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.

Public Health Relevance

In the US, RSV is responsible for 20% of all hospitalizations for infants and young children, at an estimated cost of $1B annually, but no effective therapeutic agent has been developed. Trellis has discovered (and patented) a novel antibody (TRL3D3) with strong preclinical data in treating RSV infection. The work proposed here will complete the preclinical development needed to gain FDA approval to initiate human clinical testing of the innovative agent.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AI122360-05
Application #
10063931
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kim, Sonnie
Project Start
2016-02-01
Project End
2021-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
5
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Trellis Bioscience, LLC
Department
Type
DUNS #
962700048
City
Redwood City
State
CA
Country
United States
Zip Code
94063
Fedechkin, Stanislav O; George, Natasha L; Wolff, Jacob T et al. (2018) Structures of respiratory syncytial virus G antigen bound to broadly neutralizing antibodies. Sci Immunol 3:
Tripp, Ralph A; Power, Ultan F; Openshaw, Peter J M et al. (2018) Respiratory Syncytial Virus: Targeting the G Protein Provides a New Approach for an Old Problem. J Virol 92: