bofutrelvir (FB2001) / Frontier Biotech - LARVOL DELTA

Structural basis for varying drug resistance of SARS-CoV-2 Mpro E166 variants. (PubMed, mBio) - "Here, we report on crystal structures of SARS-CoV-2 Mpro E166V in complex with nirmatrelvir, ensitrelvir, and bofutrelvir...These studies shed light on the molecular mechanisms of a key Mpro drug resistance mutation and may help inform the design of next-generation inhibitors.IMPORTANCEUsing a combination of high-resolution X-ray crystallographic and biochemical analyses, we reveal the molecular mechanisms by which a mutation in the severe acute respiratory syndrome coronavirus 2 main protease (Mpro) confers strong resistance against clinically relevant antiviral drugs that inhibit Mpro activity. The results presented here may help inform the design of next-generation inhibitors to combat the problem of therapy resistance."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Inhibitory efficacy and structural insights of Bofutrelvir against SARS-CoV-2 Mpro mutants and MERS-CoV Mpro. (PubMed, Commun Biol) - "Structural analysis of the crystal complexes showed that changes in interactions at the S1 subsite in the mutants and the loss of hydrogen bonds at the S4 subsite in MERS-CoV Mpro are critical factors contributing to the diminished inhibitory activity. These insights reveal the necessity of ongoing structural analysis to adapt therapeutic strategies."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The zymogenic form of SARS-CoV-2 main protease: A discrete target for drug discovery. (PubMed, J Biol Chem) - "Additionally, we observed positive modulation of precursor activity at low concentrations of inhibitors. Our findings help expand understanding of the SARS-CoV-2 viral life cycle and may facilitate development of strategies to target preMpro for inhibition or premature activation of Mpro."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Structural basis of main proteases of coronavirus bound to Bofutrelvir. (PubMed, J Mol Biol) - "Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population...Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to Mpros from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the Mpro of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Development of Broad-Spectrum Antiviral Drugs (ICAR 2024) - "In addition, 2 antiviral drug candidates, FB2001(Bofutrelvir, an anti-COVID-19 drug candidate) and Thioraviroc (an anti-HIV drug candidate), have completed Phase I and entered Phase II or Phase III clinical studies...Prof. Liu has published 16 books as chapter author as well and obtained 137 patent certifications."

Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease

A Study of FB2001 for Inhalation in Healthy Chinese Adults (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Frontier Biotechnologies Inc. | Not yet recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19 (clinicaltrials.gov) - P2/3 | N=1336 | Recruiting | Sponsor: Frontier Biotechnologies Inc.

New P2/3 trial • Infectious Disease • Novel Coronavirus Disease

Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study) (clinicaltrials.gov) - P2/3 | N=1188 | Recruiting | Sponsor: Frontier Biotechnologies Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2023 ➔ Dec 2023 | Trial primary completion date: Mar 2023 ➔ Nov 2023

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

The Safety and Efficacy of FB2001 in Healthy Subjects and Patients With COVID-19 Infection (clinicaltrials.gov) - P1/2 | N=88 | Completed | Sponsor: Frontier Biotechnologies Inc. | Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

In vitro and in vivo evaluation of the main protease inhibitor FB2001 against SARS-CoV-2. (PubMed, Antiviral Res) - P1, P1/2, P2/3 | "Taken together, our study suggests that FB2001 is a promising therapeutic agent in COVID-19 treatment and can be combined with remdesivir to achieve improved clinical outcomes. Owing to its good safety and tolerability in healthy human (NCT05197179 and NCT04766931), FB2001 has been approved for Phase II/III clinical trial (NCT05445934)."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

A Study of FB2001 for Inhalation in Healthy Chinese Adults (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Frontier Biotechnologies Inc.

New P1 trial • Infectious Disease • Novel Coronavirus Disease

Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study) (clinicaltrials.gov) - P2/3 | N=1188 | Not yet recruiting | Sponsor: Frontier Biotechnologies Inc.

New P2/3 trial • Infectious Disease • Novel Coronavirus Disease

The Safety and Efficacy of FB2001 in Healthy Subjects and Patients With COVID-19 Infection (clinicaltrials.gov) - P1/2 | N=88 | Recruiting | Sponsor: Frontier Biotechnologies Inc. | Trial completion date: Mar 2022 ➔ Aug 2022 | Trial primary completion date: Feb 2022 ➔ Jul 2022

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Bridging Study of FB2001 in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Frontier Biotechnologies Inc. | Recruiting ➔ Completed | Trial completion date: Mar 2022 ➔ Jun 2022

Trial completion • Trial completion date • Infectious Disease • Novel Coronavirus Disease

Exploratory Study of Aerosol Inhalation of FB2001 for Post-exposure Prophylaxis of COVID-19 Close Contacts (clinicaltrials.gov) - P1/2 | N=60 | Not yet recruiting | Sponsor: Ruijin Hospital

New P1/2 trial • Infectious Disease • Novel Coronavirus Disease

A Bridging Study of FB2001 in Healthy Subjects (clinicaltrials.gov) - P1; N=32; Recruiting; Sponsor: Frontier Biotechnologies Inc.

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease

The Safety and Efficacy of FB2001 in Healthy Subjects and Patients With COVID-19 Infection (clinicaltrials.gov) - P1/2; N=72; Recruiting; Sponsor: Frontier Biotechnologies Inc.; N=32 ➔ 72; Trial completion date: Dec 2021 ➔ Mar 2022; Trial primary completion date: Aug 2021 ➔ Feb 2022

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The Safety and Efficacy of FB2001 in Healthy Subjects and Patients With COVID-19 Infection (clinicaltrials.gov) - P1/2; N=32; Recruiting; Sponsor: Frontier Biotechnologies Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The Safety and Efficacy of FB2001 in Healthy Subjects and Patients With COVID-19 Infection (clinicaltrials.gov) - P1/2; N=32; Not yet recruiting; Sponsor: Frontier Biotechnologies Inc.

Clinical • New P1/2 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases