VIS410 for Influenza A
Our lead product candidate, VIS410, is a monoclonal antibody, or mAb, that we have designed and engineered to target all known strains of influenza A and is being developed to treat hospitalized patients with influenza A. VIS410 is designed to terminate the viral replication cycle and is directed against a Hierotope on hemagglutinin, which is a surface protein of influenza viruses used for binding and entry into cells.
In our Phase 2a Challenge Study of VIS410, healthy subjects were inoculated with a pandemic H1N1 strain of the influenza A virus and randomized to receive either a single treatment of VIS410 or placebo 24 hours following infection. This study achieved with statistical significance its primary endpoint of a median reduction in the level of virus in the nasal secretions over the course of the illness. At a pre-specified interim analysis following enrollment of 31 of a planned 60 healthy subjects, we observed a 91% reduction in the level of virus in the nasal secretions in the VIS410 group and, as a result, stopped the efficacy portion of the trial early. The median time period for resolution of symptoms was two days shorter for the VIS410 treatment group as compared to the placebo group. There were no serious adverse events in the trial, and VIS410 was generally well tolerated with a pre-treatment regimen containing generic anti-histamines and non-steroidal anti-inflammatory drugs, or NSAIDs.
We are conducting a global Phase 2a clinical trial in approximately 150 ambulatory patients diagnosed with influenza A and plan to initiate a global Phase 2b clinical trial in the first half of 2017 in approximately 400 hospitalized patients diagnosed with influenza A who require oxygen support. Assuming positive results, following the Phase 2b clinical trial, we plan to meet with the U.S. Food and Drug Administration, or the FDA, and the European Medicines Agency, or EMA, to discuss our Phase 3 program and the possibility of one pivotal Phase 3 clinical trial being sufficient to support a biological license application, or BLA, in the United States, and a marketing authorization application in the European Union, for VIS410 for the treatment of hospitalized patients with influenza A.
We have been awarded a contract from the U.S. Biomedical Advanced Research and Development Authority, or BARDA, an agency of the U.S. government’s Department of Health and Human Services, that includes a forty-month base period with committed funding of $38.6 million for the development of VIS410 and options that, if exercised in full by BARDA, would extend the contract to sixty months and increase the total funding for the development of VIS410 to $214.0 million. If BARDA exercises all of its options under the terms of the contract, we expect BARDA will reimburse us for a large portion of the development costs for VIS410 for the treatment of influenza A. Under our contract with BARDA, we retain the commercial rights to VIS410, but have granted to the U.S. government a nonexclusive, worldwide, royalty-free license to practice or have practiced any patent on an invention that is conceived or first reduced to practice under the contract.
Influenza is an infectious disease that causes illness in humans worldwide with symptoms that range in severity from mild to life-threatening. The majority of seasonal influenza infections result in mild illness with symptoms that include fever, headache, fatigue, cough and sore throat. Some infections, however, result in severe disease, which can involve rapidly progressive pneumonia, respiratory failure and, in some cases, death. Severe disease is more commonly observed in high-risk groups, including infants, pregnant women, the elderly, individuals with underlying medical conditions, such as chronic heart and lung disease, and patients with disease- or treatment-related immunosuppression.
Each year, human influenza A viruses cause epidemics, which are sudden outbreaks that spread rapidly and affect many people at the same time, with influenza A being responsible for the majority of such outbreaks. Influenza A viruses are categorized into subtypes based on two proteins on the surface of the virus: hemagglutinin (H) and neuraminidase (N). There are 18 different hemagglutinin subtypes, which are designated by the abbreviations H1 through H18, and 11 different neuraminidase subtypes, which are designated by the abbreviations N1 through N11. Immunity to influenza acquired from vaccination or previous natural exposure is usually specific to the strain of the virus and declines over time, leading to the need for repeated annual vaccination.
According to the CDC, approximately 35 million people suffer from influenza infections in the United States each year, resulting in as many as 400,000 hospitalizations and as many as 49,000 deaths. The WHO reports that globally there are as many as five million severe influenza cases annually, leading to as many as 500,000 deaths. Our analysis of a large database of hospitalizations in the United States showed that 59% of hospitalized influenza patients require a supplemental oxygen support or positive pressure ventilator support during their hospitalization. This analysis also showed that the average length of hospital stay for patients was seven days, and the average charge per hospital day was approximately $12,000 for influenza patients requiring ventilator support and approximately $8,000 for influenza patients who did not require ventilator support. In addition to seasonal infections, epidemics that spread across countries and continents, or pandemics, are caused by influenza strains that have high human-to-human transmission and, if the strain causes severe disease, can lead to a high mortality rate. An H1N1 strain of the influenza A virus caused the 1918 Spanish influenza pandemic, which is estimated to have resulted in approximately 50 million deaths worldwide. Evolving avian influenza or bird flu viruses, such as H5N1 and H7N9, which have a high associated mortality rate and the potential to infect and readily transmit in humans, pose a major health risk. The avian H7N9 influenza strains that emerged in 2013 have mortality rates as high as 42% in infected individuals.
As of 01/15/17