Galectin Therapeutics, Inc. (NASDAQ: GALT) is a clinical-stage biopharmaceutical company leading the charge in the development of novel therapies targeting galectin proteins, which play a crucial role in various disease processes. The company's unwavering focus on galectin science and drug development has positioned it at the forefront of tackling chronic liver disease and cancer.
Business Overview and History
Galectin Therapeutics was founded in July 2000 and incorporated in the state of Nevada in January 2001, originally under the name Pro-Pharmaceuticals, Inc. The company later changed its name to Galectin Therapeutics Inc. on May 26, 2011, reflecting its strategic shift towards developing therapies that target galectin proteins.
The company's drug candidates are based on its method of targeting galectin proteins, which are key mediators of biologic and pathologic functions. Galectin Therapeutics uses naturally occurring, readily-available plant products as starting material in manufacturing processes to create proprietary, patented complex carbohydrates with specific molecular weights and other pharmaceutical properties. These complex carbohydrate molecules are then formulated into acceptable pharmaceutical formulations.
In January 2013, Galectin Therapeutics submitted an Investigational New Drug (IND) application to the FDA with the goal of initiating a Phase 1 study in patients with NASH and advanced liver fibrosis to evaluate the safety of belapectin, the company's lead product candidate, and pharmacodynamics biomarkers of disease. The FDA indicated that Galectin Therapeutics could proceed with the US Phase 1 clinical trial for belapectin with a development program aimed at obtaining support for a proposed indication of belapectin for treatment of NASH with advanced fibrosis.
Over the next several years, Galectin Therapeutics conducted a Phase 1 trial and two larger Phase 2 trials - the NASH-FX trial and the NASH-CX trial. The NASH-FX trial did not meet its primary endpoint, but belapectin was found to be safe and well tolerated. The NASH-CX trial demonstrated a favorable safety profile and clinically meaningful efficacy results in patients without esophageal varices at baseline, as shown by a decrease in portal pressure associated with the prevention of development of varices. However, the difference from placebo in the overall patient population was not statistically significant.
The company's lead product candidate, belapectin, is a proprietary, patented compound derived from natural, plant-based starting materials. Belapectin has demonstrated promising results in preclinical and clinical studies for the treatment of liver fibrosis, severe skin disease, and various cancer indications, including melanoma and head and neck squamous cell carcinoma.
Galectin Therapeutics' research and development efforts have primarily focused on the role of galectin-3, a key mediator of biological and pathological functions. Preclinical studies have shown that galectin-3 knockout mice do not develop liver fibrosis in response to toxic insults, highlighting the importance of this protein in the fibrotic process. This finding has provided a strong rationale for targeting galectin-3 as a therapeutic approach.
The company's lead indication for belapectin is the treatment of metabolic dysfunction-associated steatohepatitis (MASH, formerly known as non-alcoholic steatohepatitis or NASH) with cirrhosis. Galectin Therapeutics has completed two Phase 1 clinical studies, a Phase 2 clinical study in MASH patients with advanced fibrosis (NASH-FX), and a Phase 2b clinical trial in MASH patients with compensated cirrhosis and portal hypertension (NASH-CX).
In February 2023, the company completed randomizations totaling 357 patients in a large, global clinical trial, the NAVIGATE trial. This seamless, adaptive, Phase 2b/3 study is designed to evaluate the safety and efficacy of belapectin for the prevention of esophageal varices in patients with MASH cirrhosis. The NAVIGATE trial is a critical milestone for Galectin Therapeutics, as it aims to address the significant unmet medical need in this patient population.
Financials and Liquidity
As of September 30, 2024, Galectin Therapeutics reported $27.06 million in cash and cash equivalents, which the company believes is sufficient to fund currently planned operations approximately through May 2025. However, the company's cash position may not be sufficient to support its daily operations after May 2025, and it will likely need to raise additional capital to continue its operations.
For the year ended December 31, 2023, Galectin Therapeutics reported a net loss of $41.06 million, with no revenue generated. The company's research and development expenses increased to $32.13 million, while general and administrative expenses decreased to $5.94 million. The company's net cash used in operations was $32.97 million for the year.
In the most recent quarter (Q3 2024), Galectin Therapeutics reported no revenue and a net loss of $11.22 million. This represents an increase in net loss compared to Q3 2023, which saw a net loss of $10.43 million. The increase in net loss was primarily due to the timing of expenses related to the company's NAVIGATE clinical trial.
Research and development expenses for the three and nine months ended September 30, 2024, were $7.59 million and $25.46 million, respectively. These expenses were primarily related to the costs associated with the NAVIGATE clinical trial. General and administrative expenses for the same periods were $1.47 million and $4.54 million, respectively.
