Securities.io is not an investment adviser, and this does not constitute investment advice, financial advice, or trading advice. Securities.io does not recommend that any security should be bought, sold, or held by you. Conduct your own due diligence and consult a financial adviser before making any investment decisions.
The Genomic And Multi-omic Revolution
The first human genome decoding started in 1990 and was first achieved in 2003. It also cost a staggering $3B.
Fast forward 20 years and genome sequencing costs have fallen to $600/genome. Or a 5,000,000x reduction in cost! And it could fall to as little as $200.
This completely changed the way we approach genomics from a medical perspective. It allows for a massive amount of data to be created and analyzed and for each person to potentially have access to advanced personalized medicine matching his unique genetic makeup.
With genomics becoming a basic medical amenity, genome sequencing companies will benefit from a quickly growing market and many applications, from nutrition and aging prevention to early cancer detection.
And this is not all. The same technology that was used to do the sequencing of the genome's DNA can also be used to create whole new scientific fields:
- Metagenomics: sequencing the genome of the bacteria that live in our guts and greatly impacts our health.
- Transcriptomes & Epigenetics: if the genome is the blueprint, the transcriptomes are how the blueprint is used in practice and in real-time. This will likely be very relevant for solving many uncurable diseases and metabolic problems.
- Agrigenomics: using genomics to improve agricultural yields and farm animal productivity.
- Ecological studies: accurately evaluating an ecosystem's health and genetic diversity.
- Synthetic Biology: The creation of new genes, traits, or entire organisms with a specific purpose: for example, plastic-eating bacteria or biofuel-producing algae.
5 Best Genome Sequencing Companies / Stocks
Illumina is the leading genomics company, by far the largest and most established in the industry, with $1.2B in revenues, which grew 11% CAGR in the last 5 years.
Like most genome sequencing companies, Illumina makes money when selling the sequencers, but mostly when selling the consumables used by the sequencers, with revenue per machine usually growing over time as it gets progressively used to full-time capacity.
The company's new genome sequencer model, NovaSeqX, is a hit, with 109 shipments in Q2 2023 and 390 shipments expected for 2023. This has accelerated the adoption of mass genome sequencing among Illumina's clients with more multi-omics analyses (mixing multiple “-omics” techniques) and larger scale for single cell and spatial analyses.
When discussing Illumina, a long explanation is required for a new genomics application, cancer detection in a blood sample called liquid biopsy. Illumina worked on this technology and then spun it off into a company called Grail.
Grail is very successful from a technical and commercial standpoint, with 7,500 providers prescribing Grail's tests and passing the 100,000 tests performed milestone in Q2 2023. It also detected 92% of cancer relapse across 6 different blood cancers.
Several years later, Illumina would reacquire this company at a much higher price.
This caused several problems. First, regulatory authorities in both the USA and the EU raised concerns about monopoly risk, with Illumina the supplier of genome sequencing machines to many of Grail's competitors.
This resulted in a €432M fine from the EU. If this ruling forbidding the acquisition is not solved, “Illumina will divest Grail within a year if it does not win challenge in EU court.”
Another set of problems came from the conditions of the costly Grail spin-off, money raising, and re-absorption into Illumina.
Activist invest Carl Icahn has attacked the company’s board and implied that potential dishonest or malicious dealings were done in favor of insiders against the interests of the company's shareholders. The SEC is also investigating the question.
So far, the CEO has been changed, another board member has departed, 4 new board members have been instated, and Illumina has published a “Stewardship-Focused Update.” You can also read more about these suspicions and accusations in this series of articles by Non-GAAP investing.
The company stock has fallen steeply from its highs of July 2021 by almost 80%, back to its 2013 levels.
This is a rather shocking situation for a large and established company like Illumina, no matter how true these accusations are or not, as it reflects poorly on its management decision to divest Grail in the first place. At the very least, this has proven to be a costly mistake.
Investors will want to assess if they are ready to tag along with Carl Icahn, a legendary and controversial activist investor with an impressive track record. And if the poor governance of the last few years is now fully priced, and maybe has damaged the company's valuation excessively.
10x Genomics is a leader in spatial biology, which studies the genome and transcriptome in 3D, allowing visualization of the activity of genes at the cellular or even intracellular level.
The company was founded in 2012, with Serge Saxonov among its founders, the director of R&D of the personalized genome testing company 23andMe.
10x Genomic grew using a mix of R&D ($1B+ investing in R&D so far) and acquisitions. Notably, its Visium platform was obtained through the acquisition of Spatial Transcriptomics in 2018.
This is also how 10x Genomics would acquire its Xenium platform by acquiring Readcoor and Cartana in 2020.
In 2020, it would also launch the Chromium platform, updated the year after to Chromium X.
Through the acquisition of Tetramer Shop in 2021, 10x Genomics would also launch BEAM (Barcode Enabled Antigen Mapping) in 2022. It allows researchers to identify components of the immune system in detail. This could be very impactful in research on immunity and new diseases.
Revenues grew by 17% year-to-year in Q2 2023, driven by Xenium sales, with the 100-unit sold milestone passed in August 2023.
