Gelesis Presents Expanded Data Showing Impact of Gelesis100 Hydrogel on Patients with Prediabetes, Untreated Diabetes, and Elevated Insulin Resistance

Individuals with prediabetes and those with untreated type 2 diabetes
had six times higher odds to achieve ≥10% weight loss compared to placebo

Individuals with high insulin resistance achieved significant drop in
HOMA-IR levels on treatment independent of their level of weight loss

BOSTON–(BUSINESS WIRE)–Gelesis,
a biotechnology company developing first-in-class mechanotherapeutics to
treat obesity and other chronic diseases related to the gastrointestinal
(GI) pathway, today announced clinical data from its pivotal GLOW study
suggesting that elevated fasting plasma glucose could be a useful and
unique predictor to identify individuals who have higher adjusted odds
to achieve significant weight loss with Gelesis100. As observed in a
previous pilot study, participants with prediabetes or untreated type 2
diabetes were particularly responsive to its lead product candidate for
weight management, Gelesis100. In addition, participants with high
insulin resistance improved their insulin sensitivity significantly on
treatment, including the non-responders (defined as those achieving less
than 5% total body weight loss). The data were presented in two posters
at ENDO 2019, the Endocrine Society’s annual meeting.

“These findings provide compelling data that Gelesis100 may have
particularly pronounced benefits for patients with elevated fasting
blood glucose and diabetes. While additional studies with a longer time
period need to be done, the metabolic and weight loss effects observed
in the GLOW study support the concept that Gelesis100 could be an option
for patients with high insulin resistance,” said Harry L. Leider, M.D.,
MBA, FACPE, Chief Medical Officer of Gelesis. “We have already
demonstrated that Gelesis100 is an effective tool for weight management.
We now have data suggesting that the hydrogel may modulate the endocrine
and metabolic systems to positive effect. We are eager to continue
exploring the mechanisms behind these findings.”

The data presented at ENDO 2019 come from subgroup analysis of the
Gelesis Loss of Weight (GLOW) study, a pivotal multicenter,
double-blind, placebo-controlled study of Gelesis100. The overarching
study showed statistically significant separation from placebo in the
ITT population and found that nearly 6 in 10 people treated with
Gelesis100 were responders who lost, on average, 10% (about 22 pounds)
of their body weight over six months.

In this subgroup analysis, researchers found that 44% of patients with
elevated fasting blood glucose or untreated type 2 diabetes were
“super-responders,” meaning they lost at least 10% of their body weight
(30 pounds on average) when treated with Gelesis100 (adjusted OR = 6.1,
P = 0.007). Interestingly they had six times the odds of being
super-responders, compared to placebo. Across the entire treatment group
in the GLOW study, baseline fasting plasma glucose was correlated with
greater weight loss (R =-0.24, P = 0.0144). The pronounced weight loss
effect of Gelesis100 treatment in this population, which is at higher
clinical risk, was also observed in the previous FLOW pilot study. The
repeated findings suggest that Gelesis100 may be a new tool for aiding
in weight management in patients at high risk of diabetes or
diabetes-related complications.

“Participants with elevated fasting blood glucose and untreated type 2
diabetes had higher odds of achieving loss of at least 10% of their body
weight. This was an important result as this population almost
invariably has lesser weight loss in behavioral and medication trials,”
said Scott Kahan, M.D., MPH, director of the National Center for Weight
and Wellness and a physician specializing in obesity.

A separate analysis found that patients with high insulin resistance – a
significant driver of diabetes – had positive metabolic responses to
treatment with Gelesis100. Insulin resistance was measured by
homeostatic model assessment – insulin resistance (HOMA-IR). Patients
with high IR at the start of the clinical trial (mean baseline HOMA=
5.0) had a statistically significant reduction in HOMA-IR over the
six-month treatment period (-22.3 +/- 9.5%, P= 0.021). Importantly this
reduction was observed both in patients that were weight loss responders
(with 5% or greater weight loss) and also in non-weight loss responders.
The HOMA-IR decrease in the subgroup overall was driven by a significant
reduction in fasting serum insulin.

The GLOW study was designed to assess change in body weight in adults
with overweight or obesity after six months of treatment with
Gelesis100. Topline results of the study were announced in September
2017. The study had two predefined co-primary endpoints: at least 35% of
patients taking Gelesis100 achieving ≥ 5% weight loss (categorical
endpoint) and placebo adjusted weight loss to be assessed in two ways
(super-superiority margin of 3% and also simple superiority). The study
met and exceeded the pre-defined categorical endpoint, with 59% of
adults in the treatment group achieving weight loss of 5% or greater. As
previously announced, the study did not meet the 3% super-superiority
endpoint but demonstrated superiority of the Gelesis100 treatment over
the placebo group (–6.4% vs. –4.4%, P=0.0007). Gelesis100-treated
individuals had twice the odds of achieving at least 5% and at least 10%
weight loss vs. placebo (adjusted odds ratio [OR]: 2.0, P=0.0008;
adjusted OR: 2.1, P=0.0107, respectively).

The overall incidence of adverse events in the Gelesis100 treatment
group was no different than placebo (71% in both groups). The most
common AEs were gastrointestinal disorders (186 AEs in 96 [43%] subjects
in the Gelesis100 arm, compared to 134 events in 72 [34%] subjects
receiving placebo), infections and infestations (94 events in 74 [33%]
subjects with Gelesis100 and 101 events in 70 [33%] subjects with
placebo), and musculoskeletal and connective tissue disorders (38 events
in 31 [14%] subjects with Gelesis100 and 45 in 34 [16%] subjects with
placebo). There were no serious adverse events (SAE) in the Gelesis100
treatment group, whereas there was one (1) SAE in the placebo treatment
group.

Gelesis100 has been extensively evaluated in clinical studies and has
been submitted to the U.S. Food and Drug Administration for review.

About Gelesis 100

Gelesis100 is a non-systemic, superabsorbent hydrogel in development for
the potential treatment of overweight or obesity. It is made by cross
linking two naturally-derived building blocks, modified cellulose and
citric acid, that create a three-dimensional matrix. Gelesis100
particles rapidly absorb water in the stomach and homogenously mix with
ingested foods. Rather than forming one large mass, it creates thousands
of small individual gel pieces with the elasticity (firmness) of solid
plant-based foods (e.g., vegetables) without caloric value. The
Gelesis100 hydrogel mass increases the volume and elasticity of the
stomach and small intestine contents, promoting fullness and potentially
increasing satiety to help patients lose weight. Once it arrives in the
large intestine, the hydrogel is partially broken down by enzymes and
loses its three-dimensional structure along with most of its absorption
capacity. The released water is reabsorbed in the large intestine, and
the remaining cellulosic material is expelled in the feces. Gelesis100
is considered a medical device because it achieves its primary intended
purpose through a mechanical mode of action. This investigational
product and its earlier prototypes have been studied in more than 450
patients (excluding patients treated by placebo) across five clinical
studies throughout the United States, Canada, and Europe and in these
demonstrating a strong efficacy, tolerability and safety profile. Other
than an increase in overall gastrointestinal adverse events (AEs), most
of which were assessed as mild, there was no difference in the incidence
and severity of AEs between the Gelesis100 and placebo groups. In both
treatment groups, most AEs were mild or moderate in intensity. No
serious adverse events were observed in the Gelesis100 group. For more
information, visit gelesis.com.

About Gelesis

Gelesis is developing a novel hydrogel platform technology to treat
overweight and 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 a weight management aid. 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

Investors
Kathryn McNeil
+1 347 204 4226
[email protected]

U.S. media
Tom Donovan
+1 857 559 3397
[email protected]