Astrazeneca Plc · LSE:AZN
Astrazeneca — American College of Rheumatology Annual Meeting 2019
42 slides from Astrazeneca's conference presentation, Nov 13, 2019
Slide 1: Investor science call: American College of Rheumatology's Annual Meeting 2019
Investor science call: American College of Rheumatology’s Annual Meeting 2019 Conference call for investors and analysts 13 November 2019
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, pe
Slide 3: Agenda
Agenda Introduction Anifrolumab Phase III TULIP 1 trial Anifrolumab Phase III TULIP 2 trial Next steps Q&A 3
Slide 4: 2019: a very busy year for the pipeline
2019: a very busy year for the pipeline Investor science events in each therapy area Oncology Cardiovascular, renal Respiratory and metabolism (and immunology) American Society of European Society of American College of Clinical Oncology (Jun) Cardiology (Sep) Rheumatology (Nov) • Meet AZN managemen
Slide 5: Speakers
Speakers Dr. Richard Furie Richard Marshall Primary Investigator, Phase II MUSE and Senior Vice President and Head of Phase III TULIP 1 trial and Chief of the Late-stage Development, Division of Rheumatology at Northwell Respiratory, Inflammation and Health, New York, US Autoimmunity Prof. Eric Mora
Slide 6: Agenda
Agenda Introduction Anifrolumab Phase III TULIP 1 trial Anifrolumab Phase III TULIP 2 trial Next steps Q&A 6
Slide 7: SLE: Clinical Heterogeneity
SLE: Clinical Heterogeneity 7 SLE, systemic lupus erythematosus. Image credit R. Furie /BSIP/ B. Tapper/C. Barry /N.Doss /AProhic /ISM
Slide 8: Current SLE Therapies
Current SLE Therapies ¢ NSAIDs* ¢ Steroids (low dose to “pulse”)* ¢ Antimalarials (hydroxychloroquine; chloroquine)* ¢ Immunosuppressives (MMF; AZA, MTX; calcineurin inh) * Chemotherapy (cyclophosphamide) * Biologics (belimumab*; rituximab; abatacept) * Miscellaneous (thalidomide/lenalidomide; quina
Slide 9: SLE: Unmet Needs
SLE: Unmet Needs ¢ Lupus nephritis * Severe extra-renal disease * Damage prevention — Flare prevention — Steroid- and immunosuppressive-sparing ¢ Remission induction
Slide 10: Importance of Type I Interferons in SLE
10 Importance of Type | Interferons in SLE * Elevated IFN-a levels’ * SLE sera induce IFN gene signatures? * IFN gene signatures in PBMC of patients with SLE * Clinical and serologic activity correlate with IFN gene expression*5 * Genetic susceptibility loci in the type | IFN pathway® * Type II IFN
Slide 11: Phase II MUSE Study: Primary Endpoint SRI(4) at Week 24
Phase 2 MUSE Study: Primary Endpoint SRI(4) at Week 24, Including Steroid Taper 60 4 a o Responders (%) & Placebo Anifrolumab Anifrolumab 300 mg 1,000 mg Delta vs placebo: 16.7 11.2 OR: 2.38 1.94 (90% Cl): (1.33-4.26) (1.08-3.49) P-value: 0.014 0.063 11 Cl, confidence interval; OR, odds ratio; SRI,
Slide 12: TULIP-1 Study Design
TULIP-1 Study Design Adults with moderately to severely active SLE Saninie size 123 sites Patient — SLEDAI 26, 21 BILAG Aor 22 B, PGA21 e + 457 randomized patients population Seropositive (ANA or anti-dsDNA or anti-Sm) Receiving standard of care US/Canada, 40.7% > Fi G hi Europe, 37.9% Treatment 2:1
Slide 13: SRI vs BICLA: Composite Disease Activity Measure
SRI vs BICLA: Composite Disease Activity Measure * Both measures are binary (responder/nonresponder) + Both measures consist of 5 components Responder Definition: SRI(4) 24-point of SLEDAI-2K from baseline No new organ system affected (BILAG-2004) No worsening in PGA No use of restricted medications
Slide 14: Efficacy: Primary and Key Secondary Endpoints
Efficacy: Primary and Key Secondary Endpoints Primary and Key Placebo Anifrolumab Plot of Treatment Difference Secondary Endpoints? (n=184) 300 mg (n=180) (95% Cl) Prim: SRI(4) at Week 52, % SRI(4) at Week 52 in IFNGS test-high patients, % Sustained OCS reduction to $7.5 mg/d Weeks 40-52. 250% reduc
Slide 15: Prespecified and Amended Restricted Medication Rules
15 Prespecified and Amended Restricted Medication Rules Composite efficacy endpoints include nonresponse classification for restricted medication use ~8% of patients were misclassified as nonresponders for NSAID use This led to a review of all restricted medication responder classification rules — A
Slide 16: Primary and Key Secondary Endpoints: Prespecified and Amended (Post hoc)
