Good morning, everyone, and welcome to the Chimeric Therapeutics webinar this morning. I'm delighted to be joined by Dr. Jason Litton, who's in California, and Professor Jennifer Eads today, who's in Philadelphia. I really want to thank them for giving up their evenings to present to you guys today. I'm going to get started with a little corporate overview, and then I will hand over to Jason and Jennifer. Okay. Share. Great. Let's get going. Please see our disclaimer. I will be making forward-facing statements. A quick summary of Chimeric, and I'm sure you've all heard me present about Chimeric before. Just to remind you, we have four phase one clinical trials active at the moment. This is under three different FDA INDs across multiple U.S. centers. Over the next 12 months, there's a lot of data that will be coming out from these particular trials. We also have a really experienced leadership team. I'm going to spend a little bit of time describing our background for you just to refresh your memory on our CAR-T expertise. With that, our lead program, CHM 2101, is the first CDH17 CAR-T in clinical trials under an FDA IND, which is very exciting. There's a lot of things happening in the CDH17 space, which Dr. Litton will touch on shortly. We also have a first-in-class CAR for brain cancer, and we also have a fantastic program with blood cancers. We won't be covering those today. We're only giving a CDH17 update today. As I mentioned, I wanted to spend a little bit of time on our leadership team. There's myself. I think you all know about me. I have a PhD in cell therapy from Monash University and spent a lot of time working here in Australia and in the U.S. on different launches in the U.S. market and here in Australia as well. Being able to run a commercial business is something that hopefully I can do well. Then we have Dr. Jason Litton, who's my Chief Medical Officer. I can't tell you how great he is in his experience, but he's a pediatric oncologist by training and has worked. We actually worked at Amgen in California at the same time, 10 years ago, I think it was. He went on to really lead the CAR-T programs at Juno Therapeutics and the NK programs at Artiva. We're very lucky to have Jason on board. Also, our Chief Scientific Officer, Dr. Stephanie Astro, who's a PhD MBA and has spent a long time in the CAR-T business working for Celgene and Kite Pharma, a couple of companies you might know. We have all worked on approved products that are now listed in the U.S., which gives us a great run for our path to market, which is fantastic. I am really grateful for the team, and it has been great working with them over the last 18 months. I cannot wait for the next 18 months. It is going to be great. With that, I would really like to hand over to Dr. Jason Litton to run through the CDH17 biology for you. Take it away, Jason. Yeah, thanks, Jenna. Thank you, Beck. It's really good to be with you tonight, this morning. I've actually been working on this particular program for about three and a half years. It's really exciting to be at this inflection point and be able to describe to you our progress. What I'll be talking about is actually the culmination of over a decade of work that's been done at the University of Pennsylvania. Dr. Eads, who's here with me tonight, has been working on this program for much longer than I have and really helped to guide where we are today with the program. She'll be able to talk about not only her experience in the very early days, kind of looking at the preclinical evidence that suggested that this was going to be an exciting new program, but also now she's seeing it being used in her patients. She'll be able to reflect a little bit on her actual clinical experience over the past several months. It's important to recognize that what we're going to talk about, as I said, is based on over a decade of work that's been done at the University of Pennsylvania under the direction of Dr. Xianxin Hua and in collaboration with Dr. Carl June and the research that he's done there that's really been foundational for the study of CAR-T cell therapy for patients. I'll take you through a little bit of the preclinical evidence that made us really excited about bringing this into the clinic. Most importantly, we were able to show, or the team at Penn was able to show, that they could target CDH17 in tumor cells and not affect the safety of the mice preclinically where it's expressed in normal cells. Based on that early preclinical evidence, Chimeric Therapeutics teamed up with Penn and launched the first CDH17 CAR-T cell therapy, which is what we're going to be talking about today. Importantly, the graphic on the right shows exactly what we're trying to do. You'll see the kind of purple cells that have green on the outside represent neuroendocrine tumors, with the green outside receptors representing CDH17 that becomes apparently expressed in these tumors. The pink cells with what is kind of a purple car on the outside is what's intended to represent our CAR-T cells, CDH17, identifying the CDH17 on the target of the neuroendocrine tumor cells, thereby identifying them and eradicating them. That's what we're hopefully going to start to see in patients really soon. The preclinical package that Dr. Hua generated actually resulted in a manuscript in Nature Cancer in May of 2022. It was picked up as the cover because it was so transformative in its potential and implications for use in patients. What Dr. Hua in this package demonstrated in the panel on the top left is if a tumor was untreated, as shown in the black line, the tumors continued to grow from about 100 millimeters cubed upwards to over 750. If we introduce the red line, the second generation CAR-T that was developed at Penn targeting CDH17, you can see that we were able to show that growth of those tumors was stopped but not completely eradicated. It was actually the third generation CAR-T cell that was represented in the blue line that first demonstrated a complete eradication in this neuroendocrine tumor that was then taken into subsequent