Slide 1: R&D presentation for investors
R&D presentation for investors Updated on 7 February 2018
Slide 2: Disclaimer
Disclaimer This presentation contains forward-looking statements which involve risks and uncertainty factors. These statements are not based on historical facts but relate to the Company’s future activities and performance. They include statements about future strategies and anticipated benefits of
Slide 3: Focus areas of Orion's R&D
Focus areas of Orion’s R&D Proprietary Products Animal Health Fermion Orion Diagnostica • CNS Orion utilises the • APIs to Orion’s • QuikRead test • Oncology R&D of proprietary proprietary system • Respiratory products to develop products • GenRead test (Easyhaler® new medicines for • Generic APIs s
Slide 4: Together we can achieve more in R&D
Together we can achieve more in R&D Late stage Research Early development development Target Hit to Lead Lead Candidate Phase I Phase II Phase III identification generation optimisation selection, and validation preclinical development 8‒24 mo. 12‒24 mo. 18‒36 mo. 12‒24 mo. 12‒14 mo. 12‒36 mo. 18‒48
Slide 5: Several academic and other collaborations both in early and late phase of development
Several academic and other collaborations both in early and late phase of development R&D presentation for investors © Orion Corporation 2018 5
Slide 6: Building the R&D future success
Building the R&D future success 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 Innovation system Competence base ROADMAP Therapy area work ODM-207 ODM-109 Bringing treatments to patients addressing unmet needs also in ODM-203 the future require capability to discover and develop less ODM-104
Slide 7: Clinical development pipeline
Clinical development pipeline
Slide 8: Key clinical pharmaceutical development projects
Key clinical pharmaceutical development projects Project Indication PHASE Registration Bioequivalence Easyhaler® salmeterol-fluticasone Asthma, COPD Registration study Bioequivalence Easyhaler® tiotropium COPD study Darolutamide (ODM-201) 1) Prostate cancer (nmCRPC) I II III Darolutamide (ODM-201) 1
Slide 9: Vision for the future
Vision for the future Orion: a company with the brain power Making Orion capable of delivering novel and muscle of Big Pharma but with the proprietary small molecule therapeutics agility of small biotech and biologics Through internal work and partnering Increase Orion’s visibility within the activi
Slide 10: Darolutamide (ODM-201)
Darolutamide (ODM-201) A novel second generation androgen receptor (AR) inhibitor for the treatment of prostate cancer In collaboration with Bayer
Slide 11: Darolutamide (ODM-201): Partnership with Bayer – Financial terms
Darolutamide (ODM-201): Partnership with Bayer – Financial terms ● Orion and Bayer will jointly develop darolutamide, with Bayer contributing a major share of the costs of future development. ● Bayer will commercialise darolutamide globally and Orion has the option to co-promote darolultamide in Eur
Slide 12: Darolutamide (ODM-201) has a unique profile
Darolutamide (ODM-201) has a unique profile Enzalutamide 19%* Darolutamide 3% ** ARN-509 29%* Enzalutamide ARN-509 Darolutamide general structure AR Antagonism IC50 (nM) Proliferation Compound affinity AR AR AR VCaP Ki (nM) WT AR IC50 (nM) (F876L) (T877A) (W741L) Bicalutamide 12 150 218 957 Agonist
Slide 13: Darolutamide clinical studies
Darolutamide clinical studies Daily Dose ClinicalTrials.gov Study Phase Populations N Status identifier (mg) mCRPC* • Chemo/CYP17 naïve ARADES I/II 134 200-1800 Completed NCT01317641 • Post chemo/ CYP17 naïve • Post CYP17 mCRPC* • Chemo/CYP17 naïve ARADES ext II 76 200-1800 Completed NCT01317641 • P
Slide 14: Darolutamide Phase III study ongoing in nmCRPC
Darolutamide Phase III study ongoing in non-metastatic castration resistant prostate cancer (nmCRPC) ● nmCRPC patients who are at high risk for developing metastatic disease are included ● Primary endpoint – Darolutamide over placebo in metastasis-free survival (MFS) ● Secondary endpoints ClinicalTr
