sobi capital markets day

Sobi Capital Markets Day

November 2013

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 financial condition, results of operations and businesses of Swedish Orphan Biovitrum. By their nature, forward-looking statements and forecasts involve risk and uncertainty because they relate to events and depend on circumstances that will occur in the future. There are a number of factors that could cause actual results and developments to differ materially from that expressed or implied by these forward-looking statements. These factors include, among other things, the loss or expiration of patents, marketing exclusivity or trade marks; exchange rate fluctuations; the risk that R&D will not yield new products that achieve commercial success; the impact of competition, price controls and price reductions; taxation risks; the risk of substantial product liability claims; the impact of any failure by third parties to supply materials or services; the risk of delay to new product launches; the difficulties of obtaining and maintaining governmental approvals for products; the risk of failure to observe ongoing regulatory oversight; the risk that new products do not perform as we expect; and the risk of environmental liabilities.

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An International Healthcare Company Dedicated to Rare Diseases

3

We Are

Here

Strategic Priorities

1. Near-term focus on growth in key therapeutic areas, with sustainable positive cash flow from operations.

2. Medium-term investments to ensure successful commercialization of our late-stage pipeline.

3. Long-term growth will come organically and through acquisitions in key therapeutic areas.

4

Early Stage Development Programmes

Haemophilia Neonatology

Inflammation Genetics

Partner Products

ReFacto AF®

Medium term investments to support commercialisation of the late stage Pipeline

Continued focus on growth in key Therapeutic Areas

An integrated solution for commercialisation of niche and specialty products

Stable contribution to revenues from drug production and royalties

A Diverse, Growing Business Platform

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What Is Special About Rare Diseases?

1. Drugs which really work.

2. Drugs which work in every patient treated.

3. Drugs which deliver sustainable value.

EFFECT SIZE

RESPONSE RATE

OUTCOMES IN LIFE

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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 risk for # 1- 3?

5. Commercial – Does the market exist? Who is, or will be there with you?

Kiobrina Fc8

Ris

k

Ris

k

2

7

Balancing Risk + Allocation of Capital

Higher investments Higher earnings Higher risk Long-term IRR

Lower investments Medium earnings Lower risk Near-term IRR

LCM with Approved Products

Pipeline Projects

Size of circle = expected revenues

2013 2014 2015 2016 2017 2018

Risk

Year

8

3

R&D Pipeline 2013

9 LCM with Approved Products Pipeline Projects

Indication Project Partner Pre-Clin. Phase I Phase II Phase III Launch

CAPS Kineret

Hemophilia A rFVIIIFc

Hemophilia B rFIXFc

Improve growth in preterm infants

Kiobrina

Oral Mucositis in Head & Neck Cancer

Kepivance

Hereditary Tyrosinemia Type 1

Orfadin Liquid

Hereditary Tyrosinemia type 1

Orfadin 20mg capsule

Alkaptonuria Orfadin

Complement –mediated disease

SOBI002

ERT SOBI003

IL-1-driven disease IL-1 Affibody


CAPS Kineret


Hemophilia B rFIXFc


Kiobrina


Kepivance


Orfadin Liquid





SOBI002

ERT SOBI003



CAPS Kineret


Hemophilia B rFIXFc


Kiobrina


Kepivance


Orfadin Liquid





SOBI002

ERT SOBI003


Hemophilia Update

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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

Hemophilia Timeline 2013 – 2014

Q4 2013 Q1 2014 Q2 2014 Q3 2013 Q4 2014 Q3 2014

Fc9: FDA PDUFA*

FC9: KIDS B-LONG Data

Fc8: KIDS A-LONG data

2013 2014

Fc8: FDA PDUFA*

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*Dates are consensus estimates based on initial filing

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

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Birgitte Volck, M.D., Ph.D. Senior Vice President, Chief Medical Officer

Late Stage Portfolio

Birgitte Volck, M.D., Ph.D.

