All right, we'll go ahead and get started with our next discussion. My name is Ben Burnett, biotech analyst at Stifel. Pleased to be here with some of the Precigen team, Helen Sabzevari, CEO, Phil Tennant, Chief Commercial Officer. Thank you all for being here.
Thank you for having us.
The format will be just Q&A, but if there are any questions from the audience, please let me know or get in. To start off, maybe just give us a quick overview of Precigen, and then we'll get into it.
Precigen is a cell and gene company that has been focused for the past four years, since 2020, on really bringing innovative sort of treatments for unmet need diseases. And in that setting, obviously, our Gorilla AdenoVerse platform, which is unique and completely differentiated than other adenoviruses that you can repeat dose, and it's keeping enhancing the immune system that can be used both in infectious diseases, in the setting of oncology right now that is in phase II, is also there. And then we have our UltraCAR-T platform, which is the overnight platform that it's truly, it's according to what we talk to everyone, and it's the future of this field because of all of the complications that the manufacturing process has, and also some of the safety issues that have been seen both on the classical CAR-T/T CRs or off the shelf.
This is uniquely offers that position that you overnight manufacture with a much lower cost, having the safety switches and ability to basically manufacture these cells in the patients directly. So the time to the disease is very fast, and it's not five days, it's not seven days, it's not 12 days, it's exactly 24 hours at the hospital. The next day, the person receives their own autologous. So we are really excited, and we have some exciting data that in 2025 we will show on that platform. But currently, we are thrilled about our adenovirus platform with PRGN-2012, Papzimeos, and moving toward finishing the submission of the BLA by the end of the year and hopefully commercialization. That's why Phil is here. We are so happy to have him and really hit the ground running.
Great. Well, I definitely want to spend some time on your RRP program and then, of course, go into some of the commercial discussions. But maybe just from a high level first, for those that aren't familiar, what is Recurrent Respiratory Papillomatosis?
Yeah. This is a disease that basically the patient, as a result of being infected with HPV 6 or 11, they develop these benign tumors in either over their vocal cord or trachea, and sometimes it also moves down to the lung, but it's a rare, devastating disease that really there is really no treatment for this disease. The current state is just surgery, surgery, and surgery. Some of these patients, they have the disease as onset of childhood. As they pass through the birth canal of the mothers, they can be infected, and then they develop this, and in the trials that we have run, we had the number of the patients that they had this disease from onset of childhood and had hundreds of surgeries over their lifespan.
Or you can have it, get it as adult through the sexual transmission of HPV 6 and 11, which then basically these benign tumors start, and usually at ages of in adulthood, people, they get that, and it's recurrent because it keeps occurring, and the surgery is not helping the situation. Some people, we are trained to think that, okay, if there is a surgery and they take something out, then it's done. It isn't done. This thing keeps coming back, and the surgeons actually, they refer to it as like mowing the grass. It just keeps coming back, and it gets worse, the situation for a patient because now you have scarring, and every time that the surgeon goes in, the risk of anesthesia plus hitting the vocal cords or the damage to the trachea becomes more and more.
So it's really daunting also for surgeons and what we are hearing from them. A lot of people think that surgeons like to do surgery. This is one that they don't like to do it, actually.
Yeah. Okay. And then Helen, and maybe this is also for you, Phil, talk about the number of patients out there in the various geographies where this has been identified.
Yeah. So, actually, in the U.S., the estimate is somewhere around 20,000 patients, adults and adolescents, and we definitely ex-U.S., there is a much larger population, excess of 125,000, but I think Phil can speak to this more.
Yeah, absolutely. Prevalence is EU4, U.K., Japan, China, 125,000-150,000. Big prevalence in China. Obviously, the economics of drug development and commercialization are different there, but yeah, prevalent populations all across the globe.
Yeah.
Are there other patient advocacy groups that you can lean on?
