Protagenic Therapeutics published preclinical data showing its lead candidate PT00114 reduced physiological and behavioral markers of chronic stress in a 14-day chronic unpredictable stress model in male Sprague-Dawley rats, according to the company.
In the study, PT00114 reduced stress-induced plasma corticosterone by 56.4 percent versus stressed, saline-treated controls (p = 0.029) after two 250 nmol/kg subcutaneous doses given on days 12 and 13.
PT00114 also increased time spent in the center of an open field arena by 282 percent versus controls (p = 0.031), with no significant change in total distance traveled, indicating the effect was not attributable to altered locomotion.
A prototypical non-peptide CRF1 receptor antagonist, CP-154,526, showed no activity on these endpoints whether dosed on days 12 and 13 or daily throughout the paradigm.
The authors and the company emphasize translational significance given prior failures of structurally distinct CRF1 antagonists in clinical trials and suggest PT00114, a synthetic analog of TCAP-1, may act upstream of or in parallel with the CRF signaling cascade.
PT00114 completed single- and multiple-dose Phase 1 studies with favorable topline safety and the company plans subsequent clinical studies in 2027. Protagenic is a clinical-stage biopharmaceutical headquartered in New York, NY and trades on OTCQB under PTIX.
