Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a
clinical-stage biopharmaceutical company, today announced the
completion of the clinical phase of the Phase 2 potential
registration-quality, double-blind, randomized, multicenter,
placebo-controlled UPLIFT1 study of TNX-601 ER2 (tianeptine
hemioxalate extended-release tablets) as a potential treatment for
major depressive disorder (MDD). Topline results from the
intention-to-treat (ITT) sample (N=132) are expected in early
November 2023.
TNX-601 ER is being developed as a monotherapy
and first-line treatment for MDD and works by a distinct mechanism
of action as compared to traditional monoaminergic antidepressants.
Tonix recently reported that tianeptine activates peroxisome
proliferator-activated receptors PPAR-β/δ and PPAR-γ. These
activities on intracellular molecular targets in neurons and glia
in the brain are believed to relate to tianeptine’s ability to
restore connectivity between neurons that atrophy under conditions
of stress, in animal models.3,4 Tianeptine is the active ingredient
of an antidepressant that has been marketed as a three-times-a-day
medicine outside the U.S. for more than 30 years. Tonix has
developed a novel, patented once-daily oral formulation.
“Because of its unique mechanism, tianeptine
avoids some of the treatment-limiting side effects of traditional
antidepressants, including sexual dysfunction and weight gain,”
said Seth Lederman, M.D., Chief Executive Officer of Tonix
Pharmaceuticals. “Tianeptine restores connectivity between neurons,
or neuroplasticity, and limits the effects of oxidative stress in
the brain in animal models of depression. In contrast to
traditional antidepressants which alter the levels of
neurotransmitters in the synapse, tianeptine directly induces
mature neurons to sprout new connections and also induces formation
of new neurons.”
“With the last patient now treated, we look
forward to analysis of the results of this registration-quality
study, which will help to inform our plans as we discuss next steps
with the U.S. Food and Drug Administration (FDA),” said Gregory
Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals. “We
would like to thank the participants, their families, and all the
investigators and researchers who have been an important part of
this journey so far.”
- Clinical Trials.gov I.D.
NCT05686408
- TNX-601 ER is an investigational new
drug and is not approved for any indication.
- McEwen, B. S., et al. Mol.
Psychiatry 2010, 15 (3),
237–249
- Sullivan, GM et al. June 1, 2023.
Poster presentation at the American Society of Clinical
Psychopharmacology, Miami, FL.
https://www.tonixpharma.com/wp-content/uploads/2023/06/ASCP-Poster-2023-A-Randomized-Placebo-Controlled-Multicenter-Trial-of-Monotherapy-with-TNX-601-ER.pdf
About the Phase 2 UPLIFT
Study
The Phase 2 UPLIFT study, TNX-TI-M201, is a
potential registration-quality, double-blind, randomized,
multicenter, placebo-controlled study to evaluate the efficacy and
safety of TNX-601 ER taken by mouth once-daily for 6 weeks for the
treatment of moderate-to-severe MDD. It is a parallel design study
with two arms, a TNX-601 ER 39.4 mg arm and a placebo arm. A total
of 132 participants were randomized in a 1:1 ratio into the two
arms across approximately 27 U.S. sites, enrolling adult patients
18-65 years old with a DSM-5 diagnosis of depression and a duration
for the current major depressive episode of at least 12 weeks. The
primary efficacy endpoint is mean change from baseline in the
Montgomery-Åsberg Depression Rating Scale (MADRS) total score at
Week 6. Key secondary efficacy endpoints include the Clinical
Global Impression of Severity Scale (CGI-S) and the Sheehan
Disability Scale (SDS).
For more information, see ClinicalTrials.gov
Identifier: NCT05686408.
About Major Depressive Disorder
(Depression)
According 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
1 Data 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
2 IMS NSP, NPA, NDTI MAT-24-month data through
Aug 2017.
3 Kubitz N, et al. PLoS One 2013, 8 (10),
e76882.
4 Rush AJ, et al. Am J. Psychiatry 2007, 163
(11), 1905-1917.
About TNX-601 ER
TNX-601 ER (tianeptine hemioxalate
extended-release tablets) is a novel oral formulation of tianeptine
designed for once-daily daytime dosing in development as a
candidate for the treatment of MDD, posttraumatic stress disorder,
and neurocognitive dysfunction associated with corticosteroid use.
Tianeptine sodium (amorphous) immediate release (dosed 3 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 no tianeptine-containing product is
approved in the U.S. and no extended-release tianeptine product is
approved in any jurisdiction. Tonix discovered a novel oxalate salt
of tianeptine that may provide improved stability, consistency, and
manufacturability compared to known salt forms of tianeptine. In
animal models, tianeptine restores dendritic arborization of
pyramidal neurons in the CA3 region of hippocampus and in the
dentate gyrus region promotes new neuron formation and integration
into hippocampal networks.1 Tianeptine’s enhancement of
neuroplasticity in animal models of stress is believed to be
mediated by activation of PPAR isoforms PPAR-β/δ and PPAR-γ, which
makes TNX-601 ER’s properties distinct from traditional
monoaminergic antidepressants in the U.S. and contributes to its
potential for clinical indications beyond MDD and stress disorders.
