Creating a Healthier Tomorrow for Patients with Kidney and Cardiovascular Diseases

We are steadfast in our approach to translating novel biologic insights into targeted therapies for patients with significant unmet medical needs. To this end, we are advancing a pipeline of promising, first-in-class candidates and programs with the potential to provide life-changing benefits.

Tenapanor for Hyperphosphatemia

Leveraging our scientific insights and discovery of the primary pathway of phosphate absorption, we have developed tenapanor for the treatment hyperphosphatemiaan electrolyte disorder in which there is an elevated level of phosphate in the blood.

Hyperphosphatemia is a nearly universal condition in more than 550,000 Americans with chronic kidney disease (CKD) on dialysis, and a major risk factor for cardiovascular morbidity and mortality. Despite the widespread use of phosphate binders, the only currently available class of therapy for this condition, a significant proportion of patients are unable to achieve and maintain target phosphorus levels. 

Tenapanor is a first-in-class, targeted small molecule with a unique mechanism of action that blocks the paracellular absorption of phosphate in the GI tract rather than binding it, creating the potential to completely change the treatment paradigm.

In clinical studies to date (see below), this novel approach to treating hyperphosphatemia has been shown to reduce phosphorus with one small pill taken twice a day, as both a monotherapy and as part of a dual-mechanism approach. On June 30, 2020 we submitted a New Drug Application to the U.S. FDA for the approval of tenapanor for the control of serum phosphorus in adult patients with CKD on dialysis. If approved, we intend to commercialize tenapanor for hyperphosphatemia in the U.S.

Clinical Trials

We have conducted three Phase 3 clinical trials evaluating the efficacy and safety of tenapanor for the control of serum phosphorus in adult patients with CKD on dialysis: two monotherapy trials (BLOCK and PHREEDOM) and one dual mechanism trial (AMPLIFY). We are also in the midst of an open label extension study evaluating the ability to achieve normal phosphorus levels (2.5 – 4.5 mg/dL) with tenapanor.

BLOCK Phase 3 Trial (n=219)

  • 12-week clinical trial, evaluating tenapanor monotherapy
  • Primary endpoint: difference in phosphorus compared to placebo between tenapanor-treated patients and placebo-treated patients in the efficacy analysis set from the beginning to the end of the randomized withdrawal period
  • Met primary endpoint and key secondary endpoints

PHREEDOM Phase 3 Trial (n=423)

  • 52-week clinical trial, evaluating tenapanor monotherapy
  • Primary endpoint: difference in phosphorus compared to placebo between pooled tenapanor-treated patients and placebo-treated patients in the efficacy analysis set from the beginning to the end of the randomized withdrawal period
  • Met primary endpoint and key secondary endpoints

NORMALIZE Open Label Extension Trial from PHREEDOM (n=171)

  • Open label extension study to evaluate the ability of tenapanor, alone or in combination with sevelamer, to achieve serum phosphorus levels in the normal range (2.5 – 4.5 mg/dL) in patients with CKD on dialysis

AMPLIFY Phase 3 Trial (n=235)

  • 4-week clinical trial, evaluating tenapanor with phosphate binders for a dual mechanism approach vs. phosphate binders alone
  • Primary endpoint: comparison of change from baseline in serum phosphorus at week 4 between tenapanor + PB (tenapanor arm) and placebo + PB (binder arm)
  • Met primary and key secondary endpoints

Tenapanor New Drug Application (NDA) submitted on June 30, 2020 for the control of serum phosphorus in adult patients with CKD on dialysis

Our global partners currently include Kyowa Kirin, Fosun Pharma, and Knight.

  • In November 2017, we executed a license agreement with Kyowa Kirin for the development and commercialization of tenapanor for cardiorenal diseases and conditions associated with them, including hyperphosphatemia, in Japan.
  • In December 2017, we executed a license agreement with Shangai Fosun Pharmaceutical Industrial Development Company Limited for the development and commercialization of tenapanor for IBS-C and hyperphosphatemia related to chronic kidney disease in China.
  • In March 2018, we executed a license agreement with Knight Therapeutics, Inc. that provides Knight with exclusive rights to commercialize tenapanor in Canada for the treatment of IBS-C and hyperphosphatemia.

 

RDX013 for Hyperkalemia

Our research platform has enabled us to identify mechanisms for amplifying potassium secretion, leading to the discovery of our lead candidate in the RDX013 program that targets potassium secretion through the lumen of the gut. Via this mechanism, we believe the candidate has the potential to lower levels of serum potassium to treat hyperkalemia (a condition of high serum potassium levels).

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. Within the population with CKD and/or heart failure in the U.S., we estimate that there are approximately 2.1 million people who have occurrences of hyperkalemia.

Unlike current treatments that bind potassium, our lead candidate in the RDX013 program represents a first-in-class, targeted therapy that could create a completely new treatment paradigm for patients with hyperkalemia if successfully developed.

Other Programs

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 benefit patients suffering from the complications of kidney and cardiovascular diseases both in-house and in collaboration with our partners.