This came after Takeda's fourth bid for Shire on Friday, of 47 pounds per share, including 26 pounds in Takeda stock and 21 pounds in cash.
The new £49/share offer represents a whopping 59.6% premium to Shire's share price on March 27, the day before confirmation that Takeda was considering an approach (up from 43.3% initially).
Shire shares slipped 0.8 percent to 39 pounds by 0850 GMT, well below Takeda's 49 pounds offer, signalling scepticism about the deal as Takeda's falling stock price erodes the bid's $64 billion headline value. The deadline could be further extended though if needed, said the Irish firm.
Shares in both companies were down, with Takeda's value sliding heavily because of investors' concerns over the risks of such a big merger.
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. But not by the direction of Takeda's share price, which they are nearly certain to be watching closer than to their own stock.
Takeda and its Board have remained disciplined with respect to the terms of the Revised Proposal and Takeda intends to maintain its well-established dividend policy and investment grade credit rating. Ambitious cost cutting will be required to make the deal pay.
But he said Shire offered an attractive portfolio. On Wednesday, March 14 the stock rating was upgraded by Numis Securities to "Buy".
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The Japanese firm first officially expressed interest in Shire last month, but has had a series of offers rebuffed.
Shire has always been seen as a likely takeover target.
Allergan Plc, the US maker of Botox, had been considering a rival bid for Shire but ruled itself out of making an offer last week.
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.
Acquiring Shire would vault Takeda, which has few late-stage experimental drugs in its pipeline, into the ranks of the world's top pharmaceutical companies.