Swedish Orphan Biovitrum Ab · OMXSTO:SOBI
Swedish Orphan Biovitrum Ab — Investor Day (November 2011)
134 slides from Swedish Orphan Biovitrum Ab's investor day presentation, Nov 29, 2011
Slide 1: Sobi Capital Markets Seminar
Sobi Capital Markets Seminar Solna, November 29 , 2011
Slide 2: Program
Program Capital Markets Seminar, 29 November 2011 13.00 Company overview and direction, incl. Current product portfolio Geoffrey McDonough, President and CEO 14.00 Financial review Lars Sandström, CFO Coffee 14:45 Development pipeline – Update on Kiobrina project Bertold Koletzko, MD, PhD, Professor
Slide 3: Disclaimer
Disclaimer In order to utilize the ‘Safe Harbor’ provisions of the United States Private Securities Litigation Reform Act of 1995, Swedish Orphan Biovitrum is providing the following cautionary statement. This presentation contains forward-looking statements with respect to the financial condition,
Slide 4: CEO Introduction
CEO Introduction Sobi Capital Day 2011 29 November 2011
Slide 5: Who We Are
Who We Are Sobi is an innovative bio-pharmaceutical company with a leading position in the commercialization of niche and rare disease products. Our operations are driven by a diversified and growth-oriented portfolio in niche and rare disease therapies. We have a late-stage pipeline with substantia
Slide 6: Our Vision
Our Vision Sobi is recognized as the leading integrated bio-pharmaceutical company … … dedicated to bringing innovative therapies and services … … to improve the health of rare disease patients and their families. 6
Slide 7: All the Components of a Great Company Are Here
All the Components of a Great Company Are Here R+D Manufacturing 1. World class protein biochemistry 1. Demonstrated competence in biologics 2. Demonstrated early stage development from manufacturing at pilot and commercial scale proof of concept to Phase III 2. Biologics process development, scale
Slide 8: Our Objectives
Our Objectives 1. To achieve positive net cash flow and profitability in our operations. 2. To efficiently commercialize our proprietary innovative medicines for rare disease patients globally. 8
Slide 9: Actions to Reach Our Goals
Actions to Reach Our Goals We intend to earn our way into our future based on operational performance. 1. Revenue growth through focus on key products 2. Ongoing cost discipline 3. Gross Margin improvement Positive cash flow from operations and working capital 9
Slide 10: Focus the Business on Strategic Building Blocks
Focus the Business on Strategic Building Blocks Development Programs Kiobrina Hemophilia Strategic Core Growth Drivers Products Three Business Lines Growth ReFacto® Specialty Platforms Distribution Portfolio 10
Slide 11: Aligning Resources in Three Business Lines
Aligning Resources in Three Business Lines ReFacto® Core Products Specialty (Manufacturing Distribution + Royalty) Portfolio SEK 608 M SEK 803 M SEK 459 M Growth 34% Growth 6% Growth 8% GM >60% GM ~60% GM <50% Inflammation Niche Genetics + Hematology Metabolism Oncology Note: 4 quarters rolling numb
Slide 12: ReFacto – A Durable Platform
ReFacto® – A Durable Platform • Partnership with Pfizer • Global sales 2010: USD 404 M • Pfizer expanding in established and ReFacto® emerging markets Royalty SEK 114 M • As the exclusive supplier, we have: • Made ReFacto® albumin free • Substantially increased capacity • Enabled expansion of Pfizer
Slide 13: Core Products – Proprietary Strategic Growth Drivers
Core Products – Proprietary Strategic Growth Drivers Ammonul® Ruconest® SEK 8 M SEK 1 M 1. Therapeutic Areas • Genetics + Metabolism • Inflammation Ammonaps® SEK 64 M 2. Focus for Growth • Room to expand in existing markets • Additional key markets reachable by us (US, Russia, Middle East) Orfadin®
Slide 14: How We Deliver Value to Customers and Partners
How We Deliver Value to Customers and Partners • Price pressure will continue Real Develop World 1. Market Access is a continuous Outcomes Innovative Therapies process throughout lifecycle 2. Centers of Excellence 3. Integrated value offering VALUE • Commercial focus Key Account Management Drive Win
Slide 15: Infrastructure in Majority of Global Innovative Markets
Infrastructure in Majority of Global Innovative Markets Nordic/Baltic/CEE HQ/R+D/Mfg SEK 472 M +Royalty/ FTE 59 SEK 608 M FTE 353 EMENA SEK 541 M FTE 72 United States SEK 319 M FTE 19 Note: United States includes 19 FTEs to be employed by Sobi as of January 2012. 15
Slide 16: Kineret – Repositioning is Creating Growth
Kineret® – Repositioning is Creating Growth • We acquired Kineret® in 2008 Sales (SEK M): Kineret 150 500 • We identified a niche where 120 400 Kineret addresses a significant medical need: 90 300 High risk RA-patients with 60 200 co-morbidities for which the short half life and safety profile of 30
Slide 17: Key Success Factor: Kineret Tech Transfer Delivery
Key Success Factor: Kineret® Tech Transfer Delivery • Sobi is transferring manufacturing for Kineret® to a CMO in Europe • Sobi purchased 500M SEK in Kineret® inventory from Amgen 2010 to support tech transfer • The tech transfer has costs in 2011 • Ordinary cost of TT • Cost of delay in TT • Valida
