There is evidence that NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-driven mechanisms may drive both peripheral and hypothalamic inflammation in preclinical obesity. NLRP3 inflammasome activation has been tied to the pathogenesis of obesity-related metabolic syndrome and its progression.
After delivering animal data to show that inhibiting the NLRP3 inflammasome induces weight loss in mice, Nodthera Ltd. has now demonstrated this effect translates to humans. In a phase Ib/II study of NT-0796, an orally available, brain-penetrant drug, subjects in both the active and placebo arms all lost weight, due to the calorie-restricted diet they received in the 28-day trial.
Aberrant NLRP3 inflammasome activation is at the root of a wide number of conditions, from heart, gastrointestinal, kidney or liver disorders to neuroinflammatory diseases such as Parkinson’s disease or multiple sclerosis. Researchers from Nodthera Ltd. have reported on NT-0796, an NLRP3 inflammasome inhibitor with an in vivo brain penetration profile.
Nodthera Ltd. claims to be first to demonstrate it is possible to modulate the NLRP3 inflammasome in the brain, after showing there were reductions in inflammatory and disease-specific biomarkers in blood and cerebrospinal fluid after seven days of daily administration of its lead product, NT-0796, an oral NLRP3 inhibitor.
LONDON – With results of its first phase I trial imminent, inflammasome specialist Nodthera Ltd. has raised $55 million in a series B round, providing funding for phase II proof-of-concept studies and to advance a second, brain-penetrant, compound to the clinic.
