Close to the Edge: Episode 12 - Helen Sabzevari
Close to the Edge: Episode 12 - Helen Sabzevari
https://asa1cadmoremedia.blob.core.windows.net/asset-ca5e2abb-46de-4eb0-a22a-985fcf27e9db/Close to the Edge Episode 12 - Helen Sabzevari - HD.mp4
ALEX PHILIPPIDIS: Howdy, and thanks for taking the time to watch Close to the Edge, the new video series from GEN Edge, where we invite leading biotech executives to discuss their science, technology, and their business strategy. I'm Alex Philippidis, Senior Business Editor with GEN, Genetic Engineering and Biotechnology News, the publication covering the biotech industry for 40 years.
KEVIN DAVIES: And I'm Kevin Davies, Executive Editor of The CRISPR Journal and GEN Biotechnology, GEN's new marquee peer-review journal launching in early 2022. More details at www.genbiotechjournal.com.
ALEX PHILIPPIDIS: Close to the Edge is the flagship video of GEN Edge, our new premium subscription channel from GEN providing in-depth exclusive news, interviews, and analysis of key trends in the biotech industry, coupled with a range of multimedia offerings, such as this one. More details of our free trial offer are at www.genengnews.com/gen-edge, G-E-N E-D-G-E.
KEVIN DAVIES: Enough with the URLs. OK, today's guest for episode 12 of Close to the Edge is Helen Sabzevari, the President and CEO of Precigen, a cell and gene therapy developer based in Germantown, Maryland. Precigen has built a pipeline of preclinical and clinical therapies by applying precision technologies to target the most intractable diseases in three core therapeutic areas-- immuno-oncology, autoimmune disorders, and infectious diseases.
KEVIN DAVIES: Welcome, Helen, to Close to the Edge.
HELEN SABZEVARI: Thank you so much for having me. It's a pleasure to be here.
KEVIN DAVIES: It's great to see you. So the cell and gene therapy fields have obviously seen intense development activity and growth over the past decade or few years, certainly, many recent approvals as well too, which is very encouraging. How do you assess the fields of cell and gene therapy today?
HELEN SABZEVARI: Definitely from my perspective and many of my colleagues', we believe that this century and definitely this decade is a decade for a cell and gene therapy. Reality of facts are that if you look at the history of the drug development, especially in the field of oncology, for instance, where we have come since early 1960s to where we are in now 21st century and in 2021, we started a journey that has been really incredible.
HELEN SABZEVARI: If you look at what the drug development field was then, starting with basic surgeries, a tremendous amount of chemotherapies leading to some of the antibody works, some small molecule inhibitors-- and now we are standing at the edge of innovation by actually changing the gene that are expressed in cells from the patients directly, for instance, to combat the cancer instead of sending in drugs from outside, is really activating your own immune system, for instance, to defend you in a best manner.
HELEN SABZEVARI: So it's a fascinating time, I think, for us in the field of cell and gene therapy and years of innovative therapies to come.
KEVIN DAVIES: Well, we're going to spend a lot of time talking about your company's approach. How would you sum up Precigen's approach to cell and gene therapy? And what sets your company apart in what has become a very crowded and competitive field?
HELEN SABZEVARI: Yeah, absolutely. Excellent question. I think from my perspective, we should be looking at what-- there is no doubt that the next arena for therapies and the 21st and 22nd century is going to be focusing on cell and gene therapy. But the issues that the field and investigators have been facing is, how do you control this? Once you change a gene, how do you control the expression of this gene?
HELEN SABZEVARI: How do you control when to turn it on and off? At what time, if there is a safety issue, how do you control that? These are, I think, some of the major aspects that has been at the heart of and difficulty in this field. Another part that a lot of the companies these days are struggling with is basically the manufacturing, having for older patient to have access to therapies, because the current phenomenon that is taking place in cell and gene therapy with the way that has been manufactured, and patients don't really have access.
HELEN SABZEVARI: It's quite difficult in manufacturing. And at the same token, it's quite costly. At the heart of when you look at our treatments, there are two points that, where at Precigen, is very important to us. First of all, we be patient centric. And secondly, how do we provide access of the new therapies to patients within a right price tag at the end of the day?
HELEN SABZEVARI: So what do I mean? Every company, I am sure, and they all believe, and we all believe that we are patient centric. But being patient centric-- of course, everyone drives to develop new drugs for their patients. But the reality is, how do you differentiate your drug that can be in a minimum amount of time be at the patients' disposal, and then with a price that everybody can use them.
