The Treasure Hunt for Novel Biomarkers and Rise of TMB

Over the years, several cancer-related biomarkers have been identified, which can be used to predict response to certain types of immunotherapy drugs. However, due to the inherent complexity of the immune microenvironment and differences in the genomic makeup of individual patients, most of these biomarkers have been proven to be insufficient in predicting how a patient is likely to respond to certain therapy types.

In order to address the aforementioned concern, researchers have shifted their focus to exploring novel biomarkers, and assessing their potential in predicting response to various types of drugs/therapies. One such biomarker that has gained a lot of traction in recent years is Tumor Mutation Burden (TMB).

What is TMB: TMB is a quantitative biomarker that reflects the total number of somatic mutations per megabase (Mb) of DNA. There are a number of factors that cause these mutations, including errors in DNA replication machinery, defects in the DNA repair process, enzymatic modification of DNA and exogenous exposures.

Why is TMB used as a biomarker: When the patient is treated with immunotherapeutic agents, the immune cells of the body (T-cells) recognize these neoantigens and initiate an immune response against them. Therefore, a high mutation load can be co-related to the presence of neoantigens and is one of the important factors that influence the activation of the immune system against tumor cells. This renders TMB a relevant tool for the identification of patients that are likely to respond to immune checkpoint inhibitor therapies.

Evolution of TMB as an immunotherapy biomarker: The figure below, highlights the evolution timeline of TMB as an immunotherapy biomarker across multiple clinical studies evaluating different indications.

How is TMB measured: Different methods have been used to measure TMB and next-generation
sequencing (NGS) stands out among various others. The following methods that are primarily used for the measurement of TMB:

• Whole Exome Sequencing
• Gene-Targeted Sequencing

Which all companies offer TMB testing services: According to a recent report by Roots Analysis that provides a comprehensive list of service providers for the novel biomarkers, there are only around 20 players that offer services specifically for TMB testing.

To get more insights about the TMB testing market, along with detailed estimates of the market opportunity, check out the report here.