Source: Flickr user stockmonkeys.com.

Investing in clinical-stage biotech stocks is incredibly risky, because any number of things can derail even the most promising therapy in human trials.

Historically, 90% of drugs entering the clinic end up in laboratory wastebaskets rather than pharmacy shelves, and sometimes a drug will fail in clinical trials because it ends up being less effective in large studies than previously hoped. At other times, a drug will come up short in the clinic because of unforeseen safety risks.

In any case, investing in clinical-stage biotech stocks isn't for the faint of heart. However, if you're willing to take on the risk of failure in hopes of being rewarded with an FDA approval of a new medicine, then here are three companies that I think should be on your radar.

No. 1: Ophthotech Corporation (ISEE)Ophthotech isn't trying to create a new therapy that dislodges current market leaders. Instead, it's developing Fovista, a drug that may help market leading therapies used to treat vision loss work better.

Fovista has already successfully boosted vision when used alongside Novartis' blockbuster Lucentis during mid-stage trials, and late-stage studies are ongoing to determine if it can similarly improve vision in patients when used alongside Regeneron's multibillion-dollar drug Eylea.

Results from final phase 3 trials are expected by the end of 2016, and if they confirm Fovista's early-stage efficacy, then Ophthotech could win an FDA go-ahead as early as 2017. If so, then Ophthotech investors could be handsomely rewarded because, following Ophthotech's positive mid-stage results, Novartis agreed to license overseas rights to Fovista in a deal worth up to $1 billion, plus milestones.

Given that Ophthotech's market cap is $1.5 billion, the Novartis deal is worth $1 billion, and Fovista could become part of a standard of care in a market valued at more than $8 billion annually, this is one clincial-stage stock that's worth considering.

No. 2: Portola Pharmaceuticals (PTLA)Next-generation anti-coagulants known as factor Xa inhibitors are replacing the use of warfarin in patients at risk of blood clots, but even though factor Xa drugs are generating billions of dollars in annual sales, they have one big problem: They lack an antidote.

That could soon change, however, because Portola has completed phase 3 trials demonstrating that its andexanet alfa reverses the anticoagulant affects of factor Xa medicines. Portola plans to file for FDA approval of andexanet alfa by the end of this year, and since andexanet alfa is an FDA-designated breakthrough therapy that will be filed under an accelerated review pathway, the drug could begin to generate revenue for Portola next year.

Additionally, Portola is using lessons it learned researching factor Xa inhibitors to craft its own factor Xa drug, betrixaban, and that drug is in a 7,000-person phase 3 trial that's expected to wrap up next year. This week, the company announced betrixaban has been granted fast-track designation by the FDA, and that means if the phase 3 study is positive, then betrixaban could get to market quickly, too.

If andexanet alfa and betrixaban win over regulators, then Portola could have two drugs with big market potential, generating sales in less than two years, and that's impressive enough for investors to be paying attention.

No. 3: Synergy Pharmaceuticals (NASDAQ: SGYP)
Ironwood's (IRWD -2.53%) anti-constipation drug Linzess, which is licensed to Allergan, is one of the fastest-growing drugs in the United States, but if a late-stage trial evaluating Synergy Pharmaceuticals' competing therapy, plecanatide, confirms phase 3 results released in June, then Linzess sales could migrate to plecanatide instead.

In the first of two phase 3 trials, plecanatide met its endpoint of reducing constipation, and importantly, the incidence of diarrhea reported by patients relative to placebo was potentially best-in-class. Although direct comparisons shouldn't be made between drugs that aren't studied in head-to-head trials, the adverse event profile of plecanatide could give it an edge against Linzess with doctors and patients.

Synergy, which maintains 100% of the rights to plecanatide, expects to release results from a second phase 3 trial soon, and if those results are good, an FDA filing could come shortly thereafter.

Given Allergan reports that Linzess sales surged 79% year over year to $112.1 million in Q2, a plecanatide approval could make a big impact on Synergy, which boasts a market cap of just $706 million.

Tying it together
There's no guarantee that Ophthotech Corporation, Portola Pharmaceuticals, or Synergy Pharmaceuticals will get the nod from regulators, or that if they do, their respective drugs will become top sellers. However, all three of these companies are in the advanced stages of development, and each of these drugs targets blockbuster markets. That's why I think all three could be a good fit for investors willing to take on some risk.