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2017-09-06

AstraZeneca: Tezepelumab significantly reduced asthma exacerbations for a broad population of patients with severe uncontro...

First-in-class treatment that blocks thymic stromal lymphopoietin
(TSLP) - an upstream driver of inflammation in asthma

Results published in New England Journal of Medicine

Late-breaking abstract at European Respiratory Society International
Congress highlights results from the PATHWAY Phase IIb trial of
tezepelumab in patients with severe, uncontrolled asthma

AstraZeneca and Amgen Inc. (Amgen) announce results from the PATHWAY
Phase IIb trial of tezepelumab that showed a significant reduction in
the annual asthma exacerbation rate compared with placebo in patients
with severe, uncontrolled asthma. Tezepelumab is a first-in-class
anti-TSLP monoclonal antibody being developed by MedImmune,
AstraZeneca's global biologics research and development arm, in
collaboration with Amgen.

The trial results are published in the New England Journal of Medicine
(http://www.nejm.org/doi/full/10.1056/NEJMoa1704064) on 7 September
and will be followed by an oral presentation on 12 September at the
ERS International Congress 2017 in Milan.

The PATHWAY trial achieved its primary efficacy endpoint, showing
annual asthma exacerbation rate reductions of 61%, 71% and 66% in the
tezepelumab arms receiving either 70mg or 210mg every four weeks or
280mg every two weeks, respectively (p<0.001 for all comparisons to
placebo). In the trial, tezepelumab was given as an add-on therapy to
patients with a history of asthma exacerbations and uncontrolled
asthma despite receiving inhaled corticosteroids/long-acting
beta-agonists with or without oral corticosteroids and additional
asthma controllers.

Significant and clinically-meaningful reductions in the exacerbation
rate were observed independent of baseline blood eosinophil count or
other type 2 (T2) inflammatory biomarkers. Tezepelumab also
demonstrated improvements in lung function at all doses and in asthma
control at the two higher doses (p<0.05 for all comparisons to
placebo). The incidence of adverse events was similar between the
tezepelumab and placebo groups. The most common adverse events (?5%)
in tezepelumab-treated patients were asthma, nasopharyngitis,
headaches and bronchitis.

Dr Jonathan Corren, David Geffen School of Medicine, UCLA and
Principal Investigator of the PATHWAY trial, said: "These efficacy
results strongly confirm that TSLP is an important mediator of
inflammation in severe asthma. Due to its activity early in the
inflammatory cascade, tezepelumab may be suitable for patients with
both T2 and non-T2 driven asthma, including those ineligible for
current biologic therapies which only target the T2 pathway."

Bahija Jallal, Executive Vice President, Head of MedImmune, said: "In
asthma patients, TSLP functions as an upstream epithelial
`master-switch' right at the start of the inflammation cascade. By
binding to TSLP, tezepelumab impacts multiple downstream inflammatory
pathways associated with asthma, as shown by striking reductions in
the level of multiple biomarkers in the PATHWAY trial, including
blood eosinophils, IgE and FeNO. This broad biomarker response is
unprecedented among respiratory biologics and reflects our commitment
to leading respiratory science for unmet medical needs."

TSLP is an epithelial cytokine produced in response to
pro-inflammatory stimuli such as allergens, viruses and other
pathogens in the lung. It drives the release of downstream T2
cytokines including IL-4, IL-5 and IL-13, leading to inflammation and
asthma symptoms. TSLP also activates many types of cells involved in
non T2 driven inflammation. Therefore, the early, upstream activity
of TSLP in the inflammation cascade has been identified as a
potential target across a broad asthma population.

- ENDS -

NOTES TO EDITORS

About Severe Asthma

Asthma affects 315 million individuals worldwide, and up to 10% of
asthma patients have severe asthma, which may be uncontrolled despite
high doses of standard-of-care asthma controller medicines and can
require the use of chronic oral corticosteroids (OCS).

Severe, uncontrolled asthma is debilitating and potentially fatal with
patients experiencing frequent exacerbations and significant
limitations on lung function and quality of life.

