- Clinically relevant doses of C21 increase blood flow in humans
- Systemic blood pressure was unaffected, and no side effects were observed
- The forearm blood flow method is a robust technique for early clinical concept testing
Gothenburg, September 22, 2022 – Vicore Pharma Holding AB (publ) (“Vicore”), a clinical-stage pharmaceutical company developing medicines stimulating the angiotensin II type 2 receptor (AT2R), today announces that intra-arterial administration of C21 results in a significant dose-dependent increase in local blood flow.
Forearm blood flow was measured by plethysmography* in healthy volunteers after intra-arterial infusion of small increasing doses of C211 leading to local blood concentrations of C21 similar to those reached with oral C21 treatment. In the injected arm, blood flow increased by 63% (p=0.026), without reducing systemic blood pressure or causing other side effects.
Vasodilation by angiotensin II type 2 receptor agonists (ATRAGs) is mediated by nitric oxide (NO) released from the endothelium, and the observed effects show that this can be achieved in man with clinically relevant doses of C21.
“A clinical effect on endothelium-derived NO is very interesting for targeting endothelial dysfunction” says Jan Nilsson, Professor in Experimental Cardiovascular Research, Lund University.
Impaired NO release is the hallmark of endothelial dysfunction, an important driver of vascular diseases including pulmonary artery hypertension (PAH), pulmonary hypertension associated with idiopathic pulmonary fibrosis (IPF), preeclampsia (PE), as well as diseases of aging such heart and kidney disease – areas with huge unmet medical needs.
“The effect of ATRAGs on blood vessels is important for PAH and IPF, and for the other indications that we are targeting with the new molecules in development, like preeclampsia and cardiorenal diseases. Studying human forearm blood flow is a simple and robust technique for early clinical concept testing and dose finding” says Carl-Johan Dalsgaard, CEO of Vicore,
About angiotensin II typ 2 receptor agonists (ATRAGs)
The AT2R is part of the body’s regeneration and repair system and is suggested to be involved in several diseases connected to ageing and cell senescence, including idiopathic pulmonary fibrosis, chronic kidney disease, heart failure as well as cognitive disorders. Stimulating AT2R has been shown to be effective in combatting disease in numerous models, and clinical validation is well advanced in chronic lung disease. Stimulating AT2R also dilates small diseased resistance vessels in animals and in humans, resulting in locally increased blood flow. Vicore is developing C21 for rare lung diseases and have a series of new ATRAGs in development for other indications, the first of which (C106) is in clinical phase 1.
This information was submitted for publication on September 22, 2022 at 08:00 CET.
* A plethysmograph is an instrument for measuring changes in volume within an organ or whole body (usually resulting from fluctuations in the amount of blood it contains).
Source: Vicore Pharma