Development of Novel Therapeutics for Chronic Inflammation by Leveraging Innate Lymphocyte Populations

Summary

• Irritable Bowel Disease (IBD) involves chronic inflammation of intestinal tissue
• Rising rates of IBD in the US and globally underscores the need for novel and effective therapeutics
• Dr. Sonnenberg has been at the forefront of interrogating the function, regulation and therapeutic potential of tissue resident ILC3s, for mediating chronic intestinal inflammation
• His work highlights a novel pathway that offers a potential new therapeutic target for treating chronic gut inflammation

Technical Overview

• Group 3 innate lymphoid cells (ILC3s) are tissue resident cells that regulate immunity, inflammation, and tissue homeostasis
• Tumor Necrosis Factor (TNF) drives chronic inflammation in Irritable Bowl Disease (IBD) and other chronic inflammatory diseases
• ILC3s produce heparin-binding EGF-like growth factor (HB-EGF) which can protect intestinal epithelium from TNF-induced cell death
• Pre-clinical studies of both acute intestinal inflammation and chronic intestinal inflammation demonstrate that HB-EGF was essential in reducing intestinal damage and inflammation
• Patients with IBD have significantly fewer HB-EGF-producing
• ILC3s in inflamed intestinal tissue compared to normal patients
• Selective activation of the ILC3-HB-EGF pathway provides a novel therapeutic target for chronic intestinal inflammation

Market Opportunity

• Disease market: Approximately 3 million Americans suffer from IBD with 70,000 new cases per year
• IBD treatment market was approximately $8.6 billion in the US in 2020 with an expected CAGR of 3.8% over the next 10 years
• TNF inhibitors have the market share of IBD therapeutics

Partnering Opportunity

Weill Cornell Medicine is seeking a strong industrial partner with whom to collaborate around a dedicated program in the Sonnenberg
lab aimed at developing new drugs to selectively activate ILC3s

Figure 1: A: Schematic of TNF induced tissue damage and beneficial effect of the ILC3-HB-EGS axis. B: Induction of the ILC3/HB-EGF pathway.