The Wellcome Trust – the UK’s largest charitable foundation, with a £16.5bn (€20.2bn) endowment – has written to chancellor of the exchequer George Osborne to raise “major concerns” about the proposed takeover of Anglo-Swedish pharmaceutical company AstraZeneca by US multinational Pfizer.

The possible takeover, which has so far been rejected by AstraZeneca, has provoked a wave of criticism in the UK and Sweden because of its potential effect on jobs.

Andres Borg, Sweden’s finance minister, has claimed Pfizer broke promises made to maintain research investment in Sweden when it bought local drug maker Pharmacia in 2002.

AstraZeneca is one of only two large pharmaceutical companies to pursue substantial research and development (R&D) activity within the UK.

In its letter, Wellcome said it had major concerns because of the importance of the pharmaceutical industry to wider biomedical research.

Wellcome’s mission is to improve human and animal health, principally through funding biomedical research and its translation into healthcare.

More than three-quarters of its £750m annual spending currently supports research in the UK.

The letter, from Wellcome’s chairman Sir William Castell and director Jeremy Farrar, said: “Pfizer’s past acquisitions of major pharmaceutical companies have led to a substantial reduction in R&D activity, which we are concerned could be replicated in this instance.

“If AstraZeneca does merge with Pfizer, we think it essential the R&D and manufacturing capability it offers to the UK is maintained and, critically, that its investment in its major R&D facility in Cambridge is not lost.”

Wellcome said it was encouraged by Pfizer’s open letter to the UK prime minister, which included a commitment to complete and operate AstraZeneca’s Cambridge R&D facility, to employ a minimum of 20% of the combined company’s R&D workforce in the UK, and to maintain manufacturing capacity in the UK.

But the letter continued: “We believe, however, that it is critical the government holds Pfizer to these commitments should its offer succeed, as the company has not always honoured similar undertakings made following past acquisitions. We would be pleased to hear how you propose to do so.”

Wellcome declined to comment on any presumed shareholding in AstraZeneca.

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