Welcome back, everyone. Next, we have Jaguar Health, Inc. It trades on the Nasdaq under the symbol JAGX and is a commercial-stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal distress. Please welcome Founder, CEO, President, and Director, Lisa Conte. Welcome, Lisa. Thank you very much. I appreciate the opportunity, and thank you, everybody who is listening and has joined. I'll start out with a few forward-looking statements, dispense with that, and let you know that Jaguar and our wholly-owned subsidiary, Napo Pharmaceuticals, are often words that are used interchangeably, and what we do is all drug discovery from plants that are used traditionally in tropical areas, trying to do more efficient discovery, development, finding novel ways to treat and cure diseases based on plants that have been in man for thousands of years, and we did take a product all the way from a tree growing in the rainforest to a first-in-class, FDA-approved, really paradigm-shifting novel mechanism of action called crofelemer, and the brand name is Mytesi. There's also a veterinary version called Canalevia. Crofelemer, the active ingredient, is plant-based. It's organic. It's sustainably harvested. It's fair trade. It's an FDA-approved drug. It is the only oral drug approved by the FDA under something called botanical guidance. Under botanical guidance, there's no practical way to bring a generic to market. While we have a full IP portfolio strategy, we have about 155 patents issued, more filed all the time. We essentially have exclusivity to infinity and beyond. We don't have the business issue of a patent cliff. Mytesi is currently approved for HIV-related diarrhea. That's a specialty market. Another word for specialty is relatively small market. Why is that our first indication? Because it was fast-tracked, priority reviewed. It was actually a request from the FDA to initially test it for people living with HIV/AIDS. The power of crofelemer is that it is truly a pipeline and a product. You can see here eight different follow-on indications. We can't do them all. And what we've prioritized in late-stage clinical development is cancer therapy-related diarrhea, which has recently completed a phase III clinical trial for Mytesi for the same formulation, the same dose, the same product that is already on the market, and then a different formulation of crofelemer for the rare disease business model of intestinal failure in short bowel syndrome and a congenital diarrheal disease, which is intestinal failure in little babies called MVID. And I'll talk about each of those through this presentation. But the key thing, the only thing that really needs to be remembered today, are three categories of robustness: financial, clinical, and I will say clinical, regulatory, and commercial. First of all, in the financial robustness, the last Q that we put out had revenues that increased 14% over the second quarter, third quarter, over the second quarter, and over the year as well. We continue to see growth quarter on quarter between about 5% and 15% and expect that to continue. The clinical robustness is really quite powerful and at a point in time right now with major clinical and regulatory catalysts. We expect to have six clinical regulatory catalysts in the next couple of months, starting in December this year, January, and February next year. And these are primarily in the rare disease area. So we'll have two phase II starting, one for short bowel syndrome, one for MVID. These are the rare disease orphan drug indications and likely have three investigator-initiated proof-of-concept studies starting in those same two indications. On the commercial robustness, the catalyst there is we just launched our third FDA-approved product, Gelclair, for oral mucositis and in particular in cancer patients. We just launched it a couple of weeks ago. So it hasn't been in our financials yet. You will see it in the Q4 financials that will be reported in the beginning of 2025. One additional clinical regulatory catalyst that's very important is happening next week. And that has to do with two poster presentations around the recently completed phase III clinical trial for cancer therapy-related diarrhea. And these are poster presentations at the San Antonio Breast Cancer Symposium, which is the largest international breast cancer-focused conference. So this trial is part of the reason why there is value opportunity at Jaguar right now, particularly with the catalyst that we have coming up. This was a very bold trial looking for prophylaxis of cancer therapy-related diarrhea in all patients with solid tumors on targeted therapy with or without cytotoxic chemotherapy, so putting a big hug around the cancer community and trying to show benefit in as broad a population as possible. We did not achieve the primary endpoint, and we had to put that out on July 23rd, and of course, we would put that out, and we took a big hit in our valuation. However, subsequently, in the prospectively defined group of breast cancer patients, which were close to 70% of patients in the trial, we did achieve statistical significance, and that analysis, as I mentioned, has been accepted for