Good morning. Before I turn the call over to management, I would like to remind you that management may make forward-looking statements relating to such matters as contained growth prospects for the company, uncertainties regarding market acceptance of products and the impact of competitive products and pricing, industry trends and product initiatives, including projects in the development stage which may not achieve scientific objectives or be stringent regulatory requirements. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially than those contemplating 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, your question not to place undue reliance on these forward-looking statements. The company's actual results may differ materially from those discussed in today's -- during this webcast for a variety of reasons, including those described in forward-looking statements and Risk Factors sections of the company's Form 10-K for the year of 2022 which was filed, March 24, 2023 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 and future events or otherwise. Additionally, please note that the company supplements its condensed consolidated financial statements presented on a GAAP basis by providing non-GAAP EBITDA and non-GAAP recurring EBITDA. Jaguar believes that the disclosed items of those non-GAAP measures provide investors with additional information that reflects the basis upon which the company management assesses and operates the business. These non-GAAP financial measures should not be viewed in isolation or as substitutes for GAAP net sales and GAAP net loss and are not substitutes for or superior to measures of financial performance and conformity with GAAP. Today's conference is being recorded. At this time, it is now my pleasure to turn the conference over to Lisa Conte, Jaguar Health's Founder, President and Chief Executive Officer. Lisa, the floor is yours.

Thank you very much and welcome to all. As you just heard, my name is Lisa Conte and I'm the Founder, President and CEO of Jaguar Health and our wholly owned subsidiary in the United States Napo Pharmaceuticals. Sometimes we use Napo and Jaguar names interchangeably. I'm also a member of the Board of Napo Therapeutics, the corporation we established in 2021 in Milan, Italy which is focused on expanding access to Crofelemer in Europe, in particular for rare disorders. I'm going to begin today by letting you know we will highlight shortly the key events that we expect in 2023 will be transformative in terms of value generation for all our stakeholders including patients and shareholders. Moving late-stage pipeline opportunities towards revenue-generating reality, this is an important theme that you will hear infused throughout today's call. Right now, I will review the key top line results for the fourth quarter of 2022. Prescription product net revenue was approximately $11.9 million for the year ended December 31, 2022 versus approximately $4.3 million for the previous year ended December 31, 2021, an increase of 178.7%. We are quite pleased with the growth trajectory of our current prescription drug business which from Mytesi is currently limited to the approved specialty market indication of HIV-related diarrhea and, as I often say, specialty often typically means a relatively small market opportunity. Regarding the company's cash position, the company had cash of approximately $15.3 million as of March 24, 2023, just a couple of days ago, the filing date of Jaguar's annual report on Form 10-K for the year 2022. I'm going to repeat that. Cash of approximately $15.3 million, as I speak this morning, an important and meaningful subsequent events in our 10-K filing that I'm often asked about. Following my update, Carol Lizak,…

Well, thank you, Lisa and thank you all for joining our webcast today. I'll begin our review of our 2022 financials. Prescription product net revenue was approximately $11.9 million for the year ended December 31, 2022 versus approximately $4.3 million for the year ended December 31, 2021, an increase of 178.7%. Prescription product net revenue of approximately $3.3 million in Q4 2022 increased 3.4% over the third quarter in 2022 and increased approximately 57% over Prescription product net revenue in the fourth quarter of 2021. Mytesi total prescription volume was approximately 5,947 in the year 2022. Due to the transition to a limited distribution specialty pharmacy model in 2022, the company cannot accurately compare prescription volume from 2021 to 2022, as there are significant differences in reporting methodology from these distribution models. In the future, the company will be able to accurately reflect growth in prescription volume using 2022 as the new baseline. Mytesi total prescription volume decreased slightly by approximately 2% in the fourth quarter of 2022 over the third quarter of 2022. Prescription volume differs from invoiced sales volume which reflects, among other factors, varying buying patterns among specialty pharmacies in the closed network as they manage their inventory levels. The loss from operations decreased by $6.3 million from $40.7 million in the year 2021 to $34.4 million in 2022, largely due to the aggregate improvement in net revenue of $7.6 million, decreased cost of sales and marketing expenses of $400,000 and warrant inducement expenses of $1.6 million in 2021 and none recorded in 2022. These were offset by the aggregate increase in R&D and G&A expenses of $3.3 million. Non-GAAP EBITDA for the year 2022 and the year 2021 were a net loss of $28.1 million and net loss of $37.5 million, respectively. Net loss attributable to…

