Proposed model of retinoid signaling in Type 2 diabetes demonstrates disease modifying mechanism for Kayothera therapies.
Kayothera, an early-stage therapeutics company developing 1st-in-class, orally-available antagonists of the retinoid pathway, announces that it is advancing a program to treat and reverse cardiometabolic diseases, with a focus on Type 2 Diabetes. The clinical use of retinoids has long been associated with rapid weight gain, hypertriglyceridemia and hyperlipidemia, while preclinical studies have suggested a causal role for retinoid signaling in pancreatic degeneration. Kayothera has advanced a series of potential therapies to reverse these retinoid-dependent effects and treat the underlying cause of Type 2 Diabetes, a disease which affects more than 500 million people, or 5% of the world’s population.
A recent publication in Nature Communications co-authored by Kayothera founders, Dr. Mark Esposito and Dr. Yibin Kang, along with Columbia University researchers, demonstrated that Kayothera’s therapies could reverse Type 2 Diabetes progression. This work demonstrated that Beta cell loss in Type 2 Diabetes is driven by ALDH1a3 activity, leading to retinoid signaling and progressive degeneration. Treatment by oral administration with Kayothera therapies reversed pancreatic decline in these mice and results in a disease-treating effect that persisted for weeks after treatment stopped. Kayothera recently presented this work at the Keystone Symposium focusing on new strategies to treat Type 2 Diabetes.
Kayothera compound KOTX1 reverses Beta cell decline in preclinical models of Type 2 Diabetes and restores Insulin production.
Advanced candidates in Kayothera’s pipeline are safe and effective, with no dose-limiting toxicities observed to date and with the ability to restore the function of diseased pancreatic islets in preclinical models of obesity and Type 2 diabetes. Kayothera plans to nominate a development candidate for cardiometabolic disease in Q4 2023.
Images from Son et al, 2023. Nat Comms.