Background: Androgen deprivation therapy (ADT) is the mainstay for the treatment of advanced prostate cancer. LHRH agonists are frequently used for ADT but these agents often result in initial surges in testosterone (T) levels. Although they do not result in initial T surges, current injectable GnRH antagonists are short term (1 month) subcutaneous (sc) depots that require a high volume loading dose followed by monthly maintenance dosing. VERU-100 is a novel GnRH decapeptide antagonist for long term suppression of T to castrate levels and is administered as a low volume sc injection without the requirement of a loading dose. Eight distinct formulations were evaluated in rats in order to select the best formulation, VERU-100. Methods: Male Sprague Dawley rats (n=3 per group) were injected sc through a 21G needle, with approximately 200μl of each formulation at a dose level of 20 mg/kg. Eight groups consisting of the distinct test formulations were evaluated. Blood samples were drawn at weekly intervals until week 4 and then bi-weekly for pharmacokinetic (PK) (Integrated Analytical Solutions) and testosterone (T) level determinations (Cornell University Animal Health Diagnostic Center). Results: Within approximately 24 hours after administration of the GHRH antagonist formulations, testosterone levels in the rats went from a mean of 7.36 ng/ml to undetectable. The T levels resulting from a single injection of the lead formulation in these studies, VH-030-002, remained undetectable for greater than 26 weeks (6 months) as did the other formulations tested. The corresponding PK analysis demonstrated that the GnRH antagonist levels were detectable for greater than 26 weeks and remained above 1 ng/ml for almost all of the study points. The T levels correlated to the exposure from the formulations, and PKPD was as consistent for GnRH antagonists. Conclusions: VERU-100 is a novel GnRH antagonist formulation that in this rodent study, with a low injection volume, resulted in undetectable T for at least six months. No surge of T is observed after administration. An IND submission is anticipated in early 2020 for the dose finding Phase 2 trial in men with advanced prostate cancer.