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• 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

How We Think About Development

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• Full integrated medical

approach across the entire lifecycle of products

• Orientation to and alignment with patient access, commercial organization and affiliates

• Unified medical platform for countries and HQ

• Informs evidence generating filing/line extension and access enabling strategies

• Country oriented partner in patient

and customer centric strategies

• Medical : Commercial peer leadership with balanced investment and priorities

Building capacity and focused efforts in support of

patient & customer focused commercialization

A Rare Journey: 30 Years With Orfadin Our Legacy in Rare Diseases

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1982 Bottle Brush plant

1989 Prof. Sven Lindstedt

1993

2005

2002 4 yr. survival 29% vs 93%

1992

Principles of Development & Medical Informed by the Patient Journey

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Symptoms

Treatment Data Capture

Outcomes Reporting

Ongoing Mgt.

Monitoring Awareness

Testing

Health System Access

Label Updates

Diagnosis + Staging

Revised Treatment Guidelines

Physicians Publications

Identification of Unmet Medical Need

Diagnosis + Treatment Outcomes Development Disease Management Optimizing Care & Advancing the Science

Guiding Principles: best integrity, ethics, scientific and technical standards

Commercial & Patient Access

Research Biology and

Process Development

Medical

+

Scientific Affairs

PV

Regulatory

Clin Ops

Biostat DM

We Pursue Novel Approaches in Development Partnering Through Early and Continous Dialogue

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A Rare Journey: 30 Years With Orfadin Our Legacy in Rare Diseases

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1982 Bottle Brush plant

1989 Prof. Sven Lindstedt

1993

2005

2002 4 yr. survival 29% vs 93%

1992

Patient voice inspires our commitments

2013 International filings /oral suspension/ 20 mg

2012 Pioneering Corporate-Academic-Public Collaboration

2010 2011 2012 2013

FDA pre-meeting

Scientific Advice EU Filing US

Kineret Pediatric Investigation Plan Approval (EU)

Filing EU Orphan Drug Designation US

Clinical study management, data analysis, study report

Cryopyrin Associated Periodic Syndromes (CAPS) Neonatal onset Multisystem Inflammatory Disease (NOMID)

Kineret for CAPS & NOMID – A Rare Journey

FDA pre-submission meeting

FDA Approval NOMID

CHMP Positive Opinion - CAPS

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R&D Pipeline 2013

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CAPS Kineret


Hemophilia B rFIXFc


Kiobrina


Kepivance


Orfadin Liquid





SOBI002

ERT SOBI003


Birgitte Volck, M.D., Ph.D. Senior Vice President, Chief Medical Officer

Kepivance – Head and Neck Cancer

Kepivance Background

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2008 proprietary product, acquired from Amgen

2013 rights to additional clinical data for Kepivance from Amgen

2005

2004

• 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

Keratinocyte Growth Factor (KGF)

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KGF is an endogenous protein in the fibroblast growth factor (FGF) family stimulating epithelial cells

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

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•Pain Narcotic analgesics

•Malnutrition/ Weight Loss PEG feeding tubes and Hospitalization

•Dehydration IV fluids

•Hemorrhage Emergency treatment

•Infections Anti-infectives

Severe Oral Mucositis – A Frequent Treatment Complication of Certain Cancer Therapy

Reference to the symptoms: Miller et al Cancer 47:207-214,1981

Clinical manifestations and treatment approaches

•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

Severe OM

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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 patients in the US each year

Current Indication: Bone Marrow Transplantation

Kepivance is administered as an intravenous bolus injection

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Kepivance Myeloablative

therapy Kepivance

3 days – 1 dose/day 3 days – 1 dose/day

Proposed Indication: Head and Neck Cancers

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• 52,500 new cases of Head and Neck cancer in US 2013 • Approximately 40% with advanced disease

• RadioChemoTherapy • Standard treatment for unresected locally advanced patients and

for high risk resected patients

• ~ 70-75 % of Head and Neck cancer patients

Head and Neck Cancer

US Incidence

Oral Cavity

~30%

Oropharynx / Hypopharynx

~30%

Larynx / Hypolarynx

~25%

Nasopharynx & Other

~15%

FDA Reported and Published Results Two Pivotal H&N Cancer Studies

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Kepivance Head and Neck Program

Long-term follow-up N=159 (20 ongoing)

Median follow-up 56 months

Long-term follow-up N=185 (appr 90 ongoing)


Long-term follow-up N=223 (appr 140 ongoing)


