Slide 1: R&D presentation for investors
R&D presentation for investors Updated on 25 October 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: 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 8: Clinical development pipeline
Clinical development pipeline
Slide 9: Orion's key clinical drug development projects
Orion's key clinical drug development projects Project Indication Phase Registration Easyhaler® tiotropium COPD Bioequivalence study Darolutamide 1) Prostate cancer (nmCRPC) I II III Darolutamide 1) Prostate cancer (mHSPC) I II III ODM-109 (oral levosimendan) ALS I II III ODM-104 (more effective COM
Slide 10: Darolutamide
Darolutamide A novel second generation androgen receptor (AR) inhibitor for the treatment of prostate cancer In collaboration with Bayer
Slide 11: Orion and Bayer's phase III trial of darolutamide for nmCRPC: primary endpoint met
Orion and Bayer’s phase III trial of darolutamide for non- metastatic castration-resistant prostate cancer: Primary endpoint was met ● Darolutamide significantly extended metastasis- free survival compared to placebo. ● The full data will be presented at an upcoming scientific meeting. ● Bayer plans
Slide 12: Financial impacts of darolutamide
Financial impacts of darolutamide ● Bayer covered the majority of the development costs and has the right to commercialize darolutamide globally. Orion has the option of co-promoting in Europe. Orion will manufacture the product. ● Milestone payments upon first commercial sales: EUR 45 million in US
Slide 13: Other late-phase clinical trials are also making progress
Other late-phase clinical trials are also making progress ● Darolutamide for metastatic hormone- ● ODM-109/orally administered levosimendan sensitive prostate cancer: for ALS: – Phase III trial ARASENS in collaboration – 3-year REFALS trial started in the spring, with Bayer ongoing. recruitment prog
Slide 14: Two trials with Bayer on darolutamide
Two trials with Bayer on darolutamide ● Patients: men with non-metastatic, ● Patients: men with metastatic, hormone- castration-resistant prostate cancer treated with sensitive prostate cancer androgen deprivation therapy (hormonal therapy) and at risk of developing metastatic ● Treatment: Darolutam
Slide 15: Darolutamide has a unique profile (Phase II trial)
Darolutamide has a unique profile (Phase II trial) 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 A
Slide 16: Darolutamide clinical studies
Darolutamide clinical studies Daily Dose ClinicalTrials.gov Study Phase Populations N Status identifier (mg) mCRPC* • Chemo/CYP17 naïve ARADES I/II 134 200-1,800 Completed NCT01317641 • Post chemo/ CYP17 naïve • Post CYP17 mCRPC* • Chemo/CYP17 naïve ARADES ext II 76 200-1,800 Completed NCT01317641 •
Slide 17: ODM-109
ODM-109 Best symptomatic treatment for Amyotrophic Lateral Sclerosis (ALS)
Slide 18: 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 19: 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 20: 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 21: ALS 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 21
Slide 22: 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 23: 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 24: ODM-104
ODM-104 New COMT-Inhibitor for Parkinson’s Disease
Slide 25: 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 26: 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 27: 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 28: 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 29: ODM-203
ODM-203 A unique and selective dual FGFR+VEGFR inhibitor for FGFR-dependent tumors
Slide 30: 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 31: 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 32: 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 33: 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 34: ODM-207
ODM-207 Unique BET inhibitor for solid tumors
Slide 35: 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 36: 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 37: 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 R&D presentation
Slide 38: 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 39: ODM-208
ODM-208 Pan-steroid hormone synthesis inhibitor (CYP11A1 inhibitor) for castration-resistant prostate cancer
Slide 40: ODM-208: Pan-steroid hormone synthesis inhibitor for CRPC
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 41: Easyhaler product family
Easyhaler product family for treatment of asthma and COPD
Slide 42: 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, budeso
Slide 43: Salmeterol-fluticasone Easyhaler launched
Salmeterol-fluticasone Easyhaler® The sixth member of the product family launched • In March 2018, Orion received positive conclusions for the salmeterol- fluticasone Easyhaler under the decentralised EU marketing authorisation procedure. • The national approval procedures started in 23 EU countries
Slide 44: The seventh product, tiotropium, is in development
The seventh product, tiotropium, is in development ● Bioequivalency study started in Q1/2018. ● The product is developed for European markets. ● Tiotropium is a long-acting anticholinergic bronchodilator used in the treatment of chronic obstructive pulmonary disease. R&D presentation for investors ©
Slide 45: Easyhaler - current portfolio
Easyhaler® - current 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. 2018 salmeterol- 2002 budesonide 1993 salbutamol fluticas
Slide 46: Building well-being
Building well-being GRION Building well-being