HELEN SABZEVARI: What we have done-- and we are really proud from that perspective-- is we have changed the field of cell and gene therapy or differentiated our company in such a way that we can genetically modify the cells from the patient overnight from the same patient. The patient comes in. Their T cells are basically separated. We are capable of genetically modifying it at the hospital site overnight.
HELEN SABZEVARI: And the next day, the genetically modified cells are infused back to the patient with control systems that you can actually monitor these cells and, if you need to be, completely eliminate them. And also, you'd really manufacture them directly in a patient. You allow them to grow in the patient with the mechanisms that we have put in. So you don't have these long manufacturing cycles which can be months and then associated with it huge price tags of hundreds of thousands of dollars, which then it makes it almost impossible for majority of patients to receive these therapies.
HELEN SABZEVARI: But more importantly, even the ones that they get it, they only receive at once because a price tag of half a million dollars is not sustainable by any means for any system in the world. So that's one of the major differences that we have in Precigen, and we are really differentiating ourselves from others.
KEVIN DAVIES: All right, well, we're going to hear more detail about many of those therapies that you have in the pipeline. Helen, you have a very interesting background, almost a lifelong interest in researching and fighting disease, especially cancer. What drew you to cancer research in particular?
HELEN SABZEVARI: So I was born actually in Iran, and I did my middle school and early high school in Iran. I was being educated. And at that time, it was fascinating because it was the timing that, in the United States, they had declared a war on cancer. And I remember in biology classes, they were discussing how the cancer field needs to be changing and some of the research.
HELEN SABZEVARI: And that for me was absolutely fascinating, that how can you treat this disease? And at the very earliest stage and also in our countries, the education is such that you declare actually a major early on in high school. You do have majors, and a lot of other countries, they have a similar system. And I remember at that time, I decided to enter to biology. And then after, obviously, just before revolution, my parents had sent me out for my studies to United States.
HELEN SABZEVARI: And I was thrilled that I could enter to a college and a university and really pursue. And I immediately became involved as basically volunteering in various big hospitals, trying to learn as much. And that was the start for me and starting working in the laboratories and learning more and more and eventually joining my PhD program and focusing in the field of cancer, immunology, and biology.
KEVIN DAVIES: Fantastic. Well, I think Alex will pick it up for here.
ALEX PHILIPPIDIS: Sounds good. Thanks, Kevin. Helen, while you were at the City University of New York, you volunteered at Sloan Kettering and Brookhaven National Lab. You earned your PhD at Scripps Research Institute, where you completed postdoctoral studies in cancer immunotherapy and autoimmunity. Now, where and how do the two cancer and immune system intersect in your view?
HELEN SABZEVARI: When I did my PhDs in the field of cancer immunology-- at that point, they used to call it immunotherapy-- and definitely, the very first postdoc that I did at Scripps in the field of immunotherapy, it became obvious to me that there were a lot of investigators that working on the biology. They understood some of the parts of the immunology and tried to apply that into cancer biology.
HELEN SABZEVARI: And then a lot of long-term immunologists-- they were all focusing on autoimmune diseases. And at that point, when I was going through this, I realized that in order to really be effective in immunotherapy, you have to understand how do you basically lose the control of the immune system to see yourself. At the very easy way of saying it, cancer, at the end of the day, is a enemy from within.
HELEN SABZEVARI: It's part of your system. The reason that the immune system usually-- which I recall-- I call it your army of your body-- doesn't recognize it-- is because it's part of you. Immune system has been trained not to recognize yourself and fight you. That's a good immune system from the childhood. It's trained to understand that, because otherwise, you will end up with all kinds of what we refer to as autoimmune diseases, because the autoimmune disease is actually your own immune system reacting to part of your body.
HELEN SABZEVARI: And when I was being trained, I realized that if I can understand the mechanisms that basically the immune system is start to react to cells, maybe we can use some of those mechanisms in a field of immuno-oncology or immunotherapy to actually see the tumor as a foreign object and react to it. So for that reason, I always felt that autoimmunity was a flip side of immuno-oncology.
