A Leader Redefining How Kidney Disease is Treated Investor - PowerPoint PPT Presentation

A Leader Redefining How Kidney Disease is Treated Investor Presentation – July 2020 Non Confidential

Forward Looking Statements This document contains forward-looking information pursuant t o applicable securities law. All information that addresses activities or development s that XORTX expect s t o occur in t he future are forward-looking statement s. Forward-looking st at ement s are based on the estimat es and opinions of management on t he date the statement s are made. However, t hey should not be regarded as a representation t hat any of the plans or obj ectives will be achieved as act ual result s may differ materially from t hose expressed or implied by the forward-looking information set forth in this document due t o risks and uncert ainties affecting XORTX, including access t o capital, t he successful completion of clinical t rials and receipt of all regulat ory approvals. The forward-looking st atement s in t his document are based on a number of assumptions which may prove t o be incorrect, including assumptions concerning general business and economic conditions, positive clinical t rials and t he availabilit y of financing. XORTX assumes no responsibilit y t o update forward-looking st at ements in t his document . 2

Key Highlights Focused on developing XORTX clinical development stage products target uric acid lowering, which has been shown clinical stage to have an important clinical effect. Significant global market opportunities. assets to treat kidney disease Three lead products in development with strong IP and established proof of concept. Three Proprietary XRx-008 for Autosomal Dominant Polycystic Kidney Disease (ADPKD) - Orphan Market Products XRx-101 for Coronavirus infection/ COVID-19 XRx-221 for type 2 Diabetic Nephropathy ( T2DN) – Large Market Positive Phase 2a clinical data U.S. Phase 2 study of Uric Acid Lowering in type 2 Diabetic Nephropathy Patients; Topline readout for T2DN Phase 2a data readout - August 2019 and Uric Acid Orphan drug Expected initiation of a pivotal registration study in Polycystic Kidney Disease within 12 opportunity in months - potentially under an SPA polycystic kidney Expected initiation of a phase 2/3 study in Coronavirus/COVID-19 with 12 Months disease . Experienced XORTX’ Senior team was responsible for Oxypurinol and Vernakalant development at Management Cardiome Pharma Team 3

Xanthine Oxidase and Uric Acid (UA): Injury  Kidney Disease Lowering UA Protects Kidney High UA Levels Predict Health in Human Clinical Trials Diabetic Nephropathy Endothelial High Blood NO Pressure Depletion Vascular Damage Normalized Blood Pressure S olet sky B et . al., Uric Acid Reduct ion Rect ifies Oxidative Prehypert ension in Obese Adolescent s, Stress Fibrosis Hypert ension 2012;60:1148-1156 Decreased Proteinuria Activation Momeni A, Effect of Allopurinol on Decreasing Renin Prot einuria in Type 2 Diabet ic Pat ient s, Int J Kid Kidney Angiotensin Dis, 4(128), 2010 System Inflammation Proteinuria Decrease and Reversal of Decline in Systemic Filtering Capacity Inflammation Decline of Filtering Goicoechea et al. (2010) Effect of allopurinol in CKD progression and CV risk. Clin J Am S oc Capacity Nephrol 5:1388-1393 4

Decreasing Uric Acid levels in Diabetes Patients may delay progression to ESRD and the need for dialysis or transplant XORTX Therapies are designed to delay or reverse progression of kidney disease, to prevent ESRD ESRD –A Life Altering Event • 4 hours per day on dialysis • In progressive kidney • Loss of ability to work full time • Dependence on family disease uric acid hastens • Pain and declining health are constant burden loss of filtering capacity of • S hortened survival – only 50% of patients survive two years kidneys • A therapy that maintains and extends kidney health can redefine kidney disease treatment in the future S ource: Curr Opin Nephrol Hypert ens – 22(2): 185-192, 2013 5

Strong Patent Protection – Covering all Uric Acid Lowering Agents Use in Progressive Kidney Disease Patent Claims Term US 9,155,740 Method of use claims covering uric acid lowering 2025 * agents (Xanthine Oxidase Inhibitors) in the * est imat ed GATT treatment of “ Diabetic Nephropathy” Acid ext ension of 4 - 5 years PCT/ US 14/ 30292 Formulations patent covering Xanthine Oxidase 2034 Inhibitors: specifically for Oxypurinol (XRx-008) Prophetic Patent A novel formulation for treatment of co-morbidity 2040 and mortality associate with coronavirus infection Note: Orphan exclusivity adds to product protection in Autosomal Dominant Polycystic Kidney Disease (ADPKD) 6

