Any deal between the two companies is still subject to the resolution of several issues, including completion of due diligence by Shire on Takeda, Shire said.
It is the fifth takeover offer from Takeda, which encompasses £27.26 in new shares and £21.75 in cash, implying a value of £49 per Shire share.
All the proposals consisted of a mix of cash and Takeda shares.
The Japanese firm first officially expressed interest in Shire last month, but has had a series of offers rebuffed.
Shire (LON:SHP) has reached a preliminary tie-up deal with Takeda Pharmaceutical, the group has said.
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Japanese pharmaceutical company Takeda has made a big breakthrough in its campaign to buy biotech firm Shire - but its investors are getting anxious. Ambitious cost cutting will be required to make the deal pay. Shire added that the deadline could be extended further, if needed. It specializes in medicines for rare diseases, as well as the ADHD drug Adderall. Shore Capital reaffirmed a buy rating and set a GBX 3,607 ($50.31) price target on shares of Shire in a research report on Monday, April 16th. It would also be the third biggest acquisition of a UK-traded company in history.
This isn't the first M&A bid for Shire - a $52 billion takeover by AbbVie had been agreed but was terminated in 2014 because of a change in United States tax rules.
Shire also announced last week it was selling its oncology business to unlisted French drugmaker Servier for $2.4 billion. If the bid is to go ahead, Shire shareholders will need to accept a bid that is 56% newTakeda shares.
Weber, who became Takeda's first non-Japanese CEO in 2015, has said publicly it was looking for acquisitions to reduce its exposure to a mature Japanese pharmaceutical market. It said it was "considering its position", and stressed that there was no guarantee on any firm offer.
Shire traces its roots back to 1986, when it began as a seller of calcium supplements to treat osteoporosis, operating from an office above a shop in Hampshire.
Last Friday, it increased its informal bid to £42.8 billion, after Shire rejected three previous overtures as too low.