Good morning, everyone. My name is Anthea Lee, biotech analyst at Jefferies. Welcome to day two of our healthcare conference in New York. Really great to have ADASET here. President Chen Shor, welcome.
Anthea, first of all, thank you for inviting us. Really glad to be here today and look forward to a great Farsha Jet.
Absolutely. And maybe before we get into Q&A, I would love to just have you give some opening remarks about ADASET for those who are not too familiar with the company and kind of key catalyst to look for in the next 6 to 12 months?
Sure, absolutely. So Adiset is a cell therapy company. We're focused on a specific type of cells, gamma-delta-1 T cells. Gamma-delta-1 T cells have some key advantages both in autoimmune diseases and in oncology. The key advantages are, first of all, they can be those completely off the shelf. There is no GVHD and no need to gene-edit the cells in order to dose them in an algyneic manner. That means that there's no need to schedule a leukophoresis, and that's a significant bottleneck. Many, most, most of the sites cannot do leukophoresis, and cell therapy is very limited to very few centers. There's no need for the leukophoresis itself. There's no need to wait for the manufacturing and get the cells. So, these are simply completely off-the-shelf for the patients. The other key advantage is that gamma-delta-1 T cells present with a very favorable safety profile compared to alpha-beta T cells or even B-specific, so I can elaborate why we believe this is the case, but this has been an experience across clinical studies. disease, and then essentially they provide the same type of, potentially the same type of therapeutic benefit potentially in autoimmune diseases and in oncology. We currently have one program for autoimmune diseases in the clinic. We have another program focused on oncology, which is a very much, significantly more advanced generation of our Gamma Delta I platform, and I'm happy to share more details about the oncology program. And we have some other, I believe, very, very exciting research program
focused on in vivo CAR-T as well. Great. I think maybe first starting with Prulacel, can you just give us an overview of the asset, the mechanism, and then also all the indications
that you're going after in the autoimmune program? Absolutely. So Prulacel, or ADA-001, is a CD20 targeted gamma-delta-1 T-cells. It was initially developed for NHL, and once we saw the data in autoimmune, we switched to autoimmune diseases. In autoimmune, we started a study that has multiple cohorts. The first cohort that we started was lupus trophitis, then we expanded to SLE, then we expanded to systemic cirrhosis, then to myositis and non-covasculitis, and we have another very small study on RA focused mostly on testing different lymphodepletion regimens. Most of the data that we expect to have in the next data cut are going to be focused on or will be the indications that we started enrolling with. So it's going to be primarily LN and SLE as well potentially systemic
sclerosis. Got it. I think one of the key pushback that I get is that, you know, PRULA cells going after CD20 versus a lot of the data generation in lupus has been in CD19. So what would you say to that? How do you think the efficacy compares there? And are there any disadvantages to CD20?
Absolutely. So all we can talk about is maybe two important points. Number one, when we look at, although we target CD20, when we look at CD19 depletion in the blood in our patients, we see complete depletion of CD19 B cells. When we look at lymph node biopsy, we see complete depletion of CD19 B cells. So, so far, both in autoimmune patients and in oncology, we haven't seen any difference. When we look at the autoimmune study, when we look at the immune reset, we see exactly the same type of immune reset as we've seen with the other autologous CD19 companies. And when we look at the efficacy overall, It looked in the same zip code of the efficacy of the alpha beta T cells. So, so far, we haven't seen any changes, and we expect to do another data cut with significantly more data in patients. So, hasn't been that much of a concern. I'll point out, when you think about Arteva, Arteva is an NK cell that is combined with rituximab that's a CD20, and they announced data a couple of, I think it was about a month ago, and they showed quite potent data. So I'm not sure if there is a big difference, but, you know, the future will tell.
Right. I think, yes, very important to note that in the clinical data that you have, and SLE and LN, if you plot everything together, it trends right in line with CD19. So on a clinical perspective, it seems to be similar. I think the mid-year update is definitely the most near term. Talk about, you know, how many patients you're expecting, 20-plus in six months, six months plus, what you're expecting from that data, and what would be good data?
