Okay, thank you everyone for joining us for the Citizens JMP Securities Hematology Oncology Summit. I apologize for the delay, it's my fault. So the next company we have our side chat is Precigen. We're very happy to have President and CEO, Helen Sabzevari, with us here to talk about the company, and for this summit at least, we're going to focus on their exciting cell therapy platform, UltraCAR-T. So, Helen, maybe just give a brief intro, please, of Precigen, and then let's dive into the UltraCAR-T platform.
Sure. Thank you, Roy, for having us. As you know, the Precigen is a cell and gene therapy company that mainly works on two platforms, one with our gorilla adenoviruses, that addresses the training of the immune system from within, and developing cancer vaccines and also vaccines for rare diseases, especially for our PRGN-2012, which is now have received both breakthrough as well as accelerated path, based on the phase I data and receiving our phase I, phase II single arm as a pivotal.
And then the other platform, our cell therapy, UltraCAR platform, which is a unique platform to Precigen, that is truly the only platform that is an overnight non-viral, CAR-T platform, that the autologous T-cells from the patients directly produced, and genetically modified by our non-viral UltraVector plasmid, with the insertion of the certain genes that allows the cells not only to express the CAR of the interest, but also have mechanisms such as membrane-bound IL-15, that allows the expansion and persistence of these cells directly within the patient's body, so there is no activation involved. This manufacturing takes place at the hospitals, and it's differentiated completely from all of the classical or allogeneic from a perspective of, first of all, we do not use lentiviruses.
It's a non-viral platform that's really advanced, and we have addressed the issues of viability, efficiency of transfection, and as well as the redosing and cost in conjunction with the device that we have generated. So it's very unique, and we are very excited. We are in three clinical trials currently, and I'm looking forward to speaking into details with each one of them today.
Okay, so the FDA recently raised some issues, potential issues, I guess, around some of the CAR-T products out there, safety concerns, pretty high profile. You don't feel that's going to be an issue for the UltraCAR-T platform? Maybe could you just give us a little more color on why you think that that's not necessarily an issue?
Absolutely. No, I'm so glad that you asked, and, you're absolutely right. In the past few weeks, we have seen a lot of activity on side of FDA and investigating, especially even the approved CAR-Ts that are currently in the market for the hematological settings. And, the gist of it is, there has been cases of CAR-Ts lymphoma that have raised in these patients. So clonal expansions of the CAR-Ts, that they have been infused into this patient, and of course, this is a major concern. Of course, the numbers are still limited, and for the field, there is a feeling that FDA currently is looking at, according to the numbers, thousands that have been treated, these are still in the single double digit.
But also, as you are aware, the number of companies had started to address the autoimmune diseases with this classical CAR-T CD19, for instance, in lupus. And addressing it with the same classical method of lentiviruses and centralized manufacturing, the field has been moving toward also using this in a chronic diseases, which is completely now different issues, because these patients, obviously, they have a chronic disease. They, they do not have a fatal disease, and the safety then becomes of a major issue. Why we think we are differentiated and we have a better platform? Actually, this was one of the things that originally when we started differentiating ourselves and going to a non-viral platform, that was one of the concerns.
When you are looking at the data that over the years has been published with the viruses in general and also including a lentivirus in the CAR -Ts, the viruses have a tendency sometimes to insert themselves into a hotspot in the genome. And what do we mean by those hotspots? When the virus has more tendency to go in one place or to one area that is hotspots or certain promoters are present, it has a tendency to turn on the certain genes. And as a result of that, the chances that by mistake, these genes, especially in a proliferative responses, can be turned on, is higher, and this has been reported in some of the literature.
Now, on top of that, when you use the lentiviruses for these, classical CAR-T or even off-the-shelf, as they are being used, the second issue is because they have to expand the cells outside for a number of weeks, you have a tendency of somewhat of a selection. And on top of that, at the end of the, let's say, 4 weeks or 8 weeks of manufacturing that all of the classical CAR-T and off-the-shelf go through, then you are the infusing the patients with billions of cells.
Now, again, on top of the chances that, the viral infection that is needed, the lentivirus, for insertion of the genes into hotspots, on top of the activating these cells for 4-8 weeks in order to get enough number of cells and making them activated, therefore, you are expanding certain clones that might should not be expanded, and then injecting billions of cell, the chances that you have that there might be a certain clones that you are injecting becomes much higher. This raises the risk factors. How are we originally, when we were looking at this platform, how did we address that? First of all, we went to the non-viral platforms, which are we are introducing with the electroporation, with transfect the autologous T-cells of the patients with the plasmids.
