Hello, and welcome to Oppenheimer's 35th Annual Healthcare Conference. I am Cheng Li, one of the biotech analysts here at Oppenheimer, and it's my pleasure to welcome our next presenting company, Galecto. Today we have Matt Kronmiller, EVP Strategy and CBO, as well as Lori Firmani, CFO at Galecto. With that, I will turn it over to Matt and Lori. Great. Thank you. Good morning. Good afternoon. We're excited to be here. We'll be discussing Galecto: transforming treatment of cancer disease and first-in-class small molecule agents. You can go to the next slide. Galecto's recently completed a strategic review, and as a result, we've enhanced our pipeline. We've identified core assets and a future direction for Galecto. Following the strategic review process, Galecto acquired an asset, BRM-1420, for AML. BRM-1420 is a novel dual ENL-YEATS and FLT3 inhibitor for multiple genetic subsets of AML. There is a promising preclinical profile showing rapid and durable anti-tumor activity with the asset. The preclinical modeling has showed potential synergistic effects with SOC, and it's also well-positioned to address emerging menin inhibitor resistance. Galecto's enhanced pipeline continues to focus on oncology. We have an innovative platform targeting core disease processes. We will be pioneers in ENL-YEATS pharmacology and a first-in-class, highly specific oral small molecule inhibitor. All of Galecto's programs are addressing diseases characterized by clear unmet medical needs and potential for multi-billion dollar market opportunities. We do have early data supporting drug activity in the ENL-YEATS inhibitor. It's estimated to cover over 30% of AML population and rapid and durable anti-tumor activity in AML models. We continue with the Galectin-3 inhibitor, historical assets for Galecto, which have had positive biomarker data and significant clinical data in cirrhosis. With our existing cash balance, we have a cash runway into 2026, which covers IND for the AML program. The next slide shows our management team at Galecto: Hans Schambye, our CEO; Garrett Winslow, our General Counsel; Matt Kronmiller; and myself, as well as an experienced board of directors. I'll turn it over to Matt to provide more details on the BRM-1420 asset. Thank you, Lori. Hi, everyone. I am Matt Kronmiller. I joined Galecto in October of last year from Bridge Medicines, which is the company that Galecto acquired the 1420 asset from. Just wanted to introduce and run through the program. As Lori said, it's a novel small molecule that inhibits ENL-YEATS and FLT3 for the treatment in AML. We have in vivo therapeutic window. It It demonstrates superior efficacy to existing FLT3 inhibitors and menin inhibitors that are approved or in the clinic in models of mixed lineage rearranged or KMT2A AML. We also front-loaded a dog cardiovascular tox study in preclinical development for the program to make sure that the asset was differentiated and did not have a Q Tc liability, which it did not. We have some in vivo models that show that it's synergistic with standard of care models and compounds in development as the treatment landscape in AML is moving towards combination therapies in earlier line settings. As Lori mentioned, the mechanism is unique and covers greater than 30% of the AML population, including potential high-risk genetic drivers. We're ideally positioned to treat initially relapse refractory setting patients that have failed prior FLT3 inhibitor and menin therapy and an optimal combination partner given the tolerability profile and the efficacy profile. We have an established regulatory pathway that's been set by companies in this space before us, and we expect to be in the clinic in 2026 with initial clinical data in 2027. The market within AML is very broad in terms of the genetic drivers of the disease. We kind of break down the ENL-YEATS portion of the mechanism, which covers the same portion of the population of AML that menin inhibitors currently do. This is the KMT2A rearranged segment and the NPM1 segment. This makes up about, combined, about 40% of the market. This patient population continues to have a high unmet medical need and will be in need of additional therapies. We had the potential to treat a broader patient population than just that. The fact that we also inhibit FLT3 allows us to treat that portion of the population, which is also 30% of AML. Obviously, these numbers on the right-hand side are greater than 100%. Much of the population has co-mutations. There are a lot of patients that have FLT3 and NPM1 co-mutations, and we would be an ideal therapy there. We did a lot of patient-derived cell line work with some academic partners that showed activity with patients that had TET2 mutations and c-KIT mutations, and also some activity with patients with higher-risk genetic drivers, including ASXL1, RUNX1, and TP53. Those will be portions of the population that we will explore further as we move towards the clinic. Our broad coverage of the AML market, again, positions us to be an ideal combination partner. I'll briefly touch on the mechanism and the history of the program. This program was originally in-licensed from David Allis's lab in Rockefeller University. David Allis, unfortunately, passed away a little bit over two years ago, but was a pioneer in the epigenetic world. Postdoc at the time, Dr. Liling Wan, she really spearheaded the work on ENL-YEATS as a target, and she has since moved on to her own lab at the University of Pennsylvania. She recognized the importance of the YEATS domain in the ENL-AF9 as a reader of acetylated histones on the MLL fusion protein, regulating transcription of key drivers of stem cell differentiation and leukomyogenesis. The main paper was published in Cancer Discovery