Hello, I'm Jonathan Miller, Vice President at SRAX. Welcome to the 2021 LD Micro Main Event with XORTX Therapeutics, ticker symbol XRX on the CSE and XRTXF on the OTCQB. XORTX Therapeutics is a pharmaceutical company with two clinically advanced products in development, XRx-008 for Autosomal Dominant Polycystic Kidney Disease and XRx-101 for coronavirus COVID-19 infection, and XRx-225 is a pre-clinical stage program for type 2 diabetic nephropathy. XORTX is working to advance its clinical development stage products that target aberrant purine metabolism and xanthine oxidase to decrease or inhibit production of uric acid. At XORTX Therapeutics, they are dedicated to developing medications to improve the quality of life and future health of patients. Please welcome XORTX Therapeutics. Welcome, everyone. Thank you for the opportunity to present at the LD Micro Conference today. XORTX Therapeutics' name is an acronym for xanthine oxidase-reducing technologies, and pays homage to the role that the enzyme and high uric acid levels play in the progression of kidney disease. This presentation and the company will be providing forward-looking statements within this presentation today. We seek safe harbor and refer you to our SEC filings on EDGAR. The focus of the company is to develop therapies, novel therapies, innovative therapies, and formulations to address the treatment needs of individuals with progressive kidney disease, especially in the case where those diseases are accelerated by modulated aberrant purine metabolism and high chronic uric acid levels. With respect to the area that we're working in, we know that the end-stage renal market globally is large, around $74 billion, and growing at a rapid pace. That rapid pace of growth can be attributed to two causes. Primarily, the rapidly increasing level of diabetes around the globe, where diabetic nephropathy affects about 40% of those individuals. With respect to COVID, related to acute kidney injury and chronic kidney injury that we see emerging as a driver of the renal disease market into the future. Our focus is to develop unique, innovative drug therapies to treat progressive kidney disease, and this is in an area where there are high medical needs, and they're largely unmet. Those areas, those fields, include Autosomal Dominant Polycystic Kidney Disease, or ADPKD, Type 2 Diabetic Nephropathy, where there is a very large market globally, and acute kidney injury due to COVID-19. What we're seeing with acute kidney injury is an accelerated form of kidney injury that persists and seems as though it will emerge as a chronic driver of kidney injury in the future. Our three programs, XRx-008 for Autosomal Dominant Polycystic Kidney Disease, XRx-101 for coronavirus infection, and XRx-225 for type 2 diabetic nephropathy, focus on developing or applying xanthine oxidase inhibitor drugs in novel formulations to treat these progressive diseases. Underpinning our opportunity is a senior drug development team with multidisciplinary skills that range from manufacturing to non-clinical to clinical studies, and it's supported by a clinical advisory board headed by Dr. Richard Johnson, a globally recognized renal, diabetes, and uric acid researcher. Our programs are in late-stage development. XRX for polycystic kidney disease is approaching phase III clinical trials in this orphan disease, and we believe this is a first-in-class opportunity to introduce uric acid-lowering drugs into this disease space. We are also looking at launching a phase III trial in the next year for acute kidney injury due to coronavirus. Both of these programs are deploying oxypurinol, a well-characterized drug, under the 505(b)(2) guidelines that the FDA has in place. That should allow the accelerated development of these programs into phase III trials and towards marketing approval. Our program XRx-225 in diabetic nephropathy is an early-stage program, and we look to advance that into animal models in the coming months. Our approach is to use a platform technology to develop new formulations designed specifically to address the disease entities that we're researching. Those are generally intended to be oral drug treatments to inhibit the xanthine oxidase enzyme, which we know both extracellularly in the circulation and in tissues can drive the development of uric acid and free oxygen radicals and accelerate disease progression, especially in the kidneys setting. We're also relying under the 505(b)(2) development rules, access to publications, clinical data, that shows that uric acid can be an accelerant to progression of kidney disease, and also show that lowering uric acid or lowering the activity of xanthine oxidase can be beneficial. As I mentioned before, we're ready to accelerate into phase III clinical trials in 2022 and look forward to moving these programs towards marketing approval. There are two mechanisms by which uric acid can be harmful. In one case, or in the crystalluria case, scenarios such as diet, lifestyle choices, obesity, or genetic factors can lead to increased levels of uric acid. Now, the normal range for uric acid is 3 mg/dL - 6 mg/dL of uric acid. Once uric acid in your circulation exceeds about 7 mg/dL, we see the formation of crystals, and those crystals are sharp, needle-like crystals that can attack or cause harm in the circulation, the coronary arteries of the heart that feed the heart muscle, the aortic arch in terms of atherosclerosis, but more specifically in the kidney, injure blood vessels by impaling those cells that line blood vessels, but also by seeding the formation of kidney