Great, everybody. Thanks again to all the organizers, the folks behind the scenes making this so easy for us. I'd like to welcome Dr. Helen Sabzevari. Helen, I hope I'm saying that correctly, or-
Absolutely.
Thank you so much. But thank you, Jo, for joining us. Precigen is a company that's doing some really interesting stuff and could have an approved product in a year, two years, in a disease with a very high unmet need, a disease, RRP, that we've gotten to know very well. We'd love to get a presentation from Precigen on all the other things also that they're doing on top of, the RRP project. So with that, Helen, please take it away, and I'll just remind everybody, we'll have about 10 minutes left, 10 to 15 minutes left at the end for Q&A.
Thank you so much, Hartaj, and I'm really glad this is the first time that we are presenting and have the opportunity to present to you and the audience. From a perspective of maybe I give... First of all, I will be making some forward-looking statements, so please make sure that you read the statements. And what I would like to do today is just give you a overall view of who we are, what Precigen does, and how we are differentiated.
So if we go to the next slide, basically, Precigen is a cell and gene therapy, but it really addresses the indications by cell and gene therapy with two platform, that one, it educates the immune system, what I consider from within, and this is our gorilla adenovirus platform, and I'll be talking about that, especially in regard to the RRP. These are vaccines that can train your own immune system to see either the infectious, the tumors, or other components that they have been designed to train the immune system. On the other side, we also have our very differentiated and unique, basically Ultra CAR-T platform. This is not the old classical CARs. This is not off the shelf. This is truly a non-viral overnight platform, which I will be going through the differentiation part of that.
And in this setting, now, as a cellular therapy, what we do is genetically modify the autologous T cells of the patient directly overnight at the hospital, and by next day, we are transferring back autologous CAR-T specific for the patients and for the indication back to the patients. So with these two platforms, in the next slide, what you see is our both clinical and the preclinical, what we have at least in regard to the usage of AdenoVerse platform, which on the top, as you can see, we have our PRGN-2012, which addresses the RRP patients, PRGN-2009, which is directed toward the HPV-related oncology indications, and both in, head and neck, as well as cervical cancers.
As far as UltraCAR-T is concerned, we have a number of clinical trials, both in phase I, phase Ibs, moving forward in hematological, as well as solid tumors, which I will describe a little bit later on. Well, let us start with: What is our strategy? A Precigen strategy is very, very clear. First of all, we start with the differentiated platforms, that we make sure that these platforms are scalable and commercially viable. And then we have a very, very specific way and strategy around the indications that we apply these platforms to in order to reduce the risk and increase the probability of success. And a good example of that is our PRGN-2012. We are moving toward the BLA filing, as we have communicated by second half of this year, and readiness for commercialization in 2025.
This is indeed will be a transformative year for Precigen, which we move from being a research, discovery, and development company to a commercialization. We also have put in place a diversified clinical pipeline based on the two platforms. So we are not one basically drug that if it makes it or it dies, then the whole platform or the pipeline is gone. And we have, as you can see, a number of based on the basically using the platforms that we have and making sure that they are functioning in the clinic well, then we bring in the next drug product, such as PRGN-2009, which uses the AdenoVerse gorilla platform, similar to PRGN-2012, but it's now in oncology indication and HPV-related cancers.
Finally, our UltraCAR-T platform, which, as I mentioned, it addresses both hematological and also solid tumors. But more importantly, we are using it as first in a class and the best in a class, not only in oncology, but in autoimmune diseases, and I will explain that more. With that in mind, let's, ah, d efinitely, this audience is not new to the RRP, and we, as you very well know, RRP is a disease, is recurrent respiratory papillomatosis, is a rare disease. It's caused by HPV 6 and 11 infection, and basically, this patient, they continue to have these recurrent benign tumors, either on the vocal cords, in the trachea. There is no therapy, current therapy except surgery for these patients.
