Swedish Orphan Biovitrum Ab · OMXSTO:SOBI
Swedish Orphan Biovitrum Ab — Investor Day (November 2013)
92 slides from Swedish Orphan Biovitrum Ab's investor day presentation, November 2013
Slide 1: Sobi Capital Markets Day
Sobi Capital Markets Day November 2013
Slide 2: Forward Looking Statements
Forward Looking Statements 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 finan
Slide 3: An International Healthcare Company Dedicated to Rare Diseases
An International Healthcare Company Dedicated to Rare Diseases 3
Slide 4: Strategic Priorities
Strategic Priorities 1. Near-term focus on growth in key therapeutic areas, with sustainable We positive cash flow from operations. Are Here 2. Medium-term investments to ensure successful commercialization of our late-stage pipeline. 3. Long-term growth will come organically and through acquisition
Slide 5: A Diverse, Growing Business Platform
A Diverse, Growing Business Platform Early Stage Development Programmes Medium term investments to support commercialisation of Haemophilia Neonatology the late stage Pipeline Continued focus on growth Inflammation Genetics in key Therapeutic Areas An integrated solution for Partner Products commerci
Slide 6: What Is Special About Rare Diseases?
What Is Special About Rare Diseases? 1. Drugs which really work. EFFECT SIZE 2. Drugs which work in every patient treated. RESPONSE RATE 3. Drugs which deliver sustainable value. OUTCOMES IN LIFE 6
Slide 7: Mitigating Risk in Drug Development
2 Mitigating Risk in Drug Development 1. Molecule – What is known about the candidate? 2. Mechanism – How will it achieve its effect? Potency + Specificity 3. Clinical – How established is the clinical design and endpoints? Connected to MoA? 4. Regulatory – How do the regulators understand value and
Slide 8: Balancing Risk + Allocation of Capital
3 Balancing Risk + Allocation of Capital Pipeline Projects LCM with Higher investments Approved Higher earnings Products Higher risk Long-term IRR Risk Lower investments Medium earnings Year Lower risk 2013 2014 2015 2016 2017 2018 Near-term IRR Size of circle = expected revenues 8
Slide 9: R&D Pipeline 2013
R&D Pipeline 2013 Indication Project Partner Pre-Clin. Phase I Phase II Phase III Launch CAPS Kineret Hemophilia A rFVIIIFc Hemophilia B rFIXFc Improve growth in Kiobrina preterm infants Oral Mucositis in Head Kepivance & Neck Cancer Hereditary Tyrosinemia Orfadin Liquid Type 1 Hereditary Tyrosinemi
Slide 10: Hemophilia Update
Hemophilia Update Hemophilia • rFIXFc PDUFA est. 1Q 2014 • KIDS B-LONG data 2H 2014 • rFVIIIFc PDUFA est. 2Q 2014 • KIDS A-LONG data 1H 2014 Biogen Idec Hemophilia Event TBD 10
Slide 11: Hemophilia Timeline 2013 – 2014
Hemophilia Timeline 2013 – 2014 Fc9: FC9: KIDS B-LONG Data FDA PDUFA* Fc8: KIDS A-LONG data Fc8: FDA PDUFA* Q3 2013 Q4 2013 Q1 2014 Q2 2014 Q3 2014 Q4 2014 2013 2014 *Dates are consensus estimates based on initial filing 11
Slide 12: Agenda
Agenda 1. Introduction Geoffrey McDonough 2. Late Stage Programs Birgitte Volck Kiobrina Kristina Timdahl Q+A Break 3. Early Stage Projects Stephen James SOBI002 Patrik Strömberg Q+A 4. Close Geoffrey McDonough 12
Slide 13: Late Stage Portfolio
Late Stage Portfolio Birgitte Volck, M.D., Ph.D. Senior Vice President, Chief Medical Officer
Slide 14: Birgitte Volck, M.D., Ph.D.
