Enzon Presents Data at 2011 AACR Meeting
Third-Generation mRNA Antagonists Continue Showing Promise in
Locked Nucleic Acid Technology to be Featured in RNA-Targeting Therapeutics Symposium
"Enzon's third-generation mRNA antagonists continue to demonstrate
potential to inhibit key tumor targets, which antibodies and small
molecules have limited ability to control and access," said
Enzon has coauthored a general discussion on the therapeutic uses of
LNA-based oligonucleotides, which will be held
LNA-Based mRNA Compound Poster Presentations
"Down-modulation of messenger ribonucleic acid (mRNA) by EZN-2968, an
hypoxia-inducible factor-1α (HIF-1α) mRNA antagonist administered in
adult patients with advanced solid tumors,"
- Study designed to determine the maximum tolerated dose (MTD) and recommended Phase II dose, evaluate safety and tolerability, determine pharmacokinetic and pharmacodynamic profile, and detect preliminary evidence of antitumor activity.
- The MTD of EZN-2968 was determined to be 18 mg/kg given weekly for 4 of 6 weeks.
- EZN-2968 was well tolerated in previously treated patients with advanced tumors.
- The best response was durable stable disease, and multiple patients had tumor shrinkage.
- Evidence for down-modulation of the HIF-1α mRNA target is supported by observations in tumor and skin.
- Additional evaluation of EZN-2968 in clinical trials is warranted.
"Results of a Phase 1, open-label, dose-escalation study evaluating the
safety and tolerability of EZN-3042, a survivin messenger ribonucleic
acid (mRNA) antagonist, administered with or without docetaxel in adult
patients with advanced solid tumors or lymphoma,"
- Study was designed to determine the MTD and recommended Phase II dose, both as a single agent and in combination with docetaxel; evaluate safety and tolerability; determine pharmacokinetic and pharmacodynamic profile; and detect preliminary evidence of antitumor activity.
- EZN-3042 was generally well tolerated in previously treated patients with advanced malignancies.
- The MTD for single-agent EZN-3042 is 6.5 mg/kg administered weekly. Enrollment in the combination arm is ongoing.
"Dual inhibition of the androgen receptor by ligand blockade and
antisense-mediated down regulation is associated with synergistic
antitumor activity in models of prostate cancer,"
- Mechanistic studies show strong evidence that the inhibition of AR by two fundamentally different modalities — LNAs and small-molecule AR inhibitors —may provide increased therapeutic benefit.
- Multiple clinically meaningful parameters indicate that EZN-4176, a novel AR mRNA antagonist, potentiates the therapeutic benefit of MDV3100, an oral AR antagonist currently in Phase III testing in patients with advanced prostate cancer.
- These indicators of enhanced therapeutic benefit were demonstrated in both castration-resistant and androgen-sensitive tumor models.
- Furthermore, preliminary data also indicate the potential of EZN-4176 in a bone tumor model.
"Targeting HER3 mRNA by a locked nucleic antisense molecule enhances the
antitumor activity of gefitinib in vivo,"
- EZN-3920 down-regulates HER3 mRNA, HER3 protein, and downstream signal transduction controlled by HER3 in human tumors model systems.
- Target inhibition is correlated with potent antitumor activity.
- In addition, the antitumor effect of EZN-3920 is additive with gefitinib, a small-molecule tyrosine kinase inhibitor of EGFR.
- These data suggest that inhibition of HER3 with EZN-3920 will yield therapeutic effects when given alone or in combination with other HER-family inhibitors currently used in patients with cancer.
- Furthermore, EZN-3920 enhances the effect of gefitinib in a non-small-cell lung cancer (NSLC) tumor model. While EZN-3920 or gefitinib alone significantly delays the growth of NSCLC tumor, the combination results in tumor regression.
The abstracts and posters are available on the Company's website at www.enzon.com.
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 Enzon's 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 Enzon's filings with the
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