Clinical Development
Idorsia aims to deliver new products with the potential to significantly change the treatment options in their target diseases. We want to bring new perspectives to the development of innovative compounds, challenging accepted paradigms to answer the questions that matter most. Our key assets have the potential to transform treatment in the target indications.
Drug Discovery and Clinical Development Idorsia’s clinical development comprises They steer the compounds from entry-into- Development Pipeline a broad spectrum of expertise clustered human studies through to submission of within multiple departments: therapy the dossier to health authorities, approval Daridorexant area units, strategic development, clinical and maintenance of the license during
Aprocitentan pharmacology, biostatistics and data the commercialization phase until loss of management, drug safety, drug regulatory exclusivity of the medicine in the major Clazosentan affairs, clinical operations and life cycle markets and beyond. Idorsia’s clinical management. Life cycle cross-functional development manages clinical programs Lucerastat teams – under the leadership of a life cycle to the appropriate scientific, medical and Selatogrel leader – bring expertise from preclinical operational standards to generate the development, clinical development and information required by health authorities Cenerimod technical operations to the efficient worldwide. ACT-539313 development of new medicines.
Other Compounds Development Pipeline
Compound Mechanism of Action Target Indication Status
Daridorexant Dual orexin receptor antagonist Insomnia Under review with health authorities
Aprocitentan* Dual endothelin receptor antagonist Resistant hypertension management Phase 3 recruitment complete
Clazosentan Endothelin receptor antagonist Cerebral vasospasm assoc. with aneurysmal Japan: NDA submitted subarachnoid hemorrhage Global: Phase 3 ongoing
Lucerastat Glucosylceramide synthase inhibitor Fabry disease Phase 3 recruitment complete
Selatogrel P2Y12 receptor antagonist Suspected acute myocardial infarction Phase 3
Cenerimod S1P1 receptor modulator Systemic lupus erythematosus Phase 2b recruitment complete
ACT-539313 Selective orexin 1 receptor antagonist Binge eating disorder Phase 2
Sinbaglustat GBA2/GCS inhibitor Rare lysosomal storage disorders Phase 1 complete
Drug Discovery ACT-1004-1239 CXCR7 antagonist Immunology Phase 1 and Clinical Development ACT-1014-6470 - Immunology Phase 1
> Development ACT-777991 - Immunology Phase 1 Pipeline
Daridorexant * In collaboration with Janssen Biotech to jointly develop aprocitentan, Janssen Biotech has sole commercialization rights worldwide. Aprocitentan Neurocrine Biosciences has a global license to develop and commercialize ACT-709478 (NBI-827104), Idorsia's novel Clazosentan T-type calcium channel blocker. ACT-709478 is currently investigated in two Phase 2 studies for the treatment of a rare form of pediatric epilepsy and essential tremor. Lucerastat
Selatogrel
Cenerimod
ACT-539313
Other Compounds Daridorexant Daridorexant is a dual orexin receptor antagonist (DORA) developed for the treatment of insomnia. The Phase 3 registration program demonstrated the efficacy of daridorexant on objective and subjective sleep parameters, and an improvement in daytime functioning, while maintaining a favorable safety profile.
Insomnia is a condition of overactive wake Available clinical data More than 800 patients continued treatment signaling that can have a profound effect The Phase 3 registration program comprised in the 40-week extension study, which on the lives of patients. Insomnia can be two three-month studies, together with a measured the effect of all three doses vs. defined as difficulty falling asleep and / or long-term double-blind extension study. placebo, generating data for long-term staying asleep, occurring at least three times Both pivotal studies are complete, having treatment of insomnia. a week for a minimum of three months. enrolled around 1,850 patients with insomnia at over 160 sites across 18 countries. As The Phase 3 registration program Insomnia is a common problem with up to insomnia often presents later in life, and demonstrated statistically significant and 10% of adults having all the symptoms that elderly patients are more susceptible to clinically meaningful improvements in sleep meet the diagnostic criteria for insomnia experience fragmented sleep, early awakening and daytime functioning which were sustained disorder. On this basis, and assuming a US and daytime sleepiness, around 40% of the over time. The results showed efficacy during Drug Discovery and Clinical adult population of around 250 million, recruited population was aged 65 years or the night and the day, in respect of sleep Development there are approximately 25 million adults in older. maintenance, sleep onset, total sleep time the US who suffer from insomnia. and daytime functioning. The nighttime Development Pipeline The placebo-controlled studies investigated symptoms were improved while preserving the effects of three doses of daridorexant the proportions of sleep stages. The Phase > Daridorexant Current status (10 mg, 25 mg, and 50 mg) on sleep and 3 program provided a deep understanding Aprocitentan The NDA was submitted to the US FDA daytime functioning parameters, objectively of the efficacy and tolerability profile of on January 8, 2021 and the MAA to in a sleep lab by polysomnography and daridorexant. Clazosentan the European Union EMA on March 2, subjectively with a daily patient diary at home. 2021 and to Swissmedic on April 20, The impact of insomnia on patients’ daytime The highest (50 mg) dose was the most Lucerastat 2021. Should approval be received, functioning was measured daily using the effective, followed by 25 mg, while the 10 mg Selatogrel the company anticipates launch in sleepiness domain score from the Insomnia dose had only a marginal effect. the US in the second quarter of 2022, Daytime Symptoms and Impacts Questionnaire Cenerimod followed by other regions thereafter. (IDSIQ) – a patient-reported outcome (PRO) A key consideration in the treatment of ACT-539313 instrument validated according to the FDA insomnia is the reversal of daytime functioning Guidance for Industry. impairment associated with sleep difficulties Other Compounds – altered mood, cognition, and tiredness. To April 2021. The study collected information Milestones date, no insomnia studies have reported on on the safety of long-term treatment as well 2021 MAA submitted to EMA (March) the effects of pharmacological intervention as allowing an exploratory analysis of the 2021 NDA submitted to US FDA (January) on daytime functioning using an adequately maintenance of efficacy. There were no new 2020 Both pivotal studies report positive results developed and validated PRO instrument. emerging safety findings. Moreover, the 2018 Initiation of Phase 3 registration program At 50 mg, daridorexant produced consistent efficacy on sleep and daytime functioning 2017 Completion of Phase 2 clinical program and meaningful improvements in scores for appeared to be maintained over the longer 2015 Initiation of Phase 1 clinical program daytime functioning across all IDSIQ domains. treatment duration. Patients on daridorexant felt more energetic Key scientific literature and less sleepy, and reported better alertness, Prior to the Phase 3 program, the safety • Dauvilliers, Y., et al. (2020). Ann Neurol 87(3): 347- cognition and mood. and efficacy of daridorexant in adult and 356. elderly patients with insomnia was evaluated • Zammit, G., et al. (2020). Neurology 94(21): 1-11. Daridorexant was well tolerated and had a in a comprehensive Phase 2 program, • Muehlan, C., et al. (2020). J Clin Psychopharmacol favorable safety profile in adult and elderly comprising two studies, one of which included 40(2): 157-166. patients. Adverse reactions reported with a zolpidem 10 mg as an active reference. Both • Muehlan, C., et al. (2020). J Psychopharmacol frequency of ≥ 2% in daridorexant-treated studies showed the desired effect on sleep 34(3): 326-335. Drug Discovery patients and greater (≥ 1%) than in placebo- maintenance and onset, with a significant • Boof, M. L., et al. (2019). Eur J Clin Pharmacol and Clinical treated patients in 3-month efficacy trials dose-response relationship; treatment was 75(2): 195-205. Development were headache, somnolence, fatigue, generally well tolerated. • Muehlan, C., et al. (2019). Curr Drug Metab 20(4): Development dizziness, and nausea. There was no excess 254-265. Pipeline of morning sleepiness, as assessed by the In addition, a comprehensive clinical • Muehlan, C., et al. (2019). Eur Neuropsychophar- > Daridorexant morning visual analogue scale (VAS), even at pharmacology program has been conducted macol 29(7): 847-857. 50 mg. The incidence of somnolence was low totaling 18 studies and including, amongst • Muehlan, C., et al. (2018). Clin Pharmacol Ther Aprocitentan and did not increase with daridorexant 50 others, studies assessing abuse liability, drug- 104(5): 1022-1029.
Clazosentan mg compared to placebo. The incidence of drug interactions, next-morning driving in • Treiber, A., et al. (2017). J Pharmacol Exp Ther adverse events of special interest, considering healthy participants, the effect of daridorexant 362(3): 489-503. Lucerastat the potential association of orexin deficiency on respiratory function in patients with • Brisbare-Roch, C., et al. (2007). Nat Med 13(2): with narcolepsy, was low, with isolated cases chronic obstructive pulmonary disease (COPD) 150-5. Selatogrel of sleep paralysis or hallucinations in the or obstructive sleep apnea (OSA), and the Cenerimod daridorexant treatment groups. pharmacokinetics of daridorexant in patients with liver and renal impairment. The program ACT-539313 The final results of the 40-week extension showed robust results which have been Other Compounds study with daridorexant became available in included in the filing with health authorities. Aprocitentan
Aprocitentan is a once-daily, potent dual (ETA and ETB) endothelin receptor antagonist (ERA), which is being investigated for the treatment of patients whose blood pressure is uncontrolled despite receiving triple antihypertensive therapy, so-called resistant hypertension.
