Discovery of Unique Molecular Pathways in Patients with Lupus Nephritis for the Development of Novel Precision Therapies

Summary

• Systemic lupus erythematosus (SLE) is an autoimmune disease that disproportionately affects females and involves a wide array of organs/systems
• Lupus nephritis (LN) is the renal manifestation of SLE and is estimated to affect 80% of pediatric SLE patients
• A more comprehensive understanding of disease pathology would greatly improve our ability to develop novel treatments for LN
• Dr. Pascual is a recognized KOL in the field of pediatric SLE
• The Pascual lab has developed a novel platform and approach to identify molecular drivers of disease activity in pediatric SLE patients
• This approach has enabled them to stratify patients into seven major molecular subgroups, which will lead to improved and precise drug discovery for this disease

Technical Overview

• The Pascual lab has developed four distinct but interconnected aims in order to study the spatial organization and pathology of LN
• These aims will allow the Pascual group to study the unique pathways activated in renal stromal cells that play an active role in disease development
• Aim 1: Spatially profile the transcriptome of pediatric LN biopsies in order to identify gene signatures in the kidney that help stratify patients based on molecular endotypes
• Aim 2: Define novel cellular subsets and activation markers in LN at a single cell resolution
• Aim 3: Find soluble biomarkers that correlate with molecular signatures in the kidney
• Aim 4: Set up an in vitro system that recapitulates the molecular pathology we observe in LN biopsies to identify and evaluate novel targets and therapies
• Dr. Pascual’s platform will enable identification of novel druggable clues about LN disease pathology and biomarkers to stratify patients and design successful clinical trials

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

Partnering Opportunity

Weill Cornell Medicine is seeking an industrial partner with deep domain expertise and a strong presence in the autoimmunity and personalized medicine space to advance the development of this platform and deploy it in order to identify novel targets for SLE

Figure 1: Diffuse proliferative lupus nephritis