Hello, welcome to the Precigen Virtual R&D Day for PRGN-2012. At this time, all participants are in listen-only mode. If anyone should require operator assistance, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Steve Harrison. Please go ahead.
Thank you, Kevin, and thank you to all joining us for this update call today. Before we begin, I'd like remind everyone that today's call will make various forward-looking statements. Investors are cautioned that our forward-looking statements are based on current expectations and are subject to risks and uncertainties that could cause actual results or outcomes to differ from those indicated by our forward-looking statements.
Please read the safe harbor statements contained in this presentation, as well as the risk factors contained in Precigen's most recent SEC filings for a more complete discussion on these risks and uncertainties. Today, I am pleased to be joined by Dr. Helen Sabzevari, President and CEO of Precigen, and Dr. Clint Allen, Senior Investigator, Surgical Oncology Program, Center for Cancer Research at NCI and Lead Investigator for the PRGN-2012 clinical trial. Following our prepared remarks, we will open the call to Q&A. In addition to audio questions, we invite our listeners to submit questions through the conference portal, and we will get to these time permitting. I will now turn the call over to Dr. Allen for some background on RRP.
Well, thanks. Good afternoon, everyone. I'm Clint Allen. I'm at the NCI. I'm a fellowship-trained laryngologist, a board-certified otolaryngologist, and I've been taking care of folks who have RRP or recurrent respiratory papillomatosis for a long time. As a way of background, RRP, as we'll refer to it, is caused by a chronic infection with either HPV type 6 or 11, human papillomavirus. These two are distinct subtypes from HPV 16 or 18, which cause cancer. HPV 6 or 11 cause RRP. Essentially, infection of the throat, voice box, and tracheal linings will lead to the development of papillomas. The pictures you see on the left-hand side, this is a normal shot on top of a voice box.
Those are the vocal cords, those two white strips, and below that is a normal trachea with nice, smooth mucosa. On the right-hand side, you can see a severe case of RRP, where papillomatous growths have developed really across all mucosal surfaces. Because of the location of these papillomas, patients will experience extreme voice disturbance. The vocal cords essentially cannot close and vibrate, which is our sound production mechanism for speaking. If the papillomas become large enough, as you see in this photo on the right, both on top and bottom, these can eventually obstruct the airway. This is a really devastating disease. This can start when you're a child, in which case we call it juvenile onset. It can start when you're an adult.
I've treated patients that had onset of RRP that first showed up in their 80s, 80 years of age. Our real problem with RRP is there is no approved systemic treatment to address the underlying problem. You know, we often tell patients the papilloma is not your problem. The problem is that, for reasons that are incompletely understood, your immune system is allowing a chronic infection with HPV 6 or 11, and the papillomas are just a manifestation of the disease. The real heart of the issue is trying to get the immune system to clear the HPV, which in case will clear the papillomas. The only treatment that we really have for this right now is repeat surgery to debulk the papillomas and maintain an open airway, both for voice and breathing.
It is not unusual for individual patients to have hundreds of lifetime procedures, including many of those being surgeries in the OR, sometimes being awake laser procedures in the office just to maintain a safe airway and a serviceable voice, so they can work and have a family life and carry on with some quality of life. If the heart of the issue to treat RRP in the future is going to be to activate the immune system to clear that underlying HPV 6 or 11 infection, which is the real cause of the problem, the question is how do we do that? Here at the NIH, we've actually done many clinical trials already using many forms of immunotherapy to try to activate those HPV-specific T-cells.
It's important here to start to distinguish what's the difference between a therapeutic vaccine, such as PRGN-2012 or a preventative vaccine like Gardasil. Gardasil is a preventative vaccine, activates the immune system against HPV in a way that you get production of antibodies, and it prevents you from getting an infection, and we know that that's very effective. In general, people who are vaccinated with Gardasil as a preventative vaccine as a young age, they will not develop RRP or other HPV-related disorders. The problem is, once you already have the infection and the virus is already inside the cells, getting a preventative vaccine like Gardasil that produces antibodies doesn't really do you any good.
