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Genome Editor Fyodor Urnov on Commercializing CRISPR Therapies and Epigenomic Tuning
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Genome Editor Fyodor Urnov on Commercializing CRISPR Therapies and Epigenomic Tuning
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Segment:0 .
[MUSIC PLAYING]
JONATHAN GRINSTEIN: Hello. And welcome to a special episode of Close To The Edge from GEN, where we invite executives and outstanding scientists from groundbreaking biotech and pharma companies to discuss their science, technology, and their business strategy. I'm Jonathan Grinstein, senior editor of the GEN media group. And I'm based in San Diego, California. In a few moments, you'll get to see my exclusive interview with Dr. Fyodor Urnov, genome editing pioneer and co-founder of Tune Therapeutics.
JONATHAN GRINSTEIN: This episode of Close To The Edge is sponsored by GEN Biotechnology, GEN's new marquis peer reviewed journal, which publishes original research and commentary across all aspects of the biotech industry. GEN Biotechnology debuted last year, and warmly invites submissions in a variety of fields, including multiomics, synbio, ag biotech, AI, and of course, gene editing.
JONATHAN GRINSTEIN: That's quite fitting because today's guest is a founding member of the editorial board of GEN Biotechnology. Fyodor Urnov is a well-known figure in the genome editing community. Indeed, his former team at Sangamo coined the term genome editing back in 2005. Fyodor is currently scientific director of technology and translation at the Innovative Genomics Institute in Berkeley, California.
JONATHAN GRINSTEIN: He's a professor of molecular and cell biology at UC Berkeley, and a co-founder with Charles Gersbach of Duke University, and President, CFO, Akira Matsuno of Tune Therapeutics, one of several biotechs pursuing epigenomic editing. I recently grabbed 30 minutes in Fyodor's hectic schedule for a wide ranging conversation about his new company and gene editing more broadly.
JONATHAN GRINSTEIN: I hope you enjoy it. Hello, everyone. I'm delighted to have our guests today on Close To The Edge, Fyodor Urnov. Welcome, Fyodor.
FYODOR URNOV: Thank you for having me.
JONATHAN GRINSTEIN: I'm a huge fan. I follow you on Twitter. I follow you so closely that I saw that you went to a Fall Out Boy concert. And I was very excited because when I was in high school, a long, long time ago, I opened for them. And so I got to hang out with them. And so that was a fun experience that we can-- we'll have to chat about at some point.
JONATHAN GRINSTEIN: But before getting too distracted on our music interests, I wanted to get to some of your work in your writings. I read through your 2021 article for molecular therapy, called "Imagine CRISPR Cures," which I'm guessing, is a reference to the John Lennon song. And your op ed for the New York Times in December of last year, titled, "We Can Cure Disease by Editing a Person's DNA. Why Aren't We?" In these articles, you lay out the improvements necessary to make CRISPR cures for n equals 1 diseases and rare diseases a reality.
JONATHAN GRINSTEIN: So where are we today in realizing your CRISPR cures on demand vision?
FYODOR URNOV: We have in front of us clinical data, the genetic therapies for severe disease can be curative. And I want to emphasize to what extent-- this wasn't a given. Genetic engineering to treat disease was proposed in 1972 by Ted Friedman at UCSD. That's 50 years ago, before Fall Out Boy. The first gene therapy trials were done at the NIH in 1989.
FYODOR URNOV: The first glimmers that gene therapy can work, 2000s. CRISPR came online 2012. First human being treated with CRISPR, 2019. And looking back at that time, it truly staggers the imagination, how this early period of incubation, 1989 through the early 2010s, where things were working, maybe, somewhat did, then there are glitches.
FYODOR URNOV: But then the field hits its stride. And we have now somewhere on the order of, I think, 15 to 20 gene therapies just for disorders of the blood alone, where we have pretty spectacular curative effects. And when I say curative, I don't mean a patient gets mildly better. I mean something like adenosine deaminase deficiency severe combined immune deficiency. Don Kohn at UCLA and Claire Booth at University College London, they had 50 children who were certain to die.
