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Kinomica Developing Phosphoproteomic Test to Guide AML Therapy


NEW YORK – UK-based proteomics start-up Kinomica aims to use mass spectrometry-based phosphoproteomics to inform drug development and patient treatment with a focus on oncology.

The company, which was spun out of Queen Mary University of London's Barts Cancer Institute, is currently focused on developing a test for identifying acute myeloid leukemia patients likely to respond to the drug midostaurin.

Kinomica was launched in 2016 to commercialize technology developed by Barts researcher Pedro Cutillas but only began operations in the summer of 2019, said Jane Theaker, the company's CEO. It has raised £1 million ($1.3 million) in funding, including an investment of an undisclosed amount by UK-based life science incubator BioCity that was announced in August 2019 and a £471,690 Innovate UK award that began in June.

The company uses mass spectrometry to analyze protein phosphorylation patterns to better understand kinase signaling involved in various biological and disease processes, most notably cancer.

Due to the importance of protein phosphorylation in cell signaling, phosphoproteomics is a large and active area of research within proteomics with a number of research groups and private companies using mass spec and other technologies for phosphoproteomic analysis. Much of this work is focused on cancer and cancer drug research, with kinase inhibitors targeting aberrant protein phosphorylation emerging as a major area of cancer drug development over the last two decades.

Researchers like Oregon Health & Science University's Gordon Mills and George Mason University's Emanuel Petricoin have made extensive use of antibody-based approaches to measure protein phosphorylation in tumor samples and, in some cases, helping to guide treatment.

The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium has also made extensive use of phosphoproteomic analyses. Last year, CPTAC researchers used proteogenomics and phosphoproteomics to investigate mechanisms of drug resistance and identify potential drug targets in triple-negative breast cancer.

Theaker said that Kinomica is distinguished by its bioinformatics platform, which is based on software developed by Cutillas and his Barts colleagues.

"The patents that we have associated with the bioinformatics workflow and the databases that we have that we can use to interrogate and predict kinase activity, that is sort of the secret sauce of the company," she said. "It's not on the sort of wet chemistry, LC-MS/MS side of things."

Kinomica currently uses a Thermo Fisher Scientific Q Exactive Plus for its work but is looking into using other platforms including potentially instruments from Sciex and Bruker.

The company is primarily targeting large pharma firms, pitching its technology as a tool for supporting drug development efforts with much of the current demand coming from companies interested in learning more about the mode of action of their drugs, said David Britton, Kinomica's chief scientific officer.

"Kinase inhibitors are one target, but the technology is applicable really anywhere you are trying to figure out what is going on in terms of cell signaling," Theaker said, noting that some of the company's customers have asked them to apply the platform to analysis of immunotherapies like CAR T-cell treatment.

Ultimately, Kinomica aims to develop clinical tests on the platform that could be used for predicting patient response to particular drugs. The Innovate UK grant was awarded to fund the company's lead project in this area, development of a test to identify patients likely to respond to the AML drug midostaurin (marketed by Novartis as Rydapt), a multi-target kinase inhibitor.

The drug is intended for patients with a mutation in the FLT3 gene, a cohort that comprises around 30 percent of the AML patient population. Only around half of patients with the FLT3 mutation show benefit from midostaurin, however. Meanwhile, research by Cutillas and his colleagues indicates that around half of patients without the mutation received benefit from the drug, suggesting that FLT3 is not a particularly effective marker of response.

"What we've discovered in our preclinical work is that by using our [phosphoproteomic] approach we can predict far better which patients are going to respond," Theaker said. "So that is kind of our flagship, proof-of-concept project that we are taking forward."

The company has partnered with organizations in the US, UK, and Canada for retrospective patient samples it is using for the work and is also working with Barts and other organizations including Novartis to collect prospective samples, with the goal of obtaining around 300 prospective samples over the next year or two, Britton said.

How such a test might be brought to the clinic will depend in part on the number of markers involved.

"It could well be pared down to a few biomarkers that you might be able to detect through an immunoassay of some sort that could be rolled out globally," Theaker said. "But there will be certain assays that will require more than just a handful of biomarkers, in which case you could do it through centers of excellence where you have centralized laboratories providing this sort of service on mass spectrometers."

She declined to give a timeline for when the company hoped to bring the AML assay to market, noting that making a prediction would be difficult given the many challenges involved in developing such a test.

While phosphoproteomics is commonly used in drug development and cancer research and has shown some promise in guiding cancer treatment, actual clinical assays have to date been few and far between. One of the more notable firms in the space was Theranostics Health, which was spun out of Petricoin's lab at GMU in 2006 and offered reverse-phase protein array-based phosphoproteomic analyses intended to guide therapy in HER2-positive breast cancer patients.

The company never found a large market for the test and was acquired by Avant Diagnostics in 2016.

Avant delisted its stock in May 2019 and is currently in the process of restructuring.