Astrazeneca Plc · LSE:AZN
Astrazeneca — American College of Rheumatology 2015
49 slides from Astrazeneca's conference presentation, Nov 11, 2015
Slide 1: Investor science conference call: American College of Rheumatology 2015
Investor science conference call: American College of Rheumatology 2015 San F rancisco, California, USA 11 November 2015
Slide 2: Forward-looking statements
Forward-looking statements In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act 1995, we are providing the following cautionary statement: This document contains certain forward-looking statements with respect to the operations,
Slide 3: Introduction
Introduction Thomas Kudsk Larsen Head of Investor Relations
Slide 4: 2015 investor science events for each main therapy area
2015 investor science events for each main therapy area Respiratory, Inflammation & Cardiovascular & Metabolic Oncology Autoimmunity Disease ACR 2015, November ACC 2015, March ASCO 2015, June • anifrolumab (previously MEDI-546) • Brilinta/Brilique • Durva + treme combo – Phase II data in lupus – Ph
Slide 5: Agenda: Meet the experts
Agenda: Meet the experts • Lupus & targeting the interferon pathway – Bing Yao, Head of Respiratory, Inflammation & Autoimmunity iMED, MedImmune • Anifrolumab Phase II lupus/SLE – Richard Alan Furie, MD, Chief, Division of Rheumatology, North Shore-LIJ Health System • Anifrolumab current & future p
Slide 6: Lupus & targeting the interferon pathway
Lupus & targeting the interferon pathway Bing Yao Head of Respiratory, Inflammation & Autoimmunity iMED, MedImmune
Slide 7: High unmet need for systemic lupus erythematosus (SLE)
High unmet need for systemic lupus erythematosus (SLE) Disease activity Chronic disease with unpredictable, recurring flares Widespread organ and tissue damage: Any part of the body, including skin, joints, heart, lungs, blood, liver, kidneys, and brain Time About 90% women, usually of childbearing
Slide 8: Lupus epidemiology in select countries
Lupus epidemiology in select countries 2015 diagnosed US (398k) EU & Japan (209k) patients 2015 medicine- US (358k) EU & Japan (188k) treated patients (90%) Patient Severe, 20% Moderate, 40% segmentation Mild, 40% Hydroxychloroquine, oral HCQ, oral and IV corticosteroids (OCS), steroids, MMF, NSAID
Slide 9: Many challenges to medicine development in lupus
Many challenges to medicine development in lupus Waxing and waning Disease assessments not nature of disease sensitive to changes Evolving knowledge of Heterogeneity of organ underlying manifestations pathophysiology Only o ne n ew medicine approval in close to 60 years and multiple failures since T
Slide 10: Anifrolumab mechanism of action
Anifrolumab mechanism of action Maturation of monocytes which enhances the Type I interferons Anifrolumab function of effector T cells Interferons Expression of BLyS from dendritic cells which drive multiple enhances survival of B cells pathways central to Expansion of plasma cells and pathogenesis
Slide 11: Mounting evidence and support for anifrolumab as a potential future medicine