Thank you, Carol and good morning to all. Q4 2022 is the sixth consecutive quarter of growth in Mytesi net revenue which we're quite pleased about. As previously announced, the transition we completed in January 2022 to a limited distribution network of specialty pharmacies resulted in a meaningful reduction in Mytesi distribution costs as well as a higher average net price. I'm very pleased to report that we significantly outperformed the industry gross to net average in the fourth quarter of 2022 as we did in the 4 previous quarters for sales of our human prescription product. For comparison, according to prescription drug data and analytics firm SSR Health, the rolling 4-quarter average gross to net discount rate in Q3 2022 was 48.9% for all U.S. prescription branded products. In 2022, the total gross to net discount for Mytesi was approximately 20%. The transition to specialty pharmacy distribution also assists in the preparation of the company's U.S. commercial distribution network for a potential future indication expansion of Crofelemer to other populations of patients with complex medical needs, such as CTD, inflammatory bowel disease and SBS. I'm also pleased to report that our innovative recently launched programs that further support patients' connection to care and medication and access services are continuing as planned. Our telehealth initiative which went live in May 2022, enables patients seeking help with their HIV-related diarrhea to be linked immediately to a provider for assistance with their medical needs. This capability prevents patients from having to wait until their next scheduled doctor visit to get help with what is an urgent problem. Additionally, as announced on March 13, we are excited to be developing an artificial intelligence-powered web portal for U.S. health care professionals to support patient access to Mytesi. We remain committed to reducing access and…

Thank you, Ian. Okay -- and Carol, thank you, Ian and Carol. So we at Jaguar, Napo and Napo Therapeutics, we're energized about all of our important activities underway in 2023 and beyond with a very, very sharp strategic focus on these key clinical milestones in 2023 which I just cannot say enough which we feel will be transformative for some value recognition for a company whose value and this industry has been hit hard in the past months and year. I do want to say in closing, uniquely about Jaguar, this past Tuesday was International Day of Ours and I want to take a moment to express how proud we are to be collaborating and interdependent with the people and tropical forest ecosystems of Peru from where we sustainably source the Latex and Dragon's Blood Tree, the plant also known as Croton lechleri from which Crofelemer is isolated and purified. It is clear that the cultural and ecological health of people and forests are intertwined at multiple levels and we wish to express our gratitude to our partners and communities in the rain forest who have been working with us and teaching us for several decades, how to sustainably manage this valuable medicinal plant within their ecosystem in support of our mission to expand Crofelemer access to all patient populations in need around the globe. And I do also want to remind everybody that Crofelemer, Mytesi is a natural product. It's organic, as I mentioned, sustainably harvested fair trade and it is the only oral drug approved by the FDA under botanical guidance. And under botanical guidance, there's no practical pathway to bring a generic to market. And so while we have well over 100 patents issued and many more that are being filed on a regular basis as you do in the pharmaceutical industry. We essentially have exclusivity forever which is a valuable and additional valuable asset and characteristic of this product as we go into business development discussions and conversations and negotiations. So this concludes our formal webcast for today and I'm going to now look at some of the questions and we will do a few Q&A as we have a little bit of time left. So give me a moment here to pull those up.

It looks like there are a few questions in there. Okay. Is the primary completion date still this month, March 2023 for chemotherapy-induced diarrhea. So as I mentioned, I'm just going to recap timing here. We expect to complete enrollment early in the second quarter. So early in the second quarter is April, beginning of May. We are standing behind that. And then that's completion of enrollment. The primary endpoint is after 3 months of treatment. So you can count forward, let's say, April, May, June, July, so the end of July, beginning of August. And then typically, in the industry, you would have about 8 weeks, plus or minus, to freeze the database upon which you get the primary endpoint released. And so that's the time frame that you can look at and give us -- the -- what we mentioned that we expect to and are targeting the primary endpoint in the third quarter of this year. So you can see the cascade of events from completing patient enrollment. Again, what we're looking for here is the statistical significance as negotiated with the FDA and there was a lot of discussion with the FDA on this trial in a positive sense. On that primary end point, because we are talking about the expansion of the indication for supplemental NDA for Mytesi already on the market, same dose, same formulation, literally the same bottle. Mytesi already on the market, already approved for chronic indications. So for example, chronic safety studies, carcinogenicity studies have already been completed and supported that chronic indication. And obviously, we have a full supply chain regulatory compliant in place to take the product from Peru to a bottle and essentially any specialty pharmacy that we're working with in the United States. So manufacturing is completed…

Sure. We did save around the distribution costs compared to 2021 and 2022. So those were the big cost savings right there. And of course, the net revenue significantly increased. For R&D, yes, there will be some increases there because of the clinical trials surrounding our main indications focus which is CTD and the SBS group. So I think those are the key savings that we had for 2022 and 2021.

