Please stand by. We're about to begin. 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 products and technology initiatives, including product 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 calls for a variety of reasons, including those described in forward-looking statements and risk factor sections of the company's Form 10-K for the year ending December 31st, 2021, which was filed March 11th, 2022, and its other filings with the SEC, which are available on the investor relations section of Jaguar's website. I'm sorry. Excuse me. Except as required by law, Jaguar Health undertakes no obligation to update or revise any forward-looking statements contained in this presentation to reflect any new information, future events, or otherwise. Additionally, please note that the company 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 assesses and 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 substitutes for or superior to measures of financial performance in conformity with GAAP. At this time, it is my pleasure to turn the call to Lisa Conte, Jaguar Health's Founder, President, and Chief Executive Officer. Lisa, the floor is yours.
Thank you, Ally. 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 Therapeutics 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 Therapeutics, 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're 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 antidiarrheal drug indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Crofelemer is also the focus of our two core pipeline indications in clinical development, each expected to bring transformative value to Jaguar in the next 12-18 months. This includes prophylaxis of cancer therapy-related diarrhea, which I'm gonna refer to as CTD throughout this presentation. Cancer therapy-related diarrhea, CTD, and SBS, short bowel syndrome, which is a catastrophic health situation which has received orphan drug designation in the United States and Europe. Let me speak to CTD, the cancer indication first. We are currently in the midst of continued enrollment for the phase III trial for CTD, and that trial is known as the OnTarget study.
We're aiming to complete 256 patient enrollment by the first half of 2023. We're in the process now of adding additional clinical trial sites, both in the United States and outside the United States, to help ensure patient enrollment, despite COVID-related restrictions in global unrest, stays on track. The successful completion of this pivotal trial will result in a supplemental new drug application filing for Mytesi crofelemer, which of course, as I mentioned, is already approved for the HIV-related diarrhea indication, and which is approved for a chronic use and has a full FDA compliance supply chain in place from the rainforest to all pharmacies in our U.S. specialty pharmacy network. As a note, safety and manufacturing are the two most common reasons that new drug applications fail.
Hence, we spent much care and communication with the FDA in the design and execution of this final clinical and regulatory step to bring crofelemer to cancer patients suffering with diarrhea. Diarrhea is the most common side effect of cancer therapy. 40% of patients with CTD discontinue their chemotherapy or targeted therapy, their life-saving treatment, because of diarrhea. This is not your garden variety traveler's diarrhea. Patients are often hospitalized for dehydration, electrolyte imbalance, and organ failure, and some patients have even died from the impact of their diarrhea during clinical trial investigation by the targeted therapy manufacturers. Our second core development focus for crofelemer in 2022 is the orphan-designated disease SBS.
An investigator-initiated proof-of-concept study is expected to be initiated and completed in 2022 at sites in the United States and Middle East, and led as a parallel clinical development effort by the skilled, focused, and rare disease experienced Napo Therapeutics management team in Europe, team leadership including a managing director, a chief medical officer, and a head of regulatory and quality. Let me expand that the investigator-initiated proof-of-concept studies may include sites in Europe as well.
This study will be for patients with CDD, congenital diarrheal disorders, a rare inherited disease causing lifelong intestinal failure and SBS, again, for which the European Medicines Agency, referred to as the EMA, the equivalent of the FDA here in the United States, granted orphan drug designation to crofelemer, as I mentioned, on December 13th, 2021 , a key event for the Napo Therapeutics rare disease business model and business plan. Why did we establish this company, Napo Therapeutics, in Europe? In Europe, the EMA is committed to enabling early access to new medicines with orphan drug status, indicating the important unmet medical need. They do this to patients through an early patient access program.
