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Mission Bio Seeks to Increase Drug Trial Collaborations, Improve Gene and Cell Therapy Efficacy


NEW YORK – Fresh off a $70 million Series C funding round, startup Mission Bio aims to further establish a name for itself in the biopharma space by mobilizing its Tapestri single-cell analysis platform for clinical cancer drug trials.

The South San Francisco-based firm will also use the funding to bolster efforts to develop customized quality control assays using its platform for biotech companies wishing to measure the efficacy of their cell and gene therapies.

Mission Bio's Tapestri platform is based on proprietary droplet microfluidic technology for single-cell sequencing, dubbed PCR-activated cell sorting (PACS). The firm has licensed the technology from the University of California, San Francisco.

Charlie Silver, CEO and cofounder of Mission Bio, explained that the technology sorts and analyzes single cells from large populations of cells based on their genotype, as well as simultaneously phenotype the cells using protein expression.

The Tapestri instrument uses hydrogel microspheres that trap DNA molecules but are permeable to enzymes and other small molecules. It captures cells in the microgel by combining a cell suspension stream with an agarose stream to form a droplet. Since the droplet is permeable to enzymes, the patient's DNA can be purified and fragmented in the droplet.

A microfluidic device is then used to merge the microgels with a droplet containing PCR reagents and a droplet containing a barcode. Lysates are sorted into different containers based on unique transcriptional signatures detected by fluorescence markers, which users can apply for downstream analysis.

Silver highlighted that Tapestri can process and prepare up to 10,000 cells in a single run.

Mission Bio launched Tapestri in late 2017, with an acute myeloid leukemia (AML) panel that runs on an Illumina MiSeq instrument. The firm updated the platform in 2018 so that customers can use it on Illumina's HiSeq instrument, and also launched a single-cell myeloid panel and a single-cell tumor hotspot panel for single nucleotide variants (SNVs) and indel hotspot mutations.

On the solid tumor side, Silver noted that Mission Bio has seen increasing interest from customers aiming to understand general tumor heterogeneity. Instead of being used for monitoring a cancer patient's progression (as is the case for hematological cancers) however, he said that users have applied the Tapestri instrument to create a "snapshot of the tumor in time."

Mission Bio also last year launched its Tapestri Designer cloud-based tool, which applies artificial intelligence and machine learning to help customers design and order single-cell DNA panels.

Pharma trials

A large piece of Mission Bio's current market, Silver noted, is supporting biopharma partners researching potential cancer therapies and conducting clinical trials.

Silver believes that single-cell DNA is a crucial analyte for clinical trials because it acts as a site of precision drug and chemical pathway interactions. He explained that pharma partners commonly use Tapestri in clinical trials to determine if a patient is a potential candidate.

"Typically, the technology is used to assess early biomarkers or signals of drug resistance by looking at how mutations play together at the single-cell level, and understanding whether the disease is evolving against the treatment, [or] developing new mutations or clones that expand in a different direction than when the patient was initially treated," Silver explained.

For example, Mission Bio is working with the Laboratory Corporation of America's Covance drug development business to offer single-cell DNA analysis services to biopharma customers on the Tapestri platform.

In an email, Marcia Eisenberg, CSO of LabCorp, highlighted that the Tapestri platform provides advantages over other technologies because it can detect lower frequency clones and help determine whether variants are linked or co-occurring in the same cell. She pointed out that Tapestri has potential applications for early identification of resistance mutations and detecting minimal residual disease in hematological malignancies.

"So far, we've had very good results using the Tapestri platform in early phase trials to evaluate response and resistance to AML," Eisenberg said. "The sensitivity provided by the assay may therefore be important for use as a surrogate endpoint for these studies."

Importantly, Eisenberg believes that Tapestri can help provide important clinical information when considering changes in therapy or the use of therapeutic combinations.

Mission Bio also inked a collaboration with Onconova Therapeutics last fall to use Tapestri for targeted single-cell DNA analysis.

Catherine Smith, an assistant professor in the department of medicine at the University of California, San Francisco, has been using the Tapestri system to study clonal selection and changes that occur with cancer treatment, specifically FLT3 inhibitors such as gliterinib (Astellas' Xospata).

Using Tapestri, Smith's team has found that significant intra-tumoral heterogeneity and selection for multiple resistant clones can occur, such as certain mutations that activate RAS signaling in the same cells as FLT3 errors, in AML patients.

"The primary advantage [of Tapestri] is in understanding the degree of cellular heterogeneity and how this changes under selective pressures of therapy," Smith noted. "We look forward to being able to use single cell multi-omics [in leukemia] to integrate single-cell information on the DNA, RNA, and protein levels in order to allow true genotype-phenotype correlation."

Silver declined to comment on how many pharma collaborators Mission Bio currently has or their identities, but said that Tapestri is baked into more than 20 commercial and academic trials for drug development.

With the proceeds from its recent Series C funding round, Mission Bio has now raised a total of $120 million to develop the Tapestri platform for cancer and gene editing applications, including multiple research grants from the US government and private funding rounds.

Cell and gene therapy

In addition to working with pharmaceutical firms on drug development, Mission Bio plans to help biotech firms developing cell and gene therapies. Since joining the National Institutes of Standards and Technology's Genome Editing Consortium in 2018, Mission Bio has been developing customized panels using Tapestri to help engineered cell and gene therapy clients validate their editing methods.

Silver said that current assays like PCR or bulk sequencing leverage workflows that require several weeks to grow clones while examining one edit at a time. In addition, neither method can determine the true heterogeneity of transduction or editing efficiency.

"This is critical for regulatory submissions as a quantitative quality control measurement to accelerate development and manufacturing of therapeutic candidates," Silver said.  

In contrast, Silver argued that Tapestri "is the only tool" capable of measuring novel delivered sequences (including ones delivered by viral vectors), edits to the genome, and immune phenotypes from the same cell. Tapestri measures the frequency of cells with each possible combination of edit, whether examining on-target or unintended off-target events.

"This is a powerful tool throughout discovery and development … for [quality control] and defining the composition of a cell therapy product and tracking those cells throughout the course of a trial while simultaneously tracking tumor genomic profile and evolution," Silver said in an email.

He believes Tapestri can potentially reduce the turnaround time to a single week because it can assess several edits and clones at once. Results are also quantitative enough for quality control and regulatory submissions.

"Turnaround time is crucial because when you're in the early stages of development, it matters how fast you can quickly integrate and optimize the assays," Silver explained. "And in later stages, that time to characterize [the results] is crucial for understanding what the product is able to do for the patient [in cell and gene therapies]."

Starting with blood cancers and genetic diseases, and eventually solid tumors, Mission Bio sees customer interest for its platform especially around CAR T-cell therapies in acute myeloid leukemia. The firm believes users can leverage Tapestri's multi-omics capabilities to identify novel cell surface biomarkers while integrating genotype information to distinguish cancer cells from non-cancer cells.

"A lot of our focus is not [on] building out a single assay, but solidifying the capabilities surrounding the therapies, so that every gene and cell therapy could use our technology as a good plug-and-play solution to characterize their products," he added.