The EZN-2208 study is expected to enroll 20 patients with solid tumors whose disease has progressed following standard therapy, or who have no acceptable standard treatment. EZN-2208 will be administered intravenously on days one, eight, and fifteen of a 28-day cycle. Avastin will be administered intravenously every two weeks. Tumor biopsies and other correlative imaging and pharmacodynamic studies will be performed at baseline and after drug administration.
About EZN-2968 (HIF-1a mRNA antagonist)
EZN-2968 is an antisense oligodeoxynucleotide that down regulates the mRNA encoding HIF-1α. The molecule is based on the locked nucleic acid (LNA) technology platform targets licensed from Santaris Pharma A/S. The LNA technology allows the antisense molecule to have high-potency resistance to nuclease destruction, and administration of the molecule intraveneously when prepared in saline (without any delivery vehicle). Reduction in HIF-1α expression would be expected to lead to inhibition of angiogenesis, the inhibition of tumor cell proliferation, and apoptosis. HIF-1α, normally activated in response to hypoxia-induced stress, is a key transcription regulator of a large number of genes important in cellular adaptation to low-oxygen conditions, including angiogenesis, cell proliferation, apoptosis, and cell invasion.
About EZN-2208 (PEG-SN38)SN38 is the active metabolite of the widely used cancer drug irinotecan, marketed as Camptosar® in the U.S. Although unmodified SN38 is 1,000 times more potent than CPT-11, it has not been converted into a viable drug candidate because of its insolubility. Using Enzon's proprietary customized linker-enhanced PEGylation technology, the Company developed EZN-2208 (PEG-SN38), which results in a compound with excellent pharmaceutical properties as shown in animal models: increased solubility, higher exposure, and longer half-life than unmodified SN38. These properties allow EZN-2208 to outperform CPT-11 in a variety of animal models of human cancers, including tumors that develop resistance to CPT-11. EZN-2208 is currently being evaluated in ongoing Phase II clinical trials in patients with metastatic breast cancer and metastatic colorectal carcinoma, and in a Phase I study in pediatric patients with solid tumors.