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We're going to keep everybody's lines muted throughout the presentation. Please submit your question by tapping the Q&A button at the bottom of your Zoom window and writing in your question. We will then consider it. Before we begin, please let me read the safe harbor statement. This segment may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements pertaining to future financial and/or operating results, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management, constitute forward-looking statements. Any statements that are not historical facts should also be considered forward-looking statements. Of course, forward-looking statements involve risks and uncertainties. William, please go right ahead.
Great. Thanks for having me. Great to be here again, and great to be with the RedChip team. My name is William Ho. I'm the co-founder and Chief Executive Officer of IN8bio. We'll start off with our typical disclaimers, but welcome today. I want to introduce everybody to IN8bio. We are a company developing novel therapeutics focused on gamma delta T cells. It's a specific subset of our white blood cells in which our scientific founder and Chief Scientific Officer, Dr. Larry Lamb, is one of the world's best experts. Today, we're one of the leading companies developing gamma delta T cells for both oncology and autoimmune disease. In our oncology programs, we have patients with aggressive cancers, both acute myeloid leukemia, or AML, and glioblastoma, who remain more than four years out progression-free. We're excited to talk about our pipeline today.
We believe that these gamma delta T cells can drive cancer remissions, consolidating the standard of care. We believe they have greater precision and safety than some of the other cellular therapies that are out there, and we have among the strongest capabilities in this field. Our expertise is driven by the first observations by our scientific founder, Dr. Lawrence Lamb. In the 1990s, he was a clinical immunologist at the University of South Carolina, where he actually made this observation. He found that patients with leukemia who had naturally high levels of these gamma delta T cells had almost four times higher survival outcomes. The survival curves are shown here in front of you. Almost a 71% long-term survival rate versus only about a 20%. He spent the better part of his life and career trying to make this observation into a therapeutic.
I think today, we are progressing our pipeline and having really exciting results. This is our pipeline. INB-400 is what we call DeltEx Allo, or allogeneic, or donor-derived gamma-delta T cells being infused with leukemia patients undergoing transplantation. Very similar to the results that I showed you just previously, we're trying to give patients who are undergoing transplantation with aggressive leukemias higher levels of gamma-delta T cells by transferring them into those patients. We are continuing to enroll and treat patients in our expansion cohort, and we expect to have a clinical update towards year-end, likely at the American Society of Hematology meeting that occurs in early December. Keep your eyes out for that, and we expect to have updates later this year. Today, I'm going to talk a little bit about our INB-619 program. That's our T-cell engager.
It's a more novel approach to T cell engagers, which is an exciting area that can target both autoimmune disease and oncology. Finally, I'm going to kick off today talking about our solid tumor program, INB 200 and INB 400. Those two programs are actually quite similar. They're in frontline glioblastoma or GBM, and the difference between these two programs is 200 was an IIT, or investigator-initiated trial, and INB 400 was our own corporate-sponsored IND that was in phase II. To kick it off, we're going to talk about INB 200 and INB 400. Glioblastoma is a devastating brain tumor. It impacts about 14,000 newly diagnosed patients in the United States every single year and another 14,000 in Europe every single year. Unfortunately, there's been no change in the standard of care since 2005. More than 20 years with no significant improvements.
What you see in front of you is actually a glioblastoma. This is a glioma. The purple represent the cancer cells, and it's a large mass that is often growing in these patients' brains. The question is, how do we improve survival? The truth is, the bulk of this tumor, this dark purple area that you see on the right-hand side, is not what often kills the patient. On the left-hand side, what you see is the bright pink healthy tissue. If you look carefully, scattered throughout that bright pink tissue are individual little dots, and those dots are the tumors that are often found inside the margin of the surgical resection, what ultimately grows back and results in the patient's death. Our goal is how do we use the standard of care to eliminate as much of the tumor as possible and then attack what's left behind?
Because if we can eliminate the residual tumors or reduce their numbers, that we can allow the patients to live longer. We took a very different approach to the standard of care or approaches to cellular therapy. We start off with newly diagnosed tumors. What you see here is a highly heterogeneous tumor in this cartoon. We treat with this conventional standard of care, radiation, and chemotherapy. We drive towards what's known as MRD, or minimal residual disease. Conventional dogma would have you continue to treat with the standard of care until you grow a large, resistant, bulky tumor like you see on the bottom right. Our particular approach, we focus on the gamma-delta T cell. We genetically engineered the gamma-delta T cell to survive combined dosing. One of the big challenges of standard of care is it kills our white blood cells.
