Galectin Therapeutics Inc (GALT) September 14, 2026 Conference Transcript

Welcome to the next session at the H.C. Wainwright 28th Annual Global Investment Conference. My name is Matt Keller. I'm a VP in the Equity Research Department, and it is now my pleasure to introduce our next presenting company, Galactin Therapeutics. And presenting for the company, we have Joel Lewis, CEO, and Kouram Jameel, CMO. Gentlemen, please go ahead.

Thank you. Thank you. Good morning, everybody. On behalf of Galactin Therapeutics, I'm pleased to provide an update on our clinical development program and share an update on our path forward as we are preparing for our phase three registration trial. Our presentation contains forward-looking statements regarding our plan and activities. For full description of these risks and plans, please refer to our SEC filing. Connecting Therapeutics is focused on developing therapies to address high and met need in patient population of MASH, thruosis with portal hypertension, and oncology. Our lead compound is balapectin, which has been in development for MASH thruosis and portal hypertension. It's a complex carbohydrate, and it's a potent inhibitor of collectin-3. Collectin-3 has been implicated across multiple chronic, fibrotic, and inflammatory conditions. In terms of matched sources and portal hypertension, we have conducted two phase 2b studies and have generated data showing palapectin-led improvement in portal pressure, reduction in incidence of new viruses, and favorable changes in multiple fibrotic biomarkers. markers. We've also done a phase 2b study in metastatic cancer, and it also had a cancer showing favorable data in combination of beta pectin and PD-1 inhibitor. In the patient landscape, it's based on the most recent epidemiology study, it's estimated that 3.3 million patients in the U.S. are afflicted with masturosis and portal hypertension. These patients are at increased risk of developing complications of chronic liver disease, such as hepatic encephalopathy, ascites, bleeding, and eventually death. If left untreated, the only definitive treatment is a liver transplant. Yet for these patients in the U.S. currently, our estimated animal liver transplant rate is around 12,000. So you can imagine the desperate high unmet need for the millions of patients where there's no FDA-approved therapy, and these are at imminent risk of developing liver complications. Based on the lethal data generated so far and the treatment landscape, we have conducted blinded market research where we interviewed both treating physicians and peers about balapectin's potential. And based on a very conservative forecasting model, we estimate the opportunity to be a multibillionaire opportunity. And once approved, palapectin could be a major player in this patient treatment landscape. As I shared earlier, Galactin-3 as a target for managing chronic inflammation and fibrosis has been studied across multiple organs, not just liver, but even kidney fibrosis, pulmonary fibrosis, by leading researchers all over the world. In liver specifically, Galactin-3 levels are increased in mastosis and portal hypertension, And once these levels are increased, there's activation of what we call hepatic stellate cell. Now, hepatic stellate cells are the primary cells that drive buildup of collagen or scar tissue in this patient population. Across multiple preclinical studies, pellet that will lead to reduction in portal pressure, reduction in collagen buildup, and favorable changes in the biomarker results. Based on the strong preclinical data, we have designed our first phase 2 study. In this study, we published in 2020, patients with NASH sources and portal hypertension were given treatment with palapectin for up to 52 weeks. The primary endpoint was assessment of a pectic vein pressure gradient, which is a goal standard to measure portal pressure. Now, portal pressure in psoriatic patients is a key predictor of developing complications and outcome. In this trial, patients who did not have varices at baseline, which was roughly half the patient population, there was significant reduction in hepatic vein pressure gradient that was also accompanied by significant reduction in incidence of new varices. Remember, development of varices based on the natural history of mashup and portal hypertension is the first complication these patients tend to develop. Based on the findings of the GT26 trial, we designed NAVIGATE trial. Here, we tested the same 2mg dose from the last trial. We also studied now a 4mg dose along with placebo. All patients were treated for 18 months of therapy, 1, 1, and 2, 1. One more unique thing about the study was we assessed the varices, of varices at baseline and at 18 months using a central, blinded, multiple reviewer setup. That's a process that also FDA approved and accepted, and we have since noticed other companies falling track and using this central, blinded adjudication of varices as an endpoint. In terms of patient population, we enrolled patients with matched throses in portal hypertension. Portal hypertension was assessed non-invasively using widely accepted biomarker and imaging data. Our primary endpoint was a composite of viruses, and I'll talk about that in the next slide. As secondary endpoint, we also looked at other complications of the liver disease, such as decompensating events, mald increase, or mortality. The two key populations that I'll be talking about, one is the overall population, or ITT, intent to treat. That's a 357 patient minus the two patients who had viruses at baseline. and per-protocol population, which is all patients who completed 18 months of therapy as protocol required and had endoscopy at baseline, endoscopy at 18 months. It's a similar definition that you'll see in the MASH trial where they have biopsy at baseline, biopsy at end of treatment. In terms of composite primary endpoint, while the key component was development of new varuses at 18 months by blinded central adjudication, we also had conservative assessment meaning if