Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or
the Company), a clinical-stage biopharmaceutical company, today
announced the U.S. Food and Drug Administration (FDA) has cleared
the Investigational New Drug (IND) application to support a Phase 2
clinical trial with TNX-601 ER (tianeptine hemioxalate
extended-release tablets), a once-daily formulation of tianeptine
as a potential treatment for major depressive disorder (MDD)1.
Tianeptine is a new molecular entity in the U.S. that is being
developed under the 505(b)(1) pathway. Tianeptine sodium
(amorphous) immediate release (IR) tablets have been available in
Europe and many countries in Asia and Latin America for the
treatment of depression over more than three decades since it was
first marketed in France in 1989. Tianeptine's activity is
mechanistically distinct from traditional monoaminergic treatments
for depression available in the U.S. including the selective
serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine
reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs),
and tricyclic antidepressants (TCAs).
“This is an important milestone as we advance
TNX-601 ER into clinical development,” said Seth Lederman, M.D.,
Chief Executive Officer of Tonix Pharmaceuticals. “TNX-601 ER is a
novel, oral, extended-release once-daily tablet. Studies from
across the globe conducted over more than 30 years show that
immediate-release (IR) tianeptine sodium formulations have
comparable efficacy to SSRIs and TCAs, fewer drug-drug
interactions, and are associated with a lower incidence of sexual
dysfunction compared with SSRIs, SNRIs and TCAs. We expect that our
new once-daily formulation will maintain these properties while
also providing convenience and adherence advantages over the
three-times-a-day dosing of these IR tianeptine sodium products. We
expect to initiate the Phase 2 trial in MDD in the first quarter of
2023, with the potential for additional future indications in
posttraumatic stress disorder and neurocognitive dysfunction from
corticosteroids.”
TNX-601 ER is being developed as a monotherapy
and first-line treatment for MDD. No tianeptine-containing product
has been approved by the FDA. The proposed mechanism of action of
TNX-601 ER is distinct from traditional monoaminergic
antidepressants, in that its principal mechanism in MDD is believed
to be through indirect modulation of glutamatergic
neurotransmission. It is notable that in multiple
placebo-controlled and comparative studies that tianeptine
demonstrates efficacy on par with both SSRIs and tricyclic
antidepressants, while showing a more favorable tolerability
profile, lacking the sedative, autonomic, cardiovascular and side
effects on memory and attention of TCAs and a low incidence of
sexual side effects, nausea, and sleep disruption as compared with
SSRIs.2,3
In addition to its glutamatergic properties,
tianeptine has weak µ-opioid receptor agonist properties and has
been linked to illicit misuse at much higher doses than those
reported to be effective in the treatment of MDD4. Previously,
Tonix was developing a naloxone-containing tablet, TNX-601 CR
(tianeptine oxalate and naloxone controlled-release) for MDD, that
was designed to mitigate the risk of parenteral abuse. TNX-601 ER
is also designed with abuse deterrent properties but without the
µ-opioid receptor antagonist naloxone. The abuse-deterrent
properties include gel forming polymers which impede extraction for
illicit misuse. In addition, the tablet’s hardness makes it
difficult to crush, cut or grind to fine particle size, which
hinders efforts to misuse by nasal insufflation or intravenous
route.
1TNX-601 ER is an investigational new
drug and is not approved for any indication.2McEwen, B.S., et al.
Neurobiological properties of the antidepressant tianeptine.
Molecular Psychiatry 2010, 15, 237-249.3Paparrigopoulos, T.J., et
al. Sleep and antidepressant medication. WPA Bulletin on Depression
2007, 11 (33), 7-11.4Lauhan, R., et al. Tianeptine abuse and
dependence: case report and literature review.
Psychosomatics 2018, 59 (6), 547–553.
About the Phase 2 Study
Tonix is proposing to conduct a
registration-quality, potentially pivotal, Phase 2, 6-week,
randomized, double-blind, placebo-controlled, parallel-group study
to evaluate the efficacy, safety, and tolerability of TNX-601 ER
monotherapy in male and female subjects aged 18 to 65 years
(inclusive), with current MDD as defined by DSM-5 criteria at
screening and a Montgomery-Åsberg Depression Rating Scale (MADRS)
total score ≥ 25 at baseline. A total of 300 participants are
planned to be randomized to two treatment arms across approximately
30 clinical trial sites in the U.S. The study is expected to have a
single unblinded interim analysis for sample size re-estimation
when the study has results of the first 50% of efficacy evaluable
patients, pending agreement on the comprehensive statistical
analysis plan with the FDA.