HELEN SABZEVARI: In immuno-oncology, you are trying to activate your immune system, your defense or army in the body, to recognize the cancer cells. And in autoimmunity, somehow, your immune system has gotten out of the control, and you're trying to bring it back in control. So if you can understand this both side, then you can actually use it in either direction. And that was the reason that I decided to do a sin in postdoc in a field of autoimmunity with knowing fully that I was going back to the field of immunotherapy.
HELEN SABZEVARI: By the way, when immunotherapy was not chic and in demand at that time because people still did not believe that you can activate your own immune system to combat the cancer.
ALEX PHILIPPIDIS: Mm. Now, earlier in your career, you came to work for the National Cancer Institute and later for Merck in roles that involved the development of cancer treatments. Which setting did you come to life working in better, the NCI or a biopharma like Merck, and why?
HELEN SABZEVARI: [LAUGHS] Very good question. Both, because I think one led to the other. The opportunity that I had at NIH as a researcher-- it really brought to front for me the translational field. There were very few teams in the late '90s that they were going all the way from bench to bed, as we used to call it-- or now we call it vein to vein-- It was very important to learn how do you discover something, and then take that to the next level after publications and really bring it to patients.
HELEN SABZEVARI: And the Laboratory of Tumor Immunology and Biology, which I joined at that point-- it was one of the very few in the world that was actually practicing this. It was a combination of researchers in the field of oncology, as well as clinicians, and really do a translational work going from discovering something and then taking it to their clinic.
HELEN SABZEVARI: So this was a great training from my perspective. I had known the research part extremely well, but the clinical and developmental side was just as important. Because others-- if you don't do that, you can be curing millions of mice. But at the end of the day, if you cannot do the development part, unfortunately, all of the great ideas will stand at the level of discovery and research.
HELEN SABZEVARI: And when I say that once I learned that through NIH, another thing that became very evident at that point to me was NIH is one of the greatest institutes in the world. It's one of a kind, truly. But at the bottom line is NIH cannot develop a drug. Pharma develops a drug, the manufacturing, everything that goes into building a drug product and molecule.
HELEN SABZEVARI: And that was one of the limitations that I felt. And for that reason, I decided also to join Merck as the head of the global immuno-oncology. And this was a marriage of really bridging academia and pharma together for me because now I had the best of both worlds-- the understanding of all the research discovery and translational biology, but now being in a position that you can actually take those ideas, develop those molecules, and put it in the clinic and test it.
HELEN SABZEVARI: That's why I say I think it, for me and the journey that I had, was perfect because it allowed me to really take the ideas from one side to the other and bridge the both training.
ALEX PHILIPPIDIS: And after Merck, joined a Cambridge-based startup called Compass Therapeutics, a developer of next-gen antibody drugs to treat cancer, what interested you in joining a startup, and what do you like about early-stage drug developers?
HELEN SABZEVARI: Yeah, I think the big pharma definitely was a great experience for me. I was very happy and successful that we were able to bring one of the major checkpoint inhibitors to not only clinic, but commercialization. And after that, what really interested me to come and form companies and join biotechs was really the concept of agility that the smaller biotechs have.
HELEN SABZEVARI: And when you have ideas, and when you have a process and technology that you can take this, I think biotechs have the capability because of their size, the agility, the teams, and the commitments that are there to move very rapidly through the drug development process. And that was very, actually, important to me to make sure that-- always in my life, I think one thing that I have been pushing for is to advance our medicine faster and make it faster and accessible to the patient.
HELEN SABZEVARI: And that is always in the corner of my mind, and I thought that the biotech would allow me to do that, and that was the reason for moving from big pharma to biotech.
ALEX PHILIPPIDIS: Kevin, over to you.
KEVIN DAVIES: Thank you, Alex. Helen, let's bring the story now pretty much up to date. How did you come to join Precigen, which I understand at the time you did join, it was a subsidiary of Intrexon, correct?
HELEN SABZEVARI: Yes, you're absolutely correct. Well, as part of all the training, ideas are very important, obviously, in drug development, discovery, and research. But there are components that will make you successful to bring a drug product. And one of the major component is the technology platforms. As you are well aware, all the biotechs-- they have to either invest to develop to produce a technology platform, which might take years.
HELEN SABZEVARI: And then they only have one, and they work on that. Or if you are lucky enough, you come into the scenario that there is a technology platform that you can use. One thing that I mentioned, for me, always is speed to development has been extremely important. The reason for that is very simple. We have a scenario at our hand that, on a daily basis, I get the numbers of the patients that every day we lose in various cancer indications.
