Surface Logix - Pipeline - SLx4090 - INTESTINAL SELECTIVE MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN INHIBITOR

SLx-4090 INTESTINAL SELECTIVE MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN INHIBITOR

SLx-4090 is a novel Microsomal Triglyceride Transfer Protein (MTP) inhibitor that is in development for the treatment of mixed dyslipidemia. Designed to act selectively in the enterocytes lining the gastrointestinal tract it prevents the formation of chylomicrons which are used to transport triglyceride (TG) and cholesterol into the systemic circulation. The novelty of SLx-4090 is that it is selective for enterocytes and is not absorbed into the systemic circulation. Previous MTP inhibitors have acted both in the intestine and in the liver, causing fat build up in the liver, an unacceptable toxicity.

SLx-4090 has completed single dose and repeat dose Phase 1 studies which have confirmed that it is active in the gut significantly blocking fat absorption but the drug is not present in the systemic circulation. A Phase 2a study in dyslipidemic patients is underway.

Treatment with SLx-4090 is predicted to reduce both post-prandial and fasting TG levels and to have an impact on cholesterol absorption. more...

Preclinical Development

Several preclinical efficacy and safety studies have been conducted with SLx-4090. In preclinical studies, a potent, selective and systemically available MTP inhibitor (failed development at Phase 2) was used as a control.

Efficacy

Animal studies were used to look at the effects of acute dosing on postprandial triglyceride levels and of chronic dosing on fasting TG levels. SLx-4090 had similar efficacy to the positive control causing significant reductions in both postprandial and fasting TG levels.

Safety

At efficacious doses no SLx-4090 was detected in plasma after six weeks of treatment. In comparison to the positive control there was no build up of fat in the liver and no increase in the levels of liver enzymes (ALT and AST).

Clinical Development

Surface Logix has completed both a single dose Phase 1 study and a repeat dose Phase 1 study with SLx-4090. Together, these studies demonstrated that SLx-4090 was well tolerated and had a significant impact on both postprandial TG levels and LDL-cholesterol levels compared to placebo. Importantly, SLx-4090 was not detectable in the plasma at any dose.

A Phase 2a study in patients with dyslipidemia is underway, and preliminary results are very promising.