Mounting evidence and support for anifrolumab as a potential future medicine High Interferon Gene Signature is Geographic Differences in Demographics, Associated with Increased Disease Activity, Clinical Characteristics, and Standard of Reduced Complement C3 and C4, and Care in Multinational Studies
Slide 12: Anifrolumab Phase II lupus/SLE
Anifrolumab Phase II lupus/SLE Richard Alan Furie, MD Chief, Division of Rheumatology, North Shore-LIJ Health System
Slide 13: Anifrolumab, an Anti-Interferon-Alpha Receptor Monoclonal Antibody in SLE
OP3223 Anifrolumab, an Anti-Interferon-Alpha Receptor Monoclonal Antibody, in Moderate to Severe Systemic Lupus Erythematosus (SLE) R Furie’, JT Merrill?, VP Werth**, M Khamashta®, K Kalunian®, P Brohawn’, G Illei’, J Drappa’, L Wang’, S Yoo® ‘Division of Rheumatology, Hofstra North Shore -LIJ Schoo
Slide 14: The type I interferon system in systemic lupus erythematosus
The type | interferon system in systemic lupus erythematosus * Central pathogenic mediator in SLE"? * Trial results for sifalimumab? and rontalizumab* have been mixed * All type | IFN signaling is mediated by the type N/A Aatrotumab | IFN-a receptor (IFNAR)> weNARA| | | rar * Inhibiting IFNAR has th
Slide 15: Key eligibility and stratification
15 Key eligibility and stratification Inclusion 1. Positive ANA and/or elevated anti-dsDNA and/or anti-Sm antibodies 2. Moderate to severe active SLE, defined as: SLEDAI-2K 26 and BILAG 2004 organ domain scores of 21A or 22B and PGA 21.0 and Clinical SLEDAI-2K score 24 points (Day 1) 3. Stable treat
Slide 16: Study design
Study design E SOC + Anifrolumab 300 mg IVQ4W = (N=99) E SOC + Anifrolumab 1,000 mg IV Q4W (N = 104) (N = 102) SOC + Placebo IV Q4W Day 1 85 113 169 281 309 365 Follow-up 2) c Cc ® ® et °o ” oO Potential steroid tapering visits Aocs tapering target yy Endpoints measured Primary efficacy measure * SL
Slide 17: Baseline demographics (mITT population)
17 Baseline demographics (mITT population) Age (years) Mean (SD) Male Sex, n (%) Female Hispanic Ethnicity, n (4) Non-Hispanic White Black Asian American Indian or Alaskan Native Other Race, n (%) mITT, modified intention-to-treat; SD, standard deviation Placebo (N=102) 39.3 (12.9) 9 (8.8) 93 (91.2)
Slide 18: Baseline disease characteristics
Baseline disease characteristics (mITT population) Anifrolumab | Anifrolumab Placebo (W=102) | {weooy | wwetogy SLEDAI-2K score Mean (SD) 11.1 (4.4) 10.7 (3.7) 10.9 (4.1) Clinical SLEDAI score Mean (SD) 9.0 (2.9) 8.9 (2.5) 8.9 (3.0) BILAG 2004 score Mean (SD) 19.8 (5.8) 19.6 (5.8) 18.6 (5.7) PGA sco
Slide 19: Baseline concomitant therapies
Baseline concomitant therapies (mITT population) Anifrolumab | Anifrolumab Placebo wwet02) | eoa) | (Wet04) Ocs n(%) 88 (86.3) 79 (79.8) 91 (87.5) ee 210 mg/day 64 (62.7) 55 (55.6) 63 (60.6) <10 mg/day 38 (37.3) 44 (44.4) 41 (39.4) Anti-malarial n(%) 75 (73.5) 76 (76.8) 68 (65.4) Immunosuppressives
Slide 20: Patient disposition (mITT population)
Patient disposition (mITT population) Anifrolumab | Anifrolumab Placebo (N=102) 300 mg 1,000 mg (N=99) (N=104) Completed treatment, n (%) 71 (69.6) 87 (87.9) 76 (73.1) Reasons for not completing treatment Withdrawal of consent, n (%) 13 (12.7) 3 (3.0) 5 (4.8) AE, n (%) 8 (7.8) 2 (2.0) 10 (9.6) Death
