<SEC-DOCUMENT>0001654954-21-007738.txt : 20210708
<SEC-HEADER>0001654954-21-007738.hdr.sgml : 20210708
<ACCEPTANCE-DATETIME>20210708060542
ACCESSION NUMBER:		0001654954-21-007738
CONFORMED SUBMISSION TYPE:	6-K
PUBLIC DOCUMENT COUNT:		1
CONFORMED PERIOD OF REPORT:	20210708
FILED AS OF DATE:		20210708
DATE AS OF CHANGE:		20210708

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:		211078900

	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>a5425e.htm
<DESCRIPTION>TEZEPELUMAB GRANTED FDA PRIORITY REVIEW FOR ASTHMA
<TEXT>
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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-size: 13px; font-family: Times New Roman">1.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
</font><font style="color: rgb(0, 0, 0); font-family: Times New Roman; font-size: 13px;">Tezepelumab
granted FDA Priority Review for asthma</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
8 July 2021 07:00 BST</font></div>
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&#xA0;</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Tezepelumab regulatory submission accepted and granted FDA Priority
Review in the US&#xA0;for the treatment of patients with
asthma</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="color: #000000; font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
Tezepelumab is the first and only biologic to consistently and
significantly reduce asthma exacerbations in a broad population
across Phase II and III clinical trials</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">
AstraZeneca's Biologics License Application (BLA) for tezepelumab
has been accepted and granted Priority Review for the treatment of
asthma from the US Food and Drug Administration
(FDA).&#xA0;Tezepelumab is being developed by AstraZeneca in
collaboration with Amgen.</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 FDA grants Priority Review to applications for medicines that
offer significant advantages over available options by
demonstrating safety or efficacy improvements, preventing serious
conditions, or enhancing patient compliance.</font><font style="font-size: 70%; vertical-align: top; color: #000000">1</font><font style="color: #000000">&#xA0;The
Prescription Drug User Fee Act date, the FDA action date for their
regulatory decision, is during the first quarter of
2022.</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 recent advances in severe asthma, many patients may not
qualify for or respond well to current biologic
medicines.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2-5</font><font style="color: #000000">&#xA0;Patients
with severe, uncontrolled asthma experience frequent exacerbations,
significant limitations on lung function and a reduced quality of
life.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2,6,7</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-size: 70%; vertical-align: top; color: #000000; font-family: Times New Roman">
&#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">
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&amp;D, said: "This decision brings us a step closer to delivering
a much-needed, first-in-class medicine for asthma patients, many of
whom remain uncontrolled and at risk of asthma attacks despite the
availability of inhaled and biologic medicines. Tezepelumab has
demonstrated reductions in exacerbations irrespective of blood
eosinophil counts, allergy status and fractional exhaled nitric
oxide, and has the potential to transform treatment for a broad
population of severe asthma 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="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
The BLA was based&#xA0;on results from the PATHFINDER clinical
trials programme, including results from the pivotal NAVIGATOR
Phase III trial. In NAVIGATOR, tezepelumab demonstrated superiority
across every primary and key secondary endpoint, compared to
placebo, in a broad population of patients with uncontrolled asthma
while receiving treatment with medium- or high-dose inhaled
corticosteroids (ICS) plus at least one additional controller
medicine with or without oral corticosteroids
(OCS).</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</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">
There were no clinically meaningful differences in safety results
between the tezepelumab and placebo groups in the NAVIGATOR
trial.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</font><font style="color: #000000">&#xA0;The
most frequently reported adverse events with tezepelumab were
nasopharyngitis, upper respiratory tract infection and
headache.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</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">
Results from the NAVIGATOR Phase III trial were published
in&#xA0;</font><font style="font-style: italic; text-decoration: underline; color: #0000FF">The
New England Journal of Medicine</font><font style="font-style: italic; color: #000000">&#xA0;</font><font style="color: #000000">in May 2021.</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">
Tezepelumab received&#xA0;</font><font style="text-decoration: underline; color: #0000FF">Breakthrough Therapy
Designation</font><font style="color: #000000">&#xA0;for patients
with severe asthma, without an eosinophilic phenotype in September
2018.</font></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">
&#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">
Severe asthma</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">
