The Japanese company last week raised its offer to almost $66 per share and lifted the cash portion of the bid after three prior proposals were rejected. The revised offer was made on Tuesday.
Under British takeover rules, Takeda must announce a firm offer or abandon its pursuit by Wednesday afternoon. A Takeda-Shire transaction would be by far the biggest.
If successful, the sweetened $60B cash/stock offer would mark the largest-ever Japanese acquisition of a western firm and propel Takeda into the top-ranks of global drug companies.
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Takeda has been expanding its takeover ambitions under Chief Executive Officer Christophe Weber, seeking growth overseas amid patent expirations and a shrinking domestic population.
Shire, which is based in Dublin but listed in London, has not yet responded to Friday's bid - nor the latest approach.
Shire confirmed it had received a better offer but did not disclose the details.
Shire's board is now considering its position and will make an announcement in due course.
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Last Friday, Takeda had lifted its cash and stock bid to the equivalent of £47 per share. The size of the Shire bid, however, has left some investors questioning the level of risk.
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.
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