BONESUPPORT. Charlotte Stjerngren Moderator

Transcription

1 BONESUPPORT Charlotte Stjerngren Moderator

2 Introduction to BONESUPPORT Emil Billbäck CEO

3 Emil Billbäck CEO of Bonesupport since March years in life science Most recently member of the Executive Management Board at BSN medical - acquired by SCA for $3.0 billion in 2017 International commercial experience with 10 years in Germany and 4 years in the US

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5 First 6 months Insights Surgeons Payors Distributors Shareholders Employees Unique product offering - CERAMENT G is a game changer Industry leading clinical data Significant market opportunity Need to optimize our US and EU commercial footprint 5

6 CERAMENT products - strong sales growth Recent decline in US sales due to Zimmer Biomet supply issues and termination of US distribution agreement SEKm LTM Quarterly Sales per Segment CAGR 2014Q1-2018Q2 TOTAL 38% NA 33% 140,0 120,0 100,0 80,0 60,0 40, EUROW 45% 20,0 0,0 EUROW NA 6

7 Strategic Review March August

8 Strategic Review - Outcome Vision to become a global orthobiologics leader, optimizing bone biology for the treatment of bone disorders 1. Evolved strategy and developed clear strategic plan more focused execution - Redefined short, medium and long term goals 2. Taking control of our US commercial destiny terminated Zimmer Biomet distribution relationship positioning ourselves to successfully launch CERAMENT G 3. Accelerating European market penetration - significantly expanding sales organization 4. Structured approach to advancing our innovations program office created 5. Clear indication priority plan in place US and Europe 6. New unified corporate culture focused on achieving a clear set of corporate goals 8

9 The CERAMENT TM platform story Michael Diefenbeck EVP R&D, Medical & Clinical Affairs, Chief Medical Officer

10 Michael Diefenbeck, MD, PhD Orthopaedic Surgeon Work experience at: BG Unfallklinik Murnau ( ) BG Kliniken Bergmannstrost Halle/Saale ( ) University Hospital Jena ( ) Consultant for orthopaedic surgery Schön Klinik Hamburg Eilbek [bone infections] Oct 2014 Foundation Scientific Consulting in Orthopeadic Surgery and Traumatology, Hamburg Feb 2016 Honorary Consultant, Nuffield Orthopaedic Centre, University of Oxford Apr 2017 Chief Medical Officer, BONESUPPORT TM Jul 2018 Head of R&D, Clinical and Medical Affairs 10

11 Overview of Synthetic Bone Graft Substitutes Calcium Sulphate First used by Dreesmann in 1892 Resorbed too quickly Minor regeneration of bone Osteoset, Stimulan Calcium Phosphate (ß- Tricalciumphosphate (TCP)) Good primary stability Almost no resorbtion TCP-scaffold remains Norian, HydroSet, Chronos, Vitoss Composites, e.g. CaSO 4 plus CaPO 4 Balanced resorbtion Herafill Alpha-BMS, Etex, Prodense, Perossal 11

12 CERAMENT - Balanced Resorbtion/Bone Generation Flowable hydroxyapatite particles delivered by a curing calcium sulphate paste Microporous matrix Porosity: 20-40% 40% Hydroxyapatite 60% Calcium sulfate 12

13 CERAMENT : Three different products Remodels into bone Remodels into bone + Elution of gentamicin Remodels into bone + Elution of vancomycin 13

14 Indications: Trauma CERAMENT BVF 14

15 CERAMENT BVF: Proximal humerus fracture Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 15

16 CERAMENT BVF: Proximal humerus fracture Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 16

17 CERAMENT BVF: Proximal humerus fracture Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 17

18 CERAMENT BVF: Proximal humerus fracture Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 18

19 CERAMENT BVF: Proximal humerus fracture Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 19

20 CERAMENT BVF: Proximal humerus fracture Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 20

21 CERAMENT BVF: Proximal humerus fracture Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 21

22 CERAMENT BVF: Proximal humerus fracture What to do now? Leave the void empty: All stress on the metal work, which might break? Fill with: Autograft: Harvest bone from the Iliac crest (pelvis)? Allograft: Not injectable, risk of transmitting deseases? Calcium Sulphate: No bone regeneration, resorbs too quick? Calcium Phosphate: Slow remodelling, might fail at some point? CERAMENT BVF : Remodels into living bone 22

