Protagenic Publishes New Preclinical Data for PT00114

Protagenic Therapeutics announced the publication of new preclinical data for its lead candidate, PT00114, in the peer-reviewed journal Behavioural Pharmacology. In a well-established rodent model of chronic unpredictable stress, PT00114 reduced both physiological and behavioral markers of chronic stress after stress had been established, while the prototypical non-peptide corticotropin-releasing factor receptor 1 antagonist CP-154,526 did not show activity on the same endpoints. As part of their pre-clinical investigation program, using a 14-day chronic unpredictable stress paradigm in male Sprague Dawley rats, the researchers evaluated PT00114 against saline as a control and CP-154,526 as a comparator. PT00114 reduced stress-induced plasma corticosterone by 56.4%, relative to stressed, saline-treated controls, after two 250 nmol/kg doses administered subcutaneously on days 12 and 13. PT00114 increased time spent in the center of an open field arena by 282% versus controls. There was no significant change in total distance traveled-indicating that the effect was not attributable to a general change in locomotion. CP-154,526 did not affect either corticosterone or time spent in the center of the open field whether it was administered on days 12 and 13 or daily throughout the entire stress paradigm These data provide further preclinical rationale for Protagenic Therapeutic's development strategy of evaluating PT00114 for the potential treatment of chronic, stress-related conditions. Protagenic has reported positive topline safety results from Phase 1 studies of PT00114 and plans to initiate subsequent clinical studies in 2027. Multiple, structurally distinct CRF1 receptor antagonists have shown robust activity in acute-stress rodent models over the past two decades but have repeatedly failed to separate from placebo in clinical trials for generalized anxiety disorder, major depressive disorder, and related conditions. The study authors note that this preclinical-to-clinical gap has been attributed, in part, to an over-reliance on acute-stress models that may not reflect the sustained, heterogeneous nature of human anxiety and depression. In this study, PT00114 retained activity while a CRF1 antagonist was ineffective in a chronic stress environment even with continuous dosing.