NodThera’s NLRP3 Inhibitor Meets Primary Endpoint of Inflammation Reversal in Phase 1b/2a Trial in Obese Subjects With Cardiovascular Risk

NodThera recently announced positive data from its Phase 1b/2a cardiovascular risk study in inflamed obese subjects, evaluating the effects of its oral, brain-penetrant NLRP3 inflammasome inhibitor NT-0796, on inflammatory, cardiovascular and metabolic risk parameters.

Obese subjects with elevated baseline C-reactive protein (CRP), measured using an hsCRP assay, were recruited. Elevated CRP is a key marker of chronic inflammatory diseases such as coronary artery disease, and one or more cardiovascular risk factors (eg, metabolic syndrome, prediabetes, diabetes, hyperlipidemia or hypertension). The study was conducted in-clinic for 28 days and energy intake was limited to 2000 kCal per day. At study end, a highly statistically significant and rapid CRP reduction in NT-0796 dosed subjects was observed compared to placebo, meeting the primary endpoint of the study. Furthermore, more than 75% of NT-0796 dosed subjects achieved a CRP reduction at day 28 to ≤2mg/L compared to less than 25% among the placebo group, a value generally regarded as a threshold for reducing cardiovascular risk.

NodThera’s study also demonstrated reductions in additional pro-inflammatory and cardiometabolic biomarkers, secondary endpoints that build on the previously reported diet-induced obesity preclinical study and Phase 1b/2a Parkinson’s disease clinical study. Key reductions in cardiovascular and metabolic biomarkers were found to be highly translatable and consistent with the importance of targeting both brain and peripheral NLRP3. While all subjects lost weight due to calorie restriction in both the active and placebo groups, the most pronounced placebo-adjusted reductions in body weight were among high-risk subgroups of NT-0796 dosed subjects, and, with the Company’s earlier preclinical data, support the anti-obesity potential of the molecule.

Preparations are underway for a Phase 2 study in obesity and other Phase 2 studies including additional cardiometabolic diseases and Parkinson’s disease.

Alan Watt, President & Chief Scientific Officer of NodThera, said “This is an impressive data set, made all the more remarkable by being achieved within 28 days. In addition to the profound anti-neuroinflammatory effects in Parkinson’s disease patients demonstrated previously, the data generated in this study of NT-0796 show improvements in inflammatory and metabolic biomarkers of CV risk that go beyond that seen with antibody and peptide therapies. With additional reductions in body weight that should be enhanced with longer-duration dosing, NT-0796 is confirmed as a highly promising therapeutic agent for chronic inflammatory indications.”

As before, NT-0796 was generally safe and well tolerated; adverse events (AEs) were mainly mild and transient, and no serious adverse events (SAEs) were observed.

Taken together, the findings demonstrate that NT-0796 successfully delivered anti-inflammatory changes in an obese inflamed population, amelioration of cardiometabolic risk factors and reductions in body weight within 28 days, indicating excellent potential for long-term, oral dosing in obese subjects.

NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision molecular chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and the ability to penetrate different areas of the brain, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Boston, MA, with additional operations in Cambridge, UK and Seattle, WA. For more information, visit www.nodthera.com.