R&D Day. 13 June 2016 Michael Oredsson Chief Executive Officer

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1 R&D Day 1 13 June 2016 Michael Oredsson Chief Executive Officer

2 Vi transformerar BioInvent Vi har skapat en bred portfölj av kliniska projekt Vi har ökat vårt kommersiella fokus Vi har säkrat finansiering för kommande studier 2

3 Marknaden för immunonkologi förväntas stiga till >30 mdr USD 3

4 BioInvent utvecklar nästa generations immunonkologiska läkemedel Två unika teknologiplattformar n-coder F.I.R.S.T Samarbeten med ledande internationella forskningsgrupper Lång erfarenhet av läkemedelsutveckling 4

5 BioInvents partners Globala läkemedelsbolag som partners Pågående Fas I-studier Pågående prekliniska studier och ett flertal projekt i discovery-fas 178 Mkr i intäkter 2012-Q

6 Tre projekt i klinisk fas under 2016 BI-1206 BI-505 TB-403 6

7 Non-Hodgkins lymfom och kronisk lymfatisk leukemi 7

8 Cancer kan överlista dagens läkemedel drabbas av non- Hodgkins lymfom varje år i västvärlden 1/3 av patienterna dör inom fem år Källa: 8

9 men BioInvents antikropp kan överlista cancern Finansierad fas I/IIstudie 9

10 BI-1206 Fas II-studie i samarbete med Cancer Research UK 10

11 Multipelt myelom 11

12 Patienter med multipelt myelom drabbas ofta av återfall Livshotande blodcancer Drabbar patienter årligen Revlimid/Velcade 8 MDR USD (2014) 12

13 BI 505 kan förhindra eller fördröja återfall Behandling med cellgifter BI-505 stimulerar immunförsvaret att äta upp cancerceller 13

14 BI-505 kan göra dagens läkemedel effektivare Finansierad fas II-studie redo för start 14

15 BI-505 Fas II-studie i samarbete med University of Pennsylvania 15

16 Barn med cancer 16

17 Även barn drabbas av cancer Medulloblastom Ewings sarkom Neuroblastom Alveolärt rhabdomyosarkom Mellan 30 och 50 procent av patienterna avlider Proteinet PIGF påverkar prognosen negativt 17

18 TB-403 är en antikropp mot PIGF Möjligheter till snabbt godkännande Finansierad fas I/II-studie redo för start 18

19 Treg & TAM Nya angreppspunkter 19

20 Regulatoriska T-celler (T-regs) så fungerar det Regulatoriska T-celler Kroppens immunförsvar - BioInvents antikroppar dödar cancerceller motverkar infektioner autoimmuna sjukdomar

21 Tumörassocierade makrofager (TAM) så fungerar det Tumörceller utnyttjar makrofager som skydd BioInvent utvecklar antikroppar som eliminerar eller ändrar funktion på denna typ av makrofager CELLGIFT CELLGIFT CELLGIFT CELLGIFT CELLGIFT CELLGIFT 21

22 Antikroppstillverkning på BioInvent 22

23 Antikroppstilverkning på BioInvent Specialiserad på terapeutiska antikroppar Mer än 25 års erfarenhet av antikroppsproduktion Certifierad GMP-tillverkare sedan 1993 Utmärkt track record som leverantör till big pharma och biotech-företag Anläggningen godkänd för produktion av prövningsläkemedel till fas I-III-studier 23

24 Antikroppstillverkning på BioInvent

25 Strategisk rational för BioInvents produktionsanläggning Stödja BioInvents interna program och behov av prövningsläkemedel Utnyttja överkapacitet för lönsamma externa kundprojekt 25

26 Vi transformerar BioInvent 26

27 Vi transformerar BioInvent Vi har skapat en bred portfölj av kliniska projekt Vi har ökat vårt kommersiella fokus Vi har säkrat finansiering för kommande studier 27

28 Långsiktig finansiering för fortsatt värdeskapande Riktad emission till Omega Funds (MSEK 43) Fullt garanterad företrädesemission (MSEK 191) 28

29 Betydande informationsflöde från tre öppna kliniska studier 29

30 Tack! 30

31 R&D Day 1 13 June 2016 Anna Wickenberg, Ph.D. SVP Clinical Development

32 Agenda Clinical Development! Highlights from ASCO! Evolving regulatory context! BI-505! Targeting residual disease in Multiple myeloma via ICAM-1! BI-1206! Treating B cell malignancies through targeting of the inhibitory Fc gamma receptor CD32b! TB-403! Treating patients with relapsing Medulloblastoma through blockade of the PlGF/Nrp1 pathway 2

