Swedish Orphan Biovitrum Ab · OMXSTO:SOBI
Swedish Orphan Biovitrum Ab — Investor Day (May 2019)
108 slides from Swedish Orphan Biovitrum Ab's investor day presentation, May 14, 2019
Slide 1: Sobi Capital Markets Day 2019
Sobi Capital Markets Day 2019 14 May 2019
Slide 2: Forward looking statements
Forward looking statements In order to utilise the ‘Safe Harbor’ provisions of the United States Private Securities Litigation Reform Act of 1995, Swedish Orphan Biovitrum AB (publ) is providing the following cautionary statement. This presentation contains forward-looking statements with respect to
Slide 3: Presenters
Guido Oelkers Philip Wood CEO Head of Haemophilia Henrik Stenqvist Norbert Oppitz Presenters CFO Head of Specialty Care Armin Reininger Milan Zdravkovic Head of Medical and Head of R&D and CMO Scientific Affairs 3
Slide 4: Introduction
Guido Oelkers Introduction CEO 4
Slide 5: We remain committed to our strategic direction
We remain committed to our strategic direction Grow US business Drive Haemophilia Develop Strengthen and strengthen penetration Immunology late-stage pipeline position in EMENAR 5
Slide 6: Welcome to the first Capital Markets Day during my tenure
I’m very pleased to welcome you to the first Capital Markets Day during my tenure 6
Slide 7: We are stronger than ever and have made significant achievements
We are stronger than ever and have over the past two years made significant achievements • New management team leading the change • Two-and-a-half times the size we were in 2016 and on a whole new trajectory • Earnings guidance for 2019 at same level as 2016’s sales • More than tripled the number of
Slide 8: New management team leading the change
New management team leading the change Guido Oelkers Henrik Stenqvist Philip Wood Norbert Oppitz Armin Reininger Milan Zdravkovic Torbjörn Hallberg CEO CFO Head of Head of Head of Medical Head of R&D, Chief General Counsel, Haemophilia Specialty Care and Scientific Affairs Medical Officer Head of Le
Slide 9: 2.5X the size we were in 2016 and on a whole new trajectory
2.5X the size we were in 2016 and on a whole new trajectory Overall evolution (SEK bn) Portfolio and sales development 12.5-13.0 • Haemophilia has been the prevailing growth engine • M&A (on market and late stage) • Step-change in geographic footprint towards 9.1 North America 2.5X • Other Specialty
Slide 10: Two deals completed – sourcing innovation is central to who we are
Two deals completed – sourcing innovation is central to who we are Biovitrum SOBI003 AstraZeneca Kineret® Sobi Synagis® MEDI8897 Elocta ® Fc technology Alprolix ® FVIII/IX BIVV001/0021 In-licencing of late- stage development KABI/ Pharmacia Swedish Orphan Novimmune ReFacto Orfadin® Emapalumab (Gamif
Slide 11: I see ample opportunity to take Sobi to the next level
I see ample opportunity to take Sobi to the next level • Fundamentally attractive market • Our portfolio is strong and well-positioned for growth • We will continue to pursue M&A 11
Slide 12: The rare disease space is very attractive in the long-term
The rare disease space is very attractive in the long-term Worldwide orphan drug market1 has … with limited pressure vs. the rest of the pharmaceuticals industry grown around 7x since 2000… USD billion • High unmet need: Approximately 7,000 rare diseases globally – around 95% have no FDA approved tr
Slide 13: Large unmet need and life-saving Sobi treatments
Large unmet need and life-saving Sobi treatments 50% Median survival of primary HLH patients <2 months fail to reach HSCT due to if HLH untreated after inadequate response to diagnosis conventional therapies Without treatment, ~57k RSV hereditary tyrosinaemia hospitalisations each (HT-1), quickly be
Slide 14: Sobi's portfolio is well positioned for growth
In summary: Sobi’s portfolio is well positioned for growth Short Term Mid-term BIVV001 MEDI8897 2019 guidance of SEK 12.5-13.0 bn revenues and SEK 5.0-5.3 bn EBITA remains unchanged 14
