Great. Hi, everyone. Welcome. Thank you for having me. My name is William Ho. I'm the co-founder and CEO of IN8bio. Nice to be here again at the Cowen Healthcare Conference in bright and early on the, on the Monday morning. Thanks for all the Cowen people for having us again. Today I'm here to talk about our company, IN8bio. We are a company developing gamma delta T cells as therapeutics for both oncology and autoimmune disease. We are focused on gamma delta T cells. It's a unique white blood cell, or what we call lymphocyte on the, on the scientific side, that we believe are powerful tools in both cancer and other diseases. We're one of the world's best experts in the development of gamma delta T cell therapeutics. Our scientific co-founder, and today Chief Scientific Officer, Dr. Larry Lamb has been working with these cells for more than 30 years. Today, we have two programs in the clinic. Both of those oncology programs have demonstrated patients in remission, progression free for more than 4 years. We're not just talking about any tumors here. We're talking about patients with acute myeloid leukemia, or AML, and glioblastoma, 2 of the worst types of cancers out there. Our expertise has enabled us to develop this program and pipeline. Not only are we developing cell therapies, today I'm also gonna talk about our new T cell engager platform. A unique platform that we believe can drive a significant advantage in the area of T cell engagers and B cell depletion, widening the therapeutic window, making these treatments more tolerable and enabling a higher dose. Very recently, in December, we raised new capital. It was... We thank all of our investors. The deal was led by Coastland Capital, Matthew Perry and his team. We had significant investors after the filings, companies like Alyeska, 683 Capital, Stonepine, and others. That financing was a total of $40.2 million, with the first tranche straight equity of $20.1 million, which will get us into the first half of 2027, and then potentially a second tranche based on milestones later this year, which would get us through 2027, into early 2028. Today I wanna talk about our pipeline and some of the data. We have a comprehensive platform. INB-100 is our leukemia program. These are patients with severe leukemias undergoing transplantation, where we give a bolus of gamma delta T cells to keep these patients in remission. We will have some announcements shortly as we continue to complete this trial. We expect to announce a data update, likely at a medical meeting, towards the end of the year. We have two programs, INB-300 and INB-500, which are currently on hold 'cause of the capital environment. These are cell therapy programs targeting CAR T and iPSCs. We have our INB-619 T cell engager platform. We'll share some of the data today. We'll talk very early on today about our INB-200 and INB-400 programs. These are our genetically modified gamma delta T cell programs to target solid tumor cancers. Our first indication was in front line glioblastoma. Just wanna mention, I don't often do this. Very recently, if you're looking at our pipeline, there was actually a publication on StockTwits actually. A gentleman named Alex, he about two weeks ago, on the 18th of February, wrote a fantastic piece. I do encourage anybody who are on the web to actually take a look at it. I was an analyst for a long time. He wrote a wonderful summary about our pipeline and the value that we're creating here at IN8bio. I wanna move forward and talk about our program. INB 200 and 400 is essentially the same. The difference was 200 was an IIT or investigator-initiated trial. INB 400 was our corporate sponsored trial, the drug product is one and the same. Our approach was a little bit different. When I started the company, my goal was how do we ultimately go from the CAR Ts targeting CD19 in the leukemias, which is what Kite and Juno started with, towards getting to an off-the-shelf but therapy for solid tumor cancers? It's the holy grail. It's a market that's 9 times bigger than that of the leukemias, yet the companies who've been developing these therapies thus far have failed. We took a different approach. This cartoon in front of you is a pictorial or cartoon describing of the approach that we took. Look, tumors are challenging. Solid tumors in particular. They are big. They have multiple defenses. They have physical blockade from fibrosis and other tissues, they're highly heterogeneous. We never believed that a single antigen or a single target could eliminate the totality of the tumor. The problem is, we in industry, we in medicine, and in investors have been trained to look at tumor shrinkage. A glioblastoma doubles every 50 to 60 days. If I get a PR or a partial response and shrink it by 30%, it's not a lot of doubling cycles until that tumor is back to where we started and growing. Our thought was how can we use everything in our armamentarium to reduce the tumor mass as much as possible? Even if I eliminated 90%, 95% or 99% of the tumor, how do I get rid of what's left? You as a patient, you don't care to see shrinkage. What you want is even