Podcasts about beam therapeutics

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Two companies, Beam Therapeutics and Verve Therapeutics, have developed lead candidates using a safer alternative to conventional CRISPR called base editing. Clinical results have been promising. FDA insiders are calling on FDA Commissioner Marty Makary to fight against agency politicization. The Trump administration, including HHS Secretary Robert F. Kennedy Jr., is accused of distorting and denying scientific truths and potentially censoring information.FDA action alerts include expansion bids for drugs by GSK and Merck. A new AI-powered solution called Generative AIPTP helps life sciences firms streamline clinical workflows. The FDA is rehiring travel staff as lapses begin to show.RFK Jr. is driving a wedge into vaccine conversations. WHO may add obesity drugs for adults to the essential medicines list. Various companies like Merck, GSK, and Roche present key data at AACR 2025.HHS will require placebo-controlled trials for all new vaccines in a radical departure from past practices. Tariffs dominate Q1 earnings, AACR excites the cancer space, CEO pay gaps are discussed, and more news and events are highlighted.

Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Bristol Myers Squibb (BMS) has acquired 2seventy, the partner of Abecma, for $286 million, ending their cost-sharing agreement. Abecma generated $406 million in 2024, with BMS paying $43 million to 2seventy as part of their profit-sharing agreement.Beam Therapeutics has achieved genetic correction in AATD, while Viking secured a 1 billion supply of an obesity pill candidate. Novavax, Roche, and other companies are also making significant moves in the industry.The editorial reflects on the five years of COVID-19 and its ongoing impacts on the life sciences industry. Stay tuned for more updates on these developments and more in the world of Pharma and Biotech.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Beam Therapeutics reported a patient death in a gene editing trial for sickle cell disease, overshadowing otherwise positive data. Beam-101 was found to be competitive with approved treatments, highlighting the need for less-toxic preconditioning treatments. Sana Biotechnology is planning workforce cuts to reprioritize focus on its type 1 diabetes program and extend its cash runway. Astrazeneca has received promising early data for candidates in its obesity pipeline. Vertex Pharmaceuticals exceeded its Q3 forecast and raised full-year revenue guidance. Sana Biotechnology is gearing up for potential approvals for cystic fibrosis and non-opioid therapy. The FDA delayed a decision on Merus' bispecific antibody and lawsuits were filed by the family of Henrietta Lacks seeking a share of profits from HeLa cells.The impact of the presidential election on biopharma is being closely monitored.

David Liu, professor of chemistry at Harvard University and co-founder of multiple biotech companies, including Beam Therapeutics and Prime Medicine.

David Liu is an gifted molecular biologist and chemist who has pioneered major refinements in how we are and will be doing genome editing in the future, validating the methods in multiple experimental models, and establishing multiple companies to accelerate their progress.The interview that follows here highlights why those refinements beyond the CRISPR Cas9 nuclease (used for sickle cell disease) are vital, how we can achieve better delivery of editing packages into cells, ethical dilemmas, and a future of somatic (body) cell genome editing that is in some ways is up to our imagination, because of its breadth, over the many years ahead. Recorded 29 November 2023 (knowing the FDA approval for sickle cell disease was imminent)Annotated with figures, external links to promote understanding, highlights in bold or italics, along with audio links (underlined)Eric Topol (00:11):Hello, this is Eric Topol with Ground Truths and I'm so thrilled to have David Liu with me today from the Broad Institute, Harvard, and an HHMI Investigator. David was here visiting at Scripps Research in the spring, gave an incredible talk which I'll put a link to. We're not going to try to go over all that stuff today, but what a time to be able to get to talk with you about what's happening, David. So welcome.David Liu (00:36):Thank you, and I'm honored to be here.Eric Topol (00:39):Well, the recent UK approval (November 16, 2023) of the first genome editing after all the years that you put into this, along with many other colleagues around the world, is pretty extraordinary. Maybe you can just give us a sense of that threshold that's crossed with the sickle cell and beta thalassemia also imminently [FDA approval granted for sickle-cell on 8 December 2023] likely to be getting that same approval here in the U.S.David Liu (01:05):Right? I mean, it is a huge moment for the field, for science, for medicine. And just to be clear and to give credit where credit is due, I had nothing to do with the discovery or development of CRISPR Cas9 as a therapeutic, which is what this initial gene editing CRISPR drug is. But of course, the field has built on the work of many scientists with respect to CRISPR Cas9, including Emmanuel Charpentier and Jennifer Doudna and George Church and Feng Zhang and many, many others. But it is, I think surprisingly rapid milestone in a long decade's old effort to begin to take some control over our genetic features by changing DNA sequences of our choosing into sequences that we believe will offer some therapeutic benefit. So this initial drug is the CRISPR