It kills your own soldiers. What we did is we hijacked the tumor's own resistance mechanism to the chemo, genetically engineered it into our gamma-delta T cells so that they could survive. The chemo kills much of the tumor, but it also drives synergies. It upregulates a signal on the surface of the residual tumor cells, here marked by the red triangles. That allows our gamma-delta T cells, because they can survive, to identify any residual tumors and attack them, and we get to lower and lower amounts of any residual tumor. This concept of going into newly diagnosed cancers in combination with chemotherapy was actually demonstrated just this past week from Allogene. In their large B-cell lymphoma trials, they combined in the frontline setting with R-CHOP and showed a significant difference in the percentage of patients who had minimal residual disease.
That's a proof of concept, and we think, proof of our particular approach. Our particular trial, again, we're going with standard of care. Here in this picture, everything above the blue line is the standard of care, what patients normally undergo across the world. Patients are surgically resected. After about four weeks, they undergo daily radiation and chemotherapy. That radiation and chemotherapy can kill white blood cells. Then there's a maintenance phase. It's six monthly cycles, five days of chemo, followed by a 23-day break. Everything that we've added to these patients is below. When they undergo surgical resection, we insert a catheter into that resection cavity. That way, we can access the tumor directly. After about three to four weeks, we take blood from the patients in a process called an apheresis. We manufacture a product.
We genetically engineer the cells so that they can survive combined dosing with chemo, and we cryopreserve it. In the maintenance phase, we had three cycles. Patients in cohort 1 received a single dose, patients in cohort 2 received three doses, and in cohort 3, they received up to six doses, once with every single month of the maintenance cycle. The hypothesis or the concept is as what you can see before. With every subsequent dose, if we can just keep the number of residual tumor cells constant, then the patient should have a longer time to progression and overall survival. If with every dose, we can reduce the numbers of residual cancer cells, then perhaps we may be able to outrun the tumor's growth and eliminate it. We ran this first trial. We actually have data here combined.
The phase I was run at the O'Neal Comprehensive Cancer Center at the University of Alabama at Birmingham. The phase II, we ran across additional centers. Our patient data is across four sites, so it's not just a single site of data. We also enrolled patients at Cleveland Clinic, Moffitt Cancer Center in Tampa, and The Ohio State University. We treated a total of 17 patients. Last year, when we dug into our data, we found 10 patients who were enrolled in a contemporaneous control arm. These patients were enrolled across the same centers. The profile of these patients don't look any different. We'll show you that momentarily. We've seen no major toxicities events or adverse events across the treatment arms. We believe the outcomes of the treatment remains consistent across the centers.
The summarized data, when we look across all of our patients that we treated and the control arms, there are not really any significant imbalances. If there are any differences, it's usually off by an N of 1. The methylation status, unmethylated patients generally do not respond to chemo, and so they progress very rapidly. The median age, older patients tend to progress more rapidly. The ages are very similar, 67 in the control. Across all our repeated dose patients, 64. The genders are very similar, off by an N of 1.
The only difference across the patients that we were able to identify is the resection type. A greater number of patients, 80% in our control cohort, had a total resection, versus only 43% in our repeat dose patients. Generally, patients who have a total gross resection, resected so that you cannot see any residual tumors, tend to do better.
You would expect the total resections to live longer and have a longer time to progression. Yet, when we look at our data across the cohorts, in the control cohort, we had a median progression-free survival of 6.6 months and a median overall survival of 13.2 months. When we look at all the patients who received more than one dose, one dose our first cohort, was the safety dose. We didn't expect it to be efficacious. When we looked across all the patients who received either three to six doses, the median time to progression was now almost equivalent to the overall survival in the control cohort. As of our last readout at the end of December, the median overall survival was not reached, but we're currently sitting at 17.2 months, and we expect to have an update, likely at a medical meeting mid-year.
Historically, we have presented at the American Society of Clinical Oncology, or ASCO, which is the largest oncology meeting every single year. On the right-hand side, we decided to take a differentiated look at it. How many of our patients are remaining progression free longer than they were expected to survive based on their age and their response rates to chemotherapy? Here, time zero is the time in which we expected them to survive. If they remain progression free longer than that expected survival outcome, these bars are to the right. Typically, patients have to progress before they die of their disease. You would expect the curves to be to the left. As you can see here, more than half of our patients treated with three to six doses remain progression free longer than they were expected to survive. This is meaningful outcomes.
These are outcomes, in many cases more than a year, that gives time with their families, time to take vacations, time to see kids graduate, time to see kids grow. As you can see here, we have a number of patients who are out fairly long-term, beyond 18 months progression free. The Kaplan-Meier curve, the traditional analysis. Here you can clearly see the separation of the curves between the patients that have received three to six doses versus the standard of care. Despite the small numbers of 10 and 14 patients, we reached statistical significance on the progression and in overall survival. We have not yet attained median, but this continues to grow, and we'll provide an update later this year. Moving on, we're going to talk about our T-cell engagers. This is a unique program that we developed in-house.