Participation in an early access program would provide patients with access to crofelemer as early as 2023, potentially impacting in a positive way their morbidity, mortality, and the cost of care for this chronic indication that has no good therapeutic options, the substantial cost of care. CDD and SBS patients with intestinal failure typically require parenteral nutrition up to 20 hours a day, seven days a week to survive at tremendous cost and with accompanying medical complications, which adds even more costs. The ability to decrease that by even 20% would provide a huge medical and quality of life improvement. In a typical rare disease business model, these substantial benefits are highly valued for a relatively small patient population.
The global SBS market of approximately 40,000-60,000 patients worldwide is expected to reach $4.6 billion by 2027, according to a report from Vision Research Reports. Napo Therapeutics operates under an exclusive license to crofelemer from Jaguar, for which Jaguar receives typical license payments, including an upfront payment, milestone payments, royalties, and transfer pricing of crofelemer. Jaguar also receives the value of the clinical data generated by Napo Therapeutics, as reciprocally, Napo Therapeutics receives the value and ability to utilize CTD, the cancer phase III data Jaguar is developing. Hence, the parallel, complementary, and geographically focused development efforts of crofelemer to these two core indications, CTD and SBS, are progressing simultaneously and collaboratively with dedicated teams respectively.
One final advantage of the Napo Therapeutics effort to Jaguar is that Napo Therapeutics is well over majority owned by Jaguar, providing the equity accretion value to Jaguar shareholders and stakeholders, which we believe is unrecognized at this time. Once again, these are the two core pipeline events transforming crofelemer from pipeline to what we believe will be tangible value in the next 12 to 18 months. What else? As we look forward to an exciting 2022 for Jaguar, 2022 is the Year of the Dog. In December 2021, we received conditional approval from the FDA's Center for Veterinary Medicine for crofelemer for chemotherapy-induced diarrhea. I'm gonna refer to that as CID, chemotherapy-induced diarrhea in dogs. This is an exciting and important, and it's important for so many reasons.
First and foremost, this is the key to canine survivability from cancer and the dog parent consideration of the cancer care decision process. There are approximately 100 million dogs in the U.S. thanks to the pandemic, post-pandemic dogs, and 25% will deal with a tumor at some point, over 50% of dogs over the age of 10. Dogs are remarkably predictive of and similar to the human CID situation. 40% of the time, the dog cannot complete its therapeutic dose of chemotherapy because of diarrhea, as is the case in humans. Extremely relevant in the dog market, though, is the comfort factor for the dog, a key factor influencing the dog parent's decision to treat the dog's cancer and the quality of life of the whole family. A dog losing control on the rug, the bed, the couch is an important consideration for the family household.
While we do not provide financial guidance, we do feel the dog CID market could be about the size of the human HIV specialty market. In the dog market, the veterinary market provides much greater predictability of the gross to net ratio since dog parents are typically paying out of pocket for treatment and medications. You can expect many PR, IR, educational, and promotional events around CID in dogs throughout 2022. Education as to the devastating impact to the patient of diarrhea in cancer therapy builds awareness regardless of whether the patient is a human or a dog. There's more Canalevia news. We completed the filing of the major sections with the CVM, Center for Veterinary Medicine, for Canalevia for a proposed exercise-induced diarrhea.
I'm gonna refer to that as EID, exercise-induced diarrhea indication, and we hope that in the fourth quarter of this year, Canalevia will be available for all working dogs suffering from EID, which includes, for example, Iditarod dogs, and this will be known as Canalevia-CA2. Our team is as tenacious and dedicated as the mushers and the teams of dogs currently competing in the Iditarod Trail Sled Dog Race, which officially kicked off March 6th in Willow, Alaska. This is the 50th anniversary of this rugged world-renowned 1,000-mi race. Interestingly, last year, Brenda Mackey, a well-known musher, had to withdraw when her dog experienced EID. Just two days ago in the race this year, musher Hugh Neff withdrew halfway into the race after his dogs developed diarrhea. Neff said he was upset he had to call it quits.
