Our discovery success in Influenza treatment
Influenza is responsible for ~36,000 deaths and over 200,000 hospitalizations annually in the US, with potential for far greater morbidity and mortality from novel emerging strains of virus, such as H5N1 “bird flu.” The associated direct medical costs, as estimated by the US Center for Disease Control (CDC) is $10 billion, with another $14 billion in lost income. Although vaccination is an important tool in the public health response to influenza, it is not sufficient. For the populations at highest risk of mortality, the very young and the very old, the vaccine typically fails to induce neutralizing antibodies in over 50% of subjects. Even in healthy young adults, the failure rate is ~15%.
The first generation of antiviral drugs, the amantadines, are of no value today as all strains of the virus are resistant to them. The second generation antivirals like oseltamavir (Tamiflu™), are also losing efficacy as the virus becomes resistant to this and other neuraminidase inhibitors. Moreover, the efficacy of this class of drugs drops significantly as the time between infection and treatment extends beyond 24-48 hours.
Like most viruses that persistently infect humans on a global scale, influenza has developed strategies for evading the immune system. Influenza’s primary strategy to defeat our immune system is to display epitopes on its major surface hemagglutinin (HA) protein that are highly immunogenic but able to mutate readily such that an effective immune response mounted in a given season affords little protection in subsequent seasons to the newly mutated viruses. A major advance in the field was the discovery by several investigators that a weakly immunogenic region of HA called the “stalk” was critical to viral function and in fact was highly conserved across strains. Antibodies to the HA stalk have been shown to neutralize virus effectively.
Trellis has surveyed ~50 million antibody producing B cells from 30 donors and cloned several hundred antibodies that show cross-strain reactivity. For each of the two major families of Flu, Group 1 and Group 2, the Trellis lead antibodies have 3-10 fold higher affinity and greater potency than the best previously reported antibodies to the stalk region. The antibodies show excellent efficacy in animal models, including full protection from an otherwise lethal challenge of several high path viral strains even when given days after infection. Trellis’ influenza program will enter its licensing phase in Q1 2012.