Tonix Pharmaceuticals Presents Development Update on Potential Smallpox and Monkeypox Vaccine TNX-801 in an Oral Presentation at the World Vaccine and Immunotherapy Congress TNX-801 is Based on the Sequence of a Natural

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals Presents Development

Update on Potential Smallpox and

Monkeypox Vaccine TNX-801 in an Oral Presentation at the World Vaccine and

Immunotherapy Congress

TNX-801 is Based on the Sequence of a Natural

Isolate of Horsepox and is Believed Closer in Structure to Edward Jenner's 1798 Vaccine than Modern Vaccinia Virus Vaccines Against

Live-Virus Vaccine Platform Leverages Tonix's

Expanding Internal Development and Manufacturing Capabilities for Biologics

CHATHAM, N.J., December 1, 2022 - Tonix

Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company,

today announced that Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals, presented data from the Company's TNX-801

(live horsepox virus vaccine) smallpox and monkeypox vaccine development program in an oral presentation at the World Vaccine and Immunotherapy

Congress 2022, being held in San Diego, Calif., November 28 - December 1, 2022. A copy of the Company's presentation is available

under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com

"TNX-801 is a live virus vaccine that

we believe is closer to the smallpox vaccines used in the U.S. and Europe before 1900 than the modern vaccinia smallpox vaccines. TNX-801

has reduced virulence in animals, and we believe it has the potential for widespread use to protect against monkeypox," said Seth

Lederman, M.D., President and Chief Executive Officer. "Recent global outbreaks of monkeypox have highlighted the need to be prepared

with a vaccine that provides durable immunity and blocks forward transmission. Tonix's live virus vaccine technology is designed

to achieve these outcomes."

The oral presentation titled, "Live

Virus Smallpox and Monkeypox Vaccine," describes the history of live virus vaccines and rationale for the development of the

Company's Recombinant Pox Virus (RPV) platform, including TNX-801 to protect against monkeypox and smallpox. The presentation describes

the origins of immunization, beginning with the first live virus vaccine invented by Dr. Edward Jenner in 1798. The inoculation procedure

was called "vaccination" and the inoculum material was initially obtained from lesions on cows affected by a mild disease

known as cowpox. However, Dr. Jenner suspected that cowpox originated from horses8,which led to immunization using material

directly obtained from horses. This procedure was sometimes called "equination". Equination and vaccination were practiced

side-by-side in Europe13,14. Today, molecular analysis of DNA sequences from archaic smallpox vaccines suggests that TNX-801

is closer than modern smallpox vaccinia vaccines to the vaccine discovered and disseminated by Dr. Edward Jenner6-8.

As presented at the Canadian Society for Virology

in June 2022, non-human primates vaccinated with TNX-801 were fully protected with sterilizing immunity from a challenge with intra-tracheal

In July 2022, the Company announced a collaboration

with the Kenya Medical Research Institute (KEMRI) to seek regulatory approval for conducting a Phase 1 clinical study in Kenya to develop

TNX-801 as a vaccine to protect against monkeypox and smallpox. The study is expected to start in the first half of 2023.

About TNX-801 and TNX-1850

TNX-801 is a live virus vaccine based on synthesized

horsepox2,3. Tonix is developing TNX-801 for percutaneous administration as a vaccine to protect against monkeypox and smallpox.

Tonix has previously reported positive data from a monkeypox challenge study in non-human primates4. Tonix is also developing

TNX-1850 (horsepox-based live virus vaccines) for the prevention of COVID-19. TNX-1850 is designed to express the spike protein from the

BA.2 variants of SARS-CoV-2. Tonix has previously reported positive data from a SARS-CoV-2 challenge study in non-human primates in which

animals were vaccinated with TNX-1800, a horsepox-based vaccine expressing spike protein from the Wuhan strain5. Tonix's

TNX-801 was synthesized2 based on the sequence of the 1976 natural isolate Mongolian horsepox clone MNR-763. Molecular analysis

of DNA sequences suggests that TNX-801 is closer than modern smallpox vaccines to the vaccine discovered and disseminated by Dr. Edward

Jenner in 17986-8. For example, recent studies9,10 have shown approximately 99.7% colinear identity between TNX-801

and the circa 1860 U.S. smallpox vaccine VK05.11 The small plaque size in culture of TNX-801 appears identical to the U.S.

Centers for Disease Control publication of the natural isolate12. Relative to vaccinia, horsepox has substantially decreased

virulence in mice2. Dr. Edward Jenner invented vaccination in 1798 and the procedure was called "vaccination" because

cow' is vacca' in Latin and the inoculum material was initially obtained from lesions on the udders of cows

affected by a mild disease known as cowpox. However, Dr. Jenner suspected that cowpox originated from horses8. Subsequently,

Dr. Jenner and others immunized against smallpox using material directly obtained from horses. The use of vaccines from horses was sometimes

called equination' from the Latin equus' which means horse'13. Equination and vaccination

were practiced side-by-side in Europe13,14.

About the Recombinant Pox Virus (RPV) Platform

Horsepox virus and vaccines based on its use

as a vector are live replicating viruses that elicit strong immune responses. Live replicating orthopoxviruses, like vaccinia or horsepox,

can be engineered to express foreign genes and have been exploited 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) manufacturable at scale, and (7) ability to provide direct antigen presentation. Relative to vaccinia, horsepox has substantially

decreased virulence in mice2. Horsepox-based vaccines are designed to be single dose, vial-sparing vaccines, that can be manufactured

using conventional cell culture systems, with the potential for mass scale production and packaging in multi-dose vials. Tonix's

TNX-801 and RPV vaccine candidates are administered percutaneously using a two-pronged, or "bifurcated" needle. The major

cutaneous reaction or "take" to vaccinia vaccine was described by Dr. Edward Jenner in 1796 and has been used since then as

a biomarker for protective immunity to smallpox, including in the World Health Organization's (WHO) accelerated smallpox eradication

program that successfully eradicated smallpox in the 1960's. The "take" is a measure of functional T cell immunity validated

by the eradication of smallpox, a respiratory-transmitted disease caused by variola.

About Monkeypox and Smallpox

Monkeypox15 and smallpox16

are diseases in humans called by the monkeypox and smallpox (or variola) viruses, respectively. Monkeypox and variola are closely related

orthopox viruses. Vaccination against smallpox with live virus vaccines based on horsepox or vaccinia protects against monkeypox. After

routine smallpox vaccination was stopped in about 1970, monkeypox has become a growing problem in Africa. Recently approximately 300 cases

have been identified outside of Africa.17 Smallpox is considered eradicated, but there are concerns about malicious reintroduction.

About Tonix Pharmaceuticals Holding Corp.1

Tonix is a 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 second 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 first 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

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

2Noyce RS, et al. (2018)

PLoS One. 13(1):e0188453

(2006) J Virol. 80(18):9244-58.PMID:16940536