Slide 18: Kineret – Strong Interest in Broader Inflammation
Kineret® – Strong Interest in Broader Inflammation Prescriptions for Kineret® Unspecified Other, 1% inflammation, 5% Gout, 5% Diabetes, RA, 11% 39% CAPS, 2% Pediatric Inflammation Juvenile RA, 31% • Sobi will file within CAPS in US and EU in 2012 Pediatric Inflammation • Critical to allow us to supp
Slide 19: Orfadin – Understanding the Growth Drivers
Orfadin® – Understanding the Growth Drivers Sales (SEK M): Orfadin 150 500 1. Addressing Clinical Needs 120 400 in Adolescents • Support Adequate Dosing 90 300 • Compliance 60 200 2. Monitoring 30 100 • Substrate and drug levels 0 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 0 3. Newborn Screening 2009 2010 201
Slide 20: Orfadin – Russia and MENA Key Growth Markets
Orfadin® – Russia and MENA Key Growth Markets Estimated patients treated with Orfadin®: 850 Russia • Orfadin® included in new orphan legislation • Sobi affiliate in place • 7 patients identified • 15–20 newborns/yr RDT Sobi Middle East + North Africa Canada: 80 Europe: 480 56% • Sobi to establish di
Slide 21: Orfadin – Active Life Cycle Management
Orfadin® – Active Life Cycle Management Liquid Formulation • Drug Candidate available • Manufacturing scale-up underway EMA • Pediatric Investigation Plan submitted May 2011 • Approval could come in 2012 • May extend orphan status in Europe until 2017 FDA • Discussion with FDA in 2012
Slide 22: Ruconest: Potential in Growing HAE Market
Ruconest™: Potential in Growing HAE Market • First and only recombinant replacement therapy for Total HAE market: Actual 2010 and hereditary angioedema (HAE) expected growth rate 2011-2015 (EUR million) EUR million patients 70 60 Total market 57,8 • Best in class efficiency: 52,4 50 39,8 43,5 47,3 •
Slide 23: Specialty Distribution Products – Regional Leadership + Diversified Growth
Specialty Distribution Products – Regional Leadership + Diversified Growth 1. Building on strong leadership position from Swedish Orphan International Other, ReFacto® 2. Specialty Hematology/Oncology SEK 114 M Co-promotion Portfolio SEK 92 M 3. Create focus on the right deals 1. Therapeutic Area ove
Slide 24: Continued Focus on Cost Discipline
Continued Focus on Cost Discipline Operating expenses as % of revenues has decreased from 55% to 49% 1. HQ personnel reduced by 40 FTEs in 2010 1200 1000 2. R&D restructuring 60 FTEs by 800 year end 2011 SEK million 600 3. Two buildings to be closed in 400 Q1 2012 200 4. Transition to higher proport
Slide 25: Increasing Leverage of R+D for Late Stage + Commercial
Increasing Leverage of R+D for Late Stage + Commercial 800 Late Stage 700 Protein Develop- 600 ment 500 SEK million 400 Clinical 300 Develop- ment 200 100 Commercial 0 portfolio 2008 2009 2010 2011 Product support Clinical Development LCM Pre-clinical Development Long acting Factors Discovery Note:
Slide 26: Sobi has Retained Strategic Development Capabilities
Sobi has Retained Strategic Development Capabilities Value creation for innovative Arexis Syntonix biologics therapies through: BSSL FIXFc 1. Protein biochemistry capabilities in late preclinical development 2. GMP biologics process develop- ment and manufacturing scale-up Kiobrina Protein Engineeri
Slide 27: Hemophilia: Demonstrates Potential of Biologics Expertise
Hemophilia: Demonstrates Potential of Biologics Expertise 2016 Commercialization in Sobi Territories 2007 BVT/Biogen Idec Partnership 2006 1H 2012 2010 FPI Pediatric BVT/Syntonix Sobi/Biogen Idec Collaboration Trials Restructured Initiated Collaboration Kabi, Pharmacia, Biovitrum Heritage in Hemophi
Slide 28: Strong Alignment with Biogen Idec to Deliver Value
Strong Alignment with Biogen Idec to Deliver Value • Potential to deliver the first long- acting factors to the global market • Hemophilia market USD 3.4B in Sobi repays Sobi share Sobi territory of development costs: • Market Development underway 1. Milestone for each to support commercialization i
Slide 29: Kiobrina – Neonatal Enzyme Replacement for Prematurity
Kiobrina – Neonatal Enzyme Replacement for Prematurity Pioneers in neonatology • Potentially significant medical value • Our own product • Global potential Neonatology is attractive • Low competition • Able to support innovation • Reachable audience Sobi can bring Kiobrina to 100,000 patients based
Slide 30: Putting It All Together
Putting It All Together Development Programs Kiobrina Hemophilia Strategic Core Growth Drivers Products Three Business Lines Growth ReFacto® Specialty Platforms Distribution Portfolio 30
Slide 31: Focus on Delivery
Focus on Delivery Operational Organic Pipeline Performance Growth Delivery 26
Slide 32: Summary
Summary 1. To achieve positive net cash flow and profitability in our operations. 2. To efficiently commercialize our Pioneer & Partner in Rare Diseases proprietary innovative medicines for rare disease patients globally. 27
