Tetraphase Pharmaceuticals is capitalizing on a fundamental advance in fully synthetic drug technology. While initially focused on the discovery of new generations of antibiotics to treat bacterial infections, the Company also sees in this technology significant opportunity for development in other arenas (i.e., inflammation, angiogenesis) where compounds in the tetracycline class have demonstrated activity.
Antibacterial
The global market for antibiotics exceeds $25 billion. Despite the need for new antibiotics, limited discovery and development efforts are underway within the biopharmaceutical industry. Only seven new antibiotics have won FDA approval since 2000, compared with 30 in the decade ending 1992—even as the emergence of bacterial resistance, and in particular of the aggressive methicillin-resistant Staphylococcus aureus (MRSA), has limited the effectiveness of many of the commonly used classes of antibiotics.
This rise in resistance, while alarming, opens opportunities for new approaches to antibiotic development. Tetracyclines are among the most successful classes of antibiotics. However, only one new compound in this class, Tygacil® (tigecycline, Wyeth), has been approved in over 30 years, largely as a result of the constraints on chemical modification inherent in semi-synthetic production methods.
Our novel approach removes that barrier. By unlocking the chemistry of this established class of antibiotics, Tetraphase stands poised to develop new tetracycline-based drugs with both oral and parenteral availability, good resistance profiles, and limited adverse events.
Inflammation
Tetracycline antibiotics have established anti-inflammatory activity. Studies suggest that this action is mechanistically distinct from the antibacterial activity of these drugs. Minocycline, for instance, interferes with matrix metalloproteinases, nitric oxide, and inflammatory cytokines, all key mediators of inflammatory tissue damage. This range of activities suggests that the Tetraphase platform could potentially yield new compounds for treating conditions such as rheumatoid arthritis and central nervous system indications.
Cancer
Before the 1960s, cancer researchers believed that the blood supply reached tumors simply because pre-existing blood vessels dilated. But later experiments showed that angiogenesis--the growth of the new blood vessels--is necessary for cancerous tumors to keep growing and spreading.
A common feature among currently recognized anti-angiogenic compounds is the ability to interfere with extracellular matrix remodeling, either by disrupting collagen deposition and cross-linking or by inhibiting collagenase. Members of the tetracycline class have such capabilities, and published data suggest that they are able to inhibit angiogenesis.
This research, coupled with the growing acceptance and application of anti-angiogenic therapies in the oncology field, provide Tetraphase with the opportunity to develop compounds capable of targeting multiple anti-angiogenic checkpoints through mechanisms unrelated to their antibiotic activities.