in November of 2022 and highlights some of the work done with a molecule that is included in what was in-licensed from Rockefeller. We have a broad patent estate, and that demonstrates the activity of a variety of other leukemia targets, including FLT3. The chart on the right here shows where 1420 is active and why it is differentiated. FLT3, obviously a very well-known target within AML, and our molecule does not have some of the same toxin tolerability liabilities that those profiles of some of the existing FLT3 inhibitors on the market. For ENL, we are, kind of if you think about it, a mechanism, we are downstream from menin. That is important when we think about treating patients that have menin resistance due to MEN1 mutations. That is something where we believe we should be effective given where we are in the pathway. Just to summarize our preclinical data to date, we have pronounced effects on HOXA9 and MEIS1, the drivers of the KMT2A and NPM1 portions of AML. These are upregulated and overexpressed in these AML subsets. We have shown a substantial reduction in elimination of blast cells in peripheral blood, bone marrow, and spleen. We see immediate cell cycle arrest and differentiation of blasts and apoptosis. Our preclinical data shows the potential for rapid onset of action, complete and durable responses, and efficacy that is potentially superior to competitors. With our tox data to date, we've done some 14-day tox studies in rat and dog and see an improved safety and tolerability profile. This is one of the first in vivo mouse models that we did, the MV4-11 model with 1420. You can see on the left-hand side the tumor volume reduction over time after dosing for eight days. The top two doses, the 50 mg and 100 mg per kg BID, show drastic tumor reduction, and that is sustained out to day 34. The important biomarkers that we mentioned earlier, the HOXA9 and MEIS1, we see a nice dose-dependent reduction in those biomarkers in this study. Next, this is another disseminating MV4-11 mouse model that we did. In this model, we compared to Gilteritinib and to Syndax's menin inhibitor Revumenib. Here, we show the survival curves in this study of the mice with the best-performing arm for 1420 and the best-performing arm for Gilteritinib on the left compared to vehicle. You can see a nice separation of the survival curves here. On the right, we compared the 1420 arm to Syndax's molecule. Again, we see a very drastic improvement in survivability in this model. These are the models that got us excited about the program. This is some of an example of some of the work that we did in terms of the patient samples and cell viability across multiple genotypes. These are things that we'll continue to explore as we look towards what patients in the clinic will be the best target population beyond FLT3 resistant and menin resistant patients. This is where we saw activity with TET2 and c-KIT and other genetic profiles beyond what makes sense beyond the ones that we previously mentioned. One of the reasons that we believe that we'll be very effective with patients that have failed menin therapy is because of the MEN1 mutations that come up with being treated with menin inhibitors. This is something that was first kind of brought to the attention of the field with a paper in March of 2023 in Nature from Scott Armstrong's lab at Dana-Farber Cancer Institute. We have this kind of highlighted the first-in-human study of Revumenib and showed the mutations that MEN1 at the Revumenib menin interface in patients that had acquired resistance. This attenuates the drug target binding, but not the interaction with the natural ligand, MLL1. This prevented inhibitor-induced eviction of menin and MLL1 from the chromatin. This is upstream from where we are in ENL-YEATS as a target. This suggests that this is a common mechanism of therapeutic resistance and that this can be addressed by our molecule 1420. There is some additional work that was shown at ASH this past December that showed that every single menin inhibitor that is in the clinic is driving mutations within MEN1, not just Revumenib. This shows that it is important to have a solution for these patients that is not just another menin inhibitor. It would be an ideal treatment for these patients if it is something that does not have the liability of driving mutations within MEN1. These are some other charts to kind of show that. We can see some dose-dependent displacement of the MLL1 peptide for Revumenib on the left. The MI-3454 molecule second to the left is the Kura compound. This also showed the Daiichi compound compared to just MLL1 peptide where we do not see a difference in the curves there. In the bottom chart on the right, we can see these are the patients that frequently get the mutation at multiple sites in MEN1, not just one. Some menin inhibitors have a profile where they are active with mutations at certain sites, but not others. This goes to the point that the solution needs to be a compound that does not have any liability whatsoever with MEN1 mutations. That is, we believe, where 1420 can be useful. There is some other work that is early, but was published in Nature Communications in late 2024 that showed that ENL was preserved in menin inhibitor resistance. This was just an example, a quick example from one patient that was treated with a menin inhibitor. You can see that, however, this patient had ALL, and after treatment with the menin inhibitor, it actually triggered lineage switch to AML. They have shown that it was only ENL that remained bound to the MLL oncoprotein target during treatment, and that this activated a granulocyte monocyte progenitor-like genes driving the resistance and the leukemia progression. This is another data set, while