Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Tonix Pharmaceuticals
Announces Results of Pre-IND Meeting with FDA for TNX-1800 as a Potential Vaccine to Prevent COVID-19
TNX-1800 is a Live Virus Vaccine Designed to Elicit
Durable T-cell Immunity
TNX-1800 is a Modified Version of Dr. Edward Jenner's
Vaccine that Eradicated Smallpox, Engineered to Express SARS-CoV-2 Spike Protein
In Animal Testing, TNX-1800 Protected Upper and
Lower Airways After Challenge with SARS-CoV-2, Suggesting an Ability to Block Forward Transmission
Phase 1 Trial of TNX-1800 for the Prevention of
COVID-19 Expected to Start in the First Half of 2022
CHATHAM, NJ, September 13, 2021 (GLOBE NEWSWIRE)
- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced
it received the official written response from a Type B pre-Investigational New Drug (IND) meeting with the U.S. Food and Drug Administration
(FDA) to develop TNX-18001 (recombinant horsepox virus, live vaccine) as a potential SARS-CoV-2 vaccine to protect against
Tonix believes the written response provides
a path to agreements on the design of a Phase 1 study and the overall clinical development plan to qualify TNX-1800 as a vaccine to prevent
COVID-19. Based on the response, the Company expects to begin a Phase 1 study in the first half of 2022.
TNX-1800 is a live virus vaccine based on the
horsepox viral vector platform designed to express the SARS-CoV-2 spike protein and to protect against COVID-19, primarily by eliciting
a T cell response. Tonix reported positive efficacy data from animal studies of TNX-1800 in the first quarter of 2021. The horsepox virus
is closely related to the vaccine developed by Dr. Edward Jenner more than 200 years ago that led to the eradication of smallpox.
Seth Lederman, M.D., President and Chief Executive
Officer of Tonix, stated, "The pre-IND meeting written response marks an important milestone in the development of TNX-1800. We
have obtained FDA concurrence and clear guidance on the proposed manufacturing, nonclinical pharmacology and toxicology studies, and the
Phase 1 clinical design." Dr. Lederman continued, "Operation Warp Speed (OWS) vaccines were available very rapidly and have
made a huge contribution to the health of the U.S. population, but they have limitations, particularly in terms of the short duration
of protection and the likely requirement for boosters. Concerns about durability of protection have led Pfizer and Moderna, the innovators
of the two most widely used COVID-19 vaccines in U.S., to file or plan to file for approval of booster shots within eight months after
the administration of each vaccine's second dose."
"It's taken longer to develop live
virus vaccines relative to the OWS vaccines," Dr. Lederman added, "but live virus vaccines for other viruses have proven to
induce durable T cell immunity, prevent serious illness after infection and block forward transmission. These properties have been demonstrated
with vaccines against smallpox, chickenpox, mumps, measles, and rubella, among others. We designed TNX-1800 as a potential single dose
vaccine using a virus that is closely related to Dr. Jenner's vaccine, which provided long term, even lifetime T cell immunity to
smallpox, prevented forward transmission of the smallpox virus, and eradicated that disease."
Dr. Lederman continued, "Unlike smallpox,
we do not expect COVID-19 to be eradicated because there are asymptomatic spreaders, a relatively long period when people are infectious
before they become symptomatic and numerous animal reservoirs. Like Jenner's smallpox vaccine, we expect TNX-1800 can potentially
be scaled up for manufacturing and will not require a costly and cumbersome cold chain for distribution and storage. We expect it will
also be glass-sparing, with 100 doses filled per vial."
"Many believe that after the COVID pandemic
passes COVID will become endemic, and it will likely remain a long-term concern", Dr. Lederman added. "Because of this, we
believe the need for new vaccine technologies will be ongoing and may lead to vaccines that are tailored to each person's health,
genetics or age using precision medicine. Ultimately, a childhood vaccination like the MMR for measles, mumps and rubella with long lasting
protection may be what's needed to control COVID in the future. Together with an expected strong and durable immune response, ability
to manufacture at scale, store and ship in standard refrigeration, a live virus vaccine like TNX-1800 could become a global product."
