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 to 100 hours. These data, together with data from preclinical studies done with BIO89-100, support weekly or every two weeks subcutaneous dosing of BIO89-100, which could provide a significant benefit for patients under chronic therapy. 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 include reductions in triglycerides (non-cholesterol fat) of up to 51% and LDL-C (bad cholesterol) of up to 37% and an increase in HDL-C (good cholesterol) of up to 36%.
A phase 1b/2a trial in NASH and a phase 2 trial in SHTG are ongoing.
FGF21 is an endogenous metabolic hormone with broad effects regulating energy expenditure and glucose and lipid metabolism. In a clinical trial, treatment with another FGF21 analog has been shown to reduce liver fat (steatosis) and reduce liver scarring (fibrosis). This effect is mediated through two potential 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 liver fibrosis. In addition to its effects on the liver, FGF21 has been shown to reduce systemic levels of lipids (triglycerides and LDL cholesterol) as well as improve glycemic control.
Hypertriglyceridemia is characterized by elevated levels of triglycerides (a type of non-cholesterol fat). 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 up to 4 million patients in the US with triglyceride levels ≥500 mg/dL. Of these patients, it is estimated that up to 56% have excessive liver fat and up to 70% have elevated cholesterol or type 2 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 beneficial metabolic benefits.