Hi, everybody, and welcome to our next company presentation. We're going to hear from CEO William Ho of IN8bio. IN8bio is based in New York City and is focused on cell therapy and immuno-oncology. Just a quick reminder, you can ask questions, but there's also a breakout room afterwards. At the end, that'll be in public breakout room number one at the end of the hall. With that, the floor is yours. Great. Thank you very much and thank you, everybody, for taking the time to attend today and to listen to our presentation. My name is William Ho. I am the Co-founder and CEO of IN8bio. We were found almost a decade ago to advance technology focused on the development of gamma delta T cells. It's a unique white blood cell or lymphocyte that we think plays a powerful role against cancer. Presentation. Oh, there you go. Hope all of you have been having a good JPMorgan as well as Biotech Showcase. Our patients who should have died still alive. This question actually came to me from one of our investors, and today one of our board members. As biotech investors and company operators, we spend a lot of time in biotech getting into the details and the nuances of response rates, mechanism, different cell cycles, et cetera. This board member came from a fairly large fund in San Francisco. At one point, I believe they were the largest hedge fund in San Francisco. We talk about what we're seeing in the biology and the mechanism. She said, "You're talking about mumbo jumbo." She's like, "At the end of the day, are those patients who should be dead still walking around?" Because in oncology, that's all that really matters. Today, I hope that in the next 20 minutes or so, by the time we finish this presentation, that you will all agree with me that we're making a difference in these patients. We actually have some patients who are walking around when, unfortunately, they should have already passed. IN8bio, as I said, is focused on developing gamma delta T cells. These particular cells encompass about 1%- 7% of the white blood cells in our body. I was on the oncology panel here at Biotech Showcase on Monday morning at 8:00 A.M. Mo, one of the panel members, said to me, "When it comes to the human body, good things come in small packages. The gamma delta T cells are powerful. They are the special operations force of our immune cells. Not only can they kill directly and effectively, but they have the ability to coordinate all the different aspects of our immune system." The reality is a proper immune response isn't just one cell activating and killing. It's more like a symphony. It's the timing of different immune cells and when and how do we recruit different components of our immune cells that allows us to drive eradication of infections, of incoming bacteria or parasites, and of cancer cells. We're focused on gamma delta T cells. We believe these cells have better tolerability, better safety. To date, in our clinical trials, we've treated many patients on an outpatient basis. We've seen no cytokine release syndrome. We've seen no neurotoxicity or ICANS and very low rates of infections. These particular cells, we think if you use them in the proper way, can help drive eradication of the tumor. Because ultimately, our goal is to keep patients in remission longer, and so we have developed a comprehensive platform that we call DeltEx. And we use these gamma delta T cells as our tool to help eradicate tumor cells in our goal to achieve our mission of what we call Cancer Zero, the safe elimination and eradication of all tumor cells in these cancer patients' bodies. We need to generate continued immune surveillance in order to eliminate cancer relapses. The fact is, whatever modality, whatever treatment that we give to patients, ultimately, all it takes is a single cell. And over time, those single cells will double, and they will continue to double until the point in which you relapse. Historically, the only way we have ever eradicated a tumor is through our immune system, the continued pressure on that tumor that prevents the ultimate relapse, and hopefully, ultimately, the eradication of the tumor cells. There was a lot of fanfare in 2014 when Kite and Juno came public. Both of those were known as developed what were known as chimeric antigen receptor T cells, where we can take white blood cells out of an individual, genetically engineer them to target tumors, and put them back in. The gamma delta T cell is nature's CAR-T cell. The reality for most infections and most tumors that we might encounter throughout our lives, we don't need a CAR-T cell. Our bodies know how to identify those cells and how to attack them and how to eradicate them. The reality is nature, biology, is far more complex than what we can achieve anywhere in a laboratory, polyclonal, meaning we can bind multiple targets. We can identify between healthy and tumor cells, healthy and sick cells. And that's what the gamma delta T cell does every single day. At IN8bio, we possess a comprehensive platform around the gamma delta T cell. This is our pipeline today. We have two ongoing clinical trials that we