Tonix Pharmaceuticals' Vaccine Candidate, TNX-1800, Selected by NIH/NIAID Project NextGen for Inclusion in Clinical Trials NIAID is conducting early phase clinical trials on select next generation COVID-19 vaccine candid

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals' Vaccine Candidate,

TNX-1800, Selected by NIH/NIAID Project NextGen for Inclusion in Clinical Trials

NIAID is conducting early phase clinical trials

on select next generation COVID-19 vaccine candidates with the intent to identify promising vaccine candidates

TNX-1800, a live virus percutaneous vaccine

candidate, is based on Tonix's recombinant pox virus (RPV) platform

Phase 1 clinical trial of TNX-1800 expected

to start in the second half of 2024

NIAID will cover the full cost of the clinical

trial; Tonix will supply the vaccine candidate

CHATHAM, N.J., November 2, 2023 - Tonix

Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates,

today announced that the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH),

will conduct a Phase 1 clinical trial with TNX-1800 (recombinant horsepox virus, live vaccine),1 Tonix Pharmaceuticals'

vaccine candidate to protect against COVID-19.

a novel vaccine platform initially targeting COVID-19, smallpox and mpox (monkeypox). The intent is to provide durable protection against

severe disease and prevent forward transmission, primarily by eliciting a T-cell immune response. TNX-1800 expresses the spike protein

of SARS-CoV-2, was immunogenic, well tolerated2 showed promise in protecting animals from challenge with SARS-CoV-2 delivered

directly into the lungs.3 A related horsepox-based vaccine, TNX-8011, protected animals against challenge with monkeypox

virus delivered directly into the lungs.4 TNX-801 is also the vector on which TNX-1800 is based and has been shown to be >1,000-fold

more attenuated than modern vaccinia virus vaccine (VACV) strains in immunocompromised mice.5 The Phase 1 trial of TNX-1800

is expected to start in the second half of 2024. NIAID will study TNX-1800 by percutaneous administration.

novel vaccine platform technology has the potential to provide durable protection from respiratory pathogens and slow their spread,"

said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "TNX-1800 will be the first vaccine candidate using

our live virus recombinant pox virus (RPV) platform technology to enter clinical trials. We hope to expand the portfolio of RPV-based

vaccines to address several other known respiratory threats including smallpox, mpox and tuberculosis. We are committed to supporting

NIAID in assembling a variety of vaccine platform options to ensure the availability of effective vaccines in the face of known and emerging

threats. We look forward to participating in the Project NextGen initiative."

is an initiative by the U.S. Department of Health and Human Services (HHS) to advance a pipeline of new, innovative vaccines and therapeutics

for COVID-19. NIAID will be conducting clinical trials to evaluate several early-stage vaccine candidates. The Phase 1 study involving

TNX-1800 is designed to assess safety and immunogenicity in approximately 60 healthy adult volunteers. Upon completion of the trial, NIAID

and Tonix Pharmaceuticals will assess the results and determine the next steps for the development of TNX-1800.

NIAID will cover the

full cost of the clinical trial, including operations and related analysis. Tonix will be responsible for providing clinical trial materials,

and upon completion will have the right to rely on the findings in regulatory filings with the U.S. Food and Drug Administration (FDA)

to support the approval of its COVID-19 vaccine and other vaccines based on the RPV platform.

Project NextGen is a $5 billion initiative to

develop the next generation of vaccines and therapeutics to combat COVID-19. Based at the HHS and led by the Administration for Strategic

Preparedness and Response's Biomedical Advanced Research and Development Authority and the NIH's NIAID, Project NextGen will

coordinate across the federal government and the private sector to advance the pipeline of new, innovative vaccines and therapeutics into

clinical trials and potential review by the U.S. Food and Drug Administration (FDA) for authorization or approval, and commercial availability

for the American people. The program will focus on several areas, including mucosal vaccines, vaccines that provide broader protection

against variants of concern and a longer duration of protection, pan-coronavirus vaccines, and new and more durable monoclonal antibodies.

