Catabasis Pharmaceuticals has announced preliminary data from a phase I trial of CAT-2003, an oral SMART Linker conjugate constructed using the company's proprietary technology, demonstrated a significant reduction in fasting and post-prandial triglyceride levels. CAT-2003 also had positive effects on other biomarkers, including reductions in apolipoprotein C-III (ApoC-III), a negative regulator of lipoprotein lipase, and apolipoprotein B (ApoB), the lipoprotein associated with VLDL and LDL cholesterol. In addition, reductions in plasma PCSK9 levels and LDL cholesterol were observed.

There were no serious adverse events reported. Data also showed the conjugated compound was absorbed following oral administration and metabolized into its active components intracellularly within target tissues.

"We believe these data support an enormous opportunity for CAT-2003 in treating patients with hypertriglyceridemia as well as a variety of other dyslipidemias," said Jill Milne, Ph.D., co-founder and chief executive officer of Catabasis. "CAT-2003 was safe and well tolerated at a therapeutic dose and produced reductions in both fasting and post-prandial triglycerides in subjects with triglycerides over 150 mg/dL. We are planning to evaluate CAT-2003 in additional trials in patients with severe hypertriglyceridemia as well as mixed dyslipidemias."

This randomized, double-blind, placebo-controlled phase I study was conducted in two parts in 99 patients. In the first part, 41 healthy adults received a single ascending dose of CAT-2003 or placebo. In the second part, 58 healthy adults and patients with mildly elevated lipids received CAT-2003 or placebo daily for 14 days. The study evaluated safety, tolerability and pharmacokinetics. Triglycerides, LDL cholesterol and biomarkers related to the mechanism of action of CAT-2003 were also assessed. A phase II study evaluating CAT-2003 in patients with hypertriglyceridemia is set for initiation this quarter.