GlobeNewswire

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

Share
  • 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 P2Y12 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 P2Y12 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 P2Y12 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 P2Y12 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 P2Y12 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 (P2Y12 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 P2Y12 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%), P2Y12 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 P2Y12 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.

Attachment

About GlobeNewswire

GlobeNewswire
GlobeNewswire
One Liberty Plaza - 165 Broadway
NY 10006 New York

https://globenewswire.com

GlobeNewswire is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.

Subscribe to releases from GlobeNewswire

Subscribe to all the latest releases from GlobeNewswire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from GlobeNewswire

Aino Health AB (publ): KALLELSE TILL EXTRA BOLAGSSTÄMMA I AINO HEALTH AB (PUBL)9.8.2020 19:15:00 CESTPressemelding

Aktieägarna i Aino Health (publ), org.nr 559063-5073 (”Bolaget”) kallas härmed till extra bolagsstämma onsdagen den 9 september 2020 i Stockholm. Med anledning av Coronapandemin (Covid-19) kommer den extra bolagsstämman att genomföras endast genom poströstning. Detta betyder att aktieägarna i Bolaget inte har rätt att närvara vid stämman, varken personligen eller genom ombud. Istället har aktieägarna rätt att utöva sin rösträtt per post genom att rösta i förväg enligt instruktionerna i denna kallelse. Rätt att delta vid stämman På grund av Coronapandemin och för att säkerställa aktieägares, anställdas och andra intressenters hälsa och säkerhet har styrelsen för Bolaget beslutat att aktieägarna inte ska ha rätt att närvara vid stämman, varken personligen eller genom ombud, och att den som inte är aktieägare inte ska ha rätt att närvara i enlighet med 20–26 §§ i lagen (2020:198) om tillfälliga undantag för att underlätta genomförandet av bolags- och föreningsstämmor. Aktieägarna har istä

Aino Health AB (publ): Aino Health decides on a fully secured rights issue of shares of approximately SEK 15.9 million9.8.2020 19:05:00 CESTPress release

NOT FOR RELEASE, PUBLICATION OR DISTRIBUTION, DIRECTLY OR INDIRECTLY, IN OR INTO THE UNITED STATES, AUSTRALIA, CANADA, NEW ZEALAND, HONG KONG, JAPAN, SWITZERLAND, SINGAPORE, SOUTH AFRICA, OR ANY OTHER JURISDICTION IN WHICH THE RELEASE, PUBLICATION OR DISTRIBUTION OF THIS PRESS RELEASE WOULD BE UNLAWFUL, BE SUBJECT TO LEGAL RESTRICTIONS OR WOULD REQUIRE REGISTRATION OR OTHER MEASURES. The Board of Directors of Aino Health AB (publ) (“Aino Health” or the “Company”) has, subject to approval at the Extraordinary General Meeting on 9 September 2020, decided to carry out a rights issue of a maximum of 10,623,319 shares (the “Rights issue”). The subscription price per share is SEK 1.50, whereby Aino Health upon full subscription in the Rights issue receives approximately SEK 15.9 million before issue costs. For every (1) existing share on the record date on 16 September 2020, two (2) subscription rights are received and three (3) subscription rights entitle the holder to subscribe for one (1)

Aino Health AB (publ): Aino Health beslutar om en fullt säkerställd företrädesemission av aktier om cirka 15,9 MSEK9.8.2020 19:05:00 CESTPressemelding

EJ FÖR OFFENTLIGGÖRANDE, PUBLICERING ELLER DISTRIBUTION, DIREKT ELLER INDIREKT, INOM ELLER TILL USA, AUSTRALIEN, KANADA, NYA ZEELAND, HONGKONG, JAPAN, SCHWEIZ, SINGAPORE, SYDAFRIKA, ELLER I NÅGON ANNAN JURISDIKTION DÄR OFFENTLIGGÖRANDET, PUBLICERINGEN ELLER DISTRIBUTIONEN AV DETTA PRESSMEDDELANDE SKULLE VARA OLAGLIG, VARA FÖREMÅL FÖR LEGALA RESTRIKTIONER ELLER SKULLE KRÄVA REGISTRERING ELLER ANDRA ÅTGÄRDER. Styrelsen för Aino Health AB (publ) (”Aino Health” eller ”Bolaget”) har, förutsatt godkännande på extra bolagsstämman den 9 september 2020, beslutat att genomföra en företrädesemission av högst 10 623 319 aktier (”Företrädesemissionen”). Teckningskursen per aktie är 1,50 SEK, varigenom Aino Health vid full teckning i Företrädesemissionen erhåller cirka 15,9 MSEK före emissionskostnader. För varje (1) befintlig aktie på avstämningsdagen den 16 september 2020 erhålls två (2) teckningsrätter och tre (3) teckningsrätter berättigar till teckning av en (1) ny aktie. Teckningsperioden löpe

