Joyce A. Sutcliffe, Ph.D., senior vp biology at Tetraphase Pharmaceuticals, described the company’s approach for generating a new class of highly potent and safe antibiotics via a novel synthesis strategy.
“Making only slight synthetic changes in current drug scaffolds can result in big differences in terms of pharmacological properties. Our company is focusing on tetracyclines, which are historically, among the most successful classes of broad-spectrum antibiotics. They are also one of the most difficult to work with—only one new compound in this class has been approved in more than 30 years, largely because of chemical-modification constraints.”
“Our process was developed by Andrew Myers, Ph.D., chair of the department of chemistry and chemical biology at Harvard University. After 10 years of research, he developed a novel and completely synthetic approach to generate new tetracycline drugs and derivatives. In the past, chemically modified tetracycline analogs have been produced using solely semisynthetic or chemical transformation of isolated natural products. This severely limited the range of new drug candidates.
“Our core technology can modify tetracycline at any position. Our approach has provided us with a platform from which multiple complementary products have been generated, allowing us to identify potent compounds with the best spectrum and pharmacokinetic properties to meet medical needs.”
Tetraphase currently has one candidate, TP-434, that has completed Phase I trials; it is anticipated that it will enter Phase II studies later this year. Tetraphase has two additional IV/oral candidates for gram-negative infections or community-acquired bacterial pneumonia that are scheduled to enter Phase I trials in 2011.
“Our lead candidate TP-434 is effective against gram-positive, gram-negative, and anaerobic pathogens, except Pseudomonas,” Dr. Sutcliffe reported. “Because of its broad spectrum, it is expected to be utilized for complicated intra-abdominal infections, hospital-acquired pneumonia, complicated urinary tract infections, and acute bacterial skin and skin structure infections.”