TRELLIS BIOSCIENCE, INC. — Department of Health and Human Services SBIR Phase II: NIAID

Description

DESCRIPTION provided by applicant Respiratory syncytial virus RSV is a leading cause of lower respiratory tract disease leading annually to deaths and million hospitalizations of young children worldwide Immune prophylaxis with a monoclonal antibody mAb Synagis tm Medimmune Inc was shown to be effective years ago to reduce complications of infection in premature birth infants but it has not shown efficacy as a post infection treatment in the much larger population of full term infants No safe and effective antiviral drugs are available and no effective vaccine has been produced to date Accordingly there remains a large unmet medical need Using a proprietary technology for screening single human B cells Trellis has cloned a native human mAb D that overcomes the limitations of Synagis providing unprecedented curative responses in animals post exposure The new mAb targets a different envelope glycoprotein one that has been implicated in sabotage of the host immune response This antibody has an affinity of pM for a highly conserved epitope It has direct antiviral activity in vitro in the presence of complement with potency fold better than Synagis In mouse models D has shown potent activity as both a direct antiviral agent and as an agent to block the lung inflammation linked to clinical pathology This dual activity is qualitatively different from Synagis or from any of the small molecule antiviral drugs under investigation for treating RSV As expected for a native human antibody D showed no binding to a panel of human tissues It has been expressed in stably transformed CHO cells at g L prior to selection indicating feasibility of generating a high expressing cell line Thus all of the goals normally associated with Phase I SBIR research have been achieved The goals of this Direct Phase II proposal are to develop a Master Cell Bank of expressing cells with the capacity of producing D at commercially useful levels andgt g L and to develop the analytical and toxicological data needed for initiation of human testing IND data package PUBLIC HEALTH RELEVANCE This Direct Phase II project will advance the development of D a native human therapeutic antibody against the Respiratory Syncytial Virus G protein with dual activity as an antiviral and anti inflammatory agent The antibody has protected animals from RSV infection by both mechanisms The project will support the development of the antibody to IND approval in preparation for initiation of clinical trials