if the surgeon's knife could remove 90% of the tumor, how do I attack that last 10%? That's what's going to get you to live longer. We take a highly heterogeneous tumor, we use whatever we have in the standard of care to shrink it as much as possible, we drive it towards what we call minimal residual disease. When the number of tumor cells are at its smallest, and that's when we attack. The challenge is that most conventional standard of care chemotherapies are what we call lymphodepleting. They kill white blood cells. If our white blood cells are gone, we have no soldiers defending the castle. Our approach was that we hijack the tumor's own resistance mechanism to the chemotherapy. We genetically engineered our gamma delta T cells so that they can survive combined dosing. We actually genetically engineered them, so they we increased what's known as the IC50 by six times. They will survive through super therapeutic doses of conventional care. Because our cells survive, the conventional chemotherapy actually drives an immune signal. It triggers a pathway called the DNA damage response, or the DDR pathway. We force the upregulation of immune signals, and because the gamma delta T cells survive, they can identify the residual tumors and eliminate them, getting to deeper and deeper remissions, even if we couldn't see the cells. That was our unique approach. When we went into the front line therapy, this picture actually depicts our treatment. Everything above the blue line is the standard of care chemotherapy. What we've added is below. When the patient is diagnosed with the tumor, we inserted a catheter. 95% of the patients undergo surgery anyways. That allowed us to bypass the blood-brain barrier, which was the big challenge of targeting glioblastomas. After about a 3 to 4-week period, we take their blood, we manufacture a product, and it is frozen and stored. When the patients get into the maintenance phase of the therapy, the patients were enrolled into 1 of 3 cohorts. Those cohorts received either 1, 3, or up to 6 doses of our gamma delta T cells every 28 days. Remember, the doubling time of a glioma or brain tumor is about 50 to 60 days. We're dosing every half cycle. The goal was if we could just keep the number of tumor cells static or the same, then patients will live longer for the time that we're dosing. If we can shrink the amount of tumor just a little bit every single time we redose, then eventually perhaps we can outrun the tumors, and we can have patients living much longer. Today I'm going to talk through the data. Last year at the American Society of Clinical Oncology, for those who aren't aware, it's the largest oncology conference in the world, and it occurs every year in Chicago in June, we presented some data. At ASCO, we actually had an oral plenary session last year at ASCO. Later in the year at the Society of Neuro-Oncology, we presented some combined data. We have combined our phase one and phase two data. Now, the phase two further enrollment was suspended in 2024 due to the capital environment, we've analyzed all of our data in totality. We've now treated patients across 4 different centers. Our first center at the University of Alabama at Birmingham, at the Cleveland Clinic, Moffitt, and Ohio State. We've treated a total of 17 patients. 14 of the patients have received repeat doses of our cells. As we found, we had about 10 patients that we could identify who, for one reason or another, signed the consent form but were never treated with our gamma-delta T cells. We found a contemporaneous control patient cohort that was very similar to our enrolled patients, and we could compare them. These are the patients who have received repeated doses. There's 14 of them here. We have dose level 2 in purple who received 3 cells. In green, dark green is dose level 3 that received up to 6. Then the 4 patients in INB-400, from 3 other centers. As you can see on the right-hand side, roughly balanced about half male, 50% were unmethylated, meaning they don't respond to conventional chemotherapies. 50% were subtotal resection, meaning because of the location of the tumor, we couldn't cut it all out. We knew we left tumor behind. Then the median Karnofsky Performance Status was 80. We didn't cherry-pick for patients who had a 90 or 100 who were fully functional. These were actually fairly dysfunctional patients. In the single-dose cohort and in the control cohort, you can see here, roughly balanced, still about half male, 62% unmethylated. Actually, here, far fewer patients had subtotal resections. Many more got total resections, meaning we cut out as much as we could see. There was no visible residual tumor left behind. These patients should arguably actually do better because we had a complete resection. Again, Karnofsky Performance Status roughly balanced at 80. When we looked at the patients and their incoming demographics, as I said, roughly balanced, although the ends are small, granted, roughly balanced, one thing that stuck out was the number of resection types. Should have biased toward the control patients actually doing better. When we look at