12 Best High Short Interest Stocks With Highest Upside Potential

9. Madrigal Pharmaceuticals Inc. (NASDAQ:MDGL)

Average Upside Potential: 34.32%

Madrigal Pharmaceuticals Inc. (NASDAQ:MDGL) is one of the best high short interest stocks with highest upside potential. On May 27, Madrigal presented new data at the 2026 EASL Congress, reinforcing Rezdiffra as a foundational therapy for metabolic dysfunction-associated steatohepatitis/MASH. Secondary analyses from the Phase 3 MAESTRO program demonstrated that the medication improved atherogenic lipid profiles, such as LDL-C and ApoB, regardless of whether patients were also receiving statin therapy.

These findings suggest Rezdiffra may offer significant cardiometabolic benefits alongside its liver-directed effects. Clinical research also highlighted the potential of the ANTICIPATE-NASH risk model to predict liver-related outcomes. In patients with well-compensated MASH cirrhosis, treatment with Rezdiffra led to progressive improvements in risk scores over two years, with a notable reduction in the proportion of patients classified as high-risk for clinically significant portal hypertension.

This supports the use of noninvasive testing to identify patients who may benefit most from intervention. Real-world evidence further validated these results, showing early and sustained improvements in liver enzymes and stiffness measurements in routine clinical practice. Studies indicated that ~half of the observed patients achieved a significant reduction in liver stiffness within 9 months of initiating treatment.

Madrigal Pharmaceuticals Inc. (NASDAQ:MDGL) is a biopharmaceutical company with a sharp focus on tackling a serious and underserved liver disease called MASH. Their flagship product, Rezdiffra, works directly on the liver to address the root causes of the condition, offering patients much-needed attention in an area where effective therapies have long been lacking.