one, to really provide life to these patients. We have a non-branded patient advocacy digital campaign called Make Cancer Less Shitty, and it's very much focused on allowing the patient voice to be heard, and that's throughout everything in clinical development. Our clinical trial for OnTarget had an endpoint of patient-reported outcomes, incorporating the patient voice into the design of the clinical trials, all the way through, making the importance known to regulatory agencies, and then, of course, education, awareness, and promotion once a product is actually approved. GelClair, which I mentioned a couple of times, which is getting launched this month, this is for oral mucositis. Oral mucositis is defined as the most significant adverse event in oncology. What does most significant mean? Let me talk about pain. It is like broken glass in your mouth all day long with a habanero pepper on top of it. It is remarkably, remarkably painful to the patient. Therefore, what happens, almost 20% of the time, patients will end up in the hospital to address the issues associated with that oral mucositis. It can be going on parenteral nutrition. It can be going off their cancer therapy, radiation therapy. Sometimes they can't swallow, so there'll have to be a breathing tube that is put in. Absolutely remarkable, the impacts of this oral mucositis, which, by the way, are the wounds that occur in the mucus associated with the upper GI tract. You can see it in the lips, the tongue, the mouth, but all the way going down the throat. For a small company doing its first launch into cancer supportive care as the beginning of our commercial commitment to cancer supportive care, it's really a quite interesting opportunity. Well, oral mucositis is anywhere from 40% to 70% reported in chemotherapy. In head and neck radiation patients and bone marrow transplant patients, you're talking about 90% incidence. So we can go out with a very focused sales force. Our first footprints can go directly to those centers of excellence, and get awareness building and refine the education and the promotion, and then hopefully, coincident with perhaps bringing Mytesi to the oncology market, we would be able to expand our footprint at some point in the future. There was just the American Society for Radiation Oncology, this past weekend in Washington, where we were first out there with our presentation of GelClair to the community and had a really fabulous response. So we are very optimistic about, again, all the stakeholders, first and foremost, those patients who are suffering so dearly with the launch of GelClair into this market. I do wanna mention Canalevia. Canalevia is crofelemer. It's an FDA-approved product by the Center for Veterinary Medicine for chemotherapy-induced diarrhea in dogs, which is quite a big issue. Over 50% of dogs over the age of ten will get diagnosed with cancer. And again, you see the same similar dynamics that to diarrhea that you see in humans. About 40% of the time, a dog will end up going off their cancer therapy because of the side effect of diarrhea. So interestingly, in the U.S., if you are a patient with a cancer diagnosis and diarrhea, and you're a dog, you can get a prescription for crofelemer. On the human side, not yet. This is not only important to the dogs, but dogs are a remarkably predictive model of what we're seeing on the human side. In fact, that mechanism internally from the gut, the inside of the gut, where crofelemer has its action, its normalizing action, you can't really tell the difference from a picture of a dog to a picture of the human of that inside of the gut. So it gives us a lot of confidence about all the populations we're going to. I'm gonna move now to our rare disease business model, and that is for intestinal failure with short bowel syndrome. Rare diseases are less than, an orphan indication is less than forty thousand in the United States. Similar dynamics in Europe. We do have orphan designation for short bowel syndrome and a congenital diarrheal disease known as MVID in both the U.S. and Europe. What happens with intestinal failure is, for example, with short bowel syndrome, the patient doesn't have enough surface area to absorb the nutrients of life, proteins, carbs, vitamins, et cetera. They end up on parenteral nutrition, and that can be for as much as, as long as 20 hours a day, 7 days a week. Obviously catastrophic for the patient, no quality of life. Very difficult to maintain and monitor exactly the makeup of that total parenteral nutrition. It costs about $500,000 a year to manage these patients without complications, and so many of them end up with complications. It can be $1 million or more. High mortality, high morbidity, high expense. You have, with a lot of orphan diseases, family, patient advocacy organizations to advocate for research and treatment for these patients. There is an approach now, and there is a product approved, which is a growth hormone approach, which I mentioned earlier on. The goal there is to grow the gut a bit, so that there can be a reduction of parenteral nutrition because of greater absorption, maybe 15%-20%. There is a product approved. It is not standard of care. It's used in single-digit% of the patients. However, it does establish a regulatory endpoint. Part of the limitations in not being standard of care is a growth hormone, for example, can't be used with cancer patients, can't be used where you have any sort of a, sort of abnormal hyperproliferative situation. There are some cardiovascular side effects. It also can't be used until about 12-18 months after surgery 'cause of bowel adaptation, and about a third of the short bowel syndrome patients are due to surgery. So what we're looking to do with crofelemer is to decrease the secretions such that we can get to that regulatory endpoint that is established, 15%-20% reduction of parenteral nutrition, and become the standard of care. Not have any of the limitations associated with surgery bowel adaptation. Obviously, none of the limitations with toxicity or, or patients who might be at risk