Slide 15: Haemophilia: competitive portfolio positions us well
Haemophilia Our competitive portfolio positions us well for the new realities Five important facts: Competitive PK profile 1. European markets are more complex than US 2. Our portfolio is differentiated and competitive 3. Sobi is totally focused on continuing our success; Individualising therapy cur
Slide 16: Immunology: preparing the future on a solid footing
Immunology Preparing the future on a solid footing Strategic Imperatives 1. Significant unmet medical need in HLH 2. First approved treatment in primary HLH 3. Good start of launch, but more to gain 4. Material opportunity in indication expansion (secondary HLH, HSCT) and internationalization 1. Pro
Slide 17: 2019 impacted by one-off adjustments
2019 impacted by one-off adjustments 14 287 AZ sales 269 4 -17 26 Inventory Base sales 7/2017-6/2018 In-market growth Delta 2018A reduction In-market growth 2018/19 17
Slide 18: Continued M&A – we are looking into all three types
Continued M&A – we are looking into all three types Bolt-ons Geography Bold move 1 2 3 • Continue to build and • Build scale geographically • Build scale across Objective partner adjacencies pipeline and commercial across franchises capabilities • Late stage, on-market • Commercial infrastructure •
Slide 19: Key messages
Key messages • Rare diseases is a highly attractive market segment • Our haemophilia business continues being competitive and has significant growth potential • Gamifant has the potential to become a material growth driver for Sobi • Synagis is a growing asset under our leadership • Kineret continue
Slide 20: Sobi rare strength
@SODI rare strength
Slide 21: Financial update
Financial Henrik Stenqvist CFO update 1
Slide 22: Strong revenue growth in focus business areas
Strong revenue growth in focus business areas SEK billion Comments 3.3 • Continued strong growth +11% q-on-q. 2.6 1.1 in Haemophilia 2.3 2.3 0.3 • Impact from Immunology 2.0 0.3 0.3 1.9 0.5 0.4 acquisitions transforming the 1.6 0.3 1.6 0.3 0.5 0.4 company 1.4 0.3 0.3 0.4 0.3 0.5 - Synagis 0.4 0.4 0.
Slide 23: Regional revenue development
Regional revenue development SEK billion Comments 3.3 0.1 • Strong growth in Europe 2.6 0.4 from Haemophilia 2.3 2.3 0.1 - Further fuelled by Gamifant 2.0 0.1 0.1 1.9 0.5 1.1 launch 1.6 0.1 0.4 1.6 0.1 0.4 1.4 0.1 0.1 0.4 0.3 0.3 • Larger footprint in the US 0.4 0.3 0.1 0.5 0.4 0.3 from Synagis intr
Slide 24: Gross profit
Gross profit SEK billion Comments 2.5 78% • Strong margin trend 76% 2.0 • Mainly driven by increased 74% sales from products like 1.5 Haemophilia , Synagis and 72% Gamifant 1.0 70% • Positive impact from improved Cogs 0.5 68% 1.0 1.2 1.1 1.3 1.4 1.7 1.7 1.9 2.5 0 66% Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 2017
Slide 25: OPEX development
OPEX development SEK million Comments 1,035 966 • Increasing investments to 32% fuel short term and long 796 725 34% term growth 703 660 666 - Immunology franchise; 601 585 36% 32% 33% Synagis takeover and 37% 35% 36% 37% Gamifant launch - Expanding R&D activities 68% 66% to capture Emapalumab 68% 6
Slide 26: OPEX development – impact from new immunology products
OPEX development – impact from new immunology products SEK billion Comments 3.3 • Opex increase from investments 2.6 23% in new assets 2.3 2.3 - Synagis 1.9 2.0 - US sales force 1.6 1.6 - Commercial activities 1.4 77% - Emapalumab 1.0 1.0 0.8 - Research project portfolio 0.7 0.7 27% 0.6 0.7 0.6 0.7
Slide 27: P&L currency exposure
P&L currency exposure Currency Mix by P&L Line Sensitivity analysis (SEK 10% change vs all other (Percent) currencies) (SEK billion) 1.3 100% 5% SEK 19% 31% EUR 46% 38% 25% 0.7 9% USD 38% 27% 38% 13% Other 11% 16% 5% Total Revenues COGS OPEX Revenues EBITA 27
Slide 28: Tax
