We get started. I know it's very good music. Okay, good morning, everyone, and thank you for joining us for TD Cowen's 45th Annual Healthcare Conference. I'm Tara Bancroft, one of the senior analysts here at TD Cowen, and it is my pleasure today to introduce you to William Ho, the CEO of IN8bio. Will, it's great to have you, great to see you again, and you can take it away with the presentation.
Thanks, everyone. Good morning, welcome. It's great to be back here at TD Cowen's Annual Healthcare Conference. Actually, about 24 years ago, I actually started my career at Cowen, so thanks for having me. It's always nice to be back. My name is William Ho. I am the co-founder and CEO of IN8bio. We are a company focused on the development of gamma-delta T cell technologies for the treatment of cancer, and today we newly announced a new program in autoimmune disease, or I&I. Traditionally, we have been focused on cellular therapies. We believe that gamma-delta T cells are powerful immune cells in our fight against cancer and now autoimmune disease. These particular cells have often been called or are known as Nature's CAR- T cell, and they have the ability to kill very effectively, but also to discriminate between healthy and tumor cells.
Our team has a comprehensive platform around gamma-delta T cells based on 30 years of knowledge from our Chief Scientific Officer and scientific founder, Dr. Lawrence Lamb. Today, across multiple clinical trials, in particular against two very challenging indications, glioblastoma and acute myeloid leukemia, we have patients with durable remissions out beyond three years and still in remission. I thank you again for attending today. Our mission as a company is to achieve what we call cancer zero, the safe elimination of all cancer cells in these patients' bodies. As I said, we have a very comprehensive platform. Very quickly, this is our platform. INB-100 is in leukemia patients undergoing transplantation with what we call DeltEx Allo, the very first allogeneically delivered gamma-delta T cell program in oncology patients.
We have three preclinical programs: INB-330, which is our non-signaling CAR-T; INB-500, our iPSC-derived gamma-delta T cells; and today we're unveiling the first data across INB-600, our gamma-delta T cell engager platform. Behind that, we have INB-200. It's an investigator-initiated trial in frontline glioblastoma with what we call our DeltEx drug-resistant immunotherapy platform to target solid tumors. Let's get at it. We have been traditionally a cell therapy company, but obviously it's been a very challenging environment for cell therapies, and as we talk to potential partners in pharma, there's still a lot of interest in the ability to bring T cells to a specific target in a way that is cheaper, faster, that can potentially be safer. We developed our T cell engager platform. Our first targeted program in this platform is INB-619. Not too surprisingly, this targets CD19 as a target.
Now, the cell therapy landscape very aggressively and rapidly moved into the autoimmune space in late 2023. We saw challenges with that. In particular, about 20 years ago, I was a sell- side analyst, and I actually did this report on lupus and autoimmune disease. As it turns out, the vast majority of autoimmune patients are actually women of maternal age, somewhere between the ages of 25 and 45. One of the challenges with cell therapy is that every cell therapy patient today undergoes lymphodepletion with fludarabine or cytarabine. It would take you all of 10 seconds to go to Grok, Gemini, or ChatGPT to find out those patients on fludarabine or cytarabine have about a 30-40% chance of permanent ovarian damage. We wanted to find an approach that could potentially be safer, faster, cheaper, and yet still very effective.
We developed this unique B cell depleting T cell engager targeting gamma-delta T cells. This is our platform. We target gamma-delta T cells. There have been a number of companies who have tried to develop gamma-delta T cells. The challenge is that gamma-delta T cells typically are at low levels, only about 1% to 7% within our blood plasma, and so there are not a lot of them. In cancer, as tumors progress, the numbers of those gamma-delta T cells also go down, such that when you run out of gamma-delta T cells, we know you're at end-stage disease. This is the first gamma-delta T cell that can actually drive T cell expansion, and we'll show you some of that today. We're quite excited. It can direct gamma-delta T cells to give it tumor specificity.
