Adaptive TCR, a Fred Hutch Spinoff, Nabs $4.5M to Uncover Immune System Secrets

3/26/10Follow @xconomy

Seattle experts in computer science and immunology are rallying around a new spinoff company from the Fred Hutchinson Cancer Research Center.

Seattle-based Adaptive TCR has nailed down a $4.5 million round of angel investment to get up and running, Xconomy has learned. The basic concept is to provide scientists with a high-speed, high-resolution look into the vast diversity of T-cells of the adaptive immune system that we all produce to ward off infections, and which sometimes go awry and cause disease.

This company wasn’t backed by the usual venture capital suspects in Seattle biotech, and it has an unusual backstory. Adaptive’s scientific co-founders are a pair of Hutch researchers who are first-time entrepreneurs in their 30s: Harlan Robins, a particle physicist who turned to genomics a decade ago to tackle its daunting math, and Chris Carlson, a geneticist and molecular biologist. Chad Robins, Harlan’s brother, has signed on as the founding president and CEO. Chad, who has a Wharton School business degree and experience with investment banking and hedge funds, wrote the original business plan and tapped his Rolodex to raise the company’s seed capital.

The founding scientific advisory board includes some big names. They include Arnold Levine of the Institute for Advanced Study in Princeton, NJ; Gerald Nepom, the director of the Benaroya Research Institute in Seattle; Edus Houston Warren of the University of Washington and Fred Hutch, as well as two other prominent genetic researchers from the UW who aren’t being named yet.

“I’ve been talking to my brother for 20 years, and saying ‘You’re a smart guy, when are we going to do a business together?’” Chad Robins says. “He’s never been interested before. Then he called me last February.”

That was a little over a year ago. Now the business is taking shape with a founding team of four employees who have subleased some office space in South Lake Union from VLST.

Adaptive TCR is built on using high-speed gene sequencing instruments that capture data from biological samples, and combining it with some pretty heavy duty math that’s executed by proprietary software.

The problem is certainly complicated enough to excite a string theorist like Harlan Robins. While scientists know that the 3 billion letters of DNA that make up a genome are consistent in every human cell, that’s not a fixed number that applies to immune system T-cells. The DNA in T-cells gets shuffled as they mature, allowing the cells to recognize a foreign invader like a virus. Humans have evolved an ability to adapt to these invaders, by building up a vast repertoire of T-cells with memory for a certain pathogen. This vast array of T-cell variation is something that scientists haven’t been able to look at in a high-volume, systematic way ever before. It creates a staggering diversity of possible ways humans respond to infection. For scientists trying to pinpoint the cause of, say, autoimmune disease, this also creates a classic needle-in-a-haystack problem.

Adaptive TCR hopes that by sequencing lots of blood samples from different individuals, and using its proprietary software, they can find some commonalities in the kinds of T-cell receptors that people form in certain situations, whether it is responding to a foreign pathogen like flu, or turning the immune system’s natural firepower on healthy tissue, like it does with rheumatoid arthritis. If scientists could find signature proteins on T-cells at the root of these immune system irregularities, then they could incorporate that knowledge into diagnostic products or use it to identify drug targets, Adaptive TCR says.

Few scientists have tried to look at these T-cell receptors in a high-output fashion before. Fewer than 30,000 T-cell receptors had been sequenced with conventional methods before the Adaptive TCR technique came along, Chad Robins says. The Adaptive TCR method claims to be able to identify 100 million T-cell receptor sequences over a four-day period.

The high-volume screening technology from Adaptive TCR “provides a sensitive and specific tool” for measuring patterns of T-cell variation, with “more resolution compared to techniques that we’ve used in the past,” says Nepom, the director of the Benaroya Research Institute. Chad Robins described it with an analogy: “These guys have invented the Hubble telescope compared to what we used to have, a pair of binoculars.”

So how is this supposed to become a business? It is starting out as a fee-for-service provider to academic and industrial customers who want to look at the diversity of T-cells. People ship their samples to Adaptive TCR’s offices, and get back a result on the T-cell diversity and repertoire from the sample. Adaptive isn’t spending big money on its own servers to host this data—those gigabytes are being stored on secure remote servers operated by Amazon Web Services.

The fee-for-service model can certainly generate revenue early on to sustain the company, but that’s not the end of the story.

Adaptive TCR has some other ideas on how to capture more of the future value that this data on T-cells might create for diagnostics and drug discovery. Autoimmune diseases—in which the immune system goes haywire and starts attacking healthy tissues like a virus—affect an estimated one out of every 12 people in the U.S. with more than 80 different conditions, according to the National Institutes of Health. They are notoriously hard to diagnose, because there’s not a good molecular tool for that, Robins says. By getting high-resolution looks at T-cell receptors, Adaptive TCR hopes to find some of the basic immune system malfunctioning at a molecular level that hasn’t been seen before, which could provide for much earlier diagnosis.

While there is a huge amount of variation in the genetics of T-cell receptors in one individual, Adaptive TCR also thinks it’s possible that there are overlapping stretches of DNA in these T-cell receptors shared between patients with an autoimmune disease like Type 1 diabetes or multiple sclerosis, Robins says. The company has a collaboration with Nepom’s team at the Benaroya Research Institute to look for those overlapping stretches, which could become valuable new drug targets.

Of course, these are still early days at the company. Harlan Robins and Chris Carlson are keeping their faculty positions at the Hutch. Much will depend on whether the early customers think they are getting their money’s worth by getting all this data on T-cell diversity over the coming year. Proof to show the value of the method will take time to emerge in peer-reviewed literature. The founders, whom I met a few weeks ago during a visit to the Hutch, didn’t sound like they are getting too carried away with themselves yet.

“These guys came up with this, and it’s my job not to screw it up,” Chad Robins says. “They’ve invented something extraordinary, but the invention still needs to be brought to the market.”

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