Intranasal Delivery of Apilimod and Nafamostat for the Treatment of COVID

Unmet Need

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic and has profoundly impacted global human health. Since its initial discovery in 2019, several viral variants have caused additional outbreaks and continue to strain healthcare systems worldwide. While vaccines for the virus do exist, with the first being approved in August 2021 in the US, there is still the need for therapies to combat viral infections in the unvaccinated population, stemming from breakthrough infections, and in immune compromised individuals. Also, the ongoing transmission of new viral variants and the uncertainty about the durability of protective immunity further support continued development of therapies to combat COVID-19 disease.

Technology Overview

Dr. Tomas Kirchhausen’s lab at Boston Children’s Hospital in collaboration with Dr. Giuseppe Balistreri of the University of Helsinki developed a technology whereby the combination of apilimod and nafamostat is delivered intranasally to combat COVID-19. The intranasal delivery of the combination potently inhibits SARS-CoV-2 infection in a mouse model of the disease.  While used alone, these drugs don’t fully block infection, when combined, they display a potent inhibitory synergy enabling use at significantly lower amounts to fully prevent infection. The potent in vitro and in vivo inhibition suggest that this technology may serve as a potential therapeutic against both current and newly arising variants and may also be complementary to existing antibody and/or antiviral therapeutics.

Applications

• Potential treatment for SARS-CoV-2 infection and potentially against all known and future variants
• Potential use with other SARS-CoV-2 therapeutics
• Very inexpensive because of low doses required

Advantages

• Method of delivery may combine well with other therapeutics.
• Neutralizes SARS-CoV-2 infection by preventing viral entry in animals and in cells in culture.
• Ease of administration - intranasal.
• Nontoxic at doses used, no known side effects (repurposed drugs).

Patents

• US Provisional: US Provisional Patent Application Number 63/329,235, Filed on April 8, 2022.

Publications

• Kreutzberger, A. et al. Synergistic inhibition of two host factors that facilitate entry of Sever Acute Respiratory Syndrome Coronavirus 2. bioRxiv, June 1, 2021.
• Kreutzberger, A. et al. Synergistic block of SARS-CoV-2 infection by combined drug inhibition of the host entry factors PIKfyve kinase and TMPRSS2 protease. bioRxiv, August 12, 2021.
• Kreutzberger, A. et al. Synergistic block of SARS-CoV-2 infection by combined drug inhibition of the host entry factors PIKfyve kinase and TMPRSS2 protease. Journal of Virology, 95(21):e00975-21.
• Kreutzberger, A. et al. Tracking infectious entry routes of SARS-CoV-2 . Submitted.