Translating a Novel Assay for Risk Stratification of Potentially Malignant Pancreatic Cystic Lesions

1. Executive Summary Pancreatic cancer has a depressing 5-year survival rate estimated at 12%. The dismal outlook is due to myriad issues, including the fact that patients are asymptomatic in early stages combined with the lack of screening tools. One window to earlier detection is through pancreatic cystic lesions detected incidentally in routine imaging analyses for diagnosis of unrelated disorders. These patients are at an increased risk for pancreatic cancer. Unfortunately, imaging is insufficient for distinguishing benign cysts from those likely to progress to cancer forcing clinicians to rely on biochemical analyses of acellular cyst fluid. The current assays display poor accuracy and require large volumes of fluid not always available limiting their clinical utility. There is a profound unmet clinical need for diagnostics that accurately grade dysplasia in mucinous pancreatic cyst fluids. The objective of current SBIR Phase I grant (CA277913-01A1 effective May 2023) is to develop and conduct clinical translation of a diagnostic assay panel using ultrasensitive detection methods to grade dysplasia in pancreatic cysts. This assay will stratify patients most at risk for progression to cancer thus providing high clinical utility. The platform: Amplified Sciences has utilized a proprietary platform to translate to the company roscopy platform is robust and readily adaptable to other proteolytic enzymes as needed for this grant. To date, the company has made strong progress on the Aims. The team has built a new direct-detection SERS ligand binding platform (prototype stage) for two of the biomarkers, and adapted the existing enzymatic activity assay for a third. Over 90 retrospective clinical samples have been procured, and all clinical testing and statistical analysis should be complete by end of Phase 1. The company is on track -ready assay protocol for full clinical validation and algorithm development in a Phase 2 grant. Several challenges have been met and overcome. Technical challenges including delays in the supply chain have been overcome by securing new suppliers for chemicals, etc. Administrative challenges include delays from securing invoices from vendors, so more frequent reminders have been implemented. Finally, commercial challenges include limited funding for market research with doctors and payers to gain the insights needed to prepare for commercial launch and challenges in accessing clinicians at large academic centers. To overcome this, the company has leveraged current clinical investigators for introductions. Finally, the current capital market for fundraising is very challenging so the company has supplemented investor funds with non-dilutive funding totaling $1M of research use only revenue and state and federal grants. Specific Aims: Aim 1: Validate a combination of three (3) protease activity markers to accurately distinguish low- grade from high-grade mucinous pancreatic cystic neoplasms. Aim 2: To develop quantitative assays for a panel of three (3) markers in low-volume mock cyst fluid samples that enable diagnostic power evaluation in a clinical sample cohort. Below employees are committed to I-Corps requirements: Diana Caldwell, CEO and Co-founder (C- er) Daniel Sheik, PhD, Director of Research and Technology John R. Ridge, Commercial and Market Access Director (Industry Expert)