Tonix Pharmaceuticals Announces FDA Acceptance of the New Drug Application (NDA) for TNX-102 SL for Fibromyalgia FDA is expected to assign a Prescription Drug User Fee Act (PDUFA) target action date and announce whether

Tonix Pharmaceuticals Holding Corp 8-K

Tonix Pharmaceuticals Announces FDA Acceptance

of the New Drug Application (NDA) for TNX-102 SL for Fibromyalgia

FDA is expected to assign a Prescription Drug

User Fee Act (PDUFA) target action date and announce whether Priority Review has been granted in the Day 74 Letter

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

analgesic, granted Fast Track designation by FDA

Fibromyalgia affects more than 10 million adults

in the U.S. who are mostly women

TNX-102 SL has the potential to be the first

member of a new class of analgesic drugs for fibromyalgia and the first new drug for treating fibromyalgia in more than 15 years, if approved

NDA based on two statistically significant Phase

3 studies of TNX-102 SL for the management of fibromyalgia; in which TNX-102 SL was generally well tolerated

CHATHAM, N.J., December 17, 2024 (GLOBE NEWSWIRE)

- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), today announced that the U.S. Food and Drug Administration

(FDA) has accepted the filing of its New Drug Application (NDA) for TNX-102 SL (cyclobenzaprine HCl sublingual tablets), a 5.6 mg, non-opioid,

centrally-acting analgesic, for the management of fibromyalgia. The FDA is expected to assign the NDA a Prescription Drug User Fee Act

(PDUFA) target action date in a Day 74 Letter. At that time, the FDA will also communicate to Tonix whether Priority Review has been granted.

TNX-102 SL was granted Fast Track designation for fibromyalgia by the FDA in July of 2024. Fast Track is designed to expedite FDA review

of important new drugs to treat serious conditions and fill an unmet medical need.

"The FDA's acceptance of our NDA represents

another step forward as we pursue our goal of delivering the first member of a new class of medicines for the management of fibromyalgia,

a condition affecting over 10 million adults in the U.S.," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals.

"The fibromyalgia community, comprised of patients and their families and support groups, has been waiting for a new drug for over

15 years. Analysis of insurance claims in the U.S., commissioned by Tonix, have shown that 18 months after diagnosis, fibromyalgia patients

were more likely to be prescribed addictive opioids than all three of the FDA-approved drugs combined."

Dr. Lederman continued, "We look forward

to working closely with the FDA throughout the NDA review period with the goal of bringing TNX-102 SL to the market to address the significant

unmet needs of the fibromyalgia community as quickly as possible. Furthermore, this is an important milestone as we advance our commercial

preparations in anticipation of a potential approval in 2025with an accomplished commercial leadership team already in place, supporting

our marketed products 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."

The NDA is supported by data from 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. The first Phase 3 trial, RELIEF, of TNX-102 SL 5.6 mg in fibromyalgia, completed in December 2020, met its pre-specified

primary endpoint of significantly reducing daily pain compared to placebo (p=0.010). In the confirmatory Phase 3 RESILIENT study in fibromyalgia,

completed in December 2023, TNX-102 SL again met the pre-specified primary endpoint of significantly reducing daily pain compared to placebo

(p =0.00005). 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. In both pivotal studies, the most common treatment-emergent adverse event was tongue or mouth numbness

at the administration site, which was temporally related to dosing, self-limited, never rated as severe, and rarely led to study discontinuation

(one participant in each study). Excluding COVID-19, systemic adverse events in each of the two studies was lower than 4.0%. Tonix believes

the submitted dossier contains the requisite safety and efficacy data from two adequate and well-controlled studies to support NDA approval.

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 a spectrum of 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

including, 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 that was 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.

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. The FDA has accepted the NDA filing for TNX-102 SL for 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 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 U.S. National Institute of Drug Abuse and Addiction. 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 in the areas of rare disease, including TNX-2900 for Prader-Willi syndrome, and infectious

disease, including a vaccine for mpox, TNX-801. In July 2024, Tonix announced a contract with the U.S. DoD's Defense Threat Reduction

Agency (DTRA) for up to $34 million over five years to develop TNX-4200, small molecule broad-spectrum antiviral agents 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.

Zembrace SymTouch and Tosymra are registered trademarks