Slide 21: SRI(4) including OCS taper
SRI(4) including OCS taper Primary endpoint Secondary endpoint * Day 169 ss Day 365 40 40 = = § 34.3 § =e 28.8 as 8 = 17.6 « 0 0 All patients All patients N=305 N=305 300mg 1,000 mg 300mg 1,000 mg Delta: 16.7% 11.2% 26.0% 13.0% OR: 238 1.94 3.08 1.84 90% Cl: (1.33, 4.26) (1.08, 3.49) (1.86, 5.09) (1
Slide 22: SRI(4) including OCS taper
SRI(4) including OCS taper it Day 169 * Day 365 Responders (%) All patients IFN high All patients IFN high N=305 N=229 (75%) N=305 N=229 (75%) 300mg 1,000mg 300mg 1,000 mg 300mg 1,000mg 300mg 1,000 mg Delta: 16.7% 11.2% 22.8% 15.0% 26.0% 13.0% 32.3% 18.8% OR: 2.38 1943.55 2.65 3.08 184-4300 2.52 90%
Slide 23: SRI(4) including OCS taper
SRI(4) including OCS taper it Day 169 = Day 365 Responders (%) All patients IFN high IFN low All patients IFN high IFN low N=305 N=229 (75%) N=76 (25%) N=305 N=229 (75%) N=76 (25%) 300mg 1,000mg 300mg 1,000mg 300mg 1,000 mg 300mg 1,000mg 300mg 1,000mg 300mg 1,000 mg Delta: 16.7% 11.2% 22.8% 15.0% -1
Slide 24: SRI(4) excluding OCS taper
24 SRI(4) excluding OCS taper Day 169 Day 365 300 mg 1,000 mg 300 mg 1,000 mg Day 365 80 5 Delta: 13.3% 16.5% 22.4% 13.6% 80 ) 60 | 60 | ¥ = 2 $ 40 | 2 40 | a a 2 e x 20 + 20 4 0 29 57 85 113 141 169 197 225 253 281 309 337 365 D: 300mg 1,000 mg ays etched acaba Delta: 22.4% 13.6% & Anifrolumab 300
Slide 25: SRI(5) in patients with baseline SLEDAI score of 5 or more
25 2 “ps0.05 compared with placebo SRI(5) in patients with a baseline SLEDAI score of 25 SRI(5) Day 169 Day 365 N=304 300 mg 1,000 mg 300 mg 1,000 mg Day 365 Delta: 10.0% 11.3% 20.1% 17.2% s & Responders (%) & nN o Response (%) nN J 0 0 29 57 85 113 141 169 197 225 253 281 309 337 365 Days 300mg 1,0
Slide 26: SRI(6) in patients with baseline SLEDAI score of 6 or more
26 Responders (%) & 3 “ps0.05 compared with placebo SRI(6) in patients with a baseline SLEDAI score of 26 SRI(6) Day 169 Day 365 N=304 300 mg 1,000 mg — 300 mg 1,000 mg Day 365 80 » Delta: 10.0% 8.4% 21.1% 16.3% 60 60 4 i ot soe oP 8 é 20 20 0 0 0 29 57 85 113 141 169 197 225 253 281 309 337 365 Day
Slide 27: SRI(7) in patients with a baseline SLEDAI score of 7 or more
27 SRI(7) in patients with a baseline SLEDAI score of 27 SRI(7) Day 169 Day 365 N=278 300 mg 1,000 mg _300 mg 1,000 mg Day 365 80 » Delta: 6.3% 8.0% 19.5% 10.2% 60 + z al ¢ FA g0 5 : E20 - &20 4 0 0 0 29 57 85 113 141 "len 225 253 281 309 337 365 300 mg 1,000 mg Delta: 19.5% 10.2% & Anifrolumab 300
Slide 28: BICLA response
28 BICLA response All patients Day 169 Day 365 20 N=302 300 mg 1,000 mg 300 mg 1,000 mg Delta: 19.8% 19.4% 27.8% 15.5% = 60 : Fa s g 20 ° 0 29 57 85 113 141 169 197 225 253 281 309 337 365 Days ® Placebo & Anifrolumab 300 mg Q4W @ Anifrolumab 1,000 mg Q4W “ps0.05 compared with placebo ad Delta=dosag
Slide 29: BICLA response
BICLA response All patients Day 169 Day 365 20 N=302 300 mg 1,000 mg 300 mg 1,000 mg Delta: 19.8% 19.4% 27.8% 15.5% 60 : 40 20 0 29 57 85 113 141 169 197 225 253 281 309 337 365 Days IFN high Day 169 Day 365 N=227 300 mg 1,000mg 300 mg 1,000 mg Delta: 19.1% 19.8% 28.3% 18.4% 0 29 57 85 113 141 169 1
Slide 30: BICLA response