Anthony Macaluso, Ph.D., Executive Vice President
of Strategic Development of Tonix, commented, "We previously reported the positive results of TNX-1800 in animals after a live SARS-CoV-2
challenge. Animals vaccinated with TNX-1800 had undetectable SARS-CoV-2 in their upper and lower airways six days after challenge with
SARS-CoV-2. Animals vaccinated with TNX-1800 manifested both neutralizing antibodies and a take', which is a skin reaction
to horsepox vaccination that also serves as a validated biomarker of functional T cell immunity."
Dr. Macaluso continued, "The 'take
is considered important because it is otherwise difficult and costly to measure the T cell response to a vaccine. Vaccines that elicit
a strong T cell response, like horsepox and closely related vaccinia virus vaccine, have been established to provide long-term, durable
immunity and to block forward transmission. In the successful campaign to eradicate smallpox, which was also spread by the respiratory
route like COVID-19, the take' was used as a biomarker for protective immunity. We believe the absence of detectable CoV-2
in the upper airways shows the potential for TNX-1800 to decrease shedding of virus and is consistent with decreased forward transmission."
Dr. Lederman added, "The reliable durability
of vaccine protection from the OWS vaccines is under review1, leading the makers of the two mRNA vaccines to take steps towards
seeking approval of booster shots and setting up the possible need for boosters on a regular basis in the future. The U.S. government
has pledged to make available booster shots for the mRNA vaccines available starting on September 20, pending FDA approval. The prospect
of boosters poses a challenging and expensive public health policy implementation in the U.S. In contrast to the short duration of protection
of the OWS COVID-19 vaccines, live virus vaccines typically provide decades or life-long protective immunity against those diseases. Live
virus vaccines activate the immune system in ways that scientists do not completely understand and have not yet been able to recreate
with other technologies."
TNX-1800 is a live modified horsepox 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. TNX-1800 is based on a horsepox vector, which is a live replicating, attenuated virus that elicits a strong immune response.
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. 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. Horsepox and vaccinia are closely
related orthopoxviruses that are believed to share a common ancestor horsepox3-7. Relative to vaccinia, horsepox has substantially
decreased virulence in mice7. Molecular analysis shows that horsepox is closer than modern vaccinia vaccines in DNA sequence
to the vaccine discovered and disseminated by Dr. Edward Jenner, which protected against smallpox, a respiratory-transmitted disease caused
by the orthopox virus, variola.4-7 Vaccine genome researchers have established the contemporaneous use of horsepox and horsepox-related
viruses in the United States as smallpox vaccines in the 1860's, and found a remarkable degree of identity with the circa 1860 U.S.
smallpox vaccine VK05 and the 1976 Mongolian horsepox isolate called MNR-76, upon which Tonix's TNX-801 is based.3,8-10
Tonix's proprietary horsepox vector is believed to be more closely related to Jenner's vaccinia vaccine than modern vaccinia
vaccines, which appear to have evolved by deletions and mutations to a phenotype of larger plaque size in tissue culture and greater virulence
in mice. The small plaque size in culture of TNX-801 appears identical to the U.S. Centers for Disease Control publication of the natural
isolate11. Tonix's TNX-1800 vaccine candidate is 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 179612
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. Tonix reported that immunization with a single dose of TNX-1800
induced "takes" and neutralizing anti-SARS-CoV-2 antibodies in non-human primates. 13
1TNX-1800 is in the pre-IND stage and has not been approved
Statement from HHS Public Health and Medical Experts on COVID-19 Booster Shots
3Tulman ER, et al. (2006) J Virol. 80(18):9244-58.PMID:16940536
4Qin et al. J. Virol. 89:1809 (2015).
5Esparza E, et al Vaccine. (2017) 35(52):7222-7230.
5Schrick L et al N Engl J Med (2017); 377:1491-1492
7Noyce RS, et al. (2018) PLoS One. 13(1):e0188453
8Brinkmann A et al, Genome
Biology (2020) 21:286 https://doi.org/10.1186/s13059-020-02202-0