Good afternoon. I'm John Newman, one of the Senior Biotech Analysts at Canaccord Genuity. Thank you for joining us at the 45th Annual Canaccord Genuity Growth Conference. We're very excited to have Marker with us today. We have the CEO, Dr. Juan Vera. Juan, welcome. Thank you. Very excited to have you with us today. I'm wondering if you could start by talking about Marker 's MAR-T cell approach and what makes this approach unique in targeting tumors in cancer. Yeah, absolutely. Happy to do so. I think that this space is well familiarized with CAR T-cells and alpha-beta TCRs, and from a mechanism of action, it's very, very different, right? Our product is a natural product that recognizes multiple different epitopes and multiple antigens, right? In fact, it recognizes hundreds of epitopes across six different tumor-associated antigens. It does so using the natural T-cell receptor recognition that is mediated by both CD4s and CD8s, right? This type of strategy, I believe, is going to be very important, especially when trying to target the complex tumor microenvironment and precisely to avoid tumor immune escape due to negative antigen downregulation. Think about MAR-T cells as a product that we take from the patient and are able to re-energize tumor-reactive T-cells present within the patient. The composition seems to be very distinct and unique from patient to patient. I believe that in a way that is reflecting the heterogeneous antigen composition within the own patient tumor. Okay, great. Thank you. MAR-T cells have a unique manufacturing process. I wonder if you could explain that for us in a bit more detail and also talk about how it's different than some of the other cell therapies. Yes, absolutely. Let me start with the similarities and the differences. The similarities are perhaps that you also require an apheresis collection, right? The manufacture takes place in a centralized facility, right? It's an autologous T-cell treatment. From that perspective, those are where the similarities start and also where they finish. The differences rely on the fact that this is not a genetically modified material, right? The manufacturing process itself relies on peptide stimulations. Those peptides are basically synthetic molecules that recapitulate the target antigens present within the tumor. In this way, you are able to raise an immune response in a natural manner, right? The manufacturing process is, in fact, very simple. The company has invested millions of dollars and multiple years to industrialize the manufacturing process. At the moment, it is a simple nine-day ex vivo process where you basically take the starting material, stimulate it with peptides and cytokines. From that point, it's virtually unmanipulated for about the remaining seven days of culture. At that point, the cells are then collected, cryopreserved, and then they can be sent to the clinical site in a cryo manner where they're administered to the patients. Okay, great. How do you select the target antigens? Do you require a tumor sample in order to have information about the patient's individual expression, or is it done differently? Yeah, very good point. I think that that's another element that differentiates our technology. Some other strategies, especially when developing a neo target, you require the knowledge of what antigens are expressed within the tumor, right? As a consequence, if you have a patient that you are interested to enroll into a study, you have to take a biopsy sample. You need to identify what particular antigen is present. That's actually the same algorithm for chimeric T-cell receptors, right? Many of them, which actually require intensity or expression of a particular antigen for patients to be treated. Our approach is target agnostic, right? From that perspective, we basically don't require a prior examination of the antigens present within the tumor, nor a tumor biopsy sample. Patients get enrolled into the study. The reason we're able to bypass that is because we're able to give the culture a very broad target profile. The antigens have been selected following a statistical approach that, in absence of prior knowledge in terms of what antigens are expressed within the tumor, we can generate an immune response at least to one, if not more, of the target antigens present within the patient. Think about this in terms of the analogy: fishing with a harpoon, where you have to see where the fish is, versus fishing with a net, right? Where you don't need to look, and you can just throw a very broad net of peptides and fish those tumor-reactive T-cells. Okay, great. In terms of the MAR-T technology, could you talk about what's known regarding how the cells expand in vivo and how they persist? Yes. One of the limitations, if I was basically to highlight in our technology, is the fact that our product is not genetically modified. As a consequence, from a technical perspective, it can be quite challenging to monitor once administered into patients. It is very different than a chimeric T-cell molecule or an alpha-beta TCR, where you can track by PCR. Now, let me tell you what we know. When we look into our Baylor clinical data, we actually have seen that natural T-cells can be engrafted in patients for multiple years. We have seen from our earlier Baylor clinical data that cells