Welcome to today's Chimeric Therapeutics investor webinar, which will focus on today's announcement of data from the company's CHM CDH17 program, which was presented at ASCO in Chicago. All participants are in a listen-only mode. There'll be an initial presentation lasting for approximately 15 to 20 minutes, followed by Q&A. If you have a question you'd like to submit, please do so using the Q&A function within Zoom, and we'll get to those later. From Chimeric, we have the CEO, Dr Rebecca McQualter, and I'll throw it to her now. Thank you so much, Matthew, and good evening from Chicago. I am live here at ASCO, which is the American Society of Clinical Oncology. It's actually one of the biggest conferences in the world. There's 50,000 people here at ASCO, and we are delighted to be one of only a handful of Aussie companies presenting data at this meeting. I'm delighted today to take you through our results, and these were presented by Professor Jennifer Eads, who is our lead investigator at Penn, from Philadelphia. Today I have the clinical and translational results, and please feel free to drop any questions into the chat, because I want to make sure that you walk away understanding these data. Let me see if I can move my slides. Great. Just in quick summary, as you're aware, we're in our dose escalation phase of the CHM CDH17 phase I portion of our phase I/II study. We do have approval from the FDA to move into phase II, but this is really the crunch time where we're making those decisions about what the correct dose looks like for our patients moving forward. I think what's been really exciting is we've received so much attention for these data at this particular meeting, and it's actually been quite overwhelming, the response that we've had. We're really excited to announce that at all dose levels, our product has demonstrated expansion, persistence, and tolerability. This is really important in a CAR T-cell product, and I'll walk you through those results specifically in a minute. Enrollment at Dose Level 3 is ongoing at our four U.S. sites. What's been really amazing is we've actually had an overwhelming response to recruitment. We actually have a line out the door still. I could fill 70 slots tomorrow if I had the money to do so. As we move into phase II, it's a really good sign. We probably get around six or seven emails a day from different institutions asking if they can be a site. There's a lot of demand for particularly younger patients with colon cancer. I'm going to take you through the entire poster, which was attached to the release today. As you're aware, CHM CDH17, or as it's registered with the FDA, it's CHM 2101, is a Cadherin 17- directed CAR T-cell therapy. This image really demonstrates why this was chosen as a CAR T target. Now, I've presented this to you many times. We really wanted to highlight why it's such a good CAR T target, because in colon cancer, the target is expressed on the tumor above. It's really easy access for the CAR T to access for the tumor killing, which is why it's made such a good target. I also wanted to highlight that colon cancer, unfortunately, is now the biggest killer of young people in the U.S. here from the ages of 20 to 40, which is really disappointing. There's actually quite a significant gap in the market here. At the moment, there's only surgery or very old chemotherapy. A lot of the checkpoint inhibitors don't work in colon cancer, attending this meeting's really brought that to light, that this is a really challenging space. The results that we've seen here are actually quite exciting because we're on the right track. We're headed in the right direction. As you've seen this multiple times, we're currently at Dose Level 3 in our dose exploration and dose confirmation phase of the study, and so now we're currently at 450 million cells. This is really important because nobody has gone this high in the solid tumor setting just yet that I'm aware of. If I've missed a study, please send it to me. We can see that there's quite a few CAR Ts that have done 250 million in the solid tumor setting, and they've done two doses. That's all we're aware of at the moment. We're at 450 million at the moment, and currently in colorectal cancer patients at the 450 million dose level. I want to say thank you to my Head of Manufacturing because we've maintained our 100% success rate, and this is very important in cell therapy manufacturing. Most of the commercial products sit around 80% success rate. We only have a handful or 15 successful manufacturing runs, but we've had 100% success rate. Thank you very much to Dr Agathe for her amazing work on our manufacturing and making sure that our product is GMP standard every single time. Let's go through the demographics that we have at the moment. Our average age is currently just under 50. We have an even split between male and female. We don't suspect that there'd be anything to lead us to believe that there'd be any difference here. I think what's the most important thing about this particular part of our presentation is the prior lines of therapy. We're aiming for a second-line treatment. They have one dose of chemotherapy, and then they'd have our therapy. What's really interesting is the spread of the lines of therapy. We've had patients that have had one line of chemotherapy. We've also had a couple of patients with 12 lines of