Shire looks set to become the centre of a takeover tussle between Botox maker Allergan and Takeda, with the pharmaceutical giant rejecting a £44 billion offer from the Japanese firm.
The Irish drug-maker said on Thursday that it had rebuffed three offers from Takeda because they "significantly undervalued the company, its growth prospects and pipeline".
Takeda, which first signalled its interest in Shire last month, put forward a £46.50 a share offer for the firm, comprised of £17.75 in cash and £28.75 of new Takeda shares.
Talks between the pair are ongoing.
Shortly after, fellow Irish firm Allergan disclosed that it is also weighing up a bid for Shire.
The Botox maker said that it is in the "early stages of considering a possible offer for Shire".
"No offer has been made. There can be no certainty an offer will be made nor as to the terms on which any such offer would be made. A further announcement will be made as appropriate," Allergan added.
Allergan has its headquarters in Dublin but with much of its operations managed out of New Jersey in the US.
Takeda said that it will remain "disciplined" with respect to the terms of another offer, which would only be made with the backing of Shire's board and after satisfactory due diligence.
Shares in Shire rose 7% in afternoon trade.
The Japanese company's rationale for acquiring Shire is to "accelerate its transformation and result in a global, value-based, R&D-driven biopharmaceutical leader", to be headquartered in Japan.
In addition, a tie-up would help realise the Japanese company's R&D strategy, drive financial value and allow it to exploit further opportunities in the US.
The disclosures from Takeda and Allergan come days after Shire agreed to sell its oncology business to French firm Servier for 2.4 billion US dollars (£1.68 billion).
The drug-maker's board has given the green light to the deal, which does not require shareholder approval and is now expected to close in the second or third quarter of 2018.
Takeda, which was founded in 1781 and employs 30,000 people, has a strong presence in emerging markets and operates in more than 70 countries.
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 US dollars (£22.6 billion).