The total value of mergers and acquisitions in the healthcare sector rose to $176.4 billion last quarter, up a whopping 44.5% from the previous quarter, according to Modern Healthcare M&A Watch. And since large drugmakers now spend almost $2.5 billion (over a 10-year period) to develop a new drug on their own, Big Pharma will keep looking for promising late-stage drugs to fill their pipelines.

Meanwhile, when a large suitor comes calling on a clinical-stage biotech, the company's stock can skyrocket overnight. In fact, just the rumor of a potential takeover can send a share price soaring.

But what clinical biotechs could be ripe for a takeover? We asked three Motley Fool contributors what companies they think make the most attractive buyout candidates. Just remember that investing in clinical-stage biotechs is extremely risky, and while it's fun to speculate on buyout targets, you should take any rumors or speculation with a large grain of salt.

Todd Campbell: Investing in hopes of a takeover isn't the best way to approach the markets. After all, acquisition rumors can often fall flat. But for investors looking for potential acquisition targets, Portola Pharmaceuticals' (NASDAQ:PTLA) promising late-stage pipeline could make it intriguing to suitors.

Portola is developing a therapy that can reverse the popular factor Xa anticoagulants that are quickly displacing warfarin as doctor's go-to drugs for keeping blood moving freely following hip transplants and in heart-disease patients. Currently, there's no antidote to factor Xa drugs available, and that means there's plenty of potential demand awaiting Portola's andexanet alfa -- if it can win regulatory approval.

In phase 3 trials, andexanet alfa reversed the effects of the most popular factor Xa drugs, and that has the company targeting an FDA filing before year-end, but andexanet alfa isn't the only drug that a suitor might find attractive. The company is also working on its own factor Xa therapy, betrixaban, which may work better than options already on the market. Results from betrixaban's late-stage studies are coming next year, and if they're good, then it wouldn't shock me if a big pharmaceutical company comes knocking.

Cheryl Swanson: Clovis Oncology (NASDAQ:CLVS) gets my vote for the next takeover target. The tiny biotech has two drugs with the FDA's coveted "Breakthrough Therapy" designation. That's remarkable a biotech with a market cap of just $4 billion, and it pretty much ensures a faster path through the FDA approval process for these drugs. Add to that a high-profile role in cancer drug development, and Clovis sits squarely in the industry's sweet spot for M&A deals.

On the other hand, rumors about a Clovis acquisition have swirled for months. Last April, Goldman Sachs slapped a buy on Clovis with a report of a possible buyout by Pfizer. The shares leapt overnight, but the chatter soon faded when no offer materialized.

Clovis' winning streak since then, however, could make a takeover more likely. In June, Clovis' ovarian-cancer drug shrank tumors in 82% of women in a mid-stage trial. Last month, Clovis announced an immuno-oncology project for its oral lung-cancer drug, to see if could work in tandem with an injectable treatment from Roche. The trial could demonstrate a positive add-on effect for Clovis' checkpoint inhibitors, a novel class of drugs expected to bring in $30 billion a year at their peak.

The downside is that either of these drugs could stumble before FDA approval. In fact, Clovis barely evaded scalping when its late-stage pancreatic-cancer drug proved a complete bust in 2012. Still, the scrappy biotech bounced back by turning its attention to its lung-cancer drug, which could launch early next year for a subset of patients with the EGFR mutation.

George Budwell: Clinical-stage biotechs don't get bought up as often as you might think. More commonly, most big pharmas or big biotechs tend to pursue companies with one or more products already on the market, even when they have to pay a premium to do so.

The truth is that clinical-stage biotechs have to offer something truly extraordinary in terms of value to become a buyout target. What bigger pharmas tend to look for, in my experience, are experimental products that both address a major unmet medical need and have been de-risked in some way.

The small-cap biotech Trevena (NASDAQ:TRVN) looks, to me, to fit these criteria nicely. Although the company has a couple of interesting clinical candidates, I think potential buyers could be sniffing around this biotech largely because of its experimental pain medication TRV-130, indicated for the treatment of acute pain.

In a nutshell, TRV-130 is targeting a market that topped $11 billion last year and is in dire need of medicines that are more effective and come with fewer side effects than morphine. Through two mid-stage studies, TRV-130 has so far drastically outperformed both placebo and morphine in the acute pain relief setting.

Trevena is currently advancing TRV-130 into a pivotal late-stage trial, but I wouldn't be surprised if the company is bought out before that trial progresses too far. Big Pharmas have historically shown huge amounts of interest in novel pain meds, especially those that have the potential to replace morphine as the go-to product for severe pain.

Cheryl Swanson owns shares of Pfizer. George Budwell has no position in any stocks mentioned. Todd Campbell owns shares of Portola. The Motley Fool has no position in any of the stocks mentioned. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.