Good day, ladies and gentlemen, and thank you for standing by. Welcome to the IN8bio Investors Call. At this time, all participants are in a listen-only mode. After this speaker's presentation, there will be a question-and-answer session. To ask a question at that time, you'll need to press star one one on your telephone keypad. Please be reminded that today's conference call is being recorded. I would now like to hand the conference over to your speaker today, Dr. Glenn Schulman. Please go ahead.
Thanks, Howard, and good morning, everyone. Thanks for joining us as we issued a press release this morning discussing the latest gamma-delta T- cell INB-100 clinical trial results that are being presented at the Tandem Meetings this week. Joining us on the call today are Mr. William Ho, Co-founder and CEO of IN8bio, Dr. Kate Rochlin, Chief Operating Officer, Dr. Larry Lamb, Co-founder and Chief Scientific Officer, Mr. Patrick McCall, Chief Financial Officer, and Dr. Lou Vaickus, our Interim Chief Medical Officer. In addition, we're very pleased to be hosting Dr. Michael Bishop from the University of Chicago. Dr. Bishop is a member of our SAB and a leading key opinion leader in the area of hematopoietic stem cell transplantation.
Before we begin, I'd like to remind you that various remarks that we may make on this call contain forward-looking statements that are made under the safe harbor provisions of the securities law, including but not limited to expressed or implied statements regarding future data results, timing of initiation, progress, and scope of clinical trials for all of IN8bio's product candidates, including INB-100. The ability of such product candidates to achieve any particular clinical outcomes, including durable complete remissions of indicated cancers, the potential of IN8bio's DeltEx platform to discover and develop innovative product candidates, and IN8bio's ability to achieve planned milestones, including data readouts from its trials. IN8bio may not actually achieve these plans, intentions, or expectations disclosed in the forward-looking statements.
Forward-looking statements involve risks and uncertainties that can cause IN8bio's actual results to differ significantly from those projected, including without limitation, the risks and uncertainties detailed in our most recent annual report on Form 10-K and recently filed 10-Q and in subsequent filings with the SEC. With all of that, I'd like to turn the call over to William Ho, Co-founder and CEO of IN8bio. Will.
Thank you, Glenn, and good morning, everyone. We are delighted that you can join us today to review the latest positive data from the phase I study of INB-100 being presented this week at the 2025 Tandem Meetings of the Transplant and Cellular Therapy meetings of the ASTCT and CIBMTR, being hosted in Honolulu, Hawaii. I will provide a brief overview of how we approach things differently here at IN8bio, why we think we have consistently delivered durable remissions for patients, and why we are so encouraged by this data. As Glenn mentioned, we have guest speakers joining us this morning. First, Dr. Bishop from the University of Chicago Medicine will discuss the challenges of treatment and relapse for leukemia patients and how a cellular therapy like INB-100 could be a benefit for AML patients. After Dr. Bishop's review, we will hear from Dr.
Lou Vaickus, our Interim Chief Medical Officer. Dr. Vaickus has deep experience in drug development, immunology, and biotechnology. He filled this role for IN8bio early on in our development and through our IPO. We welcome him back. I'll just pass it to Dr. Vaickus to say a few words about his background.
Good morning, everyone. I've been in industry for over 30 years. I've helped to get approvals on seven marketed products and have been in the Chief Medical Officer's role for several oncology companies. Prior to industry, I was in academia for 11 years with fellowships at the Mayo Clinic and Stanford and was on faculty at the University of Iowa and Roswell Park Cancer Institute. It's great to rejoin the IN8bio team, so thanks, Will, and back to you.
Great. Thanks, Lou. Today, Dr. Vaickus will review the INB-100 trial and the clinical data being presented at TCT in detail, after which I will review the historical control data that was generated by the Center for International Blood and Marrow Transplant Research, or CIBMTR, and the Kansas University Cancer Center, or KUCC, and how that relates to the durable response rates we have observed to date with INB-100. IN8bio has taken a different approach from the beginning, and few, if any, other companies have announced data where patients have remained in durable long-term complete remissions from an allogeneic or donor-derived therapy while maintaining their quality of life. Recently, a competing company once again announced data where the complete remission rates dropped precipitously after three months and significant safety issues arose, leading them to drop the program. The question should be why.
We, too, have run programs and treated patients from multiple centers. We have changed our manufacturing processes, moved them from various locations, and faced innumerable challenges. I think it's underappreciated for a cellular therapy company that we did all of this ourselves. We hold this knowledge and know-how in-house, and to date, we have consistently reported durable remissions and a manageable safety profile across our trials. We believe we approach things differently. Our approach with gamma-delta T cells has been driven by the work of our scientific founder and Chief Scientific Officer, Dr. Lawrence Lamb. We call him Larry. He is a world expert in the field of gamma-delta T cells and is credited with making the first observation that higher levels of gamma-delta T cells are associated with better survival outcomes almost 30 years ago.
As a company, we are a science and data-driven company, and we have designed our programs and clinical trials with the patient in mind. We are focused on the only thing that matters for cancer patients: survival. Today, we have patients across two difficult indications, acute myeloid leukemia, or AML, and glioblastoma, or GBM, treated with different protocols and at different centers who remain alive and in remission for over three years. The question we always ask ourselves is, how do we keep patients alive longer with a tolerable therapy that maintains their quality of life? What is it that causes patients to relapse and to ultimately die from progression, and how do we change that?
