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A kidney relief  drug worth €673m
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A kidney relief drug worth €673m

10.10.2012 - British-Swedish Astra Zeneca pays Californian start-up Ardelyx up to €673m to get hold on exclusive rights for their NHE3 inhibitor programme.

After a setback this summer with an anti-obesity drug, Astra Zeneca is trying to pick up pace by getting hold on a new class of drugs. The small molecules developed by Ardelyx from Fremont (USA) target a sodium transporter on the surface of the intestinal epithelia. Astra Zeneca sees promising options for the treatment of diseases ranging from cardiovascular defects to diabetes or chronic kidney problems. On 8 October, the two companies announced a worldwide exclusive licensing agreement for Ardelyx’s NHE3 inhibitor programme worth up to €673m. The lead compound – Phase 2-ready RDX5791 – showed activity against constipation-predominant irritable bowel syndrome (IBS-C) and is also clinically tested in end-stage renal disease (ESRD) and chronic kidney disease (CKD). Under the terms of the agreement, Astra Zeneca will pay €27m up-front. Development milestones could rinse another €184m into Ardelyx’ pockets. With launch and commercialisation milestones and tiered double-digit royalties, the whole deal could yield up to €673m. Ardelyx will fund Phase II trials and Astra Zeneca further clinical development.

Aside from RDX5791, several other compounds all targeting the main transporter of sodium in the intestines, NHE3, are also subject to the deal. The effect of RDX5791 can be compared with living on a low-salt diet. Preventing the uptake of sodium ions into the body unburdens failing kidneys to eliminate excess sodium. Blocked sodium will be excreted with the faeces instead. A positive systemic effect is that no sodium will accumulate in intravascular and interstitial tissues, so hypertension and oedema formation could be effectively averted. Beyond NHE3 inhibitors, Ardelyx has three separate non-systemic preclinical compounds that are all not covered by the Astra Zeneca deal. Although targeting different molecules in the gut, they share a common property in that they are not absorbed by the gastrointestinal epithelia and are passed through the gastrointestinal tract without being altered.

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