Preclinical Data Also Show DA-1726 Effectively
Reduces Body Weight and Glycemic Control
Data Presented in One ePoster Theater
Discussion and Two General Poster Presentations at the American
Diabetes Association 83rd Scientific Sessions
BOSTON, June 27,
2023 /PRNewswire/ -- NeuroBo Pharmaceuticals,
Inc. (Nasdaq: NRBO), a clinical-stage biotechnology company on
a quest to transform cardiometabolic diseases, today announced that
DA-1726, a novel oxyntomodulin (OXM) analogue functioning as a
glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor
(GCGR) dual agonist, had been shown to elicit superior weight loss
efficacy compared to Semaglutide (SEMA) and Tirzepatide (TIR) in
preclinical testing. This, and other data, was presented in one
ePoster theater discussion and two general poster presentations at
the American Diabetes Association's 83rd Scientific Sessions, held
June 23-26, 2023.
"DA-1726, a long acting OXM analog that binds and activates both
GLP-1 and glucagon receptors using a well understood mechanism, has
shown weight loss efficacy, despite similar or higher food intake,
in a dose-dependent manner, that is better than SEMA in
diet-induced obese (DIO) rats (32.6% for DA-1726 at a high dose
compared to 24.0% for SEMA, p<0.05)," stated Yuna Chae, DA-1726 Project Manager, Dong-A ST
Research Center. "Additionally, the high-dose DA-1726 increased the
expression of the thermogenic-related gene (Ucp1) in white adipose
tissues, supporting increased energy expenditure, and the gene
expression in white adipose tissue was increased. This suggests
that major genetic changes related to energy expenditure are
directly related to weight loss. As a result, we believe that
DA-1726 will have similar, superior weight loss effects in humans
utilizing its novel mechanism of action."
"In preclinical mice models, DA-1726 also showed the ability to
improve plasma glucose insulin and Homeostatic Model Assessment for
Insulin Resistance (HOMA-IR) as compared to Cotadutide (COTA),
another OXM analog. Importantly, DA-1726 showed superior plasma
triglyceride (TG) reduction and a similar reduction of total
cholesterol (T-CHO) compared to COTA. In a comparative preclinical
mouse study with GLP1R/glucose-dependent insulinotropic polypeptide
receptor (GIPR) dual agonist, Tirzepatide (TIR), DA-1726 showed
similar efficacy on weight loss, despite consuming more food.
However, DA-1726 was more efficacious in improving plasma metabolic
parameters such as glucose, TG, and T-CHO compared to TIR,
indicating differential metabolic effects caused by GCGR agonism.
Taken together, these data suggest that DA-1726 is a well-balanced
GLP-1 receptor and glucagon receptor dual agonist and we anticipate
that DA-1726 will have effective weight loss and glycemic control
in humans," concluded Ms. Chae.
"DA-1726 is a long-acting, novel peptide drug candidate in
preclinical development with therapeutic promise for obesity and
NASH, in preparation for a phase 1 clinical trial for obesity,"
stated Joe Hooker, Interim President
and Chief Executive Officer of NeuroBo. "Presenting two general
posters and one ePoster theater discussion at this important
scientific meeting provided us the ability to highlight positive
preclinical data for DA-1726 as a potential treatment for obesity,
and data showing superior effectiveness as compared to competitor
peptide therapeutics including SEMA. During the second half of this
year, our goal is to advance DA-1726 through the IND process.
Assuming acceptance by the U.S. Food and Drug Administration, we
plan to initiate a phase 1a safety study during the first half of
2024 and anticipate a data readout in the second half of 2024."