Tax Tax development (SEK million) • Lower ETR driven by reduced tax rate in Sweden (the dominating country from a tax perspective) 300 110% - Marginal impact from Synagis and US tax 250 90% - Impact from increased costs in Switzerland (emapalumab) has a marginal negative impact on 200 70% ETR 150 50
Slide 29: Cash flow
Cash flow Operating cash flow development (SEK million) • Continued strong cash conversion • Cash conversion and operating cash flow will 800 110% have a seasonal impact due to Synagis 700 90% 600 64% 70% 500 58% 55% 58% 52% 50% 400 50% 300 30% 200 10% 100 324 173 580 257 277 564 711 538 388 0 -10%
Slide 30: Financing and leverage
Financing and leverage Maturity profile of credit facilities (SEK billion) • Net Debt SEK 5.6 bn • Pro forma leverage of 1 • Underlying strong cash flow decreases leverage • Considerable debt capacity for further M&A 0.3 0.3 • Funding is M&A driven, leverage of 3-4 0.2 0.1 0.0 0.0 2019 2020 2021 202
Slide 31: Summary
Summary • Building new pillars of growth: Immunology • Continuous strong and balanced growth • Strong ongoing trend in gross margin • Maintained strong profitability – despite focused investments in growth areas • Low leverage and continued strong cash generation – creating headroom for M&A 31
Slide 32: Sobi rare strength
@SODI rare strength
Slide 33: Haemophilia
Philip Wood Head of Haemophilia Haemophilia Armin Reininger Head of Medical and Scientific Affairs 1
Slide 34: Haemophilia is chronic disease that affects peoples' lives
Haemophilia is chronic disease that affects peoples’ lives Haemophilia touches all stages of a life-span with clinical, psychological and social implications that require customized care Infant Child Adolescent Adult Elderly (Caregiver) (Caregiver) • Diagnosis • Early treatment • Independence • Thin
Slide 35: Clotting in healthy individuals vs people with haemophilia
Clotting in healthy individuals Clotting in people with haemophilia 35
Slide 36: Haemophilia clinical manifestation and consequences
Haemophilia clinical manifestation and consequences HAEMOPHILIA BLEEDINGS HAEMOPHILIA COMPLICATIONS • Joint bleeding - • Joint arthritis/arthropathy haemarthrosis • Flexion contractures • Muscle hemorrhage • Chronic pain • Soft tissue • Muscle atrophy • Life threatening-bleeding • Compartment syndro
Slide 37: Haemophilia also has significant psycho-social impact
Haemophilia also has significant psycho-social impact In 2018, Sobi undertook a large-scale, pan-European ethnographic study of the lives of people living with haemophilia Germany 9 patients Spain 1 clinics 18 51 9 patients 2 clinics UK 11 patients Germany Ireland 2 clinics 10 patients 12 patients H
Slide 38: People with haemophilia perceive their lives as entirely normal
In general, people with haemophilia and their carers perceive their lives as entirely “normal” Living Well with Haemophilia, Ethnographic Research (2018) 38
Slide 39: Day by day, people with haemophilia often act cautiously
But day by day, people “The days without with haemophilia often treatment are my act cautiously – finding it ‘worrying days’.” difficult to know what their treatment allows them to do Nick’s (child) mother considers him to be completely safe on On non-treatment days she believes his factor levels ar
Slide 40: Many feel they have to make trade-offs on activity levels
and many feel they have to make trade-offs on activity levels based on assumptions about future quality of life “Will I be in a wheelchair when I Mia (20s) is aware that the grow older? Will I be able to be bleeds she has now will affect her mobility in the future. there for my grandchildren? Theref
Slide 41: Patient understanding of factor levels seldom matches medical view
The patient’s understanding and perception of factor levels seldom match the medical community’s view While HCPs have a clear, clinical understanding of …people living with haemophilia develop mental models protection and activities based on factor levels… of their own to make sense of protection Ac