FYODOR URNOV: And they were basically cured by gene therapy or in two cases, by bone marrow transplant. I mean, think about that. Similarly, as one looks at what CRISPR has been doing clinically recently, look at the data from clinical trials for sickle cell disease from CRISPR Therapeutics and Vertex. They show data where they treat people who have had multiple episodes of pain before being administered their own CRISPR edited cells.
FYODOR URNOV: And they've shown at multiple meetings that dozens and dozens of human beings are now free of pain episodes in the case of sickle or needs for transfusion in the case of thal. Look at Antalya. Antalya is treating TTR amyloidosis. And within a month of being administered a teaspoon of CRISPR, it's astonishing. You have 95% reduction in the bloodstream of these human beings of this toxic protein.
FYODOR URNOV: So blood is editable. The liver is editable. Major companies, biotech and pharma is really stepping in here, is showing how well it works. Nobody is celebrating this in the rare disease space because the quote, "rare diseases" under the current system are just going to be left by the roadside.
FYODOR URNOV: There's just not enough human beings with a disease number 75 to justify the commercial investment in taking that medicine through development clinical trials then regulatory approval. And this is not Debbie Negative or Debbie Downer, this is Debbie Realist. And we have examples where companies took on genetic therapies that they simply couldn't figure out how to commercialize.
FYODOR URNOV: Don Kohn, whom I mentioned earlier, has this pretty painful list. It's-- I think it has, at last demonstration, 17 diseases where lentiviral gene therapy was curative. And the list is growing. And only four of them are commercialized for about three of the others, commercialization has been halted. And none of the recent ones are being commercialized. So as Don says, the list of diseases we've cured is growing at the bottom.
FYODOR URNOV: And the list of diseases that are commercialized and approved is shrinking from the top. [LAUGHS] I mean, I'm laughing, but I'm really not. I think the realization that CRISPR can be this powerful is now a definitive component of the momentum that the system has to change. I am unaware, unfortunately, of a single gene editing trial, anywhere in the world, in the-- in-- for genetic disease that will be all academic and all non-profit, other than the one we have, which is led by the University of California, San Francisco, and Dr. Mark Walters.
FYODOR URNOV: It gives me zero pleasure to say that we are the only ones. There should be 100 trials such as this, literally, 100, because believe me, the patients are out there. And the technology is there. It's just that-- So as we think about getting as closer to a world where these diseases are not left by the wayside, I'm going to say that we are probably 20% of the way in. And I'm also going to say that the remaining 80% are going to be more challenging than the first 20.
FYODOR URNOV: And the first 20% of the way that we're in, basically shows that academic and nonprofit centers have all the relevant expertise to design a CRISPR medicine, to administer it to animals, and in a few cases, really get the program to a point where if only we could manufacture the medicine affordably, if only we could go through clinical trials affordably, if only there was a regulatory framework where we would not be burdened by studies that are million dollars in years length, which is what currently the costs are.
FYODOR URNOV: So the next three to five years, I see as almost a moral must for our field. We have to take the momentum that CRISPR can be cured, the gene therapy can be curative. We have to take the established fact that academic and nonprofit institutions across the world-- I am sitting literally in the center of one of them. Our sister campus, UCSF, is a world leader in developing these therapies.
FYODOR URNOV: Our sister campus just down the road, metaphorically speaking, UCLA, is another leader. We, at the University of California, Berkeley are a CRISPR center of excellence. There are other places like that. Children's Boston, University of Pennsylvania, Penn Medicine, Seattle Children's, Saint Jude. What currently doesn't exist is a way to support these institutions and create a dedicated manufacturing and regulatory framework for them, where within the realm of academic nonprofit medicine, they can start rapidly developing de-risking and administering these cures for n of 1.
