Nod Sera Co., Ltd.
(“NodThera” or “we”)
NodThera presents preclinical data demonstrating reversal of obesity and inflammation with clinical-stage brain-penetrating NLRP3 inflammasome inhibitor
-
Data published in Journal of Pharmacology and Experimental Therapeutics
-
NodThera’s brain-penetrant NLRP3 inhibitor matched weight loss with the GLP-1 receptor agonist semaglutide (Wegovy®) or caloric restriction, while enhancing improvements in disease-related biomarkers of cardiovascular inflammation and lipid metabolism .
-
Study showing that NLRP3 activation in the brain is involved in promoting obesity shows that obesity can be reversed with brain-penetrating NLRP3 inhibitors
-
Furthermore, the combination of NLRP3 inhibitors and GLP-1 receptor agonists has been shown to be additive in weight loss in as yet unpublished data.
-
NodThera’s lead candidate NT-0796 is currently in Phase Ib/IIa development for cardiometabolic diseases and Parkinson’s disease.
Boston, Massachusetts, February 19, 2024 – NodThera, a leading clinical-stage biotech developing brain-penetrating NLRP3 inhibitors to treat chronic inflammatory diseases, today announced that its clinical-stage investigational compound has been shown to improve diet-induced obesity (DIO) and inflammation in animal models. announced the presentation of preclinical data demonstrating that it reverses the disease.
The data is published below. Journal of Pharmacology and Experimental Therapeutics In a paper entitled “Reversal of high-fat diet-induced obesity, systemic inflammation and astrogliosis by the NLRP3 inflammasome inhibitors NT-0249 and NT-0796”1.
The NLRP3 inflammasome is a highly validated anti-inflammatory drug target, and these findings indicate that NLRP3 plays an important role in the control of obesity and obesity-associated inflammation through the regulation of hypothalamic gliosis. Masu. NodThera’s two structurally distinct NLRP3 inhibitors in clinical development, NT-0796 and NT-0249, have both generated extensive preclinical and clinical data demonstrating brain penetration and broad anti-inflammatory effects NT-0796 has been shown to reduce neuroinflammation in the clinic.
In this latest publication, NodThera researchers demonstrate for the first time the ability of NT-0796 and NT-0249 to reverse DIO in a mouse model and compare the effects of the GLP-1 receptor agonist (GLP-1RA) semaglutide. We offer a comparison of (Wegovy ®) and calorie restriction. All three treatment approaches statistically significantly reduced body fat in DIO mice, but only one reduced disease-associated cardiovascular inflammatory biomarkers such as fibrinogen, sVCAM-1, suPAR, and PCSK9. NLRP3 inhibitors alone, suggesting that they may further reduce cardiovascular risk in DIO mice. Obese population. NodThera further considered alternative treatment scenarios where NLRP3 inhibitors could be used in combination with her GLP1-RAs or as follow-on therapy for patients who are intolerant to GLP-1RA drugs. Unpublished preclinical findings indicate that the combination of brain-penetrant NLRP3 inhibitors and low-dose GLP-1RAs has an additive weight loss effect, and that administration of brain-penetrant NLPR3 significantly lowers his body weight after discontinuation of GLP-1RA therapy. Stable weight maintenance was demonstrated. Inhibitors prevent weight regain.
Obesity is a global health concern and increases susceptibility to chronic diseases such as diabetes and diabetes.
It causes cardiovascular disease, at least in part, by promoting systemic inflammation.
Alan Watt, CEO of NodThera, said: “These remarkable findings are the first in the field of NLRP3 inflammasome research, and show that in obese mice fed a high-fat diet, brain-penetrating NLRP3 inhibition and the resulting anti-inflammatory effects Our results suggest that it not only reverses but also prolongs the metabolic effects.’ Although there is no doubt that GLP-1 receptor agonists have produced important results in the management of obesity, their adverse event profile is well established and poses challenges for some patients. Our brain-penetrant NLRP3 inhibitors deliver robust weight loss and broad cardiometabolic benefits by targeting a novel molecular mechanism with the convenience of oral administration and an excellent safety profile. An ongoing Phase IIa study in obese people at cardiovascular risk will further validate these preclinical findings. ”
References:
-
Reversal of high-fat diet-induced obesity, systemic inflammation, and astrogliosis by NLRP3 inflammasome inhibitors NT-0249 and NT-0796. Peter Thornton, Valerie Reader, Zofia Digby, Pamela Smolak, Nicola Lindsay, David Harrison, Nick Clarke, Alan P. Watt. Journal of Pharmacology and Experimental Therapeutics March 2024, 388 (3) 813-826; DOI: https://doi.org/10.1124/jpet.123.002013
For more information about NodThera, please contact:
Nod Sera
Phone number: +44 (0) 1223 608130
Email: info@nodthera.com
ICR concilium
Amber Fennell, David Daley, Skyna Virge
Phone number: +44 (0)20 3709 5700
Email: nodthera@consilium-comms.com
About Nodsera
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 combines a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise, and precision molecular chemistry. Its two main clinical candidates are oral small molecule NLRP3 inflammasome inhibitors, which are differentiated and potentially best-in-class drugs with pronounced anti-inflammatory effects and the ability to penetrate different regions of the brain. It has a demonstrated clinical profile and offers clear opportunities for multiple treatments. signs. The company is backed by top investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures, and Sofinnova Partners. NodThera is headquartered in Boston, Massachusetts, with additional operations in Cambridge, UK, and Seattle, Washington. For more information, please visit www.nodthera.com or follow us on LinkedIn.