Some of these patients, since they have this disease from childhood, that because of passage through the birth canal, they basically, they get infected from their mothers. Some of them, they have had upward of 300 surgeries in their lifetime. Other patients in adult, usually this gets transferred through their sexual transmission. It's a devastating disease, which affects, in United States, it's estimated, and this might be a conservative estimate, between 15,000-20,000 patients. As I mentioned, the surgeons, they just have to go in and continuously clean. There is no other options for these patients. With that in mind, knowing our Adeno-associated gorilla platform basic capability, and why would I say that? Because this platform is not your typical AAV platforms. They are not typical viruses.
These gorilla viruses, they are differentiated from the rest, first of all, by the capacity of the number of genes that they can have. We are at 12 kb, whereas if you look at the AAVs, lentiviruses, all the others, they are below 5 kb. So you can imagine how many epitopes and genes we can put in there. But more importantly, the humans, they either have no pre-immunity at all to this or very little, because they have not been exposed to. What does that mean in practicality? You can keep repeat dosing, and that's what we have done, not only in RRP, but in oncology. And we have shown that we have treated patients sometimes upward of 16 times, and you keep enhancing their immune and T- cell responses.
That's what it makes this platform very, very unique, and it has shown an excellent safety profile. The way it works is basically you vaccinate subcutaneously, as you see here. It's like receiving a flu vaccine. You train your T cells to the specific epitopes that are in your vaccine. You expand them, and these T cells are now the new army, that they will fight the indication. In this case, it's the RRP. It's very important, the mechanism of action here, because surgery is like, for this patient, is like, basically, mowing the lawn, right? It keeps coming back, and it gets worse. However, with this vaccination, what it does, it gets to the root of the problem, which is the infection of this tissue and the surrounding tissue. So your army of the T cells, they come in and clean up.
That's what it does specifically. So with that, what we have done is basically, these patients, they receive a regimen of four vaccination in a span of 85 days. When you talk to the patients of RRP or the KOLs or investigators, I think everyone unanimously tells you, if you reduce the number of surgery, you have done incredibly well. We put a higher bar than that. What we did was, first of all, using this platform, not only can we reduce the number of surgeries, but more important, can we at least eradicate requirement of any surgery for at least 12 months? And we sort of refer to this patient, so this endpoint, as a complete response. And we did one other thing.
In order to make sure that we are addressing the most severe patient population, we didn't go to patients that they had one or two surgeries per year. We went to a severe patient population, that they had minimum of three and above. The average number of surgeries in our patient population has been above six. So with that, we put a very, very tough endpoint, and on our Phase 1, which you see the data, we went after the dose level 1, dose level 2. In our dose level 2, this is the result in the first 12 patients that you see here. What we saw, which was absolutely so exciting, both for the patient and us, was 50% of these patients, that every year they had required number of surgery, you can see some of them with eight, four, 10, eight.
After 12 months of follow-up, they did not require any surgery. No surgery whatsoever. 50% of these patients, they went to a complete response. And I am really excited to tell you that we have been following these patients for now past 24 months, and they are still in a complete response, and they have not required any surgery. If you look at the total reduction in the number of surgery, 83% of our patients reduced their number of surgery. But it has been very, very important in conjunction with the great safety, and our investigators, they refer to this, the safety is like receiving a flu vaccine. We have not seen any DLTs, no grade threes, very low-grade fever, and maybe some rash at the site of the sub-Q injection.
What's also very interesting is the correlation between the complete responders and the immune response that we have generated in this patient, which we published in Science Translational Medicine last year. So it's quite exciting, and based on this, FDA actually granted us the first time for any company to receive a breakthrough designation in this indication. Also, an accelerated approval path last year in July and August of last year, and also agreed that our phase I single-arm pivotal, plus the phase II single-arm pivotal, which we had finished in 2023, can serve as a pivotal trial without requirement of a phase III randomization. Currently, as we have communicated, in the second quarter of this year, we will be reporting the total result of our phase II, and we are looking forward to that.
