Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Tonix Pharmaceuticals Initiates Enrollment in Clinical
Trial of TNX-2100, a Diagnostic Skin Test to Measure Functional T Cell Immunity to SARS-CoV-2
Potential Uses Include: Biomarker of Immunity to
SARS-CoV-2; Personalized Approach to Timing COVID-19 Vaccine Boosters; Public Health Surveillance; and Serving as an Endpoint for COVID-19
Topline Data Expected in First Half 2022
CHATHAM, N.J., January 11, 2022 (GLOBE NEWSWIRE)
-- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced
that the first participant was enrolled in a dose-finding study for TNX-2100 (SARS-CoV-2 epitope peptide mixtures for intradermal administration),
an in vivo skin test to measure delayed-type hypersensitivity (DTH) to SARS-CoV-2 (CoV-2), the virus that causes COVID-19. DTH
is a measure of functional T cell immunity.
"The SARS-CoV-2 skin test is designed
to measure T cell immunity," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "In other infectious
diseases, T cell immunity prevents serious disease and blocks forward transmission. Because antibodies are easier to measure, there has
been more discussion about antibodies rather than T cells as a biomarker of immunity to SARS-CoV-2. However, T cells, not antibodies,
are the body's major defense against viruses. The skin test has the potential to serve as: 1) a biomarker for T cell protective
immunity and durability of vaccine protection; 2) a personalized approach for vaccine boosters; 3) a method to stratify participants in
COVID-19 vaccine trials with a more complete picture of immune status; 4) an endpoint in COVID-19 vaccine trials for vaccines that elicit
T cell immunity, and 5) public health surveillance. We believe the TNX-2100 skin test has the potential to address the unmet need for
a rapid, sensitive, and specific test that may indicate current or past infection with SARS-CoV-2 and potentially predict protective immunity.
We also believe the skin test has the potential to inform strategies to protect individuals and communities from COVID-19."
T cell immunity to SARS-CoV-2 is believed to
provide an important element of protective immunity against serious COVID-19 illness after infection with SARS-CoV-2. T cell immunity
to several viruses is known to persist substantially longer than antibody immunity, often present when there is no measurable antibody
response, and in many cases provides a more durable protective immunity that may last for years to decades. For example, T cell immunity
has been detected to SARS-CoV-2 in some individuals who do not make antibody responses and in others after their antibody responses have
waned and become undetectable over time. A complete picture of a patient's immune status requires assessment of both antibody titers
and T cell immunity.
Skin tests that elicit DTH responses are well-established
methods for the detection of antigen-specific T cell responses. Tests of this kind are known as in vivo diagnostics because they
require injection of small representative peptides into the skin. A positive result is evidenced by a skin reaction surrounding the site
of the injection produced by local infiltration of functional antigen-specific T cells. This reaction, also called "induration",
has been shown to be dependent on the presence of memory T cells. Both the CD4+ and CD8+ fractions of T cells participate in this response.
Herbert Harris, M.D., Ph.D., Executive Vice President
of Translational Medicine at Tonix said, "There is continued uncertainty about the durability of protection provided by mRNA vaccines
for COVID-19 and the number and frequency of boosters required to maintain protective immunity. This skin test, with its potential to
allow for measurement of functional T cell immunity to SARS-CoV-2, could provide a personalized approach to determining the need for a
booster. A personalized approach to boosters has advantages over the lock-step boosters-for-everyone strategy, which is expensive, exposes
people to unknown risks and is unlikely to be sustainable."
This dose finding, multi-cohort study is designed
to evaluate the safety and efficacy of intradermally-injectedTNX-2100, synthesized SARS-CoV-2 peptide antigens and assess the presence
and magnitude of DTH reactions.
The study is expected to be conducted in the U.S.
in approximately 90 healthy adult subjects (30 subjects per cohort) who are either uninfected/unexposed healthy individuals (Cohort 1),
who are confirmed to have recovered from SARS-CoV-2 infection, independent of vaccination status (Cohort 2), or who have received a complete
SARS-CoV-2 vaccine course with no known history of natural infection (Cohort 3). The study schedule will consist of a baseline/skin test
administration at visit 1 (Day 1) at which time baseline assessments are to be completed, the skin test is performed, and appropriate
test samples are collected. Follow-up visits to monitor safety and evaluate the presence or absence of DTH reactions will be conducted
at visit 1 (Day 1), visit 2 (Day 2), visit 3 (Day 3), visit 4 (Day 4), and visit 5 (Day 5). Safety monitoring will continue through visit
6 (Day 30) and visit 7 (Day 180).
