During the presentation, please feel welcome to submit questions using the Zoom Q&A interface at the bottom of your screen. After the presentation, we'll open to your questions. With that, Will, I'll turn it over to you.
Great. Thanks, Alex. Hi, everyone. Great to be here. We've had some great meetings today, and we're really happy to be introducing IN8bio to the broader group. IN8bio today is a clinical- stage biotech company developing novel treatments for both autoimmune disease and oncology powered by gamma- delta T cells. We are one of the world's best experts in the field of gamma- delta T cells, and we believe these are powerful cells that can help us cure and treat disease. Myself, I am the co-founder of the company. My background, I'm a biochemist by training. I've been working in biotech for over 25 years. 17 years of those were spent on Wall Street. I started off at Cowen in a healthcare investment banking group.
I ended up in equity research, was eventually Bank of America's lead biotech analyst, and then was recruited to New Leaf Venture Partners to launch and run their public efforts. New Leaf Venture Partners was the spin-out out of the Sprout Group, which was DLJ's venture arm started in 1969. I started IN8bio through a fund that I had launched called Aleph Point Capital. In about 2015, I met our scientific founder, Dr. Larry Lamb. Dr. Lamb is one of the world's best experts in the area of gamma- delta T cells. He's been working with these cells since 1992. When we first met, he was a professor of medicine at the University of Alabama at Birmingham, and he resigned his academic tenure and joined us full-time as our Chief Scientific Officer in 2019. Very recently, we announced that we brought on board Oksana Poliakova.
Dr. Poliakova is also an expert in the field of gamma- delta T cells, but she focuses mostly on T cell engagers and antibodies. We recruited her from LAVA Therapeutics, where she was the Chief Scientific Officer. LAVA was responsible for the first generation of T cell engagers, and previously, she worked at both Adicet Bio and GammaDelta Therapeutics, two gamma-delta T cell companies that were acquired by Takeda in 2021. She started her career at GSK. We're excited in finding therapies to treat both autoimmune disease and oncology. We believe these are two sides of the same problem or essentially two sides of the same coin. On one side, I have an immune system that is underactive, and the immune system fails to identify and to kill transformed cells that ultimately grow into cancers.
On the other, I have a patient whose immune system is too strong or too robust and starts attacking itself, triggering autoimmune disease. We believe we can use gamma-delta T cells to address both of these issues. Now, why the gamma-delta T cells? Since the 1960s, we've used the euphemism, the war on cancer, and part of that is because immune cells are our soldiers. We use immune cells to attack the targets in our bodies. There are numerous types of white blood cells. We have the CD8 T cell. We have the regulatory T cell. We have the CD4 helper T cell. We have natural killer T cells, and we have the gamma-delta T cells.
These are all individual soldiers within our immune system, and we think the gamma-delta T cell is the most powerful because it is the frontline soldier who can see the battlefield, but also the soldier that has the radio and can communicate with all the rest of our armamentarium. We think that is the power of the gamma-delta T cell. Because at the end of the day, if you think of our immune system, it's not just a single instrument in the symphony, right? If you think of one immune cell as, for example, the cello. The cello itself, while it can create music, doesn't make all of the symphony. It's how the individual instruments from the brass to the string to the percussion all come together to form the symphony and the music.
Our core thesis is we can use these powerful cells to coordinate all of the immune system to target both autoimmune disease and cancer. Today, I want to start with our discussion on our T cell engagers. In particular, T cell engagers for autoimmune disease. Autoimmune disease has been an area of tremendous interest of late. In particular, a gentleman by the name of Georg Schett from the University of Erlangen-Nuremberg in Germany, published in The New England Journal of Medicine in 2021 unique data using a CD19 CAR T. CAR T is a chimeric antigen receptor T cell. Here what we do is we take a blood draw from an individual.
We genetically modify those white blood cells outside of the body to target a specific target, in this case CD19, and then we reinfuse them back into that individual to hunt and seek down that target. In oncology and in some autoimmune diseases, the results have been remarkable, essentially cures of disease. What Dr. Schett demonstrated is that we can use these CD19- targeting CAR Ts to target and eliminate B cells. B cells are a specific subset of white blood cells in our bodies that actually drive autoimmune disease. By resetting the immune system, we can essentially cure certain severe autoimmune diseases. This has generated a tremendous wave of interest in autoimmune disease and in approaches that target B cells. As I said, autoimmune diseases is generally driven by B cells that produce monoclonal antibodies that attack our own body.
