Hello, everyone. Welcome to the H.C. Wainwright Eighth Annual MASH Virtual Conference. For our next presentation, we have Galectin Therapeutics. Joining us today is the Galectin team, and presenting for us today is Dr. Khurram Jamil. He's the CMO of Galectin. Dr. Jamil, we're very happy to have you with us today. Please go ahead with your presentation.
Thank you, Thomas. Good morning, everybody. We are excited to share an update on Galectin Therapeutics, a company dedicated to developing novel therapies for chronic liver disease and cancer. Our focus today is on our lead compound, belapectin, and the progress we have made in our clinical program. We'll cover our unique approach, strategic initiatives, and significant market opportunities we're addressing. Thank you for your interest and time in our company today. This presentation contains forward-looking statements, which are based on current expectations and assumptions. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected here. We encourage investors to consider these risks when evaluating our company. Please refer to our SEC filing for a detailed discussion of these risk factors. Galectin Therapeutics is a company that's pioneering galectin-based therapies, with our flagship product, belapectin, leading the way.
Belapectin is a potent inhibitor of galectin-3, a protein implicated in multiple fibrotic and inflammatory processes. We have secured fast-track designation from FDA, underscoring the potential importance of our work. Our current clinical focus is on MASH cirrhosis, a severe liver condition with no FDA-approved treatment, as well as combination therapy in oncology. Our patent protection extends through twenty thirty-five, providing a strong foundation for future growth. We're a lean organization. Every member of the leadership team brings at least two decades of pharma, biotech, or corporate governance experience. This experienced team, along with our dedicated board members, is driving our innovation forward. I joined Galectin Therapeutics earlier this year, motivated by the opportunity to work on belapectin, which targets a pathway distinct from all other anti-fibrotic treatments currently in development. I've had the privilege of leading multiple compounds through approval with FDA and ex-U.S. regulatory agencies.
Our expertise gives us confidence to successfully navigate complex regulatory landscape and achieve planned milestones. Our pipeline focuses on addressing critical unmet need in MASH cirrhosis and oncology. Belapectin is our lead candidate, with clinical trials designed to assess its efficacy in preventing the progression of liver disease. In oncology, we're exploring its potential to enhance the effectiveness of checkpoint inhibitors, offering new hope for our patients. Additionally, our discovery program is actively identifying new galectin-3 therapies on our portfolio. This focused approach allows us to channel our resources and expertise where they can have the most impact. Galectin-3 is a lectin protein, which is highly expressed in fibrotic liver. Its upregulation is a key driver of fibrosis and inflammation, making it an attractive target for therapeutic intervention.
It acts as a molecular glue that facilitates the adhesion of cells and the activation of macrophages, which are essential to the disease process in MASH cirrhosis and cancer. By inhibiting galectin-3, we aim to disrupt these pathological pathways and provide significant clinical benefit. Our research has shown that targeting galectin-3 can lead to a reduction in fibrosis and inflammation, offering novel approach to treatments. Galectin-3 inhibition has been a potential target for a number of other conditions, including pulmonary fibrosis and heart failure. We've also generated encouraging clinical data beyond what's being shared today. This unique mechanism of action underpins the development of belapectin alone, and also potentially as a combination therapy for multiple indications. Belapectin, as the name indicates, is a pectin or complex carbohydrate. It has demonstrated substantial anti-fibrotic preclinical properties in preclinical studies, making it a promising candidate for treating fibrotic diseases.
It effectively reduces the expression of galectin-3, thereby mitigating the chronic inflammation and fibrosis associated with MASH. Preclinical studies have also shown a decrease in NAFLD activity score and a significant reduction in hepatic fibrosis in animal models. Importantly, belapectin has a favorable safety profile, even at high doses, with minimal adverse events reported. This robust preclinical data supports development as a potentially safe and effective treatment for these patients. Before I share the clinical data, I would like to briefly highlight the significant market opportunity in MASH cirrhosis indication. The market for MASH cirrhosis therapy is both vast and underserved, with a growing patient population and no FDA-approved therapy in these patients. In the U.S. alone, the prevalence of MASH cirrhosis is increasing, driven primarily by rising rates of obesity and diabetes.