Hypertension (high blood pressure) is one designed a single placebo-controlled once-daily. The study consists of 3 of the most common cardiovascular risk study which efficiently addresses both sequential treatment periods. The first is a factors, and its prevalence continues to rise. the short-term efficacy of aprocitentan double-bind treatment period designed to According to a recent study, there are more and the durability of its effects in long- demonstrate the effect of aprocitentan on than 1 billion people living with hypertension term treatment. The study has completed blood pressure after 4 weeks, compared to worldwide. Left uncontrolled, hypertension enrollment with 730 patients being placebo. Patients then enter a treatment can lead to life-threatening conditions such randomized at approximately 180 sites period where they receive aprocitentan as stroke, ischemic heart disease, or kidney in around 20 countries, and results are 25 mg for 32 weeks. This is followed by disease. targeted mid-2022. a randomized double-blind withdrawal treatment period where patients will Drug Discovery and Clinical Patients whose blood pressure remains Patients with a history of resistant remain either on aprocitentan 25 mg Development high despite receiving at least three hypertension underwent a thorough or switch to placebo for 12 weeks. The antihypertensive medications from different screening and run-in period. This confirms latter treatment period is designed to Development Pipeline classes, including a diuretic, at optimal doses the diagnosis of resistant hypertension by demonstrate the durability of the blood are categorized in hypertension guidelines excluding pseudo or apparent resistant pressure lowering effect of aprocitentan. Daridorexant and the medical community as having hypertension. During the screening period, Patients will then enter a 30-day safety
> Aprocitentan resistant hypertension. the patient’s background antihypertensive follow-up period. therapies were transitioned to a Clazosentan standardized triple combination of a calcium channel blocker (amlodipine), an Lucerastat Current status Collaboration Agreement with Janssen In June 2018, Idorsia initiated PRECISION, angiotensin receptor blocker (valsartan), Biotech Selatogrel a Phase 3 study to demonstrate the and a diuretic (hydrochlorothiazide). In December 2017, Idorsia entered into antihypertensive effect of aprocitentan a collaboration agreement with Janssen Cenerimod when added to standard of care in patients Patients with true resistant hypertension Biotech, Inc., to jointly develop aprocitentan ACT-539313 with resistant hypertension. Idorsia, in were then randomized to receive and any of its derivative compounds consultation with regulatory agencies, aprocitentan 12.5 mg, 25 mg, or placebo or products. Both parties have joint Other Compounds development rights over aprocitentan. pressure, with clinically relevant effects Idorsia is overseeing the Phase 3 observed at 10 mg, 25 mg, and 50 mg, with development and regulatory submission no additional effect at 50 mg. The effect of for difficult-to-control hypertension. The aprocitentan was shown to cover a 24-hour costs are shared equally between both period. partners. Janssen will oversee the Phase 3 development and submission for any The overall incidence of adverse events additional indications and will have the sole observed in the aprocitentan groups worldwide commercialization rights. (ranging from 22.0% to 40.2%) was similar to that seen in the placebo group Drug Discovery and Clinical Available clinical data (36.6%). Overall, the most common Development In a Phase 2 dose-response study, patients events were hypertension, headache and with hypertension received monotherapy nasopharyngitis. Development Pipeline with four doses of aprocitentan or placebo (lisinopril was used as a positive control) for Milestones Daridorexant eight weeks, using a randomized, double- 2018 Phase 3 study initiated
> Aprocitentan blind study design. A total of 490 eligible 2017 Collaboration agreement with Janssen Biotech patients were randomized, with 430 patients 2017 Positive results for the dose-response study Clazosentan successfully completing the double-blind 2015 Initiation of Phase 2 dose-response study treatment period. Blood pressure was 2014 Initiation of Phase 1 clinical program Lucerastat measured carefully with an unattended Selatogrel automated office blood pressure device. The Key scientific literature results are shown in the charts below. No • Iglarz M, et al. Clin Sci 2010; 119:453-63 Cenerimod changes in heart rate were observed for any ACT-539313 dose of aprocitentan. There was a clear dose response on both diastolic and systolic blood Other Compounds Clazosentan
Clazosentan is a fast-acting, selective endothelin A (ETA) receptor antagonist being developed as an intravenous infusion for the prevention of vasospasm-related delayed cerebral ischemia in patients following an aneurysmal subarachnoid hemorrhage.