Slide 33: Capital Markets Day – Financials
Capital Markets Day – Financials Lars Sandström CFO 29 November 2011
Slide 34: Underlying Business Growing 7%
Underlying Business Growing 7% + SEK 250 M - SEK 440 M Yearly growth 7% • Currency headwind , discontinued 2 200 products and licensing revenues 2 000 have decreased revenues with approx. SEK 440 M 1 800 SEK million • Organic revenue growth have 1 600 increased revenues with more than 1 400 SEK 250
Slide 35: All segments showed growth 2010 and 2011
All segments showed growth 2010 and 2011 Revenue growth @ CER • ReFacto 2011 is exceptional • Validation batches for scale-up (SEK 40 M) ReFacto® 34% • Inventory build-up to support dual chamber (Manufacturing syringe for Pfizer -8% + Royalty) • Strong sales efforts have increased sales for Kineret®
Slide 36: Gross Margin Impacted by Currency and Non-recurring Items
Gross Margin Impacted by Currency and Non-recurring Items 70 • Currency impact 6 percentage 68 points 66 • Tech Transfer costs and higher Percentage 64 supply cost from Amgen for 62 Kineret® impact with 4 percentage Short Term Effects points 60 58 • In 2011 the average price for ReFacto® Manufacturi
Slide 37: Drivers of Growth and Profitability by Segment
Drivers of Growth and Profitability by Segment Revenues Strong underlying growth as Geographical expansion and Growth from launch Pfizer focus on emerging life cycle management products and addition of markets. contributing to growth. new products. Gross margin Leverage effect of larger New CMO for
Slide 38: Spending Control and Leveraging Infrastructure
Spending Control and Leveraging Infrastructure Operating Expenses • Synergies SEK 100 M from 1200 Biovitrum/Swedish Orphan International merger 1000 • Investments in Marketing & Sales organization have off-set savings in 800 Administration SEK million 600 • Restructuring 2011 with full effect as of
Slide 39: Factors Influencing Working Capital
Factors Influencing Working Capital 2000 • The build up of inventory is 1500 mainly due to the supply of Kineret® in 2010 1000 SEK million 500 • Increase in 2011 of receivables related to 0 ReFacto® -500 -1000 2009 2010 Sept 30, 2011 Inventories Accounts receivables Other current receivables Account
Slide 40: Balance Sheet Write Downs Q4-11, Limited Cash Flow Effects
Balance Sheet Write Downs Q4-11, Limited Cash Flow Effects Asset Product Amount Comments Inventory Kineret® SEK 70-80 M Re-valuation of validation batches of Kineret® from tech transfer in order to value inventory at commercial value Kepivance® SEK 30 M Reduced, but stabilized revenue, requires writ
Slide 41: Summary
Summary • Underlying growth in all business lines • Short term effects impacting margin during the year • Continued operating discipline Focus on positive cash flow and profitability 36
Slide 42: Q+A Development Programs
Q+A Development Programs Kiobrina Hemophilia Strategic Core Growth Drivers Products Three Business Lines Growth ReFacto® Specialty Platforms Distribution Portfolio 42
Slide 43: Kiobrina
Kiobrina Sobi Capital Seminar, 2011 We provide valuable medicines to patients with rare diseases
Slide 44: Agenda
Agenda • Kiobrina –Enzyme Replacement Therapy in preterm infants -Introduction and Clinical Program An van Es- Johansson , M.D, Head of Clinical Development , Sobi -Improving Growth of premature Babies: How and Why Berthold Koletzko, M.D, PhD, Professor Pediatrics Dr. von Hauner Children’s Hospital
Slide 45: Improving growth of premature babies: why and how?
Improving growth of premature babies: why and how? Berthold Koletzko, MD PhD c Professor of Paediatrics NSS Dr von Hauner Children's Hospital 4 ~\ Univ. of Munich Medical Centre Dr. von Haunersches Munchen, Germany Kinders p ital office. kolefzko@med.uni-muenchen.de KLINIKUM
Slide 46: Outline of presentation
Outline of presentation 1.Preterm infants: current challenges and role of substrate supply 2.Poor growth: implications 3. Benefits of improved fat absorption through human breast milk lipase (BSSL) office. kolefzko@med.uni-muenchen.de
Slide 47: Premature birth
Premature birth e Premature birth: <3/7 weeks (=12.5 % of infants) e Low birth weight (LBW): birthweight <2500 g (6.5 %) e Very low birth weight (VLBW): birthweight <1500 g (0.7 %) office. kolefzko@med.uni-muenchen.de
Slide 48: Preterm Birth Rate (% of live births)
Preterm Birth Rate (% of live births) Preterm birth rates, USA 20 1s Births to black mothers 16- 144 All births 10- Births to white mothers 8 6+ 0 a. T T » “, % Ar © °: S x “6, % my 6 SSK IIS IKI III ILE E EES Muglia & Kaiz, N Engl J Med 2010;362:529-35. Trends in most other high-income countries si
Slide 49: High and increasing survival rates
High and increasing survival rates even in the most immature preterm infants North American tertiary perinatal centers Gestational age | Since 1990 2010 24 weeks | 52% 61% 25 weeks 70 % 79 % 26 weeks 83 % 87 % office. kolefzko@med.uni-muenchen.de Lorenz, Saudi Med J 204 1;32:885-94.
