Full Press Release Details
TONIX PHARMACEUTICALS HOLDING CORP.
Tonix Pharmaceuticals Announces Trial Design of
New Phase 2 Clinical Study of TNX-1300 for Cocaine Intoxication
New Trial Design is Single-Blind, Placebo-Controlled,
Potential Pivotal Study, Pending FDA Agreement
Expected to Include Women Based on Reproductive
Toxicology Studies, Pending FDA Agreement
Planning to Include Patients Who Have Received
Naloxone to Increase Enrollment
CHATHAM, N.J., June 27, 2022 - Tonix Pharmaceuticals
Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced the design of a new Phase
2 clinical trial of TNX-1300 (T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution) for the treatment of cocaine intoxication.
This new protocol has the potential to serve as a pivotal trial. TNX-1300 is a recombinant enzyme that efficiently degrades and metabolizes
cocaine in cocaine users, as demonstrated in a prior Phase 2a randomized, double-blind, placebo-controlled clinical study, providing support
of the use of TNX-1300 as a treatment for cocaine intoxication.1 The Company plans to submit the new protocol to the U.S. Food
and Drug Administration (FDA) .
A positive Phase 2a study of volunteer cocaine users
in a controlled laboratory setting has been previously completed. 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.
"The design of the new Phase 2 trial
has the potential to serve as a pivotal trial," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "There
are approximately 505,000 emergency room visits annually involving cocaine use, with approximately 61,000 of the visits involving detox
services to treat cocaine overdose. In 2020, about 19,447 overdose deaths involving cocaine occurred in the U.S.2 We believe
that TNX-1300 has the potential to be a new treatment option for the substantial morbidity and mortality caused by cocaine intoxication."
"The new study replaces the Phase 2
open-label trial with TNX-1300 for cocaine intoxication originally expected to start in the second quarter of 2022, which was designed
to evaluate feasibility of enrollment," said Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals. "We expect
to be able to include women in this study, pending FDA agreement, since we have now completed the required reproductive toxicology studies
in which no incidents of toxicity were observed. Additionally, we will now admit patients into the study who might have received naloxone
due to the intoxication symptoms they are presenting. Based on our learnings from the feasibility study, excluding patients who had received
naloxone at the time of intoxication was a hindrance to enrollment. Both of these changes in the new protocol should improve our ability
to enroll appropriate patients in a more timely manner."
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. By targeting the cause rather than
the symptoms of cocaine intoxication, the
Company believes 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 standard of care alone for the treatment
of signs and symptoms of acute cocaine intoxication in approximately 60 emergency department patients presenting with cocaine intoxication.
During the treatment period, subjects assigned to receive TNX-1300 will receive a single IV injection of TNX-1300 administered over 2
minutes or less; whereas subjects assigned to receive standard of care alone will receive a single IV saline injection over 2 minutes
or less. Both groups will be observed according to the site's emergency department protocol. For both study arms, signs and symptoms
of cocaine intoxication will be assessed at pre-determined time points after treatment (30 minutes and then at 60, 90, 120, 180, and 240
minutes). After randomization, blood samples will be drawn at specific time points. The primary endpoint of the study is reduction of
systolic blood pressure associated with acute cocaine intoxication identified at study baseline comparing TNX-1300 and standard of care
after 60 minutes. A variety of secondary endpoints will be measured, including reduction of circulating cocaine, cocaethylene and ecgonine
methyl ester levels after at multiple post-baseline timepoints. Safety assessments will consist of incidence and severity of treatment-emergent
adverse events, adverse events of special interest, 12-lead ECGs, and vital signs.
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 rDNA 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.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 i.v. doses, was well tolerated and rapidly reduced cocaine effects after cocaine 50 mg i.v.
About Cocaine Intoxication and Overdose
Cocaine is an illegal recreational drug which
is taken for its pleasurable effects and associated euphoria. 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 role in creating positive feeling. 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 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, preferably by ambulance in case cardiac arrest occurs during transit.
There are approximately 505,000 emergency room visits for cocaine abuse each year in the U.S., of which 61,000 require detoxification
services. According to the National Institute on Drug Abuse, in 2020 the number of
overdose death involving cocaine reached 19,447
individuals.2 According to a recent report by the U.S. Centers for Disease Control and Prevention,7 among all 2019
U.S. drug overdose deaths, approximately nearly 1 in 5 involved cocaine. In 2019, Black Americans experienced the highest death rate for
overdoses involving cocaine, at 10.7 per 100,000.8
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2 National Institute on
Drug Abuse (NIDA) National Institute on Drug Abuse - https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates;
accessed June 19, 2022
NC. Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus
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IA. Crystal structure of a bacterial cocaine esterase. Nat
Struct Biol. 2002. 9(1):17-21.
RA. Biochemical characterization and structural analysis of a highly proficient cocaine
esterase. Biochemistry.
2002. 41(41):12297-307.
CG. Thermostable variants of cocaine esterase for long-time protection against cocaine toxicity. Mol
Pharmacol. 2009. 75(2):318-23.
accessed June 19, 2022
8 Kariisa M, Seth P, Scholl
L, Wilson N, Davis NL. Drug overdose deaths involving cocaine and psychostimulants with abuse potential among racial and ethnic groups
- United States, 2004-2019. Drug Alcohol Depend. 2021 Oct 1;227:109001. doi: 10.1016/j.drugalcdep.2021.109001. Epub 2021 Aug 28.
Tonix Pharmaceuticals Holding Corp. *
Tonix is a clinical-stage
biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease