Slide 1: R&D presentation for investors
R&D presentation for investors Updated on 26 October 2017
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 in early and late development
Several academic and other collaborations both in early and late phase of development 5 2017 R&D presentation for investors © Orion Corporation
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 Work forROADMAP the future ongoing Therapy area work ODM-207 ODM-109 Bringing treatments to patients addressing unmet needs also in ODM-203 the future require capability to discov
Slide 7: Clinical development pipeline
Clinical development pipeline 7 2017 R&D presentation for investors © Orion Corporation
Slide 8: Key clinical pharmaceutical development projects
Key clinical pharmaceutical development projects Project Indication PHASE Registration Bioequivalence Easyhaler® salmeterol-fluticasone Asthma, COPD Registration study Darolutamide (ODM-201) 1) Prostate cancer (nmCRPC) I II III Darolutamide (ODM-201) 1) Prostate cancer (mHSPC) I II III ODM-109 (oral
Slide 9: R&D portfolio: Human proprietary projects in research and development phase
R&D portfolio: Human proprietary projects in research and development phase High Antiandrogen COMT-i Darolutamide Easyhaler ODM-104 pipeline Probability of success Levosimendan Technical feasibility Alpha2C ODM-109 ORM-12741 FGFR-i BET-i ODM-203 ODM-207 Pain Oncology NDD Pain Pain Pain NDD Pain NDD
Slide 10: R&D development portfolio is maturing and more confirmatory programs expected
R&D development portfolio is maturing and more confirmatory programs expected in the portfolio Number of projects MEUR 14 140 12 120 On hold 10 100 8 80 Confirmatory phase 6 60 Exploratory 4 40 phase 2 20 0 0 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017* * non-probabilitized projections 10 2017
Slide 11: 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 12: Darolutamide (ODM-201)
Darolutamide (ODM-201) A novel second generation androgen receptor (AR) inhibitor for the treatment of prostate cancer In collaboration with Bayer 12 2017 R&D presentation for investors © Orion Corporation
Slide 13: Darolutamide: 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 14: 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 Antagonism IC50 (nM) Proliferation AR affinity Compound AR AR AR VCaP Ki (nM) WT AR (F876L) (T877A) (W741L) IC50 (nM) Bicalutamide 12 150 218 957 Agonist
Slide 15: 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 16: Darolutamide Phase III study 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 – Overall
Slide 17: Darolutamide Phase III study 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 18: ODM-203
ODM-203 A unique and selective dual FGFR+VEGFR inhibitor for FGFR-dependent tumors 18 2017 R&D presentation for investors © Orion Corporation
Slide 19: 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 20: ODM-203 has strong in vivo antitumor activity
ODM-203 has strong in vivo antitumor activity ClinicalTrials.gov identifier: ODM-203 (targeted FGFR+VEGFR inhibitor) Solid tumours I II NCT02264418 600 FGFR xenograft model (RT4) Angiogenic kidney cancer model (Renca) 500 400 300 200 100 0 0 2 4 6 8 10 12 14 16 18 20 Treatment day Vehicle control p.
Slide 21: 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 22: 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 23: ODM-207
ODM-207 Unique BET inhibitor for solid tumors 23 2017 R&D presentation for investors © Orion Corporation
Slide 24: 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- Structure different than chemical properties JQ1** derivatives Phase I ongoing Patent applications ODM-207 filed • ODM-207 is an investigational small molecule that has a unique chemical structure d
Slide 25: 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 26: ODM-207 inhibits 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 26 2017 R&D prese
Slide 27: 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 27 2017 R&D presentatio
Slide 28: ORM-12741
ORM-12741 Alpha-2C adrenoceptor antagonist for symptomatic treatment of Alzheimer’s disease In collaboration with Janssen 28 2017 R&D presentation for investors © Orion Corporation
Slide 29: Collaboration with Janssen
Collaboration with Janssen ● Licence agreement announced on 19 December 2013 (includes 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
Slide 30: ORM-12741 Phase 2a results
ORM-12741 Baseline ● Highly potent and selective alpha-2C adrenoceptor antagonist ● Rodent models predict beneficial effects on 1 hour after cognition and neuropsychiatric symptoms (NPS) dosing (30 mg) ● Phase 1 studies (healthy subjects) – Possible to administer orally – Well tolerated Quality of M
Slide 31: 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 is used in the ongoing Phase 2a study Objectives To evaluate efficacy of ORM-12741 on agitation & aggression an
Slide 32: ODM-104
ODM-104 New COMT-Inhibitor for Parkinson’s Disease 32 2017 R&D presentation for investors © Orion Corporation
Slide 33: 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 34: 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 levodopa (85% of PD patients receive levodopa). ● However, like all medicines, levodopa is not perfect –
Slide 35: Levodopa elimination 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 levodop AADC a Carbidopa AADC-i Dopamine Dopamine Body Brain AADC = Aromatic amino acid decarboxylase COMT = Catechol-O-
Slide 36: Target indication
Target indication ● The target indication of ODM-104 is Parkinson´s disease with end-of-dose motor fluctuations - the same as the currently approved indications of Comtess®/Comtan® and Stalevo®. Patients on levodopa/AADC inhibitor treatment with or without entacapone can be directly switched to the
Slide 37: ODM-109
ODM-109 Oral levosimendan Best symptomatic treatment for Amyotrophic Lateral Sclerosis (ALS) 37 2017 R&D presentation for investors © Orion Corporation
Slide 38: 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 39: 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 40: 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 41: Salmeterol-fluticasone Easyhaler
Salmeterol-fluticasone Easyhaler Easyhalers for treatment of asthma and COPD 41 2017 R&D presentation for investors © Orion Corporation
Slide 42: Easyhaler portfolio expanding
Easyhaler® portfolio expanding 2004 formoterol 1994 • Salmeterol-fluticasone 2014 budesonide- formoterol Easyhaler® Easyhaler® beclomethasone Easyhaler® Easyhaler® in registration phase in Europe • Favorable bioequivalency study results at the end of 2016 • We have utilised the learnings from budeso
Slide 43: Building well-being. Together.
Building well-being. Together.