"We believe the number of suitable potential acquirers who could recognize massive synergies with Amylin has just grown from one to almost any large pharma with a primary care salesforce and endocrine interest," wrote Leerink Swann LLC analyst Joshua Schimmer.

Schimmer didn't note any specific Big Pharma companies that might be interested, but plenty have shown some sort of involvement and interest in the endocrine system -- glands that secrete hormones such as insulin and can spur diseases by not producing or responding to the hormones correctly. For a disease such as Type 2 diabetes, drugs like Amylin's are meant to control blood glucose levels and weight.

Pfizer Inc. has been a big player in endocrine research, and does have a diabetes drug it gained with the acquisition of BioRexis Pharmaceutical Corp. in 2007, but the drug is still in early-stage development.

The drug is similar to Amylin's Byetta, which was the first of its kind for treating diabetes and had sales of $385.1 million for the first nine months of 2011. Unless something goes awry with Pfizer's early-stage drug, that could prevent any kind of deal.

Other Big Pharma companies that have shown interest in endocrine drug development, particularly in diabetes, include AstraZeneca plc and Roche Holding AG. AstraZeneca has partnered on an oral pill with Bristol-Myers Squibb Co. that is awaiting regulatory approval, though it has faced some trouble after being tagged as a cancer risk. Even if it gets approved, the pill uses a different method of action than San Diego-based Amylin's drug.

Byetta and its follow-on, Bydureon, an extended-release version of the compound exenatide approved in Europe and awaiting a green light in the U.S., were at the crux of Amylin and Lilly's partnership. The companies had been entangled in litigation related to the drugs, but settled Tuesday, Nov. 8, with Indianapolis-based Lilly returning rights for both versions to Amylin. In return, Amylin is paying Lilly $250 million up front with more than $1 billion more in milestones and revenue sharing still possible.

As previously reported in The Daily Deal, Lilly was considered the most likely bidder while the two companies were still together. Schimmer thinks the end of the partnership will heat up M&A speculation, particularly because activist investor Carl Icahn owns 9.9% of Amylin shares. Alexander Denner, who is affiliated with Icahn, also has a seat on Amylin's board, as he previously had at ImClone Systems Inc., which sold to Lilly for $6.5 billion in 2008.

"This may take some time to materialize since discussions had not commenced," Schimmer wrote. "That said, Icahn's board presence is sure to add fuel to the speculative fire."

Schimmer did state that Big Pharma companies that could be interested in Amylin exclude Sanofi, GlaxoSmithKline plc and Novo Nordisk A/S, which have drugs that would compete with Amylin's.

Amylin's stock fell about 10% after the announcement Tuesday to $9.82. It hovered around that price most of Wednesday, giving it a market cap of approximately $1.44 billion.