early, that shows that targeting ENL might improve outcomes for these patients that have acquired resistance to menin therapy. This highlights some of the in vitro modeling that was done with 1420 that showed that it was either additive or synergistic in a combination to standard of care and menin inhibitors. You see, the top left chart, there are four different relative cell lines in AML shown. I mean, combining 1420 with azacitidine, Gilteritinib, a FLT3 inhibitor, venetoclax, or Syndax's menin inhibitor. In almost all, we were synergistic, and if we were not synergistic, we were additive. We think that this is incredibly important. If we think about where the molecule would fit in the treatment landscape of AML beyond just as the monotherapy in the relapse refractory setting, it's imperative that you have a good profile to combine with venetoclax. As menin inhibitors potentially move to be more part of standard of care, it's important that we have a good profile to combine with them. The previous slides, I think, showed that mechanistically, it makes a lot of sense for us to be a combination partner as well. I mentioned that we front-loaded a dog cardiovascular study to make sure that we didn't have any QTc liability. This is something that we thought we needed to make sure it was important to differentiate ourselves versus FLT3 inhibitors versus menin inhibitors and make sure that we had the best combination profile with other molecules. As we can see in the chart on the right, we did not have any QTc prolongation shown with 1420. So far, we've done 14-day dose range finding studies in rats and dogs. The current standard of care has encountered several safety tolerability profiles, including diarrhea, anemia, fatigue, elevated LFT. Our initial studies show no deaths, no target organ toxicity, and no changes in clinical chemistry. We had some effects on white blood cell counts, hematocrit, and hemoglobin that were mild and manageable. We also saw a reduction in reticulocytes that is easily monitorable in the clinical setting and reversible. The reason why we mentioned that and feel it's important is that we think this is attributable to kind of the inhibition of ENL /AF9 and can serve as an indirect surrogate of target engagement. In the dog study, the 200 mg per kg, we reached it with an MTD, but that represents a very significant exposure multiple for what we need to see for efficacy, and that's around an 8X or 8X exposure multiple. For us, that was incredibly attractive and encouraging to see. We expect to initiate GLP tox studies in the middle of 2025 with full results in the fourth quarter. This is our timeline to the first-in-human studies. As I said, we expect to right now, we are doing our GLP API campaign. We expect that we will be initiating GLP 28-day tox studies in the middle of 2025 with full data in the fourth quarter. That allows us to have an IND submission by either the end of 2025 or early 2026 with the initial to initiate the phase one study shortly thereafter in 2026, with initial phase one A dose escalation data expected in 2027. That data will be incredibly important in value creating for us. Similar data for menin inhibitors created a lot of value for those companies. It is important so we are leveraging some of the existing pathways and clinical designs from these previous molecules that I mentioned. All in cost for us to get to the phase one B expansion cohorts beyond with our existing cash is about $30 million. That will take us through that initial efficacy data, opening up the phase one B expansion cohorts and through 2027. This is just kind of we end up on our summary slide as Lori mentioned. We are incredibly excited about the ENL FLT3 molecule. We believe that its profile creates strong differentiation in multiple subsets of AML, which continues to be in need of new therapies in the relapse refractory setting and as we look towards earlier line setting. With that, open up the chat. Great. Thanks for the presentation, team. Just a reminder to our audience, if you have any questions, just feel free to submit the question using the Q&A box at the bottom of your screen. I can kick off the discussion with a few questions. I'm wondering if you can talk about how you're thinking about the clinical study of the 1420 molecule and what kind of the ideal patient population you want to target first. Yeah, absolutely. In the phase one A dose escalation, for us, we're going to be targeting patients that have, in the relapse refractory setting, that have FLT3 mutations. Also, patients that, whether they have failed a previous FLT3 inhibitor or not, given where we will be in the treatment lines, they will most likely have already failed a FLT3 inhibitor treatment. Also, we'll be looking at patients with KMT2A rearrangements and NPM1 mutations that have failed menin inhibitor therapy. That's going to be the initial target population. As I said, we're exploring whether we will be also looking at patients that have other mutations that we mentioned, some of the higher risk ones. We have data with our academic collaborators that show that we have activity there. We'll be exploring those options as well. There are a lot of patients that have NPM1 and FLT3 co-mutations. Those patients kind of are ideally fit within the target population that we go after. That is where we will focus. Our focus is to make sure that we are collaborating with the right clinical sites and the right PIs that have experience with menin inhibitors and know and see these patients that have acquired menin resistance. That is what we will be focusing in the dose escalation and most likely in the phase one B expansion cohorts as well. Got it. That makes sense. Just curious, any learnings you can just