This condition can lead to severe complications if left untreated or resolved, including liver failure and the need for liver transplant in the end stages. It's estimated that there are more than five million patients with MASH cirrhosis in the U.S., yet there are less than nine thousand liver transplants performed every year for those who have advanced cirrhosis and end-stage liver disease, highlighting the desperate need for new treatment options. The economic burden and the dire need for effective treatments present a substantial market opportunity for belapectin. Our goal is to address this significant unmet medical need with belapectin and provide a solution for our patients. Belapectin is uniquely positioned to be potentially the first-to-market therapy for cirrhosis portal hypertension patients. The lack of FDA-approved therapy for this stage of liver disease highlights the urgent need for effective therapies.
With the potential to prevent the progression to more severe complications, belapectin could significantly improve patient outcomes. In a blinded market research conducted earlier this year, we received favorable feedback from both treating physicians and peers. The total addressable market is estimated at currently more than multibillion dollars. We believe that our clinical development efforts will pave the way for belapectin to become a key player in this therapeutic area. Cirrhosis represents the combination of decades of liver injury. Portal hypertension is the earliest and most important consequence of cirrhosis and underlies most of the clinical complication of the disease. Hepatic venous pressure gradient, or HVPG, is a direct measure of portal pressure.
As you can see here on this slide, that, the outcomes are significantly worse unless the disease can be halted before HVPG gets above 10 mmHg, which is known as clinically significant portal hypertension. That's where we believe belapectin will fit into the current treatment paradigm, with the goal to prevent progression of liver disease and in actually reversing the portal hypertension. Currently, there is no FDA-approved treatment to treat portal hypertension, to reverse portal hypertension or cirrhosis in chronic liver disease. Belapectin has shown promising results in phase I and II clinical trials to date. These studies have shown its impact in cirrhosis with portal hypertension, specifically in reducing portal pressure and preventing the formation of new varices in patients without pre-existing varices. It has been well tolerated across various dose levels, with no significant safety concerns reported.
Our data supports the continued development of belapectin in registration trials. In this phase IIb clinical trial, evaluating belapectin in patients with MASH cirrhosis, 162 patients were enrolled across three dose groups, receiving 2 or 8 milligrams per kilogram lean body weight of belapectin or placebo over a 54-week infusion. Secondary endpoints included MASH cirrhosis diagnosis through biopsy, assessment through biopsy, as well as varices through endoscopy. While the trial didn't meet its primary endpoint in overall patient population, showing no statistically significant difference in change in portal pressure at one year between the two belapectin doses and placebo, in a key subgroup of patients without varices at the time of randomization, belapectin significantly reduced portal pressure compared to placebo in 2 milligram dose group at one-year mark.
We know from published clinical trial data across many other interventions that even a one millimeter HG drop in portal pressure leads to significant clinical benefits. Hence, this was a key finding from the trial. Besides significant reduction in portal pressure, it was also shown that none of the subjects in the two-milligram cohort developed varices at the end of therapy. There are significantly more patients developed varices in the placebo cohort. We have since published the PK data that showed eight milligram dose overshot the optimum PK exposure levels. Hence, in the ongoing studies, we are only testing two and four milligram dose levels. Based on the encouraging results from the phase IIb study, we have ongoing NAVIGATE study, which is an adaptive, seamless phase IIb/III registration trial.
It's assessing the safety and efficacy of two doses of belapectin against placebo, and each patient will receive infusion for over eighteen-month period. At interim analysis, an independent data monitoring committee, DSMB, will use a predetermined criteria to provide recommendation on stopping the study for overwhelming efficacy, futility, or proceeding to phase III study. In terms of patient population, study is enrolling patients with MASH cirrhosis who meet the portal hypertension criteria using the latest treatment guidelines, which includes liver stiffness measure and platelet count. The primary endpoint is development of new varices, assessed through a central review of EGD upper endoscopy videos. This robust and unique process is accepted by FDA, thus alleviating the need for invasive liver biopsy and also mitigate the well-established limitation of using liver biopsies as primary endpoint.
