Ardelyx, Inc. · NASDAQ:ARDX
Ardelyx — Technical Presentation (2014)
12 slides from Ardelyx's technical presentation, 2014
Slide 1: Tenapanor, a minimally absorbed NHE3 inhibitor, reduces dietary phosphorus absorption in healthy volunteers
Tenapanor, a minimally absorbed NHE3 inhibitor, reduces dietary phosphorus absorption in healthy volunteers David Rosenbaum,1 Susanne Johansson,2 Björn Carlsson,2 Andrew G Spencer,1 Bergur Stefansson,2 Mikael Knutsson,2 Jeffrey Jacobs,1 Dominique Charmot1 1Ardelyx Inc., Fremont, CA, USA; 2AstraZenec
Slide 2: Disclosures
Disclosures ● David Rosenbaum, Andrew G Spencer, Jeffrey Jacobs and Dominique Charmot are employees of, and have ownership interest in, Ardelyx ● Susanne Johansson and Bjӧrn Carlsson are employees of, and have ownership interest in, AstraZeneca. Bergur Stefansson and Mikael Knutsson are employees of
Slide 3: Tenapanor reduces sodium and phosphorus absorption
Tenapanor reduces sodium and phosphorus absorption ● Tenapanor (AZD1722) Stool sodium Sodium excretion (mmol/day) 25 is a first-in-class small- molecule inhibitor of 20 the Na+/H+ exchanger 15 isoform 3 (NHE3) 10 ● Two healthy volunteer 5 studies1 show that tenapanor reduces 0 Placebo 3 mg 10 mg 30
Slide 4: Studies of tenapanor in healthy volunteers
Studies of tenapanor in healthy volunteers Multiple ascending-dose Dose-regimen study2 study1 Tenapanor HCl 30 mg once daily, 15, 30 or Once-daily tenapanor HCl 3, 10, 30 or 60 mg twice daily, 30 mg three times daily 100 mg or placebo for 7 days or placebo for 7 days Formulation study3 Food-effect s
Slide 5: Tenapanor was generally well tolerated and minimally absorbed
Tenapanor was generally well tolerated and minimally absorbed ● No serious adverse events ● No clinically significant changes in othera serum or urinary electrolytes – Serum sodium, potassium, calcium or creatinine – Urinary potassium or creatinine ● No significant changes in other clinical laborato
Slide 6: Learning from phosphate binders
Learning from phosphate binders ● Healthy volunteer studies of sevelamer hydrochloride provide a useful benchmark for developing new treatments for patients with hyperphosphatemia Stool phosphorus Urinary phosphorus 35 7.5 mmol/day increase 35 3.4–10.6 mmol/day decrease Phosphorus excretion (mmol/da
Slide 7: Tenapanor increased stool phosphorus over placebo
Tenapanor increased stool phosphorus over 7 days Multiple ascending-dose study (q.d.) 30 Phosphorus excretion (mmol/day) 25 20 15 10 5 0 Placebo Tenapanor Tenapanor Tenapanor (n = 8) 3 mg q.d. 10 mg q.d. 100 mg q.d. (n = 8) (n = 8) (n = 8) ● Stool phosphorus increases of 4.3–7.1 mmol/day vs placebo
Slide 8: Tenapanor increased stool phosphorus over placebo (continued)
Tenapanor increased stool phosphorus over 7 days (continued) Dose-regimen study 50 Phosphorus excretion (mmol/day) 40 30 20 10 0 Placebo Tenapanor Tenapanor Tenapanor Tenapanor Tenapanor (n = 21) 30 mg q.d. 15 mg b.i.d. 30 mg b.i.d. 30 mg t.i.d. 60 mg b.i.d. (n = 11) (n = 12) (n = 12) (n = 12) (n =
Slide 9: Increases in stool phosphorus were consistent with decreases in urinary phosphorus
Increases in stool phosphorus were consistent with decreases in urinary phosphorus Stool phosphorus Urinary phosphorus Phosphorus excretion 50 50 40 14.9 mmol/day 40 12.0 mmol/day (mmol/day) Formulation 30 30 study 20 20 10 10 0 0 Day −1 Tenapanor Day −1 Tenapanor (n = 16) 15 mg b.i.d. (n = 18) 15 m
Slide 10: Conclusions
Conclusions ● Tenapanor, a small-molecule inhibitor of NHE3, was generally well tolerated and minimally absorbed in healthy volunteers ● Tenapanor reduced absorption of dietary phosphorus – Increases in stool phosphorus – Concomitant decreases in urinary phosphorus ● Increases in stool phosphorus we
Slide 11: Tenapanor is under investigation for treating hyperphosphatemia in a phase 2 study
Tenapanor is under investigation for treating hyperphosphatemia in a phase 2 study ● Patients with chronic kidney disease on maintenance hemodialysis (NCT02081534) ● Data anticipated in first half of 2015 Change in Primary serum Randomization endpoint phosphorus Tenapanor 1 mg b.i.d. Expected number
Slide 12: Acknowledgements
Acknowledgements ● The investigators acknowledge and thank the study participants, the study centres and the clinical teams ● Medical writing support was provided by Richard Claes and Steven Inglis of Oxford PharmaGenesis Ltd, UK, and was funded by AstraZeneca 12