Shire's board of directors started looking at offloading the oncology business in December, and said that the process considered "multiple potential strategic buyers" across Europe, Japan and the US.
The agreement comes as Takeda's chief executive Christophe Weber is reported to be in the U.S. canvassing investor support for a potential bid for Shire, and will no doubt complicate attempts to put a fair value on the business with just a few days to go before the Japanese company must propose an offer or press pause for six months as required under European Union takeover laws.
Shire said on Monday it would consider returning proceeds from the sale to shareholders through a share buyback and that further selective disposals of non-strategic assets were possible. A Takeda spokesman declined to comment.
The UK Takeover Panel gave the Japanese firm a deadline of April 25 to announce a firm intention to bid or walk away.
Shire also had debt of around $19 billion as of the end of 2017.
Shire's chief executive Flemming Ornskov called the deal a "key milestone" for the firm, which clearly demonstrates the value embedded in its portfolio.
Jefferies analysts said the sale "should boost Shire's negotiating position on asking price in the current offer period with Takeda".
If a deal were to be struck, it would see the hunter become the hunted after Shire itself went on the acquisition trail only two years ago when it bought Baxalta for 32 billion United States dollars (£22.6 billion). The transaction covers the transfer of Shire's in-market products Oncaspar and ex-U.S. rights to Onivyde. Oncology is therefore a small part of Shire's business, but was highlighted by Takeda as one of three therapeutic categories that could be bolstered by merging the two companies. Servier also gets the experimental drug calaspargase pegol for leukaemia and an early-stage immuno-oncology pipeline.
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