FYODOR URNOV: Why don't we have that? Well, we've never had a technology like CRISPR that was so versatile. In other words, the reason that there isn't some wonderful environment where you can develop and deliver a CRISPR cure in six months is we've never had a reason to build it. Now, we do. The momentum to have the regulatory manufacturing and logistical and clinical environments now align with the promise of the technology comes from the fact that the technology has demonstrated definitive curative potential.
FYODOR URNOV: Again, I don't want to be Negative Nancy I'm. Just Nancy, the realist.
JONATHAN GRINSTEIN: Yeah, I saw a tweet, I think, that you shared yesterday that at the going rate for some of these things, it may take a couple thousand years if we don't make some major changes. And it's interesting, the centralization of this all would be fantastic. It'll be interesting to see which one gets there first, whether it's the finances or the regulation of it. But yeah, we definitely need all hands on deck for this.
FYODOR URNOV: I agree.
JONATHAN GRINSTEIN: Sorry? Go ahead.
FYODOR URNOV: I agree. I think you said it right.
JONATHAN GRINSTEIN: Yeah. Yeah. So switching gears slightly, moving into what you work on, both in the lab and your-- I'm sure, Tune. Can you give me the SparkNotes version of epigenome editing for dummies? What can gene-- epigenetic editing do that-- genetic editing tools like these, and prime editing can't. I'm really curious as to how durable the effect is.
JONATHAN GRINSTEIN: And if it's not a one shot and done treatment, why would you go this route as opposed to using a genetic tool like CRISPR for permanent changes?
FYODOR URNOV: So I really hope you booked three hours for this interview, because-- I'm joking. The SparkNotes-- but I don't want to say for dummies, the SparkNotes for people who are curious and interested in this sort of thing. Why does fiber protect from colon cancer? It is because in your colon, the fiber gets fermented to make a chemical called sodium butyrate.
FYODOR URNOV: And sodium butyrate enters the cells of the lining of the colon. And it changes chemical marks on genes that protect those colon cells from cancer. And those marks, on the protein environment of the genes and on the DNA itself, don't change what the genes say. Those marks change what the genes do.
FYODOR URNOV: So next time you have some oatmeal, close your eyes and visualize that fiber being fermented in your colon, making butyrate. And the butyrate entering the cells that line your colon, entering the nucleus. And that chemical, keeping the genes that protect you from cancer on. So first of all, fiber is good for you, both for cardiovascular disease and colorectal health.
FYODOR URNOV: And this is just a great example of how our genes learn from experience, because that's literally what epigenetics is. Yes, we leave this mortal coil with more or less the same DNA that we are born with. But what our genes do in our lifetime changes? Not just because we age, but because we go through various exposures, like I just gave you an example, this dietary fiber. And we know, from striking public health evidence, how powerful keeping a healthy epigenome can be.
FYODOR URNOV: In the United States and in many developed countries, if a woman chooses to become pregnant, her treating physician, her physician will recommend that she take a dietary supplement called folate. Now what is this folate thing? What it is is less interesting than what it does. It allows the developing fetus to have a healthy epigenome specifically in its spine.
FYODOR URNOV: So it prevents the prevalence of a severe inborn error of development called spina bifida. And there is definitive epidemiologic evidence that dietary folate in a woman who chooses to have a biological child, before conception and through pregnancy, will keep the genes in the developing fetus and the baby that contribute to normal spine development, it will keep them in a healthy state. By that, I don't mean it will change their DNA.
FYODOR URNOV: No, it won't change their DNA. It will change what the genes do. So the epigenome is the sum total of these little marks from experience that our genes acquire as we go through development and through life. And we've known about this since the 1960s. We've known that our DNA is enveloped in proteins that have these covalent marks.