HELEN SABZEVARI: And for some people, this might be, oh, this is very morbid, Helen. Every day, you start with looking at the number for that day. But for me, that is a reminder that if I delay, and if my team delays for one day, this is how many people we lost that day. And I think from my perspective, this is why we are doing what we do, and it's is a continuous reminder every single day when I turn my computer on, because that tells me, I cannot lose a minute, left alone, losing a day.
HELEN SABZEVARI: So with that in mind, when I was looking at the opportunities that were being offered to me, at that time, Intrexon had a greatest number of the platforms in biotechnology that was not really completely used and/or advanced. However, when I saw the opportunity that existed, and the years that will save, if I didn't have to establish every one of those platform from this ground zero, it was like finding a gold mine, because as a drug developer, there is nothing more important that if you have the ideas, and if you have the technology that you can merge it to you, and then you have the road that basically is like a marathon.
HELEN SABZEVARI: You run it, and the faster you run, the more life you're going to save. And that was really, after looking at Intrexon, seeing the capabilities and technologies that Intrexon had-- that was, I would say, the single most important reason that I joined Intrexon as the head of the health at that time.
KEVIN DAVIES: All right, so you joined as head of R&D, and then I think by last year, 2020, you were elevated to President and CEO of the new Precigen, which was now, I think, redirected or refocused more into drug development. So can you just tell us a little bit about the evolution of Intrexon onto Precigen?
HELEN SABZEVARI: Sure. When I joined Intrexon, Health was one of many subsidiaries of Intrexon. Intrexon and had a very global vision of using, basically, DNA technology in various aspects of life. And as I mentioned, the technologies existed. The platforms were there, but they were not fully realized in a sense of, how do you pair it with various diseases?
HELEN SABZEVARI: At the same token, I always have a saying, even though I come from academia, in drug development, one thing that is very important-- we don't run academic exercises. We run drug development programs. And there is a major difference here, because the treatment, at the end of the day, is focused on a patient, not the mice. And there is a limited amount of time with the limited budgets that you have to advance these programs to the levels that will be beneficial for the patient.
HELEN SABZEVARI: So when I looked at the totality of what we had from 2000, I joined, I believe, Intrexon in mid-August of 2017. And by 2018, we had reshaped and refocused the Health and started to advance the platform and basically take back some of the platform that was not being advanced in a proper fashion and by various partnerships that existed out there.
HELEN SABZEVARI: And we completely reshaped their portfolio, the technology-- we advanced them to what I consider commercially viable platforms, because there is always platforms that you can even run phase I trials with them. But they never would stand the commercially viable pressures that you have to meet for the FDA approval. And we wanted to make sure that this platform were advancing to that level.
HELEN SABZEVARI: And as a result, the portfolio went so well, and we were able to bring various programs to the clinic, and by the end of 2019, that the decision was made that really Intrexon and now Precigen is-- the focus and the value would stand within the Health, and we decided to refocus the company. And then I was offered to become a CEO and president of Precigen as of January of 2020, which has--
KEVIN DAVIES: I can ask you about your more personal experience as a CEO in a second. But first, I just want to help the audience better understand Precigen's focus, which goes beyond cancer immunotherapies to include autoimmune disorders infectious diseases. I think you have programs in hepatitis as well. As far as cancer drug development goes, what are the key challenges that you're trying to overcome at Precigen?
HELEN SABZEVARI: Yeah. I think for the cancer development and focusing on immuno-oncology is really to coming up with the innovative, I think, drug products that is rapidly accessible to patients in a right price. And it really takes the bar for the treatment to the next level. And It's not the same thing over and over again, but something that it substantially changes the paradigm in the field.
HELEN SABZEVARI: And that's what we have been focusing in regard to the immuno-oncology. And then from the perspective because of the training that myself and many of the immunologists at Precigen here, which is an outstanding team, by the way-- I'm privileged to stand next to these individuals. With our training, we realize that, as I mentioned, the opposite side of coming up with treatments for immuno-oncology is, if we understand how to unleash the immune system, we also can use the same mechanism to put a leash back on the immune system for autoimmunity.
HELEN SABZEVARI: So the strategy that we took was very, very focused, actually, for autoimmunity to maximize, basically, our technology platform and our portfolio and get number of shots on the go with using the same technology, but now-- and our knowledge from immuno-oncology to apply that to autoimmunity and infectious disease-- but keeping it very focused, because I think that's also very important in drug development that you know how to manage a portfolio that doesn't get out of hand, that you are not just following molecules for the sake of loving them but not being valuable to the patient.
