All right, good afternoon, everyone. Welcome to the 2025 Jefferies Global Healthcare Conference. My name is Clara Dong. I'm one of the biotech analysts here at Jefferies. We're very pleased to have Chen Schor, President and CEO of Adicet , join us today for this fireside chat. Welcome.
Good afternoon, and very happy to be here and look forward to a productive session, Clara.
Great. Before we go into details of your programs, Ken, why don't you just give us an overview of Adicet and what are the advantages does γδ T-cells have over other T-cell therapy?
Sure, absolutely. Adicet is considered to be the leader in the field of off-the-shelf γδ one CAR T-cell therapy. I'll talk a little bit about the potential advantages compared to other therapies in a second. In terms of pipeline, we have two clinical programs. One of them is off-the-shelf γδ one CAR T-cell therapy targeting CD20 for lupus, lupus nephritis, and other autoimmune diseases. The other program is γδ one CAR T targeting CD70 for renal cell carcinoma. We also have two preclinical programs that we're very, very excited about, and we'll share more data about these preclinical programs I would expect later this year. Regarding advantages, I'll probably divide the answer into the autoimmune field and then to solid tumors. When it comes to an autoimmune field, the key advantages of γδ one T-cells are, one, they're off-the-shelf.
We don't need leukophoresis. There is no personalized manufacturing. It's completely off-the-shelf. Two is better tolerability. As we all know, αβ T-cells or B specifics are associated with secretion of IL-6 upon activation of the αβ, which leads to CRS and ICANS, sometimes grade three or even grade four we've seen in autoimmune diseases, which really limits the dosing to more academic centers. γδ T-cells are better tolerated. Upon activation, they don't secrete high amounts of IL-6 and have lower incidence and severity of CRS and ICANS. On top of being off-the-shelf, I would expect them over time to be available in community settings. In terms of efficacy, when we look at CD19 positive B cells, we see complete depletion both from the blood and from lymph nodes.
I'm happy to expand also about the PK and tissue tropism because I think that's a significant advantage of γδ one T-cells in autoimmune diseases. These are the key advantages in autoimmune, in summary, off-the-shelf, well tolerated, potentially available in community settings, and reset of the immune of the B cell compartment in the blood and in the lymph nodes and other tissues. In solid tumors, we have two additional advantages. One is innate and adaptive anti-tumor activity, which is helpful to address heterogeneity in the tumor. The second advantage is tropism to tissues and ability of the γδ one T-cells to show their activity even in an environment that's generally lower in nutrients and hypoxic.
Fantastic. Maybe let's start with 001, CD20 targeting therapy in autoimmune disease. Maybe to start, could you give us a high-level overview of this program and what's the key differentiation of this program? Maybe talk about the targeting strategy as well. Why do you think CD20 is an ideal target for autoimmune?
Sure, absolutely. First of all, we started this target in oncology. In oncology, we developed a program for DLBCL and MCL. In MCL, the CR rate was comparable to autologous cell therapies as well as the durability. The median duration of complete response, I believe, was 17 and a half months in MCL, so really comparable to autologous. In DLBCL, we primarily enrolled post-CAR-T patients that did not respond well to Yescarta. There we saw, again, the same CR rate as autologous cell therapies like Yescarta, but lower durability given that these patients failed primarily Yescarta. What we have seen from the data in NHL, one, was that the PK of ADI-001 was really comparable to the PK that we see with CD19 autologous CAR T in autoimmune. That was quite pleasing to see this type of PK just like in autoimmune patients with the CD19 autologous CAR T.
The second thing that we've seen that actually makes sense, but we had the data from the study, was we had biopsies from lymph nodes. What we found was that the exposure of γδ one CAR Ts, and specifically ADI-001 in the lymph nodes, was approximately five- to tenfold higher compared to autologous CAR T. That's a key benefit of γδ T-cells. When we looked at CD19 B cell depletion in the lymph nodes, we saw complete depletion of CD19 B cells in the lymph node. That is extremely important, as published by the autologous CAR Ts. Without depletion in the lymph nodes, one would not expect to see durable activity of therapies. That is what we've learned from oncology. We're targeting CD20. Most of the clinical data with the autologous CAR T has been with CD19.