preclinical models. Two of them are shown here, one in gastric cancer and the other in pancreatic cancer, showing that the CDH17 directed CAR-T, as we know it, CHM 2101, completely eradicated these two xenograft tumor models in addition to four others that are not shown here. This was really compelling and really exciting and something that hadn't been shown by targeting CDH17 previously. What this led to is an aggressive program to bring this construct into the clinic. We partnered with Penn initially and Dr. Eads to open clinical sites at University of Pennsylvania, Sarah Cannon Cancer Center in Nashville, University of Chicago in Chicago, Illinois, and most recently, Emory University in Atlanta, Georgia. Our IND was cleared in November 2023. We actually had another important milestone this year where in April of 2025, we were granted fast track status, which is an important regulatory designation that really streamlines our ability to interact with the agency in real time, with the FDA in real time, as we start to understand both the safety and, more importantly, the efficacy that we're seeing in patients. The manufacturing side of the house, which I take no credit for, but there are others that are doing a great job, have actually executed on 10 successful manufacturing runs in the GMP compliant manufacturing center that's in Philadelphia. We're currently enrolling patients with colorectal cancer, gastric cancer, and neuroendocrine cancers at the four trials listed above. So far, we've treated eight patients, and we have plans to treat two additional patients. We expect to treat about 15 patients in the phase one study, and we can talk through the study design in just a minute over the next several months. Here we have the study design. It's a flexible, adaptive phase one/two clinical trial where we're going to be exploring three dose levels. Dose level one, which has already been complete and demonstrated safety, is 50 million CAR-T cells administered once after standard lymphodepletion. The dotted line there is intended to represent the adaptive nature of this study where we can continue to enroll additional patients at any dose level once we've established its safety. As I said, we've now established the safety of dose level one. We are treating patients in dose level two, and I'll show you this progress in just a minute and have the opportunity to treat additional patients at dose level two, either in parallel to treating patients in dose level three or prior to treating patients at dose level three if we have a reason to continue to explore it. Once we've identified our recommended phase two dose, the orange box in the middle of the slide, we intend to launch three parallel indication-specific cohorts where we'll explore both the efficacy and safety of each of these indications to determine if there are differences. I think what we're going to talk about with Dr. Eads in a couple of minutes is we are potentially seeing some differences between indications that may be important for us to learn more about before we select that recommended phase two dose. On the next slide, we start to describe actually the clinical data that we're reading out. I mentioned that we've completed and demonstrated safety of dose level one, 50 million cells. We treated four patients at that dose level. It's actually a relatively low dose in the world of CAR-Ts where we expected it to be safe, and we were happy to see that it was. We were even happier to demonstrate that one of the subjects treated at that dose level continues on study. She's actually a patient of Dr. Eads that we'll talk about in a couple of minutes. It really seems like even with that low cell dose, she's deriving real benefit. In addition, we've now established safety in two patients treated at dose level two, and that's 150 million cells per dose. As you can see, we've tripled the dose level and continued to demonstrate safety. Again, we'll be able to reflect on some of that clinical experience in just a minute. We have the opportunity, as we mentioned, to go up to dose level three, which is 450 million cells, and recruitment is underway. Next slide. Just mentioning our experience from dose level one, four patients treated. One of those subjects was a patient with a neuroendocrine tumor who actually experienced cytokine release syndrome, which we'll talk about in a few minutes, grade one, while she was in the expansion phase of the study. She experienced stable disease on this study until demonstrating progression at day 150. I think we have some important learnings from that subject. In addition, patient three continues to experience stable disease, and we'll talk about her as well. On the next slide, we're describing what we're starting to see at dose level two. Here's where, as I mentioned, we're using 150 million cells per dose, which is within a dose level that we would expect to start to see important anti-tumor activity. In fact, that is what we're starting to see. The first patient treated at dose level two, patient number five, actually showed tumor shrinkage from their target lesions per RECIST of 12%. Per RECIST, it's still called stable disease. From a clinical standpoint, seeing this patient's target lesion and burden of disease decrease by more than 10% gives us real hope that we may be at a dose level where we're starting to see clinically relevant anti-tumor activity. The next few patients have only recently been treated, so we're not in a position where we can talk about what we've seen beyond the fact that they have been treated safely. On the next slide. Finally, I mentioned that there are just a couple more patients that we're waiting to treat, and the dose level with which we treat them will be determined by our safety monitoring committee that meets periodically to determine dose level changes. I think it's probably a good opportunity now for me to introduce Dr. Eads. Dr. Eads, thank you for being here. Dr. Eads is a Professor of Internal Medicine at the University of Pennsylvania. She's a medical oncologist and clinical researcher who specializes in neuroendocrine tumors in particular, but more broadly treats and does research in the care of patients with gastrointestinal cancers. Dr. Professor Jennifer Eads is the physician lead for GI clinical research at the University of Pennsylvania, and she's also the Director of the National Clinical Trials Network across the country in the U.S. She serves on various advisory boards and committees, and she is also a key member of the Neuroendocrine Tumor Research Foundation, which is a foundation that we collaborate closely with and are proud to partner with on research. Jennifer, thank you for being here. Welcome. Oh, I think you're muted, actually. That's okay. Yes, sure. Thank you so much for having me. I appreciate it. Yeah, let's, you know, we went in a lot of detail about the ongoing clinical trial, but maybe to pull the lens back a little bit and reflect on the patients that you're taking care of every day. What is, you know, the typical advanced neuroendocrine tumor patient that comes into your clinic? Are they generally relatively well? Do they have comorbidities? What are kind of the considerations that come into play when you think about what kind of therapies that you want to offer to them? Yeah, sure. Neuroendocrine tumors are actually very different than most other types of cancers and definitely different than many other types of gastrointestinal cancers in the sense that it's a relatively indolent disease. Now, that's not universally true, but for the most part, these patients can live for a number of years. We are pretty strategic about how we approach their treatment and really focus on quality of life issues because being on treatment perpetually is a real challenge. The standard first-line treatment for a patient with a well-differentiated tumor who has metastatic disease is a hormonal therapy. It's a somatostatin analog, and that can help to control the disease over a period of years sometimes and can be helpful for managing any associated hormone-mediated symptoms that a patient might have. That's really the only true treatment standard in the sense that it's the first thing that we do, but all the other treatment options that we use for patients, it's sort of a physician's choice. We have a number of things at our disposal. We are a very multidisciplinary disease. I collaborate with people in interventional radiology and nuclear medicine, and then, you know, we have some medical oncology therapies as well. For patients who have extensive liver involvement, we oftentimes use something called liver-directed therapy, which is a procedure that focuses specifically on treating the tumor within the liver. The liver can oftentimes be the organ that we get into the most trouble with in this disease, so we tend to treat it quite aggressively. We also do a lot of surgical debulking, even for patients who have metastatic disease. The other sort of big therapy that has come on the scene in the last several years is something called PRRT or peptide receptor radionuclide therapy, which is essentially a targeted IV radiation therapy that can be very effective for people. We have some small molecules that are used that generally don't shrink tumors too much, but rather keep things stable. All of these treatments have their own set of side effects. In selecting what treatment is the best for any particular individual, it's really an assessment of how extensive is their disease burden, what organs or what have you are involved, is the liver extensively involved versus not, and then what comorbid conditions does a patient have, meaning there are some types of treatments where we may not be able to utilize them if a patient has underlying kidney problems or blood count issues or what have you. The kind of patients that we have really been looking for in terms of this trial and administration of CAR-T cell therapy are those patients who are, especially because it's still, you know, a first-in-human trial, we're in the early phases of investigating this agent, we're looking for patients who have relatively stable disease but have progressed on that first line of standard somatostatin analog therapy. We're choosing not really to include patients who have extensive liver involvement, one, because liver-directed therapy, at least at this point, is probably the right thing to do for them, but also because with this being a new agent, we really want to make sure, you know, from a safety standpoint, that that's a good idea. Really the only thing that's required at this point is having received that front-line somatostatin analog therapy. It's a multidisciplinary discussion. There's a lot that goes into treating or deciding what treatments to offer these patients. When they hear about options where they may be able to receive one treatment and then be left alone for an extended period of time, that is something that's very attractive to them. Let's continue on that thread for a minute because I want to tell the story or talk a little bit about your patient who's now nine months out with advanced colorectal cancer, and if you can kind of talk about her prior therapy and what her expectations were and what her clinical experience has been since then. Sure, yeah, she has had a rectal cancer for several years and essentially has been intermittently on and off of chemotherapy or received radiation to certain lesions, surgical resection of certain lesions, and has really been perpetually on treatment for the last several years. When I met her, she was getting pretty exhausted by the extensive period of time from which she'd been on chemotherapy, and it really gets to be a grind with the toxicities and the fatigue. She's a young woman. She has children. She is an active person. She likes to be outside. She was really excited to see that she had maybe an opportunity to receive something that would give her a good break. She tolerated her lymphodepleting chemotherapy well. She tolerated her cell therapy infusion well. She really did great. Now here we are eight, nine months out from her receipt