Cerulean's Dynamic Tumor Targeting™ Platform creates NDCs that are designed to provide safer and more effective cancer treatments. We believe our NDCs concentrate their anti-cancer payloads inside tumors while sparing normal tissue because they are small enough to pass through the "leaky" vasculature present in tumors, but are too large to pass through the pores of healthy blood vessels. Once inside tumors, we believe our NDCs are actively taken up into tumor cells where they slowly release their anti-cancer payload, providing a durable inhibition of their targets. An NDC consists of an anti-cancer payload that is chemically conjugated to a polymer backbone with a linker.
NDCs are designed to target tumor cells while sparing normal tissue, providing patients with potentially safer and more effective cancer therapy.
NDCs Are Designed to Target Tumors
Cerulean's NDCs are designed to take advantage of unique characteristics of tumor vasculature. With an aggressive rate of growth, tumors are in need of a constantly increasing supply of oxygen and therefore overexpress factors that cause blood vessels to grow. This results in a highly disorganized blood vasculature that surrounds tumors and is made up of immature blood vessels with large, "leaky" pores. NDCs can easily pass through these leaky pores; however, they are too large to pass through the small pores of most blood vessels found in normal tissue. In addition to the vasculature changes in the tumor microenvironment, tumor cells scavenge for building blocks of growth, including lipids and proteins, from their surrounding environment via process called macropinocytosis. Clinical data show that Cerulean’s NDCs are taken up inside tumor cells via macropinocytosis and subsequently release their payloads inside the tumor cells over an extended period of time. As clinical evidence of selective entry of CRLX101 in tumor tissue, we obtained differential post-therapy biopsies of tumor tissue and adjacent normal tissue from nine gastric patients. In nine of nine patient biopsies, taken between 24 and 48 hours after a single dose of CRLX101 was administered, the presence of camptothecin associated with CRLX101 was observed in the tumor tissue. In contrast, no definitive evidence of either the nanoparticle or camptothecin contained within the nanoparticle was observed in neighboring normal tissue.
NDCs Are Designed to Spare Normal Tissue
Current cancer therapies' toxicities are commonly due to the exposure of normal tissue to highly toxic anti-cancer drugs. Cerulean's NDCs appear to remain largely stable in the bloodstream, bypassing most normal tissue, until they concentrate in tumors.
NDCs Could Enable Combination Therapy
Cancer is a multi-faceted disease that is rarely adequately addressed by one therapy. Our NDCs have the potential to enable synergistic combination therapies that were previously not possible due to side effects.