AstraZeneca and Ardelyx have entered into a worldwide exclusive licensing agreement for Ardelyx’s NHE3 inhibitor programme, including the phase II-ready lead compound RDX5791, for the treatment of complications associated with end-stage renal disease (ESRD) and chronic kidney disease (CKD). NHE3 is the sodium–hydrogen antiporter 3, a protein essential in the absorption of sodium in the intestines.

Under the terms of the agreement, AstraZeneca will pay $35 million up front, with development milestones of $237.5 million and milestones related to launch and commercialisation, as well as tiered, double-digit royalties. AstraZeneca will assume the subsequent development costs and Ardelyx will conduct clinical trials in phase II. As part of the transaction, Ardelyx has secured an option to co-promote the product in the US, subject to agreed limitations. Additional financial details were not disclosed.

Ardelyx has evaluated RDX5791 in a phase II a clinical trial in constipation-predominant irritable bowel syndrome (IBS-C) and in two phase I clinical studies in healthy subjects for its ability to divert sodium absorption in the gastrointestinal tract. Through its unique mechanism of action, RDX5791 is believed to decrease the absorption of dietary sodium and thus divert sodium excretion from the kidney (urine) to the faeces, sparing the kidney and the cardiovascular system from unhealthy exposure of both sodium and fluid accumulation. On this basis, the companies plan to develop RDX5791 for use in ESRD and CKD in addition to IBS-C, and intend to evaluate possible development in other diseases that are a consequence of sodium and fluid overload.

“This licensing agreement accelerates our strong commitment to developing new medicines for people with renal complications, including those resulting from diabetes,” said Gunnar Olsson, vice president and head of CVGI Innovative Medicines, AstraZeneca. “There is a significant unmet medical need to address the challenges caused by sodium and excess fluid in people with renal impairment. With a novel mechanism of action, RDX5791 has the potential to have a major impact on how doctors treat these patients. We are tremendously excited to join forces with the Ardelyx team and draw on their depth of knowledge and insight.”

“We’ve been impressed with our interactions with AstraZeneca throughout this process and are confident with their commitment to develop this molecule successfully. AstraZeneca has been aggressive about pursuing novel medicines, making them among the best possible worldwide partners for validating Ardelyx’s unique approach to drug development,” commented Mike Raab, CEO of Ardelyx. “RDX5791 is our first clinical example of how our technology can be used to develop non-absorbed, small molecule therapeutics. We are delighted that AstraZeneca recognizes the potential of this compound.”