23 CERAMENT BVF: Proximal humerus fracture Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 23

24 CERAMENT BVF: Proximal humerus fracture Follow-up radiograph at 6 weeks Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 24

25 CERAMENT BVF: Proximal humerus fracture Follow-up radiograph at 4 months Radiographs provided by Dr. Aagard and Dr. Isacsson, Helsingborg 25

26 Indications: Bone Infections CERAMENT G and V 26

27 CERAMENT : Three different products Remodels into bone Remodels into bone + Elution of gentamicin Remodels into bone + Elution of vancomycin 27

28 Major Benefits from Local delivery of Gentamicin in the Bone 1) Stravinskas M et al, Bone Joint Res. 2016; 5:

29 Bone infection: Case report 38 y.o. female,sprained left ankle, no comorbidity Diefenbeck M, Schmidt HGK, presented at the OBIC meeting 2014 at Oxford Septische Knochen- und Weichteilchirurgie, Schön Klinik Hamburg Eilbek 29

30 Bone infection: Case report 24 th Jul 2013: Aspect of wound 8 weeks after surgery 30 th May 2013: Surgery (ORIF) Diefenbeck M, Schmidt HGK, presented at the OBIC meeting 2014 at Oxford Septische Knochen- und Weichteilchirurgie, Schön Klinik Hamburg Eilbek 30

31 Bone infection: Case report Acute osteomyelitis after ORIF of a lateral malleolus fracture (left) using a plate 24 th Jul 2013: Injection of CERAMENT G Diefenbeck M, Schmidt HGK, presented at the OBIC meeting 2014 at Oxford Septische Knochen- und Weichteilchirurgie, Schön Klinik Hamburg Eilbek 31

32 Bone infection: Case report Acute osteomyelitis after ORIF of a lateral malleolus fracture (left) using a plate 2nd Aug 2013: 9 days after surgery Diefenbeck M, Schmidt HGK, presented at the OBIC meeting 2014 at Oxford Septische Knochen- und Weichteilchirurgie, Schön Klinik Hamburg Eilbek 32

33 Bone infection: Case report Acute osteomyelitis after ORIF of a lateral malleolus fracture (left) using a plate 5 th Jun 2014: 11 months after surgery Diefenbeck M, Schmidt HGK, presented at the OBIC meeting 2014 at Oxford Septische Knochen- und Weichteilchirurgie, Schön Klinik Hamburg Eilbek 33

34 Bone infection: Case report Acute osteomyelitis after ORIF of a lateral malleolus fracture (left) using a plate 4 th Feb 2017: 3 years and 6.5 months after surgery 34

35 Summary Advantages of CERAMENT BVF Remodels into living bone within 6 to 12 months Off the shelf, easy to handle and inject No need to harvest autograft from the patient s pelvis No need to use allograft (donor) (risk of transmitting diseses) Advantages of CERAMENT G and V All of the above plus: High level of local antibiotic concentration Enables a one-stage management of bone infections Can be used prophylactically in high risk injuries 35

36 Sahlgrenska University Hospital Department of Orthopaedic Surgery, Sahlgrenska University Hospital our experiences with Cerament G Anders Jönsson, MD, PhD

37 Sahlgrenska University Hospital Sahlgrenska have 16,800 staff 5,400 nurses 3,700 assistant nurses 2,600 doctors (> 100 orthopaedic surgeons) 1,200 physiotherapists, occupational therapists, nutritionists, speech therapists, medical counsellors etc. 1,200 hospital technicians and biomedical analysts 2,700 administrators 96,000 medical care events Turnover: SEK: billion (43.8 mill/day)

38 Orthopaedic Surgery (n=550) Paediatric orthopaedics Spine Surgery Musculoskeletal oncology Sports Traumatology Replacement Foot surgery Orthopaedic Trauma (Fracture care) - 24 specialists - 5 residents Sahlgrenska University Hospital

