Benzinga | Nov 16, 2020 07:09AM EST

Tonix Pharmaceuticals Reports Positive Immune Response Results from COVID-19 Vaccine Candidate TNX-1800, Following Vaccination of Non-Human Primates

Anti-SARS-CoV-2 Neutralizing Antibodies Elicited in All Eight TNX-1800 Vaccinated Animals

Skin Reaction or "Take," a Validated Biomarker of Functional T cell Immunity, Elicited in All Eight TNX-1800 Vaccinated Animals

CHATHAM, N.J., Nov. 16, 2020 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (NASDAQ:TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced preliminary results following vaccination of non-human primates with TNX-1800 (modified horsepox virus, live vaccine), a live attenuated COVID-19 vaccine candidate engineered to express the SARS-CoV-2 (CoV-2) spike protein after vaccination. The research is part of an ongoing collaboration between Southern Research Institute, the University of Alberta and Tonix.

"We are pleased that all eight animals vaccinated with TNX-1800 manifested "takes", a skin reaction which is a validated biomarker of functional T cell immunity, and that vaccination was associated with neutralizing antibodies in each case," said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. "'Take' has a long history as a validated biomarker for T cell immunity. 'Take' is 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, have been established to provide long-term, durable immunity and to block forward transmission. Single dose horsepox and vaccinia vaccination led to the eradication of smallpox, which, like CoV-2, is transmitted by the respiratory route. In the successful campaign to eradicate smallpox, 'take' was used as a biomarker for protective immunity."

Dr. Lederman continued, "Our hope and our goal is to produce a vaccine that will provide long term immunity with a single dose using a proven technology that can be readily scaled up for manufacturing and that does not require a costly and cumbersome cold chain for distribution and storage. These results encourage us to advance TNX-1800 to human Phase 1 trials in 2021, when we expect to have Good Manufacturing Practice, or cGMP, quality TNX-1800 available. We have previously announced that our manufacturing partner is FUJIFILM Diosynth Biotechnologies."

Key features and results:

* STUDY DESIGN: This on-going study of non-human primates compares TNX-1800 (modified horsepox virus encoding CoV-2 spike protein) to TNX-801 (horsepox virus, live vaccine) at two doses. A control group received a placebo. Each of these five groups (TNX-1800 high and low dose; TNX-801 high and low dose and placebo) includes four animals.

* NEUTRALIZING ANTI-CoV-2 ANTIBODIES: At day 14 after a single vaccination, all eight of the TNX-1800 vaccinated animals made anti-CoV-2 neutralizing antibodies (?1:40 titer) and, as expected, none of the eight TNX-801 vaccinated control animals, or any of the four animals in the placebo group, made anti-CoV-2 neutralizing antibodies (?1:10 titer). The level of neutralizing anti-CoV-2 antibody production was similar between the low and high dose TNX-1800 groups ((1 x 106 Plaque Forming Units [PFU]) and 3 x 106 PFU, respectively).

* TOLERABILITY:TNX-1800 and TNX-801 were well tolerated at both doses.

* SKIN TAKE BIOMARKER: Further, as an expected additional outcome, all 16 animals vaccinated with either dose of TNX-1800 or the control TNX-801 manifested a "take", or cutaneous response, signaling that the horsepox vector elicited a strong T cell immune response.

* DOSE: These results support the expectation that TNX-1800 at the low dose of 1 x 106 PFU is an appropriate dose for a one-shot vaccine in humans, and indicate that 100 doses per vial is the target format for commercialization, which is suited to manufacturing and distribution at large scale.

* CONCLUSIONS: Together, these data show that TNX-1800 induces a strong immune response to CoV-2 in non-human primates. These data confirm that "take" is a biomarker of a strong immunological response to TNX-1800's vector, horsepox virus vaccine, and also indicate that "take" is predictive of a neutralizing antibody response to TNX-1800's cargo COVID-19 antigen, which is the CoV-2 spike protein.

* NEXT PHASE: In the second phase of the study, the TNX-1800 vaccinated and control animals will be challenged with CoV-2. Results are expected in the first quarter of 2021.

About TNX-1800

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. Horsepox and vaccinia are closely related orthopoxviruses that are believed to share a common ancestor. Tonix's TNX-1800 vaccine candidate is administered percutaneously using a two-pronged, or "bifurcated" needle. TNX-1800 is based on a horsepox vector, which is a live replicating, attenuated virus that elicits a strong immune response. 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. 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. 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 mice1. 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