of cancer, or in fact, cancer patients, could be used with or without a growth hormone approach. There are five clinical efforts that are starting in the fourth quarter of this year, so major, major catalysts in 2024. Those are three investigator-initiated trials, and with published proof of concept data, with investigator-initiated trials added to phase 2 data, and there's two global phase II studies that will have their first patient in the fourth quarter of this year, one for short bowel syndrome, one for MVID. These have been about two years in the making, talking to KOLs, doing regulatory filings. Anyway, with that package, there's an opportunity for reimbursed early patient access in Europe, and we do have a footprint called Napo Therapeutics, which is a private company, about 90% owned by Jaguar, that is focused exclusively on rare diseases, and in particular, has the skill sets for this commercial promotional opportunity for early patient access. I'm gonna move now, in the interest of time, leaving some time for discussion, to— These were the second quarter results that we put out, financial results, so our net revenue did increase about 16%. This is primarily driven by HIV-related diarrhea. Overall, that market, well, it's a specialty market. Another word for specialty is a relatively small market. It'll never be more than about a $20- or $30-million market. However, net revenue will be growing, obviously going forward from the fourth quarter on by the revenue generation from GelClair. So we are a high-volume stock. We have been hit hard for any number of reasons, but we have really important clinical and regulatory catalysts in the fourth quarter, including the first one that we announced today, of course, which is these important clinical, statistically significant results in the pre-specified breast cancer group, the largest group in our OnTarget trial for cancer therapy-related diarrhea. So, let me finish with that, and so I can leave a few questions if you'd like to, Robert. Yeah, that would be great. Thank you very much, Lisa, for the presentation there. Yeah, we have a couple minutes left. Let's just start with the news from this morning here. Maybe help people understand what your regulatory intention is now with this data. Oh, thank you. That's a great question, so this data is the cornerstone of a briefing package that is being put together for the FDA, and our goal here, of course, is this study was done with crofelemer, with the commercial product that's already on the market. Full CMC package, manufacturing package. It's approved for chronic indications, so full chronic safety package, so what is the opportunity from a totality of benefit to be able to, as efficiently as possible, get this product to cancer patients, and of course, with today's data, specifically breast cancer patients, so that's what we'll be looking for in a discussion with the FDA. Can we, with this data, get this product to breast cancer patients, and whatever commitments thereafter need to be made, we'll do it. All right, great. Transitioning here on GelClair, just help people understand, what are patients being treated with right now for oral mucositis? Oral mucositis is so painful, and I can speak to that because I had an odd reaction to a COVID drug, and I got Grade 4 oral mucositis. It is incredibly painful. So what they give you is something called magic mouthwash, which is not so magic. It's basically different mixtures. It's compounded with lidocaine, and so it just numbs your mouth. It lasts for, like, five minutes, if it lasts that long. That's what you get, and it's numbing. It just, you know, you bite the side of your lip. You can't taste anything. You can't really eat anyway. And so what the promise is with GelClair is muco-adhesion, almost like a bandage, how difficult it is to put a bandage on mucosal membranes, and to promote healing, pain relief, and just overall a program of the preventative downstream effects from oral mucositis, which often are going on opioids and oxycodone, which, as we all know, has another whole set of side effects for the patients, particularly elderly patients, which get a little loopy and can fall down. It's amazing just how quickly an otherwise healthy patient who has to undergo cancer care or radiation can go completely downhill on all their physical functions. All right. All right, that's helpful to understand. Maybe last question here. On the rare disease side, you know, all these clinical activities here in the fourth quarter, you know, talk about more broadly, what is the company's business strategy, as it relates to rare diseases here? Yeah, you know, well, there are, as you know, many companies that only focus on rare diseases, and we don't. It's a component of our business model. I heard a very interesting fact at a conference last week, that ten years ago, the top ten selling drugs in the United States served about a 120 million patients, and now it's about 16 million patients because of rare disease, orphan indications, and also very specific targeted therapies, and I could see a marriage in the very near future of our focus on cancer supportive care, our focus on rare diseases with success, merging those two and getting into some very specific, targeted oncology agents, that would be rare diseases and orphan drugs, and leverage our success in both of those communities. Okay. All right, that's good. Well, let's. We're just at the end of time here, so we'll leave it there. Again, thank you very much for your participation, as always, in the conference. I wanna remind everyone, if you've not already scheduled your one-on-one meeting, and would like to do so, shoot me an email, Blum@lythampartners.com, or again, visit the landing page for the conference here, lythampartners.com/fall2024. Again, from there, click on the Investor Registration button. So we have a number of additional presentations coming up here today, but Lisa, again, thank you very much for your participation. It's always appreciated. Thank you, Robert. Well, nice to see you, as always. Same here. Bye.