Slide 42: Higher expectations for protection beyond bleeds
Higher expectations for protection beyond bleeds No safety compromises across age groups Long-term Long-term protection protection from of joint health Real-world impact bleeds on patients’ lives Removal of burdens of haemophilia 42
Slide 43: Clotting factor replacement can manage all clinical situations
Clotting factor replacement can manage all clinical situations a patient can experience throughout the entire life1,2 Clotting factor replacement therapy provides: Acute Long-term Surgical bleed control prophylaxis management Acute bleed Necessary surgical AND Long-term prophylaxis AND control can b
Slide 44: Benefits of extended half-life technologies in haemophilia treatment
Benefits of extended half-life technologies in haemophilia treatment Standard Half Life factors1-5 Extended Half Life factors6-15 • frequent injections • higher protection for longer • delayed start of prophylaxis • improve bleed prevention • suboptimal adherence to therapy • optimize number of week
Slide 45: Fc technology used in Elocta and Alprolix
Fc technology used in Elocta® and Alprolix® Natural components and a natural metabolic pathway1–5 Elocta (rFVIIIFc) and Alprolix (rFIXFc) A human cell line6 utilise: Well-established Fc technology to extend half-life2,3,7 1 Peters et al. J Thromb Haemost 2013; 2 Dumont et al. Blood 2012; 3 Powell et
Slide 46: Elocta and Alprolix best-in-class EHL products
Elocta and Alprolix best-in-class EHL products Well-established safety and efficacy profiles – real-world experience from thousands of patients Replacing the missing factor – fundamental in haemophilia treatment Standard of care in many countries Suitable for people with haemophilia across all age g
Slide 47: Elocta – individualising therapy is gaining further momentum
Elocta – individualising therapy is gaining further momentum Sales revenues (SEK M) Quarterly FY 2018 product revenues of 1,250 SEK 3,261 M (1,557) 1,000 955 995 • 109 per cent revenue growth 880 (98 per cent at CER) 800 750 Q1 product revenues of SEK 991 M 655 (649) 550 500 425 • 53 per cent revenu
Slide 48: Alprolix – continued impressive performance
Alprolix – continued impressive performance Sales revenues (SEK M) Quarterly FY 2018 product revenues of 400 SEK 974 M (363) 340 • 168 per cent revenue growth 305 (153 per cent at CER) 300 265 255 Q1 2019 product revenues of SEK 337 M (153) 200 • 120 per cent revenue growth 155 130 (110 per cent at
Slide 49: Our market shares will approach our patient share over time
Our market shares will approach our patient share over time Sobi value market share Sobi prophylaxis patient share Per cent, end-of-2018 Per cent, end-of-2018 Haemophilia A 15% 20% Haemophilia B 22% 28% Total Haemophilia 16% 21% Based on company estimates in the Sobi territory 49
Slide 50: Growth fuelled by SHL-to-EHL and on-demand-to-prophylaxis conversion
Growth further fuelled by SHL-to-EHL conversion and on demand-to- prophylaxis conversion Good opportunity for Elocta to expand its position in the FVIII market Patients, treated for haemophilia A, in Sobi territories1 Our thoughts: Impact from new therapies • Switches will accelerate with increased
Slide 51: Elocta experience across age groups and clinical situations
Elocta experience across age groups and clinical situations Lifetime of a person with haemophilia A 1. Mahlangu et al. Blood 2014 2. Young et al. J Thromb Haemost 2015 3. Nolan et al. Haemophilia 2016 4. Konkle et al. EAHAD 2019 Poster P039 5. Su et al. ISTH 2017 Poster PB-1783 6. Quon et al. Haemop
Slide 52: A-LONG: rFVIIIFc and its prolonged haemostatic protection
A-LONG: rFVIIIFc and its prolonged haemostatic protection Sequential PK after 50 IU/kg FVIII and rFVIIIFc (n=28)a Compared with FVIII, rFVIIIFc showed 100 on average: rFVIII rFVIIIFc • 33% lower clearanceb (2.0 versus 3.0 mL/h/kgc) Mean FVIII activity (IU/dL) • 56% higher AUCb 10 (51.2 versus 32.9 I
