Research breakthrough in treatment of TB and MDR-TB

FASgen Inc.'s compound, FAS20013, has emerged from an intense multi-year program of pre-clinical studies that clearly validate its potential as an ideal new drug for the treatment of tuberculosis and MDR-TB, the disease caused by organisms that are resistant to the drugs now commonly used to treat TB. Initial clinical trials in both TB and MDR-TB are scheduled for later this year.

FAS20013 is characterized as an ideal anti-TB agent based on compelling new findings. Its potent killing activity is directed specifically against slow growing mycobacteria that cause the disease rather than at a broad array of non-pathogenic organisms, which merely enhances the emergence of drug- resistant strains. No resistance has been encountered to FAS20013 in clinical isolates, nor have resistant organisms been induced in the laboratory despite multiple attempts. The short-term killing power of FAS20013 is greater than currently used drugs; for example, FAS20013 will kill more organisms in a 4-hour exposure than isoniazide or rifampin can during a 12- to 14-day exposure. The compound is very effective in killing MDR-TB organisms that are resistant to multiple drugs now in use. A series of recent laboratory experiments indicates the superior effect to current drugs of FAS20013's ability to "sterilize" TB lesions and kill the TB organisms surviving in the latent infections that exist in one-third of the world's population. Therapeutic evaluation of FAS20013 in a model TB infection in mice has repeatedly shown its effectiveness as well as freedom from adverse side effects. The compound is up to 100% orally bioavailable. To date no dose limiting toxicity has been encountered, even when doses 10 times the effective dose were administered.

The novel target and mechanism by which FAS20013 kills TB organisms (mycobacteria) has not been exploited previously for therapeutic purposes. Within a very few minutes, elements responsible for the organism's essential energy production are severely damaged as the concentration of ATP and function of the enzyme ATP synthase fall to near nil. Shortly thereafter the synthesis of vital cellular proteins and cell-wall mycolic acids is severely impaired; a chain of events that leads promptly to death of the organism. The Company has published this data (JAC 54, 722-729, 2004) and surrounded its discoveries with a series of world-wide intellectual property rights, including its most recently issued composition patent for FAS20013, "Antimicrobial Compounds". The recently reported finding by investigators from the Johnson & Johnson Research Laboratories of a diarylquinoline compound with anti-mycobacterial activity that targets the "proton pump" adjacent to the ATP site is supportive of the findings of FASgen's investigators. "We were pleased to learn of J&J's discovery as it confirms the target and mechanism of our earlier work and thus adds strength to our intellectual property position," said Albert H. Owens, Jr., M.D., FASgen's President and Founder.

Significance: No new drug has been approved for the treatment of tuberculosis for over 40 years. FASgen's findings suggest that there is finally a new anti-TB agent that can address the ever-increasing problem of multi-drug resistant TB as well as the widely-prevalent latent TB infections that, on reactivation, are the source of new cases. The Company's clinical trial program is aimed at significantly shortening the lengthy courses of therapy now required to control active TB infections. "We believe FAS20013 has the potential to dramatically redefine and increase the size of the market by making a therapy available to patients that are currently not treated at all or fail to comply with current treatment," said Eric F. Stoer, Chairman of the Board at FASgen, Inc.

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