apply from those menin inhibitors and also if there's maybe potential fast track in those refractory patients there? Yeah, absolutely. I think there's a lot of learnings that we can gain from Syndax and Kura and other menin inhibitor programs. There are a couple of things that we can do in terms of targeting the right patients. There's also things that we can do in terms of targeting having the right clinical protocol. I think something that everyone deals with in this space is the differentiation syndrome. You can construct the protocol in a certain way to mitigate that risk. We will certainly do that. There's also certain biomarkers and genes that those programs looked at that helped them better understand where they were being effective and how they're being effective. That's something that we'll replicate as well. It is also helpful that these clinical sites where menin inhibitor clinical trials are active, this will be a great source for us because they will know and have these patients that have acquired menin resistance. That is something where we want to be active. Yep. Got it. I think Matthew also mentioned there's synergistic or additive effects of 1420 with other modalities. There's a bunch of mechanism like the FLT3, like menin inhibitor or venetoclax. Is there anyone you will prioritize when you are thinking about the combination strategy going forward? When are you planning to start some early combination study? Yeah. For us, we're targeting combination studies in the clinic. Hopefully, it depends on FDA discussions. The time to start thinking about that is when you've already initiated your two phase one B expansion cohorts for monotherapy to satisfy Project Optimist requirements. Once those are up and running is when you can start to think about doing some of those combination settings in the clinic. For us, the first priority is, one, you can combine with 7 + 3 with fit patients or venetoclax and azacitidine with unfit patients or venetoclax and azacitidine with patients that are refractory to or failed chemotherapy. It'll be a venetoclax focus in terms of combination to start, just given the feedback we've gotten from strategics and what they would like to see. I think some of the slides that I showed on menin resistance, it makes all the sense mechanistically where we are to combine with menin inhibitors as well. I think that is something that we'll absolutely, when we are at that point, where to think about it in the clinic a couple of years from now, I think menin inhibitors will be more prevalent in earlier line settings. I think that is going to be one of the target combinations that we'll be looking at early on. It just makes so much sense mechanistically. I think we can really show some synergy there. Got it. I think you mentioned there's some potential mutation can be sensitive to 1420, including TET2, RUNX1, maybe DNMT3. Those are also typical or common mutation in MDS. I'm just curious, any thoughts on maybe testing 1420 in MDS maybe down the road? Yes, absolutely. I think that one of the things that we learned about being active with TET2, and we have a broad portfolio of other molecules, not just 1420. We also have a molecule that is very selective that we can use to test for, very selective with ENL, that inhibit ENL-YEATS. That has showed a lot of activity with TET2 mutations as well. That is something that we are going to be looking to test kind of in the background as we are progressing 1420 towards the clinic, which is our main focus right now. We are discussing with some of our academic collaborators and partners a way that we can potentially look at how the targeted ENL can be effective in MDS and with TET2 mutations. It is something that we are kind of working on in the background. If given the opportunity, we'd love to kind of expand the treatment landscape with the target indications where we can look at for this program. That is something that we need to learn more about, but early data that we see is actually really interesting and encouraging. We will hopefully know more as 2025 progresses. Got it. I guess lastly, you presented some GLP tox data with 1420. I'm curious if you can compare that with other menin inhibitor and also how would you expect the safety profile for 1420 in the clinical study? Yeah. We're highly encouraged with the tox work that we've done to date. I think it gives us a really great exposure multiple versus the levels that we need to see for efficacy. I think when we compare it to some of the FLT3 inhibitors that are on the market, it's got a very, very favorable profile. When we look at menin inhibitors, we'll know more when we're in the clinic, but we definitely know that we don't have the QTc liability that some of the other menin inhibitors do. I think that for us, that's the key there. We don't really know too much about the differentiation syndrome yet. I think we'll look to see what that is in the clinic. Like I said, we have the clinical protocol to try to mitigate some of those risks. Right now, we have the levels that we have gotten to and seen limited toxicity issues in animal studies is highly encouraging for what we can do hopefully in the clinic. Got it. Just lastly, any pre-clinical data we should expect to see this year from 1420? We're looking to do a couple of studies hopefully in some FLT3 refractory patients' cell lines and some menin resistant cell lines. We're exploring exactly what to do. We're hoping that we can share some of that data later in 2025. Got it. Thank you. I think we can wrap it here. Thank you again to Lori, Matt, for joining us today. Congrats again on the progress. We look forward to future updates. Thank you. Thanks a lot. Thank you, Cheng. Appreciate it. Thank you for having us. Bye.