Orion Oyj Class A · OMXHEX:ORNAV
Orion Oyj Class A — Investor Presentation (February 2019)
44 slides from Orion Oyj Class A's investor presentation, Feb 6, 2019
Slide 1: R&D presentation for investors
R&D presentation for investors Updated on 6 February 2019
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 • Central nervous system • Orion utilises the R&D of • APIs to Orion’s • Oncology proprietary products to proprietary products • Respiratory develop new medicines • Generic APIs (Easyhaler product for animals. • Contract developme
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: 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 6: Orion's R&D vision for the future
Orion’s R&D vision for the future 1 Brain power and muscle of a Big Pharma, the agility A preferred partner for other pharma companies and Increased visibility within the academic community and of a small biotech. research institutions. capabilities to recruit and retain “the best and the brightest”
Slide 7: Clinical development pipeline
Clinical development pipeline
Slide 8: 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 9: Darolutamide
Darolutamide A novel second generation androgen receptor (AR) inhibitor for the treatment of prostate cancer In collaboration with Bayer
Slide 10: Orion and Bayer's phase III trial of darolutamide for nmCRPC
Orion and Bayer’s phase III trial of darolutamide for non-metastatic castration-resistant prostate cancer: Primary endpoint was met ● Darolutamide significantly extended ● Bayer is having discussions with health metastasis-free survival compared to authorities regarding the submission for placebo. T
Slide 11: 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 12: 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 13: 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 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 134 200-1,800 Completed NCT01317641 • Post chemo/ CYP17 naïve • Post CYP17 mCRPC* • Chemo/CYP17 naïve ARADES ext II 76 200-1,800 Completed NCT01317641 •
Slide 15: ODM-109
ODM-109 Best symptomatic treatment for Amyotrophic Lateral Sclerosis (ALS)
Slide 16: 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 17: ODM-109 (ALS): REFALS phase III trial
ODM-109 (ALS): REFALS phase III trial 450 patients Primary endpoints • Levosimendan • 12 weeks: 1-2mg/day Slow vital capacity (300 patients) (Breathing • Placebo capacity compared to normal subjects) (150 patients) • 48 weeks: Approx.100 clinical sites ALS functional rating scale (Overall • US, Cana
Slide 18: 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 19: 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 19
Slide 20: 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 21: 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 22: ODM-104
ODM-104 New COMT-Inhibitor for Parkinson’s Disease
Slide 23: 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 24: 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 25: 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 26: 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 27: ODM-203
ODM-203 A unique and selective dual FGFR+VEGFR inhibitor for FGFR-dependent tumors
Slide 28: 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 29: 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 30: 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 31: 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 32: ODM-207
ODM-207 Unique BET inhibitor for solid tumors
Slide 33: 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 34: 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 35: 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 36: 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 37: ODM-208
ODM-208 Pan-steroid hormone synthesis inhibitor (CYP11A1 inhibitor) for castration-resistant prostate cancer
Slide 38: 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 39: Easyhaler product family
Easyhaler product family for treatment of asthma and COPD
Slide 40: 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 41: 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 42: 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 43: Easyhaler product family is expanding
Easyhaler product family is expanding 2018 Tiotropium development started R&D presentation for investors © Orion Corporation 43
Slide 44: Building well-being
Building well-being GRION Building well-being