A Novel and Unique Set of Human Antibodies to Human Resistin and to Human Resitin-like Molecule Beta (RELMB) that can be used to Target these Proteins in Human Disease

Unmet Need
Diseases resulting from pulmonary remodeling, such as Pulmonary Arterial Hypertension (PAH), Hypertrophic Cardiomyopathy (HCM), Pulmonary Fibrosis (PF) and Chronic Obstructive Pulmonary Disease (COPD) are fatal diseases 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 therapy to treat these conditions has yet to be discovered.

Technology Overview
JH researchers have identified two proteins, Resistin and Resistin Like Molecule Beta (RELMβ), that are central to the etiology of pulmonary remodeling diseases. The researchers identified clinical biomarkers to stratify PAH patients according to mortality risk and further developed a therapeutic antibody to delay, prevent or reverse pulmonary remodeling that is associated with disease.  Animal model results confirmed that an antibody against Hypoxia Induced Mitogenic Factor (HIMF; the murine homologue of Resistin and RELMβ) was completely successful  in blocking the cell proliferation, migration, increased vasculogenesis, and gene expression associated with pulmonary remodeling. An inhibitory therapy targeting one or both of these proteins is predicted to treat pulmonary remodeling diseases.

Stage of Development
Human lung endothelial, bronchial and vascular smooth muscle cell assays have confirmed blocking activity of the lead antibodies.  In silico testing of candidate antibodies were analyzed for epitope based immunogenicity, aggregation risk, and physicochemical characteristics and manufacturability.  Select lead antibody(ies) are being synthesized as IgG1 and IgG2 for comparative testing in animal models, toxicology, and PK studies. Humanized animal models of PH have been developed.

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