Hello, everyone. Welcome to H.C. Wainwright Annual Global Investment Conference. My name is Li Chen, and I'm your equity research associate at H.C. Wainwright. It's my pleasure to introduce Chen Schor, President and CEO of Adicet Bio. Please go ahead.
Sure. First of all, thank you for inviting us to your conference. It's a pleasure to be here. I'm Chen Schor, President and CEO of Adicet, and looking forward to today's presentation. At Adicet, we're considered to be the leaders in the field of CAR gamma delta T cells, and we'll review today data both from our autoimmune program and from our first program in solid tumors with ADI-270. This is our forward-looking statement. I assume you've seen one, and then we'll move to the next slide. So we're developing broad pipeline of CAR- T therapies based on a specific type of cells called gamma delta 1 T cells that we're developing for autoimmune diseases and for cancer. We're very proud of this pipeline.
It's a result of years of focused research, how to best leverage the activity of these cells to fight diseases, primarily autoimmune diseases and cancer. This morning, we announced a strategic prioritization of our pipeline, specifically for ADI-001, where we're gonna focus our development resources for ADI-001 in the field of autoimmune diseases, which is a large and a growing market. As a result, we closed enrollment for our MCL study, and we have top-line data in hand that we share today, and I'll review this data with you today.
The results that we have in MCL, together with the PK profile that we have, together with the B-cell depletion profile that we've seen with ADI-001 in patients, suggest very strong potential for ADI-001 in autoimmune indications, and this is why we're focusing with this specific program on autoimmune indications. We'll talk about ADI-270. ADI-270 is the first CAR gamma delta 1 T cells to enter clinical development in solid tumors. ADI-270 stands on the shoulders of ADI-001 with additional bolt-on technologies that optimize its potential activity for CD70 tumors, starting with renal cell carcinoma and expanding to other tumor types. Let's jump in and review the different programs. I'm happy to be surrounded by a great executive team.
Each of us has a lot of experience in their respective functions, and we're all working together as a team to promote our pipeline. Let's jump into the data. So far, all the data that we have from ADI-001 really supports a very nice profile for the treatment of autoimmune diseases, and I'm gonna review at the highest level these properties, and then every single property, we have data to back up why we see this activity so far. The first one, when we look at the activity of ADI-001, which is an off-the-shelf gamma delta 1 T cells that target CD20, we see that the exposure of ADI-001 in the blood is actually consistent with the exposure of autologous CD19 T cells in the blood of patients with different autoimmune diseases.
If you look at the Cmax, if you look at the day 28 persistence, and if you look at the AUC, overall, the exposure is consistent with what we've seen with the autoimmune field. Consistent with this exposure, when we look at the B-cell depletion of ADI-001 in the peripheral blood, we see very nice and complete CD19 B-cell depletion in the plasma, consistent with what we've seen from academic studies in systemic lupus, in lupus nephritis, in systemic sclerosis, and in myositis, so same exposure and same B-cell depletion. A big advantage of gamma delta 1 T cells is their trafficking to tissues. When we think about many of the autoimmune diseases, in many cases, we have B-cell islets in the organs. So, for example, when it's lupus nephritis, there might be some B-cell islets in the kidneys.
When it's systemic sclerosis, it might be in the lungs. Generally, in order to see durable complete responses in autoimmune diseases, tissue trafficking is something that we wanna see, and gamma delta 1 T cells are known for their best-in-class tissue trafficking compared to other cell types. Another key advantage of gamma delta 1 T cells, and we've seen that in our clinical trials to date, is that, unlike alpha beta T cells, we don't see a very significant peak in IL-6, and with IL-6, what we see with alpha beta T cells is high incidence and more severe grades of CRS and ICANS. When we look at our data, we don't see these high peaks of IL-6, and we see significantly reduced risk of CRS and the ICANS, and that is another advantage in the field of autoimmune.
Another advantage of gamma delta 1 T- cells is their being off the shelf, and being off the shelf, these cells eventually will be rejected by the host, by the patient, within about three months. That's what we've seen in oncology, and that essentially minimizes to completely eliminates the risk of T- cell malignancies, which is a risk that we know exists with autologous CAR-T, at least in oncology. So generally, these products are available off the shelf, very favorable safety profile, and we expect to eventually be able to dose these products in the community settings. I'm gonna move forward a little quicker with the slide, just knowing the time that we have. Exposure.
