Non-clinical safety profile and pharmacodynamics of two formulations of the anti-sepsis drug candidate Rejuveinix (RJX).

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.

Rejuveinix Shows a Favorable Clinical Safety Profile in Human Subjects and Exhibits Potent Preclinical Protective Activity in the Lipopolysaccharide-Galactosamine Mouse Model of Acute Respiratory Distress Syndrome and Multi-Organ Failure.

Background: New treatment platforms that can prevent acute respiratory distress syndrome (ARDS) or reduce its mortality rate in high-risk coronavirus disease 2019 (COVID-19) patients, such as those with an underlying cancer, are urgently needed. Rejuveinix (RJX) is an intravenous formulation of anti-oxidants and anti-inflammatory agents. Its active ingredients include ascorbic acid, cyanocobalamin, thiamine hydrochloride, riboflavin 5' phosphate, niacinamide, pyridoxine hydrochloride, and calcium D-pantothenate. RJX is being developed as an anti-inflammatory and anti-oxidant treatment platform for patients with sepsis, including COVID-19 patients with viral sepsis and ARDS. Here, we report its clinical safety profile in a phase 1 clinical study (ClinicalTrials.gov Identifier: NCT03680105) and its potent protective activity in the lipopolysaccharide galactosamine (LPS-GalN) mouse model of ARDS. Methods: A phase 1, double-blind, placebo-controlled, randomized, two-part, ascending dose-escalation study was performed in participating 76 healthy volunteer human subjects in compliance with the ICH (E6) good clinical practice guidelines to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RJX (Protocol No. RPI003; ClinicalTrials.gov Identifier: NCT03680105). The ability of RJX to prevent fatal shock, ARDS, and multi-organ failure was examined in the well-established LPS-GalN mouse model of sepsis and ARDS. Standard methods were employed for the statistical analysis of data in both studies. Findings: In the phase 1 clinical study, no participant developed serious adverse events (SAEs) or Grade 3-Grade 4 adverse events (AEs) or prematurely discontinued participation in the study. In the non-clinical study, RJX exhibited potent and dose-dependent protective activity, decreased the inflammatory cytokine responses (interleukin-6, tumor necrosis factor alpha, transforming growth factor beta), and improved survival in the LPS-GalN mouse model of sepsis and ARDS. Histopathological examinations showed that RJX attenuated the LPS-GalN induced acute lung injury (ALI) and pulmonary edema as well as liver damage. Conclusion: RJX showed a very favorable safety profile and tolerability in human subjects. It shows potential to favorably affect the clinical course of high-risk COVID-19 by preventing ARDS and its complications.