It is depicted here where the B cell is represented by the purple cell. Autoimmune disease is a tremendous unmet need. It impacts one in six women in their lifetime. It is estimated to impact 24 million Americans every single year. Treating autoimmune disease has come up with numerous blockbuster drugs, including Humira, Enbrel, Rituxan, among others. So a tremendous unmet need. On the T cell engager side, a tremendous amount of deal flow just this year. This year in 2026, earlier in the year, we saw Ra Pharmaceuticals acquired by UCB for a total consideration of $2.2 billion and $2 billion upfront in phase I. [Arcellx] was acquired by Kite Pharma Gilead for $1.7 billion, also in phase I. We also saw [Kali Therapeutics] do a deal with Sanofi for a partnership for $180 million upfront in phase I.
In fact, just last week, GSK did a deal with a Chinese company for a preclinical asset for total consideration of $750 million. Also, a tremendous amount of deal flow and current interest in T cell engagers. What I want to note is on the right-hand side, the target. BCMA, CD19, CD20 are all targets found on the surface of B cells. What you will note is all of these were targeting B cells, but they all use another target called CD3, and that is important. The vast majority of people creating B cell depleting therapies target CD3. So this cartoon on the left-hand side depicts essentially what we are trying to do. I have a target, either BCMA, CD19, or CD20, which is found on the surface of the B cell.
On the other side, I have another receptor that is found on the surface of the T cell, in this case, CD3. We bring the T cell together with the B cell so that the T cell can kill and eliminate the B cells and drive an immune reset. What we found is that immune reset can potentially cure certain autoimmune diseases. Now, what is the challenge of targeting CD3? Targeting CD3, the challenge is, as I showed you earlier in this picture of different immune subsets, CD3 can be expressed on every single one of these subsets, so every immune cell. So when I target CD3, I activate all of them. As we talked to some investors this morning, I used a new analogy.
I have been undergoing some small renovations at home, and if you think about all the immune cells as appliances and electricity and lighting, by targeting CD3, it is like I turned on every single appliance and every single light, the air conditioner, every heater, portable heater, and an induction stove in my house at the same time. One risk is by doing that, I trigger the main breaker. I can trigger the breaker, and I cause everything to turn off. In terms of our immune system, that is exhaustion.
I am overwhelming the system, the breaker trips, and everything turns off. On the other side, I have another risk. In fact, this risk may be actually more dangerous, and that is that when I turn everything on at the same time, I might trigger an electrical short circuit that results in electrical fire in the wall and burns down the whole house.
And that's when we have an immune response that is so strong it causes something called cytokine release syndrome, or CRS. When we develop CD3-based engagers, CRS impacts 60%-80% of the patients, and 10% are Grade 3, meaning they're potentially in the ICU. Because of that, we can't dose high enough. We have to reduce our dose in autoimmune disease because where I will tolerate toxicities if I have cancer because I'm going to die, I can't do that if I have an autoimmune disease like rheumatoid arthritis and my knees hurt. We want to be able to use gamma-delta T cells and the biology behind gamma-delta T cells to be more precise so that we can dose higher and target more of the B cells. We created a unique engager.
It's a first-in-class engager that targets CD19 on one end, the gamma-delta T cell receptor on the other end, and we have a unique expansion domain, what we called here in this picture GDED, that causes gamma-delta T cells to expand so that we can better eliminate our target cells, in this case, the B cells. What we want to do is use the biology of gamma-delta T cells as a scalpel and not the sledgehammer. There are a lot of people developing CD3, and they're doing unique engineering, like masking and cleavable linkers and affinity tuning the binding domains. But at the end of the day, I can do all kinds of things, but a sledgehammer remains a sledgehammer when I need a scalpel. We're very excited. Last year in the fall at the American College of Rheumatology, we published our first data.
I'll get into some of the scientific data here. PBMC is peripheral blood mononuclear cells. That's essentially just blood. CD19 is a marker found on the surface of B cells. You can see here the CD19 positive cells in blood is under 1%, here, 0.77%. What we did here in the middle is we added a CD19 positive leukemia cell line. It's a B cell tumor called NALM-6. As you can see, when we dropped it into that blood culture, the numbers of CD19- positive cells increased to 66%. So 2/3 of our culture are now CD19 positive. All we did is we took the same culture, and we dropped in our engager, our INB-619. What you see is the CD19- positive compartment drops. It's now below even 1%.
