Strap yourself in because the multi-billion-dollar market for genomic sequencing is about to go through a major shakeup. While competitive pressure in the lower-throughput segment of the sequencing business has been building for some time from the likes of Thermo Fisher, PacBio and Oxford Nanopore (and potential new entrants: Singular, Element and others), Illumina’s prized, high-throughput NovaSeq franchise has so far gone untouched…until now. Though it would be foolish to discount Illumina’s entrenched dominance in this segment of the market, a recent patent infringement win by BGI (BGI lost a key patent contest a few months earlier but should be able to enter most markets by YE 2023) and Ultima Genomic’s de-stealthing mark the first time that the crown jewel of the genomic sequencing market is coming under competitive threat.
How did we get here? The human genome project was completed in 2003. It was a project of daunting proportions that took an army of researchers starting in the first Bush administration over a billion dollars and more than twelve years to finish. Today, thanks to advances in next-generation sequencing technologies (NGS), a single individual can sequence a human genome in 24 hours at under $1,000. The implications of this have been profound and we need to look no further than the global Covid pandemic to understand how this has impacted our daily lives. Our ability to sequence the viral genome (and those of the variants) in record time and use highly flexible RNA technology to accelerate vaccine development and manufacturing are nothing short of a triumph of humanity…feats that were barely possible ten years ago.
Nothing epitomizes the HealthTech revolution more than the advent of clinical genomics. Solexa and Illumina enabled this revolution through improving accuracy and decreasing costs, but the pace of marginal price declines has slowed as of late. In 2014 Illumina started offering the $1,000 whole genome and today we estimate that the marginal price for whole genome sequencing (WGS) is in the range of $600…a significant decline no doubt, but still only 40% in ~8 years. The news of Ultima’s de-stealthing ushers in the era of the $100 genome…Now…with a novel platform that enables further price reductions.
Where are we going? Bringing a $100 genome to market was accomplished by not accepting that status quo and rethinking how to sequence at scale. By combining large, open substrates with novel chemistry, ultra-fast optics and machine learning at scale, Ultima has built a platform that breaks the $100 barrier…with more to come. To be sure Illumina is not standing still, and its self-declared Chemistry X program also holds the promise to drive significant improvements in read lengths, cycle times and cost.
All of this promises to be highly impactful for the two real winners here: First and foremost, researchers. Academics and clinical investigators will now have access to very high throughput platforms of the highest quality, allowing them to do five times more on fixed budgets, thereby unleashing their scientific creativity. It will unlock the potential of single cell analyses to drive our understanding of the origins of disease. It will dramatically expand population wide genome studies that will help us to better understand rare diseases. And it will drive orthogonal approaches such as multi-omics – to combine genomic analysis with that of proteins (proteomics), the metabolome (metabolomics) and other downstream cellular activities to allow us to screen for diseases very early on when they are curable. Doing so will put behind us many of the traditional, now obsolete tradeoffs confronted by the industry: accuracy or cost, speed or resolution, sensitivity or specificity ultimately allowing us to get ahead of disease.
The second major group of winners are patients, our loved ones, who will ultimately benefit from laboratory translations that will improve how we screen for, diagnose, and monitor disease. In the process, it will drive significant progress in personalized medicine and preventive care models. By “stacking the deck” with discrete patient populations harboring genetic and epigenetic signatures that synch with matched drugs, clinical investigators will be better able to tailor protocols from the get-go. Regulators will like this and physician guideline committees will likely be strong advocates of matching tailored drug therapies to discrete patient populations.