RiboGene's Discovery Programs
Introduction (Back to Top)
RiboGene Inc. (Hayward, CA) has been issued two U.S. patents for its drug discovery technology based on translational control of gene expression. RiboGene core discovery programs focus on compounds that inhibit or interfere with pathogen specific translation mechanisms (PSTMs). The company believes that targeting PSTMs may lead to the discovery of drugs that are effective against either drug-resistant pathogens or pathogens for which current therapies are not effective.
The first of the new patents (U.S. Patent 5,871,923: "Methods for screening for antimycotics") relates to high throughput screening methods used to identify agents that inhibit translation in fungal cells. Translation is the cellular process by which cells use genetic information to make proteins. Translation in fungal cells and human cells is very similar, creating difficulties when fungal translation is required but translation in human cells is undesirable. This patent covers the discovery of therapeutics that effect fungal translation without adversely effecting the translation systems of human cells.
The second patent (U.S. Patent 5,874,231: "Methods of screening for non-hormone compounds which effect modulation of polypeptide translation") involves screening methods used to discover non-hormone agents which may regulate the interaction between cellular components and translation factors. Normally, in response to a hormone, certain components of a cell and particular molecules are altered in a way that affects the rate or efficiency of translation. Treating hormonal disorders with current treatments, such as insulin and hypoglycemic drugs, can cause side effects and can be inconvenient to administer. Although RiboGene's main focus is on infectious disease, this patent represents an additional application of its core drug discovery research technology.
"The proprietary screening methods described in these patents will enable us eventually to discover potential drugs that are translation-specific," said Charles J. Casamento, chairman, president, and CEO of RiboGene. "Current treatments for fungal infections and hormonal disorders have potentially harmful side effects. In the case of fungal infections, drugs that can safely inhibit translation could have numerous treatment applications. The ability of drugs to re-create the translational responses to a hormone may also have application in certain hormonal disorders such as diabetes."
RiboGene's Business (Back to Top)
Infectious diseases have increased significantly during the past 20 years and are now the third most common cause of death in the United States. Worldwide sales of antiinfectives were approximately $33.0 billion in 1996, and constituted the second largest pharmaceutical sales category. The antibacterial, antifungal, and antiviral markets are estimated to be approximately $26.0 billion, $4.0 billion, and $3.0 billion, respectively, based on 1996 sales.
Three antibacterial drugs that have each generated in excess of $1.0 billion in worldwide sales annually, and one antifungal drug has generated nearly $1.0 billion. Of the 100 best-selling brand name drugs worldwide, 20 are antiinfectives addressing bacterial, fungal, and viral infections. Despite the rosy picture for this therapeutic category, the clinical efficacy of many bacterial and fungal antiinfectives is being threatened by emerging strains of drug-resistant pathogens. In the antiviral area, only a limited number of effective therapeutics is currently marketed.
RiboGene has established programs for antibacterial, antifungal, and antiviral drugs. Within each program, the company's drug discovery process consists of four phases:
- Target Identificationthe selection and characterization of PSTM targets
- Assay Developmentthe design and implementation of screening systems to identify small-molecule compounds active against the PSTM targets
- Lead Discoverythe screening of compound libraries to identify small-molecule lead compounds
- Lead Optimizationthe refinement of lead compounds in order to develop drug candidates
RiboGene's PSTM targets exploit the difference between fungal and human translation.
RiboGene's PSTMs represent a new class of targets for drug discovery that is different from, and provides advantages over, traditional drug discovery techniques. Anti-infective drug discovery has historically used a limited number of biological targets, restricting the discovery of new drugs effective against drug resistant pathogens. By focusing discovery efforts on drugs that are effective inhibitors of PSTMs, RiboGene believes that it may be possible to discover drug candidates for which pathogens have not already developed resistance.
Because RiboGene selects only PSTM targets that are essential for the life of the pathogen and appear to bear little or no resemblance to their human counterpart, its targets are expected to show better safety and efficacy profiles than existing therapies.
RiboGene's Discovery Programs (Back to Top)
Antibacterial: RiboGene principal targets in the lead discovery phase, deformylase and ppGpp degradase, on which the company collaborates with Dainippon Pharmaceutical Co., Ltd. (Osaka, Japan). RiboGene has several additional antibacterial targets that are in the assay development phase, to which it has retained its rights.
Antifungal: Two compounds directed toward two targets, EF3 and GCN4, are in the lead optimization phase, and several others are in various phases of early research and development.
Antiviral: Focuses exclusively on the hepatitis C virus (HCV). RiboGene has one target, HCV IRES, in the lead discovery phase and one target, HCV NS5A/PKR, in the assay development phase.
For more information: Charles J. Casamento, President, RiboGene Inc., 26118 Research Rd., Hayward, CA 94545. Tel: 510-732-5551. Fax: 510-732-7741.
By Angelo DePalma