FDA Clears Investigational New Drug Application for TNX-102 SL for Treatment of Major Depressive Disorder

Tonix Pharmaceuticals announced that the US Food and Drug Administration (FDA) has cleared the Investigational New Drug (IDA) application for development of TNX-102 SL (cyclobenzaprine hydrochloride) for treatment of major depressive disorder (MDD) in adults.¹ With millions of patients suffering from bipolar disorder every year, this investigation may provide a new treatment option for major depressive disorder.

Seth Lederman, MD, chief executive officer of Tonix Pharmaceuticals, said in a press release, “we believe TNX-102 SL offers a promising approach for individuals suffering from MDD. The unique pharmacological profile of TNX-102 SL is designed to target the disruptive sleep which is often associated with depression. Prior studies of TNX-102 SL in fibromyalgia and posttraumatic stress disorder showed promising signals for improvement of depressive symptoms on the Beck Depression Inventory-II and the Montgomery-Asberg Depression Rating Scale (MADRS), respectively. We are excited to advance TNX-102 SL and look forward to evaluating its potential as a new treatment option for those affected by depression.”

With IND clearance, research will proceed with the phase 2 HORIZON study. The study is a 6-week, randomized, double-blind, placebo-controlled study of TNX-102 SL as first-line monotherapy in adults with MDD. Approximately 360 patients are planned to enroll, at about 30 research sites in the United States. Patients eligible to participate are 18 years or older and experiencing a moderate to severe major depressive episode. This research will compare the 5.6 mg sublingual tablet dosing of TNX-102 SL to placebo, with a primary endpoint of change in MADRS score from baseline to week 6. Other secondary endpoints include global impression scores, anxiety ratings, and multiple measures of sleep disturbance. This phase 2 study will assist in determining if TNX-102 SL has a clinically meaningful effect in treatment of major depressive disorder.

“TNX-102 SL is designed to target the disturbed sleep of depression, which is a novel mechanism of action,” added Gregory Sullivan, MD, chief medical officer of Tonix Pharmaceuticals, in a press release. “TNX-102 SL has been generally well tolerated in registrational studies of fibromyalgia patients. In the fibromyalgia studies, TNX-102 SL treatment was associated with a low incidence of side effects common with traditional antidepressants like weight gain, blood pressure changes, sexual dysfunction and cognitive issues.”

TNX-102 SL is a sublingual tablet form of cyclobenzaprine hydrochloride, enabling fast transmucosal absorption and reducing production of norcyclobenzaprine (a persistent active metabolite) in bypassing first-pass hepatic metabolism.² The drug is a tertiary amine tricyclic with potent binding and antagonist activity at 5HT_2A serotonergic, alpha-1 adrenergic, H₁ histaminergic, and M₁ muscarinic receptors. This medication is currently approved by the FDA for treatment of fibromyalgia, under the brand name Tonmya. It is also currently in development as a daily treatment for acute stress reaction/acute stress disorder under an IND. TNX-102 SL also has active INDs for indications for post-acute sequelae of COVID-19, posttraumatic stress disorder, alcohol use disorder, and agitation in Alzheimer disease.

Tonix intends to begin enrollment for the phase 2 HORIZON study in mid-2026. Research on TNX-102 SL under the IND will begin with the planned study design.

References

1. Tonix Pharmaceuticals announces FDA IND clearance for phase 2 study of TNX-102 SL for the treatment of major depressive disorder. Press release. November 24, 2025. Accessed November 24, 2025. https://ir.tonixpharma.com/news-events/press-releases/detail/1603/tonix-pharmaceuticals-announces-fda-ind-clearance-for-phase

2. TNX-102 SL. Tonix Pharmaceuticals. Accessed November 24, 2025. https://www.tonixpharma.com/tnx-102-sl/