Development of manufacturing controls for ORL1: a fluorescent imaging agent for in vivo molecular imaging of melanomas

The National Cancer Institute awarded Orlucent, Inc. $1,556,529 on September 3, 2026, under the Cancer Detection and Diagnosis Research program (CFDA 93.394) to develop manufacturing controls for ORL1, a fluorescent imaging agent for in vivo molecular imaging of melanomas.

The award funds a direct-to-Phase II project centered on establishing chemical manufacturing controls and regulatory-compliant production processes for ORL1, which Orlucent's skin fluorescent imaging system uses to detect melanomas. In preliminary studies, ORL1 demonstrated 100% sensitivity and 95.7% specificity in distinguishing melanomas from non-melanomas. The project's four aims include verifying the manufacturing process and controls for ORL1 drug substance and drug product according to current good manufacturing practice standards; developing and adapting test methods for quality control and stability studies; producing three technical lots to demonstrate manufacturing reproducibility and validate quality control methods; and manufacturing three GMP-compliant registration lots with comprehensive quality control testing and a two-year stability program to support regulatory submission. The work emphasizes establishing and documenting the manufacturing process, developing robust test methods, conducting forced degradation studies, optimizing processes for small lot sizes, and characterizing a reference standard to define a two-year expiration date for ORL1.

Performance occurs at Orlucent's Los Gatos, California facility from September 3, 2026, through August 31, 2028. The assistance type is a project grant.

Abstract

This direct-to-phase II project focuses on developing chemical manufacturing controls for ORL1, a fluorescent imaging agent used by orlucent's skin fluorescent imaging (SFI) system for in vivo molecular imaging of melanomas. In our preliminary studies, ORL1 has shown 100% sensitivity and 95.7% specificity in distinguishing melanomas from non-melanomas. The long-term goal is to enhance melanoma diagnosis by reducing unnecessary biopsies and improving early detection through advanced molecular imaging technologies. Aim 1 will verify the manufacturing process and controls for ORL1 drug substance (DS) and drug product (DP) according to current good manufacturing practice (cgmp) standards. Key activities include drafting a master batch record, integrating standard operating procedures (sops), work instructions (WIS), and implementing a comprehensive control strategy. Aim 2 will develop and adapt test methods for quality control and stability studies, ensuring compatibility with the small manufacturing lot sizes for ORL1. Aim 3 will produce three technical lots of ORL1 DS and DP to demonstrate manufacturing reproducibility, validate quality control methods, and establish a fully characterized reference standard. Aim 4 will involve manufacturing three GMP- compliant registration lots of ORL1 DS and DP. Comprehensive quality control testing will be performed, and a two-year stability program will be initiated to support regulatory submission. The research design emphasizes establishing and documenting the manufacturing process, developing and validating robust test methods, conducting forced degradation studies, and optimizing processes for small lot sizes. The project will validate quality control methods, characterize a reference standard, and conduct stability studies to define a two-year expiration date for ORL1. By ensuring that ORL1 meets GMP FDA regulatory requirements, this project will pave the way for the SFI system to improve melanoma diagnosis, reduce unnecessary biopsies, and enable earlier, more accurate detection of melanoma through innovative molecular imaging.