TY - JOUR T1 - Stable nebulization and muco-trapping properties of Regdanvimab/IN-006 supports its development as a potent, dose-saving inhaled therapy for COVID-19 JF - bioRxiv DO - 10.1101/2022.02.27.482162 SP - 2022.02.27.482162 AU - Morgan McSweeney AU - Ian Stewart AU - Zach Richardson AU - Hyunah Kang AU - Yoona Park AU - Cheolmin Kim AU - Karthik Tiruthani AU - Whitney Wolf AU - Alison Schaefer AU - Priya Kumar AU - Harendra Aurora AU - Jeff Hutchins AU - Jong Moon Cho AU - Anthony J. Hickey AU - Soo Young Lee AU - Samuel Lai Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/03/01/2022.02.27.482162.abstract N2 - The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries around the world, can effectively trap SARS-CoV-2 virus-like-particles in fresh human airway mucus. IN-006, a reformulation of Regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.Competing Interest StatementMM, ZR, and JH are employees of Inhalon Biopharma/Mucommune, and hold shares in Inhalon Biopharma. HK, ML, CK, and KK are employees of Celltrion, Inc. SKL is founder of Mucommune, LLC and currently serves as its interim CEO. SKL is also founder of Inhalon Biopharma, Inc, and currently serves as its CSO as well as on its Board of Director and Scientific Advisory Board. SKL has equity interests in both Mucommune and Inhalon Biopharma; SKL's relationships with Mucommune and Inhalon are subject to certain restrictions under University policy. The terms of these arrangements are managed by UNC-CH in accordance with its conflict of interest policies. ER -