Breakthrough High-Accuracy, High-Throughput Colorectal Cancer Screening Platform

Project Summary/Abstract Screening for colorectal cancer (CRC) and precancerous lesions, such as advanced adenoma (AA), represents a significant healthcare challenge. Current approaches, including colonoscopy and stool-based tests, suffer from limitations such as invasiveness, inconvenience, cost, and variable sensitivity. Addressing this need, we propose leveraging Intus Biosciences' Titan-1 platform lab developed test, designed for non-invasive high-throughput fecal microbiome profiling with at-home sample collection, as a novel CRC screening tool. Training the Titan-1 machine learning algorithm with a limited CRC/AA sample dataset of 57 CRC fecal samples yielded CRC screening results equivalent to existing fecal CRC screening tests. We show that results improve as more data is used for training the machine learning. This approach is unique in that it offers the opportunity to enhance sensitivity and specificity for CRC detection by augmenting the Titan-1 training dataset with a surprisingly small number of additional CRC samples. By doubling the number of control samples to a few hundred, and simultaneously adding about 100 additional CRC samples, we anticipate exceeding current sensitivity and specificity benchmarks of existing market leading products. Furthermore, the platform can detect precancerous AA lesions, and we propose to improve AA detection by incorporating 100 AA samples into the Titan-1 training dataset, aiming for sensitivity and specificity in excess of 75%, with a stretch goal of 96%. Initial results with 35 AA samples showed modest sensitivity similar to results with 35 CRC samples, but we hypothesize that additional AA samples will yield significant sensitivity improvements, similar to CRC detection results. If Phase 1 is successful Phase 2 will focus on FDA submission for CRC and AA screening device approval, demonstrating superior sensitivity and specificity compared to existing devices, along with comprehensive safety and performance data. The final product will decrease invasiveness, inconvenience, cost and will significantly increase convenience and accessibility compared to colonoscopy and will provide a more sensitive non-invasive test for precancerous lesions. Preliminary discussions with FDA advisors suggest that Phase 1 results will be instrumental in initiating discussions with the FDA regarding Titan-1 device approval.