AstraZeneca : Lynparza

Meet AZN management: ASCO 2020

Virtual breakout 3:Lynparza

Susan Galbraith, Greg Rossi

IR moderator: Nick Stone

1 June 2020

Webinar is being recorded

Forward-looking statements disclaimer

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 with respect to the operations, performance and financial condition of the Group, including, among other things, statements about expected revenues, margins, earnings per share or other financial or other measures. Although the Group believes its expectations are based on reasonable assumptions, any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual outcomes and results to be materially different from those predicted. The forward-looking statements reflect knowledge and information available at the date of preparation of this document and the Group undertakes no obligation to update these forward-looking statements. The Group identifies the forward-looking statements by using the words 'anticipates', 'believes', 'expects', 'intends' and similar expressions in such statements. Important factors that could cause actual results to differ materiallyfrom those contained in forward-looking statements, certain of which are beyond theGroup'scontrol, include, among other things: the risk of failure ordelay in delivery of pipeline or launch of new medicines; the risk of failure to meet regulatory or ethical requirements for medicine development or approval; the risk of failure to obtain, defend and enforce effective intellectual property (IP) protection and IP challenges by third parties; the impact of competitive pressures including expiry or loss of IP rights, and generic competition; the impact of price controls and reductions; the impact of economic, regulatory and political pressures; the impact of uncertainty and volatility in relation to theUK'sexit from the EU; the risk of failures or delays in the quality or execution of theGroup'scommercial strategies; the risk of failure to maintain supply of compliant, quality medicines; the risk of illegal trade in theGroup'smedicines; the impact of reliance on third-party goods and services; the risk of failure in information technology, data protection or cybercrime; therisk of failure of critical processes; any expected gains from productivity initiatives are uncertain; the risk of failure to attract, develop, engage and retain a diverse, talented and capable workforce; the risk of failure to adhere to applicable laws, rules and regulations; the risk of the safety and efficacy of marketed medicines being questioned; the risk of adverse outcome of litigation and/or governmental investigations; the risk of failure to adhere to increasingly stringent anti-bribery and anti-corruption legislation; the risk of failure to achieve strategic plans or meet targets or expectations; the risk of failure in financial control or the occurrence of fraud; the risk of unexpected deterioration in theGroup'sfinancial position; and the impact that the COVID-19 globalpandemic may have or continue to have on these risks, on theGroup'sability to continue to mitigate these risks, and on theGroup'soperations, financial

results or financial condition. Nothing in this document, or any related presentation/webcast, should be construed as a profit forecast.

Lynparza: ovarian cancer

The most comprehensive PARPi1development programme in ovarian cancer

Study 19: 3L+

SOLO-2: 2L maintenance

Source: Study 19, abstract 5501, ASCO 2016; and SOLO-2, 2 - Late Breaking Abstract, SGO 2017.

SOLO-1: 1L maintenance

PAOLA-1: 1L (HRD+ve2)

• 1. Poly ADP ribose polymerase (PARP) inhibitor.

• 2. Homologous recombination deficiency (HRD) positive, including tBRCAm.

Source: SOLO-1, ESMO 2018; and PAOLA-1, ESMO 2019.

ASCO 2020: continued advancement

of science supportingLynparza Phase III SOLO2 •Final OS for maintenance treatment in BRCA3-mutated PSR4OC5 Other •Phase IIIb OPINION IA6: maintenance of non-germline BRCA1/2-mutated PSR OC •Phase III:Lynparzaor the combination of cediranib andLynparzato standardplatinum-based CTx7in recurrent platinum-sensitive OC •Phase II LIGHT: PSR ovarian cancer by BRCA mutation and HRD status

3. Breast cancer susceptibility gene 1/2 mutation 4. Platinum-sensitive relapsed 5. Ovarian cancer 6. Interim analysis 7. Chemotherapy.

Lynparza: SOLO2 final OS

Maintenance treatment for PSR OC patients with gBRCA positive tumours

PFS: 63% maturity with a

median follow up ~22 months

Significant improvements in TFST1and time to second subsequent therapy at the initial trial analysis

1. Time to first subsequent therapy.

Source:The Lancet Oncology2017; 18: 1274-84.

SOLO2: median OS improved by 12.9 months with

maintenanceLynparzaover placebo (p-value: 0.0537) Adjusting for subsequent PARPi therapy in placebo patients median OS improved by 16.3 months forLynparza vs. placebo; HR 0.56 (0.35-0.97)2

TFST: 28% of patients (vs. 13% of placebo patients) werealive and had not received subsequent therapy at 5 years

2. Prespecified adjusted OS analysis (RPSFT model, re-censored): to adjust for subsequent PARP inhibitor therapy in placebo

group. The RPSFT model (re-censored) adjusts for the 38% of placebo patients who received subsequent PARP inhibitor therapy. RPSFT: rank preserving structural failure time model. Source: abstract 6002, ASCO 2020.

Lynparza: PAOLA-1

1L maintenance treatment with bevacizumab

PAOLA-1: 1L ovarian cancer

1L (complete response; partial response; or non-evidence of disease) Randomisation (2:1)Lynparza(two years) + bevacizumab1 Placebo (two years) + bevacizumab1 Progression-free survival (PFS1) Follow up for second progression (PFS2) or death2 Overall survival

PAOLA-1 representative of patients with advanced OC; selection was not restricted by surgical outcome or BRCA mutation status

Maintenance therapy

1. Bevacizumab: 15mg/kg, every 3 weeks for a total of 15 months, including when administered with chemotherapy 2. Secondaryendpoints.

Source: abstract 935PD, ESMO 2017.

PAOLA-1: biomarker subgroups

~1 in 2 Approved women with advanced OC are HRD+ve 1L maintenance treatment in the US with bevacizumab for HRD+ve advanced OC HRD-ve3; n=277;34% HRD status unknown; n=142;18%HRD+ve; n=387;48%

PAOLA-1 demonstrated the predictive value of HRD testing >37 months mPFS for patients treated withLynparza+ bevacizumab

3. HRD negative. Source: ESMO 2019.