It's actually 10x lower than the original culture, demonstrating that we can eliminate all of the B cells. This was the first marker showing that we can potentially have efficacy. But then what we're trying to do is see, can we have a wider therapeutic window? Can we avoid the toxicities? Here we took blood from three healthy donors. We did an increasing dose of our T cell engager, as you can see on the bottom. In red, what we're looking is at the chemicals or what we call cytokines that drive killing of the target cells. You see a nice linear increase in that deep red crimson color, showing that we have what's called a linear dose response. The higher the dose, the deeper the red.
Now, what's interesting is on the cytokine release syndrome causing cytokines like IL-6, you can see the blue is flat across the board. There is no dose response because we actually don't secrete any IL-6 from gamma-delta T cells. This was the first hint that we can create a T cell engager that potentially has better toxicity profile and could potentially, we believe, be best in class. But how do we show that? Last year, I went to the team and said, "Look, this is exciting biology, but if we're going to be behind other people, we have to show that we can potentially be best in class." We went out and bought Amgen's blinatumomab and Roche's mosunetuzumab, two FDA-approved drugs, one targeting CD19, the other targeting CD20. On the left-hand side, you can see the structure of blinatumomab. On the right-hand side, mosunetuzumab.
In the middle, our own structure. What we did is we went into the literature and found the FDA-approved doses of both of those drugs, and we did a series of 5x dilutions. We diluted from their FDA-approved dose by 5x , and by 5x , and by 5x again. Then we took a very high concentration of our own therapeutic, and we did the same dilution series. We ran those assays to see how effective is our killing. You can see here, at every single dose, although it takes a day or two longer because we need to expand the gamma-delta T cells first, the green line can fall equivalent or below both the yellow and the blue lines, demonstrating that our INB-619 can be equivalent or better than two FDA-approved drugs at depleting the B cell concentration.
Now, what I did say earlier, if you look at our high dose, we started really high, 5,000 pM or 5 nM, because we want to look at the cytokine profile and look at the risk of toxicities. On the right-hand side, I'll point out mosunetuzumab in blue. That dotted line doesn't go below more than about 55%. You're getting just over half of the depletion of the B cells, and that's a very low concentration of mosunetuzumab. It's a subtherapeutic dose. You can see the number there. It's 28 pM. Those numbers are important because next what we did is we went to go look in those cultures at how much of those chemicals, those cytokines that drive cytokine release syndrome are we causing. In all of these, our figures are those in green.
As you can see, in some of these, you have to squint to actually see any green. We know IL-6 is the validated biomarker for cytokine release syndrome. Why do we know that? When patients are in the ICU and near death's door, we actually treat patients with a drug called tocilizumab. Tocilizumab is an anti-IL-6, and so if we don't have IL-6, we don't need the anti-IL-6. What was interesting in those numbers that I just showed you is that our high dose at 5,000 pM is showing the equivalent IL-6 production as the lowest dose of mosunetuzumab. 5,000 pM show the same cytokine secretion as 28 pM, 178x difference, demonstrating that we can widen the therapeutic window. We're really excited about our T cell engager. We think we have unique properties that make our therapy potentially best in class.
We can get deep B cell depletion. We can target tissue-resident cells because of the properties of gamma-delta T cells. We do not secrete IL-6, so should not be impacted by cytokine release syndrome, but we also increase the numbers of gamma-delta T cells. Gamma- delta T cells are innate immune cells that have both antibacterial and antiviral properties. We think we can actually eliminate, not eliminate, but reduce the infections that are associated with the use of T cell engagers. We are excited. We expect to present our first animal data this fall. Keep a lookout for those. Next, I want to talk a little bit about our glioblastoma program. This is one of our programs that is originally in cell therapy. Glioblastoma is a disease that impacts almost 30,000 Americans and Europeans every single year.
At the current prices of cell therapy, it is a potential blockbuster, and the standard of care has not changed since 2005. Patients generally live about 15 months and unfortunately progress by month seven. In July, we published our phase I data in the Journal of Clinical Oncology. This is one of the leading peer-reviewed journals in the oncology landscape. Our therapy, the patients are newly diagnosed. They get a surgical resection. We insert a catheter. After a three to four week break, we take a blood draw from them. We genetically engineer their cells to be resistant to chemotherapy so we can combine dosing. They go on with their standard of care therapy, and in the maintenance phase, it is six cycles, 28-day cycles. It is five days of chemo, followed by a 23-day break.
What we did is we added an injection of our gamma-delta T cells directly into the catheter that we inserted into their brains. The phase I/II study was conducted, and we treated patients across four centers at UAB, Ohio State, Moffitt Cancer Center, and Cleveland Clinic. We demonstrated we can double time to progression.
