Shire Adds to Rare Disease Portfolio with Acquisition of Lumena Pharmaceuticals, Bringing Late Stage Compounds for Rare GI/Hepatic Conditions

Dublin And San Diego (ots/PRNewswire) -

- Acquisition of Lumena Pharmaceuticals, a biopharmaceutical company with
late stage rare disease pipeline assets
- Adds to Shire's rare diseases portfolio and leverages this expertise, and is a
perfect combination with Shire's already strong Gastrointestinal (GI) presence
- Adds LUM001 in Phase 2 development for four rare and devastating hepatic
diseases, two pediatric and two adult with a potential 2016 approval and LUM002 a
Phase 2-ready candidate for the treatment of non-alcoholic steatohepatitis (NASH)
- Very attractive opportunity to develop treatments for significant unmet need
in rare cholestatic liver diseases as well as a treatment for non-alcoholic
steatohepatitis (NASH)
- Shire will acquire Lumena Pharmaceuticals for an upfront payment of $260
million in cash, plus a payment for net cash at closing, and near-term contingent
milestone payments related to ongoing clinical trials
- These two compounds, and Shire's full portfolio, will be discussed in more
detail at an Investor Day later in 2014.

Shire plc and Lumena Pharmaceuticals, Inc., a biopharmaceutical
company with rare disease pipeline assets, announce the acquisition
of Lumena Pharmaceuticals by Shire.

Chief Executive of Shire, Flemming Ornskov, MD comments:

"Our pipeline and strategic focus on rare diseases is even further
strengthened with the acquisition of Lumena Pharmaceuticals, which
also complements our strong GI presence. These attractive potential
treatments may offer new hope to patients with rare cholestatic liver
disease and further contribute to Shire's future growth. We are
excited by the possibilities of these new assets in liver disease. We
have the resources, the infrastructure and the operating capacity to
invest in these new potential growth drivers which add further value
to Shire's innovative pipeline."

President and CEO of Lumena Pharmaceuticals, Mike Grey comments:

"I believe that this transaction is a significant win for all
parties involved, especially the patients, and the future of LUM001
as a treatment for rare cholestatic liver diseases looks brighter
than ever. Shire has deep rare disease experience, a global
infrastructure, and the commercial expertise to deliver LUM001 to
patients around the world. The Lumena team will work closely with
Shire to finish the ongoing Phase 2 clinical programs as part of our
commitment to the patient populations we have championed since we
formed Lumena Pharmaceuticals."

Strategic rationale and background on Lumena Pharmaceuticals

The acquisition of Lumena strengthens Shire's already valuable and
robust pipeline. It complements Shire's strategic focus on Rare
Diseases and provides a future growth path for Shire's
Gastrointestinal business, which generated revenues of over $800
million in 2013. In acquiring Lumena, Shire is gaining experience in
liver disease with the opportunity to leverage its existing GI
commercial infrastructure. In addition, there is a good fit with
Shire's recent acquisition of Fibrotech, which has brought pipeline
programs to address unmet patient need in other fibrotic conditions
including renal impairment.

Lumena Pharmaceuticals brings to Shire two new oral therapeutic
compounds; LUM001, in Phase 2 with four potential orphan indications
and LUM002, ready to enter Phase 2 later in 2014.

LUM001 and LUM002 are both inhibitors of the apical
sodium-dependent bile acid transporter (ASBT), which is primarily
responsible for recycling bile acids from the intestine to the liver.
Blocking bile acid transport with ASBT inhibitors reduces bile acid
absorption and has the potential to improve liver function and
relieve disease symptoms (such as extreme itching associated with
cholestatic liver diseases), and may slow disease progression.

These rare cholestatic liver diseases are primarily treated by
hepatologists and gastroenterologists and can be covered by a small,
specialty sales force consistent with Shire's model.

Shire does not expect the acquisition of Lumena to result in a
change to its previously stated earnings guidance for 2014.

About LUM001

LUM001 is a novel, once-daily, orally-administered, potent and
selective ASBT inhibitor that works by preventing recycling of bile
acids back to the liver and is thought to reduce bile acid
accumulation, improve liver function and potentially relieve the
extreme itching associated with cholestatic liver disease.

LUM001 is currently in Phase 2 clinical development for four rare
cholestatic liver disease indications; two pediatric and two adult
with a potential 2016 launch. These potential indications are:
Alagille syndrome (ALGS), progressive familial intrahepatic
cholestasis (PFIC), primary biliary cirrhosis (PBC) and primary
sclerosing cholangitis (PSC).

Some of the key characteristics of cholestatic liver diseases are
elevated bile acids, leading to progressive liver damage that can
cause liver failure, and pruritus, or severe itching. Pruritus is
generally the most debilitating symptom afflicting children and
adults with these diseases.

Surgical intervention, which lowers bile acid levels, has been
shown to relieve symptoms and slow disease progression in patients
with ALGS and PFIC - this is currently the only treatment option for
these patients. Patients with cholestatic liver diseases may
ultimately require liver transplants.

By reducing serum bile acids, LUM001 may offer a novel therapeutic
approach for alleviating the pruritus and progressive liver damage
associated with cholestatic liver diseases.

The prevalence of each of the four diseases is as follows:

Indication US prevalence EU prevalence
3 per 100,000
ALGS 9476 individuals 3 per 100,000
<1 per 100,000
PFIC 3159 individuals 1 per 100,000
40 per 100,000
PBC 126,979 individuals 30 per 100,000
14 per 100,000
PSC 44,222 individuals 3 per 100,000

(Source: Lumena Pharmaceuticals Applications for Orphan
Designation):

LUM001 has received orphan drug designation for all four potential
indications in both the United States and the European Union.