We believe to achieve our goals, we need to get the deeper responses and to have persistence of cells to keep pressure on the tumor and to continue to have surveillance against any wayward cancer cells, even if we can't see them or detect them through our available assays. If we can get deeper and delay the regrowth of cancer cells, we believe that patients will live longer. The second is tolerability. As Larry often says, shrinking the tumor doesn't matter if the patient dies from the therapy or if the quality of life is significantly impacted. We've observed few additional toxicities to date from the addition of gamma-delta T cells. Across all of our trials to date, we have seen no cytokine release syndrome, or CRS, no tumor lysis syndrome, neurotoxicities, or ICANS, and few significant infections. This, we believe, differentiates us from our competitors.
Finally, we are targeting the heterogeneity of cancer cells. The very challenge of targeting difficult cancers such as high-risk AML is that they are heterogeneous, so we can't kill all of the cancer cells. If the patient ultimately relapses, it means that we didn't get all of the cancer cells even with the transplant. The cancer cells were simply below the level of detection by the available assay. Cancer cells are smart, and they also downregulate the cancer targets scientists use to find them. They cloak themselves from the immune system. One of the advantages of the gamma-delta T- cell is that they possess multiple weapons that allow them to target this heterogeneity. They are often called nature's CAR T cell. Numerous peer-reviewed papers have demonstrated that higher levels of gamma-delta T cells are associated with better survival outcomes.
This includes in trials of melanoma patients treated with checkpoint inhibitors or even in the CD19 targeted CAR T, where two papers came out last year in 2024. We believe our gamma-delta T cells can continue to persist and conduct immune surveillance to attack any residual tumor cells and to ultimately prevent relapse. Despite advances like post-transplant cyclophosphamide, which reduces mortality from graft versus host disease, or GVHD, relapse remains a significant concern, especially in older patients who receive reduced-intensity conditioning regimens, what are known as RICs. I will now turn the call over to our distinguished guest and key opinion leader, Dr. Michael Bishop, who will delve deeper into the challenges of relapse after allogeneic hematopoietic stem cell transplantation. Mike.
Thank you, Will, and good morning, everyone. As was introduced, I'm Dr. Michael Bishop, Director of the Hematopoietic Cellular Therapy Program, Director of the David & Etta Jonas Center for Cellular Therapy, and Professor of Medicine at the University of Chicago. I have been involved in hematologic transplant medicine for over 30 years and have focused on both patient care and clinical research. My research focuses on the prevention and treatment of relapse after stem cell transplantation, looking at therapeutic approaches to prevent and treat disease recurrence after transplant. This is such a critical area, and I have chosen to focus my research here because, simply put, relapse after transplant is the most serious problem facing patients today. Unfortunately, this often leads to poor outcomes and patients' deaths soon afterwards.
We truly need therapeutic approaches that can maintain patients in remission, particularly in the haploidentical transplant setting where the risk of relapse has been and remains very high. Today, I will provide an overview of acute myeloid leukemia and haploidentical stem cell transplantation, the significant risk associated with relapse, and provide some context for the maturing and promising data that is being shown in the phase I trial of INB-100. Next slide. Here are my disclosures. I have worked with a number of cellular therapy companies and participate on scientific advisory boards, including IN8bio, because I believe in the potential power of novel therapies to improve outcomes by decreasing the risk of relapse in patients undergoing transplant. Next slide. Acute myeloid leukemia, or AML, is an extremely big problem in the United States.
There are approximately 20,000 new cases per year, and more than half of those patients, 11,500, who die every year. As many of you know, allogeneic stem cell transplantation remains a cornerstone treatment for patients with hematologic malignancies like AML. However, despite advancements in managing transplant-related complications, such as graft versus host disease and infections, relapse remains the leading cause of death after transplantation. Importantly, the median age for a patient with acute myeloid leukemia is generally between 60 and 65 years. This is significant because when we look at the data, we can see a clear association where older patients experience poorer outcomes. For example, if a patient is under the age of 50, relatively younger, you have a pretty good chance that you could be cured of your leukemia. If you're 50 or older, you can see that this drops off dramatically as age progresses.
As a matter of fact, for those patients 65 or older, the chance of cure is only about 15-20%. In many cases, this is due to increased medical problems as patients age. They develop frailty and have other issues such as social or economic that may prevent them from getting to an allogeneic stem cell transplant or receiving fully myeloablative conditioning regimens prior to their transplant. Next slide. However, when we look at data from the Center for International Blood and Marrow Transplant Research, better known as the CIBMTR, we have seen that over the last 20 years, there appears to be improvement in survival after allogeneic stem cell transplantation. When we look more closely, this is primarily due to improvement in treatment-related mortality due to better management of infections and major organ toxicities.
Thirty years ago, when I started in this field, I would see a patient with a fungal infection and know that they were going to die. Today, I would say it's relatively rare for a patient to die from a fungal or most viral infections. The sad thing is that the incidence of relapse has not changed over time, and it has actually gone up. This is due to the fact that we are able to get patients through the early portion of the transplant, where the majority of transplant toxicities occur. Patients are able to live long enough to, unfortunately, develop relapse of their malignancy. Again, I'm going to repeat this over and over again during my talk because this is the most significant hurdle we are facing in transplant, and this is what I'm trying to prevent. That is, I'm trying to prevent relapse.