stones. There are two types of kidney stones, generally speaking, oxalate kidney stones and uric acid kidney stones. We see over time the development of crystals in individuals who have high circulating uric acid, and that can lead to mechanical injury or tearing apart of kidney tissue that then further aggravates inflammation and, of course, accelerates the development of kidney damage. There's another mechanism that's important, and that is the mechanism that happens at the level of the kidney. Certainly in Autosomal Dominant Polycystic Kidney Disease, we see the progression of kidney disease from a fist-sized kidney that's functioning in a healthy 20-year-old to, for almost half of all individuals who have Polycystic Kidney Disease, football-sized kidneys in their 50s with end-stage renal failure. The process that underpins this is manyfold, but we do know from an intracellular standpoint that uric acid levels can injure kidney cells. We also know of publications that suggest that fine crystals of uric acid can wedge within the tubules of the kidney, block those tubules, seed the generation of new cysts, and also accelerate the growth of those cysts. Both of those cause external pressure on the kidneys, on the kidney tissue that's healthy, and that squeezes the nutrient and oxygen flow and results in the dropout of the very important nephron units that preserve, that provide filtering capacity. With the dropout of those units, we see decline in filtering capacity and so injury. In Autosomal Dominant Polycystic Kidney Disease, we believe there's an addressable market of about 130,000 patients. This is the largest single genetic cause of kidney disease and represents about 5% of all individuals who lose their kidneys to end-stage renal failure. For those individuals who have failing kidneys or have lost their kidneys, their only therapeutic options really are dialysis or a kidney transplant, and we know how difficult it is for individuals to obtain kidney transplants. Dialysis can be helpful. It can preserve life on a week-by-week basis, but it comes with a cost in terms of time, in terms of burden on family, and a decreased ability to carry on an occupation. The only approved drug in Autosomal Dominant Polycystic Kidney Disease is tolvaptan. This is a drug that addresses about 5% of individuals. It's in year three after approval and is set to generate approximately $1 billion in revenue this year. We believe the drug therapy that we're developing, XRx-008, can address a substantially larger segment of the market, more likely in the range of 35%-65% of all individuals with progressive kidney disease due to Autosomal Dominant Polycystic Kidney Disease. Our therapy, XRx-008, is designed to slow or even reverse perhaps the decline of kidney function. We know that this accelerating loss of kidney filtering capacity happens at various times between age 30 and 60 in Autosomal Dominant Polycystic Kidney Disease patients. While dialysis saves lives for those individuals with chronic kidney disease. We know that that is a substantial burden, and the prognosis for survival beyond two years is poor. We believe that any therapy that can maintain or slow the progression of kidney disease when it's in its mild or moderate form can buy years of life for individuals and redefine the way that kidney disease treatment happens in the future. When one looks at the literature that's been published to date and tries to tie this together with disease progression, we know that serum uric acid concentrations in Autosomal Dominant Polycystic Kidney Disease are higher than one would expect, even for individuals with chronic kidney disease. We know that the level of kidney stone formation, which is an indicator of hyperuricemia, is about 4 to 6-fold higher in ADPKD patients than in healthy individuals. We know that serum uric acid has been associated in other publications with the genesis, so the starting of new cysts, the accelerated growth of those cysts, and the decline of glomerular filtration rate. When one takes that together and looks for additional information, perhaps the best clinical trial out there, which is a mirror of what's been done in diabetic nephropathy, is this study by Han on the right-hand slide of this screen. In this case, patients were carefully characterized as having declining glomerular filtration rate. They also had slightly increasing serum uric acid year-over-year, and they were treated with a uric acid lowering agent. In this case, uric acid was lowered with a year of treatment of xanthine oxidase inhibitor, and what was found was an associated increase in glomerular filtration rate. These patients started in the clinical trial losing about 4.5 mL/min of filtering capacity per year. This disease is accelerating, so next year we'd expect that loss to be greater. What we found, or what was found in this study was that after a year of treatment, glomerular filtration rate, rather than declining, so losing 4.5 out of perhaps 60 milliliters per minute of filtering capacity, actually gained. This is about threefold greater than this red line, which is the threshold for FDA approval using the estimated glomerular filtration rate change in patients with ADPKD. We're very excited about the opportunity to advance our XRx-008 program into patients in a phase III registration trial. oxypurinol, we know is perhaps the best tolerated of any xanthine oxidase inhibitor that's available. It is being prepared in a novel proprietary formulation of XRx-008 for the purpose of delivering it to individuals with autosomal dominant polycystic kidney