IN8bio, a company developing cellular therapies using gamma delta T cells. With us presenting is William Ho, the CEO, the chief executive officer. Please go ahead.
Thank you, Robert. Nice to see everyone. Nice to be here. Again, my name is William Ho. I am the co-founder and CEO of IN8 Bio. We are a company that's been around for about 10 years, and we are focused on developing the technology for my scientific founder and today Chief Scientific Officer, Dr. Larry Lamb. Larry is one of the world's best experts in a subset of immunology, or the study of white blood cells, around gamma delta T cells.
Today, we have two ongoing cell therapy programs, one in leukemia patients undergoing transplantation and one in glioblastoma, both with patients who are beyond three years progression-free. More recently, we have developed an internal program targeting T cell engagers against the gamma delta T cell, and this can potentially be used against both oncology and autoimmune. Just as a quick summary, this is our pipeline.
So INB-100 is our allogeneic or donor-derived cell therapy program in leukemia patients undergoing transplantation. We have given guidance that we are currently enrolling an expansion cohort, and we expect to complete enrollment and dosing of those patients near term, with updated phase I data expected towards the end of this year. In addition, as I just mentioned, INB-619 is our T cell engager platform targeting CD19 that can be used in both autoimmune and oncology, and we'll talk about that program momentarily.
And finally, to target solid tumors, INB-200 and INB-400 is our genetically modified gamma-delta T cell program to target solid tumors. Look, when we talk about oncology and targeting tumors, some solid tumors, like glioblastoma, is the holy grail. This picture in front of you is actually a glioma. It's a brain tumor.
You see the big bulk and the mass of cells in the dark purple, but the reality is, in a tumor, it's not that big mass of cells in the middle that kills you. The surgeon's knife can actually remove that. If you look carefully on the left-hand side, within that healthy pink tissue, there are individual little dots, and those are the tumors that are often left behind, and that's what ends up growing back and results in patient progression and ultimately death.
These tumors are highly heterogeneous, and we started with the question of: how do you target the heterogeneity of these solid tumors? And that is an invention that our scientific founder, Dr. Lamb, came up with. One of the most immunogenic or most powerful immune signals in our body is the DNA damage response, or the DDR pathway.
All of us get DNA damage every single day. For those of you who are in Florida, every time you walk outside, the sun shining on you drives damage in those skin cells. But we don't walk around with tumors because our body knows how to fix them. We either fix the strands, and then correct the damage, and everything's okay, or the cells commit suicide in a process called apoptosis. If either of those occurs, then the person is safe.
As it turns out, biology built in a backup system just in case cells that have DNA damage can't be fixed and won't commit suicide. We actually upregulate innate immune markers on the surface of those damaged cells to tell your immune system, "Hey, something's wrong here. I can't fix it. It won't die.
Eat this and get rid of it." And we found a way to take advantage of that. Many conventional chemotherapies work through an effect called alkylating, meaning they drive DNA double-stranded breaks. What we found is that we can use this alkylating or DNA-breaking effect of chemotherapy to force the upregulation of immune markers on the surface of cancer cells, even if they're resistant to that chemo. And that's what you're seeing on the right-hand side, that top.
Those are chemotherapy-resistant glioma cells, and as much as 600% increase in those markers can be achieved. Below, that's the cancer stem cell population. Again, we can upregulate multiple markers. The challenge is that the dose in which we can accomplish this, it also kills the white blood cells. And so what we did is we hijacked the tumor's own resistance mechanism to the chemotherapy.
We genetically engineered it into our gamma-delta T cells so that they can survive combined dosing. We initiated a clinical trial, what we call INB-200, which was the investigator-initiated trial, and INB-400, which is the corporate-sponsored multicenter study. Last year, at the Society of Neuro-Oncology, we provided updated data. Here, we are treating patients in the newly diagnosed glioblastoma setting. Patients are diagnosed with glioblastoma, and they're enrolled.
They received, across three cohorts, either one, three, or up to six doses of our genetically modified gamma-delta T cells. The patients, they come in, almost 90% of them get surgical resection. During that resection, we insert a catheter so that we can deliver cells directly into the tumor bed. After a 3 to 4 week break of rest, we take their blood, and w e manufacture a product.
