Our pipeline of gut-restricted therapies is concentrated on providing better medicines in two therapeutic areas: GI and cardiorenal diseases.

OUR GASTROINTESTINAL PORTFOLIO

Tenapanor for Irritable Bowel Syndrome with Constipation (IBS-C)

Tenapanor, invented and developed internally by scientists at Ardelyx, is a first-in-class, proprietary, oral, experimental medication that works exclusively in the gut and is in late-stage clinical development. It has a unique mechanism of action that, in IBS-C, acts by inhibiting, or blocking, the NHE3 transporter in the GI tract to reduce the absorption of dietary sodium into the blood stream. Blocking NHE3 results in an increase in the amount of sodium in the gut. This increased sodium in the gut leads to an increase of fluid in the gut, which loosens stool, helping to relieve constipation. We have also seen a desired benefit in the abdominal pain component of IBS-C in our studies to-date. The mechanism of abdominal pain is currently under investigation to be detailed in future manuscripts.

Tenapanor has been specifically designed to work exclusively within the GI tract, thereby significantly reducing the amount of drug that is absorbed into the bloodstream and the potential side effects that could occur.

IBS-C is a burdensome GI disorder affecting a significant number of people. It is characterized by significant abdominal pain, constipation, straining during bowel movements, bloating and/or gas.

Tenapanor’s safety and efficacy for the treatment of IBS-C is being evaluated in the Phase 3 T3MPO program. Data from T3MPO-1 were reported in May 2017, and data from T3MPO-2 are expected early in the fourth quarter of 2017. We are also conducting a long-term safety study, T3MPO-3, for tenapanor in patients with IBS-C, in which we enrolled patients who completed T3MPO-1 or T3MPO-2. We plan to complete that study in late 2017.

Learn More About Our Ongoing Trials in IBS-C

The T3MPO-1 trial achieved statistical significance for the primary endpoint and seven of eight key secondary endpoints. The primary endpoint, the combined responder rate for six of 12 weeks, showed that a greater proportion of tenapanor-treated patients compared to placebo-treated patients (27.0% vs 18.7%, p=0.02) had, from baseline, at least a 30 percent reduction in abdominal pain and an increase of one or more complete spontaneous bowel movements (CSBM) in the same week for at least six of the 12 weeks of the treatment period. Tenapanor was well-tolerated, consistent with the experience across previous clinical trials.

Positive data from the Phase 2b trial of tenapanor in patients with IBS-C were reported in October 2014.

IBS-C

IBS-C presents a significant burden on patients, the healthcare system and the U.S. economy. While estimates vary, it is projected that approximately 11 million people in the U.S. suffer from IBS-C.

RDX8940

RDX8940 is a minimally absorbed, oral TGR5 agonist for which we submitted an IND in late 2016. We are considering pursuing multiple GI indications for the development of RDX8940. Given pre­clinical data we’ve generated, we are evaluating the development of RDX8940 for the treatment of patients with nonalcoholic steatohepatitis (NASH), a serious and devastating condition affecting the liver, and other gastrointestinal indications.

TGR5 is an important receptor present on the surface of cells that line the GI tract that is activated in response to the bile acids the body secretes when we ingest food. As part of a normal physiological response, the binding of bile acids to TGR5 stimulates the production of critical metabolic hormones such as those involved in the maintenance of the body’s reaction to nutrients and the maintenance and care of the structural integrity of the gut. In people with certain conditions, the body’s regulation of critical hormones is disrupted and the body does not properly manage sugar and fat metabolism. Two of the many potential outcomes of this are inflammation and the accumulation of fat in the liver, which can cause NASH.

Elevated levels of phosphorus in the blood, a metabolic disorder known as hyperphosphatemia, is a very common and difficult-to-treat condition in patients with end-stage renal disease (ESRD) who require dialysis.

