Investor enthusiasm for the sector enabled these companies to raise tens of millions with their initial public offerings even though they didn’t have a product on the market. Investors were betting the experimental drugs they were developing would one day win approval from regulators – a process that routinely takes years.

Recently, as many of these same companies sought to raise more cash, they have encountered a very different environment.

Many investors have turned skittish about investing in biotech stocks. Triangle companies also find themselves competing with a flock of biotech companies nationwide that went public over the last few years and also are seeking to raise cash.

These companies “have made it now two or three years and are running out of money,” said Dick Kouri, chief evangelist at the Center for Innovation Management Studies at N.C. State and former executive director of biosciences management at the school. “So they are all coming back to the well at the same time.”

Heat Biologics, one of the five Triangle biotech companies that went public in 2013 and 2014, encountered turbulence when it filed plans in January to sell $12.5 million in newly issued stock to investors.

That goal proved to be overly optimistic; the Durham company ended up settling for a little more than half that amount. On Wednesday, Heat Biologics completed the sale of $6.8 million in stock and warrants.

“It’s a reflection of the market,” said analyst Rahul Jasuja of Noble Life Science Partners.“It has nothing to do with the fundamentals of the company itself.”

The market for biotechnology stocks is notoriously cyclical, and right now it’s definitely in a down cycle. The Nasdaq Biotechnology Index has fallen 25 percent from the beginning of the year.

Among other things, biotech stocks have been hurt by the broader market’s struggles and a backlash triggered by companies that overpriced their drugs. That has made some investors wary given that biotech stocks are considered risky because the best-laid plans for experimental drugs can be derailed by poor test results.

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