chemotherapy. That means they've had multiple years of chemotherapy to keep their cancer at bay, and these are all Stage 4 metastatic patients. These patients haven't been given a good prognosis, and the chemotherapy's been working a little bit, but not enough. That's where we've stepped in. I think it's important to acknowledge that if you've had multiple years of chemotherapy, it means you've been unwell for multiple years, and despite the fact that it's working, your quality of life is generally poor for multiple years. I think the biggest differences that we've noticed with our therapy is people have one dose and then they've been feeling very well. They don't have that chemotherapy toxicity that's very common with most of these patients. That's been one of the biggest messages coming back from all the feedback from everybody here at the meeting. Onto the results. I really want to make sure that this is very clear. There's something called treatment emergent adverse events, and this is what we expect to happen throughout the drug protocol. Every patient has experienced a Grade 4 treatment emergent adverse event. This is because of the protocol that we use to prepare their body for the cell therapy. We do lymphodepletion, which means that we remove all of the T- cells that they've already made, so that when we put the CAR T- cell product in, it's the dominant T- cell in the body. This is how it works. We expect to see this, we expect Grade 4, we expect neutropenia, as it's called, which means that you lose a lot of blood cells. We're doing this on purpose, so we really expect it. It's documented in all cell therapies, this is what we expect. The treatment-related AEs is what is caused by our product. This is what we're really focused on. We've had patients experiencing CRS, and that's cytokine release syndrome. This happens when we put the product into the patients, their immune system gets really revved up and starts to release cytokines. Now, we expect to see this with cell therapies, and it's very well documented that if you see CRS in patients, you're typically going to have a good response. This is normal standard of care kind of practice, if you like, when it comes to cell therapies. This has been very well documented for over 20 years. We have had our first dose limiting toxicity in our very first patient at Dose Level 3. He's had Grade 3 diarrhea, and we're watching this very carefully. We don't have the complete picture of what's happened yet. We've got biopsies, we've got tumor biopsies, we've got healthy tissue biopsies that are all being run at the moment. What we really want to understand from that dose limiting toxicity is it the CARs that are moving into the healthy tissue, or is it the CARs just being way too prolific and his particular T- cell type has expanded in a greater kind of way than we expect them to? There's two possible scenarios there that we haven't been able to determine just yet. Our translational scientific team, led by Dr. Stephanie Astrow, they're working on that right now. Because we have had our first DLT, that means for Dose Level 3, we are go slow. Instead of dosing a patient every seven days, we have to dose the patient every 28 days. What's happening now is we're probably dosing a patient every 40 days to be conservative. We don't want to hurt anybody. We're okay to go slow. I think we want to make sure that we determine that this is not the product working on healthy tissue. We don't think that that's the case at the moment from what we've seen, but we're still yet to find out. As we work through that, we'll be go slow. I think that we've successfully dosed a second patient. She's fine. She had a little bit of CRS, which is what we expect from a CAR T- cell therapy. We've got the third and fourth patients ready to dose as well. The safety monitoring committee have been really engaged, and I'd like to thank them for their work on this, and we'll continue to monitor all of these patients. I'm very pleased to say that the patient that experienced the dose limiting toxicity is doing very well. We did have to dampen his CARs a little bit and switch them off, so his results won't be sensational as we expected. That's okay. I think we're moving in the right direction, and we're excited that the second patient's doing really well. Hopefully that makes sense, and I've been able to separate the treatment emergent AEs and then the treatment-related AEs. I want to move on to our results, and I mentioned earlier that in every single patient, we've seen expansion and persistence, and this is the key to any kind of response in cell therapy. Here at the meeting, this particular graph got the most attention. This was described as beautiful, sensational, exceptional. I can't pick any more adjectives that were thrown at us while we were there. As you can see, in every single patient, everybody has had expansion, which means that the product is expanding in the body, and we can start killing that tumor more effectively. The persistence is really key. The persistence means that these particular cells are hanging around, they're doing their surveillance, and they're doing their proactive tumor killing. This is really what we want to see. Unfortunately, as a patient moves off the study, we're unable to collect their blood any longer. We only have them until they're on the study. I don't know if you can