orziloben (SEFA-6179) / NorthSea Therap - LARVOL DELTA

SEFA-6179, An Engineered Medium-Chain Fatty Acid, Prevents the Progression of Biliary Fibrosis in a Murine Model of Primary Sclerosing Cholangitis (ACS-CLINCON 2025) - "We hypothesized that SEFA-6179 may reduce liver fibrosis in a murine model of PSC. Female Mdr2-/- C57Bl/6 mice received one of three treatments from 6 to 12 weeks of life via daily orogastric gavage: vehicle control (medium chain triglycerides; MCT), positive control (MBX-8025, selective PPAR-δ agonist, 10mg/kg), or SEFA-6179 at 3 doses (15, 35, 70mg/kg). Treatment with SEFA-6179 reduced liver fibrosis compared to vehicle and prevented the progression of fibrosis in a murine model of PSC. SEFA-6179 warrants further investigation as a potential therapeutic intervention to prevent disease progression and reduce the need for liver transplantation."

Preclinical • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • ABCB4

A medium-chain fatty acid analogue prevents endotoxin liver injury in a murine model. (PubMed, Sci Rep) - "SEFA-6179 is currently in Phase II clinical trials. These findings support the potential application of SEFA-6179 in high-risk, PN-dependent patients."

Biomarker • Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Hepatology • Infectious Disease • Inflammation • Liver Failure • Septic Shock • Short Bowel Syndrome • IL6 • TNFA

NorthSea Therapeutics Announces Expansion of Leadership Team with Key Industry Veteran Hires (Businesswire) - "Topline data from SEFA-1024 Phase 2a clinical trial in SHTG expected in 3Q 2025; Interim data from Orziloben Phase 2a clinical trial in IFALD expected by 1H 2026..."

P2a data • Hepatology • Severe Hypertriglyceridemia

An Engineered Medium-Chain Fatty Acid Analogue Protects against Lipopolysaccharide-Induced Liver Injury in a Murine Model of Intestinal Failure-Associated Liver Disease (Quick-Shot) (ACS-CLINCON 2024) - "SEFA-6179 pretreatment normalized liver enzymes and inflammatory marker (IL-6) compared to vehicle in a “two-hit” murine model of IFALD and LPS-induced inflammation. Based on this and previous data, SEFA-6179 is currently in a clinical trial in patients with IFALD."

Preclinical • Gastrointestinal Disorder • Hepatology • Infectious Disease • Inflammation • Liver Failure • Short Bowel Syndrome • IL6

An Engineered Medium-Chain Fatty Acid Analogue Protects Against Lipopolysaccharide-Induced Liver Injury in a Murine Model of Intestinal Failure-Associated Liver Disease (AAP-NCE 2024) - "Pre-treatment with SEFA-6179 normalized liver enzymes and reduced downstream pro-inflammatory cytokines, IL-6 and TNF-alpha, compared to vehicle in a "two-hit" murine model of PN-induced hepatosteatosis and LPS-induced inflammation. These findings have clinical implications for short bowel syndrome or otherwise PN-dependent patients who are at risk of both chronic hepatosteatosis and CLABSIs. Based in part on this work, SEFA-6179 is now in a Phase 2 clinical trial in patients with IFALD."

Preclinical • Gastrointestinal Disorder • Hepatology • Infectious Disease • Inflammation • Liver Failure • Pediatrics • Short Bowel Syndrome • IL6 • TNFA

A STRUCTURALLY ENGINEERED MEDIUM CHAIN FATTY ACID ANALOGUE AMELIORATES BILIARY FIBROSIS IN TWO MURINE MODELS OF PRIMARY SCLEROSING CHOLANGITIS (DDW 2024) - "In two murine models of primary sclerosing cholangitis with different mechanisms of liver injury, SEFA-6179 prevented the progression of liver fibrosis. Combined with our previous findings, SEFA-6179 ameliorates biliary fibrosis across multiple species and models, suggesting substantial translational potential."

