Full Press Release Details
Tonix Pharmaceuticals 8-K
Pharmaceuticals Completes Clinical Stage of Phase 2 PREVENTION Study of TNX-1900 for the Prevention of Migraine Headaches in Chronic
results expected early December 2023
formulation of intranasal oxytocin contains magnesium (Mg2+), shown to potentiate the analgesic effects of oxytocin on the oxytocin receptor
blocks release of CGRP, a key peptide in the pathogenesis of migraine, from trigeminal ganglia neurons while limiting systemic exposure
N.J., October 26, 2023 - Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products
and a pipeline of development candidates, today announced the completion of the clinical phase of the Phase 2 proof-of-concept, double-blind,
randomized, placebo-controlled PREVENTION1 study of TNX-19002 (intranasal potentiated oxytocin) as a potential
treatment for the prevention of migraine headaches in chronic migraineurs. A total of 88 patients were enrolled in this multi-site study
in the U.S. Topline results are expected in early December 2023.
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. Its unique,
multimodal mechanism of action includes an ability to inhibit the release of the trigeminal neuropeptide calcitonin gene-related peptide
(CGRP) in blood vessels within the brain, its lining and the brainstem, and to suppress signaling in pain neurons. Tonix believes that
by engaging and activating oxytocin receptors in the trigeminal ganglia, TNX-1900 has the potential to help those suffering from chronic
is being developed as a novel, non-CGRP antagonist approach to treatment for chronic migraineurs," said Seth Lederman, M.D., Chief
Executive Officer of Tonix Pharmaceuticals. "There are an estimated four million individuals in the U.S. suffering from this debilitating
condition, and despite several classes of migraine preventives available, there remains an unmet need for novel approaches."
the last patient now treated, we look forward to analysis of the results of this proof-of-concept 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."
Trials.gov I.D. NCT05679908
is an investigational new drug and is not approved for any indication.
the Phase 2 PREVENTION Study
Phase 2 PREVENTION study is a double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of
TNX-1900 taken prophylactically on a daily basis to prevent chronic migraine. There are three arms: two treatment regimens of TNX-1900
and one placebo in a 1:1:1 ratio in a total of 88 participants across approximately 26 U.S. sites. After a four-week Run-In phase to
confirm chronic migraine criteria are met, there are 12-weeks of a double-blind Treatment phase with study drug, followed by a 2-week
safety Follow-Up phase. The primary efficacy endpoint is mean change in the number of migraine headache days between the 28-day Run-In
phase and the last 28-days of thTreatment phase. Key secondary efficacy endpoints include proportion of patients experiencing a
50% reduction in the number of migraine headache days, mean change in the number of days using migraine abortive medications, and mean
change in a migraine-specific quality of life measure.
more information, see ClinicalTrials.gov Identifier: NCT05679908.
is a neurological condition that typically manifests in a throbbing moderate to severe headache which lasts at least four hours, often
on one side of the head and aggravated by routine physical activity. It can also be accompanied by nausea, vomiting, visual disturbances,
and sensitivity to bright light and loud noises1. Epidemiological studies indicate that globally, approximately 1.2 billion
individuals suffer from migraines annually.2 In the U.S., approximately 39 million Americans suffer from migraines and
among these individuals, approximately four million experience chronic migraines (15 or more headache days per month, at least eight
of which are migraines).2 The current FDA approved drugs for migraine prevention in chronic migraine include Botox (onabotulinumtoxinA),
and the anti-CGRP/CGRP-R monoclonal antibodies Aimovig (erenumab), Vyepti (eptinezumab), Ajovy (fremanezumab)
and Emgality (galcanezumab).
International Classification of Headache Disorders, 3rd Edition. Cephalalgia. 2018. 38(1):1-211.
et al., Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin. 2019. 631-649.
(intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development as a candidate for prevention in 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 system1 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 release2. 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 binding3 as well as its
inhibitory effects on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models4.
Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children5. 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 antibodies6. 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.
DC, et al. Transl Psychiatry. 2021. 11(1):388.
A, et al. Cephalalgia. 2016. 36(10):943-50.
FA and Chadio SE. Biochem J. 1989. 257(2):611-4.
Q, et al., Psychiatry Clin Neurosci. 2018. 72(3):140-151.
DC et al. 2017. US patent US2017368095.
A, et al. Trends Pharmacol Sci. 2016. 37(9):779-788.
Pharmaceuticals Holding Corp.*
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 study 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- / and neuroplasticity in tissue culture. TNX-1900 (intranasal potentiated oxytocin), is
in development as a preventive treatment in chronic migraine, and the clinical phase of a Phase 2 proof-of-concept study is now completed
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