TNX-1800 (recombinant horsepox virus) is a live virus vaccine for percutaneous administration that is designed to express the spike protein

of the SARS-CoV-2 virus and to elicit a predominant T cell response. The RPV platform is based on a horsepox vector, which is a live replicating,

attenuated virus that has been shown to be >1,000-fold more attenuated than modern VACV strains in immunocompromised mice.5

Horsepox and the vaccinia vaccine viruses are closely related orthopoxviruses that are believed to share a common ancestor. Molecular

analysis shows that horsepox is closer than modern vaccinia vaccines in DNA sequence to the vaccine discovered and disseminated by Dr.

Edward Jenner. 6-9 Live replicating orthopoxviruses, like vaccinia or horsepox, can be engineered to express foreign genes

and have been explored as platforms for vaccine development because they possess; (1) large packaging capacity for exogenous DNA inserts,

(2) precise virus-specific control of exogenous gene insert expression, (3) lack of persistence or genomic integration in the host, (4)

strong immunogenicity as a vaccine, (5) ability to rapidly generate vector/insert constructs, (6) readily manufacturable at scale, and

(7) ability to provide direct antigen presentation. Relative to vaccinia, horsepox has substantially decreased virulence in mice.4,6

The current formulation is a frozen liquid, but we believe that future lyophilized versions can be stored and shipped at standard refrigeration.

Horsepox-based vaccines are designed to be single dose, vial-sparing vaccines that can be administered without sterile injection, manufactured

using conventional cell culture systems with the potential for mass scale production, and packaged in multi-dose vials. Moreover, we believe

the low dose of TNX-1800 makes this technology amenable for future implementation in microneedle delivery systems.

TNX-801 (recombinant horsepox virus) is a live

virus vaccine based on horsepox4-7 in pre-clinical development to prevent smallpox and mpox. Tonix reported positive preclinical

efficacy data, demonstrating that TNX-801 vaccination protected non-human primates against lethal challenge with monkeypox.4 Tonix

has received official written response from a Type B pre-Investigational New Drug Application (IND) meeting with the U.S. Food and Drug

Administration (FDA) to develop TNX-801 as a potential vaccine to protect against mpox disease and smallpox.10 Tonix believes

the FDA feedback provides a path to agreement on the design of a Phase 1 /2 study and the overall clinical development plan. The Phase

1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an

IND. More than 30,000 people have contracted mpox in the U.S. so far during the 2022-23 epidemic,11 The recent cluster of

mpox in Chicago revealed breakthrough cases of mpox in individuals who had been vaccinated with the currently authorized non-replicating

vaccine, which is administered in two doses.12 In contrast, TNX-801 is delivered percutaneously with only one dose and therefore

may achieve higher rates of community protection by eliminating drop-out between doses and limiting forward transmission. Moreover, relying

on only one approved mpox vaccine at present is a risk for the global supply chain that has already led to insufficient availability

of vaccines to meet global health needs, especially in Africa. TNX-801 has the potential to make a global impact on mpox and the risk

of smallpox because of its durable T-cell immune response, the potential to manufacture at scale, and the use of a lower dose than non-replicating

Pharmaceuticals Holding Corp.*

Tonix is a biopharmaceutical company focused on commercializing,

developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial

subsidiary, markets Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg under a

transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch

and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix's development portfolio

is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix's CNS development

portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix's lead

development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia,

having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late

December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Enrollment

in a Phase 2 proof-of-concept study has been completed, and topline results were reported in the third quarter of 2023. TNX-1900 (intranasal

potentiated oxytocin), is in development as a preventive treatment for chronic migraine, and enrollment has been completed in a Phase

2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric

obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. 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 fourth quarter of 2023. Tonix's rare disease development 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 development 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 rejection

and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix's infectious

disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine

platform or recombinant pox vaccine platform for other infectious diseases, including TNX-1800, in development as a vaccine to protect

against COVID-19. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum

small molecule oral antivirals.

*Tonix's product development candidates are

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

Zembrace SymTouch and Tosymra are registered trademarks