Relapse in this patient continues to be the primary cause of death. The reality is stark. If a patient relapses, they die. Once acute myeloid leukemia progresses, there are virtually no effective treatment options left for that patient. In acute leukemias, especially AML, the risk of relapse is tremendous. In fact, some patients are not offered a transplant because their risk of relapse is considered to be too high and not worth undergoing the potential toxicity of the transplant. Next slide. Why is transplant our best treatment option, and what impacts the variables outcomes that we observe? These are the data from a retrospective match case analysis, which was based on what is known as the Acute Myeloid Leukemia Working Group 99 trial. They conducted a case-matched-based analysis and demonstrated that transplant resulted in superior outcomes as compared to chemotherapy alone in patients with intermediate and poor-risk disease.
On this slide, the solid lines are those patients who got a transplant, and the dashed line are those patients who got conventional chemotherapy alone. When you look at the Kaplan-Meier and cumulative incidence curves to the right, you see that conventional chemotherapy patients had about a 75% chance of dying of their leukemia, while allogeneic transplant reduced this risk by greater than 50%. Transplant outcomes are also shown to be highly dependent on the patient's risk profile. We break up acute myeloid leukemia into good, intermediate, and poor risk based upon chromosome or cytogenetic analysis. Good risk makes up about 20% of all acute myeloid leukemia. Intermediate risk makes up about 50-60%, and poor risk makes up approximately 20-30%. Here you can see the marked higher incidence of relapse among those patients in the intermediate and poor-risk groups. Slide 6 and 7.
We know that patients can be further grouped by looking at the molecular mutations associated with their disease, even when their cytogenetic analysis is normal, which places them in the intermediate risk category. The standard of care at any good institution is to perform an analysis of molecular probes on the patient's leukemia, including one that is known as NPM1. Now, an NPM1 mutation actually is associated with a little bit better prognosis, but if you have a FLT3 mutation, it's actually worse. FLT3 is seen in a large percentage of normal chromosomes, and you can see that the relapse rate increases with this molecular mutation. These mutations are the things determining the outcomes of patients. As you see from these Kaplan-Meier curves in terms of leukemia-free survival and overall survival, patients with a FLT3 mutation do worse.
To further understand the risk of relapse, an analysis was performed on 30,000 patients reported to the European Blood and Marrow Transplant Group to determine how multiple clinical prognostic factors affect outcomes. What they found is that if a patient had a FLT3 mutation, were of older age, and had more than one course of chemotherapy to get in remission, those were the most important variables for relapse and poor outcomes after transplant. Taking all of these factors together, they were able to identify a group of patients who were at risk for poor leukemia-free and overall survival. Today, patients with a FLT3 mutation would generally receive maintenance therapy after transplant with a FLT3 inhibitor. Remember also today that patients in the INB-100 trial received a single infusion of gamma-delta T cells and no maintenance therapy. Next slide. What are good risk patients? What are the bad risks?
I'm going to show you some data looking at relapse after transplant. We first need to get the patients through the first 100 days, as that is the most difficult time period in the transplant. Even with the transplant-related toxicities, relapse is seen in 25-35% of patients within the first 100 days of transplantation, regardless of the type of donor that they received, be it a match-related, a match-unrelated, or a haploidentical. When you get beyond 100 days, greater than 50% of patients' deaths are due to relapse. If I haven't made the point yet, relapse is bad. Next slide. To show you how bad relapses are, I will show you what happens to those patients who relapse after a transplant. Today, the IN8bio team will show some updated data they pulled from the CIBMTR.
This historical data looked at nearly 1,800 patients, dividing them into patients who received their transplant between 1992 and 2000 and those who received them between 2001 and 2010. The trend is the same between the two groups. Notice that the one-year survival for those patients who relapse after an allogeneic transplant is somewhere around 25%. If you break it down further, the median time, that is the time that I always try to think is key and try to emphasize, the median time from transplant to their disease coming back is just seven months. Matter of fact, you see that 82% of all patients will have their disease come back within the first two years, including 43% of relapsing within the first six months.
However, if your disease stays in remission longer after transplant, once you get to that two or three years, like some of the INB-100 patients, the chance of living after relapse gets a little bit better. Matter of fact, those patients, the rare group of patients who relapsed after three years, about approximately 10%, they have about a 50% chance of surviving a one year or more after relapse. To put it in perspective, here is the Kaplan-Meier curves based upon when the time of relapse, and it is bad. No matter what age you are, if you relapse after transplant, it is bad. We need something to do better with this group of patients. Next slide. Through our use of risk stratification, we have learned that the best way to improve transplant outcomes is to induce a state of minimal residual disease prior to the transplant.
Now, that doesn't mean that the patients are cured. They still need to go on to allogeneic transplant. There is still a risk of relapse. The early post-transplant period is an area of tremendous opportunity to prevent relapse, because as you remember, that is where the majority of relapses occur, the first six months. Why does that occur? When we do an allogeneic transplant, we are giving the patient a new immune system. What do we immediately do after the transplant? We suppress that new immune system because we don't want the patients to develop graft versus host disease. This is followed by a buildup of a new immune system, which takes approximately six months at least after the transplant. This is why it's an area of opportunity, because we can do preemptive therapy to try to prevent early relapse.