If we look at the light green, the Cmax of ADI-001 in the blood is actually higher than autologous CAR-T. If you look at day 28, exposure of ADI-001, it's actually higher than autologous CAR-T. If you look at the darker green, it's overall comparable with autologous CAR-T. These are the two dose levels that we're moving into clinical development with ADI-001 in multiple autoimmune diseases. So same exposure as autologous CAR-T overall, and the same AUC when we look up to day 28. B-cell depletion. Although we're targeting CD20, we actually measure CD19 positive B cells in the blood. You can see here, these are data from 24 patients. Twenty-three out of the 24 patients had a complete depletion of their CD19 positive B- cells in the blood. So same exposure, same B-cell depletion in the blood.
When we look at the patien--derived B cells, so we actually get cells from patients, whether it's patients with lupus, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, Sjögren's disease, all autoimmune diseases. If we provide ADI-001 to these patient-derived cells, we see complete and consistent depletion of their CD19 B cells. Very consistent with what we've seen in patients. One of the questions that we received from investors in the past was: "Would you expect that CD20 will also deplete plasmablasts?" And the best answer to this is actually can come from data from Roche. Roche has a CD20-targeted antibody, obinutuzumab.
It's been tested in 125 patients with lupus nephritis, and you can see the top graph on the right, you can see the obinutuzumab was dosed on week one and week two, and you can see complete depletion of plasmablasts in the blood, and then they slowly recover. Week 24, they provided two doses, week 24 and 26. Again, complete depletion of plasmablasts in the blood. What we learn is that we've seen very durable, complete responses from cell therapies in autoimmune diseases, and we haven't seen that with antibodies. There's been data to suggest why this could be the case, published by the Schett Group. This is extracted from a publication from a little less than two weeks ago, where investigators Schett and affiliated investigators tested 10 patients.
Five patients received autologous CD19 CAR-T, and five patients received rituximab. On the left, you can see that in both cases, there was complete depletion of CD19 positive B cells in the blood. On the right, you can see that CAR-T did deplete, CD19 B- cells from lymph nodes of patients, which generated this, durable response, while antibodies do not, at least in the case of, rituximab. So again, very supporting the notion that, tissue tropism and trafficking into tissues and B-cell depletion in the tissues is very important in the field of, autoimmune. As I mentioned, we, reported our MCL data, today and are focusing on autoimmune. The data are actually very favorable. So far, we've dosed 10 patients, with MCL. These were patients that, were late-line patients. They've progressed,...
The median number of prior lines of therapies was three. About 30% of the patients failed autologous CAR-T. When you look at the overall response rate, 80%. When you look at the CR rate, 60%. And when you look at the median durability of response, seventeen and a half months. So very favorable data in MCL and consistent with efficacy data of autologous CAR-T in MCL. It's just a smaller market, and data that we have also support activity in autoimmune. So talking about autoimmune, as I mentioned, tissue tropism is very important. This slide summarizes data from eight or nine different publications, showing that the gamma delta 1 T cells traffic to tissues that are very important for autoimmune diseases, whether it's kidneys, as I mentioned, for lupus nephritis or ANCA vasculitis, or lung, which is important for systemic sclerosis.
And hence, we're embarking on a pretty comprehensive clinical development plan. We picked four indications initially, systemic lupus and lupus nephritis, systemic sclerosis, and ANCA vasculitis. We cleared the IND for all these indications, and we're now activating sites in multiple territories to run the study. The next slide describes the design of the study. It's actually pretty simple. These are three arms: one arm for SLE or lupus nephritis, one arm for systemic sclerosis, and one arm for AAV or ANCA vasculitis. We condition the patients using a standard CyFlu regimen consistent with what Schett used. Then we provide a single dose of ADI-001. We know that that single dose shows very nice B-cell depletion, and then we follow up on the patients. In terms of the endpoints, the endpoints are outlined on this slide.
The primary endpoints are safety, but the secondary endpoints are associated with the PK, the dynamics of B-cell recovery, autoantibodies, how long it takes the host cells to recover, and the specific disease scores in every disease. So in SLE, it's SLEDAI, and you can see the endpoints in other diseases. Bottom line, we're activating sites. We expect to see clinical data in the H1 of next year. We expect those clinical data to be in lupus nephritis, in SLE, and systemic sclerosis, and maybe also ANCA vasculitis. I'm saying maybe just because it's a relatively rare indication, so we don't know if we'll see those patients in the study. We believe that the data that we have so far with ADI-001 really optimizes the probability of success in this study.