We can drive it to B cells. We can actually drive aplasia of the B cell compartment, and today we're announcing this program for both oncology and autoimmune disease. These are the first data that we're showing. On the top left over here, this is an assay looking at B cell depletion. This is at a 1 to 1 effector-to-target ratio, which is very low over only a 24-hour incubation period. You can see very potent elimination of the B cell compartment. Many of our competitors with CD3-based T cell engagers are only getting somewhere between 50% to 60%. Below, instead of combining with gamma-delta T cells, we're combining with peripheral blood mononuclear cells. Just taking the blood cells within the lymphocytes within your blood compartment and incubating it in combination with our engager. You can see here that we are also completely eliminating the B cell compartment.
A powerful and very potent T cell engager to target CD19 and to try to drive towards B cell aplasia. Here's the expansion data. As I said, our T cell engager is unique. It binds, it's a pan gamma-delta T cell engager, so it binds both the V delta 1 and the V delta 2 components of the gamma-delta T cell compartment. The historical expansion protocol for V delta 2s is to use zoledronate. We have both a positive and negative control. You can see on the left on the absolute numbers, we are driving delta 2 expansion to the equivalent amount of zoledronate, but we're also driving the other compartments as well.
That allows us to take advantage of the rapid innate functions of the V delta 2 compartment, their potential antigen presenting abilities, but also on the V delta 1, they're known to be resistant to T cell exhaustion, a problem with CD3-based T cell engagers. Some data have demonstrated that the V delta 1 compartment PD1 is actually a marker of activation for gamma-delta T cells, and those cells are tissue resident, allowing us to target residual B cells in solid tumor tissues, potentially allowing us to get to deeper B cell depletion. On an absolute basis or on a relative basis, you can see it's about 50/50 between the delta 1 and the delta 2 compartment. This is the very potent T cell engager. We are in the picomolar range.
You can see the IC50s, a very potent T cell engager, and we are actually also demonstrating actual microscopy. These are B cells combined in a 1 to 1 ratio with gamma-delta T cells, incubated for 24 hours on the right-hand side, combined with the engager, and you can see a lot of dying cells under apoptosis. We are excited about this platform. We have unique therapeutic advantages. Many T cell engagers in development, they have challenges with toxicities, cytokine release syndrome, ICANS, or neurotoxicities. To date, in the clinic, we have two trials, one in glioblastoma, one in leukemias, including acute myeloid leukemia, and we have not observed any cytokine release syndrome or neurotoxicities to date, even though we have delivered gamma-delta T cells directly into the brains of some of these patients.
We're excited about the potential for a therapy that reduces the toxicities for some of these B cell depletions. As well, unlike the cell therapy approach, we don't have to lymphodeplete these patients. It is a T cell engager. Manufacturing is cheaper. It simplifies the delivery process for patients. There's no lymphodepletion, no risk of ovarian damage from additional chemotherapies. Here, we're targeting the gamma-delta T cell receptor, less risk of driving to exhaustion for these cells, less risk of the toxicities, but also showing the potent B cell depletion relative to the competition. We're excited about this platform. We will present additional scientific data at medical meetings this spring. Moving forward, our INB-100 program is in leukemia patients undergoing transplantation. Here, we are going forward targeting acute myeloid leukemia, or AML, patients.
In the area of challenging leukemia, such as acute myeloid leukemia, the goal is always transplantation. There are a lot of therapies in development today, whether they're FLT3 inhibitors, IDH inhibitors, or even the newest menin inhibitors. The challenge with patients with leukemias is that at the end of the day, the stem cells in the bone marrow are faulty. Your bone marrow itself is spitting out leukemic blasts. It's a little bit like the old Dutch fairy tale where there's a dam, there's a crack in the dam, and it's leaking, and the little boy has his finger in it preventing the leak. Invariably, the dam breaks. Patients relapse. The only way to cure leukemic patients, such as AML patients, is to give a transplant to reset the bone marrow so that potentially they can be cured.