FYODOR URNOV: And these-- I'm sorry, covalent marks is not SparkNotes, chemical marks. Chemical marks. And those chemical marks do some-- have something to do with what the genes do. And-- but for pretty much that entire period until about 20 years ago, we were like astronomers staring at the stars, like we can count them, but we can't fly to them.
FYODOR URNOV: Then about 20 years ago, some really amazing work that came out of a number of academic institutions, and then ultimately, got taken up by a biotechnology company, where I have to disclose an emotional conflict of interest. I worked there for a decade and a half, so my heart skips a beat in a positive way when I speak about this. I realize that you can engineer proteins that will recognize a specific gene inside a living cell, and change its epigenome.
FYODOR URNOV: What does that mean in practical terms? Well, imagine a gene that got aberrantly silenced for some reason of environmental exposure. Maybe, we can wake it. Imagine a gene that is producing something unwanted. Well, maybe we can build a protein that would engage that gene and turn it off. We don't have to imagine. This is all reality.
FYODOR URNOV: So studies over the past 20 years have given us a proof of concept that you can turn genes on and off, on demand. So not wait for mother nature to smile benevolently on us, but we can turn genes on and off, on demand, by building these epigenome editors. Notice the epi- prefix, so they're not gene editors. So they don't change the DNA, but they change what the genes do.
FYODOR URNOV: So you build an epigenome editor. And it will go inside a human cell. It can go inside a T cell. It can go inside a brain cell. And for a specific gene, turn it on and off. One thing I want to emphasize, though, is we, humans, have a great ability of proposing technologies, and then getting it to work as a proof of concept.
FYODOR URNOV: And then it just sits there. And then other technologies come on board, and ultimately, it's the constellation of things that makes things real. I mean, my favorite example is the surface of this weapon of mass destruction. So the surface of the iPhone is made out of something called Gorilla Glass, which Corning actually engineered in the 1960s for use in windshields.
FYODOR URNOV: It never caught on, and just sat there on the shelf until Steve Jobs decided that he wants to make his phone with an unbreakable glass cover. And so there was an older technology that had existed that now, I don't know how many of these there exist, a lot. And they all have a coating of a glass that was developed by Corning in the 1960s for a completely different reason.
FYODOR URNOV: So I think it's just a great example of how multiple threads of technology come together to have a 1 plus 1 equals 7 effect. So I think this is true for epigenome editing. We know-- we've known that we could do this since the early 2000s. But as you think about the ability to engineer new kind of proteins, both in terms of engaging the DNA and in terms of changing the epigenome, as we think about ways to rapidly profile their potency, like, do they do what we need them to do?
FYODOR URNOV: And how specific are they? Do they go somewhere else and turn some other gene on? And as we think about ways to deliver them to specific cells in the body or organs in the body, all of that has undergone not just an incremental change in the past 20 years. It's undergone a step change, where we can now look at experiments where you take a large animal, not a mouse, a large animal, like a non-human primate, which is, basically, science speak for, monkey.
FYODOR URNOV: And inject it with a teaspoon of an epigenome editor formulated, which is science speak for, mixed with a lipid nanoparticle, which, of course, everybody knows because lipid nanoparticles is what-- is the chemical basis for Moderna and Pfizer vaccines for SARS-CoV-2. And you inject it into the circulation of a monkey. And inside that lipid nanoparticle is an epigenome editor engineered to turn off a gene that contributes to cardiovascular disease.
FYODOR URNOV: And lo and behold, within a couple of weeks of administering this epi editor, the gene goes off. And I want to emphasize, I mean, this is an amazing achievement. And the gene stays off, I should say, for as long as it's-- the system has been looked at. I know you asked about persistence. I'll get to that in a sec. And what I think is remarkable about this result is we've always wanted to be able to tweak genes on and off, not just like all the way off and all the way on, but just-- think of it as a soundboard, staying with the music analogy.