see my mouse there. You can see we've got persistence out to 400 days. This is quite exceptional. We haven't seen this documented for this duration before, but she still has 3% CARs in her blood, which is amazing. We know that in that particular patient, they're doing their surveillance, and she's had no new tumors pop up. This is very important. Even though you'll see our results on the next slide, we've only hit stable disease in the majority of patients. There's actually been not many new tumors that we can see, which has been quite exceptional. The CARs are proactively killing. They're looking for new tumors that are emerging and getting rid of them before we can even see them. We're really delighted with these results. I'm moving to the end of my presentation here. As I mentioned, 82% of our patients have achieved stable disease. This is really important in this particular setting. As I mentioned, they were all reliant on chemotherapy. There's not much else that works for these patients. As I mentioned, we had one patient out to 15 months, one patient to 12 months. We still have three on study and two to treat, which has been really fantastic. For example, that first patient that was out to 15 months, they progressed her off the study because she developed obstructive pneumonia and needed some different treatment. She received that treatment and had to move off the study. Her tumor didn't grow necessarily, but she's been now two years chemo-free, and this has been significant. Her hair's grown back. I think I've mentioned her to you before. To be two years chemo-free seems to be getting attention of the medical oncologists here at ASCO. We're really delighted. Even though it's stable disease, there's no new tumors in that particular patient, so the CARs are working. I think one story that we heard from our investigator meeting yesterday morning, was that a lot of the tumors look like they're hollowed out in the middle. The very first patient that was treated, who had the pelvic mass with the necrosis in the middle, we're seeing a lot more examples of that. We're working with Penn to try to quantify that, to see how we can ensure that we're capturing that central necrosis appropriately. We've had a tumor shrinkage spread from 12% to 100%. In two patients, they've had smaller nodules completely disappear. However, their result has been stable disease because their liver mets have stayed the same size, or four out of five mets have stayed the same, and then one's completely gone. We can see the CARs are actively working. We just don't know how to measure that appropriately just yet. Now, it's not our job to change the paradigm of how cancer is measured in patients. We'll let Penn lead that fight for us. We're really working on that to make sure that our results are captured appropriately. To close my presentation today, we're really proud of the results that we've presented here at ASCO. I'm really proud that we've achieved tolerability in these heavily pre-treated patients. I think the most important thing is that to see someone two years off chemo with one small dose of CHM CDH17, makes our job really worthwhile. We're going to continue at Dose Level 3, and then we'll have some decisions to make about phase II. Whilst I've been here, there's been significant commercial interest in the product. We've also been captured by competitive intelligence. As someone who used to work for a big company that used to hire the competitive intelligence, we had quite a lot of interest yesterday in our data. I think it'll be getting interesting from here on in. Thank you so much. Matt. Thanks, Rebecca. Just as a reminder to the audience, if you have a question you'd like to submit, please use the Q&A option within Zoom. We'll jump into those now. The first one is, Rebecca, will the endpoints for phase II be the same as in phase I? If endpoint are not applicable, will the efficacy be evaluated as in phase I results? For phase II, even though we have approval from the FDA, we will go back and consult our Fast Track team. We're very lucky to have that Fast Track team. It'll be slightly different because right now we're not really powered to make any statistically significant claims. It's very late here in Chicago. We can't claim overall survival yet or progression-free survival. We really want to make sure that our phase II is powered that way. We can have those types of claims in our indication. We're really thinking about that. That will be our focus, is to make sure we have enough numbers in the study, that we can really demonstrate an overall survival benefit. Thank you. The next question is what are the competing treatments, and how does CDH17 compare with them in terms of efficacy? That's really hard to say because we have a handful of patients, and a lot of the treatments out there have thousands and thousands and hundreds of thousands of patients, if not millions for some of the chemotherapies. Standard of care right now is chemotherapy, and surgery if that's applicable, but sometimes that's not applicable. One of our very first patients had a colon cancer that wrapped around his spinal column, and they weren't brave enough to take it out via surgery. Chemotherapy wasn't penetrating, that's why he was eligible for our trial. It's a bit hard to say, but I think that's kind of the competitive landscape. We're competing with 