Sure, absolutely. So indeed, we expect to have a little more than 20 patients. All of them will have at least six months follow-up. Some of them will have nine months follow-up. Some of them will have 12 months follow-up. We expect, at least in LN, look at the slid eye, look at all the relative kidney function. In SLE, we expect to take a look at the slidai. We're going to look at are patients still taking immunosuppressants, are patients still taking any steroids. We may also have the systemic throsis data set. It's coming very soon. We might just combine them all into one clinical update. In terms of what we want to see, we want to see overall efficacy in the same zip code of the autologous cell therapies. The key advantages that we see from PrulaCell is the fact that it's off-the-shelf, the fact that there's no manufacturing, no leukophoresis, the fact that it's very well tolerated and can really be dosing outpatient settings to so many more patients compared to the very few centers that can do cell therapy and leukophoresis.
Got it. Given that this is a much larger data update, 20-plus patients, how are you thinking about how to interpret that? I mean, understandably, with the five-patient data, you would look on an individual basis. Do you feel like this is kind of critical mass to be able to see this on a mean basis, or would you still be watching out for patient data more so?
You're absolutely right. Once you get to this type of number of patients, you want to look at everything and understand the totality of the picture, not uncomparable to other larger data sets that have been reported by some of the bigger companies.
Got it. And in terms of that sleet eye curve, is there kind of a slope or a score that you're hoping that most patients reach? Just talk about a little bit more about the thresholds of mild, medium, severe, and remission, and what you're looking there numerically.
Sure, absolutely. That is a very good question. So in terms of where you expect, it's a little different between SLE versus LN. The magnitude of the reduction in the SLIDA score is usually correlated to how many years the patient had the disease. Most importantly, the chronicity of the patient, because sometimes they have damage that is really unreversible. You sometimes see that in LN patients, because if LN patients had a high chronicity score, their kidney might be so damaged that the protein urea, you're going to see it for long term, and you might never see it disappear. Most of the reduction that we expect to see in the slida usually happens within the first three months, and then it continues to decline over time. And again, overall, we expect the same type of data that we've seen from the autologous.
In terms of how quick responses are, would you say that LN is also slower given, you know, that that disease is very different from SLE, non-renal SLE?
Absolutely. When I mentioned this, LIDA, you see most of the markers go down in the first three months and then continue to slowly decline. You're absolutely right. In LN, in many cases, the protein era takes much more time to resolve. Consistent across many data sets.
Understood. So should we kind of see this data set as LN on its own and then non-renal SLE on its own? Or do you feel like this is good enough to be able to like see it as a whole and like look at the clinical profile in both indications? Sure, absolutely. So we're going to have most of
the patients will be in LN. We'll have a very good picture about the LN. We will have some patients with SLE. I don't remember exactly the number, but it's going to be in the single digit and potentially we'll have patients in systemic cirrhosis. So we'll be able to take a look at
all these data sets. Okay. And what are you looking for in terms of determining which to
go forward to or going forward with both? Absolutely. So initially we expect to consider LN as a first indication. We've seen examples by other companies where they started from LN and and then they expanded to SLE as they enrolled more SLE patients. It certainly has been done even in a pivotal study context, essentially extending from LN to SLE. In systemic cirrhosis, it seems like a pretty small number of, single-digit number of patients can potentially lead to starting to think about the pivotal study.
Got it. This is also a much longer follow-up data, six months, nine months, 12 months. At what point is data enough to be able to assess durability and what kind of signals are you hoping to see? Is it kind of additional decline, as you kind of mentioned, or is stabilization good enough?
It depends on the indication. When you look at the endpoint from a regulatory perspective, it seems to be that six months is the right time frame for LN and SLE. When you look about systemic cirrhosis, not a lot of data out there, but it might be 12 months. It looks like single-arm studies are possible. Of course, the longer the durability, the better. But when you talk to physicians, if they can get one treatment and they see 12 months, Essentially, patients getting rid of most of their symptoms, if not all, stop taking immunosuppressants, stop taking steroids, or reduce the steroid dose to something that's very, very low. Essentially, the patient is symptom-free and doesn't take a drug that takes a big toll on their lives. So I think six months is from a regulatory perspective, and the longer, the better.
