New research on safety of intracoronary delivery of adenovector reported in cover story of Molecular Therapy

December 01, 2001

SAN DIEGO, California - December 3, 2001 - Collateral Therapeutics, Inc. (Nasdaq: CLTX) announced that preclinical in vitro and in vivo results reported in the December 2001 issue of Molecular Therapy showed that male reproductive cells (germ cells) were unaffected following intracoronary delivery of Collateral's adenovector (adenovirus serotype 5 - Ad5). These findings confirm other research studies in which potential risks associated with inadvertent germ line transmission following adenoviral administration have been shown to be highly unlikely.

In the study, led by Robert E. Braun, Ph.D. Associate Professor of Genetics at the University of Washington, gene expression after adenovirus delivery was analyzed from a series of both in vitro and in vivo studies. The in vitro studies demonstrated that germ cells grown in cell culture were refractory to infection by Collateral's adenovector. To assess the risk of germ line transmission in vivo, researchers used a mouse model to deliver human recombinant Ad5 carrying a germ cell-specific promoter fused to a reporter gene directly into the left ventricular cavity of the heart. They observed that the reporter gene protein was not expressed in developing spermatids or mature sperm, with analyses performed at multiple time points after administration to evaluate all major stages of germ cell development. Importantly, the in vivo studies did not detect infection of the reproductive stem cells. The positive results from these studies are consistent with other recent studies using different models and routes of delivery. However, this is the first study that directly assessed the ability of an adenovirus to result in gene expression in extremely large numbers (i.e., millions) of germ line cells, and the first to assay infection of the reproductive stem cell population.

"This study provides significant new information further supporting the safety of the use of the adenovirus as a vehicle to deliver therapeutic genes in man at least using Collateral's intracoronary route of administration," said Jeffrey Friedman, M.D. vice president of development of Collateral Therapeutics. "In particular, it provides important data which reinforces our prior views about the apparent safety of Collateral's proprietary approach of intracoronary delivery of genes to enhance angiogenesis as well as improve heart function. Furthermore, our unique approach allows delivery of genes at the time of cardiac catheterization without causing injury to the heart as in other techniques that require the heart to be punctured in order to deliver a therapeutic gene."

"In the U.S., the adenoviral vector has been used in approximately one third of all gene therapy clinical trials, with adenovirus serotype 5 being the most widely used. These adenoviral vectors have now been used in investigational studies designed to evaluate the safety and efficacy of gene therapy in patients with cancer, cardiovascular disease and inherited disorders. According to the Office of Biotechnology Activities, National Institutes of Health, in the past decade, approximately 144 gene therapy clinical trials using adenoviral vectors have been conducted and of all patients who have participated in gene therapy trials, nearly 1 in 5 patients has been administered an adenoviral vector," said Christopher J. Reinhard president and chief operating officer of Collateral Therapeutics. "Our lead product candidate, GENERX™, uses the adenovirus serotype 5 to administer human growth factor, FGF-4, for the potential treatment of stable angina due to coronary artery disease. We are excited about these new studies, which further support the growing body of knowledge regarding the safety profile of adenoviral vectors for cardiovascular gene therapy, and we are pleased with the clinical progression of GENERX."

GENERX, a non-surgical angiogenic gene therapy, is being developed by Schering AG, Germany (NYSE: SHR) under an agreement with Collateral Therapeutics. This important new research effort at the University of Washington was undertaken as part of the current global development program for GENERX, which is focused on evaluating the safety and efficacy of GENERX in stable angina patients. GENERX is now in large-scale clinical trials in the U.S. and is expected to be in large-scale clinical trials in Europe in January 2002. Upon completion, it is expected that results of these studies, along with data from the other development activities could be used to support a marketing application for product registration to the U.S. Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA).
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Collateral Therapeutics, Inc., headquartered in San Diego, is a leader in the discovery and development of innovative gene therapy products for the treatment of cardiovascular diseases. Collateral Therapeutics is developing non-surgical cardiovascular gene therapy products focused on: (1) angiogenesis, as a treatment approach for coronary artery disease, peripheral vascular disease and congestive heart failure; (2) myocardial adrenergic signaling, as a treatment for congestive heart failure; and (3) heart muscle regeneration, to improve cardiac function for patients who have suffered a heart attack.

Statements in this press release that are not strictly historical may be "forward-looking" statements, which involve risks and uncertainties. There can be no assurance that Collateral Therapeutics, Inc. or its partners will be able to commercially develop cardiovascular gene therapy products, that necessary regulatory approvals will be obtained or that any clinical trials will be successful or that the proposed treatments will prove to be safe and/or effective. The actual results may differ from those described in this press release due to risks and uncertainties that exist in the Company's operations and business environment, including, without limitation, the Company's early stage of product development and the limited experience in the development of gene therapies in general, its dependence upon proprietary technology and current competition, history of operating losses and accumulated deficits, the Company's reliance on collaborative relationships, and uncertainties related to clinical trials, safety, efficacy, the ability to obtain the appropriate regulatory approvals, patent protection and market acceptance, as well as other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission in the Company's most recent periodic reports on Form 10-K and Form 10-Q as well as reports on Form 8-K and other reports filed from time to time. Given these uncertainties, prospective investors are cautioned not to place undue reliance on such forward-looking statements. All information in this press release is as of its issue date. The Company disclaims any obligation to update such factors or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future events or developments.

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Collateral Therapeutics

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