Preclinical safety assessment of Supernitro-a novel treatment for acute pulmonary hypertension

Purpose and goal

Attgeno AB is a company founded by researchers at the Karolinska Institutet, Sthlm. The research is focused on finding new vasodilating drugs based on nitrogen oxide (NO)-delivery. After several years of basic research, a new patented NO donor, Supernitro (PDNO), has been presented for the treatment of acute pulmonary hypertension. he purpose of the project was to carry out the necessary preclinical safety studies and plan an upcoming phase 1 in humans as well as make a market analysis for the Supernitro product. The project has been successfully implemented in all parts.

Expected results and effects

Purpose of the project: 1. Safety assessment in animals. A literature study was conducted to plan animal safety studies for a human phase 1 studie. This toxicological plan was presented to the Swedish MPA and a trial protocol was prepared. Four animal studies have been conducted with the maximum tolerated dose and 14 day GLP daily dose in the rat and dog. The test animals tolerate a 150-500-fold higher dose than the one that provides the maximum treatment effect. 2. A protocol for a Phase 1 study in humans has been prepared. 3. Market analyzes in Europe and the US have been carried out.

Planned approach and implementation

Safety studies in animals have been planned and implemented by Karolinska Institutet - Swetox. GLP studies were conducted at Accelera Italy since could not run the 14-day GLP studies. Bioiochemical analyzes from these GLP studies are analyzed at Swetox. The GLP studies resulted in an additional cost paid by Attgeno. The cost of the GLP study in rats is reported in accrued costs. The cost for the GLP study in dog has not been reported because it was outside projected. Uppsala University and Danderyd Hospital have, according to plan, worked with the planning of the protocol for a Phase 1 study.