CombinatoRx Inc. takes its name from its approach to drug discovery a cocktail, or combination, approach.
What this means is that the company takes molecules that have little or no effect on their own, but when combined with other molecules become an effective medicine. Boston-based CombinatoRx has two approaches: taking an existing drug and making it better, and creating a new treatment by combining molecules into a cocktail.
What the company is doing is “fundamentally different than what most people have been doing,” said Alexis Borisy, president and CEO of CombinatoRx.
The company was officially started in March of 2000 by Borisy and four others: Curtis Keith, now vice president of research; Brent Stockwell, now on the scientific advisory board; Michael Foley, also on the scientific advisory board; and Jacob Goldfield, chairman. To date, the privately held company has raised $17.5 million, and expects to close a new round of funding in the first half of this year, Borisy said.
The company is working on discovery of a new class of medicines named “system biology therapeutics,” which target multiple disease pathways simultaneously. Often, multiple mechanisms and pathways are required for a particular biological system to function. If there is more than one pathway, one agent may not be effective, but may become highly effective when combined with agents that overcome the redundancy in pathways.
Borisy said the company has active leads in cancer, immunoinflammatory diseases and anti-infectives. For example, the company has what he called a “late preclinical” program that is getting close to the clinic.
“It is composed of two separate molecules, either one of which would have no cancer effect, but when you put them together, you have a potent anticancer on par with the best anticancer agents out there,” Borisy said.
The company also has other CRx its name for its systems biology therapeutics including an orally available TNF-alpha inhibitor that may have applications in several disease areas, including rheumatoid arthritis, psoriasis and inflammatory bowel disease. In the area of infectious disease, CRx 201 is an antifungal agent that has shown significant activity against resistant strains, the company said.
Borisy said that the industry as a whole has been focused on single new targets, including about 500 targets on which all drugs have been based. But he pointed out the 30,000 or so genes provide perhaps 5,000 to 10,000 good new single targets. He maintained that this drug-for-every-protein-target approach might not be the best one.
“What we think is that [this approach] will not ultimately cure human disease,” Borisy said.
CombinatoRx’s combination approach, he said, is the result of trying to be in front of a new wave that could have a substantial impact on the industry.
The technology platform consists of combination high-throughput screening designed specifically for screening combinations of molecules, phenotypic cell-based assays, multipoint informatics and combination structure/mechanism activity relationship analysis.
Daniel Grau, vice president of business development, said the company is now in confidential partnerships and is in “active negotiations” with other companies that could be disclosed later this year, since CombinatoRx has more leads that it can move into the clinic on its own.
Borisy pointed out that 18 months ago the foundation of the company was a “powerful idea” that was “pure theory.”
Today, its 45 employees are all focused on riding this new wave of discovery.