Today, even with the best therapies that we have, within 100 days, about 25% of the patients will relapse. Within one year, up to 50% of the patients will relapse. Often, investors will ask if patients are in MRD negativity. MRD is minimal residual disease. It is an assay. Unfortunately, even if a patient is MRD negative, it doesn't mean that there are no residual leukemic cells in their bone marrow. It simply means that the number of leukemic cells is below the sensitivity of the assay, usually about one in a million cells. If half of the patients are relapsing, it means that all it takes is a single cell, one cell to float around to avoid detection by the immune system that replicates. That replication over time eventually results in a relapse.
Our goal was to give gamma-delta T cells so that they can continue to conduct immune surveillance. If we can keep pressure on the tumor or the leukemic cells and keep the leukemic cells from expanding, the hypothesis was that we can potentially create leukemic cures, and we can reduce the rate of relapses from 50% to something better. We have run this trial. It is being conducted at the University of Kansas. It is in leukemia patients undergoing transplantation. These are older patients. The median age was 68. We combined AML, CML, MDS, and ALL in the beginning. Going forward, we are looking to target AML specifically. It was being run at a single center. We are in the process of adding additional centers, and we will have additional announcements this spring.
The patients that we've enrolled, we provided this data at the TCT Tandem Transplant meeting a couple of weeks ago in Honolulu, Hawaii. We enrolled 17 patients. We've treated 16. These were complex diseases. We had patients who had deletion of chromosome 7, trisomy of chromosome 8, concurrent IDH mutations, concurrent FLT3 mutations, TP53 mutations, and they received no maintenance therapy, only a single dose, and we watched and observed. Today, we have multiple patients who have long-term durable remissions who are out three years and beyond who had very complex diseases. Some of our patients should have had a relapse rate of about 80-90%. To date, we have had three relapses: patient 9, 11, and 15. 15 was close to the one-year mark. The others were beyond the one-year mark.
Patient 9 was an ALL patient who went through seven prior lines of therapy, including CAR-T, double-hit TP53 mutation. Patient 11 was an MDS/MPN overlap patient who also had a double-hit TP53 mutation, and patient 15 was an MDS patient. Today, we do believe that the etiology and disease progression of AML patients are very different than those from MDS or other diseases. We are going forward in a single indication with AML as our target, but we have multiple patients. Every single patient has gone beyond the 100-day mark. If you go to the American Society of Hematology or the ASH conference and look at the Kaplan-Meier curves, they all start relapsing immediately. In these diseases, unfortunately, if you relapse, you most likely pass from your disease. We always get the question from people, "Well, this is a single center. It's a single arm.
What does the actual data look like? We actually pulled the real-world historical control data, both from the CIBMTR, which is the national database that everybody pulls from. We looked at CIBMTR across 684 patients in AML, which is arguably the worst disease than the other leukemic indications. They are seeing a 33% relapse rate at one year and a 25% mortality rate at one year. People then came to us and said, "KU's just really good at it." They are right. The University of Kansas is excellent. They are a number eight top transplant center in the country for large transplant centers. As it turns out, the patients that they receive are actually sicker. They are a tertiary referral center, so they get complex disease.
When we looked at their patients, I'll focus on the AML patients, they actually had 43% relapse at one year and 33% died. To date, across all of our patients, we've had one single patient relapse before the one-year mark. We've had in AML, no patients relapse within the one-year mark, and all of our patients remained alive through that mark. We are very excited about this. We will continue to enroll patients. We are currently running an expansion cohort. We are trying to get up to 25 total patients, add a couple of additional centers, and we are seeking to add a parallel observational arm as a potential prospective control, just so patients get an, or investors and others get an idea of how these patients can look on a prospective basis. We will continue to execute on this trial, and we will have additional updates later this year.
