12 Best High Short Interest Stocks With Highest Upside Potential

In this article, we will discuss the 12 Best High Short Interest Stocks With Highest Upside Potential.

On May 29, Melissa Brown, Managing Director of Investment Decision Research, joined BNN Bloomberg to assess the health of the US economy. Brown stated that her primary concern is not high valuations or concentrated earnings growth, but rather the inflation pressures that are driving up bond yields. She explained that while moderate inflation can signify economic growth, it reaches a tipping point where it negatively impacts stocks and bonds. She noted that while stock investors appear unconcerned (perhaps viewing the current environment as transitory), bond investors are showing clear concern by pushing longer-term yields upward. Although yields might be flattening slightly, they remain significantly higher than they were a month ago.

According to Brown, inflation exceeding the Fed’s 2 percent target is concerning because it shifts the economic balance, potentially preventing companies from raising prices while wages rise or causing consumers to face costs they cannot sustain. She observed that consumers are currently forced to spend on necessities like food and gasoline, which compels them to cut back on other areas of spending. Brown suggested that earnings have remained strong for the first quarter due to a “stock market wealth effect,” where those invested in the market are experiencing significant gains and spending freely, essentially compensating for the lack of spending from those focused only on necessities. She characterized this as a precarious way to generate earnings and noted that this disconnect explains the record low consumer sentiment index of 44.8, as consumers express pessimism in surveys while continuing to spend in specific parts of the economy.

Regarding investment opportunities, Brown expressed a preference for markets outside the US. She noted that while the US market has been strong, many non-US markets have outperformed it, and these other markets may have more room to grow since they led for many years before the current year. She stated that, in the absence of a global recession, there are likely more opportunities outside the US than within it.

Our Methodology

We sifted through the Finviz stock screener to compile a list of stocks with a short percentage of float between 15% and 25%. We then selected 12 stocks that had an upside potential of over 25%, and limited our final selection to companies that have recently reported noteworthy developments likely to impact investor sentiment. These stocks are also popular among elite hedge funds and are ranked in ascending order of their upside potential.

Note: All data was sourced on June 1. 

Why are we interested in the stocks that hedge funds pile into? The reason is simple: our research has shown that we can outperform the market by imitating the top stock picks of the best hedge funds. Our quarterly newsletter’s strategy selects 14 small-cap and large-cap stocks every quarter and has returned 498.7% since May 2014, beating its benchmark by 303 percentage points (see more details here).

12 Best High Short Interest Stocks With Highest Upside Potential

12. Bentley Systems Inc. (NASDAQ:BSY)

Average Upside Potential: 27.88%

Bentley Systems Inc. (NASDAQ:BSY) is one of the best high short interest stocks with highest upside potential. On May 7, Bentley Systems announced its financial results for Q1 2026. The company reported total revenues of $424.2 million, marking a 14.5% year-over-year increase, while subscription revenues reached $392.5 million. ARR grew to $1,494.5 million, reflecting a constant currency growth rate of 11.5%, with a net income per diluted share of $0.30.

Leadership highlighted a strong start to the year, driven by solid market fundamentals and consistent execution, particularly within the Resources and Public Works/Utilities sectors. Management emphasized the company’s commitment to advancing AI initiatives across its portfolio, aiming to integrate AI-driven workflows that enable engineering firms to leverage their proprietary knowledge more effectively at a machine scale.

On the financial operations front, the company maintained robust profitability and cash flow, reporting $187.9 million in free cash flow. Bentley Systems Inc. (NASDAQ:BSY) also optimized its capital structure by repaying 2026 convertible notes and securing a new $550 million term loan, which increased total borrowing capacity to $1.85 billion. This move aims to enhance financial flexibility for strategic priorities, including potential acquisitions and shareholder returns.

Bentley Systems Inc. (NASDAQ:BSY) develops infrastructure engineering software. The company provides integrated software solutions used across professional disciplines, infrastructure sectors, geographies, and different stages of the infrastructure lifecycle.

11. Spyre Therapeutics Inc. (NASDAQ:SYRE)

Average Upside Potential: 32.09%

Spyre Therapeutics Inc. (NASDAQ:SYRE) is one of the best high short interest stocks with highest upside potential. On May 5, Spyre Therapeutics reported a strong Q1 2026, supported by a public offering that resulted in $1.2 billion in pro forma cash, providing a financial runway into late 2029. While R&D expenses rose to $60.4 million due to clinical trial advancements, the company maintained its strategic focus on developing long-acting antibodies for inflammatory bowel and rheumatic diseases.

The company achieved significant clinical progress, notably reporting positive Phase 2 induction data for SPY001 in ulcerative colitis. With the SKYWAY rheumatoid arthritis sub-study now over-enrolled and timelines accelerated, Spyre remains on track to deliver six proof-of-concept readouts across its primary clinical trials throughout 2026.

Looking ahead, management is prioritizing the ongoing enrollment of its IBD combination therapies in the SKYLINE trial. By focusing on these differentiated pipeline assets, Spyre Therapeutics Inc. (NASDAQ:SYRE) aims to redefine current standards of care while executing a disciplined capital strategy to support long-term growth.

Spyre Therapeutics Inc. (NASDAQ:SYRE) is a US biotechnology company focused on developing medicines for people living with inflammatory bowel disease and rheumatic diseases. It develops advanced antibodies engineered for prolonged activity and formulated for delivery as monotherapies.

