CicloMed’s lead drug development project targets bladder cancer
The first product in CicloMed’s drug development pipeline, Ciclopirox Prodrug, holds promise as a novel new agent targeting non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Bladder cancer is a disease with serious unmet need, as patients often endure a lifetime of monitoring, surgical procedures, immunotherapy and chemotherapy treatments.
Preclinical studies have indicated that Ciclopirox Prodrug, also known as CPX-POM, exhibits activity against human bladder cancer cell lines (muscle-invasive and non-muscle-invasive), as well as in a murine model of bladder cancer. CPX-POM has received FDA clearance to proceed to Phase I, and is currently being evaluated in a first-in-human trial in patients with advanced solid tumors.
The drug candidate
Ciclopirox Prodrug is a patented compound that is rapidly and completely metabolized in blood to its active metabolite, Ciclopirox, which has been marketed as the active pharmaceutical ingredient in topical antifungal drug products first approved in 1982. Ciclopirox has been demonstrated to act as an anticancer agent in vitro and in vivo, in part by inhibiting the Notch signaling pathway via inhibition of the gamma-secretase complex. Overexpression of the Notch signaling pathway has been associated with progression from non-muscle invasive to muscle invasive bladder cancer.
However, Ciclopirox has limited utility as an anticancer agent due to poor oral bioavailability, and poor water solubility. Ciclopirox Prodrug overcomes these development challenges and selectively delivers Ciclopirox to the entire urinary tract following intravenous or subcutaneous administration.
Discovered by a multidisciplinary team of researchers at The University of Kansas Cancer Center's Institute for Advancing Medical Innovation, Ciclopirox Prodrug was licensed to CicloMed LLC in November 2015 as part of a unique public-private partnership to take promising anticancer agents discovered at this NCI Cancer Center from “bench to bedside” – from laboratory research to clinical trials.
Partnering with The University of Kansas Cancer Center, Cmed and Sarah Cannon Research Institute, CicloMed has begun a Phase l clinical trial to evaluate the safety, dose tolerance, pharmacokinetics and pharmacodynamics of IV Ciclopirox Prodrug in patients with advanced solid tumors, including patients with metastatic bladder cancer. This trial will identify the recommended Phase II dose (RP2D) for subsequent clinical trials. The principal investigator of this multisite, first-in-human Phase I clinical trial is Dr. Howard A. “Skip” Burris III.
Dr. Scott Weir & Dr. John Taylor discuss Ciclopirox Prodrug.