Three of the best-performing pharmaceutical stocks over the past year have been clinical-stage biotech and biopharmaceutical companies -- businesses that aren't making profits but have promising drugs, or more often, drug candidates.

Though a few candidates will become breakout successes, the overwhelming majority of clinical-stage drugs never make it to market, and 11 biopharmaceuticals went bankrupt last year, according to a BioPharma Dive report. So it should come as no surprise that such companies carry some of the biggest risks -- and offer some of the biggest rewards -- in the healthcare sector.

Woman scientist looking at a test tube.

IMAGE SOURCE: GETTY IMAGES

These three have already rewarded investors who bought a year ago, though Relmada remains far below the 10-year-high of $71.60 it set in 2014. The question now is, how much higher can any of them go from here?

Relmada is turning old drugs into new ones 

Shares of Relmada Therapeutics (NASDAQ:RLMD) have risen more than 484% in the past year. The New York City-based clinical-stage biotech specializes in drugs that affect the central nervous system.

Relmada doesn't have any revenue yet, but it has four drugs in its pipeline. One of them, REL-1017 (dextromethadone), looks promising as a treatment for major depression disorder (MDD). According to Relmada, REL-1017 fared well in its phase 2 trials and the company plans to start two phase 3 trials in the fourth quarter.

Its other three drugs are REL-1015 (LevoCap ER), REL-1021 (MepiGel), and REL-1028 (buprenorphine). LevoCap ER is a time-release formulation of Levorphanol, a powerful synthetic opioid which has been used as a pain reliever for nearly 80 years. MepiGel is a topical version of local anesthetic mepivacaine, used for treating neuropathies that occur in diabetes, neuralgia, and HIV-associated neuropathy. And buprenorphine is used to treat opiate use disorder as well as chronic pain.

As of March 31, the company had $115 million in cash; given that it spent $14 million last year, it has enough in the bank to possibly last for another eight years or so before it needs to either turn a profit or seek out other sources of funding.

Neoleukin has been a fast starter

Neoleukin Therapeutics (NASDAQ:NLTX), a Seattle-based biopharmaceutical that just went public last August, is up more than 500% since then. For its therapeutics, the company uses de novo proteins -- entirely new proteins designed using models that require extraordinary computing power to predict their structure (as opposed to ones already existing in the body) -- to treat immunological disorders. The company was launched by the researchers at the University of Washington who discovered the de novo proteins it's developing. While Neoleukin is a start-up, it has some history behind it as it merged with Aquinox Pharmaceuticals last summer.

Last week, Neoleukin announced positive preclinical findings for its versatile anti-tumor drug candidate NL-201 when tested on animals. The company said it plans to present an Investigational New Drug Application (IND) to the FDA by the end of the year.

Neoleukin says NL-201 mimics interleukin-2 (IL-2), an immune-signaling molecule that is produced by the body's T-cells as a response to infections. NL-201 is more stable than IL-2 immunotherapies and lacks their side effects, such as significant toxicity and lower effectiveness when binding with nontargeted cells. Current IL-2 immunotherapies are typically used in patients with melanoma and renal cell carcinoma.