This year, investors flocked to companies trying to solve two of today's biggest health problems: COVID-19 and cancer. Players in these fields took the three top spots in 2020 biotech share performance, each surging more than 1,000%. In fact, they weren't only the best performers in biotech. They posted steeper gains than any other stock with a market value of $200 million or more -- all industries included.

As we look for stocks to buy in the coming year, it's natural to consider the current year's strong performers. After all, this might be just the beginning of their share growth story -- even if recent increases were big. So, without further ado, let's take a closer look at Novavax (NVAX -0.72%), Vaxart (VXRT 2.93%), and Cardiff Oncology (CRDF -1.73%) to determine whether these shares may climb even higher in 2021.

Stacks of coins with plants growing on top are shown on a table witha glowing arrow pointing upward.

Image source: Getty Images.

1. Novavax

Novavax's stock soared 3,072% this year as investors bet on its investigational coronavirus vaccine. The company took center stage in July, when Operation Warp Speed (OWS) invested $1.6 billion in the program. OWS is the government initiative to shepherd a vaccine to market by January. Novavax scored more points with investors when it reported positive data from its phase 1 trial and as it ramped up production capacity. If the vaccine candidate receives an Emergency Use Authorization (EUA) from the Food and Drug Administration, the company plans to deliver about two billion doses by mid-2021.

Now, the question is whether new elements may drive this superstar stock higher in the coming year. The answer is yes. Novavax launched a phase 3 trial in September and expects to report initial data in the early part of the first quarter. If those results are encouraging, we can expect positive share performance. And if trial readouts result in a regulatory green light, the stock could climb even higher.

Part of Novavax's 2020 story is that it released phase 3 results from its potential flu vaccine called NanoFlu in March. This data demonstrated that it was superior to the flu vaccine from Sanofi that's on the market. The company is preparing to file for FDA approval for NanoFlu, which could really accelerate its upward trajectory if it's accepted and launches to the market. Much farther down the road, if Novavax's plan to develop a combined flu/coronavirus vaccine is successful, the shares could skyrocket -- again. Considering these potential catalysts, Novavax remains on my buy list.

2. Vaxart

Vaxart's shares jumped 2,125% this year as it wowed investors with the possibility of a coronavirus vaccine that doesn't involve a shot at all. The company's candidate is a tablet taken orally. Preclinical data has been positive, and Vaxart launched a phase 1 study in October.

The one negative for Vaxart is that it lags behind peers from a timeline perspective. Thirteen programs are in phase 3 trials right now. And two much bigger rivals -- Moderna (MRNA -1.56%) and Pfizer (PFE -0.11%) -- have already applied for EUAs. So, it's very likely that a few vaccines may hit the market before Vaxart even enters late-stage trials.

However, I won't write off Vaxart that easily. If the company's program eventually is successful, it could unseat bigger players. Here's why: An oral vaccine would please patients and providers. Patients will love the idea of a pill instead of a jab. It's one dose, compared to some of the leading vaccine candidates which require two doses. And providers will find the room temperature stable tablet easier and cheaper to store than a traditional vaccine that requires refrigeration.

Vaxart has a spot on my buy list, but only for aggressive investors. Without any human data on the investigational vaccine at this point, the program and the stock remain high risk.

3. Cardiff Oncology

Cardiff stock climbed 1,573% this year. The oncology company is developing onvansertib for solid tumor and blood cancer indications. The idea is to develop a treatment to overcome patient resistance to today's standard-of-care drugs. Onvansertib is a Polo-like Kinase 1 (PLK1) inhibitor. That means it's meant to block PLK1 expression, and therefore tumor growth. Some research has shown there may be a relationship between chemotherapy resistance and overexpression of PLK1. So, Cardiff is evaluating onvansertib in combination with chemotherapy.

Most of Cardiff's share gains actually came in September after a positive clinical data report. In a phase 1 trial in a type of metastatic colorectal cancer, the onvansertib treatment controlled disease in 10 out of 11 patients. So, only one patient's disease progressed. This is encouraging. But the investigational drug's human trials still are phase 2 or earlier.

Also, while PLK1 inhibitors are promising, challenges remain. This type of drug has presented issues such as toxicity at certain levels and discrepancies among study results.

All of this, and the fact that onvansertib is Cardiff's only drug candidate make me cautious about the stock. I'll keep Cardiff on my watchlist. But I won't consider buying until onvansertib produces positive later-stage clinical data.

Two out of three

Two of the top three stocks of 2020 may have farther to go in the coming year. And that's great news for those of us seeking winning stocks to buy right now.

Before you buy, though, consider how much risk you can afford. Novavax's coronavirus vaccine program is closer to market than that of Vaxart. And Novavax plans to submit its investigational flu vaccine to regulators soon. That gives it an additional chance for a commercialized product in the near term. Vaxart is an earlier stage company, meaning possibilities for revenue will come much later. Of the two, Novavax offers a bit less risk.

Unfortunately, it's impossible to predict whether the companies' vaccine programs will be successful. But one thing is certain: If they are, the sky may be the limit for their share prices and they could land on the list of top market performers for 2021, too.