Nice.
Okay. Good afternoon, everyone. Welcome to Guggenheim Healthcare Innovation Conference. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. It is my pleasure to welcome our next presenting company, Adicet. From the company, we have President and Chief Executive Officer Chen Schor. Chen, why don't you maybe make some opening comments? Tell us the story of Adicet, what you're doing, what data you—maybe just what you're doing and what are some of the key milestones, and then we'll go into some of the data that you have generated.
Absolutely. Yatin, first of all, thank you for inviting us. Always a pleasure to be here in this conference, and thank you guys for coming and for the people that will listen online. Adicet is the leader in the field of gamma delta CAR T cell therapies. Gamma delta CAR Ts are uniquely positioned to win in the field of autoimmune diseases and solid tumors. The key advantages of gamma delta T cells are that they can be provided in an off-the-shelf manner to patients. They penetrate tissues very, very well, and they can exert their activity in the tissues, and that's very, very important for autoimmune diseases and for solid tumors. Our autoimmune program is progressing very well. We're enrolling for seven different indications.
We announced data that provide very significant proof of concept less than a month and a half ago, and we're on track to have a very meaningful year next year with multiple data readouts across different indications, both in the first half of next year and in the second half of next year. We are excited. We are enrolling patients, and we look forward to the coming few months.
Very good. Chen, thank you so much. Recent disclosure that you make on the LN and SLE side, could you just maybe touch and put those data in context to us? I think this is the first time we saw an allo product showing efficacy, which is in line with the auto, and also the construct has a CD20, which also you sort of de-risked. Just talk about that and then the meaningfulness of these data.
Absolutely. So indeed, we announced recently data in LN and SLE. We started enrolling LN patients, and then we expanded to SLE. We announced data on the first seven patients. The duration of follow-up was between two months to nine months. In the LN patients, patients generally had a disease duration of about 2 to 22 years. They took anywhere between three to seven prior lines of therapies. The patients with LN had pretty significant protein in their urea. We essentially conditioned the patients and provided them one dose that's provided off-the-shelf. Starting with safety, we saw an excellent safety profile that's very important in rheumatology because we do not want HemOnc to oversee high-grade CRS and ICANS in these patients. We want to enable these to be provided to many, many patients. So indeed, we did not see any high-grade CRS or high-grade ICANS.
We saw no ICANS at all, and we saw only two cases of CRS Grade 1, which was fever for like a day, maybe two. Very, very well tolerated profile, unlike some of the alpha beta cell therapies that have shown some Grade 3 ICANS, which is a key issue. In terms of efficacy, we've seen efficacy that's very consistent with autologous cell therapies. SLEDAI scores come down gradually in a very consistent way. PGA comes down gradually in a very consistent way. In terms of kidney function, out of the five LN patients, three patients had a complete renal response, which was also a DORIS remission, and two of the patients had partial renal response. All the patients, including the SLE patients, of course, completely discontinued their immunosuppressants. Out of the seven patients, all of them reduced their steroids to below 5 mg of prednisone equivalent.
Four of them were 0, and three of them were below 5. Overall, very, very nice efficacy. All the responses were ongoing. This seems to show efficacy consistent with autologous CAR T without the hustle of the autologous CAR T dosing and with a safety advantage that should enable us to dose in a community setting or definitely in hospitals that do not necessarily compete on beds for CAR T oncology.
Got it. Can you touch on the durability? Because the one question that we hear a lot from investors is the durability. I think, like you said, the follow-up is between two to nine months. How should we think about durability? You also share data on immune reset. So contextualize that data for us and put that in perspective.
Yeah, that's actually a very good question. There are actually two publications that we can tease information from. One is by Schet at ULR in 50 patients that received autologous CAR T, and one by a Columbia group from about two months ago that looked at data from 97 patients. What you see is that for patients that experienced immune reset, not for patients that have been taking necessarily antibodies or B-specifics, but patients that took CAR T cell therapies and experienced immune reset, the durability is actually quite promising. You see very few relapses. It does happen that you see relapses, but generally, these therapies are very, very durable. In our data, we analyze the immune reset, and we've seen a very, very clear immune reset. Indeed, we're targeting CD20, but we've seen complete depletion of CD19 B cells in the blood.
We've seen complete immune reset in patients. We actually did BCR cloning, and we looked at the BCR clones before dosing and after dosing, and essentially, you see a complete reset of the immune system. Also, in our oncology, we analyze lymph node biopsies, and we've seen complete CD19 B cell depletion in the lymph nodes. Have we shown immune reset? I believe the answer is yes, absolutely.