Aneurysmal subarachnoid hemorrhage and is a significant problem in Japan with an Available clinical data (aSAH) is a rare condition involving sudden incidence more than twice as high as in many Several studies have built our understanding life-threatening bleeding occurring in the other countries of the world. of the role of clazosentan in preventing subarachnoid space. It is caused by the or reversing cerebral vasospasm. In 2006, rupture of an aneurysm – a weak, bulging results were reported for clazosentan in spot on the wall of a cerebral artery. Current status: Global registration study the prevention of angiographic vasospasm Emergency surgical repair (endovascular In February 2019, Idorsia initiated REACT, in patients with aSAH. The Phase 2 dose- coiling or microsurgical clipping) is required a placebo-controlled Phase 3 study to finding study, CONSCIOUS-1, demonstrated to stop the hemorrhage. investigate the efficacy and safety of dose-dependent prevention of vasospasm. clazosentan for the prevention of clinical Drug Discovery and Clinical The bleeding and the release of a deterioration due to vasospasm-related This was followed by two Phase 3 studies, Development vasoconstrictor (endothelin) by the delayed cerebral ischemia in adult CONSCIOUS-2 and CONSCIOUS-3, to neighboring vascular endothelium can patients following aSAH. The Phase 3 assess the effect of clazosentan on the Development Pipeline lead to cerebral vasospasm (constriction study incorporates the learnings from the incidence of cerebral vasospasm-related of arteries in the brain) usually occurring clazosentan program to identify patients morbidity and all-cause mortality. In 2010, Daridorexant between 4 and 14 days after aneurysm at high risk of vasospasm and delayed CONSCIOUS-2 showed that the 5 mg/h
Aprocitentan securing. This diminishes blood flow to cerebral ischemia, the optimal dose, the dose of clazosentan, administered by the brain and about one third of patients best measure to demonstrate efficacy continuous intravenous infusion, did not > Clazosentan consequently experience worsening of their and an optimized patient management allow a statistically significant treatment neurological condition. Cerebral vasospasm guideline to ensure patient safety. The effect to be observed, resulting in the Lucerastat is one of the leading secondary causes of study aims to randomize approximately premature termination of CONSCIOUS-3. Selatogrel disability and death in those that experience 400 patients – treated either with However, an exploratory analysis of the aSAH. microsurgical clipping or endovascular data collected in CONSCIOUS-3 showed Cenerimod coiling – at around 95 sites across 15 that a higher dose of clazosentan (15 mg/h), ACT-539313 The prevalence of aSAH is estimated to be countries, and results are targeted for the administered by continuous intravenous between 6 and 9 per 100,000 worldwide second half of 2022. infusion, significantly reduced cerebral Other Compounds vasospasm-related morbidity and all-cause The studies confirmed the well-documented basis, a registration program was initiated mortality, with a 44% relative risk reduction safety profile of clazosentan, which has with clazosentan in Japan in May 2016. (p=0.0074). now been administered to approx. 2000 patients around the world. The side effects In November 2020, Idorsia announced The 15 mg/h dose also significantly of clazosentan are managed based on clear positive top-line results from the Japanese reduced the incidence of delayed ischemic protocol guidelines: hypotension can be registration program investigating neurological deficit with a 54% relative mitigated using blood pressure control clazosentan in adult Japanese patients risk reduction (p=0.0038). In addition, with vasopressors in the ICU, while lung post-aSAH. The program consisted of two clazosentan reduced the need for rescue complications (such as pulmonary edema) studies assessing the efficacy and safety therapy for vasospasm. Clazosentan did not can be managed by aiming to maintain of clazosentan in reducing vasospasm- Drug Discovery show any effect of clazosentan on long-term euvolemia by avoiding excessive fluid related morbidity and all-cause mortality and Clinical clinical outcome. administration. events. The two studies followed the same Development design, with one enrolling 221 patients Development More recently, a pilot study evaluating the Clazosentan has been granted orphan drug whose aneurysm was secured by surgical Pipeline early effect of clazosentan on reversing designation in Europe (2003) and the US clipping and the other enrolling 221 Daridorexant established cerebral vasospasm in large (2006), leading to regulatory exclusivity patients whose aneurysm was secured by proximal cerebral artery segments at 3 protection of 10 and 7 years, respectively. endovascular coiling. Aprocitentan hours post-initiation suggests that, with
> Clazosentan early administration, clazosentan has the In Japan, clazosentan has regulatory data potential to improve large-vessel vasospasm. Current status: Japanese registration protection after approval, leading to eight Lucerastat In a post-hoc analysis of the effect of program years’ exclusivity. clazosentan on reversing established A Phase 2 study in Japanese and Korean Selatogrel cerebral vasospasm in the entire cerebral patients showed that 10 mg/hr of Both studies showed that clazosentan Cenerimod vasculature (including smaller distal vessel clazosentan administered by continuous reduced the occurrence of cerebral segments and the cerebellar arteries), a intravenous infusion significantly reduced vasospasm-related morbidity and all-cause ACT-539313 clearly visible improvement was observed in vasospasm and vasospasm-related mortality within 6 weeks post-aSAH with Other Compounds vessel diameter at 3 and 24 hours. morbidity and mortality events. On that