The company also earned in September 2023 a critical victory against its main rival, Nanostring. Nanostring is for now banned from selling its CosMx Spatial Molecular Imager (SMI) instruments in most of the EU for infringing on 10x Genomic patents.
The company is still at an early stage, somewhat similar to the early days of Illumina. For now, spatial biology is confined to the world of academic and fundamental research. But like many biotechnologies, it might one day become widespread, slowly become a medical tool, and then into a “routine” test. In any case, the growing pool of installed machines should drive sales of consumables and revenue growth.
Oxford Nanopore is using a unique genome sequencing technology relying on flow cells. This allows DNA to be “read” when crossing the nanopores, not through chemical means but directly by measuring an electric current. So, in a way, this is the first time a computer can read a genetic sequence (DNA & RNA) in real-time.
Another unique advantage of the company's technology is that it can read longer genetic sequences than conventional sequencing methods. Long sequences and real-time reading can help to get better and quicker results, which is important for cancer analysis or infectious diseases like antibiotic-resistant bacteria.
Lastly, the electrical measurement allows for smaller and more portable sequencers, an improvement to the massive machines used until now. This allows the company to produce a wide array of sequencers, including slower, smaller, and much cheaper machines, starting at $1,000. This could radically expand the sequencing market, with mobile or low-cost sequencing not an option previously.
Oxford Nanopore's revenues grew by 46% CAGR in the last 4 years, thanks to 7,300 customers in Q2 2023, of which 640 were acquired in the last 12 months.
Because of its radically new technology, it is unclear where Oxford will fit in a more mature genome sequencing ecosystem.
It could fully replace the incumbent technology of chemical/optical reading of genomes.
Or it could become a successful but niche application for low-volume or mobile sequencing or for sequencing requiring a high-accuracy reading of long genetic sequences.
The company also plans to expand into a reading of proteins, post-translational modification of proteins or small molecules, and other measurements at the very edge of life sciences.
Started a few years after Illumina, PacBio has been the smaller player in genome sequencing since. Despite its smaller size, the company's equipment has stayed on the top level of performance.
PacBio recently acquired Omniome in 2021, giving it an advantage in accuracy for reading very long or short genetic sequences. This advantage was reinforced with the later acquisition of Apton for $110M in August 2023, which also specialized in short read, high throughput (SR-HI).
PacBio's Onso systems are now starting to ship to customers, and its launch has been described by the company as the “best start in PacBio history”. It will specialize in short sequences, while its Revio HiFi System will be able to read long sequences and work 24/7, making it read 1,300 full human genomes per year (roughly 4/day). Later, the Revio HiFi will be replaced by the HT SBB system, which will likely integrate Apton technology.
Pacbio expects long sequences to grow much quicker than the broader NGS market and claims its systems are 10x more accurate than the competition.
Interestingly, it could also bring down the total cost of genome sequencing. Short sequences need to be reassembled in a comprehensive whole without getting too technical. So a $500 short read genome can quickly need extra analyses costing an extra $1000 to be actually useful as a diagnostic tool.
So a $950 Revio long sequence analysis, being more accurate, avoids this step and comes out cheaper for diagnostic application.
PacBio's focus on high-precision/long-sequence analysis should give it an edge in diagnostics for the next few years. PacBio management believes this could boost the company's market penetration in human genomics from 5% to 10% and in oncology (cancer) from 1% to 5%.
While PacBio is mostly focused on its decades-old competition with Illumina, it might also have to contend with Oxford Nanopore in the diagnostic/long-sequence market.
With a history of being the smaller competitor to Illumina, PacBio is a little bit the underdog of the field and not a new “exciting” startup. This does not mean it is not competitive, and if it succeeds in capturing the niche market it is currently specializing in, it might positively surprise the market by differentiating itself from its historical rival.
NanoString was launched in 2003 to leverage the digital molecular barcoding technology invented at the Seattle Institute for Systems Biology.
By 2008, it had launched its first product, nCounter, which was a great progress in transcriptomics (the study of mRNA). nCounter carried the company forward while it developed the next steps. In 2019, it launched the GeoMx, followed by the CosMx and the digital platform AtoMX.
GeoMx is designed to study RNA expression in whole tissues and can also analyze 150+ proteins, more targets than 10x's Xenium. CosMx Single Molecular Imager (SMI) instead can look at a single cell and what happens inside for RNA and up to 64 protein targets, and possibly up to 120 in 2024.
NanoString was instrumental in the explosion of scientific publications using spatial biology. No less than 7,117 publications mention NanoString machines from various fields like research on cancer, infectious disease (including COVID-19), immunology, agriculture, or neurology.
NanoString is engaged in a bitter legal battle with 10x Genomics. The recent court order by the EU patent regulator would affect 10% of NanoString should the company not win its appeal. So, while not a death blow, this is still bad news for a young company with negative cash flows.
Markets are clearly concerned about the long-term viability of NanoString, with the stock below $2/share, down from a high of $79 in 2021, and its IPO price of $9.1/share in 2013.
Investors will want to assess the company’s plans to reach profitability in 2025 and determine if the price decline is excessive and represents an opportunity, considering that the company has reduced its cash burn by 50% in Q3 2023.