Insert Therapeutics, Inc., (Insert) a majority-owned subsidiary of Arrowhead Research Corporation, announced today that Insert is planning with City of Hope Comprehensive Cancer Center a broad-based Phase I clinical trial for Insert's lead drug candidate, a combination of its patented polymer technology, Cyclosert, and the anti-cancer compound camptothecin. Insert's ultimate goal is to obtain regulatory approval to market a chemotherapeutic agent with dramatically enhanced therapeutic effectiveness.
Commenting on the announcement, R. Bruce Stewart, President of Arrowhead Research Corporation, stated, "City of Hope is widely recognized as one of the best cancer treatment facilities in the world. It is an excellent center to conduct the trial."
Insert is in final rounds of preclinical testing and concurrently is actively engaged in the scale-up of the drug to produce cGMP-grade clinical materials. As a first step leading up to the study with COH, Insert will be filing an Investigational New Drug application with the US Food and Drug Administration. Upon clearance of regulatory requirements, Insert will sponsor an open-label, dose-escalation Phase I study in patients with unresectable or metastatic solid tumors. Based on results from the Phase I study, Insert plans to follow up with a disease-specific Phase II study also at the City of Hope.
Discovered in the 1960s, camptothecin is a naturally occurring, water-insoluble alkaloid that has established potent activity against a broad spectrum of cancer types. While analogues of camptothecin (e.g., irinotecan and topotecan) continue to realize nearly $1 billion of annual sales worldwide, to date, camptothecin has not been commercialized due to its poor solubility and its unfavorable pharmacokinetics/pharmacodynamics. Recent animal studies conducted by Insert demonstrated that treatments with camptothecin using the Cyclosert delivery system resulted in protracted reduction and/or elimination of tumors. Further, the tests showed that the reoccurrence of tumors after treatment was much less than other treatment groups, including irinotecan.
Insert's patented Cyclosert delivery system is based on linear, repeating units of cup-shaped molecules of glucose called cyclodextrins. By responding to biological mechanisms and micro-environmental conditions, these polymers can be "tuned" to allow controlled release of their payload into selected tissues or tumor cells. The polymers were developed at Caltech in the lab of Dr. Mark Davis, a professor in Chemical Engineering and founder of Insert, and licensed exclusively to Insert. Dr. Davis is a Member of the National Academy of Engineering and a recipient of the Alan T. Waterman Award, given by the National Science Foundation annually to only one scientist in the United States across all disciplines. Dr. Davis was the first engineer to win this award for his work in rationally designed materials.