Good morning, and thanks for joining us to have a conversation with Will Ho, CEO and Co-founder of IN8bio. IN8bio is a clinical-stage biopharmaceutical company developing gamma delta T cell therapies and gamma delta T cell engagers for cancer and autoimmune diseases, built around the ability of these cells to distinguish between healthy from diseased tissue. The preclinical pipeline is anchored by INB-600, a novel gamma delta T cell engager platform with INB-619, a CD19-targeting engager for oncology and autoimmune disease, now moving into IND-enabling studies. Initial in vivo preclinical data is expected in the second half of this year. On the clinical side, DeltEx DRI for newly diagnosed glioblastoma was published in the JCO on July 1st, with repeat dose patients reaching median progression-free survival of 16 months against a roughly 6.9-month standard of care benchmark.
The company is now seeking for a regulatory path with the FDA. The other molecule, INB-100, is an allogeneic product in development for high-risk leukemias. We expect a clinical update from that in late 2026. To discuss the gamma delta franchise and what's coming up over the next, say, 12 months, let's get started with Will. Will, glad to see you.
Good to see you, R.K.
Appreciate you accepting our invitation and talking to our audience today. Will, as an introduction to IN8bio, could you walk us through what the long-term strategy is? You now have not only a clinical cell therapy franchise in glioblastoma, but also a wholly owned engager platform.
How different, obviously, are these two businesses, not only in terms of capital but also in timelines?
Thanks, R.K. Yes. Hi, everybody. Great to see everyone. It is a nice packed room. Our business, we have actually two sides. We have the historical cell therapy, and today we have a T cell engager platform. Our company background is based on the science and research of our scientific founder, Dr. Larry Lamb. He has been working with these cells, these gamma delta T cells, since the early 1990s and is one of the world's best experts in these particular cells. On the cell therapy side, look, I am not going to beat around the bush too much, but it has been a challenging environment broadly for cell therapy. We are really excited. We had great data that got presented in the Journal of Clinical Oncology.
We had an ASCO presentation, and we will give an update on our median overall survival later this year, likely at The Society for Neuro-Oncology meeting in November. Timelines for that are obviously longer. It would require a registrational trial and additional data to get through to the market, but GBM is a significant unmet need with very little competition given that the last product approved was Temodar in 2005. On the T cell engager side, look, T cell engagers are hot. We have seen three major deals so far this year in the autoimmune sector. We saw Ouro get acquired by Gilead for almost $1.7 billion. You saw Candid get acquired for UCB for $2 billion, and you saw Kali do a deal for $180 million upfront by Sanofi. All of those with a handful of phase I data.
Obviously, that is a much faster and quicker route to returns. Strategically, look, I was a long Wall Streeter. I spent 17 years on Wall Street. We understand we need to generate returns to our shareholders, and we are executing, and we continue to execute to deliver data, and in the long term, to generate shareholder returns.
Gamma delta T cells is not something everybody talks about every day. What is it? How different are they from other T cells? What is the real biological argument here that you are making?
Look, we love gamma delta T cells. We think they are highly differentiated. When the CAR Ts came out, when Juno and Kite came out, everyone was focused on the alpha-beta T cell. The reason why was they are plentiful. You take your blood and 70% of the T cells are all alpha-beta T cells. The gamma delta T cells comprise only 1%-5%. People make this mistake. They think, "Oh, those cells are in low numbers. They must not be important." One of my friends who is actually an immunologist from Stanford, she actually said one day, "Actually, those cells that are in small numbers, those are the powerful ones.
Those are the ones that can recruit the rest of the immune system." Gamma deltas have unique properties, and we think we can leverage that for novel products that are potentially more precise, function more like a scalpel rather than a sledgehammer, and have much better safety profiles, both on the cell therapy side and on the T cell engager side. Across all of our clinical trials to date, we have not seen major DLTs or SAEs. We have not seen any cytokine release syndrome to date. Despite the fact that we are putting cells directly into the brain, we have not seen any ICANS or neurotoxicity.
Talking about the clinical data itself—
Yeah.
—on the INB-200 program, as I said, the data got recently published at JCO, which showed a median PFS of 9.9 months across all 13 treated patients, and 16.1 months for the repeat dose patients. This is against a 6.9 month benchmark. What does the JCO data change for you, in terms of not only investigator interest, but also in terms of talking with the FDA for the path forward?
To talk a little bit about our data, I am going to actually update that data. The JCO publication was actually made last fall. It takes quite a while to get through editorial review. At ASCO, we updated the data. We included the phase II data where we had four patients that were dosed from three additional centers. In totality, we have dosed patients across UAB, Moffitt Cancer Center, Cleveland Clinic, and The Ohio State University.
I think it is more powerful when you have results that are duplicated from multiple centers, so it is just not one magical surgeon. When we look across all of the data, the median progression-free survival is 13 months. The median overall survival at last count as of mid-May was 19 and a half months. Then we found we had a handful of patients, we found 10, that had consented but never received their treatment.