N=186+55 resected stage hr II-IVB SCC

120 µg/kg vs PBO (1:1); 15 weeks 20

04

01

18

N=188 unresected stage III-IVB SCC

180 µg/kg vs PBO (1:1); 15 weeks

Phase III

20

02

04

02

N=60

20, 40, 60, 80 µg/kg vs PBO, 12 weeks

N=101 60 µg/kg vs PBO, 12 weeks 9

90

11

9

97

01

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Phase II

Phase I/II

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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)

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Time to Severe OM (Days) (Protocol-specified Secondary Endpoint)

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20020402

Median time to severe OM:

35 vs 47 days (raw p=0.026)

Median time to severe OM:

32 vs 45 days (raw p=0.022)

20040118

Secondary Endpoint: Median Duration (Days) of Severe OM

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Short-term Safety Data: Summary of Adverse Events

20020402 20040118

Placebo

(N=91)

n(%)

Palifermin

(N=94)

n(%)

Placebo

(N=92)

n(%)

Palifermin

(N=93)

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)

Treatment-related AEs 10 (11) 33 (35) 10 (11) 27 (29)

Study discontinuation Due to AE 1 (1) 5 (5) 5 (5) 3 (3)

Study treatment discontinuation due to AE

5 (5) 6 (6) 5 (5) 11 (12)

Deaths during acute OM evaluation period*

3 (3) 7 (7) 1(1) 1 (1)

*Deaths occurring during the OM evaluation phase or within 30 days from the last dose of investigational product

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Secondary Efficacy Endpoints Adjusted and Unadjusted P-values

End Point A (402) B (118)

Kepivance® (n=94)

Placebo (n=94)

P-values Kepivance® (n=92)

Placebo (n=94)

P-values

Duration of severe OM (days) 5 26 Raw: 0.016 Adj: 0.112

4.5 22 Raw: 0.037 Adj: 0.187

Time to onset of severe OM (days)

47 35 Raw: 0.026 Adj: 0.157

45 32 Raw: 0.022 Adj: 0.154

Total opioid analgesic (mg IV morphine equivalent)

283 498 Raw: 0.238 Adj: 0.684

61 171 Raw: 0.669 Adj: 0.789

Patient-reported MTS score (0-4)

1.74 1.92 Raw: 0.071 Adj: 0.285

1.46 1.60 Raw: 0.626 Adj: 0.789

Incidence of xerostomia (month 4)

67% 80% Raw: 0.046 Adj: 0.231

76% 63% Raw: 0.035 Adj: 0.187

Incidence of unplanned breaks in chemotherapy

52% 45% Raw: 0.342 Adj: 0.684

30% 40% Raw: 0.164 Adj: 0.654

Incidence of unplanned breaks in radiotherapy

15% 15% Raw: 0.958 Adj: 0.958

15% 14% Raw: 0.789 Adj: 0.789

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Data shown as median or % of patients; p-values shown as non-adjusted (raw) or adjusted by the Hochberg’s procedure

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 completed pivotal phase III trials

• Additional post-hoc analysis suggests stronger treatment effect in primary and some secondary endpoints

• Favorable long-term safety follow-up

• Preparing to discuss the potential for a sBLA filing with the FDA

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Kristina Timdahl, M.D. Vice President, TA Head Medical, Neonatology

Kiobrina – a Pioneering Project in Neonatology

Kristina Timdahl, M.D.

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•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

•1992-1998 Physician internship ,General Practice, Stockholm County Council

•1992 M.D. Karolinska Institute, Stockholm, 2006 Diploma in Pharmaceutical medicine , Stockholm

The Preterm Infant

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Preterm Birthrates Are Increasing

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Beck et al, OMS 2009

8 – 8.9 %

< 8%

9 – 9.9%

≥ 10%

Number of Preterm Infants in Europe and US

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Annual no of live births 11 300 000

Preterms <W 37 1 070 000

PBM/Formula 56 000 (34%)

Breast milk 68 000 (42%)

Mixed feeding 38 000 (24%)

Preterms <W 32 160 000

References: • www.cdc.gov/nchs/data/series/sr_05/sr05_011e.pdf • Statistical pocketbook, 2006, “Key figures on Europe” • European foundation for care of the newborn infants, EU

benchmarking report 2009/2010 • EURO-PERISTAT project in collaboration with SCPE, EUROCAT &

EURONEOSTAT,2004, OECD (2011) • OECD Family Database, OECD, Paris, Cyprus public maternity

units, 2007-2009 • http://www.cdc.gov/nchs/data/series/sr_05/sr05_011e.pdf • Feasibility Survey, Prepared by PPD for Biovitrum, 2010, Q21 • UN Population database, World Population Prospects, the 2010