Birgitte Volck, M.D., Ph.D. • 2012- Sobi Senior Vice President, Chief Medical Officer • 2007-2012 Amgen Regional and HQ • 2004-2007 Genzyme Nordic & BELux • 2001-2004 Pharmexa Biotech DK HQ • 2000-2001 Aventis DK affiliate • 1991-2000 MD CPH University PhD CPH University » Arthritis and Biomarkers 1
Slide 15: How We Think About Development
How We Think About Development • Full integrated medical • Informs evidence generating approach across the entire filing/line extension and access lifecycle of products enabling strategies • Orientation to and alignment • Country oriented partner in patient with patient access, commercial and custom
Slide 16: A Rare Journey: 30 Years With Orfadin
A Rare Journey: 30 Years With Orfadin Our Legacy in Rare Diseases 2005 2002 4 yr. survival 29% vs 93% 1993 1992 1989 Prof. Sven Lindstedt 1982 Bottle Brush plant 16
Slide 17: Principles of Development & Medical
Principles of Development & Medical Informed by the Patient Journey Diagnosis + Treatment Disease Management Outcomes Development Optimizing Care & Advancing the Science Ongoing Health Mgt. System Access Commercial & Revised Treatment Patient Access Guidelines Medical Symptoms + Physicians Scientifi
Slide 18: We Pursue Novel Approaches in Development
We Pursue Novel Approaches in Development Partnering Through Early and Continous Dialogue 18
Slide 19: A Rare Journey: 30 Years With Orfadin
A Rare Journey: 30 Years With Orfadin Our Legacy in Rare Diseases 2013 International filings /oral suspension/ 20 mg 2012 Pioneering Corporate-Academic-Public Collaboration 2005 2002 4 yr. survival 29% vs 93% 1993 Patient voice inspires our 1992 commitments 1989 Prof. Sven Lindstedt 1982 Bottle Brus
Slide 20: Kineret for CAPS & NOMID – A Rare Journey
Kineret for CAPS & NOMID – A Rare Journey Clinical study Kineret Pediatric management, Investigation Plan data analysis, Approval (EU) study report FDA pre-submission FDA Approval FDA pre-meeting meeting NOMID 2010 2011 2012 2013 Orphan Drug Scientific Advice EU Filing Filing EU CHMP Positive Design
Slide 21: R&D Pipeline 2013
R&D Pipeline 2013 Indication Project Partner Pre-Clin. Phase I Phase II Phase III Launch CAPS Kineret Hemophilia A rFVIIIFc Hemophilia B rFIXFc Improve growth in Kiobrina preterm infants Oral Mucositis in Head Kepivance & Neck Cancer Hereditary Tyrosinemia Orfadin Liquid Type 1 Hereditary Tyrosinemi
Slide 22: Kepivance – Head and Neck Cancer
Kepivance – Head and Neck Cancer Birgitte Volck, M.D., Ph.D. Senior Vice President, Chief Medical Officer
Slide 23: Kepivance Background
Kepivance Background • Kepivance (palifermin) is a recombinant human keratinocyte growth factor • Palifermin was developed to reduce the severity and duration of oral mucositis and related clinical sequelae 2013 rights to additional clinical data for Kepivance from Amgen 2008 proprietary product, ac
Slide 24: Keratinocyte Growth Factor (KGF)
Keratinocyte Growth Factor (KGF) KGF is an endogenous protein in the fibroblast growth factor (FGF) family stimulating epithelial cells 24
Slide 25: Kepivance increases epithelial thickness and enhances recovery after injury
Kepivance increases epithelial thickness and enhances recovery after injury Adapted from Sonis * ROS=reactive oxygen species, chemically reactive molecules containing oxygen like oxygen and peroxides 25
