New Imeglimin Data Demonstrating Pancreatic Beta-Cell Protection Presented at the American Diabetes Association 78th Scientific Sessions | Financial Buzz

New Imeglimin Data Demonstrating Pancreatic Beta-Cell Protection Presented at the American Diabetes Association 78th Scientific Sessions

POXEL
SA (Euronext – POXEL – FR0012432516), a biopharmaceutical company
focused on the development of innovative treatments for metabolic
disorders, including type 2 diabetes and non-alcoholic steatohepatitis
(NASH), today announced that an oral presentation was made at the
American Diabetes Association (ADA) 78th Scientific Sessions
showing important new benefits relating to Imeglimin’s unique mechanism
of action in a preclinical model. The abstract titled, “Imeglimin
Protects Ins-1 Cells and Human Islets Against High Glucose and High
Fructose-induced Cell Death by Inhibiting the Mitochondrial PTP Opening”
was presented in a scientific session.

“Loss of insulin-producing beta-cells contributes to type 2 diabetes and
its progression. These preclinical data demonstrate Imeglimin’s ability
to prevent beta-cell death by fructose- and glucose-induced toxicity
through its unique mechanism of action of inhibiting the mPTP opening, a
mitochondrial channel involved in cell death,” said Professor Eric
Fontaine, MD, PhD, Grenoble Alpes University, an author of the
presentation who managed this study. “These data, combined with
previously reported data demonstrating Imeglimin’s beneficial effects on
beta-cell preservation and function in several different clinical and
preclinical studies, are striking and highlight Imeglimin’s potential
not only to treat type 2 diabetes disease, but also delay its
progression.”

“We are continuing to generate further differentiating data that are
additive to Imeglimin’s strong and consistent clinical results. The
potential of Imeglimin to preserve beta-cells from cell death could be
particularly important for patients who experience an early beta-cell
failure, such as Japanese patients. These results are particularly
interesting given the improvement of beta-cell function observed in the
Phase 2b clinical study,” said Thomas Kuhn, CEO of Poxel. “Working with
our partner Sumitomo Dainippon Pharma, we have made significant progress
advancing the Phase 3 Trials of IMeglimin for Efficacy
and Safety (TIMES) program for Imeglimin in Japan with the
initiation of all three pivotal Phase 3 trials, and we are on track for
the TIMES 1 efficacy data in the first half of 2019. In addition, we are
working closely with our partner Roivant Sciences to advance Imeglimin
into a Phase 3 program in the US and Europe.”

Imeglimin is an orally-available drug candidate with a novel mechanism
of action that has been observed in clinical studies to demonstrate
glucose lowering benefits by simultaneously targeting all three key
organs which play an important role in the treatment of type 2 diabetes:
the liver, muscles and the pancreas. Imeglimin has demonstrated in
preclinical studies the potential to address mitochondrial dysfunction,
which is believed to be at the core of type 2 diabetes pathophysiology.
Imeglimin has completed Phase 1 and Phase 2 development in over 1,200
subjects in the US, EU and Japan.

About the StudyIn a preclinical model of human pancreatic
islet cells, researchers investigated if Imeglimin could prevent mPTP
opening and cell death induced by high glucose or fructose
concentrations in INS-1 cells and human pancreatic islets. mPTP status
in intact cells was assessed by confocal microscopy by measuring
mitochondrial membrane potential (TMRM) and NAD(P)H (autofluorescence).
Cell viability was measured by flow cytometry. In INS-1 cells and human
islets, 30 mM glucose or 2.5 mM fructose for 24 hours led to PTP opening
(increase in the NAD(P)H/TMRM ratio), this phenomenon being prevented by
100?M Imeglimin. Compared to normal glucose concentration (100%), cell
viability significantly decreased (p<0.05) in cells exposed to 30 mM
glucose (76±5% and 47±18% in INS-1 cells and human islets, respectively)
and to 2.5 mM fructose for 72 hours (78±3% and 35±11% in INS-1 cells and
human islets, respectively), but remained unchanged when these cells
were preincubated with 100?M Imeglimin (in 30mM glucose: 94±3% and 98±3%
/ in 2.5mM fructose: 96±4% and 79±6% in INS-1 cells and human islets,
respectively).

Together, these results demonstrate that Imeglimin is able to prevent
high glucose and fructose-triggered cell death through the inhibition of
an mPTP opening and that an mPTP-targeted strategy can prevent beta-cell
death. These data show that in addition to its beneficial effect on
beta-cell function, Imeglimin may also have the potential to preserve
beta-cell mass in a dysmetabolic environment.

The presentation at the ADA is available on the Company’s website under
“Scientific Publications” or by using the following link http://poxel.com/our-science/scientific-publications.php.

About ImegliminImeglimin is the first clinical candidate in
a new chemical class of oral agents called Glimins by the World Health
Organization. Imeglimin has a unique mechanism of action (“MOA”) that
targets mitochondrial bioenergetics. Imeglimin acts on all three key
organs which play an important role in the treatment of type 2 diabetes:
the liver, muscles and the pancreas, and it has demonstrated glucose
lowering benefits by increasing insulin secretion in response to
glucose, improving insulin sensitivity and suppressing gluconeogenesis.
This MOA has the potential to prevent endothelial and diastolic
dysfunction, which can provide protective effects on micro- and
macro-vascular defects induced by diabetes. It also has the potential
for protective effect on beta-cell survival and function. This unique
MOA offers the potential opportunity for Imeglimin to be a candidate for
the treatment of type 2 diabetes in almost all stages of the current
anti-diabetic treatment paradigm, including monotherapy or as an add-on
to other glucose lowering therapies.

About Poxel SAPoxel uses its development expertise in
metabolism to advance a pipeline of drug candidates focused on the
treatment of metabolic disorders, including type 2 diabetes and
non-alcoholic steatohepatitis (NASH). We have successfully completed the
Phase 2 clinical program for our first-in-class lead product, Imeglimin,
which targets mitochondrial dysfunction, in the U.S., Europe and Japan.
Together, with our partner Sumitomo Dainippon Pharma, we are conducting
the Phase 3 Trials of IMeglimin for Efficacy
and Safety (TIMES) program for the treatment of type 2
diabetes in Japan. Our partner Roivant Sciences
will be responsible for Imeglimin’s development and commercialization in
countries outside of Poxel’s partnership with Sumitomo Dainippon Pharma,
including the U.S. and Europe. Our second program, PXL770, a first in
class direct adenosine monophosphate-activated protein kinase (AMPK)
activator, is in Phase 1 and we plan on developing it for the treatment
of NASH. PXL770 could also have the potential to treat additional
metabolic diseases. We intend to generate further growth through
strategic partnerships and pipeline development. (Euronext: POXEL, www.poxelpharma.com)

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