CONDITIONS FOR RIKSBANK BID PROCEDURE KOMMUNINVEST BONDS7.8.2020 16:20:00 CESTPress release

Sveriges Riksbank Bid procedure details Kommuninvest Bonds, 2020-08-11 Maturity dateLoanISIN codeCouponVolume, SEK million2021-09-152109 SE00069950641.00 %500+/- 2502023-02-222302 SE00096629430.75 %500+/- 2502024-10-022410 SE00104692051.00 % 500+/- 250 2026-02-042602 SE00137454520.75 % 500+/- 250 Maximum volume 2 BLN in total Settlement date 2020-08-13 Bids have to be entered by 11.00 on AUG 11, 2020 Highest permitted bid volume: 500 SEK million in issue 2109, 2302, 2410, and 2602. Lowest permitted bid volume: 50 SEK million Bids only through counterparties approved by the Riksbank RESULT OF AUCTION WILL BE PUBLISHED NO LATER THAN 11.15 (CEST) ON AUG 11, 2020 For more information, please contact: Trading desk at the Riksbank + 46 8 696 6970 General and special terms and conditions can be retrieved at http://www.riksbank.se

CONDITIONS FOR RIKSBANK BID PROCEDURES SEK GOVERNMENT BONDS7.8.2020 16:20:00 CESTPress release

Sveriges Riksbank Bid procedure details Government Bonds, 2020-08-14 Maturity dateLoanISIN codeCouponVolume, SEK million2029-11-12 1061SE00112819220.75 %500 +/- 2502032-06-01 1056SE00045172902.25 %500 +/- 250 Settlement date 2020-08-18 Bids have to be entered by 10.00 on AUG 14, 2020 Highest permitted bid volume: 500 SEK million in issue SGB 1061 and 500 SEK million in issue SGB 1056 Lowest permitted bid volume: 50 SEK million Bids only through counterparties approved by the Riksbank RESULT OF AUCTION WILL BE PUBLISHED NO LATER THAN 10.10 (CEST)ON AUG 14, 2020. For more information, please contact: Trading desk at the Riksbank + 46 8 696 6970 General and special terms and conditions can be retrieved at http://www.riksbank.se

CONDITIONS FOR RIKSBANK BID PROCEDURES SEK COVERED BONDS7.8.2020 16:20:00 CESTPress release

Sveriges Riksbank Bid procedure details Covered Bonds, 2020-08-13 Maturity dateLoanISIN codeCouponVolume, SEK million2023-09-20 5533 SE00104427311.25 %1,000 +/- 5002022-12-21 575 SE00105465721.50 %1,000 +/- 500 2023-06-011587SE00104413031.50 %1,000 +/- 5002023-03-15192SE00101332071.00 %1,000 +/- 5002022-12-212212SE00102970851.00 %400 +/- 2502023-09-20516SE00091903901.25 %400 +/- 2502023-06-21144SE00111674281.00 %400 +/- 250 Settlement date 2020-08-17 Bids have to be entered by 10.00 on AUG 13 2020 Highest permitted bid volume: 1,000 SEK million in issue 5533 1,000 SEK million in issue 575 1,000 SEK million in issue 1587 1,000 SEK million in issue 192 400 SEK million in issue 2212 400 SEK million in issue 516 400 SEK million in issue 144 Maximum volume 5 billion SEK in total Lowest permitted bid volume: 50 SEK million Bids only through counterparties approved by the Riksbank RESULT OF AUCTION WILL BE PUBLISHED NO LATER THAN 10.15 (CEST) ON AUG 13, 2020. For more information, please cont