Rx3 recieves two NIH grants

Company wants to fight drug-resistant organisms.

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SAN DIEGO—Rx3 Pharmaceuticals Inc. wants to regain some of the ground that the health­care world has lost in the war between anti­biotics and drug-resistant organisms, and it hopes to make great strides in that effort with two new grants from the National Institutes of Health totaling $1.5 million. The grants complement the three-year, SBIR Phase I grant in the amount of $3 million that the company was awarded at its incep­tion in 2004, as well as commercial research revenues it is currently receiving, says Dr. John Finn, Rx3  president.
Given the highly competitive nature of the grant market in recent years, Finn says the government support is a strong valida­tion of the value of the company's work. The most recent grant will go, in large part, to expanding staff and research and develop­ment facilities to further advance preclinical antibiotic research efforts.
The goal to be achieved with the first of the two awards is to further develop potent antibacterial agents that kill a broad array of pathogenic bacteria by inhibiting more than one enzymatic target simultaneously.
"There's been this race between man and bugs that's been going on for the last 50 years at least, and in many ways, the bugs are win­ning," Finn notes. "If you inhibit a single bacterial target, you'll get mutations over time that increas­ingly eat into your drug's efficacy, and you generally start to see resis­tance develop within one to three years of a drug's introduction"
Rx3 is focusing heavily on struc­tural biology techniques, Finn says, to hit more than one target.
"The widespread bacterial resis­tance we've seen develop to drugs like trimethoprim has severely reduced their ability to treat infec­tions," Finn says. "We're working to understand changes in molecu­lar recognition that lead to resis­tance and we're developing com­pounds that have potent activity versus a second target. What this does is take the good properties of a drug like trimethoprim that hits a lot of Gram-positive and Gram-negative organisms and gives you a second target to fill in the gaps. If you hit an organism from two very different pathways simultane­ously with one small molecule, it's hard for target-based resistance to emerge."
The goal of the second grant is to discover compounds that inhibit specific cell wall targets and that act synergistically in combination with certain existing antibiotics.
"The majority of antibiotics hit the very last steps of bacterial cell wall synthesis," Finn says. "What we're trying to do and what the pharmaceutical industry has been interested in for at least 10 years is to hit the earliest steps of cell wall biosynthesis. So, our compounds would be synergistic with cephalo­sporins, for example, which means you can take the most widely pre­scribed class of drugs and make it so much better."
As the aims of either or both grants are achieved, Rx3 will qualify for substantially increased funding by applying for Phase II funding to further the research, the company reports.

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