39 Our experience 2015 autumn - First contact with Bonesupport and Cerament G and V - Visit at the Bone Infection Unit, Oxford - First surgery performed Further knowledge transfer and more surgeries Growing own experience - One main topic at The Gothenburg Fracture Days meeting Growing confidence and more successful treatments Sahlgrenska University Hospital

40 Our experience (cont.) Our indications: - primary osteomyelitis (OM) - fracture related infections (FRI) Multidisciplinary approach - close patient monitoring together with Infection specialists - surgical planning and execution together with Plastic surgeon(s) One séance surgery vs. multiple operations - decreased suffering for the patient - less cost for the society - free up hospital resources Sahlgrenska University Hospital

41 Our experience (cont.) Number of surgeries (upd) Higher degree of successful treatments - to our knowledge only one patient with a negative outcome. The reason for this failure is known and can easily be avoided Sahlgrenska University Hospital

42 Case report A 30 year male with discomfort of the proximal tibia for about 13 years and episodes of skin redness, soft tissue swelling and pain alternating with symptom-free periods. Classic symptoms of osteomyelitis. 12 months postop: no recurrence of osteomyelitis, and remains clinically well and fully weight-bearing Sahlgrenska University Hospital

43 Sahlgrenska University Hospital Case report Postop 1 month A 57 year male with discomfort of the proximal right thigh for about 20 years. Open femur fracture in -83. Lengthening procedure in the early nineties. Several reoperations and periods of swelling, pain and redness. Regress of symptoms after treatment with systemic antibiotics. A more severe period in Referred to us. Radical surgery in April 2018, intramedullary evacuation and administration of Cerament G and stabilised with an intramedullary nail. At follow up in late July, fully weight bearing, no pain. Normalised hematologic values.

44 The Future Expanded indications? - infected joint replacements - prophylactic use Increasing patient numbers - more patients are sent from adjacent regions - lowering the threshold for surgical intervention Less administration of systemic antibiotics postoperatively - shorter hospital stay - significant lower over all treatment costs We gain more knowledge and experience for the benefit of our patients We maybe can contribute to the level of supporting scientific evidence Sahlgrenska University Hospital

45 Sahlgrenska University Hospital

46 Significant Market Opportunity Emil Billbäck CEO

47 Global Market for Bone Void Filling: USD 3.0 bn Total Global Market for Bone Void Filling 3.8 m procedures p.a. 1 Bonesupport current addressable market 650 k procedures p.a. 3 Total Global Market for Bone Void Filling is worth USD 3.0 bn, with growth of +5% p.a. 1 Current addressable market (USD 580 million, +5% p.a. 2 ) is defined as EU5 & US for the following indications: Trauma Osteomyelitis Revision Arthroplasty Foot & Ankle Ortho oncology Excluded from addressable market is geographies outside EU5 & US, and the following indications: Dental Spine Cranio-Maxillofacial 1. Market Value Source: AMR & SMR Market Outlook Reports based on 2015 sales estimates Reference 2. BONESUPPORT mkt sizing calculation 3. APEX HC US/EU Quantitative Market Research 47

48 Bone Grafts Account for Significant Part of Our Addressable Market Current addressable market EU5 +US: 650k procedures p.a. (USD 580 million Does not include Autograft) % US Procedures % EU Procedures 19% 23% 31% 30% Autografts Allografts 27% 31% 34% 5% DBM Synthetic BVF graft substitutes 310 k procedures 340 k procedures Bone Grafts (ex DBM) currently represent 42-61% versus Synthetic Bone Grafts with 27% - 34% of procedures 48

49 Commercial Activities Clear Target Indications Current addressable market EU-5 +US: 650k procedures p.a. (USD 580 million does not include Autograft) * * Trauma Simple Trauma 159 k procedures * Complex Trauma 196 k procedures Foot & Ankle (Diabetes) 114 k procedures Infection Osteomyelitis 19 k procedures Joint reconstruction Revision Arthroplasty 117 k procedures 5%-27% infection rate 1 Approximately 40% infection rate 2 Ortho Oncology Skeletal tumors 44 k procedures *Infection present or an important potential risk EU focus Osteomyelitis Complex trauma USA focus Broader range of indications are being targeted with BVF 1. Morgenstern, M., Vallejo, A., McNally, M. A., Moriarty, T. F., Ferguson, J. Y., Nijs, S., & Metsemakers, W. J. (2018). The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. Bone & joint research, 7(7), Bonesupport estimate based on market data analysis

