Galapagos’ service division BioFocus DPI and nonprofit drug maker Institute for OneWorld Health announced last week that that they have expanded their 2006 collaboration to use BioFocus’ high-throughput, cell-based functional screen to identify new drugs made by Roche against infectious diarrhea.
The new deal, which is scheduled to last until the end of the year, “is really to highlight how well the biology and assay development [in the first part of the agreement] has gone,” Kate Hilyard, vice president of biological sciences for BioFocus, told CBA News this week.
“Building on BioFocus DPI’s expertise and familiarity with the current program, the Institute for One World Health expanded BioFocus’s role so the assays developed on behalf of iOWH could be used to screen the Roche compound library to identify compounds with certain characteristics,” James Hickman, vice president for communications and fund development for OneWorld Health, told CBA News in an e-mail.
BioFocus said its assay will screen 700,000 compounds that Roche provided OneWorld Health as part of a separate agreement signed in April. The target of interest for this project is the cystic fibrosis transmembrane conductance regulator gene.
Though others have been able to create cell lines around the target, “it is a difficult target to work on,” Hilyard said, because as a chloride channel, it is an integral membrane protein.
CFTR is also implicated in cystic fibrosis, and Hilyard said that it is “naturally predisposed to misfold, so it is hard to get it to traffic to the membrane, which is what happens in CF with the mutations.”
“We hope that the output from this screening campaign will feed into the drug discovery work that we are already doing to help build a pipeline of potential drug candidates for this target.”
Since the OneWorld alliance started, BioFocus has developed a number of assays for the target. “For some of the assays, we have taken what is known in the literature and developed the assay more, and in other examples, we have actually created cell lines with the target in them, such that we could develop robust, reproducible assays,” said Hilyard.
She did not elaborate on how those assays work.
In terms of deliverables or milestones, Hilyard said “we hope that the output from this screening campaign will feed into the drug-discovery work that we are already doing to help build a pipeline of potential drug candidates for this target.”
“For any drug target, one really needs to try a number of options, because one can never be quite sure what compound(s) will make it all the way to the clinic,” said Hilyard. “This is just a way of increasing our chances of success to create a broad drug pipeline.”
If any interesting compounds are identified in the high-throughput screen, the next step would be to put those into a medicinal chemistry program “to see if we can do drug discovery on them to make them into drugs,” Hilyard said.
The San Francisco-based Institute for OneWorld Health develops anti-infective agents for the developing world. In 2006, the firm received a $46 million grant from the Bill & Melinda Gates Foundation to expand its hunt for adjuvant treatments for traditional anti-diarrheal drugs.
Also that year, BioFocus announced that it had entered into a drug discovery collaboration with OneWorld Health to apply its medicinal chemistry expertise in hopes of identifying new drug candidates for OneWorld Health’s diarrheal disease program.
This ongoing collaboration aims to develop new anti-secretory drugs, which inhibit the loss of fluid in the intestine. These drugs will be used as adjuncts to oral rehydration therapy against life-threatening enterotoxigenic Escherichia coli and cholera, which are responsible for nearly 40 percent of all reported cases of infectious diarrhea in the third world.
One other company that is developing a treatment for infectious diarrhea is Mumbai, India-based Glenmark Pharmaceuticals, with its compound crofelemer. San Francisco-Calif.-based Napo Pharmceuticals, Glenmark’s exclusive worldwide licensee for the indication of acute infectious diarrhea, pediatric diarrhea, and diarrhea in those living with HIV/AIDS, announced last April the completion of a phase 2 trial of crofelemer for the treatment of adult infectious diarrhea. Napo anticipates a filing an NDA by the end of 2008. The US Food and Drug Administration has granted crofelemer fast track status for diarrhea associated with irritable bowel syndrome and HIV/AIDS.