Asthma is a heterogeneous disease affecting an estimated 339
million people worldwide.</font><font style="font-size: 70%; vertical-align: top; color: #000000">6,9</font><font style="color: #000000">&#xA0;Approximately
10% of asthma patients have severe asthma.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2,6</font><font style="color: #000000">&#xA0;Despite
the use of inhaled asthma controller medicine, currently available
biologic therapies and oral corticosteroids (OCS), many severe
asthma patients remain uncontrolled.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2,3,6</font><font style="color: #000000">&#xA0;Due
to the complexity of severe asthma, many patients have unclear or
multiple drivers of inflammation and may not qualify for or respond
well to a current biologic medicine.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2-5</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">
Severe, uncontrolled asthma is debilitating with patients
experiencing frequent exacerbations, significant limitations on
lung function and a reduced quality of life.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2,6,7</font><font style="color: #000000">&#xA0;Patients
with severe asthma are at an increased risk of mortality and
compared to patients with persistent asthma have twice the risk of
asthma-related hospitalisations.</font><font style="font-size: 70%; vertical-align: top; color: #000000">10-12</font><font style="color: #000000">&#xA0;There
is also a significant socio-economic burden, with these patients
accounting for 50% of asthma-related costs.</font><font style="font-size: 70%; vertical-align: top; color: #000000">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">
Clinical trials</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">
Building on the Phase IIb PATHWAY trial, the Phase III PATHFINDER
programme included two trials, NAVIGATOR</font><font style="font-size: 70%; vertical-align: top; color: #000000">8,14</font><font style="color: #000000">&#xA0;and
SOURCE.</font><font style="font-size: 70%; vertical-align: top; color: #000000">15,16</font><font style="color: #000000">&#xA0;The
programme includes additional planned mechanistic and long-term
safety trials.</font><font style="font-size: 70%; vertical-align: top; color: #000000">17-19</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">
NAVIGATOR is a Phase III, randomised, double-blinded,
placebo-controlled trial in adults (18-80 years old) and
adolescents (12-17 years old) with severe, uncontrolled asthma, who
were receiving standard of care (SoC). SoC was treatment with
medium- or high-dose ICS plus at least one additional controller
medicine with or without OCS. The trial population included
approximately equal proportions of patients with high (&#x2265; 300
cells/&#xB5;L) and low (&lt; 300 cells/&#xB5;L) blood eosinophil
counts. The trial comprised a five to six week screening period, a
52-week treatment period and a 12-week post-treatment follow-up
period. All patients received their prescribed controller medicines
without change throughout the trial.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</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 primary efficacy endpoint was the&#xA0;annualised asthma
exacerbation rate (AAER) during the 52-week treatment period. Key
secondary endpoints included the effect of tezepelumab on lung
function, asthma control and health-related quality of
life.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</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>
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<tr>
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<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-weight: bold; color: #000000">
NAVIGATOR primary endpoints</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</font></font></div>
</td>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Endpoint</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Timepoint</font></div>
</td>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Annual exacerbation rate</font></div>
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Results</font></div>
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<font style="font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
Tezepelumab added to SoC vs placebo added to SoC</font></div>
</td>
</tr><tr>
<td style="vertical-align: middle; width: 19%; border-left: 0.5pt solid #000000; border-bottom: 2px solid #000000">
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Tezepelumab</font></div>
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Placebo</font></div>
</td>
</tr><tr>
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AAER -</font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Overall patient population</font></div>
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<td style="vertical-align: middle; width: 11%; border-left: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Over 52 weeks</font></div>
</td>
<td style="vertical-align: middle; width: 19%; border-left: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
0.93 (95% CI: 0.80-1.07)</font></div>
</td>
<td style="vertical-align: middle; width: 21%; border-left: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
2.10 (95% CI: 1.84-2.39)</font></div>
</td>
<td style="vertical-align: middle; width: 34%; border-left: 0.5pt solid #000000; border-right: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
56% reduction (95% CI: 47-63%; p&lt;0.001)</font></div>
</td>
</tr><tr>