Your question is a very valid question. It just so happens that we've always measured both in the blood and in the biopsies CD19 B cells. There's significant overlap between B cells that express CD19 versus CD20. It's not perfect. Bottom line, we enrolled about 40 patients. We've always measured CD19 positive B cells, and we've seen complete depletion both in the blood and in the lymph nodes.
Fantastic. As you mentioned, you've accumulated some data from oncology indications such as mantle cell lymphoma and DLBCL in the past. How should we think about the transferability of, especially ADI-001 cell persistence and B cell depletion? How should we think about the durability?
Sure. I actually think this is an important question, and I would assign significant weight to what we've learned from the study in NHL. Because in autologous CAR T, what we've learned in the field of autoimmune is that the cells persist, you know, kind of averaging the numbers, about 30 to 90 days. The CAR T essentially is gone. Autologous CAR T is gone in autoimmune diseases. Indeed, we see the B cell compartment starting to recover somewhere in that timeframe. As the autologous CAR T disappears from the system, we start seeing the B cell recovery. The primary reason that we see this efficacy is likely this immune reset, being able to deplete all the CD19 positive B cells both in the blood and in the lymph nodes. That's the goal.
That is why I believe that the data in NHL educate us a lot about what we can expect in autoimmune diseases. Because when you look at the exposure of ADI-001, primarily in the dose level 3E8 and 1E9, we see persistence in the range of 30-90 days. We see complete CD19 B cell depletion. I think this really educates us about what we want to see and what we expect to see in autoimmune patients, as well as the learning from that tolerability, which makes sense that we will see less incidence and severity of CRS and ICANS.
Got it. For 001, it's being studied in the phase one in lupus nephritis, and you recently also expanded the enrollment to include SLE as well. Maybe can you talk about the rationale for starting with lupus first, and then what's the current status of enrollment for the phase one study?
Sure, absolutely. Essentially, our strategic decision-making was, let's start with the LN and SLE. Technically, LN got clearance first, and then SLE got clearance second. We're now expanding to myositis and systemic sclerosis and oncovasculitis. We're enrolling patients with SLE, whether they have the nephritis component or they do not have the nephritis component. One of the key reasons we started with this is because in this field, there's such a strong proof of concept for the potential efficacy of CAR T, leading to essentially significant improvement in the disease course and immunosuppressant-free, essentially remission or almost remission for these patients, which is something that we've never seen before in this field. So far, there's continued organ damage, even if these patients are taking immunosuppressants. Every now and then, they flare, and their organ damage decreases over time.
Great. You have also expanded 001 into more autoimmune diseases other than lupus. Could you share what are the criteria when you're selecting those indications? Could you also talk about the study design for other indications as well?
Sure, absolutely. First of all, in terms of the indications, we started, as I mentioned, with SLE given the proof of concept. We then expanded to, I believe the second indication was systemic sclerosis. Why? Because there is some evidence that CD20 may help these patients. There is a huge unmet medical need in systemic sclerosis. Eventually, it can present a lung component. There is significant tissue tropism of γδ T-cells to the lung. That can be a significant positive to see efficacy in these patients. That was systemic sclerosis. Myositis, there is quite significant proof of concept in this field. A little less than SLE, but still proof of concept with SLE. Also, vasculitis. There is certainly data that suggests that the CD20 antibodies can work in vasculitis. There is a significant kidney component in vasculitis.
We know that γδ T-cells have tropism to the tissues. In terms of the design, the starting dose level in the study is 3E8. Actually, some of the first few patients that were enrolled to the SLE/LN arm were enrolled at a lower dose level, 1E8, which is just an older version of the protocol that we had in those sites. Generally, in the protocol, the starting dose is 3E8. The next dose level, and the only additional dose level, is 1E9. Patients generally progressed on a couple of lines of therapies, and they need something to help them in a meaningful way.