You're sort of making a point that there is a relation between immune reset and durable responses, right, based on those data.
Absolutely.
Okay. How are these patients doing now?
Obviously, we've done the most recent data cut was about a month and a half ago, so we don't do any data cut every month, but as of last time we looked at it, all the responses were ongoing.
Very good. How would you contextualize or compare these data to auto CAR T or other CAR T cell sponsors that have generated data in LN and SLE?
I would say very consistent. When you look, for example, at BMS in their initial data release, it was seven patients, duration of two to nine months, very, very consistent with our data set. Based on that data set, they moved to a pivotal study. If you look at the data from recent ACR, both from BMS , primarily from BMS , I want to say, but also a few other data sets from cell therapies, those responses seem to be durable. What we've seen so far in the seven patients is completely consistent with autologous cell therapy.
Got it. Now, what are you planning to show? How many more patients are you going to enroll? What is the next plan for LN and SLE? I have regulatory questions separately, but just on how many more patients and then the next data set.
Sure, absolutely. We have now 25 centers open to enrollment. I want to say we're enrolling very well. We see the results of the favorable safety profile. We see the results of not a big concern for ICANS or CRS. The efficacy data, obviously, were very helpful. We see quite robust enrollment, and we expect to report this data in the first half of next year. We see quite significant interest in systemic sclerosis as well.
Okay. Yeah, we'll discuss that. Maybe just one question on the lymphodepletion approach. You're using a standard lymphodepletion, right? How is the adoptability, or do you hear anything from physicians that is that an impediment at all?
No.
Okay.
That's a very short answer. It's actually, the answer is no. Many of the patients with LN or SLE have taken cyclophosphamide in the past. That's nothing new. Many of them have taken azathioprine in the past. Fludarabine is not that different. Not at all. I want to say before they start the first patient, they're saying, "Oh, we've never dosed Syflu together." Once they did the first patient, it's not even a question.
I see. Very good. Okay. On the regulatory front in LN and SLE, what are the next steps? When are you going to meet with the FDA, and how should we think about a phase III or a pivotal program in LN, SLE, or combined or separate?
Absolutely. We expect to meet the FDA in the first quarter of next year and then hopefully start the pivotal study in the second quarter of next year. The examples that we can look at with cell therapies in LN or SLE are all single-arm studies. If you look at autologous, they're focusing on a study in LN, and they are running a 35-patient single-arm study with an endpoint of complete renal response. If you look at BMS, they're running an 80-90 single-arm study. I want to say 90-patient single-arm study, interestingly, in LN and SLE, and the primary endpoint is a DORIS remission, and the secondary endpoint is complete renal response.
If you look at Novartis, initially, Novartis started a randomized study in about 150 patients in LN, and they recently met with the FDA and updated the design of their study to a single-arm study in LN and SLE in 180 patients. It is a bigger study. We currently expect to start with LN, potentially expand to LN and SLE, and the size of the study, we assume it is going to be somewhere in the range of 30-90 patients. Of course, we want to meet with the FDA, confirm their approach here, but the examples that we see are the examples that I mentioned.
Will it be most likely a CRR or a DORIS?
Most likely, I want to say CRR,
Because that's what LN is.
And if we expand to SLE, then maybe you change it to a DORIS.
To a DORIS, yeah.
In our case, all the CRRs were also DORIS.
Yeah, exactly. Okay. You just mentioned about SSC. It's not just SSC. You are enrolling in six additional or five additional indications, right? IIM, SPS, AAV. Are you seeing more interest in one indication versus the other? Maybe touch a little bit on the SSC side.
We actually see enrollment almost as a function of the prevalence of the disease. It's funny. We see it started. We started the protocol with LN and SLE. As soon as we started showing data in LN and SLE, SSC patients started showing interest. The physicians that enrolled, the rheumatologists that enrolled LN and SLE, once they see the data, they pretty quickly come with patients with systemic sclerosis. We see some interest from myositis patients and ANCA vasculitis. We're certainly not pushing necessarily these indications. The other indication that we're enrolling as a separate study is a study in RA.
Okay.
In SSC, we started seeing enrollment, and we're seeing nice interest in SSC.
Okay. When are we going to get data from SSC?
We expect in the first half of next year, the first data set, and potentially another data set in the second half of next year.
Okay. The disclosure for SSC will be similar to what you did with LN, where you have enough patients, enough follow-ups so that you answer both the volume question and the durability question.
We started enrolling a month or two ago. I do not remember exactly when the press release went out, but enrollment is going well. You can do the math and see. Generally, what you see, for example, from BMS that has just announced data in ACR is you start to see efficacy within the first three months, and it slightly improves into the sixth month.