About DepressionAccording to
the National Institute of Mental Health, an estimated 21 million
adults in the U.S. in 2020 experienced at least one major
depressive episode1, with highest prevalence among individuals aged
18-25 at a rate of 17.0%. For approximately 2.5 million adults in
the U.S., adjunctive therapies are necessary for depression
treatment.2,3 Depression is a condition characterized by
symptoms such as a depressed mood or loss of interest or pleasure
in daily activities most of the time for two weeks or more,
accompanied by appetite changes, sleep disturbances, motor
restlessness or retardation, loss of energy, feelings of
worthlessness or excessive guilt, poor concentration, and suicidal
thoughts and behaviors. These symptoms cause clinically significant
distress or impairment in social, occupational, or other important
areas of functioning. The majority of people who suffer from
depression do not respond adequately to initial antidepressant
therapy.4
1Data Courtesy of SAMHSA on Past Year
Prevalence of Major Depressive Episode Among U.S. Adults (2020).
Retrieved
from http://www.nimh.nih.gov/health/statistics/major-depression.shtml.2IMS
NSP, NPA, NDTI MAT-24-month data through Aug 2017.3Kubitz N, et al.
(2013) PLOS One,. 8(10):e76882. doi: 10.1371/journal.pone.0076882.
PMID: 24204694.4Rush AJ, et al. (2007) Am J. Psychiatry 163:11, pp.
1905-1917 (STAR*D Study).
About TNX-601 ERTNX-601 ER is a
novel oral formulation of tianeptine hemioxalate designed for
once-daily daytime dosing that is now in the IND (Investigational
New Drug) stage of development for the treatment of MDD. Tianeptine
sodium (amorphous) immediate release (dosed three times daily) was
first marketed for depression in France in 1989 and has been
available for decades in Europe, Russia, Asia, and Latin America
for the treatment of depression. Tianeptine sodium has an
established safety profile from decades of use in these
jurisdictions. Currently there is no tianeptine-containing product
approved in the U.S. and no extended-release tianeptine product
approved in any jurisdiction. Tonix discovered a novel hemioxalate
salt of tianeptine that may provide improved stability,
consistency, and manufacturability compared to known salt forms of
tianeptine. Tianeptine is believed to work in depression as an
indirect modulator of the glutamatergic system, without direct
binding NMDA, AMPA or kainate receptors. Tianeptine reverses stress
induced increases in AMPA receptor trafficking, restoring
hippocampal long-term potentiation and reversing the neuroplastic
changes from stress and corticosteroid exposure. Tianeptine and its
MC5 metabolite are also weak µ-opioid receptor agonists, that
present a potential abuse liability if illicitly misused in large
quantities (8-80 times the therapeutic dose for depression). In
patients who were prescribed tianeptine for depression, the French
Transparency Committee found an incidence of misuse of
approximately 1 case per 1,000 patients treated1 suggesting low
abuse liability when used at the antidepressant dose in patients
prescribed tianeptine for depression. Clinical trials have shown
that cessation of a therapeutic course of tianeptine did not appear
to result in dependence or withdrawal symptoms following
6-weeks2,3,4–6, 3-months7, or 12-months8 of treatment.
Tianeptine’s reported pro-cognitive and anxiolytic effects as well
as its ability to attenuate the neuropathological effects of
excessive stress responses suggest that it may also be used to
treat posttraumatic stress disorder. TNX-601 ER is expected to have
patent protection through 2037.
1Haute Authorite de Sante;
Transparency Committee Opinion. Stablon 12.5 Mg, Coated Tablet, Re-
Assessment of Actual Benefit at the Request of the Transparency
Committee. December 5, 2012.2Emsley, R., et al. J. Clin.
Psychiatry 2018, 79 (4)3Bonierbale M, et
al. Curr Med Res Opin 2003, 19(2):114-124.4Guelfi,
J. D., et al. Neuropsychobiology 1989, 22 (1),
41–48.5Invernizzi, G. et
al., Neuropsychobiology 1994, 30 (2–3),
85–93.6Lepine, J. P., et al. Hum.
Psychopharmacol. 2001, 16 (3), 219–227.7Guelfi, J.
D. et al., Neuropsychobiology 1992, 25 (3),
140–148.8Lôo, H. et al., Br. J.
Psychiatry. Suppl. 1992, No. 15, 61–65.