Therapeutics /Vertex drug. Now we can say it's actually a drug approved drug, which is a Crispr Cas9 nuclease programmed to cut a DNA sequence that is involved in silencing fetal hemoglobin genes. And as you know, when you cut DNA, you primarily disrupt the sequence that you cut. And so if you disrupt the DNA sequence that is required for silencing your backup fetal hemoglobin genes, then they can reawaken and serve as a way to compensate for adult hemoglobin genes like the defective sickle cell alleles that sickle cell anemia patients have. And so that's the scientific basis of this initial drug.Eric Topol (03:12):So as you aptly put— frame this—this is an outgrowth of about a decade's work and it was using a somewhat constrained, rudimentary form of editing. And your work has taken this field considerably further with base and prime editing whereby you're not just making a double strand cut, you're doing nicks, and maybe you can help us understand this next phase where you have more ways you can intervene in the genome than was possible through the original Cas9 nucleases.David Liu (03:53):Right? So gene editing is actually a several decades old field. It just didn't quite become as popular as it is now until the discovery of CRISPR nucleases, which are just much easier to reprogram than the previous programmable zinc finger or tail nucleases, for example. So the first class of gene editing agents are all nuclease enzymes, meaning enzymes that take a piece of DNA chromosome and literally cut it breaking the DNA double helix and cutting the chromosome into two pieces. So when the cell sees that double strand DNA break, it responds by trying to get the broken ends of the chromosome back together. And we think that most of the time, maybe 90% of the time that end joining is perfect, it just regenerates the starting sequence. But if it regenerates the starting sequence perfectly and the nuclease is still around, then it can just cut the rejoin sequence again.(04:56):So this cycle of cutting and rejoining and cutting and rejoining continues over and over until the rejoining makes the mistake that changes the DNA sequence at the cut site because when those mistakes accumulate to a point that the nuclease no longer recognizes the altered sequence, then it's a dead end product. That's how you end up with these disrupted genes that result from cutting a target DNA sequence with a nuclease like Crispr Cas9. So Crispr Cas9 and other nucleases are very useful for disrupting genes, but one of their biggest downsides is in the cells that are most relevant to medicine, to human therapy like the cells that are in your body right now, you can't really control the sequence of DNA that comes out of this process when you cut a DNA double helix inside of a human cell and allow this cutting and rejoining process to take place over and over again until you get these mistakes.(06:03):Those mistakes are generally mixtures of insertions and deletions that we can't control. They are usually disruptive to a gene. So that can be very useful when you're trying to disrupt the function of a gene like the genes that are involved in silencing fetal hemoglobin. But if you want to precisely fix a mutation that causes a genetic disease and convert it, for example, back into a healthy DNA sequence, that's very hard to do in a patient using DNA cutting scissors because the scissors themselves of course don't include any information that allows you to control what sequence comes out of that repair process. You can add a DNA template to this cutting process in a process called HDR or Homology Directed Repair (figure below from the Wang and Doudna 10-year Science review), and sometimes that template will end up replacing the DNA sequence around the cut site. But unfortunately, we now know that that HDR process is very inefficient in most of the types of cells that are relevant for human therapy.(07:12):And that explains why if you look at the 50 plus nuclease gene editing clinical trials that are underway or have taken place, all but one use nucleases for gene disruption rather than for gene correction. And so that's really what inspired us to develop base editing in 2016 and then prime editing in 2019. These are methods that allow you to change a DNA sequence of your choosing into a different sequence of your choosing, where you get to specify the sequence that comes out of the editing process. And that means you can, for the first time in a general way, programmable change a DNA sequence, a mutation that causes a genetic disease, for example, into a healthy sequence back into the normal, the so-called wild type sequence, for example. So base editors work by actually performing chemistry on an individual DNA base, rearranging the atoms of that base to become a different base.(08:22):So base editors can efficiently and robustly change A's into G's G's, into A's T's into C's or C's into T's. Those four changes. And those four changes for interesting biochemical reasons turn out to be four of the most common ways that our DNA mutates to cause disease. So base editors can be used and have been used in animals and now in six clinical trials to treat a wide variety of diseases, high cholesterol and sickle cell disease, and T-cell leukemia for example. And then in prime editors we developed a few years later to try to address the types of changes in our genomes that caused genetic disease that can't be fixed with a base editor, for example. You can't use a base editor to efficiently and selectively change an A into a T. You can't use a base editor to perform an insertion of missing DNA letters like the three missing letters, CTT, that's the most common cause of cystic fibrosis accounting for maybe 70% of cystic fibrosis patients.