Clinical biotech Rezera (formerly NodThera Inc.) has reported positive topline findings from a Phase 2 study of ruvonoflast, an oral NLRP3 inhibitor being developed for inflammatory cardiovascular and neurologic diseases, clearing the way for the program to move toward Phase 3 development in peripheral artery disease (PAD).

In the RESOLVE-1 trial, ruvonoflast achieved its primary endpoint by reducing high-sensitivity C-reactive protein (hsCRP), a biomarker of systemic inflammation, through 24 weeks of treatment. The company is now targeting the first half of 2027 to begin a Phase 3 PAD study after reaching agreement with regulators on key elements of the trial design. Full RESOLVE-1 results are expected to be presented at a medical conference in the fourth quarter of 2026. RESOLVE-1 was designed as a randomized, double-blind, placebo-controlled Phase 2 trial enrolling participants both with and without type 2 diabetes.

Two ruvonoflast dosing regimens were evaluated: 150 mg once daily and 150 mg twice daily. Both dosing groups demonstrated reductions in hsCRP compared with placebo through Week 24. Importantly, the study was not specifically enriched for participants with elevated hsCRP at baseline. According to Rezera, reductions were nevertheless observed across participants with and without type 2 diabetes, suggesting that the drug’s anti-inflammatory activity could potentially extend across a broad cardiometabolic population.

The findings build on earlier clinical data in patients with elevated cardiovascular risk and substantial inflammatory burden, in which ruvonoflast produced an 82% reduction in hsCRP after four weeks of treatment. Together, the data indicate dose-dependent activity and provide the company with a clinical basis for evaluating doses as high as 450 mg per day in later-stage development.

The effect of treatment was not limited to hsCRP. Rezera reported corresponding reductions in several thrombo-inflammatory biomarkers, which the company said indicate engagement of multiple components of the NLRP3 inflammatory pathway.

NLRP3 is an upstream component of the innate immune system that has been implicated in chronic inflammation and cardiovascular disease. By targeting the pathway upstream, Rezera is seeking to modulate inflammatory processes associated with atherosclerotic disease rather than focusing on an individual downstream marker. The company also reported no meaningful effect on body weight.

“RESOLVE-1 results are a key milestone in the development of ruvonoflast, establishing dose-dependent clinical effects in a broad cardiometabolic patient population and demonstrating a favourable safety profile that supports advancement of this unique NLRP3 inhibitor into Phase 3,” says Dr. Jyothis George, MBBS, PhD, Chief Medical Officer at Rezera.

Ruvonoflast was generally well tolerated across the treatment groups in RESOLVE-1. Rezera said the safety analysis showed no evidence of drug-related liver toxicity, while rates of infections and serious infections were not increased. No serious adverse events were considered related to treatment.

The Phase 2 findings add to a broader clinical dataset comprising more than 400 participants across five ruvonoflast trials. Participants have received doses ranging from 150 mg/day to 450 mg/day, with individual studies lasting as long as nine months. The company has also reported clinical findings involving patients with elevated cardiovascular risk and high inflammatory burden, as well as participants with neuroinflammation.

Rezera has been working with regulators to establish the framework for its next-stage PAD trial. The company said it has reached alignment on core elements including the study endpoints, enrollment size, duration and safety considerations. The Phase 3 trial is expected to begin during the first half of 2027.

PAD represents a significant potential market for a therapy targeting inflammation. The condition affects more than 230 million people worldwide, according to Marc Bonaca, MD, MPH, executive director of the Colorado Prevention Center and professor of medicine at the University of Colorado Anschutz.

“Ruvonoflast has demonstrated significant reductions in multiple measures of inflammation, a core driver of disease in PAD, giving us a potential novel therapeutic approach for a disease with great unmet need,” Bonaca says. He added that ruvonoflast’s ability to penetrate tissues and inhibit the NLRP3 pathway upstream could provide a mechanism distinct from existing approaches to PAD management.

More information can be found by emailing Rezera@argotpartners.com.