poster presentation and will all be at San Antonio next week, and there are, in fact, two poster presentations associated with that clinical trial, which we're very excited about. Our goal here is to have that as the cornerstone of a briefing package we put together for the FDA. Of course, our mission here is to get Mytesi, get crofelemer approved so that it can be available for education and promotion to breast cancer patients from the data that we have, and if necessary, to do a confirmatory additional trial as well. To give you some idea of what we're talking about here, we don't put out a specific financial guidance. However, if we look at chemotherapy-induced nausea and vomiting as an analogy, that is a prophylactic market. It's typically those agents are taken for the first three days in cytotoxic chemotherapy for six to nine months or so. That's about a $4 billion market. Easily half that market is valued as a generic. What we're talking about with cancer therapy-related diarrhea, prophylaxis, targeted therapy that patients in the metastatic situation are staying on essentially for the rest of their lives, and even in a curative situation, nine to 18 months, with a cause of diarrhea mechanistically that is very targeted by the mechanism of action, the normalization of diarrhea and gut function that comes from crofelemer. So this is blockbuster in terms of the benefit it can have to patients and blockbuster all our stakeholders, including our shareholders. When we get to short bowel syndrome, this is a typical rare disease business model. So relatively small population, high morbidity, high mortality, high expense taking care of these patients, complications, and very motivated, activated patient groups, support groups, parents' groups. Third-party analysis puts that market in anywhere to $5 to $12 billion with no intervention standard of care at this point. So wide open for us to come in as standard of care. And you will hear more about that. What's important about crofelemer as a paradigm-shifting mechanism of action is what it does do and what it doesn't do. So what crofelemer does do is it normalizes gut function. It normalizes abnormal ion flow, abnormal active secretion of chloride ions into the gut, which brings water based on osmosis. And that's where you get the diarrhea. That's where you get the dehydration. So crofelemer is locally acting. You take it orally, goes into the intestine, has its normalizing function, and then out it goes. So what it does not do is you don't have systemic absorption. You don't have drug-drug interactions. You don't have secondary metabolites causing problems later on. It's a strong reason why safety is a hallmark of this product. In a dozen years on the market, complicated patients, we have not seen any adverse drug-related events. Also, what do you think of when you think of anti-diarrheal? You think of Imodium, loperamide. These are opioids. They work by the mechanism of constipation. You can't stay constipated chronically. So as a non-opioid, we don't have that risk of constipation. And also, it's why we have clinical trials from the most mild traveler's diarrhea to the most complicated patients, cancer patients, AIDS patients, IBS patients. We focus on those complicated patients where there really are no alternatives that can be safely used on a complicated basis. So safety, again, a huge hallmark of this product. So if we go into our development programs, let's talk a little bit more about the cancer trial. It was called the On Target Trial. Targeted therapies are targeted mechanism of action. That's where the name comes from. This was a very patient-oriented program. Patients involved in the design of the trial. Again, it was ambitious. It was a big hug, trying to get as many different types of patients in as possible, patient-reported outcomes, and the endpoints that affect the comfort of the patient, the dignity of the patient. This is not a garden-variety diarrhea like you or I might deal with if you have a bad meal. There's typically four grades of side effects. Grade one and two are typically considered tolerable toxicities. That is the most insulting thing you can say to a cancer patient. Tolerable to whom? There are 21 different side effects, known side effects associated with cancer therapy. Imagine dealing with grade one or two of all of them, not to mention grade three or four. Grade two diarrhea, for example, is up to seven loose, watery stools a day with urgency. So who is that tolerable to? However, there's more. When we look at third-party research, about 40% of cancer patients go off their therapy or go to a subtherapeutic dose specifically because of the side effect of diarrhea. And now you're talking about an impact on the outcome of the cancer treatment. And you're definitely getting the attention of the oncologist. There's also a study that shows that it costs almost three times as much to take care of a cancer patient managing diarrhea, hydrations, going to the hospital, dehydrations. There have even been patients who have died in some of the clinical trials of the targeted therapy manufacturers. And now you're getting the attention of the payers as