Strategic partnerships are an integral part of our corporate strategy. XORTX Therapeutics is working with a number of development and commercialization partners with proven competence in garnering new approvals, successfully launching products and are committed to developing novel products that meet the needs of both patients and physicians.
XORTX is developing two products to treat progressive kidney disease in patients with autosomal dominant polycystic kidney disease (ADPKD) or diabetic nephropathy (DN). The Company’s ADPKD program is a fast track approach to reposition a new formulation of Oxypurinol in this rare disease. Oxypurinol is a drug that has been extensively studied and characterized as safe and effective for decreasing uric acid in a patient’s blood. Recent clinical trials have shown that uric acid concentration in the blood is a risk factor for these patients and that decreasing uric acid has the potential to lower this risk factor and potentially slow the deterioration of kidney function. XORTX’s XRx-008 program, uses Oxypurinol, a drug with a well characterized clinical safety and effectiveness history in a patent pending formulation for this purpose. XORTX is also evaluating several drug candidates for use in treating diabetic nephropathy under the XRx-221 program and in preparation for Phase 2 clinical trials.
Pilot clinical studies published in recent years, suggests that blood concentrations of uric acid may be a causative in hypertension, inflammation, metabolic syndrome, diabetes and health consequences of diabetes such as diabetic nephropathy/kidney injury. The Company’s patent portfolio, and similarly this therapeutic approach, continues to be validated in a number of independent studies that show that by decreasing serum uric acid (SUA) can reduce markers of inflammation, progression of kidney injury including protienuria, glomerular filtration rate, hypertension, insulin resistance, and chronic kidney disease, in a clinically meaningful way. XORTX is dedicated to growing its patent portfolio to strengthen and broaden the Company’s position in this field.
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
ADPKD is an orphan indication disease affecting perhaps 1:500-1:2000 individuals and a leading cause of end stage kidney renal disease. It is a disease representing up to 5% of all patients who have kidney failure before the age of 60 years and is amongst the fastest progressing forms or kidney disease.
Evidence from a variety of recent studies has accumulated, supporting the concept that serum uric acid (SUA), when increased above the upper limit of normal is a “causative” mediator of hypertension, with strong secondary basic evidence suggesting a role of hyperuricemia (elevated serum uric acid) in the development of insulin resistance, diabetes and diabetic nephropathy.
Diabetic Nephropathy- A Health Consequence of Diabetes
DIABETES is prevalent worldwide and represents and EPIDEMIC in the US:
- According to the CDC, diabetes affected 11.3% (~25.6 Million) of the U.S. population age 20 or older in 2010, with about 1.9 million people being newly diagnosed each year (2).
- In 2005–2008, based on fasting glucose or hemoglobin A1C levels, 35% of U.S. adults aged 20 years or older had pre-diabetes (metabolic syndrome) (2).
- Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage kidney disease in the United States and worldwide.
- In the U.S., diabetic nephropathy accounts for about 45% of new cases of ESRD(3).
- About 30% of patients with type I or type II diabetes develop evidence of nephropathy (3).
A NOVEL SOLUTION:
XORTX’s business model is built upon strong basic science, and recent clinical science successes, including:
- Animal and epidemiological studies that have demonstrated an association between increased serum uric acid and hypertension (4,5).
- Two recently completed Phase 2 Trials have demonstrated uric acid lowering agents are effective at reducing blood pressure in new onset adolescent hypertension (6,7).
- Animal and epidemiological studies have demonstrated a statistically significant association between serum uric acid greater than the upper limit of normal and insulin resistance (8, 9), thus strongly suggesting that XOIs may be a potent option to treat pre-diabetes and diabetes.
- Recent evidence has emerged in the last decade to suggest uric acid has several reported effects by which it may cause diabetic nephropathy (10).
- Three observational studies in patients with diabetes have generated a substantial body of evidence that serum uric acid levels are strong determinants of the development of diabetic nephropathy and the loss of kidney function among individuals with diabetes, both Type 1 and Type 2 (11,12,13).
- Two randomized controlled trials in patients with CKD and/or diabetic nephropathy demonstrated xanthine oxidase inhibition can decrease uric acid concentration and significantly improved kidney function (14, 15).
Given the wealth of data on currently approved XOIs and novel mechanism of action, the introduction of these agents for the treatment and prevention of hypertension, diabetes and diabetic nephropathy represents a highly de-risked opportunity for developing new medical therapies in areas of large unmet medical need.
For more information please contact XORTX Therapeutics Inc.