Luisrojasstock/iStock via Getty Images
Luisrojasstock/iStock via Getty Images
Galectin Therapeutics (NASDAQ:GALT) has a major milestone approaching towards the end of 2024, which is going to be the release of data from the phase 2b NAVIGATE study. This particular study is exploring the use of Belapectin for the prevention of esophageal varices in patients with NASH cirrhosis. I believe that investors should focus on this biotech, because it is gearing up to report topline results from the phase 2b/3 NAVIGATE study in Q4 of 2024. This is going to be an interim analysis, which if successful, will inform the company of whether or not it can accomplish two additional catalysts. The first of which would be the potential to file for regulatory approval of Belapectin to treat this patient population.
The second of which is going to be the ability to move towards the adaptive design of the phase 2b/3 NAVIGATE study, which will ultimately allow for the release of final data analysis. Hopefully, the drug proves itself here in being able to treat patients with NASH cirrhosis, but even if it doesn't, it still has another shot on goal in the pipeline. That is, there was some preliminary data released showing that Belapectin together with Keytruda might be able to treat patients with melanoma or head/neck squamous cell carcinoma [HNSCC]. Matter of fact, Galectin received a "Study May Proceed letter" from the FDA, stating that it could initiate a phase 2 study using Belapectin in combination with Keytruda for the treatment of patients with advanced or metastatic HNSCC. However, I believe this may be on the back burner for now because of financing constraints. Having said that, this is a backup in the pipeline to move forward with, just in case Belapectin doesn't succeed in the interim analysis from the phase 2b/3 NAVIGATE study.
As I stated above, Belapectin is being explored in the ongoing phase 2b/3 NAVIGATE study for the treatment of patients with NASH cirrhosis. However, it is very important to note what specific patients are being targeted for this patient population. The goal is to only treat patients who have portal hypertension due to NASH Cirrhosis, but no esophageal varices as of yet. NASH Cirrhosis is a huge unmet medical need, and there are no approved treatment options for it. NASH Cirrhosis is an extension of non-alcoholic steatohepatitis [NASH], now also referred to as MASH. In NASH, patients liver damage occurs because of fats, leading to fibrosis. This early process of disease is known as NASH. However, eventually all of the healthy tissue of the liver becomes replaced with scarred tissue over time, leading to what is known as NASH cirrhosis. It is said that about 20% of patients with NASH fibrosis progress to NASH cirrhosis over the course of several years or decades. Having this advanced liver disease can lead to liver failure, liver cancer and other life-threatening events. What sets Galectin apart from the many other biotechs in the NASH space is the population being targeted. That is, it is the only biotech exclusively focusing on the cirrhotic stage of NASH, that is, before such patients have developed esophageal varices.
The global non-alcoholic steatohepatitis market size is expected to grow to $14.53 billion by 2028. Above I stated that 20% of patients will progress to NASH cirrhosis. However, this market opportunity might be broken down a bit further. Why is that? That's because the goal of Galectin Therapeutics is to not target the entire NASH cirrhosis patient population. Instead, the goal is to only go after patients who have portal hypertension, but have not yet developed esophageal varices. For instance, you have many biotechs developing NASH drugs in various stages of clinical testing. Thus, there is a huge amount of biotechs crowding out this particular space of NASH fibrosis patients. However, where more biotechs need to dive into is NASH Cirrhosis, which is another portion of the NASH population not yet adequately addressed. Madrigal Pharmaceuticals (MDGL) received FDA Accelerated Approval of its drug Rezdiffra [resmetirom] for the treatment of patients with NASH fibrosis. One primary thing to note here is that such approval was for stage F2 to F3 fibrosis NASH patients.
The phase 2b/3 NAVIGATE study is exploring the use of two doses of Belapectin versus placebo in preventing esophageal varices in patients with NASH cirrhosis. Patients are randomized into the following cohorts of this trial as follows:
The data is approaching rapidly towards the end of this year and the reason why is because Galectin Therapeutics announced the end of enrollment of this late-stage study in January of 2023. The primary endpoint of this study is going to be the prevention of esophageal varices. Esophageal varices are enlarged veins of the esophagus and occur because of advanced liver disease. It stems from the liver being heavily damaged, which results in blood flow being blocked in this organ. About 50% of patients with cirrhosis end up with swollen veins. The goal of Belapectin is to reduce the number of patients who develop esophageal varices, as stated above.
