Enzon Announces the Initiation of Two Phase I Studies in Collaboration with the National Cancer Institute
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/
"HIF-1α is a key element of the signaling cascade that promotes tumor
growth and metastases in a wide range of cancers," said
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.
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.
Forward Looking Statements
There are forward-looking statements contained herein, which can be
identified by the use of forward-looking terminology such as the words
"believes," "expects," "may," "will," "should," "potential,"
"anticipates," "plans," or "intends" and similar expressions. Such
forward-looking statements involve known and unknown risks,
uncertainties and other factors that may cause actual results, events or
developments to be materially different from the future results, events
or developments indicated in such forward-looking statements. Such
factors include, but are not limited to the timing, success and cost of
clinical studies for Enzon's product candidates; the ability to obtain
regulatory approval of product candidates, Enzon's ability to obtain the
funding necessary to develop its product candidates, market acceptance
of, and demand for, Enzon's product candidates and the impact of
competitive products, pricing and technology. A more detailed discussion
of these and other factors that could affect results is contained in our
filings with the
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