Also, as we have communicated, the second half of 2024 for a BLA submission, and in 2025, we are getting ready for commercialization and approval. So it's a really and truly a transformative year for Precigen, and I'm very proud of our patients, first of all, investigators and our team that have advanced this program since April of 2021 to now, 2024, that we are moving toward the BLA submission. With that in mind, this is the key characteristics and potential of RRP. Obviously, it reduces not only the surgical burden, but actually a complete response, and 50% complete response, which is unprecedented. It has a durability of response, as I mentioned. Not only we have followed these patients for 12 months, but now they are past 24 months, and they are still in a full response.
It's a very easy and preferred method of administration. It's just a subcutaneous injection in the arm or in the leg. Very easy, not painful. It doesn't require any other device or anything else, can be done in any basically office of ENT surgeons. And finally, I think the safety that it's quite—the safety is very, very favorable and as our investigators say, is like a flu vaccine or even better. So with that in mind, this is a sort of a view. We have applied a similar type of using the same platform for our PRGN-2009, which, by the way, we have now our Phase IIs, both in head and neck, as well as in cervical cancer.
And just to give you a little bit of view, because of the time span that we have, we reported at ASCO that in Stage IV patients that they were HPV-infected oncology indications such as cervical and head and neck, for the first time, we reported 30% of these patients that they have failed everything, including checkpoint inhibitors. We had 30% objective responses, partial response, complete response. With our complete responses, actually with a very durable response, well over a year. So we are looking forward, and we have done discussions with the FDA. This is moving. It's in phase II/phase III, and we are looking forward to the next data reading for this. And finally, let me just say a few words about our UltraCAR-T platform. So if we go to the next...
Our UltraCAR-T platform, we really moved with this platform in order to address the deficiencies that existed in the CAR- T, classical CAR- Ts off-the-shelf and TCR, which was the use of lentivirus, which can insert itself in the hot spots, and we see the safety issues that are being raised, even in approved products currently. The cost of it, which is quite high, majority of the price tag of the approved drug is because of the manufacturing cost that is associated with the lentivirus.
It's a long period of time, even when they have shortened it, even when they have put it as a off-the-shelf, it only has gone to weeks, and you are exhausting a number of cells and then putting it with a very high cost, and these cells can live for a very short period of time, unless they become malignant, which now you see in some of the cases that it's arising. And finally, the centralized manufacturing that is associated with the both cost and time to patients. We address this, first of all, with advancing and scaling a non-viral platform that address the issues that the non-viral platforms they had before, which was rate of transfection, viability of the cells. We scaled it by generating our own device, which is the UltraPorator, which no other company has. This machine can do 4 billion T cells....
And transfect them with the genes of interest and our UltraV ectors under 12 minutes. This is what you need in manufacturing: reduce the time, scale it, and introduce safety mechanism. The way we have done that is our plasmids, they include not only the CAR of your interest, but also they all have, every single one of them, they have safety switches in them that in the case that anything goes wrong, you will eliminate—you can eliminate these cells. Why is it important? Exactly for the reasons that you're just now seeing with some of the approved drug products, that the CARs had become malignant, and you—in that setting, you cannot eliminate them. With this technology, you can eliminate them. Luckily, we have never had to, actually initiate this in our clinical trial, but it is there if it's needed.
And finally, we have a mechanism that you truly manufacture these cells directly in a patient body. Our membrane-bound IL-15, which I refer to as a backpack of these CARs, it allows these CAR-Ts to get inside the body. It in a very controlled fashion, it maintains them if they don't see the antigen, in the cases of solid tumor, or it allows them to expand when they see the antigen, and they persist. And all of this is done overnight at the hospital without any Precigen employee, just the technicians that they are in the hospital. It's a semi-closed system, and the next thing, the cells are generated, QC'd, and infused back to the patient.
This, we have been very, actually thankful to FDA, very we have a close, interaction to get this, unique technology to the clinic. As we speak, there are a number of sites that this is happening at, and this clinical trial is ongoing. In this table, you see the differentiation of our Ultra CAR, which I went through specifically, and this is what it makes us, not another me-too or CAR- T or off-the-shelf. This is genuinely unique, and it's paradigm-shifting as far as we are concerned, and we are the only company that, as far as we know, that has this capability. With that, if we go to the next, this is our Ultra CAR-T basically clinical portfolio.
