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03.09.2019 - 17:35

GlobeNewswire: Phase 2 data of selatogrel, Idorsia’s highly-selective P2Y12 receptor antagonist, presented at ESC 2019

Phase 2 data of selatogrel, Idorsia's highly-selective P2Y12 receptor
antagonist, presented at ESC 2019 Phase 2 clinical data demonstrated that
subcutaneous administration of selatogrel resulted in a potent, rapid and
sustained platelet inhibition effect, and was safe and well tolerated The
company is preparing for a Phase 3 study for the treatment of a suspected acute
myocardial infarction

Allschwil, Switzerland - September 3, 2019
Idorsia Ltd (SIX: IDIA) today announced that the positive results of two Phase
2 clinical studies with selatogrel, a highly-selective P2Y 12 receptor
antagonist, were presented at the European Society of Cardiology 2019 Congress
in Paris, France. The company is now in the process of preparing for a Phase 3
study to investigate the efficacy and safety of selatogrel following
subcutaneous self-administration for the treatment of a suspected acute
myocardial infarction (AMI) in adult patients with a history of AMI.

An AMI, or heart attack, is a life-threatening condition that occurs when
blood flow to the heart muscle is suddenly decreased or completely cut off. It
is usually caused by a blood clot or blockage in one or more of the coronary
vessels supplying blood to the heart muscle. An AMI requires immediate
treatment and medical attention, as any delay in intervention can result in
irreversible damage to the heart muscle. The American Heart Association
estimates that each year more than 600,000 persons living in the US will suffer
their first heart attack and around 200,000 will suffer a recurring heart
attack.

AMI is associated with a 30% mortality rate and about half of these deaths
occur prior to arrival at the hospital. As a result, early action is crucial
for survival, however there are no treatment options available for the critical
time from onset of AMI symptoms to first medical contact. The need for an early
intervention has been highlighted by the guidelines of the European Society of
Cardiology and the American College of Cardiology / American Heart Association,
which identified the prehospital phase as the most critical and reiterated that
efforts must be made to reduce the delay for treatment initiation to reduce
death.

About selatogrel
Idorsia is developing selatogrel, a potent, fast-acting, reversible, and
highly-selective P2Y 12 receptor antagonist, for single subcutaneous
self-administration for the treatment of a suspected AMI in patients with a
history of AMI.

Martine Clozel, MD and Chief Scientific Officer, commented:
"It is well documented that AMI is caused by blood vessel occlusion, driven by
the formation of a platelet-rich thrombus which can be prevented by P2Y 12
receptor antagonists. This therapeutic class has been used in the treatment of
millions of patients globally and as such, the safety and efficacy profiles are
well-established. However, until now the method of administration or the
delayed onset of effect means that currently available treatments do not have
the desired profile to cover the critical time from onset of AMI symptoms to
first medical contact. Scientists at Idorsia have discovered selatogrel, which
has great potential to fill this gap for early treatment of AMI."


About the clinical development of selatogrel
Subcutaneous administration of selatogrel by a healthcare professional has
been studied in two Phase 2 clinical studies in patients with stable coronary
artery disease (CAD) and in patients with AMI, which were both presented at ESC
2019.

Phase 2 study in adults with stable CAD presented at ESC
Professor Robert Storey, BM, Professor of Cardiology, University of Sheffield,
UK, gave an oral presentation entitled "Selatogrel, a novel P2Y 12 receptor
antagonist, achieves rapid, consistent and sustained platelet inhibition
following single-dose subcutaneous administration in stable CAD patients".

The study was a multicenter, double blind, randomized, placebo-controlled
study assessing the pharmacodynamics, pharmacokinetics, tolerability and safety
of a single subcutaneous injection of selatogrel either in the thigh or in the
abdomen at 2 different doses in adults with stable coronary artery disease. In
the study, 345 patients (mean age 65 y; 20% female; 31% diabetes) received
selatogrel 8 mg (n=114), selatogrel 16 mg (n=115) or placebo (n=116). 97% were
on background therapy with aspirin (or its derivative carbasalate) and 35% on
oral P2Y 12 receptor antagonist (clopidogrel 23%, prasugrel 4%, ticagrelor 8%).
The primary objective of the study was to characterize inhibition of platelet
aggregation relative to placebo. Platelet reactivity was assessed by VerifyNow
PRU (P2Y 12 reaction units) test before and 15 min, 30 min and 1, 2, 4, 8 and
24 h after injection. Light-transmittance aggregometry (LTA; ADP 20 uM) was
also performed.