statistical significance (p<0.01 for both studies). The composite endpoint was Idorsia Japan submitted a new defined by at least one of the following: drug application with the Japanese All death / New cerebral infarction due Pharmaceuticals and Medical Devices to cerebral vasospasm / Delayed ischemic Agency on March 1, 2021. This will allow neurologic deficit due to cerebral for commercialization and launch in Japan vasospasm and adjudicated blindly by an in the first half of 2022, should approval independent committee. The effect of be received. clazosentan on all-cause morbidity and mortality was also significant (p<0.05) in a pre-planned analysis of the pooled studies Milestones Drug Discovery and Clinical whereas a numerical trend was observed 2021 NDA submitted to Japanese PMDA Development in each study on this endpoint. Further 2020 Japanese registration program reports positive analysis is ongoing, including additional results Development Pipeline analysis of data of the pooled studies. 2019 Global Phase 3 study initiated 2016 Japanese registration program initiated Daridorexant There were no unexpected safety findings 2006 Orphan status granted in the US
Aprocitentan in these registration studies. Treatment- 2003 Orphan status granted in Europe emergent adverse events occurring > Clazosentan >5% in the clazosentan group (with a Key scientific literature difference of >2% compared to placebo) • Fujimura, et al. Cerebrovasc Dis 2017;44:59–67. Lucerastat were vomiting and signs of hemodilution • Macdonald R L, et al. Stroke. 2012; 43(6):1463-9. Selatogrel or fluid retention (i.e. hyponatremia, • Macdonald R L, et al. The Lancet. Neurology, 2011; hypoalbuminemia, anemia, pleural 10(7):618-625. Cenerimod effusion, brain and pulmonary edema). • Macdonald R L, et al. Stroke 2008; 39:3015–3021. ACT-539313 • Roux S. et al. J Pharmacol Exp Ther 1997; 283:1110-1118. Other Compounds Lucerastat Lucerastat is an oral inhibitor of glucosylceramide synthase, offering a potential new treatment approach for patients living with Fabry disease, irrespective of mutation type.
Fabry disease is a rare, life-threatening, early diagnosis is essential to manage the treatment on neuropathic pain over a lysosomal storage disorder caused by symptoms as soon as possible and reduce 6-month period, as measured by Idorsia’s mutations in the GLA gene leading to the risk of developing serious complications. Fabry disease neuropathic pain instrument a deficiency or dysfunction of alpha- (developed in accordance with health galactosidase A (alpha-Gal A), an enzyme Lucerastat, an oral inhibitor of authority guidance). At the end of the that normally breaks down a fatty substance glucosylceramide synthase (GCS), acts by double-blind period, patients will have the known as globotriaosylceramide (Gb3) in the reducing the synthesis of the lipid Gb3 as option of entering an open-label extension cells of the body. Over time, this may result oppose to supporting the breakdown of study to determine long-term safety in a build-up of Gb3 deposits throughout the Gb3, thus reducing damaging build-up. This and to explore long-term efficacy and body, particularly in the kidneys, heart and is known as Substrate Reduction Therapy disease-modifying potential, as measured Drug Discovery and Clinical nervous system. (SRT). Since this mechanism is independent by estimated glomerular filtration rate Development of the deficiency or dysfunction of alpha- (eGFR), left ventricular mass index and The diagnosed prevalence of Fabry disease galactosidase A, it should not be limited to biomarkers of Fabry disease. The study Development Pipeline in 2018 was approximately 7,500 patients in specific mutations in the GLA gene. was fully randomized in February 2021, the US and the EU-5 (i.e., France, Germany, Preclinical studies have shown that with 118 patients being randomized to Daridorexant Italy, Spain and the UK). lucerastat is rapidly absorbed and is widely lucerastat or placebo in a 2:1 ratio. Results
Aprocitentan distributed to most tissues, including the of this study are therefore expected in the The symptoms range from neuropathic central nervous system, kidney and heart. fourth quarter of 2021, should all patients Clazosentan pain (primarily in the hands and feet) and continue into the open label extension gastro-intestinal, skin and eye problems, to study. > Lucerastat hypertension, progressive kidney damage, Current status Selatogrel cardiomyopathy and stroke. In May 2018, Idorsia initiated MODIFY, a Lucerastat for Fabry disease has received Phase 3 study to determine the efficacy orphan drug designation in the US and the Cenerimod Since most symptoms are non-specific, and safety of lucerastat oral monotherapy EU and is under review in Japan. In 2018 ACT-539313 Fabry disease is often undetected or in adult patients with Fabry disease. The and further in 2020, the EMA agreed with misdiagnosed. As the disease is progressive, study aims to determine the effects of the company's paediatric investigation Other Compounds plan for lucerastat for the treatment of Key scientific literature pediatric patients with Fabry disease. • Guérard N, et al. Clin Pharmacol Ther. 2017; Idorsia has already initiated activities 103:703-11. according to the agreed plan. • Guérard N, et al. J Clin Pharmacol. 2017;57:1425- 31. • Guérard N, et al. Orphanet J Rare Dis. 2017; 12(1):9 Available clinical data • Welford R, et al. Molecular Genetics and Metabo- In an exploratory study in patients with lism. 2017;120 (Abstract 360): S139. Fabry disease, treatment with lucerastat in addition to enzyme replacement therapy Drug Discovery and Clinical induced a marked decrease in plasma levels Development of metabolic substrates associated with the development of the disease. Development Pipeline The study also indicated that lucerastat is Daridorexant well tolerated in patients with Fabry disease.
Aprocitentan In an animal model of Fabry disease, Clazosentan treatment with lucerastat reduced Gb3 levels and related biomarkers in dorsal root > Lucerastat ganglia, the kidneys and the heart. Selatogrel Milestones Cenerimod 2018 Phase 3 study initiated ACT-539313 2016 Phase 1b study completed
Other Compounds Selatogrel
Selatogrel is a potent, highly selective, fast-acting and reversible P2Y12 receptor antagonist, being developed for the treatment of acute myocardial infarction (AMI) in patients who are at high risk of recurrent AMI. It is self-administered subcutaneously via a drug delivery device (autoinjector) upon occurrence of symptoms suggestive of an AMI.
An AMI, or heart attack, is a life-threatening fulfill this medical gap: upon symptoms administered (on top of standard-of-care) condition that occurs when blood flow to suggestive of a heart attack, patients would upon occurrence of symptoms suggestive the heart muscle (myocardium) is suddenly self-inject selatogrel as early as possible and of an acute myocardial infarction. decreased or completely cut off by a blood immediately call for emergency medical The primary efficacy endpoint is the clot in one or more of the coronary vessels. help. occurrence of death from any cause, or An AMI requires immediate treatment, non-fatal AMI after any study treatment as any delay in intervention can result in self-administration. The study will enroll irreversible damage to the heart muscle Current status approximately 14,000 patients who are at and adverse clinical outcomes. According In late 2019, Idorsia entered into a global high risk of recurrent AMI, at around 250 to the US Centers for Disease Control and development agreement with Antares sites in about 30 countries. Drug Discovery and Clinical Prevention, each year more than 800,000 Pharma, a US-based leader in autoinjector Development persons living in the US will suffer a heart and rescue pen technologies, to design and A Special Protocol Assessment has been attack. customize an autoinjector for selatogrel. agreed with the FDA. This indicates the Development Pipeline The Antares autoinjector was selected FDA is in agreement with the adequacy Although the management of AMI has for its robustness, reliability, ease-of-use and acceptability of specific critical Daridorexant improved in recent decades, morbidity and and emergency-ready capabilities – key elements of overall protocol design (e.g.,
Aprocitentan mortality associated with AMI remain high. characteristics necessary due to the nature entry criteria, dose selection, endpoints The majority of deaths occur outside the of AMI. Idorsia has confirmed the usability and planned analyses) for a study intended Clazosentan hospital. Early action is crucial for survival of the Antares autoinjector through to support a future marketing application. and to preserve heart muscle. human factor validation studies. Lucerastat The FDA has also designated the > Selatogrel Besides aspirin, there are no treatment Idorsia is initiating an international, investigation of selatogrel for the options currently available for the critical multi-center, double-blind, randomized, treatment of a suspected AMI in adult Cenerimod time from onset of AMI symptoms to placebo-controlled, parallel-group, Phase patients with a history of AMI as a “fast- ACT-539313 first medical contact. The development 3 study to assess the clinical efficacy and track” development program. This of selatogrel in an autoinjector aims to safety of 16 mg selatogrel when self- designation is intended to promote Other Compounds communication and collaboration between Available clinical data • Neumann FJ, et al. 2018. Eur Heart J the FDA and pharmaceutical companies for Two published Phase 2 studies, one in 2019;40(2):87–165 drugs that treat serious conditions and fill patients with chronic coronary syndromes • Storey R. F, et al. Eur Heart J 2019;0, 1-9, an unmet medical need. and one in patients with AMI showed doi:10.1093/eurheartj/ehz807 fast and reversible inhibition of platelet • Sinnaeve P, et al. J Am Coll Cardiol. 2020 SOS-AMI has been designed as a patient- aggregation. Subcutaneous administration May 26;75(20):2588-2597. doi: 10.1016/j. centric study in collaboration with of selatogrel 16 mg has demonstrated a jacc.2020.03.059. PMID: 32439008. patients. Patients participating in SOS-AMI rapid onset of action, within 15 minutes, • Juif P, et al. The Journal of Clinical Pharmacology will be trained by qualified professionals with the magnitude of the effect extending 2019, 59(1): 123-130. doi:10.1002/jcph.1296 appointed at each study site, on how to over approximately eight hours. Selatogrel Drug Discovery and Clinical recognize AMI symptoms, on how and was safe and well tolerated in both studies, Development where to self-inject treatment, and to call and there were no treatment-emergent for emergency medical help immediately. serious bleeds. Development Pipeline Trainers will use standardized material mirrored across all countries, which has Milestones Daridorexant been developed with the support of 2021 Initiation of Phase 3 registration study
Aprocitentan education experts, feed-back from post- 2019 Drug-device development agreement with MI patients, and in alignment with current Antares Pharma Inc. Clazosentan guidelines. The patient is empowered 2018 Positive results for the Phase 2 studies through focused education to take Lucerastat action. In addition, regular interaction Key scientific literature > Selatogrel is performed by telephone with the • Benjamin EJ, et al. Heart Disease and Stroke designated site trainer, minimizing the Statistics—2019;139(10):e56-e528. Cenerimod burden on the patient, particularly during • Adnet F, et al. Emerg Med J. 2011;28(10):884–6. ACT-539313 times of a global pandemic. • Norris RM. BMJ 1998;316(7137):1065–70. • Ibanez B, et al. 2017. Eur Heart J 2018;39(2):119–77 Other Compounds Cenerimod
Cenerimod is a highly selective sphingosine-1-phosphate 1 (S1P1) receptor modulator, given as an oral once-daily tablet, which potentially offers a novel approach for the treatment of systemic lupus erythematosus (SLE) – a disease with a significant impact on patients and limited treatment options.
