Antibacterial pro-drugs for osteomyelitis

The novel compounds from Targanta's bone-seeking antibiotic development program are intended for the treatment and prevention of osteomyelitis (bacterial infection of the bone), a debilitating and difficult infection. The primary pathogens recovered from bone infections are typically gram-positive bacteria; Staph aureus and coagulase-negative staphylococci together are responsible for three of every four clinical cases in the U.S.

The spread of drug resistance among these and other pathogens is cause for alarm. At present, no antibacterial agent is approved for marketing with an osteomyelitis indication. The current standard-of-care parenteral treatment regimen is long, expensive and inconvenient, and is associated with numerous inherent complications. As such, there is an unmet need for osteomyelitis antibiotics with good efficacy and without the need for daily intravenous drug administration.

Targanta's synthetic chemists couple potent, proven antibiotics to bone-targeting moieties, thereby generating molecules that bring the antibiotics to the bone where their therapeutic potential will be maximized. In this manner, the toxicity of current standard-of-care high-dose therapy should be minimized. Diverse classes of antibiotics currently used in the clinic have been coupled to bone-seeking moieties, thereby allowing Targanta's chemists to tailor the antibiotic's well understood potency and pharmacokinetic behavior to the infecting bacteria.

Targanta applies a comprehensive set of in vitro, cell-based and in vivo assays to characterize its bone-seeking antibiotic candidates. Established animal models of S. aureus bone infection are used to evaluate Targanta's candidate compounds for further testing. Iterative cycles of synthesis and evaluation are then used to optimize the compound's stability, pharmacokinetic behavior, and activity. Targanta has already created several proprietary bone-targeting antibacterial pro-drugs that are highly effective at binding to infected bone where they regenerate the antibacterial agent in high concentration to maximize bactericidal effects.

A number of product candidates are currently being tested in various osteomyelitis models.