Abstract Title: A Novel GLP1R/GCGR Dual Agonist,
DA-1726 Elicits Weight Loss Superior to Semaglutide in Diet-Induced
Obese Rats
Poster: 1676
Authors: Tae-Hyoung Kim,
Il-Hun Jung, Kyumin Kim,
Hyung Heon Kim, Mi-Kyung Kim, Yuna
Chae
Presenter: Yuna Chae, Dong-A
ST Research Center
Session: General Poster Session
Date and Time: Monday, June 26,
2023, 11:30 AM - 12:30 PM
PDT
Location: Poster Halls B-C
DA-1726 showed superior weight loss efficacy compared to
Semaglutide (SEMA) in diet-induced obese (DIO) mice. In this
study, a dose-response of DA-1726 was evaluated to determine the
maximum efficacy in DIO rats which are known for translatability to
human studies. The half-life of DA-1726 was longer in rats compared
to mice, however the in vitro activity of DA-1726 against rat
glucagon receptor was less potent than in mice, and plasma protein
binding was approximately 10-fold higher in rats. Therefore, the
effective dose for rats was set higher than for mice. DA-1726 was
injected twice a week for approximately 4 weeks, and a
dose-dependent and significant weight loss effect was observed. The
minimum effective dose in DIO rats was found to be 250 nmol/kg.
Then, the maximum body weight loss effects of DA-1726 (500 and 1000
nmole/kg) and SEMA were compared in the DIO rat model. DA-1726
showed an excellent weight loss effect compared to SEMA (32.6% for
DA-1726 at a high dose vs. 24.0% for SEMA, p<0.05). The low-dose
DA-1726 group showed a similar effect compared to SEMA in spite of
consuming more food. The high-dose DA-1726 group showed similar
food intake as SEMA, however it led to a higher weight loss effect.
After repeated dosing, the high-dose DA-1726 increased the
expression of energy metabolism-related genes (Ucp1, Ppargc1a) in
white adipose tissues (WAT), supporting increased energy
expenditure. In order to confirm whether this increased gene change
was a direct effect leading to weight loss or an indirect effect
caused by weight loss, changes in gene expression were assessed
after single dosing. DA-1726 (250 and 500 nmol/kg) induced small
but significant weight loss 3 days after a single injection (-7.6%
and -9.5% vs. control). However, the genes expression (Ucp1,
Ppargc1a) in WAT was increased only in the 500 nmol/kg-treated
group suggesting a direct effect. Therefore, DA-1726 is expected to
elicit significant weight loss effects in humans with a new
mechanism of action.
DA-1726 showed equal
or greater efficacy with higher food
intake compared to Semaglutide in reducing body
weight
DA-1726 showed significant increase in
white adipose tissue gene
expression suggesting energy expenditure's
direct impact on weight loss
Abstract Title: Differentiated Metabolic Effects of
DA-1726, a Balanced GLP1R/GCGR Dual Agonist
Authors:
Il-Hun Jung, Tae-Hyoung Kim,
Su Jin Lee, Hyung Heon Kim, Mi-Kyung
Kim, Yuna Chae
Poster: 1668
Session: ePoster Theater
Date and Time: Sunday, June 25,
2023, 12:10 PM – 12:20 PM PDT
Location: Exhibit Hall (ePoster Theater A)
Session: General Poster Session
Date and Time: Monday, June 26,
2023, 11:30 AM - 12:30 PM
PDT
Location: Poster Halls A-B
The pharmacological effect of DA-1726 was evaluated compared to
other competitor peptides. DA-1726 showed superior efficacy
compared to another GLP1R/GCGR dual agonist, Cotadutide (COTA), in
reducing body weight (14.4% for DA-1726 and 6.4% for COTA vs.
diet-induced obese (DIO) mice control at 30 nmol/kg, p<0.05) and
improving plasma glucose, insulin, and Homeostatic Model Assessment
for Insulin Resistance (HOMA-IR) (-91% for DA-1726 vs. -52% for
COTA) in DIO mice. In addition, DA-1726 showed superior plasma
triglyceride (TG) reduction and similar reduction of total
cholesterol (T-CHO) compared to COTA. The data suggests that the
balanced dual agonist DA-1726 was superior to a GLP1R-biased dual
agonist in metabolic effects. Additionally, enhanced glucagon
action of GLP1R/GCGR dual agonists may increase the risk of
hyperglycemia when GLP1R agonism is reduced. DA-1726 was injected
for 3 weeks and a glucose tolerance test was performed at 72 hours
after the last dosing. DA-1726 did not impair glucose tolerance
even at minimal plasma concentrations during repeated dosing up to
100 nmol/kg. In the case of repeated dosing of 100 nmol/kg, the
plasma drug concentration at 72 hours after the final injection is
similar to the concentration that induces about 50% activation of
receptors under 4% human albumin condition. In a comparative study
with a GLP1R/glucose-dependent insulinotropic polypeptide receptor
(GIPR) dual agonist, Tirzepatide (TIR), DA-1726 showed a similar
maximum efficacy on weight loss (31.2% for DA-1726 and 31.3% for
TIR vs. DIO control, p<0.05). However, DA-1726 was more
efficacious in improving plasma metabolic parameters such as
glucose, TG, and T-CHO compared to TIR, indicating differential
metabolic effects caused by GCGR agonism. Taken together, this data
suggests that DA-1726 is a well-balanced GLP1R/GCGR dual agonist
that effectively reduces body weight and glycemic control.