Severe, uncontrolled asthma can lead to a dependence on OCS, with
systemic steroid exposure potentially leading to serious short- and
long-term adverse effects, including weight gain, diabetes,
osteoporosis, glaucoma, anxiety, depression, cardiovascular disease
and immunosuppression. There is also a significant physical and
socio-economic burden of severe, uncontrolled asthma with these
patients accounting for 50% of asthma-related costs.

T2 inflammation driven (T2 high) asthma is present in over two-thirds
of patients with severe asthma and is typically characterised by
elevated levels of T2 inflammatory biomarkers, including blood
eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO).
Conversely, approximately one-third of patients with severe asthma do
not present with features of an activated T2 inflammatory pathway,
and no biologic treatment options currently exist for these patients
whose non-T2 driven disease is uncontrolled on established standard
of care therapies.

About Tezepelumab

Tezepelumab is the first of a new kind of potential new medicines
targeting TSLP. Tezepelumab is a human anti-TSLP monoclonal antibody
that specifically binds human TSLP and prevents interaction with its
receptor complex. Blocking TSLP with tezepelumab may prevent the
release of pro-inflammatory cytokines by immune cells targeted by
TSLP, and thus prevent asthma exacerbations and improve asthma
control. Due to its activity early in the inflammation cascade,
tezepelumab may be suitable for a broad population of patients with
severe, uncontrolled asthma, including those whose asthma is not T2
driven. A previous proof-of-concept inhaled allergen challenge study
in patients with mild, atopic asthma, demonstrated that tezepelumab
inhibits early and late asthmatic responses and suppresses biomarkers
of type 2 inflammation. The results were published in the New England
Journal of Medicine in 2014. Tezepelumab is being developed in
collaboration with Amgen.

About the PATHWAY Trial

The PATHWAY trial was a Phase IIb 52-week, randomised, double-blind,
parallel group, placebo-controlled trial designed to evaluate the
efficacy and safety of three dose regimens of tezepelumab, 70mg and
210mg every four weeks and 280mg every two weeks, as an add-on
therapy in patients with a history of asthma exacerbations and
uncontrolled asthma receiving inhaled corticosteroids/long-acting
beta-agonist with or without oral corticosteroids and additional
asthma controllers.

About AstraZeneca in Respiratory Disease

Respiratory disease is one of AstraZeneca's main therapy areas, and
the Company has a growing portfolio of medicines that reached more
than 18 million patients in 2016. AstraZeneca's aim is to transform
asthma and COPD treatment through inhaled combinations at the core of
care, biologics for the unmet needs of specific patient populations,
and scientific advancements in disease modification.

The Company is building on a 40-year heritage in respiratory disease
and AstraZeneca's capability in inhalation technology spans both
pMDIs and dry powder inhalers, as well as the innovative
Co-SuspensionTMDelivery Technology. The company's biologics include
benralizumab (anti-eosinophil, anti-IL-5r?), which has been accepted
for regulatory review in the US, EU and Japan, tralokinumab
(anti-IL-13), which is currently in Phase III, and tezepelumab
(anti-TSLP). AstraZeneca's research is focused on addressing
underlying disease drivers focusing on the lung epithelium, lung
immunity and lung regeneration.

About MedImmune
MedImmune is the global biologics research and development arm of
AstraZeneca, a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialization of
small molecule and biologic prescription medicines. MedImmune is
pioneering innovative research and exploring novel pathways across
Respiratory & Autoimmunity, Cardiovascular & Metabolic Diseases,
Oncology, and Infection and Vaccines. The MedImmune headquarters is
located in Gaithersburg, Md., one of AstraZeneca's three global R&D
centres, with additional sites in Cambridge, UK and Mountain View,
CA. For more information, please visit www.medimmune.com

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular & Metabolic Diseases
and Respiratory. The Company also is selectively active in the areas
of autoimmunity, neuroscience and infection. AstraZeneca operates in
over 100 countries and its innovative medicines are used by millions
of patients worldwide.

For more information, please visit www.astrazeneca.com and follow us
on Twitter @AstraZeneca.

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