Developing Treatments for Orphan Kidney Disease - Diabetic - PowerPoint PPT Presentation

Developing Treatments for Orphan Kidney Disease - Diabetic Nephropathy and Polycystic Kidney Disease CSE | XRX INVESTOR PRESENTATION – FEBRUARY 2018 Non Confidential

FORWARD LOOKING STATEMENT This document contains forward-looking information pursuant to applicable securities law. All information that addresses activities or developments that XORTX expects to occur in the future are forward-looking statements. Forward-looking statements are based on the estimates and opinions of management on the date the statements are made. However, they should not be regarded as a representation that any of the plans or objectives will be achieved as actual results may differ materially from those expressed or implied by the forward-looking information set forth in this document due to risks and uncertainties affecting XORTX, including access to capital, the successful completion of clinical trials and receipt of all regulatory approvals. The forward-looking statements in this document are based on a number of assumptions which may prove to be incorrect, including assumptions concerning general business and economic conditions, positive clinical trials and the availability of financing. XORTX assumes no responsibility to update forward-looking statements in this document. INVESTOR PRESENTATION 2 JUNE 2018

ABOUT XORTX XORTX Therapeutics is developing therapies to treat kidney disease where no • therapeutic option exists, and based on XORTX patent protection. XORTX has two “first-in-class” opportunities: 1/ Large Market – Type 2 Diabetic Nephropathy; Granted US 9,155,749 2/ Orphan - polycystic kidney disease; Composition/Formulation of Oxypurinol – PCT 2014 PKD Foundation recognition of XORTX and commitment to collaborate with XORTX • towards the goal of developing a new class of highly active and potentially important treatments for patients with polycystic kidney disease. Future Steps Towards Strategic Vision • OTC – QB listing, followed by NASDAQ uplisting • License proprietary Xanthine Oxidase Inhibitor for Diabetic Nephropathy from Japan Pharma Co. • Two Phase II ready programs - Q3 2018 INVESTOR PRESENTATION 3 JUNE 2018

MANAGEMENT Dr. Allen W. Davidoff, Mr. Dave Matthews, Dr. Alan Moore, Ph.D., Brian Mangal Ph.D. CMA, MBA Clinical and Regulatory Co-founder, CEO CFO Co-founder, Chief Director, BD • 15 years drug development • 25 years in senior finance • Extensive clinical • 15 years of clinical experience focused on roles in the life sciences and development experience development experience clinical and regulatory technology sector working and 23 years of senior was former Director of program development as with companies ranging management experience in Biostatistics for Cardiome senior management in from start-ups through to pharmaceutical R&D. During Pharma Corp, Led Biotmetrix pharmaceutical R&D (two large, profitable his esteemed career, he has of Cardiome’s clinical IND applications, two phase multinationals in North completed 11 investigational programs. Clinical I studies, seven phase II America and Europe, new drug (“IND”) development experience studies, and one NDA including Aspreva applications or supplemental includes design, analysis and • Former Chief Scientific Pharmaceuticals, Genome IND’s, 15 phase I studies, 12 reporting on over 50 clinical Officer, VP Product DX, and Contextual phase II studies, 7 phase III trials, three FDA Development/ co-founder of Genomics Inc. studies and 2 new drug submissions, one TPD Stem Cell Therapeutics Corp. applications. Most recently submission, a successful (now Trillium TRIL: NASDAQ CEO of BetaStem Inc. EMEA submission. Prior to and TSX) and Senior Scientist Cardiome, Everest Clinical and Head of Pharmacology, Research, specializing in Cardiome Pharma Corp. dealings with NIH in the US and Biostatistician at Pharmacia/Pfizer, worked on the successful NDA for Linezolid and numerous successful trials with Celecoxib. INVESTOR PRESENTATION 4 JUNE 2018

CAPITAL STRUCTURE Market Capitalization ~$16 million Common Shares Outstanding 62,919,691 Warrants 4,004,740 Options 4,561,000 Fully-diluted Shares Outstanding 71,385,431 Cash on Hand $900,000 Current Burn Rate ~$60,000 per month Public Listings XRX : CSE | XRTXF : OTCQB Securities Registration Options TSX up-listing, NASDAQ up-listing INVESTOR PRESENTATION 5 JUNE 2018

THE PROBLEM & OPPORTUNITY • US Population - ~360 million Diabetes Facts • ~9.5% of North Americans • Progressive Kidney Disease ~46 million • ~40% of patients with diabetes develop • Diabetes ~32 million evidence of nephropathy • Diabetic Kidney Disease - ~10 million • In the US, diabetic nephropathy (DN) • AD-Polycystic Kidney Disease -~120,000 accounts for about ~45% of new cases of ESRD (3%) Progressive Kidney Disease ~10,000,000 patients with DN • Accelerating decline of filtration (GFR) • Increased creatinine • Increased urine protein loss ~700,000 patients per year in end • Abdominal pain stage renal disease • Declining health / wellness INVESTOR PRESENTATION 6 JUNE 2018