Great. In terms of the patient enrollment, are there any differences in terms of the inclusion and exclusion criteria compared to the landmark study from Germany?
Sure, absolutely. The German study was, as you know, an IST done under emergency use laws that exist or regulation that exists in Germany. There was not any formal inclusion-exclusion criteria, but rather patients were selected primarily based on their medical history. Generally, patients with shorter disease duration were selected into this study. I would say that our inclusion criteria are at least, for example, in SLE, they need to progress on at least two different therapies, including corticosteroids that they probably used. Still, the disease progresses, and they need a different drug. It is not inconsistent with inclusion-exclusion criteria with other industry players. If you look at the designs of companies like Novartis or BMS or other types of companies that develop in this field, this is the type of inclusion-exclusion criteria that they have.
Okay. For the preliminary clinical data you are reporting in the second half of the year, can you talk about what investors should be looking at? What should we expect to see, especially in terms of the patient number, the follow-up time, and the indications?
Sure, absolutely. We expect the initial data set to focus on SLE and LN patients. We talked to a couple of investors, and we asked them, "What do you guys want to see?" The feedback was at least six patients with at least three months follow-up. We expect to have that, definitely, potentially more. I believe this is the right thing to do in order to provide investors a good picture of the potential efficacy and safety. The reason I believe this is right, if you look at the EULAR abstracts, there is one abstract that I think people should really focus on. That abstract is coming from Columbia University, from, I believe, Dr. Norman Gómez. That abstract, there is going to be a poster, I think it is in poster session three. I am not sure what date it is, but the abstract is available.
That abstract summarized the activity of 11 different CAR Ts. It looked into the efficacy using the SLEDAI-2K score. You can see overall how the efficacy plays out for the SLEDAI-2K from all the different studies. When I look at the data from SLE and LN, they're all SLE patients. I look at the SLEDAI-2K because this combines all the metrics. Of course, we'll look at the B cell depletion. In LN, we look at the kidney function, although we know that proteinuria is quite variable, but we'll certainly look at the kidney function. I would say SLEDAI-2K will give us a very good picture for the cross-organ efficacy of a CAR T.
Got it. We are also seeing some emergent data from cell therapy in autoimmune disease in the field. What are the key learnings from the recent development in the field for your development strategy of γδ T-cell in autoimmune diseases?
Can you repeat the first sentence we're also seeing?
Based on the data from cell therapy in autoimmune diseases, yeah, what are the key learnings and how does it inform your development strategy of γδ T-cell?
Sure. From everything that we've seen, we've seen that cell therapies and focus initially on SLE lead to a very significant improvement in the SLEDAI score, leading to essentially halt of the disease. If you look at the publication from Euler by G`omez from Columbia, you can see that it kind of goes down to around the disease score four or five. Essentially, you take an autoimmune patient that progressed for a while, you give them a once-and-done therapy, you see that the disease score significantly improves, and then they have an immunosuppressant-free, essentially, disease halt. That's huge for these patients. I think the key learning is that we could see a completely new class of therapies, just like TNF alpha came into the market and became more than a $10 billion market.
I believe that cell therapies could make a huge impact on the lives of autoimmune patients and provide a very significant commercial opportunity as well. In multiple diseases, certainly SLE, but also other diseases where there's data supporting efficacy.
Fantastic. We discussed a lot about autoimmune diseases. Maybe let's discuss a little bit about your development in solid tumor as well. You have ADI-270 targeting CD70 for renal cell carcinoma. Tell us, why are you going after renal cell carcinoma? Where do you see the differentiation for 270 in this indication?
Sure, absolutely. Going to the basics, γδ one T-cells, we know that they home to tissues, and they have innate and adaptive anti-tumor activity, and they can be dosed off the shelf. That kind of the fundamentals lend themselves to autoimmune and solid tumors. In solid tumors, our first program is CD70. We do have another program in solid tumors that is targeting prostate cancer. We are targeting CD70 for RCC. We are actually targeting CD70, not using a single-chain FV. There are a couple of companies with clinical programs targeting CD70 with a single-chain FV. We are using CD27. CD27 is the natural receptor for CD70. It requires a lower antigen expression on the cell. Potentially more potent activity in CD70-positive tumors. Another advantage of targeting CD70 is the activated T-cells that come to reject the graft.