50 Unlocking the Significant Potential of CERAMENT Gain share from other synthetic BVFs Osteoinductive scaffold that remodels to host bone ease of use Growing registry of supportive clinical data Gain share from autograft/allografts Autografts increase surgery time on average with 26 minutes 1 and up to 39% of patients have pain from the donor site up to 2 years after surgery 2 Allografts have disease transmission risk % failure rate has been reported 3-5 Upcoming CERTIFY Data randomized study vs Autograft Create a new prophylaxis market with CERAMENT G Target complex trauma patients with a high risk of developing a bone infection FORTIFY trial designed to demonstrate the clear benefits that CERAMENT G delivers lower infection rates Optimal commercial platform Taking control of our US commercial activities Expanding our EU sales footprint 1. Lohmann et al. Economic impact of cancellous bone grafting in trauma surgery. Archives of Orthopaedic and Trauma Surgery, July 2007, Volume 127, Issue 5, pp Silber et al. Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion. Spine 2003;28(2): Zheng et al. Mechanism of bone allograft failure. J Bone Joint Surg Br 2002 vol. 84-B no. SUPP III Delloye et al. Bone allografts What they can offer and what they cannot. J Bone Joint Surg Br May 2007 vol. 89-B no

51 Evolved Strategy with Focused Execution Emil Billbäck CEO

52 BONESUPPORT s Evolved Strategy Vision to become a global orthobiologics leader - optimizing bone biology to treat bone disorders The path to this vision rests on the following strategic pillars: Innovation Leading clinical evidence and HEOR data Effective commercial platform. supported by: A resourceful and team centric organization with passionate and talented people Business operations that ensure high service levels Clear corporate goals 52

53 Progressing our innovative product portfolio Extending our product offering Short term next 2 years Plan to commercialize products with osteoinductive and osteogenic properties, synergistic to CERAMENT, enabling address of a broad spectrum of orthopedic applications focused on the US Strategic Partnerships with Collagen Matrix and MTF Biologics recently signed Our launch of the Demineralised Bone Matrix (MTF Biologics) in 2019 will provide improved access to a significant US commercial opportunity Mid term 2 to 4 years Plan to launch new combination products based on CERAMENT Plan to launch CERAMENT procedural kits 53

54 Progressing our innovative product portfolio Pipeline focused on enhanced bone growth Capitalise on CERAMENT s unique drug eluting properties for the local delivery into the bone of drugs/cells well known to enhance bone growth multiple therapeutic options Products under pre-clinical evaluation: CERAMENT plus bisphosphonates CERAMENT plus bone morphogenic protein (BMP) CERAMENT plus bisphosphonates and BMP CERAMENT plus biologic agents (stem cells, bone marrow aspirate, blood.) Positive pre-clinical data - published/presented on CERAMENT plus bisphosphonates and BMP Expect to begin clinical application of the first CERAMENT bone growth enhancing products in

55 Generating Randomized Clinical Data to Open Up Significant Commercial Opportunities Michael Diefenbeck EVP R&D, Medical & Clinical Affairs, Chief Medical Officer

56 Clinical Evidence of Bone Graft Substitutes 56

57 Clinical Evidence of Bone Graft Substitutes 57

58 Clinical Evidence of CERAMENT 58

59 Industry-leading clinical data 150 papers/abstracts 2 key examples CERAMENT BVF CERAMENT G Displaced Intra-Articular Calcaneal Fractures Treated with Open Reduction and Internal fixation and Bone Void Filling with an Injectable Calcium Sulfate/Hydroxyapatite Bone Graft Substitute. Papadia et al. (ArchTrauma Res 2018; 7: 2-6) Antibiotic Containing Bone Substitute in Major Hip Surgery: A Long Term Gentamicin Elution Study Stravinskas et al. (JBJ Infection 2018; 3: 68-72) Results In all fractures, the BGS was completely resorbed at 12 months on radiographs The AOFAS score indicated an excellent outcome in 11, a good outcome in 8, and a fair outcome in 1 fracture. Results The elution from CERAMENT G showed a strong burst and high gentamicin concentrations for the first week Complete gentamicin elution was obtained after 30 days The study results support the use of an injectable, in situ hardening calcium sulfate/hydroxyapatite BGS in DIACFs. The gentamicin elution from CERAMENT G is efficient and could potentially be used to prevent infection in patients treated for trochanteric hip fractures or uncemented hip revisions. Strength of clinical data provides KOL support and drives surgeon preference 59

