Acura Pharmaceuticals, Inc. provided an update on its development of LTX-03 (Hydrocodone Bitartrate and Acetaminophen) Tablets using Acura’s LIMITx technology intended to mitigate risks associated with overdose of the hydrocodone. In conjunction with a third party formulation developer, the formulation and manufacturing process for LTX-03 has been optimized for commercial scale. Acura’s partnered commercial manufacturer has received hydrocodone quota from the Drug Enforcement Administration and is in the process of acquiring specific auxiliary equipment for the identified manufacturing process. Acura has also completed a non-clinical small animal study to identify the benefits of a reduction in peak plasma drug concentrations (Cmax) on opioid induced respiratory depression (OIRD). LIMITxTM Technology is designed to retard the release of active drug ingredients when too many tablets are accidentally or purposefully ingested by neutralizing stomach acid with buffer ingredients, but to also deliver efficacious amounts of drug when taken as a single tablet with a nominal buffer dose. Acura’s clinical testing to date indicates a reduction in opioid Cmax of up to 65% may be achieved in overdose situations. However, little is known about the influence of Cmax on OIRD particularly at overdose levels. In study APT-RDR-300 all doses above 100 mg/kg demonstrated with statistical significance (p<.05) SpO2 measured OIRD at all time points post-dosing. The 100 mg/kg dose was not statistically significant for OIRD at any time point post-dosing. The mortality rate was correlated with higher doses. In all animals exhibiting OIRD, OIRD was acutely evident within 30 minutes of dosing which was consistent with the Cmax of the hydrocodone dose. Increased Cmax was generally associated with an increased prevalence of acute OIRD (SpO2 =70%). Approximately 50% of animals reaching this acute OIRD level resulted in death Due to a high variability in the pharmacokinetics and pharmacodynamics observed in the study, no further associations were possible. Acura believes the results of this study generally support the development of opioid products with a reduction in Cmax in overdose situations. The Company is assessing the results to determine if additional clinical or non-clinical OIRD studies should be performed. Five groups of 11 Sprague-Dawley rats were orally administered doses of hydrocodone ranging from 100mg of drug per kg of body weight (mg/kg) up to 300 mg/kg. 8 subjects in each group were measured for respiratory depression assessing peripheral oxygen saturation (SpO2) of the blood over a 4 hour observation period. 36 subjects were analyzed as successfully completing the dosing. The additional 3 subjects in each group provided blood samples analyzed for hydrocodone at .5, 1, 2 and 4 hours post-dosing.