Enzon Pharmaceuticals, Inc. (Nasdaq: ENZN) presented data from its
pipeline programs at the 2010 AACR (American Association for Cancer
Research) annual meeting in Washington, DC.
“We are pleased to present new data from our novel pipeline programs.
Our Customized PEG linkers continue to improve the delivery of cytotoxic
molecules,” said Dr. Ivan Horak, President of Research and Development
and Chief Scientific Officer of Enzon. “Additionally, our novel locked
nucleic acid (LNA)-based mRNA antagonists continue to show promise for
inhibition of tumor growth in a variety of cancers.”
The Posters and Abstracts that were presented included:
Customized PEG Linkers Improve the Pharmaceutical Properties of
Cytotoxic Small Molecules (Poster 2645)
A series of releasable customized PEG linkers have been developed to
improve the delivery of cytotoxic molecules. PEG-conjugates were
synthesized with improved solubility and in general, increased the
exposure time of the parent molecule.
LNA Antagonists (GIL2, Beta-Catenin,
Androgen Receptor (AR))
PEG-SN38 showed markedly improved solubility leading to significantly
enhanced therapeutic efficacy in various xenograft models (including
tumors refractory to CPT-11). These encouraging results led to the
clinical evaluation of PEG-SN38 (currently in Phase II program).
The releasable PEG-BE linker system, used in PEG-Daunorubicin
conjugate, is an excellent example of releasable PEG-linker Technology
whereby small molecules can be released in controlled fashion.
In case of PEG-Ara-C, optimal pharmacokinetic properties are achieved
by applying releasable Customized Linker Technology™. Certain
PEG-Ara-C conjugates showed remarkable activity against solid tumors
as well as ascites model consistent with improved bioavailability of
The mRNA antagonists are being developed by Enzon under a license with
Santaris Pharma A/S.
Targeting the hedgehog pathway by LNA (locked nucleic acid)
oligonucleotide based-GLI2 RNA antagonists, EZN-4482 and EZN-4496,
in vivo (Abstract 600)
The Hedgehog (Hh) signaling pathway mediates cell growth and
differentiation in the embryonic development and in some adult cells.
Aberrant activation of signaling has been described as causal factors in
a wide variety of human cancers as well as chemotherapy resistance.
EZN-4482 and EZN-4496 are two LNA-based GLI2 mRNA antagonists.
Conclusions from the data reported included:
in vivo characterization of two
novel β-catenin RNA antagonists, EZN-3889 and EZN-3892 (Abstract 601)
EZN-4482 and EZN-4496 were demonstrated to silence GLI2 expression
with or without transfection in vitro.
The LNA based GLI2 antagonists potently and specifically inhibited
GLI2 mRNA expression and tumor growth in two tumor models.
Specific silence of GLI2 expression EZN-4482 in vivo can lead to
inactivation of Hh signaling pathway as indicated by down-modulation
of GLI1 and Ptch1 expression
The efficacy observed with EZN-4482 in vivo may be due, in part, to
silence of in mouse stromal GLI2 mRNA.
GLI2 RNA antagonist may be an effective therapy to treat a broad
spectrum of cancers including ones that fail treatment with a small
EZN-3889 and EZN-3892 are able to potently inhibit β-catenin mRNA and
and inhibit the growth of numerous cancer cell
lines. Inhibition of β catenin using these LNAs results in the
inhibition of spheroid formation in the SW480 β-cell line. Both LNAs are
with >90% knockdown of β-catenin mRNA β
observed in mouse liver. Excitingly, treatment of mice bearing Colon-EZN
tumors intravenously with EZN-3892 results in significant inhibition of
tumor growth. A wide therapeutic window exits for EZN-3892 making the
therapeutic development of these LNAs highly desirable.
Silencing of the androgen receptor (AR) with a novel mRNA antisense
oligonucleotide causes antitumor effects in xenograft models of prostate
cancer (Abstract 602)
The AR is a ligand-activated transcriptional factor that plays an
important role in prostate cancer. While androgen-deprivation therapies
typically inhibit tumor growth, tumor recurrence due to the castration
resistant form of the disease frequently occurs and leads to mortality.
AR antagonist, EZN-4176, inhibits the growth of CWR22 tumors and
down-regulates mRNA of AR and its regulated genes such as PSA and
The antagonist also down-regulates AR protein level in CWR22 tumors.
The compound distributes to multiple organs including prostate and
Results demonstrate the down regulation of mRNA and AR protein level
in C4-2B tumors resulting in apoptosis.
EZN-4176 inhibits transcription activity of AR in C4-2B tumors and
inhibits growth of the C4-2B tumors.
The abstracts and posters can be found on the Company’s website at
Enzon Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to
the discovery and development of innovative medicines for patients with
cancer. Enzon’s drug development programs utilize several cutting-edge
approaches, including its industry-leading PEGylation technology
platform, Customized Linker technology™ and mRNA antagonists using the
Locked Nucleic Acid™ (LNA) technology. Enzon’s receives a royalty
revenue stream from licensing partnerships for other products developed
using the proprietary PEGylation technology. Further information about
Enzon and this press release can be found on the Company’s web site at
Forward Looking Statements
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identified by the use of forward-looking terminology such as the words
"believes," "expects," "may," "will," "should,” "potential,"
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forward-looking statements involve known and unknown risks,
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or developments indicated in such forward-looking statements. Such
factors include, but are not limited to the timing, success and cost of
clinical studies; the ability to obtain regulatory approval of products,
market acceptance of, and continuing demand for, Enzon’s products and
the impact of competitive products and pricing.
A more detailed
discussion of these and other factors that could affect results is
contained in our filings with the U.S. Securities and Exchange
Commission, including our annual report on Form 10-K for the period
ended December 31, 2009.
These factors should be considered
carefully and readers are cautioned not to place undue reliance on such
No assurance can be given that the
future results covered by the forward-looking statements will be
achieved. All information in this press release is as of the date of
this press release and Enzon does not intend to update this information.