#South Korea #Seoul #Resolve Therapeutics #RSLV-132 #RSLV-145

Overview of the Research Presentations at the World Stroke Conference

At the recent 18th World Stroke Congress held from October 21 to 23, 2026, in Seoul, Resolve Therapeutics, LLC presented innovative preclinical data focused on the potential of nuclease therapy for treating acute ischemic stroke (AIS). The research highlights two prominent candidates: RNase-Fc fusion protein RSLV-132 and the bispecific RNase/DNase-Fc fusion protein RSLV-145. These proteins are designed to mitigate the harmful effects of pathogenic extracellular nucleic acids, which play a critical role in AIS pathogenesis.

Background on the Study

AIS poses a significant health challenge worldwide, often leading to severe complications if not treated promptly. Emerging evidence points to cell-free nucleic acids as key players in the development of AIS, with neutrophil extracellular traps (NETs) contributing to thrombosis and tissue injury during reperfusion. Specifically, NETs can obstruct effective thrombolysis, the process used to dissolve blood clots. The two presentations at the conference explored strategies to degrade these harmful entities to improve clinical outcomes for AIS patients.

Key Findings from the Presentations

The first e-poster presentation, titled "In Vitro NET Degradation and Inhibition", shared results from experiments demonstrating RSLV-145’s ability to degrade pre-formed NETs effectively. This was achieved in a dose-dependent manner, showcasing a notable decrease in NET-associated DNA within a mere five minutes of treatment (with statistical significance p<0.0001). In contrast, RSLV-132, which does not possess DNase activity, exhibited no effect on existing NETs.

Further analysis showed that both candidates could reduce NET formation prompted by RNA-containing immune complexes, again with RSLV-145 showing superior results. This novel mechanism of action supports the rationale for harnessing nuclease therapy in AIS treatment.

The second e-poster, titled "In Vivo Efficacy with Tenecteplase," examined these compounds' effects in a murine model of AIS. Here, RSLV-132 and RSLV-145 were administered alongside the thrombolytic agent tenecteplase following stroke onset, yielding significant benefits such as a 35% decrease in infarct volume on Day 3 post-stroke, as compared to the control group receiving only a vehicle treatment (p=0.014). Notably, the performance on neurobehavioral tests, such as the accelerating rotarod, was preserved in the combination therapy groups—illustrating improved functional outcomes when compared to administering tenecteplase alone, which did not show statistical significance.

Mechanistic Insights into Nuclease Therapy

The dual action of these therapeutic agents lies in their ability to degrade pathogenic nucleic acids, addressing two core issues in AIS: the resistance to thrombolysis and the amplification of reperfusion injury. By digesting NET DNA, RSLV-145 could potentially enhance thrombolytic efficacy, while the degradation of extracellular RNA may help mitigate collateral tissue damage during blood flow restoration.

Gábor Illei, MD, PhD, MHS, the clinical strategy leader at Resolve Therapeutics, emphasized the importance of these studies, stating, "These findings encapsulate the complementary strategies driving the rationale for implementing nuclease therapy in stroke scenarios."

Future Implications

As the data from these presentations shed light on the promising potential of RSLV-132 and RSLV-145, Resolve Therapeutics aims to continue advancing these investigational therapies through clinical studies. The results presented at the World Stroke Congress not only underscore the importance of addressing unmet medical needs in ischemic stroke care but also demonstrate how innovative approaches, like nuclease therapy, could reshape treatment paradigms.

Conclusion

The future of stroke management may very well be enhanced by the understanding and application of nuclease therapy, with the potential to change patient outcomes in a condition characterized by significant morbidity and mortality. Continued exploration of these mechanisms will be critical as healthcare advances toward more effective stroke interventions.