In 2020, coronavirus vaccine stocks have been amazing investments, particularly the small biotechs. Novavax (NASDAQ:NVAX), for example, is up over 2,000%. I actually bought shares in January, so I've been riding that wave all year. My family added to our position last week at $85 a share, so I'm bullish on Novavax, even at these prices. Of course, it was more profitable to buy at $4 a share, when the market hated it.

While buying unloved stocks is definitely risky, the rewards can be great. Here are five cold stocks that are good candidates to heat up in 2021.

The year 2021 with a green arrow zooming up

Image source: Getty Images.

1. Adaptive Biotechnologies

So far, there has been almost no hype about Adaptive Biotechnologies (NASDAQ:ADPT). The stock had its initial public offering last year, opening at $39 a share, and it's now trading hands at $48. That's a boring 20% gain. Nothing to get excited about, right? Wrong! What this company is doing is amazing: mapping 30 billion immune receptors in the human body. It's like Lewis and Clark, except with the human immune system. While Adaptive isn't profitable yet, this science is incredibly valuable. Last year, pharmaceutical giant Roche (OTC:RHHBY) gave Adaptive $300 million in cash for the right to use its maps in developing cancer drugs. And, of course, mapping the human immune system is valuable in numerous other ways. For instance, when COVID-19 hit, Adaptive was able to quickly map 135,000 T-cell receptors in the human body for scientific researchers. While the vaccine race currently focuses on antibodies, many scientists believe that T-cells are actually more important in fighting infection. Adaptive's maps of our immune system will help drugmakers find the next generation of vaccines that will make us truly immune to COVID-19 and other diseases.     

2. Axsome Therapeutics

Axsome Therapeutics (NASDAQ:AXSM) achieved the best returns in the stock market in 2019, rising an incredible 3,600%. But in 2020, the stock has been ice-cold. The company has no coronavirus vaccine, and Mr. Market has lost all interest, dropping its price by about 30% from $104 back in January to $73 now. And yet the company is anything but a boring loser; its focus on the central nervous system means it has drugs in clinical trials for depression, Alzheimer's, migraines, smoking cessation, narcolepsy, and fibromyalgia. (One drug is for three of those indications.) But what makes me really bullish about this stock is how many drugs are in phase 3 trials -- all of them. Specifically, two phase 3 trials are starting up, two phase 3 trials are ongoing, and two drugs have already succeeded in phase 3. Over the next year or two, Axsome should transition from an unprofitable biotech to one with multiple revenue streams. My Foolish colleague Zhiyuan Sun estimates Axsome's market opportunity at $60 billion over the next five years. Nobody knows how much of that market Axsome will win, but with a market cap of $2.7 billion, the stock is incredibly cheap given this opportunity.

3. bluebird bio

Back in 2017, bluebird bio (NASDAQ:BLUE) was on fire, running from a price of $62 a share at the beginning of the year all the way up to $222 on Dec. 11. Since then, it's fallen to $46 a share. But while this is obviously disappointing for shareholders, the company itself is doing fantastic. It is likely that bluebird bio has found what looks to be a near-cure for sickle cell disease. Specifically, in the clinical trial for bluebird's treatment, sickle cell patients are seeing a 99.5% reduction in the worst symptoms of the disease. While the sickle cell drug won't hit the market until late 2022, smart investors should hang on to their bluebird shares and maybe buy some more. The drug, lentiglobin, promises to be a blockbuster. As for 2021, circle March 27 on your calendar. That's the date when the U.S. Food and Drug Administration (FDA) promises to say yea or nay on another drug with massive potential -- bluebird's drug for multiple myeloma, bb2121.    

4. Blueprint Medicines

Two cancer drugs from Blueprint Medicines (NASDAQ:BPMC) were approved by the FDA this year. That kind of great news usually makes biotech stocks spike dramatically. But in the year of COVID-19, the market response to Blueprint's striking success seems rather muted. That might be because Blueprint elected to sell half the rights to its lung cancer drug to Roche (OTC:RHHBY) back in July, prior to the FDA approval. While that might have been a smart move at the time, in retrospect the company would have done better to wait for the good news. Nonetheless, this dual approval from the FDA certainly validates the company's science. And the Roche deal wasn't bad -- Blueprint sacrificed some future wealth to put cash in the bank now, and the partnership will mean immediate opportunities to ramp up sales and marketing. When Blueprint starts reporting major drug revenues next year, the stock should take off.

5. BridgeBio Pharma

What's fascinating about gene therapy is the possibility that a company might actually find a cure for an awful disease. Unfortunately, if only a tiny number of people have a disease, there's not much of a market opportunity for drugmakers. So a lot of wonderful academic research has just been sitting on the shelf. BridgeBio has figured out a way to finance this research and turn it into actual treatments, approaching the field like venture capitalists and making small investments in multiple biotech start-ups. "The most common outcome is going to be failure," as the company says in a video -- but several small investments made very early can lead to a few huge winners. For instance, BridgeBio invested $1 million in Eidos Therapeutics (NASDAQ:EIDX) in 2016, and then later bought 63% of the company for almost $75 million. That company is now valued at $3 billion. You might think the stock market would be wildly enthusiastic about BridgeBio's plan to merge scientific research with finance theory. But the COVID-19 scare has been distracting, and BridgeBio investors only have a 26% gain for the year.

Under the radar now, but not for long ...  

Sooner or later, we'll have a vaccine for COVID-19, and the disease that has sent the world into quarantine will at last recede in importance. When that happens, the stock market might start to notice some of the incredible scientific advances all these other biotechs are making.

It might be a good idea to make small investments now, while nobody is talking about these stocks. All of these companies are doing great. It's just the stocks that are cold right now.