Tonix Pharmaceuticals Presented Data on the Potential Mpox Vaccine TNX-801 in "Using Synthetic Biology to Battle Mpox" Talk at Immunology Symposium at the University of Alberta TNX-801 vaccination demonstrated efficacy i

Tonix Pharmaceuticals Presented Data on the Potential

Mpox Vaccine TNX-801 in "Using Synthetic Biology to Battle Mpox" Talk at Immunology Symposium at the University of Alberta

TNX-801 vaccination demonstrated efficacy in protecting

animals from lethal challenge with clade I monkeypox and is in development as an mpox vaccine

New data show improved tolerability in immunocompromised

animals and no evidence of spreading to blood or tissues even at high doses

Tonix's synthetic horsepox vaccine platform

has been selected by NIH's Project NextGen for clinical testing

CHATHAM, N.J., September 9, 2024 - Tonix Pharmaceuticals

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

of development candidates, today announced data presented at a symposium hosted by the Department of Medical Microbiology & Immunology

and the Li Ka Shing Institute of Virology to celebrate the career and honor the retirement of Tonix's collaborator, David Evans,

Ph.D., FCAHS, Emeritus Professor, Department of Cell Biology, University of Alberta. A copy of the Company's presentation is available

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

The presentation titled, "Using Synthetic Biology

to Battle Mpox", detailed the Company's vaccine platform, led by TNX-801 (horsepox, live virus vaccine for percutaneous

administration) for preventing mpox (formerly known as monkeypox). TNX-801 is an attenuated live-virus vaccine based on synthesized horsepox

that has been shown to provide single-dose immune protection against a monkeypox challenge with better tolerability than 20th

century vaccinia live-virus vaccines in animals.

TNX-801 is structurally closer to 19th century

live-virus vaccinia vaccines than 20th century versions. 1-3 Genomic sequencing of archaic smallpox vaccines has

shown that vaccines used prior to 1900 would be called horsepox' today.1-3 While effective against smallpox as

single-dose vaccines, 20th century vaccines have diverged from horsepox-like progenitors to have greater virulence and toxicity

than TNX-801 in animals. The U.S. Food and Drug Administration (FDA) recently approved ACAM2000 from Emergent Technologies for preventing

mpox.4 ACAM200 is a live-virus vaccine derived from a 20th Century vaccinia vaccine. ACAM2000 carries a Black Box

warning on its package insert labeling warning of tolerability issues, including myocarditis and pericarditis, encephalitis, encephalomyelitis,

encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major, eczema vaccinatum

resulting in permanent sequelae or death, and risks in certain individuals that may result in severe disability, permanent neurological

sequelae and/or death.5

The Jynneos vaccine from Bavarian Nordic is a non-replicating

vaccinia vaccine that is FDA-approved for mpox with a two-dose regimen requiring sterile injection.6 Single-dose TNX-801 has

advantages over non-replicating vaccinia vaccines which require two doses. Percutaneous TNX-801 has advantages over vaccines which require

The durability of protection from 19th century

live-virus vaccinia vaccines was believed to last decades or even be live-long. Consequently, single-dose TNX-801 is believed to stimulate

long-lived T cell immunity. Consequently, TNX-801 will not require multiple repeated doses at six-month intervals like mRNA vaccines.7

Also, the stability of live-virus vaccines, particularly in lyophilized form, eliminates the need for ultra-cold storage which complicates

the widespread use of mRNA vaccines in Africa, where they are needed most right now.

Tonix's focus on single-dose vaccines adheres to recommendations

by the Bipartisan Commission on Biodefense8, and the U.S. National Academies of Science (NAS).9 For example, the

NAS report highlights the difficulty of a case-contact or "ring" vaccination strategy with even a two-dose regimen.9

In the presentation, Tonix highlighted positive preclinical

efficacy data, demonstrating that TNX-801 protected animals against lethal challenge with intratracheal clade I monkeypox virus.10

An outbreak of Clade I mpox has recently been declared a Public Health Emergency of International Concern (PHEIC) by the World Health

Organization (WHO).11,12 Starting from an outbreak in the Democratic Republic of the Congo, clade I mpox has spread to several

Central African Countries and cases have been reported in Sweden, Thailand and Singapore. According to the U.S. Centers for Disease Control

and Prevention (CDC), and other experts, there is a significant risk that clade I strain may appear in the U.S.13 Clade I mpox

is typically associated with higher case fatality rates than clade II mpox.

After a single dose vaccination, TNX-801 prevented clinical

disease and lesions and also decreased shedding in the mouth and lungs of animals challenged with clade I monkeypox.10 These

findings are consistent with TNX-801 inducing mucosal immunity and suggest TNX-801 has the ability to block forward transmission, similar

to Dr. Edward Jenner's vaccinia vaccine, descendants of which eradicated smallpox and kept mpox out of the human population.