In February 2017, we reported positive data from the first Phase 3 clinical trial in these patients. The responder population (n=80 out of 164) had a mean reduction in serum phosphorus from baseline to the end of the eight-week treatment period of 2.56 mg/dL, with a reduction of up to 5.7 mg/dL. Notably, in this group, 33 percent of patients had a reduction in serum phosphorus of greater than 3 mg/dL. The study demonstrated a statistically significant difference in change of serum phosphorus levels from the end of the eight-week treatment period to the end of the four-week randomized withdrawal period between the tenapanor-treated group and the placebo-treated group in the responder patient population (mean -1.01 mg/dL, median of -1.3 mg/dL) and met its primary endpoint (95% CI -1.44, -0.21; LSmean -0.82mg/dL; p=0.01). Only 7.8 percent of patients discontinued treatment due to GI side effects.

We plan to initiate a second Phase 3 trial of tenapanor in this patient population in mid-2017.

Learn More About Our Completed Trial in Hyperphosphatemia

In February 2015, we reported positive data from our Phase 2b clinical study evaluating tenapanor for the treatment of hyperphosphatemia in ESRD patients on dialysis. The study met its primary endpoint by demonstrating a statistically significant dose-related decrease in serum phosphorus levels for tenapanor-treated patients compared to patients receiving placebo.

Hyperphosphatemia

Hyperphosphatemia is commonly seen in patients with end-stage renal disease (ESRD), the most advanced stage of chronic kidney disease, who are on dialysis. Hyperphosphatemia is characterized by a build-up of excess phosphorus, a vital element that is normally kept in balance by the kidneys, with excess phosphorus removed and excreted in urine. In patients with kidney failure, phosphorus that comes from the food we eat builds up to abnormal levels and leads to bone disease, heart disease and is correlated with a higher risk of death in those patients.

RDX7675

RDX7675 is an oral, non-absorbed (meaning it works exclusively within the GI tract), potassium-binding polymer that is being evaluated for the treatment of hyperkalemia, a potentially life-threatening condition that results from elevated blood potassium. Utilizing our unique approach to chemistry, we have developed RDX7675 as a patented improvement to sodium polystyrene sulfonate (SPS), an FDA approved polymer that has been the standard of care for the treatment of hyperkalemia for more than 50 years. Through the use of insights from our experiences and platform capability, we have made several critical physical and chemical modifications to this polymer to eliminate sodium, optimize binding capacity and improve mouth feel in a pleasant-tasting and easily ingestible formulation.

We have initiated a clinical trial assessing the onset-of-action (a trial evaluating the time it takes to begin lowering potassium) and a larger Phase 3 clinical trial evaluating the safety and efficacy of RDX7675 for the treatment of hyperkalemia. Data from the onset-of-action trial are expected in the third quarter of 2017. These will be the first efficacy and safety data from RDX7675 in a patient population with hyperkalemia.

Learn More About our Ongoing Trials in Hyperkalemia

In 2016, we announced positive results of a clinical study in healthy volunteers evaluating once-daily, twice-daily and three-times-daily doses of RDX7675. The study demonstrated that RDX7675 effectively binds potassium in the GI tract and that it was generally well-tolerated at all doses in the study. In addition, in the once-daily dose group we observed a very similar effect on potassium binding as was seen in the two- or three-times-daily dosing groups with the same total daily dose. Based on these data, we determined that once-daily dosing is the most appropriate dosing regimen for further evaluation in the treatment of hyperkalemia in our upcoming trials.

A separate study was conducted in healthy volunteers to evaluate the palatability of oral formulations of RDX7675 compared to SPS. RDX7675 consistently outperformed SPS, in all aspects of the taste assessments, including mouth feel, texture and flavor.

HYPERKALEMIA

Hyperkalemia is a potentially life-threatening condition in which blood levels of potassium are elevated above normal. Potassium is a nutrient that is critical to the normal function of nerve and muscle cells, including those in the heart. Normal potassium blood levels are tightly balanced and maintained primarily by the kidneys. For people with heart failure, chronic kidney disease and diabetes, and particularly those also taking highly beneficial renin-angiotensin-aldosterone system inhibitors (RAASi), there is a greater risk of developing hyperkalemia due to the side effects of those drugs and the kidney’s limited ability to keep potassium in balance.