A potential tie-up between Bristol Myers Squibb and AstraZeneca is looking less and less like a good deal to Wall Street.

After rising in premarket trading Monday, Bristol Myers stock reversed course and slid 1.1% to $64.62. AstraZeneca's U.S.-listed shares fell even further, sinking 8.2% to $155.72.

The two companies have discussed a merger in recent months, the Financial Times reported, citing unnamed sources. An AstraZeneca spokesperson declined to comment on the report, while Bristol Myers Squibb didn't immediately respond to a request from Barron's.

The merger would be one of the biggest pharma deals ever. AstraZeneca's market capitalization stood at $264 billion as of Friday's close, while Bristol Myers Squibb had a total valuation of $133 billion.

There has been a surge in Big Pharma M&A activity in 2026 as cash-rich drugmakers seek to replenish their pipelines before the expiration of a slew of major patents. Most of those deals have consisted of established drugmakers like Eli Lilly snapping up smaller biotechs with promising pre-commercial assets -- nothing of the scale proposed here.

While a megamerger would combine the portfolios of two multinational pharma giants, UBS analyst Matthew Weston questioned whether the deal would make sense for AstraZeneca, noting that takeover processes can slow down drug development.

"Given the historic challenges of mega-deals in Pharma causing R&D productivity to stagnate, and the apparent breadth and depth of the in-house AstraZeneca pipeline, we are surprised by the press reports over the weekend," Weston wrote in a research note on Monday.

Barclays analysts were similarly cautious. While the firm believes an acquisition of Bristol Myers would offer a buyer -- particularly one like AstraZeneca, which boasts established oncology and cardiovascular franchises -- a significant degree of financial securities, "this wouldn't be for very long."

Analysts noted that short-term financial momentum driven by Bristol Myers' blockbusters Eliquis and Opdivo are set to lose steam starting in 2028 as key patents begin to expire and both drugs face U.S. generic and biosimilar competition.

To replace that lost revenue, Bristol Myers is banking on next-generation therapies that have hit clinical trial delays. As Barclays sees it, the company's runway is getting tighter as it races to get these "company-defining catalysts" to market.