Revision

http://www.cdc.gov/nchs/data/series/sr_05/sr05_011e.pdf

http://www.cdc.gov/nchs/data/series/sr_05/sr05_011e.pdf

Advances in Neonatal Care Have Led to Dramatic Reductions in Mortality

Widespread incubator use

Total Parenteral nutrition (TPN)

Surfactant prophylaxis

Increased focus on breast feeding

Neo

nat

al d

eath

s p

er 1

,00

0 li

ve b

irth

s

Obstetric practice

Neonatal mortality rate (deaths under 28 days per 1,000 live births)

Newborn nutritional care

Antibiotics and infections

management

Respiratory complications management

Neonatal intensive care

system

Newborn thermal care

England & Wales

USA

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*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

*

Preterm Infants Do Not Achieve Normal Growth

43

Duration of Hospital Stay and Growth

44

0

10

20

30

40

50

60

70

80

12 15.6 17.8 21.2

Days to discharge*

Days to discharge*

• Time from regaining birtweight to discharge ,transferred,age 120 days or reaching 2000g • Ehrenkranz RA Pediatrics 2006

g/kg/day

(n=124) (n=122) (n=123) (n=121)

• Respiratory disorder

• Retinopathy of prematurity (ROP)

• Brain injury

• Necrotizing enterocolitis

• Infections

• Poor growth

A reduction in the neonatal morbidity is a key factor in improving outcome

School-age outcome • Behavioral problems

• Impaired cognitive functions

• Learning problems

40 %

Early childhood outcome • Impaired mental development

• Cerebral Palsy

• Visual problems and deafness 10 %

Adult outcome?

References: Vohr B 2000, Valcamonico 2007

Short and Long-term Morbidity Remains High

45

The 3rd Trimester Key for Neurodevelopment

• 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’t make LC-PUFAs. They must come from their nutrition which depends on absorbing and using them efficiently

Adapted from Counsell S J et al.4 (A.) 25 weeks; (B.) 28 weeks; (C.) 30 weeks; (D.) 33 weeks; (E.) 39 weeks.

MRI images of the brain developing between 25 – 39 weeks gestation

46

References: • Volpe JJ 2009,Child Neurol 2009 • Lapillonne, J Pediatr 2013 • Lucas A, BMJ 1998

Prematurity Associated With Disability at 18-24 months

47

Cerebral Palsy Hearing loss Mental retardation Vision impairment

Growth Failure is Associated With Poor Neurodevelopment Outcome at 18-22 Months

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0

5

10

15

20

25

30

12,2 14,5 16 18,4

Severe NDI

Bayley <70

Severe CP

Weight gain g/kg/day

0

5

10

15

20

25

30

12,2 14,5 16 18,4

Severe NDI

Bayley <70

Severe CP

Reference: Growth and Neurodevelopmental Outcomes in Extremely Premature Infants Poindexter, Hinz, Langer, Ehrenkranz : new data from PAS 2013

As the rate of weight gain increase the incidence of adverse outcomes decrease significantly

Per

cen

t

Fresh Breastmilk is Key for Growth & Development

49

• 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 digestion and absorption must be very efficient

Bile Salt Stimulated Lipase (BSSL) is a Key Component of Fresh Breastmilk

50

• 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 important for energy and brain growth

• Pasteurized milk and formulas do not contain BSSL

References: • Howles PN, et al. Am J Physiol 1999 • Hurst NM. J Perinat Neonat Nurs 2007

• Lindquist S Curr Opin Clin Nutr Metab Care 2010

51

Figure 1. Effect of breast-feeding versus formula feeding on cognitive developmental score: covariate-adjusted mean differences for matched composite observations. (Adapted from Andersson 1999)

References: Anderson JW, et al. Am J Clin Nutr 1999

Cognitive function was significantly higher in breast-fed infants at 6-23 months of ages, and was stable across successive ages

A meta-analysis of 11 studies revealed that fresh breastmilk is associated with

significantly enhanced cognitive development scores compared to formula (p<0.001)

Fresh Breastmilk is Associated With Better Cognitive Development in Preterm Infants

Our Question

52

What if we could restore BSSL activity in preterm infants who do not receive fresh breastmilk?

