NodThera's NLRP3 Inhibitor Promising in Phase 1b/2a Obesity Trial

NodThera's NLRP3 inhibitor has shown promise in tackling obesity and inflammation. In a recent phase 1b/2a trial, patients with obesity and elevated levels of C-reactive protein (CRP)—a biomarker for chronic inflammatory diseases like coronary artery disease—were treated with NT-0796 or a placebo over a span of 28 days. The trial results revealed a significant reduction in CRP levels among those who received NT-0796 compared to the placebo group, achieving the study's primary goal.

A notable aspect of the trial was that over 75% of the patients in the NT-0796 group experienced a CRP reduction of 2mg/L or more, a level associated with decreased cardiovascular risk. In contrast, fewer than 25% of the placebo group achieved this threshold. Additionally, the study observed reductions in other pro-inflammatory and cardiometabolic biomarkers, extending the findings from mouse weight loss studies and a phase 1b/2a study in Parkinson’s disease patients.

Both the active and placebo groups saw weight loss due to calorie restriction, yet the NT-0796 cohort, especially those at higher risk, exhibited more significant placebo-adjusted weight reductions. These findings, coupled with earlier preclinical data, underscore the anti-obesity potential of NT-0796.

Building on these encouraging results, NodThera is preparing for a 26-week phase 2 study focused on obesity, alongside other mid-stage trials targeting a range of cardiometabolic diseases and Parkinson’s disease. Earlier in the year, preclinical studies in mice indicated that NT-0796 could induce weight loss almost on par with Wegovy, a notable obesity treatment. Researchers highlighted that NLRP3 inhibitors have a unique advantage over GLP-1 receptor agonists in halting cellular inflammatory responses triggered by obesity-related molecular patterns.

In a recent phase 1b/2a study concerning Parkinson’s patients, NT-0796 led to average reductions in key pro-inflammatory biomarkers, supporting its broad therapeutic potential. NodThera's President and Chief Scientific Officer, Alan Watt, Ph.D., characterized the recent findings as "an impressive data set" achieved within just 28 days. He emphasized that the data not only confirmed the compound's significant anti-neuroinflammatory effects in Parkinson’s disease patients but also demonstrated improvements in inflammatory and metabolic biomarkers indicative of cardiovascular risk. These benefits appear to surpass those seen with antibody and peptide therapies.

Watt further highlighted that the body weight reductions observed in the study are likely to be more pronounced with prolonged dosing. This positions NT-0796 as a promising therapeutic candidate for various chronic inflammatory conditions.