33 Three clinical development stage projects 3

34 ASCO reports on immune oncology ASCO CHICAGO June 2016 Advance Of The Year: Cancer Immunotherapy 1. unleashing the body s natural immune response to cancer 2. help the immune system find and destroy cancer cells 4

35 ASCO highlights for BI, hematology oncology Also in the novel agent era, high dose melphalan and autologous stem cell transplantation (ASCT) should remain the preferred treatment for younger patients with newly diagnosed multiple myeloma as it provides clear benefit in PFS and OS (Abstract #8000) A meta analysis of 3 randomized trials showed that lenalidomide maintenance increases OS in patients with MM without dramatically increasing secondary malignancies, and concluded that maintanance lenalidomide should be the SoC for patients undergoing ASCT (Abstract #8001) Data from a phase I/II study showed durable responses and high response rates in patients with r/r ALL, NHL, and CLL treated with CD19+ CAR T cells (Abstract #102) Data from CASTOR, phase III study with daratumumab in combination with bortezomib and dexamethasone in r/r myeloma patients cut the risk of disease progression or death by 61% compared with the standard combo alone and increased the ORR to 83% vs 63% (Abstract #LBA4) Phase I trial with anti PD1, pembrolizumab in combination with len+dex, shows 50% ORR in r/r MM, with little activity as single agent (Abstract #8010). Many other trials with checkpoint inhibitor combinations in heme-onc ongoing. 5

36 Evolving regulatory environment Fast Track designation Breakthrough Therapy designation Accelerated Approval pathway Priority Review designation Conditional Marketing Authorization Accelerated Assessment Adaptive Pathways pilot Priority Medicines Scheme (PRIME) 6

37 New drug product approvals 2015 In total 89 new drugs approved 25 were biologics 21 approvals within malignant diseases Examples from heme/onc Imbruvica for MCL and CLL Venclexta for CLL Darzalex for MM 7

38 BI-505 Targeting residual disease in Multiple myeloma via ICAM-1 8

39 BI-505 executive summary 9

40 Rationale for anti-icam-1 therapy in myeloma Expressed on surface of multiple myeloma plasma cells Van Riet et al., BJH, 1991 Huang et al., Cancer Research, 1995 Mediates protective interactions of myeloma cells with bone marrow macrophages Contact-dependent protection of myeloma cells from chemotox by bone marrow macrophages via CD18/ICAM-1 10

41 BI-505 pre-clinical efficacy 11

42 BI-505 MoA in pre-clinical models Fc:FcgR dependent Macrophage dependent Induces bone marrow macrophage infiltration Induces ADCP (phagocytosis) 12

43 Phase 1 clinical data Multi-center dose-escalation study Advanced relapsed/refractory MM 34 patients, dose mg/kg q2w Mostly grade 1-2 AEs w/o dose relationship No MTD reached, optimal biologic dose identified (10 mg/kg) based on receptor saturation. No objective responses; 7/29 at doses >0.09 mg/kg had stable disease for days 13

44 Phase 2 design considerations Promising pre-clinical efficacy data and attractive MoA to target residual disease Benign safety profile in patients No clear single-agent efficacy in phase-1 in advanced R/R patients Based on MoA, efficacy may be best in targeting low levels of treatmentresistant disease Consolidation/maintenance setting in combination treatment Use response rate and response depth as primary endpoint due to long expected PFS Assess minimal residual disease to further understand depth of response In depth correlative analyses to understand MoA in bone marrow Randomized controlled design 14

45 BI-505: phase II study design 15

46 Tumor load is one of the best predictive factors for relapse 16

47 Acknowledgements Alfred Garfall, MD Brendan Weiss, MD Edward Stadtmauer, MD Nina Luning Prak, MD PhD 17

48 BI-1206 Treating B cell malignancies, CLL/NHL, through targeting of the inhibitory Fc gamma receptor CD32B 18

49 BI-1206 executive summary 19

50 Rationale for anti-cd32b therapy in B cell malignancies CD32b is expressed throughout B cell development and in different B cell cancers CD32b is a negative regulator of therapeutic antibody efficacy, operating both on tumor and immune cells, and BI-1206 blocks this. Tumor CD32b expression predicts clinical response to antibody therapy with rituximab 20

51 Rationale for anti-cd32b therapy with BI-1206 CD32b is expressed throughout B cell development and in different B cell cancers CD32b is a negative regulator of therapeutic antibody efficacy, operating both on tumor and immune cells, and BI-1206 blocks this. Tumor CD32b expression predicts clinical response to antibody therapy with rituximab 21

