First of its kind drug, to reverse effects of cocaine intoxication, awarded grant

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shutterstock cocaine

An enzyme that efficiently degrades and metabolizes cocaine has been given a ‘cooperative agreement grant’ from the National Institute on Drug Abuse (NIDA) part of the National Institutes of Health.

The recombinant enzyme is a double-mutant cocaine esterase 200 mg intravenous (IV) solution and treats cocaine intoxication, which refers to the state of when cocaine has deleterious effects on several body systems – in particular cardiovascular.

Physiological effects

TNX-1300 demonstrated activity on reversing the physiological effects of IV cocaine challenge in people who use cocaine in a prior phase 2a randomized, double-blind, placebo-controlled clinical study.

Last year (2021), more than 24,900 people in the U.S. died from drug overdoses involving cocaine.

Seth Lederman, president and chief executive officer of Tonix Pharmaceuticals, said: “This grant award underscores the unmet need for safe and effective treatments for cocaine intoxication and validates the progress we have achieved to date with TNX-1300.

Serious issue

“Cocaine intoxication remains a serious issue in the U.S. where there is currently no specific pharmacotherapy indicated treatments. By targeting the cause rather than the symptoms of cocaine intoxication, we believe TNX-1300 may offer significant advantages to the current standard of care for cocaine intoxication.”

Tonix recently announced the design of a new single-blind, open-label, placebo-controlled, randomized phase 2 clinical trial of TNX-1300 for the treatment of cocaine intoxication. The phase 2 study, which has the potential to serve as a pivotal trial, is anticipated to start in the fourth quarter of 2022, pending US Food and Drug Administration (FDA) agreement.

TNX-1300 has been granted Breakthrough Therapy designation by the FDA. As a biologic and new molecular entity, TNX-1300 is eligible for 12 years of U.S. market exclusivity upon approval by the FDA, in addition to expected patent protection through 2029.

Illegal

Cocaine is an illegal recreational drug taken for its pleasurable effects and associated euphoria, as well as mental alertness, in some cases. Pharmacologically, cocaine blocks the reuptake of the neurotransmitter dopamine from central nervous system synapses, resulting in the accumulation of dopamine within the synapse and an amplification of dopamine signaling which reinforces the drug taking. With the continued use of cocaine, however, intense cocaine cravings can occur, resulting in a high potential for continued use and addiction, as well as the risk of cocaine intoxication. 

TNX-1300 (T172R/G173Q double-mutant cocaine esterase 200 mg, IV solution) is being developed under an Investigational New Drug (IND) application for the treatment of cocaine intoxication. TNX-1300 is a recombinant protein enzyme produced through rDNA technology in a non-disease-producing strain of E. coli bacteria.

Coca plants

Cocaine esterase (CocE) was identified in bacteria (Rhodococcus) that uses cocaine as its sole source of carbon and nitrogen and that grows in soil surrounding coca plants. The gene encoding CocE was identified and the protein was extensively characterized. 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 six hours at body temperature. In a phase 2 study, TNX-1300, at 100 mg or 200 mg IV doses, was well tolerated and rapidly reduced cocaine effects after a cocaine 50 mg IV challenge.

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