well. What's very important to us is that patient voice. We have started a program, a non-branded program, about two years ago called, it's a digital program, primarily Make Cancer Less Shitty, tongue-in-cheek, purposeful there. I've met personally with almost four dozen different patient advocacy organizations, particularly the metastatic patient voice. Metastatic patients, quite honestly, didn't used to live very long, didn't have much of a voice. Now with targeted therapy, they're living five, 10, 15 years. The key there is living. They don't just want to exist. We are committed to the supportive care of the cancer patient and picking off those 21 different side effects, those major unmet medical needs one by one. To that end, we did just launch a couple of weeks ago a product called Gelclair, which is for oral mucositis. Oral mucositis are those wounds that occur on the mucus of your mouth, your tongue, your throat, your esophagus. It is the most painful side effect that patients can deal with: can't open your mouth, can't talk, can't eat, can't drink. About 19% of the time, head and neck cancer patients will end up in the hospital because of mucositis. But even worse, over the majority of the time, the reporting is that they end up going off or to a subtherapeutic dose or take a holiday from the therapy. This is our first commercial footprint into cancer supportive care, and what's very interesting is about anywhere the reports are 30%-75% of cancer patients will deal with mucositis. But when you're dealing with head and neck radiation patients, bone marrow transplant patients, the reporting is over 90%. Essentially, everyone is going to be dealing with mucositis. And so it's an opportunity for us in a very focused commercial way to launch the product into these centers of excellence for head and neck radiation, for bone marrow transplant, learn about reimbursement, learn about what the appropriate educational and promotional language is. And then we can be prepared in a year or so to expand into the entire oncology marketplace. And hopefully, with success, that would coincide with Mytesi expanded indication to cancer therapy-related diarrhea, particularly in breast cancer patients. This is also another wide open space. Nobody owns this marketplace. So we have an opportunity to come in and provide soothing and with soothing an opportunity for healing and allow those patients, first and foremost, some comfort and equally important to be able to stay on their therapy. Again, we don't put out guidance, but just to give some ballpark of what we're looking at here, Mytesi net revenue for 2023 was about $9.6 million going forward. At our run rate, it would be around $10-$12 million. For Gelclair to be in that same range, it would be close to 4% of the market that we're addressing right now, which is the very focused head and neck radiation and bone marrow transplant market. Interestingly, there's a great article that came out today in a Pet Vet publication. It's virtually available as well. We'll have it listed on our website. And this is about the similarity of cancer therapy, particularly targeted therapy, between humans and dogs. And we do have crofelemer approved by the Center for Veterinary Medicine of the FDA, conditionally approved under Canalevia-CA1. And this is crofelemer for chemotherapy-induced diarrhea in dogs. In the United States, if you are a patient with cancer and diarrhea and you're a dog, you can get a prescription for crofelemer. On the human side, not quite yet, but we're getting there. Very similar dynamics about 40% of the time. The patient will go off the targeted therapy. What's interesting that we have found in the veterinary area that focus and attention and prioritization of the comfort of the patient is even more important. You can't talk to your dog. You can't say, "Just suck it up. It's going to be terrible. We'll get through this." And also the quality of life of the whole family. Nobody wants a dog that has lost control that's in an apartment, in a bed, on a rug. So it's very important for these patients, the dogs and their families. It's quite analogous and predictive of what we see in the human market as well. And interestingly, what we see sometimes anecdotally is that the manufacturers of the cancer agents often point to Canalevia as an opportunity for the patient to be able to stay on their anticancer agents, which would be a wonderful situation in the human area as well, again, for all stakeholders. If we go to rare diseases, rare diseases are defined in the United States as less than 200,000 people. It's a very interesting business model. There are some companies that completely focus on it. For us, it's a particular business strategy for the indications of crofelemer for intestinal failure, short bowel syndrome, and congenital diarrheal diseases. Some of the advantages have to do with the fact that because you have small patient populations, you have smaller clinical trials, less expensive clinical trials, and greater communication and in some sense flexibility, adjustment with regulatory agencies, which we have seen. What happens in intestinal failure with short bowel syndrome? Typical