First, the sequencer market. Most of the companies here are absolutely focused on 'omics: Illumina, Element, Complete, Singular, Ultima Genomics, PacBio and ONT sell only 'omics products. Their nearly all just sequencing products - Illumina has its array business whose health confounds all of us sequencing snobs who thought it would disappear years ago and PacBio does sell some of their Circulomics DNA purificaiton products for use upstream of mapping workflows such as BioNano Genomics and Nabsys. But all genomics. Then there are two big science conglomerates playing here: ThermoFisher with Ion Torrent/Genenexus and Roche now entering with Axelios.
All of these companies sell library prep reagents as well. Illumina has a big business here, as I would call their single cell RNA, proteomics and spatial RNA products all library prep - each is read out on a sequencer. Plus they already have a suite of DNA and bulk RNA library preps. Roche has been in the library prep business for just short of two decades, acquiring Kapa back in 2015 and NimbleGen back in 2007. ThermoFisher might sell more library prep kits for Illumina than for Ion Torrent, though I doubt they break that out publicly.
And then there are all the other companies in the library prep space.
There's more conglomerates, such as Danaher (having acquired IDT), QIAGEN, Agilent, Tecan, Beckman Coulter, Revvity.
NEB isn't really a conglomerate - they build organically not by acquisition (yes, they acquired a lyophilization company once and perhaps some other small buys). A legend and an institution, nearly as old as myself.
10X Genomics isn't a sequencer maker, but a hardware-dependent library prep maker.
Twist is a major player in gene synthesis, but also in library prep reagents.
TaKaRa is the rare example of a Japanese company in this space - I won't dive into the geography of the players, but perhaps another time (though main conclusion: the space is heavily dominated by the US).
Promega is a minor player, but another grand old molecular biology reagents house.
Then there's upstart Watchmaker Genomics - I remember meeting them in 2020 when they were still embryonic and now they are a major player in library prep reagents.
seqWell is another up-and-comer, growing over a decade. Active Motif is another small but not single product company. Lexogen yet another.
And then there is a very long tail of companies that often have a single product.
As hinted above, there is a lot of merger-and-acquisition in this space. Trying to work out the entire tree of corporate deal making that built ThermoFisher could easily tie up a day - Olink is the most recent major buy of theirs in NGS land. Danaher bought IDT which itself bought a few companies or pieces. Tecan bought NuGEN. This is a contrast to the sequencer hardware space where acquisitions have been limited - PacBio's short read excursion had two acquisitions to get hardware technology plus the Circulomics bit; Element acquired Loop Genomics early in their history, Illumina's made a few choice buys (most notably Epicentre for Nextera library prep technology) - and of course got the sequencing tech by buying out Solexa. Illumina picked up both their single cell (Fluent) and protein (SomaLogic) schemes by acquisition. Roche's sequencer is based on two purchases. But nothing like the reagents market - I went to many a party at AGBT sponsored by reagent companies that have been devoured by other companies in this space.
If we switch from companies to application areas, there's some interesting patterns. There are some spaces which are very, very crowded - nearly everybody it seems has a double stranded DNA prep and bulk RNA-Seq methods are a dime-a-dozen (well, not the kits themselves!). If you're performing short read HiC, you're probably choosing between Arima Genomics, Dovetail Genomics or Phase Genomics - and both long read companies have a solution for their platform. Conversion chemistries for short read scanning of methylation - lots of those. But single stranded DNA prep - Claret is the one company that pops to mind. Short read scanning of RNA modification?
The not-quite-single product companies are organized around a technique or general area. seqWell's products are all based on tagmentation, Lexogen has many variations on RNA sequencing with short reads and Active Motif sells kits to probe chromatin structure every which way.
Now note how few of the names above presented at JP Morgan. Sure, the big conglomerates, 10X and Twist were all there. It's nearly impossible to see NEB accepting an invitation if given - but surely the seqWells or Active Motifs or Lexogens of the world would be thrilled to be invited. Ultima is super-focused just like Alithea Genomics - but only one of those two was speaking
Why such a different structure? If you want to build sequencer hardware, the pattern has been to pile up a lot of fresh IP (we have yet to see clones of out-of-patent early sequencers) and that costs a lot of money. Also to build up production facilities and buy expensive inventory of parts - more money. And development and testing isn't cheap - and the bar keeps going up. Nowadays nobody takes you seriously until you deliver multiple Genome In A Bottle datasets - used to be you could knock off a small phage genome and be taken seriously. Lots of informatics to develop too - at a minimum there is basecalling but usually so much more. And you don't just build - you must sustain all that plus sales, marketing and customer support. Numbers such as half a billion dollars are thrown around as the ante to launch a new sequencing platform; most likely it is worse.
Reagents still can come from relatively modest capitalization, particularly if you can leverage other building blocks that are out there. Want to design a new RNA-Seq scheme? Many companies have modular library schemes that can be treated as composable Lego bricks - either tell your customer to use them or many of those companies are happy to "white label" their reagents for inclusion in your kit. Many reagents don't require special informatics support, or if they do it's a very limited set of tools. Sure, you will probably have some sales and marketing staff and a small field applications scientist team that handles customer support, but it can be far more focused than one dealing with installing complex instruments plus the chemistry plus the informatics.
But of course that doesn't make it easy to break in. If you try to go head-to-head in one of the big markets, you'd better have a serious edge. I'm told that Watchmaker's key was have kits that delivered well on all the data performance metrics but were significantly faster - cutting workflows that often had to be split over two days into a reasonable single day. There's a lot of good kits for general WGS or bulk RNA, is yours really superior on some key metric (time? cost? quality?) while competitive on the others?
So lots of niche products - there's so many interesting XXX-Seq protocols coming out of academia that it isn't hard to polish up the methods and kit up the reagents - but how many users are there really for that method? Of course, lightning may strike and an area goes from obscure to ubiquitous, or you may really have a performance edge that people start caring about - Claret's single stranded DNA preps may be measurably more accurate for cell free DNA - but proving that and selling that point may still be hard.
It will keep kibitzers like me plenty busy. There's easily a dozen kit makers who exhibited at ASHG and/or AMP last year that I've omitted out of forgetfulness; perhaps by next fall's ASHG another dozen will have emerged from stealth or the back door of some academic building. And perhaps some other names will be swept up. Two single cell companies were slurped up last year: Scale Biosciences by 10X and Parse Biosciences by QIAGEN (and at remarkably different valuations, $30M vs. $225M respectively). There's even a serious market rumor that QIAGEN will be bought by one of the bigger conglomerates, fueled in part by the planned retirement of QIAGEN's CEO.
So a much more dynamic market of companies in the library prep space than with the hardware those libraries feed. Let's hope it stays that way - not only is it mildly entertaining, but advances in library prep kits just like in sequencer tech have been important in expanding the reach and scale of sequencing applications.
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