Vicore Pharma has completed a two-part Phase I study in healthy male volunteers and has thereby passed an important milestone in the company’s development. The results show that all the objectives in the two Phase I studies have been met; C21 is well tolerated, safe in high doses and exhibits consistent blood levels. In addition, a Phase I extension study performed on obese men further revealed beneficial metabolic effects with C21.
The company can now continue the development of the C21 to a future drug for the treatment of idiopathic pulmonary fibrosis.
In addition, based on the exceptionally positive results for C21 in preclinical efficacy models, the company is planning on exploring the compound for a second indication where fibrosis is a significant aspect of the pathology. A disease with orphan drug status is of particular interest to the company.
Orphan drug designation
C21 has been granted orphan drug designation for idiopatic pulmonary fibrosis (IPF) by the European Medicines Agency (EMA) and Food and Drug Administration (FDA). Orphan drug designation can be obtained for medicinal products intended for a safe and effective treatment, diagnosis or prevention of rare diseases. C21 will, among other regulatory benefits, have market exclusivity from the time the product is authorized and 10 years thereafter (EU) corresponding 7 years (US). Other benefits of orphan drug designation include reduced R & D expenses and assistance from the Authorities in the form of scientific advice relating to the design of future clinical trials, as well as fee waivers.
Renin angiotensin system
The renin-angiotensin system, RAS, is an important hormone system. It regulates several organ functions, either via blood circulation, or via its effects on local tissues. Angiotensin II is a key substance in this system and it exerts its effects when binding to two receptors, the AT1 receptors and AT2 receptors.
Angiotensinogen is a plasma protein that is produced in the liver. During the catalysis of the renin released from the kidneys when the perfusion of the renal tissue decreases, angiotensinogen splits into angiotensin I. This is part of the body’s blood pressure regulation. Angiotensin I proceeds to split into the biologically active angiotensin II that control blood pressure and volume in the cardiovascular system.
ACE inhibitors are drugs that lower blood pressure and reduces morbidity and mortality during heart failure by inhibiting the enzymatic degradation of angiotensin I to angiotensin II.
AT1 receptor is known as the receptor that regulates blood pressure.
AT1 blockers are, in recent years well-known drugs for lowering of blood pressure. AT1-blockers also reduces morbidity and mortality during heart failure.
AT2 receptor is highly expressed in the embryonic stage. In adults, the receptor is active only for various conditions and has been shown to mediate programmed cell death.
C21 effects the AT2 receptor by enhancing the healing effect when incurred medical conditions where AT2 receptor is activated.
Exploring the function of the AT2 receptor, as well as investigating the medical potential of AT2 agonistic molecule entities have both been an important target of academic research for the past 10-15 years.
The AT2 receptor is expressed in the fetus where it supports organ development and differentiation. In adult healthy tissue, however, this arm of the RAS is essentially dormant and only low numbers of AT2 receptors can be detected. In contrast, when organs or tissues have been compromised by disease or harm, the AT2 receptor is again up-regulated to restitute morphology and function.
These beneficial effects constitute the protective actions of RAS, with stimulation of the AT2-R being the key mediator. The ability to restore heart function after myocardial infarction, to reduce inflammation in several conditions, and to regenerate neural tissue are all a consequence of AT2 receptor stimulation.
AT2 receptor agonism (AT2RA) is therefore an attractive novel approach with wide therapeutic implications.
The reference list includes relevant publications on the AT2 receptor platform and C21 original publications and reviews.
Reference list (PDF)
Follow the links on the marked C21 publications to view the abstracts.
A drug that has affinity for, and stimulates physiological activity, via cellular receptors that are normally stimulated by naturally occurring substances.
A peptide that is produced by a biochemical reaction caused by the enzyme renin. Angiotensins occur in several forms: the two most important are angiotensin I, which is inactive, and angiotensin II, which is the active form.
A substance that tends to nullify the action of another; in pharmaceutical terms, a drug that binds to a receptor without eliciting a biological response.
The Angiotensin II type 2 receptor or AT2R is regarded as the “protective” receptor of the renin-angiotensin system. Many effects seen after stimulation of the ATR counteracts effects mediated via the AT1 receptor thus counteracting cytokines and growth factors. The AT2R belongs to a family of G protein coupled receptors. In contrast to theubiquitous AT1 receptor, the AT2 receptor is predominantly expressed during embryonic development. In adults however it is mainly expressed after injury and in different disease states
Idiopathic pulmonary fibrosis (IPF)
IPF is a chronic and ultimately fatal disease characterized by a progressive decline in lung function. The term pulmonary fibrosis means scarring of lung tissue and is the cause of worsening dyspnea (shortness of breath). Fibrosis is usually associated with a poor prognosis. IPF usually occurs in adult individuals of between 50 and 70 years of age, and affects more men than women.
RAS, renin-angiotensin system
The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood pressure and water (fluid) balance.
When blood volume is low, the kidneys secrete renin. Renin stimulates the production of angiotensin. Angiotensin causes blood vessels to constrict, resulting in increased blood pressure. Angiotensin also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water into the blood. This increases the volume of fluid in the body, which also increases blood pressure.
If the renin-angiotensin-aldosterone system is too active, blood pressure will be too high. There are many drugs that interrupt different steps in this system to lower blood pressure. These drugs are one of the main ways to control high blood pressure (hypertension), heart failure, kidney failure, and harmful effects of diabetes.
A specific molecule on the surface or within the cytoplasm of a cell that recognises and binds with other specific molecules, such as the cell molecules that bind with hormone or neurotransmitter molecules and react with other molecules that respond in a specific way.
Summary term for the work done to meet the authorities’ formal requirements regarding, for example, pharmaceutical, or biocide registration.
Preclinical research is a stage of research that begins before clinical trials (testing in humans) can begin, and during which important feasibility, iterative testing and drug safety data are collected.
The main goals of pre-clinical studies are to determine the safe dose for first-in-man study and assess a product’s safety profile.
Phase I study
Phase I trials are the first stage of testing in human subjects. Normally, a small group of 20–100 healthy volunteers will be recruited. This phase is designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These trials are often conducted in a clinical trial clinic, where the subject can be observed by full-time staff