Absolutely. The RRP patient advocacy group, it has been really, we have been partnering and advancing the cause of the RRP because, as this disease for a long period of time, people didn't know anything about it. And like other rare diseases, it has been misdiagnosed for many, many scenarios. Actually, up to recent years, there is not even a payer code for this disease because people, they go in, they are having a problem with their voice, they are losing their voice, or they can't breathe. And there is misdiagnosis of what the, and then when they run out of every other solution, all of a sudden then they realize, oh my God, this is RRP. And then the whole process starts. So I think it is extremely important for the patient advocacy group, and they have done a great job.
We just had in June, basically 11. We had the RRP day with the patient advocacy group, and I basically really point out for people that they have not heard it. I think it's available on our website that they should watch this because it really tells the story of the need of this patient when they have been taking their child of two years old on a monthly basis to a surgery room and being treating them, and some of them having gone through the surgeries themselves in adulthood and what they go and what the patient journey is. So that has been extremely important for education, not only of the public, but also really the regulatory perspective as well as moving these innovative processes forward.
Where are these patients treated today? What types of physician offices?
Go ahead.
Yeah, it's a mixture of, I mean, we think the main academic, the main treating center is the academic centers who are geared up to do this type of surgery frequently and often, but a lot of the surgeries, the lower grade surgeries, if you like, can be done in the physician's office, and there's probably a 50/50 split actually in terms of in-office surgeries and academic operating sort of operating room surgeries as well, but when we come onto the market, we do expect there to be that concentration of patients in the academic centers.
One of the reasons Phil is absolutely correct, over the years, because of the misdiagnosis that happened, then certain centers have become specialized in this. But now the awareness is becoming all over, basically among the head and neck, even surgeons and also laryngologists, all of them. RRP has been now, especially in the past year with the effort of advocacy groups and also innovations such as platforms that we have has become front and center.
Maybe to dive into the diagnosis aspect of this, what is your sense of the diagnosis rate? When you're kind of thinking about some of these numbers, I think you mentioned 20,000 patients in the U.S. Is that, is that an estimate of the identified population?
Yeah, this is from all the people and actually experts and investigators that we speak to. They feel it's an underestimation because obviously there has not been a very clear. It's not like bladder cancer that the patients, they have a pay codes and they go in and they immediately get identified in that category. So for those reasons and for investigators and all of the doctors that they see these patients, they really, their understanding is that there is an underestimation here.
Yeah, there was an analysis in October which looked at other rare disease areas where new therapeutic entrants had come into the market, and consistently you saw an increase in diagnosed prevalence, sometimes to the tune of tens of percentages higher than the original estimate. So we do expect there because of the awareness and the advocacy, we do expect there to be an increase in that prevalence as we go forward, at least for the first few years.
Yeah. Okay. And then I think we've talked about this in the past, but we get some questions around Gardasil. This is sort of a kind of a broad-acting prophylactic vaccine. Why doesn't that work better in RRP?
Yeah. So that's a great question. For all the prophylactic vaccines, it works because it starts the immune system prior to the infection. So the immune system has not been, for the lack of better word, it has not been diminished or lost the battle. When you look at these diseases, where the issue is, and even in cancer, it's the same thing. When the immune system has been losing the battle and then you come in at the very end of it with the therapy, that might be good. If you just start the battle or war with it, it's not sufficient. They cannot generate enough basically high- affinity T cells.
And also from the Gardasil perspective, there is another issue because the platform that they are on, you can only give it in a very limited number of times that you can give it because these are regular, if you recall, viruses, viral vector deliveries that after giving it once or twice, basically you're shooting a blank, so you cannot keep pushing the immune system over that threshold. Now, when you come to a setting of a therapeutic that the patient already has this infection, especially for years, and the infection has really sort of spread in the tissues around and exists in that niche, the cells that they are in the body of this patient, they already have been battered in a sense.
Now, what you have to do is have a platform that it can really push and generate new high- affinity T cells and can do that in a consistent manner. With our PRGN-2012 or PAPZIMEOS , what we have done and on the same exact basically Gorilla Adenovirus background, we have shown it also in cancer, you can keep giving this number of times. And in some of our cancer patients, they have received it 16 times, and you keep seeing enhancement of the immune system. So the mechanism of action is different, and it pushes toward the high- affinity T cells, which the prophylactic would not. And by the way, the majority of the patients that they enter to our trial, they had already received the Gardasil because when the patients are being diagnosed, there was nothing for the RRP patients.
