Science
The presence of circulating cfRNA in the form of ribonucleoproteins (RNPs) is the hallmark of Sjogren’s disease and Systemic lupus erythematosus (SLE). When these RNA molecules make their way into cells, they trigger a robust immune response via activation of RNA sensor molecules and downstream cytokine production. Clinical studies with RSLV-132 demonstrate that dramatically increasing RNase activity in the plasma of SLE or Sjogren’s patients improves the symptoms associated with the chronic inflammatory response.
In patients suffering multiple, life-threatening traumatic injuries (polytrauma), damaged tissues release large amounts of cfRNA into circulation. These RNA molecules are subsequently taken up into cells of the immune system where they trigger a robust immune response. This inflammatory response, known as systemic immune response syndrome, or SIRS, is correlated with poor clinical outcomes. Enzymatically digesting cfRNA with RSLV-132 is hypothesized to reduce the incidence of SIRS and improve clinical outcomes in these polytrauma patients by preventing activation of RNA sensors and cytokine production. Working with the world’s leading trauma surgeons at Duke University, we are currently conducting an observational clinical trial in polytrauma patients investigating the impact of cfRNA in polytrauma.
Ischemic stroke involves a life-threatening blockage of blood flow to regions of the brain. The standard of care involves immediate treatment with tissue plasminogen activator, tPA. In about 50% of ischemic stroke patients, tPA is ineffective due to the presence of neutrophil extracellular traps, or NETs, within the cells of the clot. Infusion of our dual mechanism nuclease RSLV-145 at the time of tPA treatment is hypothesized to digest the NETs with the DNase enzyme activity of the molecule rendering the clot sensitive to tPA. Following revascularization of the brain tissue, many patients experience reperfusion injury, which is thought to be mediated by cfRNA. In this case, prolonged treatment with RSLV-145 would eliminate cfRNA with the RNase portion of the molecule thereby reducing reperfusion injury to the brain tissue. Preclinical studies are underway in murine stroke models and ex vivo analysis of clots from ischemic stroke patients.
RSLV-132
Our mid-stage clinical candidate is a fully-human Fc fusion protein comprised of RNase fused to an engineered Fc domain. RSLV-132 has demonstrated an excellent safety profile in 5 clinical trials, is completely non-immunosuppressive and effective in removing pathogenic extracellular RNA from plasma. Our lead indication is Sjögren’s Disease where a large confirmatory phase 2 study is currently ongoing, following up on a positive smaller phase 2 Sjogren’s study. In addition to Sjögren’s Disease we are exploring the efficacy of RSLV-132 in multiple additional chronic and acute indications.
RSLV-145
Our pre-clinical candidate RSLV-145 is a bispecific nuclease Fc fusion protein that contains both RNase and DNase catalytic activity. RSLV-145 is a potent antagonist of the inflammatory properties of both extracellular RNA and DNA with potential therapeutic utility in lupus, lupus nephritis, vasculitis and autoimmune diseases that involve NETosis (the formation of dense lattices containing RNA and DNA that act as a scaffold for autoantigens that bind to autoantibodies). Through digestion of extracellular RNA, DNA and NETs, RSLV-145 prevents activation of the immune system. RSLV-145 is currently being assessed across multiple indications.
RSLV-145 effectively prevents NET formation