KEVIN DAVIES: Yes. We've reported over the last couple of years of persist-- no, persistent isn't quite the right word, but still recurring, lingering dosing problems with companies that are attempting to do replacement gene therapy. So even though the vectors are much safer than they were, say, 10, 15 years ago, there are still adverse events being reported. Do you encounter any analogous dosing challenges that you have to overcome?
HELEN SABZEVARI: So up to this point, currently, we have actually three clinical programs that are in our UltraCAR-T's gene therapy. And also, one program with our AdenoVerse for HPV cancers. And I am really proud to say, up to this point, as we have reported a number of trials, that now they have-- some move from phase I to phase II.
HELEN SABZEVARI: We have shown great safety on many of these. In regard to redosing, your point is so, so correct. And the issue that field has faced in regard to redosing and safety concerns that has happened both in conventional CARs but also off-the-shelf therapies-- it's at the center, actually, of our differentiation from the others, because everyone else, in order to have some level of effect-- and this has been only at the level of hematological indications, for instance, with the CAR-Ts-- is they are infusing hundreds of millions, if not billions, of cells into a patient body at once.
HELEN SABZEVARI: And then as a result of that-- and there is no mechanism of control of these cells, by the way. They don't have any switch to turn them on and off or eliminate them in case of safety. And basically, these cells enter. The analogy that I always give is, perhaps because I like old-fashioned movies-- these old fashioned movies that they have this 16th century, and the armies come into a battle, and they stand in front of each other.
HELEN SABZEVARI: And then you see hundreds of thousands hitting each other. And then obviously, there is a tremendous damage to both sides and also the area. This is exactly what happens when you send billions of cells into a body and unleashed.
KEVIN DAVIES: Yeah.
HELEN SABZEVARI: And unfortunately, that is what we have seen in the field, that many of-- even though the concept of the gene therapy is correct, and activating your own cells or off the shelf, but the reality is you have to control this. And sending millions of cells that, by the way, only survive for two weeks, three weeks maximum-- this is like you spend billions of dollars on an army that can only go on for two or three weeks.
HELEN SABZEVARI: And then your country is without a defense. And that's exactly what happens in the body. And this has been the biggest challenge for all of the companies that are in this field because they spend hundreds of thousands of dollars for manufacturing send this. They have a very short-lived army. And then basically, that's the end of it, because they cannot redose with a lot of toxicity, which is associated with this high dose.
HELEN SABZEVARI: We do it completely reversed. We send an army that is young, is not super-activated outside, so they are not exhausted. But they are young. They go in. They get trained, and they expand as they need. And they persist, by the way. We have studies that we have now both preclinical and in clinic that we have shown that these cells can go for months upon months post-infusion.
HELEN SABZEVARI: And when they see the tumor, they expand. When they don't see the tumor, they are persisting but quiet. And this allows these cells to be reused in the body. At the same token, because the numbers are not tremendous, you do not create that kind of safety issues. And to this point, we have shown excellent safety up to this point, as we have doses [INAUDIBLE]..
KEVIN DAVIES: That's great. I'm sure that's a Game of Thrones reference, so we can update your analogy, but I'll let you work on that after the program. Speaking of challenges, what have you personally found most rewarding and challenging as the chief executive of a public company?
HELEN SABZEVARI: I think, for me, obviously, the reward always is. The same the reward is working with great minds and the teams that are really dedicated to patient to develop a drug for a patient. I have a saying-- I take this drug development and putting treatment for the patient extremely personally. The day it's not personal to me, is the day that I would retire, because this is our life.
HELEN SABZEVARI: This is not a job anymore. And this is what we are fighting for, for somebody else's life and for our own life, at the end of the day, from a perspective that nobody is immune to catching or having the diseases. So for me, that is my biggest privilege to have the ability to do what I was trained with, what I love to do, and doing it next to a group and a team that is just outstanding.
HELEN SABZEVARI: Challenges-- there is always challenges to every work that you do from the perspective of trying to come up with the next innovation, trying to make sure that you beat the timeline that even you had yesterday, because that's what makes the difference. That's where it changes somebody's life at the end of the day. If I can beat that timeline that I set up yesterday, even by minutes, by hours, or by days, that makes a lot of difference.