Slide 53: Improved patient protection with individual dosing
Improved patient protection with individual dosing rFVIII rFVIIIFc 3 x 30 IU/kg 3 x 30 IU/kg per week per week (Mon, Wed, Fri) (Mon, Wed, Fri) Injections/week Weekly factor consumption Factor VIII level 1 Simulations shown are an example for rFVIIIFc only, and are based on a hypothetical 73
Slide 54: Elocta: Individualising therapy improves patient outcomes
Elocta: Individualising therapy improves patient outcomes Overall Spontaneous Joint Spontaneous Joint IP: Individualised prophylaxis IQR: Interquartile range OD: On-demand treatment SOURCE: Adapted from Nolan et al. ASH 2018 Poster 1192 54
Slide 55: Continuous improvement in joint health score after long-term Elocta prophylaxis
Continuous improvement in joint health score after long-term Elocta prophylaxis • Assessed using modified Haemophilia Joint Health Score in adolescents and adults • Benefits were seen despite pre-existing target joints and also in patients with severe SEM arthropathy • mHJHS components with the grea
Slide 56: Improved quality of life in patients on Elocta prophylaxis
Improved quality of life in patients on Elocta prophylaxisa,1 Improved health scores “Sports & Leisure,” “Physical Health” and “Feeling” in adult subjects (≥17 yrs) vs. A-LONG baselinea,1 *p≤0.01; Error bars stand for standard error of the mean aAs of third ASPIRE interim data cut (11 January 2016)
Slide 57: Summary – Elocta: Features and outcomes
Summary – Elocta: Features and outcomes • Elocta represents an innovative treatment option, with demonstrated efficacy and a well-established safety profile for people with haemophilia A1-3 • Elocta is the first and only FVIII using Fc technology to achieve half-life extension via a natural recyclin
Slide 58: How we will continue to grow
How we will continue to grow Our sources of business, our value proposition • In future replacement factors will remain dominant - The natural solution, with corresponding safety - This is a highly conservative market, safety conscious • Evolution of standards of care - Prophylaxis remains key focus
Slide 59: Sobi rare strength
@SODI rare strength
Slide 60: Immunology
Norbert Oppitz Immunology Head of Specialty Care 70
Slide 61: Why Immunology will drive Sobi's future
Why Immunology will drive Sobi’s future 1 We have deep understanding within Immunology Immunology is at the core of what we do Kineret: extensive expertise in commercialisation and mining new indications 2 The immunology market is poised to grow to total USD 113 B by 2023, with immuno-oncology becom
Slide 62: Immunology drug market projected to grow at 8% CAGR
Immunology drug market projected to display solid growth at a CAGR of 8% from 2016 to 2023 Global immunology drug sales, USD billions 120 100 +8% p.a. 80 60 40 20 0 2016 2017 2018 2019 2020 2021 2022 2023 SOURCE: GBI Research 62
Slide 63: Sobi currently has three strong assets in immunology
Sobi currently has three strong assets in immunology 63
Slide 64: Synagis
Synagis 64
Slide 65: Introduction to RSV and Synagis
Introduction to RSV and Synagis What is respiratory syncytial virus? What is Synagis (palivizumab)? • Seasonal viral infection causes ~57,000 hospitalisations • Seasonal immunoprophylaxis, not vaccine, that is the only annually in the US in children under 5 marketed product to protect against RSV •
Slide 66: Synagis integration is going well
Synagis integration is going well 135/135 FTE offers accepted. Employees transferred on Day 1 Integration workstreams managed 16 by a central Integration Management Office “The integration was seamless. The priority we of TSA tracking towards successful cutover, have is to continue to 100% with firs
Slide 67: Large number of eligible pre-term babies not receiving Synagis
