There may be no other industry as prone to hit-or-miss investments as biotechnology. An astounding 90% of drugs that enter phase 1 clinical trials never reach commercialization, and that means failure is far more common than success. As a result, many biotech companies research a slate of drugs in hopes of having at least one pan out. That's not the case, however, for these three companies. All three have just one drug under development, and that makes them some of the biggest all-or-nothing plays in the industry.

Todd Campbell: Puma Biotechnology (NASDAQ:PBYI) is one of the biggest all-or-nothing plays in biotechnology, if not the biggest. The company has just one clinical-stage drug to its name -- PB-272, also known as neratinib, which Puma licensed from Pfizer in 2011, yet it boasts an eye-popping $6.5 billion market cap. 

Last spring, Puma's shares tumbled 50% following revelations that neratinib patients were suffering from severe diarrhea, but that tumble was followed up last summer by a massive 295% rally after late-stage trial data for neratinib in breast cancer sparked hope that the company's founder, Alan Auerbach, would orchestrate a buyout reminiscent of the $1 billion acquisition he inked with Johnson & Johnson for his prior company, Cougar Biotechnology, in 2009. Since then, bulls and bears have battled over neratinib's safety and whether a suitor will emerge, causing a series of sharp pops-and-drops.

An additional study on neratinib to back up plans to file an application for approval in early 2016 and data readouts from a slate of ongoing trials combining neratinib with other cancer-fighting drugs could make or break any potential buyout, which makes Puma one of 2015's biggest hit-or-miss biotech stocks.

Leo SunGeron Corporation (NASDAQ:GERN) looked like it was doomed last year, when the FDA placed a full clinical hold on imetelstat, the only drug in its pipeline.

Imetelstat is an experimental treatment for myelofibrosis, a bone marrow disorder that disrupts the production of red blood cells. But last November, that hold was lifted, and it signed a licensing deal with Johnson & Johnson's Janssen unit, which entitles it to up to $935 million in milestone payments and royalties if imetelstat is commercialized. The deal includes a $35 million upfront payment to Geron.

Geron is considered an "all-in" bet for a simple reason. Last year, Geron reported only $1.3 million in revenues from royalties and licenses. If imetelstat is placed on another clinical hold or rejected, Geron has no other drugs to fall back on, and additional indications for imetelstat could become irrelevant. Meanwhile, J&J has the right to terminate their partnership at any time because of safety concerns. Imetelstat belongs to a new class of drugs known as telomerase inhibitors -- but to date, none has been approved.

Of course, if imetelstat is approved, it won't have many competitors. The only approved dedicated treatment for myelofibrosis is Incyte's Jakafi. More importantly, Geron will gain steady revenue from J&J and be able to expand its pipeline. 

Cheryl Swanson: One-trick pony Esperion Therapeutics (NASDAQ:ESPR) scored a win a few days ago, when the FDA lifted a clinical hold on its oral cholesterol drug. ETC-1002's results against hard-to-control cholesterol thus far have been impressive, and the drug is now set to gallop into late-stage clinical trials.

By itself, ETC-1002 reduces levels of LDL, or "bad," cholesterol in clinical trials by 30%. When combined with a drug from Merck, it spurs almost a 50% plunge. The drug is well tolerated and works through a dual mechanism that has the potential to regulate both lipid and carbohydrate metabolism, according to the company.

Apart from ETC-1002, Esperion has only one other drug, a preclinical metabolic treatment. FierceBiotech reported that CEO Tim Mayleben said the company's all-hands-on-deck devotion to ETC-1002 makes Esperion effectively a one-trick pony. But, it added, "that's not so bad if you're riding Seabiscuit."

Take that comparison with a mountain-sized grain of salt, although the company has a few similarities to the featherweight Depression-era racehorse. Right now, Esperion is up against Big Pharma rivals Amgen and Regeneron Pharmaceuticals, along with partner Sanofi. Those companies are in pretty much a dead heat with their PCSK9 cholesterol programs, a market estimated at $10 billion a year. And there's another horse in the race, Pfizer, which has its own preclinical oral drug under development.

PCSK9s are all injectables, and Esperion plans to position its once-a-day pill as an easier, less expensive solution. Esperion has all the usual high risks of any small clinical stage drug company. But with a phase 3 starting later this year and a drug that's a lot easier to take than the injectables now racing toward a very large market, this is a company worth watching.