Enzon Strengthens Clinical Pipeline with Oncology Compound.

Business Editors/Health/Medical Writers

BRIDGEWATER, N.J.--(BUSINESS WIRE)--Nov. 19, 2003

Enzon Pharmaceuticals, Inc. (NASDAQ:ENZN) announced today it has agreed to a collaborative development program with the National Institutes of Health (NIH). The terms of the development program will be governed by a Collaborative Research and Development Agreement (CRADA) which is in the final stages of approval at the NIH. The development program will center on the recombinant immunotoxin SS1P. Enzon and the NCI plan to initially develop SS1P in pancreatic and ovarian carcinomas. Phase 2 trials are set to start in the second half of 2004.

This compound is currently in phase 1 clinical development at the National Cancer Institute (NCI) under the supervision of Dr. Ira Pastan. Dr. Pastan is the Head of the Laboratory of Molecular Biology and a widely recognized leader in the field of immunoconjugates in cancer treatment. Responsibilities for development of the SS1P compound will be shared between Enzon and the NCI.

"We are extremely excited to be able to collaborate with Ira Pastan, a recognized leader in the field of immunotoxins," comments Uli Grau, Enzon's CSO. "Pancreatic adenocarcinoma is one of the deadliest cancers, and the prospect of introducing a potent drug in this indication is particularly compelling. Under this collaboration, Enzon will also use its considerable skills in macromolecular engineering to explore further improvements of recombinant immunotoxins."

SS1P is a fusion protein consisting of a disulfide linked antibody fragment linked to domains II and III of Pseudomonas exotoxin A. The antibody fragment targets mesothelin, a cell surface antigen overexpressed in mesothelioma, ovarian and pancreatic cancers. Importantly, mesothelin is not expressed in normal pancreas, pancreatitis (inflammation of the pancreas), or benign pancreatic adenoma.

The SS1P molecule is an ingenious example of protein engineering: the native Pseudomonas exotoxin protein consists of three domains: domain I targets cell surface receptors, domain II functions to translocate the molecule across a cell membrane and into the cell interior, and domain III catalyzes irreversible ADP ribosylation and inactivation of elongation factor 2 (EF2). It thereby shuts down protein synthesis and leads to cell death. A single Pseudomonas exotoxin molecule can kill a cell. In the SS1P molecule, domain I is replaced by the disulfide-linked antibody fragment targeting mesothelin. Thus SS1P targets the highly lethal toxin only to cells expressing mesothelin.

Enzon has also applied for an exclusive license which, if executed, will give Enzon worldwide commercialization rights and includes access to a large patent estate consisting of several dozen US and international patents and patent applications, claiming, among other things, the composition and production of the SS1P molecule, as well as its therapeutic application in cancers expressing mesothelin. The proposed worldwide license would be exclusive in the fields of cancers expressing mesothelin. Completion of the license agreement is expected in early 2004.

The CRADA will be for an initial period of 3 years and includes an option to extend. Aside from the clinical development of SS1P it also includes a research project to further optimize SS1P using Enzon's proprietary macromolecular engineering technologies.

Enzon will discuss this product further at a live webcast, which the Company is hosting on Thursday, November 20, 2003, in New York City from 11:30 - 2:30 pm EST. The live event can be accessed on the Internet at http://www.videonewswire.com/Enzon/112003. An archive of the event will also be available through November 27, 2003.

Enzon Pharmaceuticals is a biopharmaceutical company dedicated to the discovery, development and commercialization of therapeutics to treat life-threatening diseases. The company has developed or acquired a number of marketed products, including PEG-INTRON, marketed by Schering-Plough, and ABELCET, which is marketed in North America by Enzon.

Enzon's science-focused strategy includes an extensive drug development program that leverages the Company's macromolecular engineering technology platform, including PEG modification and single-chain antibody (SCA(R)) technologies. Internal research and development efforts are complemented by strategic transactions that provide access to additional products, projects, and technologies. Enzon has several drug candidates in various stages of development, independently and with partners.

Except for the historical information herein, the matters discussed in this news release include forward-looking statements that may involve a number of risks and uncertainties. Actual results may vary significantly

based upon a number of factors, many of which are described in the Company's Form 10-K, Form 10-Q's and Form 8-K's on file with the SEC, including without limitation, Enzon's ability to complete and execute the CRADA and the commercialization and license agreement described above, Enzon's ability to sustain profitability and positive cash flow; risks in obtaining and maintaining regulatory approval for indications and expanded indications for Enzon's products; market acceptance of and continuing demand for Enzon's products; timing and results of clinical trials and the impact of competitive products and pricing. All information in this press release is as of November 19, 2003, and the Company undertakes no duty to update this information.

This release is also available at http://www.enzon.com