will have data updates in the next six months. INB-100 is in leukemia patients. We've made the decision to focus on acute myeloid leukemia or AML patients undergoing transplantation. INB-300 is our unique non-signaling CAR-T platform. These CAR-T can actually distinguish between healthy and tumor cells, allowing us to target what was previously considered undruggable. INB-500 is our iPSC or induced pluripotent stem cell derived gamma delta T cells. We're one of the few that have created iPS derived T cells, and very recently, we announced the INB-600 T cell engager platform. A little bit fortuitous, T cell engagers are hot right now. You're seeing a deal almost every single week. But we created a unique gamma delta T cell based T cell engager, and I'll tell you a little bit about it later on. Then finally, behind that, our INB-200 and INB-400 programs are our solid tumors. Our first indications were in glioblastoma. I'm really excited about this data. In November, we actually had an oral presentation at the Society for Neuro-Oncology. Unfortunately, in September, we had to suspend the phase II. The cost of running that GBM, we had to restructure, reduce our burn. We raised some additional capital. We currently have cash to get into early 2026. We'll have data across many of these programs throughout this year. Gamma delta T cells are ultimately associated with greater survival outcomes. This data was actually identified by my Chief Scientific Officer, Dr. Lawrence Lamb. He made the first observations in the 1990s. He found that patients with higher levels of gamma delta T cells had more than a four times higher survival rate, almost a four times higher survival rate than those who had low to normal. We've been trying to make this observation into a therapeutic, expanding gamma delta T cells, developing gamma delta T cells outside of the body so that we can infuse them into patients so that they have these higher levels and generate better outcomes. In our INB-100 program, we are increasing gamma delta T cell levels. This comes from our clinical trial in the phase I. In patients, we are demonstrating that we gave a three times higher concentration of cells between cohort one and cohort two. Yet, we got eight times higher levels of gamma delta T cells, almost 50 times higher numbers of cells in those patients who did not receive an infusion of gamma delta T cells. Surprisingly, this data demonstrated that we're generating both in vivo expansion and persistence of an allo or donor derived gamma delta T cell product one year after the infusion. First time anybody has demonstrated that. We're quite excited about what we're demonstrating. More importantly, we are crossing the threshold of the number of cells previously that have been observed to be associated with better survival outcomes. This trial, as I said, our goal was to give this dose of gamma delta T cells so that they will float around your body, conduct surveillance so that when that one leukemic cell starts to come back, they can kill it. Our hypothesis was that if we can have scavengers that continue to survey against leukemic expansion, then the patients will not relapse. These patients, unfortunately, for many leukemias, your bone marrow is dysfunctional. Your bone marrow itself, as it conducts what's known as hematopoiesis, is producing leukemic cells and spitting out blasts. The only way to potentially generate a cure is to give a bone marrow transplant so that I can reset the bone marrow. But about half of the patients ultimately relapse. If they're relapsing, it means there was tumor left behind. And so our goal was to give this infusion of the cells so that we can scavenge and ultimately prevent relapses. This is the trial design. It was a single center study originally. It was being conducted at the University of Kansas. It was a dose escalation. We were going from 10 to the six cells per kilogram to 10 to the seven cells per kilogram. We made the decision to stop dosing at the second dose cohort because of the data that we showed where we got eight times the number of cells. We didn't think we needed another eight times the number of cells because we're already seeing fairly robust data. This trial was run in AML, CML, MDS, and ALL patients. These are the patients that we had dosed and reported on to date. This data cutoff is as of September 30th. The first 10 patients treated. Every single patient made it beyond one year. These patients were sick. We had patients who had seven prior lines of therapy, deletion of chromosome 7, trisomy or an addition of chromosome 8, concurrent FLT3 or IDH mutations, a single dose with no maintenance therapy. We have multiple patients beyond three years. Typically, a quarter of the patients are expected to relapse by 100 days, half of them by about one year. Every single patient that we treated made it. And we're demonstrating durable remissions, especially in the AML patients. These are the data to date. Three patients have crossed the three year mark. Every patient crossed the one year mark. We did have two patients relapse. Both of them were TP53 mutations. One had ALL that had seven prior lines of therapy. And one was an MDS MPN patient who generally doesn't do well. One patient, about 15%, are usually expected to pass of non-treatment related mortality. We had one patient who developed idiopathic pneumonia syndrome and passed. We're doing quite well. Of the AML patients in this cohort, there were eight of them. At 19.7 months, none of them have relapsed to date. We received FDA guidance last year. We do know what the registrational path is. But what we're doing currently is we're expanding the first 10 patients to about 25 patients. We're currently enrolling those patients. We're expanding the number of centers. We're looking to add one to two. We're going through the contracting and the IRB processes now. And this year, in the first half of the year, we do expect to present our first look at the expansion patient cohorts. There will be a portion of them. And we will look at much of the real world data, both at the University of Kansas as well as through the CIBMTR database. We're excited about what we're doing. We believe we are keeping patients in durable remissions longer. But ultimately, my goal when I started the company is to target solid tumors. As you know, it's the Holy Grail. It's a market that's nine times bigger than that of the leukemias. But treating solid tumors is hard. This is a glioma. It's a brain tumor. You can see the vast quantity of tumor cells in the dark purple. The reality is this purple mass isn't what kills you. If you look within the healthy pink tissue on the left, all those individual little dots, those are tumor cells. The mass can be removed by a surgeon's knife. But it's what we can't see. It's what's left behind that ultimately kills us. And our goal was to try to target those particular cells, use the gamma delta T cells to target them. And so INB-200 is our solid tumor program, what we call drug resistant immunotherapy. This is the data that we've just demonstrated to date. As a quick summary, in blue on top are patients who received a single dose. I'll talk about the protocol momentarily. In purple, our patients who received up to three doses. In green, our patients who received repeated doses up to six doses. We're now starting to see a dose response. The more doses we gave the patients, they're living longer. Here, each dose is depicted by the orange circle. If they relapsed, it's by the red circle. The red square is if they died. Here, the two pink bars on the left is the median progression-free survival of the Stupp protocol. The last drug approved for glioblastoma was in 2005. For 20 years, the median progression-free survival has not changed from six to seven months. The median overall survival is only 14 to 16 months. Based on their age and what we call the MGMT status, the little orange tick marks is where we expect each patient to progress, and the little vertical green bar is where we expected them to die. We're doing quite well. These patients, as I said, were in the front line setting, newly diagnosed glioblastoma. They're treated with a standard protocol of surgical resection, radiation, chemotherapy, and in the maintenance phase, they receive one dose or five days of chemo for every 28 day cycle. What we did is we added on. We gave these patients an infusion of these gamma delta T cells delivered through a catheter that sits beneath their scalp that they don't notice that we can infuse directly into the tumor bed on day one of every 28 day cycle, and so the data, these are the patients that we treated. It's a mixture of methylated, unmethylated patients. Unmethylated means that those tumors are not responsive to chemo. They usually progress by about four months. Median age is 68, so they're quite old already, and the mixture of total and subtotal resections. Subtotal resections means the tumor is in a location that you could not cut out. So you left them behind. As you can imagine, those patients progress very rapidly. But here, we also had one patient who was an IDH mutant, patient nine. IDH mutants, they generally do better. They live quite a while. But Servier actually ran a study. They presented the phase III data last year. In the control arm of that study, the median progression-free survival was at 11.1 months. At 28 months, 100% of the control arm relapsed. I know it's an N of one. But our patient has extended progression-free survival over 40 months, surpassing 100% of the people in the control arm of that study. Here, we're actually showing where our progression-free survival is. Every patient who received a single dose went slightly longer than expected. But they all progressed by 8.26 months. And they all eventually died. Across all of our patients, at 9.9 months is the median progression-free survival. If we look at the patients from the purple down, anyone who received more than one dose, you can see we're improving the median progression-free survival by about 89% over the typical standard of care and by 50% over those patients who received only a single dose. It is now sitting at 12.4 months. So we're pretty