In a Phase 1a clinical trial in healthy volunteers, BIO89-100 demonstrated a favorable tolerability profile as well as robust and durable biological effects on key lipid parameters after a single dose. In the study, the pharmacokinetic profile of BIO89-100 was generally dose-proportional with a half-life of 55-100 hours. Furthermore, at single doses of 9.1 mg and higher, BIO89-100 demonstrated significant improvements versus baseline in key lipid parameters measured at 8 and 15 days. The mean changes versus baseline included reductions in triglycerides (up to 51%) and LDL-C (up to 37%) and an increase in HDL-C (up to 36%). These data, together with data from pre-clinical studies done with BIO89-100, support weekly or every two weeks subcutaneous dosing. This longer dosing interval could provide significant value to patients who are typically asymptomatic from their liver disease and will require chronic therapy.
Given the potential of BIO89-100 to meaningfully reduce triglycerides, we also intend to develop BIO89-100 for the treatment of severe hypertriglyceridemia (SHTG). SHTG is defined as patients with triglycerides ≥500 mg/dL. While currently approved SHTG therapies decrease triglyceride levels, they have limitations. To the extent that we can show in subsequent human clinical trials that BIO89-100 significantly decreases both triglyceride and LDL-C levels and improves other metabolic parameters, we believe that BIO89-100 could be a differentiated therapy in this indication.
A phase 1b/2a trial in NASH is ongoing, and a phase 2 trial in SHTG is planned.
FGF21 is a metabolic hormone that regulates energy expenditure and glucose and lipid metabolism. It has been clinically shown to reduce liver fat (steatosis). It is also thought to exert effects on liver fibrosis through two pathways. First, by improving metabolic regulation, it reduces ongoing liver injury, thus giving the liver time to heal. Second, FGF21 generates an on-target effect to increase adiponectin, a hormone released from adipose tissue that can, among other functions, suppress the development and progression of hepatic fibrosis.
Hypertriglyceridemia is characterized by elevated levels of triglycerides (a type of lipid). When levels of triglycerides are severely elevated (≥500 mg/dL), the condition is known as SHTG and is associated with an increased risk of NAFLD, NASH, and cardiovascular diseases, as well as acute pancreatitis. It is estimated that there are 2.5 million to 4 million patients in the US with triglyceride levels ≥500 mg/dL. Of these patients, it is estimated that 42% have dyslipidemia and 27% have diabetes. This patient population is expected to increase due to the triple epidemic of obesity, metabolic syndrome, and Type 2 diabetes. A large portion of these patients are unable to achieve treatment goals with existing therapies. In third-party studies, up to 50% of treated SHTG patients were unable to reduce their triglyceride levels to <500 mg/dL, despite using certain approved drugs. Further, while these therapies may decrease triglyceride levels, they generally do not have broader metabolic benefits.