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Western University Spins Out New Phosphoproteomics Firm Precision Proteomics

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NEW YORK (GenomeWeb) – Western University researcher Shawn Li has launched a new biotech firm, Precision Proteomics, to commercialize phosphoproteomics technology developed in his lab.

The company recently completed a C$1 million (US$760,000) funding round led by Canadian life science investment firms Sino Western Bridge and Novatio Ventures. In addition to funding, these companies are providing Precision Proteomics with guidance and management, Peng Fu, Novatio's founder and CEO, told GenomeWeb this week.

Precision Proteomics' core technology is a set of affinity reagents that Fu said significantly improve phosphotyrosine enrichment, allowing for deeper phosphoproteomics studies. The company plans to use this technology as a tool for drug target discovery and drug and companion diagnostics development and aims to both build a pipeline of proprietary products and a pharma services business, he said.

As one of the key processes involved in cellular signaling, protein phosphorylation is a major point of interest for life science research, and phosphoproteomics is among the most active areas of research within proteomics. Protein kinases, which phosphorylate proteins, have become major targets of drug research, with a number of kinase inhibitors on the market and many others in clinical trials and development pipelines.

At the same time, within proteomics there is a growing appreciation of the need to not just quantify protein expression but to better understand the various modification states of the proteins being measured. Phosphoproteomics is at the forefront of this trend, with a number of researchers and some commercial firms looking at protein phosphorylation data to, for instance, unravel protein signaling pathways in diseases like cancer or actually help guide patient treatment decisions.

As with proteomics in general, there are two main ways of measuring the phosphoproteome — immunoassays and mass spectrometry. Among immunoassays, the reverse phase protein array, which uses antibodies to measure phosphoproteins of interest in cell lysate spotted in array format, is a popular tool that is used for phosphoproteomic analyses in studies including the National Cancer Institute's Cancer Genome Atlas project and the I-SPY trials.

The approach requires only small amounts of sample, making it well suited to clinical research looking at, for instance, patient tumor biopsies where only small amounts of material may be available. It is somewhat limited, however, in how many phosphoproteins it can analyze in a given sample. A typical experiment will measure in the low hundreds of analytes.

Mass spec, on the other hand, can look at thousands of phosphoproteins in a given experiment, but typically requires large sample sizes. Additionally, some form of enrichment is needed prior to analyses.

In the case of serine and threonine phosphorylation, researchers commonly use titanium dioxide or immobilized metal ion affinity chromatography (IMAC) to enrich phosphopeptides for mass spec. Phosphorylated tyrosine, meanwhile, is typically enriched using antibodies. However, Peng noted, this approach is relatively expensive and inefficient.

To get at this challenge, Li and his colleagues developed phosphotyrosine binding reagents based on the SH2 protein domain, which recognized tyrosine-phosphorylated proteins. While naturally occurring [email protected] domains have relative low affinity for phosphorylated tyrosines, the researchers found that by making alterations to the domain's binding pocket they could significantly boost its affinity.

In a paper published this month in Nature Chemical Biology, Li and colleagues at Western, the Chinese Academy of Sciences, and China's Qingdao University, used the new reagents for a phosphoproteomic analysis of nine human cell lines, identifying 19,570 tyrosine-phosphorylated peptides and 10,030 unique tyrosine-phosphorylation sites. This, the authors noted, compares to recent work in HeLa cell lines that identified only 1,475 such sites. Another study looking at roughly 200 lung cell lines using an antibody-based enrichment approach netted 4,551 tyrosine-phosphorylation sites, they wrote.

"We think the key advantage of this technology is the ability to do deeper profiling of the ability to profile the phosphotyrosine kinome at unprecedented resolution, which in turn provides real insights into the actual state of activation of key disease pathways" Peng said. He added that Precision Proteomics was now in discussions with various pharma companies about applying its technology to their drug development programs, though he said that it had not established any collaborations yet.

"We think the technology can better personalize drug development has applications in the discovery of new drug targets and development of companion diagnostics and also in validating and developing new therapies including targeted therapies and immunotherapies," he said, noting that the company plans to focus on oncology and autoimmune disease.

In addition to offering the approach as a service to pharma firms, Precision Proteomics also hopes to build an internal pipeline of drug candidates and diagnostics, Peng said. He said the company has identified several drug target leads that it plans to pursue and also has "proprietary companion diagnostics that [it] will be developing itself."

While Li is Precision Proteomics' founder and CEO, the company will in the initial stages rely heavily on Novatio and Sino Western Bridge for management personnel.

"We are an early-stage life sciences investor, and we have a very hands-on approach," Peng said. "We provide early capital in combination with the skill set of our team." Novatio currently has three of its partners helping with management of Precision Proteomics, he said, adding that "as we advance the various development programs and partnership discussion we will be looking to build out the rest of the Precision team."

The company is currently working out of Li's lab at Western, "but we will be looking to acquire our own lab space as we build out the company," Peng said. "That will in part be dependent on the state of our discussions with pharma companies and also what we ultimately decide in terms of how we want to carry forward the proprietary programs that we have planned."

One thing the company does not plan to do is market the reagents as a tool for outside researchers.

"That is not really where we think the value of this technology lies," Peng said. "I think there is much more value in utilizing this in drug development [and] development of companion diagnostics. Our thinking is we are going to tackle those higher value applications."