Surface Logix Achieves Objectives With SLx-4090 In Phase 2a Clinical Trial
"The Phase 2a trial showed that SLx-4090 was efficacious and well tolerated in patients," said Dr. Warwick Tong, Senior Vice President of Commercial Development of Surface Logix. "We were particularly pleased to see, in both dosing regimens, drops not only in postprandial triglycerides but also in fasting LDL-cholesterol levels in just 14 days. Importantly, SLx-4090's adverse event profile was indistinguishable from that of placebo. We saw no effect on liver function tests, which is consistent with the compound being undetectable in the plasma, and no impact on bowel habit."
"We were also pleased to see clinically significant weight loss in patients who received SLx-4090," added Dr. William Prince, Chief Development Officer of Surface Logix. "We attribute this to the decreased uptake of triglycerides, a significant source of calories in the diet. Given that obesity is a major and growing health concern, we believe SLx-4090's potential to cause weight loss represents a significant opportunity for therapeutic intervention."
SLx-4090 is a novel, oral, non-systemically available inhibitor of microsomal triglyceride transfer protein (MTP) that acts by blocking the formation of particles known as chylomicrons in enterocytes, thereby reducing the uptake of triglycerides and cholesterol into the lymphatic circulation and ultimately, the systemic circulation. Designed to exert its effect only in enterocytes, SLx-4090 avoids mechanistic toxicities in the liver (where MTP inhibition causes fatty liver) and other organs. MTP inhibitors that have been brought into development by others lack this critical feature and have therefore encountered significant toxicity concerns in the clinic, which will severely limit their therapeutic potential. SLx-4090 has potential not only in dyslipidemia but also in obesity as a result of the compound's ability to restrict caloric absorption by reducing the uptake of triglycerides. An excellent safety profile is paramount in both indications.
"The industry generally considers the intestine a barrier through which to drive compounds into the systemic circulation - that is, as an obstacle to be overcome," commented Dr. Paul Sweetnam, Chief Scientific Officer of Surface Logix. "In the case of MTP inhibition, Surface Logix viewed the gastrointestinal tract not as an obstacle, but as an ally in our quest for a viable therapeutic. By applying our expertise in the biophysics of small molecule-lipid and interfacial interactions through the use of our Pharmacomer(TM) Technology Platform, we were able to design a compound that takes advantage of these interactions. SLx-4090 effectively eliminates the major stumbling block of systemic bioavailability encountered by other MTP inhibitors and therefore offers tremendous commercial potential."
The results from the trial provide further confirmation of the ability of the Pharmacomer(TM) Technology Platform to enable Surface Logix scientists to design specific pharmacokinetic performance into a molecule while optimizing potency and selectivity. Surface Logix endowed SLx-4090 with its unique enterocyte-targeting nature in order to differentiate it from conventional systemically available MTP inhibitors.
About the trial:
The Phase 2a study of SLx-4090 was a randomized, double-blind, placebo- controlled trial. A total of 24 dyslipidemic subjects received an oral dose of 200 mg of SLx-4090 or placebo once daily or three times daily for 14 days. Postprandial triglycerides were measured at frequent intervals daily. Fasting LDL-cholesterol was measured at the beginning and end of the study, as was body weight. Subjects were monitored for adverse events and pharmacokinetic sampling was performed at regular intervals.
About SLx-4090 in Dyslipidemia and Obesity
SLx-4090 is a novel non-systemically available microsomal triglyceride transfer protein (MTP) inhibitor being developed for the treatment of dyslipidemia (high cholesterol and triglyceride levels in the bloodstream). Designed to act only in enterocytes, SLx-4090 inhibits fat and cholesterol uptake but avoids the mechanistic toxicities of MTP inhibition in the liver and other organs such as the heart, testis, ovary and eye. Surface Logix is also exploring the use of SLx-4090 in other metabolic disorders, including obesity and diabetes.
Dyslipidemia currently affects about 10% of the global population, with 25% of these patients having elevated triglyceride levels. In addition, there is an increasing prevalence and medical need for lipid-modifying drugs in obese patients and patients with type 2 diabetes, as a high proportion of type 2 diabetic patients have abnormal concentrations of lipoproteins. In the U.S., Japan and Europe, it is estimated that there are more than 240 million people with abnormal lipoprotein levels. Of these, more than 55 million are estimated to have low levels of high density lipoprotein (HDL) and/or high triglyceride levels.
Obesity is a substantial and growing problem in the US and in the rest of the developed world. Approximately 100 million adults in the US are overweight or obese. Dietary fat is a significant contributor to obesity. Restricting caloric absorption by limiting the uptake of dietary fat through inhibition of the triglyceride transport function of MTP in the gastrointestinal tract represents a significant opportunity for therapeutic intervention.
About Surface Logix, Inc.
Surface Logix uses its expertise in biophysical chemistry to create and develop novel small molecule drugs (NCEs) with superior intrinsic drug-like properties that are clearly differentiated from competitive products. The company is advancing multiple internal programs focused primarily on cardiovascular, metabolic, inflammatory and fibrotic diseases. For more information, please visit http://www.surfacelogix.com.
Surface Logix, Inc.
http://www.surfacelogix.com
Suprafaþa de Logix atinge obiectivele cu SLx-4090, în studiul clinic de Fazã 2a - Surface Logix Achieves Objectives With SLx-4090 In Phase 2a Clinical Trial - articole medicale engleza - startsanatate