5 Small-cap Biotech ETFs to Watch

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May 21, 2025

Thanks to exchange-traded funds (ETFs), investors don’t have to be tied to one specific stock. When it comes to biotech ETFs, they give sector participants exposure to many biotech companies via one vehicle.

ETFs are a popular choice as they allow investors to enter the market more safely compared to investing in standalone stocks. A key advantage is that even if one company in the ETF takes a hit, the impact will be less direct.

All other figures were also current as of that date. Read on to learn more about these investment vehicles.

1. ALPS Medical Breakthroughs ETF (ARCA:SBIO)

AUM: US$80.23 million

Launched in December 2014, the ALPS Medical Breakthroughs ETF tracks small- and mid-cap biotech stocks that have one or more drugs in either Phase II or Phase III US FDA clinical trials. Its holdings must have a market cap between US$200 million and US$5 billion.

There are 100 holdings in this biotechnology fund, with about 60 percent being small- and micro-cap stocks. Its top holdings include Verona Pharma (NASDAQ:VRNA) at a weight of 5.31 percent, Alkermes (NASDAQ:ALKS) at 4.41 percent and Axsome Therapeutics (NASDAQ:AXSM) at 4.24 percent.

2. Tema Oncology ETF (NASDAQ:CANC)

AUM: US$63.67 million

The Tema Oncology ETF provides exposure to biotech companies operating in the oncology industry. It includes companies developing a range of cancer treatments, including CAR-T cell therapies and bispecific antibodies.

Launched in August 2023, there are 52 holdings in this biotechnology fund, of which about half are small- to mid-cap stocks and 4 percent are micro-cap stocks. Among its top holdings are Revolution Medicines (NASDAQ:RVMD) at a 6.05 percent weight, Roche Holding (OTCQX:RHHBF,SWX:RO) at a weight of 5.08 percent and Eli Lilly and Company (NYSE:LLY) at 4.87 percent.

3. Tema GLP-1 Obesity and Cardiometabolic ETF (NASDAQ:HRTS)

AUM: US$51.5 million

Launched in November 2023, the Tema GLP-1 Obesity and Cardiometabolic ETF tracks biotech stocks with a focus on diabetes, obesity and cardiovascular diseases. The fund was renamed on March 25 from Tema Cardiovascular and Metabolic ETF. More than three-quarters of its holdings are based in the US.

There are 47 holdings in this biotechnology fund, with about 75 percent being large-cap stocks and 18 percent mid-cap. Its top holdings are Eli Lilly and Company at a 9.92 percent weight, Abbott Laboratories (NYSE:ABT) at 4.77 percent and AstraZeneca (NASDAQ:AZN) at 4.14 percent.

4. ProShares Ultra NASDAQ Biotechnology (NASDAQ:BIB)

AUM: US$44.19 million

The ProShares Ultra NASDAQ Biotechnology ETF was launched in April 2010 and is leveraged to offer twice daily long exposure to the broad-based NASDAQ Biotechnology Index, making it an ideal choice “for investors with a bullish short-term outlook for biotechnology or pharmaceutical companies.” However, analysts also advise investors with a low risk tolerance or a buy-and-hold strategy against investing in this fund due to its unique nature.

Of the 268 holdings in this ETF, the top biotech stocks in the ETF are Gilead Sciences (NASDAQ:GILD) at a 6.06 percent weight, Vertex Pharmaceuticals (NASDAQ:VRTX) at 5.99 percent and Amgen (NASDAQ:AMGN) at 5.84 percent. Additionally, over a third of its holdings are in United States Treasury Bills.

5. Direxion Daily S&P Biotech Bear 3x Shares (ARCA:LABD)

AUM: US$43.42 million

The Direxion Daily S&P Biotech Bear 3x Shares ETF is designed to provide three times the daily return of the inverse of the S&P Biotechnology Select Industry Index, meaning that it rises in value when the index falls and falls in value when it rises. Leveraged inverse ETFs are designed for short-term trading and are not suitable to hold long-term. They also carry a high degree of risk as they can be significantly affected by market volatility.

The top three life science holdings in this ETF are Exact Sciences (NASDAQ:EXAS) at a weight of 2.23 percent, Alnylam Pharmaceuticals (NASDAQ:ALNY) at a weight of 2.15 percent and Neurocrine Biosciences (NASDAQ:NBIX) at 2.03 percent.

Securities Disclosure: I, Meagen Seatter, hold no direct investment interest in any company mentioned in this article.

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