So the first thing that the doctors do, they say, well, it doesn't help, let's vaccinate with Gardasil, but it doesn't have any effect really. And the patient continued to have the surgeries. And I think in our setting, more than 70, close to 80% of the patients that they came to our trials, they already as adults have received and it didn't work. The same concept also worked for a checkpoint inhibitor. And I should point out recently at ESMO, for instance, Merck finally, I think they actually had finished this trial in, if I correct, in 2019 or 2020, but they showed the data on the checkpoint inhibitor. And what we saw was there is, first of all, six months of treatment with a very high toxicity that the patients, they had a grade three toxicity, 25% of them that you cannot reverse.
And then on top of that, the durability of the response was very short. Every three weeks, these patients had to go and get an infusion. And then on top of that, no complete responders. And it was just reduction in the number of surgeries. And this is what, and so I think for that reason, we believe with PAPZIMEOS and PRGN-2012, this is really uniquely differentiated from all of this. And actually also, I should say a lot of our patients that they came in, they already had received checkpoint inhibitors prior because there is nothing for this patient. They tried everything, and it doesn't work. They keep needing the surgery.
And then some of our complete responders and partial responders, they already had all of these prior treatments off-label that have or as a clinical trial, not off-label, I should say, in clinical trials that they participated, which unfortunately for the patients, they had failed, and then they came to our trial, which led to 50% complete responders.
So that's great context. Yeah.
Yeah. So given that you have a potential best in class with the high affinity response, what's the cost to the system right now for these people that have multiple surgeries on an annual basis that would translate into, besides the quality of life and other advantages?
Let me just repeat for the webcast, so I think the question is around what is the cost to the system right now given the current standard of care, which involves surgeries?
Yeah, that's an excellent question. I will start, and I am sure Phil can add to this. Based on what we have seen, first of all, there is a large cost of surgeries for this patient. If you, in some of our patient population, they have 10 surgeries per year. So you can imagine the cost that it goes. Actually, the patients that we are treating, the most severe one at minimum of three and above. And so there is a cost of hospitalization, the cost of the surgery, but more importantly, these patients, they cannot work on a continuous basis or at all because even after a surgery, there is a period of basically healing, which right when they finish that, they have to start going to another surgery.
The majority of the time is the income that is completely lost or the cost of the also what they have to pay on top of their insurances. One of the studies that we have seen is that they estimate that the cost, and this is on basically a limited number of patients that they have been identified. It's hundreds of millions in the U.S. for this patient population. There would be obviously a tremendous need that the surgery will be removed because that's not a treatment, that's a band-aid. Then we basically come in with the therapy, as we have shown up to this point, with the durability of a response that not only saves the patient's life because you are not exposed to the anesthetic and the continuous risk of the surgery, but also allows the patient to have a normal life.
But Phil?
No, I was just going to say that hundreds of millions estimate is surgery alone. And you would imagine that the bigger impact is that more intangible quality of life, lost productivity stuff, which is difficult sometimes to put a number on, but that is exactly what we hope to do when we're building our health economic arguments is to map all of that out so you understand the true burden of the disease. But the several hundred millions just for the surgery, just for the procedures.
Thank you. There are several different ways to kind of characterize efficacy in RRP. I think we've seen the Derkay score, sort of a disease assessment score. There's a, I think, a voice assessment score, VHI, that you've talked about surgery, the frequency of surgery.
What do you hear from patients and physicians is the most meaningful that you would use to drive adoption and then maybe kind of talk to your data on those endpoints?
It's really number one thing is the reduction in the number of the surgery, and also if you can eliminate the surgery. That is what when you talk to the patients that they have had, there was a patient that had 800 surgeries. So I mean, this is not even imaginable for us and for someone to go through this number of surgeries. And when you look at that, these patients, they all unanimously say that if you can reduce. And then when we were able to actually really go to a complete response, which was not a requirement for not having any surgery for a minimum of 12 months. And then, of course, we have been following this patient and we have shown that our patients, the durability of response is much longer than 12 months and they continue to be in a response.
