Astrazeneca Plc · LSE:AZN
Astrazeneca — ASCO Genitourinary Cancers Symposium 2022
35 slides from Astrazeneca's conference presentation, Feb 23, 2022
Slide 1: Investor science conference call: ASCO GU Cancers Symposium 2022
Investor science conference call: American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium 2022 Conference call for investors and analysts 23 February 2022
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 of 1995, AstraZeneca (hereafter ‘the Group’) provides the following cautionary statement: this document contains certain forward-looking statements wit
Slide 3: Speakers
Dr Fred Saad Susan Galbraith Principal Investigator PROpel, Executive Vice President, Professor and Chief of Urology, Oncology R&D University of Montreal Hospital Centre, Canada Sunil Verma Dave Fredrickson Senior Vice President, Speakers Executive Vice President, Global Head of Oncology, Oncology B
Slide 4: Agenda
1 Introduction: AstraZeneca @ ASCO GU 2022 Agenda 2 Lynparza Phase III PROpel trial 3 Opportunity and unmet need in mCRPC 4 Other ASCO GU highlights 5 Closing and Q&A 4
Slide 5: Introduction
1 Introduction Susan Galbraith Executive Vice President, Oncology R&D
Slide 6: Comprehensive portfolio to combat cancer
Comprehensive portfolio to combat cancer Diverse pipeline with potential for orthogonal combinations Tumour drivers Oncogenic truncal drivers Redirect local immunity Immune and resistance and mechanisms of resistance Awaken dormant immune cells engagers DNA damage Synthetic lethality response exploi
Slide 7: ASCO GU 2022
ASCO 19 abstracts with Data GU 2022 three oral presentations highlights • Lynparza + abiraterone in 1st-line mCRPC • Two Oral presentations PROpel Phase III trial • One Mini-oral presentation • Lynparza + Imfinzi in 1st-line urothelial carcinoma • 16 Posters BAYOU Phase II trial • 19 Abstracts accep
Slide 8: Lynparza and abiraterone
Lynparza and abiraterone Success in Study 08 paved the way for PROpel in 1st-line mCRPC Study 081 PARP-signaling and Phase II trial AR-signaling pathway interaction may explain combined effect Lynparza + abiraterone2-4 PARP involved in androgen- NHA-induced HRR deficiency receptor–dependent increasi
Slide 9: Lynparza PROpel
2 Lynparza PROpel Dr Fred Saad Principal Investigator, PROpel Phase III trial
Slide 10: PROpel trial design
PROpel A global randomised double-blind Phase III trial Olaparib 300 mg bid Primary endpoint Patient population + • Radiographic progression or death (rPFS) • 1L mCRPC abiraterone 1000 mg qd* • Docetaxel allowed at by investigator assessment mHSPC stage n=399 • No prior abiraterone Full dose of ola
Slide 11: Baseline patient characteristics
Baseline patient characteristics Well-balanced between treatment arms Olaparib + abiraterone Placebo + abiraterone (n=399) (n=397) Median (range) age, years 69.0 (43–91) 70.0 (46–88) ECOG performance status, n (%) 0 286 (71.7) 272 (68.5) 1 112 (28.1) 124 (31.2) Symptomatic,* n (%) 103 (25.8) 80 (20.
Slide 12: Primary endpoint: rPFS by investigator assessment
Primary endpoint: rPFS by investigator-assessment 34% risk reduction of progression or death with olaparib + abiraterone 12-month rate 1.0 71.8% 24-month rate 0.9 Olaparib + Placebo + 63.4% 51.4% 0.8 abiraterone abiraterone 33.6% (n=399) (n=397) 0.7 Probability of rPFS Events, n (%) 168 (42.1) 226 (
Slide 13: Secondary endpoint: rPFS by blinded independent central review
Secondary endpoint: rPFS by blinded independent central review* 39% risk reduction of progression or death, highly consistent with the primary analysis 1.0 12-month rate 73.8% Olaparib + Placebo + 0.9 24-month rate abiraterone abiraterone 60.6% 53.7% 0.8 (n=399) (n=397) 34.1% 0.7 Events, n (%) 157 (
Slide 14: Subgroup analysis of rPFS
Subgroup analysis of rPFS rPFS benefit observed across all pre-specified subgroups Number of Median rPFS, HR (95% CI) patients, n months All patients 796 24.8 16.6 0.66 (0.54‒0.81) Age at randomization <65 227 NR 16.4 0.51 (0.35‒0.75) ≥65 569 22.0 16.7 0.78 (0.62‒0.98) ECOG performance status at bas
Slide 15: Secondary endpoint: overall survival
Secondary endpoint: overall survival 28.6% maturity; trend towards improved OS with olaparib + abiraterone 1.0 0.9 Olaparib + Placebo + abiraterone abiraterone 0.8 (n=399) (n=397) 0.7 Probability of OS Events, n (%) 107 (26.8) 121 (30.5) 0.6 0.5 Median OS NR NR (months) 0.4 0.86 (0.66‒1.12) 0.3 HR (
Slide 16: Secondary endpoints: TFST and PFS2
Secondary endpoints: TFST and PFS2 TFST and PFS2 results support longer-term benefit with olaparib + abiraterone Time to first subsequent therapy or death Time to second progression or death (TFST) (PFS2) 1.0 1.0 Probability of not experiencing first subsequent Probability of second progression-free
Slide 17: Overall safety profile
Overall safety profile A relatively small increase in discontinuations for olaparib vs placebo, discontinuation with abiraterone was similar between treatment arms Olaparib + abiraterone Placebo + abiraterone n (%) (n=399) (n=397) Any AE 387 (97.2) 376 (94.9) Any AE CTCAE Grade ≥3 188 (47.2) 152 (38