We engineer their gamma delta T cells to be resistant to being killed by chemotherapy. In the maintenance phase of the standard of care, we treat patients with five doses of chemotherapy on every 28-day cycle.... What we've done is on the first day of chemotherapy, we've added an infusion of these genetically modified gamma delta T cells through that catheter directly into the tumors, the patient's tumor. This describes the treatment protocol. Here, everything above the blue line is what's known as the Stupp protocol.
Globally, the standard of care since 2005. What we've added is below. So as I said, we insert a catheter, we apheresis or draw blood from the patient to manufacture a product, and in the maintenance phase, patients will receive up to six doses. In cohort 1, we gave a single dose.
In cohort 2, we gave three doses, and in cohort 3, we gave up to six doses. Glioma cells double every 60 days. Here, we are treating the patients every 28 days. The hypothesis was that if our cells can identify and kill enough tumor cells just to keep the tumor cells, the number of tumor cells the same every month, then we can prolong the time to progression. If we can reduce that number just a little bit every single month, then maybe we can outrun the growth and potentially eradicate all of the tumor cells.
And so we ran this clinical trial, and last year at the Society of Neuro-Oncology in November, we presented that data. Patients in our trial have been treated across four centers, so it's not just a single center who has a super surgeon.
We were treated at the University of Alabama at Birmingham, at Cleveland Clinic, Moffitt, and the Ohio State. In total, we've treated 17 patients with our cells. As we were preparing some of the data for this presentation, we actually discovered that we had 10 patients contemporaneously enrolled who had consented, but for one reason or another, unfortunately, were not treated. In some cases, they declined treatment, in other cases, we were not able to manufacture a product.
But we had 10 patients who matched the profiles of our patients, and we're presenting that data again today. We've seen no major toxicity signals. We've seen no major adverse events, such as cytokine release syndrome or neurotoxicity to date, and we believe the treatment activity remains consistent across all the different centers.
Of our active arm, what we consider those patients who received three or up to six doses of our gamma-delta T cells. You can see here the median age is 64, half of them are male, about half of them are unmethylated, or they do not respond to chemotherapy, and only about or about 60% had a partial or subtotal resection.
That means because of the location of the tumor, we were not able to cut out the totality of the tumor, and we left tumor behind. Those patients tend to do worse. Also, we had a median Karnofsky Performance Status of about 80 on a scale that goes up to 100. So we didn't cherry-pick for the healthiest patients available, who were bound to do better.
On the control cohort, here, again, we dosed, we had 13, with 10 receiving only the standard of care. The median age, again, was 67. The 60% are male, 60% are unmethylated or non-responsive to chemo. But here we had a reduction in the number of subtotal resections. More patients were able to achieve gross total resections and should have done better. In a table format, these are the data. There are no significant imbalances, except for a resection type that should favor the control arm.
Here's our data. On the top, in red, those are the patients who received only the standard of care Stupp protocol, our control arm. In blue, those patients who received a single dose, each dose marked by the orange circle. In purple, they received up to 3 doses, and in green, up to 6 doses.
If the patient progressed, that's marked by the red circle, and if the patient unfortunately died, that's marked by the red square. You see here that in the control arm, they achieved a median progression-free survival of 6.6 months, and in patients who received 3 to 6 doses, we almost doubled that to 13 months. We have numerous patients who have remained two years progression-free with their glioblastoma and alive.
Today, we have a patient who had a grade 4 IDH mutant glioma, who remains alive and progression-free over 4.6 years. Almost unheard of. When we look at the data in a table format, the control patients achieved a median PFS of 6.6 months and median OS, or overall survival, of 13.2 months.
In our repeat dose patients, we achieved a median PFS of 13 months, almost matching the overall survival of the other cohort. And today, as of the end of December 2025, we are at an overall survival of 17.2 months, and that is still climbing. We expect to provide an update at a medical meeting mid this year. We conducted an additional analysis on the right-hand side. We actually analyzed the patients based on their age and their MGMT status. Those who are MGMT unmethylated don't respond to chemo and should progress and die faster.
