DNA sequencing will play an important role in the business of consumer genomics startup Navigenics, In Sequence has learned.
The company, which officially launched last week (see In Sequence 11/6/2007), will initially use microarray-based whole-genome genotyping to provide customers with common SNP variants associated with an increased risk for certain common complex genetic diseases. But it plans to supplement these scans with targeted sequencing, and also wants to adopt whole-genome sequencing in the future.
“We absolutely will be layering in sequencing in the short term, in a very targeted way,” Navigenics cofounder and chief science officer Dietrich Stephan told In Sequence last week.
The company is currently testing its first product, a $2,500 whole-genome scan and risk analysis for more than 20 common diseases such as prostate cancer and diabetes, in a “prerelease” and plans to launch its service more widely early next year.
At an additional cost, customers can obtain updates to their analysis, as more scientific studies establish links to diseases.
Navigenics will genotype its customers on the Affymetrix Genome-Wide Human SNP Array 6.0, which covers more than 900,000 SNPs as well as numerous copy number variations. “Today, we are just testing for common variants that predispose to common human diseases,” Stephan said. “And we believe that the Affy 6.0 can capture the vast majority of those in one shot.”
The company decided to start with common SNPs because the technology was readily available, and because these markers account for the majority of risk factors for common diseases, he added.
However, some genetic diseases, both common and infrequent, are caused by rare genetic variants that differ between families. To capture those variants as well, Navigenics will employ DNA sequencing, initially “most likely” using traditional Sanger sequencing, Stephan said. “For the diseases that we are focusing on, if there are any genes or regions of the genome that require sequencing to capture any additional risk variants, we will be layering that in.”
In parallel, Navigenics is planning to “ramp up the whole-genome sequencing effort,” Stephan said, but is still waiting for the cost of high-throughput sequencing to drop, and its accuracy to improve, before bringing any next-generation technology into the company. “We are very conservative in terms of wanting to make sure the technology is stable, and can be done in a diagnostic laboratory setting, before we implement it,” he said.
Stephan also does not believe in the value of exon sequencing, which focuses on protein-coding parts of the genome and assumes that these are functionally most important. “We have evidence that there is much more of the genome that is functional and can predispose to disease,” he said.
In order to avoid conflicts of interest, Stephan took a leave of absence from his post as deputy director of discovery research at the Translational Genomics Research Institute in Phoenix, but he still maintains a laboratory at TGen. His research team is “exploring all of the next-generation sequencing technologies,” Stephan said, currently focusing on new strategies for selecting portions of the genome, using microarray technology from Febit, and analyzing these with Illumina’s Genome Analyzer. But the researchers have also “worked extensively” with both Applied Biosystems and 454 Life Sciences, and plan to be early adopters of Helicos’ new sequencing platform, he added.
It is hard to predict what demand for Navigenics’ services will be like, but according to focus-group studies the company conducted, three-quarters of the population is interested in learning about disease risks that they can “do something about,” be it by modifying their behavior or getting more frequent checkups. Far fewer people want to learn about risks for diseases that are impossible to prevent or treat. For this reason, Navigenics will “for the first [few] years probably, only be giving information on ‘actionable’ diseases,” Stephan said.
“We are very conservative in terms of wanting to make sure the technology is stable, and can be done in a diagnostic laboratory setting, before we implement it.”
Navigenics’ studies suggested that people are willing to pay for these risk profiles out of pocket, and the company is confident that customers will not be deterred by the $2,500 initial price. “As volume increases and we start understanding how to do it right, we will slowly come down in price point so that everyone can have access, I believe,” Stephan said.
The company is not the only one planning to provide genome-based information directly to consumers, and not the only firm to use DNA sequencing. Last month, Cambridge, Mass.-based startup Knome said it plans to sequence entire genomes for its customers (see In Sequence 10/30/2007).
Google-backed 23andMe has partnered with Illumina to generate whole-genome genotyping data but has not said much about its offerings yet (see BioArray News 8/7/2007).
In addition, a variety of other companies provides gene-based lifestyle and nutrition advice or ancestry information, usually by testing for a small number of markers.
But Navigenics wants to differentiate itself from its competitors in several ways. Though the company will provide data directly to customers, in the future, it plans to “slowly start to plug into the established medical system” as legislation addresses privacy concerns. “The only reason that this information is going directly to the consumer is that it’s the only possible way to get them this information in a private way,” Stephan said. But Navigenics has already teamed up with medical centers like the Cleveland Clinic, Georgetown University, Mayo Clinic, Scripps Health, and Partners HealthCare in order to integrate genetic information with “mainstream medicine, and eventually … the reimbursement system,” Stephan said.
Secondly, the company focuses exclusively on medical risk assessment, while some others are “either doing one-off testing, … or they are blending it with the sort of ‘fun genetics,’ which I think dilutes their ability to really understand medical risk, and how to educate physicians and counselors, and get reimbursement,” he said. Although Navigenics does study genetic markers that indicate an individual’s ancestry, for example, it does so only to define the medical risk for a certain disease, which might be influenced by ancestry, more precisely, but does not provide the ancestry information to the customer. “We don’t want to be diluted by getting into genealogy,” he said.
Stephan and David Agus, a clinical oncologist, jointly founded Navigenics and raised initial funding about a year and a half ago. The company recently closed a Series B funding round, led by MDV-Mohr Davidow Ventures, a new investor, who was joined by A-round investors Kleiner Perkins Caufield and Byers and Sequoia Capital. To date, the company has raised more than $25 million in total funding.
Navigenics shares two of its VC investors — MDV and KPCB — with next-generation sequencing developer Pacific Biosciences (see In Sequence 4/24/2007). MDV has also invested in 23andMe.
“I think all of us had [this idea] that someday, we will be able to sequence the whole genome of a person, put it in a big computer, push a button, and get a rank-ordered list of the diseases that you are at risk for, and also understand the environmental exposures that you have, put together in place a prevention plan that’s focused, so that you can live a longer and healthier life,” Stephan said. “We all know that that’s coming someday.”