Top 5 Small-cap Biotech Stocks of 2025
The NASDAQ Biotechnology Index (INDEXNASDAQ:NBI) is trading at three year highs despite market volatility, responding to breakthrough innovations and increased deals involving NASDAQ biotech stocks.
After dropping to a low of 3,637.05 in October 2023, the index climbed to a nearly three year peak of 4,954.813 on September 19, 2024. While the index pulled back to 4,530.69 in August 2025, it staged a robust recovery in the second half of the year, closing at 5,766.59 on December 29, 2025, a gain of approximately 34 percent for the year.
The top NASDAQ biotech stocks have seen sizeable share price increases over the past year. For those interested in investing in biotech companies, the best-performing small-cap biotech stocks are outlined below.
Data was gathered on December 29, 2025, using TradingView’s stock screener. Small-cap biotech stocks with market caps between US$50 million and US$500 million at that time were considered for this list.
1. SELLAS Life Sciences Group (NASDAQ:SLS)
Year-to-date gain: 210.19 percent
Market cap: US$477.18 million
Share price: US$3.35
SELLAS Life Sciences Group is a late-stage biopharmaceutical company focused on novel cancer immunotherapies.
The company’s approach involves “teaching” the immune system to recognize and kill cancer cells by targeting specific proteins that are overexpressed in tumors. Its flagship asset is galinpepimut-S (GPS), a vaccine-like immunotherapy for patients with acute myeloid leukemia (AML) who are in remission but at high risk of relapse. Its secondary asset, SLS009, is a highly selective CDK9 inhibitor currently showing promise in Phase 2 trials for various blood cancers.
The company’s share price surged on December 29 after SELLAS shared an update on a Phase 3 REGAL trial evaluating GPS as a maintenance therapy in patients with AML.
The trial is designed as a blind survival study, with the end point triggered on the 80th patient death. In the update, the company reported that 72 deaths had occurred as of December 26. Because it is taking longer than expected for the trial to complete, which was previously anticipated to happen before the end of 2025, investors are speculating that the patients in the trial are living significantly longer than the historical average.
2. IO Biotech (NASDAQ:IOBT)
Year-to-date gain: 129.47 percent
Market cap: US$144.28 million
Share price: US$2.16
IO Biotech is developing immune-modulating therapeutic cancer vaccines based on its T-win technology platform, designed to activate T cells to target both tumor cells and the immune-suppressive cells.
The clinical-stage biopharmaceutical company’s lead cancer vaccine candidate is IO102-IO103, which has the brand name Cylembio. IO102-IO103 has breakthrough therapy designation from the US Food and Drug Administration (FDA) when used in combination with Merck’s (NYSE:MRK) anti-PD-1 therapy Keytruda for the treatment of advanced melanoma based on positive Phase…
