5 Best High Short Interest Stocks With Highest Upside Potential

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1. Summit Therapeutics Inc. (NASDAQ:SMMT)

Average Upside Potential: 91.12%

Summit Therapeutics Inc. (NASDAQ:SMMT) is one of the best high short interest stocks with highest upside potential. On May 31, Summit Therapeutics announced positive Phase III overall survival/OS results from the HARMONi-6 trial, which evaluated ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in patients with advanced squamous non-small cell lung cancer/NSCLC.

The study showed that the ivonescimab regimen reduced the risk of death by 34% (HR 0.66), marking the first time a Phase III trial has shown a statistically significant OS benefit over standard PD-(L)1 inhibitor and chemotherapy combinations in the first-line setting. At a median follow-up of 21.4 months, patients receiving ivonescimab achieved a median OS of 27.89 months compared to 23.69 months for those on the tislelizumab regimen. The benefit was consistent across PD-L1 expression subgroups, and the 24-month OS rate reached 64.7% for the ivonescimab arm.

These findings, simultaneously published in The Lancet, confirm the potential of ivonescimab to transform front-line treatment paradigms for NSCLC. Ivonescimab maintained an acceptable and manageable safety profile consistent with prior trials, with no new safety signals reported.

Summit Therapeutics Inc. (NASDAQ:SMMT) is a biopharmaceutical firm.

While we acknowledge the potential of SMMT to grow, our conviction lies in the belief that some AI stocks hold greater promise for delivering higher returns and have limited downside risk. If you are looking for an AI stock that is more promising than SMMT and that has 100x upside potential, check out our report about the cheapest AI stock.

READ NEXT: 10 Best Future Tech Stocks to Buy According to Billionaires and 10 Best Low Risk Stocks to Buy in 2026.

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