Oxford Nanopore at JP Morgan: Native DNA Advantage

January 16, 2024

By Allison Proffitt 

January 16, 2024 | This was Oxford Nanopore Technology’s first live presentation at the JP Morgan Healthcare Conference and CEO Gordan Sanghera might be the only sequencing exec ever to bring a sequencer to pass around the audience. “I want it back, please,” he joked, of the MinION, which starts at $1,999 for the sequencer and kit. 

Sanghera gave last year’s presentation via zoom after Oxford Nanopore’s October 2021 listing on the London Stock Exchange, but, of course, Oxford Nanopore has been a sequencing force for more than a decade. In fact, Oxford Nanopore has had the most consistent leadership of the current players. The Oxford Nanopore executive team has been together for fifteen years, Sanghera said. The MinION was commercially launched in 2015.

Since the company’s founding by Sanghera and Spike Wilcocks in 2005 as a spinout from Oxford University, “We developed tens, hundreds, and thousands of electronic application-specific integrated circuits that underpin the foundation of this platform,” Sanghera said. “We have developed this technology from the bottom up, including the consumables and the flow cells and the kits.”

And since the listing on the London Stock Exchange, Sanghera said, Oxford Nanopore has delivered on promised growth of 30% year-over-year, and expects a greater than 65% margin in 2026. “I say that with confidence, because it’s not just economies of scale. There is manufacturing innovation, and we will build on that innovation to hit our target on margin,” said Sanghera. He predicts reaching a break-even point by the end of 2026. 

Oxford Nanopore’s aim, Sanghera said, is to deliver one single platform to meet all sequencing needs beyond single point mutations. He rattled off appropriate applications: epigenetics, liquid biopsies, circulating tumor and cell-free DNA, fragmentomics, RNA transcriptomics, proteomics and more. Later, during the Q&A, he reported traction in hard-to-diagnose diseases, multi-factorial genetic disorders, and rapid, real-time insights for newborns.

“I promise I’d only do one Lord of the Rings [reference],” he said, “One ring to rule them all. One platform to enable and analyze all these multi-omic, nuanced drivers of biology.” 

The Oxford Nanopore approach is to push DNA through a very small pore, recording base identity as the strand moves at a rate of 450 bases per second. Each pore is an individual, nanoscale sequencer. Converting the signal—current as a function of time—into DNA reads requires very high compute capabilities. Oxford Nanopore has partnered with NVIDIA for more than a decade to achieve that, he said. The company is also partnering with Apple to integrate the MinION with a next-gen iPad.

Better Accuracy, Better Biology

The key differentiator, Sanghera emphasized, is that the DNA is native. “That means we see everything. We do not make a PCR copy where we remove all of the high definition and color and produce a black and white single point mutational analysis tool,” he said. “No other sequencing platform provides that, which gives you unparalleled rich insights into the drivers of functional genomics and disease.”

Oxford Nanopore achieves more than 99% accuracy today in the field including Q40+ accuracy on telomere-to-telomere complete genomes (“on Nanopore only”). When that is polished—“to fix some homopolymer issues”—the platform has reached Q50+. “It’s been 20 years! I’ve been lying awake at 5:00 every morning to say, ‘This is the most comprehensive, end-to-end human genome.’” 

This level of completion and accuracy moves away from the single point mutation view of biology, Sanghera said. There are multiple drivers of biological function and application to disease understanding starting with small variants. We’re equivalent to sequencing-by-synthesis, yet we can do large, more complex variants: structural variation, copy number variation, and repeat expansions… That means we can uncover the dark genome.” 

Regions of the genome unmarked by short read sequencing coupled with large, complex variants represent the basis of over 35% of known diseases, Sanghera said. “That’s commercially low-hanging fruit for Oxford Nanopore.”

Sequencing Tools 

While Sanghera emphasized the single Oxford Nanopore platform, the sequencers themselves come in a range of sizes—from the handheld MinION with two flow cells to the GridION (96 flow cells) and PromethION kits in various sizes (up to 1,246 flow cells). On the lowest throughput end of the range, Sanghera included MinION and PromethION P2 as “personal sequencers”. These are often the customer’s introduction to the platform. Sanghera reported more than 7,000 customers and the average spend is about $6,000. At the high-throughput end of the range, the PromethION P24 and P48, platforms have about 90 customers with an average spend of $600,000. Oxford Nanopore in investing in its commercial team to reach and serve these high-throughput customers. 

Currently, the system can sequence one genome per flow cell, but we have a roadmap and there is a capacity for two to four genomes per flow cell, Sanghera said. “This gets us, for four comprehensive genomes, to $200 [per genome]… and we are very confident on that.” 

While all three leading sequencing platforms highlighted consumable growth in their presentations, Oxford Nanopore’s consumable percentage was by far the highest reported: 75% of revenue comes from consumables, Sanghera reported. “People are sequencing! They are pushing the boundaries of biology with our highly differentiated platform.”

The life sciences research tools market is $6.2 billion, Sanghera calculated. “But the opportunity to cross the chasm to applied clinical has not been met yet.”

He sees a change coming, though. “Pre-Covid, we were knocking doors open; now it’s becoming normal that some percentage of a population-scale program will require long reads,” Sanghera said. Long reads offer access to, “the dark genome,” methylation, structural variation, and more. “Eventually, somebody is going to wake up $200 gets everything, instead of them paying another $500 for a bisulfate methylation map and then $1,200 for some short-long read thing that Illumina provides. You’re going to get it all for $200. I think it’s time.”