Tonix Pharmaceuticals Achieves Enrollment of First 50 Percent of Participants in the RESILIENT Study, a Potentially Pivotal Confirmatory Phase 3 Study of TNX-102 SL for the Management of Fibromyalgia Results from Planned

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals Achieves Enrollment of First

50 Percent of Participants in the RESILIENT Study, a Potentially Pivotal Confirmatory Phase 3 Study of TNX-102 SL for the Management of

Results from Planned Interim Analysis of First 50

Percent of Participants Expected Second Quarter 2023

Topline Results Expected Fourth Quarter 2023

Positive Outcome in RESILIENT, Together with Results

from Previous Positive Phase 3 RELIEF Study, Would Support Submission of an NDA

CHATHAM, N.J., December 19, 2022 - Tonix

Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that

the first 50% of participants have been randomized in the Phase 3 RESILIENT study of TNX-102 SL (cyclobenzaprine HCl sublingual tablets)

5.6 mg for the management of fibromyalgia. An interim analysis by an Independent Data Monitoring Committee (IDMC) of the first 50% of

randomized participants for a potential sample size adjustment or early stop for futility is expected in the second quarter of 2023.

TNX-102 SL is in mid-Phase 3 development for

the management of fibromyalgia, a chronic pain disorder that afflicts between 6 and 12 million adults in the U.S., of which 90 percent

are women. Despite dissatisfaction with currently marketed products, no new treatment for fibromyalgia has been approved by the FDA since

In December 2020, Tonix reported positive results

from the first Phase 3 study (RELIEF) of TNX-102 SL 5.6 mg for the management of fibromyalgia (primary endpoint, p=0.010). Several

secondary measures in RELIEF highlighted the broad effects of TNX-102 SL across several cardinal symptoms of fibromyalgia beyond pain.

In March 2022, Tonix reported results of a subsequent Phase 3 study (RALLY) in which TNX-102 SL did not achieve statistical significance

on the primary endpoint (p=0.115). Relative to the previous positive Phase 3 study (RELIEF), RALLY had an unexpected increase in

study participant adverse event-related discontinuations in both the drug and placebo groups. TNX-102 SL was generally well tolerated

in both studies with an adverse event profile comparable to prior studies, and no new safety signals observed.

"We are pleased to have reached this important milestone in

our ongoing development of TNX-102 SL for fibromyalgia. RESILIENT is a potentially pivotal and confirmatory Phase 3 study, and we look

forward to the IDMC's assessment of interim results in the second quarter of 2023," said Seth Lederman, M.D., Chief Executive Officer

of Tonix Pharmaceuticals. "Fibromyalgia is a complex syndrome in which many patients remain unsatisfied by existing treatment options.

Approximately one-fourth of people with fibromyalgia resort to prescription opioids for analgesia1. TNX-102 SL is a centrally

acting analgesic that has the potential to be a new non-addictive, non-opioid bedtime medication for the management of fibromyalgia with

broad spectrum symptom coverage."

1Sarmento, CVM, et al. (2019) "Opioid prescription

patterns among patients with fibromyalgia." J Opioid Manag. 15(6):469-477. doi: 10.5055/jom.2019.0537. PMID: 31850508

About the Phase 3 RESILIENT Study

The RESILIENT study is a double-blind, randomized,

placebo-controlled trial designed to evaluate the efficacy and safety of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in the management

of fibromyalgia. The two-arm trial is expected to enroll approximately 470 participants in the U.S. The first two weeks of treatment

consist of a run-in period in which participants start on TNX-102 SL 2.8 mg (1 tablet) or placebo. Thereafter, all participants increase

their dose to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. The primary endpoint is the daily

diary pain severity score change (TNX-102 SL 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical

rating scale scores), analyzed by mixed model repeated measures with multiple imputation. An interim analysis by an Independent Data

Monitoring Committee will be conducted on the primary endpoint based on the first 50% of enrolled participants for a potential sample

size adjustment or early stop for futility.

For more information, see ClinicalTrials.gov

Identifier: NCT05273749.

Fibromyalgia is a chronic pain disorder that

is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts an estimated

6-12 million adults in the U.S., approximately 90% of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative

sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety

and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently

are disabled. Physicians and patients report common dissatisfaction with currently marketed products.

TNX-102 SL is a patented sublingual tablet formulation

of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite,

norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities

at the 5-HT2A-serotonergic, 1-adrenergic, H1-histaminergic, and M1-muscarinic receptors, TNX-102 SL is in development as a daily

bedtime treatment for fibromyalgia, PTSD, Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder

and agitation in Alzheimer's disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408

in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No.

10736859 in August 2020. The Protectic protective eutectic and Angstro-Technology formulation claimed in the patent are

important elements of Tonix's proprietary TNX-102 SL composition. These patents are expected to provide TNX-102 SL, upon NDA approval,

with U.S. market exclusivity until 2034/2035.

Tonix Pharmaceuticals Holding Corp.*

clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and

prevent human disease and alleviate suffering. Tonix's portfolio is composed of central nervous system (CNS), rare disease,

immunology and infectious disease product candidates. Tonix's CNS portfolio includes both small molecules and biologics to

treat pain, neurologic, psychiatric and addiction conditions. Tonix's lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl

sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second

quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a

chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022 and expects

interim data in the third quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has

been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the first

quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is expected to

enter the clinic with a Phase 2 study in the first quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is

a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2

study expected to be initiated in the first quarter of 2023. Tonix's rare disease portfolio includes TNX-2900 (intranasal

potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA.

Tonix's immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including

TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of

allograft and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be

initiated in the first half of 2023. Tonix's infectious disease pipeline consists of a vaccine in development to prevent

smallpox and monkeypox, next-generation vaccines to prevent COVID-19, and a platform to make fully human monoclonal antibodies to

treat COVID-19. TNX-801, Tonix's vaccine in development to prevent smallpox and monkeypox, also serves as the live virus

vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to

be initiated in Kenya in the second half of 2023. Tonix's lead vaccine candidate for COVID-19 is TNX-1850, a live virus

vaccines based on Tonix's recombinant pox live virus vector vaccine platform.

product candidates are investigational new drugs or biologics and have not been approved for any indication.

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

and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those

indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA

clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks

related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties

of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development

efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant

risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update

or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year