Preclinical proof of concept validation of a novel endoscopic treatment for urethral stricture disease

PROJECT SUMMARY/ABSTRACT CeleFlux is developing a medical device which enables urologists to provide long-lasting, minimally invasive urethral reconstruction to treat male urethral stricture - via endoscopic delivery of a temporary tissue graft implant. Urethral stricture disease progressively narrows the urethral lumen, similar to a band of scar tissue. This results in painful and frequent urination and dramatically reduced quality of life. Current treatment options are suboptimal, requiring a choice between (1) minimally invasive (endoscopic) intervention associated with high recurrence rates; or (2) highly effective but long, complex open reconstructive surgery. The latter requires a specialized skill set, and consequently availability of urethral reconstruction is limited. General urologists typically cannot offer definitive treatment to men with recurrent stricture. Repeated endoscopic intervention worsens the stricture and turns a curable condition into a chronic disease. We aim to change that by bridging the gap between the two approaches. CeleFlux is commercializing a technology empowering general urologists to deliver curative treatment for bulbar urethral stricture, approaching the efficacy of open reconstruction. Our medical device innovation simplifies a procedure to reconstruct the urethra with a tissue graft endoscopically. The graft is delivered to the target site via a temporary implant which is removed 14 days later. The result is a urethra widened by a healthy graft, durably alleviating the symptoms of urethral stricture. The clinical need, user requirements, and product-market fit were validated through extensive customer discovery with general (target users) and reconstructive urologists (disease state experts). Key hurdles include achieving engraftment with our device, and safe removal of the temporary implant. In this proposal, we will evaluate and address these in a large animal model. We aim to demonstrate that a graft delivered endoscopically via our temporary implant is comparable to a graft delivered via open surgery (the gold standard). We also aim to demonstrate that the temporary implant can be removed 14 days later without disruption to the adhered graft. The resulting outcomes will illustrate the feasibility of our innovation, drive future commercialization-focused activities, and support our goal to shift the current clinical paradigm for men with recurrent bulbar urethral stricture disease - away from chronic management and toward durable reconstruction.PROJECT NARRATIVE Urethral stricture disease is devastating to the quality of life of affected men, in great part because the most widely available endoscopic treatment is simple and minimally invasive but rarely curative - leading to chronic management of the disease. Graft-based urethral reconstruction has excellent long-term outcomes but has limited availability as it is a complex open surgery performed by a select group of reconstructive urologists. This proposal aims to evaluate the preclinical feasibility of a device that simplifies minimally invasive graft-based urethral reconstruction, such that is can be performed by general urologists - making durable treatment widely accessible and changing the current treatment paradigm.