It remains to be seen if the phase 3 study will ultimately end up being successful, but there was positive data released from a prior study demonstrating that Belapectin was able to reduce both HVPG [reduction of portal hypertension] in a statistically significant manner along with a great finding in terms of prevention of esophageal formation. It was said that from baseline to week 54, treatment with a 2 mg/kg/LBM dose of drug resulted in a statistically significant change in HVPG. This is a good finding, but a more important item from the phase 2b study data that was released, was how this very same dose resulted in none of the patients developing esophageal varices. This is depicted as follows:
A bit of a backstory is that the company attempted to target the entire NASH cirrhosis patient population, but failed to do so. However, it pressed on towards the advancement of this phase 2b/3 NAVIGATE study, because of what was observed in a subpopulation of patients without esophageal varices. This is what I showed above, whereby Belapectin appears effective in patients who have not yet developed this form of disease. If the very same data of greatly preventing esophageal varices compared to placebo is shown in this study, then it will be in good shape to move on with this program. In particular, it might be in a position to be allowed to file for Accelerated Approval of Belapectin to treat this specific NASH cirrhosis patient population. Of course, that's if the FDA allows such an Accelerated Approval pathway. Regardless, meeting on the primary endpoint of the phase 2b/3 NAVIGATE study is likely to be met with the stock price trading exceedingly higher.
According to the 10-Q SEC Filing, Galectin Therapeutics had cash and cash equivalents of $20.4 million. The truth is that it is low on cash and has been funded by its chairman with lines of credit over the years. The chairman of the company is Richard E. Uihlein and is the largest individual stakeholder in Galectin Therapeutics. There is still $30 million of funding available from the $60 million line of credit provided by the chairman. Despite the cash it can tap into, it believes that it has enough to fund its operations through at least December 31st of 2024. I believe that it is going to need to raise cash at least before the end of 2024. With topline data from the phase 2b/3 NAVIGATE study being released at the end of this year, it is not clear whether it will have to raise cash before or after the release of such clinical data analysis. Management can go either way, therefore, this is something to consider if deciding to invest in this stock.
There are several risks for investors to keep an eye on before investing in Galectin Therapeutics. The first risk to consider would be with respect to the advancement of the phase 2b/3 NAVIGATE study itself, which again uses Belapectin for the prevention of esophageal varices in patients with NASH Cirrhosis. There is no guarantee that the primary endpoint of this study, prevention of esophageal varices, will be met in a statistically significant manner. Even though the prior study showed that 0 out of 25 patients developed esophageal varices, there is no assurance that a larger pool of patients will end up with a similar or superior outcome.
A second risk to consider would be with respect to the IND clearance that the company received with respect to advancing Belapectin in combination with Keytruda for the treatment of patients with advanced or metastatic Head and Neck Squamous Cell Carcinoma [HNSCC]. Clearance was given by the FDA to begin a phase 2 study, but it has yet to be started due to the current financing situation. The risk is that there is no guarantee that Galectin will ultimately be able to obtain funding to initiate such a mid-stage study. Even if such a study is initiated, there is no assurance that a positive outcome will come out of it.
A third risk to consider would be with respect to the financial position that this biotech is in. It believes that it only has enough cash on hand to fund its operations through December 31st of 2024. That means it is likely going to need to raise cash before the end of this year. It may choose to raise cash either before or after the release of results from the phase 2b/3 NAVIGATE study.
This is a biotech to keep an eye on because of the release of results from the phase 2b NAVIGATE study, which is using Belapectin for the prevention of esophageal varices in NASH Cirrhosis. The hope is that the study will be successful, because there are no approved drugs to treat this specific patient population. Above, I displayed the crowded NASH fibrosis market, but what sets Galectin Therapeutics apart from many other biotechs is that it is focusing on a space that is not crowded. If it can achieve positive results from the phase 2b/3 NAVIGATE study, then it will prove Belapectin inhibitors have a place in treating patients with advanced liver disease. Not only that, but then the company would be in a good position to advance this drug for advanced HNSCC either alone or with a partner willing to fund such a program. Based on the ability of the drug to not allow the formation of esophageal varices in a prior phase 2 study in NASH Cirrhosis patients, plus the release of interim results expected in Q4 of 2024 from the NAVIGATE study, I believe that investors could benefit from any potential gains made.