BOSTON, Jan. 29 /PRNewswire/ -- Surface Logix today announced positive
results in the Company's Phase 2a clinical trial of SLx-4090 in
dyslipidemia (high cholesterol and triglyceride levels in the bloodstream).
The randomized, double-blind, placebo-controlled Phase 2a study in 24
patients with dyslipidemia demonstrated that SLx-4090 caused clinically
significant reductions in postprandial triglycerides and LDL-cholesterol
and was well tolerated. The trial was designed to examine the safety,
tolerability, pharmacokinetics and effect on lipid profiles in patients
administered repeat oral doses of SLx-4090 either three times daily or once
daily for 14 days. The Company intends to initiate a Phase 2b study of
SLx-4090 in dyslipidemia in the third quarter of 2008.
"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.
Contact:
Leland Webster, Ph.D., M.B.A.
Surface Logix Inc.
Vice President, Corporate Development
617.746.8520
Media:
Sarah Cavanaugh
MacDougall Biomedical Communications Inc.
781.235.3060
SOURCE Surface Logix, Inc.
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Related links:
http://www.surfacelogix.com
CONTACT:
Leland Webster, Ph.D., M.B.A., Vice
President, Corporate Development, Surface Logix Inc.,
+1-617-746-8520; Media, Sarah Cavanaugh, MacDougall Biomedical
Communications Inc., +1-781-235-3060
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