Slide 50: The smaller the baby, the more important is nutrient supply
The smaller the baby, the more important is nutrient supply Fetal Growth From 8 to 40 Weeks eat be i at eo at 12 Weeks Weeks e Fetal weight doubles in only 6 weeks (30236 wks) e Preterm care aims at matching fetal growth office. kolefzko@med.uni-muenchen.de
Slide 51: Weight doubles in only weeks
Weight doubles in only 6 weeks Preterm infant, now 1000 g e Jan. 10: 2000 g e 120 kcal/day e 6 9 fat/day e 150 mL milk/day office. kolefzko@med.uni-muenchen.de
Slide 52: Weight doubles in only weeks
Weight doubles in only 6 weeks Preterm infant, Extrapolated to an now 1000 g adult, now 70 kg e Jan. 10: 2000 g e Jan. 10: 140 kg e 120 kcal/day e 8400 kcal/day e 69 fat/day e 420 g fat/day e 150 mL milk/day e 10,5 L milk/day office. kolefzko@med.uni-muenchen.de
Slide 53: Preterm babies develop malnutrition on a regular basis
Weight (grams) Preterm babies develop malnutrition on a regular basis 2000 || 1500 1000 — 500 24 28 32 36 Postmenstrual Age (Weeks) Ehrenkranz 2007 office. kolefzko@med.uni-muenchen.de
Slide 54: Preterm babies develop malnutrition on a regular basis
Weight (grams) p 2000 || 50th 1500 1000 500 - reterm babies develop malnutrition on a regular basis —Y ° Catch up Intrauterine growth 24-25 weeks 24 28 32 36 Postmenstrual Age (Weeks) office. kolefzko@med.uni-muenchen.de Ehrenkranz 2007
Slide 55: Poor growth may delay hospital discharge
Poor growth may delay hospital discharge by up to ~4-5 weeks 2000 || 1500 —_ ° o o Weight (grams) 500 24 28 32 36 Posimenstrual Age (Weeks) office. kolefzko@med.uni-muenchen.de
Slide 56: Slow weight gain in preterms
Slow weight gain in preterms e Later discharge from hospital e # Complications (e.g. hospital acquired infections) e Disturbed parent child interaction, may affect bonding and development e High resulting costs office. kolefzko@med.uni-muenchen.de
Slide 57: Preterms: executive function
Preterms: VY executive function at age 8 yrs 13; @ term 12. @& preterm Block Picture Verbal Inform Set Inhibition Selective Sustained design compr compr proc shifting attention attention Mean birthweight 1200 g office. koletzko@med. uni: muenchen.de Bayliss et al Early Hum Dev 2007;83:247
Slide 58: Rapid brain growth and development
Rapid brain growth and development requires energy and building blocks Fat >50% of Fractional Anisotropy b) sx I > lt 4 , brain structure om mm. PR oR fen H.Preissl http:/Awww.bic mni.megill.ca/fnihpdvinfosimage_gallery.htmi# 1 week 3 months 1 year 2 years 10 years
Slide 59: Morley 1999
8547 90 + Morley 1999 <12. 3.g/d 12.3-14.7 g/d 14.7-17.1 g/d office. kolefzko@med.uni-muenchen.de >17.1 g/d early weight gain/day
Slide 60: Weight gain and neurodevelopment
60 are unit predic 490 a, USA, followed to 18-22 mon corr. age Neurodevelopment. impaired (%) x 20 15 10 12 16 {8 24 weight gain (g*kg'*d"') office koletzko@med.uni-muenchen.de Cerebral palsy (%) 12 16 18 v4 weight gain (g*kg'*d"')
Slide 61: Importance of early fat supply
Importance of early fat supply e Main energy source (for energy expenditure and growth) e Building block in all cell membranes, including brain e Supplies essential fatty acids and lipid soluble vitamins (A,D,E,K) office. kolefzko@med.uni-muenchen.de
Slide 62: Birth weight and body fat
birth weight = only 20g body fat I. 1000 g Oo ae
Slide 63: Birth weight and body fat
1000 g birth weight = only 20g body fat 5
Slide 64: Absorption of dietary fat
Absorption of dietary fat 100% 90; 80; 70> Healthy Preterms, Preterms, adults fresh breastmilk bottle milk Mean of results of Séderhjelm ef al 1952, Williamson et al 1978, Atkinson et al 1981, (n ie) lip ase) Chappell ef al 1986, Camielii ef al 1997, Andersson et al 2007 office. kolefzko@med.uni-mue
Slide 65: Poor lipid digestion and absorption in preterm babies: consequences
Poor lipid digestion and absorption in preterm babies: consequences Short term e Loss of energy, essential fatty acids, fat-soluble vitamins and calcium Long term e Slow growth > impaired neurodevelopment e Poor bone mineralization office. kolefzko@med.uni-muenchen.de
Slide 66: Dietary fat absorption chain
Dietary fat | V Absorption > V Energy intake | Vv Growth —] Vv Development office. kolefzko@med.uni-muenchen.de
Slide 67: Human breast milk contains Bile salt Stimulated Lipase (BSSL)
Human breast milk contains Bile salt Stimulated Lipase (BSSL) Asn-187 Catalytic triad (S-194, D-320, H-435) 712-722 Two S-S bridges (C-64/C-80, C-246/C-257) Heparin-binding site PVPPTGDSGAP Bile-salt binding site(s) (consensus repeat sequence) O - Glycosylation sites office. kolefzko@med.uni-muenche
Slide 68: Better preterm growth with more fresh breast milk
Better preterm growth with more fresh breast milk (lipase +) vs. pasteurized milk (lipase -) Weight gain (g*kg'*d-') 155 10; 5; = <20% ™>20-<80% + >80% fresh BM fresh BM fresh BM Montjaux-Régis et al, Acta Paediatr. 201 1; 100(12): 1548-54. office. kolefzko@med.uni-muenchen.de
Slide 69: Conclusions
Conclusions e Small preterm infants now achieve good survival but less than satisfactory long-term development e Poor growth is very common and predicts delayed hospital discharge and poor development e One key reason is poor absorption of fat (& calories) e Adding breast milk lipase (BSSL) to paste
Slide 70: Thank you for your kind attention!
