Oyster Point Pharma announced preclinical data in non-human primates and in vitro models evaluating OC-01 (varenicline) nasal spray against SARS-CoV-2 and the alpha and beta variants, the viruses that cause COVID-19 disease. Administration of OC-01 (varenicline) nasal spray, a highly selective nicotinic acetylcholine receptor agonist, protected rhesus macaques against SARS-CoV-2 nasal infection. The results were published at https://biorxiv.org/cgi/content/short/2021.06.29.450426v1.
“We believe this is the first in vivo and in vitro data illustrating a nicotinic acetylcholine receptor agonists’ potential to inhibit viral entry and disrupt the replication of the SARS-CoV-2 virus and variants,” said Jeffrey Nau, PhD, MMS, president and CEO of Oyster Point. “We believe that OC-01 (varenicline) nasal spray has the potential to complement the current global vaccination strategy and prevent infection and reduce transmission of the SARS-CoV-2 virus with a mechanism of action that may have broad activity across multiple variants.”
On Day 1, using a viral infection model and following two administrations of 100 μl of OC-01 (varenicline) nasal spray (0.6 mg/ml varenicline) into each nostril, animals were challenged with a very high viral inoculum (approximately 70 thousand plaque-forming units) of active SARS- CoV-2, via both intranasal (nose) and intratracheal (lung) routes. Animals then received two additional administrations of OC-01 (varenicline) nasal spray into each nostril on Day 1, followed by four times daily for the following four days. Administration of OC-01 (varenicline) nasal spray resulted in inhibition of cellular entry and replication of SARS-CoV-2, illustrated by a decrease of detectable SARS-CoV-2 subgenomic RNA (sgRNA) by approximately 2 logs compared to controls with complete absence in all animals at 3 days and 5 days post-challenge.
In control animals treated with the same lot of virus inoculum, nasal swabs reached a peak of approximately 10 million SARS-CoV-2 sgRNA copies within two days of viral challenge and were present throughout the course of the study. The absence of sgRNA indicates that the SARS-CoV-2 virus had not significantly infected nasal mucosa cells to start the transcription process of building new infectious virions. The absence of sgRNA following this very high viral inoculum also suggests the possibility of transmission may be substantially reduced after treatment with OC-01 (varenicline) nasal spray.
SARS-CoV-2 has been shown to predominantly enter the human body via nasal epithelial cells, specifically ciliated and mucous secreting cells of the nasal mucosa, according to studies conducted in 2020 and 2021. Therefore, the nasal cavity represents a highly susceptible mucosal surface for infection and amplification within the respiratory tree. The nasal cavity also allows for treatment with topical compounds that can be delivered in higher local concentrations with potentially lower systemic exposure that may not be achievable when administered as an oral tablet or IV infusion.
In a separate study, in collaboration with the Trudeau Institute, researchers evaluated the in vitro antiviral activity of varenicline against SARS-CoV-2 and SARS-CoV-2 alpha and beta variants using Calu-3 (human airway epithelial cells) and Caco-2 (colon epithelial cells) cell lines. “Varenicline has demonstrated potent antiviral activity against SARS-CoV-2 and variants, alpha and beta, in cell culture. The promising in vitro and in vivo data suggest a clinical path forward for OC-01, which could prove a potential treatment in preventing severe COVID-19 symptoms and the spread of infection. Further studies investigating the mechanism of action and its effect on other variants of concern, such as the gamma and delta variants are ongoing,” said Priya Luthra, PhD, Trudeau Institute Principal Investigator.
Additionally, OC-02 (simpinicline), a highly selective nicotinic acetylcholine receptor agonist was evaluated for in vitro antiviral activity against the SARS-CoV-2 alpha variant using Calu-3 cell lines. Simpinicline demonstrated potent antiviral activity against the SARS-CoV-2 variants in cell culture with an IC50 of 0.04 μM. Further studies investigating the antiviral effect on other variants of concern are ongoing.
Given the results of both the in vivo and in vitro studies, OC-01 (varenicline) nasal spray and OC-02 (simpinicline) nasal spray warrant further investigation as an antiviral agent for pre-exposure prophylaxis, post-exposure prophylaxis, and/or prevention of transmission of SARS- CoV-2. Additional in vivo and in vitro studies are ongoing.
OC-01 (varenicline) nasal spray and OC-02 (simpinicline) nasal spray have not been proven safe or effective to prevent SARS-CoV-2 infection or treat COVID-19 in humans nor has OC-01 (varenicline) or OC-02 (simpinicline) nasal spray been approved for any use by the U.S. Food and Drug Administration (FDA). The Prescription Drug User Fee Act (PDUFA) target action date for OC-01 (varenicline) nasal spray is October 17, 2021, with a planned U.S. launch in the fourth quarter of 2021, if approved by the FDA.
Oyster Point Pharma plans to present additional data at the upcoming Oyster Point Analyst Day, planned for July 15, 2021. Please use the following link to register for the Analyst Day (https://media.rampard.com/20210715/).