Hundreds of small-cap biotech stocks are available for investors. All of them come with relatively high levels of risk. With that high risk, though, also comes the potential for high returns.

But which small-cap biotech stocks have the best risk-reward profiles? Celldex Therapeutics (NASDAQ:CLDX), Idera Pharmaceuticals (NASDAQ:IDRA), and NewLink Genetics (NASDAQ:NLNK) stand out from the crowd. Here's why these three small-cap biotech stocks could be smart picks this fall.

Gloved hand holding beaker with money in it and under it

Image source: Getty Images.

Celldex Therapeutics: Big catalysts are coming

Celldex Therapeutics stock hasn't been a winner so far this year, with its share price dropping close to 30%. A major factor behind the plunge was disappointing results announced in June from an early-stage study of Celldex's varlilumab (varli) in combination with Bristol-Myers Squibb's Opdivo in advanced-stage colorectal and ovarian cancer. Better days could be ahead, however.

Several big catalysts are coming up in the next year. Most important for Celldex is top-line data from its Metric study of glembatumumab vedotin (glemba) in patients with metastatic triple negative breast cancers that overexpress gpNMB. Those results are expected to be announced in the first half of 2018. Good news could lead to the biotech's first regulatory filing.

Results from the glemba/varli arm in another phase 2 study targeting treatment of metastatic melanoma are expected this fall. Celldex also anticipates reporting data from a phase 1 study of CDX-0158 in treating patients with advanced refractory gastrointestinal stromal tumors (GIST) and other KIT-positive tumors by the end of 2017.

With Celldex stock taking such a beating so far this year, anything positive from these studies could easily lead to a nice rebound. And if the metric results for glemba are positive, I think Celldex stock price could easily double from the current level. 

Idera Pharmaceuticals: Making a splash in Spain 

It's been a much better year for Idera Pharmaceuticals. The biotech stock is up nearly 50% so far in 2017. Earlier this year, Idera's share price was up more than 70% year to date.

The latest positive news for Idera came a couple of weeks ago when the company presented at the annual European Society for Medical Oncology (ESMO) conference in Madrid, Spain. Idera announced data from the dose-selection stage of a phase 1/2 trial evaluating IMO-2125 in combination with Bristol-Myers Squibb's Yervoy in treating melanoma. Six out of nine patients receiving the IMO-2125 combo experienced clear disease control. 

Idera's results presented at ESMO, while still early, were encouraging. The company plans to initiate a late-stage study of IMO-2125 in combination with Yervoy in the first quarter of 2018. In addition, Idera expects to report data from a phase 2 study of another pipeline candidate, IMO-8400, in treating inflammatory disease dermatomyositis in the first half of 2018.

If the upcoming study results are positive, Idera stock will move even higher. The company also appears to be in good shape financially, with enough cash to fund operations through the fourth quarter of next year. 

NewLink Genetics: Up from an update

NewLink Genetics has given shareholders a roller coaster ride in 2017. By April, the stock had more than doubled. Less than three months later, NewLink stock had given up all of those gains and more. In the last couple of weeks, though, the biotech has mounted a big comeback on the strength of updated clinical results for its IDO-inhibitor indoximod.

Like both Celldex and Idera, NewLink Genetics is targeting treatment of melanoma. Earlier results from the company's phase 2 study of indoximod combined with Merck's (NYSE:MRK) Keytruda showed a complete response rate of 12%. However, NewLink's latest update showed a 20% complete response rate along with a median progression-free survival rate of 12.9 months.

The biotech could have more good news on the way. NewLink expects to announce updated data from its phase 2 trial of indoximod plus gemcitabine and Celgene's (NASDAQ:CELG) Abraxane in treating patients with metastatic pancreatic cancer by late 2017 or early 2018. 

NewLink appears to be running behind Incyte (NASDAQ:INCY) with its IDO-inhibitor program. However, as long as indoximod delivers positive results in upcoming studies, the stock should perform well. 

Keith Speights owns shares of Celgene. The Motley Fool owns shares of and recommends Celgene. The Motley Fool recommends Celldex Therapeutics. The Motley Fool has a disclosure policy.