Company focused on addressing high unmet needs in patients with MASH cirrhosis and oncology. Our focus today will be on our lead compound, belapectin, which is currently in development for MASH cirrhosis and portal hypertension. We'll be sharing a program update and also how our team is utilizing novel clinical endpoints with this unique mechanism of action and driving significant shareholder value, and aiming to address very high unmet need in these patients. Thank you for your time. Our presentation contains forward-looking statements based on current expectations and assumptions, and these projections are subject to risks and uncertainties. We encourage investors to consider those risks when evaluating our company. Please refer to our SEC filing for details. Galectin Therapeutics is focused on developing galectin-3 inhibitor mechanism action-based therapies. Our current clinical focus is on MASH cirrhosis.
This is an indication where there is no FDA-approved treatment, and there's a very high unmet need, as well as cancer patients, especially in advanced melanoma and head and neck squamous cell carcinoma. We're exploring the use of our lead compound, belapectin, as a combination therapy to improve patient outcomes. We have received Fast Track designation, which underlies the potential importance of our work. Our patent extends to 2035, establishing a strong foundation for future growth. We are a lean but agile organization. Every member of our leadership team brings at least two decades of pharma, biotech, or corporate governance experience. This experienced team, backed by a dedicated board member, is driving our innovation forward.
I joined the company early this year, motivated by the opportunity to work with belapectin, which is a unique mechanism of action, distinct from all other, any other therapy in development right now in MASH cirrhosis. I've been able to. I've been privileged to work on multiple therapies over the year and lead them to approval in hepatology and other therapeutic areas over the last twenty years, both in FDA and ex-US regulatory agency, so our experienced team gives us confidence to navigate this complex landscape and regulatory environment and deliver growth for our patients and to our stakeholders, so our pipeline is focused on developing belapectin to address these high unmet need areas. Belapectin is in development in phase IIb/III adaptive trial design for patients with MASH cirrhosis and portal hypertension, and we look forward to sharing the results before the end of the year.
We've also explored its use in as a combination therapy in head and neck squamous cell carcinoma and metastatic melanoma to improve the effectiveness of immunotherapy. We have a discovery group, which is actively exploring and discovering other, or molecules and formulations for the same mechanism of action, which is galectin-3 inhibition. We believe our focused approach, backed by our expertise in this area, gives us confidence to deliver growth and execute. Galectin-3 is a lectin protein. It's well known and implicated in fibrosis, not just in liver, but other organs such as lungs, brain, heart, and not just the preclinical data from Galectin, but it's been many other academic institutes who have done studies to show that inhibiting galectin-3 is a appropriate target for anti-fibrosis. In MASH cirrhosis or fibrotic liver, galectin-3 is upregulated.
So what that means is it leads to increased apoptosis or adhesion of cells and also increased macrophage activation. These are the hallmark of progressive fibrosis, liver disease, and cirrhosis. Hence, targeting this area gives us confidence that we will be able to disrupt the pathological process and lead to the appropriate reversing of the disease. The goal here is to effectively halt galectin-3 inhibition and lead to reversal of the progression of fibrosis in this patient population. And it's also beyond the data that I will be sharing today. Today, there have been preclinical data that's generated in other indications, such as pulmonary fibrosis and heart failure, just to name a few. Belapectin, as the name indicates, is a pectin or complex carbohydrate.
It has been shown in preclinical studies to effectively target galectin-3 and inhibit that, and by doing so, lead to potent anti-fibrotic effects. In the preclinical studies that we have generated, we have conducted so far and published, it has lead to higher rate of NAFLD activity score reduction, as well as anti-fibrotic effect, as measured by smooth muscle actin, as well as hepatic collagen fibrosis effects. We have seen in preclinical studies that by inhibiting galectin-3, there's a strong, potent anti-fibrotic effect. Furthermore, we have also seen that even at higher doses in preclinical models, the dose is very well tolerated. That gives us confidence that it's potentially efficacious and safe and gives us the confidence to execute that in the human clinical studies that we have designed so far.
So before I share our clinical data, I just briefly highlight the high unmet need and market opportunity in NASH cirrhosis. So the market for NASH cirrhosis is both vast and underserved. As I shared earlier, there is no FDA-approved treatment for NASH cirrhosis or for portal hypertension, and there is no therapy to reverse or halt once patient develop portal hypertension. All you're trying to do at clinic, clinically, is trying to symptomatically manage these patients. As we see here, there are roughly five million patients in the U.S. who have liver cirrhosis from NASH based on independent epidemiological work.
