The 73rd Annual Meeting of the American Academy of Dermatology, San Francisco ; March 20-24, 2015 Poster ID: 909

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1 The 73rd Annual Meeting of the American Academy of Dermatology, San Francisco ; March 2-24, 215 Poster ID: 99 Clinical Efficacy and Safety of Brodalumab (KHK4827), Anti-Interleukin-17-Receptor A Fully Human Monoclonal Antibody, in Japanese Patients with Moderate to Severe Plaque Psoriasis: An Open-Label Extension (OLE) Study ( Study). 1 Yoshinori Umezawa, 2 Hiroaki Niiro, 1 Hidemi Nakagawa, KHK4827 Study Group 1 Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan 2 Clinical Education Center, Kyushu University Hospital, Fukuoka, Japan Research funded by Kyowa Hakko Kirin Co., Ltd. HN has received research support from Kyowa Hakko Kirin Co., Ltd. 215 Kyowa Hakko Kirin Co., Ltd. Tokyo, Japan Reference Poster ID : 365

2 The efficacy and safety of brodalumab in Japanese patients with moderate to severe plaque psoriasis. INTRODUCTION Psoriasis is a chronic T-cell-mediated inflammatory disease. The IL-17A, 17C, 17F, 17A/F heterodimer and 17E(IL-25) ligands share a common receptor subunit interleukin-17-receptor A (IL-17RA) for intracellular signaling. These cytokine has been known to play a major role in the pathogenesis of psoriasis. Brodalumab (KHK4827, also known as AMG 827) is a fully human immunoglobulin G2 monoclonal antibody that binds to human IL-17RA and blocks the biological activities of IL-17A, 17F, 17A/F, and IL-17E. Phase 2 studies of brodalumab have been shown to significantly improve symptoms of plaque psoriasis and psoriatic arthritis in 12 weeks 1,2. OBJECTIVE To evaluate the efficacy and safety of long-term exposure to brodalumab in patients with moderate to severe plaque psoriasis who have completed Phase 2 study( study). METHODS Study Design This was an OLE study following the treatment period in Phase 2 study. (Week 12 in Phase 2 study is defined to be the initial day of this study) Enrolled patients had been assigned to brodalumab at 7 mg or placebo group in Phase 2 study would be randomized to 14 or 21 mg and had been assigned to brodalumab at 14 or 21 mg group in Phase 2 study would maintain the same dose in this study. Patients received brodalumab as a subcutaneous injection with 14 or 21 mg q2w for 52 weeks. Outcome Measures Efficacy evaluation included the percent improvement in the PASI score, the proportion of patients with the spga of clear or almost clear ( or 1), and were assessed from the first administration of study drug in the Phase 2 study. Change in Percentage improvement in NAPSI and PSSI score and DLQI from the first administration of study drug in the Phase 2 study. ACR 2, ACR 5 and ACR 7 response (only in patients with psoriasis arthritis) Safety evaluation included treatment-emergent adverse events, anti-brodalumab antibody and changes in laboratory parameters. Study Population Patients with moderate to severe plaque psoriasis (BSA 1% and PASI 12) had completed the treatment period in Phase 2 study. 1. Papp et al, N Engl J Med. 212;366: Mease PJ, et al, N Engl J Med. 214;37: IL-17, interleukin-17; q2w, every 2 weeks; PASI, Psoriasis Area and Severity Index ( - 72); spga, Static physician's global assessment ( - 5) ; NAPSI, Nail Psoriasis Severity index ( - 32) ; PSSI, Psoriasis Scalp Severity index ( - 72); BSA, body surface area; DLQI, Dermatology Life Quality Index (-3) ; ACR, American College of Rheumatology

3 SD, standard deviation; BMI, body mass index; PASI, Psoriasis Area and Severity Index ( - 72); spga, Static physician's global assessment ( - 5), Nail psoriasis severity index ( - 32); PSSI, Psoriasis scalp severity index ( - 72); DLQI, Dermatology Life Quality Index ( - 3); The efficacy and safety of brodalumab in Japanese patients with moderate to severe plaque psoriasis. BACKGROUND Table 1. Patient Demographics and Clinical Characteristics at 2 Study Baseline Characteristic 14mg (N=73) 21mg (N=72) Age (yrs), mean (±SD) 45.3 (±11.8) 45.6 (±11.8) Sex (male), n (%) 56 (76.7%) 6 (83.3%) Body Weight, mean kg (±SD) (±18.9) (±16.15) BMI, mean kg/m 2 (±SD) 27.9 (±6.1) 26.1 (±5.13) Duration of Disease of Psoriasis, mean years (±SD) (±9.35) (±9.77) Psoriatic Arthritis, Yes, n (%) 1 (13.7%) 11 (15.3%) Prior Biologics, n (%) 6 (8.2%) 1 (13.9%) Prior Systemic or Photo Therapies, n (%) 58 (79.5%) 58 (8.6%) PASI score, mean (±SD) (±11.28) (±12.2) spga score, n (%) (6.8%) 36 (49.3%) 29 (39.7%) 3 (4.1%) 7 (9.7%) 35 (48.6%) 28 (38.9%) 2 (2.8%) BSA involvement, mean (±SD) (±22.6) (±23.32) DLQI, mean score (±SD) 11.2 (±7.2) 9.5 (±6.8) Fig.1 Patient disposition chart A total of 145 patients who completed the Phase 2 study treatment period were randomized to brodalumab 14 or 21 mg. A total of 133 patients completed week 52 and were evaluated for efficacy and safety (Fig.1). There were 12 discontinued patients during the study : 9 patients in 14 mg group and 3 patients in 21 mg group (Fig.1).