Those who are older also progress and die faster. And we ranked the patients based on their age and MGMT status and looked how many patients remained progression-free longer than they should be alive. In the control arm, that was only a single patient, or 10%.
In our treated patients, we hit 57%. Graphically, that looks like this. On top are patients who received repeated treatments. Here, time zero is their expected date of death. We have numerous patients who went beyond a year where they should have died, progression-free. We have a number of patients who are going towards two years in the same circumstances, where there's only a single patient in the control cohort.
We're excited about this. We've looked at it on a traditional Kaplan-Meier. Here on the left-hand side is progression-free survival. On the Kaplan-Meier curve, we achieved a p-value of under 0.05 with the numbers that I stated earlier. On the overall survival, we have not yet matured our active arm.
We have not hit a p-value of 0.05, but you can see the separation of the curves, and we will be providing an update on that data later this year. Lest we think these results are simply an accident, we also have histopathology. We analyzed the patients, and in some cases, we had paired biopsies, biopsies when they were first diagnosed, and then biopsies again when they relapsed.
On the left-hand side, we have a patient receiving standard of care. They're methylated, so do respond to chemo, and they had a total resection. This patient relapsed at 7.5 months. But importantly, when you see the histopathology between the top and the bottom, you don't really see a significant difference.
Whereas on the right-hand side, one of our treated patients who received up to six doses, they were methylated, they had a subtotal resection. They didn't progress, or unfortunately, they progressed at about 10 months. But quite clearly, you can see the infiltration of gamma-delta T cells, as well as traditional CD3 and CD8 T cells.
We're excited about this program. We're going to go and package this data and go seek guidance from the FDA on any potential registrational path forward, and we expect to come back to investors in Wall Street later this summer with some of that guidance. Moving forward, I want to talk about our T cell engager platform. T cell engagers is a hot area where a tremendous number of business development deals continue to be conducted. We developed our T cell engager internally.
We made this decision when in 2023, all of our competitors in the cell therapy landscape moved from oncology to autoimmune disease. We did not chase that because we didn't believe in cell therapies for autoimmune disease. One, autoimmune disease is a disease of women, generally of younger age, and autoimmune patients treated with CAR-Ts need lymphodepletion.
The Cy causes permanent ovarian damage in about 40% of the patients. In addition, we learned that many rheumatologists actually have a buy and bill business model, and they have infusion centers across their business. A CAR-T would change the reimbursement landscape. But when we looked at the engager, the vast majority of T cell engagers that are in development focus on targeting CD3 to bind the T cell.
Unfortunately, when I target CD3, I target not only the alpha-beta compartment, but the gamma delta compartment, the NKT compartment, and the T reg compartment. All of this causes a cytokine soup, resulting in an uncontrolled immune response that's called the cytokine release syndrome. 60%-80% will experience any cytokine release syndrome, with 10% being grade three or greater, meaning you are entered into the ICU. Because of this toxicity in autoimmune disease, we dose reduce.
The dose is roughly nine times lower than what's used in oncology. And so what we've seen is that we have not been able to achieve deep B-cell depletion and immune reset. The therapeutic window is too narrow, and so we believe we can do better. We believe we can overcome these challenges, despite the engineering that's done with some of these companies, including masking or cleavable linkers.
We thought that the biology of gamma-delta T cells were unique enough that we could create a differentiated product. So INB-619 is our CD19 targeting T cell engager. We have a cassette-like targeting domain, here targeting CD19. We have a domain that targets the gamma-delta T cell receptor, both the delta one and the delta two gamma-delta T cells. And we have an undisclosed domain that we call a gamma-delta expansion domain.
This allows us to significantly increase the number of gamma-delta T cells and drive their expansion, which has been a limitation of some of the older gamma-delta T cell engagers, such as those created by Shattuck Labs or Lava.
