Enzon Pharmaceuticals, Inc. (Nasdaq: ENZN) today announced the initiation of Phase I clinical studies, in collaboration with the National Cancer Institute (NCI), for two of the Company’s novel oncology product candidates, EZN-2968 and EZN-2208 (PEG-SN38). Both EZN-2968 and EZN-2208 have been shown to down-modulate HIF-1α, a subunit of HIF-1. HIF-1 is frequently overexpressed in cancer cells, where it is involved in the upregulation of gene products essential for tumor invasion, migration, angiogenesis and production of vascular endothelial growth factor (VEGF). The studies are being sponsored by the NCI under Clinical Trials Agreements with Enzon. The first study will explore the safety and effectiveness of EZN-2968, an LNA-based antisense oligonucleotide, in patients with solid malignancies predominantly involving the liver. The second study will explore the modulation of HIF-1α in solid tumors after treatment with EZN-2208 combined with Avastin® (bevacizumab, Genentech/Roche), a humanized antibody targeting VEGF-A. Anti-angiogenic agents such as Avastin have limited efficacy, potentially as a result of the induction and up-regulation of hypoxia-inducible factors such as HIF-1α in the hypoxic conditions of the post-treatment tumor. Such effects may be offset by treatment with ENZ-2208, a topoisomerase inhibitor that down regulates HIF-1α in addition to having a cytotoxic effect. “HIF-1α is a key element of the signaling cascade that promotes tumor growth and metastases in a wide range of cancers,” said Ivan Horak, MD, Enzon’s President of Research and Development and Chief Scientific Officer. “These two Phase I studies build on a growing body of clinical and preclinical evidence demonstrating the potential of both EZN-2968 and EZN-2208 to inhibit this important target. We look forward to collaborating with the NCI in further understanding the promise demonstrated by these two product candidates.” The EZN-2968 study is expected to enroll 22 patients with solid tumors, predominantly involving the liver. EZN-2968 will be administered as a two-hour intravenous infusion once a week for three consecutive weeks, followed by a three-week period without drug. Tumor biopsies and other correlative imaging and pharmacodynamic studies will be performed at baseline and after drug administration.