What We Do

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

PROGRAM
INDICATION
RESEARCH
PHASE 1
PHASE 2
PHASE 3
MARKETED
GI Programs
Tenapanor
IBS-C
(NHE3 Inhibitor)
RDX8940
Various GI Indications
(TGR5 Agonist)
Cardiorenal Programs
Tenapanor
ESRD Hyperphosphatemia
(NHE3 Inhibitor)
RDX7675
Hyperkalemia
{Potassium Binder)
RDX013
Hyperkalemia
(Potassium Secretagogue)
Research
RDX011, RDX023, RDX024
Various GI and Cardiorenal Indications

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.

WITHOUT TENAPANOR
WITH TENAPANOR
NHE3 imports sodium (Na+) in exchange for protons (H+)
Tenapanor blocks NHE3, increasing sodium outside cells/in the gut
Increased sodium increases water in the gut, which loosens stool, alleviating constipation
Mechanism of abdominal pain alleviation is currently under investigation to be detailed in future manuscripts

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 studied in two Phase 3 clinical trials, T3MPO-1 and T3MPO-2, from which we anticipate results by mid-year 2017 and the end of 2017, respectively. We are also conducting a long-term safety study, T3MPO-3, for tenapanor in patients with IBS-C, in which we are enrolling patients who have completed T3MPO-1 or T3MPO-2. We plan to complete that study by the end of 2017.

Learn More About Our Ongoing Trials in IBS-C

Positive data from the Phase 2b trial of tenapanor in patients with IBS-C were first reported in October 2014. At the 50 mg twice-daily dose, the study met its primary efficacy endpoint of an increase in the complete spontaneous bowel movement (CSBM) responder rate. The overall responder rate, or dual composite endpoint percent, was achieved in 50 percent of patients receiving tenapanor 50 mg twice-daily versus 23.6 percent receiving placebo (p<0.001). An overall responder was defined as a patient who was an overall CSBM responder and who experienced at least a 30 percent decrease in abdominal pain from baseline in the same week for six of 12 weeks. The study also demonstrated clinically meaningful improvements in pain and other measures of discomfort, and that tenapanor was well-tolerated.

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.

LEARN MORE ABOUT 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.

 

OUR CARDIORENAL PORTFOLIO

Our cardiorenal portfolio is focused on addressing the important needs of patients with various metabolic disorders that are common in people with heart or kidney disease.

Tenapanor for Hyperphosphatemia

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 hyperphosphatemia, acts by inhibiting, or blocking, the NHE3 transporter in the GI tract to reduce the absorption of dietary sodium, which in turn, increases the number of protons in a cell. These increased protons cause specific tight junction resistance between cells, which then limits the amount of dietary phosphate that can pass from the gut into the blood. Importantly, the effects appear to be selective to phosphate with no apparent impact on other ions, nutrients or macromolecules.

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.

 

WITHOUT TENAPANOR
NHE3 imports sodium (Na+) in exchange for protons (H+)
Tenapanor blocks NHE3, increasing sodium outside cells/in the gut
Increased protons cause specific tight junction resistance between cells, reducing phosphate absorption
WITH TENAPANOR
Tenapanor blocks paracellular transport, the major phosphate pathway in the gut
Tight junctions use different combinations of claudin proteins to achieve ion specificity
Clinical and preclinical data suggest no effect on other molecules

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.

If successful, tenapanor will be the only approved, small molecule therapy for the treatment of these patients, who currently rely on phosphate binders to manage their hyperphosphatemia. It is currently being studied in a Phase 3 clinical trial for the treatment of hyperphosphatemia in patients with ESRD who are on 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 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.

Learn More About Our Trial in Hyperphosphatemia

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.

LEARN MORE ABOUT HYPERPHOSPHATEMIA

Eliminating the Pill Burden

Conventional dialysis and dietary restriction of foods and drinks high in phosphorus are the first step in controlling hyperphosphatemia, but this is often not enough in the majority of ESRD patients. Historically, the only other way to manage elevated phosphorus has been to require ESRD patients to take large amounts of oral phosphate binders. This requires patients to take multiple tablets, or single large chewable tablets with every meal and snack. This added pill burden is a significant challenge for dialysis patients as the amount of fluid they are allowed to drink each day is severely restricted. As a result of these challenges, a large proportion of patients have uncontrolled blood phosphorus levels, significantly increasing their risk of poor health outcomes and even death. With tenapanor, which we are evaluating to be a twice-daily dose of a small pill similar to the size of a baby aspirin, we are aiming to significantly reduce that pill burden for these 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 first half 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.

LEARN MORE ABOUT HYPERKALEMIA

PARTNERING

OUR PARTNERING STRATEGY

As part of our financial goals and commercial strategy, we may choose to establish collaborations with the world’s major pharmaceutical and biotechnology companies to expand our reach. If you are interested in partnering with a leader in the field of GI and cardiorenal diseases, please contact us.

partnering@ardelyx.com