52 Rationale for anti-cd32b therapy CD32b is expressed throughout B cell development and in different B cell cancers CD32b is a negative regulator of therapeutic antibody efficacy, operating both on tumor and immune cells, and BI-1206 blocks this. CD32b expression predicts clinical response to antibody therapy with rituximab 22

53 Phase 1/2a design considerations Promising pre-clinical efficacy data and attractive MoA for B cell lymphomas with strong data in CLL and MCL models No significant preclincial toxicology findings First In Man study Efficacy may be best in combination with tumor targeting mab, like anti- CD20, rituximab Traditional 3+3 dose escalating phase I Establish ph2 dose based on safety and receptor saturation Single agent and anti-cd20 expansion combination arms Relevant number in both CLL and MCL to look for signals of effect Explore other NHL types Focus on B cell PD markers Possibility to continue treatment if response is observed 23

54 A signal seeking Phase I/IIa safety Study with BI-1206 and rituximab in Patients with CD32b+ B cell malignancy First In Man 5-8 sites in UK is planned to participate Coordinating PI Prof Andrew Davies, Southampton 24

55 BI-1206: phase I/IIa study design, part A 25

56 BI-1206: phase I/IIa study design, part B 26

57 Acknowledgements Andrew Davies, PhD, MD Investigators and staff at all sites Hayley Farmer, PhD CRUK team 27

58 TB-403 Treating patients with relapsing Medulloblastoma through blockade of the PlGF/Nrp1 pathway 28

59 TB-403 executive summary 29

60 Rationale for anti-plgf therapy in medulloblastoma TB-403 treatment led to inhibition of primary tumor growth and spinal metastasis and longer survival PlGF activates prosurvival pathways in Medulloblastoma through NRP1 NRP1 expression is linked to poor survival in children with medulloblastoma 30

61 Phase-1/2a design considerations Promising pre-clinical efficacy data Tested in clinical trials in adult populations with no significant safety findings Higher doses are needed to reach tumor site in medulloblastoma Challenges in recruitment of pediatric medulloblastoma population foreseen Traditional 3+3 dose escalating phase I Expansion cohort to search for signal of effect in medulloblastoma Single agent and SoC combination data Inclusion of other Primitive Neuroectodermal Tumor patients (PNET) in phase I, based on PlGF expression data 31

62 TB-403: phase I/IIa study design, part A 32

63 TB-403: phase I/IIa study design, part B 33

64 Acknowledgements Giselle Scholler, MD Amy Lee Bredlau, MD NMTRC investigators and staff 34

65 Tack 35

66 1 R&D Day 13 June 2016 Björn Frendéus, Ph. D. Chief Scientific Officer

67 The BioInvent drug development offer cutting edge, highly integrated, translational science 2

68 Why antibodies? Antibodies to checkpoint inhibitors have transformed cancer therapy 3

69 Mechanisms of resistance/unresponsiveness to checkpoint inhibitor therapy Intrinsic resistance (including cancer type specific, e.g. Colorectal, Pancreatic, TNBC) Immune suppressive tumor microenvironment Tumor-associated myeloid cells, Treg Low immunogenicity of tumor cells Low (immunogenic) mutational burden Decreased antigen presentation (APCs (MΦ/DC, Treg) Antibody biology i.e. suboptimal choice of antibody MoA Adaptive resistance (in response to checkpoint inhibitor therapy) Other checkpoints upregulated e.g. Tim-3, Lag-3, ICOS in response to anti-pd1/pdl1 therapy 4

70 Role of FcγRIIB, T reg and TAM in the cancer-immunity cycle 5

71 The BioInvent offering: From bedside, to bench, to bedside 6

72 The F.I.R.S.T platform: Combined target and antibody discovery 7

73 The F.I.R.S.T Immune Oncology platform 8

74 F.I.R.S.T Bench to Bedside example Overcoming Resistance to Antibody Therapy 9

75 F.I.R.S.T CLL target identification 10

76 Several Activating but only one inhibitory FcgR Fc receptors as regulators of immune responses Falk Nimmerjahn* and Jeffrey V. Ravetch JANUARY 2008 VOLUME 8

77 FcgRIIb de-sensitizes immune effector cells and mutes antibody therapeutic activity γ γ γ 12

78 FcgRIIb on target B-cells reduces rituximab efficacy through internalization 13

79 In vivo Proof-of-concept 14

80 BI-1206 enhances therapeutic activity of clinically relevant antibodies against different targets in vivo 15

81 14-BI : A signal seeking Phase I/IIa safety study with BI-1206 and rituximab in CD32b positive B-cell malignancies 16

82 BI-505: Combatting residual disease by targeting ICAM-1 and macrophage scavenging of myeloma 17

83 T REG program outline 18

84 F.I.R.S.T TAM 19