Billionaire activist investor Carl Icahn has reportedly set his sights on Bristol-Myers Squibb (NYSE:BMY), a $90 billion-market-cap biopharma that's carving out an important leadership position in immuno-oncology. If past is prologue, Icahn's about to start advocating for big changes at Bristol-Myers Squibb, and those could include an outright sale. Finding a buyer, however, might not be easy.

First, here's what's at stake

The crown jewels of Bristol-Myers Squibb are the immuno-oncology drug Opdivo and the anticoagulant Eliquis, which Bristol-Myers Squibb splits with Pfizer, Inc. (NYSE:PFE).

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Opdivo is a PD-1 targeting drug that makes it more difficult for cancer cells to avoid detection by the immune system. The drug has won FDA approval for use in multiple cancers, but Opdivo is best known for its use in treating lung cancer and melanoma. In the fourth quarter, Opdivo's sales were an eye-popping $1.3 billion.

Eliquis is a factor Xa inhibitor that prevents blood clots from forming in patients with conditions like atrial fibrillation. It's also used to reduce the risk of clots following hip or knee surgery. Because Eliquis outperformed the top-selling anticoagulant warfarin in clinical trials, it's the fastest-growing medicine in its class. Last year, Eliquis sales totaled $3.3 billion, up 80% from 2015.

The domestic contenders

Pfizer should be at the top of any list of potential biopharma suitors. The company's been on the mergers-and-acquisitions hunt since its $160 billion deal to combine with Allergan fell through early last year. Pfizer's also made it a focus to expand its cancer-drug lineup beyond the kidney cancer drug Sutent and the breast cancer drug Ibrance. Last fall, Pfizer landed 50% of the rights to the top-selling prostate cancer drug Xtandi when it outbid Sanofi (NASDAQ:SNY) to acquire Medivation for $14 billion.

Pfizer's $203 billion market cap, deep pockets, and willingness to do deals makes it an intriguing acquirer, but it already has its own PD-L1 drug awaiting a FDA decision in Merkel cell carcinoma, and it's also already conducting trials in lung cancer. Thus it may not be as interested as other companies in Opdivo.

Bristol-Myers Squibb could also be a good fit for Amgen (NASDAQ:AMGN), a $127 billion-market-cap biotech looking for ways to offset the risk of generic competition to some of its top-selling drugs. Amgen's multibillion-dollar drugs Enbrel, Neupogen, and Neulasta are all at risk of losing market share because of patent losses.

Amgen has a number of cancer drugs in its pipeline, but they primarily address hematological cancer, so an argument could be made that Bristol-Myers Squibb's immuno-oncology focus would complement its own programs rather than cannibalize them. Amgen is also partnering with Kite Pharma on next-generation chimeric antigen receptor T-cell therapies that could be the next big advance in treating leukemia and lymphoma, so it's clearly interested in immunotherapy.

Gilead Sciences (NASDAQ:GILD) could also kick Bristol-Myers Squibb's tires. Gilead Sciences has more than $30 billion in cash, and its management has said over and over that it wants exposure to oncology. So far, its efforts have fallen short. In 2014, the company won approval from the U.S. Food and Drug Administration for the use of Zydelig in chronic myeloid leukemia, but with annualized sales of about $160 million, it's more of a niche drug than a market leader.

Lately, sales of Gilead Sciences' megablockbuster hepatitis C drugs have been sliding due to competition and a maturing market, and that's hurt its share price. Unquestionably, Gilead Sciences needs to make a splash to reinvigorate growth, but the company's been shy about paying up for acquisitions, and since its shares have fallen, a shares-plus-cash offer for Bristol-Myers Squibb may not win over Icahn and others.

Across the pond

Roche Holdings (OTC:RHHBY) and Sanofi are two big European companies that also could be interested in buying Bristol-Myers Squibb, but perhaps it's Sanofi that makes the most sense.

Undeniably, Roche is a Goliath with the firepower to make a deal happen, but its interest in Opdivo is probably muted by the fact that it has already won FDA approval for its own PD-L1 drug, Tecentriq, in lung cancer. Roche is also knee-deep in conducting other studies of Tecentriq that could expand its use.

Sanofi isn't much bigger than Bristol-Myers Squibb, but it's been eagerly attempting to acquire peers to boost its growth and sidestep the risk of generic competition to its Lantus, a best-selling diabetes drug. In the past year, Sanofi has been outbid for both Medivation and Actelion.

Buying Bristol-Myers Squibb, however, might be too expensive for Sanofi. The company doesn't want to overpay, which is why it's being outbid, and with Bristol-Myers Squibb already selling at about 5 times sales, I'm not sure it would be willing to offer enough of a premium to make Icahn jump.

Looking forward

Carl Icahn's success in biotech includes helping ImClone land a $6.5 billion deal with Eli Lilly in 2008 and Forest Labs land a $25 billion deal with Actavis (now Allergan) in 2014. However, not all of Icahn's bets on biopharma have led to acquisitions. For example, Icahn owned shares in Biogen for years before he finally sold in 2011, without a deal getting done. Last year, he bought shares in Allergan, but he only held them for about six months.

Regardless, investors shouldn't buy Bristol-Myers Squibb for its M&A possibilities, or because of Icahn. Instead, they should focus on its opportunities to expand Opdivo's label, develop additional oncology drugs, and grow profit. Overall, I think that a solid argument can be made for owning Bristol-Myers Squibb shares regardless of Icahn's position, so his interest in it is simply gravy.

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.