CollabRx was set up by Jay "Marty" Tenenbaum and Raphael Lehrer to slash the cost and time of developing drug therapies (see "Collaboration and the Long Tail of Disease," Bio-IT World, March 2009). Its new service, CollabRx ONE, applies those resources to help identify bespoke therapies for latestage cancer patients. The goal of the service, which costs between $50-100,000, is to provide a deep understanding of the individual patient's disease by marrying genomic and computational analysis, and match the aberrant target or pathway with a potential therapy.
"In every case we have actionable hypotheses that the doctors have not previously considered. It's not cheap, but we're working hard in order to be able to reduce costs... and we're actively seeking collaborations with major medical institutions," says Tenenbaum.
Lehrer, who is in charge of CollabRx ONE, has been a friend of Tenenbaum 's for 20 years. After getting his PhD in physics from Harvard, Lehrer left research and moved into consulting and biotech, spending five years at Gene Logic working on toxicogenomics platforms and drug repositioning efforts, before finally joining forces with Tenenbaum.
CollabRx ONE has an informatics platform that builds tools for integrating a variety of data streams-gene expression, SNP analysis, copy number variant (CNV) analysis, sequence data-and potentially provides decision analysis. The small informatics group in California is led by co-founder and chief technology officer Jeff Shrager (best known for writing an application called BioBike). Meanwhile, the wet-lab analysis is outsourced to CLIA-certified labs.
Lehrer says the innovations are chiefly in trying to distinguish signal from noise using so few samples. "Happily I'm a physicist," he says. "Hopefully you create ideas you happen to have training for!" The informatics group handles tasks such as pathway analysis (using Ingenuity's IPA) and data visualization, customizing ways of visualizing the data given the variety of data types.
Once the analysis is complete, CollabRx ONE staff meet with the patient's oncologist and discuss their findings, hopefully to advise on potential drugs or drug combinations, based on information on drugs that are either FDA approved or in clinical trials. Tenenbaum says his group is applying selective use of proteomics and "trying to understand the values of wholegenomes sequencing."
CollabRx has formed a joint project with Alacris Pharmaceuticals called TREATiooo, to add whole-genome sequencing to the CollabRx ONE offering. By sequencing 1000 genomes of cancer sufferers, TREATiooo will not only provide potentially life-saving information about individual cancers, but create a compendium of cancer genome information that will inform What the Data Say
"We look for what the data are telling us, and how that matches the therapies," says Lehrer. Leading the analysis is Bob Coopersmith, a former Gene Logic colleague. "We push back and forth conclusions and alternate explanations, discuss discrepant observations," says Lehrer.
Although the project is in its early days, Lehrer says progress based on the first half-a-dozen patients is extremely promising. "It's important for us to connect with the oncologist and that the oncologist buys into what we're doing." In nearly every case, "the oncologist has been pretty excited," although it's too early to predict how that might translate into clinical success.
The work bears an emotional toll. One patient, thought to have 12 months to live, died ina matter of weeks before the team could implement their findings. In other cases, there are signs of a partial, but only partial, response to drug. Nevertheless, for Lehrer and Tenenbaum, that's encouraging. In the case of a lung cancer patient on Avastin, CollabRx analysis revealed the likely involvement of two different key pathways. "The second was going untreated, and that suggested a combination of drugs, or one drug that could hit both pathways." But the oncologists must follow the standard of care, which typically means changing the drug regimen only after the patient becomes fully resistant.
The recommended drugs are likely to be off label. "They may or may not be cancer drugs. They may or may not be generic. They may or may not be reimbursed," says Lehrer. "Oncologists may have tried it, but the reaction is often, ?I wouldn't have considered using that kind of drug, but based on what you're showing me, that makes sense.'"
Lehrer stresses that the results are always communicated to the patient's oncologist, "because they are the ones who need to decide whether what we've found is something that should be tried, or if additional studies should be done. Depending on circumstances, it is valuable to have the patient there as well."
CollabRx ONE is continuing to evaluate new technologies, studying whether a potential data source can add value to an actionable hypothesis. Lehrer says: "If it is adding value, are previous sources now redundant? Obviously it's not worth doing SNP analysis if you're doing whole-genome sequencing." K.D.
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Forfurther information on CollabRx ONE, see the video interview with Marty Tenenbaum: www.bio-itworld.com/lsw/jtenenbaum.
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