Slide 1: Strategic Collaboration in Oncology: Trastuzumab Deruxtecan (DS-8201)
Strategic Collaboration in Oncology Trastuzumab Deruxtecan (DS-8201) Conference call for investors and analysts 29 March 2019
Slide 2: Important information
Important information The securities proposed to be offered pursuant to the equity placing referred to herein will not be and have not been registered under the US Securities Act of 1933, as amended, and may not be offered or sold in the United States absent registration or an applicable exemption f
Slide 3: Speakers
Speakers Pascal Soriot Dave Fredrickson Executive Director and Executive Vice President, Chief Executive Officer Oncology José Baselga Marc Dunoyer Executive Vice President, Executive Director and R&D Oncology Chief Financial Officer 3
Slide 4: DS-8201: a transformative medicine
DS-8201: a transformative medicine AstraZeneca & Daiichi Sankyo collaboration to maximize utility and value • Oncology is one of our 3 core strategic TAs, Breast Cancer one of our 4 oncology pillars • Transformative medicine for the treatment of Breast Cancer – Taxane free* treatment of HER2+ cancer
Slide 5: Building on our rich heritage in Breast Cancer
Building on our rich heritage in Breast Cancer Adds a late stage high value asset to our innovative pipeline 2020s Trastuzumab deruxtecan (DS-8201) • Imfinzi 2010s 2000s • Capivasertib 1980s 1990s • Oral SERD 1970s Sources: (1) FDA first approval history for each historical AstraZeneca asset, (2) ex
Slide 6: High unmet medical need in HER2+, HER2 low and HER2 mutant tumours
High unmet medical need in HER2+, HER2 low and HER2 mutant tumours across multiple cancer types Potential transformational medicine Prevalence of HER2 Innovative and highly potent ADC molecule status across cancer types HER2 positive 1 Her2-Low HER2m HER2 status Taxane free* treatment in HER2+ breas
Slide 7: Trastuzumab deruxtecan (DS-8201): An innovative asset with longevity beyond 2030
Trastuzumab deruxtecan (DS-8201) An innovative asset with longevity beyond 2030 Tezepelumab ** DS-8201 * AKT Inhibitor Monalizumab * Lokelma Tagrisso Calquence Imfinzi * PT010 PT027 Fasenra ** Lynparza * Farxiga Bydureon Brilinta 7 Notes: *Exclusivity period projected to extend beyond patent expiry
Slide 8: Speakers
Speakers José Baselga Executive Vice President, R&D Oncology 8
Slide 9: Significant survival gains in HER2+ breast cancer, but substantial unmet need persists
Significant survival gains in HER2+ breast cancer, but substantial unmet need persists Metastatic Breast Cancer Survival Survival Probability 9 Source: Seah et al. JNCCN 2014
Slide 10: DS-8201: A State of the Art Second Generation ADC
DS-8201: A State of the Art Second Generation ADC Designing Better Characteristics for Potentially Enhanced Clinical Benefit Drug Design Attributes Clinical DS-8201 T-DM1 Implications Payload Topoisomerase-1 Tubulin inhibitor Validated topo-1 inhibitor mechanism Drug More drug antibody High: 7-8 Low
Slide 11: DS-8201: Unprecedented efficacy in late line HER2+ metastatic breast cancer
DS-8201: Unprecedented efficacy in late line HER2+ metastatic breast cancer Pertuzumab + T-DM1 T-DM1 T-DM1 DS-8201 (Aug ’18 DCO)1 trastuzumab (1L, failed)3 (2L)4 (3L+)5 + chemo (1L)2 mPFS 18.5m 14.1m 9.6m 6.2m Not published DoR 20.2m 20.7m 12.6m 9.7m 20.7m ORR 80.2% 59.7% 43.6% 31.3% 59.5% Median pr
Slide 12: HER2+ breast cancer: Patient flow and landmark studies
HER2+ breast cancer: Patient flow and landmark studies Stage I – IIIa BC Stage IIIb – IV BC NeoSphere (Neoadjuvant) Pertuzumab + trastuzumab + CTX 46% pCR Neoadjuvant Tx KATHERINE APHINITY (Adjuvant) (Post Neoadjuvant) Post Neoadj Adjuvant Tx Pertuzumab + trastuzumab + CTX T-DM1 94% 3-yr iDFS 88% 3-
Slide 13: DS-8201: Breakthrough efficacy in HER2 low breast cancer
DS-8201: Breakthrough efficacy in HER2 low breast cancer Confirmed ORR mDoR mPFS All (N = 51) 44.2% (N=43) 9.4m 7.6m IHC 2+ (n = 24) 54.5% (N=22) 11.0m 13.6m IHC 1+ (n = 27) 33.3% (N=21) 7.9m 5.7m HR+ (n = 45) 47.4% (N=38) 11.0m 7.9m Prior CDK4/6 inhibitor (n = 15) 33.3% (N=12) NR 7.1m 13 Source: SA
Slide 14: DS-8201 in HER2 low: Compelling data vs benchmarks in HR+ breast cancer
DS-8201 in HER2 low: Compelling data vs benchmarks in hormone receptor positive (HR+) breast cancer Palbociclib + ET DS-8201 DS-8201 Alpelisib Chemo 3L+ 3L+ Endocrine 1L/2L 3L+ (n=22*, (n=21*, 1L1 2L2 2L2 PIK3CAm3 (4 studies)4 IHC2+) IHC1+) 11m mPFS 25m 10m 5m ~4m 13.6m 5.7m (Positive Ph3) ORR 42% 1