<td style="vertical-align: middle; width: 15%; border-left: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
AAER - Baseline eosinophil counts&#xA0;&lt;300
cells/&#xB5;L</font></div>
</td>
<td style="vertical-align: middle; width: 11%; border-left: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Over 52 weeks</font></div>
</td>
<td style="vertical-align: middle; width: 19%; border-left: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
1.02 (95% CI: 0.84-1.23)</font></div>
</td>
<td style="vertical-align: middle; width: 21%; border-left: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
1.73 (95% CI: 1.46-2.05)</font></div>
</td>
<td style="vertical-align: middle; width: 34%; border-left: 0.5pt solid #000000; border-right: 0.5pt solid #000000; border-bottom: 2px solid #000000">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
41% reduction (95% CI: 25-54%; p&lt;0.001)</font></div>
</td>
</tr></table>
</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">
CI: confidence interval</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">
As part of prespecified analyses, the AAER over 52 weeks was also
assessed in patients grouped by baseline blood eosinophil count,
fractional exhaled nitric oxide (FeNO) level, serum specific
immunoglobin E (IgE) status (perennial allergen sensitivity
positive or negative).</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</font><font style="color: #000000">&#xA0;These
are inflammatory biomarkers used by clinicians to inform treatment
options and involve tests analysing a patient's blood
(eosinophils/IgE) and exhaled air (FeNO).</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">
There were no clinically meaningful differences in safety results
between the tezepelumab and placebo groups in the NAVIGATOR
trial.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</font><font style="color: #000000">&#xA0;The
most frequently reported adverse events for tezepelumab were
nasopharyngitis, upper respiratory tract infection and
headache.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</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">
NAVIGATOR is the first Phase III trial to show benefit in severe
asthma irrespective of eosinophils by targeting&#xA0;thymic stromal
lymphopoietin (TSLP).</font><font style="font-size: 70%; vertical-align: top; color: #000000">8</font><font style="color: #000000">&#xA0;These
results support the&#xA0;</font><font style="text-decoration: underline; color: #0000FF">US Food and Drug
Administration Breakthrough Therapy Designation</font><font style="color: #000000">&#xA0;granted to tezepelumab in September 2018 for
patients with severe asthma, without an eosinophilic
phenotype.</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">
SOURCE is a Phase III multicentre, randomised, double-blinded,
parallel-group, placebo-controlled trial for 48 weeks in adult
patients with severe asthma who require continuous treatment with
ICS plus long-acting beta2-agonists, and chronic treatment with
maintenance OCS therapy. The primary endpoint is the categorised
percentage reduction from baseline in the daily OCS dose, while not
losing asthma control.</font><font style="font-size: 70%; vertical-align: top; color: #000000">16</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">
Patients who participated in the NAVIGATOR and SOURCE trials were
eligible to continue in DESTINATION, a Phase III extension trial
assessing long-term safety and efficacy.</font><font style="font-size: 70%; vertical-align: top; color: #000000">17</font></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">
&#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">
Tezepelumab</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">
Tezepelumab is a potential first-in-class human monoclonal antibody
that inhibits the action of TSLP, a key epithelial cytokine that
sits at the top of multiple inflammatory cascades and is critical
in the initiation and persistence of allergic, eosinophilic and
other types of airway inflammation associated with severe
asthma.</font><font style="font-size: 70%; vertical-align: top; color: #000000">20,21</font><font style="color: #000000">&#xA0;TSLP
is released in response to multiple triggers associated with asthma
exacerbations, including allergens, viruses and other airborne
particles.</font><font style="font-size: 70%; vertical-align: top; color: #000000">20,21</font><font style="color: #000000">&#xA0;Expression
of TSLP is increased in the airways of patients with asthma and has
been correlated with disease severity.</font><font style="font-size: 70%; vertical-align: top; color: #000000">20,22</font><font style="color: #000000">&#xA0;Blocking
TSLP may prevent the release of pro-inflammatory cytokines by
immune cells, resulting in the prevention of asthma exacerbations
and improved asthma control.</font><font style="font-size: 70%; vertical-align: top; color: #000000">20,22</font><font style="color: #000000">&#xA0;Tezepelumab
acts at the top of the inflammation cascade and has the potential
to help address a broad population of severe asthma patients
regardless of their type of inflammation.</font><font style="font-size: 70%; vertical-align: top; color: #000000">20,22</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">
Amgen 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">
In 2020, Amgen and AstraZeneca updated a&#xA0;</font><font style="text-decoration: underline; color: #0000FF">2012 collaboration
agreement</font><font style="color: #000000">&#xA0;for tezepelumab.
