Tonix to initiate Prader-Willi Syndrome Phase 2 Trial of TNX-2900

Tonix Pharmaceuticals plans to progress its TNX-2900 programme for the treatment of Prader-Willi syndrome (PWS) into a Phase 2 clinical trial. TNX-2900 is a proprietary magnesium-potentiated intranasal oxytocin formulation designed to improve receptor binding and decrease dose-related inconsistencies in receptor activity.

The programme has received both Orphan Drug and Rare Pediatric Disease designations from the 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.

“We are pleased to advance TNX-2900 into a Phase 2 trial for PWS, a condition with unmet needs for new medicines with activity and tolerability,” said Dr Seth Lederman, Chief Executive Officer of Tonix Pharmaceuticals. “Families caring for children with PWS face significant challenges and burdens. Among them is hyperphagia which drives persistent food-seeking behaviours that require constant supervision and often result in obesity and serious medical complications. With an average life expectancy of less than 30 years, treatment of PWS remains an urgent and unmet need. By addressing limitations of traditional oxytocin delivery, we believe TNX-2900 has the potential to become an FDA-approved therapy targeting the oxytocin receptor in PWS and provide meaningful benefit for patients and families living with this rare disorder.”

Research suggests PWS is associated with a functional deficiency of oxytocin, a neuropeptide that regulates satiety and feeding behaviours through the oxytocin receptor. Oxytocin treatment addresses several key features of PWS expressed in the MAGEL2 (MAGE-like 2) knock-out mouse. Intranasal oxytocin therapy has shown benefits in infants with PWS.  Carbetocin has a different spectrum of activity on oxytocin and vasopressin receptors than oxytocin and carbetocin has not been tested to our knowledge in the MAGEL2 knock-out mouse. Oxytocin has 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 to further enhance oxytocin receptor binding and signalling, with the goal of providing more consistent and selective receptor activation while minimizing off-target vasopressin effects. In vitro and in vivo in animals Mg++- containing formulations reduce these inconsistencies.

Tonix plans to conduct a Phase 2 randomised, double-blind, placebo-controlled, parallel-design study to evaluate the safety, tolerability and efficacy of TNX-2900 in male and female participants with PWS, ages 8 to 17.5 years. Eligible participants will be randomised 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 behaviour, caregiver burden, and quality of life measures, as well as safety and tolerability outcomes.