Kiobrina – a Pioneering Project in Neonatology

53

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 demonstrate improved growth which may:

• Reduce morbidity

• Reduce length of stay in NICU

• Improve neurodevelopment

Phase II Double-blind Placebo Controlled Crossover Study - Growth Improved after 1 Week Treatment

54

References: • Casper C, Carnielli VP et al Submitted • Carnielli VP et al Abstract PAS 2011 , • Maggio L et al Abstract PAS 2011 • Montjaux et al Abstract PAS 2011

18

16

14

12

Placebo (Formula /pasteurized milk)

Kiobrina + Formula/pasteurized milk

* p<0.001

16.9*

13.9

Gro

wth

Ve

loci

ty (

g/k

g/d

)

Target growth (>15 g/kg/day)

• 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 were born before week 32 of gestational age

Pivotal Trial to Read Out 1Q 2014 Double Blind, Placebo Controlled, Randomized

55

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,

tolerability and safety , neurodevelopment etc.

Top line results: Q1 2014

Top Line Results to Include Growth, Safety and Hospital Outcomes

Growth Safety + Neurodevelopment 1yr Hospital Neurodevelopment 2yrs

4 wks 3 mo 12 mo 24mo

IQ

8 yrs

Growth velocity

Head circumference

Safety

Tolerability

Readiness for hospital discharge

Safety

Tolerability

Growth

Phase III study

Top line results

Q1 2014 56

China

Korea

Bridging Studies (based on EU File)

*Lat AM: Brazil, Mexico, Argentina, Venezuela *MENA: Saudi, Iran, Israel, Egypt, Turkey, UAE, Qatar, Kuwait, Oman

US

US Pivotal Study

Russia

Australia

Latin America*

MENA*

Filin

g B

ase

d o

n

EU D

oss

ier

Cu

rre

nt

Ph

ase

III S

tud

y

EU

EMA Approval Basis for Initial Expansion

2015 2017 2018+

Timelines are indicative

57

Stephen James, Ph.D. Vice President, Head of Drug Design and Development

Early R&D Portfolio

Stephen James, Ph.D.

59

• 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, Scotland

• BSc (Hons) (St. Andrews, 1988); PhD (Leeds, 1991) in Biochemistry

Where Do We Come From?

Pharmacia Refacto process

development

Kabi/Kabi Pharmacia Heparin

Recombinant FVIII Genotropin

Biovitrum Kineret

Kepivance FIXFc

FVIIIFc Kiobrina

Sobi SOBI002

60

The Sobi Drug Design & Development Model

Biological research

Process development

Discovery Clinical

development

Research

Exploratory development

Process development

Technology transfer

61

Our Focus: Biologics Development and CMC

• Protein engineering and optimization

Research

• Pharmacology, toxicology, DMPK, bio analysis method devt.

Exploratory Development

• Upstream, midstream and downstream processes, protein analysis & characterization, formulation

Process Development

• Scale-up, Manufacturing

Technology Transfer

62

Our Model in Action: Kiobrina

Biological research

Process development

[Substrate]

0 20 40

Rate

0

20

40

2006: Acquisition of Arexis and

Kiobrina project BSSL produced in ovine bioreactor

2006-2011: CMC process development in CHO cells, full enzyme characterization and preclinical

development package

2011-2012: technical transfer to commercial

manufacturer

63

Our Model in Action: FIXFc

Analytical method development for release,

virus validation, drug substance and drug product formulation

Technical transfer for commercial scale

production

Clone selection and cell bank

characterization Upstream & downstream process development

Biological research

Process development

64

How Do We Think About Innovation?

65

Transformational Impact on Rare

Disease

Biologicals Research &

Process Development

Sustainable Value

Proposition

Balancing Risk + Allocation of Capital

Higher investments Higher earnings Higher risk Long-term IRR

Lower investments Medium earnings Lower risk Near-term IRR

LCM with Approved Products

Pipeline Projects

Size of circle = expected revenues

2013 2014 2015 2016 2017 2018

Risk

Year

66


CAPS Kineret


Hemophilia B rFIXFc


Kiobrina


Kepivance


Orfadin Liquid





SOBI002

ERT SOBI003


R&D Pipeline 2013

67

Affibody Platform for c5 Inhibition

Versatile

Scalable

Platform potential

Small

Affibody

• Biotech company focused on developing biopharmaceuticals based on Affibody® molecules and Albumod™

• Commercial relationships with a numerous companies

• Founded in 1998 in Stockholm, Sweden.

