Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Tonix Pharmaceuticals Announces
Initiation of Enrollment in the MGH Phase 2 POWER' Study of TNX-1900 (Intranasal Potentiated Oxytocin) for the Treatment
of Pediatric Obesity
Preliminary Data Suggest that Oxytocin May Simultaneously
Reduce Energy Intake and Increase Energy Expenditure
TNX-1900 (Intranasal Potentiated Oxytocin) May Serve
as a Novel Neuroendocrine Weight-Loss Therapeutic for this Patient Population
CHATHAM, N.J., July 10, 2023
- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced
that the first participant was enrolled in the Phase 2 POWER' study of TNX-1900 (intranasal potentiated oxytocin) for the
treatment of pediatric obesity at the Massachusetts General Hospital (MGH). The aim of the study is to investigate the efficacy and safety
of TNX-1900 as a novel therapeutic agent to induce weight loss and improve indicators of cardiometabolic risk in adolescent patients with
obesity. Tonix is providing active drug and placebo for the POWER study as part of a drug donation agreement with MGH. MGH is the sponsor
of the National Institutes of Health-funded trial, being conducted under an investigator-initiated IND.
The 12-week double-blind,
placebo-controlled trial has a target enrollment of 75 participants 12-18 years old with obesity.
"More than two-thirds of the U.S. population
suffers from obesity or is overweight1," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals.
"Available pharmacologic treatment options for weight loss in children are limited by safety/tolerability problems and failure to
achieve sustained weight loss. It is essential to develop safe and effective therapeutic strategies for weight loss, particularly in adolescents,
who are understudied while being at greatest risk for long-term comorbidities."
Elizabeth A. Lawson, M.D., M.M.Sc., Director, Interdisciplinary
Oxytocin Research Program in the Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and principal investigator
(along with Madhusmita Misra, MD, and Miriam Bredella, MD) of the study added, "Studies in animals have shown that oxytocin, a hypothalamic
peptide hormone, simultaneously reduces food intake and increases energy expenditure, leading to weight loss. Intranasal oxytocin is well-tolerated
and in our studies of adults, results in reduced caloric intake, increased fat burning, and improved insulin sensitivity. The goal of
the double-blind POWER study is to assess whether intranasal administration of oxytocin will decrease weight as a consequence of decreased
caloric intake and increased energy expenditure, and improve metabolic risk markers in adolescents with obesity."
About the Phase 2 POWER Study
The Phase 2 POWER investigator-initiated study is
a randomized, double blind, placebo-controlled study to evaluate the efficacy and safety of TNX-1900 for the treatment of pediatric obesity.
The 12-week trial has a target enrollment of 75 participants 12-18 years old with obesity (BMI 95th percentile for
age and gender). Subjects will be randomized to receive TNX-1900 or placebo and will be studied at the Translational and Clinical Research
Center at Massachusetts General Hospital. Subjects will self-administer TNX-1900 or placebo as two sprays total (one spray in each nostril)
before meals and at bedtime for 12 weeks. The primary endpoint is 12-week change in body mass index standard deviation score (BMI-SDS)
For more information, see ClinicalTrials.gov Identifier:
About Pediatric Obesity2
Childhood obesity is a serious health problem in the
United States, with approximately one in five children and adolescents affected. Many factors can contribute to excess weight gain including
behavior, genetics and taking certain medications. Obesity-related conditions include high blood pressure, high cholesterol, type 2 diabetes,
breathing disorders such as asthma and sleep apnea, polycystic ovary syndrome (in females), and joint pathology.
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 within the central nervous system (CNS). 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 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 oxytocin's 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-CNS, 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 patients greater control. In addition to chronic
migraine, TNX-1900 will be developed for treatment of episodic migraine, binge eating disorder, and craniofacial pain conditions. Tonix
also has a license with the University of Geneva for the use of TNX-1900 in the treatment of insulin resistance and related conditions.
TNX-2900 is another intranasal potentiated oxytocin-based
therapeutic candidate, being developed for the treatment of Prader-Willi syndrome, or PWS. The technology for TNX-2900 was licensed from
the French National Institute of Health and Medical Research. PWS, an orphan condition, is a rare genetic disorder of failure to thrive
in infancy, associated with uncontrolled appetite later in childhood.
1Ogden CL, Carroll MD, Flegal
KM. Prevalence of obesity in the United States. JAMA 2014;312:189-90.
2Centers for Disease Control
3Yeomans DC, et al. Transl
Psychiatry. 2021. 11(1):388.
4Tzabazis A, et al. Cephalalgia.
2016. 36(10):943-50.
5Antoni FA and 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