Slide 15: Darolutamide Phase III study ongoing in mHSPC
Darolutamide Phase III study ongoing in metastatic hormone sensitive prostate cancer (mHSPC) ● mHSPC patients candidate for ADT (hormonal therapy) and docetaxel (chemotherapy) are included. Treatment Darolutamide with ADT and six cycles of docetaxel ● Primary endpoint – Darolutamide over placebo in
Slide 16: ODM-203
ODM-203 A unique and selective dual FGFR+VEGFR inhibitor for FGFR-dependent tumors
Slide 17: Angiogenic indications with altered FGFR signalling
Angiogenic indications with altered FGFR* signalling Tumor type Genomic alterations of FGFRs and FGFs Breast (luminal) ~35% (FGFR1 amp, FGFR2 amp, FGFR4 amp, FGFs) NSCLC-SCC ~20% (FGFR1 amp, FGFR2 amp) Bladder (invasive) ~15% (FGFR3 fusions, FGFR1 amp, FGFs) Prostate ~14% (FGFR1 amp, FGFR2&3 fusions
Slide 18: ODM-203 has strong in vivo antitumor activity
ODM-203 has strong in vivo antitumor activity ODM-203 (targeted FGFR+VEGFR inhibitor) Solid tumours I II FGFR xenograft model (RT4) Angiogenic kidney cancer model (Renca) 600 500 400 300 200 100 0 0 2 4 6 8 10 12 14 16 18 20 Treatment day Vehicle control p.o. Selective FGFRi (12.5 mg/kg) ClinicalTri
Slide 19: Rationale for combining FGFR and VEGFR inhibition
Rationale for combining FGFR* and VEGFR** inhibition Constitutively active FGFRs are oncogenic in non-clinical studies Both VEGFR and FGFRs are drivers for angiogenesis, a hallmark of tumorigenesis FGFR amplifications have an impact on patient survival in studied cancer types (breast, lung, and gast
Slide 20: ODM-203 – current status
ODM-203 – current status ODM-203 (targeted FGFR+VEGFR inhibitor) Solid tumours I II KIDES trial with Phase II expansion ongoing ● The trial is investigating – Safety and tolerability of ODM-203 in subjects with advanced solid tumours – Efficacy of ODM-203 in slowing the growth of solid cancerous tum
Slide 21: ODM-207
ODM-207 Unique BET inhibitor for solid tumors
Slide 22: ODM-207 – A unique BET inhibitor for solid tumours
ODM-207 – A unique BET* inhibitor for solid tumours Potent and selective BET* inhibitor Good physico-chemical Structure different than properties JQ1** derivatives Patent applications Phase I ongoing ODM-207 filed • ODM-207 is an investigational small molecule that has a unique chemical structure de
Slide 23: Target: BET proteins which regulate expression of oncogenes
Target: BET proteins which regulate expression of oncogenes ● BET proteins occupy regulatory elements of DNA (superenhancers) in many key oncogenes – They increase the expression target oncogenes ● BET target genes include: Myc, MycN ODM-207 • Binds to BET proteins • Inhibits transcription of key on
Slide 24: ODM-207 inhibits the tumour growth in enzalutamide-resistant xenograft
ODM-207 inhibits the tumour growth in enzalutamide- resistant 22Rv1 prostate cancer xenograft Effect of ODM-207 on tumour volumes Effect of ODM-207 on tumour weights ODM-207 inhibits Myc in in vivo efficacy study From poster Björkman et al., presented in EORTC-NCI-AACR in 11-12/2016 R&D presentation
Slide 25: ODM-207 – current status
ODM-207 – current status ODM-207 (BET protein inhibitor) Cancer I BETIDES phase I/II trial ongoing ● The trial is investigating – PK, safety and tolerability, and antitumour activity of ODM-207 in subjects with advanced solid tumours ClinicalTrials.gov identifier: NCT03035591 R&D presentation for in
Slide 26: ORM-12741
ORM-12741 Alpha-2C adrenoceptor antagonist for symptomatic treatment of Alzheimer’s disease In collaboration with Janssen
Slide 27: Phase IIa clinical trial completed – the efficacy objectives not met
Phase IIa clinical trial completed – the efficacy objectives not met ● Orion has completed a Phase IIa clinical trial in the development of an alpha-2c adrenoceptor antagonist (ORM-12741). ● The trial, conducted in collaboration with Janssen Pharmaceuticals, Inc., investigated the efficacy of two di
Slide 28: Collaboration with Janssen