Preclinical • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • ABCB4

A STRUCTURALLY ENGINEERED MEDIUM CHAIN FATTY ACID ANALOGUE AMELIORATES BILIARY FIBROSIS IN TWO MURINE MODELS OF PRIMARY SCLEROSING CHOLANGITIS (SSAT 2024) - "In two murine models of primary sclerosing cholangitis with different mechanisms of liver injury, SEFA-6179 prevented the progression of liver fibrosis. Combined with our previous findings, SEFA-6179 ameliorates biliary fibrosis across multiple species and models, suggesting substantial translational potential."

Preclinical • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • ABCB4

A Study of NST-6179 in Adult Subjects With Intestinal Failure-Associated Liver Disease (IFALD). (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: NorthSea Therapeutics B.V. | Not yet recruiting ➔ Recruiting | Phase classification: P2a ➔ P2 | Initiation date: Jun 2023 ➔ Jan 2024

Enrollment open • Phase classification • Trial initiation date • Hepatology • CRP

A medium-chain fatty acid analogue prevents hepatosteatosis and decreases inflammatory lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. (PubMed, PLoS One) - "SEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both β- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis."

Journal • Preclinical • Hepatology

Absorption of an Engineered Medium Chain Fatty Acid Analogue in Two Short Bowel Syndrome Minipig Models. (PubMed, JPEN J Parenter Enteral Nutr) - "In two SBS-IF minipig models, SEFA-6179 had substantially decreased absorption compared with pre-resection minipigs. Dose optimization for different intestinal anatomy and function may be required. We describe a new SBS-IF pseudojejunostomy model that may improve the translation of preclinical research to patients with SBS-IF who have enterostomies."

Journal • Gastrointestinal Disorder • Hepatology • Short Bowel Syndrome

A Study of NST-6179 in Adult Subjects With Intestinal Failure-Associated Liver Disease (IFALD). (clinicaltrials.gov) - P2a | N=36 | Not yet recruiting | Sponsor: NorthSea Therapeutics B.V.

New P2a trial • Hepatology • CRP

A medium chain fatty acid analogue prevents intestinal failure-associated liver disease in preterm Yorkshire piglets. (PubMed, Gastroenterology) - "In a preterm piglet model of IFALD, SEFA-6179 treatment prevented biochemical cholestasis and steatosis, and reduced bile duct proliferation and fibrosis. SEFA-6179 is a promising first-in-class therapy for the prevention and treatment of IFALD that will be investigated in an upcoming phase II clinical trial."

Journal • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Failure • PPARA

Study of NST-6179 in Healthy Subjects (clinicaltrials.gov) - P1 | N=70 | Completed | Sponsor: NorthSea Therapeutics B.V. | Recruiting ➔ Completed | Trial completion date: Jan 2023 ➔ May 2022

Trial completion • Trial completion date • Gastrointestinal Disorder • Hepatology • Short Bowel Syndrome

A STRUCTURALLY ENGINEERED FATTY ACID (SEFA-6179) PREVENTS CHOLESTASIS, STEATOSIS, AND FIBROSIS IN A PRETERM PIGLET MODEL OF INTESTINAL FAILURE-ASSOCIATED LIVER DISEASE (DDW 2022) - "SEFA-6179 prevents cholestasis, steatosis, and fibrosis in a preterm piglet model of IFALD. Based on the data presented above, SEFA-6179 has entered a Phase I clinical trial and is expected to begin a Phase II trial in Q1 2023."

Late-breaking abstract • Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Short Bowel Syndrome

NorthSea Therapeutics Initiates Phase 1 Trial of SEFA-6179, Targeting the Orphan Indication Intestinal Failure-Associated Liver Disease (Yahoo Finance) - "NorthSea Therapeutics B.V...announces it has initiated a Phase 1 study with SEFA-6179 in adult subjects, targeting the initial orphan indication of the treatment of IFALD...The final results are anticipated in Q3 2022 and will support the initiation of a global Phase 2 study in patients with IFALD, scheduled to start in Q1 2023."

New P2 trial • P1 data • Trial status • Gastrointestinal Disorder • Short Bowel Syndrome