A New Approach to Treating Chronic and Acute Inflammation
Listen to the LFA podcast with Dr. Posada describing Resolve’s phase 2 SLE study
Our Science
RNA and DNA molecules are continually released into the plasma compartment through normal biologic processes, such as cell death. These cell-free nucleic acids are normally rapidly digested and removed from circulation through the action of DNase and/or RNase enzymatic activity. Endogenous plasma nuclease enzyme activity is therefore critical in the maintenance of homeostasis.
Cell-free RNA and DNA are potently inflammatory, and prothrombotic. If unchecked, their accumulation in the plasma compartment causes immune activation and subsequent tissue and organ damage. In several disease states, nuclease activity is known to be impaired, resulting in the accumulation of circulating cell-free RNA or DNA molecules in the plasma. These circulating cell-free nucleic acids have been shown to trigger inflammatory cascades which have a multitude of harmful effects depending on their location.
Resolve has developed RSLV-132 and RSLV-145, two nuclease Fc fusion protein drugs which effectively digest RNA or RNA and DNA respectively, removing it from circulation and eliminating inflammation at its source. These drugs are mimetics of normally circulating proteins and serve to significantly increase plasma nuclease activity.
Clinical experience to date with RSLV-132 has demonstrated that increasing RNase catalytic activity is very safe and has the added benefit of not being immunosuppressive.
RSLV-132 is not recognized by the body as foreign and does not result in anti-drug antibodies. Furthermore, three clinical trials with RSLV-132 have revealed that increasing plasma RNase activity improves patient symptoms associated with SLE, Sjogren’s syndrome, and long covid.
Resolve Therapeutics is currently pursuing additional, selected opportunities in clinical indications with high unmet medical need where there is clear evidence of the role of nucleic acids driving the disease process. Numerous published preclinical studies with RNase in animal models supports the clinical evaluation of RSLV-132 and RSLV-145 in the following diseases:
- Cardio-protection following revascularization in ST segment elevated myocardial infarction (STEMI)
- Post-acute inflammatory damage to brain tissue following subarachnoid hemorrhage
- Arterial and venous thrombosis
- Alzheimer’s disease
