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PrecisionLife Pivots to In Silico Target Validation, COVID-19 Drug Repurposing

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CHICAGO – In November, British bioinformatics firm RowAnalytics rebranded as PrecisionLife, taking the name of its technology platform, in part because it has modified its business model.

As RowAnalytics, the firm intended to sell its software tools to pharmaceutical companies for rare-disease drug discovery. By 2018, leadership had realized that the company was capable of forming true partnerships with drug companies for a broader set of conditions.

"We've changed to doing a large number of early discovery projects in a range of different disease areas, basically taking novel targets that address unmet medical needs even in quite prevalent diseases," said Cofounder and CEO Steve Gardner. "We're now getting targets that we can validate in silico."

Founded in 2013 and based in Long Hanborough, UK, near Oxford, PrecisionLife makes an artificial intelligence-driven bioinformatics platform to support the practice of precision medicine. The company runs its US commercial and technical operations out of an office in Cambridge, Massachusetts.

The platform works through triage processes to make sure that investigators have the necessary supporting evidence. Then data goes through patient-derived cellular assays for biological validation, according to Gardner.

"At that point, we're looking to form either direct licensing partnerships or collaboratives and investment-based deals," Gardner said. Notably, PrecisionLife announced shortly after the corporate name change that it had entered into a drug discovery partnership for amyotrophic lateral sclerosis with British biotech startup PharmEnable, assisted by researchers from the Sheffield Institute for Translational Neuroscience and the Maurice Wohl Clinical Neuroscience Institute at King's College London.

He said the company expects to disclose additional deals in the next couple of months.

Since 2017, PrecisionLife has partnered with Harvard University's Martinos Center for Biomedical Imaging and with Envision Genomics on Giro Health, a precision health initiative that seeks to improve diagnosis and personalize treatments for complex neurological and neurodegenerative diseases, including ALS and Alzheimer's disease.

The still-active Giro Health program has identified some compounds that have shown to be active in patient-derived cellular assays for ALS, according to Gardner, though nothing has been published in a peer-reviewed study. Gardner said that Giro Health's work has since broadened to include other conditions, including Parkinson's disease, asthma, rheumatoid and psoriatic arthritis, and septicemia.

This month, PrecisionLife joined countless other bioinformatics vendors in making its platform free for COVID-19 researchers around the world. This company is going a step further than some others, putting its analytics team into COVID-19 projects as well, particularly those looking at host response to the SARS-CoV-2 virus.

A study released this week — after Gardner spoke to GenomeWeb — suggested that host factors have more bearing than genetic differences on disease outcomes among COVID-19 patients.

PrecisionLife can help in this regard because of its skill with what Gardner called "high-resolution patient stratification." He defined this as a deep understanding of the detail of genomic and nongenomic features that enable the technology to categorize patient cohorts.

"What's different between them? What drives that difference of response?" Gardner said. Some features will be genomic, others epidemiological or environmental, including comorbidities and smoking status.

"We want to [understand] the predictive signals that we can identify that will be able to stratify those patient populations and assign a level of risk and ideally an optimum response for each of them," Gardner said. "If their genomic drivers are different, then likely, we should be able to target different pathways."

Using the PrecisionLife multiomics analysis platform and data from the UK Biobank, in-house researchers have already identified genetic risk factors for sepsis, allowing them to name 59 candidates for drug repurposing that might help increase the survival rate of late-stage COVID-19 patients. They released their findings this month on preprint server MedRxiv.

The researchers noted that sepsis has been observed in about 59 percent of those hospitalized for COVID-19, citing a March paper from The Lancet. Sepsis has a mortality rate of about 20 percent.

"Applying a series of heuristics that we have developed we can rapidly identify candidates that may be therapeutically beneficial for select subsets of the patient population and to identify and efficiently prioritize those with the greatest repurposing potential for further investigation," the article said.

Previous genome-wide association studies have "failed to identify more than a handful of genetic variants" that point to sepsis risk, according to the preprint. 

The PrecisionLife researchers identified mutations in 70 genes associated with sepsis risk, some of them novel, that they said could "reasonably be considered to be potentially relevant" because about 61 percent of these mutations also were present in severe COVID-19 patients, according to the preprint.

"Of the 70 sepsis risk genes we identified, 13 of them are targeted by active chemical compounds," found in the Canadian DrugBank and European ChEMBL reference databases. "Seven of those genes are targeted by licensed drugs and could therefore represent potential drug repurposing opportunities," the researchers wrote.

They identified a total of 59 current drugs that could be repurposed to test with the 13 targets.

The patients PrecisionLife has analyzed from UK Biobank's COVID-19 population all wound up in high-acuity hospital wards, and some had to be intubated.

"We've started to identify signal that's associated with those patients, and that's leading us to understand the particular risk factors for the most severe forms of disease, those that are leading to that sort of high-dependency, late-stage disease and ultimately, unfortunately, death," Gardner said.

Gardner said that some outside companies and organizations have reached out since PrecisionLife offered access to its platform. He did not disclose any names.

He said that health systems are interested in uncovering not only the biomarkers for risk, but also identifying drugs already in their formularies that could be prescribed for COVID-19 symptoms. Researchers and pharma companies are looking to get to first-in-human trials as quickly as possible with existing compounds that could help segments of the COVID-19 patient population.

"It's not exactly repurposing, but more how do we use the existing formulary?" Gardner said.

During a video chat with GenomeWeb, Gardner had a poster-sized "hairball" graph on the wall behind him, with thousands of SNPs depicted as dots representing various patient subgroups for schizophrenia.

"If you can stratify at that level of resolution, you can start to understand the risk factors for that particular patient subgroup and what we can do about it," Gardner said. "We can map all of the known chemistry that's active against those targets onto those communities and make some great suggestions about what might be suitable as a repurposing opportunity."

This is the same strategy PrecisionLife is following for COVID-19. However, one challenge with a novel disease is that there aren't yet large genomic datasets that might be available for other conditions, even rare disorders.

In addition to the UK Biobank records, PrecisionLife is trying to get new data by working with Health Data Research UK, a London-based institute for health data science. The company also has a source for data on patients in Denmark, according to Gardner.

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