While biotech may be the next big thing, making money through it isn’t easy. Indeed, investing in biotech stocks is often more of an art than a science. And considering these companies are solely focused on scientific endeavors, that’s not what many investors want to hear.

For every Moderna (NASDAQ:MRNA), which shot to wealth and fame on its MRNA-based COVID vaccine, there’s a CureVac (NASDAQ:CVAC), another MRNA play, down 45% in the last year. Even the biggest biotech stocks, like Eli Lilly (NYSE:LLY) and Johnson & Johnson (NYSE:JNJ), can see their values hit hard by a single adverse decision from the Food and Drug Administration (FDA).

This is the difference between today’s biotech and the last generation’s PC boom. Harmful drugs will kill you. They must undergo multiple rounds of expensive testing before they can be approved. Even approval is no guarantee of success.

A safer play may be to buy an ETF like the iShares Biotechnology ETF (NASDAQ:IBB), which is up 5% over the last year. That said, underfunded investors approaching retirement, and young investors hungry for profit, can’t reach their goals that way.

For those seeking outperformance, here are three biotech stocks worth considering. Each have relatively high upside potential, but also carry higher risk. That said, if you’re still feeling venturesome, these are some opportunities to investigate.

Spectrum Pharmaceuticals (SPPI)

Most drug companies with a price below $1 per share are considered “pre-revenue.” These companies are primarily focused on conducting clinical trials in the hopes of gaining approvals on new drugs. Spectrum Pharmaceuticals (NASDAQ:SPPI), based in Boston, is an exception. SPPI stock was recently trading for 58 cents per share, a market cap of $118 million.

Spectrum makes Rolvedon, given as an injection to reduce infections in some cancer patients. The FDA approved Rolvedon in September.

The approval of Rolvedon initially tanked the stock, as investors saw how small the market might be. However, since the start of the year, the stock has risen sharply.

Spectrum is expected to report earnings on March 16. Analysts are hoping for revenue of $45 million in 2023. That’s not enough for a profit, but could spark interest in the company if its sales growth remains high.

Beyond Rolvedon, the company is working on Poziotinib, an immunotherapy pill targeting some forms of breast cancer. That drug is undergoing a Phase 2 trial. Overall, this among the biotech stocks holding excellent potential, alongside higher-than-average risk.

Vaccinex (VCNX)

Vaccinex (NASDAQ:VCNX), based in Rochester, NY, is working on Pepinemab, a treatment for Huntington’s Disease. 

Pepinemab is an infusion that blocks SEMA4D, a protein implicated in central nervous system disorders. Pepinemab recently completed a Phase 2 study.

In the study, 18 monthly infusions were given to 265 patients, half of whom had the disorder. There was little change in patient condition, but enough positives to get approval to move onto Phase 3. Vaccinex is now enrolling patients in a study combining Pepinemab with Merck’s (NYSE:MRK) Keytruda for head and neck cancers.

VCNX has a market cap of $25 million and recently made a $3.8 million offering at 53 cents, with most shares bought by management. The company had sales of just $50,000 in its most recent quarter and reported a loss of $4.7 million, 11 cents per share.

That said, Pepinemab is not Vaccinex’s only asset. ActiveMAB, a platform for developing antibody drugs, maybe more critical to the investment case. A prescription from Surface Oncology (NASDAQ:SURF), which licensed ActiveMAB in 2021, has just entered human trials. If Vaccinex can prove the value of the ActiveMAB platform, Pepinemab’s problems may not matter.

All investors can do now is wait and hope. Vaccinex traded recently at 59 cents, down from $1.53 last February.

Atossa Therapeutics (ATOS)

Atossa Therapeutics (NASDAQ:ATOS), a Seattle-based company, is named after the wife of an ancient Persian King. The company first focused on breast cancer, but is now working on the breathing side effects of radiation treatment for cancer.

Shares spiked in 2021, when Atossa was briefly a COVID play, and quickly fell again when the company tried to capitalize by authorizing more common stock. Over the last year, ATOS stock declined 38%.

That said, the company’s newfound focus is on endoxifen, which deals with problems caused by the best-known breast cancer drug, tamoxifen. Atossa has patented oral and cream versions of endoxifen. Both low- and high-dosage versions are being tested in clinical trials.

Atossa raised a lot of money in 2021 and still had over $117 million in cash in September. Negative free cash flow was just $5.5 million in the most recent quarter, meaning it can see its research through to results. Most insiders have been buyers recently, at prices from 37-53 cents per share. 

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On the date of publication, Dana Blankenhorn held no positions in any companies mentioned in this article. The opinions expressed in this article are those of the writer, subject to the InvestorPlace.com Publishing Guidelines.