Scaling Lymphoma Diagnosis: A Cost-Effective Gene Expression Assay for Broad Implementation

Abstract Lymphoma is a potentially curable cancer, yet timely and accurate diagnosis remains a significant barrier to care, particularly in hospitals outside of metropolitan centers that lack consistent access to expert hematopathologists. Standard diagnosis involves iterative immunohistochemistry and complex interpretation, with turnaround times of weeks and diagnostic discordance rates exceeding 20%—leading to treatment delays, unnecessary procedures, and higher costs. These challenges are especially acute in community hospitals and resource- constrained settings. Raiz Diagnostics has developed LymphomaDx, a low-cost, same-day diagnostic assay that identifies both the presence and subtype of lymphoma using gene expression profiling from formalin-fixed, paraffin-embedded (FFPE) core needle biopsies. The assay combines proprietary chemical ligation probe amplification (CLPA) with a locked machine learning algorithm to diagnose lymphoma without requiring pathology morphology review. Preliminary data demonstrate that LymphomaDx achieves 94% concordance with expert consensus, outperforming individual reviewers, and functions effectively even with low-input tissue. The project is significantly de-risked by validated proof-of-concept data, exclusive rights to core IP, and secured access to over 2,500 annotated biopsy specimens across multiple institutions. This Phase II proposal will advance the clinical deployment and regulatory readiness of LymphomaDx through the following specific aims: · Aim 1: Generate CLPA expression data from 2,500 clinically suspected lymphoma cases to train and validate a diagnostic classifier. Performance benchmarks include ≥95% sensitivity/specificity for lymphoma detection and ≥90% top-1 accuracy in key subtypes (e.g., DLBCL, FL, HL, CLL/SLL). · Aim 2: Validate LymphomaDx V2 as a CLIA-compliant lab-developed test (LDT), including reproducibility, analytic sensitivity, diagnostic concordance, biopsy equivalency, and QC metrics. · Aim 3: Initiate QSR-compliant product development and submit an FDA pre-submission (Q-sub) to establish regulatory pathway and kit development. Expected outcomes include a fully validated, CLIA-ready assay, clinical-grade performance data for multiple lymphoma subtypes, and foundational regulatory documentation for future FDA clearance. The test will be positioned for rapid launch as a Laboratory Developed Test (LDT) in CLIA-certified labs, with strong potential for expansion as an in vitro diagnostic (IVD) kit. With over 260,000 suspected lymphoma biopsies annually in the U.S. alone, LymphomaDx addresses a $700M+ domestic diagnostic market. The ability to deliver expert-level accuracy in hours—using infrastructure already present in most clinical labs—positions LymphomaDx to transform the diagnostic pathway for lymphoma, reduce costs, and expand access to life-saving therapies.