Ultra-precision diagnostics for ALK+ non-small cell lung cancer

Background & Significance: Identifying ALK-positive lesions, which are highly responsive to treatment with Crizotinib or Alectinib, is a high-priority for managing patients with ALK+ Non-Small Cell Lung Cancer (NSCLC). A blood-based companion diagnostic (liquid biopsy) could monitor NSCLC patients post-treatment for tumor recurrence without tissue re-biopsy, and also identify non-symptomatic ALK+ individuals for earlier, more effective treatment with ALK kinase inhibitors. Expansion of this approach to other major oncogenic mutations has potential as a non-invasive cancer screening tool that would be transformative for healthcare. Objective & Innovation: AleloPharma Inc. is achieving solutions for personalized precision medicine using AleloMAX, an innnovative high-dimensional molecular detection system that allows ultra-specific detection of target nucleic acids with an impressive 1-absolute copy per reacting assay limit-of-detection (LOD) that effectively eliminates both false positives and false negatives. We aim to offer clinicians a cutting-edge diagnostic capable of accurately detecting ALK translocations among cell-free RNA in the blood plasma of affected patients. Approach: A proof-of-principle study, supported by preliminary LOD data obtained with synthetic ALK constructs, is proposed to develop a liquid biopsy test to detect ALK translocation variants in a kit for use in clinical labs. • Specific Aim 1: Develop an ultra-specific and ultra-sensitive molecular detection platform for EML4-ALK gene fusion translocations in ALK+ NSCLC. We will probe EML4-ALK fusion RNAs using synthetic, in vitro-transcribed mRNAs encompassing the distinct EML4-ALK oncogenic variants. • Specific Aim 2: Demonstrate AleloMAX-ALK’s superior resolution power in ultra-specific molecular probing and limit-of-detection (LOD) analysis in a clinical proof-of-principle study. The EML4-ALK diagnostic platform will be tested using plasma- and/or blood-derived nucleic acid samples obtained from ALK+ NSCLC patients, ALK- NSCLC patients, and healthy control volunteers. Team & Commercialization: Led by a distinguished team with a track record of groundbreaking research in molecular pharmacology, oncology and cellular biology, we are uniquely positioned to tackle this challenge. Our clear roadmap includes patenting all IP and aspires to launch a diagnostic that will have significant clinical utility. Feasibility & Impact: The assay is expected to detect low levels of EML4-ALK mutations in blood of individuals with ALK+ NSCLC. AleloMAX demonstrated diagnostic superiority in prior studies of the NSCLC biomarker POGLUT-1, SARS-CoV-2 and RSV with impressive results. Assay parameters established in this project will be developed as a kit for use in a Phase II study to establish its clinical utility as a companion diagnostic for NSCLC. Successful development of an ALK+ cancer diagnostic will be expanded to include assays for RET, ROS1 and other onco-mutations with additional AleloMAX liquid biopsy assays to monitor a broader panel of cancers. Conclusion: Combining innovation and tangible clinical benefit, our initiative represents a transformative shift in early detection and management of cancer that will positively impact patient survival.