can survive in patients for more than 10 years with the ability of repopulating and expand if needed, right? On our own data, we're still collecting durability, but we have seen that the cells expand and persist for as long as six months, which is the longest follow-up we have so far in our multicenter clinical data. Thank you. Could you talk just briefly about the pipeline portfolio and what specific programs you're most excited about? We can get into some specific questions about individual programs. Yes, absolutely. If we look into our pipeline, we are really concentrated into our lead asset, which is MT-601. I believe that this asset will be able to be advanced for approval or a pivotal study in a very short period. With that in mind, we are advancing MT-601 in lymphoma, particularly the LBCL. I'm happy to tell you more of that in just a moment. One of the things that is quite interesting in our pipeline is that you will see the same asset, MT-601, in solid tumors. I believe that that's another element that makes this approach very different, especially because I believe that the promise that has been put out there in terms of CAR T-cells being able to perform clinically in solid tumors has been, to an extent, disappointed. I believe our treatment is going to be able to deliver on that promise, right? The reason for that is, again, anchored on the broad target profile and how our drug can be advanced into solid tumors. From our pipeline, I think that it's quite attractive and unique that we're advancing the same asset, MT-601, not only in lymphoma, which is our lead clinical indication, but also in pancreatic cancer, which is a clinical area of which we have proof of concept from Baylor College of Medicine. Okay, great. For the MT-601 program in lymphoma that you just mentioned, could you talk about what your data have shown thus far there? Yes, absolutely. The best way to characterize that clinical data is perhaps that, again, this clinical program was developed from Baylor College of Medicine. The first intent here for us was to recapitulate those results now in a multicenter clinical data. I have to say, from the data that we have so far, we have been able, we have successfully done so, right? We performed a data cut, I believe it was September last year, where we actually have reported an overall response rate of 77% and a CR rate of 44%, right? We actually have, in terms of the durability, which we continue to collect, but we have reported publicly, three patients with more than six months durability and one of these patients that have gone for more than a year, right? I still think that it's quite significant in terms of the fact that these patients have a significant medical need and the treatment has been very well tolerated. No ICANS, and the only CRS that has been reported has been fever, level one CRS that responded in absence of any treatment. Okay, great. Could you also talk about what the treatment options are today for patients that relapse after CAR T therapy? The CAR T therapies have been great and they work really well, but unfortunately, some patients do relapse. I'm just curious as to what options they have at that point. Yes, absolutely. I mean, one of the major limitations I think that CAR T-cells have is, without a doubt, the short-term durability. We look into the treatment option for this group of patients. If you're looking to the LBCL, you have treatments such as bispecifics. I think that from the distance, it might give the impression that there are available treatments as well as multiple drugs being developed in the market. However, if you start looking closely, you identify that, for example, in the particular case of bispecifics, glofitamab, which is perhaps the best available drug in that particular space, you have multiple limitations that can be summarized by, one, multiple PIs or physicians don't consider those to be curative. Two, there are significant toxicities associated with this, including CRS, that restrict the application to sophisticated and centralized academic institutions. It requires continuous and multiple administrations, in some cases up to two years. If that was not bad enough, I think that the most devastating thing is that these drugs are now moving as an early line of treatment, most likely before CAR T-cells. If you fast forward perhaps a year or two from now, it's likely that a patient that has failed CAR T-cells, these drugs are not going to be available. Therefore, I think that when we look into the current landscape, we see that there are not really good drugs currently available. I don't think that the landscape is going to change any time in the near future. Okay. Do you have a sense in terms of approximately the number of patients, just roughly, that might be eligible for your treatment on an annual basis? Yeah, absolutely. I mean, without a doubt, this is a growing population with a high unmet medical need. This is really unfortunate. I think that when we look at the global market, we basically see that about 8,000 patients, with lymphoma patients, have been treated with CAR T- cells specifically for 2024. If we assume that about 40%- 60% of these patients will relapse by looking into the data within the first year, we can calculate that a drug like MT-601 could have a market opportunity that