Competitive Landscape Analysis - Well Differentiated Compared to Landscape Current Agents are Ineffective at Best CLASS IP ADVANTAGES LIMITATIONS Uricosurics Varied Decrease uric acid absorption/ reuptake Inappropriate: Increase kidney stone formation Uricase Off Patent Acute IV use Cannot be used chronically Xanthine Oxidase Inhibitors Allopurinol Off Patent Decreases UA production and serum uric acid Only approved for GOUT ~2-3 mg/ dL. Only works well in ~28% of individuals Well Characterized Modest effect (~2-3 mg/ dL) Acceptable side effect profile S ide effects: Rash, Liver Enzymes, Kidney Febuxostat 2019 Higher Potency - decreases UA production and Only approved for GOUT and Cancer serum uric acid ~2-6 mg/ dL * Recent FDA Boxed Warning Oxypurinol 2034 Decreases UA production ~2-3 mg/ dL Modest effect (free acid) Improved tolerability Poor Bioavailability XRx-008 2034 Decreases UA production ~2-3 mg/dL Comparable efficacy to Allopurinol Improved tolerability 3X increase in Bioavailability XRx-101 2040 Inhibits Xanthine Oxidase, decreases uric None observed to date acid production Clean safety profile and improved tolerability 7

XRx-008 in Polycystic Kidney Disease (PKD) XRx-008: A Novel Formulation of Oxypurinol • XRx-008 - a proprietary formulation of Oxypurinol with 3X increased bioavailability – wholly owned by XORTX Therapeutics Inc. and developed “ In- house” • Increased tolerability increases compliance and supports chronic dosing • Increased bioavailability increases oral dosing range • Independent Phase 2 clinical trials show Oxypurinol lowers uric acid, improves vascular function • Negotiating Phase 3 Registration Trial with FDA and Company also intends to seek S pecial Protocol Assessment • XRx-008 - pre-IND work and FDA Investigational New Drug application (IND) meeting completed, Orphan Drug Designation (ODD) application initiated • Orphan Drug Classification: ~150,000 U.S . patients 8

XRx-008 – Uric Acid Lowering in ADPKD Provides Clinically Meaningful Benefit Serum uric acid (SUA) concentrations Decreasing uric acid in ADPKD patients reverses the are higher in APDKD patients than rate of glomerular filtration rate decline. controls. (Mej ias et al. Hyperuricemia, gout, and (Han et al.) autosomal dominant polycystic kidney disease. Am J Med Sci 1989; 297: 145– 148) Seru rum Uri ric Aci cid ( mg/dL) Higher SUA is associated with increased eGFR (ml/min/1. 1.73m 73m^2/ ^2/yr) kidney volumes , increased End S tage Exceeds FDA 2 Renal Disease (ES RD), and ADPKD disease 7 improvement progression. (Helal, 2013) necessary for approval 1 p=0.001 p=0.001 5 Acid (mg/dL) ! ^2) 73m^2) Gains ~ +2.2 3 1.73m 0 (ml/min/year) Increased SUA is strongly associated R change (ml/min/1. 1 with endothelial dysfunction (ED) via um Uric Ac -1 -1 decreased nitric oxide bioavailability. -1 -1 n Serum (Khosla, 2005, Zoccali 2006, Kurowska 2002, Portaluppi -2 -2 -3 -3 2004) hange in -3 -3 e-GFR Chang -5 -5 Losing ~ -4.5 In early stage ADPKD patients, uric acid (ml/min/year) -4 -4 -7 -7 levels (p<0.001) and eGFR (p<0.001) PreTx (-1yr) Post Tx (1yr) PreTx (-1yr) Post Tx (1yr) -9 -9 predict ED. (Kocygit et al. Clinical Practice, Nephron -5 -5 Time e (yrs rs) Time e (yrs) Clin Pract 123:157-164, 2013.) (n=32) (Han M, et al., Hyperuricemia and Deterioration of Renal function in ADPKD, BMC Nephrol 15:63-2014) 9

XRx-008 –Autosomal Dominant Polycystic Kidney Disease (ADPKD) Development Timeline: ** Planning to Initiate Pivotal S tudy under S P A in second half of 2020 ** 2020 2021 2022 2023 2024 2025 Mfg GMP (9 mont hs) Finalize IND Finalize ODD BA S t udy Prot ocol/ S P A Ph III Ph3 Pivotal Study under SPA - (30 months) NDA filing ( Accelerated Review) GMP - Good Manufacturing Process Standards IND - Investigational New Drug ODD - Orphan Drug Designation M arketing BA - Bio-availability Study in Man Approval SPA - Special Protocol Assessment NDA - New Drug Application for marketing 10