Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Tonix Pharmaceuticals Announces Publication of Paper
in Viruses Highlighting the Company's Development of a Vaccine to Protect Against Monkeypox and Smallpox (TNX-801)
Preclinical data demonstrate the efficacy of TNX-801
vaccination against monkeypox virus challenge in an animal model
Phase 1 trial with TNX-801 for the prevention of monkeypox
and smallpox is expected to start in the second half of 2023
CHATHAM, N.J., February 9, 2023 - Tonix Pharmaceuticals
Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced the publication of a
paper entitled, "Single Dose of Recombinant Chimeric Horsepox Virus (TNX-801) Vaccination Protects Macaques from Lethal Monkeypox
Challenge," in the journal Viruses. The publication demonstrates that a single dose vaccination with TNX-801
was effective at protecting non-human primates from infection with monkeypox virus. The article can be accessed online at https://www.mdpi.com/1999-4915/15/2/356.
"The global monkeypox outbreak that started
in the spring of 2022 reinforced the importance of protecting the population using live virus vaccines," said Seth Lederman, M.D.,
Chief Executive Officer of Tonix Pharmaceuticals. "Consequently, there is a need for an effective and safer, single dose, live replicating
vaccine against monkeypox virus. Given the encouraging preclinical data to date, one potential approach is to use a live virus vaccine
based on horsepox, such as TNX-801."
Ph.D., FCAHS, Professor and former Vice-Dean (Research) Faculty of Medicine and Dentistry at the University of Alberta and an investigator
in the study and author of the publication, said, "It is often forgotten that vaccines don't always produce sterilizing
immunity and so it's very exciting to be able to report that a horsepox-based vaccine works so well in such a challenging infection
The publication describes data from animals in which
eight out of eight vaccinated with TNX-801 were fully protected with sterilizing immunity from a challenge with intra-tracheal monkeypox
(central African, or Congo Basin, clade). The vaccinations with TNX-801 were well tolerated as indicated by the lack of any overt clinical
disease. These data show that the immunity generated by TNX-801 was able to provide protection against a lethal challenge with monkeypox
virus and is the first study to demonstrate the efficacy of TNX-801 vaccination against monkeypox virus challenge in a non-human primate
model. Synthetic horsepox virus is the basis for the Company's TNX-801 vaccine in development to protect against monkeypox and smallpox
and for the Company's Recombinant Pox Virus (RPV) platform to protect against other pathogens, including SARS-CoV-2.
About TNX-801 and TNX-1850
TNX-801 is a live virus vaccine based on horsepox2,3.
Tonix is developing TNX-801 for percutaneous administration as a vaccine to protect against monkeypox and smallpox. Tonix is also developing
TNX-1850 (horsepox-based live virus vaccine) for the prevention of COVID-19. TNX-1850 is designed to express the spike protein from the
BA.2 variant 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 strain4. Tonix's
TNX-801 is based on the sequence of the 1976 natural isolate Mongolian horsepox clone MNR-763.2 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 17985-7.
For example, recent studies8,9 have shown approximately 99.7% colinear identity between TNX-801 and the circa 1860 U.S. smallpox
vaccine VK05.10 The small plaque size in culture of TNX-801 appears identical to the U.S. Centers for Disease Control publication
of the natural isolate11. 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 horses7. 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'12. Equination and vaccination were practiced side-by-side in Europe12,13.
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. 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
Monkeypox14 and smallpox15
are diseases in humans caused 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. Since May of 2022, approximately
30,000 cases have been identified in the United States.16,17 There are two distinct clades of the monkeypox virus: the central
African (Congo Basin) clade, and the west African clade which is associated with the recent outbreak. Historically, the Congo Basin clade
has caused more severe disease than the west African clade. In recent times, the case fatality ratio for the virus is about 3-6%.18
In November, 2022, the WHO began using a new preferred term "mpox" as a synonym for monkeypox.19 Smallpox is considered
eradicated, but there are concerns about malicious reintroduction.
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. 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 second quarter of 2023. TNX-1900
(intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is being studied in a potential pivotal Phase
2 study that initiated enrollment 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 second quarter of 2023. Tonix's infectious
disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801, a next-generation vaccine to prevent COVID-19,
TNX-1850, a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600, and humanized anti-SARS-CoV-2 monoclonal antibodies,
TNX-3800, recently licensed from Curia. 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 the second half of 2023.
1All of Tonix's 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
3Tulman ER, et al. (2006)
J Virol. 80(18):9244-58.PMID:16940536
4Tonix Press Release March
5Schrick L et al. (2017)
N Engl J Med. 377:1491.
6Qin et al. (2015) J. Virol.