We did not see any major adverse events, and in the clinic, we have never seen a case of cytokine release syndrome to date. No major safety concerns. The general hypothesis was that if we treated with the standard of care, we know glioblastomas double every 50- 60 days. The brain does not have a lot of space. The thought was in the maintenance phase, if we were treating every 28 days, if all we did was keep the number of residual tumor cells the same, we could extend the time to progression.
If we shrank it, we can improve that much more. The summary of the data that was presented this year at ASCO, our median progression-free survival went from 6.6 months- 13 months. Our median overall survival went from 13.2 months-19.5 months . We have not hit median yet. This was as of May 15th. We expect to present data later this fall, and historically, we have presented at Society for Neuro-Oncology or the SNO meeting that occurs in November. The traditional Kaplan-Meier curves look like this. Even despite the small numbers on progression-free survival, you can see the separation of the curves. We will provide an update on overall survival.
What we have said is we expect to go to the FDA this year and provide guidance on what the potential registrational path forward is. Then we will come to the street and see what is the possibility of bringing forth a program and what is the best mechanism. Our goal as shareholders aligned with all of you is to find the path forward that has the greatest returns over the shortest amount of time for the least amount of invested capital. We did do a financing last December. We brought in just over $20 million. That deal was led by Coastlands Capital. Coastlands, who was founded by Matthew Perry, who was president of Biotechnology Value Fund or BVF, a biotech specialist over the last 25 years.
It had participation from the likes of Alyeska, Franklin Templeton, the mutual fund, and a bunch of healthcare specialists, including 683 Capital Management, Stonepine Capital Management, Dellora Investments, and others. That deal came with only pre-funded warrants, no warrants. There is a second close driven by our animal data coming up over the next couple of months, which could bring in additional $20 million that would get us all the way through the IND. We are excited. We have numerous data sets.
We have the cash on hand to hit our milestones. We expect to present the additional animal data this fall. We are excited. We are in a hot field with T cell engagers. Our gamma-delta T cell biology is unique. We recognize the challenges in cell therapy that is occurring across the landscape, but our clinical trials demonstrated activity in cancer patients.
We are demonstrating the ability of the gamma-delta T cells to kill their targets and to reduce the tumor burden and have long-term survivors. Our programs are designed to be safer and to widen the therapeutic window. We are excited to be announcing numerous catalysts this year, and I will pause there and take questions. Thank you.
Thank you, Will. That was a great presentation. I will give one reminder that folks can submit questions using the Zoom Q&A interface at the bottom of your screen. I will kick us off. One thing I wanted to just point out, right, is that you guys have been a gamma-delta T cell company for years.
Yes.
There's also been years of skepticism along the way. I am curious to hear what some of your recent publications and data releases have changed about the way partners or investors have looked at you.
I think that the challenge was everybody historically was focused on the CD8 and CD4 T cells, right? Part of that was because of the CAR T data, because everybody uses CD4 and CD8 T cells. Quite frankly, early on, the reason why those were used was because they are plentiful. They encompass about 70% of the immune cells within our body. Quite frankly, when I was doing cell therapy, when I start with the 70% number, it is easy to get a dose, right, because I started with 70%. If I increase it by 5x, then I have quite a large number of cells. The gamma-delta T cells are much less in number. In fact, in healthies, they encompass only about 1%-5%.
If I am only at 1%-5%, I need more than 12 to X the dose just to get to the equivalent starting place. They are hard. But what was not recognized, I think, it was thought that, "Oh, the plentiful cells are the powerful ones." I actually have a friend who was a longtime investor who is actually an immunologist from Stanford, and what they said was, "Actually, people are mistaken. It is the cells that come in low numbers that are the ones that are really powerful." Right? As I said, the reason why we like gamma-delta T cells is because they are the soldier on the front line of the battlefield that can see the battlefield, that can identify the locations of friendlies versus foes, and to call in the entirety of the armamentarium.
The most feared person on the battlefield is the one with the radio, right?
Absolutely.
I think our publications are demonstrating. I think for a long time people would say, "Oh, it'll be the next quarter that the data will fail just like everybody else. It'll be the next quarter, next quarter." Now we're getting to years, and the data remains consistent. I think we are consistently demonstrating that if you use gamma-delta T cells properly based on their biology, that you can have robust results where you are showing activity like this. Right now, I think the challenge with our market cap is less with our results and of late is just cell therapy. Cell therapy has been a very challenging area. Even in the last month or so, we saw Novartis and Bristol cancel a couple autoimmune indications.
