Genelabs Discloses Discovery of a Novel Class of Antiviral Compounds FromIts RNA-Binding Proprietary Technology
REDWOOD CITY, Calif., April 20 /PRNewswire/ -- Genelabs Technologies, Inc. (Nasdaq: GNLB) reported today the discovery, utilizing its proprietary technology, and the characterization of a novel class of small molecules synthesized by the company that have inhibitory activity against several RNA viruses. James A.D. Smith, President and Chief Executive Officer said, "RNA viruses have been elusive targets for drug discovery and represent an area of significant medical need. They include some of the most pernicious viruses such as hepatitis C (HCV), yellow fever, Dengue and West Nile virus to name a few. We are extremely pleased that our RNA-binding drug discovery program has produced a novel class of compounds that display potentially broad-spectrum antiviral activity."
(Photo: newscom.com )
Genelabs scientist Alexander Belyaev, M.D., Ph.D., explained, "All RNA viruses and some DNA viruses use double-stranded RNA (dsRNA) during the process of replication. Double-stranded RNA is not otherwise present in uninfected human cells and is therefore a highly specific target for antiviral substances. Through our RNA-binding drug discovery program, Genelabs has produced an initial generation of compounds that bind tightly to dsRNA and exhibit antiviral activity. The potency of the antiviral effect of the compounds is directly correlated with their affinity to dsRNA."
Antiviral activity was demonstrated against members of a class of viruses that belong to the Flaviviridae family, which includes yellow fever, banzi, HCV, West Nile, Dengue, Russian tick borne encephalitis and Japanese encephalitis. Because no reliable system exists to test compounds against HCV in cell culture, yellow fever and banzi viruses are often used as models to determine antiviral activity that might be applicable to HCV. The most active member of the Genelabs-discovered class of compounds tested to date is GL047064. The antiviral EC50 for GL047064 against yellow fever virus is 19 micromolar and against banzi virus is 2 micromolar. Ribavirin, the positive control, required a concentration four to six times greater to achieve a comparable antiviral effect. In general, the Genelabs compounds did not show toxicity in several tested cell lines at 1000 micromolar, the highest concentration tested, or up to 500 times the effective antiviral concentration.
By binding to and stabilizing dsRNA, the compounds Genelabs has discovered are expected to directly inhibit viral replication and also to stimulate host defense mechanisms. Because the Genelabs compounds inhibit the ability of dsRNA to unwind, the expected build-up of dsRNA in the infected cell may alert the body's immune system to recruit potent host defense mechanisms, such as induction of interferon, to further combat the infection. Some of the Genelabs compounds inhibit viral helicase activity at low nanomolar concentrations, indicating that the compounds prevented dsRNA strand separation, the function performed by helicases, which is a necessary step in viral replication. Genelabs is currently conducting in vivo studies to evaluate the antiviral effect in animals as well as evaluating the in vitro antiviral effect on other viruses. The company is also continuing to elaborate on this class of small molecules for the possible identification of even more potent compounds.
Genelabs uses a directed combinatorial chemistry approach to synthesize compounds for initial screening to determine whether they bind to dsRNA. This binding is detected and quantified by a new proprietary fluorescence-quench assay developed by Genelabs scientists.
Dr. Belyaev was scheduled to present these data for the first time on April 21 at the 13th Annual International Conference on Antiviral Research sponsored by The International Society for Antiviral Research (ISAR). An abstract containing these data was included in the conference materials distributed at the meeting. Under ISAR procedures, Genelabs sought a waiver from ISAR's requirements that certain data presentations must be accompanied by compound structure disclosure. The company was advised yesterday that the waiver would not be granted and, in order to protect the company's intellectual property rights for the design, composition and structure of its novel compounds, respectfully withdrew from its scheduled Friday presentation.
Genelabs' RNA-binding drug discovery program is funded in part by a $13.6 million grant from the Defense Advanced Research Projects Agency (DARPA), under its Unconventional Pathogens Countermeasures program. DARPA is interested in the application of Genelabs' drug discovery technologies for the creation of compounds that can be developed as drugs to address infections caused by pathogens that may be used in biological warfare. Broad-spectrum antivirals may be applicable in such a setting as well as for diseases that present significant commercial opportunities.
Genelabs Technologies, Inc. is a biopharmaceutical company engaged in the discovery and development of a new class of pharmaceutical products that selectively regulate gene expression or inactivate pathogens by binding directly to DNA or RNA, the fundamental material of genes. By acting directly on the genetic material, Genelabs' technology can be applicable to a wide range of therapeutic applications including diseases such as cancer and autoimmune disorders and diseases caused by bacteria and viruses. The company has a near-term product opportunity in GL701, which has completed two Phase III clinical trials as a new therapy for systemic lupus erythematosus (SLE). Genelabs intends to submit a New Drug Application to the US Food and Drug Administration on a rolling basis for GL701 for SLE, beginning in the second quarter of 2000.
Except for historical information, the statements in this news release are forward-looking and are subject to uncertainties and risks that could cause actual results to differ materially from the statements made. Uncertainties and risks include, without limitation, risks associated with the success of research and product development programs, the company's capital requirements and history of operating losses; uncertainties and risks regarding the company's ability to raise needed additional capital or consummate strategic or corporate partner transactions on favorable terms or at all; the adequacy of the company's GL701 clinical trial processes and whether the results of those clinical trials and other supporting information will be sufficient to support regulatory submissions and/or approvals; delays regarding the regulatory approval process including the timing and scope of approval received, if any; uncertainties and risks regarding market acceptance of GL701 as a treatment for SLE; the company's limited manufacturing and marketing experience; and the validity, scope and enforceability of patents related to GL701. The company has not submitted applications for regulatory review in the US or other countries, and the regulatory authorities have not yet made a determination as to the safety or efficacy of GL701 for SLE. Please see the information appearing in the company's filings with the Securities and Exchange Commission, in particular information under the caption "Risk Factors" in the company's 1999 Form 10-K, for more discussion regarding these uncertainties and risks and those associated with the company's research programs, early stage of development and other risks which may affect the company. The company does not undertake any obligation to update these forward-looking statements to reflect events or circumstances after the date of this release.
Genelabs' press releases are available by fax 24 hours a day at no charge by calling PR Newswire's Company News On-Call at 800-758-5804, extension 115-419. They are also posted on the Internet at genelabs.com and prnewswire.com .
CONTACT: Debra Catz Bannister, Vice President, Corporate Communications and Investor Relations of Genelabs Technologies, Inc., 650-562-1424.
SOURCE Genelabs Technologies, Inc.
CO: Genelabs Technologies, Inc.
ST: California
IN: MTC BIO
SU:
04/20/2000 08:02 EDT prnewswire.com |
