London-listed drugmaker Shire Plc said it was willing to recommend a deal with Takeda Pharmaceutical Co to its shareholders, after the Japanese company sweetened its acquisition offer to 46 billion pounds (64 billion US dollars).

The development, first reported by Reuters, represents a major breakthrough for the companies in their negotiations, following a pursuit that started on March 28 when Takeda said it was considering a bid for Shire. Since then, Takeda has made five offers, the latest on Tuesday.

Shire said in a statement it had agreed to extend a Wednesday regulatory deadline for the deal talks to conclude to May 8 in order to allow Takeda to carry out more due diligence and firm up its bid. Shire added that the deadline could be extended further, if needed.

Takeda’s shares slid almost 6 percent in early Tokyo trade on Wednesday as investors fretted over its ability to finance the cash and stock deal.

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.

Takeda added in its own statement that it intended to maintain its dividend policy and investment-grade credit rating following the deal.

Shire focuses on treatments for rare diseases and attention deficit hyperactivity disorder. A deal would be the largest ever overseas acquisition by a Japanese company and propel Takeda, led by Frenchman Christophe Weber, into the top ranks of global drugmakers.

It would significantly boost Takeda’s position in gastrointestinal disorders, neuroscience, and rare diseases, including a blockbuster hemophilia franchise.

But the transaction would be a huge financial stretch, since Shire is worth considerably more than the Japanese group. Ambitious cost cutting will be required to make the deal pay.

Dealmaking has surged in the drug industry this year as large players look for promising assets to improve their pipelines. A Takeda-Shire transaction would be by far the biggest. Shire has long been seen as a likely takeover target and was nearly bought by US drugmaker AbbVie Inc in 2014, until US tax rule changes caused the deal to fall apart. Shire also has a track record of acquisitions, but its biggest ever deal – the 32 billion US dollars purchase of Baxalta in 2016 – was widely criticized by shareholders.

Dublin-based Shire, a member of Britain’s benchmark FTSE 100 stock index, said Takeda’s fifth offer was worth 49.01 pounds per share, comprised of the equivalent of 27.26 pounds per share in new Takeda shares and 21.75 pounds per share in cash. Under these terms, Shire shareholders would own half of the combined company.