In8bio, Inc. (INAB) June 2026 Conference Transcript

I'm Robert Laboyer, Senior Biotechnology Analyst at Noble Capital Markets. Our next presenting company is InnateBio, a company developing gamma T-cell technology for cancer and other applications. With us here to present is Will Ho, the CEO. Please go ahead.

Thanks, Robert. Hi, everybody. Thanks for making the time today, and really thanks a lot for noble capital markets for having it. My name is William Ho. I am the CEO and co-founder of Innate Bio. We've been around for about 10 years. Very quickly, my background, I've been in biotech for over 25 years, about 17 years of those spent on Wall Street across investment banking, equity research. I was at one point Bank of America's lead biotech analyst. And then on the buy side, I was recruited to New Leaf Venture Partners where I launched their public portfolio and ran the portfolio for four years. It was about 2014 when I was trying to figure out how do we go from the CD19 CAR-Ts that Kite and Juno came public with to come to potentially off-the-shelf therapies for solid tumors. That's when I came across Dr. Larry Lamb. Larry is our chief scientific officer and scientific co-founder. At that point, he was a professor of medicine at the University of Alabama at Birmingham, and he is one of the world's best experts in the field of gamma delta T cells. He's been working with these cells for over 30 years, since the early 1990s, and in 2019, he resigned his tenure and joined us full-time as our CSO. Today, Innate Bio is the leading company developing gamma delta T cells in both oncology and autoimmune disease. We have a robust pipeline. We are currently heavily, heavily focused on our INB 619. This is our T-cell engager for autoimmune disease and oncology. We have a program, what we call Deltex Aloe. Those are allogeneic donor-derived gamma-delta T-cells in leukemia patients undergoing transplantation. And then finally, our INB 200 and 400 program is our Deltex drug-resistant immunotherapy for solid tumors. Just this This past weekend, we had a presentation at the American Society of Clinical Oncology, and I'll share with you some of that data today. We look for numerous milestones throughout the year, INB 619, we expect to present animal model data sometime late third quarter, early fourth quarter this year, INB 100, we expect to have an update, likely at a medical meeting at the end of the year, potentially at the American Society of Hematology and we look to update our INB 200 and 400 overall survival data at a medical meeting likely in November. And so I want to move forward and a lot of people ask what is the Gamma Delta T cell? The Gamma Delta T cell is a white blood cell. In particular we believe these are one of the most powerful cells in our immune system. When we think about white blood cells, we think of them as the soldiers in our body. They are the soldiers that fight against infection via viruses or bacteria. But what makes the Gamma Delta T-cells special? We thought about this and we put this very simple cartoon together. The Gamma Delta T-cell is the frontline soldier that has the ability to communicate with the entirety of the immune system, and that's what makes them powerful. They're the guys or gals at the front line that have the radio. They can call in support or through artillery or the Air Force and they can identify where the friendly forces are versus the foes to prevent friendly fire. And so we're excited about bringing forward our platform, what we call DeltaX, around the Gamma Delta T cells. One of the leading areas in which there is interest in our program is around t-cell engagers in particular around autoimmune disease this field actually came about from some early data from george shett from the university of erlingan in 2021 and beyond he has published a series of papers in leading healthcare journals such as the new england journal of medicine lancet and nature medicine what he demonstrated is that by using cd19 targeted CAR T's. CD19 is a target that is found on the surface of B cells. We can eliminate B cells to drive immune reset and potentially create cures in autoimmune disease. And so with that data, much of the cell therapy industry went from oncology companies to autoimmune companies in 2023. We thought there's a better way. Instead of the one-and-done CAR-T that caused significant toxicities and have significant drawbacks to both the business of rheumatologists and to female patients, we thought we can create a T-cell engager to deplete the B-cell compartment. This has been an area of tremendous interest. Just this year, there were three major deals accomplished in the sector. Very recently, Candid Therapeutics was acquired by UCB for $2 billion. Earlier, Oro was acquired by Gilead for almost $1.7 billion. And then also, Cali Therapeutics did a deal with Sanofi for $100 million up front. All of these deals done this year. If you look on the right-hand side on the targets, you'll see that all of these targets, It's something found on the surface of a B-cell, either B-cell maturation antigen or BCMA, CD19 or CD20, and all of them target CD3. The estimated total addressable market for autoimmune disease this year is estimated to be above $130 billion and is growing at over 8% a year. And so what have we done different? When we look at the T-cell engagers, over 95% of them all target CD3. CD3 is a target found on the surface of a T-cell. What a T-cell engager, or TCE, does is shown in this cartoon on the left-hand side. It's the molecule in the middle. On one side, we bind the T-cell. On the other side, we bind the target on our target cell of interest, in this case, CD19. and it brings the T cell and the target cell together and triggers activation of the T cell to kill its target. But there are limitations. In particular, when I target CD3 broadly, it targets a whole host of cells and it causes T cell exhaustion, meaning the T cells are tired. They're no longer functional and they can't kill. They also broadly