Discovery of Unique Molecular Pathways in Patients with Lupus Nephritis for Precision Therapy Development

Summary

• Systemic lupus erythematosus (SLE) is an autoimmune disease caused by autoantibody production against a range of nuclear and cellular antigens leading to renal, vascular, and neurological manifestations
• Lupus nephritis (LN) is the severe, renal manifestation of SLE, affects >80% of pediatric SLE patients and is associated with a 20% incidence of end stage renal disease (ESRD)
• Dr. Pascual is a world-renowned pediatric SLE clinician and translational scientist who has developed a novel platform to screen and validate molecular drivers of SLE pathogenesis
• The Pascual lab deploys a multi-modal genomics approach to interrogate a proprietary SLE patient-derived biobank for drug target / biomarker discovery, immune cell mapping, and development of novel LN therapeutics

Technical Overview

• The Pascual group has developed four distinct drug discovery pillars which utilize a novel biobank of LN patient tissues to leverage insights into drug targets and clinical disease biomarkers:
• Aim 1: Spatial transcriptome analysis of pediatric LN biopsies to characterize phenotypic and molecular signatures that define patient-specific disease endotypes
• Aim 2: Describe relevant LN immune cell populations and disease activity markers (e.g. chemokines) at a single cell resolution
• Aim 3: Screen for soluble, accessible kidney biomarkers which correlate with LN disease stage, activity, and drug response
• Aim 4: Design in vitro culture system which recapitulates LN molecular pathology to enable novel target discovery, validation, and drug screening campaigns

Market Opportunity

• Disease market: Approximately 3.4 million people globally suffer from SLE with 400,000 new cases per year
• SLE therapeutics market was estimated to be ~$1 Billion in 2021 with an expected CAGR of 8.4% through 2022
• Patients with active LN are treated with aggressive immunosuppressive agents that can trigger serious side effects
• Dr. Pascual’s platform and biobank represents a powerful tool to therapeutics companies focused on drug development for lupus nephritis or characterizing immune cell populations implicated in the multi-organ manifestations of SLE

Partnering Opportunity

Weill Cornell Medicine is seeking an industrial partner with deep expertise in developing innovative precision therapeutics for autoimmune diseases to leverage this platform for novel SLE target identification, validation, and drug discovery

Supporting Data / Figures

Figure 1: Histopathology of diffuse proliferative lupus nephritis, featuring capillary immune deposits, glomerular sclerosis, and hematoxylin bodies.