In the last three weeks or so, we saw Selecta, Arsenal Bio, TScan kill cell therapy programs, and that's just because of a malaise around cell therapy. We saw that coming, which is why we pivoted and developed our T cell engager. T cell engagers are similar to monoclonal antibodies, multibillion-dollar platforms, and ones that sit more aligned with pharma's methodology with respect to allogeneic or off-the-shelf dosing and with their commercial distribution pathways.
Great context. Thank you. Question from the audience, too, about funding and capitalization. At what point or at what stage are you in talking with larger, more mature pharmaceutical companies to help fund research or out-license some of what you're working on?
Look, we constantly have ongoing discussions with pharma and biotech, both large and small. I think when we look at our platforms, I think for glioblastoma, if there is the potential to partner something like that, I think we have to get guidance from the FDA on what the registrational path and what a trial will look like so that we know what the bounds are. We're in the process. We've been very thorough this year on analyzing the landscape and what potential registrational pathways may look like. We expect to announce that later this year, and then we can start having some of those discussions there. I think there may be some potential to out-license our leukemia program.
We've demonstrated the safety of allogeneic cells, and we have some really long-term survivors who are out five and six years who probably should not be today.
Finally, on the T cell engager space, I will say there is a tremendous, as we saw with the deal flow, there is a tremendous amount of interest in T cell engagers. It seems every month there is another deal on the T cell engager space. But what we have done here is unique and novel. It is a little bit different than what everybody else has said. There were a first generation of gamma-delta-based T cell engagers like LAVA that did not work. There were not enough gamma-delta T cells to expand. We knew that, and we addressed that with our expansion domain. We will show data we can generate the expansion of, or we have shown data we can generate the expansion of gamma-delta T cells.
We will show our first in vivo data later this year, and I think we want to just show the first in vivo data. Much of the data I just showed you today was in vitro in culture, and now we have to prove that in vivo, and I think there will be tremendous amount of interest.
Helpful context. Thank you. Maybe just as we come up on time, for folks who may be familiar with newer generation immunology, oncology treatments, and maybe even cellular therapies and T cell engagers, but might be new to IN8bio, what would you say to them about why now could be a great time to consider investing?
Look, I think the first in vivo data, the first proof in concept in animals is critical, right? Because we showed the biology, the mechanism of action, all of that works. Some of what we did is very new, and some people just want to see, "Oh, I want to make sure you are not killing all the animals." Right? So when you have a first in new biology. Look, I think everybody is going after autoimmune disease.
Everybody is going after CD19, CD20, BCMA. Almost everybody is doing their own flavor of CD3. As I said, you are turning on all the lights, all the appliances, everything at one time. Our industry tends to go and everybody follows whatever the flavor of the month is. Right? Right now is CD3-based engagers, and you are doing all kinds of engineering, masking, cleavable linkers, affinity tuning, whatnot.
We looked at it and looked at the biology of gamma-delta T cells and said, "We can do things better." I always found that when I was investing that the biggest returns aren't generated when I'm surrounded by a crowd and with everybody. You can generate small returns. The time to generate the biggest returns I always found was when I was terrified. Nobody else believes me, I'm standing there by myself, but I can't find any flaws in my thesis. To some of the investors, some people said, "Why now?" Look, I think there's a tremendous disconnect between our valuation, where the market deals are going, and what our biology looks like. Because some of the conversations we said today, I said, "It doesn't make sense." Of course, Wall Street, as anybody knows, information flow flows, but there's mispricing.
If there wasn't mispricing, we're not making alpha from our investments. I like to go back to the whole concept of, in biology, you get information to here and information to here, and there's always a gap. The best way I always thought to fill that gap was what, I think it was Seth Klarman who said in his book, Margin of Safety. The best margin of safety is low valuation. I spent a year on a trading desk. I was telling this story to someone this morning. You have analysts who are MD PhDs who are expert in the science and think, "I know everything." They invest in biotech in this sector.
Then you have on the other side, traders who know nothing about the biology, may know nothing about the approach, but know when they see a 5:1 or 10:1 or 20:1 payout ratio. The best is if you can combine both, right? Great biology, sound biology, sound research with the valuation that's low that provides a potential upside. We're excited. We're looking forward to presenting data this fall and looking forward to sharing more with everybody as the months throughout this year come to fruition.
Great. With that, we're at time. I'd like to thank you, Will, for sharing the IN8bio story with us, and also thank everybody listening for spending time with us today.
Thank you, everybody, and thank you for those who have supported us and for joining us on our journey.