Large number of pre-term babies eligible for Synagis not currently receiving treatment Fully All adherent in-label Prescription First dose Subsequent doses patients patients (18k) (63k) Identified root • Physicians unfamiliar with • Physician offices unfamiliar • Caregivers not taking causes for AAP
Slide 68: 2019 Synagis brand plan guided by three priorities
2019 Synagis brand plan guided by three priorities A B C Secure Synagis access Activate all in-label patient Leverage clinical data to for <29wGA and populations at risk of deepen engagement with CHD/CLD patients contracting RSV external stakeholders • Ensure all stakeholders are • Present recent da
Slide 69: Gamifant (emapalumab)
@sobl Gamifant (emapalumab)
Slide 70: Gamifant addresses a high unmet medical need in HLH
Gamifant addresses a high unmet medical need in HLH HLH is a rare but dramatic health crisis that presents as a heterogeneous syndrome of rapidly progressive, life-threatening disease ~200 • High fever • Hyperferritinemia • Hepatosplenomegaly Patients with primary HLH • Infection • Coagulation • Liv
Slide 71: Two types of HLH: primary and secondary
Two types of HLH: primary and secondary1-4 • Genetic mutations cause primary HLH Primary • Can be suspected on the basis of family history (pHLH) • Patients are more frequently infants or children • An infection is often the trigger of the disease Secondary • Also called acquired HLH (sHLH) • Can oc
Slide 72: Expansion strategy for emapalumab
Expansion strategy for emapalumab - promising start in Q1 Maximise potential of emapalumab Execute the US Prepare for Expand Expand launch launch in EU geographically the label • Approval by FDA • Expected • Canada • sHLH paediatric in November approval in • Japan • sHLH adult 2018 end of 2019 • Mid
Slide 73: Emapalumab – significant potential beyond primary HLH
Emaplumab – significant potential beyond primary HLH 1 800 1. Significant economic 100 opportunity sJIA/MAS 2. High unmet medical needs 700 – 06 study ongoing 3. Studies to unlock 1 000 opportunities on the way or submitted malignancy and non-malignancy –10 study; submitted to FDA Total US patients
Slide 74: Kineret
@sobl Kineret
Slide 75: Kineret – a great growth story
Kineret – a great growth story • Launched in US 2001 and EU 2002 Kineret revenues, SEK M - EU: RA, CAPS and Still’s disease 1 400 - US: RA and NOMID 1 200 • Sobi acquired Kineret from Amgen 1 000 in 2008, first full-year sales in 2009 800 600 400 200 0 2012 2012 2014 2015 2016 2017 2018 NA EMENAR Ro
Slide 76: Increased scientific interest in anakinra
Increased scientific interest in anakinra 200 1250 Number of patients treated with anakinra 160 1000 Number of publications 120 750 80 500 40 250 0 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Number of publications Number of patients RA trials and other RA publi
Slide 77: Many possible indications for Kineret beyond the current label
Many possible indications for Kineret beyond the current label Kineret label so far ... Additional indications being considered Currently approved Idiopathic Recurrent Pericarditis (IRP) • Syndrome in which the sack that surrounds the heart (pericardium) gets ▪ Rheumatoid arthritis inflamed. (RA) •
Slide 78: Sobi rare strength
@SODI rare strength
Slide 79: R&D
Milan Zdravkovic R&D Head of R&D, Chief Medical Officer 1
Slide 80: A rare disease R&D pipeline with increasing value
A rare disease R&D pipeline with increasing value Therapeutic area/ Indication Product/Project Pre-clinical Phase 1 Phase 2 Phase 3 HAEMOPHILIA Haemophilia A Elocta/PUP A Haemophilia A BIVV001* Haemophilia B Alprolix/PUP B Haemophilia B BIVV002* Primary HLH Emapalumab** Secondary HLH Emapalumab** RS
Slide 81: Haemophilia BIVV001
Haemophilia BIVV001 BIVV001 is a Sanofi programme Sobi has elected to add BIVV001 to the collaboration agreement with Sanofi but has not yet opted in. 81
Slide 82: The effect of VWF on FVIII half-life