DA-1726 showed
similar efficacy with higher food
intake compared to Tirzepatide in reducing body
weight
Copies of the presentation materials are available on the
NeuroBo Pharmaceuticals website
at https://www.neurobopharma.com/presentations.
About NeuroBo Pharmaceuticals
NeuroBo Pharmaceuticals,
Inc. is a clinical-stage biotechnology company on a quest to
transform cardiometabolic diseases. The company is currently
developing DA-1241 for the treatment of Non-Alcoholic
Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM), and is
developing DA-1726 for the treatment of obesity. DA-1241 is a novel
G-Protein-Coupled Receptor 119 (GPR119) agonist, which promotes the
release of key gut peptides GLP-1, GIP, and PYY. In preclinical
studies, DA-1241 demonstrated positive effect on liver
inflammation, lipid metabolism, weight loss, and glucose
metabolism, reducing hepatic steatosis, hepatic inflammation, and
liver fibrosis, while also improving glucose control. DA-1726 is a
novel oxyntomodulin (OXM) analogue that acts as a glucagon-like
peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual
agonist. OXM is a naturally-occurring gut hormone that activates
GLP1R and GCGR, thereby decreasing food intake while increasing
energy expenditure, thus potentially resulting in superior body
weight loss compared to selective GLP1R agonists.
For more information, please
visit www.neurobopharma.com.
Forward Looking Statements
Certain statements in this
release may be considered forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including without limitation, statements about the closing of the
offering of securities. Forward-looking statements are predictions,
projections and other statements about future events that are based
on current expectations and assumptions and, as a result, are
subject to risks and uncertainties. Many factors could cause actual
future events to differ materially from the forward-looking
statements in this release, including, without limitation, those
risks associated with our ability to execute on our commercial
strategy; the timeline for regulatory submissions; the ability to
achieve results in human clinical trials that are similar to those
received in preclinical animal trials; NeuroBo's ability to achieve
similar results in future preclinical trials; regulatory steps and
potential regulatory approval of NeuroBo's current and future
product candidates, the ability to realize the benefits of the
license agreement with Dong-A ST Co. Ltd., including the impact on
future financial and operating results of NeuroBo; the ability to
integrate the new product candidates into NeuroBo's business in a
timely and cost-efficient manner; the cooperation of our contract
manufacturers, clinical study partners and others involved in the
development of our current and future product candidates; our
ability to initiate and complete clinical trials on a timely basis;
our ability to recruit subjects for our clinical trials; costs
related to the license agreement, known and unknown, including
costs of any litigation or regulatory actions relating to the
license agreement; changes in applicable laws or regulations;
effects of changes to NeuroBo's stock price on the terms of the
license agreement and any future fundraising; and other risks and
uncertainties described in our filings with the SEC.
Forward-looking statements speak only as of the date when made.
NeuroBo does not assume any obligation to publicly update or revise
any forward-looking statements, whether as a result of new
information, future events or otherwise.
Contact:
Rx Communications Group
Michael Miller
+1-917-633-6086
mmiller@rxir.com
View original content to download
multimedia:https://www.prnewswire.com/news-releases/neurobo-pharmaceuticals-novel-glp1r-and-gcgr-dual-agonist-da-1726-shown-to-elicit-superior-weight-loss-efficacy-compared-to-semaglutide-and-tirzepatide-in-preclinical-models-301863706.html
SOURCE NeuroBo Pharmaceuticals, Inc.