We need methods to try to control the disease until the new immune system can completely take over. Next slide. We have looked at a variety of ways to prevent relapse post-transplant, and unfortunately, the results to date overall have been poor. We have tried using chemotherapy agents. We've looked at using FLT3 inhibitors, and they have tried a great number of other small molecules, and people are also interested in using immunotherapy that's targeting CD33 and now menin inhibitors. However, I will show data from a few trials illustrating that this has resulted in less than hoped-for outcomes. Next slide. This was a randomized trial performed at the MD Anderson Cancer Center using azacitidine as post-transplant maintenance. Unfortunately, they saw no difference in relapse-free survival or in overall survival. Next slide. Another approach to prevent relapse is to use FLT3 inhibitors as post-transplant maintenance in patients with FLT3 mutation.
In this large U.S. randomized trial, patients with FLT3 mutations were randomized to receive the FLT3 inhibitor midostaurin post-transplant. Although this trial closed early due to poor accrual, they were able to report the available data, which again, unfortunately, demonstrated no difference in either relapse-free or overall survival. Next slide. Our relapse problem is still our most significant problem after transplant. We are still in a bad place in terms of needing therapies to prevent relapse after transplant, because right now, I can tell you that once you have reached the point where you're needing treatment for relapse, the outcomes are very poor. We do not want to get to that point. There are no good therapies currently for patients who relapse after allogeneic transplant. Yet despite this, we still know that the best chance for these patients is a transplant, particularly for patients with intermediate and poor-risk AML.
It remains the treatment of choice for patients who are transplant eligible. Relapse is the number one cause of death after allogeneic transplant, and novel preventive therapies, such as cellular therapies, are the best tactic to prevent relapse. The data clearly show us that prolonged progression-free survival is critical. We know that the longer the patients stay in remission, the greater likelihood of long-term survival. This is particularly important in acute myeloid leukemia, where there remain very few or no treatment options if their disease recurs. If INB-100 continues to demonstrate durability and lasting remissions, it could significantly shift how we approach post-transplant care. With that, I will pass it back to Will.
Thank you, Dr. Bishop, for that overview and insights. I'd now like to pass the call over to Dr. Lou Vaickus, IN8bio's Interim Chief Medical Officer. Lou?
Thanks, Will.
We should be on to slide 24 that shows a phase I trial to reduce leukemic relapse. This is an investigator-sponsored open-label single-center phase I study that's evaluating the safety and efficacy of up to three dose levels of expanded activated allogeneic gamma-delta T cells, 1 times 10 to the 6 cells per kilogram body weight, 3 times 10 to the 6, or 1 times 10 to the 7 cells per kilogram body weight. This study was conducted to prevent relapse and prolong survival in leukemia patients undergoing haploidentical stem cell transplantation. On the second row, the treatment regimen is shown. Following a reduced-intensity conditioning regimen consisting of fludarabine, cyclophosphamide, and total body irradiation, patients undergo a haploidentical stem cell transplant from a donor, followed by a dose of post-transplant cyclophosphamide to reduce the risk of graft versus host disease.
Within seven days of neutrophil engraftment, which occurs about two to three weeks later, the gamma-delta T cells are infused. The first response assessment is at day 28 post-transplant, and the patients are tracked for safety, disease relapse, and overall survival. For this study, key eligibility criteria include adults with AML, CML, myelodysplastic syndrome, or acute lymphoblastic leukemia who are approved to undergo an allogeneic transplant according to NCCN guidelines. Please note again that these are patients who have at least intermediate or high-risk features, the unfavorable ones Dr. Bishop spoke about, and thus are at a high risk of relapse. The primary endpoint for this dose escalation study is dose-limiting toxicity, or DLTs, that are defined as severe grade 3 to 4 acute events after the infusion of gamma-delta T cells, as well as the incidence of graft versus host disease.
Two doses were ultimately evaluated, including dose level 1 of 1 times 10 to the 6 gamma-delta T cells per kilogram and dose level 2 of 3 times 10 to the 6 gamma-delta T cells per kilogram, with the latter being declared the recommended phase II dose, or the RP2D. We are currently expanding the number of patients at dose level 2 up to 25 total patients and are in the process of bringing on additional centers in addition to the University of Kansas. The next slide is a diagram of the study design, slide 25, and you can better visualize what I just explained. I want to repeat a few aspects of the study design. The same donor provides both the stem cells and gamma-delta T cells gotten from a peripheral blood apheresis.
The gamma-delta T cells are then activated, expanded, and purified, and alpha-beta T cells are removed. The product is then cryopreserved and is ready for infusion, all of this being done by the IN8bio team while the stem cell transplant is occurring. As you can see from the diagram, the gamma-delta T cells are infused right after neutrophil engraftment, and this is considered the period of vulnerability that Dr. Bishop also spoke about when the immune system is down and recovering and the leukemic cells have a chance to grow back. On the next slide, we have the demographics of these patients entered to date. They include the initial patients as well as the additional seven patients enrolled in the expansion cohort. The median age is older, 68.
The majority of the first 10 patients were AML patients in their first complete remission, and many patients are considered high risk based on poor genetics and mutations. All patients received a reduced-intensity conditioning regimen, again, to reemphasize, has a higher risk of relapse. Finally, despite having mutations such as IDH or FLT3, as Dr. Bishop described earlier, none of these patients received maintenance therapy. To date, a total of 16 patients have been dosed with gamma-delta T cells, and one is waiting to be dosed. We're very encouraged by the 18.8-month median follow-up that has been observed to date for the 16 evaluable patients. Total follow-up across all AML patients is 20.1 months, and the median follow-up for the initial eight AML patients is close to two years, being 23 months as of January 17, 2025. On the next slide is shown the safety profile.
