fezagepras (PBI-4050) / Liminal BioSci, SRAM - LARVOL DELTA

A Comparative Study With ING-006, Nintedanib, Nerandomilast and Bexotegrast Using the In Vivo CAM-Patient-Derived IPF Model (ATS 2025) - "ING-006 also demonstrates superior inhibitory activity over fezagepras (formerly PBI-4050) in ZQ-16 stimulated-pErK lung fibroblasts as well as through inhibition of fibrotic gene expression. CAM-IPF is an efficient method to predict antifibrotic activity. Among other compounds currently used or under investigation for IPF treatment, ING-006 shows superior antifibrotic activity in fibroblasts and lung tissue xenografts from IPF patients, making it a promising candidate for IPF treatment."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • ACTA2 • COL1A1 • COL3A1 • CTGF • SERPINE1 • TGFB1

Human IPF lung tissue implanted on the chick chorioallantoic membrane as a novel in vivo model for antifibrotic drug testing (ICLAF 2022) - "Daily treatments of the xenografts with nintedanib and PBI-4050 significantly reduce their size, fibrosis-associated gene expression, and collagen deposition. Similar effects are found with GLPG1205 and fenofibric acid, two drugs that target the immune microenvironment. Our CAM-IPF model represents the first in vivo model of IPF that uses human lung tissue. This rapid and cost-effective assay could become a valuable tool for predicting the efficacy of antifibrotic drug candidates for IPF."

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

A Healthy Volunteer Study to Compare Fezagepras (PBI-4050) With Sodium Phenylbutyrate (clinicaltrials.gov) - P1 | N=8 | Terminated | Sponsor: Liminal BioSciences Ltd. | N=16 ➔ 8 | Recruiting ➔ Terminated; Sponsor has decided to discontinue development of fezegepras based on initial pharmacokinetic results

Enrollment change • Trial termination

Liminal BioSciences Announces Discontinuation of Fezagepras Development (PRNewswire) - "Liminal BioSciences...announced that it has discontinued development of fezagepras...based on results from the Phase 1a single ascending dose ('SAD') clinical trial, which indicated that fezagepras was significantly inferior compared to Sodium Phenylbutyrate as a nitrogen scavenger. The Phase 1a SAD clinical trial of fezagepras initiated in May 2022 was designed as a head-to-head comparison with Sodium Phenylbutyrate to provide us with further data to determine whether fezagepras was worth developing for one of the potential indications where nitrogen scavenging is beneficial. The recommendation to stop the development program for fezagepras was not based on safety concerns. 'We have come to this decisive, data driven conclusion early in Q3 in line with previously issued guidance.'...We look forward to updating the market on our expected milestones for our GPR84 and OXER1 antagonists' preclinical candidates targeting inflammatory, metabolic, and fibrotic conditions."

Discontinued • Idiopathic Pulmonary Fibrosis

"$LMNL Liminal BioSciences Announces Discontinuation of Fezagepras Development https://t.co/0mVa0n9huv" (@stock_titan)

Human Lung Tissue Implanted on the Chick Chorioallantoic Membrane as a Novel In Vivo Model of IPF. (PubMed, Am J Respir Cell Mol Biol) - "Daily treatments of the xenografts with nintedanib and PBI-4050 significantly reduce their size, fibrosis-associated gene expression, and collagen deposition. Similar effects are found with GLPG1205 and fenofibric acid, two drugs that target the immune microenvironment. Our CAM-IPF model represents the first in vivo model of IPF that uses human lung tissue. This rapid and cost-effective assay could become a valuable tool for predicting the efficacy of antifibrotic drug candidates for IPF."

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

A Healthy Volunteer Study to Compare Fezagepras (PBI-4050) With Sodium Phenylbutyrate (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Liminal BioSciences Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open

A Healthy Volunteer Study to Compare Fezagepras (PBI-4050) With Sodium Phenylbutyrate (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Liminal BioSciences Ltd.

New P1 trial

"$LMNL Liminal BioSciences Provides Update on Its Lead Drug Candidate Fezagepras https://t.co/X8cU9csIx1" (@stock_titan)

A Healthy Volunteer Study of PBI-4050 (clinicaltrials.gov) - P1; N=65; Completed; Sponsor: Liminal BioSciences Ltd.; Recruiting ➔ Completed; Trial completion date: Jun 2021 ➔ Oct 2021; Trial primary completion date: Jun 2021 ➔ Oct 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date • Fibrosis • Immunology • Inflammation

Liminal stops plan to advance fibrosis drug after seeing PK data (FierceBiotech) - "Liminal BioSciences has stopped plans to advance fezagepras in two indications after getting a look at interim pharmacokinetic results. The biotech had planned to move into a phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a phase 1b/2a study in hypertriglyceridemia next year...Liminal began a multiple-ascending dose study....Based on the full data, Liminal said it will 'determine the choice of any other potential indication(s) for further development of fezagepras.' Liminal is yet to share details of the pharmacokinetic profile seen in the study."

