DARATUMUMAB, A CD38 MONOCLONAL ANTIBODY IN PATIENTS WITH MULTIPLE MYELOMA Data from the dose-escalation part of the FIH study Abstract #8512

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1 DARATUMUMAB, A CD38 MONOCLONAL ANTIBODY IN PATIENTS WITH MULTIPLE MYELOMA Data from the dose-escalation part of the FIH study Abstract #8512 Henk Lokhorst, Torben Plesner, Peter Gimsing, Hareth Nahi, Monique Minnema, Ulrik Lassen, Jakub Krejcik, Jacob Laubach, Steen Lisby, Linda Basse, Paul Richardson University Medical Center Utrecht, Netherlands; Vejle Hospital, Denmark; Rigshospitalet, Copenhagen, Denmark; Karolinska Institutet, Stockholm, Sweden; Genmab A/S, Copenhagen, Denmark; Dana-Farber Cancer Institute, Boston, MA, USA

2 Disclosures Genmab: Advisory Board, research support Johnson & Johnson: Advisory Board Mundipharma: Advisory Board Celgene: Research support

3 A Human CD38 mab with Broad-Spectrum Killing Activity Human IgG1k monoclonal antibody Broad spectrum mechanisms of action including CDC, ADCC, ADCP, apoptosis induction and inhibition of enzymatic activity In development for multiple myeloma Here we present data from the dose-escalation (part 1) of the FIH study in patients with relapsed or relapsed and refractory multiple myeloma

4 : GEN501 Phase I/II Study of Monotherapy in Relapsed or Relapsed and Refractory Multiple Myeloma Objectives Primary Establishment of the safety profile of daratumumab Secondary To establish the pharmacokinetic profile of daratumumab Evaluation of the efficacy of daratumumab according to International Myeloma Workshop Consensus Panel 1, Blood 2011;117: (IMWG) Evaluation of the immunogenicity of daratumumab

5 Main Inclusion Criteria Patients with advanced Multiple Myeloma requiring systemic therapy Patients with relapsed or relapsed and refractory disease with at least 2 prior lines of therapy and without further established treatment options Patients with ECOG performance status 0-2 Patients having a life expectancy >3 months

6 Trial Design PART 1 Doseescalation cohorts Open label, weekly i.v. infusion, 8 weeks Dose-escalation: 3+3 scheme mg/kg PART 2 Expansion cohorts Ongoing Several cohorts and dose schedules are being tested - start with pre-dose at 10% of the full dose, max 10 mg - three weeks delay after first full dose - governed by independent data monitoring committee

7 Patient Characteristics (Part 1: N=32) Cohort No subject Age a No of prior treatment Refractory to Len and Bort Len/Thal b Bort b Dex/Steroid other b Chemo b,c Auto/Allo b 1 mg/kg (42-76) 5 (2-8) e 88% / 71% 100% 88% / 41% 100% 65% / 12% 2 mg/kg 3 64 (60-71) 8 (6-10) e 100% / 100% 100% 100% / 100% 100% 100% / 0% 4 mg/kg 3 64 (62-66) 3 d (3-8) 67% f 100% / 33% 100% 100% / 33% 100% 67% / 33% 8 mg/kg 3 60 (56-68) 8 d (6-12) 100% f 100% / 67% 100% 100% / 67% 100% 100% / 33% 16 mg/kg 3 55 (54-59) 4 d (4-5) 67% f 100% / 67% 100% 100% / 33% 100% 100% / 67% 24 mg/kg 3 58 (50-69) 6 d (4-6) 67% f 100% / 67% 100% 100% / 33% 100% 67% / 0% PART mg/kg (50-69) 5.5 (3-12) 75% 100% / 58% 100% 100% / 42% 100% 83% / 33% Allo: allogeneic stem cell transplantation, Auto: autologous stem cell transplantation, Bort: bortezomib, Chemo: chemotherapy, Len: lenalidomide, No: number, Thal: thalidomide a: median (range), b: number of patients exposed to the drug, c: vincristine, doxorubicin, cyclophosphamide, melphalan and others, d: revised after additional data collection, e: data not collected, f: data collected retrospectively