He planned to take his dogs to a friend's house in Ruby to decide what to do next. Imagine in the future what he could do next is treat the dogs with Canalevia for EID once we have it approved by the CVM. Other exciting plans for 2022 include continuing efforts to forge license and business development relationships in key markets around the globe for crofelemer, our pipeline within our product. Also, multiple investigator-initiated trials that are ongoing that may come to conclusion for other chronic situations such as functional diarrhea and irritable bowel syndrome. Several new initiatives in the commercialization of Mytesi for people living with HIV/AIDS to address new behaviors during the pandemic, such as adopting a telehealth option for patients. You'll hear more from Ian on that topic.
Finally, a third key clinical milestone for 2022 is the filing of an investigational new drug application with the FDA in the middle of this year for the symptomatic relief of diarrhea from cholera with lechlemer. Lechlemer is a different chemical collection of proanthocyanidins different from crofelemer, extracted from the Croton lechleri tree, the same tree from which we get crofelemer, and which we believe defines lechlemer as a distinct product from crofelemer under FDA botanical guidance, which is the guidance upon which crofelemer is approved. Lechlemer has a lower manufacturing cost than crofelemer and works by the same novel anti-secretory mechanism of action. We are planning to initiate phase I clinical trials, the lechlemer study, in the second half of 2022, as I mentioned, for the symptomatic relief of diarrhea from cholera, which is what kills patients with cholera.
It's not the cholera infection. It's the dehydration from the massive diarrhea. In support of this clinical activity, we received comprehensive animal toxicity preclinical services supported by NIAID for four preclinical studies. We plan to pursue a Tropical Disease Priority Review Voucher for lechlemer under the FDA's financial incentive program to develop drugs for tropical diseases such as cholera, which provides for an immediate return on investment. Upon the approval of the product for the cholera indication. On a financial note, before I hand the conversation over to Carol Lizak, I wanna highlight the fact that as of March 11th, this past Friday, the company's cash position was approximately $18.5 million, and Jaguar had a public float exceeding $75 million.
Therefore, the company remains shelf-eligible, an SEC designation that provides continuing flexibility to issue registered shares quickly and opportunistically, including in connection with potential future business transactions such as potential asset acquisitions, purchases of products, payments for services, license deal, and an at-the-market financing program we've had in place and currently have in place. Additionally, as announced, Jaguar received a letter from Nasdaq's listing qualification staff on February 17th, 2022, indicating that the bid price for the company's common stock for the last 30 consecutive business days had closed below the minimum $1 per share required for continued listing. We have a six-month compliance period and plan to meet the requirements for continued listing on Nasdaq through value recognition of our various milestones and pipeline progress, as I've discussed. At this time, there are no plans for Jaguar to conduct a reverse split.
Lastly, I'd like to let all of you participating today know that we will have a brief Q&A segment at the end of this webcast to address questions, if any, submitted in writing. Questions can be submitted via the webcast link for today's event that appears on the Events and Presentations page of the Investor Relations section of Jaguar's website. The URL for Jaguar's website is jaguar.health. We'll now move along to key financial results for the fourth quarter of 2021. Carol, you are on.
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 in prescription volume, an indicator of growth in patient demand, increased 10.4% in the fourth quarter of 2021 as compared to the prior quarter, an increase of 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 over year. As part of the process of transitioning to the closed 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 inventory drawdown of approximately 1,300 bottles of Mytesi and the transition to distribution through the closed specialty pharmacies network improved the Mytesi gross-to-net revenue ratio. Mytesi sales volume distributed through the recently established and expanding closed network of third-party specialty pharmacies was 100% of total sales in the fourth quarter of 2021. Compared to approximately 38% in the third quarter of 2021.
Loss from operations was approximately $10.8 million and $9.5 million during the fourth and third quarters of 2021 respectively, an increase of $1.3 million, largely from increased R&D expenses of approximately $2.2 million due to our clinical trial costs from CTD and other indications. Increased G&A expenses of approximately $700,000, mostly from the annual shareholder meeting and offset by the increased net revenue in the fourth quarter of 2021, as previously stated. For the year 2021, the loss from operations was $40.7 million compared to a loss of $26.6 million for the year 2020, an increase of $14.1 million year-over-year. The increase was attributable to the $8.7 million increase in R&D expenses.