And so, we created this unique B-cell depleting T cell engager, and the first thing that we had to do is test this with varying levels of gamma-delta T cells, can we tightly kill the B cells? And so here we had three donors. The concentrations of gamma-delta T cells range from 0.4%-4.4%, and yet we see a tight clustering of the EC50s. The EC50 here is actually 36 picomolar, an incredibly potent T cell engager and B-cell depleter.
This data here, on the left-hand side, we're looking at absolute counts of gamma-delta T cells. On the right-hand side, we're seeing relative concentrations, and what we see is that we drive expansion of both the delta 1 and the delta 2 compartments of the gamma-delta T cells.
Simply by adding our engager to a mixture of CD19-positive cancer cells and gamma-delta T cells, we see the difference. Here on the left, we have gamma-delta T cells combined with Nalm-6. It's a ALL cell line expressing CD19. And on the right-hand side, all we did was added our engager. Quite clearly, you can see differences in the number of B-cells. Many of these cells are undergoing chromatin dissociation, so within hours, this plate is actually cleaned. But what really drove our interest is the cytokine data.
Here, we're looking at various cytokines expressed by gamma-delta T cells. The killing cytokines on top, where we show a nice linear dose response, but the CRS cytokines, such as IL-6, are completely flat. And so we chose to test these compounds head-to-head against commercially available B-cell depleters.
We looked at Amgen's blinatumomab, two scFvs binding CD19, and also compared to Roche's mosunitumab, a full fragment antibody that binds CD20. As you can see, the size of our molecule was, was somewhat between those two. Here, we're looking at killing curves across various concentrations. Across each concentration, you can see our data, the green line. INB-619 is as potent, if not more potent, than each of these commercially available compounds.
I'll note that the concentrations are on the bottom, on the left-hand side. These are 5x serial dilutions. We started very high. We used 5 nanomolars or 5,000 picomolar of our compound on the left. We started with the FDA-approved concentrations of each of these drugs, did the dilutions.
On the right-hand side, at 200 picomolar, you see we still completely deplete the B-cells relative to what you see with Mosunitumab, which is in blue. Why that's important is the following data. These are some of the cytokines that drive CRS, along with TNF-alpha. I'll focus on IL-6 because IL-6 is the validated biomarker for CRS. We treat those patients with CRS with an anti-IL-6 antibody, tocilizumab.
But here, our 5,000 picomolar dose shows the equivalent IL-6 production of 28 picomolar of mosunitumab, a 178 times difference, showing the widening therapeutic window and our potential to be able to dose these patients at higher doses with less toxicity to drive deeper B-cell depletion and hopefully immune reset. We recently did a financing. It was led by Coastland Capital.
The financing will allow us to take this through mice data, so we expect to show B-cell depletion data in mice by late this summer. That would trigger an additional second tranche of the financing, an additional $20.1 million, which will bring our cash position and available runway all the way through 2027. We've built a fantastic team. Myself, I've been in the biotech industry for 25 years. I've been across investment banking, sell side research.
I was on the buy side at New Leaf Venture Partners, where I launched their public effort and ran the crossover portfolio for 4 years. We have Pat McCall, our CFO, a CPA by training, who worked at Silicon Valley. Dr. Lou Vaickus, our Interim Chief Medical Officer. Kate Rochlin, our Chief Operating Officer, a Ph.D. from Weill Cornell.
And finally, Dr. Lawrence Lamb, our scientific founder and chief scientific officer. We're making a lot of progress, or we're making a lot of progress with gamma-delta T cells. We have the funding to get through this year and hit a number of milestones, FDA guidance on our GBM program on a potential regulatory path forward, as well as on our T-cell engager, getting mouse data later this summer. And finally, INB-100 leukemia data, potentially showing reduced amounts of relapse, late this year at a medical meeting.
We've seen long-term durable remissions in oncology for more than four years across two difficult indications. We're making a lot of progress. We're driving value, and I want to thank you for your time and attention today. With that, I'll see if there's any questions.
Well, thank you for that presentation, Will. That was really interesting. First question that I have is on the glioblastoma data and the difference between the Stupp regimen and your outcomes is dramatic.
Yes.
I was wondering if there were any other applications in solid tumors that this could be extended to?