Slide 26: Severe Oral Mucositis – A Frequent Treatment Complication
Severe Oral Mucositis – A Frequent Treatment Complication of Certain Cancer Therapy Severe OM •Breakdown of oral mucosa results in inflammation, pain, and often treatment and activity limiting disability •Tumor location and radiation field the most predictive risk factors Clinical manifestations and
Slide 27: Current Indication: Bone Marrow Transplantation
Current Indication: Bone Marrow Transplantation Kepivance is indicated to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support There are approximately 10,000 – 15,000 addressable
Slide 28: Proposed Indication: Head and Neck Cancers
Proposed Indication: Head and Neck Cancers • 52,500 new cases of Head and Neck cancer in US 2013 • Approximately 40% with advanced disease Head and Neck Cancer US Incidence Oropharynx / Larynx / Nasopharynx Oral Cavity Hypopharynx Hypolarynx & Other ~30% ~30% ~25% ~15% • RadioChemoTherapy • Standard
Slide 29: FDA Reported and Published Results
FDA Reported and Published Results Two Pivotal H&N Cancer Studies 29
Slide 30: Kepivance Head and Neck Program
Kepivance Head and Neck Program 970149 N=60 Phase I/II 20, 40, 60, 80 µg/kg vs PBO, 12 weeks Long-term follow-up N=159 (20 ongoing) Median follow-up 56 months 990119 N=101 Phase II 60 µg/kg vs PBO, 12 weeks 20020402 N=188 Long-term follow-up unresected stage III-IVB SCC N=185 (appr 90 ongoing) 180 µ
Slide 31: Primary Endpoint: Incidence of Severe Oral Mucositis
Primary Endpoint: Incidence of Severe Oral Mucositis (OM)* *Grade 3 or 4 OM at least once during the acute evaluation phase (up to week 12-15) 31
Slide 32: Time to Severe OM (Days)
Time to Severe OM (Days) (Protocol-specified Secondary Endpoint) 20020402 20040118 Median time to severe OM: Median time to severe OM: 35 vs 47 days (raw p=0.026) 32 vs 45 days (raw p=0.022) 32
Slide 33: Secondary Endpoint: Median Duration of Severe OM
Secondary Endpoint: Median Duration (Days) of Severe OM 33
Slide 34: Short-term Safety Data: Summary of Adverse Events
Short-term Safety Data: Summary of Adverse Events 20020402 20040118 Placebo Palifermin Placebo Palifermin (N=91) (N=94) (N=92) (N=93) n(%) n(%) n(%) n(%) All adverse events (AEs) 85 (93) 92 (98) 89 (97) 91 (98) Severe AEs 46 (51) 62 (66) 41 (45) 46 (49) Serious AEs 25 (27) 35 (37) 51 (55) 31 (33) Tr
Slide 35: Secondary Efficacy Endpoints
Secondary Efficacy Endpoints Adjusted and Unadjusted P-values End Point A (402) B (118) Kepivance® Placebo P-values Kepivance® Placebo P-values (n=94) (n=94) (n=92) (n=94) Raw: 0.016 Raw: 0.037 Duration of severe OM (days) 5 26 Adj: 0.112 4.5 22 Adj: 0.187 Raw: 0.026 Raw: 0.022 Time to onset of seve
Slide 36: Kepivance in Head and Neck Cancer Our Approach 2013
Kepivance in Head and Neck Cancer Our Approach 2013 • High prevalence of Oral Mucositis in Head and Neck cancer patients undergoing Radio-Chemotherapy has and large unmet medical need • Recently acquired Kepivance data in Head and Neck cancer are compelling • Revisiting data assessment from for two
Slide 37: Kiobrina – a Pioneering Project in Neonatology
Kiobrina – a Pioneering Project in Neonatology Kristina Timdahl, M.D. Vice President, TA Head Medical, Neonatology
Slide 38: Kristina Timdahl, M.D.
Kristina Timdahl, M.D. •2013- VP TA Head Medical Neonatology, Sobi •2008- Medical Director, Kiobrina Biovitrum and Sobi •2007-2008 Group Director ,Early Development •2003-2007 Global Senior Clinical Research Physician, Astra Zeneca Neuroscience •1998-2003 Medical Affairs Nordic affiliate, Wyeth •199
Slide 39: The Preterm Infant
The Preterm Infant 39
Slide 40: Preterm Birthrates Are Increasing
Preterm Birthrates Are Increasing ≥ 10% 9 – 9.9% 8 – 8.9 % < 8% Beck et al, OMS 2009 40
Slide 41: Number of Preterm Infants in Europe and US
Number of Preterm Infants in Europe and US References: • www.cdc.gov/nchs/data/series/sr_05/sr05_011e.pdf Annual no of live births • Statistical pocketbook, 2006, “Key figures on Europe” • European foundation for care of the newborn infants, EU 11 300 000 benchmarking report 2009/2010 • EURO-PERISTA
Slide 42: Advances in Neonatal Care Have Led to Dramatic Reductions in Mortality
Advances in Neonatal Care Have Led to Dramatic Reductions in Mortality England & Wales Neonatal mortality rate (deaths under 28 days per 1,000 live births) USA Obstetric practice Widespread Newborn Neonatal deaths per 1,000 live births incubator use thermal care Increased focus Total Parenteral Newb
Slide 43: Preterm Infants Do Not Achieve Normal Growth
Preterm Infants Do Not Achieve Normal Growth * *The skeleton and internal organs begin to develop during the first trimester (Pilling, Elder et al. 2008) Ehrenkranz RA et al. Pediatrics 1999;104:280–289. Ehrenkranz RA et al. Pediatrics 2006;117:1253–1261 43
Slide 44: Duration of Hospital Stay and Growth
Duration of Hospital Stay and Growth Days to discharge* 80 70 60 50 40 30 Days to discharge* 20 10 g/kg/day 0 12 15.6 17.8 21.2 (n=124) (n=122) (n=123) (n=121) • Time from regaining birtweight to discharge ,transferred,age 120 days or reaching 2000g • Ehrenkranz RA Pediatrics 2006 44
Slide 45: Short and Long-term Morbidity Remains High
Short and Long-term Morbidity Remains High • Respiratory disorder Early childhood outcome • Impaired mental development • Retinopathy of prematurity (ROP) • Cerebral Palsy 10 % • Visual problems and deafness • Brain injury School-age outcome • Necrotizing enterocolitis • Behavioral problems • Impair
Slide 46: The 3rd Trimester Key for Neurodevelopment
The 3rd Trimester Key for Neurodevelopment MRI images of the brain developing between 25 – 39 weeks gestation • The brain is a fatty organ. Nutrition and accretion of LC-PUFAs (omega-3 fatty acids) important during the 3rd trimester • LC-PUFAs important for brain and retina development • Babies can’
Slide 47: Prematurity Associated With Disability at 18-24 months
Prematurity Associated With Disability at 18-24 months Cerebral Palsy Mental retardation Hearing loss Vision impairment 47
Slide 48: Growth Failure is Associated With Poor Neurodevelopment Outcome
Growth Failure is Associated With Poor Neurodevelopment Outcome at 18-22 Months As the rate of weight gain increase the incidence of adverse outcomes decrease significantly 30 25 20 Per cent Severe NDI 15 Bayley <70 10 Severe CP 5 0 Weight gain g/kg/day 12,2 14,5 16 18,4 Reference: Growth and Neurod
Slide 49: Fresh Breastmilk is Key for Growth & Development
Fresh Breastmilk is Key for Growth & Development • Composition of fresh breastmilk contains nutrients and several unique and essential bioactive components such as enzymes, cytokines and immune factors • Since half of the nutritional energy requirement in newborns come from dietary lipids, their dig
Slide 50: Bile Salt Stimulated Lipase (BSSL) is a Key Component of Fresh Breastmilk
Bile Salt Stimulated Lipase (BSSL) is a Key Component of Fresh Breastmilk • Bile salt stimulated lipase (BSSL) is an essential digestive enzyme in fresh breastmilk • BSSL uniquely compensates for the immature pancreas of the newborn • BSSL has the ability to hydrolyze all the major lipids that are i
Slide 51: Fresh Breastmilk is Associated With Better Cognitive Development
