Our Science
IL-22: unlocking the power of the gut-brain-liver axis to treat metabolic disease and more
Interleukin-22 (IL-22) is a naturally occurring, non-immunomodulatory cytokine which selectively targets epithelial tissues, including those that play important roles in metabolic processes, such as the gut and liver. IL-22 also plays well-established roles in mucosal immunity and host defense, modulation of lipid metabolism, and tissue protection and repair. With its versatile biology, IL-22 holds first-in-class potential to address a range of metabolic diseases impacted by changes to the gut-brain-liver axis. The gut-brain-liver axis is a multidirectional network that enables communication between core systems in the body and plays important roles in health and disease. Recent advancements underscore the significance of this axis and its implications in the occurrence and development of several diseases, including obesity, type 2 diabetes, and conditions characterized by epithelial injury, such as inflammatory bowel disease (IBD).
Novel approach harnessing the benefits of innate biology
Cytoki is pioneering a new class of medicines designed to channel IL-22 signaling to address diseases involving changes to the gut-brain-liver axis, offering a wholly differentiated mechanism by which to address obesity and type 2 diabetes, amongst other indications. Our lead IL-22 analog, CK-0045, has demonstrated outstanding preclinical efficacy both as a standalone therapeutic and when used in combination with existing standard of care treatments, inducing dose-dependent reductions in body weight and direct beneficial impacts on cardiometabolic risk factors, including: • Increased insulin sensitivity • Normalization of blood glucose • Improved liver health • Reduction of plasma lipid concentrations CK-0045 has also demonstrated potential to address inflammatory bowel disease (IBD) by directly inducing epithelial healing—a novel treatment approach complementing the existing anti-inflammatory standard of care and further positioning IL-22-based treatments for widespread impact.
Our long-acting lipidated IL-22 analogs
Cytoki’s IL-22 analogs are precisely engineered to extend circulation time in the body and enable subcutaneous delivery, offering first-in-class potential to address obesity and type 2 diabetes. In-licensed from Novo Nordisk, our lead program CK-0045—which is undergoing Phase 1 clinical evaluation in healthy volunteers with and without obesity—leverages commercially proven lipidation technology for turning short-lived native proteins into potent therapeutics with long half-life and native-like characteristics. Unlike other technologies commonly used to increase therapeutic half-life, lipidation is a minimal modification of a protein comprising attachment of a small fatty acid chain. This modification protects the protein from fast clearance and degradation. 1. Lipid tail non-covalently binds to circulating serum albumin 2. Lipidated IL-22 travels through the blood stream with serum albumin 3. An equilibrium exists between free and albumin-bound lipidated IL-22 4. Free lipidated IL-22 engages with relevant receptors
