Orion Oyj Class A · OMXHEX:ORNAV
Orion Oyj Class A — H1 2018 Earnings Presentation
44 slides from Orion Oyj Class A's earnings presentation, Jul 18, 2018
Slide 1: R&D presentation for investors
R&D presentation for investors Updated on 18 July 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 • CNS Orion utilises the • APIs to Orion’s • Oncology R&D of proprietary proprietary • Respiratory products to develop products (Easyhaler® new medicines for • Generic APIs product family) animals. • Contract development for pharm
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 ODM-104 the future require capability to discover and develop less
Slide 7: Clinical development pipeline
Clinical development pipeline
Slide 8: Orion's key pharmaceutical development projects
Orion's key pharmaceutical development projects Project Indication Phase Registration Easyhaler® salmeterol-fluticasone Asthma, COPD Bioequivalence study Registration Easyhaler® tiotropium COPD Bioequivalence 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: An androgen receptor targeted therapy for prostate cancer
Darolutamide: An androgen receptor targeted therapy for prostate cancer Darolutamide (ODM-201) is an androgen receptor antagonist that has ● Binds to the androgen receptor with high affinity ● Prevents efficiently androgen receptor signaling ● Low blood–brain barrier (BBB) penetration, potentially r
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: Two studies in phase III proceeding
Two studies in phase III proceeding ● Patients with non-metastatic, castration- ● Patients with metastatic, hormone-sensitive resistant prostate cancer at high risk for prostate cancer developing metastatic disease ● Treatment: Darolutamide with androgen ● Endpoints: deprivation therapy (hormonal th
Slide 14: 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 15: 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 commercialize darolutamide globally and Orion has the option to co-promote darolutamide in Euro
Slide 16: ODM-109
ODM-109 Best symptomatic treatment for Amyotrophic Lateral Sclerosis (ALS)
Slide 17: ODM-109: Oral levosimendan for ALS
ODM-109: Oral levosimendan for ALS ● First patients recruited in July ● The aim is to apply for marketing authorisation for the Phase III clinical trial (REFALS). in the US and Europe. ● By enhancing respiratory muscle function ● Levosimendan has been granted an Orphan Drug in ALS patients, orally a
Slide 18: ODM-109: REFALS phase III trial
ODM-109: REFALS phase III trial Levosimendan 1-2mg/day (300 patients) 80-100 450 clinical sites patients in US, Canada, Costs of the trial: Placebo (150 patients) Western Europe, ~ EUR 60 million Australia approximately over three years Primary 12 weeks 48 weeks endpoints: SVC% ALSFRS-R + Survival =
Slide 19: ODM-109: Oral levosimendan for ALS
ODM-109: Oral levosimendan for ALS ● ALS (Amyotrophic lateral sclerosis) is a fast progressing and fatal neurodegenerative disease: − Leads to diaphragm and skeletal muscle weakness and eventually paralysis and death typically due to respiratory failure. − No symptomatic treatments for muscle functi
Slide 20: ALS (Amyotrophic lateral sclerosis) as a rare disease
ALS (Amyotrophic lateral sclerosis) as a rare disease 1−2∕ ~16,800 ~12,500 ~450−500 100,000 Patients Patients Patients Incidence in the US in 2017 in Europe in Finland R&D presentation for investors © Orion Corporation 2018 20
Slide 21: Promising findings from LEVALS phase II study completed in 2016
Promising findings from LEVALS phase II study completed in 2016 ● The cross-over part of Phase II clinical trial with orally administered levosimendan (ODM-109) for treatment of patients ● The first phase II study aimed to demonstrate beneficial effects of levosimendan on respiratory function of ALS
Slide 22: 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 23: ODM-104
ODM-104 New COMT-Inhibitor for Parkinson’s Disease
Slide 24: 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 25: 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 26: 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 27: 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 28: ODM-203
ODM-203 A unique and selective dual FGFR+VEGFR inhibitor for FGFR-dependent tumors
Slide 29: 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 30: 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 31: 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 32: 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 33: ODM-207
ODM-207 Unique BET inhibitor for solid tumors
Slide 34: 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 35: 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 36: 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 37: 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 38: ODM-208
ODM-208 Pan-steroid hormone synthesis inhibitor (CYP11A1 inhibitor) for castration-resistant prostate cancer
Slide 39: ODM-208: Pan-steroid hormone synthesis inhibitor for castration-resistant prostate cancer
ODM-208: Pan-steroid hormone synthesis inhibitor (CYP11A1 inhibitor) for castration-resistant prostate cancer ● Steroid hormones stimulate the growth of hormonally regulated cancers, such as most breast prostate and breast cancers. ● Hormonal treatments have proven highly Steroid production effectiv
Slide 40: Easyhaler product family
Easyhaler product family Easyhalers for treatment of asthma and COPD
Slide 41: Orion's Easyhaler is a dry-powder inhaler developed in-house
Orion’s Easyhaler® is a dry-powder inhaler developed in-house ● Diverse treatment options for asthma and COPD by utilizing the same inhaler technology. ● Orion has developed Easyhaler-adapted dry powder formulations of several well-known generic active substances: salbutamol, beclometasone, budesoni
Slide 42: Easyhaler portfolio
Easyhaler® portfolio • Dispensing mechanism was 2014 budesonide- 2004 formoterol Easyhaler® 1994 beclomethasone invented by Orion’s own R&D in formoterol Easyhaler® the 1980s, and the first Easyhaler Easyhaler® was launched in 1993. • Currently five products in portfolio, but portfolio is expanding.
Slide 43: Portfolio expanding
Portfolio expanding Salmeterol-fluticasone Easyhaler® Tiotropium Easyhaler® in registration in development • Favorable bioequivalency study results • Orion has in 2018 commenced a project to in 2016. develop a tiotropium formulation for European • Positive conclusions under the EU's markets. decentr
Slide 44: Building well-being
Building well-being GRION Building well-being