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Gilead Sciences (NASDAQ:GILD) may not be a household name, but it's been a true game-changer among biotech's elite for years.

Gilead's biggest medical contribution is its trio of hepatitis C drugs, Sovaldi, Harvoni, and the most-recently approved Epclusa. Gilead's HCV therapies helped push what had been a 50-50 shot of an effective cure as recently as 2011 to a cure rate of 90%-plus in the vast majority of patients. Though hepatitis C isn't a quick killer, the co-morbidities that can arise over years and decades very well could lead to the death of a person infected with the disease.

Not surprisingly, given the effectiveness of its once-daily HCV regimens, Gilead Sciences has been able to charge top-dollar for its therapies. At the wholesale level, Sovaldi and Harvoni cost $84,000 and $94,500, respectively, for a standard 12-week treatment. Some patients are lucky enough to only need eight weeks of treatment, while others with liver cirrhosis who aren't treatment naive could require up to 24 weeks of treatment.

In addition to its HCV line, Gilead has been leading the charge in the fight against HIV/AIDS. Core drugs such as Truvada, Atripla, Complera, and Stribild have been working to suppress the replication of the HIV virus in patients for years. Newly approved TAF-based, single-tablet, HIV therapies Descovy and Genvoya look to further the progress that Gilead has made in recent years in controlling a serious and still unresolved disease.

Through the first half of 2016, Gilead's HCV franchise generated nearly $8.3 billion in sales, while its HIV franchise delivered almost $5.4 billion in revenue.

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Gilead's share price weakness could make it a takeover candidate

Yet for Wall Street this hasn't been enough. Shares of Gilead Sciences have been in a fairly steady decline since June 2015, with shares losing more than 35% of their value over that time span. Wall Street's concern centers on the idea that Gilead is no longer a growth company, with recent data helping to back up Wall Street's claim. Larger gross-to-net discounts offered to insurers have weighed on Gilead's HCV sales, with blockbuster Harvoni, the second-best-selling drug in the world in 2015, seeing its sales fall to $5.58 billion through the first-half of 2016 from $7.19 billion during the same timeframe last year.

Gilead Sciences has also suffered through a rare misstep with its cancer drug pipeline. In 2014, simtuzumab, a then-promising cancer drug, failed to meet its primary goal of improving progression-free survival in a midstage study for treatment-naïve advanced pancreatic cancer patients. The company and its shareholders were stung once again when Gilead announced that it was halting about a half-dozen trials researching Food and Drug Administration-approved cancer drug Zydelig. Safety concerns surrounding Zydelig, vis-a-vis an FDA warning letter to doctors, as well as what seemed to be superior cancer drugs hitting the market, necessitated the move on Gilead's part.

This has left Gilead with a few paths to success. Either the company can continue to focus on HCV and HIV, with a growing focus on hepatitis B and nonalcoholic steatohepatitis research, or it could go shopping as it did when it acquired Pharmasset for $11 billion in 2011 to get a hold of sofosbuvir, which would eventually go on to become Sovaldi and form the base of its HCV franchise. The uncertainty as to what Gilead will do next, and the company's falling valuation, could open the door for potential suitors to swoop in.

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What companies might be interested in Gilead?

Understandably, Gilead Sciences wouldn't be your run-of-the-mill acquisition target. Even with its stock down more than 35% from its 2015 high, it still possesses a $103 billion valuation. This valuation effectively eliminates a lot of companies from making a bid.

What I'd suggest with some certainty is that Johnson & Johnson (NYSE:JNJ), Novartis, and Amgen are the unlikeliest of candidates to make a play for Gilead Sciences.

Johnson & Johnson CEO Alex Gorsky has previously hinted that J&J's strategy isn't to make large acquisitions. J&J often does much better with small purchases and collaborations, where it can influence the drug development process and potentially get in on game-changing drugs for a fraction of the price they would be if they're successful in phase 3 studies. 

As for Novartis and Amgen, their areas of focus tend not to align well with Gilead Sciences' focus on virology. Novartis has been pushing Roche to become the world's No. 1 cancer drug developer, while Amgen has been focusing on its cancer drug pipeline and its newly founded cardiovascular segment. There's little reason for either company, in my opinion, to consider buying or merging with Gilead Sciences.

Now Pfizer (NYSE:PFE) or Merck (NYSE:MRK) (as a stretch), could be a different story.

Both Pfizer and Merck believe virology is critical to their long-term success, meaning Gilead's HCV and HIV franchises would likely be a good fit for both businesses, resulting in immediate cost-savings and bottom-line improvement. More importantly, buying Gilead would give an acquirer access to what's likely to be $15 billion or more in annual operating cash flow, even with bigger gross-to-net discounts for its HCV franchise.

Image source: Pfizer.

The reason I'd suggest Merck is a bit of a stretch to buy Gilead is that Merck's acquisition strategy can best be described as "bolt-on." Merck is often looking for small- and mid-cap acquisitions that complement its existing product portfolio and pipeline, such as its $8.4 billion buyout of Cubist Pharmaceuticals, announced in late 2014, to bolster its acute hospital care drug segment. Merck isn't entirely opposed to the idea of big acquisitions, but management has made its intent to focus on "bolt-ons" pretty clear during quarterly conference calls.

Pfizer, though, could be a perfect suitor for Gilead. Pfizer has a history of going big or going home when it comes to acquisitions. It purchased Pharmacia for $60 billion in stock back in 2003, gobbled up Wyeth for $68 billion during the depths of the Great Recession, and more recently failed to orchestrate a $160 billion merger with Allergan. Pfizer also has a tendency to gobble up large-cap companies, as evidenced by its $16 billion deal to acquired Hospira in 2015, and its $14 billion deal to buy Medivation, announced last month. Perhaps the only drawback for Pfizer at the moment is that it's orchestrated more than $35 billion in acquisitions (including its Anacor Pharmaceuticals buy) in less than a year.

However, buying Gilead could be a ridiculously smart move for Pfizer, even if Gilead's growth prospects are a bit uncertain. Pfizer is paying well over 20 times EBITDA for Medivation to get its hands on half of Xtandi's revenue stream. Xtandi is a rapidly growing and quite effective advanced prostate cancer drug. In contrast, Gilead is valued at just five times its EBITDA. Even if Pfizer were to pay a hefty premium for Gilead, it would be nabbing Gilead for a discount compared with its recent acquisitions (and would presumably get $15 billion-plus in free cash flow in the process).

Understandably, buying a company solely because you think it'll be bought out isn't a smart investment thesis. Luckily, Gilead's strong cash flow and big market share in HCV and HIV make it a potentially attractive long-term buy-and-hold nonetheless.

If Gilead's stock keeps dropping, it's possible we could begin to see interest from Big Pharma or Big Biotech in the company.

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.