Idorsia – Reaching out for more

1 Idorsia Reaching out for moreThe following 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.

2 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. Idorsia - Reaching out for more | April 2019215 June 2017 Idorsia - Reaching out for more | April 20193 The purpose of Idorsia is todiscover, develop and bring more,innovative medicines to have more ideas, we seemore opportunities and we wantto help more - Reaching out for more | April 20194We strengthened our cash position so that we can continue to invest in our bright future Strengthened financingWe appointed a leader to build our global commercial organization and make strategic decisions on how to commercialize our broad range of assetsChief Commercial OfficerWe completed demerger activities, with all core systems now running independently of ActelionOperational independenceAdvancing pipelineWe advanced our pipeline, bringing four products into Phase 3 development2018 HIGHLIGHTSI dorsia - Reaching out for more | April 20195 Idorsia Today>750 Highly qualified professionals11>1 bn> 550 State-of-the-artlaboratory workspacesCompounds in the pipeline.

3 With four in late-stage developmentSwiss francs in cashIdorsia - Reaching out for more | April 20196 Our Strategic Priorities1 Deliver at least three products to market2 Build a commercial organization3 Bring Idorsia to profitability in a sustainable manner4 Create a pipeline with a sales potential of CHF 5 billion5 Utilize state-of-the-art technologies5key priorities to ensure the company s success over the first 5 yearsIdorsia - Reaching out for more | April 20197 Diversified and balanced pipeline: CNS, cardiovascular and immunological disorders & orphan diseasesMore in the pipeline Promising compoundsVasospasm associated with aneurysmal subarachnoid hemorrhageClazosentanEndothelin receptor antagonistStatus: Phase 3 InsomniaACT-541468 Dual orexin receptor antagonistStatus: Phase 3 Fabry diseaseLucerastatGlucosylceramide synthase inhibitorStatus: Phase 3 Acute Coronary SyndromeSelatogrelP2Y12 receptor antagonistStatus: Phase 2 Systemic lupus erythematosusCenerimodS1P1receptor modulatorStatus: Phase 2 Orphan CNS diseasesACT-519276 GBA2/GCS inhibitorStatus: Phase 1 EpilepsyACT-709478T-type calcium channel blockerStatus: Phase 1 AnxietyACT-539313 Selective orexin 1 receptor antagonistStatus: Phase 1 Nasal polyposisACT-774312 CRTH2 receptor antagonistStatus: Phase 2 ResistanthypertensionmanagementAprociten tanDual endothelin receptor antagonistStatus: Phase 3In collaboration with Janssen Biotech, Inc.

4 Cancer Immunotherapy / ImmunologyACT-1004-1239 Status: Phase 1 Idorsia - Reaching out for more | April 20198 Lucerastatin FabrydiseaseLucerastat is investigational, in development and not approved or marketed in any - Reaching out for more | April 20199 Fabry disease is a rare inherited lysosomal storage disorderin which a particular lipid(a fat-like substance) can t be broken down by the body, leading to its build-up in the cells of the body organs which results in cell and organ damageFabry disease is often undetected or misdiagnosedAs the disease is progressive, early diagnosis is essentialto manage the symptoms as soon as possible and reduce the risk of developing serious complicationsFabry diseaseIdorsia - Reaching out for more | April 201910 Lipids are fat-like substances such as fatty acids, oils, waxes and steroids. A well-known example is cholesterol Lipids are stored naturally in the body s cells and organs and are vital to their healthy functioning Normally, the body is able to process lipids effectively, which keeps them within healthy levelsWhat is the role oflipids in the body?

