Good afternoon, everyone, and thank you for joining the 27th Annual H.C. Wainwright Global Investment Conference 2025. My name is Daniel Smith, and I'm an H.C. Wainwright Equity Research Associate in Biotechnology. With that said, let me introduce our presenters for the session. I'd like to welcome Michael Breen, Executive Chairman and CEO of GT Biopharma, and Dr. Jeffrey Miller, Consulting Senior Medical Director of GT Biopharma. We're developing trispecific killer cell engager camelid nanobodies to combat cancer and HIV. GT Biopharma trades on the NASDAQ under the ticker GTBP. Gentlemen, the floor is yours.
Thank you, Daniel. Welcome, everyone, to the GT Biopharma presentation, and thank you for your interest in our company. My name is Michael Breen. I'm the Executive Chairman and CEO here at GT Biopharma. As you can see, we're currently displaying the disclaimer with regard to the presentation that we're about to go into, so please take a moment to familiarize yourself with that disclaimer. Before we move on to the main presentation, I would like to highlight a number of important points relating to our company, which Dr. Miller will come on to in due course. We are a clinical-stage oncology company and are currently conducting a phase I trial for blood cancer and acute myeloid leukemia in particular.
Our technology is a platform technology, meaning we use the same technology for other molecules in our platform, but we simply change out the binder part of the molecule depending on the cancer that we are targeting. We have in excess of six candidates currently in our pipeline. Finally, we are also targeting to file an IND for solid tumors by the end of the calendar year, and the solid tumor oncology market is exponentially greater than the blood cancer market. I would like to pass over to Dr. Miller. He is a key opinion leader in the NK cell and NK engager space, and he serves as our Consulting Senior Medical Director here at GT Biopharma. He is also the current Director of the Masonic Cancer Center at the University of Minnesota and NCI-designated Comprehensive Cancer Center, and a Professor of Medicine at the University of Minnesota.
He has more than 20 years of experience studying the biology of NK cells with over 170 peer-reviewed publications. Dr. Miller.
Thank you, Michael. Thanks everybody for being here today. I just wanted to really quickly get into a brief introduction and then some of our science. As many of you know, we're talking about natural killer cells today. NK cells are white blood cells. We all have them. Their role is really to recognize and kill cancer cell targets. This is a depiction of an NK cell under an electron microscopy, recognizing a tumor target. What I'm going to talk about is this handshake here. This is really our tri-protein, really making an immunologic synapse with the NK cell surface to the cancer target in vivo. As Michael already mentioned, we have a number of different targets that are under development. I'm going to talk very briefly about GTB-3650, which is ongoing now, and this started with GTB-3550, and then our different solid tumor TriKEs.
Just to give you a very brief introduction, our trispecific killer cell engagers have three functional components outlined here. In orange, we have an anti-CD16 ligating antibody, to really one of the most prominent protein activating receptors on the NK cell surface, which is CD16. We then bring an IL-15 molecule to the immunologic synapse, and again, a number of different tumor-associated antigen targets. This cartoon really supports how that immunologic synapse is formed. I'm going to talk about several of these targets in the interest of time, really focusing first on the CD33, the myeloid leukemia cell target, then the pan-solid tumor target. At the end, I'm going to briefly mention our interest in targeting B-cell malignancies and autoimmune disease. The structure of our engagers is really one of two types, either a single chain Fv or a nanobody.
I'm going to talk about briefly the advantages of the nanobody platform, which we have discovered really enhances the potency of these molecules compared to the single chain Fv antibodies that we used previously. Just as a very basic primer into what is going on here in this microwell, we have three AML tumor targets labeled in green and one NK cell labeled in blue. In the gray background, we have added this TriKE material to this microwell, and this is a time-lapse videotape of really the concept of serial killing. You see one NK cell eventually going on to kill other targets. If I showed you a control well without the TriKE, we don't get this serial killing phenomena. This is critically important, and we think that this is going to correlate with our clinical activity.