; pe «Thank you for your kind attention! ORICE. KOIRIZKO@OMER. UNI-Muenchen. ae
Slide 71: Preterm infants lack BSSL
Preterm infants lack BSSL • Natural component of breast milk • Naturally occurs in mother’s milk • Inactivated by heating hence lacking in pasteurized milk • Not present in formulas • Important for growth • Important for absorption of Omega 3- and 6 Lindqvist Curr Opin Clin Nutr Metab Care 13:314–32
Slide 72: Kiobrina is a homologue to the natural BSSL enzyme
Kiobrina is a homologue to the natural BSSL enzyme • Recombinant human BSSL • Animal derived product free • Given orally with formula or pasteurized milk • Prevents growth restriction in preterm infants not receiving fresh mother’s milk Target indication: Enzyme replacement therapy to restore BSSL a
Slide 73: Sobi Competencies well suited to delivering Kiobrina
Sobi Competencies well suited to delivering Kiobrina Development and manufacturing progressing according to plan • Pediatric Investigational Plan approved • Inhouse protein development • EMA approved endpoints and clinical capabilities program • Clinical development organisation • FDA discussions on
Slide 74: Phase II data show Kiobrina significantly accelerated growth
Phase II data show Kiobrina significantly accelerated growth after only one week of treatment Growth velocity 18 g/kg/day 16.9* 16 Target growth >15 g/kg/day 14 13.9 12 * p<0.001 Placebo Kiobrina Formula /pasteurized milk Formula/pasteurized milk 74
Slide 75: Nutrition and growth velocity predict Intelligence Quotient
Nutrition and growth velocity predict Intelligence Quotient at 7.5-8 years in 598 preterms 105 Intelligence Quotient @ 7.5-8 yrs 100 95 Growth velocity 90 <12. 3 g/d 12. 3-14.7 g/d 14.7-17.1 g/d >17.1 g/d 75Morley 1999 office.koletzko@med.uni-muenchen.de
Slide 76: Phase III Study in Broad EU Geography
Phase III Study in Broad EU Geography • Placebo controlled double blind study • 4 weeks treatment • ~430 patients, <32 weeks • 11 Countries, 70 sites 76
Slide 77: Endpoints Relevant to Physicians and Payers
Endpoints Relevant to Physicians and Payers • Primary efficacy: rhBSSL Pasteurized breast milk/ • Growth velocity (g/kg/day) infant formula • Secondary endpoints: • NICU stay • Early Development Placebo Pasteurized breast milk/ Suckle feed infant formula Temperature control • Tolerability Less infec
Slide 78: Understanding the Value of Kiobrina
Understanding the Value of Kiobrina • Earlier discharge • Improved development • Longterm health from NICU • Fewer complications outcomes • Lower incidence acute • Cerebral Palsy complications • Readmission to hospital • Learning disabilities • Concomitant medication Treatment period Follow-up 12 mo
Slide 79: Understanding the Value of Kiobrina
Understanding the Value of Kiobrina • Reduced Hospital Utilization Cost per week for 1 patient in a • Reduced Illness due to prolonged Neonatal Intensive Care Unit hospitalization EUR 10 500- 17 500 • Developmental delay Benefit – health outcomes and improved developmental • Functional deficits and
Slide 80: Every year about 630 000 infants are born < week 32
Every year about 630 000* infants are born < week 32 A preterms’ challenging start in life Many preemies experience a tough start in life. Your baby might have lung problems, low blood sugar or yellowing of the skin. More alarming concerns could be infections, bleedings into the brain or learning- a
Slide 81: About 300 000 preterms do not receive breast milk
About 300 000 preterms born <week 32 do not receive breast milk Breast milk contains all nutrition these infants require • Reasons for not receiving fresh breast milk • Medical conditions • Different cultural traditions Receive Receive breast milk formula or pasteurized milk *Beck et al, Bull World
Slide 82: Market in Europe is estimated to about 29 000 patients
Market in Europe is estimated to about 29 000 patients 56% of preterm infants receive formula or pasteurized milk in EU today Breast milk Formula or pasteurized ~ 29 000 milk Kiobrina treatment - 4 weeks Preterm infants born < week 32 1 http://epp.eurostat.ec.europa.eu + Federal State Statistic Serv
Slide 83: EU PIII program allows reaching additional markets
The approval of the EU PIII program will allow us to reach out to additional markets 101 000 target preterms/year Bridging Study 3 000 6 000 patients 3 000 6 000 31 000 EU Dossier 1 000 95 000 patients 28 000 29 000 EU MENA* Australia Lat. AM* Russia Korea Japan *Lat AM: Brazil, Mexico, Argentina, V
Slide 84: Kiobrina into our growing infrastructure in US
We are planning to have Kiobrina into our growing infrastructure in US • North America • Meeting with FDA in H1 2012 • To seek a partner for development in the US North America 24 000 • China • Out-license development and marketing rights and receive milestones and royalties China 175 000 84
Slide 85: The Life Cycle Program - a growth opportunity