cause toxicities. cytokine release syndrome occurs in 60 to 80% of patients, with about 10% being grade 3, meaning they're hospitalized in the ICU. We believe the limitations in this window creates a necessity to reduce the dose, and accordingly, we're not achieving complete elimination of the b cells and achieving complete immune reset we believe we can do better we have created a novel t cell engager using gamma delta t cells and our technology addresses all three of these issues we have a mechanism of action that does not drive t cell exhaustion gamma delta t cells don't secrete IL-6 and secrete lower levels of TNF-alpha, which I will show you momentarily. And so we don't believe we will have the same risk of CRS. In particular, in the clinic, we have not seen any CRS across two trials to date. And finally, because we can widen the therapeutic window, we think we can dose higher and get deeper B-cell depletion. And so I'm going to talk about our INV619. This cartoon here shows essentially what we're trying to accomplish. The orange represents the T-cell engager. The gray cell on the right-hand side is the T-cell, and your target cell, in this case a B-cell, is on the left-hand side. And so we are bringing the T-cell and the B-cells together and then activating the T-cell to kill. We believe that we have a unique program that can be used for autoimmune disease the challenge in autoimmune disease is that if i get too much cytokine secretion i get too much excitement of the immune system i create all these toxicities and so we created a unique knob a novel engager based on the biology of gamma delta t cells it's shown here on one side we have a binding domain that attracts cd19 in the middle we target gamma delta t cell receptors broadly. And then we have an undisclosed gamma delta T cell expansion domain that drives expansion of the gamma delta T cells. Last year, I told my team, look, this is a crowded field, but if we want to compete, we have to show that since we're not first in class, that we can potentially be best in class. So I had us buy FDA approved and commercially available B cell depletors and ran the assays head-to-head on the left hand side we have amgen's blunitubumab a cd19 and cd3 targeting engager last year it sold about 1.6 billion in sales on the right hand side we have roche's mosnatumab a cd20 a cd3 targeting uh b cell depleter that was recently approved and last year sold about 120 million in sales and in the middle is our imb619 We ran the assays head-to-head. In here, we took the FDA-approved doses of both drugs. We went into the literature and found those concentrations. We did 5x or 5x dilution series across a number of doses. And so we wanted to see both the potential efficacy and the potential risk for cytokine release syndrome. As you can see here, our data is the green line. across every dose, the green line is equal to or below both the yellow and the blue lines, showing at least equivalent, if not greater, B-cell depletion across all these dose cohorts. Importantly, I want to show on the right-hand side of the low dose shown here that mosinutumumab doesn't get full depletion. It's just over 50%. And that's a very low dose, about 28 picomolars versus we want to see the cytokines at a high dose in particular ours on the left hand side which is at 5 000 picomolars that difference is important because of the cytokine data these are some of the cytokines associated with cytokine release syndrome il-17a il-6 tnf-alpha and il-10 we know that il-6 is the validated biomarker for crs when When patients get severe CRS, they are treated with tocilizumab. It's an anti-IL-6 antibody. As I said, gamma-deltas don't secrete IL-6, but they can be driven by other cells such as the myeloid cells or the macrophages triggered by TNF-alpha. As you can see, the levels of TNF-alpha across all doses are multiples less than both blinitunumab and mosinitunumab. As a result, the high dose under IL-6, the left-hand column in green, the high dose at 5,000 picomolars of our IMB619 had the same IL-6 secretion as 28 picomolars of Masu. It's 178 times. In some of the other cytokines, you really have to squint to see some of the green. And so we believe this will demonstrate a wider therapeutic window and less risk of cytokine release syndrome, allowing us to dose higher to get B-cell depletion. We're initiating animal models, and we look forward to presenting updated animal models or our first animal model data later this year. Moving forward, I'll talk a little bit about our leukemia program, IMB100. There was very recently, if you look at our social media, a publication out of a group in Copenhagen in Nature's Journal, Stem Cell Transplantation. It showed that patients with leukemia undergoing transplantation at 28 days who had higher levels of Gamma Delta T cells had better survival outcomes. And we are increasing Gamma Delta T cell levels. Historical data in our trial, we had looked at patients undergoing transplantation with no infusion of gamma delta T cells. Our cohort one that received one times 10 to the six cells and then cohort two that received three times 10 to the six cells. And you can see a dose related increase as far out as one year. We had 49 times higher dose relative to the untreated patients. So we can generate higher levels of gamma delta T cells. This trial is being run at the University of Kansas and Ohio State. Patients with leukemia who have undergone a haplotransplantation with reduced intensity conditioning are given a bolus of gamma delta T cells. And the goal is that the gamma delta T cells will hunt any residual tumor cells and prevent relapse. The last data that we presented has been actually quite a while. It was in January of last year at the TCT conference. There we showed at one year, patients in our trial with acute myeloid leukemia who had received a bolus of gamma delta T cells had no relapses and no deaths at one year. When we looked at the historical data of patients treated at the University of Kansas, it's