the totality of our data, these are the swimmers plots. At the top in red are the patients who received no treatment. In blue, patients who received a single dose. Each dose is marked by an orange circle. If the patients progressed, it's marked by the red circle, and if the patients died, it's the red square. In purple are the patients who received up to 3 doses, and in green below, the patients who received up to 6 doses. As you can see, we are actually seeing a dose response. In our data, the control cohort demonstrated a median progression-free survival of 6.6 months and a median overall survival of 13 months. When we look at our own patients who received more than 1 dose, Sorry, previously, the overall survival is 13.2 months. When we look at our patients who received more than one dose, our median progression-free survival is 13 months, meeting the overall survival of the other arm. Currently, our median overall survival is sitting at 17.2 months, but it's still climbing. It's actually not reached. We expect to have additional updates later this year at a medical meeting, likely mid-year and late year, where we will provide updates on the overall survival statistics. What we have seen is that the survival is directly correlated with the total dose. The greater the area under the curve, the longer the survival. We are currently working on publication of this data. You should look out for that in the coming little while. We are seeking guidance from the FDA based on this data, what our regulatory path forward is. On a different analysis, when you look at the totality of the data, again, control patients, 6.6 months, 13.2 months OS. Our repeat dose patients, 13 months, currently at 17.2 months. We have cut this data in multiple ways. No matter how we look at it, the biggest prognostic factor associated with survival is more doses, and the biggest prognostic factor associated with relapse is unmethylated patients. We believe that this pattern holds even for the unmethylated patients who typically do not respond to conventional chemotherapy. On the right-hand column, we have a unique way to looking at it. We mapped everyone out based on their age and their MGMT status. MGMT is the marker that demonstrates whether or not patients will respond to chemo or not. Those who are unmethylated typically will relapse within five months and often will die before one year. We said, "What% of patients, based on their age and their MGMT status, survived progression-free longer than we expected them to live?" When we plotted it out in a forest plot, you can see here in the patients who received three to six doses, we had over 50% of the patients remaining progression-free longer than they were expected to live, versus only a single patient among all the patients who received either a single dose or no doses. Not by accident. The traditional Kaplan-Meier curve, where we censor the patients who have not progressed or remain alive. On the left-hand side, this is progression-free analysis. Despite the small ends of 10 and 14, we hit a P value less than 0.05. On the right-hand side, this is overall survival. If you look at the vertical tick marks, you'll see, we haven't hit median overall survival, as there is a tick mark right before where the dotted blue line is, which is the median. That patient is currently driving the median. The longer that patient remains alive, the longer our overall survival is going to be. As I said, we expect to present updated data later this year. Moving on, I wanna talk a little bit about our T-cell engagers. T-cell engagers has been a hot area, especially around autoimmune disease. In 2023, it seemed like every single one of our cell therapy competitors and compatriots all became autoimmune companies. We didn't believe that the cell therapies were going to in the long term, work very well in autoimmune disease. Unfortunately, cell therapies require lymphodepletion and requires treatment with Fludarabine. Flu/Cy causes ovarian damage. There's a number of women in this, in this room. Generally, autoimmune diseases occur post-pregnancy, during the maternal years, often impacting women. About one in six women will have an autoimmune disease in their lifetime. The problem with dosing with Fludarabine is Cytoxan can cause permanent ovarian failure in about 40% of women. Any women in this room would risk in those years, would risk having ovarian failure? Again, no one in this room put up their hands. I have spoken to rooms from 5 people to 400. I have yet to have a single woman in the maternal age put up their hand. That is the challenge. How do we avoid lymphodepletion? How do we fit into the current paradigm of rheumatologists? In fact, our understanding is that the dose in autoimmune disease is 9 times lower than the dose of the engagers used in oncology. In autoimmune disease, your condition isn't lethal. You're not going to tolerate the side effects. That has resulted in lower dosing and an inability to deplete B cells. We looked at the landscape, the vast majority, 95%, 98% of the T-cell engagers out there target CD3 as a target. There's lots of engineerings, there's masking, there's cleavable linkers, and other things that we do to try to make CD3 tolerable. The fact is, when we target CD3, we target not only the alpha beta T cell compartment, but we target gamma delta T cells, NKT cells, Tregs, and that creates a cytokine soup. All of the cytokines that are produced by hitting all these different cells drive cytokine release syndrome. Cytokine release syndrome impacts 60%-80% of patients treated with the T-cell engagers. 