This trial will also evaluate other liver-related complications as outcomes, secondary outcomes, as well as mortality rates and liver transplant rates. A quick update on NAVIGATE trial. We have finished enrollment in the phase 2b portion of the study. A total of three hundred and fifty-seven subjects have been enrolled across the three dose groups, and currently undergoing the eighteen-month blinded infusion therapy. There have been five DSMB meetings held so far in the trial, and each time, the independent committee has affirmed the safety profile of the drug. In fact, the discontinuation rate due to adverse events in the blinded NAVIGATE trial is much lower than what we have observed in other MASH cirrhosis trials or even with GLP-1 agonist trials reported so far. The planned interim analysis is scheduled for December this year.
This trial is a critical step towards regulatory approval and eventual commercialization of belapectin. Before I end, I want to highlight briefly our cancer immuno specialty therapy program and some of the data we have published so far. We're exploring the use of belapectin in combination with PD-1 inhibitor pembrolizumab or Keytruda in patients with advanced melanoma, as well as head and neck squamous cell carcinoma. The combination targets the immunosuppressive microenvironment of the tumor, potentially enhancing the effectiveness of immunotherapy. Our phase 1 study has yielded promising results. As you can see here, the complete response rate, as well as objective responses observed in patients with metastatic melanoma and head and neck cancer, ranged from 33% to 50%. This suggests that belapectin can improve patient outcomes by augmenting the body's immune response against cancer.
We're excited about the clinical application of this approach and continue to explore the advancement of program with potential partners. In summary, Galectin Therapeutics is a company with unique focus and promising future. Our lead compound, belapectin, addresses significant unmet medical need in both MASH cirrhosis and oncology. We have a strong pipeline and a highly experienced leadership team driving our initiatives. With an upcoming major clinical milestone on the horizon, we're well-positioned for growth and value creation. We believe that our innovative therapies have the potential to make a significant impact on patient care in an area with huge unmet medical need. In closing, we're dedicated to advancing our clinical programs and providing new treatment options for patients with chronic liver disease and cancer. We're excited about the upcoming readout at the end of the year and look forward to sharing the results with all of you.
Please feel free to reach out with any questions or for further information. Thank you for your interest and attention in Galectin Therapeutics.
Thank you so much for your presentation, Khurram. Perhaps one question from me, as you just pointed out, a significant catalyst for both, belapectin and Galectin would be the phase 2b interim data readout in fourth quarter. Just wondering, what would we consider as a baseline level of efficacy you would expect to see? And then after that, what would be the regulatory process following that?
So obviously, we'll be assessing in a blanket manner through DSMB that both two dose levels. There are two doses being tested, two and four milligram, and each dose will be tested against placebo to see which dose has the best response at eighteen months. Response being the primary endpoint, which is prevention and development of new varices. So either dose effectiveness or both dose effectiveness will be the our base case to see that there is you know some effect of each dose, and then based on the data, as well as secondary outcome data that we'll be collecting, we'll have engagement with regulatory agency for path forward. As I shared, beyond the development of varices, which is a key marker of disease progression in portal hypertension, we'll also have all the other liver complications as part of our predefined secondary outcomes.
We'll be very interested to see what the effect there is on that, those secondary outcomes, and look forward to sharing that with community, with FDA, and everybody.
Thank you so much again for your presentation, Khurram, and certainly look forward to that interim data readout. Very memorable moment for Galectin, for sure. Thank you again for joining us today, and I also wanna thank everyone in the audience for joining this presentation as well. Thank you so much, and please hope everyone have a good rest of the conference.
Thank you, Tommy, for the opportunity.