In the case, that's the allogeneic cell therapy or ADI-270, do express CD70. So our program, ADI-270, actually also attacks the activated T-cells, and that might lead to higher Cmax and potentially higher persistence. So CD27 versus CD70, the key advantages are these two that I mentioned. In addition to that, we're going to have the innate and adaptive anti-tumor activity, which hopefully will help, as well as the tissue tropism to tissues and ability to be active in tissues. So that's the rationale for CD70.
Now ADI-270 is being studied in the clinics. Could you talk about the design of the study and when should we expect clinical data?
Sure, absolutely. The inclusion call for patients that progressed on two lines of therapies, primarily PD-1 and VEGF targeted therapies, we're actively enrolling. We expect to have data in the second half of this year. Again, when we guided for data, we mentioned that we expect at least six patients with three months follow-up for this data set as well.
For the initial data, what should investors be looking for? What kind of clinical metrics are you able to share?
Sure. There are different data sets by different companies. Right now, the first thing that I would look at in terms of what is available to these patients that progress on PD-1 and VEGF is the HIF-2α inhibitors. The HIF-2α inhibitors provide about 20% overall response rate and a median PFS of about five months. I think that kind of defines what one should expect from something if we want to go after post-PD-1, post-VEGF. If you go to a different line of therapy, you should compare it to the relevant comparator. That is the type of activity that people should expect, or at least a data set that suggests that this is something that you can achieve.
Are any other tumor types applicable for the CD70 targeting strategy?
Yes, absolutely. There are multiple cancers that express CD70. The reason we decided to start with RCC is because about 80% of the patients with clear cell RCC have CD70 expressed on their tumor. There is certainly a host of almost 20 other cancers where some of the patients have CD70, but this will require, obviously, a component diagnostics to screen the patients and enroll only the relevant patients.
Fantastic. In the beginning, you also mentioned you have a preclinical program as well. Can you just give us a teaser of what they are about?
Yeah, absolutely. We will have data. We will share, I would expect, some more in the second half of this year. What I would say is, Adicet was founded in 2015. If I had to describe Adicet, the first five years was how can we manufacture γδ one CAR T-cells. About 1%-3% of donor material is γδ one T-cells. Developing the right technology and the right antibodies to be able to manufacture in a reproducible way in Adicet and with different CDMOs, γδ one CAR T took us approximately five years. The next five years, we invested in putting two programs into the clinic. Then about five years of research, how can we make these cells much, much, much more potent? That is what we have been doing for the last five years.
These programs are now maturing into preclinical programs that perform really, really well. I would expect more in the second half of this year.
Fantastic. Could you tell us what's the company's plan and focus for the rest of 2025 and 2026, and what are the key catalysts and milestones investors should be looking forward to?
Absolutely. I'll start with our autoimmune program. I would expect data in SLE and LN in the second half of this year, potentially data in other indications as well in the second half of this year. Next year, both in the first half and in the second half, I would expect clinical data on more patients and more durability data on existing patients in a host of autoimmune diseases. This would be essentially at least three different data points over the next 18 months. ADI-270, I would also expect data in the second half of this year and potentially updates next year as well. The two preclinical programs are on their path into an IND and into clinical development. There's going to be more data coming from these preclinical programs.
Overall, we have a diversified pipeline right now with two clinical programs and with two preclinical programs all progressing. What I like about it, we have multiple shots on goals, both in autoimmune and in oncology. ADI-001 has been significantly de-risked in oncology and may have benefits in multiple autoimmune diseases. This will create a host of milestones throughout the second half of this year and into next year.
Fantastic. Thanks very much for the great discussion, Chen, and thanks for spending time with us. We will wrap up our session here. Thanks very much, everyone, for attending this session.
Thank you for inviting us. Thank you.