SLE, the most common form of lupus, is of the receptor, so that the lymphocyte fatigue, using patient-reported outcome an autoimmune disease. In SLE, the body’s can no longer sense S1P. As a result, the instruments, as well as the effects on SLE immune system malfunctions and attacks lymphocytes are held in the lymph nodes, biomarkers. Randomization was completed the body’s own tissues, which can affect reducing the availability of these key players by the end of February 2021, with 427 the skin, joints, gut, blood cells, lungs, in inflammation to the affected organs patients enrolled. Therefore, the results and other organs. It is estimated that 1.5 and tissues. The effect of cenerimod on are targeted for the fourth quarter of million Americans, and at least five million lymphocyte trafficking is reflected by the 2021. people worldwide, have a form of lupus, dose-dependent, sustained and reversible and that 90% of people living with lupus reduction in circulating lymphocyte counts In December 2017, the FDA designated are women, with most developing the observed upon administration of cenerimod. the investigation of cenerimod for Drug Discovery and Clinical disease between the ages of 15-44. There is the treatment of SLE as a “fast-track” Development a higher prevalence of lupus among people development program. This designation of Asian and Afro-Caribbean origin than in Current status is intended to promote communication Development Pipeline Caucasians. Following a Phase 2 safety study in and collaboration between the FDA and patients with SLE, in December 2018, pharmaceutical companies for drugs that Daridorexant While the cause of SLE is not fully known, Idorsia initiated CARE, a multiple-dose, treat serious conditions and fill an unmet
Aprocitentan T and B lymphocytes are considered the efficacy and safety study with cenerimod, medical need. key immune system cells playing a key for the treatment of adult patients Clazosentan role in the development of SLE. T and B with moderately to severely active, lymphocytes have S1P receptors on the autoantibody-positive SLE. The aims of the Lucerastat 1 surface which enable the lymphocytes to study are to assess the safety and efficacy Selatogrel detect the signaling molecule sphingosine- of cenerimod treatment at four different 1-phosphate or S1P, which is responsible dose levels; to determine the appropriate > Cenerimod for lymphocyte trafficking from the lymph dose, patient population and endpoints ACT-539313 nodes to the blood. Cenerimod binds to the for further development in SLE; and to
S1P1 receptor which leads to internalization evaluate the effects on quality of life and Other Compounds Available clinical data Milestones In a Phase 2 proof-of-concept study 2018 Initiation of a multiple-dose efficacy and safety investigating the effect of cenerimod on study circulating lymphocytes, disease activity, 2015 Initiation of a Phase 2 safety study safety and pharmacokinetics in SLE patients, cenerimod dose-dependently reduced Key scientific literature total lymphocyte count from baseline to • Hermann V, et al. Lupus Science & Medicine end of treatment (p< 0.001). In addition, 2019;6:e000354. doi:10.1136/lupus-2019-000354 the antibody-producing B cells, which are • Juif P-E,et al. Int. J. Mol. Sci. 2017, 18, 2636; elevated in patients with SLE and critical to doi:10.3390/ijms18122636 Drug Discovery and Clinical the disease process, were markedly reduced • Piali L, et al. Pharmacol Res Perspect. 2017 Development by cenerimod. The study provided promising Dec;5(6). data, with an early indication of efficacy • Borchers AT, et al. Autoimmun Rev. 2010; Development Pipeline being numerical reductions in mSLEDAI-2K 9(5):A277-87. (one of the measures of disease activity) and • Pons-Estel GJ, et al. Semin Arthritis Rheum. 2010; Daridorexant in anti-double-stranded DNA antibodies. This 39(4):257-68.