In the H1 of next year, we also expect to have clinical data with our second clinical program, ADI-270. ADI-270 is our first program going into solid tumors and generally going after CD70-positive tumors. Everything about this program is differentiated, except for the target that we've heard about, which is CD70, and that is very important because not all programs are created equal. Let me go through the differentiation, and every statement that I'm saying regarding the differentiation is backed up by data that are outlined in the deck. I'm not sure if we'll have time to review all the data. First, how we engage the tumor. So we use CD27, which is the natural receptor for CD70, to target those CD70 tumors.
What this gets us is the ability to show nice cytotoxicity also in tumors that express relatively low CD70, and not only tumors that express only high CD70. That's one advantage of using CD27. The second advantage is that CD27 is another costimulatory domain, so this is a third-generation CAR that we're developing. The third advantage, one of the mechanisms that the patient rejects the graft or gamma delta T- cells in this case, is by activated T- cells. Guess what? Activated T cells express CD70, so ADI-270 would be able to fight back the rejection of the cells, which means that we would expect higher Cmax and potentially higher persistence with this program. So this differentiates us in terms of Cmax, persistence, and activity in lower CD70 tumors. The second differentiating factor, we have a TGF-beta dominant negative receptor.
There's been recently data by AstraZeneca using different cell therapy with TGF-beta that shows that using TGF-beta dominant negative receptor can improve efficacy in solid tumors. We have this baked into our product. And the third advantage is that gamma delta 1 T cells have innate antitumor activity, and we know that tumor heterogeneity is a common theme in solid tumors. We actually can show very nice cytotoxicity for also cancer cells that do not express CD70. Let's jump to data. I'm gonna skip this slide. This slide shows that 270 is less susceptible to rejection, both by T- cells and NK cells. On the left here, you can see that the gamma delta T- cells in red are susceptible eventually to rejection by T cells.
But if you use CD27, you can see in blue that they are less susceptible by the rejection of T cells. Generally, on the right side, you can see that gamma delta T cells are generally less susceptible to rejection by NK cells. Bottom line, this should translate to better Cmax and potentially, better persistence in patients. We talked about, TGF-beta. I'm gonna focus on the right side. One of the ways to test, how, the efficacy of a CAR T cells is how many times can they kill tumor cells? And as you can see on the right side, all cells with, TGF-beta, without TGF-beta, in the presence of TGF-beta, have a great first attempt in killing.
But in the presence of TGF-beta, if we do not have TGF-beta DNR, you start to see diminishing activity, and that's what we see here on this slide, and that should potentially improve the efficacy in solid tumors. There are some clinical data that suggest that that's the case from a different program. Here, I'm gonna focus in the middle. What we do here, we compare the activity of ADI-270 compared to two clinically relevant CD70 alpha/beta CAR Ts that are in clinical development. What you can see is that ADI-270 shows very nice cytotoxicity, also when CD70 is low, unlike what you can see with alpha/beta approaches with a single-chain Fv targeting CD70. This slide shows the innate cytotoxicity of our cells.
If you take tumor cells, and you knock down the CD70, you can see that alpha/beta T cells in red and in green show minimal cytotoxicity, while gamma delta T- cells show pretty nice cytotoxicity. So we're excited about this program. I'm gonna skip a couple of slides. This is the design of the program. The starting dose is 3E8 , going to 1E8 . Patients that show some benefit to ADI-270 can receive a second dose of ADI-270 during the first six months. So we actually believe that this should translate to pretty good disease control rate, and hopefully some overall response rate and nice durability. We're very excited about the H1 of next year.
We expect to have data in a couple of autoimmune diseases with the ADI, with ADI-001, as well as data in renal cell carcinoma with ADI-270. We're very well-funded into the H2 of 2026, so we expect to generate significant data and hopefully upside to investors. So thank you for your interest. I know I've been quick, so if there are questions, I'll come around to answer some questions. Thank you.
Any questions? Okay. If not, thank you for a great presentation, and thank you everyone for joining us.
Thank you.