Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Pharmaceuticals Expands Pipeline with Mid-stage Biologic Candidate TNX-1300
Cocaine Intoxication
2 Program Granted Breakthrough Therapy Designation by FDA
Room Visits for Cocaine Abuse Total More than 500,000 Annually in U.S.
YORK, May 23, 2019 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage
biopharmaceutical company focused on developing small molecules and biologics to treat psychiatric, pain and addiction conditions
as well as to improve biodefense, announced today that it has in-licensed a Phase 2 asset, TNX-1300 (T172R/G173Q double-mutant
cocaine esterase 200 mg, i.v. solution)* for the treatment of cocaine intoxication. TNX-1300 is designated as a breakthrough
therapy by the U.S. Food and Drug Administration (FDA).
formerly RBP-8000, is a recombinant enzyme that efficiently degrades and metabolizes cocaine in cocaine abusers, as demonstrated
in a Phase 2 randomized, double-blind, placebo-controlled clinical study, providing support of the use of TNX-1300 as a treatment
for cocaine intoxication.1
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 of cocaine intoxication,
rather than the symptoms like other medicines in emergency usage, we believe TNX-1300 may offer significant advantages to the
current standard of care for cocaine overdose. TNX-1300 was developed by Columbia University, University of Kentucky and University
of Michigan, and in-licensed by Tonix from Columbia University. Financial terms were not disclosed.
is an excellent strategic fit within our focus on breakthrough psychiatry and non-opiate centrally-acting analgesic treatments
and expands our pipeline into addiction treatment with a disruptive therapeutic technology in mid-stage clinical development,"
said Seth Lederman, M.D., Tonix's President and Chief Executive Officer. "TNX-1300 also represents our first in-licensed
product, as we have historically developed products and technologies internally through our own discovery and R&D efforts.
This transformative product meets our standards for innovation, value and impact."
Lederman continued, "There are approximately 505,000 emergency room visits annually due to cocaine abuse, with approximately
61,000 of the visits involving detox services to treat cocaine overdose. In 2017, about 13,900 deaths occurred in the U.S. due
to cocaine overdose.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."
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 in-licensing transaction also includes an inventory of investigational
drug product, which will be requalified for Good Manufacturing Practice (GMP) purposes.
(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 (formerly known as RBP-8000) 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.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 interrupted cocaine effects after cocaine 50 mg i.v. challenge.1
Cocaine Intoxication and Overdose
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 other parts of the body, 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, over 13,900 individuals died of cocaine overdose in 2017.7 According to a
recent report by the U.S. Centers for Disease Control and Prevention8, and covered by news reports9,10,
among all 2017 U.S. drug overdose deaths, approximately 20% involved cocaine. Overdose deaths involving
cocaine increased 34 percent from 2016 to 2017.
Tonix Pharmaceuticals Holding Corp.
is a clinical-stage biopharmaceutical company focused on developing small molecules and biologics to treat psychiatric, pain and
addiction conditions as well as to improve biodefense, through potential medical counter-measures. Tonix's lead program
is for the development of Tonmya ** (TNX-102 SL)***, which is in Phase 3 development as a bedtime treatment for PTSD. Tonmya
for PTSD has been designated a Breakthrough Therapy by the FDA. Tonix is also developing TNX-102 SL as a bedtime treatment for
fibromyalgia and agitation in Alzheimer's disease under separate INDs to support potential pivotal efficacy studies. The
fibromyalgia program is in Phase 3 development and the agitation in Alzheimer's program is Phase 2 ready. In fibromyalgia,
TNX-102 SL acts as a non-opioid, centrally-acting analgesic that would provide a new therapeutic option for fibromyalgia patients.
The agitation in Alzheimer's disease IND has been designated a Fast Track development program by the FDA. TNX-601 (tianeptine
oxalate) is in the pre-IND application stage, also for the treatment of PTSD but by a different mechanism
from TNX-102 SL and designed for daytime dosing. TNX-601 is also in development for a potential indication - neurocognitive dysfunction
associated with corticosteroid use. A Phase 1 clinical formulation selection pharmacokinetic study of TNX-601 will be conducted
outside of the U.S. in 2019. Tonix's lead biologic candidate, TNX-801, is a potential smallpox-preventing vaccine based
on a live synthetic version of horsepox virus, currently in the pre-IND application stage.
(T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution) is an investigational new biologic and has not
been approved for any indication.
has been conditionally accepted by the U.S. Food and Drug Administration (FDA) as the proposed trade name for TNX-102 SL for the
SL (cyclobenzaprine HCl sublingual tablets) is an investigational new drug and has not been approved for any indication.
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.
National Institute on Drug Abuse (NIDA) - https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates;
accessed May 11, 2019
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.
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.
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.
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.
Overdose Death Rates - National Institute on Drug Abuse - https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates;
accessed May 11, 2019
Kariisa, M, Scholl, L, Wilson, N, Seth, P, Hoots, B. Drug Overdose Deaths Involving
Cocaine and Psychostimulants with Abuse Potential - United States, 2003-2017. MMWR Weekly / May 3, 2019 / 68(17);388-395
- https://www.cdc.gov/mmwr/volumes/68/wr/mm6817a3.htm?s_cid=mm6817a3_w; accessed May 11, 2019