In this Phase IIB proposal, we seek funding to complete the IND-enabling development of CF-404, a mixture of three native human monoclonal antibodies (mAbs). Activity has been established in mouse models against representatives of all major circulating strains of influenza A and B. By providing a pan-influenza treatment, we avoid delays associated with strain typing, with improved outcomes expected from the prompt treatment. We specifically propose here to address regulatory issues relating to delivery of the mAb mixture by inhalation. Our background work demonstrated that inhaled delivery provides superior efficacy compared to systemic delivery, at ~10-fold lower dose. The inhalation technology from industry leader Aerogen Pharma is established as suitable for hospitalized patients, including those on a ventilator. Due to drug resistance to the existing influenza therapeutic drugs, there is a high need for our product. The first class of small molecule therapeutics, the amantadines, are now largely useless due to drug resistance. The second class, neuraminidase inhibitors, are currently experiencing similar emergence of resistance. The newest class, polymerase inhibitors, has already shown worrisome signs of early emergence of drug resistant strains (10% in the Phase 3 trials). By contrast, intensive selection in vitro for virus that escapes our mAbs has shown that resistance is likely to be far less common than for the small molecule antivirals. The impact of CF-404 is thus expected to be high.

Public Health Relevance

Although mAbs are the fastest growing segment of the pharmaceutical industry, most of the effort has been focused on cancer and inflammatory diseases. Extension to infectious diseases has lagged due to low funding by pharmaceutical companies, making grant funding particularly important in this field. Trellis Bioscience specializes in cloning human mAbs with favorable properties for clinical development using our patented CellSpot? technology. In addition to the three influenza mAbs, our pipeline of products nearing IND stage includes mAbs for Respiratory Syncytial Virus (RSV), cytomegalovirus (CMV), and for a bacterial biofilm- associated protein implicated in antibiotic resistance. Each of our four programs is focused on post-infection therapy and is thus complementary to vaccine efforts. The scientific premise is that the combination of pan- influenza activity of our product, CF-404, with enhanced potency via inhaled delivery, will improve outcomes for hospitalized patients. This product profile, including low susceptibility to emergence of drug resistance, is well differentiated from competing drugs in a market projected to remain well over $1 billion annually for the next decade.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1)
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Krafft, Amy
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Trellis Bioscience, LLC
Redwood City
United States
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Vigil, Adam; Estélles, Angeles; Kauvar, Lawrence M et al. (2018) Native Human Monoclonal Antibodies with Potent Cross-Lineage Neutralization of Influenza B Viruses. Antimicrob Agents Chemother 62: