Tonix Pharmaceuticals announces data presentations on TNX-102 SL

Tonix Pharmaceuticals Holding announced data in two oral presentations and a poster presentation at the 11th Global Conference on Pharmaceutics and Novel Drug Delivery Systems, held September 19-21, 2024, in Rome, Italy. Prof. Marino Nebuloni, Director, Qualified Person, Redox Analytical Science Srl, in an oral presentation titled, “Mannitol as Eutectic Forming Agent for Improved Sublingual Delivery of Cyclobenzaprine HCl,” described the eutectic formation of cyclobenzaprine HCl and mannitol and how it provides a stable product that dissolves rapidly and delivers cyclobenzaprine by the transmucosal route efficiently into the bloodstream. The eutectic protects cyclobenzaprine HCl from interacting with the basifying agent that is also part of the formulation and required for efficient transmucosal absorption. The work described included studies by Giorgio Reiner and his team at APR Applied Pharma Research S.A. and the team at Tonix. Bruce Daugherty, Ph.D., Executive Vice President, Research at Tonix Pharmaceuticals, in the second oral presentation titled, “Pharmacokinetic Properties of TNX-102 SL, a Sublingual Formulation of Cyclobenzaprine Hydrochloride,” outlined the clinical pharmacology of TNX-102 SL via single dose and multiple dosage administration. The formulation of TNX-102 SL was designed specifically for sublingual administration and transmucosal absorption for bedtime dosing to target disturbed sleep, while reducing the risk of daytime somnolence. Clinical pharmacokinetic studies indicated that the addition of a basifying agent was necessary for efficient transmucosal absorption. The addition of a basifying agent resulted in higher levels of exposure during the first 2 hours after dosing and resulted in deceased levels of the long-lived active metabolite, norcyclobenzaprine in both single dose and multiple dose studies, consistent with bypassing first pass hepatic metabolism. At steady state after 20 days of dosing TNX-102 SL, the dynamic peak level of cyclobenzaprine is higher than the background level of norcyclobenzaprine. In contrast, after 20 days of dosing oral cyclobenzaprine, the simulated peak level of cyclobenzaprine is lower than the simulated background level of norcyclobenzaprine. Tonix believes that TNX-102 SL’s dynamic levels of cyclobenzaprine exceeding norcyclobenzaprine levels after steady state modeling of chronic dosing, contributes to the durability of its clinical benefits. Dr. Daugherty also presented evidence showing that cyclobenzaprine interacts as an antagonist at four different receptors in the brain, which are believed to play roles in sleep quality supporting the multi-functional mechanism of TNX-102 SL. The presentation also illustrated the prevalence of fibromyalgia and the unmet need for new treatments in the U.S., despite the availability of three FDA-approved drugs. In the Phase 3 RESILIENT study in fibromyalgia, TNX-102 SL met the pre-specified primary endpoint of significantly reducing daily pain as compared to placebo. TNX-102 SL also demonstrated broad syndromal benefits with statistically significant improvement in all six pre-specified key secondary endpoints including those related to improving sleep quality, reducing fatigue, and improving patient global ratings and overall fibromyalgia symptoms and function. TNX-102 SL was well tolerated with an adverse event profile comparable to prior studies and no new safety signals were observed. Siobhan Fogarty, Executive Vice President, Product Development at Tonix Pharmaceuticals, in the poster presentation titled, “The Importance of In Vitro Discriminatory Tests in the Development of a Sublingual Dosage Form of TNX-102 SL Tablets,” presented the development of in vitro techniques used to assess characteristics of the TNX-102 SL tablet including dissolution, “disintegration time” and a proprietary “wetting time” test. These in vitro tests assessed the impact of the particle size, excipient variation and compression force. The data presented indicate that a dissolution test does not discriminate between tablets made with intentional modifications to particle size, excipient content or compression strength. However, both “disintegration time” and “wetting time” are sensitive tests to discriminate differences in particle size, concentration of the excipient Pearlitol Flash and compression strength.