This is something that our investigators and the KOLs and the people that they are treating the patients, they are saying they have never seen anything like this. The reason for that is that now that is the most meaningful, I think, primary endpoint, and that's what we picked at. Of course, we have been following the Derkay score, which is more of a research tool really in the field, which basically analyzes where the tumors are or the numbers and of course, which one at the quality, voice quality, which is important. What we have shown is very, very consistent actually relationship between not requiring any surgery and the significant drops in the Derkay score and the VHI. It goes hand in hand.
Okay. I want to ask one more kind of commercial question that I want to just ask a few around your upcoming BLA submission. Just given kind of your estimate of adoption and the number of patients that are out there and kind of the call points that you would use, what do you see the commercial opportunity for PRGN-2012?
First, we're thrilled to be able to bring this to market, hopefully with the approval and excited by the overall opportunity. We've looked at a number of analogs in rare diseases, orphan drugs. We've looked at, we've obviously spoken to payers, we've spoken to physicians to try and get a handle on the impact that this can have, and obviously, we're not going to give a number as such, but we believe the opportunity is significant and really attractive for us. From a rare disease perspective, all the usual things you would expect to think about when you're preparing for a launch are in play. You just have to be a little bit more focused and deliberate given the small number of HCPs and the small number of patients.
But all the things that go into a launch plan are obviously part of our launch plan, but with some nuances because of the small number of potential targets. So yeah, a significant opportunity. We're very excited about it.
Yeah. And maybe I can just add to what Phil mentioned. Clearly, this drug has been designated by FDA as a gene therapy. And it really commands, as you can imagine, the prices of the gene therapy drugs. And I think maybe Phil can add on in regard to the discussions with the payers that.
Yeah, we think there's, you know, we've looked at payers in terms of when they would get more active in terms of managing at different price points, and we feel there's, we've identified what we believe is a window within which we can operate in terms of the price that we would charge. We're doing a bit more work to pressure test that, but we're pretty comfortable based on all the information we've got that we're going to be in a sweet spot.
Okay. That's great. And then with regards to the BLA, and I fully understand that there's going to be some sensitivity around what you can say. This is an ongoing dialogue you're having with the FDA, but what can you convey around the level of comfort that you feel the FDA's discussed with regards to your efficacy data and also your safety data?
Yeah. Now, actually, we have been really in very much in alignment with the FDA. I have to point back to the history. FDA gave us an accelerated path in August of 2023. We are the first company that received that based on a single arm pivotal on our phase one. And of course, the result of phase two, which at that time we still were conducting, but we showed the full result at ASCO, which was extremely consistent with our phase one data. You cannot ask for a better repeat in the setting of a clinical setting. So FDA has been very much outspoken about this as what we received in regard to accelerated approvals. And of course, we have been in very close discussions with the FDA.
And as we just mentioned in our press release just last week, that we had our pre-BLA meeting also with the FDA in full alignment. And we are all set to finish submission by the end of this year. So we are looking forward to that. I don't go into more details on that because of all the other aspects and the competition, but it's just for us; it's very, very important. And we are keeping the timelines and full alignment with FDA. So we are excited about this.
Okay. That's great. I guess just one more question on that. So one novel aspect of this is that the technology, this is I think a first for this type of technology. So I guess what's given you comfort around, I guess, both the kind of manufacturing piece of this and also just the safety piece?
Yeah. No, that's a great question. On a manufacturing side of this, first of all, since the Gorilla AdenoVerse platform is fully owned by Precigen and also we have the team that actually developed this platform and they manufactured it. So this is a team of 20 to 30 years of experience in this field. And we have our own commercial manufacturing onsite, which has been very important. It was our GMP facility that produced all the material for a clinical trial and now our commercial facility that continues with the same experience. And I think this was also has been part of our pre-BLA meeting and alignment with the FDA. And I think that's we are very excited about that. From a safety perspective, again, part of the reason for advancing this drug so rapidly, it has been the safety of this.
