Tonix Pharmaceuticals Presented Data and Analyses of TNX-102 SL Treatment Effects on Fibromyalgia at the Annual European Congress of Rheumatology (EULAR) 2025 TNX-102 SL is a sublingual formulation of cyclobenzaprine des

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals Presented Data and

Analyses of TNX-102 SL Treatment Effects on Fibromyalgia at the Annual European Congress of Rheumatology (EULAR) 2025

TNX-102 SL is a sublingual formulation of

cyclobenzaprine designed for transmucosal delivery and durable activity in treating fibromyalgia: FDA PDUFA goal date of August 15, 2025

TNX-102 SL demonstrated statistically significant

improvement in the primary endpoint of reduction in fibromyalgia pain in two double-blind randomized placebo-controlled Phase 3 studies

If approved by FDA, TNX-102 SL would become

the first member of a new class of non-opioid analgesic drugs for fibromyalgia and the first new drug for treating fibromyalgia in more

CHATHAM, N.J., June 16, 2025 (GLOBE NEWSWIRE)

- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company) presented data in a poster presentation at the Annual

European Congress of Rheumatology (EULAR) 2025, held June 11-14, 2025, in Barcelona, Spain. A copy of the Company's poster, titled

"Advancing Fibromyalgia Treatment: Transmucosal Sublingual Cyclobenzaprine (TNX-102 SL) Targets Non-restorative Sleep and Provides

Sustained Pain Reduction" is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com. TNX-102

SL (cyclobenzaprine HCl sublingual tablets) is a non-opioid analgesic designed for daily bedtime dosing with an FDA Prescription Drug

User Fee Act (PDUFA) goal date of August 15, 2025.

"Fibromyalgia is a complex and invisible

chronic pain condition which drives many patients to be prescribed chronic opioids which are associated with addiction and overdose,"

said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "To address the chronic symptoms of fibromyalgia, potential

therapeutic options must provide durable benefits. TNX-102 SL has shown statistically significant, durable activity (14 weeks) in reducing

fibromyalgia pain in two Phase 3 studies. Designed to target the sleep disturbance of fibromyalgia, TNX-102 SL harnesses the therapeutic

activity of cyclobenzaprine in part by reducing in the level of the active metabolite norcyclobenzaprine relative to oral cyclobenzaprine.

Norcyclobenzaprine is believed to interfere with the durability of oral cyclobenzaprine's treatment effect in off-label chronic

dosing regimens and in a failed double-blind randomized placebo-controlled trial.1 TNX-102 SL now has the potential to be the

first new treatment option for fibromyalgia patients in 15 years."

TNX-102 SL is designed for transmucosal absorption

to bypass first-pass hepatic metabolism. The poster presentation shows the day 20 steady state blood levels from a study of nightly TNX-102

SL dosing in which the peak level of cyclobenzaprine exceeds the level of the active metabolite norcyclobenzaprine during sleep time.

In contrast, with nightly oral cyclobenzaprine dosing, pharmacokinetic simulations show that norcyclobenzaprine accumulates to higher

levels, and the cyclobenzaprine peak level does not exceed the norcyclobenzaprine level during sleep time.

The poster includes data from the RESILIENT

Phase 3 study evaluating the efficacy and safety of TNX-102 SL with a primary endpoint of reducing daily pain numeric rating scale scores

after 14 weeks of treatment. TNX-102 SL significantly reduced pain and improved clinical outcomes in fibromyalgia patients while demonstrating

a favorable tolerability profile. TNX-102 SL employs a novel mechanism targeting the sleep disturbance in fibromyalgia by acting as a

potent antagonist at four post-synaptic receptors, each of which is known to regulate sleep.

Fibromyalgia is a common chronic pain disorder

that is understood to result from amplified sensory and pain signaling within the central nervous system, called central sensitization.

Brain imaging studies have localized the functional disorder to the brain's insula and anterior cingulate cortex. Fibromyalgia afflicts

more than 10 million adults in the U.S., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, non-restorative

sleep, fatigue, and brain fog (or cognitive dysfunction). Other associated symptoms include mood disturbances, including depression, anxiety,

headaches and abdominal pain or cramps. Individuals suffering from fibromyalgia often struggle with their daily activities, have impaired

quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products.

Fibromyalgia is now recognized as the prototypic nociplastic syndrome. Nociplastic pain is the third primary type of pain in addition

to nociceptive pain and neuropathic pain. Many patients present with pain syndromes that are mixtures of the three primary types of pain.

