By Kevin Davies
July 18, 2011 | Following the widely publicized demise of plans to locate the Ignite Institute for Individualized Health in northern Virginia, the institute has found a new home as part of a three-way partnership at the Fox Chase Cancer Center in Philadelphia. Only it won’t be called Ignite anymore.
Ignite has been rolled into pre-existing plans at Fox Chase to build a center for personalized medicine, says Jeff Boyd, senior vice president of Molecular Medicine. “The Ignite Institute and Fox Chase are working together with Life Technologies to launch what is now the Cancer Genome Institute at Fox Chase,” says Boyd. Ignite’s founder, Dietrich Stephan, serves as consulting chief scientific officer of the new institute.
While searching for a home for Ignite, Stephan had forged a provisional deal with Life Technologies for 100 next-generation sequencing (NGS) instruments. “After the big Ignite deal in Northern Virginia went away, the relationship between Life and Ignite went with it,” says Boyd. A new partnership between Fox Chase and Life Technologies was announced in June, although the Ignite name was notable for its absence in the news release.
“We didn’t mention Ignite [when that was announced] – that was intentional,” Boyd explains. “We got tired of negative reporters who want to dig into what happened to Ignite [in Northern Virginia] and dredge up that experience.”
“Dietrich’s grand plan was to do personalized medicine in any number of manifestations -- pediatrics, neurological, cancer, all in one big institute. But he saw that it made a lot of sense to step back and silo things out. He’s landed here at Fox Chase with respect to the oncology piece of his vision. We had a similar vision.”
For his part, Stephan says he “criss-crossed the country multiple times, looking for a situation where we could land the whole shebang. It’s hard to build a $150-million research building.” But Stephan says there were many organizations eager to get into this space, even if they couldn’t support a full-bore TGen /Broad Institute model. “So my idea was to break Ignite into five disease models and decentralize” (see below).
In 2009, Fox Chase had established its own self-funded nascent Institute for Personalized Medicine. “Most of the leaders in this space believe this is the future, especially in the cancer arena,” says Boyd. “We’re not going to get any further with combinations of cytotoxic drugs. Combination therapies are clearly what we need to be thinking about, hence analysis of the tumor, and at some point exomes, transcriptomes and whole genomes. Something with ‘ome!”
Fox Chase management hired Price Waterhouse as consultants to decide how to evolve the institute into the clinical arena. “They were helping us build a business plan, which required a lot of philanthropy to develop a larger institute of personalized medicine. We were introduced to Dietrich, and he introduced us to Life Technologies.” Stephan says he felt “a lot of allegiance to Life Technologies. They wanted to stick with me. When Fox Chase started looking real, I brought Life Technologies in to bring closure to that deal.”
Boyd says Fox Chase had a lot to offer as an intellectual, medical and technology partner. “We’re a free standing NCI-funded comprehensive cancer center, a north east location, we have an incredible biosample repository, top Phase 1 clinical trial center, and brand new, state of the art lab space available.”
Details of the Life Technologies deal are confidential, says Boyd, but he does say it is a multidisciplinary partnership involving state-of-the-art technology, “both from deep sequencing as well as from an IT/bioinformatics standpoint. They’re an enormous company with a lot of depth. This project is quite complex, more than just grinding up tumors and looking for mutations in pathways.”
For genome analysis to become a routine part of clinical care, Boyd stresses that many issues have to be worked out. “Patient flow, charging, informed consent, CLIA, etc. I think Life Tech is looking to us to represent how one would do that, how we’d create such an institute. We could establish a model for other institutions to follow that would benefit the field.”
Fox Chase currently uses some Illumina instrumentation, but Boyd says he is “satisfied that the SOLiD 4 has the sensitivity and specificity that is comparable to anything Illumina has to offer.” But he is also making a bet on the scalability of the Ion Torrent semiconductor sequencing technology.
The Fox Chase Cancer Institute is currently deploying six SOLiD instruments in an R&D setting, plus a couple of Ion Torrent machines. “Once we get plugged in, sign informed consent documents, and so on, we’ll have a Fall start for enrolling patients. We’ve sequenced dozens of exomes, transcriptomes, from all manner of samples – fresh tissue, frozen tissue, microdissection, paraffin-embedded, but haven’t embarked on patient care yet.”
“I think we’re going to leapfrog the 5500 XL and once the Ion Torrent has reached the stage where we can think about whole exomes and genomes, we’ll shift from SOLiD 4s to ultimately [Life Technologies’] third-generation instrument, based on the Ion Torrent technology. We’re quite optimistic that will become the industry standard.”
N = 1
Boyd says the institute will create its own model of patient care, focusing on “a rigorous analysis” of druggable targets and genes in cancer-related signaling pathways. The institute will see most kinds of cancer, although it does not care for patients with brain cancer or pediatric cases.
“We won’t fiddle with the standard of care for new cancer patients,” says Boyd. “Pancreatic cancer, stage IV ovarian cancer, breast cancer, lung cancer, those might be examples where we utilize genome sequencing out of the gate.”
Initially, Boyd will offer transcriptome analysis in tandem with exome sequencing to provide insight into druggable pathways. “That comes as a package. We’re not offering full genome yet. But we don’t think it will be many years until we offer full genome. It’s a clinical decision: each patient will have to be considered uniquely in terms of life expectancy, cost, etc. It is expected to decrease substantially. There’ll be individual decisions made for each patient in consultation with their medical oncologist at the center.”
While Boyd hesitates to say when full genome sequencing will become routine for cancer care, he does believe there is promise in looking at exome sequencing clinically, rather than focusing on just a group of “hotspot” genes frequently mutated in cancer. He says his group will remain at the front edge of the technology bell curve.
Fox Chase admits 8,000 new patients/year, a number that will increase as the genome center unfolds. “It’s both extraordinarily exciting and a little terrifying at the same time. But we’ve chosen to devote a lot of energy and resources to it, and we’ve cast our lot,” says Boyd.
Stephan expects the center to sequence a couple of hundred patients this year, ramping up to 2,500 patients annually.
The other four areas under Stephan’s original Ignite umbrella were pediatrics, metabolic disease, cardiac disease and neurology. Stephan has found another north-east home for his interests in pediatrics, or “germline disease,” in Boston. “Children’s Hospital had been thinking about something similar [to me]. I spent time with that team. They’ll be putting $100 million into a 5-year effort called The Gene Partnership.”
The Gene Partnership (TGP) is billed as “a cutting-edge research initiative that combines the innovation of genomic research and IT to create the richest longitudinal knowledge base of genetic and clinical pediatric data in the world.” Stephan has high hopes for TGP, of which he is the executive director.
“I’m an emissary of sorts for this, focusing on the provider side. They’ll blow the doors off this at Children’s,” says Stephan. “If this ever takes root as an integral part of medicine, it has to be monetarily sustainable.” Stephan says a number of Boston biotech veterans, including venture capitalists Noubar Afeyan and Stanley Lapidus (co-founders of Helicos Biosciences), were among “a true rock-star team” to discuss the Gene Partnership concept. “Ultimately, the hospital had enough faith to make the investment.”
With engagements at Fox Chase and Children’s Hospital to manage, Stephan has no immediate plans to expand into the other three areas once targeted by Ignite. “I think I’ve got enough going on right now,” he says.