70-year-old chemotherapies, like FOLFOX, and that's very old, very traditional. It does work a little bit, significant toxicity. The patients are very unwell and lose all their hair. I think the checkpoint inhibitors haven't been successful in colon cancer, so there's really been a gap, and I think there's some applicable cancers where PD-1 might work, but that's not always the case. We've had a lot of GI oncologists come up being very interested in this space. What we'd really like to see is a bigger market entry. That will be the second-line space. You have your first dose of chemotherapy, you'll quickly fail that, then your T- cells will be right for manufacturing. We don't want them to have 12 lines of therapy because their T- cells don't perform very well during manufacturing. I think what's something interesting that was brought to my attention today, now that we've kind of seen this lady, and it's only one, right? Let's put a filter on that. It's one patient. Because she's been two years chemo-free, we've actually become cheaper than two years of chemo in the U.S. When that person said that to me, I said, come on, we're a cell therapy. We're pretty expensive. They were like, no, two years of chemotherapy is a little bit more than what your cost of goods are. If we start to see more of those examples, which I hope we do, then it'll be easy for us to make a case that we deservedly belong in second line. The patients will perform better, their quality of life will be better, they can contribute to society for longer. That cost analysis is going to be more positive for us, and that's what we're really aiming for. Thank you. The next question is there dose-dependent efficacy, i.e., does the efficacy improve at higher dose levels? That's a good question. We'll find out. I can't wait to tell you. I can't wait to see myself. We suspect so, but we'll have to wait and see. Following on from that, what is the probability that Dose 3 can be taken forward in phase II? I think if we don't see any more toxicity, that was just an unlucky patient, sometimes you get an unlucky patient, then I think then we'll take that forward. If we see more toxicity, this is a normal part of clinical trials. This is the dose finding. This is why we're doing what we're doing. If this is too high, we might go back to 300 million, for example. We also might split and do two 300 million doses. That's also been discussed at a safety monitoring committee. Until we kind of collect that tangible result, we can't make a decision. Now we've had one patient with a dose-limiting toxicity at Dose Level 3, and the second patient's fine. At the moment we're 50/50. As soon as we dose the next couple of patients, we'll find out. Thank you. Someone's quoted your comment around huge attention and demand and promising data so far, has asked, is big pharma really interested as well, or just the clinicians? Oh, yeah. I've been really surprised at the big pharma interest. Everyone's saying that cell therapy's not the flavor anymore. I think in this particular space, there's no other options. Innovation's pretty hard for these particular patients. We've had a fair bit of big pharma interest. I'm working really hard to make sure that we continue those discussions. Another question just away from today's webinar slightly, but when is our number one shareholder going to place their nominated Non-Executive Director onto the Board of CHM? I'll ask her next week when I see her. Good question. I don't know. Very good. Next question that's just come through is what's the plan for gastric cancer, given that no gastric cancer patients have been recruited at this stage but is specified as a phase II cohort? Yeah. We also have Orphan for gastric cancer. Thank you for your question. Gastric cancer's a little bit tricky because 50% of gastric cancers don't express Cadherin 17. We really want to make sure we validate our therapy before we move into that space. I think we're doing proactive testing on Cadherin 17. We don't want to spend the money in patients that it won't work in. The plan that we have moving into phase II, once we complete these CRCs, make a decision, and get the funding for phase II, then it'll be really easy for us to pre-screen gastric cancer patients. Our translational lead, Dr. Stephanie Astrow, has been working on this biomarker assay for us, and I think she's really shown that it's working in the right way. We've seen everybody that's had higher levels of Cadherin 17 have expansion and persistence as we expect. That's been validated, which has been really good, so we can move safely into gastric cancer for phase II. I think it's going to be important that we pre-screen those patients and make sure that they're ready to go. We don't want to have an expensive medicine in someone that doesn't express Cadherin 17. Another question that's just come through. Many of the patients have received multiple lines of therapy during dose finding. Do you expect the dose escalation median to be lower than four? It was citing that the median was four total lines of therapy. Of chemotherapy prior doses? Yeah. Yeah. Correct. In terms of the real world, this is going to be very different. As we move into phase II and get more patients, this is going to be very different. I think the sites that we're working with now are really looking for those younger patients that have only had one