PacBio: Year of Expansion, Whole-Genome Clinical Goals

By Allison Proffitt

January 15, 2021 | In his first J.P. Morgan Healthcare Conference presentation on behalf of Pacific Biosciences yesterday, Christian Henry, PacBio’s August-announced CEO, laid out a route to the clinic for PacBio’s HiFi sequencing reads, and set a 2021 goal of expansion across the business: improving commercial footprint, driving product development pipelines, and establishing market leadership in whole-genome clinical sequencing.

“Perhaps most importantly—we’re really trying to improve and drive our collaborations with key opinion leaders so we can bring whole genome sequencing into the clinic,” Henry said in yesterday’s presentation. “It’s very clear that whole genome sequencing using HiFi chemistry improves diagnostic yield, and we’re working hard to make sure that we can have those proof statements as we start to scale up.”

Invitae Partnership: Clinical Whole Genomes

Key to that effort is the PacBio-Invitae partnership that the two companies announced on Wednesday, the day between the two company presentations. The multi-year collaboration aims to develop a production-scale high-throughput clinical whole-genome sequencing platform leveraging HiFi chemistry. “This is perhaps one of the most exciting collaborations we’ve entered into as a company,” Henry said.

“We anticipate developing a sequencer with a scale that’s unprecedented for long reads and will enable us to deliver a medically-relevant genome at prices substantially lower than $1,000. We believe that will help open adoption in routine medical care, and we also think that will give Invitae the opportunity to dramatically scale their whole genome testing capabilities.”

The partnership launches immediately, Henry said, and he expects to develop the sequencer over the next few years with “substantial funding” from Invitae, and then to transition into a supply agreement. Hopefully, he said, Invitae will move many of their different assays onto the platform so they can offer whole genome sequencing capability at prices that are affordable.

Invitae shares the same vision as PacBio, Henry said: “Whole genome sequencing in clinical applications is the path forward. For PacBio, this could be our killer application. We’re uniquely positioned; our technology is uniquely capable.”

Henry emphasized messaging around the value of the genome, not just price. “What we’re bringing to the table is really a clinical-grade genome that others can’t provide. The value of that genome will be different, I believe, than others in the market… I’m confident that we can deliver a product at high value at a competitive value proposition.” Yet when asked if payers are ready to pay widely for whole-genome sequencing, Henry conceded that it still comes down to price.

Expanded Development Pipelines

The planned Invitae platform, however, is not PacBio’s single focus. “This is what’s so exciting!” Henry said. “We need to develop a multi-product portfolio so we can provide the right product to the right customer in multiple parts of the market. This Invitae program will leverage our core technology, of course, and I’m sure we’ll get benefits in both directions, but this is a completely separate product than other products we already had in development. There’s no plan at this point to slow any of that down.”

He outlined all the areas in which PacBio is working to accelerate development in service of whole genome sequencing workflows. “We need to improve our platform so we can create the scale required to create this notion of the Genome as a Platform—solving different disease conditions across different parts of one’s life,” Henry said, echoing terminology Sean George used in his Tuesday presentation for Invitae. “We believe the whole genome will be critical to healthcare much like medical imaging is today.

Thus PacBio is working to increase automation and reduce sample input in the library prep stage so that more sample types can be used. In the core sequencing technology, PacBio is seeking wide-scale improvements in sample loading, platform density, and faster polymerases, all while maintaining the “exquisite accuracy that is one of the key aspects of our technology that differentiates us from others.” Finally, Henry identified many opportunities to improve data analytics including improvements to raw base calling, simplifying the workflow, refining secondary analysis, reducing costs, and implementing reporting in the cloud.

“You’ll see us, over the next several years, work in all these different areas to hopefully enable this concept of Genome as a Platform,” he said.

Commercial Expansion: Doubled Footprint

But until then, Henry also said the company plans to pursue an aggressive commercial expansion, more than doubling the commercial footprint, adding commercial expertise to the executive team, and increasing the company’s digital presence.

Henry predicted the Sequel IIe to be the primary platform the company is shipping in the foreseeable future. The Sequel IIe started shipping in November 2020, offering on-instrument data processing while also being cloud enabled. The company boasts 90% storage reduction and 70-85% reduction in data analysis and a compute savings of $700 per genome. The platform opened doors to new customers, Henry said, who didn’t have the compute infrastructure or budgets for prior generations of PacBio sequencers.

The company has shipped “several” of the Sequel IIe platforms since launch and reported a combined install base of Sequel II and Sequel IIe at 203 platforms.

2020 did bring some nice deployments of the Sequel II system. Henry highlighted that LabCorp is using the Sequel II in its work to characterize SARS-CoV-2 and was recently awarded a CDC contract to provide genomic sequencing of samples of SARS-CoV-2, the virus that causes COVID-19, Henry reported. And the Wellcome Sanger Institute increased its Sequel II investment to support its Darwin Tree of Life project, sequencing all eukaryotes in Britain and Ireland.