The Life Cycle Program - a growth opportunity Longer treatment period Mixed feeding 45 000* Launch: Preterm infants <w 32 * EU, Russia, Turkey, US, Canada, Brazil, Mexico, Argentina, Venezuela, Japan, Korea, Australia, Saudi, Iran, Israel, Egypt 85
Slide 86: Summary on Kiobrina
Summary on Kiobrina •Kiobrina addresses significant medical need in preterm infants •Kiobrina has potential to generate both short term and long term health care value •Global incidence >300 000 patients of <week 32 preterm infants annually •Market access supported by EU filing >100 000 patients •LC
Slide 87: @sobl
87 @sobl
Slide 88: Long-Lasting Coagulation Factors for Prolonged Protection in Hemophilia
Long-Lasting Coagulation Factors for Prolonged Protection in Hemophilia Sobi Capital Markets Seminar, 2011 We provide valuable medicines to patients with rare diseases
Slide 89: Agenda
Agenda • Unmet Medical Needs in Hemophilia - The role of long lasting products Erik Berntorp, Prof. MD, PhD Malmö • Recombinant Long Lasting Coagulation Factors -The Fc Fusion projects We provide valuable medicines to patients with rare diseases Glenn Pierce MD, PhD, Biogen Idec • The Hemophilia Mar
Slide 90: Unmet Medical Needs in Hemophilia
Unmet Medical Needs in Hemophilia -The role of long lasting products Prof. Erik Berntorp, Prof. Erik Berntorp, MD, PhD, Professor, Lund University Research group leader Lund University. Clinical coagulation research, Clinical Sciences, Malmö Head physician Malmö Centre for Thrombosis and Haemostasis
Slide 91: Hemophilia A and Hemophilia B: Two Separate Diseases
Hemophilia A and Hemophilia B: Two Separate Diseases With the Same Clinical Manifestations Acute trauma or spontaneous hemorrhage joint bleeds (hemarthroses) soft tissue bleeds closed space bleeds- major mortality • intracranial • retroperitoneal • retropharyngeal 91 91
Slide 92: Hemophilia Therapies
Hemophilia Therapies: • Intravenous administration • On-demand • FVIII or FIX infusions to stop bleeding episodes • Regular prophylaxis • Regular infusions to maintain a minimum FVIII or FIX level to avoid bleeds • 2-4 infusions per week due to short half-life • Treatment by • Family, health-care pr
Slide 93: Benefits of Prophylaxis
Benefits of Prophylaxis • Reduction in bleeding frequency • Preservation of joint structure in young patients • May reduce; • other morbidities (e.g. ICH) • risk of inhibitor formation when started early • May improve quality of life and productivity and reduce healthcare utilization 93
Slide 94: Prophylaxis with Short-Acting Factors has Significant Hurdles
Prophylaxis with Short-Acting Factors has Significant Hurdles • Clotting factors have short half-lives in circulation • rFVIII has a biological half-life of ~12 h • rFIX has a biological half-life of ~18h • Prophylaxis requires intravenous injections as often as every other day • ~150-180 ( or more)
Slide 95: Prophylaxis with Longer-Lasting Factor Products May Provide Several Advantages
Prophylaxis with a Longer-Lasting Factor Products May Provide Several Advantages • Allow reduced injection frequency; • Goal is to achieve substantial reduction (by approximately 50-100/year) • Improve adherence to prophylaxis • Avoid need for central catheter implantation • Reduce total factor cons
Slide 96: Long-Lasting Products Improve Protection in On-Demand Patients
Long-Lasting Products Have Potential to Improve Protection in On-Demand Treated Patients No. of injections given when bleedings occur. One More than injection three 30% injections 70% of EU patients 19% on demand treated use more than Two Three 1 injection/bleed injections injections 26% 25% 96 Sobi
Slide 97: Long-Lasting Products – the Next Treatment Advance for Hemophilia
Long-Lasting Products – the Next Treatment Advance for Hemophilia Removal of Improved half-life human-derived in development components Recombinant Plasma-derived Recombinant long-lasting factors factors factors In development Improved Safety Potential for Improved • Eliminated potential Outcomes fo
Slide 98: Two Fc Projects rFVIIIFc and rFIXFc
Unmet Medical Needs in Hemophilia -Two Fc Projects rFVIIIFc and rFIXFc Glenn Pierce, MD, PhD, SVP and CMO Hemophilia R&D at Biogen Idec
Slide 99: FcRn Recycling – a Natural Pathway for Prolonged t1/2
FcRn Recycling – a Natural Pathway for Prolonged t1/2 • FcRn is responsible for the long circulating t1/2 life of Fc-containing proteins • FcRn recycles Fc-containing proteins to cell surface, avoiding lysosomal degradation • Immunoglobulins (antibodies) utilize this pathway to circulate for a prolo
Slide 100: R&D for Longer Half-life of FVIII and FIX
R&D for Longer Half-life of FVIII and FIX Glyco-pegylated FIX FIX albumin fusion FIX Fc fusion FIX Phase 3 Clinical Phase 1 Clinical Phase 3 Clinical (Glyco)Pegylated FVIII FVIII Fc fusion FVIII Phase 3 Clinical Phase 3 Clinical 100
Slide 101: Traditional Fc Fusion Proteins are Dimeric
Traditional Fc Fusion Proteins are Dimeric Model of Orencia Two effector molecules Fc fusion technology has been utilized in approved products for over a decade • Enbrel® (etanercept) • Orencia® (abatacept) • Nplate® (romiplostim) • Arcalyst® (rilonacept) • Amevive® (alefacept) Dimeric Fc 101