About LUM002

LUM002 is a novel, once daily, orally-administered, highly potent
and selective inhibitor of ASBT, in development for the treatment of
nonalcoholic steatohepatitis (NASH), a common and often "silent"
liver disease characterized by fat deposits in the liver and
inflammation which can progress to significant fibrosis.

While the underlying cause of liver injury in NASH is not fully
known, it is strongly associated with obesity, Type 2 diabetes, high
cholesterol and triglycerides, and other metabolic disorders.
Approximately 6 million individuals in the US are estimated to have
progressed to NASH and some 600,000 to NASH-related cirrhosis
(Source: World Gastroenterology Organisation Global Guidelines June
2012).

By blocking bile acid reabsorption, LUM002 is thought to modulate
colonic bile acid concentrations and receptor signaling on cells in
the lower portion of the GI tract. This signaling is believed to
result in the secretion of peptides that regulate insulin release
from the pancreas, glucose metabolism and the synthesis of
cholesterol and fatty acids.

Therapeutic strategies aimed at modulating insulin resistance and
normalizing lipoprotein metabolism have significant potential to
benefit patients with NASH.

Phase 1 safety trials in healthy volunteers and a Phase 1b trial
in patients with metabolic disease have been completed. The next step
is to initiate a Phase 2 clinical trial in patients with NASH -
anticipated to begin in the second half of 2014.

NOTES TO EDITORS

About Lumena Pharmaceuticals

Lumena Pharmaceuticals is a privately held, San Diego-based,
biopharmaceutical company founded in 2011 by Pappas Ventures. Other
investors include Alta Partners [http://www.altapartners.com ],
RiverVest Venture Partners [http://rivervest.com ], New Enterprise
Associates, Adage Capital Management and RA Capital Management.

Citi acted as the exclusive financial advisor to Lumena.

About Shire plc

Shire enables people with life-altering conditions to lead better
lives.

Our strategy is to focus on developing and marketing innovative
specialty medicines to meet significant unmet patient needs.

We provide treatments in Neuroscience, Rare Diseases,
Gastrointestinal and Internal Medicine and we are developing
treatments for symptomatic conditions treated by specialist
physicians in other targeted therapeutic areas.

http://www.shire.com

FORWARD - LOOKING STATEMENTS - "SAFE HARBOR" STATEMENT UNDER THE
PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995

Statements included in this announcement that are not historical
facts are forward-looking statements. Forward-looking statements
involve a number of risks and uncertainties and are subject to change
at any time. In the event such risks or uncertainties materialize,
Shire's results could be materially adversely affected. The risks and
uncertainties include, but are not limited to, that:

- Shire's products may not be a commercial success;
- revenues from ADDERALL XR are subject to generic erosion and revenues from
INTUNIV will become subject to generic competition starting in December 2014;
- the failure to obtain and maintain reimbursement, or an adequate level of
reimbursement, by third-party payors in a timely manner for Shire's products may
impact future revenues, financial condition and results of operations;
- Shire conducts its own manufacturing operations for certain of its Rare
Diseases products and is reliant on third party contractors to manufacture other
products and to provide goods and services. Some of Shire's products or ingredients
are only available from a single approved source for manufacture. Any disruption to
the supply chain for any of Shire's products may result in Shire being unable to
continue marketing or developing a product or may result in Shire being unable to do
so on a commercially viable basis for some period of time.
- the development, approval and manufacturing of Shire's products is subject to
extensive oversight by various regulatory agencies and regulatory approvals or
interventions associated with changes to manufacturing sites, ingredients or
manufacturing processes could lead to significant delays, increase in operating costs,
lost product sales, an interruption of research activities or the delay of new product
launches;
- the actions of certain customers could affect Shire's ability to sell or
market products profitably. Fluctuations in buying or distribution patterns by such
customers can adversely impact Shire's revenues, financial conditions or results of
operations;
- investigations or enforcement action by regulatory authorities or law
enforcement agencies relating to Shire's activities in the highly regulated markets in
which it operates may result in the distraction of senior management, significant
legal costs and the payment of substantial compensation or fines;
- adverse outcomes in legal matters and other disputes, including Shire's
ability to enforce and defend patents and other intellectual property rights required
for its business, could have a material adverse effect on Shire's revenues, financial
condition or results of operations;
- Shire faces intense competition for highly qualified personnel from other
companies, academic institutions, government entities and other organizations. Shire
is undergoing a corporate reorganization and the consequent uncertainty could
adversely impact Shire's ability to attract and/or retain the highly skilled personnel
needed for Shire to meet its strategic objectives;
- failure to achieve Shire's strategic objectives with respect to the
acquisition of ViroPharma Incorporated may adversely affect Shire's financial
condition and results of operations; and other risks and uncertainties detailed from
time to time in Shire's filings with the U.S. Securities and Exchange Commission,
including its most recent Annual Report on Form 10-K.

For further information please contact:
Shire
Investor Relations: Jeff Poulton, jpoulton@shire.com, +1-781-482 0945

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

Media: Jessica Mann, jmann@shire.com, +44-1256-894-280

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

Lumena Media contact: Heidi Chokeir, Ph.D., Canale Communications,
Heidi@canalecomm.com, +1-619-203-5391

ots Originaltext: Shire plc and Lumena Pharmaceuticals
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