The rates are, despite all the GLP-1 data coming out in the last few years, the rate of cirrhosis is still rising based on the obesity epidemic we have and higher, increasing rate of diabetes in the US. If cirrhosis is not halted or reversed, progression of cirrhosis leads to end-stage liver disease, liver failure, and decompensation. The only option at that stage patients have is getting a new liver. If you look at the numbers purely, with five million incidents of cirrhosis in the US and roughly less than nine thousand liver transplant a year, there is a significant unmet need for any therapy that could reverse the condition and halt the progression. Otherwise, these patients have very poor outcome.
Our main motivation is to try to bring this therapy and give physicians and patients an option that can reverse cirrhosis and portal hypertension. Indeed, based on our unblinded market research earlier this year, there was very high enthusiasm by both physicians and payers for a therapy that could likely achieve it. And look, in terms of adoption rate, the projection was 50% to 100% potential adoption for any therapy that can successfully reverse or halt the progression of liver disease. And looking at the number of patients from various epidemiological studies, you're looking at potentially a multi-billion dollar opportunity. We feel like belapectin, with its current stage of development, has potentially a unique opportunity to be the first-to-market therapy for NASH cirrhosis and portal hypertension. Now, cirrhosis represents many years of liver injury.
It's the culmination of liver injury that leads to fibrosis and liver becoming scarred and nodular. And, one of the hallmark of the condition is portal hypertension, meaning the pressure in the circulation going to liver is very high. And HVPG, or hepatic vein pressure gradient, is a direct measure of portal pressure. And as I'm trying to show here, that if your HVPG gets 10 mm Hg or above, it's called as clinically significant portal hypertension. Now, why that's important is the patient outcomes are far worse, exponentially worse, once they get to that tipping point of 10 mm Hg or worse.
So that's where we believe belapectin fits into the treatment will fit into the treatment paradigm, trying to catch these patients before they develop, get to clinically significant portal hypertension and potentially reverse this condition, or even at least halt it, so they don't get to those exponentially worse outcomes. So far in the clinical study that I'll highlight some of the data, we have seen belapectin can effectively reduce the progression of liver disease as measured by reduction in or development of new varices. And what we also have seen is it, it's able to do a reduction in hepatic vein pressure gradient, and even at higher dose, it's been relatively well-tolerated. So that risk-benefit profile is favorable. That gives us confidence to proceed this drug through the development program.
In this phase IIb study, a total of 164 patients were randomized to three dose groups, testing 2 and 8 milligrams of belapectin, 8 milligrams per kilogram of lean body weight, versus placebo, 54 to placebo, over a 52-week duration of infusion, alternate weeks. The primary endpoint was change in hepatic vein pressure gradient from baseline to week 54. We also evaluated improvement in NASH cirrhosis on biopsy, as well as looked at their progression of liver disease through endoscopy, upper endoscopy, looking at the varices development. The varices are engorged vessels in esophagus, and development of varices is one of the clinical signs, one of the first signs that patients' liver disease have progressed enough.
Obviously, all these patients are patients with cirrhosis who also have diagnosis of portal hypertension. For the primary endpoint, where there was no statistical significant in difference of between placebo cohorts and two or eight milligram cohort, what we observed in this trial is that in the case cohort of patient, which was roughly half the patient population, those patients who did not have any varices at the baseline, there was a significantly greater reduction in hepatic vein pressure gradient in two milligram cohort compared to placebo. It's worth noting that even a one millimeter Hg drop in hepatic vein pressure gradient has shown in independent studies to lead to significantly better clinical outcome. Having seen a significant drop in portal pressure in this cohort was very reassuring for us.
Indeed, in this cohort, it led to the same clinical finding that there was none of the patients who had varices at the baseline in this two milligram cohort developed varices at the end of the 52-week infusion. And it was significantly lower than placebo, where you see the response rate at 18%. So 18% of subjects in placebo cohort, and still lower in the 8-milligram cohort. And that's the reassuring data that has led us to design the NAVIGATE adaptive phase IIb/III studies. In this ongoing NAVIGATE study, which is a phase IIb/III adaptive trial design, we're testing two doses of belapectin, which is two milligram per kilogram lean body weight versus and four milligram versus placebo. Now over 18-month duration. Just to reiterate, last phase IIb, we gave infusion for 12 months.