60 Clinical Evidence of CERAMENT BONESUPPORT TM has two level I studies ongoing: 60

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62 CERTiFy - A prospective, multicenter, randomized study investigating the use of CERAMENT BVF in tibial plateau fractures Treatment: Reconstruction the subchondral bone defect. Fixation of the fracture Randomization to autologous iliac crest bone graft or CERAMENT BVF to prevent the articular surface. subsidence of the Country: Centres: Investigator (PI): Method: Design: Status: Germany 20 Level one trauma centre Prof. Pol M. Rommens, Mainz Prospective Randomized Clinical Trial 136 patients Non-inferiority: CERAMENT as good as autograft, taken from the pelvis of the patient Completely enrolled, 6 month follow-up finalized 62

63 CERTiFy Recruitment and follow up completed. Preparing for publication Forecast Date Completed Site selection 2012 EC approval 2013 First patient in April 2013 Last patient in Dec 2017 Last visit for primary endpoint June 2018 Publication early

64 CERTiFy designed to increase CERAMENT BVF market penetration and provide HEOR access data Successful study outcome could drive: CERAMENT BVF will be the only synthetic bone graft substitute with level 1 randomized clinical data - will allow share capture in all geographies including the US Planned publication would support improved reimbursement both in Germany and other geographies Successful outcome of the study will open up a large market opportunity for CERAMENT BVF access to patients who otherwise would have received an autograft CERTiFy has the potential to change the established Standard of Care 64

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66 Clear need to generate robust clinical evidence to demonstrate the benefits of local antibotics in open fractures Meta-analysis with eight studies (only one RCT) Only one Level one evidence / RCT so far (Moehring et al.) Morgenstern M., et al. (2018). The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. Bone & joint research, 7(7),

67 FORTiFY - A Prospective, Randomized Multicenter Controlled Trial of CERAMENT G as Part of Surgical Repair for Open Tibial Diaphyseal Fractures. Countries: Centres: Investigator: Method: Design: Status: USA and Europe 30 Level-One Trauma Centers Douglas Dirschl Prospective, Randomized Clinical Trial, 230 patients Superiority: CERAMENT G is better than the standard of care Enrolment in line with plan 67

68 FORTIFY Study Efficacy Responder analysis of a composite at 12 months: Absence of secondary procedures (surgical or nonsurgical) intended to promote fracture union Absence of deep infection at the fracture site Improvement of 5 points in patient-reported function on SF-36 Physical Component Score Safety Incidence of serious device-related adverse events and imaging core lab-reported incidences of osteolysis and non-union at 12 months HEOR Length of stay (LOS) Number of resubmissions Number of secondary procedures 68

69 Timeline FORTIFY Clinical Study Forecast Date Completed Site selection US/EU FDA IDE approval 2016 First patient in May 2017 Last patient in 2019 Last visit for primary endpoint Final PMA module submission

70 Generating Randomized Clinical Data to Further Improve Our Competitive Positioning BONESUPPORT already has the industry-leading database of clinical and pre-clinical data Only company currently generating randomized clinical data to show: o The benefits of CERAMENT BVF versus autograft CERTiFy o The benefits that CERAMENT G when used to reduce the occurrence of bone infections in patients with open fractures FORTIFY These data will provide compelling clinical and economic arguments to both surgeons and payors 70