intestine is 20 to 25 feet. Short bowel syndrome may be five feet or less. There's not enough surface area to absorb the nutrients like fats, proteins, carbs, vitamins, etc. So these patients often end up on parenteral nutrition, IV nutrition, 20 hours a day, seven days a week. Obviously, catastrophic for quality of life, catastrophic for the patient, highly expensive. This can cost as much as $500,000 a year, all sorts of complications, which can double that and also bring on not only morbidity but mortality issues as well. Interestingly, there is a product approved which is not standard of care. It's called Gattex, and it's a growth hormone. And the goal with this product is to grow the intestines a bit such that there's more surface area and the endpoint can be the reduction of parenteral nutrition by about 15%-20%. It's not standard of care because there's toxicity associated with it. Also, can't give a growth hormone to, for example, a patient with cancer or a risk of cancer or any abnormal hyperproliferative disease, obviously. But nevertheless, it has set a regulatory endpoint and a pricing structure. So it's priced anywhere from $200,000 in Europe to $500,000 a year in the United States. What crofelemer is looking to do is to decrease the secretions a bit, an antisecretory agent, such that the patient can get to that same endpoint, reduce their parenteral nutrition by about 15%-20%, and at the same time, look at quality of life. We have endpoint measures in our clinical trials where we're also looking at the quality of life of the family and the caregivers and also perhaps provide some reduction in stool volume and better stool formation. Crofelemer, the safety profile, wouldn't have any of those limitations of a growth hormone. We could be used with or without the growth hormone. We could be used in any patient. Also, about a third of the patients in the short bowel syndrome area are a result of surgery, and there is a period of time of bowel adaptation before you could ever use a growth hormone approach. As I mentioned, we have five catalysts starting this month, December, over the next three months, December, January, and February, two phase II clinical trials, three, possibly even more investigator-initiated trials. The value of those investigator-initiated trials is that with proof of concept data, which could come in as early as three to four months after the initiation of an investigator-initiated trial, there is an opportunity for reimbursed early patient access in Europe while the product is continuing to go through full clinical development and approval, a program that does not exist in the United States. Because of that, we have a footprint that is very much focused on skill sets associated with early patient access, education, promotion. In Italy, it is called Napo Therapeutics. MVID is intestinal failure congenital in a baby. A baby is born. It is an ultra-rare disease. Interesting, these patients have a fully intact gut, but it's not functioning. So there's no potential treatment at all. You couldn't use a growth hormone. The gut is already fully intact. Yet they are in the same situation, parenteral nutrition their entire life. Our strategy is to get crofelemer through early patient access and accelerated programs in Europe on the market for these patients first. This is the same formulation as the short bowel syndrome product. We could potentially get approval globally on a single-digit number of patients because of how ultra-rare it is and how severe the situation is for these patients. The two phase II clinical trials that we'll be starting, one in short bowel syndrome, one in MVID, again, expected this month and in January, are global to address the global need of these rare diseases. I'm going to move on in the interest of time to leave some opportunity for questions. We do have an early stage program in the psychoactive and psychedelic area. That is a joint venture that we did with a company called Filament Health. It's called Magdalena Biosciences. It's focused on what are those second-generation products after we all hear about psilocybin, MDMA, ketamine, the remarkable clinical work and breakthroughs that are going on in a regulatory perspective and clinical perspective for some mental health disorders. What are the second-generation novel mechanisms of actions as we did with crofelemer that we could bring to this area? We do have three pending INDs: ADHD, schizophrenia, and anxiety. This is funded through a joint venture. It's completely non-dilutive funding. It was a way for us to mobilize an asset for the good of the mobilization of that asset and all our stakeholders and in particular for the patients in this area. Our goal is to bring these opportunities to IND, first proof of concept in the clinic, and then seek a partner for final development and commercialization with partners that are well-funded that are focused on this particular commercial area. As I mentioned, we did have 15% growth in our revenue Q3 over Q2. That is crofelemer, Mytesi, a bit of Canalevia, and that will continue to grow as we add on sales from Gelclair from Q4 and beyond. So we are a high-volume, highly