XORTX Therapeutics Inc. (NASDAQ: XRTX), a late-stage clinical pharmaceutical company focused on developing innovative therapies to treat progressive kidney disease, announced that recent research supports the company's approach to treating kidney disease by inhibiting xanthine oxidase (XO). The research, published in peer-reviewed journals, highlights a genetic link to the over-expression of XO and its role in several diseases, including kidney disease.

Xanthine oxidase (XO) is an essential enzyme in the uric acid metabolic pathway, playing a vital role in the breakdown of purine nucleotides. The breakdown products of XO, including uric acid (UA) and reactive oxygen species (ROS), can negatively impact the circulatory system and tissues during disease. XORTX-sponsored studies in rodent models of polycystic kidney disease (PKD) have suggested that over-expression or over-activity of XO could be a crucial target for treating this disease.

Although evidence for XO over-expression in human PKD is lacking, recent research shows that higher XO expression is associated with several conditions, including hyperuricemia, sepsis, organ failure, sepsis-associated acute respiratory distress syndrome (ARDS), kidney dysfunction, diabetes, and kidney failure. This growing body of research indicates that targeting XO could be a valuable therapeutic strategy for a range of kidney diseases.

The company's CEO, Allen Davidoff, Ph.D., commented on the research, emphasizing the potential of pharmacologic targeting of XO, particularly where increased XO activity is associated with non-diabetic or diabetic kidney diseases. He stated that the discoveries highlight an opportunity to develop a personalized therapeutic approach for individuals whose genetic factors predispose them to disease. XORTX believes its expertise in developing XO inhibitors, protected by a patent portfolio that anticipated this opportunity, positions the company to deliver targeted therapeutics to at-risk individuals.

Clinical Trial in ADPKD

XORTX is moving forward with a planned clinical trial in patients with autosomal dominant polycystic kidney disease (ADPKD) to test XORLO™, its proprietary formulation of oxypurinol. The trial will also provide an opportunity to further understand the role of newly identified genetic factors in individuals with PKD. The results of this trial will be crucial in determining the efficacy of XORLO™ and the validity of the genetic link to XO over-expression in PKD.

Potential for Precision Medicine

This research underscores the potential for a precision medicine approach, where treatment decisions are guided by individual genetic risk variants. This could expand XORTX's market opportunities beyond ADPKD to other kidney diseases, such as diabetic kidney disease and chronic kidney disease, as well as conditions like sepsis and diabetes. While this approach holds immense promise, it's crucial to remember that the link between genetic factors and XO over-expression in human PKD still needs further validation.

Key Considerations for Investors

Investors should be aware of the following:

• While preclinical research is promising, human evidence for XO over-expression in PKD is still lacking. This gap in knowledge adds an element of risk to XORTX's strategy.
• The path from preclinical research to approved drugs is long and uncertain. Investors should monitor the outcomes of the planned ADPKD clinical trial as a key indicator of the company's future prospects.

The Future of XO Inhibition

If the genetic link to XO over-expression is further validated, XORTX's strategic positioning in the XO inhibitor space could be a significant advantage. The company's existing patent portfolio, which anticipated this opportunity, may provide a competitive edge in developing targeted therapeutics. The potential for a precision medicine approach could broaden XORTX's market opportunities and expand its potential revenue streams. However, the lack of current human evidence for XO over-expression in PKD is a risk factor that could impact the success of their lead program. Investors should closely monitor the outcomes of the planned ADPKD clinical trial as a key indicator of the company's future prospects.

XORTX is actively pursuing its goal of developing innovative therapies for progressive kidney disease. The company's focus on XO inhibition, combined with its commitment to precision medicine, makes it a compelling player in the fight against kidney disease. The upcoming clinical trial in ADPKD patients will be a crucial step in validating the genetic link to XO over-expression and assessing the potential of XORLO™ as a targeted therapy for this devastating condition.