Biotech

The data discussed in an oral presentation and during two poster sessions highlight important new insights on the potential of several compounds for the treatment of type 2 diabetes as well as related metabolic diseases.

LYON, France–(BUSINESS WIRE)–POXEL SA (Euronext – POXEL – FR0012432516), a biopharmaceutical company
focused on the development of innovative treatments to treat type 2
diabetes, today announced the presentation of novel data on its lead
drug candidate, Imeglimin, and its direct adenosine
monophosphate-activated protein kinase (AMPK) activator, PXL770, at the
European Association for the Study of Diabetes (EASD) Annual Meeting in
Munich, Germany. The data discussed in an oral presentation and during
two poster sessions highlight important new insights on the potential of
each compound for the treatment of type 2 diabetes as well as related
metabolic diseases.
“These exciting results for Imeglimin represent significant progress in
further understanding the benefits beyond glycemic control that
Imeglimin can deliver, specifically the potential for beneficial
protective effects in the early stages of vascular dysfunction, which is
key in the treatment of type 2 diabetes,” commented Thomas Kuhn, CEO of
Poxel. “In addition, we are very enthusiastic about the AMPK target and
the data for PXL770, which have been consistent in a variety of animal
models. Our studies highlight the therapeutic potential of AMPK
activation by PXL770 for the treatment of type 2 diabetes, especially
for patients with cardiovascular risk and other metabolic disorders,
such as hepatic steatosis and metabolic syndrome.”
Imeglimin has completed Phase 2 development in over 850 subjects in the
US and EU and is currently being studied in a 300-patient Phase 2b
clinical trial in Japan. PXL770, a first-in-class direct AMPK activator,
which regulates cellular energy metabolism and is considered to mimic
the effects of long-term exercise, is in Phase 1 clinical development.
Imeglimin
The Imeglimin preclinical study in diabetic mice was designed to
investigate the compound’s effect on endothelial dysfunction, which is
the first step in the development of vascular diseases and a
contributing factor to atherosclerosis in type 2 diabetes. To measure
endothelial function, pressure or acetylcholine induced vasodilatation
was assessed in diabetic mice treated with an increasing dose of
Imeglimin. The study demonstrated that one week of treatment with
150mg/kg Imeglimin prevents endothelial dysfunction induced by severe
hyperglycemia in the mice suggesting that Imeglimin could provide
protective effects on micro and macro-vascular defects induced by
diabetes. These results further strengthen Imeglimin’s therapeutic
profile as vascular diseases remains a key complication of type 2
diabetes.
PXL770
The two studies conducted on PXL770 evaluated the effects of the direct
AMPK activator on fat metabolism and body weight in several model
systems. In the first study, presented in an oral presentation on
September 14th, 5-week old mice fed with a high fat or normal
diet were treated with 75mg/kg PXL770 or a control vehicle. Mice on a
high fat diet treated with PXL770 gained less weight than pair-fed
control animals despite identical caloric intake. Furthermore, an
increase in total energy expenditure and a significant increase in fat
oxidation could be observed in the PXL770 group compared to the high fat
control animals. Finally, over the 4 to 5-week treatment period, PXL770
significantly improved fasting glycemia and glucose tolerance by 32%
(p<0.001)and significantly reduced fat mass by 53% (p<0.0001)
compared to control animals, confirming the results seen in previous
studies.
In the second study, the inhibitory potency of PXL770 on de novo
lipogenesis was evaluated in primary mouse and human hepatocytes as well
as in vivo in nine-week-old mice. PXL770 dose dependently
decreased liver de novo lipogenesis with a high potency in all
model systems. The results are consistent with previous studies showing
a decrease in fatty acid synthesis following PXL770 treatmentconfirming
the role of AMPK in this metabolic pathway.
Overall, both studies solidify PXL770’s potential to treat type 2
diabetes and other cardiovascular risk factors, such as lipid disorders
and obesity, and also its potential to improve the treatment of hepatic
lipid metabolism disorders.
PXL770 is currently in Phase 1. In the first part of the Phase 1 study,
the results indicate that PXL770 exhibits a favorable safety and
tolerability profile with no safety signals. During the Phase 1 study,
Poxel observed a different metabolic pattern in humans compared to
animals that were treated with PXL770. Therefore, based on regulatory
guidelines, Poxel will need to further evaluate the profile of the
metabolites, which may be pharmacologically active, prior to starting
the second part of the Phase 1 study. As a result of this additional
preclinical work, the start of the second part of the Phase 1b study
will be delayed until 2017.
The posters and oral presentation presented at the EASD Annual Meeting
are available on the Company’s website under “Scientific Publications”
or by using the link http://poxel.com/our-science/scientific-publications.php.

  • Imeglimin Improves Vascular Dysfunction in Type 2 Diabetes Animal
    Models
  • PXL770, a novel direct AMPK activator, inhibits hepatic de novo
    lipogenesis for the treatment of metabolic disorders
  • PXL770, a novel direct AMPK activator, improves metabolic disorders
    in diet induced mice model of obesity and diabetes

About Imeglimin
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. Imeglimin’s
unique mechanism of action targets mitochondrial bioenergetics. This
distinct mode of action compared to existing treatments for type 2
diabetes makes Imeglimin a prime candidate in monotherapy and to
complement other treatments such as metformin or sitagliptin.
About PXL770
PXL770 directly activates adenosine monophosphate-activated protein
kinase (AMPK), an enzyme that acts as an energy sensor and regulator,
maintaining cellular homeostasis, thus playing an important role in the
management of diabetes. In addition to its anti-diabetic properties,
PXL770 has the potential to treat lipid-related abnormalities, which are
present in a vast majority of diabetic patients and are the cause of
cardiovascular incidents among this population, as well as other
metabolic disorders.
About Poxel SA
Poxel uses its development expertise in metabolism to advance a pipeline
of drug candidates focused on the treatment of type 2 diabetes. We have
successfully completed our Phase 2 clinical program for our
first-in-class lead product, Imeglimin, which targets mitochondrial
dysfunction, in the U.S. and EU and have fully enrolled a Phase 2b
clinical study in Japan. Our second program, PXL770, a direct AMPK
activator, is in Phase 1 development. We intend to generate further
growth through strategic partnerships and pipeline development.
Euronext: POXEL, www.poxel.com

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