Improvement and validation of the Spring System for Permanent Relief of Urinary Obstruction related to Benign Prostatic Hyperplasia (BPH)

ABSTRACT Benign Prostatic Hyperplasia (BPH) is the most common cause of obstructive lower urinary tract symptoms in men. As the prostate progressively enlarges with age, it obstructs the flow of urine from the bladder, leading to urinary straining, frequency, urgency, and nocturia. At Zenflow, we have developed the Spring System, which consists of a single-wire nickel titanium (nitinol) coil implant designed to permanently relieve BPH-related urinary obstruction, and a flexible transurethral delivery system that includes a cystoscope with built-in visualization. We developed this solution to meet the long-standing clinical need for a safe, effective, cost-efficient, office-based BPH therapy that provides durable symptom relief in a single procedure without side effects. The device aims to improve upon previous technologies such as stents and the prostatic urethral lift device. Between 2014 and 2017, we developed the first-generation Spring System and successfully completed preclinical work including cadaver and chronic animal studies, then first-in-man studies. In 2017, we were awarded a Phase II NIH SBIR grant. This project involved development of a refined design to improve clinical safety, effectiveness, and ease of use. The goal of this Phase II project was, in conjunction with ongoing pilot clinical trials, to prepare Zenflow for a US pivotal IDE study. While the aims of this project were successful, clinical testing revealed opportunities for further improvements to the Spring System, which we believe will result in an even safer and more reliable procedure that reaches a new frontier in effectiveness, and will also expand the range of anatomical configurations that the system can treat. These improvements fall into two categories which we offer to test under the current grant proposal: in Specific Aim 1 we will improve the implant and delivery system to yield a more effective procedure that can treat a broader range of patients, and in Specific Aim 2 we will improve our proprietary single-use cystoscope to enable better visualization and allow urologists to place the implant more accurately and confidently. Next, in Specific Aim 3 we will validate all improvements described above, we will test the full Spring System in cadavers to demonstrate functionality of the Spring System in simulated use by a urologist. The system will be tested on two cadavers at the end of year 1 after completing all implant and delivery system work described in Aim 1, then two more at the end of year 2 after completing all scope developments in Aim 2. Successful completion of both of these studies will represent completion of our Phase II work. We will incorporate the results of the Aim 1 implant work into our US pivotal IDE study. The Aim 2 Scope improvements will be incorporated into later clinical studies. While we developed the Spring Scope specifically to place the Spring Implant, it could be used for deployment of implants to treat conditions such as urethral strictures or painful bladder syndrome, delivery of drugs or energy to treat BPH-related LUTS, prostate cancer, or other conditions. We will continue to explore these possibilities and file intellectual property on alternative applications.NARRATIVE Benign Prostatic Hyperplasia (BPH) is the most common cause of obstructive lower urinary tract symptoms (LUTS) in men. In the US, more than 50% of men in their 60s and 90% of octogenarians present with LUTS. Zenflow has developed the Spring System consists of a single-wire nickel titanium coil implant designed to permanently relieve BPH-related urinary obstruction, and a flexible transurethral delivery system that includes a cystoscope with built-in visualization. The aim of this project is to further improve the implant and the delivery system in order to yield a safer and more effective procedure that can treat a broader range of patients.