disease. Historically, it's received an NDA approvable letter because it's been used in over 700 patients to lower uric acid, especially in patients with allopurinol-intolerant gout. It was developed as an agent for allopurinol-intolerant gout. It is eligible for an Orphan Drug Designation in ADPKD, and that's important for additional protection for this program. We're in the process of developing the phase III protocol for ADPKD, where we'll seek a Special Protocol Assessment. Now we look to differentiate this drug from others on the market, primarily because some of its physical properties make it ideal. It has a very clean toxicity signal because of its experience in 700 patients that's well-characterized. It's minimally metabolized and excreted. We know that it works through intracellular and extracellular action. When one thinks of the crystal effects but also the tissue effects, we think it's ideally suited for this purpose. We think it's compatible with the only drug approved in this space, tolvaptan, but we think it can penetrate much further into the market and be adopted more widely in this setting. This program is currently completing manufacture of active pharmaceutical ingredient and looks to initiate a phase III registration trial in 2022. The competitive landscape is thin. tolvaptan is approved, but only addressing about 5% of all individuals with ADPKD. lixivaptan is under development. It may or may not have similar side effect profile to tolvaptan. bardoxolone and venglustat have had their developmental concerns where it's hard to predict their progress at this point. We see for the ADPKD space an opportunity for XRx-008 to advance into registration trials and gain approval for the treatment of individuals with progressing ADPKD. Our patent portfolio is built on three pillars. Formulations, unique formulation claims, composition, if you will, for the method of use that addresses comorbidities and mortality associated with advancing polycystic kidney disease or type 2 diabetic nephropathy or in the case of COVID infection, hospitalized patients show substantial linkage between their acute kidney injury and mortality. We have a succession of patents that claim this protection. The final pillar is the Orphan Drug Designation, which provides exclusivity of seven years in the U.S. and 10 years in Europe and Japan. We currently have two patents granted in the U.S. and in Europe, methods of use for covering uric acid lowering agents to treat diabetic nephropathy. In Europe and pending in the U.S., unique formulations of xanthine oxidase inhibitors, specifically supporting the XRx-008 program, and two provisional patents in the COVID coronavirus space, covering the use of any uric acid lowering agent to treat and protect against acute kidney injury, and in the future, chronic kidney injury associated with coronavirus or respiratory virus infection. We're also looking for that Orphan Drug Designation in the near future. Our cap table is about nine million shares outstanding, about 13% held by insiders, about 65% held by outsiders, and then in addition, warrants and options outstanding that give rise to a fully diluted share count of approximately 12 million shares. We currently have about $4.11 million in our treasury. Our management team is composed of myself, Amar Keshri, Chief Financial Officer, and Dr. Stephen Haworth, Chief Medical Officer. This is underpinned by 12 or so individuals who have worked in the xanthine oxidase inhibitor space, and specifically on oxypurinol over the last decade, and this multidiscipline team is able to bring each of the development steps to bear in a way that's unique and contains, holds an understanding of the FDA's perspective on this class of drugs for progressive kidney disease. Our clinical advisory board is composed of three nephrologists, headed by Dr. Richard Johnson, a global authority on the harmful effects or the health consequences of high uric acid in a number of diseases, including diabetes and progressive kidney disease. Dr. Anjay Rastogi in California at the ADPKD clinic at UCLA, Dr. Petter Bjornstad, a diabetic nephropathy specialist, and Dr. Charles Edelstein, an acute and polycystic kidney disease thought leader. We also have two cardiovascular experts on our team, Dr. Henk Dekkers and Dr. Federico Maese. Our board of directors is composed of individuals who have market experience, such as Bruce Rowlands and Ian Klassen, drug development experience and licensing experience in the form of William Farley, substantial finance experience and public market experience in Paul Van Damme, and legal advice and counsel with Jacqueline Le Saux. We're working in a space where there is a growing market and grossly undertreated population across the three areas where we're focused. Our lead program for ADPKD, XRx-008, is for Autosomal Dominant Polycystic Kidney Disease. We believe there's a substantial body of evidence suggesting that we can address this disease in a meaningful way and provide to the market a robust therapy that can address perhaps even half of all individuals with advancing ADPKD. The successful completion of our phase III clinical trial in ADPKD should provide the optimal information for registration with the FDA for marketing approval and advancing this program into the United States. We also have a strong drug development team, R&D team, and management team that we think is ideally suited to advance this program and the other programs that we have in our pipeline to marketing approval and revenue. Thank you for your attention, and please note our contact information as noted here.