68

Transformational Impact on Rare

Disease

Biologicals Research &

Process Development

Sustainable Value

Proposition

Generation of Affibody C5 Inhibitors

69

2010: Functional characterization

2009: Affibody screening

2009: Affibody selection

2010: Affinity maturation

2014: Phase I

2011: Lead optimization

2013: Pre-clinical development completed

Patrik Strömberg Ph.D. Principal Scientist, Nonclinical Safety and Pharmacology

Introducing SOBI002 – A Novel Biologic inhibitor of C5

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 Medical Biochemistry, Karolinska Institutet

71

The Affibody Technology Platform Consists of Two Innovative Protein Domains

The Affibody Ligand

72

The Albumin Binding Domain (ABD)


• 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 clearance due to the small size

The Affibody Ligand

73


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 the plasma half-life for fusion partners by piggybacking on albumin

74

Affibody Molecules Refold Rapidly after Heat-induced Unfolding

Circular Dichroism Spectra Functional activity

75

The Albumin Binding Domain Extends In Vivo Stability and Plasma Persistence

Rat PK study

1 week

Affibody (i.v. s.c.)

Affibody-ABD fusion (i.v. s.c.)

76

The Size of an Affibody-ABD Fusion Protein Is Less Than 10 per cent of an Antibody

Affibody-ABD fusion 12 kDa

Antibody 150 kDa

77

Can We Apply Affibody Technology to Rare Diseases?

78

The Complement System

Classical Pathway antigen/antibody

complexes

Lectin Pathway carbohydrate binding

Alternative Pathway Spontaneous C3 surface activation, amplification

Lytic Pathway membrane attack

complex, Neisseria

Anaphylatoxin Inflammation,

chemotaxis

C5 activation

C5 convertase

C5 convertase

C3 activation

C3 convertase

C3 convertase

Proximal complement Terminal complement

Opsonization phagocytosis, microbes, IC

Cell activation Immune regulation

etc.

Complement regulatory proteins: C1-INH, C4BP, Factor H, Factor I, CR1,

DAF(CD55), CD59, MCP(CD46), Carboxypeptidase-N, etc.

Activation of C1

Activation of MBL

Spontaneous C3 activation

Amplification

C4 + C2 C4b2a

C3bBb

C2, C3, C4 fragments

C3a

C5a

C5b

C6 + C7 + C8 + C9n

MAC C5b-9

C4b2a3b

C3bBb3b

Properdin

C3b

C3b

fB + fD

C5aR CD88

C3aR

C5b-9

79

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, both validated and exploratory

Schrezenmeier and Höchsmann, Transf Apheres Sci, 2011

80


2009: Affibody selection

Phage display

2011: Lead optimization

PK/PD, process feasibility, preclinical immunogenicity assessment

2009: Affibody screening

ELISA, functional assays

2010: Functional characterization

In vitro, in vivo, species cross reactivity

2010: Affinity maturation

Library design, phage display selection and screening

81


i. Selection by phage display Human C5 as target protein

ii. Screening for target binding ELISAs, competition assay etc.