The primary endpoint, patients (responders) having PRU < 100 starting at 30
min and lasting ≥3 h after a single study treatment injection, was achieved in
89% of patients receiving selatogrel 8 mg, and 90% of patients receiving
selatogrel 16 mg compared with 16% in the placebo group (P < 0.0001).
Inhibition of platelet aggregation was observed as early as 15 min post-dose,
PRU values (mean±SD) were 10±25 with selatogrel 8 mg, 5±10 with selatogrel 16
mg and 163±73 with placebo. PRU levels were maintained at 2 and 4 h for both
doses and gradually returned to pre-dose levels by 24 h post-dose.
Light-transmittance aggregometry (LTA) results were consistent with the
VerifyNow results. Pharmacodynamic responses were similar for thigh and abdomen
injection sites and were consistent across the different subgroups (age, sex,
BMI, presence of chronic kidney disease or diabetes). Selatogrel was well
tolerated: mild dyspnea (or moderate dyspnea, n=1, with 16 mg) occurred in 5%
and 9% of patients with selatogrel 8 mg and 16 mg, respectively, vs 0% with
placebo; dizziness occurred in 4% and 4% vs 1%, respectively, without
significant hemodynamic or ECG changes. Bleeding events occurred in 9.6% and
4.3% of patients with selatogrel 8 mg and 16 mg, respectively, vs 6.9% with
placebo. All bleeding events were of mild intensity except one of moderate
intensity, which was reported in the placebo group. No major bleeding event was
reported during the study.

Prof. Robert Storey commented:
"Pivotal trials of anti-platelet drugs in patients with AMI have demonstrated
the importance of rapid onset of action yet, more recently, we have learnt that
the onset of action of oral anti-platelet drugs may be delayed by hours in this
setting. In this context, the properties of selatogrel that we have
demonstrated in patients with CAD are particularly exciting and demonstrate the
potential for further advancing the early management of AMI by delivering rapid
and consistent platelet inhibition with a simple single subcutaneous
administration."

Phase 2 study in adults with AMI presented at ESC
Professor Peter Sinnaeve, MD, Department of Cardiology, University Hospitals
Leuven, Faculty of Medicine, University of Leuven, Belgium, gave an oral
presentation entitled "Inhibition of platelet aggregation after subcutaneous
administration of a single-dose of selatogrel, a novel P2Y 12 receptor
antagonist, in patients with acute myocardial infarction" .

The study was a multi-center, open-label, randomized, exploratory study to
assess the onset of platelet aggregation inhibition after a single subcutaneous
injection of selatogrel in adults with acute myocardial infarction. In this
study, 47 patients (median age 69 y; 72% male; 62% STEMI; 94% Killip class 1)
received 8 mg (n=24) or 16 mg (n=23) selatogrel. Study-treatment concomitant
medications included acetylsalicylic acid (98%), P2Y 12 receptor antagonists
(96%), heparins (94%), statins (94%), nitrates (68%) and morphine (38%). Blood
samples were collected at baseline and at 15, 30, and 60 min post-dose and
platelet reactivity (expressed as PRU) was evaluated using VerifyNow. The
primary objective of the study was to assess the inhibition of platelet
aggregation 30 minutes after a single subcutaneous injection of selatogrel.

The response to treatment as defined by PRU < 100 at 30 min post-dose, was
achieved in 91% and 95% of patients with selatogrel 8 and 16 mg, respectively.
Response rates were independent from STEMI/NSTEMI diagnosis, age and sex. PRU
below 100 was observed as early as 15 min (8 mg: 75% of patients; 16 mg: 91% of
patients) and sustained for up to 60 min post-dose (8 mg: 75% of patients; 16
mg: 96% of patients). Overall, 43% of patients had ≥1 treatment-emergent
adverse event (TEAE), which were mainly of mild/moderate intensity. Ventricular
tachycardia ([VT] 8 mg: 4/24; 16 mg: 3/23) was the most frequent TEAE and was
reported as serious AE in two patients: one patient receiving 8 mg and one
patient receiving 16 mg selatogrel. Post-procedural hemorrhage (of mild
intensity) occurred in one patient after percutaneous coronary intervention
with radial access.

Prof. Peter Sinnaeve commented:
"The concept that "time is muscle" in relation to AMI has been around for
nearly 30 years, yet we still don't have anything to offer our patients in the
time between onset of AMI symptoms and first medical contact, which can often
be several hours. The anti-platelet effect and safety profile observed in this
Phase 2 program of selatogrel suggests that it has the potential to overcome
limitations of available oral P2Y 12 receptor antagonist therapies in the early
management of AMI. Any reduction in the delay for treatment initiation could
mean the difference between life and death, so we must evaluate this
opportunity."

Guy Braunstein, MD and Head of Idorsia Global Clinical Development, added:
"The Phase 2 data demonstrate that subcutaneous administration of selatogrel
16mg in patients with stable CAD and patients with AMI has a rapid onset of
action, within 15 minutes, with the effect extending over 4-8 hours. Based on
the speed at which selatogrel takes effect, the duration of that effect, and
the safety and tolerability profile, self-administration of selatogrel at the
very onset of symptoms of a suspected AMI has potential as a highly innovative
approach to AMI management."

