By Allison Proffitt
January 24, 2017 | To start with, the technology Two Pore Guys is currently shopping uses only one pore. But the two-pore vision still drives the company, and serves as its namesake.
Sequence-through-pore is “really old tech”, Dan Heller, CEO of Two Pore Guys (2PG) says. The trouble is DNA passes through silicon pores too quickly to read. Slowing it down to a useful rate is the challenge—groups like Oxford Nanopore use biological nanopores “as a ratchet” Heller says. 2PG has a different approach: opposing pores, both pulling the DNA toward them, but at different voltages or strengths.
“You are able to slow down DNA without reducing the voltage, which is what you need for the signal,” Heller explains. “Now you have a really nice motor—an apparatus—by which you can control the motion of DNA, while not having to reduce the signal.”
But first, Two Pore Guys is focusing on proteins. “It turns out… pulling these things in two directions isn’t really necessary for detecting proteins and larger structures,” Heller says. “Two-pore control will be used for sequencing, but we’re not doing that right now.”
Today, Two Pore Guys is gearing up to offer a single-pore detection system that can read anything from small molecules to much larger complexes. “What we have now is a platform and a business model where we approach all the companies that already have these diagnostic assays, and say, ‘You can put it on our platform, and go to market at the point of care and not have to do any new R&D,’” Heller says.
The single nanopore platform can detect small molecule drugs, nucleic acids in specific sequences, viruses, bacteria, cell free DNA, genes, and specific mutations. In short, 2PG makes the detection system for a primer that a partner makes.
It’s a universal detection platform, Heller says. All the consumables are identical: a handheld, battery-operated device, dehydrated reagents on acrylic-looking strips that users insert into the device. In 2PG product videos, sample is collected with a swab, swished in liquid, and dripped onto the reagent strip. Output can be read on the device screen, or transmitted to a phone or computer.
Heller insists that Two Pore Guys doesn’t need to customize anything for its partners. “We make the same consumable no matter what.” And for that reason, he sees a wealth of applications spanning industries: safety testing in food processing plants or in the grocery, seed fingerprinting, tracking drug metabolism, bacteria detection, and myriad other agricultural, veterinary, and human health applications. The company is agnostic to assay and policy, he said.
Seeking Assays
Heller has a background in computer science; his first startup in 1990 worked with electronic mail. In 2010, he came to the University of California, Santa Cruz, to start a center for entrepreneurship. There he met Bill Dunbar, one of the earliest nanopore researchers whose name is on some of the Oxford Nanopore patents. Together they founded Two Pore Guys in 2011. Heller is president and CEO; Dunbar is Chief Technology Officer, Nanopores and Analytics. Two years later Trevor Morin joined as Chief Scientific Officer.
Until last year the company was funding itself, working in stealth mode, and had filed 23 patents. In 2016 Two Pore Guys announced a $7 million seed round. 2017 has been its coming out party including meetings at the J.P. Morgan Healthcare Conference. Now 2PG is actively seeking partners, Heller said.
Proof of Concept
Immediately before J.P. Morgan, the company announced a collaboration with oncologists at the University of California, San Francisco (UCSF), to evaluate the platform in the detection of cell-free, circulating tumor DNA (ctDNA) from blood and urine.
2PG compares its platform to a glucometer and says it’s easy enough to use to home. If successful, the company hopes the new device could be a revolutionary way to monitor patients for the recurrence of cancer from home on a daily basis.
“If successful” is, of course, the key caveat. The collaboration with UCSF should produce more data.
Andrew Ko, professor of Hematology/Oncology and a specialist in gastrointestinal cancer, will use the platform to concentrate ctDNA from the patient samples using existing extraction kits.
“It is a pilot study for patients with GI cancers, such as pancreatic and colorectal tumors, that harbor known KRAS mutations based on prior tumor tissue testing,” Ko told Diagnostics World in an email. “The idea is to determine whether we can use Two Pore Guys’ nanopore sensing device to detect these same KRAS mutations in these patients’ blood.” In this proof-of-concept study, 2PG will make the assay, though that isn’t the company’s planned business model.
Ko was very positive about the likelihood that the 2PG platform could be used by patients at home eventually. “While this initial effort is intended simply to generate some preliminary data regarding both the accuracy and feasibility of this technology, the ultimate goal is to apply it as a potential user-friendly, cost-effective (and even home-based) way of detecting cancer early, monitoring cancer recurrence/progression, and assessing patients’ response to ongoing treatment,” he wrote. “This is achievable but will require a successor study involving a larger, carefully designed, multicenter collaborative effort to confirm its clinical utility, so I’d say is still at least a couple of years away.”
Ko hopes to launch the study next month, and accrue patients within three to six months and data not long after.