71 Our HEOR Activities are focused on CERAMENT G/V Emil Billbäck CEO

72 Bone infections significantly impact healthcare costs Infection management is needed to make trauma care more cost efficient One of the most challenging complications in musculoskeletal trauma surgery is the development of infection 1 Length-of-stay (LOS) in hospitals has been reported to be the most important variable driving healthcare costs of open tibial fractures 1 Deep infection has been shown to lead to a 6-fold increase of LOS and 5-fold increase in total healthcare costs of open tibial fractures 1 CERAMENT G & V reduce infection risk through antibiotic elution 1 Hoekstra et al. Economics of open tibial fractures: the pivotal role of length-of-stay and infection Health Economics Review (2017) 7:32 72

73 CERAMENT G/V managing bone infections more cost effectively with less surgeries and less hospitalization 0-2 weeks 5-6 weeks 7 + weeks 3-4 weeks One-stage surgery to manage infection Promotion and protection of bone healing Plus Systemic Antibiotics One and only surgery: Injection of CERAMENT G/V Two-stage surgery to manage infection Plus Systemic Antibiotics Bone Healing Plus Systemic Antibiotics First Surgery: designed to clear infection Placement of non resorbable antibiotic carrier Second Surgery: Removal of nonresorbable antibiotic carrier plus undertake bone grafting Fewer surgeries are of clear benefit to the patient and to hospital resources Publication 1 showed that patients with chronic Osteomyelitis showed effective eradication of infection in 96% of patients in a single stage procedure with CERAMENT G 1. Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulfate/ hydroxyapatite biocomposite. McNally et al. (Bone joint J 2016; 98-B:

74 Using CERAMENT G/V Delivers Clear Economic Benefits UK Demonstrating the economic and hospital capacity benefits of one stage treatment with CERAMENT G versus the full range of other treatments currently performed on patients with osteomyelitis o Study led by Nuffield Orthopaedic Centre, Oxford University Hospitals o Timeframe -5 years ( ) o The study will highlight - Economic Impact of Single Phase Treatment vs England Average Initial data shows that USING CERAMENT G reduces the LoS and procedure rate in hospitals o Full economic analysis to be completed in the coming months. All countries are looking to reduce re-admissions, and secondary infections to free up capacity and resources in terms of staff time, ward space and theatre time Germany Optimizing CERAMENT G/V reimbursement - gain ZE code (Zusatzentgelt, ZE) - for CERAMENT G/V o If awarded, an incremental ZE Code would be activated in 2020 Also developing a site specific Reimbursement filing tool 74

75 Preparing for CERAMENT G Launch Initial US HEOR Activities US Commenced review of reimbursement, and access options for CERAMENT G Will generate a Health Technology Assessment publication plan for FORTIFY based on the following study data : o o o 28 day readmission Total length of stay Adverse event costs We expect to have a compelling HEOR data package in place ahead of the planned launch of CERAMENT G in

76 Accelerating Our European Market Penetration Emil Billbäck CEO

77 Our European Business At a glance Sales 2017 FY: SEK 51.2 million 53.9% CAGR ( ) Sales 2018 H1: 25.0% growth over direct sales reps in Aiming for 27 direct sales reps at end % Product split 75% CERAMENT BVF CERAMENT G/V Key changes 2018: 1. Significantly expanding our sales footprint 2. Performance metrics for distributors 3. Indication priority action plan 4. Sales productivity tool box Direct Sales Force Hybrid Distributor market 77

78 Germany A Key Target Market Situation in May 2018 Four sales reps in Germany 4% 5% 1% Large market opportunity to capture 3% 1% 1% 1% Confidence to invest based on: High penetration in selected specialty clinics (University clinics) 10 top accounts represent 52.6% of total sales in Germany. - Sales growth 1 of these accounts was 129% There are around 55 clinics with similar size/ opportunity as the top 10 accounts BONESUPPORT s products have very low penetration in densely populated areas, representing a population of around 45 million Hannover 2% 1% Düsseldorf Köln 2% Frankfurt 2% 2% 13% Heidelberg 12% 7% Stuttgart 1.6 m 2.9 m 10% 6.2 m Freiburg 12.8 m 17.9 m 3% 12% Munich 1% Dresden 1% Primary Sales Coverage X% (share of total country sales) Mapping geographic origin of 85% of sales 1. Latest Twelve Months (LTM) sales growth May 2018 vs May

