Shire : Top-Line Results for Phase 2 Trial of SHP607

   Shire Announces Top-Line Results for Phase 2 Trial of SHP607 in Extremely
                               Premature Infants

  * Top-line SHP607 study results in extremely premature infants showed no
    impact on primary endpoint of reducing the severity of Retinopathy of
    Prematurity

  * Top-line analysis of secondary endpoints showed clinically relevant effects
    on severe complications related to lung and brain damage

  * These data support further development of SHP607 in preterm infants; Shire
    plans to meet with regulatory authorities to discuss clinical path forward
    for phase 3 clinical program focusing on several complications of
    prematurity

Lexington, Mass. - June 30, 2016 -- Shire plc (LSE: SHP, NASDAQ: SHPG) today
announced that its Phase 2 study evaluating an investigational protein
replacement, SHP607, did not meet its primary endpoint of reducing the severity
of retinopathy of prematurity (ROP), a rare eye condition. The study, however,
demonstrated clinically relevant effects in secondary endpoints related to the
development of severe bronchopulmonary dysplasia (BPD), a chronic lung disease,
and severe intraventricular hemorrhage (IVH), a type of brain injury, both of
which have lifelong negative implications for normal development.

SHP607 is a recombinant human version of the naturally-occurring protein
complex of insulin-like growth factor 1 (IGF-1) and its most abundant binding
protein, IGF binding protein-3 (IGFBP-3).

The Phase 2 study included 121 extremely premature infants (born between 23
weeks and 27 weeks +6 days) randomized at birth to either SHP607 or standard
neonatal care, and treated continuously until an equivalent gestational age of
30 weeks. IGF-1 is a growth factor that plays a major role in the development
of the growing fetus in the uterus. It is supplied by the mother until about 30
weeks of gestation when the fetus begins producing the growth factor on its
own. Levels of IGF-1 dramatically decrease in infants born extremely premature
(before 28 weeks of gestation), thereby increasing the risk for complications
related to the lungs, brain, eyes, and other organs.

The Phase 2 top-line data showed a 53% reduction in the incidence of severe
BPD, as defined by oxygen challenge testing, in all assessed patients that
received SHP607, as compared to untreated infants; and an 89% reduction in
those who achieved the prespecified target drug exposure, based on serum
concentrations of IGF-1, as compared to untreated infants. The data also showed
a 44% reduction in the incidence of severe IVH (Grade III and IV on centrally
read ultrasounds) in all assessed patients that received SHP607, as compared to
untreated infants; and a 64% reduction in those who achieved the prespecified
target drug exposure based on serum concentrations of IGF-1, as compared to
untreated infants. The secondary endpoint of time to discharge from neonatal
intensive care was not met.

Approximately 28,000 infants in the U.S. are born extremely premature - before
28 weeks of gestation.  The overall death rate (16%) in the Phase 2 trial was
consistent with mortality rates in this fragile population. There were more
deaths in the treatment arm (20%) as compared to untreated babies (12%);
however, no deaths were considered related to treatment. There were no serious
adverse events related to the investigational medicinal product.

Research suggests that 60% of extremely premature infants experience one or
more severe complications related to prematurity, which include: IVH (grade ?
3); BPD; or ROP.  Severe complications can have life-long implications for the
developing infant.

'This is the first controlled clinical trial to confirm the crucial role of
IGF-1 in maturation of extremely preterm children,' said Professor Neil Marlow
of the University College London Hospitals, UK, and one of the clinical trial
investigators. 'The reduction in BPD and IVH, as the two most important
morbidities suffered by these children, are welcoming and a first in neonatal
medicine. It will be important to confirm these findings in additional clinical
studies.'

Philip J. Vickers, Ph.D., Head of Research & Development, Shire, said,
'Although the study did not meet its primary endpoint, we are extremely
encouraged by the topline secondary endpoints related to lung and brain. For
severe complications related to the lung and brain, there are no approved
treatment options, and these data support our commitment to further investigate
the potential systemic benefits of SHP607 in this population where the unmet
patient need is substantial.'

Later this year, Shire expects to begin discussions with regulatory authorities
about a phase 3 clinical program focusing on clinically relevant complications
of prematurity.

About the Trial

The Phase 2 study (ROPP-2008-01) was a multicenter, randomized, controlled
study that compared SHP607 to standard neonatal care in 121 premature infants
born at a gestational age of between 23 weeks and 27 weeks+6 days.  Infants
randomized to active treatment received a standardized dosage of 250 µg/kg per
day as a continuous 24-hour infusion from the day of birth (Day 0) through
postmenstrual age (defined as gestational age plus time elapsed from birth) of
29 weeks + 6 days, at which point the infant's body would begin producing
enough IGF-1 to maintain sufficient levels in the blood.  The target drug
exposure was defined as at least 70% of measured IGF-1 levels within the normal
intrauterine range and at least 70% of the intended duration of therapy based
on gestational age.  After the short-term treatment phase, all participants
were followed to a postmenstrual age of 40 weeks ± 4 days.

For more information, visit https://clinicaltrials.gov/ct2/show/NCT01096784.

Shire is enrolling patients from the Phase 2 study into a five-year
observational long-term outcomes study.  More information is available at
https://clinicaltrials.gov/ct2/show/NCT02386839?term=PEDAL+Shire&rank=1.

About SHP607SHP607 is a recombinant human biologic protein complex of insulin-like growth
factor-1 (IGF-1) and its principal binding protein, IGF binding protein 3
(IGFBP3) [rhIGF-1/rhIGFBP-3].  In clinical trials, this replacement protein
complex was provided to extremely preterm infants through intravenous infusion,
beginning within the first 24 hours of life and delivered continuously until
endogenous production of IGF-1 begins naturally at approximately 30 weeks
postmenstrual age.

For further information please contact:

Investor Relations

Sarah Elton-Farr               seltonfarr@shire.com        +44 1256 894157

Ian Karp                       ikarp@shire.com             +1 781 482 9018

Robert Coates                  rcoates@shire.com           +44 1256 894874

Media

Gwen Fisher                    gfisher@shire.com           +1 484 595 9836

Debbi Ford                     debbi.ford@shire.com        +1 224 727 2079

NOTES TO EDITORS

About Shire

Shire is the leading global biotechnology company focused on serving people
with rare diseases and other highly specialized conditions. We strive to
develop best-in-class products, many of which are available in more than 100
countries, across core therapeutic areas including Hematology, Immunology,
Neuroscience, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine
/ Endocrine and Hereditary Angioedema; a growing franchise in Oncology; and an
emerging, innovative pipeline in Ophthalmics.

Our employees come to work every day with a shared mission: to develop and
deliver breakthrough therapies for the hundreds of millions of people in the
world affected by rare diseases and other high-need conditions, and who lack
effective therapies to live their lives to the fullest.

www.shire.com

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