Benzinga | Feb 8, 2021 07:02AM EST

Tonix Pharmaceuticals Receives Pre-IND Meeting Written Response From FDA Providing Guidance On Product Development And Clinical Testing Protocol For COVID-19 Skin Test

Pre-IND Meeting Written Response from FDA Provides Guidance on Product Development and Clinical Testing Protocol

Intradermal Test is Designed to Measure SARS-CoV-2 Specific Delayed Type Hypersensitivity (DTH), the Classic Method of Measuring T Cell Immunity to Tuberculosis and Other Pathogens

Multiple Potential Uses Include Functional Measure of T Cell Immunity to SARS-CoV-2; Aid to COVID-19 Diagnosis and Public Health Surveillance; Endpoint for COVID-19 Vaccine Trials

CHATHAM, N.J., Feb. 08, 2021 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (NASDAQ:TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced it has received the written response from the U.S. Food and Drug Administration (FDA) to a Type B pre-investigational new drug (IND) meeting package describing its technology and plans to develop a diagnostic skin test, TNX-2100 (SARS-CoV-2 epitope peptide mixtures for intradermal administration), to measure the delayed-type hypersensitivity (DTH) reaction to SARS-CoV-2 (CoV-2), the virus that causes COVID-19.

TNX-2100 is designed to measure T cell immunity to CoV-2. There currently is no standardized laboratory test available to measure T cell immune responses to CoV-2. T cell immunity to CoV-2 persists longer than antibody immunity, is sometimes present in the absence of a measurable antibody response and is believed to provide an important element of protection against serious COVID-19 illness after infection with CoV-2.

"We believe TNX-2100 has the potential to measure T cell immunity to CoV-2 and therefore serve as an aid to COVID-19 diagnosis to support patient care, public health surveillance and vaccine trials," said Seth Lederman, M.D., Tonix's President and Chief Executive Officer. "Our proposed skin test has the potential to serve as: 1) a biomarker for cellular immunity and protective immunity; 2) a method to stratify participants in COVID-19 vaccine trials by immune status; 3) an endpoint in COVID-19 vaccine trials, and 4) a biomarker of durability of vaccine protection."

The only currently available methods to detect T cell immunity to CoV-2 require expensive, multi-step sample preparation and in vitro T cell stimulation in highly specialized laboratories using methods that have not been amenable to standardization. When fully developed, the TNX-2100 skin test is expected to provide clinicians, patients, employers and public health officials with information of potential diagnostic, safety and predictive significance in a timely and cost-effective manner, including the durability of immune responses in vaccinated, convalescent and exposed individuals, clusters, workplaces and populations.

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 CoV-2 virus. TNX-2110 (CoV-2 multi-antigen peptides) represents multiple proteins from CoV-2. TNX-2120 (CoV-2 spike peptides) represents only the spike protein. TNX-2130 (CoV-2 non-spike peptides) represents non-spike proteins. Each of these three tests 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 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 CoV-2 would be expected to respond only to TNX-2120 (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 way as skin tests for tuberculosis, or TB, sold as Tubersol(r) or Aplisol(r) or generically as the Mantoux tuberculin purified protein derivative (PPD) test. A thin gauge needle is used to apply the three separate peptide mixtures into the skin, or intradermally, on the inner surface of the forearm between the wrist and the elbow. The test may be administered in a variety of settings: ranging from a doctor's office to a remote outpost without running water or in inclement or extreme weather. 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 to inform estimates about the sensitivity and specificity of the test as a marker of T cell immunity in individuals pre- and post-COVID-19 vaccination, who are recovered from COVID-19, and some with active CoV-2 infection.

"Based on guidance provided by FDA in their written response, we believe we have the information necessary to respond to queries and file the IND application in the second quarter of 2021," said Herbert Harris, M.D., Ph.D., Tonix's Executive Vice President for Translational Medicine. "The Company has manufactured peptides under current good manufacturing process or cGMP. We expect clinical trials of TNX-2100 can be initiated, upon FDA clearance of the IND application, in the second half of 2021."

In parallel to developing TNX-2100 as a potential diagnostic tool, Tonix is developing TNX-1800, a live replicating vaccine for COVID-19 designed to elicit primarily T cell immunity. Tonix announced positive immune response data in non-human primates in the fourth quarter of 2020 and expects to release data from non-human primate studies involving challenge with SARS-CoV-2 in the first quarter of 2021.

Tubersol(r) is a trademark of Sanofi Pasteur

Aplisol(r) is a trademark of Par Pharmaceutical, Inc.