Collaboration with Janssen ● Licence agreement announced on 19 December 2013 (ORM-12741 and other compounds). ● Orion received USD 31 million upfront payment which is mainly used against current ongoing additional Phase IIa study costs. ● Orion is eligible to receive milestone payments from Janssen
Slide 29: ORM-12741
ORM-12741 ● Highly potent and selective alpha-2C Baseline adrenoceptor antagonist ● Rodent models predict beneficial effects on 1 hour after cognition and neuropsychiatric symptoms dosing (30 mg) (NPS) ● Phase 1 studies (healthy subjects) – Possible to administer orally – Well tolerated Quality of M
Slide 30: Phase 2 study on efficacy of ORM-12741 in AD
Phase 2 study on efficacy of ORM-12741 in AD ORM-12741 (alpha-2c adrenoceptor antagonist) Alzheimer’s disease I IIa ● New formulation improving pharmacokinetic (PK) properties of ORM-12741 was used in the Phase 2a study Objectives To evaluate efficacy of ORM-12741 on agitation & aggression and other
Slide 31: ODM-104
ODM-104 New COMT-Inhibitor for Parkinson’s Disease
Slide 32: New COMT-inhibitor ODM-104 for Parkinson's disease treatment
New COMT-inhibitor ODM-104 for Parkinson’s disease treatment ODM-104 (more effective COMT inhibitor) Parkinson’s disease I II ● In phase I, ODM-104 has been in well tolerated and superior to entacapone by improving COMT inhibition and levodopa pharmacokinetics in man. ● Optimized carbidopa component
Slide 33: Treatment of Parkinson's disease with levodopa
Treatment of Parkinson’s disease with levodopa ● Levodopa is the most effective medicine for treating Parkinson’s disease (PD). ● As PD progresses, most people will eventually require the use of Too much levodopa levodopa (85% of PD patients Dyskinesia can cause involuntary receive levodopa). moveme
Slide 34: Levodopa elimination can be reduced by inhibiting AADC and COMT
Levodopa elimination can be reduced and treatment effect improved by inhibiting breakdown enzymes AADC and COMT 3-OMD (inactive) COMT COMT-i ODM-104 Long- Levodopa Levodopa acting levodopa AADC Carbidopa AADC-i Dopamine Dopamine Body Brain AADC = Aromatic amino acid decarboxylase COMT = Catechol-O-m
Slide 35: Target indication
Target indication ● The target indication of ODM-104 is Parkinson´s disease with end-of-dose motor Levodopa + carbidopa fluctuations - the same as the currently approved indications of Comtess®/Comtan® and Stalevo®. Levodopa + carbidopa ODM-104 + + Comtess® / Comtan® ● Patients on levodopa/AADC inhi
Slide 36: ODM-109
ODM-109 Best symptomatic treatment for Amyotrophic Lateral Sclerosis (ALS)
Slide 37: LEVALS phase II study - levosimendan in ALS patients
LEVALS phase II study - levosimendan in ALS patients ODM-109 (oral levosimendan) ALS I II ● The first phase II study aimed to demonstrate beneficial effects on respiratory function. ● Double-blind, cross-over design with 3 treatment periods. ● Cross-over part of the study is followed by an open-labe
Slide 38: Amyotrophic lateral sclerosis - ALS
Amyotrophic lateral sclerosis - ALS ● Orphan disease with prevalence of ~1 patient/25,000 ● Degeneration of motoneuron leads to skeletal muscle weakness including diaphragm. ● Causes premature death (3 years median survival time from symptom onset). ● Decreases Quality of Life of both patient and ca
Slide 39: Data supporting development of ODM-109 for ALS
Data supporting development of ODM-109 for ALS Levosimendan enhances force generation of diaphragm muscle fibers obtained from a rat model of heart failure and from COPD and non-COPD patients (ex vivo experiments). Levosimendan improves human diaphragm function in healthy subjects in vivo. Levosimen
Slide 40: Easyhaler product family
Easyhaler product family Easyhalers for treatment of asthma and COPD
Slide 41: Easyhaler portfolio expanding
Easyhaler® portfolio expanding Salmeterol-fluticasone Easyhaler® • In registration phase in Europe since 2014 budesonide- 2004 formoterol 1994 4/2017 Easyhaler® beclomethasone • Favorable bioequivalency study results formoterol Easyhaler® Easyhaler® at the end of 2016 • Learnings from budesonide-for
Slide 42: Orion
Orion Building well-being GRION Building well-being