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Enzon's PEG-SN38 Shows Anti-Tumor Activity in Resistant Preclinical Tumor Models.


-- PEG-SN38 and Customized Linker Technology[TM] data presented at AACR AACR American Association for Cancer Research
AACR Anglo-American Cataloging Rules
AACR Australasian Association of Cancer Registries
AACR African Armed Conflicts Resolved
 annual meeting --

BRIDGEWATER, N.J. -- Enzon Pharmaceuticals, Inc. (Nasdaq: ENZN) today announced new preclinical data showing that treatment with PEG-SN38, Enzon's PEGylated SN38 compound, resulted in significant tumor growth inhibition Growth inhibition (GI) is a medical term pertaining to cancer therapy and the specific reduction in growth of tumors and oncogene cells by a chemical compound, mechanical therapy (e.g.  in mice resistant to Camptosar([R])(irinotecan HCl injection) and outperformed Camptosar in mice when given as a second round therapy. Additionally, PEG-SN38 demonstrated long-lasting antitumor an·ti·tu·mor   also an·ti·tu·mor·al
adj.
Counteracting or preventing the formation of malignant tumors; anticancer.

Adj. 1.
 activity in mouse models of human breast and pancreatic cancers. The data were presented at the American Association for Cancer Research Wikipedia is not the place for advertisement or self-advertising.

The American Association for Cancer Research (AACR) is an organization based in Philadelphia, Pennsylvania, that focuses on all aspects of cancer research including basic, clinical and translational
 (AACR) annual meeting in Los Angeles Los Angeles (lôs ăn`jələs, lŏs, ăn`jəlēz'), city (1990 pop. 3,485,398), seat of Los Angeles co., S Calif.; inc. 1850. , April 14-18, 2007.

"This exciting new data showing PEG-SN38's activity in resistant tumors combined with the continuing anti-tumor activity demonstrated at EORTC-NCI-AACR last fall, adds further merit to our planned clinical program set to begin later this year," said Jeffrey H. Buchalter, Enzon's chairman and chief executive officer. "In addition, I'm pleased to see the continued validation of our Customized Linker Technology platform which may provide a unique approach for more efficient delivery of antisense antisense, DNA or RNA manipulated in a laboratory so that its components (nucleotides) form a complementary copy of normal, or "sense," messenger RNA (mRNA; see nucleic acid).  technologies, including Locked Nucleic Acid A locked nucleic acid (LNA), often referred to as inaccessible RNA, is a modified RNA nucleotide. The ribose moiety of an LNA nucleotide is modified with an extra bridge connecting the 2' and 4' carbons.  (LNA LNA Low-Noise Amplifier
LNA Locked Nucleic Acid (Link Technologies Ltd.)
LNA Linolenic Acid
LNA Licensed Nursing Assistant
LNA Launch Numerical Aperture
LNA Ladies National Association
LNA Leading National Advertisers, Inc.
)."

Study Details

EZN-2208, a novel polyethyleneglycol-SN38 conjugate conjugate /con·ju·gate/ (kon´jdbobr-gat)
1. paired, or equally coupled; working in unison.

2. a conjugate diameter of the pelvic inlet; used alone usually to denote the true conjugate diameter; see
, has potent antitumor activity in a panel of human tumor xenografts (Abstract #1494)

Data from this study showed that PEG-SN38 administered to Camptosar-resistant mice (those that did not respond to Camptosar treatment) resulted in a 25 percent decrease in tumor volume. Additionally in Camptosar-sensitive mice (those that initially responded to Camptosar treatment), tumor growth resumed after a second dose of Camptosar, while mice switched to PEG-SN38 therapy experienced tumor regression followed by slow tumor growth.

Additional data showed that PEG-SN38 caused continued anti-tumor activity for over 90 and 120 days respectively in breast and pancreatic cancer models.

Customized positive PEG linkers for the delivery of antisense molecules (Abstract #4731)

This study demonstrated the utility of Enzon's Customized PEG Linkers to effectively deliver antisense molecules systemically. Effective systemic delivery of second- and third-generation antisense technology approaches, such as LNA and short interfering RNA RNA: see nucleic acid.
RNA
 in full ribonucleic acid

One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic
 (siRNA), is the biggest hurdle to fully realize their therapeutic potential in people. In this study, Enzon demonstrated that customized PEG linkers improved the stability of these molecules and efficiently released the native antisense. Safety and efficacy will be determined in future preclinical studies preclinical studies,
n.pl a term used to describe research done before a clinical study. May be laboratory or epidemiologic research.
.

In vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment.

in vi·tro
adj.
In an artificial environment outside a living organism.
 and in vivo in vivo /in vi·vo/ (ve´vo) [L.] within the living body.

in vi·vo
adj.
Within a living organism.



in vivo adv.
 evaluation of PEGylated anti-Bcl2 siRNA conjugates in a Bcl-2 over-expressing lung cancer lung cancer, cancer that originates in the tissues of the lungs. Lung cancer is the leading cause of cancer death in the United States in both men and women. Like other cancers, lung cancer occurs after repeated insults to the genetic material of the cell.  model (Abstract #4726)

This study describes the in vitro and in vivo efficacy of a PEGylated siRNA compound in a lung cancer model. The development of siRNA as therapeutics has been limited due to their inefficient delivery, poor stability and suboptimal Suboptimal
A solution is called suboptimal if a part of the solution has been optimized without regards to the overall objective.
 pharmaceutical profile. Results showed that the PEGylated siRNA created using Enzon's proprietary Customized Releasable PEG Linker Technology had an improved pharmaceutical profile compared to the native siRNA, and also resulted in down-regulation of its targeted gene, Bcl-2, a gene often over-expressed in people with lung cancer.

About PEG-SN38

SN38 is the active metabolite active metabolite Therapeutics A drug metabolite with therapeutic activity similar to the parent compound, which must be considered in therapeutic pharmacokinetics  of the widely used cancer drug irinotecan, marketed as Camptosar[R] in the U.S. Although unmodified SN38 is 1,000 times more potent than Camptosar, it has not been converted into a viable drug candidate because it is insoluble. Using Enzon's new PEGylation technology, the Company developed PEG-SN38 (EZN-2208), 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. Preclinical data presented at the 18th annual EORTC-NCI-AACR (European Organization for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research) meeting showed that these features led to greater efficacy over Camptosar in breast, colorectal and pancreatic cancer models.

About PEGylation and Customized Linker Technology[TM]

One of Enzon's core capabilities has been in engineering improved versions of injectable therapeutics through the chemical attachment of polyethylene glycol polyethylene glycol (PEG): see glycol.  or PEG. In some cases, PEGylation can render a compound therapeutically effective, where the unmodified form had only limited clinical utility. Currently, there are five marketed biologic products that utilize our proprietary PEG platform, two of which Enzon markets, Adagen([R]) and Oncaspar([R]), and three for which Enzon receives royalties, PEG-INTRON([R]), Pegasys([R]), and Macugen([R]). Specific advantages of PEG may include: increased efficacy; reduced dosing frequency; reduced toxicity and immunogenicity immunogenicity /im·mu·no·ge·nic·i·ty/ (-je-nis´it-e) the property enabling a substance to provoke an immune response, or the degree to which a substance possesses this property. ; increased drug stability; and enhanced drug solubility.

Enzon's Customized Linker Technology utilizes linkers designed to release the native molecule at a controlled rate. The customized linkers expand the utility of the Company's existing PEGylation technology, and offer a choice of releasable or permanent linkages to match each drug's requirements. It improves the pharmacokinetic and pharmacodynamic profile of a drug. Through the customized attachment of PEG, that covers the spectrum of stable and customized releasable linkers, we can potentially overcome the pharmacologic limitations for a broad universe of molecules and generate compounds with substantially enhanced therapeutic value over their unmodified forms.

About Enzon

Enzon Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to the development, manufacturing, commercialization of important medicines for patients with cancer and other life-threatening conditions. Enzon has a portfolio of four marketed products, Oncaspar([R]), DepoCyt([R]), Abelcet([R]) and Adagen([R]). The Company's drug development programs utilize several cutting-edge approaches, including its industry-leading PEGylation technology platform used to create product candidates with benefits such as reduced dosing frequency and less toxicity. Enzon's PEGylation technology was used to develop two of its products, Oncaspar and Adagen, and has created a royalty revenue stream from licensing partnerships for other products developed using the technology. Enzon also engages in contract manufacturing for several pharmaceutical companies to broaden the Company's revenue base. Further information about Enzon and this press release can be found on the Company's web site 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; 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 transition report on Form 10-K Form 10-K

A report required by the SEC from exchange-listed companies that provides for annual disclosure of certain financial information.


Form 10-K

See 10-K.
 for the year ended December 31, 2006 and our quarterly reports on Form 10-Q Form 10-Q

See 10-Q.
. These factors should be considered carefully and readers are cautioned not to place undue reliance on such forward-looking statements. 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.
COPYRIGHT 2007 Business Wire
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2007, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Date:Apr 17, 2007
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