NEW YORK – Mission Bio is looking to capture a larger portion of the single-cell analysis market with new copy number variation detection capabilities and a custom panel builder for its Tapestri platform.
The firm has been marketing its targeted DNA panels for single-nucleotide variant analysis so far. CNV detection is "actually something the platform has been capable of, it's embedded in the core technology," said Mission Bio CEO and Cofounder Charlie Silver. "We just enabled it with software at the backend and demonstrated applications that show how this can be used."
These new capabilities, officially released last month, may help boost another recent initiative, an online custom panel design tool called Tapestri Designer that was launched in March.
Already, early adopters have used this tool in anticipation of the CNV abilities. At VIB, a biotechnology research institute in Belgium, Toon Swings, a scientist who helps researchers incorporate new technology, including Tapestri, said he has worked on projects that designed custom panels to include amplicons likely to show CNV events.
"We already have the data available," he said. "We'll run the pipeline on that data to detect whether we can see both SNVs and CNVs."
Tapestri Designer "really has enabled the [custom panel] business overall," Silver said. "It has grown and continues to grow. The custom panel business is now as big as catalog panels." Silver declined to say which customers, or how many, were designing custom panels but the company has been offering them since early 2018.
Founded in 2012 by University of California, San Francisco bioengineering researcher Adam Abate, Silver, and others, Mission Bio moved into single-cell analysis with Tapestri in 2017. The South San Francisco-based firm has raised more than $40 million in funding, including a $30 million Series B round announced in December 2018.
Unlike some competitors, the firm has focused on single-cell DNA analysis, rather than gene expression. 10x Genomics also offers a CNV assay, but Swings said it cannot do both CNV and SNV analysis at the same time. 10x's solution "is genome-wide and random," Swings said. "The power of Mission Bio is, it's targeted and has high coverage." Detecting both types of changes to the genome is important, he said, because "in most cancers, both have clinical relevance for the disease."
Swings is the project lead for Tapestri at VIB, where he acts as a liaison between researchers and the company. He said VIB received Tapestri under an early-access collaboration and with an evaluation agreement, but that the institute provides the funding to run samples on it.
One scientist Swings has worked with is Marlies Vanden Bempt, a research coordinator at the VIB-KU Leuven Laboratory of Translational Genetics. Her project, called the VIB Grand Challenges Program Pointillism, is looking at tumor tissue from patients before and after therapy with immune checkpoint inhibitors.
"We started with only single-cell RNA sequencing, so it's super interesting to have the complementary approach of targeted DNA sequencing," she said. "We initially didn't plan to look at CNVs, but since it's possible, we expanded our project to go deeper into that."
"The hypothesis is that we'll see big changes, not only in mutations but also in copy numbers," she added.
She said breast and ovarian cancers are often driven by copy number changes, and Mission Bio's new CNV capability "creates a whole new opportunity to study copy numbers in breast cancer that we could not do before."
The VIB researchers have not yet run their data through the new CNV analysis pipeline. But Hannah Viernes, Mission Bio's senior director of marketing, said the firm has worked with researchers at the Francis Crick Institute in England, including Samra Turajlic, a visiting scientist from the Royal Marsden Hospital in London, to validate the technology using renal cell carcinoma samples. "We demonstrated it was able to recapitulate and call the same CNVs as in bulk samples," Viernes said. "We were also able to show different clonal subpopulations not detectable with bulk methods."
"Access to both SNVs and CNVs at the single-cell level, from the same cell, gives us higher resolution to explore tumor evolution and disease progression," Turajlic, who declined to be interviewed, said in a statement. “We look forward to analyzing these novel data types to help us better resolve the genetic and cellular heterogeneity in cancer."
Silver said the firm has also seen interest from researchers working on chimeric antigen receptor cell therapies. "Copy number variation can give you a really specific readout on viral integration, so now you have a very analytical measurement of how many copiers are integrated into products for cell therapies," he said. "As an assay, it's been a breakthrough for the space."
Swings suggested that the CNV capabilities might help stratify patients for clinical trials and reveal predictive markers for response to treatment. "You can sometimes predict treatment resistance by knowing one cell already has a CNV that confers resistance," he said. If done on a single-cell level, rather than bulk, this analysis might help doctors anticipate that a treatment would fail.
Because Tapestri panels are targeted, one must know beforehand where to look for CNVs. But paired with shallow sequencing of clinical samples, VIB has been able to design custom panels using Tapestri Designer, including a 29-gene melanoma panel and a head and neck cancer panel, to include areas that might show CNV events.
Custom panels are also helping Mission Bio break into the CRISPR genome editing market, where researchers are using its panels to validate their edits, Silver said.
Oncology will remain a focus for Mission Bio, he said, and the firm is "looking closely" at the use of Tapestri for monitoring minimal residual disease.
At VIB, researchers in other fields have taken notice now that the institute is keeping its instrument. "We're actually ending the evaluation phase," Swings said. "We've been using it for almost a year and generated data. Now some of our research groups are already proceeding with the next samples."
There has also been interest from researchers studying brain disease to use the platform, he added, as well as those studying other diseases where CNVs are prevalent. "The fact [CNV analysis] became available has piqued interest," he said.
Swings hasn't designed a panel for the brain researchers yet but is looking forward to using Tapestri in that area. "Stepping away from cancer will be very interesting," he said.