Fresh Breastmilk is Associated With Better Cognitive Development in Preterm Infants A meta-analysis of 11 studies revealed that fresh breastmilk is associated with significantly enhanced cognitive development scores compared to formula (p<0.001) Cognitive function was significantly higher in breast-
Slide 52: Our Question
Our Question What if we could restore BSSL activity in preterm infants who do not receive fresh breastmilk? 52
Slide 53: Kiobrina – a Pioneering Project in Neonatology
Kiobrina – a Pioneering Project in Neonatology Recombinant human bile-salt stimulated lipase (rhBSSL) • Same amino acid sequence and properties as native BSSL • Enzyme therapy in preterm infants unable to receive fresh breast milk • Restores the natural lipase activity The research aims to demonstra
Slide 54: Phase II Crossover Study - Growth Improved after 1 Week Treatment
Phase II Double-blind Placebo Controlled Crossover Study - Growth Improved after 1 Week Treatment • Two parallel prospective randomized double-blind crossover studies (n=63) • Kiobrina or placebo, was administered in pasteurized milk, or preterm infant formula • One week of treatment • All infants w
Slide 55: Pivotal Trial to Read Out 1Q 2014
Pivotal Trial to Read Out 1Q 2014 Double Blind, Placebo Controlled, Randomized Population • > 400 Preterm Infants born < 32 weeks GA Feeding • Formula or pasteurized breast-milk Primary endpoint • Improve growth velocity Secondary endpoints • Head circumference, time to hospital discharge, tolerabil
Slide 56: Top Line Results to Include Growth, Safety and Hospital Outcomes
Top Line Results to Include Growth, Safety and Hospital Outcomes Phase III study Growth Hospital Safety + Neurodevelopment 1yr Neurodevelopment 2yrs IQ 4 wks 3 mo 12 mo 24mo 8 yrs Growth velocity Readiness for hospital discharge Head circumference Safety Safety Tolerability Tolerability Growth Top l
Slide 57: EU Dossier Current Phase III Study
EMA Approval Basis for Initial Expansion Timelines are indicative 2015 2017 2018+ Current Phase III Study Korea EU US China Latin America* Filing Based on EU Dossier Australia Bridging Studies US Pivotal Study (based on EU File) MENA* Russia *Lat AM: Brazil, Mexico, Argentina, Venezuela *MENA: Saudi
Slide 58: Early R&D Portfolio
Early R&D Portfolio Stephen James, Ph.D. Vice President, Head of Drug Design and Development
Slide 59: Stephen James, Ph.D.
Stephen James, Ph.D. • 2011- VP, Head of Drug Design & Development, Sobi • 2008- Head of Research, Biovitrum and Sobi • 1997-2008 Various project and department director positions, PnU, Pharmacia Corp and Biovitrum • 1991-1997 Group Leader Inositol Lab and University Research Fellow, Dundee, Scotlan
Slide 60: Where Do We Come From?
Where Do We Come From? Kabi/Kabi Pharmacia Heparin Recombinant FVIII Pharmacia Genotropin Refacto process development Biovitrum Sobi Kineret SOBI002 Kepivance FIXFc FVIIIFc Kiobrina 60
Slide 61: The Sobi Drug Design & Development Model
The Sobi Drug Design & Development Model Biological Process Clinical Discovery research development development Research Exploratory development Process development Technology transfer 61
Slide 62: Our Focus: Biologics Development and CMC
Our Focus: Biologics Development and CMC Research • Protein engineering and optimization Exploratory Development • Pharmacology, toxicology, DMPK, bio analysis method devt. Process Development • Upstream, midstream and downstream processes, protein analysis & characterization, formulation Technology
Slide 63: Our Model in Action: Kiobrina
Our Model in Action: Kiobrina Biological Process research development 40 Rate 20 0 0 20 40 [Substrate] 2006: Acquisition of Arexis and 2011-2012: technical Kiobrina project transfer to commercial BSSL produced in manufacturer 2006-2011: CMC process development in CHO ovine bioreactor cells, full enz
Slide 64: Our Model in Action: FIXFc
Our Model in Action: FIXFc Biological Process research development Clone selection Technical transfer for and cell bank commercial scale characterization Upstream & downstream Analytical method production process development development for release, virus validation, drug substance and drug product
Slide 65: How Do We Think About Innovation?
