Full Press Release Details
TONIX PHARMACEUTICALS HOLDING CORP. 8-K
Tonix Pharmaceuticals Announces Agreement
and Initiation of Enrollment in Phase 2 Trial with the University of Washington to Study TNX-1900 (Potentiated Intranasal Oxytocin) for
Social Anxiety Disorder
Social Anxiety Disorder Affects 15 Million
U.S. Adults and is More Common Among Women than Men
CHATHAM, N.J., July 17, 2023 (GLOBE NEWSWIRE)
- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a
biopharmaceutical company, today announced that the first participant has been enrolled in a Phase 2 investigator-initiated, proof-of-concept
study of TNX-1900 (potentiated intranasal oxytocin) for enhancing social safety learning in social anxiety disorder (SAD). Tonix entered
into an agreement with the University of Washington to examine the potential role of TNX-1900 with Angela Fang, Ph.D., Assistant Professor,
Department of Psychology, University of Washington as the principal investigator.
"We are excited to collaborate with
the University of Washington and Dr. Fang on the development of TNX-1900 for social anxiety disorder," said Seth Lederman, M.D.,
Chief Executive Officer of Tonix Pharmaceuticals. "In the past decade, there has been an increase in studies examining oxytocin's
effects on social cognition and behavior in animals and humans due to translational discoveries showing that intranasal oxytocin appears
to reach central nervous system targets1. Specifically, evidence suggests that oxytocin may enhance the importance of social
cues or have anti-anxiety properties2,3. These studies have shown that intranasal oxytocin may hold therapeutic promise for
psychiatric disorders involving social deficits3-5. TNX-1900 is a proprietary formulation of oxytocin that contains magnesium,
which Tonix has shown in animal models potentiates the action of oxytocin at oxytocin receptors and potentially improves the consistency
of treatment by reducing paradoxical high-dose inhibition."
"For psychiatric disorders characterized
by severe social avoidance, such as social anxiety disorder, social learning has been disproportionately understudied despite its role
in the acquisition of fear in models of anxiety," said Dr. Fang. "Social anxiety disorder is a disabling psychiatric disorder.
Past research has focused on the observational, or vicarious, acquisition of fears, but little is known about how social information (such
as observing others experiencing safety) can promote safety learning. To address this issue, we will study the effects of vicarious extinction
learning on the recovery of conditioned fear."
The Phase 2 study is a randomized, double-blind,
placebo-controlled trial, such that all participants will be randomized to receive a single dose of either TNX-1900 or matching placebo
nasal spray. 100 subjects are planned to enroll: 50 with a primary diagnosis of SAD, and 50 demographically-matched healthy controls.
The primary objective of the Phase 2 study is to examine the potential role of TNX-1900 in enhancing vicarious extinction learning in
SAD, compared to healthy controls.
About Social Anxiety Disorder
Social anxiety disorder (SAD) is characterized
by persistent fear of one or more social or performance situations in which the person is exposed to unfamiliar people or to possible
scrutiny by others. The individual fears that he or she will act in a way (or show anxiety symptoms) that will be embarrassing and humiliating1.
SAD affects 15 million adults or 7.1% of the U.S. population, is more common among women than men, and typically begins around age 135-8.
Individuals with SAD report experiencing symptoms for 16 years before seeking help9.
MR, et al. Nat Commun. 2020. 11, 2783.
AS, et al. Pharmacol Res. 2019. 146, 104324.
G, et al. Biol Psychiatry. 2007. 62(10), 1187-90.
SG, et al. Biol Psychiatry. 2016. 79(3), 194-202.
5Meyer-Lindenberg A,
et al. Nat Rev Neurosci. 2011. 12, 524-538.
M & Aderka IM. J Clin Psychol. 2018. 74(10), 1730-1741.
M, et al. Clin Psychol Rev. 2017. 56, 1-12.
et al. J Anxiety Disord. 2012. 26(1), 12-19.
9Wang PS, et al. Arch Gen Psychiatry. 2005. 62, 603-613.
TNX-1900 (intranasal potentiated
oxytocin) is a proprietary formulation of oxytocin in development as a candidate for prevention of chronic migraine and other conditions.
In 2020, TNX-1900 was acquired from Trigemina, Inc. who had licensed the technology underlying the composition and method from Stanford
University. TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nasal
cavity. Oxytocin is a naturally occurring human peptide hormone that also acts as a neurotransmitter in the brain. Oxytocin has no recognized
addiction potential. It has been observed that low oxytocin levels in the body are associated with increases in migraine headache frequency,
and that increased oxytocin levels are associated with fewer migraine headaches. Certain other chronic pain conditions are also associated
with decreased oxytocin levels. Migraine attacks are caused, in part, by the activity of pain-sensing trigeminal neurons which, when activated,
release of calcitonin gene-related peptide (CGRP) which binds to receptors on other nerve cells and starts a cascade of events that is
believed to result in headache. Oxytocin when delivered via the nasal route, concentrates in the trigeminal system3 resulting
in binding of oxytocin to receptors on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals
returning from the site of CGRP release.4 Blocking CGRP release is a distinct mechanism compared with CGRP antagonist
and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor. With TNX-1900, the addition of magnesium to the oxytocin
formulation enhances oxytocin receptor binding5 as well as its inhibitory effects on trigeminal neurons and resultant
craniofacial analgesic effects, as demonstrated in animal models7. Intranasal oxytocin has been shown to be well tolerated
in several clinical trials in both adults and children6. Targeted nasal delivery results in low systemic exposure and lower
risk of non-nervous system, off-target effects, which could potentially occur with systemic CGRP antagonists such as anti-CGRP antibodies8.
For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. The Company believes nasally targeted
delivery of oxytocin could translate into selective blockade of CGRP release from neurons in the trigeminal ganglion and not throughout
the body, which could be a potential safety advantage over systemic CGRP inhibition. In addition, daily dosing is more rapidly reversible,
in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control.
In addition to chronic migraine, TNX-1900 will be developed for treatment of episodic migraine, binge eating disorder, craniofacial pain
conditions, and insulin resistance. Tonix also has a license with the University of Geneva to use TNX-1900 for the treatment of insulin
resistance and related conditions.
1NIH, National Institute of Mental
2Anxiety & Depression Association
3Yeomans DC, et al. Transl Psychiatry.
4Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.
5Antoni FA & Chadio SE. Biochem J. 1989. 257(2):611-4
6Yeomans DC, et al. 2017. US patent US2017368095
7Cai Q, et al. Psychiatry Clin Neurosci. 2018. 72(3):140-151
8MaassenVanDenBrink A, et al. Trends Pharmacol Sci. 2016. 37(9):779-788
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 markets Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg. 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 CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management
of fibromyalgia with topline data expected in the first quarter of 2024. TNX-102 SL is also being developed to treat Long COVID, a chronic
post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter
of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major
depressive disorder (MDD), is also currently enrolling with topline results expected in the first quarter of 2024. TNX-4300 (estianeptine)
is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer's disease and Parkinson's disease.
TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, is currently enrolling with topline data expected in
the fourth quarter 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 third 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