iii. Functional screening Hemolysis assays

Cross-species activity

0

50

100

150

HEM

OLY

SIS

(%) Human Av Cyn Av Rat Av Mouse Av

CP62

8CP

629

CP62

3CP

625

CP62

6CP

627

0

0,5

1

1,5

2

2,5

3

3,5

Z05994

Z06002

Z06007

Z06010

Z06024 X X

Z06009 X

Z06003

Z06008

Z06015 X X X

Z06039

Z05995

Z06004 X

Z06016

Z06025

Z06009

Z06033

Z06009

Z05996 X

Z06009

Z06017

Z06026

Z06029

Z06034

Z06012

Z05997 X X

Z06018

Z06027

Z06030

Z06010

Z06018 X

Z06001

Z06010

Z06019 X

Z06009

Z06011

Z06009

Z05998 X

Z06011

Z06020

Z06028

Z06031

Z06035

Z06003

Z05999

Z06005

Z06012

Z06021

Z06021

Z06032

Z06036 X X X X X X X X X

Z06000 X

Z06013

Z06022

Z06014 X

Z06037

Z06040

Z05998

Z06006

Z06014 X

Z06010

Z06011

Z06038

Z06041

Z06001

Z06003

Z06009

Z06023

Z06009

Negative Control

Positive Contro

lBlank

hC5

Z expression

0

0,5

1

1,5

2

2,5

3

3,5

X

Z06110

Z06114

Z06122 X

Z06136

Z05998

Z06144

Z06103

Z06003

Z06106

Z06022 X X

Z06081

Z06145

Z06104

Z06056

Z06115

Z06063 X

Z06063 X

Z06146

Z06105

Z06111

Z06116

Z06123

Z06131

Z06065

Z06141

Z06010

Z06106

Z06112

Z06117

Z06124

Z06132 X

Z06142

Z06043

Z06107 X

Z06118

Z06125

Z06133 X

Z06143

Z06018

Z06108

Z06113

Z06097

Z06126

Z06134

Z06020

Z06005 X

Z06054

Z06043

Z06097 X

Z06058

Z06137

Z06012

Z06121

Z06009

Z06097

Z06119

Z06127

Z06012

Z06138

Z06042

Z06147

Z06031

Z06003

Z06120

Z06128

Z06135

Z06139

Z06009

Z06148 X

Z06012

Z06121

Z06129

Z06004

Z06140

Z06031

Z06063

Z06109

Z05998

Z06094

Z06130

Z06058

Negative Control

Positive Contro

lBlank

hC5

Z expression

0

0,5

1

1,5

2

2,5

3

3,5

Z06023 X

Z06054

Z06063

Z06008 X

Z06011

Z06095

Z06042

Z06021

Z06055

Z06019

Z06072

Z06080

Z06086

Z06004

Z06009

Z06009

Z06009

Z06064

Z06073

Z06081

Z06087

Z06042

Z06043

Z06010

Z06056

Z06065

Z06012

Z06005

Z06088

Z05998

Z06021

Z06048

Z06057

Z06009

Z06054

Z06064

Z06027

Z06096

Z06011

Z06021

Z06011

Z06066

Z06074

Z06079

Z06089

Z06097

Z06044

Z06049

Z06058

Z06067

Z06075

Z06082

Z06090

Z06098

Z06045

Z06050

Z06059

Z06068

Z06076

Z06009

Z06091

Z06099

Z06046

Z06051

Z06060

Z06069 X

Z06083

Z06092

Z06100

Z06009

Z05995

Z06061

Z06070

Z06077

Z06084

Z06093

Z06013

Z06047

Z06052

Z06062

Z06009

Z06078

Z06085

Z06094

Z06101

Z06013

Z06053

Z06031

Z06071

Z06079

Negative Control

Positive Contro

lBlank

hC5

Z expression

0

0,5

1

1,5

2

2,5

3

3,5

Z06149

Z06153

Z06003

Z06164

Z06138

Z06177

Z05995

Z06004 X

Z06027

Z06157

Z06165

Z06056

Z06178

Z06183

Z06187

Z06043

Z06043 X

Z06166

Z06172

Z06179

Z06005

Z06021

Z06040

Z06154

Z06158

Z06167

Z06173

Z06065

Z06177

Z06188

Z06150

Z06003

Z06159

Z06168

Z06078

Z06027

Z06184

Z06170

Z06078

Z06155

Z06160

Z06169

Z06174

Z06180 X

Z06021

Z06043

Z06003

Z06161

Z06126

Z06000

Z06009

Z06014

Z06189

Z06003

Z06156

Z06021

Z06026

Z06175

Z06138

Z06097

Z06010

Z06151

Z06005

Z06017

Z06170

Z06021

Z06181

Z06185

Z06000

Z06010

Z06009

Z06009 X

Z06118

Z06021

Z06032

Z06190

Z06004 X

Z06162

Z06005

Z06176

Z06182

Z06186

Z06191

Z06152 X

Z06163

Z06171

Z06009

Negative Control

Positive Contro

lBlank

hC5

Z expression

0

0,5

1

1,5

2

2,5

3

3,5

X

Z06196

Z06000 X

Z06212

Z06217

Z06221 X

Z06011

Z06197

Z06201

Z06207 X

Z06218

Z06003 X

Z06097

Z06009

Z06202

Z06053

Z06009 X

Z06222

Z06004

Z06192

