Emerging Drug Developer: Trius Therapeutics

Upstart Trius Therapeutics bolts ahead with fast-pace development plan

When Jeff Stein, PhD, joined Sofinnova Ventures as a venture partner three years ago, he had already fleshed out the basic outline of a business plan. He would in-license a promising, early-stage anti-infective compound, combine that program with the resources of a fledgling company where he was chairman of the board and rely on a specially crafted discovery platform to gin new therapeutic candidates.

That kernel of an idea--combined with some high-profile venture contacts--has grown into a San Diego-based company that has attracted $50 million of biotech investment funds in slightly more than a year. Following an ambitious $20 million Series A, Stein has just closed a $30 million second round that is designed to fuel Trius Therapeutics into a late-stage study of its lead drug candidate--an oxazolidinone antibiotic dubbed TR-701.

“I joined Sofinnova with the aim of creating an anti-infectives company,” recalls Stein. “That’s an area that Sofinnova has wanted to invest in for quite some time. They had looked, but hadn’t found one suitable. At the same time I was chairman of Rx3 Pharmaceuticals, a very small anti-infectives company that was supported by government grants. My strategy was to in-license a compound, combine that with Rx3 to create Trius, with a lead candidate and discovery engine for preclinical compounds.”

First, though, Stein had some extensive traveling to do.

“I spent a year and a half looking worldwide, evaluating licensing opportunities. I found one in Korea (held by Dong-A Pharmaceutical), did due diligence and started the licensing process and working on the Series A. That was the basis of Trius Therapeutics. And over the summer of 2007 I recruited a clinical/regulatory team to advance the clinical development of 701.”

Trius has yet to complete its Phase I study of TR-701, but Stein says that it’s well on its way to proving itself and taking the next step into a mid-stage study. And he adds that there’s a good scientific basis for optimism at a point when most developers would be hedging their bets and cautiously outlining minimal expectations for safety data.

“Anti-infectives are different from other therapeutic areas,” says Stein. “Animal efficacy data is 100 percent predictive of human efficacy. There’s never been an anti-infective that showed efficacy in animal models that didn’t show efficacy for humans.”

Trius’ key step now is demonstrating the drug can be safely administered and has the appropriate pharmacokinetics profile for a successful product.

“That’s highly predictive of future success,” adds Stein. 701 “is eight-fold more potent than Zyvox from preclinical animal models. Recent data in Phase I show that it has a superior half-life supporting once daily dosing and a broader safety window.”

The criteria for winning regulatory approval for an anti-infective--in a world in which every new approval ushers in a therapy that immediately begins to lose effectiveness--is that it can’t be greater than 10 percent less effective than the standard of care, says Stein, a hurdle Trius plans to clear in a Phase III trial comparing 701 to Zyvox.

The CEO says the company will be submitting an application for fast-track status with the FDA as it pursues research into 701’s effectiveness against “complicated skin and soft tissue infections, specifically MRSA.” That pathogen is now becoming prevalent in communities and crossing over to hospitals--a key unmet medical need with a drug that is being developed for both oral and IV delivery.

“Right now we’re in Phase I with the oral (formulation). We will initiate an oral Phase II (this year) with a parallel intravenous Phase I. And those will converge at Phase III. We’ll start next year on Phase III”--which will probably require about 600 recruits and around two years to complete.

After that, Trius can also expand its research into 701 as a therapy for hospital-acquired pneumonia.

The competing anti-infectives in the field are primarily delivered intravenously, notes Stein. And while researchers at Trius had discussed limiting their development program to an oral form of the drug, the leadership was persuaded that they need to develop both oral and IV formulations, so the therapy can be available when doctors first strike back against an infection in the hospital, looking for a fast dose and a quick response.

Trius has two preclinical candidates that it has identified from its structure-based drug design platform technology. And Stein plans to bring one of those candidates into the clinic next year.

“Structure-based drug design employs the three-dimensional structure of the target,” explains Stein, “using X-ray crystallography to determine the 3-dimensional coordinates of the site you wish to target and the design of molecules that can inhibit specific enzymes for antibacterial qualities. The first criteria is the selection of an appropriate target. It has to be essential; the inhibition of that target in fact will lead to the death of the pathogen. And it has to be druggable.”

While Stein laid out a clear path for starting Trius, the future could follow one of several different trails. 

“I guess in the best of worlds this Series B will be the last institutional round,” says Stein. “We would like to evaluate the IPO market late next year, otherwise there’s a possible M&A or substantial partnership.”

A partnership at the end of a successful Phase II study is a possibility, he acknowledges. “To fund Phase III trials, you need a partnership or an IPO.” But he also notes that Trius now has the resources to advance 701 into a late-stage study. And with worldwide rights to 701 outside of Korea, he’s intrigued by the possibility of retaining marketing rights on a drug that won’t require a vast sales force to promote.

But it’s still too early for any serious partnership negotiations, even in a field that has attracted keen interest from a variety of Big Pharma companies.

“We have shared data with all of the large pharma companies with an interest, and they are tracking it.”

Emerging Drug Developer: Trius Therapeutics