Gelesis Presents Preclinical Data Showing Proprietary Hydrogel Prevents Harmful Effects of a High-Fat Diet

Mice fed high-fat diet and treated with Gel-B (GS300 prototype)
hydrogel were protected against the development of fatty liver and
associated metabolic disorders

Preclinical data suggest Gel-B targets gut-related pathophysiologies
that drive insulin resistance, NAFLD and NASH

BOSTON–(BUSINESS WIRE)–Gelesis,
a biotechnology company at the forefront of developing
mechanobiology-based therapies to treat chronic diseases related to the
gastrointestinal (GI) system, today announced compelling preclinical
data suggesting that the Company’s proprietary hydrogel, Gel-B (GS300
prototype), prevents the harmful effects of a high-fat diet on the liver
and associated metabolic disorders. The late-breaking poster was
presented at the International Liver Congress 2019, held this week in
Vienna, Austria.

Preclinical data presented by Gelesis last month at ENDO, The Endocrine
Society Annual Meeting, demonstrated that Gel-B treatment, designed with
specific mechanical properties, restored gut barrier function in mice
after severe intestinal wall injury and prevented unwanted substances
from reaching the circulatory system. Those findings suggested potential
therapeutic utility for Gel-B in minimizing the low-grade systemic
inflammation and diseases associated with gut barrier dysfunction.

The latest data presented today suggest that Gel-B not only has a
protective effect on the gut barrier but may also work to prevent liver
and metabolic disorders associated with high-fat diets. In the study,
mice fed a high-fat diet and treated with Gel-B were protected from
developing non-alcoholic fatty liver disease (NAFLD), insulin resistance
and excessive weight gain.

“There is a rising epidemic of non-alcoholic fatty liver disease
worldwide and a desperate need for therapeutic agents. These data
suggest a unique approach to treat fatty liver diseases by restoring the
normal function of the gut barrier and warrant further investigation,”
said Arun Sanyal, M.D., a gastroenterologist at the Virginia
Commonwealth University School of Medicine and advisor to the Company.
“This research demonstrates an improvement in GLP-1 levels, change in
gut flora and upregulation of tight junctions, all of which could
improve the integrity of the gut wall and prevent fat accumulation and
other harmful substances from reaching and inflaming the liver.”

In the study presented at EASL, mice were divided into four groups:
low-fat diet, high-fat diet and high-fat diet enhanced with either low
or high doses of Gel-B, a proprietary non-systemic hydrogel previously
shown to restore gut barrier function in a preclinical model. Gel-B
prevented the development of fatty liver in all mice in the high dose
group and most of the mice on the low dose, despite being fed with a
high fat diet (45% lard) for 18 weeks. Those treated with Gel-B along
with the high-fat diet also showed significant improvements across
multiple measures of metabolic function as compared with the high-fat
control (mice on the same diet without Gel-B). Among the observed
changes: mice on Gel-B treatment had a significant reduction of insulin
resistance as measured by homeostatic model assessment – insulin
resistance (HOMA-IR), decreased insulin levels and higher levels of
GLP-1, a gut hormone known to affect liver health.

“We’re excited to share new insights into the effects of this new
investigational approach on the gut barrier. Preclinical studies
indicate that Gel-B protects against the negative effects of a high-fat
diet by enhancing the intestinal barrier properties through a mechanical
action leading to closing the gaps between intestinal epithelial cells,
which make up the first layer of defense in the gut,” said Elaine
Chiquette, Pharm.D., Chief Scientific Officer at Gelesis. “We continue
to collaborate with key researchers to understand additional mechanisms
of action, such as changes in microbiome and gut hormones, to advance
our understanding of Gel-B effects on gut and liver health.”

Gelesis’ proprietary hydrogels are orally administered and made from two
naturally derived building blocks – modified cellulose cross-linked with
citric acid – that create a three-dimensional matrix to achieve specific
mechanical properties through the GI.

About Gelesis

Gelesis is developing a novel hydrogel platform technology to treat
overweight, obesity and chronic diseases related to the GI pathway.
Gelesis’ proprietary approach is designed to act mechanically in the GI
pathway to potentially alter the course of chronic diseases. The
company’s lead product candidate, Gelesis100, has been submitted to the
FDA for review as an aid to weight management. Additionally, Gelesis is
developing its second candidate, Gelesis200, a hydrogel optimized for
weight loss and glycemic control in patients with type 2 diabetes and
prediabetes. Novel hydrogel mechanotherapeutics based on the Gelesis
platform technology are also being advanced through a pipeline in other
GI inflammatory conditions where gut barrier and gut permeability
potentially play a role, such as non-alcoholic steatohepatitis (NASH)
and inflammatory bowel disease (IBD).

The Gelesis executive and advisory team includes some of the world’s
leading experts in obesity, materials science, chronic disease research
and commercialization. Gelesis was co-founded by PureTech Health (LSE:
PRTC), a biopharmaceutical company focused on the Brain-Immune-Gut (BIG)
Axis. For more information, visit gelesis.com or
connect with us on Twitter @GelesisInc.

Contacts

Kathryn McNeil
+1 347 204 4226
[email protected]