FYODOR URNOV: A bit more bass. A touch less treble. A bit more on the drums, and certainly, less cowbell. That sort of thing. This is what epigenome editing lets you do. It's like you can flip a gene on. You can flip a gene off. But you can also adjust its output. Is that SparkNotes enough?
FYODOR URNOV: Because I'm happy to talk about clinical applications. But at a high level, epigenome editing is, you can turn a gene on or off, or multiple genes at once in human cells or organs, both in a dish and in a monkey, so far. And you will see your gene of interest go on and off based on what you've just told it to do. And you don't need to change the DNA sequence. You don't need-- you simply inscribed new molecular makeup on that gene, without changing what the DNA says.
FYODOR URNOV: And the gene politely obliges. That's the SparkNotes.
JONATHAN GRINSTEIN: Yeah. I-- epigenetics is just fascinating. But my first insight into it made my mind explode was all of our cells in our body have the same DNA. How do we have all these different cells? It's just like-- it's just-- from a developmental biologist perspective, it's just-- it's completely mind-blowing. I want to get into Tune Therapeutics.
JONATHAN GRINSTEIN: And before getting into the nitty gritty of it, I wanted to take a moment to pay homage to your mentor, Alan Wolffe. And I wanted to ask, is Tune Therapeutics the realization of a dream that started 25 years ago with you and Alan Wolffe?
FYODOR URNOV: Absolutely. So for your audience who doesn't know who Alan was, he believed in epigenetics and its molecular basis, chromatin, as being the key to real insight into how human genes work, before, pretty much, most people did. And at the time, in the 1990s, when euchromatin existed, but people thought that chromatins gets out of the way so that the real action can begin, we now know that's not the case.
FYODOR URNOV: But at the time, let's just be clear, it wasn't front and center in the mind of people working on gene control, and certainly not in the minds of people who are thinking of building therapies. And Alan was remarkably ahead of its time-- his time on two ways. First of all, he just thought about chromatin as just incredibly deep, even though we didn't truly know how deep the rabbit hole goes.
FYODOR URNOV: Second, he was young. He passed away, tragically, in an accident in 2001. I believe he was 42. And by then, as you look at his professional output in the previous 20 years, it's just staggering. He was the youngest laboratory chief appointed to a chief of laboratory position at the National Institute of Health in its entire history. He wrote the definitive monograph on chromatin and epigenetics, which literally was on the table of everyone working in the field at the time.
FYODOR URNOV: And I don't think I will ever forget, probably, the single most impactful conversation of my professional life, when Alan Wolffe shows up at my bench in his lab, in, I believe, probably somewhere around the late winter of 1999. And Alan was English. So he said, ah, Dr. Urnov, I have just had the most remarkable visit.
FYODOR URNOV: And he proceeded to describe the vision of engineering gene control using chromatin epigenomic-based principles, using a class of engineered proteins called zinc fingers. And I could see-- when Alan was excited, you could always tell. At the same time, you could always tell when Alan was not excited. And I just-- Alan, as far as I was concerned, is Yoda, except much younger.
FYODOR URNOV: So his depth, and his brilliance, and his vision was just like-- I could not believe my luck that I got to work in his lab. And he basically described this vision. And he said, there's a biotechnology company in someplace called Point Richmond, California. I said, well, that's amazing, Alan. Thank you for telling me. And then Alan left.
FYODOR URNOV: And then six weeks later, he comes back. And this, again, is a conversation I will remember on my deathbed. He calls me into his office and goes, Dr. Urnov, I have a question for you. How committed are you to a career in academia? And I remember thinking, oh, my God, he doesn't think I have it in me to be an academic scientist. What have I done?
FYODOR URNOV: And it turns out that what Alan meant was he was inviting me to join him at Sangamo. And to be very clear, I wasn't alone. A number of us went. The best professional move of my life. And when we joined, we had this extraordinary moment where the field had just begun to realize what epigenetics could really do. And we had just begun to characterize these amazing molecular machines that inscribe epigenetic code.