Slide 102: Proprietary Monomer Technology Applied to rFVIIIFc & rFIXFc
Proprietary Monomer Technology Applied to rFVIIIFc & rFIXFc Model of Model of rFVIIIFc rFIXFc • rFVIIIFc: Single B-domain-deleted rFVIII fused to dimeric Fc region of human IgG1 • rFIXFc: Single FIX fused to dimeric Fc region of human IgG1 102
Slide 103: rFIXFc Commercial Scale Production in Place
rFIXFc- Commercial Scale Production in Place Building on Sobi Process Development Work Cell culture (Human cell line) Scale-up in Bioreactor Purification Formulation and Fill • Biochemical characterization • Preclinical efficacy and safety • Clinical studies Cell bank Pharmaceutical Grade rFIXFc 103
Slide 104: Two Diseases: Two Programs
Two Diseases: Two Programs rFIXFc rFVIIIFc Phase I/II Completed Completed Phase III, Pivotal Studies B-LONG A-LONG No of Patients to be included 105 150 Start Date December 2009 November 2010 Data Read Out H2:12 H2:12 Pediatric Studies in Previously H1:12 H1:12 Treated Patients Starting Orphan Drug
Slide 105: US and EU Regulatory Requirements
US and EU Regulatory Requirements USA EU • Specific guidelines have not been • Guidelines state pediatric trials published. Development plans have must be completed before filing been developed in consultation with the agency No of Patients required • Pediatric data is not required for FVIII FIX reg
Slide 106: Recombinant FIXFc
{ biogen idec HEMOPHILIA Recombinant FIXFc @sobl
Slide 107: Phase I/II trial: rFIXFc
Phase I/II trial: rFIXFc Improved PK of rFIXFc Compared to Historical Data for BeneFIX® 14 PTPs Global Study with severe Dose Escalation study USA, Hong Kong 6 doses 1-100 IU/kg hemophilia B 7 Centers PK parameter Elimination T½ (hours) rFIXFc n=11 mean 57 h (42–75 h) *BeneFIX® n=56 mean 19 h (11–36
Slide 108: Phase I/IIa Study Results
Phase I/IIa Study Results • There were no drug-related serious adverse events • Dysguesia (abnormal taste in the mouth; n=1) and headache (on the dosing day; n=1) were reported • No inhibitor or anti-rFIXFc antibody formation after single dose • No allergic reaction • Pharmacokinetic results of rFIX
Slide 109: Phase III Pivotal Study for FIXFc: B-LONG
Phase III Pivotal Study for FIXFc : B-LONG An Open-Label, Multicenter study • Evaluation of the Safety, Pharmacokinetics and Efficacy of rFIXFc in the Prevention and Treatment of Bleeding in Previously Treated Subjects With Severe Hemophilia B Enrolling sites: ~20 Countries ~75 Centers Sample Size:
Slide 110: B-LONG Addressing both On Demand and Prophylactic Treatment
B-LONG Addressing both On Demand and Prophylactic Treatment Arm 1 Low Dose Prophylaxis Sequential PK (BeneFIX® vs rFIXFc) Arm 2 High Dose Prophylaxis Screening Arm 3 On-demand Regimen Arm 4 Surgery 110
Slide 111: rFIXFc Kids B-LONG Global Pediatric Study
rFIXFc ”Kids B-LONG” Global Pediatric Study in Patients < 12 Years Starting in H1 2012 Primary Outcome Measures: • Frequency of inhibitor development Secondary Outcome Measures: • Number of annualized bleeding episodes • Assessments of response to treatment with rFIXFc for bleeding episodes Screenin
Slide 112: Recombinant FVIIIFc
biogen idec | HEMOPHILIA Recombinant FVIIIFc @sobl
Slide 113: Phase I/II Trial: rFVIIIFc
Phase I/II Trial: rFVIIIFc Improved PK of rFVIIIFc Compared to Advate® 16 PTPs Comparative PK Global Study with severe evaluation USA, Israel, Hong Kong hemophilia A In 15 patients vs Advate ® 6 Centers PK parameter Elimination T½ (hours) rFVIIIFc n=15 mean 19 h (18-22 h) Advate®n=15 mean 11,5 h (10
Slide 114: Phase I/IIa Study Results
Phase I/IIa Study Results • No drug-related serious adverse events • Most adverse events were unrelated to study drug † • One drug-related AE: dysgeusia (abnormal taste in the mouth) • No inhibitor or anti-rFVIIIFc antibody formation after single dose • Pharmacokinetic results of rFVIIIFc demonstrat
Slide 115: Phase III Pivotal Study: A-LONG
Phase III Pivotal Study: A-LONG An Open-Label, Multicenter study • Evaluation of the Safety, Pharmacokinetics and Efficacy of rFVIIIFc in the Prevention and Treatment of Bleeding in Previously Treated Subjects With Severe Hemophilia A Enrolling Sites: ~25 Countries ~90 Centers Sample Size: ~150 subj
Slide 116: A-LONG Study Addresses Both On Demand and Prophylactic Treatment
A-LONG Study Addresses Both On Demand and Prophylactic Treatment Sequential PK (Advate® vs rFVIIIFc) Arm 1 Low Dose Prophylaxis Surgery subgroup Screening Arm 2 High Dose Regimen Surgery subgroup Arm 3 On-demand Regimen Surgery subgroup 116
Slide 117: rFVIIIFc Kids A-LONG Global Pediatric Study
rFVIIIFc ”Kids A-LONG” Global Pediatric Study in Patients < 12 Years Starting in H1 2012 Primary Outcome Measures: • Frequency of inhibitor development Secondary Outcome Measures: • Number of annualized bleeding episodes • Assessments of response to treatment with rFVIIIFc for bleeding episodes Scre
Slide 118: Longer Half-Life of FVIII and FIX: Sobi/Biogen Idec Ahead of Competition