The entirety of the safety profile in all patients, regardless of whether the AEs were treatment-related or not, is shown here. We've had no treatment-related deaths, no cytokine release syndrome or neurotoxicities as have been seen with CAR T products, low rates of infections, and no unexpected adverse reactions to date. Almost all of these events are on par with what you would expect with patients undergoing allogeneic transplantation and not receiving gamma-delta T cells, so we're very pleased with this safety profile. Importantly, no change in the adverse event profile was observed as we progressed from dose level 1 to dose level 2, the higher dose level.
On this next slide, which is slide 29, if we can jump to that, this is a swimmer's plot of all the patients treated to date, and we believe that INB-100, the gamma-delta T cell addition, is demonstrating durable remissions in complex and high-risk AML patients. These are swimmer's plots where you can see all patients treated with gamma-delta T cells and the long survivals that have been noted to date. The ones in blue are cohort 1, the ones in purple cohort 2, and then the ones in green are the more recently added expansion cohort subjects. Two patients, an ALL patient with seven prior lines of therapy, including a CAR T failure, which is patient 009, and an MDS myeloproliferative disorder overlap patient 011, both with one of the worst mutations you can have, a TP53 mutation, relapsed at 14.7 and 12.4 months respectively.
A single MDS patient relapsed before one year at 348 days in the expansion cohort. One patient, 007, died due to idiopathic pulmonary syndrome at about 15.5 months that was related to the allogeneic transplant and not the gamma-delta T cells. To put some of this in perspective, up to 20% of patients may die in the first year due to non-relapse mortality. This puts our overall progression-free survival rate at 81.3% for 16 evaluable patients and one-year progression-free survival at approximately 91%, with a one-year overall survival at 100%, with 11 patients crossing this one-year mark. Across all AML-treated patients to date, no patient has experienced a relapse through 20.1 months of median follow-up. I'll now pass the call back to Will.
Great. Thanks, Lou. As has been discussed extensively on this morning's call, relapse remains the primary concern for patients with leukemia.
Our goal with INB-100 is to increase progression-free survival or disease-free survival by providing durable immune surveillance with these expanded and activated allogeneic gamma-delta T cells. We previously announced last year that we had a type B meeting with the FDA and that relapse-free survival is a time-to-event endpoint that is acceptable as a primary endpoint for randomized control studies in AML. We are targeting AML as our path forward because the data suggests these leukemias are distinct diseases with different prognostic factors and a different natural history. To date, we have not observed a patient relapse across our AML patients after nearly two years of follow-up. There is a significant market opportunity in AML in the United States, and it is a significant unmet medical need. As discussed, higher levels of gamma-delta T cells have been repeatedly found to be associated with improved outcomes. This is Dr.
Lamb's early publication where patients undergoing a transplant with naturally higher levels of gamma-delta T cells demonstrated more than a three-and-a-half times greater survival than those who were low to normal. Dr. Lamb has spent much of his career figuring out how to make this observation into a therapeutic, and we believe we are achieving this goal. Additional analysis from a third party out of Copenhagen University Hospital and published and peer-reviewed in 2019 supports this survival advantage. Just read the title of this paper. Importantly, we are increasing the levels of gamma-delta T cells. As we have previously reported, we looked at our gamma-delta T cell persistence in leukemia patients undergoing transplantation. Historical data from Dr. Lamb's lab are shown in the black bars. Patients without an infusion of gamma-delta T cells generally have low levels of gamma-delta T cells that decline over time.
Data from this INB-100 trial are shown with patients in cohort 1 in blue and those in cohort 2 in green. What you see in both cohort 1 and 2 is that we see elevations of gamma-delta T cells from day 30 through day 365. What is most important is that the dose difference between cohort 1 and 2 is three times, but we are seeing an eightfold increase in gamma-delta T cells at day 60 between cohorts 1 and 2, matching the title of that prior paper that I showed you from Copenhagen. This suggests not only persistence but also in vivo expansion of these cells. The dashed gray line is demonstrating that we are also surpassing the number of gamma-delta T cells previously observed to be associated with survival benefits.
The advent of post-transplant cyclophosphamide increased the availability of hematopoietic stem cell transplantation to greater numbers of patients while reducing the risk of GVHD. In leukemias such as AML, transplanting patients is important to essentially reset the bone marrow and hopefully wipe out all of the cancerous leukemic cells. However, these patients still relapse, and unfortunately, when that happens, they most likely die from progression. The first publication of the Hopkins Protocol by Dr. Leo Luznik, who is now Section Chief of the Department of Hematology and Oncology at the Baylor College of Medicine, demonstrated a relapse rate as high as 50% at one year. As a reminder, Dr.
Luznik spoke at our R&D day a little while back and indicated that relapse rates were high as his data was in a phase I trial and in early first-in-human trials like our trial for INB-100, you enroll the sickest patients first. Today, Dr. Vaickus presented data demonstrating that our INB-100 is demonstrating long-term durable remissions in multiple patients with high-risk AML. We now have three patients with complex high-risk disease who received no maintenance therapy and are still in remission more than three years later. What is really new in today's data? We are excited because today, in order to put the data we have generated with INB-100 in perspective, we have gathered historical progression-free survival and overall survival data from two organizations.
