The advantages of single-cell analysis, especially for oncology research, are clear to scientists and clinicians, as examination of individual cells results in new insights into genetic mutations and interactions. Although a number of lab tool companies have developed techniques for single-cell analysis of RNA, on the other hand, Mission Bio is addressing single-cell DNA analysis. Last year, the company launched its first products, the Tapestri system and fixed panels for acute myeloid leukemia (AML), a type of cancer of the white blood cells. The Tapestri platform uses a droplet-based microfluidic platform and barcoding prior to downstream library preparation and sequencing to detect rare cells within a tumor that may harbor mutations implicated in disease.
As Mission Bio CEO Charlies Silver told IBO, “Other single-cell players work largely in RNA, rather than DNA (as we do). DNA is more stable than RNA, and more clinically relevant, therefore allowing it to provide actionable insights and better guide targeted treatments.” In addition, clinical settings are more experienced with DNA analyses than RNA analyses. “Other companies in the space are solely on the research and discovery side of single-cell, for this reason—DNA, while it is a more stable analyte, is harder to access, so you don’t see others playing on the clinical side yet,” he explained. “But given DNA’s role in the clinic for targeted therapies, and matching most of the genetic testing that is done today with targeted DNA sequencing panels, Mission Bio and Tapestri are in a strong position for the translational and clinical markets, rather than R&D alone.”
The diagnosis and monitoring of AML was the first application for the platform suggested by thought leaders, according to Mr. Silver. “Our partners guided us toward AML as it’s a disease that unfortunately has a very high mortality rate, and a staggering 50% of leukemia patients relapse. This relapse is often a result of those cell populations that evolve in response to therapies and thus evade treatment,” he explained. “Leukemia is a disease that has been very well studied, so we know the landscape of genomic mutations that drive the disease, and moving forward it is essential to understand how these mutations work together across the cell population to drive either response or resistance to therapy. As drug companies continue to introduce new treatments to market, this insight is invaluable to creating better, more dynamic and effective therapies.”
“That’s where our technology comes in for really routine use; once a patient has been diagnosed with a disease, how do you monitor what’s going on in that patient to identify the rare cells that are not responding to therapy?”
The Tapestri platform’s single cell-level sensitivity provides new insight into disease biology and the outcome of treatment. “Looking at rare variants is an important signature of disease, but once you have disease what is important is understanding the biology of the cells themselves. It’s how those mutations work together in single cells,” said Mr. Silver. Examining mutations on a cell-by-cell basis is especially valuable in drug development and clinical research. “That’s where our technology comes in for really routine use; once a patient has been diagnosed with a disease, how do you monitor what’s going on in that patient to identify the rare cells that are not responding to therapy?”
In contrast, current approaches that rely on bulk sequencing cannot provide a similar level of sensitivity, said Mr. Silver. “That’s where the cells become very important, and that’s where sequencing, digital PCR, and those conventional technologies—which is averaging across mutations and mixing up all the cells—fall short. We provide a solution that gives you excellent sensitivity for understanding which cells have those mutations, and then based on that, which ones are causing the disease to progress or relapse.” The cost is also competitive, according to him. “It’s been important for us to make sure the cost structure works for these customers so they can run at-scale at the front-end development level, but also the production level once they are ready for market. We recently announced Tapestri compatibility with Illumina NovaSeq and HiSeq sequencers, which reduces sequencing costs from roughly $1,000 down to $200 per run, so researchers can do even more with their budgets.”
The company eventually hopes to commercialize a laboratory-developed test (LDT) or IVD for such applications. “It’s something we’ve been thinking about, absolutely,” commented Mr. Silver. “Many of our customers are cancer centers running these clinical research studies, so they often ask us when this will be available to them in a clinical setting, either as an LDT or eventually as an IVD. So it’s definitely on our minds as a next step.”
This month, Mission Bio announced $30 million in new Series B funding. Investors include Agilent Technology, Cota Capital and LabCorp. The money will be used to broaden the company’s global reach as well as invest in solutions for new applications.
“…as you add multiple edits onto a cell, it naturally becomes a single-cell problem—when you average those edits across the whole population, like bulk sequencing or PCR tends to do, you wash out the information of which edits are hitting which cells.”
And while the company is focusing on the blood cancer market, having recently launched a panel for chronic lymphocytic leukemia, the technology continues to find applications in other markets. One of the most promising is quality control of CRISPR gene editing. “Our activity in that space is supporting the therapeutic gene editing companies, including CAR-T players. The problem for them, especially with the next generation of CAR-Ts, is they are making multiple edits onto cells to improve the specificity of a drug. Very often they’ll knock out some activity and knock in some other activity which makes these drugs more effective,” he told IBO. “There is a whole class of these CAR-Ts in gene-edited therapeutics coming to market over the next few years. For all of these players, as you add multiple edits onto a cell, it naturally becomes a single-cell problem—when you average those edits across the whole population, like bulk sequencing or PCR tends to do, you wash out the information of which edits are hitting which cells.”
The company’s activities in this field include membership in the National Institute of Standard and Technologies Genome Editing Consortium, which aims to establish a common lexicon, standard data format, reporting requirements, assays for qualifying results and reference materials for gene editing techniques such as CRISPR. Other members include drug developers and CRISPR tool companies, The Consortium’s work will be instrumental in informing FDA thinking about CRISPR therapeutics. “We joined the consortium with the only single-cell DNA analysis platform enabling unparalleled insight into the precise changes happening within and across each cell,” noted Mr. Silver. “But we also work with others within the consortium to understand what’s needed and how we can support their efforts. It’s a benefit to our partners and the industry more generally to have real precision technology to validate what they’re doing.”
In total, MissionBio has raised more than $50 million in total and is growing the publication count for its Tapestri platform, including a recent paper detailing the first single-cell atlas of AML. The company expects more publications and the new funding to further demand for its technology.