We are not only with our PRGN-3005, which addresses the MUC16, the unshed portion for the ovarian cancer, and as you know, no one else at the moment has been moving toward the solid tumors. This is very, very exciting, and we have shown data at ASCO for this. PRGN-3006 addresses our AML patient. These are patients that they have 3-4 months to live at the stage 4. So you can imagine that the regular CAR-Ts, they can't even, the manufacturing doesn't allow it to get to the patients, and we have been doing that. We also have the next generation of CAR-T, PRGN-3007, addressing the ROR1 in both hematological and solid tumor.
We have an umbrella trial that is ongoing and addressing not only CLL, CML, but also, for instance, triple-negative breast cancer and other solid tumors, such as lung cancer. Finally, our CD19, which now we have the full rights back to this, and we, with our platform and next generation, it allows us to be the best in the class as we move into the ALL indication. But also, we believe for autoimmune immune indications such as lupus, we will be not only the best in the class, but the first in the class. So let me just show you a highlight of this. It's this is our PRGN-3006. Last year, we presented at ASH, and we showed our phase I data, which was quite exciting, with a very favorable safety data.
But more importantly, for the first time in this patient population, we saw 27% objective responses, partial and complete responders in this setting. What you see on the left hand, this is the CAR of interest that has the safety switch. It has targets, the CD33 and membrane-bound IL-15. There is a lot of talk about the small molecule inhibitors and the mutation in this patient population. As you know, that only addresses, like, FLT3 mutation and IDH1. These are 6%-7% of this patient, and eventually, when they receive these, small molecules, after six months or a year, they relapse, and these patients have no other option. Why CD33 CAR is very important? Because 90% of the blast cells of this patient, they have CD33, whereas if you look at the mutation, maybe 6%-7%, they have that.
So what we are hoping with the data that we have shown and the data that we are generating phase 1b, to move this very rapidly to the front line of AML, and it can also be combined with other therapies, such as the small molecule inhibitors. What you see in that graph, it's very important—this is these cells being manufacturing themselves in the patients. As they are infused, few million cells in one dose, they can expand, and you can see their own maintenance. And on the far right-hand side, this is an example of one of the patients. This patient is a AML, which also they have some of the lymphatics and the metastasis, and those black dots that you see is all metastasis.
After receiving only one dose, 28 million cells, it cleared all of it, except one spot that is on top of the head, and that patient, for that one spot, was not a complete responder, however, a partial responder. So you can see the power of this UltraCAR-T within a patient. Then finally, the next, this is our new CD19 UltraCAR-T next generation, which not only has all of the components, but it has one other component in it. It has a mechanism to downregulate the PD-1. Therefore, you do not need to combine this with any checkpoint inhibitor. Why is that important? First of all, you don't have to add a cost of a checkpoint inhibitor, which on top of a $400,000-$500,000, it becomes an impossibility.
Secondly, you don't add the toxicity of this because these cells, they downregulate only within the UltraCAR-T and doesn't affect the rest of the cells, and that's important. On the right-hand side, you see a head-to-head conventional CAR-T, which is what it is out there, versus this UltraCAR-T of CD19, and this is why we say we believe that we have the potential to be the best in the class in the oncology, hematology indication. As you see, it has eradicated the tumor in all of the animals. But at the same token, as we move toward autoimmune diseases, it becomes very, very important that in chronic diseases, first of all, you, the safety, it becomes much more prominent as when you're looking at the stage four of the cancer patients.
Therefore, the tolerance of the regulatory organization is much less for anything that can cause any kind of issue. And here, not only we can redose for autoimmunity, which in a chronic disease you need it, at a much lower price tag, because this is non-viral, and we don't have centralized manufacturing, it happens in a hospital overnight with much lower cost. But also you have the safety switches in there. In a case anything goes wrong, you can basically eliminate. With that, I finally put the final slides, which is our CAR-T. This is truly our vision of precision medicine, that a patient can walk in to a hospital and basically they get diagnosed. The oncologist would write up a prescription that I need the UltraCAR-T to mesothelioma, to the MUC16, to the CD19. The next day, that is produced.
