Discovering New Mechanisms to Solve Significant Medical Challenges

For decades, the gut had been under-recognized as a viable site for new therapeutic points of intervention for treating disease. Using our discovery model, which recreates environments within certain areas of the gastrointestinal tract and kidney, Ardelyx scientists have been able to elucidate new and previously unexploited ion transport mechanisms. Focusing on these mechanisms, we are creating targeted, small molecule drugs that are orally active but with limited systemic absorption, aiming to develop potent and efficacious therapies that minimize the side effects and drug-drug interactions frequently encountered with traditional, systemically absorbed medicines.

Our novel biological insights have enabled us to develop a pipeline of drug candidates that specifically target these mechanisms, with the potential to benefit large populations of underserved patients.

Our lead candidate tenapanor,

discovered and developed by Ardelyx, is a first-in-class, targeted therapy for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. Tenapanor has a unique mechanism of action and acts locally in the gut to inhibit the sodium/hydrogen exchanger 3 (NHE3). This results in a conformational change of the epithelial cell junctions, reducing permeability specific to phosphate, resulting in decreased phosphate absorption through the paracellular pathway, the primary pathway of dietary phosphate absorption.

Tenapanor has the potential to provide a novel approach for the treatment of hyperphosphatemia (elevated serum phosphorus), a major co-morbidity factor in people with CKD and a significant unmet medical need.

Based on our successes to date in translating our scientific insights into promising targeted therapies, we are continuing our efforts and applying our expertise to uncover additional breakthroughs to develop first-in-class therapeutics to benefit patients.

Our discovery platform has also enabled the systematic study of  the biological mechanisms of potassium secretion and has led us to the discovery of our lead candidate in the RDX013 program that pharmacologically targets potassium secretion through the lumen of the gut, thus lowering levels of serum potassium. High serum potassium, a condition called hyperkalemia, is a common problem in patients with kidney and heart disease and can cause a significantly increased risk of death because of the potential for heart conductance issues

 

Our First Discovery

Our unique discovery platform and deep understanding of the primary mechanism of sodium transport in the intestine resulted in our discovery and development of IBSRELA® (tenapanor), a first-in-class therapy that received approval in the U.S. for the treatment of adults with irritable bowel syndrome with constipation (IBS-C). We are pursuing strategic collaborations for IBSRELA for IBS-C in the U.S. and have established commercialization agreements with Fosun Pharma in China and Knight in Canada for this indication.

Scientific Publications

Hyperphosphatemia

2018. Nephrology Dialysis Transplant. The Effects of Tenapanor on Serum Fibroblast Growth Factor 23 in Patients Receiving Hemodialysis with Hyperphosphatemia.

2017 11. American Society of Nephrology Kidney Week 2017. Gastrointestinal Tolerability of Tenapanor to Treat Hyperphosphatemia in Patients on Hemodialysis.

2017 11. American Society of Nephrology Kidney Week 2017. Efficacy of Tenapanor to Treat Hyperphosphatemia in Patients on Hemodialysis.

2017. Journal of the American Society of Nephrology. Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis.

2016 09. Clinical Pharmacology in Drug Development. Preclinical and Healthy Volunteer Studies of Potential Drug–Drug Interactions Between Tenapanor and Phosphate Binders.

2015 11. American Society of Nephrology Kidney Week 2015. A Phase 2 Study on the Effect of Tenapanor on Albuminuria in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

2015 11. American Society of Nephrology Kidney Week 2015. Tenapanor, a Gastrointestinal NHE3 Inhibitor, Reduces Serum Phosphate in Patients with Chronic Kidney Disease Stage 5D and Hyperphosphatemia.

2014 11. American Society of Nephrology Kidney Week 2014. Tenapanor, a Minimally Absorbed NHE3 Inhibitor, Reduces Dietary Phosphorus Absorption in Healthy Volunteers.

2014 11. American Society of Nephrology Kidney Week 2014. Tenapanor Inhibits Phosphorous Absorption and Protects Against Vascular Calcification in Nephrectomized Rats.

2012 05. 49th ERA-EDTA Congress. RDX5791, a Non-systemic NHE3 Inhibitor for the Treatment of Fluid and Sodium Overload, Shifts Sodium Excretion from Urine to Feces in Healthy Subjects.