Many went through the exact same process, but at the end, decided not to receive treatment. Those patients had a median progression-free survival of 6.6 months and median OS of 13.2 months. We almost doubled progression-free survival. We will provide an update on our OS at SNO this year. But what I thought was more incredible was actually if you go back to our ASCO presentation and our R&D presentation, we actually have paired biopsies. We have paired biopsies at first diagnosis and at relapse in patients that received the therapy and those that did not. We see a significant difference in that tumor microenvironment. We see multiples increases in not only gamma delta T cells, but CD4 cells, CD8 cells. We see differences in the macrophage population. We see a 90% reduction in tumor density. We are actually having an impact on these patients.
If all I ever showed you was just the data looking at the survival, of course, I do not expect everyone to believe me. But now we used AI and we have histopathology, and we can actually quantitate those data, and we see the difference in those tumor microenvironment. What we are looking at doing is taking the totality of the data that we have in hand and having a conversation with the FDA to seek a regulatory path. R.K. and I have known each other for probably over almost 23 years. When I was on the sell side, we were at the same shop at one point. He knows I am incredibly detailed. We have looked at every single possibility of what potential registrational path would look like, single-arm studies, what data sets are out there. We have looked at randomized studies. We have looked at one-to-one, two-to-one.
We have a good idea of what a reasonable study will look like. We're going to the FDA and seek guidance on whether or not they would agree.
For just another 30 seconds, let's spend on this topic, especially on the safety, right? You don't see, or you have not seen any dose-limiting toxicities, neither CRS nor ICANS, as you said. For a therapy, this one which is to be delivered intracranially at the time of resection, what should investors understand in terms of not only of the surgical expertise that's required, plus also the manufacturing logistics? Do you think that's a limitation at all in terms of adoption?
Look, I don't think it's a limitation in terms of adoption, given that. I mean, go back and look at our financials, right? You can go back and count how many patients we've treated over that last couple of years, and our burn has been roughly $20 million or so per year in totality. You can go back and look at our R&D. You can tell that it doesn't cost us that much to manufacture, right? A lot of it is logistics and thinking about the cell therapy manufacture. On the safety side, going into the brain, to be honest, we were afraid when we first dosed patients. We thought, "Oh, we're going to put this thing into the head." The clinicians were afraid. But we have not seen any CRS. We've not seen any neurotoxicity.
That was at a time when Juno and others were seeing neurotoxicity for the first time in the JCAR015 studies. That's why we brought in Bianca Santomasso from Memorial Sloan Kettering onto our scientific advisory board because she was the immunologist and neuro-oncologist that did all the JCAR015 tox work. The reason why they don't is because these cells are special. They don't secrete IL-6, right? When you go back to our T cell engager data, go back and look at our deck that's online. There's no IL-6 production. We know cytokine release syndrome, the validated biomarker is IL-6 because when patients are crashing, we treat them with tocilizumab, the anti-IL-6 antibody. We think that is why we haven't seen the safety effects. We also haven't seen any infections, right? We've had conversations.
Since ASCO, we have had conversations with more than 30 KOLs from across the country, the top centers, the top neuro-oncologists. I think almost all of them are very excited about this. Some of them were surprised that we did not see infections from the catheter. Part of that is because gamma delta T cells are naturally innate immune cells, so they are naturally antibacterial and antiviral. We think that will play an an important role on the T cell engager side as well.
Talking about the T cell engager.
Yeah.
You have this program, especially with 619—
Yes
INB-619. Can you expand on what INB-619 is and—
Yeah
—at this point, what are you thinking of in terms of indications and taking it forward?
We're really excited about our T cell engager. Look, in 2023, every single company of our competitors went from being an oncology CAR T company to an autoimmune company almost overnight because they could raise money. Quite frankly, we thought there would be a challenge. One of our lawyers is actually here, actually asked me the question, "Do you believe this is going to work?" I said, "I'm not so sure." Why? Because CAR T requires lymphodepletion. That requires the combination of Flu/Cy. It takes about 30 seconds for you to go online. There's a 1973 paper in The New England Journal of Medicine, cytarabine causes ovarian failure in about 40% of women. Autoimmune disease is a disease of women generally between the ages of 20 and 50. I'll ask the same question I've asked in almost every room when people ask me this question.
How many women in this room would take the risk of ovarian failure?
None.
None. I have spoken in rooms from 5 to 400. I have yet to have a single individual raise their hand. Lymphodepletion is an issue, but also we ran a trial in glioblastoma. It is hard enough getting neuro-oncology, heme onc, transplant, all to collaborate inside a comprehensive cancer center. Now bring rheumatology, who's in a different building. These doctors are siloed. It becomes challenging. When we looked at the T cell engager space, we were excited. Our INB-619 is a trispecific engager. On one side, we target CD19, a target that is validated by all of Georg Schett's data. I've actually personally had the conversation with Dr. Schett. They have never seen a subclone, so they've never seen a CD20 or BCMA come out after deep lymphodepletion with CD19. The second target is a conserved region on the gamma delta T cell receptor.