The only immune cell in the body that can detect and kill a cell, such as an epithelial cell lining your throat or voice box infected with HPV, is a T-cell. Specifically, therapeutic vaccines are designed to activate the immune system in a different way that specifically leads to activation of T-cell-based HPV-specific responses. In our previous immunotherapy clinical trials that were using primarily immune checkpoint blockade for RRP, We learned that patients with RRP tended to not have strong or activated but suppressed HPV-specific T cells in their papilloma. When we gave other forms of immunotherapy, there weren't good T cells to unleash. This really led us to change our strategy and come up with the idea that we needed to really develop a therapeutic vaccine to induce new or expand existing HPV-specific T cells.
I think this is really the key moving forward for RRP to address the underlying problem, which is the infection. Papillomas are not the problem. Papillomas are what cause the symptoms, lead to the frequent surgery, lead to the devastating side effects. It's the underlying HPV infection that's the problem. Treatment strategies moving forward need to be aimed at addressing that underlying issue.
Thank you, Dr. Allen, and thank you for this, thorough background on this, terrible condition. I'd now like to turn the call over to Dr. Helen Sabzevari, who will now take us through the background on the PRGN-2012 Adenovirus immunotherapy.
Thank you, Steve. As Dr. Allen has mentioned, I think it has become clear that what we need to do for this patient population is really to invoke their immune system and generate a high specific T-cells to HPV 6 and 11 epitopes that stops this chronic infection. By using our AdenoVerse platform, which is a library of gorilla vectors that are well-differentiated from others, we thought that we can bring a drug product for this patient population that might be changing the paradigm here. I should say a little bit about our gorilla adenoviral vectors.
When I say they are differentiated, first of all, from a perspective of the seropositivity, when you look at the healthy volunteers, and we have done this both in the United States and across in other continents, you can see that the volunteers, usually we do not have either seropositivity or pre-immunity to these vectors, or if there is, it's very slight. Unlike other viruses such as Ad5 or retroviruses, lentiviruses, and other families of these viruses. Why is that important? The importance here is if you don't have seropositivity, you can do a repeated dosing of these vaccines.
In this clinical trial, as well as in other clinical trials that we have used a similar backbone of viruses for cancer also, we have shown that you can prime and boost number of times over a period of time, and we have had patients that they have been over a year and a half vaccinated in our oncology trials, and you can continuously enhance the immune responses, specifically the T-cell responses. As far as the neutralizing antibodies are concerned, they stay, they come up, and they stay at bay, and you do not keep increasing this neutralizing antibody. This is one of the major differentiation factor of this platform.
Another part here that is important is really the capacity of these adenoviral vectors, that they have a much larger capacity than, for instance, Ad5, that is below 5 KB, and here you have up to 12 KB. Why is that important? You can put a much more comprehensive epitope designs in there or number of genes that it can go in there and present it to the immune system. On the right-hand side, I just mentioned that what you are looking at, the graph, the bar graph, this is PBMC from the RRP patient population that, as Dr. Allen mentioned, they don't have really a specific T-cell responses. This is after being exposed to PRGN-2012. You can see clearly that you are inducing a specific T-cell responses to HPV 6 and 11 epitopes.
In the next few minutes, what I'd like to share with you is a video of the mechanism of action of our gorilla adenovirus platform, and specifically in regards to the PRGN-2012, and showing you that actually by designing the epitopes that are specific to HPV 6 and 11 within these vectors, you can directly induce T-cell specific to HPV 6 and 11 in patients directly, that they have a high affinity, that they can basically recognize the infected papillomas and infected cells and destroy them. Let's look at the video together here.
Thank you to Dr. Sabzevari . I'm now gonna turn the call back to Dr. Allen, who's gonna walk us through the data for this trial.
Let's talk about our completed phase I clinical study. This is a first-in-human study to evaluate the safety and efficacy of PRGN-2012. We opened this up for adult RRP patients who had what we categorized as severe RRP. In other words, they required three or more interventions in the one year prior to enrollment. This likely captures 25%-30% of the most severe RRP. We brought them in, we did a standard of care surgical cleanout, then administered four doses of subcutaneous, it's a subcutaneous injection, PRGN-2012 over a three-month period, 85-day period. We exposed patients to two dose levels. Three patients got dose level one, which is 1 x 10^11 viral particles. After demonstrating safety, an additional 12 patients received dose level two, which was 5 x 10^11 viral particles.
