Tonix Pharmaceuticals Announces Initiation of Enrollment in MGH Phase 2 POWER Study of Intranasal Potentiated Oxytocin for the Treatment of Pediatric Obesity

Tonix Pharmaceuticals Holding Corp. recently announced 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 US population suffers from obesity or is overweight,” said Seth Lederman, MD, 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, MD, MMSc, 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.”

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) versus placebo. For more information, see ClinicalTrials.gov Identifier: NCT04551482.

Childhood obesity is a serious health problem in the US, 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 system 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. 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 binding as well as oxytocin’s inhibitory effects on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models. Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children. 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 antibodies. 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.

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 is expected to be 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, classes of broad-spectrum small molecule oral antivirals. For more information, visit www.tonixpharma.com.