Zurich, Switzerland, February 5, 2020 – Inositec, a pioneer in the development of life-saving small molecule drugs based on myo-inositol hexaphosphate (IP6), announced today that positive proof-of-concept data on INS-3001, a novel cardiovascular calcification inhibitor, were published in Nature Communications (DOI: 10.1038/s41467-019-14091-4). INS-3001 was found to be a potent and well tolerated inhibitor of pathological soft tissue calcification in preclinical studies. Calcification, particularly in arterial walls and cardiac valves, leads to an increase in cardiac events. Inositec is developing INS-3001 for a number of cardiovascular indications caused by calcification, including aortic valve stenosis.
This paper describes designing chemical modifications to IP6 to produce more potent inhibitors with improved pharmacokinetic properties that may enable its convenient administration in an ambulatory care setting. IP6 has been previously found to inhibit cardiovascular calcification progression but has to date been investigated primarily in clinical trials using intravenous infusion during hemodialysis sessions.
“These peer-reviewed data show that INS-3001 is well tolerated, has excellent calcification inhibition potency, and a pharmacokinetic profile that could make this a potential treatment option to a wide variety of patients suffering from the deleterious effects of cardiovascular calcification. We have now rigorously validated the scientific foundations supporting the role of INS-3001 in several potential therapeutic indications, the first of which that Inositec will be targeting is aortic valve stenosis,” stated Dr. Mattias Ivarsson, CEO of Inositec. “We’d like to thank the valuable contributions from our collaborators on all our research to date, particularly in advancing this paper to publication.”
A small library of IP6 analogs were synthesized and screened for their ability to inhibit calcification and for their resistance towards hydrolysis. The lead candidate, INS-3001, was found to display superior efficacy, as well as more favorable pharmacokinetic and tolerability profiles than IP6. It potently stabilized calciprotein particle growth and consistently demonstrated low micromolar activity in different in vitro models of cardiovascular calcification. INS-3001 also largely abolished the development of cardiovascular calcification in rodent models, while not causing toxicity related to serum calcium chelation. The published data furthermore suggest a mechanism of action independent of the etiology of cardiovascular calcification, whereby INS-3001 disrupts the nucleation and growth of pathological calcification regardless of its underlying cause.