Zealand Pharma

Legal Proceedings Report • Nov 20, 2013

Copenhagen, 2013-11-20 07:30 CET (GLOBE NEWSWIRE) -- Company Announcement

No. 26/2013

-- Zealand-discovered peptide has the potential to be the first medicinal
therapy to protect against tissue damage following reperfusion
-- The first patient has been treated in this Phase II study, conducted at
Rigshospitalet in Denmark, a world leading Cardiac Center, and which is
expected to enroll a total of 600 patients with myocardial infarction

Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL) (“Zealand”) today announces
that the first patient has been treated in a Phase II Clinical Proof-of-Concept
study of danegaptide. Danegaptide is a novel Zealand invented dipeptide with
potential as a first-in-class medicinal treatment to reduce tissue damage
caused by reperfusion.

The objective of this Phase II study is to assess the efficacy and safety of
danegaptide in reducing tissue damage from reperfusion injuries in patients
with an acute myocardial infarction (ST-segment elevation myocardial
infarction, STEMI) when added to standard treatment in the form of balloon
dilatation (primary PCI). The study is a randomized, double-blind,
placebo-controlled study, which will be conducted at Rigshospitalet in
Copenhagen. It is expected to enroll a minimum of 600 STEMI patients, who will
be randomized to treatment with either a high or a low dose of danegaptide or
placebo in connection with a PCI procedure. Rigshospitalet treats more than 40%
of Denmark’s approximately 2,500 incidences of STEMI annually and is one of the
world’s leading and highly specialized Cardiac Centers.

The primary study endpoint is assessing the therapeutic effect of danegaptide
in the reduction of tissue damage, measured as myocardial salvage index three
months after the PCI procedure, by use of magnetic resonance imaging. The
myocardial salvage index is a documented, strong prognostic marker for cardiac
outcome (e.g. death and heart failure). Secondary study endpoints include
clinical events of heart failure, re-hospitalizations for heart failure,
pharmacodynamic effects and safety of danegaptide when added to the standard
treatment of STEMI patients.

Commenting on the start of the danegaptide study, Dr. Thomas Engstrøm, PhD,
DMSc, Lead Investigator and Chief Physician, the Heart Center, Rigshospitalet,
Copenhagen University Hospital, said: “Over the past 15 years we have advanced
the treatment of myocardial infarction substantially with the introduction of
PCI, including mainly balloon dilatations, saving many patients’ lives. At
Rigshospitalet, we have pioneered balloon dilatations as first line treatment
in this indication, and today such interventional procedures have become the
established standard in most parts of the world. Despite having optimized also
the logistics for bringing patients with an MI to the hospital as fast as
possible, we still see severe cardiac tissue damage in many patients, which
lead to reduced cardiac function and quality of life. The problems are to a
large extent caused by reperfusion injuries following the therapeutic
intervention, and danegaptide has demonstrated promising potential to help
protect against this type of tissue damage. If successful, danegaptide could
play a major role in enhancing the clinical outcome of percutaneous coronary
intervention (PCI) after an acute MI and deliver important benefits to patients
and society.”

Commenting on the announcement, David Solomon, President and Chief Executive
Officer of Zealand Pharma, said: “The commencement of this Phase II Clinical
Proof-of-Concept study of danegaptide is a key event for Zealand in-line with
our ambition to optimize and increase the value of our proprietary clinical
pipeline of peptide candidates. Danegaptide has demonstrated great potential
as a novel approach to help reduce cardiac tissue damage with additional
potential in other forms of reperfusion injury, and we are excited about the
unique opportunity of working with Rigshospitalet to further explore the
therapeutic profile of this Zealand peptide.

“Rigshospitalet’s Heart Center is renowned for its clinical expertise. We are
proud to be working with this esteemed team which has conducted several other
important studies that have helped to change the international guidelines for
the treatment of patients with myocardial infarction.”

Danegaptide has shown promising therapeutic properties in several relevant
preclinical MI models assessing cardiac reperfusion injury. In a Phase I
program, including 153 healthy subjects in three studies, danegaptide has been
shown to be safe and well tolerated.

The danegaptide Phase II Clinical Proof-of-Concept study is expected to
complete in the 2nd half of 2015.

