Tonix Pharmaceuticals Enrolls First Patient in Phase 3 RELIEF Study

Tonix Pharmaceuticals Holding Corp. recently announced that the first patient was enrolled in the Phase 3 RELIEF study (TNX-CY-F304). RELIEF is a potential pivotal study of TNX-102 SL* (cyclobenzaprine HCl sublingual tablets) 5.6 mg, a non-opioid, centrally-acting analgesic, taken daily at bedtime for the management of fibromyalgia.

“Tonix is dedicated to improving the lives of the millions who suffer from fibromyalgia, and enrolling the first patient in the RELIEF study is an important step towards achieving this goal,” said Seth Lederman, MD, Tonix’s President and Chief Executive Officer. “Our two prior randomized, double-blind, registration-quality studies of TNX-102 SL in fibromyalgia evaluated TNX-102 SL at 2.8 mg, whereas the RELIEF study will evaluate TNX-102 SL at the 5.6 mg dose. In the prior studies, TNX-102 SL 2.8 mg was well tolerated, and the most common side effect was transient tongue numbness in a subset of patients. RELIEF is an adaptive-design study for which the primary endpoint is change from baseline in mean pain. We believe the mechanism of action of TNX-102 SL is the improvement of sleep quality. We expect results from an unblinded interim analysis in the second half of next year and topline results in the first half of 2021 based on the currently-planned sample size.”

Supported by the previous safety and efficacy findings of TNX-102 SL in fibromyalgia and posttraumatic stress disorder (PTSD), Tonix believes that using the 5.6 mg dose of TNX-102 SL in the new Phase 3 RELIEF fibromyalgia study has the potential to provide clinical evidence to support the efficacy and safety of TNX-102 SL for the management of fibromyalgia. The registration of TNX-102 SL 5.6 mg for the fibromyalgia indication is expected to be supported by the long-term safety exposure data from the PTSD program for TNX-102 SL 5.6 mg. The active ingredient of TNX-102 SL, cyclobenzaprine, is not associated with a risk of addiction.

The RELIEF study is a double-blind, randomized, placebo-controlled adaptive design trial designed to evaluate the efficacy and safety of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in fibromyalgia. The trial is expected to enroll approximately 470 patients across approximately 40 US sites. For the first two weeks of treatment, there will be a run-in period in which patients will start on TNX-102 SL 2.8 mg (1 tablet) or placebo. After the first two weeks, all patients will have the dose increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for 12 weeks. The primary endpoint is daily diary pain severity score change from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation.

The RELIEF study is expected to have one unblinded interim analysis when the study has results from approximately the first 50% of efficacy-evaluable patients, pending agreement with the U.S. Food and Drug Administration (FDA). Additional details about the RELIEF study are available at www.theRELIEFstudy.com or clinicaltrials.gov (NCT04172831).

Fibromyalgia is a chronic pain disorder that is thought to result from amplified sensory and pain signaling. Fibromyalgia afflicts an estimated 6-12 million adults in the US, and physicians and patients report widespread dissatisfaction with currently marketed products. Common symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled.

Tonix is a clinical-stage biopharmaceutical company focused on discovering and developing small molecules and biologics to treat psychiatric, pain and addiction conditions. Tonix’s lead product candidate, TNX-102 SL*, is in development for posttraumatic stress disorder (PTSD), fibromyalgia, agitation in Alzheimer’s disease and alcohol use disorder (AUD). TNX-102 SL is in Phase 3 development as a bedtime treatment for PTSD (trade name Tonmya**) and fibromyalgia. The Phase 3 RECOVERY trial (P302) in PTSD is currently enrolling and results from an interim analysis are expected in the first quarter of 2020 and topline data are expected in the second quarter of 2020 if the sample size remains the same. The Company has started enrollment in the Phase 3 RELIEF trial in fibromyalgia. The agitation in Alzheimer’s disease program is Phase 2 ready and the development for AUD is in the pre-Investigational New Drug (IND) application stage. Tonix is advancing two other PTSD therapeutic programs in the pre-IND stage, with different mechanisms than TNX-102 SL and designed for daytime dosing: TNX-601 CR (tianeptine oxalate controlled-release tablets) and TNX-1600 (a triple reuptake inhibitor). TNX-601 CR is in clinical formulation testing outside of the U.S. and is expected to be IND-ready in 2020. Tonix‘s programs for treating addiction conditions also include TNX-1300*** (double-mutant cocaine esterase), which is in Phase 2 development for the treatment of cocaine intoxication. Tonix’s preclinical pipeline includes TNX-1500 (anti-CD154), a monoclonal antibody being developed to prevent and treat organ transplant rejection and autoimmune conditions, and TNX-1700 (rTFF2), a biologic being developed to treat gastric and pancreatic cancers. Finally, TNX-801 (live virus vaccine for percutaneous [scarification] administration) to potentially prevent smallpox and TNX-701 (undisclosed small molecule) to prevent radiation effects are being advanced as medical countermeasures to improve biodefense. For more information, visit www.tonixpharma.com.

*TNX-102 SL (cyclobenzaprine HCl sublingual tablets) is an investigational new drug and has not been approved for any indication.

**Tonmya has been conditionally accepted by the U.S. Food and Drug Administration (FDA) as the proposed trade name for TNX-102 SL for the treatment of PTSD.

***TNX-1300 (T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution) is an investigational new biologic and has not been approved for any indication.