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Pacific Biosciences Makes Progress on Sequencer Development, Amends Invitae Deal


NEW YORK – Pacific Biosciences said on Wednesday that it has made progress on the development of two sequencing platforms and announced that it is amending payment terms for its collaboration with Invitae on a high-throughput whole-genome sequencer.

The Invitae collaboration is one of three R&D projects PacBio officials mentioned on a call with investors following the release of the firm's first quarter financial results. The company is also developing a short-read sequencing platform based on technology acquired with Omniome and a next-generation long-read sequencer.

The WGS platform for Invitae "is going very well," PacBio CEO Christian Henry said, but macroeconomic factors, including Invitae's plans to limit its cash burn, have led the partners to renegotiate the financial terms of their deal. Invitae will no longer make payments during the R&D phase of the collaboration and, in return, will pay an increased price on the instrument and consumables later on.

"The other aspects of the collaboration will continue," Henry said. "For example, we expect Invitae will continue to leverage their internal resources to assist in the development of scaled workflows, bioinformatics pipelines, and other aspects of the project." The amended agreement "does not reflect either company's enthusiasm for the collaboration, the development timelines, performance to date, or other product specifications," he added.

PacBio plans to drop more info on its short-read sequencer at the Advances in Genome Biology and Technology meeting next month, Henry said, noting that it is "on track for commercial shipment in the first half of next year." The mid-throughput platform will offer Q40 accuracy, or a one error in 10,000 base calls, for 90 percent of reads, he added.

"We're also achieving our internal milestones towards the development of our next-gen long-read sequencers," he said.

PacBio will enter AGBT riding a wave of success with HiFi sequencing, a protocol that harnesses circular reads to boost accuracy. The firm's Sequel IIe version of its instrument creates HiFi reads on board, and a new update provides methylation calls on CpG motifs for all reads.

The Sequel IIe instrument has fans at the Broad Institute's Genome Platform, which ordered 18 of the instruments in Q1, bringing its PacBio fleet to 23 sequencers. In an email, PacBio suggested that the instruments would be used to sequence 10,000 whole genomes for the National Institutes of Health's All of Us research project. "That is one of the projects we are involved in but we are expecting to apply long reads to many other projects as well," David Cameron, director of communications at the Broad, said in an email.

Henry called the Broad a "lighthouse account" and a validation of the HiFi technology. "They see lots of opportunity in numbers of samples and projects … and they will help push us as much as anyone else," he said.

Regarding consumables pull-through for PacBio's instruments, Henry said the Broad will boost pull-through, though this will be dampened by the institute's volume pricing deal.

Henry also mentioned that plant, pest, and microbial sequencing workflows developed as part of a collaboration with Corteva Agriscience, announced last month, will be made available to the research community "sometime in 2023."

AGBT may also bring more clarity on Illumina's plans to eat into the long-read sequencing market with its "Infinity" method for stitching together short reads, likely acquired from Australian startup Longas Technologies. Illumina claims it can provide contiguous data for DNA regions 10 kb in length with 90 percent less input material. Henry took time on the call to tout the advantages of using native DNA in long-read sequencing, saying it was less prone to biases associated with amplification and preserved information lost through that process.

"We have seen time and time again, over the past decade, numerous attempts at synthetic long-read approaches, which were all eventually abandoned. We believe native long reads will continue to provide the most accurate, contiguous, and complete genomic and epigenomic information with ever increasing applications," he said.

"I think at the end of the day, our growth is likely to be unhindered by Infinity," Henry added.

Henry also framed PacBio's short-read play — another sure-to-be-hot topic at AGBT — as a way to "change the narrative" on pricing.

"In terms of cost per G[b], it will be competitive with the emerging players and the existing players," he said, but the company would prefer to "talk about the price [needed] for an answer. … What really matters is, 'How many G[b]s do you need to get that answer?' And that's really where I think we're going to shine more than the other emerging players."

Henry noted that the firm would not provide more specific information on its next-generation long-read sequencer, neither on its specs nor its timeline. "We want to make sure that we maximize our opportunity with the Sequel IIe platform while we have it," he said. He suggested that HiFi sequencing would continue to be a feature of whatever comes next.

"Our mantra is, we have to increase the throughput very significantly," he said. "The development programs are going very well, and we continue to hit our internal milestones."