Shire Receives FDA Fast Track Designation for SHP607 for the Prevention of Chronic Lung Disease in Extremely Premature Infants

Shire Receives FDA Fast Track Designation for SHP607 for the Prevention of Chronic Lung Disease in Extremely Premature Infants

Cambridge, Mass. - September 12, 2017 - Shire plc (LSE: SHP, NASDAQ: SHPG), the biotech leader in rare diseases, today announced that the United States Food and Drug Administration (FDA) has granted Fast Track designation for SHP607 for the prevention of chronic lung disease in extremely premature infants. SHP607, currently in phase 2 clinical development, 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).  IGF-1 plays an important role in the development of the fetus in the uterus.

The SHP607 Fast Track designation is supported by preclinical data and Phase 1 and 2 studies. The FDA's Fast Track process is designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. However, it does not guarantee that the FDA will ultimately approve SHP607 or the timing of any such approval.

"We are pleased to achieve this regulatory milestone as we progress this very important clinical development program," says Howard Mayer, M.D., Shire's Head of Research and Development, ad interim. "There are no approved treatment options for chronic lung disease for premature infants, and we are aiming to change that. We are continuing to advance the SHP607 clinical program, which is well aligned with Shire's focus on bringing innovative therapies to patients with rare diseases worldwide."

About the SHP607 Clinical Development Program

Prior to Shire adding SHP607 to its clinical development pipeline in 2013 when it acquired privately held Premacure AB, a Phase I clinical trial was conducted and its results showed that the levels of IGF-1 were increased to within physiological levels and that administration of the investigational protein to preterm infants. Shire took over Premacure's Phase 2 clinical trial, reporting topline results in June 2016, which did not meet the study's 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. There were no serious adverse events related to the investigational medicinal product.

Following the phase 2 study results, Shire initiated discussions with regulatory authorities in the United States, Europe and Japan to discuss an appropriate regulatory review pathway for SHP607. As a result of those discussions, Shire is in the process of developing a phase 2b/3 clinical trial SHP607 targeting a primary endpoint focused on chronic lung disease in extremely premature infants. Key secondary endpoints being explored include BPD and IVH.

Shire is currently conducting a five-year observational long-term outcomes study of patients who had been enrolled in the phase 2 study.

About IGF-1 and Complications Related to Extremely Premature Infants

IGF-1 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.    

Approximately 28,000 infants in the United States are born extremely premature - before 28 weeks of gestation. Research suggests that 60% of extremely premature infants experience one or more severe complications related to prematurity, which include: IVH; BPD; or ROP. Severe complications can have life-long implications for the developing infant.  

For further information please contact:

NOTES TO EDITORS

About Shire

Shire is the leading global biotechnology company focused on serving people with rare diseases. 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, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology.

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

Forward-Looking Statements

Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such 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, the following:

• Shire's products may not be a commercial success;
• increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire's future revenues, financial condition and results of operations;
• Shire conducts its own manufacturing operations for certain of its products and is reliant on third party contract manufacturers 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 manufacture of Shire's products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to, among other things, significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
• certain of Shire's therapies involve lengthy and complex processes, which may prevent Shire from timely responding to market forces and effectively managing its production capacity;
• Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;
• 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 affect Shire's revenues, financial conditions or results of operations;
• Shire's products and product candidates face substantial competition in the product markets in which it operates, including competition from generics;
• adverse outcomes in legal matters, tax audits 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 the Company's revenues, financial condition or results of operations;
• inability to successfully compete for highly qualified personnel from other companies and organizations;
• failure to achieve the strategic objectives, including expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all with respect to Shire's acquisitions, including NPS Pharmaceuticals Inc., Dyax Corp. or Baxalta Incorporated may adversely affect Shire's financial condition and results of operations;
• Shire's growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products;
• a slowdown of global economic growth, or economic instability of countries in which Shire does business, as well as changes in foreign currency exchange rates and interest rates, that adversely impact the availability and cost of credit and customer purchasing and payment patterns, including the collectability of customer accounts receivable;
• failure of a marketed product to work effectively or if such a product is the cause of adverse side effects could result in damage to Shire's reputation, the withdrawal of the product and legal action against Shire;
• 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 significant legal costs and the payment of substantial compensation or fines;
• Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire's revenues, financial condition or results of operations;
• Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which has increased its borrowing costs may decrease its business flexibility; and

a further list and description of risks, uncertainties and other matters can be found in Shire's most recent Annual Report on Form 10-K and in Shire's subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in "ITEM 1A: Risk Factors", and in Shire's subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire's website.

All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise.