Tonix Pharmaceuticals Reports Positive COVID-19 Vaccine Efficacy Results in Non-Human Primates Vaccinated with TNX-1800 and Challenged with Live SARS-CoV-2

On Mar 17, 2021

Tonix Pharmaceuticals Holding Corp. a clinical-stage biopharmaceutical company, 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. Immunogenicity and protective efficacy of single-dose TNX-1800 were assessed at two dose levels (n=4 per group). At Day 41 after the vaccination, animals were challenged with live SARS-CoV-2 through intra-nasal and intra-tracheal routes. Protection was assessed at Day 47, six days after challenge. The research is part of an ongoing collaboration between Southern Research, the University of Alberta and Tonix.

“We are pleased that all eight animals vaccinated with TNX-1800 had undetectable SARS-CoV-2 in their upper and lower airways 6 days after challenge with SARS-CoV-2,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “Today’s results are from the second phase of a study in which TNX-1800 vaccinated and control animals were challenged with SARS-CoV-2. Last Fall, we reported that all eight of animals vaccinated manifested ‘takes’, a skin reaction to horsepox vaccination which is a validated biomarker of functional T cell immunity, and that vaccination was associated with neutralizing antibodies in each case. The positive results of the protection from live CoV-2 challenge that we are reporting today validate the capacity for TNX-1800 to protect against COVID-19, and also validate the ‘take’ after TNX-1800 vaccination as a biomarker for functional T cell immunity.”

Dr. Lederman continued, “ ’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, 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. We believe the absence of detectable CoV-2 in the upper or lower airways shows the potential for TNX-1800 to decrease shedding of virus and is consistent with decreased transmission.”

“Although many successful vaccines have been put into use around the world, much remains unknown about COVID-19, its emerging variants, and the durability of current vaccines,” Dr. Lederman continued “We designed TNX-1800 as a single dose vaccine using a vector known to provide long term T cell immunity. This was originally demonstrated by the vector’s use as the backbone of Edward Jenner’s smallpox vaccine which typically provided lifetime immunity with a single dose. Moreover, by preventing forward transmission of the smallpox virus, it became a defining force in establishing herd immunity.Like Jenner’s smallpox vaccine, TNX-1800 can be scaled up for manufacturing and will not require a costly and cumbersome cold chain for distribution and storage. It will also be glass-sparing, with 100 doses filled per vial. These features, coupled with the results announced today, encourage us to advance TNX-1800 to human Phase 1 trials in the second half of 2021 when we expect to have Good Manufacturing Practice, or cGMP, quality TNX-1800 available.”

The Company believes the findings also demonstrate the flexibility of the horsepox vaccine platform and its capability to be tailored to other diseases of interest in military and civilian populations.

Key features and results:

STUDY DESIGN: This study of non-human primates compared TNX-1800 (modified horsepox virus encoding CoV-2 spike protein) to TNX-801 (horsepox virus, live vaccine) at two doses. Also 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) included four animals.
CoV-2 CHALLENGE: At day 41 after vaccination (or placebo), each animal was exposed to SARS-COV-2 by intra-tracheal (1 x 10⁶ TCID₅₀) and intra-nasal (1 x 10⁶ TCID₅₀) administration.
DETECTION OF SARS-COV-2 in Upper and Lower Airway: Upper airway virus was studied by oropharyngeal swabs and lower airway virus by tracheal lavage using qRT-PCR to determine the number of genome copies of SARS-CoV-2 present in the samples. Six days after challenge, no (0/8) samples taken from animals vaccinated with TNX-1800 showed infection (more than 1,000 genome copies of SARS CoV-2) in either upper or lower airway samples. In contrast, all (8/8) animals vaccinated with the control vaccine TNX-801 showed infection in either the upper or lower airway samples as did all (4/4) monkeys vaccinated with vehicle control.
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). At 6 days after CoV-2 challenge, TNX-1800 vaccinated animals showed neutralizing antibody titers of (≥1:1280 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). For unvaccinated animals challenged with SARS-CoV-2, neutralizing antibodies were measurable after vaccination (≥1:40 titer) that were lower and appeared later than neutralizing antibodies in TNX-1800 vaccinated animals.
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 elicits 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 well suited to manufacturing and distribution at large scale.
CONCLUSIONS: Together, these data show that TNX-1800 induces protection against SARS-COV-2 infection in non-human primates. These data confirm that “take” is a biomarker of protection of upper and lower airways from SARS-CoV-2 challenge, and a biomarker of immunological response to TNX-1800’s cargo COVID-19 antigen, which is the CoV-2 spike protein.
NEXT PHASE: Phase 1 human study targeted to start in the second half of 2021, following Investigational New Drug (IND) clearance by the U.S. Food and Drug Administration (FDA) and the production of GMP material.

Anthony Macaluso, Ph.D., Executive Vice President, Strategic Development at Tonix said, “In addition to their impact on the development of a COVID-19 vaccine, these data also demonstrate the utility of horsepox as a vaccine platform that can be used to address many other diseases of interest to the military and the general public. The horsepox platform has the following attributes favorable for vaccine development: strong induction of both B and T cell immunity; amenability to genetic modification; and the ability to express multiple genes, either alone or in combination. In addition, the horsepox vaccine platform allows for rapid scalability of manufacturing, which is a key advantage of the horsepox virus over other platforms such as non-replicating viruses, DNA/RNA, or protein subunit vaccines.”