Our primary outcome measure for this study was safety, of course. In terms of efficacy, the way we assessed whether patients benefited clinically was comparing the number of clinically indicated interventions that they required in the one year after completing the clinical trial compared to that same patient's need for clinically indicated interventions in the one year before the clinical trial.
The patients were referred to the NIH for the clinical trial, and after the clinical trial, the patients were referred back to the same physician, the same otolaryngology surgeon that they had prior to the clinical trial to remove as much bias as possible. The patient and the physician making clinically indicated decisions about what was needed after the clinical trial was exactly the same as that partnership before the clinical trial.
We have several objective and subjective measures of response, namely the Derkay score and the Voice Handicap Index. We'll go after that, we'll go over that in the coming slides. As I said, we enrolled 15 patients. These were all adult onset. We had 10 male, five female. two of our patients had juvenile onset. In other words, they developed RRP initially when they were children or adolescents, and that RRP disease severity maintained into adulthood. The remainder of the patients did not develop RRP until they were adults. This is a patient population, these 15 patients have very severe disease. These patients had an average of over six surgeries in the year prior to the clinical trial, and I cannot underline enough how devastating this is for patients.
The surgeries and the interventions that these patients require to have six or more of them in a year, these are often general anesthesia procedures where they're asleep for sometimes multiple hours, depending on the severity of the disease. It's a huge stressor on the body and for most people, undergoing six or more interventions in a year for any indication will be devastating, but especially for an indication that involves your airway, which leads to very high-risk surgeries. Complications can be very, very severe . A summary of treatment of emergent adverse events can be summarized by saying that this drug is extremely well-tolerated. Almost all patients develop what we would characterize as an injection site reaction.
This is a subcutaneous injection, and what most people get is something very analogous to the flu vaccine, and we often tell people that they're gonna have side effects that's probably better than what they experience after the COVID shot. People typically get about one day or often less of injection site redness. A little bit of swelling, a little bit of tenderness. It's almost all grade 1, occasional grade 2. It never limits their activity in any way. Patients also get what we would characterize as like a viral prodrome, typically for one to two days. Low-grade fever, chills, some fatigue. Every once in a while, we'll have someone where it lasts two days. It's always self-limiting. We don't give them medicine or anything like that. Very well tolerated. All grade 1, grade 2 adverse events.
No grade 3, no grade 4, certainly no dose-limiting toxicity. Next slide. Here's a more complete summary of these. We'll let you peruse these. I won't go through them in detail. Again, very common. Occurs in almost all patients. In fact, we tell patients to expect it. We say, Listen, especially after this first shot, you're gonna have one to two days of injection site soreness, you're gonna feel like you're coming down with a cold, and it's gonna go away. Very rarely see it go beyond two days. Very well tolerated. Next slide. Let's look at some initial efficacy data. What you're looking at here is what we called a swimmer plot. On the Y-axis, you see patient number one, two, and three. These are the three patients that received dose level 1, that lower dose of the vaccine.
Four shots after a standard of care clean-out. Everything you see to the left of that middle zero line indicates the number of clinically indicated interventions that each patient required in the year before. To the right, in the green bars, these are the number of clinically indicated interventions the patients required in the 12 months after the clinical trial. You can see, even with dose level one, the lower dose, we see a substantial reduction for several of the patients in the number of clinically indicated interventions in the year after. A different way of looking at the same data is to ask the question: After the clinical trial, how long did it take for the patient to require another clinically indicated intervention indicative of disease recurrence?
You can compare that to the surgery interval in the 12 months before. For these three patients, what we see is a mean surgery interval of 55 days, and a post-treatment interval or basically time to recurrence of 180 days. Every surgery matters in these patients. If you asked me what a significant reduction in the number of clinically indicated interventions is, the answer is any. To have any patient go from eight surgeries a year and only require three in the year after, that is profoundly significant for that patient. Next slide. What you're looking at here is very similar swimmer plot data, but for dose level 2. Again, on the left-hand side, patients four through 15. Again, each received that higher dose of the vaccine, four shots in the adjuvant setting.
