NodThera Announces First Patients Dosed in RESOLVE-2 Clinical Trial Evaluating Oral NT-0796 in Combination with a GLP-1 Receptor Agonist

• NT-0796 is an oral, brain-penetrant NLRP3 inhibitor that selectively regulates chronic inflammation, a key driver of cardiometabolic diseases
• Expects to complete the ongoing NT-0796 monotherapy trial (RESOLVE-1) and NT-0796 combination trial with GLP-1 receptor agonist (RESOLVE-2) by 3Q 2026

BOSTON, Oct. 27, 2025 (GLOBE NEWSWIRE) -- NodThera, a clinical-stage biotech pioneering a paradigm shift in the treatment of chronic inflammatory diseases through NLRP3 inhibition, today announced that the first patients have been dosed in its Phase 2 RESOLVE-2 clinical trial (RESolution Of infLammation to treat obesity and cardioVascular disEase) investigating NT-0796, its oral, brain-penetrant NLRP3 inhibitor, in combination with the GLP-1 receptor agonist (GLP-1RA) semaglutide.

“RESOLVE-2 study is a key component of our strategy to develop NT-0796 as a transformative cardiometabolic therapy, as we believe NT-0796 has the potential to reduce cardiovascular risk, to improve metabolic health, and to reduce the burden of related comorbidities,” said Dr. Jyothis George, M.D., Ph.D., FRCP, FACE, Chief Medical Officer of NodThera. “Through our clinical plans, including multiple Phase 2 studies evaluating NT-0796 across cardiometabolic diseases, which will be the longest trials to date for any NLRP3 inhibitor, we seek to reproduce compelling improvements on a range of parameters like IL-6, fibrinogen and hsCRP which reduced rapidly by approximately 80% in patients at high cardiovascular risk.”

RESOLVE-2 is a randomized, double-blind, placebo-controlled Phase 2 clinical trial that will evaluate the safety and efficacy of NT-0796 in combination with GLP-1RA. The trial is expected to enroll approximately 60 people living with obesity, all of whom will receive GLP-1RA, with one half randomized to NT-0796 and the other half to placebo (ClinicalTrials.gov NCT07220629). Similar to RESOLVE-1, the ongoing randomized, double-blind, placebo-controlled Phase 2 clinical trial of NT-0796 monotherapy, endpoints in RESOLVE-2 include changes multiple inflammatory and metabolic biomarkers, safety, tolerability and change in body weight. NodThera expects to complete both trials in 3Q 2026.

"Addressing chronic inflammation in the brain and body remains a substantial unmet need for patients with cardiometabolic diseases," said Melanie Davies, Professor of Diabetes, Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre. “NT-0796 has so far demonstrated a unique ability to target the root cause of obesity and related diseases by reducing residual inflammation. I look forward to RESOLVE-2’s readout next year.”

About NT-0796

NT-0796 is an oral, brain-penetrant NLRP3 inhibitor that selectively regulates chronic inflammation, with an excellent tolerability profile. It is being developed to address the spectrum of cardiometabolic disorders including atherosclerotic cardiovascular disease risk reduction and management of body weight. Clinical data from NodThera’s study in people living with obesity and increased cardiovascular risk demonstrated NT-0796’s anti-inflammatory effect, reducing multiple markers of cardiometabolic risk including high sensitivity CRP reductions comparable to injectable biologics blocking IL-1 and IL-6. In addition, NodThera has published clinical data showing rapid reduction in neuroinflammation, concordant with reductions in peripheral inflammation.

For reduction or maintenance of weight, NT-0796’s mechanism aims to resolve hypothalamic inflammation, thereby restoring multiple dysregulated pathways in obesity, and resetting the body’s set point to defend fat mass. In clinical studies to date, NT-0796 has demonstrated a robust safety and tolerability profile, with no gastrointestinal side effects reported. Preclinical data published in the Journal of Pharmacology and Experimental Therapeutics demonstrate how NLRP3 inhibition has the potential to reverse diet-induced obesity and inflammation, matching weight loss driven by the GLP-1RA semaglutide as a monotherapy. Additionally, in preclinical data published in the journal Obesity, NT-0796’s effect on weight loss was enhanced when combined with semaglutide.

NT-0796 is currently being investigated in two Phase 2 trials in patients living with obesity, as a monotherapy in the RESOLVE-1 trial (ClinicalTrials.gov NCT07055516), including patients with and without type 2 diabetes, and in combination with GLP-1 receptor agonists in the RESOLVE-2 trial (Clinicaltrials.gov NCT07220629).

About NLRP3

NLRP3 activation mediates the release of proinflammatory cytokines, including IL-1β, IL-18 and IL-6, driving chronic inflammation in cardiometabolic, neurological and other diseases. NLRP3 Inhibition offers an alternative approach to therapeutic blockade of individual cytokines like IL-1β, IL-18 and IL-6.

About NodThera

NodThera, a US and UK based biotech developing best-in-class NLRP3 inhibitors, is pioneering a paradigm shift in the treatment of diseases driven by chronic inflammation. NodThera has built an advanced pipeline of multiple clinical-stage small-molecule NLRP3 inhibitors. Compelling first-in-class clinical data, including in patients with cardiometabolic and neurological diseases, is fuelling rapid clinical development towards multiple approvals.  

NodThera 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, Massachusetts, with R&D base in the UK. Learn more at www.nodthera.com or follow the Company on LinkedIn.

Investors and Media
Argot Partners
nodthera@argotpartners.com    

Legal Disclaimer:

EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.