Sobi has elected to add BIVV001 to the collaboration agreement with Sanofi but has not yet opted in. The effect of VWF on FVIII half-life1-3 • In circulation, >95% of FVIII is bound to VWF, which stabilises and protects FVIII from degradation • In particular the D’D3 region of VWF interacts with the
Slide 83: BIVV001: Combining D'D3 and XTEN to rFVIII Fc fusion
Sobi has elected to add BIVV001 to the collaboration agreement with Sanofi but has not yet opted in. BIVV001: Combining D’D3 and XTEN to rFVIII Fc fusion to break the VWF ceiling XTEN insertions1: ▪ Hydrophilic sequences comprised of natural amino acids ▪ Provide protection, increase half-life A2 Ba
Slide 84: BIVV001: Combining D'D3 and XTEN to rFVIIIFc fusion
Sobi has elected to add BIVV001 to the collaboration agreement with Sanofi but has not yet opted in. BIVV001: Combining D’D3 and XTEN to rFVIIIFc fusion to break the VWF ceiling IIa Upon thrombin activation: ▪ Removes B domain XTEN A2 IIa ▪ Disrupts D’D3 interaction ▪ Removes D’D3/XTEN IIa ▪ Results
Slide 85: BIVV001: Single dose extends FVIII half-life to 44h
Sobi has elected to add BIVV001 to the collaboration agreement with Sanofi but has not yet opted in. BIVV001: Single 65 IU/kg dose extends FVIII half-life to 44h and shows 18% activity post-infusion (N=2)1,a The average FVIII activity post-infusion at 5 days was 40% and at 7 days was 18% Day 5 BIVV0
Slide 86: Immunology Emapalumab
Emapalumab (Gamifant) is approved in the US for the treatment of adult and paediatric (newborn and older) patients with primary haemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy Immunology Full prescribing informa
Slide 87: Haemophagocytic lymphohistiocytosis (HLH)
Haemophagocytic lymphohistiocytosis (HLH) • HLH is a clinical syndrome of hyper- Fever inflammation, driven by high interferon (IFN)-γ production, characterized by severe hyperferritinaemia, fever, severe cytopaenia, Haemophago- cytosis and coagulation defects, organomegaly (spleen and cytopaenia li
Slide 88: IFN is elevated in primary HLH
IFN is elevated in primary HLH Results from 9 patients with familial HLH (age range: 2-63 months) >50 No. 1 20 No. 2 No. 4 IFN (U/mL) 15 No. 6 No. 7 10 No. 8 No. 9 5 Control 0.1 Controls FHL FHL active remission FHL, familial HLH 1. Henter et al. Blood 1991 88
Slide 89: Defect in killing by cytotoxic T cells leads to elevated IFN
Defect in killing by cytotoxic T cells leads to elevation of IFN and severe inflammation1-2 Normal cytotoxic function During a normal immune IFN response, infected cells CD8+ T cell present antigen to CD8+ T cells, inducing activation and Perforin cytotoxic response that aims TCR to kill the infec
Slide 90: Defect in killing by cytotoxic T cells leads to elevated IFN
Defect in killing by cytotoxic T cells leads to elevation of IFN and severe inflammation1-2 Defective cytotoxic function In pHLH, a defect in the IFN CD8+ cytotoxic activity of CD8+ T T cell cells and NK cells results in a failure to lyse infected cells. Perforin This results in increase TCR secre
Slide 91: Emapalumab: anti-IFN antibody
Emapalumab: anti-IFN antibody • Emapalumab is a high affinity, fully human IgG1 emapalumab anti-IFN monoclonal antibody (mAb) that binds to soluble and receptor-bound forms of IFN • When IFN binds to its receptors, IFNg it results in dimerisation and activation of signalling that results in the
Slide 92: Emapalumab clinical data in primary HLH
Emapalumab clinical data in primary HLH: In patients failing conventional therapy, 63% responded to emapalumab 100 • The primary efficacy endpoint of study NI-0501-04 Overall Response Rate was the Overall Response Rate (ORR) at end of 80 treatment 64.7% 63% • Overall response was evaluated using an
Slide 93: Overall survival – secondary endpoint
Overall survival – secondary endpoint Among patients who failed Overall survival probability estimate was 73% conventional therapy, 20/27 patients 1.0 (95% CI: 52% to 86%) at 12 months were alive at last observation* 0.8 Survival Probability 0.6 Among all treated patients, Overall survival probabili
