TARGETED DOCETAXEL-NANOCOLLOID FOR THE TREATMENT OF OVARIAN CANCER - DESCRIPTION (provided by applicant): PROJECT SUMMARY This proposal is a Phase 1 proposal in response to The National Institute of Health Small Business Innovation Research (SBIR) Program call for proposals for the Cancer Diagnostics and Therapeutic Agents Enabled By Nanotechnology (SBIR [U43/U44]) [Program Announcement Number: PA-10-286]. Nemucore Medical Innovation, Inc.'s (NMI) goal for this Phase 1 SBIR proposal is to fully determine the controlled release, targeting, cytotoxicity, pharmacokinetics, and efficacy profile for a novel integrins v3 and v5 targeted docetaxel (DTX) encased in a nanocolloid created with a proprietary layer-by-layer manufacturing process, designated NMI-700, for treatment of integrin expressing ovarian cancers. NMI's long- term goal is to couple NMI-700 with a companion diagnostic utilizing AutoGenomic's INFINITI" platform to screen for integrin expressing ovarian tumors in order to stratify patients into a cohort who would most benefit from this unique treatment. Part of the challenge with standard chemotherapeutic agents is the retention and distribution of the agent, which can be solved with the use of the NMI's long circulating nanocolloid technology developed for encapsulating poorly soluble drugs, such as DTX. Integrin targeting is highly applicable for ovarian cancer because most of ovarian cancers differentially express integrins compared to other adult tissues. Therefore design of NMI-700 incorporates a number of key attributes, which respond to physical limitations of DTX by mitigating solubility issues and to clinical observations that limiting systemic exposure that reduces drug toxicity, clearance, and inactivation through targeting and controlled release of sequestered DTX. For newly diagnosed ovarian cancer patients, a majority of whom rapidly progress to a chemoresistant state, NMI's nanomedicine offers a solution that is urgently needed for treating patients with refractory disease, which is generally incurable, and the goal of
further treatment changes from one of cure to one of palliation. It is anticipated that the pre-clinical studies will advance to subsequent clinical trials where patients will be segregated into potential responders using the companion INFINITI" diagnostic. By the end of the grant period NMI should have much of the data needed to proceed to the next stage of preclinical development and to further the advancement of this unique integrin-targeted/DTX nanomedicine into the clinic. NMI anticipates that development of NMI-700 product will provide the following benefits: ¿ Provide a new highly cytotoxic treatment for tumors of a patient population in desperate need for a clinical solution. ¿ Advance the development of nanomedicine, a key compliment to the promise of personalized medicine. ¿ Commercialize a new method of manufacture for solubilizing poorly soluble drugs.
