SCO-792 Enteropeptidase inhibitor

Amino acids perform multiple essential physiological roles in humans, and their importance in human health has been extensively studied in preclinical and clinical research. Enteropeptidase is a pivotal gut-localized enzyme that activates protein digestion events in mammals. SCO-792 is an orally available enteropeptidase inhibitor with first-in-class potential that inhibits gut amino acid intake into human circulation. In Phase 1 and 2 trials, SCO-792 demonstrated its safety and tolerability in humans.

Patients with inborn metabolic disorders affecting amino acid metabolism have clinically challenging conditions. Typical examples include phenylketonuria (PKU), maple syrup urine disease (MSUD), or homocystinuria (HCU). Dietary restriction of natural proteins, thereby reducing the intake of phenylalanine, branched-chain amino acids, and methionine, is a validated treatment for patients with PKU, MSUD, and HCU, respectively. However, adherence to lifelong dietary restrictions is a huge challenge for patients. Considering these factors, SCO-792-mediated inhibition of gut amino acid intake is a rational strategy for meeting unmet medical needs in treating amino acid-related disorders.

In a clinical trial, SCO-792 effectively decreased plasma amino acid levels derived from the diet or protein drinks, with an excellent safety profile in healthy individuals. This demonstrates a clinical proof-of-mechanism of SCO-792-mediated enteropeptidase inhibition for amino-acid-related diseases. Hence, SCO-792 is a potentially novel treatment solution for PKU, MSUD, HCU, and other amino acid metabolism disorders where dietary restriction of natural proteins is therapeutically effective.

Circulating amino acids also physiologically regulate the glomerular filtration rate, an indicator of human kidney function. Hence, a sustained intake of excess dietary protein likely impairs kidney function. Therefore, we suggest a novel strategy for inhibiting gut amino acid intake into the circulation to improve kidney function.

In preclinical studies, SCO-792 was highly effective in rodent models with nephrotic syndrome, a disease defined by severe proteinuria leading to hypoalbuminemia. In addition, in a Phase 2 proof-of-concept study, 12-week treatment with SCO-792 resulted in a clinically significant reduction in the urine albumin-to-creatinine ratio from baseline in patients with diabetic kidney disease (DKD). These suggest that SCO-792 may be a novel treatment option for nephrotic syndrome and DKD. Detailed information is available upon request.