PBI-4547 / Liminal BioSci - LARVOL DELTA

Randomized Controlled Trial Assessing PBI-4547's Impact on Glycemic Control, Diabetic Nephropathy, and Obesity in Type 2 Diabetes Mellitus Patients (ADA 2024) - "Oral PBI-4547 significantly improved glycemic control, lessened albuminuria, and induced weight loss in obese T2DM patients, indicating its potential as an all-encompassing diabetes therapy. Further large-scale, long-term studies are needed to verify these outcomes and determine its safety profile."

Clinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

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

Fatty acid mimetic PBI-4547 restores metabolic homeostasis via GPR84 in mice with non-alcoholic fatty liver disease. (PubMed, Sci Rep) - "In Gpr84 mice, PBI-4547 treatment failed to improve various key NAFLD-associated parameters, as was observed in wildtype littermates. Taken together, these results highlight a detrimental role for the GPR84 receptor in the context of meta-inflammation and suggest that GPR84 antagonism via PBI-4547 may reflect a novel treatment approach for NAFLD and its related complications."

Journal • Preclinical • Genetic Disorders • Hepatology • Immunology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

Single Ascending Dose Study of PBI-4547 in Healthy Subjects (clinicaltrials.gov) - P1; N=24; Terminated; Sponsor: ProMetic Pharma SMT Limited; N=40 ➔ 24; Trial completion date: Sep 2020 ➔ Oct 2019; Suspended ➔ Terminated; Trial primary completion date: Sep 2020 ➔ Oct 2019; PK data from first 3 cohorts does not support study continuation.There was no safety concerns

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination

PBI-4547 Improves Glucose Metabolism and Insulin Resistance, and Reduces Liver Damage in a High-Fat Diet Mouse Model of Obesity and Metabolic Syndrome (ADA 2018) - "Taken together, these results suggest that PBI-4547 offers the potential as a novel therapy for nonalcoholic fatty liver disease, obesity and associated metabolic syndrome."

Preclinical • Biosimilar • Diabetes • Fibrosis • Immunology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

Liminal Biosciences reports fourth quarter and 2019 year end results (Yahoo Finance) - "Liminal BioSciences Inc....today reported its financial results for the fourth quarter and year-ended December 31, 2019....Anticipated 2020 Milestones: Continued clinical development of...PBI-4547."

Clinical

Single Ascending Dose Study of PBI-4547 in Healthy Subjects (clinicaltrials.gov) - P1; N=40; Suspended; Sponsor: ProMetic Pharma SMT Limited; Trial completion date: Nov 2019 ➔ Sep 2020; Trial primary completion date: Nov 2019 ➔ Sep 2020

Clinical • Trial completion date • Trial primary completion date

Single Ascending Dose Study of PBI-4547 in Healthy Subjects (clinicaltrials.gov) - P1; N=40; Suspended; Sponsor: ProMetic Pharma SMT Limited; Recruiting ➔ Suspended

Trial suspension

PBI-4547 RESTORES METABOLIC HOMEOSTASIS IN A HIGH FAT DIET MODEL OF NON-ALCOHOLIC FATTY LIVER DISEASE: CROSS-TALK BETWEEN LIVER AND ADIPOSE TISSUES (AASLD 2019) - "These results indicate that PBI-4547 offers the potential as a novel therapy for NAFLD, diabetes and associated metabolic syndrome."

Single Ascending Dose Study of PBI-4547 in Healthy Subjects (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: ProMetic Pharma SMT Limited; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Single Ascending Dose Study of PBI-4547 in Healthy Subjects (clinicaltrials.gov) - P1; N=40; Not yet recruiting; Sponsor: ProMetic Pharma SMT Limited

Clinical • New P1 trial

Prometic reports financial results for second quarter 2019 (Yahoo Finance) - "'We are now focused on progressing the development of our novel products...PBI-4547 to address serious unmet patient needs in life threatening diseases...Current near-term priorities for the Company's leadership team are as follows: Initiation of Phase 1 clinical studies for PBI-4547."

New P1 trial

PBI-4547 Orchestrates a Cross Talk between Liver and White Adipose Tissues to Correct Metabolic Reprogramming (ADA 2019) - "These results indicate that PBI-4547 offers the potential as a novel therapy for NAFLD, diabetes and associated metabolic syndrome."

Late-breaking abstract

Oral treatment with PBI-4547 promotes beta-oxidation and energy expenditure, and reverses liver damage and white adipose tissue fibrosis in high-fat diet and ob/ob mouse models of NAFLD. (EASL-ILC 2019) - "PBI-4547 is a potential novel therapy for NAFLD, obesity, and associated metabolic syndrome. PBI-4547 decreases liver and WAT profibrotic markers, and promotes and energy expenditure."

Preclinical

Prometic reports fourth quarter and 2018 year-end financial results (PRNewswire) - "Prometic is planning a phase 1 clinical study for...PBI-4547. This study is also expected to commence before the end of 2019 following successful financing."

New P1 trial