Miami, Florida, United States, October 21, 2026
Resolve Therapeutics, LLC, a clinical-stage biotechnology company developing nuclease-based therapies for inflammatory diseases and acute brain injury, has announced new preclinical findings for its investigational candidates RSLV-132 and RSLV-145 at the 18th World Stroke Congress, held October 21–23, 2026, in Seoul, South Korea. The research explores whether these experimental therapies could enhance the effects of tenecteplase, a thrombolytic medicine used to dissolve blood clots, in acute ischemic stroke. The company presented two electronic posters examining the ability of its candidates to break down neutrophil extracellular traps (NETs) and improve outcomes in a mouse model of stroke. The findings provide scientific support for further investigating nuclease therapy as a potential adjunct to existing stroke treatment approaches. Acute ischemic stroke occurs when a blood clot obstructs blood flow to part of the brain, depriving brain tissue of oxygen. Although thrombolytic medicines can restore circulation in eligible patients, treatment effectiveness may be limited by several biological factors. Resolve Therapeutics is investigating whether degrading extracellular DNA and RNA could help improve clot-dissolving treatment and limit tissue injury. The results remain preclinical and require further validation before their potential relevance to human patients can be established.
RSLV-145 Targets Neutrophil Extracellular Traps
One presentation examined RSLV-145, a bispecific RNase/DNase-Fc fusion protein designed to degrade extracellular RNA and DNA. The research focused on NETs, web-like structures released by neutrophils, a type of immune cell. Although NETs contribute to the body’s defense against infection, they can also participate in inflammation and clot formation. NET-rich blood clots have been associated with resistance to thrombolytic treatment, making NET degradation a potential research strategy for acute ischemic stroke. In laboratory experiments using neutrophils from healthy donors, RSLV-145 degraded preformed NETs within five minutes in a concentration-dependent manner. At concentrations of 17.5, 87.5 and 175 nanomolar, the experiments recorded 59%, 38% and 36% of NET-associated DNA remaining, respectively. The reported reductions were statistically significant compared with baseline. Researchers also found that RSLV-145 inhibited NET formation induced by RNA-containing immune complexes. RSLV-132, an RNase-Fc fusion protein without DNase activity, also reduced induced NET formation but did not degrade preformed NETs. These findings suggest that the dual enzyme activity of RSLV-145 may provide an additional mechanism for targeting extracellular DNA structures. However, laboratory activity alone cannot establish whether this approach will improve clinical outcomes in people experiencing a stroke.
Nuclease Candidates Improve Outcomes in Mouse Stroke Model
A second presentation evaluated both investigational candidates alongside tenecteplase in a mouse model of acute ischemic stroke. Researchers administered a single intravenous dose of RSLV-132 or RSLV-145, at 10 milligrams per kilogram, together with tenecteplase 30 minutes after stroke onset. By Day 3, both combination-treatment groups demonstrated 35% lower brain infarct volumes than the vehicle control group, with statistically significant differences reported for each combination. Tenecteplase alone produced a 21% reduction in infarct volume, which was not statistically significant compared with the vehicle group. Both combination groups also maintained performance on an accelerating rotarod test through Day 3 and demonstrated significant recovery in cerebral perfusion between 60 and 120 minutes after treatment. The combination of tenecteplase and RSLV-145 additionally produced a statistically significant improvement in the adhesive tape-removal test compared with vehicle. These assessments measured different aspects of neurological function and brain recovery in the experimental model. The results suggest that combining nuclease candidates with thrombolytic treatment warrants further investigation, but animal-model outcomes cannot reliably predict the magnitude of benefit or safety in human patients.
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Resolve Therapeutics Advances Stroke Drug Development
Resolve Therapeutics is developing therapies intended to address the biological mechanisms underlying acute and chronic inflammation. RSLV-132 has previously been evaluated in five clinical trials, with the company reporting a safety profile similar to placebo and no anti-drug antibodies observed in those studies to date. The candidate is also being investigated in a Phase 2b clinical trial for Sjögren’s disease. In contrast, RSLV-145 remains in preclinical development for acute brain injury, including ischemic stroke and subarachnoid hemorrhage. The company’s latest presentations strengthen the scientific rationale for evaluating extracellular nucleic acid degradation as a potential therapeutic strategy. Further research will be needed to establish appropriate dosing, safety, treatment timing and clinical benefit when these agents are combined with thrombolytic medicines. The findings do not establish that either candidate is effective for treating stroke in humans, and neither should be considered an approved stroke therapy on the basis of these results. Future studies will determine whether the encouraging laboratory and animal findings can translate into a clinically meaningful treatment approach. The research marks a preclinical development milestone for Resolve Therapeutics’ nuclease-based stroke program, addressing an important unmet need in acute neurological care.
Source: Resolve Therapeutics press release