This reflects the important R&D activities associated with, for example, the conduct of the pivotal phase III trial for CTD, including increased personal related expenses, manufacturing expenses, and contract manufacturing costs in anticipation of a potential launch upon successful clinical trial results. Sales and marketing expenses increased by $2.3 million related to the expanding market access through specialty pharmacy channels. G&A expenses increased by $2.7 million, largely from the shareholder meetings, non-cash stock-based compensation, audit and accounting services. For the year 2021, the net loss was $52.6 million compared to a net loss of $38.6 million for the year 2020, an increase of $14 million year-over-year.
In addition to the loss from operations, interest expense increased by $5.6 million from $2.8 million for the year 2020 to $8.4 million for the year 2021, primarily due to the royalty interest agreement. A non-cash change in fair value of financial instruments and hybrid instruments designated at fair value option or FVO losses decreased $800 ,000 from a loss of $2.7 million for the year 2020 to $1.9 million for the year 2021, designated at FVO. The non-GAAP recurring EBITDA for the year ended December 31, 2021 was a net loss of $37. 5 Million as compared to $24.2 million for the year 2020. That concludes my recap of high-level financials for the fourth quarter and year-to-date 2021.
I will now hand the discussion over to Ian Wendt, Jaguar's Chief Commercial Officer.
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 one-time 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 at a higher average net price and assists in the preparation of our U.S. commercial distribution network 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 prescribed Mytesi and includes services such as a higher level of support for prior authorizations, appeals, adherence counseling, and home delivery options. While patients often visit retail pharmacies for short-term or uncomplicated medical needs, specialty pharmacies focus primarily on serving patients with complex and chronic medical conditions like HIV.
Additionally, in early 2022, we are rolling out new innovative programs that further support identifying appropriate Mytesi patients and connecting them to care and medication access services. The first program delivers digital Mytesi and disease state education directly into a provider's EHR or electronic health record system so that they learn about Mytesi at the moment they are seeing their HIV patients. This technology allows us to intelligently deliver ads to a provider based on the profile of the patient they are seeing in their exam room. This is strictly a one-way communication. We do not receive any protected health information related to this program. The next program is a telehealth initiative that will enable patients seeking help with their HIV-related diarrhea to be linked immediately to a provider for assistance with their medical needs.
This will prevent patients from having to wait until their next scheduled doctor visit to get help with an urgent problem. Both of these programs are designed to drive incremental brand awareness among prescribers who have not written for Mytesi previously and among patients who have not been able to receive immediate care for their HIV-related diarrhea. Turning to the animal health side of our business, we're referring to 2022 as Jaguar's Year of the Dog. Launch activities remain underway for Canalevia-CA1 in the U.S. veterinary market for the treatment of chemotherapy-induced diarrhea, also known as CID, in dogs. This included CID treatment forums on January 16th and March 6th for veterinarians, veterinary oncologists, and members of the media during two well-attended national gatherings.
The Veterinary Meeting and Expo, also called VMX, that conference was in Orlando, and the Western Veterinary Conference, WVC, in Las Vegas. Dogs, as with humans, discontinue their disease-modifying chemotherapy approximately 40% of the time due to diarrhea, and the reception of Canalevia-CA1 among general practice vets and veterinary oncologists who have learned about the product has been extremely positive. Later in 2022, we're looking forward to the expected addition of another dog-focused product to the animal health portfolio, Canalevia being conditionally approved for exercise-induced diarrhea, another rare MUMS indication. That concludes my comments. Thank you all for your time today, and I'll now pass the conversation back to Lisa.