This is eighteen-month duration of therapy. You also note that we are testing two and four milligram doses here. We found it from the big PK analysis that our four eight milligram dose in the last study overshot the optimum exposure levels. Hence, the two milligram, which showed that encouraging finding and four milligram dose is being tested. The trial is designed in an adaptive manner. What that means is, later this year, we'll have interim blinded interim analysis, and then an independent data monitoring committee will assess the results. There are three permutations. Either there's a high hurdle for the efficacy.
If you achieve that, you stop study early for overwhelming efficacy, or you continue to phase III study, where you will enroll at least 210 patients, but this time in two-to-one randomization, so only one of the two belapectin dose will be moved to the phase III, or you stop early for lack of efficacy. So those are three permutations at the interim analysis, which is scheduled to be before the end of this year. Into the patient population, we're enrolling patients again with NASH cirrhosis and portal hypertension. We're using the clinical criteria for diagnosis.
So unlike a biopsy, which is obviously well known even though it's been used for F2, F3, NASH patients, and it has its own inherent drawbacks, being not only an invasive test, but also evaluating biopsy for diagnosis of condition and response. We know the well-documented risk of ballooning findings by central pathology. Our NAVIGATE study is using the clinical guidelines by Baveno and AASLD, which allow using your liver stiffness measure and platelet count to diagnose portal hypertension in a patient who has a history of cirrhosis based on the biopsy finding. We're using clinical criteria. Our primary endpoint is looking at through EGD upper endoscopy again, and presence and absence of varices. Again, that's using endoscopy, which is being read by a blinded central reader.
Again, that's novel to our program, and we have already had agreement with FDA on use of this method for our primary endpoint. Again, what this does is alleviates the need for invasive biopsy, with its limitation and risk factors, and also introduces something that's clinically appropriate. Because endoscopy is commonly done in patients who have advanced liver disease and cirrhosis to monitor them for progression of liver disease and if they develop varices, to manage them. So we feel like our endpoint is well aligned with clinical practice. Apart from this primary endpoint, which is based on presence or absence of varices, we'll be looking at other secondary outcomes that are of interest to clinicians, patients, and payers, such as liver-related outcomes, mortality outcomes, transplant rate, complication resources, just to name a few. In terms of update, where we are as of today.
We have completed the enrollment for NAVIGATE trial. All 357 subjects have been randomized to the phase 2b portion of the study. They are completing the 18-month duration of therapy. This trial was conducted across five continents. More than 100 trial sites enrolled a patient. We have had five DSMB meetings during the course of the study, and every time, that independent committee affirmed the safety profile of the drug, and trial continued. We look forward to sharing the results of the interim analysis before the end of the year, and very excited about sharing that with the community as well as obviously with investors. Before I wrap up, just a few words about our cancer immunotherapy program.
We have done a phase I study exploring belapectin as combination with PD-1 inhibitor, pembrolizumab or Keytruda, we all know that, looking in patients with metastatic melanoma or head and neck squamous cell carcinoma. Now, this combination therapy is hypothesized to affect the tumor immunosuppressive microenvironment of the tumor and thus potentially increasing the response rate to immunotherapy. Indeed, in this small study, what we observed was that the patient who received the combination therapy, the objective response rate varied from 33%-50%, which was higher than the single therapy. Also, more importantly, from a safety point of view, the combination therapy had lower incidence of GI-related adverse events compared to the Keytruda alone.
These are exciting findings, and we are encouraged by the data and actively exploring partnership opportunities to further advance this program as well. To summarize, Galectin Therapeutics is focused on developing belapectin and galectin-based inhibition therapies to address high unmet need in patients with NASH cirrhosis and portal hypertension and oncology, among other areas. Our experienced team is dedicated to advance our pipeline and make sure that we successfully execute our program and share the data with public. This is an area with very high unmet need. There is no FDA-approved treatment for NASH cirrhosis and portal hypertension. And it, belapectin or Galectin-3 inhibition, is a novel mechanism action that is not being judged or evaluated by any other company active in clinical development.
We feel this is potentially not only a strong mechanism of action for NASH cirrhosis, but also as a potential complementary therapy or combination therapy could be explored in many indications. Then thank you again for your time and attention today.