line of therapy, where we can see that the therapies and the cost of the therapy is going to really benefit them in the long term. If we think about do we choose, unfortunately, an 85-year-old person whose T-cells are probably exhausted and will suffer during manufacturing or a 40-year-old patient who has a lot of life to give, maybe has small kids. That will be kind of the decision-making points, I think, moving forward into phase II. It is better the fewer chemotherapy runs that they've had, their cells perform much better during manufacturing, and they're happier. They glow at the end is kind of a sign that we look for. The product's a bit more active. We'd like to have that earlier line. I think, as I mentioned before, the earlier lines that we have is the bigger market potential. We don't want to put ourselves, like some of the blood cancer CAR T that's last line therapy, and that's written in their indication. These poor patients have been through it, and then they have to go through cell therapy, expecting a complete response. That's probably not realistic. Actually, one thing I forgot to mention is that in this particular setting for these Stage IV metastatic patients, if we see a complete response, like I'm going to call Jesus because that's so rare, and we've never really seen it before. That's not the expectation here. I think the big pharma community and the clinicians here have really been excited by stable disease, which has surprised me. I thought they were looking for PRs and CRs, as we say. The stable disease has really brought a lot of attention to us, and I think that's the gold standard. I think I've mentioned before about this chemotherapy-free, progression-free survival, and that's sort of the goal for these Stage IV metastatic patients. Now, in a neoadjuvant setting or a Stage I patient, we would expect a lot more. For these patients that are given the short window, this has actually been a really good outcome. The next question is, how long would a phase II trial run for CDH17? Look, my manufacturing team are amazing. We can do multiple runs in a week. It will be dependent on how much cash I have. Realistically, it would be dependent on indication. If we do three indications, it'll be dependent on toxicity. I'm not going to give you a timeframe, but I think 18 months to two years is reasonable to do a phase II, given the toxicities or patient X didn't turn up because their cat was feeling unwell. As I've mentioned before, human trials have human problems. A phase II, we could get through pretty quickly. I think the standard at the FDA is we'd only need 70 patients at the moment. Now, that might change. The administration's changing things all the time, it's a little bit unpredictable for us. If we only need 70 patients, we can do that reasonably fast. We've got the demand for it. We know what we're looking for now. We have a bit of experience under our belt, so it's a bit easier for us to work with the sites that we have. Another question that's come through. Any update on MD Anderson trial on AML? What is the possibility of CHM's treatment being included in standard of care? Yeah. Thank you for that question. We gave an update two weeks ago about the 60% complete response rate. That's also received a lot of attention, which I've been really surprised at. Working with the MD Anderson team, who are here, we've got a meeting tomorrow, actually. They are really keen to include NK cell therapy in their AML treatment guidelines, and they're the biggest AML center in the U.S. here. They're very optimistic about that, so we think that we've got a really good shot. We've got to talk about how we go into phase II, how that's going to be funded, what that looks like. We haven't got to those discussions just yet, but it's been really encouraging the amount of questions that we've received about that program. I think what's interesting is they've still got a lot of translational data that we need. We need to understand, is the response durable? That means does that last, right? It's really nice to have complete responses in AML, but you want to make sure that they're sustainable. We don't need tens of thousands of doses of natural killer cells to maintain that response. That's what we're really looking for and waiting for that kind of data to come through. Because I'm here, I'm going to make sure that I maximize my time here and meet with everybody I possibly can. Yeah, we're really excited about that particular trial. Thanks, Rebecca. I'll just give it back to you to provide a closing comment. Thank you so much. Thank you for joining me late here in Chicago. We've had, so far, a fantastic ASCO, and there's two more days to go. I think if I summarize what I presented today, we're really delighted in the results that we've seen. 82% of our patients have achieved stable disease. Most notably, we've seen that expansion and persistence, which has been incredibly received by all of our entire audience here. The tolerability has been really good as well. Even though we've had one dose-limiting toxicity, it was well-controlled, and we really trust the team here at UChicago, which we've spent a bit of time with, that they're looking after the patients really well. I want to say thank you to you all for your support, because we couldn't do this without you, and we're really excited to see what comes next. Thank you.