Z06065

Z06203

Z06004

Z06000

Z06219 X

Z06224

Z06174

Z06198

Z06011

Z06011

Z06213 X

Z06009

Z06225

Z06021

Z06199 X

Z06004

Z06000 X X

Z06148

Z06193

Z06013

Z06140

Z06208

Z06214 X X

Z06052

Z06194

Z06009

Z06204 X X X

Z06019

Z06226

Z06009

Z06175

Z06205

Z06209

Z06215

Z06078 X

Z06227

Z06009 X

Z06028

Z06210 X X

Z06031

Z06208 X

Z06063

Z06206

Z06009

Z06055

Z06220

Z06223

Z06074

Z06195

Z06200

Z06175

Z06211

Z06216

Negative Control

Positive Contro

lBlank

hC5

Z expression

0

0,5

1

1,5

2

2,5

3

3,5

Z06228

Z06232

Z06236

Z06241

Z06095

Z06247

Z06251

Z06011 X

Z06009

Z06134

Z06020

Z06245

Z06156

Z06020 X X X

Z05998

Z06242 X X

Z06047 X

Z06229

Z06126 X

Z06208

Z06021

Z06009

Z06046

Z06004

Z06004 X X

Z05996 X X

Z06252

Z06112 X

Z06095 X

Z06009 X

Z05996

Z06065

Z06257 X

Z06021

Z06237

Z06243 X

Z06248

Z06253

Z06004

Z06000

Z06233

Z06095

Z06244

Z06246 X

Z06254

Z06140

Z06230

Z06234

Z06238 X X

Z06249 X

Z06168

Z06231

Z06235 X X

Z06216

Z06250

Z06255

Z06258 X X

Z06239

Z06013

Z06140 X

Z06256

Z06175

Z06140

Z06137

Z06240 X X

Negative Control

Positive Contro

lBlank

hC5

Z expression

82

Identifying Clusters of Leads Combining Sequence Information and Screening Assay Data

Cluster 2

Cluster 1

83

Affibody ligand

Human Cyno Mouse Rat

Z05519 + ++ - (+)

Z05518 + + - -

Z05283 +++ - - -

Z05538 + ++ ++ ++

05692 ++ +++ - ++

Z05692 ++ ++ (+) (+)

Z05477 ++++ ++++ ++++ ++++

Z05363 (+) (+) - (+)

Functional activity (hemolysis)

Affinity Maturation Increased Affinity 100-fold

Leads after affinity maturation Parent molecule

Displacement binding to human C5

84

Lead Optimization - Designing the Fusion Protein

• Order of domains

• Multiple C5-binding domains

• Different linkers

• Without ABD

Anti C5 Affibody ligand

Albumin binding domain (ABD)

Anti C5 - ABD

(Anti C5)2 - ABD

ABD - Anti C5

Anti C5 - ABD - Anti C5

85

Lead Optimization - Selecting the Best Design

i. In vitro activity Hemolysis assays

ii. Pharmacokinetics in rodents i.v. and s.c.

Rat PK study

> > 1. 2. 3.

1.

2.

86

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

Albumin

Complement factor C5

SOBI002

SOBI002 - A Small Designed Fusion Protein

C5 targeting domain Linker

Albumin binding domain

88

Preclinical Development of SOBI002

CMC process development

• Upstream

• Downstream

• Formulation

• Characterization

Toxicity studies

• Dose-range finding study in monkey

• GLP study monkey

• GLP study rat

Pharmacology

• In vitro pharmacology

• In vivo pharmacology

• Pharmacokinetics

Plan for FiH study

• Scientific advice

• Advisory board

• FiH protocol

89

Biological research

Process development

Plan for First-in-Human (FiH) Study

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 within dose cohort, sequential dose- escalation study

Start-up phase

Single-dose escalation

Part A

Repeated-dose escalation

Part B

Close-out phase

90

First-in-Human Study with seamless SAD and MAD design

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

Conclusions

91

If FiH is successful:

• Validation of the therapeutic potential of the Affibody platform

• Durable C5 suppression opens up many promising therapeutic utilities

SOBI002 preclinical profile:

• Potent and well tolerated in animals

• Predicted PK to support weekly subcutaneous dosing in humans

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