could represent a revenue of about $1.7 billion a year, right? I think that this population is just set to increase in the future, as well as CAR T- cells moving into an earlier line of treatment and treating more patients. It's possible that by 2030, this population could create a market opportunity of about $3 billion for a drug like MT-601. Okay. Do you require lymphodepletion before infusion of the MAR-T cells into patients? Yeah, that's an excellent question. Looking to the earlier Baylor clinical data, we actually have significant clinical experience in absence of lymphodepletion. Even in absence of lymphodepletion, we have seen objective responses which are durable. In the data set that I mentioned earlier on, where I characterize an overall response rate of over 70% and a CR rate over 40%, that particular data set combines both patients that have been treated with or without lymphodepletion. What I can tell you today is that even with the incorporation of lymphodepletion, we have not seen a detrimental effect in the safety profile, which is super important. The other thing that I can tell you about that is that now we have tracking data by looking into the individual alpha-beta TCRs that, without a doubt, lymphodepletion can influence the expansion and the persistence of the T-cells. It's my belief that given the favorable safety profile and the expansion that we have seen, the incorporation of lymphodepletion now into our study has the potential to further improve the clinical activity. Okay. I know the current study for MT-601, the phase one, is enrolling patients that are relapsed after CAR T. What I'm curious about is going forward, thinking about the potential pivotal study design, could that study enroll patients that were treated perhaps with bispecifics previously? Yeah, I mean, absolutely. Let me share my current viewpoint on that. I think that especially given the fact that when you look at CAR T-cells or CAR relapse, it's a very fluid clinical landscape. What we're considering that would be the most attractive patient population would be to enroll patients in the pivotal study that are DLBCL, CAR, and/or bispecific relapse. If I was to guess, I think that in the future, most patients at that stage will have relapsed both, especially as we see bispecifics moving into an early line of treatment. Okay. I wanted to talk for a moment about manufacturing, which is obviously a really critical piece of the cell therapy story. I think Marker has a really unique position here. Could you talk a bit about the manufacturing? I think you are collaborating with a third-party CDMO. Just curious if you could talk about how you anticipate the manufacturing kind of evolving as you go forward and you move through clinical studies and then towards commercialization. Yes, absolutely. Let me characterize this, that the objective here is basically to de-risk our operations, right? I think that if I look at a company like ours that is cell therapy and autologous, I perhaps categorize two major areas of risk. One is clinical operations, and then the other one is manufacturing. From a clinical operation, I think one thing is super important is being able to recapitulate academic data in a multicenter setting, which I think we have been able to do so at this stage. The second element, which is manufacturing, is also being able to recapitulate manufacturing capabilities across multiple different sites, right? I think that one thing that is important to recognize is the clinical data that we characterize today is actually produced from two different vendors, right? We have previously performed successful tech transfer, and we now have data from two different GMP facilities providing samples into our clinical study. The incorporation of a vendor now, which is also in Houston, where the headquarters for the companies are located, is with the objective of incorporating a vendor that we believe has the capacities of providing sufficient supply for the pivotal study as well as for commercial launch. With that in mind, basically tackle one of the critical elements for the future development of the registration study. Okay, great. We talked a bit about the pipeline earlier, and we know that you're advancing programs other than MT-601. I'm wondering if you could talk a little bit about some of the other programs and the potential timelines and milestones there. Yes, absolutely. I mean, I think that what I would say to that is we remain very focused on the future of the company and the now, which is basically, in my viewpoint, the success of the company will be on the execution of MT-601 on the lymphoma study, which we're very excited. If we fast forward beyond that, what I would like to portray is a future that will be far more attractive as we could extend MT-601 into solid tumors. We are now advancing MT-601 into metastatic pancreatic cancer. We actually have received funds from the government, CPRIT, and NIH, and we have more than $10 million that will be advanced to explore the clinical activity of MT-601 in pancreatic cancer, right? Investors should think about this almost as a free option, given the fact that we'll be using revenue derived from the government. In addition to that, we're also exploring, via support from the government, via grants, the use of an off-the-shelf