asapiprant (BGE-175) / BioAge Labs, Shionogi - LARVOL DELTA

The prostaglandin D2 antagonist asapiprant ameliorates clinical severity in young hosts infected with invasive Streptococcus pneumoniae. (PubMed, Infect Immun) - "Asapiprant-treated mice had enhanced antimicrobial activity in circulating neutrophils, elevated levels of reactive oxygen species (ROS) in lung macrophages/monocytes, and improved pulmonary barrier integrity indicated by significantly reduced diffusion of fluorescein isothiocyanate (FITC)-dextran from lungs into the circulation. These findings suggest that asapiprant protects the host against pneumococcal dissemination by enhancing the antimicrobial activity of immune cells and maintaining epithelial/endothelial barrier integrity in the lungs."

Journal • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Hospitalized Adults With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure (clinicaltrials.gov) - P2 | N=194 | Terminated | Sponsor: BioAge Labs, Inc. | Completed ➔ Terminated; The incidence of COVID-19 hospitalization cases decreased to a level that continued enrollment was no longer feasible

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

Efficacy of the DP1 receptor antagonist BGE-175 in mouse models of SARS-CoV and SARS-CoV-2 is associated with improved dendritic cell migration and reduced lung neutrophilia (OPTIONS XI 2022) - P2 | "BGE-175 is a clinical stage compound with an accumulated safety profile from 18 clinical studies and more than 2000 study participants. A Phase 2 study in hospitalized adults with COVID-19 is in progress (NCT04705597)."

Preclinical • Acute Respiratory Distress Syndrome • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Hospitalized Adults With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure (clinicaltrials.gov) - P2 | N=194 | Completed | Sponsor: BioAge Labs, Inc. | Recruiting ➔ Completed | N=312 ➔ 194 | Trial completion date: Sep 2022 ➔ Jun 2022 | Trial primary completion date: Sep 2022 ➔ Mar 2022

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

Eicosanoid signaling as a therapeutic target in middle-aged mice with severe COVID-19 (IMMUNOLOGY 2022) - "Further, treatment with a PTGDR antagonist, Asapiprant, protected aged mice from lethal infection. PTGDR antagonism is one of the first interventions in SARS-CoV-2-infected animals that specifically protects aged animals, suggesting that the PLA2G2D-PGD2/PTGDR pathway is a useful target for therapeutic interventions."

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

Eicosanoid signaling blockade protects middle-aged mice from severe COVID-19. (PubMed, Nature) - "Further, treatment with a PTGDR antagonist, asapiprant, protected aged mice from lethal infection. PTGDR antagonism is one of the first interventions in SARS-CoV-2-infected animals that specifically protects aged animals, suggesting that the PLAG2D-PGD/PTGDR pathway is a useful target for therapeutic interventions."

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

Machine learning-driven identification of drugs inhibiting cytochrome P450 2C9. (PubMed, PLoS Comput Biol) - "We experimentally validated the developed approach and provided the first identification of the drugs vatalanib, piriqualone, ticagrelor and cloperidone as strong inhibitors of CYP2C9 with IC values <18 μM and sertindole, asapiprant, duvelisib and dasatinib as moderate inhibitors with IC50 values between 40 and 85 μM. Metabolism assays allowed the characterization of specific metabolites of abemaciclib, cloperidone, vatalanib and tarafenacin produced by CYP2C9. The obtained results demonstrate that such a strategy could improve the prediction of drug-drug interactions in clinical practice and could be utilized to prioritize drug candidates in drug discovery pipelines."

Journal • CYP2C9

Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Hospitalized Adults With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure (clinicaltrials.gov) - P2; N=312; Recruiting; Sponsor: BioAge Labs, Inc.; N=132 ➔ 312; Trial completion date: Nov 2021 ➔ Sep 2022; Trial primary completion date: Nov 2021 ➔ Sep 2022

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

Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Participants ≥ 60 Years of Age and Hospitalized With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure (clinicaltrials.gov) - P2; N=132; Recruiting; Sponsor: BioAge Labs, Inc.; Trial primary completion date: May 2021 ➔ Sep 2021

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

BioAge’s Phase 2 trial to reverse immune aging - P2, N=132; "'We have shown that BGE-175 can dramatically improve outcomes in mouse models of COVID-19,' says Dr Perlman. 'Because some of the rapidly spreading variants of SARS-CoV-2 are vaccine-resistant, it is critically important to develop COVID-19 treatments, like BGE-175, that are likely to be equally effective against infections with these more contagious and potentially more lethal strains.'"

Clinical data • Media quote

BioAge Initiates Phase 2 Trial of BGE-175 to Treat COVID-19 by Reversing Immune Aging, a Key Cause of Morbidity and Mortality in Older Patients (Businesswire) - "BioAge Labs, Inc....announced that it has commenced a Phase 2 clinical trial of BGE-175...for treating COVID-19 patients aged 60 or older. Top-line results are expected in 2021....'DP1 signaling becomes dysregulated with aging and adversely affects the immune response of older animals to SARS-CoV-2 and other viral challenges. We have shown that BGE-175 can dramatically improve outcomes in mouse models of COVID-19,' said Dr. Perlman....The randomized, placebo-controlled, parallel-group, multicenter, double-blind study will recruit patients ≥ 60 years old hospitalized for COVID-19 who are not yet in respiratory failure. A total of 132 participants will receive daily doses of BGE-175 or placebo (66 in each group) for up to 14 days."

Media quote • P2 data • Trial status • Infectious Disease • Novel Coronavirus Disease

Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Participants ≥ 60 Years of Age and Hospitalized With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure (clinicaltrials.gov) - P2; N=132; Recruiting; Sponsor: BioAge Labs, Inc.; Not yet recruiting ➔ Recruiting; Trial completion date: Apr 2022 ➔ Sep 2021; Trial primary completion date: Feb 2022 ➔ May 2021

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

Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Participants ≥ 60 Years of Age and Hospitalized With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure (clinicaltrials.gov) - P2; N=132; Not yet recruiting; Sponsor: BioAge Labs, Inc.

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • PCR