The cells, patients, of a patient can be frozen. If the patient needs another dose, they can receive another dose at a very lower cost. If there is a mutation and heterogeneity in that tumor, and you need to give a different call, you can do that. So with that view, I'm really excited that we had the opportunity to at least give you a glimpse of what Precigen does. Hartaj?
Great. Thank you, Helen. This is great. I mean, you've got a lot, you have to go over. So, thank you for, you know, giving us, leaving some time here, on the back end for some, just some quick questions. I'll just check online also if there were any questions. I guess, you know, the first question I would have, is, Helen, you know, assuming you go ahead and file in the second half of this year with the FDA, you know, knock on wood, your phase II data is good, and you file in the second half, would you still be required to run a confirmatory trial? And if so, what would that kind of look like?
Yeah. Yeah, and you're absolutely correct. Actually, anyone that receives the accelerated path for any trial, they have to run a confirmatory, but you just have to initiate a confirmatory trial. You do not need to finish that. You can receive the approval, and you can have your drug commercialized while you are running your confirmatory trials. In regard to the design of the confirmatory trial, the FDA has very much agreed with our design from a phase I, phase II, which are exactly the same, and they have granted that we run the exact same design. No randomization and a single arm with the same exact design for a confirmatory.
And one other thing that I have to also add, which we were very excited with the FDA recommendation. This is the first time that the FDA actually seeing our data, not only 50% complete responses, but also that we had the 83% reduction in number of surgery. They have recommended to us that it would be great if you repeat dosing, especially in the patients that are not in a complete response, and maybe you can rescue those patients as well. Not only by... obviously, we had reduced their number of surgery, but maybe push toward the complete responses, and we will have an arm that will address that as well. So we are excited about this.
... That's great, Helen. You know, just, we are kind of over the time, but maybe a last question, which is that, you know, you're treating patients, you said on an average with six surgeries per previous year. These are really severe patients. We've talked to RRP physicians. You know, there's academic research that suggests that the cost of RRP to the healthcare system is $70,000-$80,000 per patient per year to $200,000 per patient per year. But they have so many surgeries over many years, and they can get worse, too, and also they can become malignant, right? Some 5% or 10% of patients. What do you think would be a good comp from a pricing point of view, assuming you get approval for your, for your therapy?
Yeah. So, currently, as you know, we have our head of commercial, James Shaffer, who is working on this and actually looking at this, speaking to the investigators, the KOLs and doctors, as well as the payers. And, it is very clear that the cost of treatment of these patients is high. And it's not just the cost of the number of surgeries, losing time from job or not being able to work, but also the quality of life for these patients. Which, you can imagine that they can't speak, some they can't breathe, and to the point that you raised with the pulmonary. So currently, we are working on that, and clearly, we will be giving guidances as we move on that.
But there is a high cost to these patients, and I think, speaking at least preliminarily to the payers as well as to others, they agree that this is a devastating disease, that requires really the patients, the, it, it's devastating to their life, as well as it can be actually also life-threatening. So... And it's a rare disease. So clearly, we are moving in that direction to define the specific cost. And one other thing I'm gonna say, Hartaj, is that, there is really one other aspects for us, is we are looking at the patient numbers, both in U.S. and ex-U.S., because there is a general consensus that there is an underestimation of the number of patients, because these patients, a lot of them, they are not diagnosed immediately or correctly.
As you can imagine, there are no codes in the system for the specific for RRP. So that's another part of the work that we are currently doing.
Yep. Helen, thank you so very much. Really excited about this. You know, RRP is a horrible disease, but even your UltraCAR-T system, talk about it more. We'll keep the conversation going, and I'm really looking forward to it.
Thank you very much, Hartaj, and thank you for the opportunity. We look forward to it.
Thank you. Thank you, Helen. Take care.
You too.