Correctly, yeah.
You start to see.
Three months, you have enough, yeah.
Yeah, I believe three months already shows you the right direction.
Okay. Okay. And then once we have the data, only then you'll go to the FDA and figure out the path forward in SSC?
Yeah. We want to see the data first, obviously, before we talk about it.
Okay. Touch a little bit on the no preconditioning or low preconditioning approach that you're using in RA. What exactly are you doing there? And then maybe if you can touch on, is there a potential to have no preconditioning in any of the studies?
Sure. Absolutely. We're just starting our journey to understand the need for lymphodepletion. We've always used lymphodepletion in our studies. RA is the first study where actually we're not necessarily randomizing, but there are two cohorts in every dose level. One cohort is on the background of standard Syflu, and one cohort is on the background of Sy. We shall see the efficacy. Cyclophosphamide is not a big deal. All these patients have taken cyclophosphamide, so there is really no concern with the cyclophosphamide. Right now, we haven't planned a study without Syflu at all. Right now, we're checking only on Sy.
Okay. And then again, the data from all of these is going to come next year?
Yes.
Okay. Okay. Can you also now talk about the manufacturing side, the cost of goods, given that this is an allo approach, very differentiated from auto? What are the considerations and who is doing the manufacturing for you?
Sure, absolutely. We get, I want to say, on a weekly basis, donations of essentially Leukopak. We have a small process to qualify every Leukopak for manufacturing. Assuming it's qualified, it goes to a GMP manufacturing. The manufacturing process takes about 14 days. We can manufacture at the company, and we so far qualified two different CDMOs. When you look at the drug product that comes out of those CDMOs, we have the same release testing in the three places, and we've dosed patients from all these manufacturing sites. The manufacturing process is quite robust. The CDMOs that we work with can manufacture globally and can manufacture on a commercial basis.
When we look at the cost of manufacturing, without guiding for any pricing in this field, we have a lot of flexibility on pricing, but almost no matter what the pricing is, our COGS, or at least cost of manufacturing, I believe will be less than 10%.
Wow. Very good. Okay. On the safety requirement, what is the safety requirement? Let's say if you go into a registration program in LN first and then SLE, what sort of a safety database would be required for you to file?
We believe, and based on some of the players that I've mentioned earlier, that the FDA will want to see a safety database of about 100 patients. That's very reasonable. That's not inconsistent with other asks that the FDA had in the past. We're in a great spot in terms of the safety database in oncology. We have about 40 patients. These studies are enrolling well in multiple types of patients. That number of 100, that's not a concern for us whatsoever.
Okay. Very good. That's on the INI side. On the oncology side, what's going on on the oncology side?
We have a program that we expect to file an IND for the program and then move it into the clinic next year. I'm actually quite excited about that program. It's targeting prostate cancer. The target is PSMA. The epitope that we're targeting on the PSMA is an epitope that is clinically validated, i.e., there is no risk about the target. We added two bolt-on technologies to these gamma delta-1 T cells. The first bolt-on technology, that's a result of four years of research and exploring many, many bolt-on technologies. Each of them is meaningful, and together, they have great strategy. The first bolt-on technology is a knockout of MET12. Knocking out MET12 improves in a very significant way the serial cell-killing capacity of gamma delta-1 T cells. They kill, and they kill, and they kill, and they kill, and they kill, and they don't get tired.
That's the first bolt-on technology. The second bolt-on technology is membrane-bound IL-12 that gets presented on the membrane once there is activation of the CAR. Once they start killing PSMA, the membrane-bound IL-12 goes up. The advantage is it's in the tumor where they kill the PSMA cells, and the IL-12 by itself has activity and essentially turns an immunosuppressive environment or a cold tumor environment to a hot tumor environment. The synergy between these two bolt-on technologies is very meaningful. That's our first kind of very significant attempt into solid tumors with something that has significant bolt-on technology.
Got it. Got it. IND next year.
Yes.
Okay. Maybe final question. How is the cash balance or cash position and the runway?
Sure. We're well-funded. We recently raised some more money. We have almost $180 million, a little less than $180 million as of September 30th, and that will take us into the second half of 2027. That includes clinical update in LN in the first half, in SSC in the first half, regulatory update, starting the pivotal study in the first half. In the second half, clinical update in LN and SLE, in systemic sclerosis, in RA, potentially some data for two and two. That's just next year. There are a lot of meaningful milestones.
Very good. Very good, Chen. Thank you so much. I think that's all I had for you. Very, very helpful.
Thank you for inviting us.
Thank you.
Great meeting you.
Thank you.
Thank you.