Project Grant R44FD006891

K9-ICT: A NOVEL URETHRAL VALVE TREATMENT FOR CANINE URINARY INCONTINENCE - PROJECT SUMMARY / ABSTRACT VENARUM MEDICAL, LLC (VENARUM) IS DEVELOPING THE CANINE INCONTROL URETHRAL VALVE SYSTEM (K9-ICT), A NOVEL URETHRAL IMPLANT SOLUTION FOR THE TREATMENT OF URINARY INCONTINENCE (UI). THIS TRANSURETHRAL, CATHETER- DELIVERED VALVE IS INTENDED TO CONTROL THE FLOW OF URINE IN ORDER TO REDUCE URINE LEAKAGE AND OTHER COMPLICATIONS OF UI. IT CONSISTS OF A NITINOL SCAFFOLD EMBEDDED IN A BIOCOMPATIBLE POLYMER WITH A COMPLETELY INTEGRATED POLYMERIC INNER VALVE WHICH IS COMPRISED OF A FLEXIBLE LEAFLET-LIKE MEMBRANE. THE K9-ICT VALVE IS PLACED IN THE MID TO PROXIMAL URETHRA AND IS DESIGNED TO SIGNIFICANTLY REDUCE URINE LEAKAGE BY RESTORING THE ABILITY TO RETAIN URINE AND VOID AT SIMILAR URINARY BLADDER PRESSURES THAT ARE SEEN IN CONTINENT DOGS. ADDED DURING PHASE I, THE VALVE WILL ALSO BE RETRIEVABLE TO MITIGATE POTENTIAL ADVERSE REACTIONS AND/OR POOR PLACEMENT. THIS PHASE II OBJECTIVE IS TO DEMONSTRATE PRELIMINARY CLINICAL SAFETY OF THE FINAL K9-ICT. CANINE UI IS A CONDITION CHARACTERIZED BY INAPPROPRIATE OR "INVOLUNTARY" PASSAGE OF URINE. CLINICAL SIGNS AND SEQUELAE OF UI INCLUDE URINE LEAKAGE, UNWANTED URINATION IN THE HOUSE, SKIN IRRITATION, AND DISCOMFORT. THE MOST COMMON NON-NEUROGENIC CAUSE OF CANINE UI IS URETHRAL SPHINCTER MECHANISM INCOMPETENCE (USMI), WHICH IS THOUGHT TO BE HORMONE-RELATED AND AFFECTS OVER 20% OF SPAYED FEMALE DOGS, EQUATING TO ROUGHLY 5 MILLION PETS IN THE U.S. NONE OF THE CURRENT TREATMENT OPTIONS FOR UI-MEDICAL MANAGEMENT, URETHRAL BULKING AGENTS, AND SURGICAL CORRECTION-ARE RELIABLY EFFICACIOUS AND ALL CARRY RISKS. VENARUM INTENDS TO LEVERAGE ITS EXPERTISE IN IMPLANTABLE DEVICE TECHNOLOGIES, VETERINARY MEDICINE AND POLYMER SCIENCE TO BRING THE K9-ICT FROM CONCEPT TO MARKET. WE HAVE EXTENSIVE EXPERIENCE WITH POLYMER-COATED NITINOL STENT TECHNOLOGY THROUGH THE ONGOING DEVELOPMENT OF A PROSTHETIC VENOUS VALVE AND ARE WELL POSITIONED TO APPLY OUR DESIGN AND MANUFACTURING KNOWLEDGE TO MEET THE UNIQUE CHALLENGE OF CANINE UI. EFFECTIVE TREATMENT OF UI REQUIRES AN UNDERSTANDING OF THE INTERPLAY BETWEEN INTRA-ABDOMINAL PRESSURE, URINARY BLADDER PRESSURE, URETHRAL PRESSURE, SPHINCTER COMPETENCY, AND THE FEEDBACK AND REFLEXES INVOLVED IN THE VOIDING MECHANISM. THROUGH BENCH AND CADAVER STUDIES IN PHASE I, VENARUM HAS DEMONSTRATED THAT THE VALVE CAN EASILY BE DELIVERED; CAN FEASIBLY PREVENT INDISCRIMINATE FLUID LEAKAGE AND PERMIT FLUID PASSAGE WITHIN A DESIRED RANGE OF PRESSURES APPROXIMATING THOSE IN CONTINENT DOGS; AND CAN BE RETRIEVED. UNDER PHASE II, VENARUM PROPOSES TO (1) OPTIMIZE AND FINALIZE THE SYSTEM COMPONENTS (I.E. VALVE, DELIVERY SYSTEM, AND RETRIEVAL TOOL); (2) PERFORM PHYSICAL AND BIOCOMPATIBILITY VERIFICATION TESTING OF THE FINAL K9-ICT SYSTEM; AND (3) PERFORM IN VIVO CANINE CLINICAL PRELIMINARY SAFETY STUDIES CONSISTENT WITH EVALUATIONS OF DEVICES INTENDED FOR HUMAN USE. VENARUM WILL CONTINUE TO ENGAGE THE VETERINARY COMMUNITY AND CANINE UI EXPERTS IN ORDER TO BUILD INTEREST IN THE K9-ICT TECHNOLOGY AND IDENTIFY AN EFFICIENT PATH TO COMMERCIALIZATION.