Zealand Pharma presents new preclinical data on novel GLP-1-gastrin dual agonist showing significant increase in pancreatic beta-cell mass and improvement of glycemic control

10/4/2012 5:10 AM EST

Zealand Pharma A/S
Press release

Zealand Pharma presents new preclinical data on novel GLP-1-gastrin dual
agonist showing significant increase in pancreatic beta-cell mass and
improvement of glycemic control

Copenhagen, 2012-10-04 11:10 CEST (GLOBE NEWSWIRE) -- Press Release
No. 8/2012



- Data on ZP3022, a novel GLP-1-gastrin dual agonist, revealed by the company in
presentations at the European Association for the Study of Diabetes 48th Annual
                                    Meeting -





Copenhagen, 4 October 2012 – Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL)
reports that new data from preclinical studies with a novel peptide agonist,
ZP3022, from the company’s GLP-1-gastrin dual agonist program, demonstrate a
significant increase in pancreatic beta-cell mass associated with a significant
improvement in glycemic control. The data were revealed by the company
yesterday in a poster presentation at the European Association for the Study of
Diabetes (EASD) 48th Annual Meeting in Berlin, Germany. 



Christian Grøndahl, Chief Scientific Officer at Zealand Pharma, commented:

“We continue to see exciting results in our GLP-1-gastrin dual agonist program,
representing a novel approach to the treatment of diabetes with potential
disease modifying properties. The new data we present at EASD from studies in
preclinical models of diabetes show that the GLP-1-gastrin dual acting peptide,
ZP3022 significantly enhances beta-cell mass associated with a significant
decrease in blood sugar. These findings further substantiate the therapeutic
rationale for GLP-1-gastrin dual agonists as a potential future new treatment
option for patients with Type 2 diabetes.  With their potential to alter the
chronic progression of the disease, there may also be a possible role for this
type of compound in the treatment of Type 1 diabetes.” 





The poster presentation is titled

“The Novel GLP-1-Gastrin Dual Agonist ZP3022 Improves Glycemic Control in ZDF
Rats” (J. Skarbaliene et al, Zealand Pharma A/S) 



Study design

In the study, 84 diabetic Zucker Diabetic Fatty (fa/fa) rats (11 weeks of age)
were stratified into seven treatment groups of n=12 with matching HbA1c and
blood glucose (BG) levels. 12 lean ZDF (fa/+) rats were used as lean controls. 



The ZDF (fa/fa) rats were dosed subcutaneously twice daily (BID) for eight
weeks with vehicle, ZP3022 (10, 40 nmol/kg), liraglutide (40 nmol/kg),
exendin-4 (30 nmol/kg), gastrin17 (80 nmol/kg) or exendin-4 plus gastrin 17 (30
+ 80 nmol/kg). Lean rats were dosed with vehicle. 



HbA1c was measured at the start and end of treatment and an oral glucose
tolerance test was performed after five weeks of treatment. Fed blood glucose
was measured every other week and beta-and alpha-cell mass was determined at
the end of the study. 



Study conclusion

Treatment with ZP3022 significantly enhanced beta-cell mass (per BW) and
improved glycemic control in diabetic Zucker Diabetic Fatty rats, as evidenced
by a significant decrease in HbA1c levels and blood glucose concentrations as
well as improvements in glucose tolerance and increased insulin levels after an
oral glucose tolerance test. Notably, ZP3022 had a significantly better effect
on beta-cell mass and glycemic control than liraglutide at equimolar dose. The
anti-diabetic effects of ZP3022 make this compound a promising therapeutic
candidate for the treatment of type 2 diabetes. 





In an oral presentation today, Trine S. R. Neerup, Zealand Pharma, presented
results from a study showing the anti-diabetic effects of ZP3022 in a diabetic
mouse model under the following title: 



“The GLP-1-Gastrin dual agonist ZP3022 increases beta cell mass via an increase
in mean islet mass in db/db mice” (D Almholt et al, Zealand Pharma A/S) 



The results and conclusions from this study was also presented at the American
Diabetes Association’s Annual Scientific Sessions earlier this year and
reported by Zealand Pharma in Press Release no. 03/2012 on 10 June 2012. 