a patient developed any other liver complication or had any discontinuation of trial due to adverse event or tips which is a shunt procedure or had glp or beta blocker use which were the prohibited medication for more than 12 months all of them were adjudicated as having met the primary endpoint in terms of patient population it reflects typical patient with mash two-thirds of the patient had hypertension and or diabetes type 2 diabetes the key criteria is highlighted in light blue and that's plated count liver stiffness and your spleen length and these are used non-invasively to assess portal hypertension and as you can see specifically around plated count it's around 130 000. and if you compare that to other recently published cirrhotic trials this is the lowest player count of any trial meaning our goal was to have enriched population for outcomes and that's exactly how we intended to do so this is patient not just who have cirrhosis but have total hypertension on top of cirrhosis now these are breakdown of primary endpoint composite overall as you can see while numerically lowered number of patients had the composite endpoint on balapectin 37.8 compared to placebo 47.7 that didn't achieve statistical significance i'll draw your attention to the incidence of new viruses that's the inside box and you'll see on the left most in the gray bar placebo 17.8 percent had new viruses compared to balapectin the dark blue shared two milligrams 10.1%. That's a 43.2% reduction in incidence of new varices. The other component of composite endpoint was numerically similar, even though less number of patients dropped out without endoscopy or varices. That's 11% on placebo compared to 6.7% on balapectin 2mg. So remember the number 21 versus 12 for the varices in the ITT population. If you look at the PERC protocol population, 21 versus 11. There's only one patient who dropped out from the per protocol population. That's a patient on 2mg dose that developed viruses shortly after randomization and did not complete the 18-month therapy as per protocol. Yet, the result becomes statistically significant in terms of difference versus placebo. The central blinded adjudication also involved looking at size of viruses small versus large why because we know large viruses are more likely to bleed and also more likely to develop other complications and equally equally importantly fda accepts development of large vertices as viable clinical outcome when we assessed broad indication trials and you can see that the overall difference of 21 versus 11 was primarily different driven by difference in the large vertices, eight versus one, balapectin versus placebo. We also assessed secondary outcome composite in terms of other liver complication, numerically slightly lower, five versus three, again, placebo versus two-milligram balapectin dose. The trial wasn't designed to show a statistical difference in the composite secondary outcome. Again, just to reiterate, it was an 18-month trial looking at only 350 patients, so this wasn't powered to show a statistical difference. But this just gives you the flavor of patient population. We have roughly 17 composite clinical outcomes in 18 months, which is a much higher number than you will see in other compensated through a patient with even a two-year trial. Safety profile is one of the strengths of the Balapectin program. There was not a single drug-related SAE reported in the entire trial, no drug-induced liver injury. The discontinuation rate due to adverse event was similar across the three cohorts. Also, the incidence of adverse event and CS adverse event was similar. No differences. And that's extremely important in our patient population, which is mastosis and portal hypertension. Why? Because this is a fragile patient population, which is at increased risk of other adverse events. So, for example, GLP-1, which is now widely studied and used in some of the patients for type 2 indication of obesity. We all know if you lose weight, you also lose some element of your muscle, up to 20%. And cirrhotic patients have what we call sarcopenia. Some of them have no muscle mass to begin with. So what you cannot do is afford to lose even more muscle mass because that will lead to complication. Same thing is potential risk of some of the FGF21 therapies of bone resorption, and you can lead to further complications. So having a tolerable safety profile is important for any drug, but it's even more important in our patient population, which is more fragile and sicker. I'll briefly share some of the biomarker data we have generated to provide mechanistic and biological proof of the efficacy data we have shown so that the clinical outcome isn't just by chance, but it's driven by the biological effect of bilepectin in this patient population. first is improvement in liver stiffness measure we see by vct or fiber scan you can see a placebo adjusted rate of 10.1 percent placebo code actually increased in the fiber scan data and again something to contrast you will see most of the trials run in compensated cirrhosis even placebo code has some improvement biomarker here it actually worsened and that tells you if you do not treat these patients they are at imminent risk of further progression of disease We also look at what we call categorical worsening of biomarker. And the cutoff we use is 30% increase in LSM or 5KPA increase. None of these cutoffs I'll be talking about today are all cutoffs. These are widely used, studied, and described as clinically meaningful changes or increases in biomarker. And one of the more things that you should keep in mind is I'm sharing all the biomarker most of the data as progression of a biomarker because our endpoint is a progression of disease so that's something also came if you are used to looking at biopsy data in mash f2 f3 where biopsy you're looking at improvement biopsy and as you're looking at improvement biomarker our endpoint is progression of disease preventing that and biomarker we're showing is preventing progression of biomarker here