8 Infusion related reactions

9 SAEs Assessed Related to Daratumumab Event PART 1 N=32 Bronchospasm 1 patient: grade 2 (2 mg/kg) (2 days later grade 3) 1 patient: grade 2 (24 mg/kg) Anemia 1 patient: grade 3 (0.1 mg/kg) (DLT) Thrombocytopenia 1 patient: grade 4 (0.1 mg/kg) ASAT > 5.2 times upper limit of normal 1 patient: grade 2 + grade 3 (1.0 mg/kg) (DLT) Cytokine release syndrome 1 patient: grade 2 (0.1 mg/kg)

10 (Part 1) Plasma Concentration 1000 plasma conc (µg/ml) plasma conc (µg/ml) mg/kg 1 mg/kg 0.5 mg/kg 24 mg/kg 16 mg/kg 8 mg/kg 4 mg/kg LOQ time (days) time (days) Presented by:

11 Response (Part 1) Maximal Change in Paraprotein Relative change in paraprotein from baseline (%) C C A A A A A A B C A A C < 1 mg/kg 2 mg/kg 4 mg/kg 8 mg/kg 16 mg/kg 24 mg/kg A A B A C A A A A A A B A B A A C A C Patient number A: serum M-component, B: urine M-component, C: Free Light Chains (FLC) 22 28

12 (Part 1) Response according to IMWG

13 (Summary of Response) Daratumumab 4mg/kg (Part 1) Max. Reduction of M-Component/FLC/BM PCs and by IMWG Criteria Cohort (mg/kg) N Max. reduction in M-component (%) Serum Urine Max. reduction in difference between involved and uninvolved FLC (%) Max. reduction in plasma cells in bone marrow biopsy (%) [Baseline value (%)] Response according to IMWG a [12.5] 89 [23] 97 [19] MR PR PR [14] 93 [7.5] - SD MR NE [31.5] 100 [2] PD PR SD b b [18.5] 17 [3.0] 91 [17.0] PR MR PR no measurable disease/normal at Baseline - data not available a Evaluation based on max. reduction in M-component or FLC b Follow up still ongoing

14 Progression-Free Survival

15 Conclusion 1/2 Daratumumab has shown a favorable safety profile as monotherapy in relapsed or relapsed and refractory Multiple Myeloma patients In part 1, where 15 of 32 (47%) heavily pre-treated evaluable Multiple Myeloma patients received 8 weeks of daratumumab as monotherapy in doses up to 24 mg/kg, a reduction in paraprotein was observed In 10 of these 32 patients (31%), this reduction qualified to a clinical response: 5 patients achieving PR (15,5%) 5 patients achieving MR (15,5%) In 8 of 12 patients (67%) at doses 4 mg/kg and above achieved a clinical response: 5 patients achieving PR (42%) 3 patients achieving MR (25%)

16 Conclusion 2/2 Biochemical response was accompanied by clearance of myeloma cells from the bone marrow At higher dose levels, observed plasma concentrations are close to those predicted Overall increased daratumumab exposure correlated with longer progression free survival Further studies: We are currently exploring an 8 mg/kg weekly schedule but will also explore higher doses and different schedules

17 Acknowledgments Special thanks to investigators, sub-investigators, research staff and patients and their families at the collaborating centers: Karolinska Institutet, Stockholm, Sweden Rigshospitalet, Copenhagen, Denmark University Medical Center Utrecht, Netherlands Vejle Hospital, Denmark Dana-Farber Cancer Institute, Boston MA, USA

Abridged version of ASCO presentation June 4, 2012, for Genmab.com/investors

Abridged version of ASCO presentation June 4, 2012, for Genmab.com/investors Abstract #809 Daratumumab a CD38 mab for the Treatment of Relapsed /Refractory Multiple Myeloma Patients: Preliminary Efficacy Data from a Multicenter Phase I/II Study Torben Plesner, Vejle Hospital, Denmark;