excited about this. This data cut off was actually as of September 30th. We'll be presenting data this year in the first half of the year on more of these patients. We had two patients, patient seven and patient 14, were actually treated during peak COVID years. Unfortunately, they died without progression. One had a heart attack. One had a pulmonary emboli. We do know that there were greater vascular events during that period. So we don't know what happened. However, when you look at it, if you exclude those two patients, the median progression-free survival is now getting as long as the expected overall survival. And so we believe we're having a real impact on these patients. In fact, you can see it visually. In two of the patients to date in which they did relapse, we have paired biopsies. So we can look at the brain tissue and look for the penetration of immune cells. The cold tumors, if you recall, on the checkpoint inhibitors aren't immunogenic. That means they have no immune cells inside those tumors. Here on the left at diagnosis, gamma delta T cells are staining a brown color. Tumor cells are staining purple. You can see the extent of which the tumor is growing in this patient's brain. When we resected this patient, you can see the smudge of purple around down the middle. But it's surrounded by dark brown cells. We're seeing an infiltration of gamma delta T cells, CD3, CD8, CD4, B cells, and other immune cells. We are turning a cold tumor hot and generating an immune response. We are continuing to conduct biologic correlative studies such as this, and we will present some of that data as well. We also enrolled a number of patients in the phase II from multiple centers. In the first half, we will also present some of that data. We're excited because I do believe that patients are going longer than expected. On the back of it, as I mentioned, T cell engagers or TCEs are hot. We did create a novel T cell engager. This engager targets the gamma delta T cell. We will have preclinical data this spring. I'm quite excited about it. The advantages of our T cell engagers in the clinic across both trials. We have not seen any cytokine release syndrome. We have not seen any neurotoxicities to date. We think that's an advantage. Many of our patients were treated on an outpatient basis. There are other T cell engager companies out there, even some who target gamma delta T cells. What we think is an advantage is our program can generate expansion of the gamma delta T cells. We will show you that data this spring. We know over time, as a patient's tumor progresses, the numbers of gamma delta T cells decline such that when you run out of them, you are essentially at end stage disease. And so we're excited by the fact that we can expand these, drive more of them. Because even if the tumor is hot, if I don't have immune cells, there's nothing to do the killing. And so we can drive expansion of these cells. As I showed you earlier, we can drive recruitment of other immune cell subsets so that we can start driving to that symphony, that music, that actual immune response that helps patients stay in remission. We have a strong team. We have a lot of milestones in the first half and throughout this year. We have clinical data in our INB-100 program as well as clinical data in our INB-200 program. We will provide updates on our T cell engager. We're quite excited about that. We think it's a very potent T cell engager. We raised some capital at the end of last year. As I said, we still have capital through this year, so well through our milestones. We're excited about all the progress and all the data we're going to present this year. This is our team. Myself, I'm the co-founder along with Dr. Lawrence Lamb. He is one of the world's best experts in gamma delta T cells. He's been working with cell therapy for over 30 years. Pat McCall and Kate Rochlin are our CFO and COO. And we have a fantastic team behind us. Some of the luminaries in the cell therapy space, like Bruce Levine and Dr. Marcela Maus from the University of Pennsylvania and Mass General. Bianca Santomasso is a neuro-oncologist from MSK. Dr. Bishop heads transplantation at the University of Chicago. Siraj Ali is an MD, PhD from Harvard, who is an expert in biomarkers. So really exciting. We have a great team. We're making a lot of progress. I think the data that I demonstrated, the question I asked in the beginning, are patients who should be dead still walking around? I think we are showing that. We have numerous patients now where they remain in remission longer than they should have been alive. And so we're excited about everything we've done with gamma delta T cells. We think they're going to play an important role in immunology and anti-cancer therapies and potentially even in autoimmune disease. There's been a huge trend of people moving from oncology into autoimmune disease. We think these therapies can create a safer, more tolerable therapy that has a lot of advantages, and so I want to thank you for attending today, and I welcome you to join us on our journey as we try to achieve Cancer Zero.