Thanks, Ian. Thanks, Carol. I'm gonna pause here for a moment to acknowledge that as we in the Jaguar, Napo Pharmaceuticals and Napo Therapeutics 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 where the topic of diarrhea is mentioned in a refreshingly public and candid manner. Peter, can you do that? Yep. We'll launch the video now, Lisa. Okay. All right. We have heard from many of our patients that it's okay to bring humor to the topic. I love Dame Helen Mirren, and love acting in theater. I have a son in the business.
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. In particular, the expectation for transformative value creation in the next 12-18 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. We'll now open the floor for written questions that have come in, which I can access right here, and I'm going to. Hang on. Okay. I'm just gonna 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 is 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. Then there's another question, when will Canalevia sales 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? 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. 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. 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.
What is very important is the learning that came into play to define the primary endpoint for the cancer study. Mytesi crofelemer is a first-in-class mechanism of action. It's an antisecretory. What it does is it normalizes stool formation. It takes the water out of the watery stools, Helen Mirren would appreciate this discussion, and makes it a formed stool. Therefore, the appropriate endpoint is looking at stool formation. In the trial, which is called the ADVENT study, which got Mytesi approved, crofelemer approved for the HIV indication, the definition of the endpoint was a responder endpoint. The patient responding and moving from watery stool to formed stools, not eliminating stools as you would have with an opioid like Imodium or loperamide, but moving to formed, normalized stool function. This is a prophylaxis study, the cancer study.
The enrollment criteria is the patient needs to be on targeted therapy, which is typically chronic therapy, which has a secretory mediated diarrhea associated with it, with or without traditional chemotherapy, and it's in solid tumors. As I said, it's prophylaxis before the patient starts the targeted therapy. It's looking at the ratio for the responder analysis, essentially the area under the curve comparing the treated patient to the placebo patient, and it's 256 patients. Same dose of Mytesi that is currently commercialized, so it's the single dose of Mytesi compared to placebo. Let's see. On crofelemer in CID, is the study enrollment impacted by COVID-19? Will there be any early reads like interim analysis before reporting the top line results?
As everybody who is in clinical trials in the United States, yes, definitely study enrollment was impacted by COVID, and it's part of the reason to stay on schedule. If you may have heard me mention that we are opening new sites, not only in the United States, but outside of the United States as well, to put as much geographical diversification in place and make sure that we stay on OnTarget, which is the name of the study, OnTarget for completing patient enrollment in the beginning of 2023. There's a question, can you give more color on the closed network specialty pharmacy strategy? How much spending does that enable you to save on an annual basis? Ian, I'm gonna turn the question over to you, please.
Sure. Yeah. Thank you. Great question, Lisa. Yeah, 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. Instead of paying through the wholesale model and through all the wholesalers, we, again, cut that cost in about half going directly to the SPs. The other piece of the value really is in terms of kind of the market access components for patients.
Really the metrics we look at there are time to first fill, so how long from when the patient gets the prescription written till they actually get the drug in their hand. SPs can do that much more quickly. The time between fills, so you know, theoretically, every patient should fill every 30 days. Often patients don't. In the retail sector, that was retail channel, that was up to 45 days in between fills. Now we have it down to in the low 30s across most of the SPs.
Patient persistency, how long do they stay on the drug, is also longer, which benefits the patients in the SP model 'cause 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.
Ian, I'm gonna give you two other questions here. Specialty pharmacy revenue was 100% of Q4 Mytesi revenue. How might that look throughout 2022?
The SP model is working quite well by many metrics that we originally kinda modeled around this transition. It's outperforming many of those metrics. We're very happy with the SP relationships that we have in place. We envision that continuing through 2022 with no significant changes. We anticipate the vast majority of the volume of Mytesi continuing to be distributed through SPs, just like as we reported in Q4.
Okay. Another question, Will, for you, Ian. Will you be creating our own telehealth platform or leveraging an existing platform?
Yeah, great question. 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. We have partnered with some of the leading industry providers in this space. We anticipate launching this in Q2. We have some great vendors supporting this rather than trying to build it on our own, which I think would be quite difficult.