5 What happens in patients with lysosomal storage disorders?Normal breakdown of lipidsWhen enzyme to break downlipid is deficientLipid (fatty molecules)Broken-down lipids exit cell to be processed furtherUnbroken-down wasteProducts collect in cellLipids can t be processed and build up in cellIdorsia - Reaching out for more | April 201911 Fabry diseaseBiochemical mechanismCerceramideGCS glucosylceramide synthaseGlcCerglucosylceramideGb3globotr iaosylceramidelysoGb3globotriaosylsphing osine -GalA -galactosidase ASMsphingomyelinSphsphingosineDysfunctio nal or absent -galactosidase A results in accumulation of Gb3in various organsPlasma MembraneLate endosome + lysosomecis-GolgilysoGb3Gb3Gb3 SphSphCerSMGlcCerGCS -GalAGb3 Idorsia - Reaching out for more | April 201912X-linked recessive genetic diseaseInheritance pattern in Fabry disease GLA gene mutation results in defective lysosomal enzyme -GalA In turn, this results in Gb3 accumulationRandom X-inactivation in Fabryfemale carriers.

6 Both genders affectedMale have generally classical phenotypeFemales have higher residual level enzyme and are affected later progress slower have more variable phenotype Idorsia - Reaching out for more | April 201913 Large spectrum of clinical, heterogeneous manifestationsClinical manifestations of Fabry diseaseBrainStrokes (in severe cases), and dizzinessNeuropathic pain Pain resulting from damage to or dysfunction of the nervous systemEyesThe appearance of the eyeschangesEarsTinnitus, hearing loss,and vertigoHeartCardiomyopathy with arrhythmia, valvular dysfunction,ischemia, left heart failureKidneysCysts, reduced kidneyfunction, progressive kidney failure SkinDark red spots orrashes, burning / tingling sensations, sensitivity to temperature and profuse sweatingDigestive Tract Abdominal pain, constipation, diarrhea, and nausea Fabrydisease Gradually progressing in severity from childhood to adulthood Major impact on quality of life Slow progressive damage to vital organs over decades Earlier deathIdorsia - Reaching out for more | April 201914 Diagnosis of Fabry diseaseClinical symptomsNeuropathic pain, GI, hearing loss, hypohydrosisClinical eventsStroke, cardiac and renal eventsPedigree analysisFamily members(between childrenand parents)

7 Enzyme assayLeukocyte -GalAGenotyping>830 mutationsBiomarkersGb3 in plasma and urineIdorsia - Reaching out for more | April 201915 Epidemiology of Fabry diseaseGroupTotalMaleFemaleEU-28 All ages7,3242,5094,815<18 years659279380<10 years26875193 USAll ages4,6071,5783,029<18 years414175239<10 years16847121 Estimated prevalence of diagnosed Fabry disease in general population (2001): per 100 Fabrydisease per yearPatients diagnosed with Fabrydisease in EU28 and US in per to - Reaching out for more | April 201916 Current therapies in Fabry diseaseNo curative therapySymptomatic treatments not satisfactoryEtiological therapies limitedEnzyme replacement therapy Fabrazyme(agalsidasebeta) (US and EU) Replagal(agalsidasealfa) (EU only) , bi-weekly Immunogenicity Partial efficacyChaperone therapy Galafold(migalastat) for patients with amenable mutation 1 capsule orally, fasted, every other dayIdorsia - Reaching out for more | April 201917 Lucerastatin Fabry diseaseAccess to most tissues, including peripheral & central nervous systemHighly soluble with complete absorptionInhibitor of glucosylceramide synthaseOral administrationLow molecular weight iminosugarRenal excretion of unchanged drugOrphan drug status granted in the US and EULucerastat is investigational, in development and not approved or marketed in any - Reaching out for more | April 201918 Plasma MembraneLate endosome + lysosomecis-GolgilysoGb3Gb3Gb3 SphSphCerSMGlcCerGCS -GalAGb3 Mode of actionLucerastatin FabrydiseaseLucerastat is investigational, in development and not approved or marketed in any inhibiting GCS, lucerastatreduces the precursor of Gb3 (GlcCer)