traded stock. We do feel our valuation has been hit very hard because of the OnTarget results from the primary endpoint for the full patients in all the different solid tumors. However, we are very much focused on the statistical significance that we've seen in the prospectively defined group of breast cancer patients. That presentation will be next week. That poster presentation at San Antonio will go from there with also a very, very strong focus on the catalyst and the upcoming catalyst in our rare disease program. So let me stop there and see if there's any questions. Lisa, thank you so much. Yes, we do have some questions. A question from Wayne, the crofelemer. If it's FDA approved, so is it intended for only humans or animals as well? You did mention animal treatments. He just wants you to clarify that. Yeah, crofelemer is the active agent, and it is approved under the brand name Mytesi, and it's currently approved for HIV-related diarrhea. And it is approved under the brand name Canalevia- CA1 for chemotherapy-induced diarrhea in dogs. So the same active ingredient, two different commercial brands. And Jim asks, with chemo-induced nausea and vomiting, would crofelemer work for this as well? Crofelemer has not been tested and is not approved specifically for chemotherapy-induced nausea and vomiting. So I'll limit my comments to what's on the label, which is very specifically for diarrhea. But you do have a good point. It's one GI tract from mucositis, nausea and vomiting, and diarrhea. But specifically, the clinical trials, the endpoints have been for stool formation. And Allison wants to know how long until Mytesi hits the market. Mytesi is currently on the market, and it's labeled for HIV-related diarrhea, non-infectious diarrhea in adult patients living with HIV/AIDS on antiretroviral therapy is the very specific label. It is interesting that the OnTarget trial is literally with the same formulation, the same dosing. And that therefore would be a supplemental NDA. The two most common reasons why NDAs fail are initially our manufacturing and safety. Obviously, we have a full supply chain in place. We have a product approved for chronic indication. So we have chronic safety. What we're looking for is that nod from a supplemental NDA, which would get filed next year after meeting with the FDA if all goes well, to expand the promotional opportunity for a product that's already on the market. And Niko wants to know the symposium that's happening next week. Are there going to be some results announced? Absolutely. Yes. Our poster presentations are on the 11th, and so then we would be announcing what's in those posters probably during the day on the 11th. So it would probably come out on the 12th, and Steve is asking how many individuals are invoiced in the trials? Enrolled in the trials probably, so the OnTarget trial was a total of approximately 290 patients. Approximately 70% of those were breast cancer patients. It was an international trial, but it's in support of a U.S. NDA filing. The HIV trial for the product that's already approved, geez, I forget. That was a couple of hundred patients as well. There are dozens of published clinical trials, as I mentioned, including two that were just recently presented at a GI conference in Philadelphia two months ago. That was an irritable bowel syndrome. There has been several hundred patients that have been tested with irritable bowel syndrome as well and some travelers' diarrhea. A slide that I jumped over quickly, we do have published trials in cholera as well. Cholera is an indication that we are pursuing under the pursuit of a tropical disease Priority Review Voucher, which is a financial reward that you get from the FDA for focusing products on tropical diseases. That is a second-generation antisecretory that's following in the footsteps of crofelemer. Last question, where are your trials held? Our trials are held in the rare disease programs that are going on now. As I mentioned, these are global in the MENA region, Europe, and the United States. Very specifically, Abu Dhabi, Dubai, Germany, Italy, and then United States. The first center, for example, MVID will be at Children's Hospital in Boston. Short bowel syndrome will be occurring at some of the major centers. I'm not sure if I'm allowed to announce their names yet, but throughout the United States. And with rare diseases, you typically have centers of excellence in certain geographical areas where patients gather for the type of excellent care that they need. Wonderful. Well, Lisa, do you have any closing remarks for our viewers today? Thank you. I have a closing remark for you. Thank you. Thank you to those who listened. And we are very excited, very focused. I do want to mention that of our team, there's 10 of us who've been together for over 15 years. There's three of us who've been together for over 30 years. We are fully committed to get this product to all the different patient populations, all the geographies, all the indications that can benefit. So thank you for the support. Wonderful. Thank you so much. Happy New Year. We'll see you in 2025. Thank you. All right, everyone, we'll be right back.