again you can see corresponding roughly 50 percent or more increase in placebo code compared to balapectin for this biomarker data. We also looked at ALF score, which is enhanced liver fibrosis score, FDA-approved biomarker for prognostication and diagnosis of patients in masturosis and portal hypertension. And these three categories are based on ALF label. And you can see at each increasing category, the incidence of viruses increases. The highest rate in ALF 11.3, which indicates cirrhosis and portal hypertension. and the biggest magnitude of change or difference is also in alpha 11.3. Again, very reassuring that the patient population you want to benefit the most, who is at risk the most, you see perhaps the most benefit. We also do what we call combination biomarker. So again, this is looking at ALF and LSM's score and looking again, widely accepted biomarker combination. Say for example, LF 30% or more increase, LF 0.5 or more increase, and LSM 30% or more increase, and you see similar concordant data, roughly 50 or 60% more patients worsened on placebo compared to belabectin. Another way of looking at how sicker patients do is look at patients who have above median level at baseline. So again, LSM change per protocol on the left side, above median in the middle and below median on the right side. And just as a footnote, you can see the mean LSM for above median was 29 kilopascal compared to below median is 15 kilopascal. And again, you can see clearly the magnitude of change in LSM was bigger in those in above median patients. Similarly, categorical change, the worsening of LSM at the 30% of 5kPa was greatest in the above median. You can see the balapectin response is much more consistent across all three population in terms of increase in LSN but the placebo response in terms of worsening was greatest in the sicker patients hence the magnitude of change gets even better in sicker patients it's consistent result across three population yet the greatest benefit in sicker patient population we also looked at what we call bavino risk category you will see often in cirrhotic patient any development program I'm talking about Bovino risk categories. Bovino's criteria are used for non-invasive assigning portal hypertension. And again, the definition that is used widely is at the bottom. The three categories, red is portal hypertension, blue is probable portal hypertension, clinical skillful portal hypertension, and the gray is low likely to clinical skillful portal hypertension or no portal hypertension. So if you compare the two gray bars in placebo, the percentage of patients who had no or low likelihood of clinical skin support hypertension increased by 7%. So 7% of patients went from danger zone to no or low. On balapectin, twice as much, roughly 15% of patients went from no portal hypertension to, again, at baseline to 18 months. So twice as many patients came out of danger zone. Again, all of these findings I've shared so far corroborate the finding I've shared earlier in the ITT and protocol roughly 43 to 50% reduction in incidence of viruses. YKL-40 is a marker of inflammation. Now the key concept is you cannot improve or resolve fibrosis if you also mitigate inflammation whether that's inflammation derived by fat or other components and YKL-40 is also a component of MIS-4 which is another marker prognostic combination marker used and whether you look at 20 percent increase or 20 percent decrease of mis4 again you'll see favorable changes in balapectin 2 milligram compared to placebo similarly pro c3 we all have probably heard about that that's like a dynamic marker of collagen buildup or fibrosis and you can see again consistently balapectin has the same trend as other markers. Pro-C4 is another marker where it impacts basement membrane and type 4 collagen implicated in multiple processes. And you can see again, a percentage of patients who have 20% increase in Pro-C4, much higher in placebo compared to palopectin, 2 milligram dose. And again, I should have mentioned the 2 milligram dose is the one we have seen consistent finding across two trials. And as we have announced publicly, 2 milligram is a single dose we're carrying forward in our planned registration trial so last of the biomarker slides we also looked at pro c3 and ctx 3 ratio pro c3 is used to have collagen buildup fibrogenesis ctx 3 indicates fibrolysis of fibrosis resolution and the ratio indicates what's the overall equilibrium or balance and you would like to see the ratio going down because that means more fibrolysis less fibrogenesis and again you can see whether you look at patient with 11.3 and above or those with ALF increase either way balapectin 2mg has fibro finding compared to placebo so to summarize in our navigate trial in overall program 2mg dose led to significantly lower incidence of new viruses in mass sources and portal hypertension the biomarker data across multiple biomarkers corroborate the findings we have seen and right mechanistic and biological proof of biomechanism of action. Two milligrams of those findings validate the findings we observed in GD2612. Our safety profile remains very favorable and lends itself well to both monotherapy and also a kind of landscape where GLP-1 therapy are underlying standard of care, especially for type 2 diabetes and obesity. And none of these patients come on that. And in fact, we have synergistic data with GLP-1 therapy that we presented last year. It's in our corporate deck. We believe balapactin, due to its mechanism of action, due to its data we have generated so far, has the potential to really meaningfully address the critical unmet need in patient-matched sources and portal hypertension. We have aligned with FDA on our phase three protocol key elements in Q2 this year. We publicly announced that we will be submitting our protocol by the end of Q3, which is the end of this month, and we remain on target as we actively pursue partnership and collaborative opportunities. opportunities. Thank you for your attention. Happy to answer any questions.