Thanks, Carol. So here's a question that I appreciate to bring up this topic. Someone was wondering, if there still future plans of attaining fast-track voucher for Cholera. So the Cholera program, it's very important and exciting program and it's Cholera mechanism of diarrhea is the pure clinical manifestation of the mechanism by which Crofelemer works and our second antisecretory agent known affectionately right now is NP-300. So we do have an approved IND for NP-300. And that -- so what this is referring to is that product is being developed with the financial return that is being targeted by us of a tropical disease priority review voucher. And what that is, is sort of a price that you get from the FDA that provides incentive to develop products for certain tropical diseases, certain rare diseases and Cholera is on that list. And so you get this prize, this voucher when you have a successfully approved new drug application and that voucher is a voucher that if you can put it to any product and it requires the FDA to review that new drug application for another product that you put it towards in 6 months or less. So it provides certainty and in some sense, greater efficiency and speed in reviewing a new drug application. And that voucher is transferable in sales and you can sell them and there is a market for them. And they sell anywhere from the lowest ever was something like $67 million. I think the highest ever was $300-and-something million. Recently, they've sold for about over $100 million. It depends on who has the voucher and who needs the voucher at the time that you want to sell it. So they're not they are somewhat rare to come across, although you've seen more in…

Yes. The CA1 or conditional approval designation that you see for Canalevia right now is an easier pathway to approval. You have to show a reasonable expectation of effectiveness and doesn't require necessarily a full effect of this trial that you might -- in the designated population that you might see for traditional approval. So it allows you to get to market faster and for less cost but it does come with some limitations. And a couple of them, just so you understand what those might be. are that it cannot be used off label. So there's a federal law in place that for CA1 designated medications, prescription medications, they have to strictly adhere to the label as indicated. And you might be aware that the veterinary community, they write off-label medications all the time and human health physicians do as well. But in this case, for CA1, there is that limitation. There's also a limitation in the size of the market. So right now, you can only seek this for -- in the canine arena for indications that would dose no more than 70,000 dogs. So there are some limitations there. And then it comes to some requirements to complete the full effectiveness trial for traditional approval within a 5-year time frame of your initial approval. So we're working on that. And ultimately, we will end up -- we anticipate having full approval in the future. We're working with the CVM on that clinical development program. But we are seeing great uptake of Canalevia-CA1 especially among better oncologists which are our primary target audiences. We engage with them in a variety of ways. In fact, I'm of in a couple of weeks at the Veterinary Cancer Society Meeting. We will have a chance to further educate an important customer group on the benefits of Canalevia-CA1.

Thanks, Ian. Okay. We have time for one more question here. We're coming up on the which we're trying to keep this to an hour. Does it which I assume is talking about Crofelemer, also work on IBS? So there are so many potential indications that reference to a pipeline within a product. There is published Phase II data for IBS, irritable bowel syndrome, with Crofelemer and we couldn't do everything. So there are target pipeline indications of Crohn's disease, inflammatory bowel disease. There are investigator-initiated trials going on right now in functional diarrhea in IBS as well. Of course, we have short bowel syndrome in CDD. So there are other indications, other important patient populations to go after in the future which is a very risk-mitigated future drug development strategy for this company because, again, it would be indications if it's Mytesi where we already have the safety, we have the chronic safety, we have the manufacturing, how can we continue to expand the label, how can we continue to expand the population that in the health care providers that Ian can educate and promote to and grow the revenue even further. And of course, the patients that can benefit even further. But right now, we are very focused can't say it enough on cancer therapy-related diarrhea, short bowel syndrome and MVID and other indications and other territories in the future. So with that, I know there's some other questions there. I can't get to all of them and some of them we've already referred to, again, the sentiment behind the question and the comments that we've made. Thank you all very much for listening. Thank you very much for your support for Crofelemer, Mytesi, Jaguar, Napo, Napo Therapeutics, we're going to get back to work here. It's going to be a very, very important year for all the stakeholders and we're really looking forward to what will be uncovered in the next 6, 7, 8, 9 months of this company. Thank you. I'll conclude now.

Thank you. This will conclude today's webcast. You may disconnect at this time and thank you for your participation.