On the left-hand side, in the gray bars is the number of clinically indicated interventions in the year before the clinical trial. To the right, the blue bars we see are the indicated interventions in the year after. You might notice some zeros. That's a big deal. Patients five, seven, 10, 11, 13, and 14 in total half, 50%, six out of 12 dose level 2 patients had what we are classifying as a complete response. In other words, these are patients that had sometimes a significant number of interventions in the year before that required no interventions in the year after. We've been doing clinical trials for years at the NIH. We've never seen any data any close to this in terms of complete response.
If we consider a partial response as patients that required 50% or fewer interventions in the year after, in total, we have seven out of 12 at dose level 2 that obtained what we would call an objective response. 10 out of 12 patients required fewer interventions in the year after, so any reduction in the year after. We had two patients that were true non-responders that required the same number of interventions the year after compared to the year before. Next slide. Again, a different way of looking at the same data is to ask how long did it take for the patient to require a surgery after the clinical trial, and then to compare that to the inter-surgery interval in the one year before.
In patients five, seven, 10, 11, 13, and 14 on the top of this swimmer plot, no surgery has been required. This data is just cut off at our last assessment of that patient. In the remaining patients, there's been some extension of the inter-surgery interval. Again, this just highlights in those six patients on top the complete responses with no interventions required. In summary, at dose level 1, which is the lower dose level, we had zero of three patients experiencing a complete response. All patients required fewer interventions in the year after compared to the year before. One patient was officially categorized as a partial response with a greater than 50% reduction in the need for surgery. In dose level 2, we have a 50% complete response rate, six out of 12 patients.
seven out of 12 patients had an what we're calling an objective response, which is the addition of the one partial responder. 10 out of 12 patients had fewer interventions in the year after compared to the year before. Another way of measuring in a semi-objective fashion the response is to try to quantify the disease based on endoscopic exam. This is done with a Derkay score. To make this explanation very short, a Derkay score is calculated by the surgeon or the clinician examining the patient, and it's based off visual quantification of the disease. We scope the patient in clinic, we'll show you some of these scope exams, and we use a standardized scale developed by Craig S. Derkay many decades ago, which objectively quantifies the amount of papilloma.
Next slide. What we see here is for 11 of the 12 patients treated at dose level 2, the pre and post-treatment Derkay score. Again, objective quantification of disease burden. This would almost be the equivalent of your RECIST criteria if this was a cancer. The post here is 24 weeks or six months after completion of the clinical trial. Of course, there's, you know, data points in between the pre and the post, I think this highlights the dramatic reduction, not only in the need for clinically indicated interventions, which is the most important outcome measure for a clinical trial like this, but also quantifies the reduction in disease burden seen with this clinical trial. Next slide. The Voice Handicap Index score is a subjective scoring method.
Basically, patients come in, you hand them a validated 10-question questionnaire that gives the patient the opportunity to express how much voice handicap they feel like they have. If they have significant voice handicap because they had heavy papilloma disease burden, their voice is gonna be really dysfunctional, and they're gonna score high on the VHI-10. As their voice gets better with papilloma disease improvement, their VHI-10 score will decrease or improve. Again, what we see here in a very similar pattern to what we observed with the objective Derkay papilloma scoring is the patient's VHI-10 scores, which again is their assessment of their voice quality, significantly improve after treatment. Next slide.
As Dr. Sabzevari had described before, you know, if a patient has pre-existing immunity in the form of antibodies that will bind and neutralize adenovirus, that can neutralize the vaccine before it has a chance to exert its positive benefit. What we've measured here are neutralizing antibodies against this vaccine specifically over time, measured after repeat administration of the vaccine. What we observe is overall very low antibody titer development against the vaccine that does not increase over time with repeat administration.
This is profoundly important, and we would expect neutralizing antibody titer levels that would actually neutralize a therapeutic vaccine like this to be in the 6,000-8,000 or even greater range. What we're observing here is very, very low neutralizing titer response with repeat administration, which is great news because it basically expands the window of possible therapeutic activity for the vaccine.