HELEN SABZEVARI: So those are the challenges. And of course, there is always making sure that we take into account all aspects that we don't miss a scientific view that we have and ensuring that we are providing the best treatment for the patient, which I'm sure that it would also translate to the best result for our investors in our company.
KEVIN DAVIES: Nicely put, yes. OK, Alex, over to you.
ALEX PHILIPPIDIS: Thanks, Kevin. Let's discuss, Helen, several recent announcements, starting with the one about some clinical progress made by therapies based on UltraCAR-T and the AdenoVerse platforms. Maybe you can talk about those therapies and the advantages both platforms confer in fighting different forms of cancer.
HELEN SABZEVARI: Sure, absolutely. I would love to. Our UltraCAR-T cell therapies, as I mentioned, what differentiates it from everyone else and how it works is basically we have developed a nonviral platform. What do I mean by that? We have now plasmids that encodes our CAR-T safety switch-- in the case that we want to eliminate cells, we can.
HELEN SABZEVARI: As well as what we refer to as a membrane-bound IL-15, which is-- this is what I always refer to as a backpack, if you want to imagine a backpack of food for the T cells. So you are giving them what they need so that you don't have to expand them outside. They basically feed on that and expand themselves or persist. And this is in a format of a DNA plasmid. And then we have a system with the UltraPorator that, instead of using lentiviruses, which everyone else in the field are using currently-- and they have to manufacture these to basically various manufacturing sites for many weeks and then do extensive testing to make sure that the virus is gone, and then they have uniform cells.
HELEN SABZEVARI: We have put UltraPorator device that actually Precigen brought forward from the discovery all the way now that it's in the clinic. And this allows the hospitals that patient walks in in the morning, the patient get eight freezes, their T cells are separated, and then they are transfected. We can have up to 4 billion T cells of the patient's genetically modified under 12 minutes.
HELEN SABZEVARI: And then these cells are left overnight. You don't need to do anything to them. They're just rested overnight. And next day, basically, they infuse [INAUDIBLE] and infuse back to the patient. So now you went from four to eight weeks of manufacturing, hundreds of thousands of dollars, to make genetically modified T cells to overnight with basically the cost that is much lower than everyone else, and the speed to the patient.
HELEN SABZEVARI: These are the T cells from the patient directly. So it's not a foreign, or allo, or off the shelf. So we have now advanced this with the mechanism also in it that allows it to grow when it needs to grow, stop when it needs to stop in the patient, and also the fact that from safety switches that we can control if these cells get out of control, by any chance. I think that was our UltraCAR-T platform.
HELEN SABZEVARI: You were referring to the clinical data that we have shown. And we were really excited on both because we have applied it to solid tumors as well as hematological one. We just recently reported on our AML. And just to give you a view on this, the AML indication, something that the patients that we are treating which are stage 4s-- they have three to four months to live.
HELEN SABZEVARI: That's not even possible for conventional therapies, CAR-T therapies, to manufacture their T cell CAR-Ts. And with this, we showed, at the lowest doses, the dose level 1 and 2-- so I give you a perspective-- we infuse somewhere around between 7 million to 27, 28 million cells total.
HELEN SABZEVARI: That's all we infuse the patient. And in the first two dose levels that we have treated, we have seen 50% objective responses, which, for this patient population, it's really outstanding and exciting. And we had two complete responses and one partial response that, in a way, that partial response-- and just one nodule was left-- otherwise would have been complete response, which would have been really three complete responses out of six patients.
HELEN SABZEVARI: And if you put that and compare it to where the state of cell and gene therapy currently is, that they infuse, for instance, even with the off-the-shelf, three cycles of 300 million cells every time-- so you are almost giving a billion cells versus 27 million cells. So you can see how the manufacturing affects, how the cost is reduced, and also how the safety is affected.
ALEX PHILIPPIDIS: Do I understand correctly? Then a reason for the lower cost is because there are fewer cells needed compared to a lot of other cell or gene therapies.
HELEN SABZEVARI: Actually, it's a number of things. The first is the manufacturing, because manufacturing overnight in a hospital-- you do not use these manufacturing facilities that it takes eight weeks. So we do manufacturing. We genetically modify the T cells overnight with the plasmid. The cost of the plasmid is within thousands of dollars. It's very cheap.
