NEW YORK – With a pair of recent high-profile publications validating one of its main proteomic assays, multi-omics firm Complete Omics is now looking to raise new funding and expand its product menu.
The Baltimore -based company provided the MANA-SRM mass spectrometry assay used in a pair of studies published this week — one in Science and the other in Science Immunology — in which teams led by researchers at Johns Hopkins University used bispecific antibodies to target cancer neoantigens present at low levels on the surface of cancer cells in vitro and in mouse models.
The studies suggest that such antibodies could be useful for treating cancers driven by mutations in proteins like TP53 and RAS that researchers and drugmakers have not previously been able to target successfully. The antibodies target mutant versions of these proteins presented on the surface of cancer cells. To target these mutants effectively, researchers must understand what mutated versions are being presented on these cells, which is where the MANA-SRM assay comes into play.
The rise of next-generation sequencing has allowed researchers to identify a large number of cancer-linked mutations, but actually detecting these mutation-associated neo-antigens, or MANAs, at the peptide level remains difficult. The fact that a mutant is present at the genetic level does not mean it will be produced at the protein level, and, even if it is, that is no guarantee that it will be processed and presented by HLA molecules.
To address this problem, Complete Omics uses MANA-SRM to detect evidence of these MANAs directly in target samples via mass spec. Qing Wang, founder and CEO of Complete Omics, developed the approach while a graduate student in the lab of Johns Hopkins researcher Bert Vogelstein, who was one of the leaders of the Science and Science Immunology studies. Wang is an author on both studies, as well.
The MANA-SRM method uses extensive fractionation to divide samples into smaller, less complex subsamples that can be analyzed at greater depth. It uses labeled peptide standards to target MANA peptides to monitor which fractions these peptides elute into. Researchers can then analyze those fractions using SRM mass spec assays to the target peptides.
Wang said that the two papers released this week provide a benchmark for demonstrating the method's sensitivity. In the studies, they were able to detect MANAs expressed at levels below ten peptides per cell.
Wang said that Complete Omics is now developing a new version of the approach that will be able to detect the presence of MANAs of interest directly from small amounts of patient tumor tissue.
In addition to its MANA-SRM work, the company is also developing a targeted mass spec assay that Wang said will measure levels of 4,550 protein markers in plasma. He said it plans to launch the panel by the end of the year, noting that this is currently the main focus of the Complete Omics assay development efforts.
If the company is, in fact, able to bring the product to market, it would mark a significant expansion over existing mass spec-based plasma protein assays, which typically measure somewhere in the range of 500 to 1,000 proteins. Affinity agent-based approaches from Somalogic and Olink are able to measure roughly 7,000 and 1,500 proteins, respectively, though in the case of Somalogic there are questions as to how specific its protein measures are. In a study published this summer in Nature Communications, proteomics start-up Seer used a version of its Proteograph system to identify roughly 2,000 proteins in an analysis of 141 plasma samples.
Wang declined to provide technical details of how the Complete Omics assay will detect these 4,550 proteins, though he noted it involved significant amounts of sample fractionation, which sets it apart from most recent plasma proteomics efforts where throughput has become a major priority. He said that running the complete assay would take around 10 hours per sample, though he said that he expects that for most samples the company would run a more targeted subset of the panel determined by what clinical questions they were trying to answer.
"We know that we are not going to do every sample [with the full assay] because it is not reasonable to profile the full set of proteins for every individual," he said. "We will work on shrinking the method into different categories of disease. If somebody, for instance, has a high risk of heart disease, we might select 20 or 30 markers [relevant to that condition]."
Complete Omics also offers genomic and metabolomic assays, and Wang said the company's ultimate goal is to combine these different approaches into diagnostic workflows. He noted, though, that the company's vision of multi-omics is somewhat different from commonly described efforts that work to integrate, for instance, genomic, proteomic, and metabolomic data from a sample. Instead, he said, he and his colleagues are pursuing a more linear approach where, for instance, a proteomic test flagging a person as being at risk of a particular cancer could be followed up by a sequencing-based liquid biopsy looking for mutations associated with that cancer, which could then be followed by a MANA-SRM style assay to help inform treatment of the disease.
Such clinical applications are still in the future, though. Wang said that in addition to finishing development of the refined MANA-SRM method and the plasma protein panel, Complete Omics is looking to set up a CLIA facility this year.
The company is also looking to raise around $30 million in new funding this year, Wang said. The company closed a $3.3 million angel round in 2019.