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 and technology 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 would cause actual results to differ materially from those contemplated from 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 that its assumptions, expectations and projections are reasonable in view of currently available information, you are cautioned not to place undue reliance on those forward-looking statements. The company's actual results may differ materially from those discussed in the call 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 ending December 31, 2021, which was filed March 11, 2022, 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 Health undertakes no obligation to update or revise any forward-looking statements continued in this presentation to reflect on new information, future events or otherwise. Additionally, please note that today's -- that the company's supplements, its condensed consolidated financial statements presented on a GAAP basis by providing gross sales, non-GAAP EBITDA and non-GAAP recurring EBITDA. Jaguar believes that the disclosure items of these non-GAAP measures provide investor with additional information that reflects the basis upon the company's management, [assets] operates the business. These non-GAAP financial measures should not be viewed in isolation or as substitutions for GAAP net sales and GAAP net loss and are not substitute for, or superior to measures of financial performance in [conformity] maybe with the GAAP. At this time, it is my pleasure to turn the call to Lisa Conte, Jaguar's Founder, President and Chief Executive Officer. Lisa, the floor is yours.

Thank you, Ali, that was quite thorough and, I understand, a mouthful. Thank you all, and welcome. As you just heard, my name is Lisa Conte. I am the founder, President and CEO of Jaguar Health and our wholly owned subsidiary in the United States, Napo Pharmaceuticals. I'm also Chairman of the Board of Napo Therapeutics, the corporation we established in Milan, Italy last year that focuses on expanding crofelemer access in Europe. Specifically, Napo Thera is initially pursuing a rare disease business model based on the orphan designation of crofelemer for short bowel syndrome, known as SBS. You'll hear me refer to it as SBS throughout this presentation, and you'll hear more about that in a moment. Also of note, Jaguar is the majority shareholder of Napo Thera, providing equity interest value to Jaguar as well as parallel product development activities for crofelemer in Europe. I'm going to begin today with a few brief updates, and then Carol Lizak, Jaguar's Chief Financial Officer, will provide a recap of key financial results for the fourth quarter of 2021. As you'll hear from Carol, we are pleased to report that fourth quarter 2021 Mytesi net revenue was approximately $2.1 million versus approximately $600,000 in the third quarter of 2021, an increase of 230%. This increase largely represents the important realization of financial benefits from Jaguar's recently completed shift to distributing Mytesi, through a closed network of specialty pharmacies, specifically, for example, a decrease in distribution costs and an improvement in our gross-to-net ratio. You'll hear more about that transition from Ian Wendt, Jaguar's Chief Commercial Officer, who will speak after Carol. As a reminder, crofelemer, under the trade name Mytesi, is our plant-based FDA-approved anti-diarrheal drug indicated for the symptomatic release of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral…

Thank you, Lisa, and thank you all for joining our webcast today. I'll begin my review of our 2021 financial results with our main focus being on the fourth quarter GAAP over the third quarter of 2021 and year-over-year performance. Mytesi new prescription volume, an indicator of growth in patient demand, increased 10.4% in the fourth quarter of 2021 as compared to the prior quarter and increased 2.1% in the year 2021 over the year 2020. Prescription volume differs from invoice sales volume, which reflects, among other factors, varying buying patterns among wholesalers in the retail channel and specialty pharmacies in the closed network as they manage their inventory levels. Mytesi net revenue during the fourth quarter of 2021 was approximately $2.1 million and approximately $600,000 in the third quarter of 2021, an increase of $1.5 million or 230% quarter-over-quarter. The transition to a closed network of specialty pharmacies has resulted in a meaningful reduction in Mytesi distribution costs and higher average net price. Mytesi net revenue for the year 2021 was approximately $4.3 million and approximately $9.4 million for the year 2020, a decrease of approximately $5.1 million year-on-year. As part of the process of transitioning to the co-specialty pharmacy network, the third and fourth quarters of 2021 were significantly impacted by the inventory drawdown of approximately 1,300 bottles of Mytesi across the company's third-party logistics warehouse, wholesalers, distributors and retail stores. Mytesi gross revenue, a non-GAAP measure, was approximately $3 million and $3.2 million during the fourth and third quarters of 2021, respectively, representing a decrease of $200,000 quarter-over-quarter. Mytesi gross revenue for the year 2021 was approximately $15.7 million and approximately $20.4 million for the year 2020, a decrease of $4.7 million year-over-year. As mentioned, the third and fourth quarters of 2021 were significantly impacted by the…