The first thing we brought to the clinic, I think this was about roughly 18 months ago, is GTB-3550, and that was a single-chain antibody ligating the NK cell, a single-chain antibody ligating CD33, which is on the leukemia blast, and again bringing in a wild-type IL-15 molecule to co-stimulate the NK cells. The design of the initial study was shown here. We give three weekly blocks of 96-hour continuous infusions. This is really designed much like blinatumomab, which has been on the market from Amgen for a number of years, just giving this as continuous infusion for safety and other reasons to really upregulate the immunologic response in a very controlled way that the FDA has been very familiar with and working with us on. We then do a disease reassessment. I'm not going into the details, but this was well tolerated, and there were no safety issues.
Probably the most important thing we learned from this first-generation TriKE is the ability to absolutely increase or expand the number of NK cells in the body. This is very different than other NK cell engagers that do not have the IL-15 component. CD16 ligation alone is not a good enough signal to expand NK cells in vivo. If you look prior to therapy, everybody's NK cells were very, very low. It's interesting at day 3, 10, and 17, while the infusion is going, these NK cells get pushed out to the peripheral circulation, get pushed out into tissues, and are really not found in the blood. On day 8, 15, or 22, three days after the infusion stops, we get this really tremendous rebound and in vivo expansion of NK cells.
The most benefit of this is really tweaking the effector-to-target ratio to have the best activity on the cancer cells. With fulminant leukemia, this is really a big important issue. This preliminary data has been reported by GT Biopharma. As you can see, there were four patients, one at the highest doses, starting at 25 mcg per kilogram a day that had blast cell reductions. This is looking at just an absolute blast readout after GTB-3550 therapy compared to before. This is really proof of concept that there's a hint of clinical activity, and this is really what brought us into our next version of the TriKE molecule. We call this a second-generation camelid or nanobody TriKE because the recognition domain for CD16 is a small single-chain antibody that's much, much more efficient.
I'm going to talk in a couple of slides about our dual camelid engager, also targeting the pan-tumor antigen B7-H3. The data that is most supportive of the advantage of this camelid sequence, which is really the proprietary ownership of GT Biopharma, is showing that if you take the camelid TriKE, and that is shown here in the purple compared to the first-generation TriKE compared to no treatment, and this is in a leukemia model. Once we add that camelid version, we see a marked increase in potency, as you can see here at the multiple doses. This is just highlighting normal antibodies and camelid antibodies that have a single recognition or VHH region. This was really the rationale for going to the second-generation platform. This is our ongoing clinical trial with GTB-3650. This is designed to give therapy in two weekly blocks, now a 72-hour continuous infusion.
Based on our GTB-3550 experience, there are then two weeks off, and the goal is to really repeat at least two cycles of therapy with the option of going up to four cycles of therapy in this next trial. Highlighted in red here, we told the FDA that we have a much more potent molecule. It's not a huge surprise that they made us start at a very low dose, and we're currently enrolling patients at the five microgram per kilogram per day dosing. We've done this thus far without meeting any toxicity whatsoever. There's no dose-limiting toxicity, and we haven't even identified fevers to date. We do predict that we're going to have to get into these higher doses to really see a clinical signal, and we're quite excited about that. Besides the clinical signal, we're already seeing early signs of the sustained immune activation.
This is a proliferation curve measuring Ki-67 by flow cytometry. At baseline, there's very little proliferation, but as early as three days of the first continuous infusion, you see that this markedly goes up and really stays up for the rest of the treatment block. We do know that the biologic activity of these TriKE molecules stays on for a longer period of time, even when the drug is stopped. We think that there's some depot effect in the body. This has really got us interested, and Michael already mentioned this. Solid tumors are much, much more common than hematologic malignancies, even though I'm a hematologist, and acute leukemia has been a major interest of mine. This is really what led us on to starting to study a novel pan-tumor antigen called B7-H3. This is not unique to us.