8 And Gb3 itselfCerceramideGCS glucosylceramide synthaseGlcCerglucosylceramideGb3globotr iaosylceramidelysoGb3globotriaosylsphing osine -GalA -galactosidase ASMsphingomyelinSphsphingosineIdorsia - Reaching out for more | April 201919 Patient survey Clinical development plan Lucerastatin FabrydiseaseLucerastat is investigational, in development and not approved or marketed in any pharmacology studiesExploratory studyConfirmatory study Pediatric studyPotential beyond initial plan SAD and MAD studies Renal impairment study tQTstudy Safety and proof of mechanism study MODIFY Study to run in parallel to MODIFY Plan agreed with EMA Better understand medical need from patient perspectiveIdorsia - Reaching out for more | April 201920 Clinical pharmacologyLucerastatin FabrydiseaseLucerastat is investigational, in development and not approved or marketed in any exposureHalf-life: approximately 6 hours twice daily dosing>85% of the dose excreted unchanged in urineNegligible food effectLow potential for drug-drug interactionDose adjustment required in subjects with renal function impairmenteGFR(mL/ m2)Dosing regimen(mg ) 601000 45 and < 60750 30 and < 45500 15 and < 30250Gu rardet al.

9 (2017) OrphanetJ Rare DisGu rardet al. (2017) J Clin PharmacolGu rardet al. (2018) Clin Pharmacol TherIdorsia - Reaching out for more | April 201921 Exploratory study designLucerastatin FabrydiseaseLucerastat is investigational, in development and not approved or marketed in any top of ERT (10 patients)D1 Monthly visitMonth 1 Admission RandomizationScreeningTreatment PeriodFollow-upD-28 / D-3 (-10)ERT (4 patients)EoSMonth 3 Monthly visitMonth 2+ 2 DaysPhone Call for patientswho received lucerastat+ 30 DaysPhone CallProspective, single-center, open-label, randomized, study in 14 male/female adult patients with Fabrydiseasereceiving enzyme replacement therapy (ERT)Phase 1bstudyIdorsia - Reaching out for more | April 201922 Primary objective To assess the safety and tolerability of for 12weeksSecondary objectives To investigate the effect of lucerastaton plasma biomarker levels following a 12-week treatment To assess the effect of lucerastaton renal and cardiac function To determine the 12-hour pharmacokinetic profile of lucerastatat steady state To identify metabolites in plasmaExploratory study objectivesLucerastatin FabrydiseaseLucerastat is investigational, in development and not approved or marketed in any 1b studyIdorsia - Reaching out for more | April 201923 Exploratory study patient demographicsLucerastat in Fabry disease All patients had comorbidities, most of them manifestations of Fabry disease None of these affected eligibility for the study Overall balanced between groupsLucerastat group 6 females, 4 males Mean age (SD): ( ), range from 18 to 67 Mean ERT duration in years (SD).

10 ( )Control group 4 males Mean age (SD): ( ), range from 21 to 62 Mean ERT duration in years (SD): ( )Lucerastat is investigational, in development and not approved or marketed in any 1b studyMedical history: Idorsia - Reaching out for more | April 201924 Exploratory study safety resultsLucerastat in Fabry diseaseLucerastat was safe and well tolerated in patients with Fabry disease over 12 weeks on top of ERTOne Serious Adverse Event, unrelated to lucerastat:Re-occurrence of atrial fibrillation in a patient with underlying hypertrophic cardiomyopathyNo specific pattern in the nature and distribution of Treatment-Emergent Adverse Events No trends for changes from baseline in:Vital signs, body weight, ECG recordings, clinical laboratory parametersLucerastat is investigational, in development and not approved or marketed in any 1b studyIdorsia - Reaching out for more | April 201925 Exploratory study biomarker results Biomarker reductionLucerastat in Fabry diseaseBiomarkerLucerastat groupControl groupPlasma ( ) ( )Urine ( ) ( ) ( ) ( ) ( ) ( )Mean % (SD) biomarker reduction from baseline at week 12 Day 1 Month 1 Month 2 VisitMonth 3-80-60-40-2002040% change from BaselineControl (n=4)Lucerastat (n=9)Lucerastat is investigational, in development and not approved or marketed in any 1b studyIdorsia - Reaching out for more | April 201926 Exploratory study conclusionsLucerastat in Fabry diseaseLucerastat was safe and well tolerated in patients with Fabry disease over 12 weeks on top of ERTP harmacokinetic findings consistent with previous studies in healthy subjectsProof of mechanism achieved with lucerastat.