Aprocitentan is very encouraging, especially considering • Govoni M, et al. Lupus. 2006; 15:110-113. that the result was seen after only 12 weeks • Rahman A, Isenberg DA. N Engl J Med. 2008; Clazosentan of treatment. 358:929-39. • Abu-Shakra M, et al. J Rheumatol 1995; 22(7):1259- Lucerastat Cenerimod was well tolerated at all dose 64. Selatogrel levels. The occurrence of adverse events was similar in all five treatment groups. > Cenerimod
ACT-539313
Other Compounds ACT-539313 ACT-539313 is a selective, potent, and brain-penetrating orexin 1 receptor antagonist, being developed for the treatment of adult patients with binge eating disorder. Preclinical studies have shown that orexins play an important role in driving compulsive binge-like consumption and that orexin receptor antagonists have reduced binge-like eating behavior in animal models.
Binge eating disorder (BED) is the most contribute to the psychopathology in BED, common eating disorder, more common Current status in addition to reducing the frequency of than anorexia nervosa and bulimia nervosa In March 2021, the company initiated the binge eating. combined. BED refers to repeated episodes recruitment into a multicenter, double- of eating unusually large portions of food blind, randomized, placebo-controlled, in a short period of time (within any 2-hour parallel-group, Phase 2 proof‑of-concept Available clinical data period) and is associated with a sense of study to evaluate the efficacy and safety In the Phase 1 studies, ACT-539313 was well lack of control over what is being eaten. of oral ACT-539313 in the treatment of tolerated at single oral doses of up to and Individuals living with the condition may adult patients with moderate to severe including 400 mg and at multiple oral doses find it difficult to stop eating even if they binge eating disorder. This is the first of up to and including 200 mg twice daily for Drug Discovery and Clinical feel uncomfortably full. Other core features study of orexin 1 receptor antagonism as a 10 days in healthy volunteers. Development of BED include significant psychological new mechanism of action for patients with distress (e.g., shame, guilt, embarrassment) binge eating disorder and was designed Milestones Development Pipeline about binge eating and the absence of following consultation with the US FDA. 2021 Phase 2 in patients with BED initiated recurrent inappropriate compensatory Daridorexant behaviors such as purging, fasting, and Study participants will be randomized to Key scientific literature Aprocitentan excessive exercise. receive either ACT-539313 at a dose of • Berger, B., et al. (2020). J Clin Pharmacol 60(7):931- 100 mg twice daily, or placebo in a 1:1 ratio 941. Clazosentan Patients with BED have significant functional over a 12‑week treatment period. The • Kaufmann, P., et al. (2020). Br J Clin Pharmacol impairment, decreased quality of life and primary efficacy endpoint is the change 86(7):1377-1386. Lucerastat psychiatric (primarily anxiety and mood from baseline to Week 12 in the number of • Kaufmann, P., et al. (2020). Prog Neuropsycho- Selatogrel disorders) as well as medical comorbidities, binge eating days per week. A binge eating pharmacol Biol Psychiatry 108:110166. including obesity, type 2 diabetes and sleep day is defined as a day with at least one Cenerimod problems. confirmed binge eating episode. The study > ACT-539313 will also assess the effect of ACT-539313 in modulating behavioral features that Other Compounds Other Compounds Idorsia has developed platforms of expertise in families of molecular targets which allow high productivity in the generation of innovative compounds potentially addressing a wide range of high unmet medical needs.
Sinbaglustat The company has closed a natural history study called “RETRIEVE” which collected disease information from pediatric patients with early onset of rare lysosomal storage disorders (LSDs). The company is now considering development options for sinbaglustat.
ACT-1004-1239 ACT-1004-1239 is a CXCR7 antagonist intended for immunology disorders currently investigated in a Phase 1 program.
Drug Discovery and Clinical ACT-1014-6470 Development ACT-1014-6470, an immunology compound, is currently investigated in a Phase 1 program. Development Pipeline ACT-777991 Daridorexant ACT-777991, an immunology compound, is currently investigated in
Aprocitentan a Phase 1 program.
Clazosentan
Lucerastat
Selatogrel
Cenerimod
ACT-539313
> Other Compounds Idorsia is an independent biopharmaceutical company based on science and innovation. The company is specialized in the discovery and development of small molecules, to transform the horizon of therapeutic options. It is headquartered in Allschwil/Basel, Switzerland and is quoted on the SIX Swiss Exchange (tickersymbol: IDIA). All trademarks are legally protected by their respective owners.
Disclaimer This fact sheet has the sole purpose to provide members of the public with general information about the activities of Idorsia. The forward-looking statements in this fact sheet are based on current expectations and belief of company management, which are subject to numerous risks and uncertainties.
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Drug Discovery and Clinical Development
Latest update: July 2021
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