Jaguar Health, Inc.

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 product in the development stage, which may not achieve scientific objectives or meet stringent regulatory requirements. Forward-looking statements are subject to risk 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 caution 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 31, 2021, which was filed March 11, 2022. and its other filings with the SEC, which are available in the Investor Relations section of Jaguars website. Except as required by law, Jaguars 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 the company supplements its consolidated financial statements presented on the 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 investors with additional information that reflects the basis upon the company's management assets 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 and comparability with GAAP at this time. It is my pleasure to turn the call to Lisa Conti, Jaguars Health Founder, President, and Chief Executive Officer.

Lisa, the floor is yours. Thank you, Allie. 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 prophyllum access in Europe. Specifically, NAPO Thera is initially pursuing a rare disease business model based on the orphan designation of crofilomer 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 crofilomer in Europe. I'm going to begin today with a few brief updates and then Carol Isaac Jaguars, 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 Mitessi 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 Mitessi 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, profilamer, under the trade name Mitessi, is our plant-based, FDA-approved antidiarrheal drug indicated for the symptomatic relief of noninfectious diarrhea in adult patients with HIV AIDS on antiretroviral therapy. Profilamer 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 to 18 months. And this includes prophylaxis of cancer therapy-related diarrhea, which I'm going to refer to as CTD throughout this presentation, cancer therapy-related diarrhea, CTD, and SES, 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 three trial for CTD, and that trial is known as the On Target 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 and global unrest, stays on track. The successful completion of this pivotal trial will result in a supplemental new drug application filing for mitesi, profilamer, 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-compliant 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 profilamer 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. And 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 profilomer 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 experience NAPO Therapeutics management team in Europe. Team leadership including a managing director, a chief medical officer, and a head of regulatory and quality. And 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 Profelimer, as I mentioned, on December 13th, 2021, a key event for the NAPOFERA rare disease business model and business plan. So, why did we establish this company, Napothera, 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. And they do this to patients through an early patient access program. Participation in an early access program would provide patients with access to profilamer 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 SPS 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 cost. 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 to 60,000 patients worldwide is expected to reach 4.6 billion by 2027, according to a report from Vision Research Reports. NAPOthera operates under an exclusive license to Crofilamer from Jaguar, for which Jaguar receives typical license payments, including an upfront payment, milestone payments, royalties, and transfer pricing of Crofilamer. Jaguar also receives the value of the clinical data generated by NAPOthera. As reciprocally, NAPO Thera receives the value and ability to utilize the CTD, the cancer phase 3 data JAGUAR is developing. Hence, the parallel complementary and geographically focused development efforts of CROFELIMER to these two core indications, CTD and SBS, are progressing simultaneously and collaboratively with dedicated teams respectively. One final advantage of the NAPO-THERA effort to Jaguar is that NAPO-THERA 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. So once again, these are the two core pipeline events transforming profilamer 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 Crofilomer for chemotherapy-induced diarrhea. I'm going to 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. Forty percent 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. But we do not provide financial guidance. We do feel the dog CID market could be about the size of the human HIV specialty market. And 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. And there's more Canalivia news. We completed the filing of the major sections with the CVM, Center of Veterinary Medicine, for Canalivia, 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 6 in Willow, Alaska. This is the 50th anniversary of this rugged, world-renowned 1,000-mile race. Interestingly, last year, Brenda Mackey, a well-known musher, had to withdraw when her dog experienced EID. And just two days ago, In the race this year, Musher U. Neff withdrew halfway into the race after his dog's 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 canolevia 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 pro polymer pipeline within a 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. And several new initiatives in the commercialization of ITESI for people living with HIV AIDS to address new behaviors during the pandemic, such as adopting a telehealth option for patients. And 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 Lequimer. Lequimer is a different chemical collection of proanthocyanidins, different from profilamer, extracted from the Croton-Lechlery tree, the same tree from which we get profilamer, and which we believe defines Lequimer as a distinct product from profilamer under FDA botanical guidance, which is the guidance upon which profilamer is approved. And Lequimer, has a lower manufacturing cost than Krelthelmer, and works by the same novel anti-secretory mechanism of action. We are planning to initiate phase one clinical trials, the Lechlemer study, in the second half of 2022, as I mentioned, for the symptomatic release 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 pre-clinical services supported by NIAID for four pre-clinical studies. We plan to pursue a tropical disease priority review voucher for Leucomere 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 Lysak, I want to 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. and 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 product, 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 17, 2022, indicating that the big prize 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. And 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 gap over the third quarter of 2021 and year-over-year performance. My testing and 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. My TESI 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 my TESI distribution costs and higher average net price. My TESI 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 closed specialty pharmacy network, the third and fourth quarters of 2021 were significantly impacted by the inventory drawdown of approximately 1,300 bottles of My Tessie across the company's third-party logistics warehouse, wholesalers, distributors, and retail stores. My Tessie gross revenues a non-GOP 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. My TESI gross revenue for the year 2021 was approximately $15.7 million and 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 by Tessie, and the transition to distribution through the closed specialty pharmacies network improved the Mitessi gross to net revenue ratio. Mitessi 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. Lossful 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 GMA 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 CTDs, 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, and 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 as FVO. The non-GAAP recurring IDCA for the year ended December 31, 2021 was at a loss of $37.5 million as compared to $24.3 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.