On November 12, 2019 NantHealth, Inc. (NASDAQ: NH), a next-generation, evidence-based, personalized healthcare company, reported FDA authorization of Omics Core℠, the first whole exome tumor-normal in vitro diagnostic (IVD) that measures overall tumor mutational burden (TMB) in cancer tissue (Press release, NantHealth, NOV 12, 2019, View Source [SID1234553286]).

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The Omics Core assay is the nation’s first FDA authorized custom-targeted whole exome sequencing platform to report both overall tumor mutation burden in tumor specimens from 19,396 protein-coding genes (whole exome) and somatic alterations (point mutations, small insertions and deletions) in 468 cancer-relevant genes.

TMB is reported via two metrics:

Total number of somatic non-synonymous exonic variants within the 19,396 genes (whole exome) surveyed.
An estimate of mutation rate by counting all somatic, synonymous and non-synonymous variants detected in gene coding regions and dividing by the approximate size of the whole exome.
"Tumor mutation burden (TMB) is now recognized as a key biomarker across multiple tumor types. Studies have shown that immunotherapy treated patients with high TMB had better outcomes compared to those with low TMB. Since the potential for TMB as a precision medicine tool is so high, it is imperative that the most accurate and comprehensive method of analysis be applied to enable physicians to determine which tumors could benefit from checkpoint inhibitors and immunotherapy," said Patrick Soon-Shiong, MD, Chairman & CEO NantHealth. "I am so proud of the scientific, regulatory and bioinformatics teams who have spent almost a decade to perfect this important test that measures the absolute number of mutations occurring in 19,396 protein-coding genes (whole exome) targeting 39 million base pairs (39 Mb) of the human genome from both a tumor and patient-matched normal control sample (tumor-normal). We believe that this comprehensive diagnostic will provide greater accuracy than the widely-used formulaic extrapolation of TMB from a limited gene panel sequence ," said Soon-Shiong.

"Omics Core is the first whole exome test for TMB authorized by the FDA, and as such, marks a watershed moment in oncology. Clinicians can now directly measure the mutations in a patient’s tumor specimen accurately via tumor-normal sequencing and have confidence that the results they receive are fully validated to help support better therapeutic decisions. Also, the breadth of a whole exome means that many more neoepitopes and novel targets may be identified to support vaccine development, novel drug development, and therapies for previously undruggable targets," said Sandeep Bobby Reddy, MD – Chief Medical Officer, NantHealth

"Multiple groups, including our own presentation at ASCO (Free ASCO Whitepaper) in 2018, have shown the importance of performing whole exome sequencing to measure the comprehensive TMB. We calculated a three-fold overestimation of TMB when extrapolating from panel-based methods, potentially leading physicians to over-prescribe checkpoint inhibitors for patients that are unlikely to respond. Given the high cost and the possibility of adverse events with these therapies, it is critical we identify the most appropriate population as accurately as possible," said Steve Benz, PhD – President, Genomics, ImmunityBio.

"Determining the tumor mutational burden from whole exome sequencing is the first step in defining neoepitopes. These unique tumor mutations are recognized by T cells and elicit an immunological anti-tumor response. Patients with high TMB typically have more neoepitopes that attract cancer killing T cells to the tumor microenvironment. Identifying neoepitopes from whole exome TMB enables the development of neoepitope-targeted vaccines for the >95% of protein-encoding genes not covered by limited gene panel tests and the >99% of genes not directly targeted by drugs today. The clearance of Omics Core based upon its analytical performance and validity in reporting TMB establishes a new chapter in the era of precision cancer immunotherapy," said Shahrooz Rabizadeh, PhD – Chief Scientific Officer, ImmunityBio.

About Omics Core

The Omics Core assay is a qualitative in vitro diagnostic test that uses targeted next generation sequencing of formalin-fixed paraffin-embedded tumor tissue matched with normal specimens from patients with solid malignant neoplasms to detect tumor gene alterations in a broad multi gene panel. The test is intended to provide information on somatic mutations (point mutations and small insertions and deletions) and tumor mutational burden (TMB) for use by qualified health care professionals in accordance with professional guidelines, and is not conclusive or prescriptive for labeled use of any specific therapeutic product. Omics Core is a single-site assay performed at NantHealth, Inc. The Omics Core assay is protected by US Patents 9,652,587; 9,646,134; 9,824,181; 10,249,384; 9,721,062; 10,242,155; 10,268,800.