of her cell therapy, and she looks amazing. She feels great. She's very active. She loves to hike outdoors. She just went on this big trip to California where she went to the redwoods and did all this amazing hiking that she otherwise may not have been able to do a few years ago. She knows that at some point this may not work for her, but she's very happy with the success that she's had so far and her opportunity to be off of treatment and have a much improved quality of life for the last several months. Yeah, that's really exciting. I'm actually just taking a peek now. She received her cells in mid-January, so she's coming up on that nine-month date really soon. Yeah, that's great. That's really important. Remembering again that she received dose level one, so a relatively low dose. The other thing that I think we're all going to be interested in learning a little bit more is we'll understand the blood levels of her CAR-T cells that remain, as in the industry we call it a persistence of the CAR-T cells over time because we think that that's probably an important indicator of the ability of those cells to continue to keep her cancer at bay. We'll have that data hopefully at our next webinar, if not sooner. We're really watching that patient closely and cheering for her. One other thing that I wanted to talk about before I hand it over to Beck, because I think it's a really interesting issue that you and I are confronting together, which is the fact that of the patients that we've treated so far, two of those patients have experienced CRS or cytokine release syndrome. They both happen, and it may be a coincidence, they both happen to be patients that have neuroendocrine tumors. Casting that aside for just a minute, I want to talk a little bit with you and get your perspective on cytokine release syndrome and why that is, A, something that we need to pay really close attention to clinically, and we're quite fortunate that it was managed at University of Pennsylvania, which probably is the most experienced in the world dealing with these issues, but also why it actually makes us potentially, if managed appropriately, excited about what may be happening in the patient. Yeah, so I mean, it's listed as a toxicity side effect of cell therapy, but the reality of the situation is that it's not necessarily a bad thing to have a little bit of cytokine release syndrome. It's an indicator that the immune system has been, you know, really triggered and activated. As long as managed appropriately, it's not necessarily a bad thing. Our first patient who had cytokine release syndrome had it to a low degree and really didn't have too much of an issue with it, didn't require any, well, I guess she was readmitted to the hospital with it and managed in the hospital, but didn't really have any significant safety concerns. The second patient, he had a more extensive experience that occurred relatively soon after his treatment. It was of a greater severity. Your slide indicated it was grade three, which essentially means that he had required treatment with some IV immune suppressants and had needed some extensive ICU monitoring for a brief period on some medicines to help manage his blood pressure. It lasted 36 hours, and he tolerated the situation pretty well. When I went to see him in the hospital, I said, you know, I don't want to hurt you, but I'm not entirely disappointed that this happened because it may reflect that something good is happening in your body. I do think that, as you alluded to, it's important with administration of CAR-T cell therapy to make sure that whoever is administering it is up to speed on what needs to be done should it occur. It's not something that we take lightly. There are medicines that can help mitigate the issues that come along with it. If that gets a person through it and it's not life-threatening, then hopefully it ends up being worth it in the end. Yeah, that's probably actually a good bridge to come back to Beck to kind of talk about maybe what some of the commercial opportunities are. Maybe we can circle back on, you know, making sure that we can deliver this medicine more broadly and see what some of those challenges might be as we start to define the value for it. Beck, I'll hand it back over to you for a minute. Thank you so much. I do have one burning question for Jennifer, if that's okay, before I jump into the commercial thing. Why are you so excited about CHM 2101 for your patients? There are several reasons. One is that, you know, Penn is an immunotherapy powerhouse. We have been, you know, sort of leading the way in CAR-T cell therapy. It's really exciting to have one that's actually been generated by a Penn scientist and has been brought to the clinical level. For me, in particular, as a neuroendocrine physician in such a population. This is a rare disease entity which oftentimes does not get the same attention from a research standpoint or any standpoint, really, as some of the, you know, the more common cancers. Just the opportunity to both offer it to patients with neuroendocrine tumors, I mean, albeit, you know, there are other disease indications as well, but especially for the neuroendocrine patients, which is what it had been originally designed with the intent of treating. To just see from the patient's side how excited they are to have an opportunity to be treated with something that is so novel. They're not, you know, the last ones to the show, as usual. I think from the scientific standpoint, it's very fascinating. From the patient care standpoint, it's very fascinating. Both of those things make me really excited to have this opportunity to treat them. Right. Very, very excited as well. We look forward to all of the more patients that you get to treat. I can't wait to see what happens. In terms of moving to the commercial things, let me share my slides again. Hang on one second. Let me press share. That would be helpful. When we think about the total global market size that this particular asset has to address, last year was about $27 billion, and it's set to grow