Here’s a scenario that captivates medical researchers: A pharmaceutical company reluctantly shelves a drug candidate whose early promise didn’t pan out after extensive testing in a target disease. But new data in genomics and other fields later reveals that the failed compound could be a blockbuster drug in an entirely different illness.
That vision has inspired many companies, from giants like Hoffmann-LaRoche in Switzerland to startups like NuMedii of Mountain View, CA. NuMedii is sifting for clues amid masses of data about marketed drugs as well as sidelined drug candidates.
Building on bioinformatics work begun at Stanford University, the startup is mining genetic data, clinical trial results, and other studies to find unexpected ways to repurpose existing drugs. By searching for common biological mechanisms that may be at work in different diseases, the method may even yield new biological insights, says NuMedii CEO Tarangini “Gini” Deshpande.
“Sometimes the connections have not been made,’’ Deshpande says.
Companies pursuing similar goals will convene near San Francisco next week for the 2nd Annual Drug Repositioning and Indications Discovery Conference (Oct. 23-24 at airport Hilton hotel in Burlingame).
Among the speakers are Stanford professor Atul Butte (an Xconomist), whose bioinformatics work with other scientists formed the basis of NuMedii’s drug evaluation platform. Through an algorithm applied to publicly available data, the researchers predicted that an anti-seizure medicine, topiramate, could be adapted as a treatment for inflammatory bowel disease—and lab studies confirmed the possibility.
NuMedii recently announced its first drug development alliance: a long-term partnership with Aptalis Pharma of Mont-Saint-Hilaire, Canada. The California startup will provide Aptalis with proposed drug candidates for the treatment of gastrointestinal disorders and cystic fibrosis. Full terms of the deal were not disclosed, but NuMedii will receive an upfront payment and possible milestone payments and royalties.
Deshpande says NuMedii also has a technology partnership with a large pharmaceutical company whose name is still being kept under wraps.
Experience has shown that old drugs can find new uses. The most startling turnaround story belongs to the former morning sickness remedy thalidomide, which was withdrawn in the 1960’s after babies were born with malformed or absent arms or legs. But thalidomide was later resurrected as a treatment for multiple myeloma.
Some drug makers have looked for fresh uses for new drugs while still developing them for a first indication. Genentech of South San Francisco created an anti-cancer antibody, Avastin (bevacizumab), designed to inhibit the formation of blood vessels that could nourish the growth of tumors. The company, now a unit of Roche, later modified the antibody to create Lucentis, (ranibizumab) a treatment for wet macular degeneration. The drug is designed to prevent abnormal growth of blood vessels in the eye and the resulting vision loss.
Roche itself has formed a global data mining initiative to repurpose existing drugs and uncover new ways to combat diseases. A Roche expert, Rama Kondru, is slated to outline the work at the Drug Repositioning conference next week. The Swiss drug company is studying more than 300 compounds that had been extensively tested before they were shelved, and is working with outside collaborators and external screening platforms.
A key element of NuMedii’s data analysis is tracking the effects that specific drugs have on gene activity—the genes that are turned on or off in cells at any one time. Diseases also create signature impacts on the pattern of gene expression. Comparing these patterns can suggest that a certain drug might help block the damaging gene activity associated with a particular disease.
The company can draw on more than one million sets of gene expression data stored in publicly available databases, and 20 percent of that trove was added in the past year, Deshpande says.
NuMedii’s database integrates many other types of data aside from gene expression study results, says Deshpande. But genomic analysis provides an in-depth look at how a drug affects the entire network of molecular interactions in the body, not just one target element of a disease.
“It’s a great starting point,’’ Deshpande says. Other data, such as clinical trial results, add to NuMedii’s systems-level portrait of a drug and its effects. A compound known to hit one disease target may be found to affect six or seven other molecular structures. This could lead to a new drug use, but it could also alert researchers to an undesirable side effect, Deshpande says. That could help pharmaceutical companies avoid expensive failures.
NuMedii is continually annotating and adding new studies from the public domain into its database, hosted at Amazon’s cloud computing service; it’s all an example of “big data” at work in pharmaceutical research. But much of the existing data on marketed drugs and experimental compounds is held in the private domains of pharmaceutical companies, Deshpande says.
Butte, who is Deshpande’s husband, has worked with the Seattle non-profit organization Sage Bionetworks to promote wider data-sharing that could boost the analytical power of disease research and drug repurposing studies.
In the meantime, NuMedii is eager to form partnerships with pharmaceutical companies to study the potential therapeutic value of their in-house drugs and experimental treatments, as well as compounds found elsewhere.
“We’re in discussions with several of them,’’ Deshpande says.
NuMedii, whose work has been supported so far by grant money and funds from collaborations, is now raising its initial round of financing, Deshpande says. The staff of four includes executives in charge of technology, assets, and corporate development.
The company is positioning itself as a drug discovery partner with pharmaceutical firms, not a technology services provider. Its product is “de-risked’’ drug candidates predicted to succeed, Deshpande says.
NuMedii’s drug vetting procedure includes an evaluation of commercial factors such as patent rights. Generic drugs with expired patents are still potentially profitable products, if their use in a new disease requires modifications such as tweaking the chemical structure or the delivery method, Deshpande says.
The Mountain View company will remain a small, early-stage discovery and early clinical development unit that partners with larger businesses that already have clinical development and marketing capabilities. But its revenue potential is limited only by the returns possible for any drug developer that turns out effective new remedies, Deshpande says.
“You really could find either the next big blockbuster, or even the next therapy for an orphan disease, using this approach,’’ she says.