SBIR Phase I: The LADDR Platform for Precise Delivery of Nucleic Acid Therapy for Head and Neck Cancer and Esophageal Cancer

Illuminate Therapeutics, Inc., Portola Valley CA

Investigators

Abstract

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is in the development of Illuminate Therapeutics’ Light Activated Drug Delivery and Release (LADDR) platform technology to improve patient outcomes in head and neck (H&N) and esophageal cancer treatment. H&N and esophageal cancers are some of the most common cancers worldwide and make up 4.5% of all new cancer cases in the US. Over 60,000 cases of H&N cancer and over 20,000 cases of esophageal cancer are newly diagnosed in the US each year. The total market for H&N cancer treatment is ~$1.2 billion in 2021, with a CAGR of 12.5% during the forecast period. The esophageal cancer market is similarly sized, with the market valued at $1.14 billion in 2021, and it is expected to grow at a CAGR of 8.50%. The LADDR platform enables precise spatiotemporal delivery of small therapeutic RNAs to tumors by a combination of nanoparticle-mediated delivery and activation triggered by external light. The use of LADDR with microRNA mimics in the treatment of cancer will preserve healthy tissues, maintaining critical tissue function while eliminating the common side effects associated with current standard-of-care treatments. This Small Business Innovation Research (SBIR) Phase I project is crucial to the commercialization of the LADDR technology by derisking two major potential issues: 1) predicting responsive and non-responsive tumors and 2) determining the impact of route of administration on LADDR’s basic pharmacokinetic/dynamic properties. The key objectives in this study are to: 1) identify microRNA-mimic-responsive and non-responsive patient-derived tumors, 2) select the predictive markers for responsive tumors, and 3) determine the basic pharmacokinetics and pharmacodynamics of the LADDR vehicle for delivering functional microRNA mimics to tumors in vivo. The research is separated into two objectives. Objective 1 will determine the breadth of each microRNA mimic’s activity in representative patient-derived tumor organoids derived from H&N and esophageal cancers and identify biomarkers of responsive and non-responsive tumors for the development of personalized therapies. Objective 2 will determine the impact of the route on LADDR’s basic pharmacokinetic/dynamic properties. The insight gained in this study will allow the identification of the functional targets of microRNA mimics in H&N and esophageal tumors and provide a proof-of-concept for therapeutic microRNA mimic delivery using light-activated LADDR vehicles in vivo. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.