Working with the CIBMTR, we were able to analyze their real-world transplant database across the United States, and they extracted AML patients treated in a similar manner to those in the INB-100 phase I trial. At one year, progression-free survival for those patients was 67.8%, and overall survival was 74.7%. By the one-year mark, 32% of the patients across the country relapsed and 25% died across all centers. We also worked with the Kansas University Cancer Center to evaluate all haplo transplants and AML patients at their site from 2016 through 2023. At one year, progression-free survival for all leukemia patients was 59.2%, and overall survival was 69.4%. By the one-year mark, 41% relapsed and 31% of the patients died at KUCC. AML patients actually did a little worse at KUCC. At one year, progression-free survival for AML patients was 57.4%, and overall survival was 66.7%.
By the one-year mark, 43% relapsed and 33% died. Despite being highly ranked and one of the top high-volume transplantation centers in the country, the University of Kansas Cancer Center's data looked worse than that from the CIBMTR. This is because it is a major tertiary referral center for the Midwest. They receive referrals for sicker patients that can't be treated elsewhere, whereas the CIBMTR data includes all centers, including local community hospitals who treat less complex disease. Despite these caveats, the patients treated with INB-100 continue to do well with low rates of relapse, including no relapses in AML patients to date. I'd like to briefly pass the call back to Dr. Vaickus to speak about the analysis of INB-100 results to date and the statistics behind them. Lou?
Thank you, Will.
In addition to presenting the KUCC data side by side next to ours, we and everyone else asks, could the INB-100 data be due to chance alone? We analyzed the outcomes of our data compared with the University of Kansas standard of care experience. Again, with all the caveats of a cross-study comparison and the relatively small number to date of the gamma-delta T- cell group, we applied some statistical analyses to these two data sets. First, we found no differences in the two groups of patients in all of the background parameters like age, gender, performance, status, and the like, so differences in the patients themselves did not appear to influence the results. For progression-free survival, the median PFS was not significant, but this was due to the long progression-free survival in the gamma-delta treated subjects to date, so a median could not be calculated.
The one-year progression-free survival, however, is significant with a p-value of 0.013. For overall survival, the median overall survival is not significant, but again, due to the long overall survival seen in the gamma delta treated patients, so a median not yet reached and couldn't be calculated. For a landmark one-year overall survival, that was trending towards significance with a p-value of 0.059. In summary, gamma delta T cells did not adversely affect subjects based on many safety and recovery measures compared with the KUCC data, and the gamma delta T cell progression-free and overall survival results are very promising. Will, back to you.
Thanks, Lou. We are very encouraged by the continued durable remissions and tolerable safety profile being demonstrated with INB-100. As we've discussed this morning, for AML patients, the biggest risk to survival is relapse.
Based on the data and historical retrospective analyses conducted, we believe that INB-100 gamma-delta T cells are expanding in vivo and persisting to provide continued immune surveillance and potentially eliminating the residual leukemic cells. Thus, no relapse. 100% of INB-100 treated AML patients have remained in complete remission or CR with a median of 20.1 months. A notable improvement over the real-world and retrospective control groups from both CIBMTR and the University of Kansas Cancer Center that we presented today. Furthermore, across all patients treated, INB-100 is demonstrating an overall one-year PFS of 90.9% and overall survival of 100%. For patients who may not have had a clear path forward in the past, INB-100 is providing hope, extending survival, and demonstrating the potential to change the standard of care. What makes this even more exciting is the safety profile that we have observed.
Gamma-delta T cells are showing that they can do the job of fighting residual cancer cells without causing significant side effects like CRS or neurotoxicity issues that have often plagued other cell therapy companies. With that, I will open up the session to questions and answers.
Ladies and gentlemen, if you have a question or comment at this time, please press star one one on your telephone keypad. If your question has been answered or you wish to remove yourself from the queue, simply press star one one again. Again, if you have a question or comment at this time, please press star one one on your telephone keypad. Please stand by while we compile the Q&A roster. Our first question or comment comes from the line of Uy Ear from Mizuho. Your line is open.
Hey, guys. Yeah, congrats on the data. My first question is for Dr. Bishop.
Just wondering, you know, based on the data that you've seen to date, what are you most impressed by? I think you also mentioned that INB-100 could potentially shift post-transplant care. Maybe could you just help us understand what else you or the field needs to see beyond the current data to realize this potential? Thanks.
Sure. Can everyone hear me? That's the first question I have.
Yes, sir.
Okay, very good. Those are really excellent questions. I actually think the data is very impressive. It comes with the caveat that it's in a small group of patients on a relative scale, and I'm sure that's going to be the greatest criticism if this was undergoing review for a manuscript. However, it was really pointed out that it's not even just the age and the performance status, but the biologic characteristics of these patients, including TP53 mutations.
If you just take TP53 mutations alone, it has a horrendous outcome. As a matter of fact, one of my colleagues just published a review article on this in Blood, which is a high-impact journal, and it brings the question as to whether or not we should even be transplanting patients at all with TP53 because the outcomes are so poor. When you take this, the biologic characteristics of the diseases that are being transplanted in this cohort of patients is probably what impresses me the most in the fact that none of them have relapsed. I've dedicated my career to relapse. As a matter of fact, we'll have our sixth international conference on relapse upcoming in Europe this summer. Again, from the first conference I organized at the NIH in 2008, it hasn't changed, unfortunately, in terms of what we're able to do.