HELEN SABZEVARI: And it's done at the site of the hospital. So the T cells of a patient never leave the hospital. Overnight, you don't need to activate them. You don't need to expand them. This is where the cost of manufacturing comes. You don't have any of those costs. So this is one of the major reasons, but we also believe that-- and that's what we are testing currently, that obviously, we are getting, because of the quality of UltraCAR and the components that they carry, you can go in with much lower cells and still see objective responses.
ALEX PHILIPPIDIS: When you talk about the costs being lower, can you either quantify by dollar or percent how much lower they are compared to gene and cell therapies that we've seen going to a million dollars or more?
HELEN SABZEVARI: Yeah. So we have not given any kind of a price on this, obviously. I try to avoid at this point in time to go there. But I can tell you, we will be logs lower.
ALEX PHILIPPIDIS: Mhm. Great and speaking of platforms, Precigen also has two other platforms-- ActoBiotics and the Multifunctional. What makes some candidates more suited for those platforms?
HELEN SABZEVARI: Yeah. So I think our ActoBiotics, which uses microbial L. lactis, which is a very safe bacteria, which we all have in our guts, to express certain genes. And especially if you are evolving the mucosal immunity, for those of us in immunology, it's basically the immune system that you have in the gut. And in autoimmunity, you want to tolerize.
HELEN SABZEVARI: And this is a great mechanism, extremely safe mechanism for delivery of these genes. And as you know, this year, we were also very happy that we were able to report on phase 2 data from ActoBiotics that met its endpoint in type 1 diabetes.
HELEN SABZEVARI: So I think for certain aspects, for certain diseases, such as diabetes, such as IBD and Crohn, as well as, for instance, celiac disease, this method of delivery-- it will be really ideal because it's re-educating the gut immune system to tolerize against the autoimmune cells. Our AdenoVerse platform, on the other hand, which is our library of the gorilla vectors that we have-- and this one is great in activating the immune system, especially the differentiation that we have with other adenovirus platforms that exist.
HELEN SABZEVARI: The major differentiation that we have is, first of all, these gorilla vectors or viruses-- really, we have not been exposed to them, so we don't have preimmunity to them. What does that mean? It means that you can give them number of times, and your immune system can still becomes activated again and again. Whereas when you are looking at the [INAUDIBLE] 5s, other retroviruses, so on and so forth, you can only give them one time, and that's it And this-- we were very excited about testing this in the clinic.
HELEN SABZEVARI: And then the second part that our gorilla AdenoVerse platform has is the basically payload capacity. What do I mean by that? If you can put one gene and express it, it's good. If you can put two genes, it's better. Why? Because then you can put a switch next to that gene, and you can turn it on and off like a lamp, which these other vectors don't have that ability.
HELEN SABZEVARI: But with the gorilla vectors, we have up to 14 kB, which means many genes with many switches. And we took advantage of that especially to build the PRGN-2009, which is our drug products that we are using for the HPV indication, the head and neck cancers, the cervical cancers, anal cancers. And we were really excited.
HELEN SABZEVARI: It's covered new epitopes that no one else has. And again this year, we reported on that for the activation of the immune system in patients that they're stage 4 in this with HPV cancers. Not only we showed excellent safety-- and Dr. Goli and our other investigators spoke to this-- but also for the first time and in combination, which we are so excited about this, that we showed 40% objective responses in patients that had failed all the checkpoint inhibitors.
HELEN SABZEVARI: Basically, these are patients that they have nothing in front of them. And the concept that now this patient is alive, for instance, has a complete response, which means the AdenoVerse vaccine has cleaned up all of this, and patient is, six months later, after all of the treatment, still is going as strong. You can imagine what it means for us as a company from perspective of what the team has developed is making a difference in someone's life, and that's very important.
HELEN SABZEVARI: So that's currently in the clinic as well and pushing forward to the next layer for, hopefully, discussions that we are having with the FDA for advancement of this fast tracking.
ALEX PHILIPPIDIS: Mhm. And that would be, if I remember, because you spoke a positive overall response rate of 40%. That would be for 2009.
HELEN SABZEVARI: Yes.
ALEX PHILIPPIDIS: Right? Yeah. PRGN-2009. Now, what sort of advancement are you looking at over the coming year in that?
HELEN SABZEVARI: Yeah. So for PRGN-2009, we are hoping to move it very rapidly to the indication, like as cervical and head and neck. And also, as I mentioned, we are in discussions with the FDA for the next path for a licensure, because as you know, for instance, in the cervical cancer for the patients, a lot of people might not be aware-- currently, the response rate indication is 15%.