Study results and conclusion

In this 8 week study, treatment of diabetic db/db mice with ZP3022 caused a
sustained increase in beta-cell mass accompanied by a significant improvement
in glycemic control as measured by HbA1c. In comparison, liraglutide also
caused improved glycemic control, but displayed only a transient effect on
beta-cell mass. 





                                      # # #





For further information, please contact:



Zealand Pharma A/S

David H. Solomon, President & CEO, Tel: +45 22 20 63 00

Hanne Leth Hillman, Vice President, Director of IR & Corporate Communication,

Tel: +45 50 60 36 89, email:  





About Diabetes

Diabetes is a long-term disease that occurs either when the pancreas does not
produce enough insulin (the hormone that regulates blood glucose
concentrations), or when the body cannot effectively use the insulin it
produces, or both. This results in raised blood glucose concentrations
(hyperglycemia). Over time, uncontrolled hyperglycemia leads to the
macrovascular and microvascular complications of diabetes. Macrovascular
complications, which affect the large blood vessels, include heart attack,
stroke and peripheral vascular disease. Microvascular complications affect the
small blood vessels of the eyes (retinopathy), kidney (nephropathy) and nerves
(neuropathy). The incidence of Type 2 diabetes is growing at an alarming rate.
Over 310 million people worldwide is living with the condition today and the
number is expected to increase to more than 550 million people in 2030. 

About GLP-1 receptor agonists

GLP-1 (glucagon-like peptide-1) is a naturally occurring peptide hormone that
is released from the intestinal L-cells within minutes of food ingestion. The
main physiological actions of GLP-1 are glucose-dependent stimulation of
insulin secretion from pancreatic beta-cells and suppression of glucagon
secretion from pancreatic alpha-cell secretion of glucagon. 

GLP-1 receptor agonists are members of an established class of diabetes drugs
approved by regulatory authorities and marketed globally as mono andadd-on
treatment for patients with Type 2 diabetes. Their use is endorsed by the
European Association for the Study of Diabetes, the American Diabetes
Association, the American Association of Clinical Endocrinologists and the
American College of Endocrinology. Several novel GLP-1 receptor agonists are in
development. 

About gastrin

Gastrin is a naturally-occurring peptide hormone that is released primarily
from G-cells in the stomach during meal ingestion. The main action of gastrin
is to stimulate the secretion of gastric acid, a fluid that assists with the
breakdown and digestion of food. Gastric acid works in conjunction with enzymes
to process nutrients from food and create waste, which is sent to the
intestines.  It has also been suggested that gastrin plays a role in pancreatic
development. 

About GLP-1-gastrin dual agonists and ZP3022

ZP3022 is a compound from Zealand Pharma’s preclinical drug discovery program
on dual acting GLP-1-gastrin peptide agonists, designed to act on both the
GLP-1 and the gastrin receptors. In preclinical disease models of diabetes
(db/db mice and Zucker Diabetic Fatty (ZDF) rats), ZP3022 has been shown to
increase beta cell mass (insulin producing cell mass) to a greater extent than
liraglutide. Moreover, ZP3022 has been shown to significantly improve glycemic
control in diabetic mice both during treatment and in a follow up period after
end of treatment. 





About Zealand Pharma

Zealand Pharma A/S (NASDAQ OMX: ZEAL) is a biotechnology company based in
Copenhagen, Denmark. Zealand Pharma specializes in the discovery, optimization
and development of novel peptide drugs and has a broad and mature pipeline of
drug candidates identified through its own drug discovery activities. The
company’s lead drug invention is lixisenatide (Lyxumia®), a once-daily GLP-1
agonist, which is licensed to Sanofi for the treatment of Type 2 diabetes. In
November 2011, Sanofi filed for registration of lixisenatide in Europe and
regulatory filing in the United States is expected in December 2012. 

Zealand Pharma has a partnering strategy for the development and
commercialization of its products and in addition to the collaboration with
Sanofi in Type 2 diabetes, the company has partnerships with Boehringer
Ingelheim in diabetes/obesity, Abbott in acute kidney injury and Helsinn
Healthcare in chemotherapy induced diarrhea. Zealand Pharma focuses its
activities in disease areas where existing treatments fail to adequately serve
patient needs and where the market potential for improved treatments through
the use of peptide drugs is high.