<SEC-DOCUMENT>0001654954-22-016532.txt : 20221215
<SEC-HEADER>0001654954-22-016532.hdr.sgml : 20221215
<ACCEPTANCE-DATETIME>20221215063200
ACCESSION NUMBER:		0001654954-22-016532
CONFORMED SUBMISSION TYPE:	6-K
PUBLIC DOCUMENT COUNT:		1
CONFORMED PERIOD OF REPORT:	20221215
FILED AS OF DATE:		20221215
DATE AS OF CHANGE:		20221215

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			ASTRAZENECA PLC
		CENTRAL INDEX KEY:			0000901832
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				000000000
		STATE OF INCORPORATION:			X0
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		6-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	001-11960
		FILM NUMBER:		221463613

	BUSINESS ADDRESS:	
		STREET 1:		1 FRANCIS CRICK AVENUE
		STREET 2:		CAMBRIDGE BIOMEDICAL CAMPUS
		CITY:			CAMBRIDGE
		STATE:			X0
		ZIP:			CB2 0AA
		BUSINESS PHONE:		011 44 20 7304 5000

	MAIL ADDRESS:	
		STREET 1:		1 FRANCIS CRICK AVENUE
		STREET 2:		CAMBRIDGE BIOMEDICAL CAMPUS
		CITY:			CAMBRIDGE
		STATE:			X0
		ZIP:			CB2 0AA

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ZENECA GROUP PLC
		DATE OF NAME CHANGE:	19930422
</SEC-HEADER>
<DOCUMENT>
<TYPE>6-K
<SEQUENCE>1
<FILENAME>a7757j.htm
<DESCRIPTION>UPDATE ON US REVIEW OF LYNPARZA PROPEL SNDA
<TEXT>
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FORM 6-K</font></div>
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File Number: 001-11960</font></div>
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AstraZeneca PLC</font></div>
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Francis Crick Avenue</font></div>
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CB2 0AA</font></div>
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AstraZeneca PLC</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">INDEX
TO EXHIBITS</font></div>
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<font style="font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">1.</font>
<font style="font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
Update on US review of Lynparza PROpel sNDA</font>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
15 December 2022 07:00 GMT</font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
<font style="color: #000000">Update on US regulatory priority
review of&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;in combination with</font></font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
abiraterone in metastatic castration-resistant prostate
cancer</font></div>
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<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
AstraZeneca and MSD&#xA0;</font><font style="color: #000000; background-color: #FFFFFF">today announced that
the US Food and Drug Administration (FDA) has informed AstraZeneca
that it will extend the Prescription Drug User Fee Act (PDUFA)
date</font><font style="color: #000000">&#xA0;</font><font style="color: #242424; background-color: #FFFFFF">by three months to
provide further time for a full review of</font><font style="color: #000000">&#xA0;</font><font style="color: #000000; background-color: #FFFFFF">the supplementary new
drug application (sNDA) for&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Lynparza</font><font style="color: #000000; background-color: #FFFFFF">&#xA0;(olaparib)
in combination with abiraterone</font><font style="color: #000000">&#xA0;and prednisone or
prednisolone&#xA0;</font><font style="color: #000000; background-color: #FFFFFF">for the treatment
of</font><font style="color: #000000">&#xA0;metastatic
castration-resistant prostate cancer (mCRPC). The companies will
continue to work with the FDA to facilitate the completion of the
agency's review</font><font style="color: #000000; background-color: #FFFFFF">.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
The sNDA&#xA0;is based on results from
the&#xA0;pivotal</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF">PROpel
Phase III trial,</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">which
were published in June 2022 in</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="font-style: italic; text-decoration: underline; color: #0000FF">NEJM
Evidence.</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">In
August 2022, the sNDA was granted</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF">Priority
Review</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">and
AstraZeneca and MSD are committed to working with the FDA to bring
this treatment option to patients with mCRPC.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
In</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">November,
the European Medicines Agency's Committee for Medicinal Products
for Human Use adopted a</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF">positive
opinion</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">recommending
approval of</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">in
combination with abiraterone and prednisone or prednisolone in the
EU&#xA0;for the treatment of&#xA0;adult patients with mCRPC for
whom chemotherapy is not clinically indicated. This combination is
also undergoing regulatory reviews in other
countries.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Lynparza</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">is
approved in the US based on results from the</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF">PROfound
Phase III trial</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">as
monotherapy for patients with homologous recombination repair (HRR)
gene-mutated mCRPC (BRCA-mutated and other HRR gene
mutations)</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">who
have progressed following prior treatment with enzalutamide or
abiraterone; and in the EU, Japan, and China for patients with
BRCA-mutated mCRPC who have progressed following prior therapy that
included a new hormonal agent.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="text-decoration: underline; color: #000000; font-weight: bold; font-family: Times New Roman; font-size: 13px">