HELEN SABZEVARI: That means out of the 100 women that they have this, only 15 women respond. 85 women will die. And when you look at that number, 15% is the number that anyone should be living with. Anyone who is in a drug development cannot be happy with this. So for us, we are advancing this very rapidly in basically what we reported, for instance, in this.
HELEN SABZEVARI: And Dr. Goli spoke to that. We have a patient that currently has received basically more than a year worth of this vaccine, and all they do is go on a monthly basis. They get a shot in the arm, and it's like receiving a flu vaccine, basically. And the patient is stable, and now patient is well over a year, year and a half in this therapy. This is a stage 4 patient.
HELEN SABZEVARI: So that's what it means for us to move this very rapidly to the next level, because there is no option. We have to change that 15%. Every move that we can make in that-- that is huge for the patients, and that's what we need to do. So that's part of the discussions that we are having. We are very excited about the cervical cancer for a licensure. And similarly, we are very excited to move it rapidly for head and neck cancers.
HELEN SABZEVARI: Again, if you look at the checkpoint inhibitors for head and neck, the approval has been also 18%.
ALEX PHILIPPIDIS: Mm. So 2009 is one lead product, and other has been AG019 and type 1 diabetes, where, as you said, there's been positive data reported this year. What does the coming year look like for AG019?
HELEN SABZEVARI: Similarly, AG019 is moving, and we are in discussions with the regulatory, both FDA and EMA at this point for a pivotal trial to move that in the direction that we can rapidly run the second trial and go, hopefully, for approval.
ALEX PHILIPPIDIS: Right. And looking ahead, Helen, what are your major goals and hopes for the next 5 to 10 years?
HELEN SABZEVARI: So I think, clearly, we are doing something that is very unique. And the most important part for us is in using the right technology platforms that we have for the right indication. And in the field of immuno-oncology, definitely we are looking to advance our UltraCAR to be a major force for the patients, both in hematological and solid tumors and, clearly, get approval for these drug products in the years to come faster, actually, as fast as we can for the patients, similarly, our AdenoVerse platform in indications such as head and neck and PRGN in cervical.
HELEN SABZEVARI: But also, one thing that is very important-- and, of course, our ActoBio, which I spoke about. But more importantly, we cannot take our eyes off the ball. One thing I have learned in my career is coming up with treatments for cancer-- this is not something nobody has a silver bullet. And nobody is going to get something overnight, 100%. What we are doing is basically pushing the ball down the field and gaining-- instead of 15%, to make it to 30% or 40%.
HELEN SABZEVARI: And then the most important thing is not to be happy just with that and keep innovating on top of what we have and with the new technology platforms that we have that we can in 3, 4, or 5, years push the ball from a 50% or 60% approval to 80% and 90%. Because at the end of the day, if we lose one patient, that is one too many for us.
HELEN SABZEVARI: It doesn't matter. We have lost a life, and I think this should not be forgotten. So as happy-- and we are really excited about the data that we have. And as we push forward for bringing these drug products to the patient, I don't think neither myself nor my team we forget any single day that, as an industry, we have to do better. We have to imagine a day that all patients have access to the drug, that the price is at the point that is not just a certain group that can receive these drugs, but it's available for everyone.
HELEN SABZEVARI: And also, all patients-- the drug is made in such a way that it can be rapidly put at the disposal of the patient. And the patient that only has a few months to live does not have to think that I will not receive this drug because I just don't have time.
ALEX PHILIPPIDIS: All right. Kevin, over to you.
KEVIN DAVIES: Well, that's about all the time we have for today's episode of Close to the Edge. Our sincere thanks to our special guest, Helen Sabzevari, the CEO of Precigen, for joining us on this episode. Helen, we were really inspired by your passion, and best of luck going forward.
HELEN SABZEVARI: Thank you so much for having me and also presenting our company to you guys. Thank you.
ALEX PHILIPPIDIS: Sure.
KEVIN DAVIES: Thanks.
ALEX PHILIPPIDIS: GEN Edge is where biotech gets down to business. You can sign up for a free introductory trial at www.genengnews.com. Close to the Edge is produced by Bobby Grandone and Liana Jabs. I'm Alex Philippidis, thanking you again for taking the time. And we'll see you next time right here on Close to the Edge. [MUSIC PLAYING]