Relief Therapeutics

Supporting patients through science and innovation

Compounds

Aviptadil

prot vertAviptadil (Vasoactive Intestinal Peptide – VIP) is an abundant biologically active endogenous human peptide acting as a ligand on specific G-protein coupled transmembrane receptors. It is one of the signal molecules of the neuroendocrine-immune network comprising anti-proliferative, anti-inflammatory, and immune-regulatory features.   Its predominant biological activity is performed in the lungs, and a vast body of experimental, pharmacological and clinical evidence suggests aviptadil to be an attractive candidate for the treatment of sarcoidosis. Since the 1970s, a number of clinical phase I/II trials using systemic (by injection) and local (by inhalation) administration of aviptadil have been performed in humans. To circumvent the side effects observed with systemic delivery, Relief Therapeutics will use inhalation of aviptadil as the route of administration for sarcoidosis patients, as inhaled drugs act quickly, minimize undesired negative side effects, avoid the hepatic first-pass metabolism, and act locally in the affected organ. Following a phase II trial in 20 sarcoidosis patients demonstrating a striking suppression of inflammatory mechanisms of the lung, in combination with amelioration of dry cough and of exertional dyspnea, Relief Therapeutics now intends to engage into a phase III clinical trial campaign (Avisarco II).

Atexakin Alfa

 

prot rougeAtexakin alfa is a low-dosage formulation of interleukin-6 (IL-6), a cytokine of 185 amino acids with pleiotropic functions in different tissues and organs.

In the nervous system, IL-6 behaves in a neurotrophic-like fashion, inducing anti-apoptotic genes expression, promoting nerve regeneration and remyelination, protecting neurons from toxic injuries. These beneficial effects of atexakin alfa treatment were confirmed in several animal models of peripheral neuropathies including diabetic neuropathy, as well as in other traumatic models such as spinal cord or optic nerve injury, and permanent focal cerebral ischemia in rat. Furthermore, in diabetic neuropathy models, atexakin alfa administration restored the vascular dysfunction associated with established diabetes, thereby completing the pleiotropic therapeutic activities of the molecule.

Over the past several years, converging data demonstrate that in type 2 diabetic patients the combination of diet and supervised physical exercise has a beneficial impact including on nerves’ integrity. Interestingly, a transient secretion of IL-6 from muscle accompanies exercise and it was possible to mimic certain of the exercise’s benefits by injection of recombinant IL-6 in humans. This confirms the beneficial effects observed with atexakin alfa in animal models of diabetic neuropathy.

All these observations suggest that providing additional IL-6, at doses mimicking physiological pulsatile elevation of circulating IL-6 levels that normally occurs during strenuous exercise, will support neuronal repair leading to the reinstatement of normal sensations and slowing down of the disease progression.

Based on previous clinical investigations as a thrombopoietic factor in different clinical settings, and treating there more than 700 patients, the maximum tolerated dose (MTD) is already established. The selected doses for the diabetic neuropathy clinical trials are considered safe as it is up to 50 times lower than MTD.

Relief Therapeutics intends to engage into a phase II clinical trial campaign with the aim to rapidly generate relevant data to drive decision on late stage development. The trial entitled “ATEXADIANE” for ATEXakin Alfa in DIAbetic NEuropathies will start with a focused, cost-contained trial assessing objective and quantifiable end points for sensory and autonomic neuropathies following limited treatment duration.