Thank you, Carol, and good morning to all. As Lisa stated, the 230% increase in fourth quarter 2021 Mytesi net revenue over the third quarter of 2021 largely represents the realization of the benefits from the company's shift to distributing Mytesi through a closed network of specialty pharmacies rather than to wholesalers that resell the product to retail pharmacies. The process of transitioning to a closed network of specialty pharmacies resulted in a onetime short-term underrepresentation of Mytesi utilization. As anticipated, Mytesi revenue, primarily in the third quarter of 2021, was impacted by this transition as wholesalers in the retail distribution channel drew down their inventory of typically more than two months volume. Our closed network of specialty pharmacies typically orders on a just-in-time inventory business model. We are pleased to report that the company completed the process of transitioning its Mytesi volume to a closed network of specialty pharmacies this past January. As a result of this transition, no significant Mytesi inventory remains in the retail distribution channel. As Carol stated, Mytesi new prescription volume, an indicator of growth in patient demand, increased 10.4% in the fourth quarter of 2021 over the third quarter of 2021 and increased by 2.1% in the year 2021 over the year 2020. The transition to a closed network of specialty pharmacies has resulted in a meaningful reduction in Mytesi distribution costs and a higher average net price and assists in the preparation of our U.S. commercial distribution network for future -- for potential future indication expansion of crofelemer to other populations of patients with complex medical needs, such as CTD and SBS. A key component of the company's market access strategy, the initiative to transition to a closed network of specialty pharmacies, is intended to help remove access barriers for patients prescribe Mytesi…

Thanks, Ian. Thanks, Carol. I'm going to pause here for a moment to acknowledge that as we in the Jaguar and Napo Pharmaceuticals and Napo Thera family are well aware, diarrhea is not always a topic that people outside of the company are comfortable discussing, although we have found it's not as much of an issue with dogs. Nevertheless, we're going to play a short video clip now that I hope you will all enjoy. A video -- topic of diarrhea is mentioned in a refreshingly public and candid manner. Peter, can you do that?

Yes. We'll launch the video now, Lisa.

Okay. [Audio-Video Presentation]

All right. We have heard from -- many of our patients said it's okay to bring humor to the topic and love Dame Helen Mirren, and love acting in theater. I have a son in the business. So thank you, Dame Mirren, for helping to destigmatize the subject of diarrhea. I am extremely pleased with all of our achievements as a company in 2021, and we at Jaguar are energized about all of our important initiatives underway for 2022 and, in particular, the expectation for a transformative value creation in the next 12 to 18 months as the value of the crofelemer pipeline can be realized. I continue to be grateful for the ongoing support and dedication of our employees, our partners in the Amazon, our stockholders and all of our other stakeholders. And we'll now open the floor for written questions that have come in, which I can access right here, and I'm going to, so hang on. Okay. I'm just going to take these in the order in which they've come in here.

Question number one, Are there Canalevia purchase orders yet? Yes, there are. Open purchase orders, and there are a list being accumulated of veterinarians who have learned about the product, for example, from the two conferences that Ian spoke about, who want to know about Canalevia and place orders when the product is available. And then there's another question. When will Canalevia sale to the public begin? We expect that to begin in the second quarter. So we're just around the corner from that. Let's see. There are many investors who say that you are not confident in investing money in your company. How can you reassure the investors in order to restore confidence? So first of all, I should let you know there are many, many blackout periods for buying or selling stock in the company for the CEO and the key officers in the company. Nevertheless, during one of those open windows, last quarter, both myself and the CFO, Carol, invested at a substantial premium, restricted stock. So we couldn't sell it, no warrants, nothing special, at about 5x where the price is now, and we're happy to do that to show our confidence in where the stock price needs to be. And this was after the reverse split that we had done last year. I also can tell you that there is not one company or Board member who has options that are in the money. So we're all rowing in the same direction with the shareholders to get the value recognition in the company. Could you discuss the endpoints for the cancer-related diarrhea indication, enrollment criteria and sample size? Yes, I can. So what is very important is the learning that came into play to define the primary endpoint for the cancer study. So Mytesi, crofelemer,…