All right. We're spending a lot of time and effort in trying to understand, why did we seem to have, I'll say cure, why did we seem to have complete responses in about half the patients and not have complete responses in the others? This is a great question. What I can tell you objectively is there are no obvious differences clinically between these patients. No difference between whether a patient has HPV 6 or 11 disease, no difference in gender or age or disease severity. But we do observe very clear differences in our scientific correlative analyses. What I can tell you in a nutshell is it seems like the HPV virus is behaving very differently within the papilloma cells between the responders and the non-responders.
One way that that manifests is that T cells that are activated by the vaccine seem to have a hard time getting into the papilloma in patients that are non-responders, but they do a very good job at getting in the papilloma in the responders. What you're looking at here on the screen are photo micrographs of multispectral immunofluorescence, where we can actually measure the density or the infiltration of T cells coming into these papillomas. In one of our responder patients, on the left-hand side, you can see very little yellow or green T cells. What you see on the right after treatment is significantly enhanced infiltration of yellow or green T cells. These are the types of correlative analyses that we're doing moving forward, and we expect this data to be very soon, both in presentation and publication format. Next slide.
Let's do a few case studies of some of our really nice responders. This first patient we're gonna go over, subject five, this is a 40-year-old male. He tries to work, he has a family. He lives far from his otolaryngologist who takes care of him in the northern Midwest, and he was driving multiple hours very frequently to get clinically indicated procedures because his papilloma was wrecking his voice. In the pre-treatment endoscopy image in the upper right-hand corner, you can see those bulky papillomatous growths really covering both of his vocal cords, as well as different parts of the voice box above the vocal cords. In the right-hand side, that is his six months after completing the clinical trial endoscopy image. That is a completely normal-looking voice box.
You could show that to any otolaryngologist in the United States. They would tell you that's a completely normal voice box. He went from requiring eight clinically indicated procedures in the year before the clinical trial to requiring none since. He is now over a year and a half out. The plot you see with the blue and red lines on the left-hand side is basically his Derkay and VHI scores indicating they're very high pre-treatment and essentially went to normal post-treatment. In the lower right-hand corner of this slide is our scientific measurement specifically of HPV specific T cells in the blood. That left-hand blue plot is showing the very high response to HPV gene products in the T cells in the blood.
The way that we test these T-cells is we have the ability to test them specifically against the parts of HPV that are encoded in the vaccine. These are not random HPV-specific T-cell responses. These are vaccine-induced T-cell responses. In this patient, we also had the ability of looking at HPV-specific T-cell responses in the papilloma tissue itself. Those blue dots in the right-hand plot on the right side of the slide there show the basically increase or change in HPV-specific T-cells that occurred after treatment compared to before. Next slide. Here we're going to show two videos of this patient. The first video is his pre-treatment endoscopy. I think this is only going to play for a few seconds.
You won't hear me while the video is playing, but as the video gets played, the scope is going to go down the back of the nose, and you'll have an opportunity to look around the bottom of the throat and the voice box, and you'll see his voice box covered with bulky papillomas. Pre-treatment video. Let's look at the second video on the right-hand side of the slide. This is his six-month post-treatment video. Again, six months after completing PRGN-2012. Let's look at that video and contrast the appearance of his voice box and vocal cords now with no papilloma. Let's play the video.
You know, we bring these people back to clinic, they basically cry their entire clinic visit because we've taken their life from someone who is having surgery every six to eight weeks, spending all their free money on costs for surgery that insurance didn't cover, not being able to work, not being able to communicate with friends and family. We've turned their life around. Few things are more satisfying than that as a clinician. Next slide. Case study number two. This is actually a 73-year-old female. You can see the appearance of her voice box in the pre-treatment endoscopy video. She has less bulky papillomas but more carpeted covering of almost her entire inside of her voice box, both vocal cords. She essentially could not speak.
When you have papillomas covering your vocal cords, it's difficult to close your vocal cords, which you need to do for coughing. This patient was actually having a lot of respiratory issues related to inability to clear secretions from her windpipe. The post-treatment endoscopy video on the right-hand side, again, is six months after completing the clinical trial.
