Our Role in RSV Research
In Dec 2009, Trellis signed a partnership with MedImmune LLC, the biologics oriented subsidiary of pharmaceutical giant AstraZeneca plc, to develop Trellis’ antibodies aimed at fighting a common childhood respiratory virus, RSV (Respiratory Syncytial Virus). The deal, potentially worth upwards of $338 million from milestone and commercial payments, calls for MedImmune to take responsibility for clinical development and marketing of the drug candidate.
RSV is a highly contagious infection of the lungs and respiratory passages that primarily affects young children and the elderly. Repeated efforts to develop a vaccine against RSV have failed, and the only current drug targeting the virus is Synagis™, developed and marketed by MedImmune. This antibody product is only approved for prophylactic use in high risk, low birth weight infants. A post-infection therapeutic antibody would address a major need not met by the current product. Although most children get RSV by age 1 without serious impact, 5-10% of these young children experience a severe course of disease characterized by serious wheezing as the lungs fill up with mucous. During RSV season (winter), it is a major reason for infants to be hospitalized, often in pediatric intensive care units. RSV is similarly a major problem in the elderly, accounting for a substantial portion of viral pneumonia cases (comparable to influenza).
In 2007, Trellis initiated a collaboration with investigators from the US Centers for Disease Control in Atlanta who had identified a new approach to fight RSV. These researchers had implicated a small region of the virus G protein in sabotage of the host immune response. Unlike the F protein targeted by Synagis, the G protein overall is highly variable across virus strains. However, this small region is highly conserved, presumably reflecting its key role in virulence.
As Trellis soon discovered, the conserved region of the G protein is also very poorly immunogenic. To overcome this challenge, Trellis industrialized the CellSpot™ technology to a level able to discover antibodies that are otherwise too rare for reliable recovery. In the end, Trellis isolated a suite of 10 native human antibodies with exquisite specificity for the conserved region of the G protein and very high affinity (a biochemical feature contributing to in vivo potency). Along the way to this final set, Trellis examined ~20 million individual antibody producing human B cells from ~30 adult donors who had recently recovered from an RSV infection.
The lead antibodies in this suite were then characterized in cell culture and animal models to generate a data package supporting the expectation of utility for the unmet need of a post-infection therapeutic. Further characterization of the top antibodies confirmed their suitability for large scale manufacturing and their low binding to human proteins (indicative of a good safety profile), properties expected from a native human monoclonal antibody.