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XORTX Shares Nature Nephrology Review

Clinical Studies Confirm Causal Relationship Between Uric Acid and Chronic Kidney Disease

CALGARY, Alberta, July 15, 2019 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (CSE: XRX; OTCQB: XRTXF; ANU1: FWB), a biopharmaceutical company focused on developing innovative therapies to treat progressive kidney disease, is pleased to recognize and highlight a recent Nature Nephrology Review article written by a global alliance of Nephrologists and thought leaders.  This important paper provides a compelling review of current knowledge demonstrating the harmful role of uric acid on the cardiovascular system and the progressive decline in kidney function.  The article also summarizes more than 10 clinical studies in man that support the conclusion that increased uric acid plays a causal relationship in development of chronic kidney disease and that decreasing uric acid has the effect of slowing or reversing kidney disease progression. Importantly, the relationship between uric acid and kidney dysfunction seems especially pronounced in individuals with diabetes and concludes that increased serum uric acid levels should be measured as a first step and necessitates treatment.  An abstract of the article is available on this link: https://www.nature.com/articles/s41581-019-0174-z.

Dr. Allen Davidoff, CEO of XORTX stated, “This publication clearly highlights the deleterious effects of uric acid on kidney health and by summarizing the clinical evidence that decreasing uric acid in patients with progressive kidney disease has tremendous potential to help individuals slow or reverse decline of kidney function.  Importantly, this paper emphasizes that for medical community steps as simple as measuring uric acid in patients can have a meaningful impact on further understanding the impact of hyperuricemia.  This is especially true in diabetes where clinical evidence suggests that uric acid lowering and management can slow or reverse kidney disease progression in a clinically meaningful way preserving healthy kidney function and quality of life.   For XORTX, this paper strongly supports the Company’s vision and focus on developing therapies to redefine how kidney disease is treated in the future.”

The paper outlines that in the past decade evidence has steadily accumulated to show that intermittent1 or chronically increased serum uric acid could act to cause injury through generation of uric acid crystals in the circulatory system or even in the absence of crystals2.  Evidence for the harmful action of uric acid is greatest in the cardiovascular system where injury to blood vessels in the form of inflammation, fibrosis and endothelial dysfunction contributes to high blood pressure and progressing vascular disease3.  Secondarily, inside cells and more specifically in the kidneys, uric acid is a bad actor inducing inflammations, tubular injury4-6 and loss of kidney function over time and is distinctly different from the gout response.

Similarly, several other reviews add to the recognition that increased serum uric acid is an independent risk factor for progression in polycystic kidney disease (ADPKD)7, type 1 diabetic nephropathy8 (T1DN) and type 2 diabetic nephropathy (T2DN)9.

The paper concludes, “In recent years, a compelling body of evidence has emerged, both experimental and clinical, that links hyperuricemia directly with the development and progression of CKD [chronic kidney disease]. In view of this, we would argue, that hyperuricaemia has a detrimental impact on kidney function and that treatment of so-called “asymptomatic hyperuricaemia” to slow or delay the progression of CKD should be a key management strategy. However, important Clinical studies are needed to characterize and advance the development of an optimized treatment strategy for individuals with progressing kidney disease regardless of etiology [initiating associated disease].” 10

References:

  1. Clifford, A. J., Riumallo, J. A., Youn, V. R. & Scrimshaw, N. S. Effect of Oral Purines on Serum and Urinary Uric Acid of Normal, Hyperuricemic and Gouty Humans. J Nutr 106, 428-450 (1976).
  2. Johnson, R. J. et al. Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes 62, 3307-3315, 2013
  3. Fieg, D., and Johnson R.J.,_Uric Acid Effects and Cardiovascular Risk_NEJM_359 17 1811-2008
  4. Roncal-Jimenez, C. et al. Heat Stress Nephropathy from Exercise-Induced Uric Acid Crystalluria: A Perspective on Mesoamerican Nephropathy. Am J Kidney Dis 67, 20-30,2016.
  5. Bjornstad, P. et al. Role of bicarbonate supplementation on urine uric acid crystals and diabetic tubulopathy in adults with type 1 diabetes. Diabetes Obes Metab 20, 1776-1780, 2016.
  6. Bjornstad, P. et al. Hyperfiltration and uricosuria in adolescents with type 1 diabetes. Pediatr Nephrol 31, 787-793, 2016.
  7. Helal et al, SUA_ Kidney Volume Progression in Autosomal Dominant Polycystic Kidney Disease,Nephrol Dial Transplant_2013_28-380
  8. TODAY Study Group. Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: the TODAY clinical trial, Diabetes Care 2013;36:1735-1741.
  9. Pilemann – Lyberg, S., Uric Acid is an independent risk factor for decline in kidney function, cardiovascular events and in patients with T1DN, Diabetes Care, 1-7, 2019
  10. Sato Y, et.al., The case for uric acid-lowering treatment in patients with hyperuricemia and CKD, Nature Reviews Nephrology (2019), July 11, 2019

About XORTX Therapeutics Inc.

XORTX Therapeutics Inc. is a biopharmaceutical company focused on developing innovative therapies to treat progressive kidney disease.  XORTX has two lead programs to develop treatments for progressive kidney disease due to diabetes, diabetic nephropathy and polycystic kidney disease.  XORTX’s XRx-008 (a proprietary reformulation of Oxypurinol) is a late stage drug development program to treat autosomal dominant polycystic kidney disease (ADPKD) and TMX-049, is a late phase 2b stage program to treat type 2 diabetic nephropathy (T2DN), under a co-development agreement with Japan’s Teijin Pharma Limited, pursuant to a non-binding Letter of Intent.  Secondary programs focus on developing therapies for health consequences that accompany pre-diabetes, diabetes and cardiovascular disease. Additional information on XORTX Therapeutics is available at www.xortx.com.

For further information, please contact:

Allen Davidoff, CEO
adavidoff@xortx.com or +1 403 455 7727

or Erik Matthews, Corporate Communications
erik@xortx.com or +1 747 203 5240

The CSE has neither approved nor disapproved the contents of this news release. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein.

This news release includes forward looking statements that are subject to assumptions, risks and uncertainties. Statements in this news release which are not purely historical are forward looking statements, including without limitation any statements concerning the Company's intentions, plans, estimates, beliefs or expectations regarding the future. Although the Company believes that any such intentions, plans, estimates, beliefs and expectations in this news release are reasonable, there can be no assurance that any such intentions, plans, beliefs and expectations will prove to be accurate. The Company cautions readers that all forward looking statements, including without limitation those relating to the Company's future operations and business prospects, are based on assumptions none of which can be assured, and are subject to certain risks and uncertainties that could cause actual events or results to differ materially from those indicated in the forward looking statements. Readers are advised to rely on their own evaluation of such risks and uncertainties and should not place undue reliance on forward looking statements. Any forward looking statements are made as of the date of this news release, and the Company assumes no obligation to update the forward looking statements, or to update the reasons why actual events or results could or do differ from those projected in the forward looking statements. The Company assumes no obligations to update any forward looking statements, whether as a result of new information, future events or otherwise.