.

                                  ***

For further information, please contact:

David H. Solomon, President and Chief Executive Officer

Tel: +45 2220 6300

Hanne Leth Hillman, Vice President and Head of IR & Corporate Communications

Tel: +45 5060 3689, email: hlh@zealandpharma.com

About danegaptide

Danegaptide (ZP1609) is a small dipeptide invented by Zealand, demonstrating
both anti-arrhythmic and cytoprotective properties.

In a pre-clinical dog model of acute myocardial infarction (MI), i.e. an acute
blood clot in the heart, danegaptide has demonstrated dose-dependent
significant reductions in infarct size. In another relevant translational model
of reperfusion injury associated with an acute MI, danegaptide significantly
reduced infarct size compared to immediate full reperfusion1. Results from an
extensive Phase I program with danegaptide, including three (3) individual
studies in 153 subjects, showed that the compound was safe and well tolerated.

Reference

1 Journal of the American College of Cardiology: Volume 61, Issue 10,
Supplement, Page E67, 12 March 2013

About Ischemic Reperfusion Injury

Ischemic heart disease is a disease characterized by reduced blood supply to
the heart and it is one of the leading causes of death in the industrialized
world. The condition is most often caused by a myocardial infarction (a heart
attack), where a blood clot blocks blood flow for a longer period of time (ST
segment elevation myocardial infarction, STEMI). In 2020, the incidence for
STEMI is predicted to be 756.700 in US, EU and Japan combined. The treatment of
acute myocardial infarction (AMI) is aimed at enabling the return of blood flow
to the ischemic myocardium, thereby limiting the size of the infarct. Treatment
options include fibrinolytic therapy, percutaneous coronary intervention (PCI)
with thrombectomy, stent implantation and, and in some cases, coronary artery
bypass grafting (CABG). Approximately 80% of STEMI patients undergo PCI
procedure.

Although timely and effective reperfusion therapy of myocardium is the most
effective method for reducing infarct size and improving the outcome in
patients with STEMI, the process of myocardial reperfusion can paradoxically
itself induce further cardiomyocyte death, a phenomenon known as myocardial
reperfusion injury. Over the recent years many health care systems have been
optimized to enable more timely and effective reperfusion and with advances in
PCI technology and antiplatelet and antithrombotic agents for maintaining the
patency of the infarct-related coronary artery. However, there are still no
effective therapeutic compounds for preventing myocardial reperfusion injury.
In this respect, myocardial reperfusion injury remains a neglected therapeutic
target for cardioprotection in primary PCI patients and novel compounds in this
field could leave patients with more viable cardiac tissue and reduced risk of
developing heart failure.

Historically, investigations of treatments to decrease the ischemia reperfusion
injury have often been based on preclinical studies in small animals with
limited translational value to humans, and to date there are no marketed
pharmacological treatments for the prevention of reperfusion injury. Both
mechanical pre- and postconditioning (series of repetitive interruptions of the
coronary blood flow during the PCI procedure) seem to protect cardiomyocytes
during reperfusion. Reducing infarct size by 15% corresponds to a reduction in
six month absolute mortality of 1% making this a meaningful marker for long
term outcomes for patients.

About Zealand

Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL) (“Zealand”) is a biotechnology
company based in Copenhagen, Denmark. Zealand 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 focus lies in the field of cardio-metabolic diseases,
diabetes and obesity in particular, and its lead drug invention is
lixisenatide, a once-daily prandial GLP-1 agonist, which is licensed to Sanofi
for the treatment of Type 2 diabetes. Lixisenatide (marketed by Sanofi as
Lyxumia®) is approved in several countries, including Europe and Japan, and
under regulatory review in a number of other countries globally. In the U.S.,
an NDA is planned to be submitted in 2015, after completion of the ELIXA
Cardiovascular outcome study.

Zealand has a partnering strategy for the development and commercialization of
its products and in addition to the license agreement with Sanofi in Type 2
diabetes, the company has partnerships with Boehringer Ingelheim in
diabetes/obesity, Lilly in diabetes and obesity, Helsinn Healthcare in
chemotherapy induced diarrhea and AbbVie in acute kidney injury.

For further information: www.zealandpharma.com l. @ZealandPharma