Terrific. Thank you. There's another question about Canalevia. Do we expect Mytesi sales to increase? We would not be investing in all these additional initiatives for patient access if we didn't feel that it was going to impact patient access, which therefore would translate to increased prescriptions and increased sales.
Yeah. That's right.
Increased activities is a representation of our confidence. How do you anticipate the lechlemer in cholera study could look in terms of number of patients, endpoints, and timing, enrollment, and completion? 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 six-18 hours, that's considered the sort of the death zone for patients with cholera. Again, it's not the cholera that kills them, it's the dehydration, and 30% is considered a life-saving impact. 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. Of course, crofelemer is already approved for HIV. Lechlmer, as I mentioned, is a second-generation anti-secretory, works by the same mechanism of action, comes from the same tree that 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. 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. We're talking patients under 100.
Really rapid enrollment, which was done in Bangladesh at the International Center for Diarrheal Disease Research, which is a center, beautiful center. It was initially established by Johns Hopkins leadership, now runs on its own, and completely devoted to cholera patients, so there's patients there all year long. That study is expected to start, as I mentioned in the second half. That will be a phase I study, and then we'll go into the phase II and the pivotal trials thereafter. This is an acute study, so these are much shorter studies, smaller number of patients and three days of treatment, so much shorter than the HIV and the cancers trials. Let's see. How do we explain the loss from last year?
The financial loss from last year is because we are, we're a commercial stage company, but we are primarily a development stage company. We have significant expense going into research and development to expand the indications of crofelemer from a specialty market indication. Very important HIV patients. This was fast-tracked by the FDA. You know, another definition of specialty market is a relatively small market versus where we're looking to go with the cancer indication and the short bowel indication and future pipeline indications such as irritable bowel syndrome thereafter. We talked about short bowel syndrome. Third-party projections for that global market are in the $5 billion range. There's no other agents that are out there for cancer therapy-related diarrhea. However, there is a supportive care market for chemotherapy-induced nausea and vomiting.
Those agents typically are used just for the first three days of a chemo cycle, yet that market is projected at about $3 billion for this year. It can give you some idea of the size of the markets that we're going after and the justification for the investment, not only in clinical trials, research and development, but the preparation for the commercial supply and all the manufacturing-related expenses. Once the product is approved, it's all about manufacturing and making sure you have product available. Okay, this is an interesting question. As a Native American herbalist and an investor, we have many plans that could change the scope of healing.
Jaguar Health is the only corporation I could find, and we believe we have probably the only corporation I could find that was looking at prescription development of traditional medicines. How can I bring the plants to the table? We're probably the only company that has a department and a chief of ethnobotanical supply and investigation. Through the website, you can send information to the company, and we will make sure it gets to our chief ethnobotanist and my co-Founder, Dr. Steven King. I've been working with him for 33 years, and I know he will be very interested in responding to you. Let's see. I think the last question is, are you going to have a reverse split again? That would be the worst idea. I'm in complete agreement with you.
There have been no discussions about doing reverse split. All the energy and efforts are focused on what we talked about, what we expect to see in 2022 near term from not only continued efforts for Mytesi but Canalevia and then the ongoing support of the clinical investigation for CTD and SBS which we feel will be transformative in value creation. The equity that we also have in Napo Therapeutics besides the license opportunity they're pursuing, and I would expect to have a license agreement in another geography of the world this year as crofelemer continues to progress. A lot of effort on PR and IR around the importance of managing diarrhea in a patient with cancer therapy, regardless of whether the education is for that patient who's a dog or a human. I will conclude with that.
I think I got all the questions. That concludes our webcast. Thank you for being up early. Thank you for listening. Thank you for your questions, and thank you very much for being a supportive Jaguar. We are very committed to this business pursuit, and we're very committed to all our stakeholders. Thank you.
With that does conclude today's call. Thank you for your participation. You may now disconnect.