Both companies will continue to share costs and profits equally
after payment by AstraZeneca of a mid single-digit inventor royalty
to Amgen. AstraZeneca continues to lead development and Amgen
continues to lead manufacturing. All aspects of the collaboration
are under the oversight of joint governing bodies. Under the
amended agreement in North America, Amgen and AstraZeneca will
jointly commercialise tezepelumab; Amgen will record sales in the
US and AstraZeneca will record sales in Canada. AstraZeneca's share
of gross profits from tezepelumab in the US will be recognised as
collaboration revenue. In all countries outside the US and Canada,
AstraZeneca will solely commercialise tezepelumab. AstraZeneca will
record all sales outside of the US as product sales and recognise
Amgen's share of gross profit as cost of sales.</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">
AstraZeneca in Respiratory &amp; Immunology</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">
Respiratory &amp; Immunology, part of BioPharmaceuticals, is one of
AstraZeneca's three disease areas and is a key growth driver for
the Company.</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">
AstraZeneca is an established leader in respiratory care with a
50-year heritage. The Company aims to transform the treatment of
asthma and COPD by focusing on earlier biology-led treatment,
eliminating preventable asthma attacks, and removing COPD as a
top-three leading cause of death. The Company's early respiratory
research is focused on emerging science involving immune
mechanisms, lung damage and abnormal cell-repair processes in
disease and neuronal dysfunction.</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">
With common pathways and underlying disease drivers across
respiratory and immunology, AstraZeneca is following the science
from chronic lung diseases to immunology-driven disease areas. The
Company's growing presence in immunology is focused on five mid- to
late-stage franchises with multi-disease potential, in areas
including rheumatology (including systemic lupus erythematosus),
dermatology, gastroenterology, and systemic eosinophilic-driven
diseases. AstraZeneca's ambition in Respiratory &amp; Immunology is
to achieve disease modification and durable remission for millions
of patients worldwide.</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">
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca</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 (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines in
Oncology 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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Contacts</font></div>
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For details on how to contact the Investor Relations Team, please
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For Media contacts, click&#xA0;</font><font style="text-decoration: underline; color: #0000FF">here</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">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">1.&#xA0;&#xA0;&#xA0;
US Food and Drug Administration. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
[Last accessed: June 2021].</font></div>
<div style="text-align: left; margin-left: 36px; margin-right: 0px; text-indent: -36px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">2.&#xA0;&#xA0;&#xA0; Wenzel S. Severe Asthma in
Adults.&#xA0;</font><font style="font-style: italic; color: #000000">Am J Respir Crit Care
Med.</font><font style="color: #000000">&#xA0;2005;172;149-60.</font></font></div>
<div style="text-align: left; margin-left: 36px; margin-right: 0px; text-indent: -36px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">3.&#xA0;&#xA0;&#xA0; Peters
SP,&#xA0;</font><font style="font-style: italic; color: #000000">et
al.</font><font style="color: #000000">&#xA0;Uncontrolled asthma: a
review of the prevalence, disease burden and options for
treatment.&#xA0;</font><font style="font-style: italic; color: #000000">Respir Med.</font><font style="color: #000000">&#xA0;2006;100:1139-51.</font></font></div>
<div style="text-align: left; margin-left: 36px; margin-right: 0px; text-indent: -36px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">4.&#xA0;&#xA0;&#xA0; Hyland
ME,&#xA0;</font><font style="font-style: italic; color: #000000">et
al.</font><font style="color: #000000">&#xA0;A Possible Explanation
for Non-responders, Responders and Super-responders to Biologics in
Severe Asthma.&#xA0;</font><font style="font-style: italic; color: #000000">Explor Res Hypothesis
Med.</font><font style="color: #000000">&#xA0;2019;4:35-38.</font></font></div>
<div style="text-align: left; margin-left: 36px; margin-right: 0px; text-indent: -36px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">5.&#xA0;&#xA0;&#xA0; Tran
TN,&#xA0;</font><font style="font-style: italic; color: #000000">et
al.</font><font style="color: #000000">&#xA0;Overlap of atopic,
eosinophilic, and TH2-high asthma phenotypes in a general
population with current asthma.&#xA0;</font><font style="font-style: italic; color: #000000">Ann Allergy Asthma
Immunol</font><font style="color: #000000">.
2016;116:37-42.</font></font></div>
<div style="text-align: left; margin-left: 36px; margin-right: 0px; text-indent: -36px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">6.&#xA0;&#xA0;&#xA0; Chung
KF,&#xA0;</font><font style="font-style: italic; color: #000000">et
al</font><font style="color: #000000">. International ERS/ATS
guidelines on definition, evaluation and treatment of severe
asthma.&#xA0;</font><font style="font-style: italic; color: #000000">Eur Respir
J.</font><font style="color: #000000">&#xA0;2014; 43:
343-73.</font></font></div>
<div style="text-align: left; margin-left: 36px; margin-right: 0px; text-indent: -36px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">7.&#xA0;&#xA0;&#xA0; Fernandes
AG,&#xA0;</font><font style="font-style: italic; color: #000000">et
al</font><font style="color: #000000">. Risk factors for death in
patients with severe asthma.&#xA0;</font><font style="font-style: italic; color: #000000">J Bras
Pneumol</font><font style="color: #000000">. 2014; 40 (4):
364-372.</font></font></div>
<div style="text-align: left; margin-left: 36px; margin-right: 0px; text-indent: -36px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">8.&#xA0;&#xA0;&#xA0; Menzies-Gow
A,&#xA0;</font><font style="font-style: italic; color: #000000">et
al.</font><font style="color: #000000">&#xA0;Tezepelumab in Adults
and Adolescents with Severe, Uncontrolled
Asthma.&#xA0;</font><font style="font-style: italic; color: #000000">N Engl J
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<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
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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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