The presentation at University of Alberta included results

from Tonix scientists at the Research and Development Center (RDC) in Frederick, Md. Data from a manuscript showed that TNX-801 is highly

attenuated relative to 20th century vaccinia vaccines in in immunocompromised animals.14 New data showed TNX-801

is unable to spread in blood or tissues in these animals, even at an approximately 100-Fold higher dose than 20th century vaccinia

In addition to characterizing TNX-801's activity and

tolerability, Tonix scientists have explored the characteristics of the monkeypox virus. The prior 2022 global clade IIb mpox outbreak,

affected over 90,000 persons in countries where mpox previously had not been endemic, including Europe and the US. The spread of clade

IIb strain mpox in 2022 underscores the pandemic potential of mpox. Data presented show that monkeypox clade IIb from a 2022 isolate in

Massachusetts is 10,000- to 100,000-fold more attenuated than clade IIa isolates from 2003. The attenuation of clade II monkeypox in the

recent 2022 outbreak may have contributed to its greater dissemination. The new and more lethal clade I monkeypox has not yet been analyzed.

"We are excited to develop TNX-801 to prevent mpox and

control mpox epidemics," said Seth Lederman, M.D., Chief Executive Officer of Tonix. "TNX-801 has conferred protective immunity

to animals with single-dose administration. We believe TNX-801 can be manufactured at scale economically with standard shipping and storing

requirements. Evidenced by the second WHO declared PHEIC involving an mpox epidemic since 2022, viral diseases are rapidly evolving and

our methods to developing effective vaccines must evolve just as rapidly. Synthetic biology is an important technology for vaccine development.

We believe the potential of TNX-801 is supported by real world evidence based on the success of horsepox-like vaccines prior to 1900 in

protecting against smallpox and containing smallpox outbreaks. When smallpox vaccination with live-virus vaccinia vaccines was employed

in Africa prior to eradication, mpox was kept out of the human population."

Dr. Lederman continued, "We recently announced a collaboration

to develop GMP manufacturing processes for TNX-801 with Bilthoven Biologics (Bbio), part of the world's largest vaccine manufacturer,

the Cyrus Poonawalla Group, which also includes the Serum Institute of India. In addition, TNX-801 has the potential to be used as a viral

vector platform, for which recombinant versions, like TNX-1800 for COVID-1911,12, can be developed to protect against other

infectious diseases that may emerge from this ever-evolving viral landscape. We are excited for TNX-1800's inclusion into the U.S.

National Institute of Health's (NIH's) Project NextGen."

TNX-801 is a live replicating attenuated vaccine based on

horsepox that is believed to provide immune protection with better tolerability than 20th century vaccinia viruses. As previously

disclosed, TNX-801 protected animals against lethal challenge with intratracheal clade I monkeypox virus.10 After a single

dose vaccination, TNX-801 prevented clinical disease and lesions and also decreased shedding in the mouth and lungs of non-human primates.10

The Findings are consistent with mucosal immunity and suggest the ability to block forward transmission, similar to Dr. Edward Jenner's

vaccinia vaccine, which eradicated smallpox and kept mpox out of the human population. On August 26, 2024, Tonix announced a collaboration

to develop GMP manufacturing processes for its mpox vaccine with Bilthoven Biologics (Bbio), part of the world's largest vaccine

manufacturer, the Cyrus Poonawalla Group, which also includes the Serum Institute of India.

On the horsepox platform, Tonix is developing TNX-1800 (horsepox

expressing SARS-CoV-2 spike protein) for protecting against COVID-19. TNX-1800 is an engineered version of horsepox that expresses the

spike protein of SARS-CoV-2. In preclinical studies of TNX-1800 highlighted in the presentation, TNX-1800 was tested for immunogenicity

and efficacy of TNX-1800 in nonhuman primates following a SARS CoV-2 challenge.14,15 TNX-1800 vaccination results in a neutralizing

antibody response that was associated with significant reduction in virus replication/shedding in the respiratory tract and tolerability.

11,12 TNX-1800 was selected by the NIH's, Project NextGen for inclusion in clinical trials as part of a select group

of next generation COVID-19 vaccine candidates with the intent to identify promising vaccine platforms. NIH plans to conduct a Phase 1

trial of TNX-1800 and cover the full cost of the study, while Tonix provides the vaccine candidate.

On August 14, 2024, the WHO determined that the upsurge of

mpox in a growing number of countries in Africa constitutes a public health emergency of international concern, the second such declaration

in the past two years called in response to an mpox outbreak. The current outbreak was caused by clade I monkeypox virus, while the 2022

outbreak was clade II monkeypox virus. The global mpox outbreak, which commenced in 2022 has affected over 90,000 persons in countries

where mpox had previously not been endemic, including Europe and the US. The spread of clade IIb strain mpox in 2022 underscores the pandemic

potential of mpox. Unlike clade IIb mpox, the clade I strain of mpox appears to be spreading to countries neighboring the Democratic Republic

of the Congo. Clade I mpox is typically associated with approximately twenty times the case fatality rates than Clade IIb mpox in Africa.

According to the U.S. Centers for Disease Control and Prevention (CDC), and other experts, there is a significant risk that the deadlier

clade I strain may appear in the U.S.13