a tertiary referral center, so they get very sick patients. In the AML patients, at the one-year mark, they typically had about 44% of patients relapse and about one-third die. When we looked at the historical data from the CIBMTR, that's the Center for International Bone and Marrow Transplant Research. It's a database covering all patients across the country who get transplantation. They typically see about one third progress at one year and 25% die. We will present an update in this data later this year, likely at the American Society of Hematology meeting at the end of the year. And we look forward to presenting that data. And then finally, I want to talk about our glioblastoma program. Glioblastoma is such an unmet need. It has been 20 years since the last standard of care was approved. That's known as the STOOP protocol. It's the combination of maximal surgical resection, followed by radiation and chemotherapy, and then maintenance chemotherapy. It was approved in 2005. In those 20 years today, about 14,000 newly diagnosed patients are diagnosed every single year in the U.S. And there's about the same in Europe. So it's about 28,000 to 30,000 patients newly diagnosed with a grade 4 brain tumor every single year. The glioblastoma is the most aggressive of brain tumors. Unfortunately, the standard of care not having changed, the median progression-free survival, or time-to-progression, is only about 6.9 months, and median survival is only just under 15 months. At the weighted average cost of the CAR-T and cell therapies today of just over half a million dollars, this is a significant multi-billion dollar opportunity. And so we're excited about advancing our treatment for glioblastoma. The reality is, in glioblastoma, much of the tumor can actually be surgically removed. Here, this is what we call histopathology. The dark purple are actually the tumor cells. That can be cut out by the surgeon's knife. And the question is, how do we ultimately get at those little residual tumor cells that are found inside the healthy tissue? And the only way to do that, ultimately, is to attack it using your body's own immune system. And that's what we do. We have programmed the gamma-delta-T cells to survive combined dosing with chemotherapy. And we can then have our gamma-delta-T cells hunt out and search for these residual cells. The treatment paradigm is indicated here. everything above the blue line is the standard of care what we've added is below so a patient on surgical resection gets a catheter over 95% of newly diagnosed patients get a surgical resection after a few weeks we take the patient's blood in a process called an apheresis we manufacture the product and cryopreserve it and then the patient undergoes daily radiation and chemotherapy. And then in the maintenance phase, it's 28-day cycles. Every single month, the patient gets five days of chemotherapy. What we've added is across three cohorts, patients received either one, three, or up to six doses of our cells. In glioma and brain tumors, the tumor generally doubles every 50 to 60 days. It's located here in the blue marks on the top. What we've done is we treat the patients roughly two times in every Dublin cycle. Our hypothesis was that if we can just keep the number of residual cells the same, the patient should go longer without progressing and overall survival should be longer. And so we ran this study at the O'Neill Comprehensive Cancer Center and then expanded it in a phase two to Moffitt, Ohio State and Cleveland Clinic. We had treated 17 patients across all of the centers. 13 of them received more than one dose, either the three or the six doses. We've seen no major toxicity, including no cytokine release syndrome or neurotoxicities. We had to suspend further enrollments in 2024 due to capital constraints, but we are presenting data here that we just announced at ASCO. When we look Look across all of our patients, as I said earlier, the historical data since 2005, the median time to progression is 6.9 months and median overall survival is 14.6 months. In our patients that receive just standard of care, the median time to progression was 6.6 months and median overall survival was 13.2 months. So not too dissimilar to what you just saw. In the patients that received 3-6 doses, our time to progression was 13 months, doubling that time, and our overall survival has not yet been reached, but the median is currently at 19.5 and still climbing. We had over half of our patients remain progression-free longer than we expected them to survive. at two years over 40% of our patients remained alive versus just 20% in the patients who received just standard of care and so the traditional analysis the Kaplan-Meier curves you can see here on the left hand side is progression on the right hand side that's overall survival despite the small numbers we have statistical significance on progression and the median overall survival continues to climb. We conducted additional analysis. Interestingly enough, we saw that despite putting gamma delta T cells in the brain, we actually see a peripheral effect. We're impacting the patient's immune system globally. We actually see a dose-dependent elevation of gamma delta T cells and T cells broadly. What's important is that when we looked at survival, we saw that survival was correlated with the number of gamma delta t cells in the blood and the number of gamma delta t cells is correlated with the total area under the curve of the dose received so we were pretty excited about this and so we've taken to additional technologies to look at cells we actually do see cells in the tumor micro environment on the left hand side this is a patient that was treated with standard care, received no gamma delta T cells. At diagnosis and at re-resection, this patient had a relapse. He had a total resection. He relapsed at seven and a half months. You can see there's no difference. Quite easy. It doesn't take an expert to see there's a difference on the right-hand side. That's a