This patient required 10 interventions in the year prior the clinical trial. She is 73 years old. 10 anesthetics for a 73-year-old that could kill you, just the surgery itself. She went to having no intervention since then. We've changed her life. She actually lived 10-hour drive away from her home laryngologist. That's a big deal for her to have no interventions in the year after. Again, there we see her baseline Derkay and VHI scores pre-treatment, now significantly reduced after treatment.
Again, in her induction, actual measurement of induction of HPV-specific immune responses in her peripheral blood in that lower right-hand plot. Next slide. Last case study we'll go after, that we'll talk about today, subject number 11. This is a 48-year-old young woman from the South, who has a young family at home. She's actually a speech-language pathologist, which is a little bit ironic because those are people that deal with voice.
You can see in the pre-treatment endoscopy video, she had this monstrous papilloma originating from her right vocal cord. It completely inhibited the ability of her vocal cords to close. She could not talk. She was having trouble breathing. The post-treatment is, again, six months after completing the clinical trial. She required eight interventions in the one year prior to try to control the growth of that papilloma.
She's had no interventions in the clinical trial since, she's now over 15 months out. Again, on the left-hand side, we see the plot of her baseline VHI voice score and Derkay score quantifying her disease papilloma that was very high pre-treatment and is basically normalized to baseline levels post-treatment. Again, in the lower right-hand corner, induction of her peripheral blood HPV-specific T-cell responses. Next slide. I went through that really fast. I'm looking forward to a lot of good questions. In summary, repeat administration of PRGN-2012 is very well tolerated. Grade 1, Grade 2 adverse events. We really tell people not much more than what you'd expect to experience with the flu shot. No dose-limited toxicities. phase I data show phase I efficacy data show strong response in RRP patients.
This is a very aggressive, heavily pre-treated patient population. 50% complete response rate as defined by no interventions required since completing the clinical trial. 83% of patients treated at dose level 2 required fewer surgeries after compared to before. We see significant improvement in the Derkay score, the quantification of that disease burden, and the VHI-10 score, which is the patient's subjective measurement of voice handicap.
We are seeing robust induction of HPV-specific T-cell responses both in the peripheral blood and in the papilloma, really validating the mechanism of the vaccine. We do not see the development of high titers of neutralizing antibodies, which is great news both for the repeat administration of the four doses on this clinical trial, as well as opening up the idea of possible retreatment in the future phase II study is ongoing We've treated a total of 32 patients. That 12-month post-data is maturing now.
Thank you. Thank you so much, Dr. Allen. I'd now like to turn the call back to Dr. Sabzevari for some additional commentary on the trial in progress.
Thank you very much, Steve. Based on what you have heard, we have done some re-research, both with publicly available sources as well as internally commissioned third-party research. As part of that research, there was an outreach to obviously number of KOLs, besides Dr. Allen. What we have heard from the KOLs really localizing is that they see the PRGN-2012 is considered as a paradigm-shifting for the patients with RRP. What is the reasons for that? Number one was the, what Dr. Allen point out, the mechanism of action, as it has been believed, the only way to move toward the cure for this patient is to build a T-cell response that is very specific to HPV 6 and 11 that can deal with this chronic infection continuously.
The second reason for them was the reduced need for surgery. Again, as Dr. Allen mentioned, not only for patients that every re-reduction, even by one surgery means a lot, but also the surgeons, they don't like this, and they don't appreciate, and they think this is a game changer. It has a very reassuring safety profile, as Dr. Allen pointed out. It's similar to receiving a flu vaccine, basically. Finally, it's the ease of administration, because now you have a drug product that's like a flu shot you can give at the offices, actually, of the physicians and surgeons. With that in mind, we also looked into the number of cases, both in United States as well as ex-U.S., and it's estimated that there are 10,000 adult cases in U.S., 6,000 juvenile.
Ex-U.S., it's up to 60,000 adult cases. However, there is not a good research being done on the juvenile, and that's part of the ongoing future studies that we are doing. The projected market for the U.S. is excess of $1 billion, and the global market for this is projected to be around $2 billion. One of the things that it becomes very important, and Dr. Allen mentioned, it's the continuous requirement of these patients for surgeries over a period of time, which can be in hundreds of thousands of dollars. A loss of work, the income that has to go toward the medical costs that these patients have, this can be millions for patients.