Slide 94: Survival post-HSCT — secondary endpoint
Survival post-HSCT — secondary endpoint Overall survival probability post-HSCT estimate was 90% (95% CI: 66% to 97%) at 12 months 1.0 Survival Probability 0.8 0.6 Overall survival probability post-HSCT estimate was 89% (95% CI: 64% to 97%) at 12 months 0.4 2 patients died after HSCT due to septic sh
Slide 95: 2019 R&D investments in emapalumab
2019 R&D investments in emapalumab • In 2019 we will make investments into clinical activities: • secondary HLH in children with autoimmune Systemic Juvenile Idiopathic Arthritis (sJIA) Developing Macrophage Activation Syndrome • adult patients with malignancy and non-malignancy induced secondary HL
Slide 96: Clinical study in secondary HLH in children with sJIA
Clinical study in secondary HLH in children with autoimmune Systemic Juvenile Idiopathic Arthritis (sJIA) developing Macrophage Activation Syndrome is supported by pre-clinical and clinical data • Phase 2 study in patients < 18 years with sJIA patients with MAS having shown inadequate response to hi
Slide 97: Adult patients with sHLH have an IFN-g signature
Adult patients with sHLH have a IFN-g signature Clinical study to be initiated in 2019 • A phase 2/3 study to evaluate the efficacy, safety, and pharmacokinetics of emapalumab in adult patients with secondary haemophagocytic lymphohistiocytosis • Initial sample size (adaptive design): 10 patients in
Slide 98: Increased serum IFNγ in children experiencing graft failure
Increased serum levels of IFNγ seen in children experiencing graft failure – Possibility for early diagnosis and intervention with targeted neutralisation of IFNγ N=15/15 Merli P et al. doi:10.3324/haematol.2019.216101 98
Slide 99: Immunology MEDI8897
@sobi Immunology MEDI8897
Slide 100: MEDI8897: extended half-life anti-RSV F monoclonal antibody
MEDI8897: extended half-life anti-RSV F monoclonal antibody • Human antibody against RSV with greater potency than palivizumab in in-vitro and pre-clinical models • Engineered to have an extended half-life thereby potentially enabling a single dose to cover an RSV season • Received Fast Track Design
Slide 101: MEDI8897 is 50-fold more active against RSV isolates than palivizumab
MEDI8897 is 50-fold more active against RSV isolates in comparison to palivizumab (in vitro) Zhu et al., Sci. Transl. Med. 9, eaaj1928 (2017) 101
Slide 102: Data from healthy preterm infants supports single-season dosing
Data from healthy preterm infants supports single RSV-season dosing with MEDI8897 t1/2 of MEDI8897 in infants was estimated to be 63–73 days. Palivizumab its 19–27 days Pediatr Infect Dis J 2018;37:886–892; Antimicrob Agents Chemother. 2012;56:4927–4936 102
Slide 103: Specialty Care SOBI003
@sobi Specialty Care SOBI003
Slide 104: SOBI003 for mucopolysaccaridosis IIIA (MPS IIIA)
SOBI003 for mucopolysaccaridosis IIIA (MPS IIIA) • A rare systemic disease with a significant CNS component due to incomplete breakdown and lysosomal storage of heparan sulfate (HS) • High morbidity and mortality • Caused by mutations in gene for sulfamidase enzyme • No treatment available for MPS I
Slide 105: Sobi rare strength
@SODI rare strength
Slide 106: Concluding remarks
Concluding Guido Oelkers CEO remarks 1
Slide 107: Key messages
Key messages • We are stronger than ever and have over the past two years made significant achievements – The business is on a whole new trajectory • I see ample opportunity to take Sobi to the next level - Fundamentally attractive market - Best-in-class products on the market, well positioned for g
Slide 108: Sobi trademark and contact details
Sobi is a trademark of Swedish Orphan Biovitrum AB (publ). © 2019 Swedish Orphan Biovitrum AB (publ) – All rights reserved Swedish Orphan Biovitrum AB (publ) SE-112 76 Stockholm ♦ Sweden https://www.sobi.com/en 108
Swedish Orphan Biovitrum AB (Sobi) — Investor Day (May 2019) on 6ix