There has been a number of papers that actually has been published on a Sleeping Beauty very clearly that they had shown this has less of a tendency, it's more random that it gets to the genome, and it not necessarily have a preference to go to a specific hotspot. That has been number one. Number two... So that's the advantage we feel over these lentiviruses. Second part of this, because we have now advanced the platform to the point that you are only with our UltraPorator, under 12 minutes, you can transfect 4 billion T cells of the patient's autologous T cells.
Because we have membrane-bound IL-15 in, and we do not need to expand these cells outside for weeks in order to activate them and reach the numbers that we need, we actually just at the site of the hospital overnight, these cells are transfected, rested, and the next day they are QC'd and infused back to the patient. This is an advantage because now you don't have this possibility of a specific clone to be expanded. What we have shown as part of our data, very, and we presented this data both at ASH and ASCO for hematological as well as solid tumors, that we could be infusing as little as 10 million- 80 million cells total, one dose, and have objective responses in the patients. So therefore, we believe that our platform has the advantage.
And one other very important factor that we have within our UltraCAR-T, the way we have designed our UltraCAR-T, not only we have the CAR of our interest, not only we have the membrane-bound IL-15, but we also have included a safety switch. That safety switch allows, if anything goes wrong with the CAR-Ts, the UltraCAR-Ts, you can eliminate them. And in our preclinical model, and as part of our INDs, which we submitted to the FDA, we have shown that in preclinical models, we can activate this switch and completely eliminate all of the UltraCAR-T. Thankfully, in our clinical trials, we have never had to activate this switch, but this is a safety switch.
For the importance of this discussion, I should mention that the CAR-Ts that are currently under investigation, for instance, for this lymphoma of the CAR-T, and in general, all the CAR classical CAR-Ts and the off-the-shelf, they do not have these safety switches. So if something goes wrong, which in the cases of the patients that have gone wrong, unfortunately, there is no way that you can eliminate this. And I think this is a major differentiation because of our platform and having the ability to insert more than one gene, which is just a CAR-T, it has allowed us to have the safety switch in every UltraCAR-T that we have in the clinic currently.
And this is a further way of making sure that there is a safety switch for our patients that they receive this, in case that anything goes wrong, not only just in case of the if there is any kind of expansion, but also if there are other safety, and you can completely eliminate this. And those are the major differences that our company and our platform has, compared to all the other CAR-Ts in a classical way with the lentiviruses or off-the-shelf that currently is out there.
Okay, and you've had impressive safety so far, you know, as you've mentioned, without activating this, this safety switch. Maybe and I want to talk a bit about how you're determining dose, et cetera. Maybe let's go to the, you know, the, the hematological lead candidate, PRGN-3006. Just what's the target, the intended patient population is? How do you see it fitting into the landscape in this, in this indication?
Actually, the reason that we started our first hematological indication was in AML, and the reason for that is very simple. Unfortunately, the patients that they have AML, and they have failed all of the therapies, they have very few months to live. So by definition, these manufacturing ways of classical CAR-Ts or off-the-shelf, it's just too long, the before they can get these cells back to the patients. These patients, as I mentioned, some of them they were even in hospice when they came to receive our treatments. So we felt that overnight manufacturing of the UltraCAR-T of their own CAR-T with our platform was a very good chance to get to this patient population very rapidly.
It targets CD33, which is expressed on more than 80%, almost 90% of all the blast cells in AML. And why is this important in conjunction here? Because it covers the blast cells in the blood as well as in the bone marrow. We can very rapidly produce the cells overnight at the hospital, and next day being infused to the patient without any expansion, activation, and making these cells, exhausted. And what also has been very important with the AML, and something that I really would want to stress, we knew that if we go after a CD33 blast cells, there are a lot of AML patients that, on the earlier stages, they have mutations, for instance, FLT3 IDH.
But this is only percentage of these patients, 10%, 5%, that they have these mutations, and there are, of course, a small molecule inhibitors that address, can address that. But what we have seen over time is, even with the usage of a small molecule inhibitor, there is relapse in all these patients. And our aim is first to show in a very late stage the safety and efficacy of our CAR-T, and eventually move this into the front-line treatments, and even in regard to the mutational, basically, patients that they have mutation in combinations. Because the patients, obviously, some of them, they have the mutation, but the escape and the relapse is because there are other clones there.
You can imagine that this has the possibility to move to the front line, and that's why we moved into the AML area and started producing the UltraCAR-T in regard for this patient indication, which is an orphan and really a patient population that have very little time to live.
Okay, and then maybe just briefly, talk about the data you had last year at ASH, and then I think you said preliminary additional data in 2024. Maybe just what to expect there in terms of patient numbers, what we should look out for?