Got it. Okay. And I guess going back to the thought about moving forward in SLE in addition to LN, it sounds to me like LN will be the first to go. There's more patients, you'll have a clearer picture, and then SLE will be kind of a decision on whether or not to expand. So what is gating that decision? Would you look to enroll more patients and then have more critical mass before you move forward? Just kind of talk us through your thinking there. Sure, absolutely.
In SLE, that's the case. It's potentially expanding the data set and understanding better the durability of the data set that we have because it's just smaller. I'll just expand also in systemic explorers. Again, it's understanding the data set and seeing when do we want to consider moving to a pivotal.
Systemic explorers. Just remind us the endpoints that you're watching out for. again what is clinically meaningful there and also how much data you provided this update
absolutely so systemic growth is very very different from SLE or from LN first of all in both cases there is an unmet medical need but in systemic growth is the unmet medical need is very very significant the drugs that are approved today do not improve the skin score they barely reduced the reduction in lung function you see some of the patients that walked into our study their skin is so thick and stiff they can't hug their own family members and they can't climb stairs like it's it's really really a terrible disease and there is no available therapies what we're looking at in the study is one lung function, and there the hope is pretty much to stabilize the lung function so it does not continue to deteriorate, and the other is the skin scores. Now gamma delta 1 T cells have troposin to the skin, quite significant troposin, so we really look at the MRSS score, and of course we're going to look at the CRIS, which is a combination of a couple of data points as well. So we'll have all
this data when we report data. Got it. And can you talk about how many patients or roundabout that you expect to provide
an update on and how long? Sure. Single digit number of patients and how long it's going to be. I don't want to guide you on how long. I'm waiting myself for the data cut. I have a sense, but I wouldn't want to mislead you. Okay.
Absolutely. How do you feel that, you know, stepping back a little bit, how do you feel that Prulacel's efficacy looks like so far compared to the autologous CAR T's? Do you feel like, given it's off the shelf and there's, you know, manufacturing efficiencies relatively, that there is potentially a discount on efficacy that Prulacel can take compared to auto CAR T's?
So, so far it looks quite similar to the autologous CAR-T efficacy. Whether there is some room for difference, I think there is. I think there is. Because when you think about the cell therapy, they're really available to very, very, very few patients in few centers. And when you think about something that's off the shelf, you can dose it in outpatient settings. So many more physicians can prescribe the drug. The commercial model is completely different. The cost of manufacturing is completely different. Where you stand in the formula is completely different. So it's really the difference between a specialty drug in few centers versus something that could be much more available.
Understood. And how are you thinking about COGS and pricing, understanding that it is kind of far away, but is there also an opportunity to differentiate on price when you eventually launch?
Absolutely. We don't have all the liabilities of autologous cell therapies and manufacturing. When you think about the cost of manufacturing an autologous cell therapy and release, it's not that much different than what it costs us to manufacture one in an off-the-shelf manner, and it's available for so many more patients. so our cogs is significantly lower and much closer I want to say to the antibodies cost of manufacturing so in terms of pricing very premature to discuss about pricing but I think there's going to be a lot of flexibility
right RA data in second half again talk us through kind of what you're looking in that cohort what gives you confidence that you could see the data there and and then also kind of what signals you're looking for to move forward.
Absolutely. Yeah, I've been asked this question a couple of times recently. So I want to remind people that the RA study was really positioned to understand whether Prulacel requires Cy-flu or Cy-only. So essentially we are enrolling, I believe, six patients in one dose level and six patients in the higher dose level, 3, 8, and 1 in 9. And in each case, we're comparing psi-flu versus psi-only. And really, the goal is to understand, do we see difference in the B-cell depletion? Do we see difference in, you know, how patients with RA in terms of their symptoms? But it's a very, very small study, and the goal of the study is to understand whether fludarabine is necessary.