79 Sales force expansion Bonesupport is attracting real talent Germany Regional Sales Director North hired: 20 years of sales & marketing experience in orthopedics Sales rep hired for the Berlin-area : 12 years of sales experience in orthopedics Sales rep hired for the Dresden-area: 7 years of sales experience in orthopedics Sales rep hired for the Frankfurt/Köln-area: 4 years of sales experience in orthopedics 7 reps now in place working to recruit a Regional Sales Director South and 3 further reps UK Sales rep hired to cover a large area in the South : 3 years of sales experience in orthopaedics Nordics A second rep hired to cover Stockholm & Northern Sweden: 10 years of sales experience in orthopedics On track to recruit two further sales reps Southern Europe (Spain, Italy, France & Portugal) Regional Sales Director hired: 20 years of sales, marketing & distribution experience in med tech/ orthopaedics 79

80 Generating Sales from Larger Indications A clear indication focused plan now in place Chronic osteomyelitis - continue to build our market leading position based on highly compelling clinical data and strong KOL support o Still significant scope to drive sales Complex Trauma is now a key priority indication - Much larger market opportunity than chronic osteomyelitis - 10 times bigger o Building KOL support in key direct sales markets o Enhanced marketing/conference activities to target key trauma surgeons o High quality clinical data anticipated CERTiFy and FORTIFY 80

81 Building a Powerful US Commercial Platform Patrick O Donnell General Manager & Executive Vice- President of Commercial Operations, North America

82 Our North American Business At a glance Sales 2017 FY: SEK 78.1 million 42.0% CAGR ( ) Sales 2018 H1: 31.9% decline versus people in commercial organization at end Aiming for 27 people by end 2018 Product split 100% 100% of sales with CERAMENT BVF Major events/ changes Developing a network of independent distributors 2. Termination of distribution agreement with Zimmer Biomet 3. Expanding the US Commercial team 4. Deals to gain access to complementary products 5. Established US Headquarters in Boston 6. Approval of Cerament G in Canada

83 Multiple benefits from our own US commercial platform Access to a bigger market opportunity Better ability to drive sales Current access limited to ~ 1/3 of the market New network can cover the whole market Replace underperforming distributor Build strong, productive surgeon relationships Improved market access - own GPO contracting Higher net margins 15-20% points on gross sales better net margin Improved commission structure for Distributor and Sales Reps Ability to expand our product offering Able to invest ahead of the CERAMENT G launch in 2021 Contracts signed contracts with Collagen Matrix and MTF Plan to add new products to our CERAMENT offering Building brand equity Market shaping initiatives planned 83

84 Accessing a Much Bigger Market Opportunity US Large joint reconstruction market New opportunity 23% 8% 7% 28% 34% Existing opportunity Zimmer Biomet Stryker DePuy Synthes Smith & Nephew Others US Extremity joint reconstruction market New opportunity 5% 7% 5% 19% 12% 21% 31% Existing opportunity Zimmer Biomet DePuy Synthes Wright Tornier Exactech Stryker Integra Others Knee, hip, shoulder and extremity joint reconstruction technologies - Technology Watch 2017 Volume 2 84

85 Building our own distribution network - Key Dates Activity May June July Aug Sept Oct April 19 Termination Notice Deadline 20th Effective Termination Date 20th Two-Month Exclusivity Period Seven-Month Non-Exclusive period 21st 21st BONESUPPORT can start to sell directly 85

86 Building our Own Distribution Network Significant Progress 18 independent distributors already under contract Primary Orthopedic Hardware: Smith Nephew, DJO, J & J, MicroPort, Medacta Distributors give us coverage of $12M (85%) of the Cerament BVF base business Distributors have a total of 425 highly-motivated sales reps ( ~ 300 Zimmer Biomet reps sold BVF) Sales Rep Training ongoing - aim to complete training by end January 2019 Signed agreement with Millstone Medical for warehouse/order fulfilment services Established ERP system to implement transactions, integrated with CRM system 86

