Tetraphase Shows What the $45M Was All About at Big Antibiotics Conference

Tetraphase Pharmaceuticals raised a big $45 million venture round back in June, and now scientists can see more clearly why it’s been able to raise all that dough.

The Watertown, MA-based company made a series of 10 different poster presentations over the past few days at the biggest antibiotics meeting of the year, the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Boston. Tetraphase showed that its lead tetracycline drug in development was effective against all but one of the major bugs it sought to kill in animals; it was well-tolerated in a convenient once-daily intravenous dose; the drug can be made into an oral pill; and that its chemistry platform has potential to generate more than just one drug.

“People are always looking for new antibiotic products, and there’s not enough in development,” says Tetraphase CEO Guy Macdonald. “People are excited about the spectrum of activity we have shown and our oral potential. We’re not a one product company. We have a platform that can develop novel and diverse profiles of antibiotics.”

Tetraphase, born in 2006 with technology from Harvard University, is setting out to custom-build new tetracycline antibiotics with properties that couldn’t be engineered via conventional fermentation methods. Tetraphase has used its new technique to synthesize antibiotics that can kill a broad variety of bugs from the two major classes of bacteria (gram positive and gram negative), and also more narrowly focused and potent drugs to kill specific bugs. While public health officials regularly sound alarm bells about antibiotic overuse contributing to the rise of drug-resistant “superbugs,” the biotech industry hasn’t developed much in the way of innovative new antibiotics versatile enough to kill a wide variety of the pathogens. Pfizer’s tigecycline (Tygacil) is the only new member of the tetracycline class approved by the FDA in the past 40 years, so Tetraphase is betting that if it can navigate the clinical trial process, it will be able to fulfill a real market need.

Guy Macdonald

Guy Macdonald

Many of the other venture-backed companies in the antibiotic market—San Diego’s Trius Therapeutics, New Haven, CT-based Rib-X Pharmaceuticals, and South San Francisco-based Achoagen—are largely focused on antibiotics that work against a specific type of bug or a certain property, which makes many of their compounds what scientists call “narrow spectrum” antibiotics. (Update and clarification 1:30 pm ET, Sept. 16): While one of Rib-X’s lead drugs, radezolid, fits this category, another advanced candidate, delafloxacin, is a “broad spectrum” antibiotic).

Tetraphase is attempting to develop its lead compound, TP-434, as a “broad spectrum” antibiotic that’s supposed to kill a whole range of bugs that resist other treatments, whether they have surface properties that make them classified as gram-negative or gram-positive pathogens. That’s thought to be especially useful for physicians seeking to treat the most severe infections people sometimes get in hospital intensive-care units, and for when physicians don’t yet have lab results to tell them exactly what kind of bug has infected the patient.

Tetraphase presented data from a series of animal studies at the ICAAC conference that suggests its new antibiotic ought to work against five of the six major bugs that cause most infections in hospitals and that are hard to treat. The list of so-called ESKAPE pathogens includes Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. Only one of those bugs, pseudomonas aeruginosa, was able to resist the Tetraphase drug in animal tests, Macdonald says.

Part of the Tetraphase R&D program looked at the lowest possible dose required to kill the pathogens, and then square that up with an initial phase human study that looked at how much people could tolerate. The Pfizer drug that’s on the market sometimes has limited use because it can cause nausea, Macdonald says, and it is given in a twice-daily dose. What’s important to Tetraphase is that it has shown the once-daily dose can kill the bugs, and that it should have a flexible enough dosing range to be made into an oral pill that people can take conveniently when they start feeling well enough to leave the hospital.

“With difficult-to-treat ESKAPE pathogens, you sometimes can’t get enough drug into the patient because of the safety profile. We think we’ve shown in the Phase I we’ll get more drug into people with a better tolerability profile,” Macdonald says.

This is all still very early in the development process, and the big test is yet to begin. Tetraphase is now gearing up to start enrolling the first of 200 to 250 patients with appendicitis, who will be randomly assigned to the new IV drug or the standard treatment, carbapenum. That study should start enrolling by year’s end, Macdonald says. And while that’s happening, Tetraphase is working on an oral pill form of the same drug that can be given on an outpatient basis, and also getting ready to begin clinical trials of two other antibiotic candidates in the first half of 2011.

It’s still early to talk about those programs, but Macdonald stressed that they are a key part of the Tetraphase strategy. Only about one-fourth to one-third of the $45 million financing is being funneled into the lead drug candidate’s clinical trials, while the rest is going toward the oral formulation work, and a pipeline of more antibiotics to come.

“We’re not a one product company,” Macdonald says. “We have a platform that can develop novel and diverse profiles of antibiotics. It’s a potential franchise.”

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