TNX-1300

Preclinical

Phase I

Phase II

Phase III

Cocaine Intoxication / Overdose
Phase II ongoing — Breakthrough Therapy Designation
Awarded Cooperative Agreement Grant from National Institute on Drug Abuse (NIDA)

Mid-Phase II

 

TNX-1300 (recombinant T172R/G173Q double-mutant cocaine esterase 200 mg, IV solution) is being developed under an Investigational New Drug application (IND) for the treatment of cocaine intoxication. It has been designated a Breakthrough Therapy by the FDA. Currently there is no specific pharmacotherapy indicated for cocaine intoxication, a state characterized by acute agitation, hyperthermia, tachycardia, arrhythmias, and hypertension, with the potential life-threatening sequalae of myocardial infarction, cerebrovascular accident, rhabdomyolysis, respiratory failure, and seizures. Patients are currently managed only by supportive care for the adverse effects of cocaine overdose on the cardiovascular and central nervous systems.

TNX-1300 is a recombinant protein enzyme produced through recombinant DNA 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.3 The gene encoding CocE was identified, and the protein was extensively characterized.3-6 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 temperature7. In a Phase 2 study, TNX-1300 at 100 mg or 200 mg IV doses were well tolerated and interrupted cocaine effects after cocaine 50 mg IV challenge.1 TNX-1300 was well tolerated with the most frequently reported adverse events being gastrointestinal disorders (including dry mouth, nausea); nervous systems disorders (including headache, dizziness) and skin and subcutaneous tissue disorders (including hyperhidrosis, dermatitis).

By targeting the cause of cocaine intoxication, rather than the symptoms like other medicines in emergency usage, TNX-1300 may offer significant advantages to the current standard of care for cocaine overdose.

 

TNX-1300 is an investigational new biologic and has not been approved for any indication.
1 Nasser AF, Fudala PJ, Zheng B, Liu Y, Heidbreder C. A randomized, double-blind, placebo-controlled trial of RBP-8000 in cocaine abusers: pharmacokinetic profile of rbp-8000 and cocaine and effects of RBP-8000 on cocaine-induced physiological effects. J Addict Dis. 2014;33(4):289-302.
2 National Institute on Drug Abuse (NIDA) – https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates; accessed May 11, 2019
3 Bresler MM, Rosser SJ, Basran A, Bruce NC. Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp. strain MB1. Appl Environ Microbiol. 2000. 66(3):904-8.
4 Larsen NA, Turner JM, Stevens J, Rosser SJ, Basran A, Lerner RA, Bruce NC, Wilson IA. Crystal structure of a bacterial cocaine esterase. Nat Struct Biol. 2002. 9(1):17-21.
5 Turner JM, Larsen NA, Basran A, Barbas CF 3rd, Bruce NC, Wilson IA, Lerner RA. Biochemical characterization and structural analysis of a highly proficient cocaine esterase. Biochemistry. 2002. 41(41):12297-307.
6 Gao D, Narasimhan DL, Macdonald J, Brim R, Ko MC, Landry DW, Woods JH, Sunahara RK, Zhan CG. Thermostable variants of cocaine esterase for long-time protection against cocaine toxicity. Mol Pharmacol. 2009. 75(2):318-23.
7 Overdose Death Rates – National Institute on Drug Abuse – https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates; accessed May 11, 2019
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