Yeah, we are very excited about the presentation at ASH that we had. At ASH, first of all, we showed that not only with one infusion of these cells in various doses, we could expand these cells directly in the patient, and these cells can persist in patients for months upon months in a very controlled fashion, and that's very, very important. These cells are not expanding to the point of becoming leukemic or lymphatic. These cells respond to the blast cells. They expand when they see the tumor cells, and then they just maintain and sustain themselves. And so because there have been mechanisms of safety put in, what we showed for the first time was close to 28% objective responses.
We had complete responders, as well as partial responders in a patient population that received between 10 million-80 million cells, total. One shot, one time, which is comparison to what all the other therapies are fraction of the billions of cells that are given. What we have seen is, first of all, a very good safety. We had CRS, that they resolved at less a Grade 2 and less, that resolved on their own, some of a majority of them. We also had no neurotoxicity, no DLTs, and what we have shown is that these cells persisted and were able to achieve objective responses, lowering the blast cells, not only in blood, but also in the bone marrow of this patient. These are some of the patients that we had. They had seven prior line of treatment that they had failed.
Some of these patients, we were able to actually bridge them to transplantation, which they were not qualified to transplant before. One of our patients that has received a transplant, this patient now has passed 2 years post-treatments with the UltraCAR-T and is still ongoing. So we are really excited about this data. We have gone, we have chose the dose, which is 1 million cells per kilogram, and as I mentioned, these cells are manufactured overnight in a clean room at the hospitals by the hospital, basically technicians there. We are in an expansion phase. We have received from the FDA a Fast Track designation, and yes, we have mentioned that, by end of 2024, we will be reporting on the data from expansion phase and preparing to have, further discussions with the FDA with the data from expansion phases.
We are looking forward to this in 2024.
Okay, great. The dose is really selected because you're seeing efficacy and manufacturing, you know, keeping it to one-day manufacturing. You're not seeing a dose-limiting toxicity or anything?
No, the dose was we have actually, objective responses that we have seen in the phase I. We have seen it as little as 28 million cells, in patients as little as giving 28 million cells. So at the dose level 2, which was between 300,000-1 million, and then at the dose level 3, which was 1 million, we have seen objective responses, and that was the reason that we chose the 1 million. Because you don't need to go... If we are seeing objective responses with very good safety, sometimes more is just more, and it can make things worse. It doesn't mean it's better.
Our UltraCAR-Ts are designed in such a fashion that they can persist, and one of the reason that lentivirus viral CARs are off-the-shelf, they have to be given, in such a high numbers and repeated fashion, in a sense, for off-the-shelf, is because these cells don't persist. If you look at the graphs, they are there for maybe a week or two weeks, and they cannot persist because they don't have the mechanism. With membrane-bound IL-15, as I always refer to this, as a backpack food for these T-cells, they can maintain themselves, and in the absence of even seeing an antigen, they can just stay quiet and maintain themselves and be around. And if the blast cells come, then they can see it and expand and basically kill the tumor cells.
Okay, great. Just in the last minute here, just wanna talk about PRGN-3007. It's engineered a bit further. Maybe you could just briefly describe what that's-
Okay
... that construct.
Our PRGN-3007, it targets ROR1, and this is an antigen that is expressed both on hematological as well as solid tumors on CLL, CML, ALL, as well as triple-negative cancers, lung cancers, and ovarian cancers. What we have done is we also have gone to the next generation. In our UltraCAR-T, not only we have the CAR-T against the ROR1 membrane-bound IL-15, our safety switch, but we also have introduced a mechanism that silences the checkpoint inhibitor in the CAR-T, in our UltraCAR-T. Why? As we all know, now the field has realized, CAR-Ts or regular Ts, when they hit the tumor microenvironment, they can be undergoing anergy or anergic because of the checkpoint inhibitors, and that's why everyone is combining checkpoint inhibitors.
But that is, first of all, it's another source of toxicity, systemic toxicity, and adds to the safety issues. But secondly, it adds to the price tag of this treatment. On top of the $400,000 that are for our classical CAR-Ts that are being charged, now you have to add another $100,000-$150,000 for that, which makes this an impossibility to sustain this kind. So now we have genetically basically modified these cells that it allows the silencing of the PD-1. You do not need to combine these UltraCAR-Ts with checkpoint inhibitors, and because they are only expressed in the CAR-Ts and nowhere else systemically, obviously, the safety and toxicity is less. And this is in a phase I, and currently in an umbrella trial.
We are moving through our doses, and we also look forward that by end of 2024, we will report on the data from a phase I and doses that has been in. And that's quite exciting because it brings in the next generation of a non-viral, overnight manufacturing UltraCAR-Ts.
Okay, great. All right, well, it looks like we're out of time. I really appreciate the insights, Helen. Thank you for spending time with us today.
Thank you very much for having us. Thank you, Roy.