Poxel’s Investigational Oral Agent - Imeglimin - Shows Unique Anti-diabetic Profile In Preclinical And Clinical Studies
6/16/2014 12:41:42 PM
• Imeglimin induces glucose-stimulated insulin secretion by improving beta cell glucose sensitivity
in Type 2 diabetic patients
• Imeglimin normalizes glucose tolerance and insulin sensitivity by improving mitochondrial function
in a diabetic pathophysiological model
• Imeglimin has a unique mechanism of action targeting the mitochondria bioenergetics
LYON, France, June 16, 2014 – Poxel SA presented data from human and animal studies with its
novel anti-diabetic agent – Imeglimin – currently in phase 2b clinical development, during the 74th
Scientific Sessions of the American Diabetes Association. The data demonstrate Imeglimin’s dual
activity on both insulin sensitizing and insulin secretion defects of Type 2 Diabetes, featuring the
innovative profile of this new anti-diabetic agent.
“These Phase 2 clinical trial and preclinical study results confirm that Imeglimin is the first treatment to
act on the two key defects of Type 2 Diabetes, namely insulin sensitizing and secretion,” said Thomas
Kuhn, CEO of Poxel. “Imeglimin acts directly on the three main organs affected by Type 2 Diabetes:
the pancreas, the liver and the muscle. Our recent data confirm that Imeglimin acts – at the organ
level - in a different manner from metformin and sitagliptin, evidencing its combination potential
already seen in two add-on trials in humans. These results validate that Imeglimin is unique among
current anti-diabetic agents.”
An oral communication entitled “Imeglimin Increases Glucose-Dependent Insulin Secretion and
Improves Beta-cell Function in Patients with Type 2 Diabetes” described the glucose-dependent
insulin secretion effect of Imeglimin administered to Type 2 Diabetes patients, using a hyperglycemic
clamp technique. Imeglimin significantly raises insulin response to glucose (p=0.035); achieving this
primary endpoint. Imeglimin increases significantly 1st and 2nd phase insulin secretion rates (p=0.034
and 0.031, respectively) and improves beta cell glucose sensitivity (p=0.034). Imeglimin has no effect
on plasma glucagon, in contrast to DPP-4 inhibitors.
Michael Roden, MD (Institute for Clinical Diabetology, German Diabetes Center, Department of
Endocrinology and Diabetology, University Hospital Düsseldorf, Düsseldorf, Germany) who presented
the work stated: “Imeglimin improves glucose sensing of the pancreatic beta cell and increases
glucose-stimulated insulin secretion, which contributes to the glucose lowering action of Imeglimin.
Given the activity of Imeglimin on both liver and muscle demonstrated in preclinical studies, Imeglimin
has a unique mechanism of action that could represent a new way of addressing the pathophysiology
underlying Type 2 Diabetes”.
A second oral communication entitled “Imeglimin Normalizes Glucose Tolerance and Insulin
Sensitivity in Improving Mitochondrial Function in a High-Fat-High Sucrose Diet Mice Model”
described Imeglimin’s benefit on glucose tolerance, insulin sensitivity and insulin signaling in both liver
and muscle in a nutrient-overload Type 2 diabetic model. Imeglimin adapts mitochondrial functioning
to this overload, leading to fat utilization. As a result, Imeglimin decreases liver steatosis, improves
insulin signaling and decreases insulin resistance, one of the two key defects of Type 2 diabetic
Dr. Vidal (INSERM U160, Faculté de Médecine Lyon-Sud, European Center for Nutrition and Health)
who headed the work commented: “we are very pleased to have achieved this important result in
understanding the mechanism by which Imeglimin exhibits insulin sensitizing effects and so contribute
to its anti-diabetic activity”.
A poster entitled “Imeglimin Decreases Hepatic Glucose Production through a Unique Mitochondrial
Mechanism of Action” was presented to ADA audience. The aim was to identify the underlying
mechanisms by which Imeglimin decreases gluconeogenesis in primary rat hepatocytes in
comparison to metformin. Imeglimin’s unique mechanism of action targets the mitochondrial
bioenergetics by inducing an increase in redox potential and a decrease in membrane potential
without modifying mitochondrial respiration by contrast to metformin.
Pr Eric Fontaine (INSERM U1055, Université de Grenoble France) whose team is broadly involved in
mitochondrial bioenergetics investigations stated: “these results are key to understand Imeglimin’s
innovative mechanism of action. Imeglimin inhibits gluconeogenesis without affecting respiratory flux,
thereby preventing Imeglimin from inducing lactic acidosis in contrast to metformin.”
About Type 2 Diabetes
Type 2 Diabetes is the most common type of diabetes. It usually occurs in adults, but is increasingly
seen in children and adolescents. In Type 2 Diabetes, the body is able to produce insulin but it is
either not sufficient or the body is not responding to its effects, leading to a build-up of glucose in the
blood. Type 2 Diabetes is a major cause of both cardiovascular and kidney diseases.
The number of people with Type 2 Diabetes is rising rapidly worldwide. This rise is associated with
economic development, ageing populations, increasing urbanization, dietary changes, reduced
physical activity and changes in other lifestyle patterns.
The International Diabetes Federation estimates that in 2011, 366 million people around the world
have diabetes. This total is expected to rise to 552 million in 2030. Each year a further 7 million
people develop diabetes. The current market is dominated by few product classes and significant
unmet needs remain for both physicians and patients.
The worldwide pharmaceutical market for Type 2 Diabetes, 60% of which is represented by oral antidiabetics,
is expected to increase from $31 billion in 2012 to $48.8 billion in 2021 (source IMS audits).
Imeglimin is the first in a new chemical class of oral anti-diabetic agents, the Glimins. Imeglimin acts
on three main target organs involved in glucose homeostasis: the liver, muscle, and the pancreas and
has therefore a distinct mode of action compared to existing treatments for Type 2 Diabetes. In that, it
looks like the best partner to complement other treatments. Imeglimin phase 2a monotherapy results
were published in Diabetes, Obesity and Metabolism in April 2012. In October 2011, Poxel reported
phase 2 results of Imeglimin as add-on therapy to metformin in patients inadequately controlled with
metformin monotherapy. This study achieved its primary end-point of superiority in HbA1c reduction
versus placebo (p<0.001). The study results are published in Diabetes Care. In November 2012,
Poxel reported phase 2 results of Imeglimin as add-on therapy to sitagliptin in patients inadequately
controlled with sitagliptin monotherapy. This study achieved its primary end-point of superiority in
HbA1c reduction versus placebo (p<0.001). The study results are published in Diabetes Care.
About Poxel SA
Poxel, founded in 2009, is a biopharmaceutical company developing innovative first-in-class drugs,
with a primary focus on Type 2 Diabetes. The company develops novel treatments before seeking
pharmaceutical industry partners. Poxel was spun out from Merck Serono and now operates
independently as a lean organization with strong in-house drug development and business expertise.
Poxel’s product pipeline consists of several first-in-class Type 2 Diabetes candidates, including
Imeglimin in phase 2b clinical development and a direct activator of AMPK, close to phase 1
development for the treatment of Type 2 Diabetes.
For more information, please visit www.poxel.com
Mrs. Pascale Malgouyres
Chief Business Officer Partner
Phone: +33 437 372 012 Phone: +49 89 210 228 0
Mr. Raimund Gabriel
Phone: +49 89 210 228 0
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