Primary and Key Secondary Endpoints: Prespecified and Amended (Post hoc) Anifrolumab 300 mg (n=180) Primary and Key Secondary Endpoints* Placebo (n=184) Plot of Treatment Difference Nominal 1 Analysis (95% Cl) P-Value® Py cified Primary: SRI(4) at Week 52, % —— Sore eee Amended 43.0 46.9 e-e—e 0.46
Slide 17: BICLA Response: Amended Medication Rules (Post Hoc)
7 BICLA Response: Amended Medication Rules (Post Hoc)? Percentage of Responders Time to BICLA Response Sustained to 52 weeks ae Week 52 difference = 16.4 Ey 70 (95% Cl: 6.7, 26.2) @ 60 Anifrolumab g 300 mg (n=180) © 50 ES 46.1 & 40 a) 32 30 29.6 o 8 20 Placebo (n=184) 10 g a 0 4 8 12 16 20 24 28 32
Slide 18: Clinical Endpoints: Amended Medication Rules (Post Hoc)
Clinical Endpoints: Amended Medication Rules (Post Hoc)? SI Response” OCS Reduction to $7.5 mg/d Annualized Flare Rate ue Weeks 40 to 52° Through Week 52° Week 12 difference = 18.7 Difference = 16.7 Rate ratio = 0.83 (95% Cl: 1.4, 36.0) (95% Cl: 3.5, 29.8) (95% Cl: 0.60, 1.14) is Nominal P=0.034 ~ N
Slide 19: Adverse Event Profile During Treatment Period
Adverse Event Profile During Treatment Period Placebo Anifrolumab Anifrolumab Adverse Event Category, n (%)* (n=184) 150 mg (n=93) 300 mg (n=180) Any adverse event 144 (78.3) 79 (84.9) 161 (89.4) Serious adverse event 30 (16.3) 10 (10.8) 25 (13.9) Serious adverse event in 22 patients in either anifr
Slide 20: Summary
20 Summary * The primary endpoint, SRI(4), was not achieved in TULIP-1 * Post hoc analyses suggest potential efficacy of anifrolumab, including steroid reduction, CLASI, BICLA and joints ¢ Anifrolumab 300 mg suppressed IFNGS and was generally well tolerated ¢ The totality of data across trials and e
Slide 21: Agenda
Agenda Introduction Anifrolumab Phase III TULIP 1 trial Anifrolumab Phase III TULIP 2 trial Next steps Q&A 21
Slide 22: TULIP-2 Study Design
TULIP-2 Study Design Adults with moderately to severely active SLE Study — SLEDAI26, 21 BILAG A or 22 B, and PGA21 Sample size population Seropositive (ANA or anti-dsDNA or anti-Sm) Receiving standard of care =135 sites 362 patients received therapy United States/Canada, 36.5% . Europe, 26.8% 1:1 ra
Slide 23: Baseline Patient Characteristics
Baseline Patient Characteristics Placebo Anifrolumab 300 mg Patient Characteristic (n=182) (n=180) Age, mean (SD), years 41.1 (11.47) 43.1 (11.95) Female, n (%) 170 (93.4) 168 (93.3) White, n (%)# 107 (58.8) 110 (61.1) Asian, n (%)* 30 (16.5) 30 (16.7) Black/African American, n (%)# 25 (13.7) 17 (9.
Slide 24: Primary and Key Secondary Endpoints
Primary and Key Secondary Endpoints Anifrolumab Treatment Treatment Significant Placebo 300 mg Difference Plot Difference Adjusted Following Endpoint? niN (%) nIN (%) (95% Cl) (95% Cl) | P-Value = Multiplicity Primary: BICLA response at Week 52 57/182 (31.5) 86/180 (47.8) H Leo 16.3 (6.3, 26.3) 0.00
Slide 25: Primary Outcome Measure: BICLA Response at Week 52
25 Primary Outcome Measure: BICLA Response at Week 52 a o > o N o Responders (% of patients, 95% Cl) 2 wo o o o Week 52 Difference: 16.3 95% Cl: 6.3%, 26.3% Adjusted P-value: 0.001 Anifrolumab 300 mg 86/180 (47.8%) Placebo 57/182 (31.5%) o 24 BO Study Week 36 40
Slide 26: Early Onset of Action - CLASI Response at Week 12
26 Early Onset of Action - CLASI Response at Week 12 Responders (% of patients, 95% Cl) Proportion of patients with baseline CLASI 210 who achieved 250% reduction 95% Cl: 4.3, 43.6 Week 12 Difference: 24.0 Adjusted P-value: 0.039 Anifrolumab 300 mg (n=49) Placebo (n=40) 20 24 28 32 Study Week 36 52
Slide 27: Early and Sustained BICLA Response
27 Early and Sustained BICLA Response 60 - Patients with BICLA response sustained to Week 52, % Time to onset of BICLA response maintained through week 52 Hazard ratio: 1.55 95% Cl: 1.11, 2.18 | Nominal P-value: 0.011 | Number of patients at risk Anifrolumab 300 mg n= Placebo n= 180 182 178 175 8 12
Slide 28: Sustained OCS Reduction to ≤7.5 mg/d
Sustained OCS Reduction to $7.5 mg/d Proportion of patients with baseline OCS 210 mg/d who achieved reduction to $7.5 mg/d from Weeks 40 to 52 80 - Difference: 21.2 95% Cl: 6.8, 35.7 70-| | Adjusted P-value: 0.014 S 60- 51.5 xx (41.1, 61.8) § & 507 g 8 § 40-7 30.2 = 20.1, 40.3 8 & 30-7 6 ) x} = 20 -
Slide 29: Adverse Event Profile During Treatment Period
