Metabolic Disease

Browse to: Diabetes | NASH

Diabetes

Diabetes is a complex metabolic disorder characterized by hyperglycemia (high blood glucose), which results when the body produces an inadequate amount of insulin – a hormone that allows blood glucose to enter cells – or when the body is resistant to the activity of insulin. Type 1 diabetes is an autoimmune disease in which insulin-producing cells of the pancreas are destroyed. In type 2 diabetes, certain cells throughout the body have a decreased response to insulin – also known as insulin resistance. Both types of diabetes can lead to long-term complications from persistent hyperglycemia, including blindness, cardiovascular disease, and kidney failure.

Of the approximately 90 million people in the United States and European Union who have diabetes, 17 million use exogenous insulin treatment – such as insulin injections and insulin pumps – to manage their disease.

Current treatments for type 1 diabetes require burdensome, chronic use of insulin pumps or multiple daily insulin injections, as well as constant treatment modification based on dietary carbohydrate intake and blood glucose monitoring. Despite the availability of new technologies for glucose monitoring and insulin administration, 70 to 80 percent of people with type 1 diabetes still have blood glucose levels that exceed their targets, increasing the risk of long-term complications.

Kriya is developing KRIYA‑839, a one-time gene therapy for diabetes expressing insulin and glucokinase, delivered intramuscularly with the objective of driving durable glycemic control and reducing or eliminating the need for exogenous insulin. Kriya is initially evaluating its gene therapy in type 1 diabetes.

Approach to Treating Diabetes with Gene Therapy

Kriya’s adeno-associated virus (AAV) gene therapy is designed to engineer the skeletal muscle, which is responsible for the disposal of approximately 70 percent of circulating glucose after meals, to counteract hyperglycemia. The approach involves one-time, intramuscular delivery of AAVs expressing insulin and glucokinase. Kriya hopes to demonstrate production of insulin in the muscle that will be secreted at tonic basal levels systemically while exerting a local effect to drive translocation of the insulin dependent glucose transporter type 4 (GLUT4) on the muscle cell surface to enhance glucose uptake. At the same time, glucokinase is expressed in the muscle to potentially drive concentration-dependent glucose influx and metabolism only when hyperglycemia occurs, in the fed state. Collectively, the gene therapy is designed to serve as a “glucose sensor” to potentially promote glucose metabolism in a manner that is responsive to blood glucose levels.

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NASH

Nonalcoholic steatohepatitis (NASH) is a condition in which excess fat deposits in the liver cause inflammation, cell damage, and fibrosis. Approximately 20 percent of people with NASH will progress to advanced liver disease and associated complications, including cirrhosis and cancer.

NASH affects approximately 40 million people in the United States and European Union.

There are currently no FDA-approved therapies for the treatment of NASH.

Kriya is developing KRIYA‑497, a one-time gene therapy for NASH expressing the native FGF21 protein, delivered intramuscularly with the objective of reducing fibrosis, reversing steatosis, and improving the overall metabolic profile of patients with later stages of NASH with liver-predominant pathology (F3 and compensated F4).

Approach to Treating NASH with Gene Therapy

Kriya’s gene therapy is designed as a one-time, intramuscular AAV gene therapy with the potential to drive endogenous expression of steady levels of the native FGF21 protein. Multiple published clinical and preclinical studies have supported the anti-fibrotic effect of FGF21 in the liver and other organ systems.

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