[Sept 2021] Presentation @ Vaccine (Virtual) Summit 2021

Prevention of Covid-19 Transmission Beyond the Needle:

DCOY101, a novel antiviral fusion peptide-based prophylactic nasal spray.

Barbara Hibner*, Peter Marschel*, Frederick E. Pierce II*, Shahin Gharakhanian**

*Research & Development Program Team, **Scientific Advisory Board,

DECOY Therapeutics, CAMBRIDGE MA, USA. [Contact: bhibner@decoytx.com].

Introduction: Covid-19 is a global health crisis with specific local features. This pandemic has revealed the complexities of global infection control involving age-driven infection patterns, levels of awareness, high viral variations, changes to vaccine immune response over time, social media, the heterogeneity of social responses and medical co-morbidities. A “one-size-fits-all” approach has proven insufficient. Vaccines are the backbone, but gap analysis points to the need for additional agents.

Methods/Results: We are developing a broad antiviral bioconjugate platform. Our lead candidate is a novel antiviral fusion peptide-based prophylactic nasal spray. DCOY101, a 41 amino acid heptad repeat C-based peptide, has been engineered to enhance half-life and target respiratory tissue. (1) DCOY101 lipopeptide inhibited S-mediated SARS-CoV-2 fusion (IC50=10nM/IC90~100nM) in 293T cells expressing ACE2 (mBio, 2020; 11:e01935). (2) DCOY101 inhibited live virus in monolayer Vero E6 cultures via a plaque neutralization assay (IC50=6nM). (3) DCOY101 enabled a 4-log reduction in viral load in a human airway epithelial ex vivo model. (4) DCOY101 is equipotent vs alpha, beta and gamma variants in a pseudotype assay. (5) Based on a close analogue, POC nasal drops QDx4 days demonstrated prophylaxis in a validated ferret transmission model, preventing infection in treated ferrets (0/6 infected) co-housed with a maximally infected ferret. All mock treated animals (6/6) became infected (de Vries RD et al., Science 2021, 371: 1379-1382).

Conclusion: Multiple prophylactic and population-friendly approaches are required to control Covid-19. DCOY101 can complement vaccines with advantages in manufacturing, self-administration, shelf life and no requirement for a cold supply chain.

Abstract: Vaccine Summit 2021 Washington DC, USA, 20-21 Sept Vol. 1, No. 1, Page 57.

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