Oral mucositis is a major complication of radiotherapy for the treatment of head and neck cancer and a major dose-limiting side effect. Our work has shown that intra-esophageal administration of plasmidlliposomes containing the transgene expressing human superoxide dismutase 2 (SOD2) (JVRSOD) protects the esophagus from radiation-induced esophagitis (a form of mucositis) in mice. The overall purpose of the Phase I section of this fast-track contract proposal is to complete the IND-enabling studies for the use of JVRSOD as a prophylactic mouthwash to reduce andlor prevent oral mucositis in head and neck cancer patients undergoing radiation treatment. The Phase I Proposal specific aims are (1) dose optimization of JVRSOD in a mouse model for protection from radiation-induced oral mucositis; (2) dosing schedule optimization of JVRSOD in the same mouse model for protection from radiation-induced oral mucositis; and (3) identification and qualification of a GMP manufacturing site. Under the Phase II Contract Proposal in this Fast-Track submission, an IND application for JVRSOD will be submitted to the FDA, cGMP JVRSOD will be manufactured, and it will be tested in humans for safety I efficacy in a Phase 1111 clinical trial with head and neck cancer patients undergoing standard of care radiation treatment