Moving forward on our solid tumor side, INB-200 is the investigational IIT. It was an investigator-sponsored study being run at the University of Alabama at Birmingham. This particular study focuses on our drug-resistant immunotherapy. Just the other day, I actually saw a Twitter or X, I guess, post by Dr. Patrick Soon-Shiong. I think most people know that he's probably one of the most successful biotechnology entrepreneurs ever created. He's created numerous companies, but he had a post about the challenge of chemotherapy in that anytime we go into cancer therapy, the frontline treatment is always some combination of surgical resection, radiation, and chemotherapy. Chemotherapy is effective at shrinking our tumors, but one of the challenges is that at the same time, it is poisonous to our immune cells.
The only way we have ever cured a cancer patient is through our immune cells recognizing all the little individual tumor cells that may remain. Yet, the standard of care wrecks that. What we've done here with our drug-resistant immunotherapy is we actually hijack the tumor's own resistance mechanism to the tumor. Most chemotherapies work by driving DNA damage. As a prior analyst, both on the sell side and a portfolio manager on the buy side, you know, when people came to me and said, I'm running head-to-head in phase three against standard of care, deep inside your belly, you're always saying, Uh-oh, because how many of those have failed over the years? Chemotherapy isn't just shrinking the tumor, but today we know it can drive what's known as an immunogenic cell death. We know we get what are known as obscopal effects.
We've seen people, they get treated, for example, with a melanoma lesion on their arm, and yet a lesion on their leg will shrink because you're driving an immune response. Chemotherapy and DNA damage is actually one of the most powerful immune responses out there, except the chemo kills your immune cells. We hijack the tumor's resistance mechanism to the chemo, genetically engineered it into our gamma-delta T cells so that they will survive six times the therapeutic dose, allowing us to drive synergistic combinations of the standard of care with an immune response that remains active. This was run in frontline glioblastoma. Patients, this year unfortunately marks 20 years since the last approval of a therapeutic in glioblastoma. In those ensuing years, we're now driving autonomous cars. We've caught rocket ships with chopsticks. We are using ChatGPT or Gemini or Grok, right?
The amount of work that those AI agents can do is actually remarkable. Like 10 seconds, you'll pull something that used to take an analyst two days. We have not made any progress in diseases like glioblastoma. It's been too long. Here, we're driving synergies. We've treated 13 patients. It's a mix of IDH wild type, one single IDH mutant. They generally live longer. I'll talk about that patient, patient 11, momentarily. A mix of unmethylated and methylated disease. Unmethylated patients do not respond to chemotherapy. The standard of care known as the Stupp protocol has a median progression-free survival of 6.9 months. Unmethylated patients, of which 54% of ours are unmethylated, relapse by about four months, four to five months. The median overall survival has remained 14 to 16 months for 20 years. We have a mix of patients, a mix of total and subtotal resections.
It may not surprise you. Subtotal resections means we left the tumor in behind because we could not operate because of the location of that tumor. Those patients progress very rapidly. The data that we presented, and we are demonstrating an extended progression-free survival. We presented this last October. I believe that our therapy is working, and we are keeping patients in remission longer today. Patients here received either one, three, or up to six doses of our genetically altered gamma-delta T cells. The first dose cohort that received a single dose is in blue on top. Those who received three are in purple in the middle, and in green at the bottom, they received up to six doses. The median standard of care progression-free survival is that six to seven-month light pink bar that you see on the left-hand side. Each dose is marked by an orange circle.
Progression is marked by the red circle. You'll know every single patient in our first dose cohort relapsed and died. The median progression-free survival was 8.26 months, just a little bit above the standard of care. Across all of our patients that received more than one dose, our median progression-free survival is currently sitting at 12.4 months. This is important. The last product, not a drug, the last product approved in glioblastoma was Novocure's Optune, the tumor-treating fields, the little hat that most investors didn't believe worked. Two years ago, Novocure presented the 2-THE- TOP study. It was a combination of tumor-treating fields with pembrolizumab in the frontline setting. The final results of the TOP study showed a median progression-free survival of 12 months. As of October of last year, we are already beyond that.