In 2022, in the New England Journal of Medicine, a clinician by the name of Georg Schett published some remarkable data of autoimmune patients who were treated with CD19 CAR T that he could generate cures. In 2023, almost all of our CAR T competitors in the cell therapy space became autoimmune companies. Just recently, in the last week in Nature Medicine, there was a publication of one patient who had three significant autoimmune diseases who were cured of all three of them. The challenge is that CAR T results in a lot of toxicities. It puts patients often to the brink of death. We wanted to see if we can create a T-cell engager. T-cell engagers are an exciting space in the autoimmune landscape. Autoimmune disease will impact one in six women. Millions of patients will have autoimmune disease.
However, with the T-cell engagers, today they are plagued by potential toxicities. The vast majority of T-cell engager companies do the same thing. They target CD3. Just recently, there were two transactions in the last three weeks. One company called Ouro was acquired by Gilead for almost $1.7 billion. There was another company, called Curon, who had a deal transaction, $180 million upfront in that transaction. Last year, a competitor in this space called Dren Bio had their phase I asset acquired by Sanofi for $600 million upfront. We think we can do better. The challenge with all of the T-cell engagers is that the vast majority of them target CD3. When I target CD3, I not only target the alpha-beta T cells, but I target NKT cells, gamma-delta T cells, Tregs. They secrete this cytokine soup that results in a lot of toxicity or T-cell exhaustion.
60%-80% of patients will have cytokine release syndrome. About 10% of them grade 3 or greater, meaning they are inside the ICU. Last year, a company called Janux reported data with their prostate cancer drug. In there, they showed 96% all grades of CRS, 8% grade 3. No different, despite engineering to try to reduce the CRS. We believe the challenge in the T-cell engager space is that many people broadly target CD3. It overactivates the immune system, it creates toxicities, and it causes T-cell exhaustion. T-cell exhaustion means that your T cells are no longer fit enough to kill. We at IN8bio have created a unique platform, one targeting CD19, so it has broad coverage across all the B cells. We're trying to generate what today is called immune reset.
We cover both the Vδ1 and the Vδ2 compartments of the gamma-delta T cells. Importantly, we overcome the limitations of the first generation of gamma-delta T cell engagers such as LAVA, where there were not enough gamma-delta T cells to kill the targets. We drive expansion of the gamma-delta T cells. I'm going to show you some of our preclinical data. Here, we show in healthy donors, one of the challenges historically is that gamma-delta T cells have highly variable numbers. Here we take three healthy donors, starting from 0.3%-4.4% of gamma-delta T cells, and we have, across all three, a very tight, what we call EC50 or kill curve. 50% of the targeted B cells can be killed at 36 picomolars, a very low concentration of our engager. Here, I'll just show you pictorially.
On the left-hand side, this is an experiment. These are B cells, a cell line called NALM-6 that expresses CD19 with our gamma delta T cells, one-to-one ratio over 24 hours. Quite clearly, on the left-hand side, you can see this plate is full of cells. On the right-hand side, all we did is we added our T cell engager, and you can see that plate is being cleared. Within hours, there would be no more B cells in that assay. What's important is that our gamma delta T cells do not secrete cytokines that drive cytokine release syndrome. When we tested it across three different donors, I'll just highlight IL-6 because that's the validated biomarker for CRS or cytokine release syndrome. To save people from CRS, we treat with an anti-IL-6 antibody. You can see this blue line is flat. There is no dose response.
Our gamma delta T cells do not secrete any IL-6. What we did last year is we ran head-to-head against two commercially available B-cell depleters. Amgen's blinatumomab here on the left-hand side, Roche's mosunetuzumab, targeting CD19 and CD20. Both of these are commercially available. We ran them in assays head-to-head. Here, we started at their FDA-approved concentrations. We did 5x dilutions. We started at a very high concentration of our own engager because we want to see the cytokine secretion that I'll show you next. Here you see at every concentration, we are at least equivalent in the green line, if not greater B-cell depletion than the commercially available. Importantly, if you look at the high and the mid, when we looked at the cytokines, you can see the various CRS-associated cytokines. In green, our compound is markedly reduced.
In fact, IL-6, as I mentioned, the validated biomarker, the high dose at 5 nanomolars or 5,000 picomolars is equivalent to the production of mosunetuzumab at 28 picomolar, 178x difference. We believe we can widen the therapeutic window, increase the dose to generate complete B cell depletion and potentially B cell or immune reset to help treat autoimmune disease. It's a significant opportunity. We're making advances here. We expect to provide some of our first animal data later this year, likely in the third or early fourth quarter. That is related to some corporate work that we did. We raised the financing in December. Coastlands Capital led that financing. We raised an initial $20.1 million in the first tranche. The mouse data from the T-cell engager will trigger a second tranche. That second tranche would get us runway through 2027 into early 2028.