10. Celcuity Inc. (NASDAQ:CELC)

Average Upside Potential: 32.11%

Celcuity Inc. (NASDAQ:CELC) is one of the best high short interest stocks with highest upside potential. On May 14, Celcuity announced amendments to its Phase 3 VIKTORIA-2 clinical trial, which evaluates gedatolisib as a first-line treatment for hormone receptor-positive, HER2-negative advanced breast cancer. The study will now expand to include a separate cohort for endocrine-sensitive patients, in addition to the original focus on endocrine-resistant cases.

Each study will operate with independent statistical plans, targeting progression-free survival as the primary endpoint. This expansion follows encouraging Phase 1b results, which showed high efficacy in endocrine-sensitive patients compared to existing standard-of-care regimens. By including both endocrine-sensitive and endocrine-resistant populations, Celcuity aims to position its gedatolisib triplet therapy as a broad-spectrum treatment option for the ~90,000 women diagnosed with late-stage HR+/HER2- breast cancer annually.

In parallel with its clinical trial updates, Celcuity Inc. (NASDAQ:CELC) is advancing the long-term development of gedatolisib by pursuing a new subcutaneous formulation. The company has filed its first patent application for this injectable version, which is intended to offer a more convenient alternative to intravenous administration for patients requiring multi-year treatment.

Celcuity Inc. (NASDAQ:CELC) is a clinical-stage biotech company that develops targeted oncology therapies for solid tumors. Their lead candidate, gedatolisib, is a kinase inhibitor of the PAM pathway undergoing multiple clinical trials.

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.

8. EPAM Systems Inc. (NYSE:EPAM)

Average Upside Potential: 35.70%

EPAM Systems Inc. (NYSE:EPAM) is one of the best high short interest stocks with highest upside potential. On May 6, EPAM Systems and Anthropic formed a multi-year partnership to accelerate the delivery of secure, enterprise-grade GenAI solutions. By combining EPAM’s engineering expertise with Anthropic’s Claude models, Claude Code, and Agent SDK, the collaboration aims to help Global 2000 clients transition from experimental AI projects to fully integrated, AI-native operational workflows.

A core component of this partnership is a major investment in talent development. EPAM Systems Inc. (NYSE:EPAM) is building a dedicated practice of 10,000 Claude-certified architects, supported by 250 specialized “Black Belt” engineers. Additionally, over 20,000 employees have already completed training through the Anthropic Academy to ensure they can effectively deploy responsible AI tools across complex enterprise environments.

The partnership focuses on addressing the growing demand for safe, reliable automation and large-scale data analysis. By bridging the gap between technological complexity and rigorous safety controls, both companies intend to establish new industry standards for autonomous AI, helping enterprises automate legacy operations and achieve sustainable growth through measurable business value.

EPAM Systems Inc. (NYSE:EPAM) is a Pennsylvania-based provider of digital platform engineering and software development services. The company offers engineering, cloud, marketing, and cybersecurity services, among others.

7. Mirum Pharmaceuticals Inc. (NASDAQ:MIRM)

Average Upside Potential: 47.54%

Mirum Pharmaceuticals Inc. (NASDAQ:MIRM) is one of the best high short interest stocks with highest upside potential. On May 30, Mirum Pharmaceuticals reported positive results from its rare liver disease programs at the EASL International Liver Congress 2026. The Phase 2b VISTAS study for volixibat in primary sclerosing cholangitis/PSC demonstrated rapid, sustained, and clinically meaningful reductions in pruritus, supporting the company’s plan for an NDA submission in H2 2026.

Data from the Phase 2b AZURE-1 study of brelovitug in chronic hepatitis delta virus/HDV showed strong efficacy, with high rates of virologic response and ALT normalization at Week 24, even in patients with advanced disease. Mirum expects topline data from its Phase 3 AZURE trials later in 2026, with potential BLA submission in 2027.

Additionally, real-world evidence for the established therapy LIVMARLI (maralixibat) in progressive familial intrahepatic cholestasis/PFIC showed improved event-free survival when compared to an external control cohort. These results reinforce the long-term clinical benefits of LIVMARLI in reducing the risk of surgical biliary diversion, liver transplantation, and death in PFIC patients.

Mirum Pharmaceuticals Inc. (NASDAQ:MIRM) is a biotech company that develops and commercializes novel therapies for rare & orphan diseases.

6. Apogee Therapeutics Inc. (NASDAQ:APGE)

Average Upside Potential: 48.85%

Apogee Therapeutics Inc. (NASDAQ:APGE) is one of the best high short interest stocks with highest upside potential. On May 27, Apogee Therapeutics secured $1.3 billion in non-dilutive financing from Blackstone Life Sciences to fund Phase 3 development and commercialization of zumilokibart. The deal includes $800 million in synthetic royalties and $500 million in senior debt, which, alongside existing cash, allows Apogee to reach profitability without further equity raises.

The funding is milestone-based, tied to Phase 3 progress and FDA approval. Blackstone’s commitment (the largest royalty financing for a pre-Phase 3 program) underscores its confidence in zumilokibart’s potential as a first-line treatment for atopic dermatitis and other inflammatory conditions.

Management noted that this partnership provides the capital flexibility needed to advance zumilokibart as a multi-indication therapy. By securing this financial foundation, Apogee Therapeutics Inc. (NASDAQ:APGE) aims to accelerate its pipeline and successfully transition from clinical innovation to commercial launch.

Apogee Therapeutics Inc. (NASDAQ:APGE) operates as a biotechnology company, offering treatment of atopic dermatitis, chronic obstructive pulmonary disease, and related inflammatory and immunology indications.

Click to continue reading and see the 5 Best High Short Interest Stocks With Highest Upside Potential.

Disclosure: None. None. Follow Insider Monkey on Google News.