Tonix Pharmaceuticals Announces First Patient Enrolled in Phase 2 HORIZON Study of TNX-102 SL for the Treatment of Major Depressive Disorder (MDD) (Form 8-K)

Tonix Pharmaceuticals Announces First Patient Enrolled in Phase 2 HORIZON Study of TNX-102 SL for the Treatment of Major Depressive Disorder (MDD)

HORIZON is a potentially pivotal, randomized, double-blind, placebo-controlled Phase 2 study evaluating TNX-102 SL (cyclobenzaprine HCl sublingual tablets) 5.6 mg as a first-line monotherapy in adults with MDD

Primary endpoint is change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6

TNX-102-SL was approved by the U.S. Food and Drug Administration (FDA) in August 2025 and launched commercially as TONMYA^® for the treatment of fibromyalgia in adults

BERKELEY HEIGHTS, N.J., June 29, 2026 (GLOBE NEWSWIRE) - Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) ("Tonix" or the "Company"), a fully integrated, commercial-stage biotechnology company, today announced that the first patient has been enrolled in HORIZON, a potentially pivotal Phase 2 study evaluating TNX-102 SL 5.6 mg as a first-line monotherapy in adults with major depressive disorder (MDD).

"We are committed to extending the science of TNX-102 SL into other conditions in which disturbed sleep quality plays important roles, including MDD," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "TNX-102 SL for MDD is designed to target poor sleep quality. Bedtime TNX-102 SL showed signals for improving depressive symptoms and subjective sleep quality in both a prior Phase 2 posttraumatic stress disorder study and two Phase 3 fibromyalgia studies. We look forward to evaluating TNX-102 SL in the Phase 2 HORIZON trial to learn if these promising signals will translate into benefits in MDD."

Dr. Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals added, "More than 21 million U.S. adults¹ experience a major depressive episode each year, and many current therapies are associated with tolerability and adherence challenges. TNX-102 SL for MDD is designed to target disturbed sleep through potent antagonism at four neuronal receptors that influence sleep quality. The quality of sleep, particularly deep slow wave sleep, is a critical factor in the nightly homeostatic neuro-restoration critical for recovery from stress-associated conditions such as MDD."

HORIZON is a 6-week, randomized, double-blind, placebo-controlled Phase 2 study evaluating TNX-102 SL 5.6 mg as a first-line monotherapy in adults with MDD. Approximately 360 patients are expected to enroll at approximately 30 sites across the United States. Eligible participants are 18 years of age or older and currently experiencing a moderate to severe major depressive episode. Participants will receive TNX-102 SL 5.6 mg taken sublingually at bedtime or matching placebo. The primary endpoint of the study is the change from baseline in MADRS total score at Week 6. Secondary endpoints include global impression scores, anxiety ratings, and measures of sleep quality and disturbance.

About Major Depressive Disorder (MDD)

MDD is a prevalent and serious psychiatric illness that affects adults of all ages, races, and backgrounds. It is characterized by persistent feelings of sadness or loss of interest, along with symptoms such as sleep and appetite disturbances, fatigue, difficulty concentrating, and thoughts of worthlessness or suicide. These symptoms must last at least two weeks and significantly impair daily functioning. In the United States, more than 21 million adults experience a major depressive episode each year. While several antidepressant medications are available, many individuals do not achieve adequate relief or discontinue treatment due to side effects such as weight gain, sleep disruption, cognitive impairment, and sexual dysfunction. MDD is associated with an increased risk of suicide and substantial impairment in quality of life, underscoring the urgent need for new, first-line therapies that are demonstrated to be both effective and well tolerated.

About TNX-102 SL

TNX-102 SL is a novel sublingual tablet formulation of cyclobenzaprine hydrochloride that enables rapid transmucosal absorption and reduces production of the persistent active metabolite, norcyclobenzaprine, by bypassing first-pass hepatic metabolism. TNX-102 SL is a tertiary amine tricyclic (TAT) and multifunctional agent with potent binding and antagonist activities at the 5-HT_2A serotonergic, α₁-adrenergic, H₁-histaminergic, and M₁-muscarinic receptors. It is currently FDA approved in the U.S. as a once-daily bedtime treatment for fibromyalgia in adults under the brand name TONMYA^® (cyclobenzaprine HCl sublingual tablets). TNX-102 SL is also in development as a daily bedtime treatment for acute stress disorder (ASD)/acute stress reaction (ASR) under an investigator-initiated IND. In addition to MDD, Tonix also holds active INDs for the following indications for TNX-102 SL: Long COVID (post-acute sequelae of COVID-19), PTSD, alcohol use disorder, and agitation in Alzheimer's disease. The United States Patent and Trademark Office issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10357465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patents are important elements of Tonix's proprietary composition. These patents are expected to provide TNX-102 SL U.S. market exclusivity until 2034. Pending patent applications related to method of use could extend exclusivity until 2044. The potential use of TNX-102 SL in MDD, ASD/ASR, and other unapproved indications is currently under clinical development, and the safety and efficacy have not been evaluated by any regulatory authority.

Citations

¹Substance Abuse and Mental Health Services Administration (SAMHSA). 2024. Key Substance Use and Mental Health Indicators in the United States: Results from the 2024 National Survey on Drug Use and Health.

Tonix Pharmaceuticals Holding Corp.

Tonix Pharmaceuticals* is a fully integrated, commercial-stage biotechnology company focused on central nervous system (CNS) disorders, infectious diseases, immunology conditions, and rare diseases where there exists high unmet medical need. TONMYA^® (cyclobenzaprine HCl sublingual tablets 2.8mg), the Company's flagship internally conceived and developed medicine, is the first new treatment for fibromyalgia in more than 15 years. Tonix's CNS commercial infrastructure supports its marketed products, including its acute migraine products, Zembrace^® SymTouch^® (sumatriptan injection 3 mg) and Tosymra^® (sumatriptan nasal spray 10 mg). Tonix is extending the science behind TONMYA in Phase 2 clinical studies to evaluate its potential in major depressive disorder and acute stress disorder/acute stress reaction. Tonix is also advancing a pipeline of infectious disease programs, including monoclonal antibody TNX-4800 (anti-OspA mAb) for Lyme disease prevention in the U.S. and TNX-801 (horsepox, live virus vaccine), a vaccine in development for the prevention of mpox and smallpox. Within immunology, Tonix is developing TNX-1500 (anti-CD40L mAb), a third-generation CD40 ligand inhibitor for the prevention of kidney transplant rejection. Finally, the Company's rare disease portfolio includes TNX-2900, which is Phase 2 ready for the treatment of Prader-Willi syndrome. To learn more, visit www.tonixpharma.com.

*Tonix's product development candidates, including TONMYA for unapproved indications, are investigational new drugs or biologics. Their efficacy and safety have not been established and have not been approved for any indication.

Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. TONMYA is a registered trademark of Tonix Pharma Limited. All other marks are property of their respective owners.