Resolve Therapeutics Presents Preclinical Data on NET Degradation and Nuclease Therapy in Acute Ischemic Stroke at the World Stroke Conference

Resolve Therapeutics Presents Preclinical Data on NET Degradation and Nuclease Therapy in Acute Ischemic Stroke at the World Stroke Conference

PR Newswire

MIAMI, Oct. 21, 2026 /PRNewswire/ — Resolve Therapeutics, LLC, a clinical-stage biotechnology company developing nuclease-Fc fusion proteins designed to degrade pathogenic extracellular nucleic acids, today announced two e-posters featuring preclinical data on its RNase-Fc fusion protein RSLV-132 and its bispecific RNase/DNase-Fc fusion protein RSLV-145 at the 18th World Stroke Congress, held October 21-23, 2026, in Seoul, Republic of Korea. One presentation examines the degradation and inhibition of neutrophil extracellular traps (NETs) by RSLV-145 in vitro; the other evaluates RSLV-132 and RSLV-145 combined with tenecteplase in a murine photothrombotic stroke model.

Resolve Therapeutics, LLC

Resolve is developing nuclease therapy as a new approach to acute ischemic stroke (AIS), based on growing evidence that cell free nucleic acids are important mediators of AIS pathogenesis. For example, thrombi rich in NETs are associated with resistance to thrombolysis, and extracellular RNA has been implicated in the extension of tissue injury during reperfusion. Therefore, digesting NET DNA could restore thrombolytic efficacy, while degrading extracellular RNA could limit reperfusion injury, providing a dual rationale for evaluating nuclease therapy in AIS.

Data was presented demonstrating the ability of RSLV-145, a dual RNase/DNase nuclease Fc fusion protein, to effectively digest pre-formed NETs and inhibit RNA-induced NET formation. A second presentation demonstrated that, when added to tenecteplase, both RSLV-145 and RSLV-132 improved several clinically important outcomes in the murine photothrombotic stroke model. The data provide compelling evidence for the continued development of nuclease therapy in AIS.

Key findings

ePoster #2338 – In vitro NET degradation and inhibition. In experiments using neutrophils from healthy donors:

  • RSLV-145 degraded preformed NETs within five minutes in a concentration-dependent manner, leaving 59%, 38% and 36% of NET-associated DNA at 17.5, 87.5 and 175 nM, respectively (all p<0.0001 versus baseline). RSLV-132, which lacks DNase activity, had no effect on preformed NETs.
  • Both RSLV-132 and RSLV-145 reduced NET formation induced by RNA-containing immune complexes, with greater inhibition observed for RSLV-145.

ePoster #2382 – In vivo efficacy with tenecteplase. In a murine photothrombotic stroke model, a single intravenous dose of RSLV-132 or RSLV-145 (10 mg/kg), administered with tenecteplase 30 minutes after stroke onset:

  • The tenecteplase-plus-RSLV-132 and tenecteplase-plus-RSLV-145 groups each had 35% lower Day 3 infarct volume than the vehicle group (Bonferroni-corrected p=0.014 for each). The 21% reduction with tenecteplase alone was not statistically significant versus vehicle.
  • Both combination groups preserved performance on the accelerating rotarod through Day 3 (Bonferroni-corrected p<0.05 versus vehicle); tenecteplase alone did not reach statistical significance.
  • Both combination groups showed significant within-animal cerebral perfusion recovery between 60 and 120 minutes after treatment; tenecteplase alone did not.
  • Only the tenecteplase-plus-RSLV-145 group showed a statistically significant improvement on the adhesive tape-removal test versus vehicle (Bonferroni-corrected p=0.014).

Taken together, the NET and stroke-model findings strengthen the rationale for advancing RSLV-132 and RSLV-145 as potential adjuncts to thrombolysis in acute ischemic stroke.

“These studies address complementary aspects of the rationale for nuclease therapy in stroke,” said Gábor Illei, MD, PhD, MHS, Clinical Strategy Leader at Resolve Therapeutics. “RSLV-145 rapidly degraded preformed NETs in vitro, both candidates reduced induced NET formation, and each improved several outcomes when combined with tenecteplase in the mouse model. Ischemic stroke is an area of large unmet medical need; we look forward to continued development of this promising new approach and ultimately evaluating these molecules in clinical studies.”

Presentation details

ePoster

Title

Authors

Session

#2338

Bispecific RNase/DNase-Fc fusion protein RSLV-145 degrades neutrophil extracellular traps (NETs): rationale for evaluation in acute ischemic stroke

Gabor Illei, James Posada (Resolve Therapeutics)

AS04 Basic Science

#2382

RNase-Fc and bispecific RNase/DNase-Fc fusion proteins augment tenecteplase (TNK) efficacy in a murine model of acute ischemic stroke

James Posada, Huaxin Sheng, Donovan Edwards, Gabor Illei (Resolve Therapeutics; Duke University)

AS04 Basic Science

The ePosters will be available on the World Stroke Congress ePoster platform throughout the meeting, October 21–23, 2026, and on the Resolve Therapeutics website https://www.resolvetherapeutics.com/ following the congress.

About RSLV-132
RSLV-132 is an investigational RNase-Fc fusion protein comprising catalytically active human ribonuclease 1 linked to an engineered human IgG1 Fc domain. The Fc domain is engineered to reduce Fc-receptor binding and cellular uptake and to support a serum half-life of approximately three weeks. RSLV-132 has been evaluated in five clinical trials, with a safety profile similar to placebo. No anti-drug antibodies have been observed in clinical studies to date.

About RSLV-145
RSLV-145 is a dual specificity DNase/RNase Fc fusion protein in preclinical development for acute brain injury. The nucleases are fused in tandem to an engineered human IgG1 Fc domain that does not bind Fc receptors, thereby preventing cellular uptake. The DNase moiety is engineered and has approximately 100-fold higher catalytic activity than wild type DNase 1. In addition, actin binding has been eliminated so it retains complete catalytic activity in human serum.

About Resolve Therapeutics
Resolve Therapeutics is a clinical-stage biopharmaceutical company developing non-immunosuppressive drugs to treat acute and chronic inflammation at its source, rather than blocking key regulatory elements of the immune system. This approach has the important advantage that the immune system is undiminished and able to respond to potentially life-threatening viral infections. RSLV-132 is the lead clinical compound and is being evaluated in a phase 2b Sjögren’s disease clinical trial. A Preclinical asset, RSLV-145 is being studied in ischemic stroke and subarachnoid hemorrhage. For more information, visit www.resolvetherapeutics.com.

Media Contact
James Posada, Ph.D.
jp@resolvebio.com
(208) 727-7010

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SOURCE Resolve Therapeutics, LLC