4 The efficacy and safety of brodalumab in Japanese patients with moderate to severe plaque psoriasis. Fig.2 Percent improvement in PASI score at week 52 (%) % 93.1 % 91.1 % 83.4 % mg Total 14 mg Total Number of Patients 21 mg mg At week 52, the mean percentage PASI improvements were 91.1% and 94.% in the 14 mg and 21 mg groups. PASI, Psoriasis Area and Severity Index ( - 72); Efficacy evaluation, Efficacy were assessed from the first adoministration of study drug in the phase 2 study

5 PASI, Psoriasis Area and Severity Index ( 72); spga, Static physician's global assessment ( - 5) ; EOS, End of study (EOS) visit is to occur at Week 52 or at the early discontinuation visit; Efficacy evaluation, Efficacy were assessed from the first adoministration of study drug in the phase 2 study The efficacy and safety of brodalumab in Japanese patients with moderate to severe plaque psoriasis. Fig.3 PASI 75 Responses over time % 94.4 % 87.5 % 78.1 % Fig.4 PASI 9 Responses over time % 81.3 % 87.5 % 71.2 % 4 21 mg Total 4 21 mg Total 2 14 mg Total 2 14 mg Total Fig.5 PASI 1 Responses over time 56.5 % 55.6 % Fig.6 spga Clear or Almost Clear ( or 1) Response over Time % 91.7 % % 69.9 % % 43.8 % 4 21 mg Total 2 21 mg Total 14 mg Total 2 14 mg Total

6 NAPSI, Nail psoriasis severity index ( - 32); PSSI, Psoriasis scalp severity index ( - 72); EOS, End of study (EOS) visit is to occur at Week 52 or at the early discontinuation visit; Efficacy evaluation, Efficacy were assessed from the first adoministration of study drug in the phase 2 study The efficacy and safety of brodalumab in Japanese patients with moderate to severe plaque psoriasis. Fig.7 Percentage Improvement in NAPSI score Fig.8 Percentage Improvement in PSSI score mg (N = 43) 21 mg (N = 46) mg (N = 68) 21 mg (N = 69) % % % % % % % % Fig.9 Clinical response of brodalumab (21 mg) NAPSI Score Baseline : 11 NAPSI Score Week 24 : The mean percentage improvements in NAPSI score at week 52 were 73.7% in the 14 mg group and 88.1% in the 21 mg group (Fig.7). The mean percentage improvements in PSSI score at week 52 were 84.6% in the 14 mg group and 82.6% in the 21 mg group (Fig.8).

7 The efficacy and safety of brodalumab in Japanese patients with moderate to severe plaque psoriasis. Fig.1 Change in DLQI Total Score Fig.11 ACR 2/5/7 Response at week 52 (EOS) mg (N = 73) 21 mg (N = 72) mg (n=8) 21 mg (n=8) ACR2 ACR5 ACR7 The mean score changes in DLQI score at week 52 were -9.3, -8.1 in 14 and 21 mg group (Fig.1). The percentage of patients with a total score of or 1 in DLQI at week 52 was 64.1% and 69.6% with the 14 and 21 mg groups. For 16 Patients with PsA, ACR 2 response rate at week 52 were 37.5% and 75.% with the 14 and 21 mg groups (Fig.11). DLQI, Dermatology Life Quality Index ( - 3); PsA, psoriatic arthritis; ACR, American College of Rheumatology; EOS, End of study (EOS) visit is to occur at Week 52 or at the early discontinuation visit Efficacy evaluation, Efficacy were assessed from the first adoministration of study drug in the phase 2 study

8 The efficacy and safety of brodalumab in Japanese patients with moderate to severe plaque psoriasis. Table 2. Adverse events and Treatment Related Adverse Events 14 mg N=73 Adverse Events, n (%) 21 mg N=72 All 63 (86.3%) 66 (91.7%) Death Serious 5 (6.8%) 5 (6.9%) Other Significant * Treatment Rerated Adverse Events, n (%) All 42 (57.5%) 4 (55.6%) Death Serious 2 (2.7%) 2 (2.8%) Other Significant * *Other significant adverse events were defined leading to withdrawal from investigational product administration except for serious adverse events. The most commonly reported adverse event was nasopharyngitis (35.2%). Ten serious adverse events (SAEs) occurred during the study (worsening of psoriasis, cellulitis, osteoarthritis, allergy to arthropod sting, varicose vein in the 14 mg group and cellulitis, infection, dermatitis contact, tibia fracture, myocardial ischaemia in the 21 mg group). Three SAEs (infection and 2 cases of cellulitis) were considered treatmentrelated. However, all of the SAEs resolved during the study. Anti-brodalumab binding antibodies were detected in 2 of 155 patients of the 14 and 21 mg groups. However, no neutralizing antibodies were detected. Identified risks attribute to blocking the IL-17 signals were neutropenia and oral candidiasis. One patient reported neutropenia (grade1) and 8 patients reported candidiasis ( all events were grade1 or 2) during the study. CONCLUSIONS Brodalumab was able to maintain its efficacy with an acceptable safety profile through 52 weeks in Japanese patients with moderate to severe plaque psoriasis in this OLE study.