NEW YORK – The protein sequencing space has a new entrant, as startup Glyphic Biotechnologies joins the raft of recently launched firms looking to tackle the proteomics and protein analysis market.
A spinout from the lab of Massachusetts Institute of Technology professor Ed Boyden, Glyphic recently closed a $6 million seed round led by OMX Ventures with participation from Mammoth Biosciences CEO Trevor Martin.
The company also plans within a year to close a Series A funding round, said Joshua Yang, its cofounder and CEO. He said it was targeting around $30 million to $35 million.
Glyphic is one of several companies formed in recent years with the goal of developing protein sequencing technologies to augment and compete with the mass spectrometry and affinity agent-based approaches that currently dominate proteomics. Emerging firms including Quantum-Si, Encodia, and Erisyon are all pursuing sequencing-based approaches, as are some more established companies like Oxford Nanopore.
Yang said the company's technology originated with work pursued by Daniel Estandian, Glyphic's cofounder and chief technology officer, while a graduate student in Boyden's lab.
"Five years ago, he and [Boyden] brainstormed all the possible ways you could conceivably use to sequence a protein," he said. They then worked through the different methods they came up with, eliminating them as their flaws became apparent. At the end of the process, they were left with the approach that forms the core of Glyphic's protein sequencing technique.
The company's approach combines highly specific probes to individual amino acids with Edman degradation, allowing it to sequence proteins by removing them and identifying them one by one. The method is most similar to that of University of Texas spinout Erisyon, which likewise uses Edman degradation in combination with amino acid-specific probes to sequence proteins.
Erisyon, however, uses probes only to a small set of amino acids, the idea being that by collecting partial sequence information, the company can identify proteins by matching them to a sequence database, much like in a traditional mass spec-based proteomics experiment.
Glyphic, on the other hand, is aiming to develop highly specific, high-affinity probes to all 20 amino acids, Yang said, though he noted that the company was still in the process of developing its portfolio of probes. He said that the main purpose of the recently raised seed funding was to support the completion of the full set of probes.
The company has also developed an approach to degrading and reading the individual amino acids that Yang said it believes will help it develop the highly specific probes its technology depends on.
One way to read protein sequences using Edman degradation is to apply the amino acid probes, observe their binding, cleave the bound amino acid at the end of the protein, and then repeat the process until you have worked your way through the length of the protein. The problem with such an approach, though, is that the binding of a given probe can be affected by the amino acids adjacent to the amino acid being probed, Yang said. He cited the example of a probe Glyphic has developed to tryptophan, noting that its activity varies significantly depending on which amino acid is next to the tryptophan being probed.
To address this challenge, the company has devised an approach wherein they perform the Edman degradation step prior to probing, first tethering the leading N-terminal amino acid to a solid support, then separating it from the larger protein, then probing this isolated amino acid so that the probe's activity can't be impacted by adjacent amino acids.
Yang said that Glyphic aims within a year's time to begin accepting samples from customers and collaborators both to validate the technology and to generate service revenue. He added that the company also hopes within that timeframe to begin manufacturing a system it could make commercially available.
"We have a lot of things moving in parallel right now," he said. "Finishing development of the binders, getting the instrumentation build-out plan done so that we can start not only providing the service but also actually start selling sequencers and consumables."
He said he anticipated that top biopharma firms would be among the first customers for the technology.
"These are companies that are willing to adopt new technologies quite rapidly and are willing to work with multiple technologies in the same space," he said.
While targeted applications will likely come first, Yang said the company envisions the instrument as capable of making single-molecule protein measurements at proteome scale.
"You start off at the low end of the development process, of course," he said. "But it is easily feasible to reach the billions of reads" that would be needed for proteomic analyses.
He added that the system would be compatible with existing and future sample prep tools that researchers might want to use to either enrich or deplete their samples.
Yang said Glyphic aimed to sell the instruments at a price point where individual labs would be able to purchase their own system as opposed to having to rely on a core facility.
The market for new proteomics technologies has been hot of late — in recent months both Quantum-Si and Nautilus went public via special purpose acquisition companies, or SPACs, at sizable valuations ($1.5 billion for the former and $900 million for the latter), though both outfits' stock prices have been largely flat since they listed.
While Glyphic has not taken the SPAC route, it has benefited from the general enthusiasm around proteomics, Yang said.
"We were able to raise money from very well-known investors in the space because I think they believe in the approach, but also because there was this large amount of capital available in the industry," he said.