Singular Earnings Call Notes

Singular release their Q3 earnings call a couple of weeks ago. I thought it might be interesting to review the new information presented here in light of what we already know from the S-1.

Recap

To briefly review, Singular are working on an approach the looks very similar to that originally executed by Solexa and currently used on the Illumina Miseq/NextSeq 550.

As in Illumina style sequencing, they perform on surface amplification of a single template to generate clusters, and then sequencing-by-synthesis to read out the sequence. The S-1 doesn’t state exactly how they are generating clusters. A quick patent search doesn’t yield anything either. Illumina use a bridge amplification approach, the initially developed by Manteia. I’ve discussed that IP elsewhere, and it appears to have expired. So my guess would be that they’re using this expired IP for cluster amplification.

The S1 also states that “We in-licensed certain patents and other intellectual property rights from The Trustees of Columbia University” so it’s likely that they’re using Jingyue Ju’s nucleotides.

Earnings Call Summary

The earnings call reveals a few further details about the G4 instrument and its stage of development. Briefly the G4 feels to me like four NextSeq 550 class instruments crammed into a single box. I say four, because the G4 is capable of imagine four flow cells independently. In spite of their assertions, I can’t see a clear cycle time advantage/throughput advantage over Illumina. But it does seem comparable, and I would expect the G4 to be able to find its niche.

The calls suggests they they are just starting to place instruments at user sites. But also, that they are planning to launch in coming weeks. That statement is a little vague, but if they’re just starting early access I imagine it may take some time to iron out the bugs before a full commercial launch.

In the section below, I’ve pulled out a few specific statements from the call for those interested.

Earnings Call Statements

The first statement of interest in the earnings call was a note on the instrument throughput:

“At the high end, we designed a single G4 instrument running four flow cells in parallel to be capable of sequencing four human genomes in less than 16 hours. This capability surpasses any other commercially available benchtop sequencer with target data output up to 600 gigabases per day”

This would place the throughput of the G4 significantly above the NextSeq 2000. But it does this my using four flow cells in parallel. In some ways it feels like they’ve crammed four NextSeq 550/Miseq style instruments in a single box.

The use of four, four lane, flow cells (rather than two as on the NovaSeq) may be an advantage for certain applications. For example, letting you cut down on multiplexing for certain applications.

“run times ranging from five to 16 hours for typical NGS applications based on cycle times that are two to three times faster than systems on the market today”

This seems similar to some Illumina kits, which have a 17 hour run time for 2x150bp reads. So, it’s not clear to me that Singular have a cycle speed advantage.

“At Harvard's Beth Israel Deaconess Medical Center, an academic core lab, the G4 integrated solution was used for spatial transcriptomics research. They achieved an average of 136 million reads per flow cell with an accuracy of 99.6 to 99.7%.”

This seems a lot less than the 600Gb/day they suggest above.

“In line with our plan, we are now executing our early access program with collaborators across our target markets, representing research centers and commercial companies. G4 instruments are placed at third-party sites in their labs and run by their technical staff as would occur in the field for commercial use.”

This statement clears up the ambiguous comments in the S-1 which stated that they “have completed our beta pilot program”. It seems like this was likely running user samples in house at Singular, and that they are now starting to place instruments at customer sites.

“Leveraging the success of our application lab, beta pilots, and early access program, we are prepared to launch in coming weeks. At launch, we will be accepting orders from thought-leading organizations who are positioned to demonstrate the capabilities of our solution and educate peers through data publications. We will soon announce pricing and specs for the instrument and our initial consumables, publish a technical report, and provide data sets to prospective customers for their thorough evaluation.”

Look forward to it!

Disclaimer: As always, you should be aware that I have equity in sequencing companies (based on prior employment) and am current working on a novel sequencing approach.