Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Tonix Pharmaceuticals Announces First Patient
Enrolled in Phase 2 CATALYST Study of TNX-1300 for the Treatment of Cocaine Intoxication
CATALYST is a Phase 2 single-blind, placebo-controlled,
proof-of-concept study in patients presenting to the emergency department
More than 27,569 individuals in the U.S.
died from drug overdose deaths involving cocaine in 2022; there is currently no FDA-approved product for cocaine intoxication
Topline results are expected in the first
CHATHAM, N.J., August 20, 2024 (GLOBE NEWSWIRE)
- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a
fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, today announced the
first patient has been dosed in the Phase 2, single-blind, placebo-controlled, proof of concept trial of TNX-1300 (double-mutant cocaine
esterase 200 mg, i.v. solution) for the treatment of acute cocaine intoxication in the emergency department (ED). TNX-1300 is a
recombinant enzyme that rapidly and efficiently degrades and metabolizes cocaine in cocaine users, as demonstrated in a prior Phase 2a
randomized, double-blind, placebo-controlled, laboratory-based clinical study, providing support for the use of TNX-1300 as a treatment
for life-threatening cocaine intoxication.1
Tonix has been awarded a Cooperative Agreement
Grant from National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), to support development of TNX-1300
for the treatment of cocaine intoxication. In addition, TNX-1300 has been granted Breakthrough Therapy designation by the U.S Food and
Drug Administration (FDA).
"Cocaine abuse and dependence are major
problems in the U.S. However, there is currently no FDA-approved treatment indicated for cocaine intoxication, a life-threatening state
characterized by acute symptoms including agitation, hyperthermia, tachycardia, arrhythmias, hypertensive crisis, myocardial infarction,
stroke, and seizures," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "In 2022, the number of
overdose deaths involving cocaine reached 27,569 individuals.2 With approximately 505,000 emergency room visits annually involving
cocaine use and approximately 61,000 of the visits involving detox services to treat cocaine overdose,3,4 we believe TNX-1300
has the potential to help address the morbidity and mortality caused by cocaine intoxication. By targeting the cause rather than the symptoms
of cocaine intoxication, TNX-1300 may offer significant advantages to the current standard of care for cocaine overdose."
The Phase 2 trial is a single-blind, open-label,
placebo-controlled, randomized study comparing the safety of a single 200 mg dose of TNX-1300 to placebo injection plus standard of care
alone for the treatment of signs and symptoms of acute cocaine intoxication. The study is being conducted in the EDs of six academic medical
centers in the U.S. It will include approximately 60 subjects presenting to the ED with cocaine intoxication. During the treatment period,
subjects randomized to receive TNX-1300 will receive a single i.v. injection of TNX-1300 administered over two minutes or less;
whereas subjects randomized to receive standard of care alone will receive a single i.v. saline injection over two minutes or less.
For both study arms, signs and symptoms of cocaine intoxication will be assessed at pre-determined time points after treatment. After
randomization, blood samples will be drawn at specific time points to assess the pharmacokinetics of TNX-1300 and levels of cocaine and
its metabolites in the plasma. The primary endpoint of the study is reduction of systolic blood pressure associated with acute cocaine
intoxication identified at study baseline comparing TNX-1300 to placebo with standard of care after 60 minutes. A variety of secondary
endpoints will be measured, including reduction of circulating cocaine and levels of its metabolites at multiple post-baseline timepoints.
For more information, see ClinicalTrials.gov
Identifier: NCT06045793
TNX-1300 (T172R/G173Q double-mutant cocaine
esterase 200 mg, i.v. solution) is being developed under an Investigational New Drug application (IND) for the treatment of cocaine
intoxication. 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 uses cocaine as its sole source
of carbon and nitrogen and that grows in soil surrounding coca plants.5 The gene encoding CocE was identified and the
protein was extensively characterized.5-8 CocE catalyzes the breakdown of cocaine into metabolite ecgonine methyl ester
and benzoic acid. Wild-type CocE is unstable at human 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.8 In a
Phase 2 laboratory-based study in volunteers who use cocaine, TNX-1300, at 100 mg or 200 mg i.v. doses, was well tolerated and
rapidly reduced cocaine effects after cocaine 50 mg i.v. challenge.1
About Cocaine Intoxication and Overdose
Cocaine is an illicit recreational drug which
is taken for its pleasurable effects and associated euphoria. In 2022, over 5 million individuals in the U.S. reported current cocaine
use, almost 2% of the population.9 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 and its
capacity to produce euphoric mood states. With the continued use of cocaine, however, intense cocaine cravings occur resulting in a high
potential for abuse and addiction (dependence), as well as the risk of acute cocaine intoxication. Cocaine intoxication refers to the
deleterious effects on several body systems, especially those involving the cardiovascular system. Common symptoms of cocaine intoxication
include tachyarrhythmias and elevated blood pressure, either of which can be life-threatening. As a result, individuals with known or
suspected cocaine intoxication are sent immediately to the emergency department (ED), preferably by ambulance in case cardiac arrest occurs
during transit. The standard of care for treating cocaine intoxication in the ED focuses on symptom management, preventing complications,
and supporting cardiovascular, respiratory, and neurological function, e.g. benzodiazepines for agitation, seizures, and sympathetic overdrive;
antihypertensives for extremely elevated blood pressure; aspirin and nitroglycerine for cardiac ischemia. There are approximately 505,000
emergency room visits for cocaine abuse each year in the U.S., of which 61,000 require detoxification services.3,4 According
to the National Institute on Drug Abuse, in 2022 the number of overdose death involving cocaine reached 27,569 individuals.2
In 2019, Black Americans experienced the highest death rate for overdoses involving cocaine, at 10.7 per 100,000.10
Nasser et al. 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.
3 Substance Mental Health Services Administration, Drug
Abuse Warning Network, 2011: National Estimates of Drug- Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN
Series D-39. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013.
4 Drug Abuse Warning Network, 2011: Selected Tables of
National Estimates of Drug-Related Emergency Department Visits. Rockville, MD: Center for Behavioral Health Statistics and Quality, SAMHSA,
5 Bresler, et al. Gene cloning and nucleotide sequencing
and properties of a cocaine esterase from Rhodococcus sp. strain MB1. Appl
Environ Microbiol. 2000. 66(3):904-8.
6 Larsen, et al. Crystal structure of a bacterial
cocaine esterase. Nat
Struct Biol. 2002. 9(1):17-21.
Turner, et al. Biochemical characterization and structural analysis of a highly proficient cocaine esterase. Biochemistry.
2002. 41(41):12297-307.
8 Gao, et al. Thermostable variants of cocaine
esterase for long-time protection against cocaine toxicity. Mol
Pharmacol. 2009. 75(2):318-23.
accessed August 18, 2024
10 Kariisa, et al. Drug overdose deaths involving cocaine
and psychostimulants with abuse potential among racial and ethnic groups - United States, 2004-2019. Drug Alcohol Depend. 2021.
Tonix Pharmaceuticals Holding Corp.*
Tonix is a fully integrated biopharmaceutical company
focused on transforming therapies for pain
management and modernizing solutions for public health
challenges. Tonix's development portfolio is focused on central nervous system (CNS) disorders, and its priority is to submit a
New Drug Application (NDA) to the FDA in the second half of 2024 for TNX-102 SL, a product candidate for which two statistically significant
Phase 3 studies have been completed for the management of fibromyalgia. The FDA has granted Fast Track designation to TNX-102 SL for the
management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction. Tonix's CNS portfolio includes TNX-1300
(cocaine esterase), a biologic in Phase 2 development designed to treat cocaine intoxication that has Breakthrough Therapy designation.