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.

Impact of COVID-19 on keratoconus patients waiting for corneal cross linking.

PURPOSE: Royal College of Ophthalmologist recent guidance recommended delaying cross-linking services during the COVID-19 pandemic. This study investigates the effects of such delays in the delivery of cross-linking services in patients with keratoconus progression. METHODS: Retrospective observational study of 46 patients with keratoconus progression, whose cross-linking was delayed due to the COVID-19 pandemic. Demographic and clinical details were obtained from assessments on the day of listing, and subsequent review on the day of the procedure. Topographic indices included keratometry of the posterior and anterior corneal surface, maximum keratometry (Kmax), thinnest corneal thickness, ABCD progression and progression based on standard criteria recommendations (1.5 D Kmax & 20 microns thinning). RESULTS: A total of 46 eyes were analysed with an average time between being listed for CXL and having the procedure done was 182 ± 65 days. The delay due to COVID-19 was of 3 months. In this time period they had a significant worsening of all keratometric indices and lost almost one line of visual acuity (0.19 ± 0.19 to 0.26 ± 0.18 LogMAR, p: 0.03). Thirty two eyes (70%) demonstrated progression in accordance with the ABCD progression criteria, while 18 eyes (39%) showed either an increase in Kmax of more than 1.5D or a thinning in corneal thickness of at least 20 µm. CONCLUSIONS: The treatment delay for the keratoconus patients caused further progression and vision worsening. We recommend that corneal collagen crosslinking needs to be considered as a high priority intervention.