Tonix Pharmaceuticals

Tonix Pharmaceuticals (Tonix Pharmaceuticals Holding Corp.) is a pharmaceutical company based in New York City that focuses on repurposed drugs for central nervous system conditions and as of 2016 was also pursuing a biodefense project.

Tonix Pharmaceuticals

Type	Public
Traded as	NASDAQ: TNXP
Industry	Biotechnology Healthcare
Headquarters	New York, New York , United States
Key people	Seth Lederman, MD – CEO
Website	www.tonixpharma.com

The company's predecessors were Tamandare Explorations Inc. which had been formed in 2007 as a mining wildcat vehicle focused on land in Nevada and the shares of which were traded over the counter, and L & L Technologies, LLC, which had been formed in 1996 by Seth Lederman and Donald Landry to repurpose drugs for CNS development. L&L had formed Janus Pharmaceuticals, Inc., which later became Vela Pharmaceuticals, Inc. to develop some of its inventions, and Vela returned those assets to L&L in 2006. L&L placed them in a subsidiary called Krele Pharmaceuticals, Inc., and that subsidiary and Tamandare Explorations Inc. performed a reverse merger in October 2011; the new entity was renamed Tonix Pharmaceuticals Holding Corp. and Lederman was named CEO.[1] It was listed on the NASDAQ exchange in 2013 under the symbol TNXP.[1]

As of 2013 its lead candidates were a reformulation of cyclobenzaprine as a tablet for sublingual administration called TNX-102 SL (formerly called VLD-cyclobenzaprine and then KRL-102), which was under development for fibromyalgia and with preclinical efforts underway for posttraumatic stress disorder, TNX-201 (a single-racemate formulation of isometheptene mucate the company was considering for some headaches), and TNX-301, (a combination drug with disulfiram and selegiline for treatment for alcohol abuse).[1]

In September 2016 Tonix reported the failure of its Phase III trial of TNX-102 for fibromyalgia and said it was abandoning that line of development.[2][3]

Tonix continued work on TNX-102 SL in PTSD; the IND for that use had been accepted in 2014.[4] In December 2016, after the Phase IIa trial was done, TNX-102 was granted Breakthrough Therapy designation by the FDA.[5] A Phase 3 trial began in February 2017, but was canceled in July 2018 after 50% of subjects were treated, for "inadequate separation on primary efficacy endpoint".[6] In March 2020, a later Phase 3 trial of TNX-102 SL for PTSD was also canceled for futility after 50% of its patients were treated.[7][8]

In July 2017 the news division of the journal, Science, reported that Tonix had been sponsoring research and collaborating with scientists at the University of Alberta, David Evans and Ryan Noyce, and that the work had led to the generation of an extinct horsepox virus using synthetic biology — the lab had bought pieces of DNA from a reagent company and had built the horsepox genome with them. This dual-use research is controversial. This invention was licensed to Tonix and Tonix announced that it intended to further develop it into a smallpox vaccine, which is a biodefense business model.[9][10][11] The research was published in 2018.[12]

In May 2019, Tonix reported in-licensing the Phase 2 asset, TNX-1300 (T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution), for the treatment of cocaine intoxication.[13][14] TNX-1300 (formerly known as RBP-8000) is being developed under an Investigational New Drug application (IND) for the treatment of cocaine intoxication.[15] TNX-1300 is a recombinant protein enzyme produced through rDNA technology in a non-disease-producing strain of E. coli bacteria. Cocaine Esterase (CocE) was identified in bacteria (Rhodococcus) that use cocaine as its sole source of carbon and nitrogen and that grow in soil surrounding coca plants.[16] The gene encoding CocE was identified and the protein was extensively characterized.[17][18][19] CoCE catalyzes the breakdown of cocaine into metabolite ecgonine methyl ester and benzoic acid. Wild-type CocE is unstable at body temperature, so targeted mutations were introduced in the CocE gene and resulted in the T172R/G173Q Double-Mutant CocE, which is active for approximately 6 hours at body temperature.[19] In a Phase 2 study, TNX-1300 at 100 mg or 200 mg i.v. doses was well tolerated and interrupted cocaine effects after cocaine 50 mg i.v. challenge.[15] TNX-1300 is designated as a breakthrough therapy by the U.S. Food and Drug Administration (FDA).