Slide 15: DS-8201: Compelling efficacy in other tumor types
DS-8201: Compelling efficacy in other tumor types HER2 expression and HER2 mutation HER2+ Gastric Cancer1 HER2+ & HER2mut NSCLC2 N=44 N=11 HER2mut Trastuzumab Ramucirumab T-DM1 DS-8201 Osimertinib Alectinib Pembrolizumab T-DM1 DS-8201 + chemo3 + chemo4 (Failed)5 EGFRm6 ALK+7 + Ctx HER2mut9 HER2mut N
Slide 16: DS-8201: ILD to be reduced by dose, less prior treatment, earlier diagnosis
DS-8201: ILD to be reduced by dose, less prior treatment, earlier diagnosis and proactive management ILD in Phase 1/2 studies1 Conclusions ▪ Higher likelihood of developing ILD All-grade Grade 5 associated with1: ➢ Higher dose (≥6.4 mg/kg) All subjects N=665 9.9% 0.8% ➢ Japanese origin: Japanese pat
Slide 17: Speakers
Speakers Dave Fredrickson Executive Vice President, Oncology 17
Slide 18: AstraZeneca Oncology building on strong growth
AstraZeneca Oncology building on strong growth Total Oncology sales New medicines Lynparza, Tagrisso, +49% FY; +61% Q4 Imfinzi and Calquence added $1.9bn $m 2,000 • Tagrisso quickly moving ahead to become the no. 1 1,750 1,500 AstraZeneca medicine in 2019 1,250 1,000 • Imfinzi strong US uptake; ex-U
Slide 19: HER2+ market today: $11bn in breast & gastric cancer
HER2+ market today: $11bn in breast & gastric cancer HER2+ patients (2018) HER2+ Sales (2018, $bn) 0k 50k 100k 150k 8.0 Gastric 7.0 Breast Neo/Adj BC 6.0 5.0 4.0 mBC 3.0 2.0 Gastric 1.0 0.0 Trastuzumab Pertuzumab T-DM1 Epi source: Kantar CancerMpact 2018 drug treated patients in first line in metast
Slide 20: DS-8201: Potential to expand HER2 market today
DS-8201: Potential to expand HER2 market today G7 treated patients (2018) 0k 100k 200k 300k 400k Current HER2+ Neo/Adj BC Treatments mBC Gastric CRC HER2+ Non-Sq NSCLC HER2 Low Pancreatic Biliary Tract* HER2mut Bladder Ovarian Head & Neck* Cervical Epi source: Kantar CancerMpact 2018 drug treated pa
Slide 21: Building DS-8201 in Breast Cancer and beyond
Building DS-8201 in Breast Cancer and beyond Neoadjuvant / adjuvant 1L metastatic 2L metastatic 3L metastatic Post neoadj: Replace trastuzumab + HER2+ Replace T-DM1 pertuzumab + chemo Replace T-DM1 Post T-DM1 Breast retreatment trastuzumab + pertuzumab + chemo HR+: Endocrine ± chemo Endocrine ± CDK4
Slide 22: AZ oncology capabilities and scale strengthen DS-8201
AZ oncology capabilities and scale strengthen DS-8201 AstraZeneca Oncology Opportunities • Clinical operations: >80 ongoing, clinical • Accelerate & expand development program development projects* ➢ New indications & combinations • Regulatory affairs: 28 major market filings for 4 key brands** • Br
Slide 23: Building our Oncology franchises
Building our Oncology franchises Significantly accelerates and expands AZ oncology portfolio Breast cancer Ovarian cancer Lung cancer Haematology Faslodex, Tagrisso, Imfinzi, Lynparza Calquence Lynparza Iressa Four disease areas with first or best-in-class cornerstone medicine 23 Source: Various AZ
Slide 24: Speakers
Speakers Marc Dunoyer Executive Director and Chief Financial Officer 24
Slide 25: Key transaction terms
Key transaction terms › Territory: Worldwide excluding Japan › Structure: co-development and co-commercialisation, 50/50 cost and profit split (ex Japan) › Supply: Daiichi Sankyo will manufacture and supply product for the collaboration › Consideration: − Non-contingent upfront cash fee of $1.35bn (
Slide 26: Capital allocation priorities unchanged
Capital allocation priorities unchanged Capital allocation priorities DS-8201 collaboration Investment in the business Accelerates Oncology strategy Progressive dividend policy Supportive Strong, investment-grade Concurrent equity placing credit rating strengthens credit profile Neutral to core EPS
Slide 27: Equity placing demonstrates commitment to credit rating
Equity placing demonstrates commitment to credit rating Equity placing to fund near-term transaction requirements and strengthen balance sheet: › Meet upfront and near term DS-8201 funding requirements − $1.35bn upfront non-contingent payment (split evenly across 2019 & 2020) − ~$1bn approval and sa
Slide 28: 2019 guidance reconfirmed
2019 guidance reconfirmed Product sales Core EPS A high single-digit percentage increase $3.50 to $3.70 Guidance at CER, post equity placing 28
Slide 29: Q&A
Q&A 29