pomotrelvir (PBI-0451) / Pardes Biosci - LARVOL DELTA

A novel cellular tool for screening human pan-coronavirus antivirals. (PubMed, Antiviral Res) - "We also compared two known 3C-like protease inhibitors and found that Nirmatrelvir is superior to Pomotrelvir in terms of pan-coronavirus antiviral activity. Furthermore, we tested 13 known antimalarial drugs and identified Halofantrine as having antiviral activity against SARS-CoV-2. Our findings suggest that this novel human cell model is a valuable and versatile tool for the screening and identification of pan-CoV antiviral drugs."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

PBI-0451 (Pomotrelvir) Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19 (clinicaltrials.gov) - P2 | N=242 | Terminated | Sponsor: Pardes Biosciences, Inc. | Active, not recruiting ➔ Terminated; Interim analysis concluded primary endpoint was not met

Trial termination • Infectious Disease • Novel Coronavirus Disease

Pomotrelvir and Nirmatrelvir Binding and Reactivity with SARS-CoV-2 Main Protease: Implications for Resistance Mechanisms from Computations. (PubMed, Angew Chem Int Ed Engl) - "Analysis of the chemical reaction to form the covalent complex has shown a similar reaction mechanism and activation free energies for pomotrelvir, nirmatrelvir and C2. We hope that these findings could be useful to design better inhibitors to fight present and future variants of SARS-CoV-2 virus."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 viral dynamics in a placebo-controlled phase 2 study of patients infected with the SARS-CoV-2 Omicron variant and treated with pomotrelvir. (PubMed, Microbiol Spectr) - "This is the first study to prospectively evaluate SARS-CoV-2 viral dynamics and the time to viral clearance in a significant number of patients using concurrently obtained results from an infectious virus assay, a rapid antigen test (RAT), and a qRT-PCR assay over a 15-day time course. These results suggest that a negative RAT assay is a good indicator of loss of infectious virus and the ability to return to normal activities."

Journal • P2 data • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Characterization of Pharmacokinetics, Biotransformation and Elimination of Pomotrelvir Orally Administered in Healthy Male Adults Using Two [C]-labeled Microtracers with Separate Labeling Positions. (PubMed, Drug Metab Dispos) - "The radioactive dose recovered in excreta was about 94% for both cohorts. While the two isotopomers of the radiolabeled-pomotrelvir showed no major differences in pharmacokinetics overall, they allowed for differential detection of their radiolabeled metabolites and appropriate characterization of their plasma exposure and excretion in urine and feces."

Journal • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Evaluation of in vitro antiviral activity of SARS-CoV-2 M inhibitor pomotrelvir and cross-resistance to nirmatrelvir resistance substitutions. (PubMed, Antimicrob Agents Chemother) - "The unprecedented scale of the COVID-19 pandemic and the rapid evolution of SARS-CoV-2 variants underscore the need for broadly active inhibitors with a high barrier to resistance. In a SARS-CoV-2 infection assay, pomotrelvir is additive when combined with remdesivir or molnupiravir, two nucleoside analogs targeting viral RNA synthesis. In conclusion, our results from the in vitro characterization of pomotrelvir antiviral activity support its further clinical development as an alternative COVID-19 therapeutic option."

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

A Comprehensive Evaluation in Clinic and PBPK Modeling and Simulation to Confirm Lack of CYP450 Mediated Drug-Drug Interaction Potential for Pomotrelvir. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The identified CYP3A4-mediated potential DDIs were evaluated clinically at a supratherapeutic dose of 1050 mg twice daily (BID) of pomotrelvir, including pomotrelvir co-administration with ritonavir (strong inhibitor of CYP3A4) or midazolam (sensitive substrate of CYP3A4)...To support the use of pomotrelvir in women of childbearing potential, the impact of pomotrelvir on the exposure of the representative oral hormonal contraceptive drugs ethinyl estradiol and levonorgestrel was assessed using the PBPK model...Therefore, pomotrelvir is not anticipated to have clinically meaningful DDIs at the clinical dose. These comprehensive in vitro, in clinic and in silico efforts indicate the DDI potential of pomotrelvir is minimal so excluding patients on concomitant medicines in clinical studies would not be required."

Journal • Infectious Disease • Novel Coronavirus Disease • CYP3A4

PBI-0451 (Pomotrelvir) Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19 (clinicaltrials.gov) - P2 | N=210 | Active, not recruiting | Sponsor: Pardes Biosciences, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2023 ➔ Jul 2023 | Trial primary completion date: Jan 2023 ➔ Jun 2023

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

MECHANISM AND RESISTANCE STUDIES OF SARS-CoV-2 MPRO INHIBITOR POMOTRELVIR (PBI-0451) (CROI 2023) - "PBI-0451 is a potent competitive inhibitor of SARS-CoV-2 Mpro and is broadly active against SARS-CoV-2 clinical isolates including omicron variants. Results from inhibitor interaction studies support the potential combination of pomotrelvir with remdesivir and molnupiravir but not nirmatrelvir. Enzymatic characterization of in vitro selected pomotrelvir resistant variants indicates they either confer no resistance or have reduced fitness."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19 (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Pardes Biosciences, Inc. | Trial completion date: Jun 2023 ➔ Jan 2023

Trial completion date • Infectious Disease • Novel Coronavirus Disease

PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19 (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Pardes Biosciences, Inc.

New P2 trial • Infectious Disease • Novel Coronavirus Disease

Study of PBI-0451 in Healthy Subjects. (clinicaltrials.gov) - P1 | N=130 | Completed | Sponsor: Pardes Biosciences, Inc. | Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

PBI-0451 AN ORALLY ADMINISTERED 3CL PROTEASE INHIBITOR OF SARS-CoV-2 FOR COVID-19 (CROI 2022) - "The effect of food and the potential for a drug-drug interaction (DDI) with ritonavir were also explored. PBI-0451 has shown favorable nonclinical properties and early clinical safety & PK that supports its continued evaluation as a stand-alone agent. Ongoing multiple-dose evaluation will further elucidate its clinical profile and inform the dose & dosing regimen selection for potential Phase 2/3 studies."

Late-breaking abstract • Cardiovascular • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of PBI-0451 in Healthy Subjects. (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Pardes Biosciences, Inc.; Trial completion date: Dec 2021 ➔ May 2022; Trial primary completion date: Nov 2021 ➔ Apr 2022

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

Study of PBI-0451 in Healthy Subjects. (clinicaltrials.gov) - P1; N=110; Recruiting; Sponsor: Pardes Biosciences, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease

Study of PBI-0451 in Healthy Subjects. (clinicaltrials.gov) - P1; N=110; Not yet recruiting; Sponsor: Pardes Biosciences, Inc.

New P1 trial • Infectious Disease • Novel Coronavirus Disease

Pardes Biosciences and FS Development Corp. II Announce Merger Agreement Creating Publicly Listed Biopharmaceutical Company Advancing Oral Antiviral Drugs to Treat and Prevent SARS-CoV-2 Infections (Businesswire) - "Pardes Biosciences, Inc....and FS Development Corp....have entered into a definitive merger agreement. Upon closing of the transaction, the company will be renamed 'Pardes Biosciences, Inc.' (Combined Company)...Proceeds from the transaction are expected to provide Pardes Biosciences with the capital needed to progress its lead product candidate, PBI-0451...Pending regulatory approval, the company anticipates initiating clinical trials later this year and plans to study PBI-0451 for prophylaxis and treatment of SARS-CoV-2 infections."

M&A • Infectious Disease • Novel Coronavirus Disease