We have a lot of milestones coming across our pipeline. INB-100, as I said, the leukemia program, will have an update towards the end of this year at the ASH Conference. INB-200 and INB-400, we expect to have additional clinical data at the ASCO conference mid-year, and then we will present additional data from our T-cell engager later this year, which, as I said, can trigger a second tranche of additional financing. Importantly, we recently announced that we're going to have an R&D day. It'll be in New York City on May 21st. We have an esteemed neuro-oncologist, Dr. David Reardon, Chief of Neuro-Oncology at Dana-Farber in Boston, who will be speaking on our behalf about his experience treating GBM patients. We will update across our pipeline, our clinical data to date, as well as the progress on our T-cell engager.
I want to thank you today for attending this webinar. We are focused on gamma delta T cells. These are powerful immune cells that can be used in both oncology and autoimmune disease. We believe we have a safer safety profile. Across our clinical trials to date, we've seen no CRS, we've seen no neurotoxicity or any severe adverse events. We are targeting large markets with very little competition, and we have demonstrated that we have proven execution, being able to consistently deliver on our milestones, delivering clinical data, and advancement of our clinical pipeline. Thank you, I'll pass it back to Greg.
Thank you, William. Thank you. William, we already have several questions submitted.
Awesome.
Yeah. For investors hearing about IN8bio for the first time, how would you describe, at a high level, what makes gamma-delta T cells special and why your approach could be meaningfully different from other companies?
Right. Look, the vast majority of cell therapy companies focused on the alpha-beta T cell. The reality is there are multiple cells involved in the immune system. When I think about the immune response, it's not just a single instrument. It's not just a bass, it's not just a trumpet, but it's the music that comes from the symphony. The advantage is the gamma-delta T cell is like the conductor. It can communicate with all the different instruments inside our immune system and tell each of them which one should go and which one should stop, and to pace and time them.
On the battlefield, as we try to target oncology, if you think about it, the advantage of the gamma delta T cell on the battlefield is it's the guy or it's the person with the radio that can call in all parts of our immune system.
Thanks for that, William. Now, you may have covered this, but I feel it's worth asking again, and these people are wondering too. Among your pipeline programs today, William, which one is it again that you believe is the most important driver of value for the company? Tell us why.
Look, near-term value or value is driven by different milestones historically in biotech. I think with respect to near-term value, I think our recent financing kind of says where many of the investors are focused, and that's on the T cell engager. As I said, very recently there have been deals, $1.7 billion for Ouro, a licensing deal with $180 million up front, all targeting these T cell engagers in autoimmune disease. We will have additional proof of concept and initial animal data later this year, and I think that is the largest near-term driver of value.
You talked about a cash runway into 2027, William. Key milestones. What key milestones should investors be focusing on in the next year and a half? How are you thinking about balancing pipeline progress with protecting shareholder value?
Look, it has been a challenging four years. We continue to advance our pipeline. Here, going back to these milestones, we've outlined some of our milestones. We have indicated we expect to have additional clinical updates. There's a lot of interest on our leukemia program. We will update those patients by the end of this year at a medical meeting. We continue to believe, as we've enrolled our expansion cohort, that we are having an impact in these severe leukemia patients, and we can make a difference. We will provide updated clinical data of our GBM program mid-year. We are also working on peer review publication of that data, so you should expect to see that sometime in the near term. We are continuing to execute on our operations to advance the T cell engager. It's an exciting opportunity, potentially worth billions.
We will demonstrate our first animal models and the ability of this T-cell engager to deplete B cells mid-year, probably in the third quarter.
Got you.
There are a couple of milestones coming up between now and the end of the year. Some of those milestones will trigger additional capital coming in with the cash that we had on hand ending 2025 with just over $27 million in cash. It gets us into the first half of 2027. The second milestone will get us through 2027, through IND for the T-cell engager and into early 2028.
30 seconds left for you, William. As IN8bio expands beyond cell therapies into gamma-delta T cell engagers and autoimmune diseases, how should investors think about your long-term vision? Are you building a multi-product company or a broader platform? Sorry, we only got 30 seconds for you to answer.
Look, I think it's important to build a platform with technology that drives value for patients and pharma companies, right? I think there's been a tremendous string of acquisitions. If we can build something of value, potentially there will be deals and acquisitions sometime in the future. Near term, we are focused on developing our gamma delta T cell platform using our knowhow to create long-term value for both investors and potentially pharma.
Well done. Thank you, William. Thank you very much. We're right up against the 11 o'clock hour. William Ho, IN8bio, INAB on the Nasdaq. For more information, call us 1-800-RED-CHIP, or write us at inab@redchip.com. Thanks a lot, William.
Thank you, guys.