Drug development is a process of repeated learning and validation, which involves high-quality and high-efficiency research, and facilitates reasonable decision-making at each research stage, thereby increasing the probability of success in research and development. As a key step in drug development, translational medicine can connect preclinical and clinical studies, so as to achieve the purpose of selecting suitable patients with certain diseases and finding suitable biological targets for diseases. It can also make reasonable suggestions for drug dosage in the appropriate efficacy window of clinical trials, achieving the cyclical validation process of "Basic Research—Translation—Clinical Studies—Reverse Translation". So how does biomarker improve the success rate of the entire drug development? Taking drugs for NSCLC indication as an example, the overall success rate in phase III clinical trials is 28%, and the success rate in targeted therapies is 31% and as high as 62% with targeted drugs guided by CDx, i.e., the application of biomarkers has significantly improved the success rate of clinical trials. In addition, the application of biomarkers in clinical trials has doubled in 2007 to 2011 vs. in 2012 to 2016 in terms of efficacy, toxicity, and prevalence evaluation.

Biomarkers play many different roles in drug clinical research, such as efficacy evaluation, risk prediction and early diagnosis of diseases, and act as markers of toxicity and drug efficacy, etc. With further understanding of biomarkers, drug clinical research has been gradually expanded into the field of companion diagnostic (CDx). Taking TMB, a new type of biomarker in immunotherapy, as an example, clinical studies have proved that patients with TMB-H and TMB-L or TMB-M have significantly different benefit coefficients in the treatment with O drugs. In June 2020, TMB-H also passed the FDA certification as a standard for companion diagnostic of Keytruda. In other words, TMB breaks through the traditional indications and has expanded its effective population in pan-cancer.

YuceBio has been continuously upgrading its prediction models on the basis of neoantigen, and has always been at the forefront of the industry. It has carried out methodological optimization and clinical validation in methodology, and published multiple articles. ioTNL is a newly developed marker that has been proved to be related to PFS/OS in 5 cohorts of second-line monotherapy for lung cancer, second-line monotherapy for malignant melanoma, first-line combination therapy for intrahepatic cholangiocarcinoma, and second-line monotherapy for nasopharyngeal cancer. ioTNL also shows excellent performance in the YuceOne^® panel test.

Tumor inflammation signature (TIS) is a marker of gene expression profile of immune microenvironment jointly developed by NanoString and Merck, which has been validated in multiple pan-cancer clinical cohorts. YuceBio obtained the first genuine test algorithm in China authorized by NanoString. Immune Exhaustion Signature (IES) is a 15-gene expression profile independently developed by YuceBio and has been validated in multi-cohort tumors. YuceBio has introduced the platform from NanoString, which can provide nCounter PanCancer IO 360 panel test and data analysis services. In addition, it integrates 34 potential immune signatures including TIS, which can quickly assess immune invasion, and develops signatures that can be used for tumor immunotherapy. The multicolor histochemistry solution is widely acclaimed as a new technology in tumor immunology research, and it is the most advanced quantitative analysis technology for tissue in situ cell phenotype at present.

bTMB: The TMB value calculated based on the number of mutations has a low correlation with tissue TMB, and a new model is needed for optimization. The bTMB value predicted by the machine learning (ML) model is closer to the tissue TMB than the bTMB value calculated based on the number of mutations.

bMSI: The YuceOne^® bTMB panel is used for bMSI test of blood samples, and the test accuracy is 88.9%.

TCR: The diversity of TCR and its dynamic changes before and after treatment are related to the efficacy of immunotherapy. The results have been published at the AACR 2020 Conference.

The immunogenicity of a tumor is related to the number of mutations, heterogeneity, and whether it can be presented.

• TMB, ITH, and HLA have been methodologically optimized and clinically validated, respectively. TMB and ITH have been validated at the pan-tumor level, and the article is being published.

• oTMB combines TMB, ITH, and HLA, the three effective indicators for predicting the efficacy of immunotherapy at the tumor genome level, and optimizes TMB to carry out the test in the YuceOne^® Plus chip at the same time.

Comprehensive evaluation and rapid decision-making—YuceOne® Plus series

YuceBio combines tumor genome + immune microenvironment + neo-antigen presentation pathway, and multi-dimensional information to aid clinical research and exploration:

YuceBio has developed a set of methods for TMB test based on YuceOne® Panel single tumor sample, and the correlation with TMB in blood control sample has reached 0.93. Additionally, it has validated the value of immunotherapy efficacy prediction in the Chinese non-small cell lung cancer cohort. The TMB method free of control samples is more convenient in clinical application, which can reduce costs while eliminating the possibility of inconsistency between matching samples. In the future, the value of clinical prediction of immunotherapy can be validated in the gastrointestinal tumor cohort.

YuceBio has obtained three patents in TMB: "Gene Chip for Tumor Mutation Burden Test and the Preparation Method and Device thereof", "A Tumor Mutation Burden Test Method, Device and Storage Medium", and "Tumor Mutation Burden Test Method, Device and Storage Media".