BICLA response All patients Day 169 Day 365 20 N=302 300 mg 1,000 mg 300 mg 1,000 mg Delta: 19.8% 19.4% 27.8% 15.5% 60 : 40 20 0 29 57 85 113 141 169 197 225 253 281 309 337 365 Days IFN high Day 169 Day 365 IFN low Day 169 Day 365 80 N=227 300 mg 1,000 mg 300mg 1,000 mg 20 N=75 300 mg 1,000 mg 300
Slide 31: Low disease activity at Day 365
Low disease activity at Day 365 Percentage of patients with SLEDAI 2K <2 40 Responders (%) 8 Day 365 300mg 1,000 mg Delta: 17.8% 15.1% OR: 2.68 2.35 90% Cl: (1.53, 4.70) (1.34, 4.11) p: 0.004 0.012 ® Placebo B® Anifrolumab 300 mg Q4W @ Anifrolumab 1,000 mg Q4W ™ Delta=dosage vs. placebo mITT populat
Slide 32: Major clinical response at Day 365
Major clinical response at Day 365 Major clinical response: + BILAG 2004 Index C score or better at Day 169 + Maintenance of response through Day 365 20 5 = 8 $10 3 g 4 0 4 Day 365 300mg 1,000 mg Delta: 12.3% 10.4% OR: 3.24 2.88 90% Cl: (1.49, 7.04) (1.32, 6.26) p: 0.012 0.025 ™@ Placebo & Anifrolum
Slide 33: Reduction in CLASI activity
33 Reduction in CLASI activity 250% improvement in patients with CLASI activity score 210 at baseline (N=77) Day 169 Day 365 Day1 300mg 1,000 mg 300mg 1,000 mg Delta: 43.6% 39.4% 32.2% 27.5% OR: 7.341 5.16 449 2.97 90% Cl: (2.56, 20.86) (1.81, 14.73) (1.67, 12.12) (1.08, 8.19) Pp: 0.002 0.010 0.013
Slide 34: Corticosteroid reduction
34 Corticosteroid reduction OCS s7.5 mg/day in patients with 210 mg/day at baseline (N=182) 60 is Responders (%) & nN o a Day 169 Day 365 300mg 1,000 mg 300mg 1,000 mg Delta: 20.5% 8.3% 29.8% 5.1% OR: 2.48 1.44 3.59 1.23 90% Cl: (1.28, 4.80) (0.75, 2.78) (1.87, 6.89) (0.64, 2.37) p: 0.023 0.358 0.00
Slide 35: BILAG 1A/2B flares
BILAG 1A/2B flares Anifrolumab Anifrolumab joan 300 mg 1,000 mg (N=99) (N=104) Patients with flares, n (%) 17 (16.7) 12 (12.1) 12 (11.5) Total number of flares 53 25 36 Total duration of follow-up, years 85.1 93.8 92.2 ® Placebo B® Anifrolumab 300 mg Q4W @ Anifrolumab 1,000 mg Q4W 35 - mITT populati
Slide 36: FACIT-Fatigue and SF-36 at Day 365
FACIT-Fatigue and SF-36 at Day 365 60 FACIT-Fatigue SF-36 ] a Pcs mcs = = 40 rs Pa 3 oo c 2 & 5 a g @ 8 20 es é 4 0 4 >3-point 23.1-point 23.8-point improvement improvement improvement 300mg 1,000 mg 300mg 1,000 mg 300mg 1,000 mg Delta: 8.0% 6.6% Delta: 9.3% 2.1% 9.9% 7.2% OR: 1.46 1.35 OR: 1.51 1.1
Slide 37: Changes in C3 and anti-dsDNA at Day 365
37 Changes in C3 and anti-dsDNA at Day 365 Complement C3* Anti-dsDNA* Mean change from baseline, mg/dl (SE) Mean change from baseline, |U/ml (SE) Day 365 Day 365 300mg 1,000 mg 300mg 1,000 mg Delta: 5.26 4.32 Delta: -45.9 19.4 Pp: 0.277 0.242 Pp: 0.067 0.144 & Anifrolumab 300 mg Q4W M Anifrolumab 1,
Slide 38: Neutralization of 21-gene type I IFN signature
38 Neutralization of 21-gene type | IFN signature* Last dose a 8 8 8 2 = J o (Median absolute deviation) & 88s Median (100-% neutralization) n So 0 29 57 85 113 141 169 197 225 253 281 309 337 365 396 422 Days ® Placebo & Anifrolumab 300 mg Q4W @ Anifrolumab 1,000 mg Q4W “Based on patients with posi
Slide 39: Adverse events: safety population