87 Strengthening our U.S. Commercial Operations Built team from 14 to 21 FTEs from May to August (not including U.S. Clinical Affairs) Attracted top-level, experienced, industry talent for key operations positions Launch ready o Established ERP system o Infrastructure in built to support direct hospital transactions and product fulfillment o Sales Operations, Customer Service, Finance/Accounting BONESUPPORT Inc. 60 William Street, Suite 330, Wellesley, Massachusetts U.S.A 87

88 Market Access Securing mid term sales acceleration BONESUPPORT Specific - GPO Contracting Initiative Utilizing third-party consulting firm with excellent GPO experience and relationships Hospital Access and Contract Strategy Focus on Fast-Setting Synthetic orthopedic (non-spine) applications contract Initial focus on GPOs whose Hospital members are currently purchasing CERAMENT BVF Making very good progress 88

89 Expanded product offering in 2019 Scaffold New Bone Formation Signals Osteoinductive, Demineralized Bone Graft (Growth Factors) Cells Osteoconductive, synthetic, HA injectable bone void filler Osteogenic, synthetic graft for delivery of autologous stem cells 89

90 Our new US Commercial Platform will deliver Talented own Commercial infrastructure in place Synergistic products through Collagen Matrix and MTF High quality distributors coming onstream Delivering CERAMENT s Significant Potential Clear indication focus More motivated sales reps focused on BVF Contracting GPOs ongoing 90

91 Financial overview Bjorn Westberg - CFO

92 Sales development US EUROW CAGR 41%, % due to CAGR 51% - ZB internal supply issues - strong uptake of CER G - chronic osteomyelitis 2018 H1 US -32% EUROW (81% (81% direct direct sales) sales) - ZB internal supply issues issues --Direct markets +24% +24% - Our ZB ZB contract termination --Indirect markets markets -10%% -10%% (large Indian order LY) (large Indian order LY) 92

93 Operating costs development (SEKm) COGS R&D Costs S&M costs G&A costs Gross margin 84.6% 84.4% 87.0% (SEKm) 2017H1 2018H1 COGS R&D Costs S&M costs G&A costs Gross margin 88.0% 84.6% R&D costs Increase due to clinical studies S&M costs Increase due to more reps and activities G&A costs Increase due to old incentive programs Certain one-time costs (like IPO prep) COGS Varies due to mix of sizes, US vs EUROW ratio Mtrl write off in Q1-18 (otherwise 86,5%) S&M costs Increase due to US build-up G&A costs 2018 H1 5.5m severance cost former CEO Cost Share programs 1.7m (8.0) 93

94 KPIs (SEK million) H1 2018H1 Net Sales Sales growth (%) Gross margin (%) Operating loss Net cash Cash at period end (Net) Cash 2017 new share issue (IPO) of SEK 518m net H1 Repayment of loan 94

95 Key drivers improving financial performance New US distribution structure Broader market access Sales direct to hospitals Significant better net margin (+15-20%) in the US Strengthened European commercial structure Sales deployment to capture large geographic potential Indication focus Short and mid term offering Regular additions to our product offering planned Products from Collagen Matrix and MTF New market launches CERAMENT G in the US (2021) New markets (Canada, Australia, Asia) Execution and prioritisation From R&D focus to more commercial focus Faster execution and clearer priorities 95

96 Financial Outlook Sales CAGR +40% (after 2019) 2018 will be a transition year Significant impact from strategic initiatives in 2019 and forward Turn to profit based on existing cash Stronger foundation now compared to 2017 US (More sales potential & better net margin) More regular product flow 96

97 Wrap up Emil Billback - CEO

98 Critical inflection points that build value Innovation Leading clinical evidence and HEOR data Effective commercial platform Expanding our Product offering Short term Collagen Matrix and MTF Biologics launches Mid term CERAMENT combinations/bundled offerings for a wide range of indications Long term Breakthrough innovation to enhance bone growth - potential to disrupt the market Focus on generating randomized clinical data CERTiFy study data early 2019 FORTIFY study data 2020 HEOR data early 2019 Building own US commercial platform 2018/2019 Enhanced market access to drive the sales of CERAMENT BVF Create optimal platform to support the planned launch CERAMENT G in 2021 European sales organization significant expansion 2018/2019 Size of European sales team to be almost doubled in