Longer Half-Life of FVIII and FIX: Sobi/Biogen Idec Ahead of Competition Phase 1 Phase 3 (Clinical trials.gov) (Clinical trials.gov) FIX Sobi/Biogen Idec Completed Start date: Dec.2009 (rFIXFc) Novo Nordisk Completed Start date: April 2011 (NN7999) Surgery study not yet recruiting CSL Behring Open n
Slide 119: Sobi and Biogen Idec Leading the Development of Long Lasting Coagulation Factors
Sobi and Biogen Idec Leading the Development of Long Lasting Coagulation Factors Summary • Long-lasting coagulation factors are a highly anticipated development • rFIXFc and rFVIIIFc are ahead of competition • The Fc technology takes advantage of a natural pathway in the body to prolong half life •
Slide 120: The Hemophilia Market
The Hemophilia Market Helena Rudberg M.Pharm.Sci. Global Director Hemophilia and Hematology, Sobi
Slide 121: Hemophilia is a $3.4B USD Market in Sobi Territory
Hemophilia is a $3.4B USD Market in Sobi Territory Hemophilia A Hemophilia B • Europe 3B USD • Europe 380 MUSD • 55% of global $ sales • 44% of global $ sales • > 50 Brands • >10 Brands • ~ 73% recombinant • ~55 % recombinant • ~22 000 patients on regular treatment • ~ 4000 patients on regular treat
Slide 122: Factor Utilization is High in Sobi Territories
Factor Utilization is High in Sobi Territories Per Capita consumption of FVIII (IU/Inhab.) • Highly developed Centers of Excellence Sweden Germany • Early recognition of the value of Ireland Hungary prophylaxis France • “Not accepting a bleed” Italy USA Spain • Strong Patient Advocacy groups Norway
Slide 123: Offering Value in the Prophylaxis and On-Demand Segments
Offering Value in the Prophylaxis and On-Demand Segments Prophylaxis vs On Demand treatment in EU • Long-lasting products in prophylaxis : 80 Potential value 70 • Reducing 50-100 injections/year • Improved protection 60 • Improved Quality of life 50 • Long-lasting products in on demand 40 treatment:
Slide 124: Partnering to Address the Needs of Prophylaxis Patients
Partnering to Address the Needs of Prophylaxis Patients Prophylactic treatment in different age groups • Prophylaxis growing in EU 90 • Well established in young children 80 • Continuing ahead of USA 70 • Focus on developing support for 60 prophylaxis also in the Adult and Elderly 50 populations 40
Slide 125: Differentiated Products Can Overcome Barriers to Entry
Differentiated Products Can Overcome Barriers to Entry rFVIII MS 2010 • High barriers for non-differentiated products 120 • Low switching rates between comparable products • Well-established relationships between healthcare and 100 industry Pfizer • Small patient population and difficult trials to c
Slide 126: Longer Lasting Agents Most Appealing as Improvement
Longer Lasting Agents Most Appealing as Improvement and Likely to Generate Switch Rank the importance of the following development of coagulation factors and the likelihood to propose a switch (on a scale from 1 to 10) Very high 10 9 8 High 7 6 Average 5 4 3 Low 2 1 Very low 0 Longer lasting agents
Slide 127: Sobi has Significant Experience in the Market
Sobi has Significant Experience in the Market Sobi contribution to ReFacto AF®Sales Estimated MS% 2010 60 50 40 MS% 30 20 10 0 Sobi Nordic Pfizer Territory ReFacto AF® MS% Advate® MS% Source: Analyst report internal analysis wholesaler data 127
Slide 128: Sobi is Engaging the Hemophilia Community Today
Sobi is Engaging the Hemophilia Community Today • Supporting education and improved management of hemophilia • Improved understanding of the teenagers • The Elderly and Co-Morbidities • Stimulating the scientific dialogue • Targeted Symposia and Workshops • Supporting the Hemophilia Community 128
Slide 129: Sobi in Hemophilia – Building on our Legacy
Sobi in Hemophilia – Building on our Legacy • An attractive European market approaching 3.5 Bn USD • Long-lasting coagulation factors are a highly desired development • The two Fc programmes address both on-demand and prophylactic therapy • rFIXFc and rFVIIIFc are ahead of the competition • Sobi est
Slide 130: @sobl
130 @sobl
Slide 131: Capital Markets Day – Wrap Up
Capital Markets Day – Wrap Up 29 November 2011
Slide 132: Summary
Summary 1. To achieve positive net cash flow and profitability in our operations. 2. To efficiently commercialize our Pioneer & Partner in Rare Diseases proprietary innovative medicines for rare disease patients globally. 27
Slide 133: Focus the Business on Strategic Building Blocks
Focus the Business on Strategic Building Blocks Development Programs Kiobrina Hemophilia Strategic Core Growth Drivers Products Three Business Lines Growth ReFacto® Specialty Platforms Distribution Portfolio 133
Slide 134: Upgrading Clarity in Market Communication
Upgrading Clarity in Market Communication Meetings with Capital Markets JP Morgan Full-year/Q4 Annual Report analysts + Seminar Health Care Earnings Call shareholders Conference Nov-Dec Nov 29 Jan 10 Feb 23 April 4 37
Swedish Orphan Biovitrum — Investor Day (November 2011) on 6ix