Do you have kind of any early data or, you know, work that you've done to point to whether you think that flu would be necessary here?
So we just started, actually we started the study a couple of months ago. It's still enrolling. It's now enrolling at the 1E9 dose level. So we just need to get the data.
Yeah, understood. And then also many other indications for Prilasal as well. So just talk us through kind of how those cohorts are enrolling and where we could see additional updates.
Absolutely. So we had to focus at some point from an execution perspective. So the focus on enrollment has been LN, SLE, and Systemics Rossis. The other indications haven't enrolled in any significant way, and we haven't focused on enrollment in these indications. So really, it's LN, SLE, and Systemics Rossis that has been the focus.
At what point do you feel like you could kind of shift your focus a little bit and accelerate more of that enrollment? I think Ellen and SLE, understandably, maybe when you move forward to your additional trial, but maybe when do you feel like you could kind of put more focus into indication expansion and feel comfortable with kind of the core indication moving forward?
Sure. At this point, we think that LN and SLE and systemic sclerosis are, you know, pretty big indications. When you think about the number of patients, that's the reason we didn't focus on the other indications. So I believe there is a lot more room to expand to other indications, but we wanted to first get a good read on these indications, see the path to potential pivotal studies. And as we go there, we can start thinking about what indications we want to expand. But, you know, focused on data first.
Yeah, makes sense. And speaking of indication expansion, have you thought about maybe expanding into MS as well, just given that there are C20 therapies there?
Yeah, MS is a great potential for cell therapy, autoimmune, a little longer endpoint. and the studies generally are much more expensive because they require MRI, but definitely something that we've been thinking about. In terms of ability to execute, when you think about how we were able to execute, we're probably one of the very, very few companies that have been able to enroll this number of patients. Most of the smaller companies have very small data set in the single digit. That required focusing, and we focused on sites that are either rheumatology sites or nephrology sites, so we can find these LNS and systemic cirrhosis patients. Moving to MS would require more focus on neurology. It's something that we can certainly consider in the future, but in order to enroll so far, we had to focus on these centers.
I understand. If you had to rank the remaining indications outside, I know it's a difficult question, outside of LN, SLE, and SSC,
how would you think about that? It's a very tough one to rank. I would love to hear how you would rank them, actually, and opine on that. No, I think it's a very tough one. Each indication is so unique from an unmet medical need perspective, from a regulatory perspective, from a competitive landscape perspective. So you really want to think about each indication.
Got it. Safety, another very important topic. Talk about what you've seen so far and how you feel or what you're kind of looking for in the additional update.
Absolutely. So I'll start with a problem. The problem with making cell therapies available to many patients, one is you need to make sure that facilities can provide the therapy. The second one is actually the safety. Now, when you think about alpha-beta T cells, whether it's an alpha-beta T cell or even be specific, a part of the activation profile of alpha-beta T cells is secretion of IL-6. That secretion of IL-6 is associated with CRS and with ICANs, which essentially is neurological toxicity. Now, we don't know who is the patient that would get CRS and ICANs Because if I, for example, I'm blessed to have great T-cell fitness and I'll get the therapy, they'll proliferate great, they will secrete a lot of IL-6, and I'm much more likely to get CRS than I can. So that's an issue with alpha-beta T-cells. With gamma-delta-1 T cells, and we have learned these during our clinical studies, the increase in IL-6 is not significant in any shape or form compared to alpha-beta T cells, and that indeed translated across all the indications into a lower rate of CRS, a very low rate of ICANs and significantly lower severity of CRS and ICANs, and the FDA knows our data. When we showed the FDA our data, they were perfectly fine with us moving, at least in LN and SLE, to outpatient dosing, and we don't need to hospitalize that patient, so that presented itself as well.
