Clinical potential of C21 highlighted in review publications


Vicore Pharma (publ) (ticker VICO) has today published an updated reference list on the latest studies with the drug candidate C21. Three recent review articles, from Australia, Denmark/Florida and India respectively, summarize the pharmacological effects of C21 in specific indication areas. The conclusion of these reviews is that C21 has the potential to become a valuable addition to current medical treatment in several patient categories: as an anti-fibrotic agent for several indications, as a blood-pressure lowering agent in resistant hypertension, and as a nephroprotective medication for diabetic nephropathy.

Anti-fibrotic potential of AT2-receptor agonists. Wang Y et al. Frontiers in Pharmacology (2017), 8: Article 564.
In this review article, Wang et al, from Monash University, Australia, summarize published in-vivo preclinical studies, which demonstrated an anti-fibrotic effect of AT2-receptor stimulation with C21. The article focuses on studies performed in models of cardiovascular and renal disease, but also discussed general mechanisms underlying the anti-fibrotic effect of AT2-receptor simulation, which is relevance also for IPF, the lead indication of C21. Collectively, these studies demonstrate that pharmacological AT2R stimulation using C21 decreases organ fibrosis, which has been most studied in the setting of cardiovascular and renal disease. In addition, AT2R-mediated anti-inflammatory effects may contribute to the beneficial AT2R-mediated anti-fibrotic effects seen in preclinical models.

Centrally mediated cardiovascular actions of the Angiotensin II type 2 receptor. Steckelings UM et al. Trends in Endocrinology & Metabolism (2017), 28: 684-693.
Angiotensin receptors are located in specific areas of the brain including cardiovascular control centres. This article reviews very recent data, which throw light on the so far only poorly understood central mechanisms of the AT2-receptor in central blood pressure control. Stimulation of the central AT2-receptors results in an inhibition of sympathetic outflow and a lowering of blood pressure, most likely via improvement in baroreflex function. Since a disturbance of baroreflex function is regarded as a cornerstone in the pathogenesis of resistant hypertension, the authors propose that central AT2-receptor stimulation should be tested as a therapeutic approach in resistant hypertension in the future.

AT2 receptor agonist C21: A silver lining for diabetic nephropathy. Pandey A & Gaikwad AB. Europ J Pharmacol,
Diabetic nephropathy remains the major cause of end-stage renal disease throughout the world. Recommended medical treatment involves tight control of blood pressure using standard antihypertensive medication including a RAS-blocking agent. This treatment delays the loss of renal function, but better therapies are urgently needed to further improve the quality-of-life and prognosis for these patients and to reduce the huge costs for Society associated with end-stage renal disease. C21 reduces oxidative stress (superoxide production), inflammation and fibrosis in the kidney, factors of importance for renal damage. The authors conclude that C21, alone or in combination with an Angiotensin receptor blocker, is a silver lining in the dark clouds of diabetic nephropathy, and that clinical studies are warranted.  

See attached reference list. 

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Ulrike Muscha Steckelings, CSO
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