Discontinued • Hypertriglyceridemia • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

Liminal BioSciences Reports Fourth Quarter and Year End 2020 Financial Results (PRNewswire) - "...'We look forward to completing our phase 1 MAD study and are planning to advance our lead drug candidate, fezagepras, to enter later-stage clinical trials and believe our program prioritization positions us to capitalize on what we hope will be a pivotal year for the Company'...Anticipated initiation of a global Phase 2 clinical trial of fezagepras in patients with idiopathic pulmonary fibrosis (IPF) in the first half of 2022..."

New P2 trial • Trial status • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

Liminal BioSciences Provides Update on Business Strategy and Focus on Small Molecule Therapeutics (PRNewswire) - "Liminal BioSciences Inc....provided an update today regarding the Company's corporate strategy for its small molecule therapeutics and plasma-derived based therapeutics platforms....The Company has decided to re-focus its resources on its small molecule therapeutics business....'We believe that this change in our business strategy will allow us to focus our resources on the development of our lead product candidate fezagepras and our small molecule therapeutics drug discovery program and to become a more capital efficient organization'..."

Commercial • Cystic Fibrosis • Idiopathic Pulmonary Fibrosis • Systemic Sclerosis

Alström syndrome: an ultra-rare monogenic disorder as a model for insulin resistance, type 2 diabetes mellitus and obesity. (PubMed, Endocrine) - "Managing a rare disease requires not only medical care but also a support network including patient associations."

Journal • Review • Alstrom Syndrome • Cardiomyopathy • Cardiovascular • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inherited Retinal Dystrophy • Liver Failure • Metabolic Disorders • Obesity • Ophthalmology • Otorhinolaryngology • Rare Diseases • Retinitis Pigmentosa • Type 2 Diabetes Mellitus

Liminal BioSciences Announces First Subject Dosed in Phase 1 Multiple Ascending Dose Clinical Trial of Fezagepras (Canada Newswire) - "Liminal BioSciences Inc....today announced that the first subject has been dosed in the Company's fezagepras Phase 1 multiple ascending dose clinical trial in healthy volunteers. The new clinical trial is designed to look at more frequent daily dosing (twice and three times daily) of fezagepras up to 2,400mg for a total of 14 days....'We are conducting this clinical trial with fezagepras to help define the optimal dosing regimen that we expect to take forward into phase 2 clinical development in patients with idiopathic pulmonary fibrosis (IPF)', said Bruce Pritchard, Chief Executive Officer of Liminal BioSciences."

Trial status • Idiopathic Pulmonary Fibrosis

A Healthy Volunteer Study of PBI-4050 (clinicaltrials.gov) - P1; N=72; Recruiting; Sponsor: Liminal BioSciences Ltd.

Clinical • New P1 trial • Fibrosis • Immunology • Inflammation

Modulation of the G-Protein-Coupled Receptor 84 (GPR84) by Agonists and Antagonists. (PubMed, J Med Chem) - "Three GPR84 antagonists (S)-2-((1,4-dioxan-2-yl)methoxy)-9-(cyclopropylethynyl)-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one (GLPG1205), sodium 2-(3-pentylphenyl)acetate (PBI-4050), and sodium 2-(3,5-dipentylphenyl)acetate (PBI-4547) have displayed therapeutic effects in animal models of several inflammatory and fibrotic diseases and are being evaluated in clinical studies. Although GLPG1205 has failed in a clinical trial for ulcerative colitis, it is undergoing another phase II clinical study for idiopathic pulmonary fibrosis. Further studies are needed to resolve the GPR84 structure, identify more endogenous ligands, elucidate their physiological and pathological roles, and fulfill the therapeutic potential of GPR84 antagonists and agonists."

Journal • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Bowel Disease • Respiratory Diseases • Ulcerative Colitis

Liminal BioSciences Reports Third Quarter Financial Results (PRNewswire) - "Key Anticipated Milestones: Anticipated initiation of Phase 1 multiple ascending dose (MAD) trial in the United Kingdom of fezagepras in healthy volunteers in Q4-2020; Anticipated initiation of a global Phase 2b clinical trial of fezagepras in patients with idiopathic pulmonary fibrosis (IPF) in H2-2021."