In terms of the broader landscape, how are you thinking about CAR-T's and lupus in general, given that, you know, you have bispecifics, you have T-cell engagers coming and, you know, pursuing this indication as well?
Sure, absolutely. So first of all, it's a huge market and there's room for everybody. Now focusing on data, T-cell engagers in oncology have shown efficacy that's a little subpar compared to autologous cell therapies. When you look at the data reported so far for T-cell engagers, this is the case again. It looks like the T-cell engagers would require some kind of a semi-chronic dosing, or I've heard it called as immune dimming. So essentially, it's a new potential class of immunosuppressants that will continuously deplete the B-cells for patients. Now, when you think about the unmet medical need of these patients, this long-term immunosuppressant leads to many problems for these patients. One of the causes of mortality, for example, in SLE and LN, is infections. So while they definitely have room in the market, in terms of the magnitude of efficacy and in terms of the potential long-term toxicity, I think that might be an issue. Now, definitely for some patients, a new class of immunosuppressants might be something that's very, very viable and desirable, but for many other patients, they would rather take a one-time therapy that will relieve them from symptoms and from the need to take those therapies for, you know, whatever the median durability is.
Understood. And I think we have a couple of minutes, so maybe we should move over to ADI21. Talk a little bit about the program, kind of what types of enhancements you've made to the asset.
Absolutely. I am very excited about the ADI-212. We recently changed the guidance that we'll file Dian Dean Q3. It's coming very soon, and then we'll enter clinical studies. The reason I'm excited about the ADI-212, it's a result of more than four years of research at ADISET. The question that we were asking ourselves is, how can we make cell therapy work much better for solid tumors, leveraging the advantages of ADI-212? So let's just think what we've done. So ADI-212 is a gamma-delta-1 T cell targeting PSMA with two important bolt-on technologies that were designed to enhance its efficacy. So let's go one by one. First of all, the target that we're engaging is PSMA. And there's been programs that have been more successful versus less successful targeting PSMA. We're targeting essentially a binding site in the PSMA that is clinically proven and is a little consistent with Pluvicto. And we know that patients that take Pluvicto as an example, most of them maintain their PSMA. And that's how you enroll them. So the binder is pretty validated, or the binding mode. Number two, we knocked out a gene called MET-12. When you knock out MET-12, the cytotoxicity and the repeat killing capacity of the cell is significantly enhanced. Essentially, the cell keeps killing and killing and killing and don't get tired. That is uncomparable to any cell therapy that I've seen, whether it's gamma delta or alpha beta or anything else that we've seen. It's a little bit like the commercial for dual cell, the dual cell that keeps killing. And then the other Bolton technology, we added a member-bound IL-12 that is presented on the cell once it engages PSMA. Now, we know that IL-12 reshapes the immune tumor microenvironment of the tumor to something that's much more friendly to cell therapy. It brings other cytotoxicity mechanism to the therapy, and it really synergizes with the MED-12. So when we look at the overall profile of the program, we think it's quite promising. We've had some early meetings with the FDA. We received some great feedback, and we expect to initiate the study very soon.
Okay, great. Just very quickly, what are the kind of feedback that you've gotten from the FDA so far, and how quickly can you move into Phase I?
Sure, absolutely. So we're actually starting to work on the Phase I now. We expect to start enrolling potentially in the fourth quarter of this year and have data next year in this program.
Okay, perfect. and lastly, remind us of your cash runway and the path to the many catalysts ahead?
Sure, absolutely. So we expect to have, in terms of catalysts, we expect to have data in LN, in SLE. We expect to go into the clinic with PSMA, potentially have data in PSMA. We're well-funded into the second half of next year, and the only thing we haven't covered, and you might hear something, and it will create a lot of noise is an in vivo program that we haven't unveiled. We've seen one program in the in vivo space that has been unveiled recently, and this is something we've been working on for a while. We haven't talked about it, but once we do, it's going to be meaningful.
Ending on a very exciting note. Thank you, Chen. Thank you, everyone, for being here. I hope you have a good rest of your conference.
Thank you, guys.