quite extensively. Unfortunately, bowel cancer in young people aged between 20 and 40 years is actually one of the fastest growing cancers in the world. I think it's growing at 300% or something I read somewhere. Unfortunately, we're going to have a lot more bowel cancer patients on our hands. I think, particularly for cell therapy in younger patients, this is a really good option. The market's only going to get bigger as we move along. Slides here. If I can just provide a brief summary, then we can open up for questions. Please pop your questions in the chat while I'm speaking here. Basically, in summary, we're moving really well, and I'm really happy with the progress that we've made. I'm really grateful to our investigators and also to Jason and his team for all the great work that they're doing. We've treated eight patients so far. We've had 10 out of 10 manufacturing runs, and a huge thank you to our manufacturing team. That's fantastic. We've seen anti-tumor activity, and I think we're only going to see more as we treat more patients. We haven't had any safety issues to date, and I think it's really important to highlight that we haven't had any off-target issues. Some of our potential competitors in this space that have CDH17 antibodies have seen off-target effects, and that's not the case in this program. We're really delighted how the program's running at the moment. I think with the fast-track designation, it gives us a really good opportunity to interact with the FDA quite frequently. For a cell therapy, we can actually be registered at the end of phase two. We don't need to do a big phase three study. We can be on the market at the end of phase two with the right partner. For us in FY26, we're really focused on completing the phase one. What does that mean? We need to complete dose level two, and the safety monitoring committee will determine what that looks like. We do have an opportunity to move up to dose level three if we see that it's appropriate. This is a really important point because if we like what we see at dose level two, there's no need for us to move up to dose level three. That will just be more of a curiosity question. We might not even need to do that. We'd really like to conclude phase one. We've already started to prepare for phase two. I know both Jason and I get emails every day from hospitals around the world wanting to be a site. That will be a really easy process for us. I think what's really encouraging is we can see that there's a lot of big pharma companies that are interested in this particular target and in CAR-T cell therapy because they have the global manufacturing networks that they established many years ago, and they're all running below capacity. That's a really great opportunity for us. I think as we move forward with all of our results, we'll have a lot of opportunities for discussion with those particular groups. With that, I will open up to questions. Let me have a quick look at what we've got. Four questions. Great. I think the first question comes into a licensing question, which I'll take. You guys can have a break for a minute. When we think about licensing, I think there's a few opportunities on the table. There's an opportunity to license CDH17 by itself, or there's an opportunity for the whole company. I think we'll take a look at those as they come forward. Once we have the data, we can kind of have whatever conversations we'd like, and I feel really confident about that. A question perhaps for Jason. Would the body become resistant to any CDH17 treatment? I'll hand that to you, Jason. One of the things that we'll continue to look for are what we call HACAs or human anti-CAR antibodies. That would be something that could potentially develop over time, especially with continued exposure to the cells. There are some non-human elements to the CAR. It's something that we haven't seen to date, though. The value proposition here ideally is that a single dose should be enough to provide that transformative medicine that we intend for it to be. Great. Thank you, Jason. Perhaps a question for you, Jennifer. You know, when we run these trials, particularly in phase one, safety is our main priority. When we're looking at any efficacy, how do we look at that when making a decision about dose escalation? Yes, in addition to monitoring these patients for safety and toxicity, we are also following them over extended periods of time to see, as we discussed in the presentation, if they've had any tumor shrinkage, how long they've been on the treatment, and how much it's been able to stabilize their disease. I think one of the things that you always have to think about in phase one trials is balancing the side effects that occur from the treatment with the efficacy. In particular, cytokine release syndrome is something that we're very keenly aware of. We don't want to push that too far to the extent where we might sort of give somebody more treatment than we would want to because that reaction could be pretty severe. We want to kind of have it happen enough so that we think that we're getting benefit. That's why I think after we treat a certain number of patients at any given dose level, we always sort of have our meeting with the safety monitoring committee and look at it in detail and try to understand, are we seeing enough activity with this? Is it okay to sort of stop escalating at this point given the toxicities that we've seen? If we're seeing really no toxicity, then should we try to escalate further to see if there's more of an effect? It's an ongoing discussion at each dose level. Right. Are there any more questions? I don't have any left in my question box. If there's no more questions, I'd really like to close today's session. Just to give you a quick summary, we're really excited about what we're seeing. We've got a lot more data to come out in the next few weeks. We're really excited about what's to come. I'd really like to thank Dr. Jason Litton and Professor Jennifer Eads for their time this evening. Thank you very much. Thank you all. Thank you.