FYODOR URNOV: I mean, to be very clear, this was 2001. And to be able to do the first experiments where we could bring in these epigenome modifiers, this is work by my colleague Philip Gregory, to native genes, and just instruct them by rewriting their epigenome-- I just remember when Philip would show the data at Sangamo meetings, I remember thinking, where is this going to go?
FYODOR URNOV: Where is this going to go? And things were really cooking, I will admit. And then in 2002, there were some papers on fruit flies and frogs from a scientist named Dana Carroll at the University of Utah, and a paper from David Baltimore's lab, with Matt Porteus as the lead author, on targeted genetic engineering using the very same zinc fingers that we were using to change the epigenome.
FYODOR URNOV: And we all went, frogs, flies, reporter genes. And then what happened is there was a severe adverse event on a gene therapy trial for bubble boy disease in France, where the physicians and scientists treated, I think, 19 children with a gene therapy vector to treat bubble boy disease. And four of them developed cancer because the virus went into the wrong place. And there we were, 2002.
FYODOR URNOV: And what we have are zinc fingers, which can let us get to a gene of interest. We have early evidence from flies, frogs, and reporter genes in human cells that we can create a double strand break and repair a mutation. And we have this unmet need. And to be honest with you, we pivoted. That literally is what happened. It's not that we didn't think that epigenome editing was exciting.
FYODOR URNOV: It was amazing. And we were all chromatin people. But just in terms of fixing a mutation for bubble boy disease felt like real, felt like we could do this. And we went after that. Now the rest is history, right, like we got gene editing to work. We named the technology, did all the first in-human clinical trials.
FYODOR URNOV: And of course, we're about to get our first approved gene editing medicine using CRISPR Cas technology. But all along, I want to be clear, there we were in Point Richmond, California, gene editing away, there was a hardy group of believers who never forgot that epigenome editing is a thing. And Charlie Gersbach, my wonderful co-founder, was one of those believers. He had his eye on that notion that you can inscribe epigenetic marks on genes.
FYODOR URNOV: And he never took his eye off. And I'm very grateful to him. And to be clear, a bunch of other mostly academic scientists, while everybody is running around, making double strand breaks, and creating interesting genetic forms, Charlie and a bunch of other academics were like, well, yeah, this is all great, but we don't have to change the DNA in order to change what the genes do.
FYODOR URNOV: So about once a week, I see a scientific result. The very first thought in my mind was I wish Alan were alive to see this, because when Alan saw a result, he really-- he uttered this slightly demonic laugh, like [LAUGHS].. I can't really do justice to the way that sounded. But that was Alan and like, oh, yes, joie de vivre mode. I will admit that when Tune showed the data that you can administer an epi editor to silence PCSK9 in a non-human primate with a durable effect, that-- the very first thought in my mind was, I wish Alan were alive to see this, because I know exactly how he would have reacted.
FYODOR URNOV: I know exactly how he would have reacted. It's bitter-- it's bittersweet. I won't sugarcoat it for you. It's bittersweet.
JONATHAN GRINSTEIN: Yeah, no, amazing story. And I mean, and then this takes us to the founding of Tune, which, I believe, was around three years ago. And--
FYODOR URNOV: Yeah.
JONATHAN GRINSTEIN: Can you tell me a bit about Tune Therapeutics? And what sets it apart from other epigenome editing companies?
FYODOR URNOV: The reason I'm silent is because I will admit that I love my field, targeted genetic and epigenetic engineering. I think we have just a tremendous history of being a large rising tide that lifts all boats. And it's a little bit hard for me to say, company number 1 is better than company number 2, because frankly, the people, for example, who started another epigenome editing company, are some of my best professional friends.
FYODOR URNOV: So I don't think-- I think what-- rather than framing it in the context of what sets Tune apart, I'd love to speak with you about what makes Tune strong.
JONATHAN GRINSTEIN: Yeah.