There have been a number of companies that have validated B7-H3 as a promising pan-tumor antigen in the format of ADCs, bispecific T-cell engagers. To our knowledge, this is the first trispecific NK cell engager targeting this B7-H3. We developed this TriKE, which is shown in this cartoon here. We showed that the camelid version, which is our proprietary sequence engager, binds to B7-H3 on tumors. That's shown here compared to a negative control cell line that knocks out this B7-H3 protein, really showing exquisite sensitivity of this target. To make a long story short, we've been trying to study these tumor masses. This is a solid tumor mass of prostate cancer cells, either treated with no treatment, interleukin 15 alone, or the B7-H3 TriKE. One of the most interesting things about this movie, and you can see there's a time lapse here.
If you can see this little box at the right-hand side, you see that with no treatment or IL-15, you see that the prostate cancer tumor mass labeled in red stays there. When the cells get killed, you could see that this target goes away. We're super excited that with this control, it's really that engagement of CD16 and the IL-15 co-stimulus that causes the tumor to be obliterated. The same thing is true with a tighter spheroid mass. This is a head and neck cancer line, and you could see that it's really only this condition. These black dots here are the NK cells added about three days of spheroid, but what the TriKE does is it allows the NK cells to really penetrate into that tumor and totally eradicate it.
The design of the trial that's going to be presented to the FDA and submitted in the next several months is really outlined as subcutaneous therapy. We realize that in the solid tumor setting, and we talked to a number of KOLs, that it's critically important to deliver this as outpatient therapy and to get away from really the cumbersomeness, I guess, if you will, of continuous infusion. We're going to give this Monday through Friday as a subcutaneous injection. This is supported by preclinical data, which I don't have time to show you here. We're going to give two weeks of therapy. This hopefully will eventually be managed on the outpatient basis, two weeks off, and then we're going to allow this to be repeated for up to four cycles or even longer if there's clinical benefit.
We currently have seven cohorts that we're planning to do a basket trial in this setting to have the most shots on goal to try to pick up which of these diseases we're going to see clinical activity. I think at least for the company, that is going to define our FDA approval developmental path, which we hope to make progress on in the next couple of years. What's unique about our TriKE molecules? We're the only immune engager with interleukin 15. Remember, this is really a combinational therapy, even though it's a linear protein sequence. We know that IL-15 provides proliferation. We know that there are other engagers out there, which many of you are familiar with. Affimed had a CD16 engager, and remember, CD16 ligation does not induce proliferation. Other engager platforms do not either.
We've tested these other components, and none of them are as potent as our IL-15 secondary stimulus, which we have in our TriKE platform. I do want to emphasize that this is protein therapy to create immunologic synapses in the body. This is not a cell therapy. These are a couple of the different cell therapies that have been out there. We're trying to achieve the goals based on the scientific progress we made in the body, which is going to be a much simpler platform to deliver therapy rather than to give it cells. We do acknowledge that there may be combinations of our TriKE molecule in a cell therapy platform that may be advantageous. At least preclinically, we've been willing to explore these as well. The last thing I want to mention now is really targeting CD19.
As many of you are familiar with, this CD19 targeting is really driven from the CAR T-cell data, which is really quite robust. I think the biggest discovery, starting in the New England Journal of Medicine a couple of years back, is that if you target CD19 in patients with lupus or lupus nephritis or a number of different autoimmune diseases, you can help the underlying autoimmune pathology of that disease. We've started to test our CD19 TriKE. We have a lot of data testing this in lymphoma and chronic lymphocytic leukemia, at least preclinically, and this data has been published. This is really our first piece of data testing GTB-7550 and its ability to deplete normal B cells. This is looking at treatment of normal B cells for 24 or 48 hours with either no treatment or a CD19 TriKE.
This is an in vitro experiment showing that we absolutely have the ability to kill normal B cells. These are not malignant B cells, and we've started early clinical testing in animal models to show that we could B cell deplete in vivo very potently as well. With that, I am going to wrap up a little bit, and this is the contact information from GT Biopharma. When I see you live, I hope to be able to take questions. Thank you.