The vast majority of patients with end-stage renal disease (ESRD) undergo periodic external blood filtering, a process known as hemodialysis. More than 300,000 patients in the United States currently depend on hemodialysis for their survival, and at least 90,000 new patients will begin hemodialysis this year. To treat ESRD by hemodialysis, vascular surgeons must create access sites in the body that allow the patient's blood to be passed through a hemodialysis machine. Unfortunately, almost 100% of the access sites will fail over time, usually due to inadequate vessel size and narrowing of the vein leading away from the site. Creating and maintaining these access sites is one of the most difficult and expensive components of ESRD treatment, and accounts for up to 50% of the total costs for each patient during the first year of hemodialysis. The annual domestic cost of hemodialysis access is estimated to be $1.5 billion, and is primarily paid through Medicare. Proteon Therapeutics has developed an innovative solution to this long-standing clinical problem. The company's first generation drug improves on current methods by permanently dilating the inflow artery and outflow vein at the time of access site creation, making the access site less susceptible to obstruction and failure. The objective of this Phase I research project is to develop a new, second generation drug candidate with improved pharmaceutical characteristics. To achieve this objective, the project will isolate and complete lab-scale synthesis of the new candidate drug. The candidate will then be purified and subjected to a series of in vitro biochemical assays to demonstrate that it retains its' intended activity. The new drug candidate will then be tested using in vivo models to demonstrate that it can deliver target levels of permanent blood vessel dilation in a clinically relevant model system. Successful completion of this SBIR Phase I research project will provide a rational basis for continuing the development of Proteon's technology into SBIR Phase II, where Proteon will seek to manufacture a cGMP-grade drug preparation, perform non-clinical toxicity and pharmacology studies, and complete a Phase I/II human clinical trial.
