Shire has now confirmed that it has thus far rejected three merger proposals from Takeda, the last one being valued at around $44 billion.

Takeda’s most recent suggestion was £28.75 per share in new Takeda shares, to be listed in Japan and in the US through an ADR listing, and £17.75 per share in cash, representing a potential value of £46.50 per share.

Based on Takeda’s current market capitalisation, Shire shareholders would have owned about 51 percent of the new group had they accepted the proposal.

However, it was unanimously rejected by Shire’s board, which concluded that it continues to “significantly undervalue” the company, its growth prospects and current pipeline.

Shire’s advisers are now in further dialogue with Takeda’s advisers to discuss whether a more attractive proposal is possible, and to understand the basis on which it would be made.

Explaining its interest in a deal, Takeda said the acquisition would create “a global, value-based, R&D-driven biopharmaceutical leader headquartered in Japan, with a balanced geographic footprint, a robust, modality-diverse pipeline and enhanced financial strength”.

The Japanese drugmaker has until April 25 to make an official offer under UK regulation, having declared in March that it was considering making a move on the firm to bolster its core therapeutic areas.