In consultation with health authorities, Idorsia is preparing a large,
international, multi-center, Phase 3 study to investigate the efficacy and
safety of subcutaneous self-administration of selatogrel for the treatment of a
suspected AMI in patients with an history of AMI. Participating patients will
be trained on when to inject and instructed on how to self-administer
treatment. An integrated drug delivery device is being developed through
usability and reliability studies to ensure functional efficacy can be
demonstrated ahead of the Phase 3 study.

Jean-Paul Clozel, MD, and Chief Executive Officer, concluded:
"As a cardiologist, I find this project incredibly exciting. I think everyone
understands that this novel concept of self-administration at onset of symptoms
could be a game-changer in the management of AMI. As a CEO, I am also excited
for the impact this product could have on the future of our company. As some of
our Phase 3 programs are approaching completion, the timing is perfect to bring
new innovative projects forward and deliver on our vision to help more
patients."

Notes to the editor

About Professor Robert Storey
Professor Robert Storey is Professor of Cardiology at the University of
Sheffield, Sheffield, UK, where he has headed a thrombosis research group since
2002 and is director of the Cardiovascular Research Unit. In addition, Prof.
Storey is Academic Director and honorary Consultant Cardiologist for the
Cardiology and Cardiothoracic Surgery Directorate, Sheffield Teaching Hospitals
NHS Foundation Trust. He has a special interest in the management of ischaemic
heart disease, including acute coronary syndromes and coronary intervention.

He was Chair of the Working Group on Thrombosis of the European Society of
Cardiology (ESC) from 2012-2014 and has been a Task Force member for ESC
guidelines on chronic coronary syndromes (2019), non-ST-elevation acute
coronary syndromes (2011 and 2015) and dyslipidaemias (2011). He served as a
member of the executive committees for the DISPERSE2, PLATO and PEGASUS-TIMI 54
studies, leading the platelet function substudies for these trials, and of the
steering committees for the TRA-CER, EPICOR, ATLANTIC and AUGUSTUS studies. He
is currently chief investigator for a phase II study of selatogrel in stable
coronary artery disease patients and a member of the steering committees for
the COMPLETE, RAPID CTCA, SENIOR RITA and CLEAR SYNERGY studies.

About Professor Peter Sinnaeve
Dr Peter Sinnaeve graduated summa cum laude from the University of Leuven,
Belgium, in 1994, and was trained as a cardiologist at the same institution. He
subsequently obtained a PhD degree in Medical Sciences, after doctoral research
in cardiovascular gene therapy. In 2002-2003, he was a post-doctoral fellow at
the Duke Clinical Research Institute in the USA as recipient of a Fullbright
scholarship. Dr Sinnaeve then joined the staff at the University Hospitals
Leuven, Belgium. He is currently professor at the University of Leuven and is a
Clinical Investigator for the Flemish Fund for Scientific Research. His
clinical expertise lies in acute cardiac care, interventional cardiology,
pericardiology, as well as cardiac rehabilitation, while his current research
focuses on antithrombotic therapies and the genomics of acute coronary
syndromes. He is active in a variety of national and international boards and
is involved in several clinical trials in cardiovascular disease as a steering
or executive committee member. To date, Dr Sinnaeve has (co)authored 162
peer-reviewed papers and 26 book chapters.

About Idorsia
Idorsia Ltd is reaching out for more - We have more ideas, we see more
opportunities and we want to help more patients. In order to achieve this, we
will develop Idorsia into one of Europe's leading biopharmaceutical companies,
with a strong scientific core.

Headquartered in Switzerland - a biotech-hub of Europe - Idorsia is
specialized in the discovery and development of small molecules, to transform
the horizon of therapeutic options. Idorsia has a broad portfolio of innovative
drugs in the pipeline, an experienced team, a fully-functional research center,
and a strong balance sheet - the ideal constellation to bringing R&D efforts to
business success.

Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June
2017 and has over 750 highly qualified specialists dedicated to realizing our
ambitious targets.

For further information, please contact
Andrew C. Weiss
Senior Vice President, Head of Investor Relations & Corporate Communications
Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil
+41 (0) 58 844 10 10
www.idorsia.com

The above information contains certain "forward-looking statements", relating
to the company's business, which can be identified by the use of
forward-looking terminology such as "estimates", "believes", "expects", "may",
"are expected to", "will", "will continue", "should", "would be", "seeks",
"pending" or "anticipates" or similar expressions, or by discussions of
strategy, plans or intentions. Such statements include descriptions of the
company's investment and research and development programs and anticipated
expenditures in connection therewith, descriptions of new products expected to
be introduced by the company and anticipated customer demand for such products
and products in the company's existing portfolio. Such statements reflect the
current views of the company with respect to future events and are subject to
certain risks, uncertainties and assumptions. Many factors could cause the
actual results, performance or achievements of the company to be materially
different from any future results, performances or achievements that may be
expressed or implied by such forward-looking statements. Should one or more of
these risks or uncertainties materialize, or should underlying assumptions
prove incorrect, actual results may vary materially from those described herein
as anticipated, believed, estimated or expected.



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