New P1 trial • New P2b trial • Idiopathic Pulmonary Fibrosis

Recent Updates on Free Fatty Acid Receptor 1 (GPR-40) Agonists for the Treatment of Type 2 Diabetes Mellitus. (PubMed, Mini Rev Med Chem) - "The agonists of FFAR1/GRP40 showed considerable potential for the therapeutic control of T2DM. Most of the small molecule FFAR1/GPR40 agonists developed were aryl alkanoic acid derivatives (such as phenylpropionic acids, phenylacetic acids, phenoxyacetic acids and benzofuran acetic acid derivatives) and thiazolidinediones. Some natural/plant derived compounds including fatty acids, sesquiterpenes, phenolic compounds, anthocyanins, isoquinoline and indole alkaloids were also reported as potent FFAR1 agonists. The clinical investigations of the FFAR1 agonists had demonstrated their probable role in the improvement of glucose control. Though, there are some problems still to be resolved in this field since some FFAR1 agonists terminated in late phase of clinical studies due to "hepatotoxicity". Currently, PBI-4050 is under clinical investigation by Prometic. Furthermore, the more investigation of pharmacophore scaffolds for FFAR1 full agonists as well as..."

Journal • Diabetes • Hepatology • Metabolic Disorders • Type 2 Diabetes Mellitus

Open-Label Rollover Study of PBI 4050 in Subjects With Alström Syndrome (clinicaltrials.gov) - P2/3; N=10; Terminated; Sponsor: ProMetic BioSciences Inc.; Trial completion date: Sep 2020 ➔ May 2020; Active, not recruiting ➔ Terminated; Terminated early due to redeployment of study site staff during Covid-19 pandemic

Clinical • Trial completion date • Trial termination • Alstrom Syndrome

Liminal BioSciences Announces Private Placement Financing of USD$30 Million (PRNewswire) - "Liminal BioSciences Inc....announced that it has entered into a private placement led by an undisclosed leading U.S. public investment fund...providing for the purchase of approximately USD$30 million of its common shares, warrants to purchase common shares of the Company and pre-funded warrants to purchase common shares of the Company...The Company intends to use the net proceeds from this private placement, together with existing cash resources at September 30, 2020 of CAD$36.0 million, to primarily fund clinical development of fezagepras..."

Financing • Idiopathic Pulmonary Fibrosis

Discovery of 9-cyclopropylethynyl-2-((S)-1-[1,4]dioxan-2-ylmethoxy)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one (GLPG1205), a Unique GPR84 Negative Allosteric Modulator Undergoing Evaluation in a Phase II Clinical Trial. (PubMed, J Med Chem) - "As the only reported antagonist of GPR84 (PBI-4050) displays relatively low potency and selectivity, a clear need exists for an improved modulator. At once-daily doses of 3 and 10 mg/kg, GLPG1205 reduced disease activity index score and neutrophil infiltration in a mouse dextran sodium sulfate-induced chronic inflammatory bowel disease model, with efficacy similar to positive-control compound sulfasalazine. The drug discovery steps leading to GLPG1205 identification, currently under phase II clinical investigation, are described herein."

Clinical • Journal • P2 data • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

[VIRTUAL] PBI-4050 restores liver and adipose tissue metabolic homeostasis, and decreases fibrosis in a high-fat-diet mouse model of non-alcoholic fatty liver disease (EASL-ILC-I 2020) - "These results indicate that PBI-4050 offers the potential as a novel therapy for NAFLD, diabetes and associated metabolic syndrome."

Preclinical • Alstrom Syndrome • Diabetes • Fibrosis • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Non-alcoholic Fatty Liver Disease • Respiratory Diseases • COL1A1 • CTGF • MMP2 • TIMP1

[VIRTUAL] PBI-4050 promotes hepatic stellate cell deactivation by shifting energy metabolism (EASL-ILC-I 2020) - "These results indicate that PBI-4050 restores HSC quiescent-like phenotype by shifting energy metabolism towards FAO and could be a potential therapy for the treatment of liver fibrosis."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • CTGF • CXCL8 • PLIN2

PBI-4050 Reduces Pulmonary Hypertension, Lung fibrosis and Right Ventricular Dysfunction in Heart Failure. (PubMed, Cardiovasc Res) - "A contributing mechanism involves reducing the activation of lung fibroblasts by IL-6, TGF-β and ET-1 by antagonism of GPR84 and reduced ERK1/2 phosphorylation. PBI-4050 is a novel promising therapy for targeting lung remodelling in group II PH."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Myocardial Infarction • Pulmonary Arterial Hypertension