Tianeptine and its MC5 metabolite are also weak mu-opioid receptor
(MOR) agonists that present a potential abuse liability if
illicitly misused in large quantities (typically abused at 8-80
times the therapeutic dose on a daily basis2). 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 treated3 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 does not appear to result in
dependence or withdrawal symptoms following 6-weeks4-8, 3-months9,
or 12-months10 of treatment. The ER formulation of TNX-601 includes
several potentially abuse deterrent ingredients, such as gel
forming polymers which impede extraction. In addition, the tablet’s
hardness makes it difficult to crush, cut or grind to fine particle
size, which potentially hinders efforts to misuse by insufflation
or intravenous routes. 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
(PTSD), and neurocognitive dysfunction associated with
corticosteroid use. TNX-601 ER is expected to have patent
protection through 2037.
1 McEwen, B. S., et al. Mol. Psychiatry 2010, 15
(3), 237–249.
2 Lauhan, R., et al. Psychosomatics 2018, 59
(6), 547–53.
3 Haute 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.
4 Emsley, R., et al. J. Clin. Psychiatry 2018,
79 (4)
5 Bonierbale M, et al. Curr Med Res Opin 2003,
19(2):114-124.
6 Guelfi, J. D., et al. Neuropsychobiology 1989,
22 (1), 41–48.
7 Invernizzi, G. et al., Neuropsychobiology
1994, 30 (2–3), 85–93.
8 Lepine, J. P., et al. Hum. Psychopharmacol.
2001, 16 (3), 219–227.
9 Guelfi, J. D. et al., Neuropsychobiology 1992,
25 (3), 140–148.
10 Lôo, H. et al., Br. J. Psychiatry. Suppl.
1992, 15, 61–65.
Tonix Pharmaceuticals Holding
Corp.*
Tonix is a biopharmaceutical company focused on
commercializing, developing, discovering and licensing therapeutics
to treat and prevent human disease and alleviate suffering. Tonix
Medicines, our commercial subsidiary, markets Zembrace® SymTouch®
(sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray)
10 mg under a transition services agreement with Upsher-Smith
Laboratories, LLC from whom the products were acquired on June 30,
2023. Zembrace SymTouch and Tosymra are each indicated for the
treatment of acute migraine with or without aura in adults. Tonix’s
development portfolio is composed of central nervous system (CNS),
rare disease, immunology and infectious disease product candidates.
Tonix’s CNS development portfolio includes both small molecules and
biologics to treat pain, neurologic, psychiatric and addiction
conditions. Tonix’s lead development CNS candidate, TNX-102 SL
(cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3
development for the management of fibromyalgia, having completed
enrollment of a potentially confirmatory Phase 3 study in the third
quarter of 2023, with topline data expected in late December 2023.
TNX-102 SL is also being developed to treat fibromyalgia-type Long
COVID, a chronic post-acute COVID-19 condition. Enrollment in a
Phase 2 proof-of-concept study has been completed, and topline
results were reported in the third quarter of 2023. TNX-601 ER
(tianeptine hemioxalate extended-release tablets) is a once-daily
oral formulation being developed as a treatment for major
depressive disorder (MDD), that completed enrollment in a Phase 2
in the third quarter of 2023, with topline results expected in
early November of 2023. TNX-4300 (estianeptine) is a single isomer
version of TNX-601, a small molecule oral therapeutic in
preclinical development to treat MDD, Alzheimer’s disease and
Parkinson’s disease. Relative to tianeptine, estianeptine lacks
activity on the mu-opioid receptor while maintaining activity and
the ability to activate PPAR-β/δ and neuroplasticity in tissue
culture. TNX-1900 (intranasal potentiated oxytocin), is in
development as a preventive treatment in chronic migraine, and
enrollment has completed in a Phase 2 proof-of-concept study with
topline data expected in early December 2023. TNX-1900 is also
being studied in binge eating disorder, pediatric obesity and
social anxiety disorder by academic collaborators under
investigator-initiated INDs. 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 fourth quarter
of 2023. Tonix’s rare disease development 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 development 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 rejection and for the
treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was
initiated in the third quarter of 2023. Tonix’s infectious disease
pipeline includes TNX-801, a vaccine in development to prevent
smallpox and mpox. TNX-801 also serves as the live virus vaccine
platform or recombinant pox vaccine platform for other infectious
diseases. The infectious disease development portfolio also
includes TNX-3900 and TNX-4000, which are classes of broad-spectrum
small molecule oral antivirals.
*Tonix’s product development candidates are
investigational new drugs or biologics and have not been approved
for any indication.
Zembrace SymTouch and Tosymra are registered
trademarks of Tonix Medicines. Intravail is a registered trademark
of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis,
Inc. All other marks are property of their respective owners.
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; risks related to the failure to
successfully market any of our products; 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, 2022, as filed
with the Securities and Exchange Commission (the “SEC”) on March
13, 2023, 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.
Investor Contact
Jessica MorrisTonix
Pharmaceuticalsinvestor.relations@tonixpharma.com (862)
904-8182
Peter VozzoICR Westwickepeter.vozzo@westwicke.com (443)
213-0505
Media Contact
Ben ShannonICR
Westwickeben.shannon@westwicke.com443-213-0495
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