Biotechnology's top performing stocks this year have already given investors envy-inspiring returns, but there's reason to believe that Calithera Biosciences (NASDAQ:CALA), Aurinia Pharmaceuticals (NASDAQ:AUPH), and Esperion Therapeutics (NASDAQ:ESPR) could still go higher. All three of these companies are run by proven winners, and each is developing drugs that target markets worth hundreds of millions of dollars, or more.

Calithera Biosciences -- up 435% year-to-date

About 93% of cancer drugs that enter clinical trials end up in laboratory trash cans, yet despite those odds, investors are flocking to small-cap biotech stock Calithera Biosciences in 2017.

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There are a few reasons why I think investors are warming up to this company's novel approach to fighting cancer. First, the company's been reporting clinical trial progress and news for its tumor metabolism pipeline, and second, Calithera Biosciences' c-suite is packed with experienced, clinical-stage biotech leaders.

Shares got their first kick-start in January when Incyte Corp. paid $45 million up front for rights to CB-1158, a drug that starves tumors of the arginase enzyme they use to suppress immune system responses. Incyte's agreed to cover 70% of CB-1158's development rights in exchange for 60% of its profit, if it's ever approved. For good measure, Incyte also bought $8 million in Calithera Biosciences stock at what now appears to be a bargain price of $4.65 per share.

More recently, investors applauded news in May that Bristol-Myers Squibb expanded its research collaboration with Calithera on CB-839, a drug that starves tumors of glutamine, a nutrient that they use to grow. The two companies were already evaluating whether adding CB-839 to Bristol's Opdivo can tackle kidney cancer, and now they plan to study that one-two punch in non-small cell lung cancer and melanoma, as well.

Additionally, the FDA granted fast-track status to a CB-839 study in June that teams CB-839 up with Novartis' popular kidney cancer drug, Afinitor. A phase 2 study of this combination is scheduled to begin soon.

The flurry of activity suggests Calithera Biosciences management is on the right track. If so, it wouldn't be the first time this team has successfully developed a cancer drug. The company's founder and CEO is Susan Molineaux, and previously, she was the CEO of Proteolix. As a refresher, Proteolix was acquired in 2009 in a deal worth up to $851 million after it created the multiple myeloma drug, Kyprolis. Afterwards, Kyprolis went on to win approval in 2012, and its sales have been growing steadily ever since. In Q1, Kyprolis produced $190 million in revenue, up 23% from Q1, 2016.

I think targeting tumor metabolism is an intriguing approach to fighting cancer, and a proven management team could help these drugs become reality. However, a bit of caution might make sense. After all, Calithera Biosciences has yet to report any phase 2 data, and that 93% clinical trial failure rate probably shouldn't be ignored altogether.

Esperion Therapeutics -- up 278% year-to-date

Sometimes, one plus one equals three; at least, that's the thinking at Esperion Therapeutics, a company that's developing a drug that can be used with statins to further reduce bad cholesterol levels.

Blocks show the calculation one plus one equals three.

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Phase 2 trials showed that adding Esperion Therapeutics' bempedoic acid to statin therapy can further reduce bad cholesterol levels by 20%, and earlier this year, the company said its phase 3 trial is fully enrolled, with data expected next year. If all goes well, an application for bempedoic acid's approval will be filed with the FDA in early 2019.

This trial's progress is undeniably good news, but investors have also gotten excited about the opportunity to combine together bempedoic acid and Zetia, a popular drug that's added to statin therapy when patients don't adequately respond to statin therapy alone. Studies show that a single tablet combination of bempedoic acid and Zetia reduced bad cholesterol levels by about 50%, and a phase 3 trial is set to begin soon. If so, then data from it could result in a FDA application in the first-half of 2019, too.

Statins are the most commonly prescribed class of drugs in the world and over 40 million people in the U.S. take them. But that won't guarantee bempedoic acid's success. What might, however, add conviction to the thinking that it becomes a blockbuster is the company's proven management. 

The company's founder is Roger Newton, a scientist who helped discover Lipitor, the most widely used statin on the planet. At its peak, Lipitor was raking in $13 billion per year in sales, and in its first 15-years on the market, Lipitor's total haul was above $125 billion. In addition to being a winning scientist, Newton's also a successful entrepreneur. After his Lipitor success, he went on to found another company that worked on cholesterol busting drugs, and he sold that company to Pfizer for $1.3 billion.

Admittedly, it's anyone's guess if he'll be as successful this time around, but there are few research teams out there with as much experience in this indication, and that's incredibly valuable.

Aurinia Pharmaceuticals -- up 223% year-to-date

In March, Aurinia Pharmaceuticals reported what it thinks are the best complete remission rates ever observed in a lupus nephritis (LN) trial. 

Inflammation of the kidneys that can eventually lead to end-stage renal failure occurs in about 60% of systemic lupus erythematosus patients, and currently, LN patients are treated with chemotherapy or CellCept, a drug approved for transplant patients that's used off-label. Unfortunately, complete remission rates for patients on these therapies are historically low.

Fortunately, that could change if Aurinia Pharmaceuticals duplicates phase 2 results in phase 3 trials. In phase 2 trials, dosing Aurinia Pharmaceuticals' voclosporin alongside CellCept produced a 49% complete remission rate that doubled the complete remission rate for CellCept monotherapy.

Because boosting complete remission rates in LN patients can significantly reduce the likelihood of LN causing end-stage renal failure, management thinks voclosporin's market opportunity could be $1 billion in the U.S. alone.

Results from phase 3 trials might not be available until 2020, and there's no guarantee that voclosporin's efficacy will be confirmed, but there's good reason to believe management's on-target with their assessment of voclosporin's market potential. Why? After all, before Richard Glickman became the CEO of Aurinia Pharmaceuticals he was CEO of Aspreva Therapeutics, the company responsible for turning CellCept into standard of care in LN.

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.