Look, the mechanism of action that targets the DNA damage response isn't limited to just glioblastoma. It's actually a fundamental biology of all of our cells.
Yes.
Arguably, it would work across numerous solid tumors. But we went into glioblastoma because of the original biology. It actually made sense. Our ultimate goal was to get towards an allo therapy for solid tumors, and I was thinking, "What's an organ that I can target where I don't have natural killer cells that are going to reject my graft?" Historically, only the brain, the eye, and the testes. And so we thought we can go directly to the brain, and prevent allo rejection when we get to an allo product.
But also, my experience on Wall Street, you know, making sure that your soldiers are on the right battlefield is critical. Eliminating unknown variables is critical. I f your soldiers are not where you think they are, then you're likely going to fail. Here, we know they're there. I showed you the histopathology, and they're there because we put them there.
Yeah.
So we eliminated one variable.
Yeah, definitely. Very impressive data.
Thank you. It's been 20 years since the last approval in glioblastoma. We're bending that curve and making a difference for these patients.
Yes, and many companies have tested things in glioblastoma with results that don't compare with yours at all.
Which is why we're hopeful that we'll have a great interaction with the FDA.
Yes. Okay. We have a question from the floor.
Yes.
The question is, in simple terms, how much longer are patients with glioblastoma living on your drug, since nothing works that well? Don't these patients pass away in weeks after diagnosis?
So the median time to progression is usually, the historical is 6.9 months. So it's the red line next to what we showed. The median overall survival is this blue line, which is about 14.6 months. So our PFS, or progression-free survival, is actually coming close to historical overall survival.
Okay. Yeah, yeah-
Our overall survival is currently 17 months. It's still maturing. I'll just mention the median is driven by this last patient, at the bottom, 0.05. That patient is at just over 17 months. They remain progression-free, and so the longer they survive, the longer our median OS will be.
Yes, and looking at those purple lanes, that's really unusual to see anything that-
You know, last year, during the Cell and Gene Therapy Forum, Dr. Marty Makary, the FDA commissioner, made a comment about when he was at Hopkins, a Grade 4 glioblastoma that was alive and progression-free at four years. And he made the] comment, "That doesn't happen by accident." This was an IDH mutant, so it's a low-grade glioma, but this was a Grade 4 patient that was treated before they changed the definition of an IDH mutant. But this patient hasn't been treated in-t hey’re out 4.6 years. They haven't been treated since month six.
Wow, that's, that's really outstanding. Okay, well, we have another question from the floor, and this person would like to know if you have enough capital to get toward the FDA approval or what-
Absolutely
-capital plans are.
We just raised the capital. So we just raised the capital. We'll have our 10-K come out in the next little while, next couple months, but we just raised $20.1 million with Coastlands Capital. Franklin Templeton participated, the mutual fund on the West Coast, many of our current and existing investors, along with some new investors.
That gives us the capital currently to get into the first half of next year, which will definitely get us through numerous milestones, including guidance from the FDA on glioblastoma, as well as the mouse data, probably by late summer. And then the mouse data on T-cell engagement will trigger an additional $20.1 million that will get us through 2027.
Okay, great. And just in the interest of time, could you reiterate some of the milestones that are coming up?
Yeah. So we are working on public peer review publication of our glioblastoma data. We are working on a filing for the FDA to gain guidance on any potential regulatory path forward. We are working towards mouse data in the IND, INB-619, T-cell engager, showing safety and efficient B-cell depletion, hopefully by the end of the summer. And then finally, late in the year, we expect to present data from our INB-100 program in leukemia.
We will, hopefully in the short term, announce that we have completed enrollment and dosing of all those patients, and then, report the data at a medical meeting, towards the end of the year, is our goal, and you can imagine where that might be.
Yeah. There are a few medical meetings-
There may be a couple.
High-profile medical meetings that would be interested in, in this type of data. Yes, a few come to mind. Okay. Well, thank you very much, Will.
Thank you very much.
This has been a really interesting presentation, and I'm looking forward to watching these milestones throughout the rest of the year.
Thank you, Robert.
Okay.
Cheers.
Thank you.
Thanks, everyone.