In some of the actually publication, it has been reported per year, upwards of $140 million for this patient population in U.S. alone. With that, I would like to now invite our audience for the question, and we would be happy to take your questions.
Thank you. We'll now be conducting a question and answer session. We ask you please limit yourselves to two questions. If you'd like to be placed in the question queue, please press star one at this time. You may also type your question to the Ask a Question feature on the left side of your screen. Our first question today is coming from Jennifer Kim from Cantor. The shareholder line is now live.
Hi. Thanks for taking my questions, and congrats on some really impressive data today. I have two questions. The first one is to Dr. Allen. If this type of systemic therapy were approved in RRP, in which patients would you consider using this? Specifically, is it patients who you're currently using off-label systemic therapies with, or is this something that could expand which patients you'd consider for adjuvant therapy? I'll save my second question for later.
Yeah. I think, you know, if this gets an FDA registration, there's gonna be, you know, a box indication. The clinical trial that we've done is patients that require three or more interventions in a year, which our best estimate is that probably captures about a third of all the patients. Those are the patients that certainly could benefit, those are the same patients that are the ones who are using these off-label, you know, potentially high toxicity drugs such as systemic bevacizumab, because, you know, there's no other options available. My hope would be that, you know, patients, for example, receiving systemic bevacizumab can come off that and try, you know, a therapy like this. That would be the sincere hope.
Okay, great. My second question is to the company. How are you thinking about pricing given the impressive efficacy and safety profile? I was wondering, the scientific correlative analysis that Dr. Allen talked about, is that something that could be used early on in treatment to see who might be a potential non-responder versus responder? Thanks.
In regard to the pricing, I think this is, we are not making a comment on that. Of course, one thing that I should say, this is a rare disease. Within the rare disease, as you can imagine, there is a range of prices that is associated with that. That is something to come, and we are looking at that. Based on modeling that have been done, you can go through the range and you can see where it might be. Obviously this is something for later on, for sure, as we get the hopefully approvals in the future and moving towards the commercialization.
In regard to the using the biomarker, and I think this is very important, clearly the correlative that you see, first of all, is extremely important in showing the mechanism of action of this vaccine. That exactly what we anticipated that this vaccine should do is actually doing in this patient, and especially creating a enhanced and robust specific T-cell responses to HPV 6 and 11. That's very important. By the way, a durable response, right? Because you have seen now that the patients that they have a complete response, they have a minimum follow-up of 12 months and actually up to date, they are ongoing, the response. That's, I think that's important from that perspective. To the point of biomarkers, you're absolutely correct.
The biomarkers can be used early on in conjunction, of course, with what we see as efficacy and establish not only the course of the treatment, but one of the things that I think Dr. Allen can speak to much better, for instance, in the patients that they have not. They have a partial response or have not responded with the safety that we see here, it can also, as the future studies go to repeat dosing, which currently, as you see, we have only one course of treatment, but that can be expanded for the future.
Thank you. Next question is coming from RK from H.C. Wainwright & Co. Your line is now live.
Thank you. Good afternoon and, thanks for holding this. In terms of repeat dosings, intervals, you know, just a quick question to the doctor. Like what do you think makes sense here? You know, is this going to be dependent on the antibody expression? Would you try to correlate with that so that you treat the patient with the proper interval such that the benefit is better each time you dose the patient?
I think that's to be determined in future studies, to be honest. I mean, we're interested in understanding from a scientific standpoint why responders are non-responders first and foremost to make the determination of, you know, does it make sense for repeat dosing? Right now all we can say is we've got this impressive clinical response rate with the first course, you know, four injections. Certainly, you know, clinical trials looking at retreatment of these are on our horizon and to be determined.
Thank you for that. You know, when you spoke about utilizing immune therapy and how the immune therapy did not. The data from that was not that impressive. But now that you have a cancer vaccine working, would you think about combining these two to get a better response, especially for those patients who seem to still have surgeries necessary?
