zevaquenabant (INV-101) / Novo Nordisk - LARVOL DELTA

Structural mechanism of CB1R binding to peripheral and biased inverse agonists. (PubMed, Nat Commun) - "The peripherally restricted CB1R inverse agonists MRI-1867 and MRI-1891 represent a new generation of compounds that retain the metabolic benefits of CB1R inhibitors while sparing the negative psychiatric effects...These structures reveal how these compounds retain high affinity and specificity for CB1R's hydrophobic orthosteric site despite incorporating polar functionalities that lead to peripheral restriction. Further, the structure of the MRI-1891 complex along with accompanying molecular dynamics simulations shows how differential engagement with transmembrane helices and the proximal N-terminus can propagate through the receptor to contribute to biased inhibition of β-arrestin signaling."

Journal • Genetic Disorders • Obesity • Psychiatry

Circulating Anandamide is an Early Blood Biomarker of Progressive Hermansky-Pudlak Syndrome Pulmonary Fibrosis (ERS 2024) - "Importantly, Zevaquenabant administration starting at day 8 post bleomycin completely reversed elevated circulating AEA levels in pale ear mice and halted progression of fibrosis, suggesting its target engagement, inhibition of the CB1R system and therapeutic efficacy. In conclusion, circulating AEA may be a prognostic blood biomarker for PF in HPS-1 patients."

Biomarker • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

In vitro and in vivo pharmacokinetic characterization, chiral conversion and PBPK scaling towards human PK simulation of S-MRI-1867, a drug candidate for Hermansky-Pudlak syndrome pulmonary fibrosis. (PubMed, Biomed Pharmacother) - "Furthermore, we developed and validated a PBPK model that adequately fits the PK profiles of S-MRI-1867 in mice, rats, dogs, and monkeys using various dosing regimens. We employed this PBPK model to simulate the human PK profiles of S-MRI-1867, enabling us to inform human dose selection and support the advancement of this promising drug candidate in the treatment of HPSPF."

Journal • PK/PD data • Preclinical • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Inhalational Delivery of MRI-1867 (Zevaquenabant) as a Novel Therapeutic Modality in Pulmonary Fibrosis (ATS 2023) - "Pulmonary fibrosis was induced in mice by O.P. administration of bleomycin (1 U/kg b.w.). Pulmonary delivery of MRI-1867 is as effective as systemic delivery in mitigating PF, and it offers a more targeted therapeutic modality that could reinforce CNS safety by reducing the therapeutic dose range."

Late-breaking abstract • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

"Presenting how inhalation delivery of MRI-1867 (zevaquenabant) can be a better therapeutic modality in pulmonary fibrosis at ATS 2023. #ATS2023 @NIAAAnews @resatcinar" (@AbhishekBasu86)

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

INV-101, a cannabinoid receptor-1 inverse agonist, reduces fibrosis in a bleomycin mouse model of IPF (ERS 2022) - "Intro: INV-101 is a peripherally acting Cannabinoid receptor-1 inverse agonist under development for the treatment of Idiopathic Pulmonary Fibrosis (IPF). INV-101 reduced Ashcroft score in a manner similar to nintedanib. Further work to understand the potential role of this new generation CB-1 inverse agonist in treating pulmonary fibrosis is warranted."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology

Safety, Tolerability, and Pharmacokinetics of Single Ascending Oral Doses of INV-101 in Healthy Male and Female Subjects (clinicaltrials.gov) - P1; N=40; Completed; Sponsor: Inversago Pharma Inc.; Active, not recruiting ➔ Completed

Trial completion

Safety, Tolerability, and Pharmacokinetics of Single Ascending Oral Doses of INV-101 in Healthy Male and Female Subjects (clinicaltrials.gov) - P1; N=40; Active, not recruiting; Sponsor: Inversago Pharma Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Safety, Tolerability, and Pharmacokinetics of Single Ascending Oral Doses of INV-101 in Healthy Male and Female Subjects (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Inversago Pharma Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open