END STAGE RENAL DISEASE – A CRISIS Diabetic Nephropathy is responsible for ~45% of end stage renal disease (ESRD) while, Polycystic Kidney Disease is responsible for ~5% ESRD - a life altering event – * 4 hours per day on dialysis * loss of ability to work full time * dependence on family * pain and declining health are constant burden * shortened survival – only 50% of patients survive two years Source: Curr Opin Nephrol Hypertens – 22(2): 185-192, 2013 Any therapy that can maintain kidney health and avoid dialysis would redefine how kidney disease is treated. No drugs are currently approved to treat progressive kidney disease • An opportunity to provide first-in-class therapy exists • INVESTOR PRESENTATION 7 JUNE 2018

OXYPURINOL – a SAFE and EFFECTIVE XOI Oxypurinol: • Well characterized as safe and effective for decreasing uric acid • Has been administered to >700 patients to date, to treat allopurinol intolerant gout, and is well tolerated in even patients sensitive to allopurinol • NDA was submitted to the FDA for the orphan disease “allopurinol intolerant gout” and received an FDA approvable letter (2005). • Despite being well characterized, Oxypurinol is not approved for clinical use anywhere in the world • XORTX’s new oxypurinol formulation/composition patent/PCT application (beyond 2034) is ideal for positioning as a treatment for orphan disease indications such as ADPKD INVESTOR PRESENTATION 8 JUNE 2018

XORTX TECHNOLOGY PLATFORM Lead Program: Autosomal dominant polycystic kidney disease (ADPKD) – an orphan disease. OXYPURINOL  Reformulation: ‘Enhanced bioavailability and improved dosing range’ filed as composition of matter - worldwide Patent - ‘PCT’ 2014 Strong reproducible clinical trial evidence: • uric acid lowering • improved endothelial function • superior tolerability compared to allopurinol Ideal for repositioning in orphan disease indications. INVESTOR PRESENTATION 9 JUNE 2018

IDENTICAL PHASE II PILOT RESULTS IN: Chronic Kidney Disease and Polycystic Kidney Disease – Demonstrate a Reproducible Benefit from Uric Acid Lowering Recent Phase II Clinical Trial Success in progressive kidney disease increases the probability for translational success of this program. Lowering and managing Blood Uric acid stops or slows kidney disease progression. Chronic Kidney Disease ( ~50% diabetic patients) Polycystic Kidney Disease GFR: Glomerular Filtration Rate n=32; 21 (n=57,56) UA: Serum Uric Acid Goicoechea et al. (2010) Effect of allopurinol in CKD progression and (Han M, et al., Hyperuricemia and Deterioration of Renal function in CV risk. Clin J Am Soc Nephrol 5:1388-1393 ADPKD, BMC Nephrol 15:63-2014) INVESTOR PRESENTATION 10 JUNE 2018

CONTROLLING URIC ACID LEVELS Promises a ‘durable’ life changing therapy for Chronic Kidney Disease Effects of SUA lowering on CKD--> DURABILITY after 7 Years Renal Events 25 20 15 Dialysis Renal Years of Quality of Life Events 10 Dialysis 5 0 SUA UnTreated Treated -5 SUA GFR –Rate -10 Decline GFR – Rate -15 Decline BIG PICTURE - Each year in the US, ~ 650,000 patients start dialysis at a cost to government of ~90,000 per patient. Recent phase II trials suggest this number can be halved which would save nearly ~$30 B per year. **The data suggests > 5 years delay in ESRD onset Goicoechea et al. (2015) Allopurinol and Progression of CKD and Cardiovascular Events: A long-term Follow-up, Am J Kid Dis INVESTOR PRESENTATION 11 JUNE 2018

Kidneys of TYPE 2 DN patients are exquisitely sensitive to uric acid injury. Diabetic nephropathy: Q1< 3.2 mg/dL NORMAL Range Q2= 4.4 mg/dL • Most common cause of chronic kidney Q3 =5.0 mg/dL Q4 > 6.2 mg/dL HIGH Range disease (CKD) and end-stage renal disease (ESRD) worldwide. (Collins et al., 2012) • A five-year observational study, showed that a 1 ± S.D. increase in uric acid was associated with a 21% increased incidence of CKD (Zoppini et al., 2012) Several large observational studies have shown that (n=1449) hyperuricemia has a pathogenic role in the development and progression of CKD (Jalal, Chonchol, Chen, & Targher, 2013; Zoppini et al., 2012). XRx-221 is a novel, highly potent uric acid lowering agent that can decrease and maintain UA, and has the potential to provide benefit to patients with T2-DN. INVESTOR PRESENTATION 12 JUNE 2018