Right. Yeah, no, it's a great, it's a great question. You know, our ongoing scientific studies on the clinical specimens from these patients should allow us to address that specific question, which just phrased in a different way, is a possible mechanism of response in the non-responders that the vaccine is actually doing its job, but those T-cells are suppressed in the body because of, you know, local and systemic immunosuppression. Do you need to unleash those T-cells with something like an immune checkpoint inhibitor? Again, hopefully, all to be determined as we continue our in-depth analysis of these clinical specimens, but it's a great question.
Thank you. Next question today is coming from Benjamin Burnett from Stifel. Your line is now live.
Great. Thank you so much and congrats on the data. Appreciate all the background here in the, in the detailed animation. Two questions. Maybe starting with you, Dr. Allen. I guess there's a number of ways to sort of characterize the disease and sort of document efficacy here. Like Derkay, staging, VHI, surgery, rate reduction.
Right.
What is the most meaningful? I guess, do you have any sense for what the FDA might focus on?
Yeah. Clinically indicated interventions. It's all that matters to the patients. It's what really matters to the physicians. You know, if you ask a patient, you know, What, what's your goal? Their goal is to not have procedures. The main reason for that is the procedures mess up their voice box just as much as the disease. You know, the disease is what leads to the need for the interventions. You know, you take someone who's required 300 surgeries, and their voice box and their windpipe just turns into like this scarred, non-functional thing that sits in their throat and almost becomes a liability.
The In my assessment, and I think the RRP Foundation and all my patients would agree with me, the most important outcome measure is preventing those procedures, which is exactly why, you know, I think our and other clinical trials are using that as a primary outcome measure. You know, having each patient serve as their own control to account for the wide variability that we see between patients. Comparing the number of interventions after compared to the year before. It's a good question.
Right. Okay. Okay, that's super helpful. To the company. I guess, you know, the effect size here seems profound and you said you've enrolled 20 patients to date in the phase II, I guess if the data continue to track with what you're seeing here, do you anticipate that the phase II in and of itself could be registrational?
That's a great question. We are currently in discussions with the FDA, productive discussions with the FDA. Of course, we are major part of the discussion is around what is the path forward, regulatory path forward as far as acceleration toward the approval and commercialization. It's to be determined, and we have mentioned that we will be communicating in regards to the path. As you know, this is first of all, it's an orphan disease, it's a rare disease, and of course, those consideration are part of the discussion.
Thank you. As a reminder, that's star one to be placed into question queue. One moment please while we pull for further verbal questions. At this time, Steve, I'd like to turn the floor over to you for any written questions.
Thank you, Kevin. We have several questions that were already covered, by the analyst questions that came in. One that sticks out here is a different question. In addition to RRP, what other conditions for HPV of this type may this product be useful for?
Yeah, it's a really, whoever wrote that, great question. You know, RRP is one disease caused by chronic HPV 6 and 11 infection. There are many other including anogenital condyloma. I don't know the exact number, but there are a massive amount of Americans every year that develop anogenital condyloma. We of course, cannot comment on whether this drug is effective for that, but I would certainly think that's part of the, you know, clinical trial consideration moving forward, is whether that could also be a use. Anogenital condyloma is probably the biggest heavy hitter, you know, other disease caused by HPV 6 and 11.
Yeah. Maybe I can add to, a little bit to that. As Dr. Allen mentioned, this is a large indication, and, depending on the publications that you look at, there are upwards of 400,000 patients in the United States.
I think at this time, Kevin, these are all the questions that have come in. I'd like to thank Dr. Allen and turn the call back to Dr. Sabzevari for some concluding remarks.
Thank you, Steve. First of all, thank you for joining us today for Precigen's R&D Day virtual event. I want to extend our thanks to our patients for participating in the trials, our investigators, specifically Dr. Allen, for their dedication and commitment to working on this rare unmet disease. Finally, to the team at Precigen, who have worked so hard over the last several years. As we have discussed today, we believe the product profile of PRGN-2012 has a paradigm changing potential. We appreciate the opportunity to share these results with you. We appreciate your time to participate in today's call. Thank you.
Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.