Notes</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Metastatic castration-resistant prostate cancer</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Metastatic prostate cancer is associated with a significant
mortality rate.</font><font style="font-size: 70%; vertical-align: top; color: #000000">11</font><font style="color: #000000">&#xA0;Development
of prostate cancer is often driven by male sex hormones called
androgens, including testosterone.</font><font style="font-size: 70%; vertical-align: top; color: #000000">12</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
In patients with mCRPC, their prostate cancer grows and spreads to
other parts of the body despite the use of androgen-deprivation
therapy to block the action of male sex
hormones.</font><font style="font-size: 70%; vertical-align: top; color: #000000">6</font><font style="color: #000000">&#xA0;Approximately
10-20% of men with advanced prostate cancer will develop
castration-resistant prostate cancer (CRPC) within five years, and
at least 84% of these men will have metastases at the time of CRPC
diagnosis.</font><font style="font-size: 70%; vertical-align: top; color: #000000">6</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">Of
patients with no metastases at CRPC diagnosis, 33% are likely to
develop metastases within two years.</font><font style="font-size: 70%; vertical-align: top; color: #000000">5</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Despite the advances in mCRPC treatment in the past decade with
taxane and new hormonal agent (NHA) treatment, there is high unmet
need in this population.</font><font style="font-size: 70%; vertical-align: top; color: #000000">6,8,9,13</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
PROpel</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
PROpel is a</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">randomised,</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">double-blind,</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">multi-centre</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">Phase
III trial testing the efficacy, safety, and tolerability
of&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;versus placebo when given in addition to
abiraterone in men with mCRPC who had not received prior
chemotherapy or NHAs in the mCRPC setting.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Men in both treatment groups also received either prednisone or
prednisolone twice daily. The primary endpoint is
investigator-assessed rPFS, with sensitivity analyses by BICR, and
secondary endpoints include overall survival, time to secondary
progression or death, time to first subsequent therapy, and quality
of life measures.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
In the PROpel Phase III trial,&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;is combined with abiraterone, an NHA which
targets the androgen receptor (AR) pathway.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
AR signalling engages a transcriptional programme that is critical
for tumour cell growth and survival in prostate
cancer.</font><font style="font-size: 70%; vertical-align: top; color: #000000">14,15</font><font style="color: #000000">&#xA0;Preclinical
models have identified interactions between PARP signalling and the
AR pathway which support the observation of a combined anti-tumour
effect of&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;and NHAs, like abiraterone, in both HRR
deficient and HRR proficient prostate cancer.</font><font style="font-size: 70%; vertical-align: top; color: #000000">16-18</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
The PARP1 protein has been reported to be required for the
transcriptional activity of androgen receptors; therefore,
inhibiting PARP with&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;may impair the expression of androgen
receptor target genes and enhance the activity of
NHAs.</font><font style="font-size: 70%; vertical-align: top; color: #000000">14,17,19</font><font style="color: #000000">&#xA0;Additionally,
it is thought that abiraterone may alter/inhibit the transcription
of some HRR genes which may induce HRR deficiency and increase
sensitivity to PARP inhibition.</font><font style="font-size: 70%; vertical-align: top; color: #000000">16,18,20,21</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
For more information about the trial please
visit&#xA0;</font><font style="text-decoration: underline; color: #0000FF">ClinicalTrials.gov</font><font style="color: #000000">.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
Lynparza</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Lynparza</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">(olaparib)
is a first-in-class PARP inhibitor and the first targeted treatment
to block DNA damage response (DDR) in cells/tumours harbouring a
deficiency in HRR, such as those with mutations in BRCA1 and/or
BRCA2, or those where deficiency is induced by other agents (such
as NHAs).</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Inhibition of PARP with&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;leads to the trapping of PARP bound to DNA
single-strand breaks, stalling of replication forks, their collapse
and the generation of DNA double-strand breaks and cancer cell
death.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000; background-color: #FFFFFF">
Lynparza</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; background-color: #FFFFFF">is
currently approved in a number of countries across multiple tumour
types including maintenance treatment of platinum-sensitive
relapsed ovarian cancer and as both monotherapy and in combination
with bevacizumab for the 1st-line maintenance treatment of
BRCA-mutated (BRCAm) and homologous recombination repair deficient
(HRD)-positive advanced ovarian cancer, respectively; for gBRCAm,
HER2-negative metastatic breast cancer (in the EU and Japan this
includes locally advanced breast cancer); for gBRCAm, HER2-negative
high-risk early breast cancer (in Japan this includes all BRCAm
