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"Bristol-Myers is deeply undervalued and the recent announcement of the Company's proposed acquisition of Celgene Corporation is poorly conceived and ill-advised," Starboard CEO Jeffrey Smith wrote in a letter to Bristol-Myers shareholders. "There is a better path forward for Bristol-Myers, either as a more profitable standalone company with a more focused, lower-risk strategy, or in a potential sale of the whole Company."
The activist fund has also nominated a slate of director candidates that it hopes to elect at Bristol's 2019 annual shareholder meeting.
Smith argued that Starboard was "surprised" to hear of the proposed acquisition on the heels of what he characterized as poor financial and stock price performances over the last few years. Bristol-Myers announced in January the deal to buy Celgene valued for a record $74 billion.
"The actions we are taking — specifically, our intent to solicit shareholders to block the proposed acquisition of Celgene — are not taken lightly," Smith added. "This view has been solidified by the numerous other large, long-term shareholders who appear to likewise believe this deal is not in the best interest of shareholders."
Bristol-Myers said in response to Starboard's letter that it "welcomes the opinions of all of its stockholders and will review Starboard's letter and respond in due course. The Bristol-Myers Squibb Board and management team are confident that our combination with Celgene will create a premier biopharma company and deliver substantial benefits to our stockholders."
Investment firm Wellington Management on Wednesday also announced its opposition. Wellington said it "does not believe that the Celgene transaction is an attractive path towards" business that "secures differentiated science and broadens the future revenue base."
Bristol-Myers stock was up 0.6 percent and Celgene sank 7.6 percent following the release of Starboard's letter. Brisol-Myers told CNBC on Wednesday that "since announcing the Celgene transaction on January 3, our Board and management team have had numerous conversations and meetings with our stockholders across our ownership base, including Wellington."
"We believe that we are acquiring Celgene at an attractive price, and that this transaction presents an important and unique opportunity to create sustainable value," the company said.
— CNBC's Lauren Hirsch contributed reporting.