That comes to your second question. I really have subscribed to the, I think, the greatest opportunity is in that period of time when the patient is severely immunosuppressed and is not able to benefit from the graft versus leukemia effects of the allogeneic graft because we're suppressing it. All of these methods to try to inhibit leukemic growth through chemotherapy and through some forms of chemoimmunoconjugates have just unfortunately been unsuccessful. Bringing in these gamma-delta T cells appears to—what it's doing is, since they have minimal to no graft versus host disease, we're getting the benefit of what would be the allogeneic graft with them and not being affected by the immune suppression thereon. I think these are impressive results.
I think the opportunity lies in that early peritransplant period, the first 100 days to 6 months, depending upon how much immune suppression they're on. We just need longer term; we need more patients, which you heard is going to occur. If those results are verified, I think this will be a practice-changing effect and actually significantly benefit patient outcomes.
Okay. Thank you. To the management team, Will, maybe just help us understand what are some of the events or goalposts that we should watch out for through this year. Thanks.
Thanks, Eli. As we mentioned, we are in the process of expanding the trial. Feedback that we had received before, as Dr. Bishop just mentioned, was the N was small. As you saw today, we have enrolled 17. There is one patient that is awaiting additional follow-up.
This expansion cohort was designed to go up to potentially up to 25. In addition, we are in the process of working through all the contracting and the scientific review and IRB to add additional centers. That, I think, will bring confidence as we bring multiple centers and more patients onto this trial. Look, I think previously when we had a discussion last year, someone asked, "Well, couldn't you by random chance have all of these patients, in particular our AML patients, do fairly well?" And some of the feedback that had been said before was, "Yes, you can get 10 AML patients to do well, but not necessarily in a row." At this point, as Dr. Vaickus demonstrated today, even with the small N, the p-values of the one-year progression-free survival are looking quite strong relative to the real-world historical controls.
Longer term, as we said, the regulatory path forward is a randomized control study in AML patients. I think based on where our data sits today, it's an exciting time to look forward to additional data, additional milestones, and de-risking this program so that in the future we can initiate that trial. We will have data throughout this year. We are going to have a very busy first half of the year across all of our pipeline programs, and then additional data from this program later in the year. Look out for additional centers and additional updates onto the number of patients that we've added to this expansion cohort and the clinical data. Thank you.
Thanks.
Thank you. Our next question or comment comes from the line of Swayampakula Ramakanth from HCW. Your line is open.
Hi, RK.
Thank you very much. This is RK from H.C. Wainwright.
Dr. Bishop, I have a quick question for you. As you said, managing relapse or not having a relapse is the best thing for a patient with AML. The data today is very encouraging, especially with nearly 91% of this population surviving one year without a relapse. However, as you have stated, some of the naysayers on this data is that it is coming from a single center. With your experience of conducting large multicenter clinical trials, what are your thoughts about how patients are being treated at different centers and what impact could that have on the data comparing to what we are seeing from the single center, especially when you start considering supportive care and also how different centers are able to handle such sensitive cell therapies?
Yeah. That is a very fair statement.
The only thing I can say is that I'm very familiar with the University of Kansas program. I know the medical director, the transplant program director there very, very well. They do, however, a large volume of patients. They really are, on a regional basis, one of the leading programs in the Midwest and serving multiple states. I take a little bit out of that. If you look at their numbers, they're treating what you would think would be the type of transplants they're performing in terms of the haploidentical as opposed to a matched unrelated donor and matched sibling donor. If you look at their volumes in this, it looks like they're treating appropriately.
Again, this haploidentical transplant approach, which had been mentioned before, had been developed by Dr. Leo Luznik as being incorporated as a relative standard of care for patients who do not have a matched unrelated or matched sibling donor. I feel, again, I think University of Kansas' reputation is very, very good. Looking at the numbers, they have large volume. You have to—I mean, you have to start somewhere. All of these do. I am sure you are familiar with, like, Orca Bio, just throwing it out there. You have to start somewhere with a—you have to do a phase one study. Stanford had to do the phase one study, and it was a single institution trial. The results were very, very good, and they took it out to a phase three trial.
I think that's exactly what you're seeing here is they chose—they actually, IN8bio chose a center where they felt that this was an established transplant program. They felt comfortable with the principal investigator, who I can just say is a good guy and is a caring physician and a very responsible investigator. That's what you want in your phase one trial. I think that's what gives you a little bit greater confidence that this, even though it's a single institution, people aren't going to go, "Well." There are certain institutions you go, "Gosh, their data is always better than everybody else's," and when they run it in a trial. I think with—I feel comfortable knowing that the data they're reporting—and again, you can't change the biological characteristics of the leukemia reported. You can't make that kind of stuff up.
That is what gives me confidence that is why this, even though it is a single institution, this data is encouraging. It needs to be replicated at additional institutions, which is what they are going to do. I do not know if they eventually get to a phase three trial. I think that would be great. I just—even the—I would like to see the—I would be happy with just getting a really good phase two trial because we are just so desperate to improve and prevent—improve leukemia-free outcomes and prevent relapse. That was kind of a long-winded answer, but I wanted to address everything that was part of your question.
Hi, RK.
Dr. Bishop.
RK, this is Will. I just want to comment.
Look, we've heard that feedback before; it's a single study, and it's being run at one site, and the results are just because the University of Kansas is really good. In December of 2024, the CIBMTR came out with a review of all national transplant centers. Yes, KU is really good. They are in the top eight of all transplant centers with high volume that transplant over 310 patients in any single year. That is why we pulled the retrospective data. The data that we presented today represents their patients that match our patients pulled from 2016 through 2023, all with a one-year follow-up. There, across the AML patients, I want to reiterate, 43% of their patients relapsed at one year, and 33% of them died. In our AML patients, we've had no patients relapse at one year and no patients die.