Novocure is generating $500,000,000 in sales, treating somewhere between 3,000-4,000 patients a year. 14,500 newly diagnosed GBM patients occur in the United States every single year. We believe we are making a difference in keeping these patients in remission. We actually have histopathology demonstrating the presence of immune cells in the brains of these patients. One that we had an oral presentation at the Society of Neuro-Oncology. The chair of the session, Dr. Puduvalli from MD Anderson, called the infiltration of immune cells striking. We are excited about this. We are continuing to follow these patients. We have patients who are still alive and in remission. We were enrolling a phase two study, and we had a number of additional patients enrolled at multiple centers.
Unfortunately, due to the environment for biotech and for cell therapy, last year in September, we had to suspend further enrollment. We are continuing to track the patients that we did treat, and we will provide updates this year. We are excited about what we are doing. We are making a real difference for these cancer patients. From a corporate standpoint, we have multiple milestones throughout this year. We announced some new data today. We will be presenting that at multiple medical meetings in the first half of this year. We will continue to have clinical updates across all of our clinical trials this summer and later this year, and we will continue to execute and hit on our milestones. We raised an additional $11.6 million last fall.
Our guidance has been that that gets us into the beginning of 2026, and we will provide an additional update when our K comes out shortly. We've built a fantastic team. Myself, I've been in biotech for this year with Mark almost 24 years on all sides of the business, on investment banking, operations, sell- side, and on the buy side, and then in an operating role now for almost 10 years. Dr. Lam, our Chief Scientific Officer, one of the world's best experts in the area of gamma-delta T cells. Patrick McCall is our Chief Financial Officer. Dr. Kate Rochlin is our Chief Operating Officer. In the interim, Dr. Lou Vaickus, who used to be, I think, head of clinical at Vertex long ago, is our interim Chief Medical Officer. We're making a lot of progress.
We're excited about gamma-delta T cells, not just the cellular therapy. Today, we announced the addition of a T cell engager, an area that's still hot in the marketplace. We have a unique T cell engager targeting CD19. We've demonstrated some data we can drive elimination of the B cell compartment. We believe that by targeting gamma-delta T cells, our platform is unique in that it can drive expansion of the gamma-delta T cell compartment. As well, we think we can potentially have a potentially safer T cell engager program as we have not observed the CRS. We have not observed the neurotoxicity or ICANS, and we don't need to lymphodeplete the patients as you do for cell therapies. Thank you very much. I'll welcome any questions, but thank you for listening.
Please join us on our journey as we try to accomplish our mission of cancer zero. Any questions?
For your new program, it has the preference of qualities versus CD3 and CAR-T. Would you see this as displacing those therapies or becoming standard of care?
Look, I think when we looked at it, we did not jump into the landscape like everybody else did. It was this race of cell therapy companies to pivot from oncology, especially the allocell therapies. Ultimately, though, I think what people did not necessarily understand is the difference between a hematologist or oncologist and a rheumatologist. I will admit, I did not understand this until I was dealing with transplanters. The hematologists are cowboys. Like, they are doing anything they can to keep their patients alive because the tumors can be so aggressive.
The fact is the rheumatologists historically have not dealt with cell therapy, have not dealt with lymphodepletion, right? In order to give a cellular therapy, a hospital has to have a FACT-accredited lab to do the dose prep, right? You don't do dose prep for cell therapy for rheumatology. Where that's historically used is in the area of transplantation and in the manufacture of products for stem cell transplant. When you're in a hospital, it is challenging because even between medical oncology and hematology, there are silos. They don't talk to each other. To get rheumatology to talk to these different groups and deal with the toxicities, we believe is going to be a challenge. Even with the T cell engagers today, we've seen toxicities. We've seen cytokine release syndrome. We've seen neurotoxicity. There was one recently that had a grade four neurotox, right?
In rheumatology, it's not acceptable. The patients are not going to die like they are in oncology. We wanted to create a unique platform that had the properties that we thought could be relevant to the rheumatology and their patients.