Tonix Pharmaceuticals Presented Data and Analyses of TNX-102 SL Treatment Effects on Fibromyalgia at 7th International Congress on Controversies in Fibromyalgia TNX-102 SL is a sublingual formulation of cyclobenzaprine d

Tonix Pharmaceuticals Form 8-K

Tonix Pharmaceuticals Presented Data and

Analyses of TNX-102 SL

Treatment Effects on Fibromyalgia at 7th International Congress on

Controversies in Fibromyalgia

TNX-102 SL is a sublingual formulation of

cyclobenzaprine designed for transmucosal delivery and durable activity in treating fibromyalgia

TNX-102 SL demonstrated statistically significant

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

FDA Prescription Drug User Fee Act (PDUFA)

goal date of August 15, 2025, for TNX-102 SL for the management of fibromyalgia

If approved by FDA, it 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 than 15

CHATHAM, N.J., March 4, 2025 (GLOBE NEWSWIRE)

-- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed

products and a pipeline of development candidates, presented data in an oral presentation at the 7th International Congress

on Controversies in Fibromyalgia, held March 3-4, 2025, in Vienna, Austria. A copy of the Company's presentation, titled "Transmucosal

Sublingual Cyclobenzaprine (TNX-102 SL) Treatment of Fibromyalgia at Bedtime to Target Non-Restorative Sleep Showed Durable Pain Reduction

in Two Double-Blind Randomized Phase 3 Studies" is available under the Scientific Presentations

tab of the Tonix website at www.tonixpharma.com following the conference.

"Since fibromyalgia is a chronic pain

condition, medicines to treat fibromyalgia need to provide durable benefits," said Seth Lederman, M.D., Chief Executive Officer

of Tonix Pharmaceuticals. "A randomized controlled study showed that oral, swallowed cyclobenzaprine fails to provide any durable

(>1 month) benefit1. In contrast, TNX-102 SL has shown statistically significant, durable activity (3 months) in reducing

fibromyalgia pain in two Phase 3 studies. The U.S. Food and Drugs Administration (FDA) has set a PDUFA goal date of August 15, 2025 for

a decision on marketing authorization. TNX-102 SL now has the potential to be the first new treatment option for fibromyalgia patients

Dr. Lederman continued, "TNX-102 SL is

designed as a bedtime treatment to target non-restorative sleep, which in turn has shown to result in reduced pain. By providing transmucosal

delivery of the tertiary amine tricyclic, TNX-102 SL results in reduced formation of the persistent active metabolite, norcyclobenzaprine

(norCBP) relative to oral delivery. NorCBP accumulates after oral delivery and its potent inhibition of the norepinephrine transporter

may relate to why oral cyclobenzaprine has transient (one month) activity in fibromyalgia, but not durable (three months) activity in

reducing fibromyalgia pain1. Fibromyalgia, has historically been overlooked. Patients' needs have been inadequately addressed

by the three approved products, which results in many patients being prescribed chronic opioids, that are believed to be ineffective,

and an actually deleterious, treatment strategy."

TNX-102 SL (cyclobenzaprine HCl sublingual

tablets) is a potent antagonist at four post-synaptic receptors, each of which is involved in regulating sleep. TNX-102 SL is designed

for rapid, transmucosal absorption and, as demonstrated in pharmacokinetic studies, bypasses first-pass hepatic metabolism resulting in

greater bioavailability of cyclobenzaprine that aligns with the sleep cycle to target non-restorative sleep. The sublingual formulation

also results in substantially reduced creation of the active metabolite norCyclobenzaprine (norCBP) due to the bypass of first-pass hepatic

metabolism. In two 14-week double-blind, randomized, placebo-controlled Phase 3 clinical trials evaluating the safety and efficacy of

TNX-102 SL as a bedtime treatment for fibromyalgia, TNX-102 SL 5.6 mg met the pre-specified primary endpoints of significantly reducing

daily pain compared to placebo after 14 weeks of treatment. In both trials, TNX-102 SL was generally well tolerated with an adverse event

profile comparable to prior studies and with no new safety signals observed.

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 and as a chronic overlapping pain condition (COPC) 2-4.

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 Long COVID. Fibromyalgia is also recognized as a Chronic Overlapping

Pain Condition, which is a group of related conditions that include chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), irritable

bowel syndrome, endometriosis, low back pain, post-concussive syndrome (also known as mild traumatic brain injury), chronic Lyme Disease,

chronic diabetic neuropathy and chronic post-herpetic neuralgia.

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.

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.

In contrast, after 20 days of dosing oral cyclobenzaprine, the simulated peak level of cyclobenzaprine is lower than the simulated background

level of norcyclobenzaprine.

1Carette S, et al. Arthritis

Rheum. 1994, 37(1):32-40. doi: 10.1002/art.1780370106

2Fitzcharles MA, et al. Lancet.

3Clauw DJ. Ann Rheum Dis. Published

4Kaplan CM, et al. Nat Rev Neurol.

Tonix Pharmaceuticals Holding Corp.*

Tonix is a fully-integrated biopharmaceutical

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, now recognized as the prototypic nociplastic

syndrome and as a chronic overlapping pain condition (COPC). 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 CNS portfolio includes TNX-1300 (cocaine esterase), a biologic in Phase 2 development designed to treat cocaine

intoxication that has FDA Breakthrough Therapy designation, and its development is supported by a grant from the National Institute on

Drug Abuse. 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 also has product candidates in development