Cell-free RNA Drives Inflammation in Multiple Diseases
Science
The Problem
RNA and DNA are continuously released into plasma through natural biological processes such as cell death, and the release of Neutrophil Extracellular Traps (NETs). These molecules are highly inflammatory, prothrombotic and must be constantly removed from circulation by endogenous nucleases to maintain homeostasis. Many individuals, through injury or disease are unable to maintain homeostasis, leading to an accumulation of extracellular nucleic acids, which triggers a robust immune response, the production of cytokines and ultimately inflammation.
The Solution
Resolve has developed a first-in-class fully-human biologic drug platform that combines potent RNases and/or DNases with an antibody Fc domain to digest extracellular nucleic acids, which reduces activation of the immune system and resolves inflammation. The platform is non-immunogenic, non-immunosuppressive and stable in plasma for multiple weeks. RSLV-132 is Resolve’s most advanced drug candidate, which has been clinically validated in multiple phase 2 trials and has been demonstrated to improve the symptoms of chronic autoimmune diseases such as SLE and Sjogren’s syndrome.
.png)
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 Sjogren’s syndrome where a large confirmatory phase 2 study is currently ongoing, following up on a positive smaller phase 2 Sjogren’s study. In addition to Sjogren’s syndrome 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.
Mechanism of Action
Interested in learning if our drug candidates would work for your indication?
Watch the video to
discover our mechanism of action.