Genome Therapeutics Initiates Phase II Study of Ramoplanin for the Treatment of Clostridium difficile-Associated Diarrhea.

Business Editors & Health/Medical Writers

WALTHAM, Mass.--(BUSINESS WIRE)--Feb. 20, 2003

Dose-response trial to evaluate safety and efficacy of novel

antibiotic in second indication

Genome Therapeutics (Nasdaq: GENE) has begun a Phase II trial of its novel antibiotic, Ramoplanin. The study will assess the safety and efficacy of Ramoplanin to treat Clostridium difficile-associated diarrhea (CDAD), a serious form of colitis caused by toxins produced by the Gram-positive bacteria Clostridium difficile (C. difficile). Ramoplanin is also being studied in a Phase III trial for the prevention of bloodstream infections caused by vancomycin-resistant enterococci (VRE).

"The medical community is faced with increasing rates of Clostridium difficile-associated diarrhea in the hospital setting accompanied by high rates of relapse, creating challenges for the healthcare community including longer hospital stays and higher costs," stated Dale Gerding, M.D., Professor and Associate Chairman, Department of Medicine, Northwestern University Feinberg School of Medicine. "Current therapies are associated with certain shortcomings as treatments for this serious infection, including high disease recurrence rates, development of resistance to vancomycin by important pathogens such as VRE and Staphylococcus aureus, and some evidence of C. difficile resistance to metronidazole in Europe."

Dr. Gerding continued, "There is a clear need for new, highly effective treatment options for this disease. This is especially true given the CDC recommendations to significantly restrict the use of vancomycin in the hospital. An ideal new therapy would not only be highly effective against C. difficile, but would also reduce the concern with current treatments that they can enhance the growth and spread of VRE."

The Phase II protocol calls for an 87 person, open-label, multi-center trial of two doses of Ramoplanin, 200 mg and 400 mg twice daily, compared to vancomycin for the treatment of CDAD, which requires a dose of 125 mg four times daily. Both agents will be administered for ten days, during which data on Ramoplanin will be collected to measure safety and efficacy. The results of the Phase II trial will guide the design of the Phase III investigation of Ramoplanin for the treatment of CDAD. Ramoplanin, a novel glycolipodepsipeptide antibiotic, has demonstrated in vitro activity against C. difficile, including strains resistant to metronidazole and vancomycin.

"By expanding the clinical program for Ramoplanin we are demonstrating the many potential clinical uses of our novel antibiotic," stated Steven M. Rauscher, President and Chief Executive Officer, Genome Therapeutics. "Ramoplanin's ability to exert its bactericidal activity in the GI tract, without being absorbed into systemic circulation, has made it an ideal candidate for the potential treatment of CDAD. We expect the pace of enrollment in the Phase II study to allow for data analysis later this year."

About Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea is the most common form of antibiotic-associated diarrheas, with approximately 400,000 cases a year reported in the U.S. One study has demonstrated that as many as 20% of hospital patients are colonized with C. difficile either prior to or during admission. Because it is a spore-forming bacteria, C. difficile is readily spread from person to person, especially in the hospital and nursing home environment. Under certain conditions, such as extended antibiotic therapy and gastrointestinal surgery, C. difficile can colonize the gut and release toxins, leading to bowel inflammation and severe diarrhea. Serious cases can occur and involve the development of fulminant colitis (severe inflammation of the colon); such occurrences can be life-threatening, especially in elder or immunocompromised populations. Current therapies for the treatment of CDAD include metronidazole and vancomycin, although these agents are associated with a 15-20% relapse rate.

About Ramoplanin

Ramoplanin is an investigational new drug in Phase III clinical development by Genome Therapeutics. A novel product of microbial fermentation first discovered by Biosearch Italia, Ramoplanin is a member of a new class of antibiotics known as glycolipodepsipeptides. Genome Therapeutics has acquired development and commercialization rights to Ramoplanin for North America from Biosearch Italia. Ramoplanin has potent in vitro bactericidal activity targeted against Gram-positive bacteria, including many antibiotic resistant strains such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA). It is also bactericidal in vitro against Clostridium difficile. Because it is not absorbed systemically from the GI tract following oral dosing and exerts its bactericidal activity in the GI tract, Ramoplanin represents a potential new concept for managing certain pathogens commonly found in the hospital and carried in patients' GI tracts. In a Phase II study, Ramoplanin was shown to be highly effective at decolonizing patients carrying VRE in their GI tracts. Ramoplanin is currently being studied for two indications: a Phase III clinical trial for the prevention of VRE bloodstream infections and a Phase II study for the treating Clostridium difficile-associated diarrhea.

About Genome Therapeutics

Genome Therapeutics is a biopharmaceutical company focused on the discovery and development of pharmaceutical and diagnostics products. The Company's first product candidate, Ramoplanin, is in a Phase III clinical trial for the prevention of bloodstream infections caused by vancomycin-resistant enterococci (VRE). Genome Therapeutics' biopharmaceutical business includes seven major product discovery alliances with several pharmaceutical companies including Schering-Plough, AstraZeneca, Wyeth, Amgen and bioMerieux. The Company's genomics services business, GenomeVision(TM) Services, provides pharmaceutical and biotechnology companies, and government and academic institutions with custom high-throughput sequencing, library construction, integrated SNP services and the PathoGenome(TM) Database.

This news release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements represent our management's judgment regarding future events. Forward-looking statements typically are identified by use of terms such as "may," "will," "should," "plan," "expect," "intend," "anticipate," "estimate," and similar words, although some forward-looking statements are expressed differently. We do not plan to update these forward- looking statements. You should be aware that our actual results could differ materially from those contained in the forward- looking statements due to a number of risks affecting our business. These risk factors include risks related to our lead product candidate, Ramoplanin, such as (i) our inability to obtain regulatory approval to commercialize Ramoplanin due to negative, inconclusive or insufficient clinical data and (ii) delays in the progress of our clinical trials for Ramoplanin, and increased cost, due to the pace of enrollment of patients in the trials or fluctuations in the infection rate of enrolled patients. We are also subject to risks related to our inability or the inability of our alliance partners to (i) successfully develop products based on our genomics information, (ii) obtain the necessary regulatory approval for such products, (iii) effectively commercialize any products developed before our competitors are able to commercialize competing products or (iv) obtain and enforce intellectual property rights. In addition, we are subject to the risk factors set forth in Exhibit 99.1 to the Company's Annual Report on Form 10-K for the year ended December 31, 2001 and those set forth in other filings that we may make with the Securities and Exchange Commission from time to time.