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ClearNote Health Expands Into Immunotherapy Monitoring


NEW YORK – After launching its pancreatic cancer test last year, ClearNote Health is further expanding applications for its epigenomic platform into therapy monitoring and other cancers. 

The firm's Virtuoso Epigenomics Platform combines genomic and epigenomic information and quantitatively measures the 5-hydroxymethylcytosine (5hmC) biomarker through a proprietary enrichment process that is used in early cancer detection. ClearNote CEO Dave Mullarkey noted that the technology has "multiple applications," and while its focus has been and continues to be on early cancer detection, it has garnered increasing interest from biopharmaceutical companies who want to use the data generated from its platform to better understand therapy effectiveness and mechanisms of resistance and monitor patient response to therapies. 

A study published last month in the Journal for ImmunoTherapy of Cancer applied the firm's technology to prediction and monitoring of immunotherapy response for non-small cell lung cancer (NSCLC) patients. The company's platform was used to generate cell-free DNA 5hmC profiles from 151 plasma samples gathered from 31 NSCLC patients who received Merck's Keytruda (pembrolizumab) or Bristol Myers Squibb's Opdivo (nivolumab) as monotherapy. The samples were gathered before therapy started and at multiple time points while on therapy. 

The researchers found that in patients who responded to therapy, "5hmC accumulated over genes involved in immune activation such as interferon-γ and interferon-α response, inflammatory response and tumor necrosis factor (TNF)-α signaling." In non-responders, 5hmC increased over epithelial to mesenchymal transition genes, they noted. Genes associated with treatment response and resistance can be captured by 5hmC profiling of cfDNA, and 5hmC profiling of pretreatment plasma samples "was able to distinguish responders from non-responders using T cell-inflamed gene expression profile, which was previously identified by tissue RNA analysis," they wrote.

Mullarkey noted that the particular genes and pathways associated with non-response could lead to new opportunities for drug discovery and development. 

San Diego-based ClearNote has other partnerships in the works to focus on this new application of its technology, such as a collaboration with Bayer announced in December to evaluate the underlying biological mechanisms for patient response and resistance to treatments for metastatic hormone-sensitive prostate cancer. ClearNote's platform will be used to monitor patient response to prostate cancer therapies. 

The company also recently announced a partnership with Personalis to offer its technology as a research service to Personalis' pharmaceutical customers. 

Mullarkey added that the firm's assay technology and workflow doesn't change, whether it's being used to detect cancer or to monitor therapy response, but he noted that for diagnosis the company feeds the 5hmC signals it detects into its own algorithm, while for pharmaceutical applications the company provides the "raw signals" and allows pharmaceutical companies to do their own custom analysis. 

The technology may also be used for companion diagnostics in the future, Mullarkey said.

He added that the firm intends to continue to pursue pharmaceutical opportunities because it is "an area of increased demand and a significant source of revenue," but that ClearNote's primary commercial focus is on diagnostic tests for detecting cancer early. 

To that end, the firm's technology is being used in the Pancreatic Cancer Early Detection Consortium, which aims to improve early detection for patients with a heritable risk for pancreatic cancer or with pancreatic cysts. The company's Avantect Pancreatic Cancer Test is being used as a surveillance tool combined with imaging and will help the company expand its test's indications for high-risk groups, Mullarkey said. The first clinical data readout for the consortium is expected in 2025. 

The test is available commercially through a physician experience program, and the company has received "hundreds of prescriptions" for the test to date in pancreatic cancer high-risk patient populations, such as those with genetic predisposition, family history of pancreatic cancer, new onset diabetes, or pancreatic cysts.

ClearNote's Avantect assay is currently offered as a laboratory-developed test, but the assay has received breakthrough device designation from the US Food and Drug Administration, and the firm intends to move forward with a future submission for regulatory approval, Mullarkey said. 

In addition, the assay has received final pricing from the US Centers for Medicare and Medicaid Services of $1,160 per test, which went into effect in January, and has generated interest from investors and commercial partners, he added.

The current focus for the Avantect test is generating further data for guideline inclusion and insurance coverage, Mullarkey noted. 

While the pancreatic cancer test is currently available, ClearNote is also working to commercialize its ovarian cancer test. Mullarkey said the test is expected to be available in the second quarter of 2024 and that the company has completed its initial independent analytical validation for the test. ClearNote intends to commercialize the test with an undisclosed partner that is already established in the Ob/Gyn field, and is also exploring broader commercialization partnerships, Mullarkey said. 

A multi-cancer test is also in the pipeline, but the company has decided to focus on single cancers for the time being, he added.