Abstract Respiratory syncytial virus (RSV) is a leading cause of serious lower respiratory tract disease in infants, leading annually to ~200,000 deaths and 3-4 million hospitalizations worldwide. Close to $1 billion has been invested by the RSV community over the past two decades in clinical trials seeking to improve upon the marketed monoclonal antibody Synagis®, which is only approved for prophylaxis of very low birth weight premature birth infants. None of these efforts, which have attacked the same viral protein as Synagis (the F protein), has yielded a new approved drug or vaccine. Based on insights into the pathology of RSV infection gained over the past ten years by numerous investigators, Trellis has chosen to target the only other major viral envelope protein (the G protein). Preclinical data support the expectation of substantially improved activity of Trellis’ monoclonal antibody TRL3D3 as a post-infection therapeutic, thereby addressing major populations not served by Synagis, including full-term infants, the elderly and immunocompromised patients. With funding from an SBIR Phase II grant, Trellis has established a commercially-attractive manufacturing process for TRL3D3. In this Phase IIB proposal, we seek funding to complete the IND-enabling work and initiate production of the first clinical lot. We also propose to explore the impact in mice of TRL3D3 on biomarkers that may have utility for establishing efficacy trends in early clinical trials.