Kayothera, Inc. Nominates KAYO-1732, a First-In-Class, Oral Inhibitor of the Retinoid Nuclear Receptor Pathway in Type 2 Diabetes and Cardiometabolic Indications as a Development Candidate

SEATTLE--(BUSINESS WIRE)--Kayothera, Inc. (“Kayothera”), a preclinical therapeutics company developing first-in-class, small molecule inhibitors of the retinoid nuclear receptor pathway, today announces that it has selected KAYO-1732 as a drug development candidate. KAYO-1732 is a novel, orally-available, small molecule inhibitor of the Aldehyde dehydrogenase 1A3 (ALDH1A3) enzyme, developed for the treatment of type 2 diabetes (T2D) and cardiovascular disorders. The compound has demonstrated an exceptional safety profile in 28-day toxicology studies and has shown dramatic disease-modifying activity in preclinical cardiometabolic models, supporting its potential as a transformative therapeutic. With the nomination of KAYO-1732 as a development candidate, Kayothera is well-positioned to advance into IND-enabling studies, clinical development planning, and strategic partnering opportunities.

KAYO-1732 represents a new paradigm for treating T2D by targeting the retinoid nuclear receptor pathway, a pathway shown to drive cardiovascular mortality and β cell failure in patients. Preclinical data, including a recent publication in Nature Communications, demonstrates that pathogenic ALDH1A3 activity is a key driver of pancreatic β cell dedifferentiation and failure, which leads to the progressive decline in insulin secretion seen in T2D. By inhibiting ALDH1A3, KAYO-1732 blocks activation of the retinoid nuclear receptors and directly reverses the loss of pancreatic β cell function. In preclinical models, treatment with KAYO-1732 led to the conversion of dedifferentiated β cells into a functional, mature state, resulting in restored glucose control and increased insulin secretion. This disease-modifying approach stands apart from many existing therapies that primarily focus on blood glucose management without addressing the underlying cause of β cell decline. The nomination of KAYO-1732 further validates Kayothera's approach, which was recently recognized as one of the winners at the American Diabetes Association's Innovation Challenge.

"The nomination of KAYO-1732 as a development candidate is a pivotal moment for Kayothera and for the tens of millions of people living with type 2 diabetes," said Dr. Mark Esposito, CSO and Co-founder for Kayothera. "For years, the retinoid nuclear receptor pathway has been an impossible target to drug in a safe and selective manner, but our unique approach and the compelling preclinical data give us confidence that we are developing a truly first-in-class therapy with the potential to fundamentally change the course of type 2 diabetes."

About Kayothera, Inc. Kayothera is a preclinical therapeutics company focused on the development of first-in-class, oral, small molecule inhibitors of the retinoid nuclear receptor pathway. This pathway plays a critical role in a variety of serious diseases, including cardiometabolic diseases and cancer. The company was founded based on discoveries from Dr. Mark Esposito’s post-doctoral research at Princeton University and professor Yibin Kang, PhD. For more information, visit www.kayothera.com.