FYODOR URNOV: Because I think as we've learned from a 30-year history of gene therapy, the more for profit entities push technologies forward, the better we will get to learnings from clinical trials and pre-clinical development that gets us all to better platforms that become-- So I think that what makes Tune strong are three things. I spent 16 years in industry. And I learned, basically, only one lesson, watching both the company I worked at, and watching my sector.
FYODOR URNOV: The only thing that matters with respect to ultimate success for a therapeutic are people. You can have a lot of money. You can have amazing technology. You can have tremendous unmet need. And at the end of the day, if you don't have the right people in the organization, it's going to fail. I think that the tunesmiths, the melody makers, you can stay with your analogies, are some of the most impressive constellation of cross-functional expertise that I have ever seen.
FYODOR URNOV: We have people who are deeply think and understand how to engineer proteins, both in terms of routing them to specific positions in the DNA, potently and specifically, and in terms of what to fuse to them in order to create specific epi states. We have people with just extraordinary skill in understanding how to read out at the cell biological level. Did we get the readout that's necessary? But also, all we've done so far is we've stayed in the same lab.
FYODOR URNOV: We've built a protein that does something to a gene in a cell, that doesn't a therapeutic make. I am just so impressed with the vigor and vision with which Tune leadership has been able to weave together a vertically integrated organization, where pretty much, at every station in the end to end journey of conceptualizing a target and then a disease therapeutic, and you write a target product profile, which is basically like, what are we treating?
FYODOR URNOV: Using what? What is it going to do? What's the biological activity? What's the minimum approvable endpoint? What's the biggest-- what's the optimal problem? From when you conceptualize a target product profile for a disease indication to when you flesh out the paths of attack of how you're going to deploy your platform, what you're going to need, what does the preclinical package look like, to actually doing all the relevant manufacturing farm talks.
FYODOR URNOV: And then ultimately, taking it through regulatory and having the clinical perspective. I think the cross-functional team that Tune has been able to build out of absolutely spectacular people is what makes it strong. So that's component number 1. Component number 2. Frankly, what these people have built. I'm no stranger to impressive science, abandoning false modesty.
FYODOR URNOV: I've worked in an organization or two that knows what they're doing. The Tune data are amazing. I remember texting Charlie at some point when a result came out. And I said, look-- when we're gathered, we actually first met for a serious conversation about building Tune in DC because we were all at a meeting for some reason.
FYODOR URNOV: It was rainy, so we were all glad to sit-in a conference room, away from the November in DC. It was not where you want to sit outside. And we sketched things out. And I texted Charlie and I said, well, this sure has taken our dreams to reality and then some, or something like that. So I think the technology and the data that have come out of Tune, I mean, as an academic founder, you feel parental.
FYODOR URNOV: You teach your baby something. And then you send them to college. And then you hold your breath and hope they write. But to have the report card come back and shine so brightly, that's strength number 2. And I think strength number 3, and I'm going to be fairly unequivocal, if I may, is the following. We have cured every mouse on Earth of every disease known to humankind.
FYODOR URNOV: The only way how to learn how to treat disease is to treat people with the disease. No amount of preclinical efficacy and safety data can teach you the key things you need to know in terms of how to actually build a medicine for that disease. So I think Tune's tremendous strength is the clarity, vigor, and vision that Tune leadership has managed to build and infuse the entire company with, with respect to a robust and healthy focus of getting Tune epi editors into the clinic.
FYODOR URNOV: And I really want to say to you, again, I'm not going to name names, but I've been in this sector for 22 years, I have seen biotechnology companies, perhaps, too enamored of their preclinical experimentation. And I think that was a mistake. You have to get-- you have to get to human beings. And I really salute Tune leadership for being, I mean, seasoned professionals.
FYODOR URNOV: These are people who have scars in a healthy way of what can go wrong in the clinic. These are seasoned professionals. And so the way that they have been--