Adverse Event Profile During Treatment Period Placebo Anifrolumab 300 mg Adverse Event Category, n (%)* (n=182) n=180) ‘Any adverse event 153 (84.1) 159 (88.3) Serious adverse event 31 (17.0) 15 (8.3) Serious adverse event in 22 patients in the study Pneumonia 7 (3.8) 3 (1.7) Gastroenteritis viral 0
Slide 30: Overall Efficacy Results Were Highly Consistent Between TULIP 1, TULIP 2 and MUSE
30 Overall Efficacy Results Were Highly Consistent Between TULIP 1, TULIP 2 and MUSE Anifrolumab 300 mg Placebo Di (95% Cl) 16.3 (6.3, 26.3) 16.4 (6.7, 26.2) 28.0 (15.1, 41.0) 18.2 (8.1, 28.3) 3.9 (6.3, 14.1) 22.4 (9.0, 35.9) 17.3 (6.5, 28.2) 18.4 (7.7, 29.1) 28.3 (13.5, 43.1) 21.2 (6.8, 35.7) 16.7
Slide 31: Clinical Implications— Anifrolumab in Active SLE
Clinical Implications— Anifrolumab in Active SLE ¢ Unmet need in SLE demands better treatments — IFN pathway is active in 60%-80% of SLE patients * Robust response vs. placebo across 3 studies — Overall disease activity — highly significant BICLA responses, early and sustained — Skin disease —early
Slide 32: Agenda
Agenda Introduction Anifrolumab Phase III TULIP 1 trial Anifrolumab Phase III TULIP 2 trial Next steps Q&A 32
Slide 33: Anifrolumab: potential first-in-class treatment for SLE
Anifrolumab: potential first-in-class treatment for SLE Important new mode Anifrolumab blocks of action validated type 1 interferon • Multiple lines of evidence CELLULAR INNATE ADAPTIVE DAMAGE IMMUNE SYSTEM IMMUNE SYSTEM indicated the role of type 1 Trigger IFNs in SLE1-3 T cell • Anifrolumab data h
Slide 34: Anifrolumab results indicate important clinical potential
Anifrolumab results indicate important clinical potential Trials exhibited consistency across Data strengths should be compelling multiple clinical endpoints at 300mg dose1-3 for clinicians and patients1 • BICLA results – improvement in all organ systems • Response seen early • OCS use reduced and s
Slide 35: Kaplan Meier survival estimates
Improvement in BICLA means all organ systems with moderate to severe disease improved from baseline Examples of organ systems measured Survival probability in patients with by BICLA in the TULIP trials1 and without organ damage2 Kaplan Meier survival estimates 1.00 No organ damage 0.75 (n=69) 0.50 O
Slide 36: Around 70-80% of moderate to severe SLE patients use OCS
Around 70-80% of moderate to severe SLE patients use OCS OCS is major contributor to organ damage Significant corticosteroid use Corticosteroid-mediated in SLE patients organ damage 100 100% Corticosteroid 90 17% independent 29% 80 80% % new SDI entries 70 Possibly 60 corticosteroid 71% 60% related
Slide 37: Anifrolumab led to early onset of response
Anifrolumab led to early onset of response BICLA response CLASI response seen at pre-specified over time in TULIP 21 measure of 12 weeks in TULIP 2* Week 0 Week 12 Source: 1. Morand E et al, ACR 2019; Late breaking abstract L17. *In patients with CLASI activity score ≥10 at baseline. 37
Slide 38: Significant healthcare burden and clear unmet need
Significant healthcare burden and clear unmet need New modalities will drive the SLE market SLE Patients (000s), Top 8 Countries SLE prevalence (US, UK, ES, IT, DE, FR, JP, CN) outlook SLE, rates 2016 2018 2025E 15% 5000 Diagnosed 556k 579k prevalence 76% 760 90% Treated 90% 90% 579 523 61% 319 9% 3
Slide 39: Next steps for anifrolumab
Next steps for anifrolumab Anifrolumab is a potential first-in-class treatment Important that blocks type 1 interferon for patients with SLE news flow • TULIP 2 demonstrated superiority across multiple endpoints vs. placebo1 Trial/milestone Phase Status Detailed results • Overall efficacy results we
Slide 40: Agenda
Agenda Introduction Anifrolumab Phase III TULIP 1 trial Anifrolumab Phase III TULIP 2 trial Next steps Q&A 40
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Slide 42: Use of AstraZeneca conference call, webcast and presentation slides
Use of AstraZeneca conference call, webcast and presentation slides The AstraZeneca webcast, conference call and presentation slides (together the ‘AstraZeneca Materials’) are for your personal, non-commercial use only. You may not copy, reproduce, republish, post, broadcast, transmit, make availabl
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