Tonix Pharmaceuticals Holding Corp. announced the publication of a research paper in the Journal Psychiatry Research. The article titled, "A Phase 3, Randomized, Placebo-Controlled, Trial to Evaluate the Efficacy and Safety of Bedtime Sublingual Cyclobenzaprine (TNX-102 SL) in Military-Related Posttraumatic Stress Disorder," by Parmenter, et al.

found that bedtime TNX-102 SL treatment is well-tolerated and showed nominal improvement in PTSD severity and sleep quality measures in the first four weeks in military-related posttraumatic stress disorder (PTSD).1 The Company believes these findings suggest a potential role for short-term bedtime TNX-102SL treatment in the immediate aftermath of traumatic events. The data support the U.S. Department of Defense (DoD)-funded Phase 2 investigator-initiated OASIS trial to evaluate bedtime TNX- 102 SL in reducing the severity of acute stress reaction (ASR) and the frequency of acute stress disorder (ASD) and PTSD. The IND supporting the OASIS trial was recently cleared, and the trial is expected to begin enrolling in the second quarter.

The trial is sponsored by The University of North Carolina Institute for Trauma Recovery and supported by a $3 million grant from DoD. In the OASIS study, 14 days of bedtime TNX-102 SL 5.6 mg will be tested in the immediate aftermath of motor vehicle collision. The study will test the potential for TNX-102 SL treatment initiated within 24 hours of index trauma to target trauma-related sleep disturbance and other ASR symptoms to facilitate recovery from ASR and to prevent PTSD.

PTSD: The Phase 3 HONOR study described in the published article was performed in military-related PTSD with the primary endpoint of improvement from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score at Week 12 comparing TNX-102 SL 5.6 mg and placebo. The study did not reach statistical significance on the primary endpoint. While there was nominal improvement by the Week 4 visit on CAPS-5 (p=0.019), the improvement relative to placebo was not sustained at Weeks 8 and 12.

The CAPS-5 ?sleep disturbance? item also showed nominal improvement at Week 4 (p=0.002), as well as at Week 8 (p=0.026), but not thereafter. The PROMIS Sleep Disturbance T-score also showed early nominal improvement with TNX-102 SL 5.6 mg at Week 4 (p=0.015).

It is also notable that when the primary endpoint was analyzed for responder rate, defined as =50% improvement on CAPS-5 total score at Week 4, 38.4% of those on TNX-102 SL were responders versus 24.4% on placebo (p=0.019). TNX-102 SL was well-tolerated and the adverse events reported were similar to those seen in prior TNX-102 SL studies. There were three participants with serious adverse events (SAEs) reported during the study: two in the placebo group and one in the active group.

None were deemed related to study drug. Administration site reactions were similar in profile to prior studies with TNX-102 SL, with oral numbness (hypoaesthesia) at the higher rate. These oral sensory adverse events (AE), oral numbness, oral tingling, and tongue discomfort were temporally-related to dosing and were rated as mild and transient (<60 min) in the majority of cases.

No new safety signals were observed. In addition to the Phase 3 HONOR study described in the published article1, Tonix has also studied TNX-102 SL in a Phase 2 (?AtEase?) trial in military PTSD5 and in a Phase 3 (?RECOVERY?) trial in civilian PTSD.6 Both studies were performed with the primary endpoint of CAPS-5 improvement at Week 12. AtEase compared bedtime TNX-102 SL at two doses (2.8 mg & 5.6 mg) and placebo.

RECOVERY compared TNX-102 SL 5.6 mg and placebo. Neither study reached statistical significance on the primary endpoint. Fibromyalgia: TNX-102 SL has shown positive results in two Phase 3 clinical trials for the management of fibromyalgia.

Tonix plans to submit a New Drug Application to the U.S. Food and Drug Administration in the second half of 2024 under the 505(b)(2) regulatory pathway for Tonmya for the management of fibromyalgia. Formulation Technology and Patents: TNX-102 SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which is designed for daily administration at bedtime with a proposed mechanism of improving sleep quality in fibromyalgia. TNX-102 SL provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism.

As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, a1-adrenergic, H1-histaminergic, and M1-muscarinic cholinergic receptors, TNX-102 SL is in development as a daily bedtime treatment for fibromyalgia. TNX-102 SL is also in development for fibromyalgia-type Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder, and agitation in Alzheimer?s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No.

9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No.

10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic?

protective eutectic and Angstro-Technology? formulation claimed in the patent are important elements of Tonix?s proprietary TNX-102 SL composition. These patents are expected to provide Tonmya, upon NDA approval, with U.S. market exclusivity until 2034/2035.

In addition, Tonix has pending but not issued U.S. patent applications directed to the transmucosal absorption of cyclobenzaprine HCl, with U.S. market exclusivity expected until 2033, for treating depressive symptoms in fibromyalgia, with U.S. market exclusivity expected until 2032, and for treating pain in fibromyalgia with U.S. market exclusivity expected until 2041.