10% of them are grade 3 or greater, meaning they're in the ICU. It's not tolerable in autoimmune diseases. If we don't trigger autoimmune disease, we also have the risk of triggering T-cell exhaustion so that your graft or your drug is no longer functional. Not acceptable. How do we differentiate ourselves? When we looked at the landscape, we found that the T-cell engagers have these challenges, a narrow therapeutic window, the risk of T-cell exhaustion, the risk of cytokine release syndrome, and it's complicated to make. You have to do a lot of phage display, you have to detune one end relative to the other to try to find the perfect molecule. We thought, can we use the biology of gamma delta T cells to create a better, more potent T-cell engager? To date, across two trials, we have seen no CRS, we've seen no ICANS or neurotoxicity, despite dosing high concentrations of cells directly into the brain. We do think there is the potential to see some CRS as Autolus has seen in their studies, but much of that T-cell signaling is due to bystander effect. We've created a novel T-cell engager. On one end, we have a cassette-like structure. We created one that binds CD19. We went to CD19 because it has the broadest of B-cell coverage, except for some of the plasma cells. In the middle, we have a gamma delta T cell. It's a pan gamma delta T cell receptor binder. It binds both the V delta one compartment and the V delta two compartment. We'll talk about why that's important afterwards. We have a unique expansion domain that we haven't publicly disclosed yet, but what drives the gamma delta T cells to expand. We knew that companies like Lava and others who were creating gamma delta T cell engagers had a problem. The gamma delta T cells encompass only 1 to maybe 8% of the total white blood cell population, and there's not enough of them to kill. We needed to expand them, and we've demonstrated that we can actually do that. This is some data. Here we're looking at three different donors, looking at B cell depletion with our gamma-delta T cell engager. You can see despite the variability in the gamma-delta T cells ranging from 0.3% to 4.4% in the blood, using just the gamma-delta T cells in the blood, we can drive B cell depletion. It's very tight. The curves you can see on the right-hand side, it has a median of 36 picomolar. Highly potent T cell engager. We do drive T cell expansion. On the left-hand side, these are absolute numbers of gamma-delta T cells. We're driving both the delta one, the delta two compartment, as well as some of the non-delta one or delta twos, or what we call delta-threes. On the right-hand side, it is a relative expansion, and we have both a negative and a positive control, showing that we get significant expansion of the gamma delta T cell compartment, and this is actually what's driving the killing of our targets. We want to go into autoimmune disease, but there are literally dozens of people trying to create T cell engagers or other ways to eliminate B cells. How do we know that we are at least competitive in the market given the safety and experience of things like Rituxan and Blinatumomab or whatnot? Myself having been on in biotech for over 25 years and having been on different sides of this business, we decided to take a risk. Last year, I directed our team to actually go head-to-head against 2 FDA-approved drugs. They're available on the market. We bought them. We went and bought Amgen's Blinatumomab, we bought Roche's mosunetuzumab, one targeting CD20, one targeting CD19, and ran the assays head-to-head. We wanted to show that we can get at least equivalent B cell depletion and have a wider therapeutic window, because if you're not as good as what's on the market already, then why bother? This is an experiment. We did five. We took the highest doses of Blinatumomab and mosunetuzumab based on the FDA approval, their labels and the preclinical studies that they demonstrated. We did 5x dilutions from their top dose. We took a very high dose of our drug, or not our drug, our product candidate. We started at 5 nanomolars or 5,000 picomolars. We did 5x dilution down. As you can see, at every single dose, we have at least equivalent, if not greater B-cell depletion than both of the FDA-approved products. I'll specifically note on this side, we start at almost 200 picomolar for Blinatumomab. Then we have 5,000 picomolar. On the right-hand side, where mosunetuzumab is not showing depletion, they're down to 28 picomolar. We're at the 200 picomolar and showing even lower killing than Blinatumomab, very similar dose. What was important is we've demonstrated we can eliminate the B