Project Summary Sostos, LLC has developed a qRT-PCR-based microfluidic 7-gene assay (CATOS-LU) that predicts recurrence or progression to metastasis of non-small cell lung cancer (NSCLC) in a patient who has undergone resection for stage 1 cancer without high-risk features at the time of surgical intervention. In retrospective/archived longitudinal clinical studies, our assay, which was developed utilizing novel artificial intelligence (AI) methods and validated via our qRT-PCR, next-generation sequencing (NGS), and proteomics, accurately predicted 1) the risk of tumor recurrence in early-stage NSCLC patients (n>1,600) including patients from a randomized phase III clinical trial JBR.10 (ClinicalTrials.gov); and 2) the clinical benefits of adjuvant chemotherapy in these patients. These results support that our technology can 1) identify early-stage NSCLC at high risk for tumor recurrence, and 2) predict the clinical benefits of chemotherapy in stage 1 NSCLC without high-risk features for earlier implementation of adjuvant chemotherapy in the course of disease management beyond the current standard of care. We have accomplished several key milestones to help demonstrate early proof-of-concept during the initial development of our product. We have submitted a set of comprehensive patent applications to strengthen our IP for our technology, addressing the clinical utility of CATOS-LU in patient snap-frozen and formalin-fixed paraffin-embedded (FFPE) tumors, which we have also discussed with the FDA. To help commercialize our technology, we intend to optimize CATOS-LU in FFPE clinical samples to better fit within the surgery/pathology/oncology workflow. In this Phase I SBIR project, we will establish a qRT-PCR assay, based upon our AI-defined 7-gene panel, focusing on stage 1 NSCLC without high-risk features (n=200), for the prediction of the recurrence risk. To enhance the clinical application and market value of our CATOS-LU within the standard of diagnostic care, we will develop our CATOS-LU of FFPE tumors in a CAP-accredited laboratory. The project will test the feasibility of integrating our proposed qRT-PCR assay of FFPE tumors into the existing hospital workflows for cost-effective in-house testing. The proposed data analysis will follow the FDA instructions that we have received and the results generated from this project will be submitted to the agency for approval. We have engaged strategic partners, including a commitment to match this project pending the award of Phase I. We request Phase I support to test the feasibility of our project and optimize our test to aid physicians in identifying these high-risk patients in the earliest stages of NSCLC. Ultimately, we intend to obtain CMS coverage/reimbursement as an LDT followed by FDA approval of our diagnostic test as an aid to diagnosis or risk score assessment for patients at high risk of recurrence of NSCLC in stage 1 without high-risk features following primary tumor resection.

Project Narrative Sostos, LLC is developing an assay that addresses the high incidence of tumor recurrence in patients with non- small cell lung cancer (NSCLC) at the time of primary tumor surgical resection. Our technology identifies NSCLC as at high risk of progression and recurrence of cancer for patients who will benefit from earlier therapeutic intervention. Using qRT-PCR of formalin-fixed paraffin-embedded (FFPE) tumors, we anticipate that our product will become part of the standard of care for early-stage NSCLC patients, at the time of surgical resection of the primary tumor, for identifying those at high-risk who would benefit from early implementation of adjuvant therapy to prevent tumor progression and recurrence – years before otherwise identified – and thus, improving overall patient care and outcome for those with lung cancer.