decapeptide levels were detectable for greater than 26 weeks and remained above 1 ngml for almost all of the study points The T levels correlated to the exposure from the formulations and PKPD was ID: 857935
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!"#"$!%&'()#*"!'(!"#"+*$*,)+'-"#,.+'/'01234445(6789:(:979;88=6;7&#x -8 ;56?BackgroundAndrogen 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 surge, current injectable GnRH antagonists are short term (1 month) subcutaneous (sc) depots that require a high volume loading dose followed by monthly high volume maintenance dosing. VERU-100 is a novel GnRH decapeptide antagonist 3 month depot formulation for long term suppression of T to below castrate levels and is administered as a low volume scinjection (1 cc) without the requirement of a loading dose. Eight distinct GnRH antagonist formulations were evaluated in rats in order to select the best formulation, VERU-100. MethodsMale Sprague Dawley rats (n=3 per group) were injected scthrough a 21G needle, with approximately 200µl of decapeptide 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. ConclusionsVERU-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.Funding -This study was supported by VeruInc.1Veru Inc., Miami, FL and 2Drug Delivery Experts, LLC, San Diego, CARobert H. Getzenberg1, Jui-Chen Lin2, Andrew Cerro2, Christopher A. Rhodes, Mitchell S. SteinerDetermination of the ability of a novel, long-acting subcutaneous GnRH antagonist, VERU-100, to castrate without a testosterone surge in a rat modelMATERIALS AND METHODSMale Sprague Dawley rats (n=3 per group) were injected 100 administration resulted in undetectable total testosterone levels for more than six months in almost all formulation variants!The decreases in testosterone levels are rapid (within hours)!No surge/flare in testosterone levels were observed!No testosterone escapes were identified!VERU-100 is a long acting 3-month depot GnRH antagonist!Novel proprietary GnRH antagonist decapeptide formulation!VERU-100 is a 3-month slow release subcutaneous depot (1 cc SQ injection) with no loading dose!Immediate testosterone suppression no initial testosterone surge!Suppression of testosterone to less than 20ng/dL!As with other GnRH antagonists, no black box warning for cardiovascular adverse effects!FDA has agreed with plans for clinical development!Single phase 2 Ðopen label, multicenter dose finding study of three doses of VERU-100 in men with advanced prostate cancer (n=60-80)!Single Phase 3 Ðopen label, multicenter study in men with advanced prostate cancer (n=100) !"###!#!!#!!!!$%#&#'&!&$&%()*+,--./01-2/3245/673-8/49,:;,)-2=3)*- 0.; 00;?,6/673*2365/-8@))A;B1C!&DC!!DB1C!D!C!!#B1C!D!C!!&B1C!D#C!!#B1C!D&C!!#B1C!DDC!!#B1C!D$C!!#B1C!DEC!!#!#&D$E'F%!$%#&#'&!&$&%()*+,-)73573)*5/)-8/49,:;,)-2=3)*- 0.; 00;?,6/673*2365/--8G))A;B1C!&DC!!DB1C!D!C!!#B1C!D!C!!&B1C!D#C!!#B1C!D&C!!#B1C!DDC!!#B1C!D$C!!#B1C!DEC!!#!#&D$E'F%!$%#&#'&!&$()*+,-)73573)*5/)--8/49,:;,)-2=3)*- 0.; 00;?,6/673*2365/-8H*; FHI3J1KH1LM12&#xG -1; 00;GN341%)$+1O&#xG -1; 00;8#&#xG -1; 00;P6Q4;638;G1:8GH@?@$0%$0.$0,$0'$0&$$0$.'&%&,%$%.%'A:RP$1S;B1:RP$1S"DA0DT?631AU33ED!"#$%%#$$&!"#$%(#$$&!"#$%.#$$&$0&$0%$0($0.$0-$0,$0$&%(.T?631AU33EDpportunity for novel androgen deprivation therapy for advanced prostate cancer Concern over initial T ÒsurgeÓ and micro-increases!Convenient 4 and 6 monthslow release !ÒBuy and billÓ model attractive to community Urologists!Most popular is 3 monthdepotGnRHAntagonistFIRMAGON¨ (degarelix)(SC) events