Few large biotech stocks have rewarded patience like Moderna (NASDAQ:MRNA | MRNA Price Prediction), and the size of that run now raises a hard question about what comes next. Moderna stock is up 545% year-to-date to $190.27, believe it or not. That figure leaves shareholders deciding whether to lock in their gains or lean further into the story.

For its part, Pfizer (NYSE:PFE) stock is up 16% year-to-date at $27.40, a healthy gain for a vaccine seller with a much broader drug lineup. Meanwhile, BioNTech (NASDAQ:BNTX) stock has gained 1% year-to-date at $96.19, leaving the other listed messenger RNA (mRNA) developer close to flat while Moderna stock has multiplied several times over.

Sector gains look modest beside that surge, with the iShares Biotechnology ETF (NASDAQ:IBB) up 21% year-to-date. For a broader market gauge, the SPDR S&P 500 ETF Trust (NYSEARCA:SPY) has advanced 14% year-to-date, trailing even the biotech fund. Those gaps frame the rally in Moderna stock as a company story.

Reuters reported last week that Moderna is set to join the NASDAQ 100, replacing Warner Bros Discovery. Index inclusion changes which funds must own Moderna stock, and that shift in the buyer base can draw fresh attention to the company. A NASDAQ 100 slot also places Moderna among the largest nonfinancial companies listed on Nasdaq, a marker of how much the market’s view of the company has changed.

Moderna sells four approved products: Spikevax for COVID-19, mRESVIA for respiratory syncytial virus, mNEXSPIKE as a next-generation COVID vaccine and mCOMBRIAX as a combination influenza and COVID vaccine. Underneath every product sits the company’s mRNA platform, which Moderna sells as its advantage because the same technology can be pointed at a new target quickly.

BioNTech works on the same underlying technology, which makes BioNTech the closest comparison to Moderna among the three companies, and its shares sit close to flat for the year, so platform enthusiasm alone hasn’t lifted every mRNA name. The difference suggests the market is paid back the specific products and pipeline at Moderna over the shared science.

Moderna’s bull case rests on the company’s oncology pipeline, including intismeran autogene, a personalized cancer vaccine developed in collaboration with Merck. A personalized cancer vaccine would reach a market Moderna’s respiratory franchise never could, and the company’s pipeline also extends into rare disease. Four approved products already give Moderna a commercial base while that oncology work develops.

However, the 545% advance in Moderna stock has already priced in a great deal of what the company’s pipeline might eventually deliver (riding a run like this is fine as long as the exit is planned, which is the whole point of our free bubble handbook). Index membership changes the buyer base for Moderna stock, while the company’s scientific case still depends on what its programs prove. It will be worth watching whether MRNA stock holds its gains once the index change takes effect.

Given how far Moderna stock has run ahead of BioNTech stock, Pfizer stock and the biotech fund, investors should adjust their holdings carefully. Investors should size their positions to reflect the gap between the 545% gain in MRNA stock and what the company’s pipeline has proved so far.

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