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Avida Biomed Developing Hybridization-Based Methylation Sequencing Panels for Cancer Dx

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This story has been updated to clarify the description of analytical validation data presented on the virtual ASCO poster.

NEW YORK – Avida Biomed, a startup founded by genomics industry veterans with clinical experience, is developing a methylation sequencing-based, targeted panel for use in diagnosing cancer.

"We want to use next-generation sequencing for liquid biopsy from cell-free DNA," Grace Zhao, Avida cofounder and head of clinical research, said. "This tech we're developing is based on highly efficient DNA hybridization capture and enrichment before amplification."

Zhao suggested that methylation sequencing with bisulfite conversion was the ideal application for its hybridization technology. Avida has a new, unconventional probe design, Zhao said, which will enable enriching for genes of interest prior to the conversion, giving the firm a key advantage, she said.  The workflow takes only one hour prior to amplification and can enable a sample-to-result time of two to three days. The panels are highly focused, between 2 kb and 1 mb.

Avida presented its Point-n-Seq targeted methylation sequencing assay in a poster at the recent virtual American Society of Clinical Oncology meeting. In a small study of samples with methylated DNA spiked in, the method was able to detect changes in methylation levels down to .003 percent. In another test of analytical validity, using unique molecular identifiers, sequencing a 24kb capture panel recovered 90 percent of molecules with raw read depth of 20,000 reads. And in a pilot study of colorectal cancer patients, Point-n-Seq achieved sensitivity of 100 percent for stage II through IV tumors, with specificity of 91 percent.

Avida is betting its tech can address longstanding problems with this kind of analysis, namely the miniscule amounts of cell-free DNA from tumor cells available in plasma. "You're looking for trace amounts to begin with, trying to separate even smaller amounts from that," said Matteo Pellegrini, a computational biologist at the University of California, Los Angeles and an expert on methylation sequencing. Getting good signal-to-noise ratio is important for methylation sequencing. "Each of these steps is lossy, so it depends, critically, on how efficient you are," he said.

"It's hard to say based on this how much competitive edge they have over other companies," Pellegrini said, noting that determining the utility of these assays prior to testing them widely is difficult. But "it looks like a pretty standard approach to optimizing all these steps," he said.

Pellegrini is a cofounder of Prosper, a direct-to-consumer epigenetic testing company, but the firm does not offer methylation profiling from blood for cancer diagnosis.

Avida joins several companies looking to use methylation profiling to diagnose disease, especially cancers. Grail, an Illumina spinoff, has raised more than $1.9 billion to develop and commercialize methylation-focused liquid biopsy tests. Freenome's test and Guardant's LUNAR assay also include methylation analysis.

Methylation analysis has often been achieved by chemically treating DNA with sodium bisulfite to mutate cytosine to thymine and spotting the changes with next-generation sequencing. Some recent methods use enzymes, which are less likely to degrade the genomic material. Single-molecule sequencing methods, including those from Pacific Biosciences and Oxford Nanopore Technologies, can directly detect methylation without the conversion step.

Founded in 2018, Avida has six employees and has yet to complete a Series A financing round. The team has drawn on its experience at firms including AccuraGen, which Zhao cofounded, and the erstwhile NimbleGen to design new hybridization probes. "It's something more dynamic and creates a very stable 3D structure," Zhao said. "Because we have highly efficient hybridization we can do it super-fast, very specifically, and enable small focused panels."

But Avida declined to disclose more detail on its hybridization tech because it had not yet secured patent protection for the design, Zhao said. The firm has also developed a new bisulfite conversion process, Zhao said.

Avida sees an opportunity to fill a gap between small qPCR panels that look at a handful of genes and larger sequencing-based panels. "For clinical use, the payors don't want to pay for big panels that don't have clinical implications," she said, when smaller 100- to 200-gene panels could be sufficient. "Our technology is filling the gap," she said.

Pellegrini suggested that, in general, these kinds of tests could be used for minimal residual disease testing as well as screening, which he said was more difficult to do.

Avida wants to distribute its technology and is considering making kits to enable uptake at contract research organizations, pharma companies, and clinical labs. It is seeking partnerships or codevelopment agreements for clinical products. "That's our roadmap, we are ready for collaborations," Zhao said.

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