cells. Do we have an advantage on the cytokines? Now, for years now, we know cytokine release syndrome, or CRS, is a big problem. When the CAR Ts first came out at the University of Pennsylvania, it just so happened that the clinician had a child who had autoimmune disease. They were seeing IL-6 get elevated in these patients who had CRS. Thankfully, they saved the patient by dosing with tocilizumab. Tocilizumab is an anti-IL-6 antibody. When patients are crashing because of cytokine release syndrome, we dose the patients with tocilizumab to eliminate the IL-6. It is the validated biomarker for CRS. When we looked at CRS-associated cytokines like IL-10, IL-6, IL-17 and TNF-alpha, you can see the marked reduction in cytokines. In the middle here, I'll highlight 'cause I just mentioned tocilizumab and IL-6, that we do get some secretion of IL-6. If you look carefully, 5,000 picomolars of our compound is equivalent in IL-6 secretion to 28 picomolar of Mosun. 178 times difference in dose, demonstrating that we can widen the therapeutic window and potentially dose higher to get B cell depletion. This program is currently preclinical. There are certain therapeutic advantages. We target both the delta one and the delta two compartment. By targeting both of these compartments, the delta twos are circulating in the blood, and they're in the lymphoid tissues, whereas the delta ones are resistant to exhaustion and are found in solid tissues. Because autoimmune disease isn't just in the blood, and we don't have to deplete just in the lymph nodes, we wanna be able to deplete also in the organs of interest. Here we've laid out a bunch of the different autoimmune indications and where the Vδ1s reside and may have an advantage. A note, last year, Sanofi acquired a company called Dren Bio. They acquired a single compound that targeted macrophages. They acquired them for $600 million in phase 1 for that single asset. You know, we're working towards the animal models. We will have animal models, initial animal models later this year. That will trigger a second tranche of our financing that we just closed, which could then lead us to non-human primates and potentially an IND for this program in 2027. We believe there are significant advantages. We target both the δ1 and δ2 cells. We overcome the historical challenges of low numbers of gamma-delta T cells by driving expansion. We're seeing that we have deep B cell depletion without the cytokines. We've made a lot of progress. Here's our team. Recently promoted Kate Rochlin, our Chief Operating Officer, to President. Patrick McCall, our CFO, is here. Dr. Lamb is our Scientific Founder and Chief Scientific Officer, and myself, I'm in charge of strategy and our capital markets efforts. I've been on Wall Street or in biotech for over 25 years. Oops. As I said earlier, we recently raised additional capital. We have a lot of milestones coming this year, a lot of continued data. We think we're significantly and severely undervalued relative to our competitors based on what we have in our pipeline and the fact that we believe we have real drugs. We are keeping cancer patients in remission for more than 4 years in some very, very difficult indications. We're proud of all of our accomplishments. Thank you very much for your attention. We appreciate, you know, all the support from our investors, both institution and retail alike. I'll leave it at that and see if anybody has any questions. Did you say the second tranche of capital gets you to 2028? Into 2028. Through 2027. The second tranche of capital is triggered by a milestone. There is a stock-based milestone that can be waived. The primary milestone is based on animal data showing efficient B-cell depletion. We are in the process of initiating the initial animal models, and we hope to have some data later this year. What did you say about the trajectory of the glioblastoma trial? Do you trial? Do you know? Currently what we did was we suspended enrollment in September 2023, understanding that we needed to preserve capital in the market environment and needing the data to mature. At this point, I think we're pretty the data is pretty robust with long-term progression-free survival and overall survival. Our goal right now is to drive publication of that data in peer-reviewed journal. Look out for that in the coming little while, we will take the data that we have at hand, go to the FDA and seek guidance on what the regulatory path forward is. I think there is the potential for certain designations and potential accelerated approval pathways or registrational pathways. that's in the in your kinda capital? Yes. All included in there. We will get guidance later this year. What we've said is probably by late summer, third quarter. The last drug approved in glioblastoma was in 2005. We have looked at all the data from the Stupp regimen that was approved in 2005, the Optune, the hat that's worn. I think this is among some of the most robust data in glioblastoma shown in over 20 years. It's a nice... For a small biotech company, it's a nice market environment to be in with very few or no competitors.