NT-0249 / NodThera - LARVOL DELTA

NLRP3 Inhibitor, NT-0796 Reduces MASH in Preclinical Models (OBESITY WEEK 2025) - "Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796...The Farnesoid X receptor agonist, Tropifexor, (0.5 mg, p.o. q.d.) was evaluated alongside... These findings indicate that NLRP3 inhibition with NT-0796 reduces key MASH-associated pathologies, including hepatic steatosis and fibrosis. Targeting hepatic NLRP3 may offer added therapeutic benefit for individuals at risk of MASH. Further translational studies are needed to explore the extent to which these mechanisms(s) may contribute to liver disease in patient cohorts."

Preclinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • NLRP3

Pharmacological Analysis of NLRP3 Inflammasome Inhibitor Sodium [(1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl][(1-methyl-1H-pyrazol-4-yl)({[(2S)-oxolan-2-yl]methyl})sulfamoyl]azanide in Cellular and Mouse Models of Inflammation Provides a Translational Framework. (PubMed, ACS Pharmacol Transl Sci) - "Significantly, NT-0249 decreased mature IL-1β levels in tissue homogenates, confirming in vivo target engagement. Our findings highlight not only the pharmacological attributes of NT-0249 but also provide insight into the extent of target suppression that will be required to achieve clinical benefit."

Journal • Preclinical • Infectious Disease • Inflammation • Targeted Protein Degradation • IL1B • NLRP3

NodThera Publishes Preclinical Data Demonstrating Reversal of Obesity and Inflammation with Clinical-stage Brain-penetrant NLRP3 Inflammasome Inhibitors (GlobeNewswire) - "NodThera...today announces the publication of preclinical data demonstrating its clinical-stage investigational compounds reversed diet-induced obesity (DIO) and inflammation in an animal model of disease....In this latest publication, NodThera’s researchers show for the first time the ability of NT-0796 and NT-0249 to reverse DIO in a murine model, providing comparisons against the effects of the GLP-1 receptor agonist (GLP-1RA) semaglutide (Wegovy) and calorie restriction. While all three therapeutic approaches led to statistically significant reductions in body fat in DIO mice, only the NLRP3 inhibitors reduced disease-relevant cardiovascular inflammatory biomarkers such as fibrinogen, sVCAM-1, suPAR, and PCSK9, suggesting their potential to further reduce cardiovascular risk in obese populations."

Preclinical • Metabolic Disorders • Obesity

Reversal of high fat diet-induced obesity, systemic inflammation and astrogliosis by the NLRP3 inflammasome inhibitors NT-0249 and NT-0796. (PubMed, J Pharmacol Exp Ther) - "In addition, a direct comparison of an NLRP3 inhibitor to a GLP-1 receptor agonist, semaglutide (Wegovy®), in the DIO model allowed an appreciation of the relative efficacy of these two therapeutic strategies on obesity, its associated systemic inflammatory response and cerebral gliosis. We report that in mice fed a high-fat, obesogenic diet, obesity is reversed by either of two inhibitors of the intracellular inflammatory mediator, NLRP3. Furthermore, NLRP3 inhibition reduces both hypothalamic gliosis and circulating biomarkers of cardiovascular disease risk beyond what can be achieved by either the GLP-1 agonist semaglutide or calorie restriction alone."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Obesity • Systemic Inflammatory Response Syndrome • FAP • GFAP • NLRP3

NodThera announces positive first-in-human data for two brain penetrant NLRP3 inflammasome inhibitors (GlobeNewswire) - P1 | N=NA | "NodThera...today announces positive data from first-in-human studies of its lead therapeutic candidates, NT-0249 and NT-0796, and provides an update on the Company’s priority clinical development programme. In the studies, both candidates were shown to clearly inhibit the NLRP3 inflammasome, a highly validated drug target that plays a pivotal role in controlling inflammatory diseases. The differentiated design characteristics of each candidate enabled them to penetrate different areas of the brain for optimal drug distribution in a range of NLRP3-driven diseases....Data from the recently completed multiple-ascending dose (MAD) cohorts of NT-0249’s first-in-human study confirm a potentially best-in-class pharmacokinetic/ pharmacodynamic (PK/PD) profile, suitable for once-daily dosing. NT-0249 demonstrated significant anti-inflammatory effects in healthy volunteers, with reductions in key inflammatory biomarkers, C-reactive protein (CRP) and fibrinogen..."

P1 data • CNS Disorders • Immunology • Inflammation • Parkinson's Disease