Our Science
Harnessing versatile, innate biology to power deeper health benefits
Metabolic disease is a growing global health concern that leads to increased cardiometabolic risks and comorbidities. Recent innovation has fueled new treatments that effectively reduce body weight for many patients but present challenges that can limit clinical impact. Patients and physicians need new approaches to treating metabolic disease that induce broader health benefits alongside improved weight management. At Cytoki, we are committed to advancing a novel class of medicines that harness natural biology of interleukin-22 (IL-22) to enable deeper disease modification and benefits that translate into improved health outcomes. IL-22 is a naturally occurring, non-immunomodulatory cytokine which selectively targets epithelial tissues, such as the gut and liver. Outside its beneficial metabolic effects, IL-22 also has well-established roles in mucosal immunity and host defense, and tissue protection and repair. With its versatile biology, IL-22 holds first-in-class potential to address a range of metabolic diseases, including obesity, type 2 diabetes, and conditions characterized by epithelial injury, such as inflammatory bowel disease (IBD).
Lipidated IL-22: A novel approach to addressing metabolic disease
Cytoki is pioneering a new class of medicines designed to channel IL-22 signaling to address metabolic disease, offering a wholly differentiated mechanism by which to address obesity and type 2 diabetes, amongst other indications. Our lead IL-22 analogue, 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 Our Phase 1 clinical study of CK-0045 in healthy volunteers signaled successful translation of these preclinical findings, demonstrating exposure-dependent reductions in body mass that were complemented by beneficial reductions in low-density lipoprotein cholesterol, blood insulin concentration, and insulin resistance – the latter particularly in participants with reduced insulin sensitivity at baseline. We have initiated Phase 2 studies of CK-0045 in individuals with obesity and type 2 diabetes. 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 analogues
Cytoki’s IL-22 analogues 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 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
