- Data published in Obesity journal show enhanced weight loss effect of NT-0796 when combined with semaglutide in preclinical obesity model
- Obese state completely reversed with 30% weight loss and reversal of hypothalamic inflammation
- NT-0796 sustained semaglutide-induced weight loss following cessation of semaglutide treatment
- NT-0796 uniquely positioned as an oral, well tolerated therapeutic to induce healthier and sustained weight loss, both as a monotherapy and in combination with GLP-1RAs
- Robust Phase 2 obesity study for NT-0796 initiating in 2Q 2025
Philadelphia, PA, April 30, 2025 – NodThera, a leading clinical-stage biotech delivering a paradigm shift in the treatment of chronic inflammatory diseases through selective modulation of the NLRP3 inflammasome, today announces the publication of preclinical data demonstrating the potential of its clinical-stage, oral NLRP3 inflammasome inhibitor NT-0796 to augment existing GLP-1 receptor agonist (GLP-1RA) obesity therapies to deliver enhanced weight loss and sustained weight management.
These data, published in the research journal Obesity, show that combined dosing of NodThera’s NT-0796 with semaglutide (Wegovy®) drove greater weight loss than either monotherapy in an animal model of obesity. Treatment with the fully brain-penetrating NLRP3 inflammasome inhibitor also sharply limited weight regain following the cessation of semaglutide therapy and reduced multiple cardiovascular, inflammatory and metabolic biomarkers.
Despite the significant achievements of GLP-1RAs in the management of obesity, their use is impacted by challenges related to tolerability and the weight regain following discontinuation of treatment. NodThera is pioneering a new approach to obesity treatment built on the growing understanding of the impact of chronic inflammation on the body and its underlying role in the complex cycle of weight regulation. These new data build on NodThera’s earlier preclinical and clinical work and support the potential of central NLRP3 inhibition to reset multiple dysregulated cardiometabolic pathways, restoring the body’s natural metabolic balance and enabling sustained and healthy weight loss.
Enhanced weight loss effects of NT-0796 and semaglutide in combination
In NodThera’s latest publication, the researchers show that weight loss induced by a combination of NT-0796 and semaglutide was nearly two-fold higher at 23% over 28 days compared to semaglutide monotherapy in a high fat diet murine obesity model. Weight loss was further enhanced on the combination therapy when animals were switched for a further 28 days to a polyunsaturated fatty acid diet, intended to be more reflective of a typical human diet. Animals receiving the combination therapy experienced continued weight loss, completely reversing their obese state, with a weight loss of >30% to achieve a weight comparable to animals fed a standard control diet. Hypothalamic (brain) inflammation was also reversed among animals maintained on the combination therapy.
Prevention of weight regain post-semaglutide treatment
In animals who were switched to NT-0796 monotherapy, following treatment with either semaglutide alone or the NT-0796 and semaglutide combination, the degree of weight regain was highly reduced compared to animals who stopped all therapy.
Potential of NLRP3 inhibition to enable a healthy weight loss
DEXA scans determined that combination therapy increased fat mass loss whilst preserving lean mass. Calorie intake was also further reduced in animals on the combination therapy, but the degree of fat mass loss observed suggests additional mechanisms, such as enhanced energy expenditure, may contribute. This supports a model consistent with the observed reduction in both peripheral and hypothalamic (brain) inflammation as a druggable mechanism in obesity pathogenesis.
Daniel Swisher, Chief Executive Officer of NodThera, commented: “These data further reinforce our belief in the potential of our brain-targeting NLRP3 inflammasome inhibitor to deliver a step change in the management of obesity. While the efficacy of existing treatments is not in doubt, there are many limitations and challenges to their real-world use by patients. The opportunity to provide patients with a highly effective oral therapy with a well-tolerated safety profile and without titration complexities is compelling and supported by our growing body of evidence indicating NT-0796’s potential as monotherapy and in combination to improve the efficacy and tolerability of existing treatments, or even as a follow-on therapy to sustain weight loss.”
Alan Watt, President and Chief Scientific Officer of NodThera, added: “By harnessing both peripheral and central NLRP3 inhibition to correct multiple dysregulated pathways in the brain and throughout the body we have the potential to bring profound cardiometabolic benefits to patients, establishing an enhanced treatment approach to weight management that would enable sustained and healthier weight loss.”
NodThera is currently preparing to initiate a robust Phase 2 obesity study of NT-0796, expected in 2Q 2025. Details about the trial’s design will be communicated upon initiation of dosing.
For more information about NodThera please contact:
NodThera
Tel: +44 (0) 1223 608130
Email: info@nodthera.com
ICR Healthcare
Amber Fennell, David Daley
Tel: +44 (0)20 3709 5700
Email: nodthera@icrhealthcare.com
About NodThera
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 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 high brain penetration, 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 Philadelphia, Pennsylvania, with additional operations in Cambridge, UK. Learn more at www.nodthera.com or follow the Company on LinkedIn.
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