TNX-2900

TNX-2900 (intranasal potentiated oxytocin) is an investigational therapy being developed for the treatment of Prader-Willi syndrome (PWS). TNX-2900 is a proprietary magnesium-potentiated intranasal oxytocin formulation designed to improve receptor binding and decrease dose-related inconsistencies in receptor activity. Tonix’s patented potentiated oxytocin formulation is believed to increase specificity for oxytocin receptors relative to vasopressin receptors as well as to enhance the potency of oxytocin.

The TNX-2900 program for PWS has received both Orphan Drug and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA), which would make Tonix eligible for a transferable Priority Review Voucher, upon approval. The FDA has cleared the Investigational New Drug (IND) application for TNX-2900 to progress into Phase 2 development.

Prader-Willi syndrome is a rare genetic disorder and the leading cause of life-threatening childhood obesity, affecting about 1 in 10,000 to 1 in 30,000 births. Prader-Willi syndrome results from the absence of expression of a group of genes, specifically related to the MAGE (melanoma antigen) gene family on the Prader-Willi critical region (15q11–q13) on the paternally acquired chromosome. Infants often present with poor muscle tone and feeding difficulties, while children and adolescents develop hyperphagia, behavioral challenges, and severe obesity and metabolic disease. Current interventions are difficult to sustain and often inadequate.

Research suggests that PWS is associated with a functional deficiency of oxytocin, a naturally occurring neuropeptide that regulates satiety and feeding behaviors through the oxytocin receptor. In the MAGEL2 knock-out mouse model for PWS and autism, administration of oxytocin has potent effects in correcting feeding deficiencies. In pediatric and adult patients with PWS, clinical trials using intranasal oxytocin have shown evidence for improvement in PWS-related behaviors/symptoms, hyperphagia, and suckling in infants.

Oxytocin has been shown to have dose-related inconsistencies in receptor activity that have been described as “high-dose suppression” or an “inverted “U” dose response. TNX-2900 is formulated with magnesium which is intended to further enhance oxytocin receptor binding and signaling, with the goal of providing more consistent and selective receptor activation while minimizing off-target vasopressin effects. Magnesium-containing formulations of oxytocin have been shown to reduce these inconsistencies in vitro and in animal models.

Tonix plans to conduct a Phase 2 randomized, double-blind, placebo-controlled, parallel-design study to evaluate the safety, tolerability, and efficacy of TNX-2900 in male and female pediatric patients with PWS. Eligible participants will be randomized to receive 12-weeks of treatment with TNX-2900 at one of three dose levels, or placebo, in a 1:1:1:1 ratio. The primary efficacy endpoint will be the change from baseline in the validated Hyperphagia Questionnaire for Clinical Trials (HQ-CT), a widely used measure of hyperphagia severity in PWS. Secondary objectives will include assessments of behavior, caregiver burden, and quality of life measures, as well as safety and tolerability outcomes

TNX-2900 is an investigational new drug and has not been approved for any indication.