Shire and Rani Therapeutics Enter into Collaboration to Evaluate Use of the Rani Pill(TM) Technology for the Oral Delivery of Factor Therapy

Shire and Rani Therapeutics Enter into Collaboration to Evaluate Use of the Rani Pill(TM) Technology for the Oral Delivery of Factor Therapy

Shire obtains exclusive rights to conduct research on, evaluate, and pursue a worldwide, exclusive license for the development and commercialization of a novel technology for oral delivery of Factor VIII

Cambridge, Mass. - December 5, 2017 - Shire plc (LSE: SHP, NASDAQ: SHPG), the biotech leader in rare diseases, and Rani Therapeutics, an InCube Labs company, today announced a collaboration to exclusively conduct research on the use of the Rani Pill(TM) technology for the oral delivery of factor VIII (FVIII) therapy for patients with hemophilia A. The collaboration agreement grants Shire an exclusive option to negotiate a license to develop and commercialize the technology for delivery of FVIII therapy following completion of feasibility studies. As part of the collaboration, Shire has also made an equity investment into Rani Therapeutics.

Rani Therapeutics has developed a novel approach for the oral delivery of large molecules, including peptides, proteins, and antibodies, using the Rani Pill, a capsule that delivers an intestinal injection without exposing medication to digestive enzymes. Once the capsule is consumed, it stays protected until it enters the small intestine and delivers medication into the intestinal wall. Since the intestines do not have sharp pain receptors, the intestinal delivery is expected to be pain free.

"Shire is proud to partner with Rani Therapeutics to pioneer the investigation of oral delivery of factor therapy for the hemophilia community," said Fritz Scheiflinger, Head of Global Research, Shire. "With Shire's in-depth scientific expertise and leadership position in hemophilia and Rani Therapeutics' deep experience in engineering and material science, we are excited by the potential of this partnership to reduce the chronic burden of hemophilia on patients' everyday lives by researching an oral option to deliver FVIII to patients. We strive to provide hemophilia patients with innovative therapies that are effective and do not expose patients to additional risks."

Hemophilia is a challenging chronic disease that causes longer-than-normal bleeding due to absent or deficient clotting factor in the blood. Those with hemophilia A are missing or deficient in FVIII, while those with hemophilia B are missing or deficient in factor IX. The aim of factor replacement therapy is for bleeding to subside when enough clotting factor has reached the source of the bleed. Currently, no oral therapies exist for the treatment of hemophilia.

"We are very pleased to collaborate with Shire on the development of oral FVIII delivery," said Mir Imran, Chairman and CEO, Rani Therapeutics. "With this technology, though early in development in hemophilia, we hope to improve compliance, quality of life and outcomes for patients with hemophilia by offering a painless and more convenient oral delivery."      

Founded in 2012 and spun out of InCube Labs, Rani Therapeutics has developed a technology platform to convert injectable drugs, such as TNF-alpha Inhibitors, interleukin antibodies and basal insulin, among others, into pills.  With its platform, the company has demonstrated absorption similar to subcutaneous injections in pre-clinical studies, and it has established partnerships with pharmaceutical companies, including Novartis, AstraZeneca and now Shire, to test its platform with selected drugs.

"Rani has the potential to disrupt the industry with its innovative approach to delivering biologics orally," said David Pyott, Member of the Board of Directors, Rani Therapeutics and former Chairman and Chief Executive Officer, Allergan Inc. "The hemophilia market is an excellent application of Rani's technology, and we are delighted that Rani is partnering with Shire, a market leader in the space."

The specific terms of this deal were not disclosed.

For further information from Shire please contact:

For further information from Rani Therapeutics please contact:

NOTES TO EDITORS

About Shire

Shire is the global leader in serving patients with rare diseases. We strive to develop best-in-class therapies across a core of rare disease areas including hematology, immunology, genetic diseases, neuroscience, and internal medicine with growing therapeutic areas in ophthalmics and oncology. Our diversified capabilities enable us to reach patients in more than 100 countries who are struggling to live their lives to the fullest.

We feel a strong sense of urgency to address unmet medical needs and work tirelessly to improve people's lives with medicines that have a meaningful impact on patients and all who support them on their journey.

www.shire.com

About Rani Therapeutics

Rani Therapeutics has developed a novel approach for the oral delivery of peptides, proteins and therapeutic antibodies which to date can only be delivered through injections. The approach and technology for Rani Therapeutics was developed at InCube Labs, a multi-disciplinary life sciences R&D lab focused on developing breakthrough medical innovations. InCube is led by Mir Imran, a prolific medical inventor, entrepreneur and investor, who has founded more than 20 life sciences companies and holds more than 500 issued and pending patents. Many of Imran's innovations have resulted in new standards of care, including the first FDA-approved Automatic Implantable Cardioverter Defibrillator. For more information, please visit: www.ranitherapeutics.com and www.incubelabs.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;
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• 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.

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