How Do We Think About Innovation? Transformational Impact on Rare Disease Biologicals Sustainable Research & Value Process Proposition Development 65
Slide 66: Balancing Risk + Allocation of Capital
Balancing Risk + Allocation of Capital Pipeline Projects LCM with Higher investments Approved Higher earnings Products Higher risk Long-term IRR Risk Lower investments Medium earnings Year Lower risk 2013 2014 2015 2016 2017 2018 Near-term IRR Size of circle = expected revenues 66
Slide 67: R&D Pipeline 2013
R&D Pipeline 2013 Indication Project Partner Pre-Clin. Phase I Phase II Phase III Launch CAPS Kineret Hemophilia A rFVIIIFc Hemophilia B rFIXFc Improve growth in Kiobrina preterm infants Oral Mucositis in Head Kepivance & Neck Cancer Hereditary Tyrosinemia Orfadin Liquid Type 1 Hereditary Tyrosinemi
Slide 68: Affibody Platform for c5 Inhibition
Affibody Platform for c5 Inhibition Affibody Versatile • Biotech company focused on developing biopharmaceuticals based on Affibody® Transformational molecules and Albumod™ Impact on Rare Disease • Commercial relationships with a Small Scalable Biologicals numerous companies Research & Sustainable V
Slide 69: Generation of Affibody C5 Inhibitors
Generation of Affibody C5 Inhibitors 2014: Phase I 2013: Pre-clinical development completed 2011: Lead optimization 2010: Affinity maturation 2010: Functional characterization 2009: Affibody screening 2009: Affibody selection 69
Slide 70: Introducing SOBI002 – A Novel Biologic inhibitor of C5
Introducing SOBI002 – A Novel Biologic inhibitor of C5 Patrik Strömberg Ph.D. Principal Scientist, Nonclinical Safety and Pharmacology
Slide 71: Patrik Strömberg, Ph.D.
Patrik Strömberg, Ph.D. • 2011- Principal Scientist, Nonclinical Safety and Pharmacology, Sobi • 2009 Project Leader R&D, Biovitrum and Sobi • 2007-2009 Senior Scientist, Preclinical Development, Biovitrum • 2002-2007 Senior Scientist, AstraZeneca Biotech Laboratory • 1995- 2002 MSc Biomedicine, PhD
Slide 72: The Affibody Technology Platform Consists of Two Innovative Protein Domains
The Affibody Technology Platform Consists of Two Innovative Protein Domains The Affibody Ligand The Albumin Binding Domain (ABD) 72
Slide 73: The Affibody Technology Platform Consists of Two Innovative Protein Domains
The Affibody Technology Platform Consists of Two Innovative Protein Domains The Affibody Ligand • Small and robust non-Ig scaffold for protein targeting • Specific targeting by randomization of surface exposed residues followed by selection by phage display • Efficiently produced in E.coli • Rapid c
Slide 74: The Affibody Technology Platform Consists of Two Innovative Protein Domains
The Affibody Technology Platform Consists of Two Innovative Protein Domains The Albumin Binding Domain (ABD) • Small protein that binds to serum albumin from many species • Engineered for reduced immunogenicity and sub-picomolar affinity • Similar molecular properties as Affibody ligands • Extends t
Slide 75: Affibody Molecules Refold Rapidly after Heat-induced Unfolding
Affibody Molecules Refold Rapidly after Heat-induced Unfolding Circular Dichroism Spectra Functional activity 75
Slide 76: The Albumin Binding Domain Extends In Vivo Stability and Plasma Persistence
The Albumin Binding Domain Extends In Vivo Stability and Plasma Persistence Rat PK study Affibody-ABD fusion (i.v. s.c.) Affibody (i.v. s.c.) 1 week 76
Slide 77: The Size of an Affibody-ABD Fusion Protein Is Less Than 10 per cent of an Antibody
The Size of an Affibody-ABD Fusion Protein Is Less Than 10 per cent of an Antibody Antibody 150 kDa Affibody-ABD fusion 12 kDa 77
Slide 78: Can We Apply Affibody Technology to Rare Diseases?
Can We Apply Affibody Technology to Rare Diseases? 78
Slide 79: The Complement System
The Complement System Complement regulatory proteins: C1-INH, C4BP, Factor H, Factor I, CR1, Classical Pathway DAF(CD55), CD59, MCP(CD46), antigen/antibody Carboxypeptidase-N, etc. complexes Anaphylatoxin C3a Inflammation, Activation chemotaxis of C1 C3aR C4b2a C4b2a3b C5aR C4 + C2 C5a CD88 C3 conve
Slide 80: C5 Inhibition - Rationale
C5 Inhibition - Rationale • C5 is a highly tractable target: • Common to all complement pathways • Proximal complement intact • Clear disease mechanism and validated therapeutic rationale for PNH and aHUS • Feasible to neutralize C5 activity with Affibody technology • Many possible opportunities, bo
Slide 81: Generation of Affibody C5 Inhibitors
Generation of Affibody C5 Inhibitors 2011: Lead optimization PK/PD, process feasibility, preclinical immunogenicity assessment 2010: Affinity maturation Library design, phage display selection and screening 2010: Functional characterization In vitro, in vivo, species cross reactivity 2009: Affibody
Slide 82: Hemolysis assays and functional screening
82 Hemolysis assays Cross-species activity iii. Functional screening Human C5 as target protein ELISAs, competition assay etc. i. Selection by phage display ii. Screening for target binding CP629 CP628 CP627 CP626 CP625 CP623 Z Z Z Z 0 0,5 1 1,5 2 2,5 3 3,5 0 0,5 1 1,5 2 2,5 3 3,5 0 0,5 1 1,
Slide 83: Identifying Clusters of Leads Combining Sequence Information and Screening Assay Data
Identifying Clusters of Leads Combining Sequence Information and Screening Assay Data Functional activity (hemolysis) Affibody Human Cyno Mouse Rat ligand Z05519 + ++ - (+) Z05518 + + - - Cluster 1 Z05283 +++ - - - Z05538 + ++ ++ ++ 05692 ++ +++ - ++ Z05692 ++ ++ (+) (+) Cluster 2 Z05477 ++++ ++++ +
Slide 84: Affinity Maturation Increased Affinity 100-fold
Affinity Maturation Increased Affinity 100-fold Displacement binding to human C5 Leads after affinity maturation Parent molecule 84
Slide 85: Lead Optimization - Designing the Fusion Protein
Lead Optimization - Designing the Fusion Protein • Order of domains • Multiple C5-binding domains • Different linkers Anti C5 Albumin binding Affibody ligand domain (ABD) • Without ABD Anti C5 - ABD ABD - Anti C5 (Anti C5)2 - ABD Anti C5 - ABD - Anti C5 85
Slide 86: Lead Optimization - Selecting the Best Design
Lead Optimization - Selecting the Best Design i. In vitro activity ii. Pharmacokinetics in rodents Hemolysis assays i.v. and s.c. Rat PK study 1. 2. 1. 2. 3. > > 86
Slide 87: Lead Optimization - Selecting the Best Design
Lead Optimization - Selecting the Best Design iii. In vivo activity Acute mouse inflammation model Zymosan induced peritonitis C5a in peritoneal lavage 1. 2. 3. > > 87
Slide 88: SOBI002 - A Small Designed Fusion Protein
SOBI002 - A Small Designed Fusion Protein SOBI002 C5 targeting domain Albumin Linker Albumin binding domain Complement factor C5 88
Slide 89: Preclinical Development of SOBI002
Preclinical Development of SOBI002 Biological Process research development CMC process Toxicity studies Pharmacology Plan for FiH study development • Upstream • Dose-range • In vitro • Scientific advice • Downstream finding study in pharmacology • Advisory board • Formulation monkey • In vivo • FiH
Slide 90: Plan for First-in-Human (FiH) Study
Plan for First-in-Human (FiH) Study First-in-Human Study with seamless SAD and MAD design Main objectives: To assess safety, tolerability, pharmacokinetics and pharmacodynamics of SOBI002 in healthy volunteers after s.c. and i.v. administration Design: Double-blind, placebo-controlled, randomized wi
Slide 91: Conclusions
Conclusions Early R&D portfolio • First example of a candidate drug from a platform collaboration • Validates the Sobi drug design & development model with partnered discovery research and Sobi biologics development SOBI002 preclinical profile: • Potent and well tolerated in animals • Predicted PK t
Slide 92: End
End Pioneer in Rare Diseases
Swedish Orphan Biovitrum — Investor Day (November 2013) on 6ix