Sure. Yes. Thank you. Isn't that a great question, Lis. Yes, essentially, there's two pieces to the value of the [SP] pharmacy, and some of those are related to cost savings and improvement in gross-to-net and payer mix. Just as an example, we save approximately -- our distribution fees are about half of what they were prior to the transition to the SP pharmacy. So instead of paying through the title model and through all the wholesalers, we sell -- again, we cut that cost in about half going directly to the SPs. But the other piece of the value really is in terms of kind of the market access components for patients. And really, the metrics we look at there are time to first fill, so how long from when the patient gets the prescription written so they actually get the drug in their hand. SPs can do that much more quickly, the time between fills. So theoretically, every patient should fill every 30 days. Often, patients don't. In the retail sector, that was -- a retail channel that was up to 45 days in between fills. Now we have it down to the low 30s across most of the SPs. And then patient persistency, how long do they stay on the drug is also longer, which benefits the patients in the SP model because they just provide better support and kind of access services related to kind of working with the payers that the SPs are just much better equipped to be able to provide.

And I'm going to give you two other questions here. Specialty pharmacy revenue was 100% of Q4 Mytesi revenue. How may that look throughout 2022?

So the SP model is working quite well by many metrics that we originally kind of modeled around this transition that's outperforming many of those metrics. So we're very happy with the SP relationships that we have in place and envision that continuing through 2022 with no significant changes. So we anticipate the vast majority of the volume of Mytesi continuing to be distributed through SPs just like as we reported in Q4.

And then another question will -- for you, Ian. Will you be creating your own -- our own telehealth platform or leveraging an existing platform?

Yes, great question. So there are a number of vendors out there who provide this technology and connectivity, specifically for pharmaceutical brands. It actually is pretty complicated in order to be able to build a platform like this. So we have partnered with some of the leading industry providers in this space. We anticipate launching this in Q2, but we have some great vendors supporting this rather than trying to build it on our own, which I think would be quite difficult.

Terrific. And then -- thank you. There's another question about Canalevia. Do we expect sales to increase? We would not be investing in all these additional initiatives for patient access if we didn't feel it was going to impact patient access, which, therefore, would translate to increased prescriptions and increased sales.

Yes, that's right.

So the increased activities is a representation of our confidence. Let's see. How do you anticipate the lechlemer in cholera study could look in terms of number of patients, endpoints and timing, enrollment in completion? So cholera is very interesting because we have already completed and published studies in cholera with crofelemer that were quite important in terms of the impact on the dehydration. Specifically, if you could decrease the dehydration by about 30% in the first 6 to 18 hours, that's considered the -- sort of the death zone for patients with cholera. And again, it's not the cholera that kills them. It's the dehydration and 30% is considered a life-saving impact. And that was achieved. Again, these are published posters with crofelemer. Crofelemer does not qualify for the tropical disease priority review, voucher financial incentive program because that program only exists for a drug for their very first indication. And of course, crofelemer is already approved for HIV. Lechlemer, as I mentioned, is a second-generation antisecretory, works by the same mechanism of action, comes from the same tree that we -- and where we sustainably harvest Croton lechleri, but is a distinct product, we believe, under botanical guidance because it's a different collection of proanthocyanidin chemical collection. So the reason why I'm saying all that is we would imagine the study design would look remarkably similar to the successful trial design that we had with crofelemer. There may be a larger number of patients as for a pivotal trial, whereas the crofelemer study was a proof-of-concept trial. But we are talking patients under 100 and really rapid enrollment, which was done in Bangladesh at the International Center for Diarrheal Disease Research, which is a beautiful center, was initially established by Johns Hopkins leadership now runs on its own…

And with that, that does conclude today's call. Thank you for your participation. You may now disconnect.