Adverse events: safety population Placeb Anifrolumab | Anifrolumab | Anifrolumab AE, n (%) pay 300 mg 1,000 mg Total (Nes) (N=99) (N=105) (N=204) At least 1 event 78 (77.2) 84 (84.8) 90 (85.7) 174 (85.3) Atleast 1 event of special interest 12 (11.9) 10 (10.1) 15 (14.3) 25 (12.3) At least 1 serious e
Slide 40: Adverse events of special interest: safety population
40 Adverse events of special interest: safety population Piscean Anifrolumab | Anifrolumab | Anifrolumab Preferred Term, n (%) (N=101) 300 mg 1,000 mg Total (N=99) (N=105) (N=204) Herpes zoster 2 (2.0) 5 (5.1)? 10 (9.5) 15 (7.4) Influenza 2 (2.0) 6 (6.1) 8 (7.6) 14 (6.9) Varicella 0 (0.0) 1 (1.0) 0
Slide 41: Conclusions
41 Conclusions + Substantial benefit was achieved across multiple global and organ-specific disease activity measures * The greater efficacy seen in patients with a high IFN gene signature supports the pathobiology of this treatment strategy + Safety and tolerability were acceptable + Phase III stud
Slide 42: Anifrolumab current & future plans
Anifrolumab current & future plans David J. Chang, MD VP and Head, Inflammation, Autoimmunity & Neuroscience, Global Medicines Development
Slide 43: Potential differentiators of anifrolumab in SLE
Potential differentiators of anifrolumab in SLE • Most advanced molecule targeting IFNAR1 First-in-class • Blocks all Type 1 interferons (not just IFN-α) mechanism of action • 26.0% treatment difference vs. placebo on SRI(4) Potential best-in-disease response at day 365 with a sustained reducti
Slide 44: TULIP trial objectives
TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) Trial objectives Primary • Evaluate the effect of anifrolumab compared to placebo on disease activity objective as measured by SLE Responder Index of ≥4 [SRI(4)] at week 52 Evaluate the effect of anifrolumab compared to placebo on: •
Slide 45: Trial design
Trial design Design Phase III multi-center, randomised, double-blind, placebo controlled trial Protocol D3461C00005 D3461C00004 number TULIP SLE 1 TULIP SLE 2 Sample ~170 sites ~140 sites size 450 patients 360 patients Trial Adults with active moderate-to-severe SLE, ANA1 (+) and/or elevated ant
Slide 46: Trial schema
Trial schema Screening period Treatment period Follow-up 8 weeks Day -30 to day -1 52 weeks Follow-up period W W W W W W W W W W W W 4 8 12 16 20 24 28 32 36 40 44 48 Randomisation Week 52 Week Primary endpoint: week 0, day 1 SRI(4) 64 Patients completing the trial are eligible for long-term ex
Slide 47: Anifrolumab development status
Anifrolumab development status Phase III SLE programme initiated • Final data available: 2018 • Regulatory submission: 2019 Life-cycle management programme • Phase II lupus nephritis trial expected to start before year-end • Phase I subcutaneous administration trial also expected to start before y
Slide 48: Questions & Answers
Questions & Answers Participants • Richard Alan Furie, MD, Chief, Division of Rheumatology, North Shore-LIJ Health System • Bing Yao, Head of Respiratory, Inflammation & Autoimmunity iMED, MedImmune • David J. Chang, MD, VP and Head, Inflammation, Autoimmunity & Neuroscience, Global Medicines Devel
Slide 49: Confidentiality Notice
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