It targets both the delta 1 and the delta 2. That means we can target both circulating and lymphoid or lymph node-resident cells, but also tissue-resident cells. Because we do not secrete the CRS cytokines, we think we can dose higher and not have the cytokine release syndrome. That has been the Dose-Limiting Toxicities. Everybody else has targeted CD3. CD3 creates a narrow therapeutic window. It is like football Sundays. You have to get between the goalposts. On one end, I am limited by T cell exhaustion, where the T cells become too tired, and they are no longer functional. On the other side, I have cytokine release syndrome. Because I am limited by these two, we dose reduce. In oncology, I can dose higher because the patients are going to die.
If I am suffering from rheumatoid arthritis or I am having a lupus flare, I am still not going to tolerate grade 3 CRS where I am put into the ICU, and you have to pull me back from death. When we started looking at the landscape, we thought, is there something about the biology of gamma delta T cells that we can use to drive deep B cell depletion? We have a third arm.
There were prior gamma delta T cell companies like Lava and others, where they were limited by the number of gamma delta T cells. As I said earlier, there is only 1%- 5%. We put what is currently an undisclosed expansion domain that drives the gamma delta T cells to expand. I will note last week we announced that we brought on board Oxana Polyakova. She will be here later in the week. She joined us full time.
We have been working with her for quite a while. She previously was the CSO at LAVA and was the founding scientist at Adaptate that created the engagers that were acquired by Takeda. Ultimately, we think our engager is differentiated because we do not target CD3. We are not going to drive the cells to exhaustion. Our structure actually functions somewhat like an in vivo CAR T and prevents exhaustion. We bind the gamma delta T cells, as I said, in the lymph nodes, in the solid tumor tissues. We do not drive CRS. You can look at our data. There is a massive difference in IL-6. Finally, what nobody has spoken about is because we cause gamma delta T cells to expand, we can reduce and hopefully prevent the infections that occurs with T cell engagers. Every T cell engager will have infections.
The rate on a monthly basis is more than 2x that of even the CAR Ts. You drive what is known as hypogammaglobulinemia. You kill the B cells. I eliminate the monoclonal antibodies, so then I have no humoral response. I do not drive ADCCs because there are no antibodies. Because gamma delta T cells are innate and because they are both antibacterial and antiviral, we can solve that problem. In our GBM studies, we have seen no catheter infections to date. Some people suggest we should have had double-digit numbers. Sorry, long.
No, that's fine. In terms of the data expected later this year on the preclinical data.
The ex vivo data actually showed two lupus donors. The complete B cell elimination, one being on the gamma delta 1 dominant and the other on the gamma delta 2 dominant. For the next set of data that's coming up, what do you think is a clear win? Also, we know that that data is something that you're banking on to get the next tranche.
We'll have data this fall. What R.K. is talking about is we had data. Look, I did what most CEOs would not have done, is I looked at data, said, "It looks great. Let's make sure it works. Let's go head to head." We bought blinatumomab and mosunetuzumab. It's kind of a ballsy move because if it doesn't work, you don't have a product. We showed greater B cell depletion, equivalent or greater without the CRS cytokines. Against mosunetuzumab, the IL-6 difference was 178 times. Now, we went into the animal models for the first time. Look, what do we have to show? You have to show B cell depletion. Preferably, you would see a dose response. I'm not going to wave my hand and say, "Well, I don't have a dose response because of X, Y, and Z." Preferably, you see a dose response.
Preferably, you can clear it both in the blood and in the spleens, and you don't see the CRS cytokines. I think that would be a win if you can see that in any animal model. But we're working on it, and we'll have the data this fall.
On the INB-100—
Yes.
—on the clinical data expected later this year, what sort of data would be seen there?
Look, it's been quite a while since we've had an update. The last update we had there was at TCT in 2005. We've continued to enroll and treat patients. I think we're just about done in treating the patients now. We'll update that data. I think that was an allogeneic cell therapy, but I'll be honest, there are headwinds there just given, nothing that we've done, but we've seen our competition. We're keeping an eye on Orca and how their launch goes. We've seen what happened with TScan Therapeutics very recently. But I think it's great proof of concept that gamma delta T cells, one, can be delivered allogeneically, two, they're active, and three, they don't cause the side effects like CRS. Really, really excited. Look, I think especially if you look at our T cell engager, severely undervalued stock from here.
We have always delivered on the data that we said we would. We will continue to execute, and I'm looking forward to bringing more data this fall.
So as a closing question, now you have an exciting engager program that's—
Yeah.
—budding into the clinical studies, and you already have a clinical program—
Yeah.
—with the cell therapy. With the resources that you have, how are you managing, or how are you thinking about managing the two programs?
I think it's something that we have to have discussions with our advisors, our board, and importantly, with our shareholders. Look, again, as a shareholder, personally, and as an ex-investor, I understand I have to deliver shareholder value. We will look at everything comprehensively and try to do the best we can to deliver shareholder value as quickly as we possibly can.
Thank you, Will.
Thank you.
Thanks for taking time and being here.