Ardelyx said today it regained all rights to its portfolio of sodium–hydrogen exchanger 3 (NHE3) inhibitors, including its lead product candidate tenapanor, after terminating a nearly three-year collaboration with AstraZeneca to develop the compounds.
The termination will cost Ardelyx up to $110 million. That includes up to $90 million consisting of a $15 million upfront fee to AstraZeneca; royalties equal to 10% of net sales of tenapanor by Ardelyx or a licensee; and 20% of non-royalty payments that Ardelyx may receive if it were to license or otherwise offer tenapanor development and commercialization rights to a new partner.
Ardelyx also agreed to pay AstraZeneca another $10 million in R&D costs toward a faster transfer of the research program from the pharma giant; and an additional $10 million for Phase III clinical trial material and other drug product inventory. AstraZeneca is required to complete the manufacture of that clinical trial material for the Phase III clinical program in constipation-predominant irritable bowel syndrome (IBS-C) patients.
However, Ardelyx said it will use part of the $77.8 million it will raise through a private placement toward developing tenapanor as well as RDX022, a non-absorbed polymer designed to treat hyperkalemia, and set to begin Phase III trials in the second half of 2016.
By ending its partnership with AstraZeneca, Ardelyx said, it will be able to speed up clinical development of tenapanor in IBS-C. The company plans to launch a Phase III clinical program in IBS-C patients in the fourth quarter of this year. Ardelyx also plans to start a Phase IIb clinical trial in the fourth quarter of this year to evaluate an optimal dosing regimen for tenapanor for dialysis patients with hyperphosphatemia.
“By regaining the worldwide rights to tenapanor, we now have a late-stage clinical asset that has demonstrated significant promise for the treatment of IBS-C and hyperphosphatemia, both of which are conditions where we believe tenapanor could potentially transform the treatment paradigm,” Ardelyx president and CEO Mike Raab said in a statement.
Tenapanor is a minimally-absorbed small molecule inhibitor of NHE3, a transporter of sodium in the gastrointestinal tract. Tenapanor has been shown to reduce the intestinal absorption of both dietary sodium and phosphorus in clinical trials. According to Ardelyx, a total of 14 clinical trials of tenapanor have been completed, with more than 1,000 subjects having been administered tenapanor to date.
Ardelyx agreed to partner with AstraZeneca in October 2012 to develop and commercialize Ardelyx's internally discovered portfolio of NHE3 inhibitors, including tenapanor.
Tenapanor’s clinical development has had its ups and downs. Most recently last month, the drug candidate missed its primary endpoint of decreasing the urinary albumin-creatinine ratio in tenapanor-treated patients compared to placebo in a 154-patient, Phase IIa trial in patients with Stage 3 chronic kidney disease patients with type 2 diabetes and albuminuria.
In disclosing that setback, Ardelyx hinted that the days of its partnership with AstraZeneca were numbered: “We believe that tenapanor can be a best-in-class treatment for IBS-C and hyperphosphatemia and we hope to accelerate the development for these underserved conditions either independently or with AstraZeneca,” Raab said in a May 5 statement.
In February, a Phase IIb trial of tenapanor in hyperphosphatemic patients with chronic kidney disease on hemodialysis met its primary endpoint—though Ardelyx shares fell 30% after the company disclosed that “the rate of diarrhea was distinctly higher than expected.”
However, a Phase IIb study of tenapanor in irritable bowel syndrome IBS-C successfully met its primary endpoint showed statistically significant and clinically meaningful improvement in IBS-C symptoms for tenapanor-treated patients compared to patients receiving placebo.
In the private placement, Ardelyx plans to sell shares of its common stock and warrants to purchase shares of common stock. New Enterprise Associates (NEA), the company's largest shareholder, has committed to invest about $50.2 million in the private placement, with a combination of new and existing investors agreeing to raise the remaining $27.6 million—including RA Capital Management, Broadfin Capital, Cormorant Asset Management, Foresite Capital Management, Rock Springs Capital Management, and a fund managed by Sabby Capital.