Nociplastic syndromes are associated with central and peripheral sensitization. Fibromyalgia can occur without any identifiable precipitating

event. However, many fibromyalgia cases follow one or more precipitating event(s) including: post-operative pain, acute or chronic nociceptive

or neuropathic pain states; recovery from an infectious illness; a cancer diagnosis or cancer treatment; a metabolic or endocrine stress;

or a traumatic event. In the cases of recovery from an infectious illness, fibromyalgia is considered an Infection-Associated Chronic

Condition. In addition to fibromyalgia cases associated with other conditions or stressors, the U.S. National Academies of Sciences, Engineering,

and Medicine, has concluded that fibromyalgia is a diagnosable condition that can occur after recovery from COVID-19 in the context of

TNX-102 SL is a centrally acting, non-opioid

investigational drug, designed for chronic use. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed

for bedtime dosing for the management of fibromyalgia. Cyclobenzaprine potently binds and acts as an antagonist at four different post-synaptic

neuroreceptor subtypes: serotonergic-5-HT2A, adrenergic- 1, histaminergic-H1, and muscarinic-M1-cholinergic

receptors. Together, these interactions are believed to target the non-restorative sleep characteristic of fibromyalgia identified by

Professor Harvey Moldofsky in 1975. Cyclobenzaprine is not associated with risk of addiction or dependence. The TNX-102 SL tablet is based

on a eutectic formulation of cyclobenzaprine HCl and mannitol that provides a stable product which dissolves rapidly and delivers cyclobenzaprine

by the transmucosal route efficiently into the bloodstream. The eutectic protects cyclobenzaprine HCl from interacting with the basifying

agent that is also part of the formulation and required for efficient transmucosal absorption. Patents based on TNX-102 SL's eutectic

composition and its properties have issued in the U.S., E.U., Japan, China and many other jurisdictions around the world and provide market

protection into 2034. The European Patent Office's Opposition Division maintained Tonix's European Patent EP 2 968 992 in

unamended form after an Opposition was filed against it by a Sandoz subsidiary, Hexal AG. Hexal AG did not appeal that decision. The formulation

of TNX-102 SL was designed specifically for sublingual administration and transmucosal absorption for bedtime dosing to target disturbed

sleep, while reducing the risk of daytime somnolence. Clinical pharmacokinetic studies indicated that relative to oral cyclobenzaprine,

TNX-102 SL results in higher levels of exposure during the first 2 hours after dosing and in deceased levels of the long-lived active

metabolite, norcyclobenzaprine in both single dose and multiple dose studies, consistent with bypassing first pass hepatic metabolism.

Cyclobenzaprine is a tertiary amine tricyclic and its active metabolite norcyclobenzaprine is a secondary amine tricyclic. At steady state

after 20 days of dosing TNX-102 SL, the dynamic peak level of cyclobenzaprine is higher than the background level of norcyclobenzaprine

during sleep time. In contrast, after 20 days of dosing oral cyclobenzaprine, the simulated peak level of cyclobenzaprine is lower than

the simulated background level of norcyclobenzaprine.

Tonix Pharmaceuticals Holding Corp.*

Tonix is a fully integrated biotechnology company

focused on transforming therapies for pain management and vaccines for public health challenges. Tonix's development portfolio is

focused on central nervous system (CNS) disorders. Tonix's priority is to advance TNX-102 SL, a product candidate for the management

of fibromyalgia, for which an NDA was submitted based on two statistically significant Phase 3 studies for the management of fibromyalgia

and for which a PDUFA (Prescription Drug User Fee act) goal date of August 15, 2025 has been assigned for a decision on marketing authorization.

The FDA has also granted Fast Track designation to TNX-102 SL for the management of fibromyalgia. TNX-102 SL is also being developed to

treat acute stress reaction and acute stress disorder under a Physician-Initiated IND at the University of North Carolina in the OASIS

study funded by the U.S. Department of Defense (DoD). Tonix's immunology development portfolio consists of biologics to address

organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is an Fc-modified humanized monoclonal antibody targeting

CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix's

infectious disease portfolio includes TNX-801, a vaccine in development for mpox and smallpox, as well as TNX-4200 for which Tonix has

a contract with the U.S. DoD's Defense Threat Reduction Agency (DTRA) for up to $34 million over five years. TNX-4200 is a small

molecule broad-spectrum antiviral agent targeting CD45 for the prevention or treatment of infections to improve the medical readiness

of military personnel in biological threat environments. Tonix owns and operates a state-of-the art infectious disease research facility

in Frederick, Md. Tonix Medicines, our commercial subsidiary, markets Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra

(sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.

* Tonix's product development candidates are

investigational new drugs or biologics; their efficacy and safety have not been established and have not been approved for any indication.

1Carette S, et al. Arthritis

Rheum. 1994;37(1):32-40.

Zembrace SymTouch and Tosymra are registered trademarks

of Tonix Medicines. All other marks are property of their respective owners.

This press release and further information about

Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release

are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by

the use of forward-looking words such as "anticipate," "believe," "forecast," "estimate,"

"expect," and "intend," among others. These forward-looking statements are based on Tonix's current expectations