If you look at the safety, all of the investigators, KOLs, and the patients, they talk about this. It's like receiving a flu vaccine, basically. It's a grade one, grade two, a little bit of a rash, maybe a little bit of a fever, and it resolves itself within a day. Extremely safe, very favorable, and with a high efficacy. And this is not typically something that you see in the drugs. It's usually there is bad safety, some efficacy, some efficacy, but if it's good safety, not efficacious enough. And this is the first time that you have this component together and this is great for the patients. Obviously, we are currently in adults, but you can imagine as you move to the pediatric population, what that means for children because safety is utmost important and then of course followed by efficacy.
Okay. The last couple of minutes, I want to ask one competition question and then I do want to, if we have time, I want to touch on your UltraCAR-T program.
Sure.
But yeah, how do you think about competition?
So typically, I'm one of those people that I never take a competition lightly. So it's my philosophy in life. And the way I deal with this and we have done scientifically and clinically is show the data, basically, and differentiate. And I think we have been very successful in our competitions to show that number one from a perspective of administration, starting with the administration of this drug, which is just a Sub-Q injection versus, for instance, DNA sort of plasmid that has to be electroporated to the patients.
This is a novel.
Electroporation, this is Inovio, which requires, it's very difficult on the patients from what we understand from investigators explaining this, all the way to the very favorable safety and then really the efficacy. When we talk about, and we have been in the most severe patient population and we have 50% complete response, more than that actually, and also close to 86%-87% reduction as a secondary points for us in the number of surgeries in patients with a very favorable safety versus the 28% response rate. And we have not seen the durability of a response from Inovio. We have a durability of response that it continues to go on and this is extremely important for this patient population. And I think at the end of the day, the ease of the administration in the offices of some of these laryngologists, which it can be done.
So I think we have differentiated ourselves from all of that, Gardasil, Inovio, which Gardasil doesn't play a role and even the checkpoint inhibitor, which they did not show the similar efficacy or safety. So we feel that we are well differentiated and that's the reason that we think that not only we will be first in the class, but best in the class. And last thing I'm going to say, it's unfortunate for the field, but from the, as we know with Inovio, for instance, they have a device that also has to be passed. And according to what they have mentioned themselves, clearly they are now, they have issues with the device that has to be resolved and they don't see even submission of their BLA until the second half of next year.
I think this is one of the complications when you have a system like that.
And then I want to just squeeze in one last question. You made it very clear that as a management team, as a company, you're focused on RRP, but you do have some other programs in the background, one of which is an UltraCAR T program being developed for AML. Just quickly kind of talk about that and.
I'm so glad you asked that. In the summertime, we did mention that we are focused on really getting our PRGN-2012 patients across the finish line, and of course, the focus has been on that, but one of the things that our team did, and I'm extremely proud, we finished our phase one B studies in an AML patient. As you know, none of the other CAR Ts has been in this space, has been able to make a dent and off the shelf, and we presented the first phase one data, 28% objective responses. Since then, we have added patients and we are really excited about the data that we see and also in conjunction with some of the biomarkers that we have established that would be extremely important in this patient population. We are looking forward to be reporting on that for the first half of next year.
Also, we are preparing right after, of course, the submissions of our BLA. We are working on to get the end-of-phase 1b meeting with the FDA and the path for a rapid regulatory advancement there.
Fantastic. Very quickly.
Life cycle management, you've got RRP, life cycle management opportunities.
Oh, life cycle management opportunities. Absolutely. A number of things. First of all, RRP, one of the things that the FDA has asked is repeat dosing for the 50% of the patients that they had a partial response, but they didn't go to complete response. This is a very unique opportunity. We will do that. But more importantly, for instance, on the side also from the genital warts, this is, as you know, millions of people in the United States and tens of millions ex-US, they are suffering from this disease. And it's caused exactly with HPV 6 and 11. And as you can imagine, that our platform and the molecule can be very, very effective in this basically indication as well as some of the also cancer arenas.
So we are extremely excited about this platform and this molecule across not only the RRP, but many other indications. And we will be discussing that.
Great. Helen and Phil, thank you.
Thank you so much for having us.