Unmet Need
Autoinflammatory responses, your body’s innate defense mechanism against infections and stressors, can become overactive and cause chronic inflammation in various tissues and organs. Inflammatory diseases affect more than 200 million people worldwide and include pulmonary hypertension, scleroderma, rheumatoid arthritis, pulmonary fibrosis, irritable bowel disease, gout, uveitis, atherosclerosis, viral lung disease, and more.
Pulmonary Arterial Hypertension (PAH) is a fatal disease for which the standards of care are palliative therapies that treat the symptoms of the disease as the patient progresses toward heart failure and death. A safe and effective disease modifying therapy to treat PAH does not currently exist.
Technology Overview
JHU researchers have developed a strategy to decrease inflammation in autoinflammatory diseases and to treat PAH by inhibiting the production of pro-inflammatory signals produced by the inflammasome. Inflammasomes are intracellular protein complexes that are made and triggered in innate immune cells in response to stress signals and mediate the release of pro-inflammatory signals. Resistin is a molecule that functions to prime and activate the inflammasome. In many autoinflammatory diseases, including PAH, there is an increase in the amounts of Resistin, leading to increased inflammasome activation. JHU researchers developed an antibody to inhibit Resistin and have demonstrated that blocking Resistin both decreases inflammation without broad inhibition of the inflammasome, and reduces tissue remodeling in PAH.
JHU researchers identified an antibody against Resistin (RGTX-23) and through animal studies confirmed that blocking Resistin stops the cell proliferation, migration, increased vasculogenesis, and gene expression associated with pulmonary remodeling in PAH. Treatment with RGTX-23 improved the survival rate of study rats.
Stage of Development
In vitro human lung endothelial, bronchial and vascular smooth muscle cell assays have confirmed blocking activity of the RGTX-23. In vivo studies in PAH rat models have shown both prevention and reversal of vascular remodeling and increased survival in animals treated with RGTX-23. Pre-clinical work, including preliminary tox, human tissue cross-reactivity, preliminary PK, and process/manufacturing, is nearly completed. IND-enabling CMC and toxicology work ongoing.
Intellectual Property:
Antibodies to human resistin.
• Compositions of matter and methods of treatment. US patent 10,822,407 issued November 2020.
• Methods of treatment. • Methods of treatment. US patent 12,233,125 issued March 2025.
Compositions and methods for treating diseases and conditions associated with activation of the NLRP3 inflammasome.
• Compositions of matter and methods. PCT patent application filed August 2023.
Publications:
Gao, L., Skinner, J., Nath, T. et al. Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension. Respir Res 25, 235 (2024).
Lin, Q., Kumar, S., Kariyawasam, U. et al. Human Resistin Induces Cardiac Dysfunction in Pulmonary Hypertension. JAHA 12, 6 (2023).
Lin, Q., Fan, C., Skinner, JT. et al. RELMa Licenses Macrophages for Damage-Associated Molecular Pattern Activation to Instigate Pulmonary Vascular Remodeling. J Immunol 203, 11 (2019).