An interim analysis is expected to be conducted after
all subjects have completed their Day 5 visit (or early terminated prior to Day 5). The purpose of the interim analysis will be to assess
the presence of DTH reactions in response to intradermal injection of TNX-2100, synthesized SARS-CoV-2 peptide antigens, and to assess
safety up to 96 hours post-administration. A full database lock will occur after all subjects have completed their visit 7 (or early terminated
TNX-2100 is a diagnostic product candidate
and has not been approved for any indication. TNX-2100 is a test comprising three different mixtures of synthetic peptides (TNX-2110,
-2120 and -2130), which are designed to represent different protein components of the SARS-CoV-2 virus. TNX-2110 (SARS-CoV-2 multi-antigen
peptides) represents epitopes of multiple proteins from SARS-CoV-2. TNX-2120 (SARS-CoV-2 spike peptides) represents only the spike protein.
TNX-2130 (SARS-CoV-2 non-spike peptides) represents non-spike proteins. Each of these three synthetic peptide mixtures is expected to
be administered as part of the same procedure, at separate locations on the forearm, and each is expected to elicit a DTH response after
approximately 48 hours in individuals with pre-existing T cell immunity to peptides in that mixture. Individuals who have been infected
by or exposed to SARS-CoV-2 would be expected to respond to all three mixtures. In contrast, a successfully vaccinated individual who
has not been exposed or infected by SARS-CoV-2 would be expected to respond only to TNX-2120 (SARS-CoV-2 spike peptides), since the currently
available vaccines only encode spike protein. In the planned clinical protocol for testing TNX-2100, positive skin test controls will
be used to confirm that study participants have intact T cell immunity and are not immunodeficient.
The test is designed to be administered in
the same manner as skin tests for tuberculosis, or TB, sold as Tubersol or Aplisol or generically as the Mantoux tuberculin
purified protein derivative (PPD) test. A thin gauge needle is used to apply each of the three separate TNX-2100 peptide mixtures into
the skin, or intradermally, on the inner surface of the forearm between the wrist and the elbow. In a typical positive test, the skin
surrounding the injection site is expected to become red, raised and hardened, or "indurated", after approximately 48 hours.
Induration above a threshold level would signify a positive result and the diameter of the induration would indicate the amount of T cell
immunity to the test peptides. DTH skin test responses are believed to reflect functional in vivo immunity. Clinical trials are
expected to correlate skin test results with clinical history and laboratory findings. to inform estimates about the sensitivity and specificity
of the test as a marker of T cell immunity in individuals who are pre- and post-COVID-19 vaccination, recovered from COVID-19; or exposed
Discovered in 1882 by Robert Koch, the DTH
reaction has been used for more than a century as a clinical test for T cell-mediated immune reactions1. In the 1940s, Landsteiner
and Chase demonstrated that the reaction was mediated by the cellular and not the antibody arm of the immune system2. The DTH
reaction has been shown to be dependent on the presence of memory T cells. Both the CD4+ and CD8+ T cells have been shown to participate
in this response. DTH skin tests have been commonly used to detect T cell responses to tuberculosis, fungal pathogens, and mumps virus.
1Black CA. Delayed type hypersensitivity:
current theories with an historic perspective. Dermatol Online J. 1999;5:7.
2Landsteiner K, Chase MW. Studies
on the sensitization of animals with simple chemical compounds: vii. Skin sensitization by intraperitoneal injections. J Exp Med. 1940;71:237.
Tubersol is a trademark of Sanofi Pasteur
Aplisol is a trademark of Par Pharmaceutical,
About Tonix Pharmaceuticals Holding
Tonix is a clinical-stage biopharmaceutical company
focused on discovering, licensing, acquiring and developing therapeutics and diagnostics to treat and prevent human disease and alleviate
suffering. Tonix's portfolio is composed of infectious diseases, central nervous system (CNS) and immunology product candidates.
Tonix's infectious disease portfolio includes COVID-19-related product candidates to prevent and treat COVID-19, to treat Long COVID
as well as to detect functional T cell immunity to SARS-CoV-2. The portfolio also includes a vaccine in development to prevent smallpox.
The Company's CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions.
The immunology portfolio includes biologics to address immunosuppression, cancer, and autoimmune diseases. Tonix's lead vaccine
candidate for COVID-19, TNX-18001, is a live replicating vaccine based on Tonix's recombinant pox vaccine (RPV) platform
to protect against COVID-19, primarily by eliciting a T cell response. Tonix expects to start a Phase 1 study in humans in the second
half of 2022. Tonix is developing TNX-21002, an in vivo diagnostic to measure the presence of functional
T cell immunity to SARS-CoV-2 and initiated a first-in-human clinical study in the first quarter of 2022. TNX-35003 (sangivamycin,
i.v. solution) is a small molecule antiviral drug to treat acute COVID-19 and is in the pre-IND stage of development. Finally,
TNX-102 SL4 (cyclobenzaprine HCl sublingual tablets), is a small molecule drug being developed to treat Long COVID, a
chronic post-COVID condition. Tonix expects to initiate a Phase 2 study in Long COVID in the first half of 2022. Tonix's lead CNS