Across all of their patients, leukemia patients, 41% relapsed at one year and 31% died. Again, across all of our patients, we're sitting at about 91% relapse-free. Even though it's a single center, pulling all the other comparable patients from their population, our data are actually looking quite well.
No, fantastic. Thank you very much, both Dr. Bishop and Will. Just a quick follow-up. In terms of the expansion phase where you're going to have 25 patients, I'm not sure if you have stated the number of centers that you're looking at. Part B is when you start thinking about the RCT, when potentially could you be starting that trial? Thanks.
We have not announced how many additional centers. We are in the process of bringing additional centers on board. We'll let the street know when we've kind of gotten through that process.
We do have type B guidance. Obviously, it's been a difficult capital markets environment. I think longer term, we want to de-risk the future registrational path forward such that we could raise the funds to run that trial.
Thank you. Thank you very much for taking all my questions.
Next question.
Thank you. Our next question or comment comes from the line of Soumit Roy from Jones Research. Your line is now open.
Good morning, everyone, and congratulations again on the really solid data. Maybe first question to Dr. Bishop. Comparing smaller trial versus potentially a little larger 25-30 patient trial, where do you see the patient variability could come from? Is it the baseline blast count well inside the CR range, or is it the age or genetic background? What do you see is the biggest challenge?
Yeah.
No, the biggest challenges are the—it's really not the age and things. I mean, because it's—I mean, just for transplant overall, it can be. In terms of relapse, it is—if a patient's coming in with increased blast in their bone marrow, that's a bad deal altogether. I mean, the relapse rates in that patient population is over 75%. What the other things that we're looking at is this measurable residual disease status. What that is, is even though a patient could be morphologically—so when they look under the microscope, they do not see an increase in blast even with using immunohistochemistry. When they use either flow cytometric analysis or they use polymerase chain reaction analysis to measure for measurable residual disease, that's really where it plays a significant role.
You're seeing all of these trials report MRD because we know MRD is probably—because most of the patients are going in in supposed remission. If you're MRD positive, you're in a world of hurt relative to the risk of relapse, which, again, in that situation, depending upon the degree of positive MRD, relapse rates is over 50%. You take the prognostic factors that were mentioned before. FLT3, which is seen in 30% of AML, is associated with a poor prognosis. TP53, which also can be a 17p deletion of the chromosome, which the specific mutation is to TP53, these patients, again, have overwhelming high incidence of relapse. Those are the factors that go into, and we're really trying to study relapse closely. Those are the factors that play the most important role.
I'm going to have to drop off in about two minutes because I'm boarding the plane to go to the Tandem Meeting and hope to hear that presentation. No, this is great. Just one quick one. A couple of the patients had chronic GVHD. If you can just compare, contrast, given the standard therapy, how this side effect looks like, is it manageable? Yeah. Infections? Yeah. Chronic graft versus host disease, and this is another area of significant interest to me. It's a major cause of morbidity. It does contribute to non-relapse treatment-related mortality. It's probably in the top five causes. Usually, patients with chronic graft versus host disease, their most significant thing is they can die from infection because they have to be so severely immune suppressed.
As compared to relapse, the number of agents that we have now that have come for the treatment of chronic graft versus host disease in the last 10 years has been remarkable. It kind of makes me jealous that the chronic graft versus host disease research is so advanced beyond the relapse. Now we have—I think there's four approved agents for the treatment of chronic graft versus host disease. There are no agents approved for the treatment of relapse after allogeneic transplant other than CAR T cells for ALL.
Got it. Thank you. We won't keep you from boarding the flight.
Okay. Thank you.
One quick question for the management. In terms of, are you still measuring cell persistence in the periphery, or that's undetectable at this stage? And have you ever disclosed any screen failure rate to enroll these 8, 10 patients?
We are, unfortunately, the protocol, we never expected that the persistence of the cell would go beyond 365 days. Of the patients who we continue to enroll, we are measuring those data. We have not collected all of them yet. Again, to date, all of the patients that we have observed, we continue to observe persistence of the cell now at 365 days. Got it. The expansion phase, the 25-patient, do you have any guideline when we can see the completion? We have said that we intend to continue enrollment and that we would expect a complete enrollment in 2025. All right. Thank you so much for taking all the questions. Thank you. We need to move on. Unfortunately, there are some other additional questions and answers. We're a little beyond our time. I'm supposed to be uptown.
I am speaking on a panel for solid tumor cancers at the BIO CEO conference in less than half an hour. I would like to conclude. We continue to progress toward the achievement of our mission of cancer zero. With the data today, we are demonstrating a mechanism of action that can target residual cancer cells and keep patients in remission. The historical data demonstrated that elevated gamma-delta T cells are associated with better survival outcomes and that we are achieving those elevated levels with a therapeutic that is demonstrating persistence. We have accomplished all of this with a manageable safety profile that has not negatively impacted the quality of life for these patients. Through leveraging our leadership and unique knowledge of the biology and manufacturing of gamma-delta T cells, we believe we are well-positioned as a leader in next-generation cellular therapy platforms for the treatment of cancer.
Today, we are achieving our long-term durable remissions on our journey to achieve Cancer Zero. Thank you for joining us.
Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day.