HER2-negative high-risk early breast cancer); for gBRCAm metastatic
pancreatic cancer; and HRR gene-mutated metastatic
castration-resistant prostate cancer (BRCAm only in the EU and
Japan).</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">In
China,&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;is approved for the treatment of
BRCA-mutated metastatic castration-resistant prostate cancer as
well as a 1st-line maintenance therapy in BRCA-mutated advanced
ovarian cancer.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Lynparza,</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">which
is being jointly developed and commercialised by AstraZeneca and
MSD, has been used to treat over 75,000 patients
worldwide.&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;has a broad clinical trial development
programme, and AstraZeneca and MSD are working together to
understand how it may affect multiple PARP-dependent tumours as a
monotherapy and in combination across multiple cancer
types.&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;is the foundation of AstraZeneca's
industry-leading portfolio of potential new medicines targeting DDR
mechanisms in cancer cells.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
The AstraZeneca and MSD strategic oncology
collaboration</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; background-color: #FFFFFF">
In July 2017, AstraZeneca and Merck &amp; Co., Inc., Kenilworth,
NJ, US, known as MSD outside the US and Canada, announced a global
strategic oncology collaboration to co-develop and
co-commercialise&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Lynparza</font><font style="color: #000000; background-color: #FFFFFF">,
the world's first PARP inhibitor, and&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Koselugo</font><font style="color: #000000; background-color: #FFFFFF">&#xA0;(selumetinib),
a&#xA0;mitogen-activated protein kinase (MEK)&#xA0;inhibitor, for
multiple cancer types.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; background-color: #FFFFFF; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; background-color: #FFFFFF">
Working together, the companies will
develop&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Lynparza</font><font style="color: #000000; background-color: #FFFFFF">&#xA0;and&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Koselugo</font><font style="color: #000000; background-color: #FFFFFF">&#xA0;and
other potential new medicines as monotherapies and as combinations.
The companies will also develop&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Lynparza</font><font style="color: #000000; background-color: #FFFFFF">&#xA0;and&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Koselugo</font><font style="color: #000000; background-color: #FFFFFF">&#xA0;in
combination with their respective PD-L1 and PD-1 medicines
independently.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; background-color: #FFFFFF; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca in oncology</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca is leading a revolution in oncology with the ambition
to provide cures for cancer in every form, following the science to
understand cancer and all its complexities to discover, develop and
deliver life-changing medicines to patients.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
The Company's focus is on some of the most challenging cancers. It
is through persistent innovation that AstraZeneca has built one of
the most diverse portfolios and pipelines in the industry, with the
potential to catalyse changes in the practice of medicine and
transform the patient experience.</font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca</font></div>
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<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal &amp; Metabolism, and Respiratory &amp;
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit&#xA0;</font><font style="text-decoration: underline; color: #0000FF">astrazeneca.com</font><font style="color: #000000">&#xA0;and
follow the Company on Twitter&#xA0;@</font><font style="text-decoration: underline; color: #0000FF">AstraZeneca</font><font style="color: #000000">.</font></font></div>
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References</font></div>
<div style="text-align: left; margin-left: 36px; margin-right: 0px; text-indent: -36px">
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<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">18. &#xA0; Asim M,&#xA0;</font><font style="font-style: italic; color: #000000">et al</font><font style="color: #000000">. Synthetic Lethality Between Androgen Receptor
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<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">21.&#xA0;&#xA0; Tarish
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Adrian Kemp</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Company Secretary</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca PLC</font></div>
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SIGNATURES</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
PLC</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">Date:
<font style="font-size: 13px">15 December 2022</font></font></div>
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<font style="font-family: Times New Roman; font-size: 13px">By: /s/
Adrian Kemp</font></div>
</td>
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<td style="vertical-align: top; width: 71%">
<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
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<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Name:
Adrian Kemp</font></div>
</td>
</tr><tr>
<td style="vertical-align: top; width: 71%">
<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
</td>
<td style="vertical-align: top; width: 29%">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Title:
Company Secretary</font></div>
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