TNX-102 SL · program

TNX-102 SL (cyclobenzaprine HCl sublingual) for Major depressive disorder

Phase 2RecruitingTonix Pharmaceuticals Holding Corp. (TNXP)

Indications for TNX-102 SL: Fibromyalgia · Approved Acute Stress Disorder · Phase 2 Major depressive disorder · Phase 2 Post-traumatic stress disorder · Discontinued

New Phase 2 monotherapy program in major depressive disorder (MDD). After a positive Type B Pre-IND meeting with the FDA (announced 18 Sep 2025), Tonix received FDA clearance of its IND and announced the potentially-pivotal Phase 2 HORIZON study on 24 Nov 2025. HORIZON (NCT07621237) is a 6-week, randomized, double-blind, placebo-controlled, parallel-group study of TNX-102 SL 5.6 mg (2 x 2.8 mg) taken sublingually at bedtime versus placebo as first-line monotherapy in adults (>=18 y) with a moderate-to-severe major depressive episode; ~360 participants at ~30 US sites; primary endpoint is change from baseline in MADRS total score at Week 6, with secondary endpoints covering global impression, anxiety, and sleep-disturbance measures. The therapeutic hypothesis is that bedtime H1/5-HT2A/alpha-1 antagonism targets the disturbed sleep of depression (described by the company as a novel mechanism of action); the MDD rationale cites exploratory depressive-symptom signals on the MADRS from the PTSD program and on the Beck Depression Inventory-II from the fibromyalgia program. TNX-102 SL is already FDA-approved as TONMYA for fibromyalgia (15 Aug 2025); MDD is a separate development indication and is not the lead/approved indication. As of this research the trial is registered as recruiting with an estimated study start of June 2026.

Data current as of

Development timeline

Phase 2Sept 2025 – Feb 2028
  1. UpcomingpendingPhase 2 HORIZON topline (MADRS change at Week 6) in MDD anticipated following an estimated February 2028 primary completion.
  2. HORIZON (NCT07621237) registered on ClinicalTrials.gov with overall status RECRUITING; estimated study start June 2026, estimated primary completion February 2028. (changed_at is an approximate month-precision anchor for the estimated June 2026 study start; exact first-patient-in date not separately citable.)
  3. FDA cleared the IND for TNX-102 SL in MDD; Tonix announced the potentially-pivotal Phase 2 HORIZON study (NCT07621237), a 6-week randomized double-blind placebo-controlled monotherapy study, with enrollment planned to initiate mid-year 2026.↗
  4. Tonix announced a positive Type B Pre-IND meeting with the FDA for TNX-102 SL in MDD; company outlined plans to file the IND and pursue an sNDA to expand the indication to MDD, citing exploratory depressive-symptom findings.↗

Readouts

  • 2028AnticipatedTopline datapendingNCT07621237

    Phase 2 HORIZON topline (MADRS change at Week 6) in MDD anticipated following an estimated February 2028 primary completion.

Clinical trials in Major depressive disorder

NCT07621237Phase 2Recruitingn=360

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of TNX-102 SL Monotherapy Versus Placebo in Participants With Major Depressive Disorder (MDD) (HORIZON)

Started Jun 2026· Primary completion Feb 2028· 📍 25 sites across 1 country (United States)

Formulations

FormulationRouteRegimenPharmacokinetics
TNX-102 SL (TONMYA) sublingual tabletsublingual transmucosal disintegrating tablet (bypasses hepatic first-pass metabolism, reducing formation of the long-half-life metabolite norcyclobenzaprine)
2.8 mg starting dose (days 1-14); 5.6 mg target dose (two 2.8 mg tablets, day 15+) once daily at bedtime; maximum 5.6 mg/day
SublingualOnce nightlyt½ 36 h · Tmax 4.3 h

Mechanism of action (compound-wide)

Cyclobenzaprine is a multifunctional, centrally acting antagonist at several aminergic GPCRs. Reported high-affinity radioligand-binding antagonism at histamine H1 (Ki ~1.3 nM), serotonin 5-HT2A (Ki ~5.2 nM), alpha-1A adrenoceptor (Ki ~5.6 nM) and muscarinic M1 (Ki ~7.9 nM) receptors. In PTSD the therapeutic hypothesis is that bedtime H1/5-HT2A/alpha-1 antagonism improves sleep quality and reduces hyperarousal, with potential disease-modifying effects on sleep-dependent trauma processing. The sublingual formulation is designed to limit the long-lived active metabolite norcyclobenzaprine.

TargetActionAffinity
H1 receptorprimaryHRH1AntagonistKi 1.3 nMⓘ
5-HT2AHTR2AAntagonistKi 5.2 nMⓘ
alpha-1A adrenoceptorADRA1AAntagonistKi 5.6 nMⓘ
M1CHRM1AntagonistKi 7.9 nMⓘ

← Full TNX-102 SL compound page (identity, identifiers, all indications)

Sources

  1. Cyclobenzaprine and Its Major Metabolite Norcyclobenzaprine Are Potent Antagonists of Human 5-HT2A, H1 and alpha-Adrenergic Receptors (Daugherty, Gershell, Lederman) — ACR/ARHP Annual Meeting (American College of Rheumatology), 2012
  2. HORIZON: A Study to Evaluate TNX-102 SL Monotherapy Versus Placebo in Participants With Major Depressive Disorder (MDD) (NCT07621237) — ClinicalTrials.gov
  3. The Skeletal Muscle Relaxer Cyclobenzaprine Is a Potent Non-Competitive Antagonist of Histamine H1 Receptors — Journal of Pharmacology and Experimental Therapeutics (JPET), 2024
  4. Tonix Pharmaceuticals Announces FDA IND Clearance for Phase 2 Study of TNX-102 SL for the Treatment of Major Depressive Disorder — Tonix Pharmaceuticals / IR
  5. Tonix Pharmaceuticals Announces Positive Pre-IND Meeting with FDA for TNX-102 SL for the Treatment of Major Depressive Disorder — Tonix Pharmaceuticals / IR
  6. TONMYA (cyclobenzaprine hydrochloride sublingual tablets) FDA Prescribing Information — DailyMed / U.S. FDA