Slide 18: Cardiac and thromboembolic adverse events
Cardiac and thromboembolic adverse events • Cardiac failure and arterial thromboembolic events were balanced between the two arms • Numerically higher venous thromboembolic events were reported for olaparib + abiraterone ▪ Pulmonary embolism was the most commonly reported venous thromboembolic event
Slide 19: Most common adverse events
Most common adverse events AE profile was consistent with the known toxicity profiles for the individual drugs Olaparib + abiraterone (n=399) Placebo + abiraterone (n=399) Any 97.2 47.2 38.4 94.9 Anemia* 46.0 15.1 3.3 16.4 Fatigue or asthenia 37.2 2.3 1.5 28.3 Nausea 28.1 0.3 0.3 12.6 Diarrhea 17.3
Slide 20: Conclusions
Conclusions • Olaparib + abiraterone led to a significant and clinically meaningful improvement in rPFS (HR 0.66 [95% CI 0.54–0.81]) over placebo + abiraterone in 1L mCRPC ‒ Benefit observed led to a median rPFS beyond 2 years ‒ Benefit was observed irrespective of HRRm status • Secondary and explor
Slide 21: Opportunity and unmet need in mCRPC
3 Opportunity and unmet need in mCRPC Dave Fredrickson Executive Vice President, Oncology Business Unit
Slide 22: Prostate is the second most common cancer in male patients
Prostate is the second most common cancer in male patients mCRPC therapies are limited; mostly monotherapy, including in first line Hormone sensitive Castration resistant Urologist-led Urologists and oncologists Urologists and oncologists Primary/ Biochemical mHSPC nm 1st-line metastatic 2nd-line+ m
Slide 23: PROpel: unprecedented clinical benefit, a potential new SoC in mCRPC
PROpel - unprecedented clinical benefit without compromising quality of life - a potential new SoC in mCRPC 300 Outcomes remain poor PROpel mg + abiraterone in advanced prostate cancer building on the success of PROfound a potential new standard of care 40% • Representative real-world population - •
Slide 24: Addition of Lynparza achieves similar absolute rPFS improvement
After almost a decade, the addition of Lynparza achieves a similar absolute rPFS improvement compared to the pivotal trial that established abiraterone as first-line SoC COU-AA-3021 (2012) PROpel (2022) Lynparza control abiraterone Dif. abi Dif. + abiraterone Median rPFS 8.2m 16.4m 8.2m 16.6m 24.8m
Slide 25: PROpel: a new treatment approach in 1st-line mCRPC
PROpel: a new treatment approach in 1st-line mCRPC 1st-line metastatic castration-resistant prostate cancer (mCRPC) - US patients NHA naïve ~50% Prior NHA use ~50% Other (~25%) Receiving NHA ( ~75%) Receiving NHA ( ~55%) Other (~45%) HRRm 20-30% Overall, ~65% of 1st-line mCRPC patients receive an NH
Slide 26: Other ASCO GU highlights
4 Other ASCO GU highlights Susan Galbraith Executive Vice President, Oncology R&D
Slide 27: New advances in urothelial carcinoma
New advances in urothelial carcinoma Phase II data advancing understanding of this aggressive cancer Imfinzi + Lynparza: Phase II BAYOU trial Enhertu: Phase II U105 trial Platinum-ineligible patients with mUC 100 Combination with nivolumab Change in Sum of Diameters from Baseline, % 80 Primary and s
Slide 28: Closing and Q&A
5 Closing and Q&A
Slide 29: Investor Relations
Chris Sheldon Josie Afolabi chris.sheldon@astrazeneca.com josie.afolabi@astrazeneca.com Tom Waldron Morgan Sanford Investor tom.waldron@astrazeneca.com morgan.sanford@astrazeneca.com Relations Christer Gruvris Philip Sparks christer.gruvris@astrazeneca.com philip.sparks1@astrazeneca.com Lauren Swale
Slide 30: Appendix
A Appendix
Slide 31: PROpel
PROpel 31
Slide 32: Olaparib and abiraterone: A randomised Phase II trial
Olaparib and abiraterone: A randomised Phase II trial • Patients with mCRPC, unselected by HRRm status, with prior docetaxel treatment • Randomized 1:1 to full dose of olaparib + abiraterone vs placebo + abiraterone • Statistically significant improvement in rPFS with olaparib + abiraterone, irrespe
Slide 33: ORR in patients with measurable disease
ORR in patients with measurable disease 10% improvement in ORR with olaparib + abiraterone OR 1.60 (95% CI 1.02‒2.53) P=0.0409* 70 ORR 60 58.4% ORR 50 48.1% 321/796 patients (40.3%) Rate (%) had measurable disease 40 by RECIST v1.1 criteria SD SD 54.0% PR 30 26.1% 28.1% PD at baseline 41.9% PR PD 19
Slide 34: FACT-P quality of life over time
FACT-P quality of life over time Quality of life comparable between treatment arms Least-squares mean change from baseline 20 in FACT-P total score* 15 Olaparib + abiraterone (n=399) Least-squares mean change from baseline in FACT-P total score* Placebo + abiraterone (n=397) 10 5 0 -5 -10 -15 -20 5
Slide 35: Use of AstraZeneca slides from conference calls and webcasts
Use of AstraZeneca slides from conference calls and webcasts 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 available to th
AstraZeneca — ASCO Genitourinary Cancers Symposium 2022 on 6ix