approach, which is very different than many of the programs that are currently being developed. It's basically the generation of a cellular inventory that can be provided to patients very quickly. We calculate about 72 hours by performing a simple, partially HLA match, right? We anticipate to treat our first patient in the second part of this year too. Okay, great. Before I ask you my last question, I just wanted to see if there are any questions from the audience at this point. I just want to know more about the strategic initiatives your company is taking to have the advantage over other competitors. I'd just like to know more about that. Yes, absolutely. I'm fully aware that when we look at this space, there is a lot of competition, particularly into DLBCL CAR relapse. What I would categorize is that our approach is different. It really comes down to how distinct our product is from a mechanism of action and from a safety profile. If you look into the space and it takes doing a clinicaltrials.gov search in terms of DLBCL CAR relapse, there are a lot of studies out there. In my opinion, none of them really address the underlying limitation, right? When you think about the target antigens that are being utilized in this space, you're talking about CD19, CD20, potentially CD22. We have to recognize, and there's also clinical evidence of that, that as you increase those number of targets, there is also a clear correlation with the increase of toxicity. I think what we provide that is different is comparable, if not superior, clinical activity. We still need more durability of the data. What makes it different is the safety profile. On the basis of the safety profile, it would make this treatment different. Great. I just have a follow-on question, Juan. The question is, you know, we've seen a lot of advance over the past decade with CAR T. We've seen, you know, first CD19, then BCMA in multiple myeloma. There's companies working on CD22. Why do you think other companies have not, or perhaps they have, why have other companies not been successful in terms of a multi-antigen targeted approach? You know, theoretically, you could imagine that a disease like cancer that is prone to a lot of mutations would potentially respond better to a multi-targeted approach from an antigen perspective. Maybe you could talk a little bit about that and just kind of your historical perspective as to why this approach has not been explored successfully. Yeah, that's an excellent question. It might require more time to fully dive into that. Let me then just provide my viewpoint on this. I think, without a doubt, this statement becomes particularly relevant for solid tumors, right? I think that we need to create treatments that are heterogeneous and that basically address the unique makeup of cancer cells, right? When we think about the targets that currently have provided a level of success, they're not cancer targets. You're talking about C19, C20, C22. These are normal, healthy targets, which in some cases have also consequences. Now people are taking advantage of those for autoimmune disease. When you look into solid tumors, that's no longer a possibility, right? Those targets are not easily accessible. I think that in the case of hematologic malignancies, definitely multiple groups have to explore the CARs that are engrafted with two or even three molecules. Something that is perhaps not that obvious is that there is crosstalk between all those different molecules. It's a point of saturation in terms of how many chimeric molecules you can load into a cell without basically affecting the signaling of an individual receptor. I think that conceptually makes a lot of sense, right, to go after multiple different targets. I think from a technology perspective, it's very difficult to do so with chimeric T-cell receptors. The final thing that I would say to that is also that it is an oversimplification of the approach, right? Because when you target, let's say, C19, C20, or C22, you're not targeting the full antigen. You're targeting just a fraction of the antigen, which is just an epitope, right? You're really extending from one to three epitopes. I think that it's going to be challenging to have that level of solution because it's anchored by the limitation of the technology, as we have seen so far. Okay, great. Thanks. One last quick question, not maybe as interesting or exciting as the last, but could you talk about your current cash position and your estimate for runway, if that's been disclosed? Yes, yes, for sure. As disclosed in last Q on March 31st, our cash equivalents are $13.7 million, which extends our capital runway into the first quarter of next year. Importantly, as also mentioned earlier on, we have been quite successful in deriving revenue from the government, including NIH, FDA, and the state of Texas via CPRIT, where we have secured more than $30 million. I think that that is valuable not just from a capital perspective, but also, I guess, the validation that these have in terms of the technology and clinical execution. Calculating that into our revenue, we extend it beyond the first quarter of 2026. Okay, great. Excellent. That's all the time we have. I wanted to thank everyone in the audience today. Also, thank you, Juan, and thank you to Marker Therapeutics. Thank you.