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Xortx Therapeutics Inc., a late-stage clinical pharmaceutical company focused on developing innovative therapies to treat gout and progressive kidney disease, highlights recent peer-reviewed, independent, published research reports that expand current knowledge that genetic factors are linked to the over-expression of xanthine oxidase (XO), high chronic uric acid concentrations in the blood and gout. These ground breaking findings further support the company’s approach to treating gout, kidney and other diseases by inhibiting XO.
Historically, high uric acid concentration in the blood has been associated with increased incidence of gout, inflammation and health consequences, attributed to diet and lifestyle choices. Xanthine oxidase is an essential enzyme within the uric acid metabolic pathway and is required for the breakdown of purine nucleotides. The breakdown products of XO, uric acid and reactive oxygen species, are released during the enzymatic reaction and may play a detrimental role in the circulatory system and within tissue during disease. Xortx-sponsored discoveries in rodent models of gout and polycystic kidney disease (PKD) implicate over-expression or over-activity of XO as a potentially important target in treating this disease. Gout is a chronic disease that is caused by an innate immune response to deposits of uric acid crystals when uric acid is high.
Recent work by TJ Major and colleagues presented evidence that in a large clinical study of 2.6 million individuals that as many as 410 genetic factors (including 149 new factors) are associated with molecular mechanisms of the inflammatory component of gout. This clinical study aligns closely with evidence for over-expression of XO in human and with work by Wang et al. suggests linkage of genetic factors to PKD. Recently, new emerging discoveries link genetic factors to specific populations and show that higher XO expression is associated with a variety of conditions including hyperuricemia, sepsis, organ failure and sepsis associated acute respiratory distress syndrome (ARDS), kidney dysfunction, diabetes, polycystic kidney disease and kidney failure. From a mechanistic standpoint, these studies advocate for a precision medicine approach in which genetic risk variants would guide treatment decisions.
Commenting on the research, Allen Davidoff, Ph.D., chief executive officer of Xortx, stated, “This pioneering into the health consequences of hyperuricemia and linkage to genetic factor in gout and autosomal dominant polycystic kidney disease (ADPKD) sponsored by Xortx and these peer-reviewed, published research papers support our belief that pharmacologic targeting of XO holds enormous therapeutic potential, specifically where increased XO activity is associated with non-diabetic or diabetic kidney diseases. These discoveries highlight an opportunity to develop a personalized therapeutic approach for individuals whose unique genetic factors predispose them to disease, and the need for xanthine oxidase inhibition to treat those individuals at risk. We believe that Xortx’s expertise in developing XO inhibitors, protected by a patent portfolio that anticipated this opportunity, combined with our therapeutic platform is ideally positioned to deliver targeted therapeutics to individuals. Our planned clinical trial using our commercial formulation of oxypurinol will bring us ever closer preparing a NDA (new drug application) for this important gout therapy.”
Xortx announces the appointment of Krysta Davies Foss as a director and the resignation of Bill Farley, Abigail Jenkins and Patrick Treanor reducing the board to five members. Davies Foss is a seasoned biotechnology executive with more than 25 years of experience advising pharmaceutical and biotechnology companies on development strategy, commercialization, and market preparedness across a broad range of therapeutic areas. She currently serves as chief executive officer of Triad Strategic Services, a leading pharma and biotech strategy consulting firm. In addition to her executive role, Davies Foss serves on multiple boards, including the Canadian Organization for Rare Disorders (CORD), and has provided strategic intelligence and advisory services to organizations ranging from incubators and early-stage startups to large multinational pharmaceutical companies. Her experience spans the full product development lifecycle, from early innovation through global commercialization.
Dr Allen Davidoff stated, “The addition of Foss adds a strong board member to the company. Her depth of strategic insight and industry leadership will be a valuable asset as the company advances its clinical programmes and long-term growth strategy. The company wishes to thank Bill Farley, Abigail Jenkins and Pat Treanor for their efforts on behalf of Xortx over the past several years.”
Xortx is a pharmaceutical company with three clinically advanced products in development: 1) Its lead programme XRx-026 programme for the treatment of gout; 2) XRx-008 programme for ADPKD; and 3) XRx-101 for acute kidney and other acute organ injury associated with respiratory virus infections. In addition, the company is developing XRx-225, a pre-clinical stage programme for type 2 diabetic nephropathy.
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