SPDR S&P Biotech ETF (XBI) Top 25 Holdings

The SPDR S&P Biotech ETF (XBI) provides investors with a pure play on the biotechnology sector. Unlike broad healthcare ETFs that mix pharmaceuticals and insurers, XBI focuses on biotech companies, ranging from early-stage innovators to established drugmakers. This focus makes it one of the most volatile but also one of the most opportunity-rich ETFs in the healthcare space.

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What makes XBI unique is its equal-weight structure. Instead of letting a handful of mega-cap drug makers dominate the fund, each holding is kept close to the same weight. That means small- and mid-cap names often have as much influence on performance as the largest players, which can lead to sharp swings in both directions.

For investors, XBI provides a means to capitalize on the upside of breakthroughs in gene editing, treatments for rare diseases, and next-generation therapies. But it also comes with risk, since many holdings rely on drug pipelines, clinical trials, and regulatory decisions. To understand what’s driving performance today, let’s look at the top holdings.

1. CRISPR Therapeutics (CRSP)

CRISPR Therapeutics leads the XBI with a 2.2% weight, and for good reason. The company is pioneering CRISPR/Cas9 gene-editing technology, which has the potential to cure genetic disorders at the source. Its leading programs target sickle cell disease and beta thalassemia, conditions with enormous unmet medical needs.

The promise is enormous: rather than managing symptoms, CRISPR’s approach rewrites the genetic code itself. But with that upside comes risk. Clinical trials and regulatory approvals remain the biggest hurdles, and setbacks could be painful for investors.

Still, the upside is transformative. If CRISPR proves its therapies to be safe and effective, it could redefine medicine in a way few companies have ever done. For XBI, CRSP is a perfect example of the fund’s moonshot exposure, high volatility, high reward, and game-changing science.

2. Moderna (MRNA)

Moderna may be forever linked with its COVID-19 vaccine, but the company is determined to show it’s more than a pandemic-era success story. Its mRNA platform has potential applications well beyond infectious diseases, including oncology, rare diseases, and personalized vaccines. Current late-stage trials in flu and RSV are critical proving grounds.

Financially, Moderna is one of the rare small-cap biotech names with scale and resources. Sitting on billions in cash, the company can aggressively fund its R&D pipeline while navigating inevitable setbacks. That balance of capital and innovation makes it a more stable anchor in an otherwise volatile ETF.

For XBI investors, Moderna offers both credibility and optionality. It’s a reminder that the fund doesn’t just include speculative clinical-stage names but also companies with proven commercial models. If mRNA technology fulfills its broader promise, Moderna could remain a top player for decades.

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3. Regeneron Pharmaceuticals (REGN)

Regeneron is one of the most established players in the ETF, making up 2% of the portfolio. With blockbusters like Eylea for eye disease and Dupixent for asthma and dermatitis, it has a stable revenue base that’s rare in the biotech-heavy XBI. That makes it one of the more defensive positions in the fund.

But Regeneron isn’t resting on its current lineup. Its R&D pipeline includes oncology, cardiovascular disease, and next-gen immunology, supported by deep partnerships with Sanofi and Bayer. This dual focus, cash flow from existing blockbusters, and investment in future drugs, helps explain why Regeneron is a cornerstone in biotech investing.

For XBI holders, Regeneron serves as ballast. While many smaller holdings swing on binary trial results, Regeneron’s proven model offers consistency. That blend of reliability and innovation makes it one of the ETF’s most valuable names.

What Investors Should Know About XBI

XBI offers one of the purest ways to invest in biotechnology, balancing established players with high-risk, high-reward innovators. Its equal-weight structure means it doesn’t lean on giants like Amgen or Gilead but spreads exposure across more than 150 companies. That makes it more volatile than most healthcare funds, but also more representative of biotech innovation as a whole.

For investors, XBI is less about steady compounding and more about capturing breakthroughs. When biotech rallies, XBI often outperforms. When sentiment turns, it can fall sharply. That tradeoff is the essence of biotech investing.

Key Insights

• Equal weight structure: No single giant dominates, and every holding has influence, from CRISPR to Amgen.
• Volatility is built in: Small- and mid-cap biotech names drive performance, which means trial results, FDA approvals, and M&A rumors can move the ETF quickly.
• Innovation upside: Investors gain exposure to cutting-edge therapies, gene editing, rare diseases, and oncology, without betting on one company.
• Not a defensive play: Unlike XLV or broader healthcare ETFs, XBI tilts aggressively toward innovation and early-stage science.

Equal Weighting for Biotech’s Biggest Breakthroughs

The SPDR S&P Biotech ETF is designed for investors who believe in the long-term growth of medical innovation but don’t want to pick individual winners. By holding a diversified basket of biotech names, it captures both the promise and the peril of the sector.

The equal-weight structure ensures small- and mid-cap innovators carry just as much weight as established players, reflecting the idea that tomorrow’s blockbuster could come from anywhere. This keeps XBI dynamic and forward-looking.

For most portfolios, XBI works best as a tactical or satellite holding rather than a core position. However, for those willing to stomach the volatility, it offers a front-row seat to the breakthroughs that are shaping the future of medicine.

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Disclaimer:

Please note that the articles on TIKR are not intended to serve as investment or financial advice from TIKR or our content team, nor are they recommendations to buy or sell any stocks. We create our content based on TIKR Terminal’s investment data and analysts’ estimates. Our analysis might not include recent company news or important updates. TIKR has no position in any stocks mentioned. Thank you for reading, and happy investing!