patient that received six doses. This patient had a subtotal resection. So because of the location of the tumor, we left tumor behind. quite clearly you can see a difference in the scans. Now we're actually using next-generation technology and AI to map out the the tumor cells here very quickly. We're seeing an increase in T cell infiltration, we're seeing a decrease in spreading, and we're seeing a reduced density of tumor, and we're seeing the granulocytes being cleared out. We can now use AI and actually quantitate this in that tumor microenvironment. We're actually seeing 18 times the number of T cells. We saw a 24% reduction in the density of the tumor burden, and we're seeing less trafficking of the tumor by 82%. Again, as I said, the granulocytes are demonstrating clearance of of that tumor microenvironment, and we saw them being reduced by 90%. So we're pretty excited about this. Not only are we seeing benefits in progression-free survival and overall survival, we're seeing the broad global biomarkers. And then when we look right at the tumors and look at paired samples, we're seeing the differences. So we're very excited, we continue to make progress. We did raise cash at the end of last year. We raised $20.1 million. It was led by Coastlands Capital. If you look at the 13F and 13Gs, it was participated with our new and existing investors that included Franklin Templeton, the Mutual Fund, Aliesca, 683, Stonehine, Delora, and others. We had 21.9 million in cash at the end of March 2026, which gives us runway into the second quarter of next year. And more importantly, we have numerous milestones coming up throughout the remainder of the year. Importantly, a lot of people will be looking for the animal data showing B-cell depletion from our T-cell engager. We will provide an update on our leukemia program at a medical meeting later this year. And in our glioblastoma program, we will update the median overall survival numbers this year while going to the FDA and getting guidance of what registrational path could potentially look like. So thank you very much for your time today. We're very excited. We're the leading company developing gamma delta T cells for both oncology and auto immune disease. We're making a lot of progress. The T cell engager is unique with a differentiated mechanism and the ability to deplete b cells without significant toxicities on the other side in oncology we have two programs demonstrating long-term durable remissions more than four years in both aml and glioblastoma we have an experienced team we continue to execute we continue to develop our milestones i invite you to to set up a meeting contact us continue to do your research and your diligence, and I welcome you to join us on our journey. With that, I'll see if there's any questions. Thank you.

Well, thank you very much, Will. That was a really interesting presentation with lots of really interesting data, so I could probably discuss this with you for the next hour, at least. One of the things about the GBM program is that having followed drugs in development for GBM. Most are improvements on existing drugs, but very few are actually doing what you're doing and really coming up with a novel therapy. The survival and some of the data you presented is really not only significant, but very clinically meaningful. So I'm very much looking forward to the updates in that program. One of the things about the drugs in development for GBM is that it's often seen as a first indication in other tumor types. Is that true here too?

Yes, I believe it is. Look, the first thing is people often ask me, why did you go to GBM, right? And the reality was I was trying to figure out how do we ultimately develop a potentially over time off-the-shelf therapy for solid tumors and the first question I asked is well what solid tumor can I deliver cells to that wouldn't be allo rejected you know what we've seen with the allocartids is if you're rejected within 10 days it was a very expensive infusion that had no efficacy right and so historically the three tissue systems that were considered immune privilege for the brain the eye and the testes about two weeks ago, we had an R&D day. At that R&D day, please do go to the investor section on our website and you can watch it. We actually had Dr. David Reardon. He's the chair of neuro-oncology at Dana-Farber come speak on our behalf. And as he said, the top three concerns about glioblastoma are delivery, delivery, and delivery. And then the fourth is heterogeneity. And so for us, we we knew these patients undergo surgical resection you know 90 percent of patients will relapse within one to two centimeters of the original resection cavity meaning that relapse is not due to metastases but is due to microscopic local residual tumor that we didn't see and so we knew we can insert a catheter and by doing that we bypass the liver you know when i was on the investment side one of the things that i learned was that if my soldiers are not on the battlefield that i think i am i'm in trouble right so we we bypass that question my approach is always eliminate as many of the unknown unknowns eliminate as many of the landmines that i'm going to step on or have the potential to step on then i'm more likely to be able to get all the way through um second heterogeneity we knew we had to do deal with heterogeneity and the gamma delta t cell can sense that through its unique receptor repertoire our particular mechanism is not limited to gbm but is actually relevant across all cell types in our body we trigger what's known as the dna damage response pathway to up regulate immune signals and that is a fundamental basis um function in our body because otherwise we'd all be walking around with tumors yeah okay Okay, great.

All right. Just in the interest of time, I will refer everyone to that R&D presentation that you refer to and look forward to following these milestones. Very interesting and looking forward to it. Thank you for presenting today.

Thanks, everybody.