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 and alleviate
suffering. Tonix’s portfolio is composed of central nervous system
(CNS), rare disease, immunology and infectious disease product
candidates. Tonix’s CNS portfolio includes both small molecules and
biologics to treat pain, neurologic, psychiatric and addiction
conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine
HCl sublingual tablet), is in mid-Phase 3 development for the
management of fibromyalgia with a new Phase 3 study launched in the
second quarter of 2022 and interim data expected in the second
quarter of 2023. TNX-102 SL is also being developed to treat Long
COVID, a chronic post-acute COVID-19 condition. Tonix initiated a
Phase 2 study in Long COVID in the third quarter of 2022 and
expects interim data in the first half of 2023. TNX-1300 (cocaine
esterase) is a biologic designed to treat cocaine intoxication and
has been granted Breakthrough Therapy designation by the FDA. A
Phase 2 study of TNX-1300 is expected to be initiated in the first
quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a
small molecule in development for chronic migraine, is expected to
enter the clinic with a Phase 2 study in the fourth quarter of
2022. TNX-601 ER (tianeptine hemioxalate extended-release tablets)
is a once-daily formulation of tianeptine being developed as a
potential treatment for major depressive disorder (MDD) with a
Phase 2 study expected to be initiated in the first quarter of
2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal
potentiated oxytocin) for the treatment of Prader-Willi syndrome.
TNX-2900 has been granted Orphan Drug designation by the FDA.
Tonix’s immunology portfolio includes biologics to address organ
transplant rejection, autoimmunity and cancer, including TNX-1500,
which is a humanized monoclonal antibody targeting CD40-ligand
(CD40L or CD154) being developed for the prevention of allograft
and xenograft rejection and for the treatment of autoimmune
diseases. A Phase 1 study of TNX-1500 is expected to be initiated
in the first half of 2023. Tonix’s infectious disease pipeline
consists of a vaccine in development to prevent smallpox and
monkeypox, next-generation vaccines to prevent COVID-19, and a
platform to make fully human monoclonal antibodies to treat
COVID-19. TNX-801, Tonix’s vaccine in development to prevent
smallpox and monkeypox, also serves as the live virus vaccine
platform or recombinant pox vaccine (RPV) platform for other
infectious diseases. A Phase 1 study of TNX-801 is expected to be
initiated in Kenya in the first half of 2023. Tonix’s lead vaccine
candidate for COVID-19 is TNX-1850, a live virus vaccines based on
Tonix’s recombinant pox live virus vector vaccine platform.
*All of Tonix’s
product candidates are investigational new drugs or biologics and
have not been approved for any indication.
This press release and further information about
Tonix can be found at www.tonixpharma.com.
Forward Looking Statements
Certain statements in this press release are
forward-looking within the meaning of the Private Securities
Litigation Reform Act of 1995. These statements may be identified
by the use of forward-looking words such as “anticipate,”
“believe,” “forecast,” “estimate,” “expect,” and “intend,” among
others. These forward-looking statements are based on Tonix's
current expectations and actual results could differ materially.
There are a number of factors that could cause actual events to
differ materially from those indicated by such forward-looking
statements. These factors include, but are not limited to, risks
related to the failure to obtain FDA clearances or approvals and
noncompliance with FDA regulations; delays and uncertainties caused
by the global COVID-19 pandemic; risks related to the timing and
progress of clinical development of our product candidates; our
need for additional financing; uncertainties of patent protection
and litigation; uncertainties of government or third party payor
reimbursement; limited research and development efforts and
dependence upon third parties; and substantial competition. As with
any pharmaceutical under development, there are significant risks
in the development, regulatory approval and commercialization of
new products. Tonix does not undertake an obligation to update or
revise any forward-looking statement. Investors should read the
risk factors set forth in the Annual Report on Form 10-K for the
year ended December 31, 2021, as filed with the Securities and
Exchange Commission (the “SEC”) on March 14, 2022, and periodic
reports filed with the SEC on or after the date thereof. All of
Tonix's forward-looking statements are expressly qualified by all
such risk factors and other cautionary statements. The information
set forth herein speaks only as of the date thereof.
Contacts
Jessica Morris (corporate)Tonix
Pharmaceuticalsinvestor.relations@tonixpharma.com(862) 904-8182
Olipriya Das, Ph.D. (media)Russo
PartnersOlipriya.Das@russopartnersllc.com (646) 942-5588
Peter Vozzo (investors)ICR
Westwickepeter.vozzo@westwicke.com(443) 213-0505
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