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to run a small-molecule chemistry group at Genentech. Nathaniel “Ned” David, along with Camille Samuels of Versant Ventures, pulled the people and concept together with Floyd Romesberg of The Scripps Research Institute in San Diego. The company went on to raise $42 million in its first two venture rounds. Judice joined in May 2004.
One of the ways Achaogen has sought to differentiate itself, compared with other antibiotic companies, is by being “platform agnostic,” Judice says. That means it will do what it takes to re-engineer an existing class of antibiotics, or mix up the dosing intensity or frequency to stay a step ahead of the bugs. It’s not just fixated on certain gram-positive or gram-negative bugs, but whatever strategy seems best to kill certain multi-drug resistant pathogens.
“It’s a bit oversimplified, but we’re in a bit of an arms race with the bacteria. They have a lot of defense mechanisms we have to overcome,” Judice says. “We’ll do anything it takes to win that battle.”
That means Achaogen’s scientists go after all sorts of chemical challenges, modifying different classes of antibiotics like aminoglycosides, beta-lactams, or fluoroquinolones. This is part of what makes Achaogen different from its competitors, according to Samuels, a member of the company’s board.
“Achaogen’s ‘special sauce’ is that it combines exceptional drug discovery/chemistry capabilities with unique insights into the clinical needs in antibiotic therapy,” Samuels says in an e-mail. “The latter is a particularly challenging skill to acquire in antibiotic drug development because developers are in the business of trying to predict future patterns of drug resistance. Because it takes so many years to get a drug on the market, antibiotic developers have to address not today’s problems but the problems that will be in emerging in 5-10 years. It really is a war between the bugs and us—and you have to be like a general strategizing about the bugs future moves based on epidemiology and clinical problems in certain, often remote, parts of the world … Whereas most companies focus on today’s obvious problems.”
It all sounds great and ambitious, but antibiotics, like all drugs, can be risky to develop. A number of antibiotic developers—San Diego-based Trius Therapeutics, Cambridge, MA-based Targanta Therapeutics, and Theravance, to name a few—have run into roadblocks and delays of various kinds in recent dealings with the FDA. And their delays happened in the late stages of development, after their drugs had already passed muster in mid-stage clinical trials, theoretically removing much of the technical risk of failure.
Achaogen hopes to avoid those snags partly by going the road less traveled in antibiotics, where there’s a strong need now and in the future, by treating gram-negative bacterial invaders. The company’s lead candidate, ACHN-490, is for multi-drug resistant gram-negative bacteria like E.coli and K. pneumoniae. The current crop of aminoglycosides are used against the gram-negative invaders, and are often effective. But they are limited in their dosing: because the drugs aren’t metabolized through the liver, they get cleared through the kidneys. An excessive dose can be toxic to the kidneys.
Scientists at Achaogen modified the absorption and distribution properties of the aminoglycoside in such a way that it would be easier on the kidneys, Judice says. By doing that, you could theoretically raise the dose, and knock down the bug before it has a chance to resist.
“We like to get in and hit them hard, hit them fast,” Judice says.
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