It's important to note that Galectin Therapeutics has incurred significant operating losses since its inception and has had no revenues to date. The company's ability to continue as a going concern is likely dependent on the top-line results of the NAVIGATE clinical trial, expected in December 2024, and its ability to raise additional capital.
Liquidity and Capital Resources
As of September 30, 2024, Galectin Therapeutics had a debt-to-equity ratio of -1.131. The company's current ratio and quick ratio were both 1.135, indicating that it had sufficient short-term assets to cover its short-term liabilities.
To bolster its financial position, on November 14, 2024, the company entered into a second supplemental unsecured $6 million line of credit with its chairman, Richard E. Uihlein. This additional financing is intended to help the company meet its working capital needs.
Upcoming Catalysts and Risks
The upcoming top-line results from the NAVIGATE trial in December 2024 are a critical catalyst for Galectin Therapeutics. If the results are positive and demonstrate the efficacy of belapectin in preventing the development of esophageal varices in MASH cirrhosis patients, it could pave the way for potential regulatory approval and commercialization, addressing a significant unmet medical need.
However, there are several risks associated with Galectin Therapeutics' business. The company's reliance on the success of its lead product candidate, belapectin, poses a significant risk, as failures or delays in the clinical development or regulatory approval process could severely impact the company's future prospects. Additionally, the company's ability to raise additional capital to fund its operations beyond May 2025 is crucial, as its current cash position may not be sufficient to support its daily operations.
Furthermore, the highly competitive nature of the pharmaceutical industry, particularly in the areas of liver disease and cancer, presents another risk for Galectin Therapeutics. The company faces competition from larger, well-established pharmaceutical companies, as well as other biotechnology firms, which may have greater resources and expertise in drug development and commercialization.
Liver Fibrosis and Cirrhosis Program
Belapectin, Galectin's lead product candidate, is being developed for the treatment of compensated NASH cirrhosis in patients with portal hypertension. Preclinical data has shown that belapectin has a significant therapeutic effect on liver fibrosis in animal models of NASH. The company has completed two Phase 1 clinical studies and two Phase 2 clinical trials (NASH-FX and NASH-CX) evaluating belapectin in NASH patients.
The NASH-CX trial, a larger multi-center study, explored the use of belapectin for the treatment of patients with well-compensated NASH cirrhosis and portal hypertension. The study demonstrated a favorable safety profile and clinically meaningful efficacy results in patients without esophageal varices at baseline, as evidenced by a decrease in portal pressure and a statistically significant reduction in the development of new esophageal varices compared to placebo.
Building on the NASH-CX results, Galectin is currently conducting the NAVIGATE trial, a seamless adaptive Phase 2b/3 clinical study evaluating the safety and efficacy of belapectin for the prevention of esophageal varices in NASH cirrhosis patients with clinical signs of portal hypertension. The trial is designed to assess the effect of belapectin on the incidence of new varices as the primary endpoint, as well as the incidence of additional clinically significant cirrhosis-related outcomes as a key secondary endpoint. The final patient was randomized in February 2023, and the top-line efficacy and safety results are expected in late December 2024.
Cancer Immunotherapy Program
Galectin Therapeutics is also exploring the potential of galectin inhibition in cancer immunotherapy. Preclinical studies have indicated that belapectin enhances the immune response to cancer cells and increases tumor shrinkage and survival in animal models of various cancers when combined with immune checkpoint inhibitors or immune cell activators.
Based on these promising preclinical results, Galectin has initiated Phase 1b clinical studies evaluating belapectin in combination with pembrolizumab (KEYTRUDA) in patients with metastatic melanoma and head and neck squamous cell carcinoma (HNSCC). The combination therapy has demonstrated a 50% objective response rate in advanced melanoma and a 33% response rate in HNSCC patients.
In the third quarter of 2022, Galectin announced that it had filed an Investigational New Drug (IND) application with the FDA for a Phase 2 trial evaluating belapectin in combination with a checkpoint inhibitor for the treatment of recurrent or metastatic HNSCC. The commencement of this trial is dependent on the timing of additional financing.
Conclusion
Galectin Therapeutics is at a critical juncture in its journey as a pioneer in the development of galectin-targeted therapies. The upcoming top-line results from the NAVIGATE trial will be a defining moment for the company, potentially unlocking a new treatment option for patients with MASH cirrhosis and portal hypertension. While the company faces significant financial and operational challenges, its unwavering commitment to leveraging the unique properties of galectin proteins holds promise for addressing unmet medical needs in liver disease and cancer. Investors will keenly await the NAVIGATE trial results, which could serve as a catalyst for Galectin Therapeutics' future growth and success.