(09:42):You can't use a base editor to insert missing DNA letters like the missing TATC. That is the most common cause of Tay-Sachs disease. So we develop prime editors as a third gene editing technology to complement nucleases and base editors. And prime editors work by yet another mechanism. They don't, again, they don't cut the DNA double helix, at least they don't cause that as the required mechanism of editing. They don't perform chemistry on an individual base. Instead, prime editors take a target DNA sequence and then write a new DNA sequence onto the end of one of the DNA strands and then sort of help the cell navigate the DNA repair processes to have that newly written DNA sequence replace the original DNA sequence. And in the process it's sort of true search and replace gene editing. So you can basically take any DNA sequence of up to now hundreds of base pairs and replace it with any other sequence of your choosing of up to hundreds of base pairs. And if you integrate prime editing with other enzymes like recombinase, you can actually perform whole gene integration of five or 10,000 base pairs, for example, this way. So prime editing's hallmark is really its versatility. And even though it's the newest of the three ways that have been robustly used to edit mammalian cells and rescue animal models of genetic disease, it is arguably the most versatile by far,Eric Topol (11:24):Right? Well, in fact, if you just go back to the sickle cell story as you laid out the Cas9 nuclease, that's now going into commercial approval in the UK and the US, it's more of a blunt instrument of disruption. It's indirect. It's not getting to the actual genomic defect, whereas you can do that now with these more refined tools, these new, and I think that's a very important step forward. And that is one part of some major contributions you've made. Of course, there are many. One of the things, of course, that's been a challenge in the field is delivery whereby we'd like to get this editing done in many parts of the body. And of course it's easy, perhaps I put that in quotes, easy when you're taking blood out and you're going to edit those cells and them put it back in. But when you want to edit the liver or the heart or the brain, it gets more challenging. Now, you did touch on one recent report, and this is of course the people with severe familial hypercholesterolemia. The carriers that have LDL cholesterol several hundred and often don't respond to even everything we have on the shelf today. And there were 10 people with this condition that was reported just a few weeks ago. So that's a big step forward.David Liu (13:09):That was also a very exciting milestone. So that clinical trial was led by scientists at Verve Therapeutics and Beam Therapeutics, and it was the first clinical readout of an in vivo base editing clinical trial. There was previously at the end of 2022, the first clinical readout of an ex vivo base editing clinical trial using CAR T cells, ex vivo  base edited to treat T-cell leukemia in pediatric patients in the UK. Ffigure from that NEJM paper below). But as you point out, there are only a small fraction of the full range of diseases that we'd like to treat with gene editing and the types of cells we'd like to edit that can be edited outside of the body and then transplanted back into the body. So-called ex vivo editing. Basically, you can do this with cells of some kind of blood lineage, hematopoietic stem cells, T-cells, and really not much else in terms of editing outside the body and then putting back into the body as you point out.(14:17):No one's going to do that with the brain or the heart anytime soon. So what was very exciting about the Verve Beam clinical trial is that Verve sought to disrupt the function of PCSK9 storied, gene validated by human genetics, because there are humans that naturally have mutations in PCSK9, and they tend to have much lower incidences of heart disease because their LDL, so-called bad cholesterol, is much lower than it would otherwise be without those mutations. So Verve set out to simply disrupt PCSK9 through gene editing. They didn't care whether they used a nuclease or a base editor. So they compared side-by-side the results of disrupting PCSK9 with Cas9 nuclease versus disrupting it by installing a precise single letter base edit using an adenine base editor. And they actually concluded that the base editor gave them higher efficacy and fewer unwanted consequences.(15:28):And so they went with the base editor. So the clinical trial that just read out were patients treated in New Zealand, in which they were given a lipid nanoparticle mRNA complex of an adenine base editor programmed with a guide RNA to install a specific A to G mutation in a splice site in PCSK9 that inactivates the gene so that it can no longer make functional PCSK9 protein. And the exciting result that read out was that in patients that receive this base editor, a single intravenous injection of the base editor lipid nanoparticle complex, as you know, lipid nanoparticles very efficiently go to the liver. In most cases, PCSK9 was edited in the liver and the result was substantial reduction in LDL cholesterol levels in these patients. And the hope and the anticipation is that that one-time treatment should be durable, should be more or less permanent in these patients. And I think while the patients who are at highest risk of coronary artery disease because of their genetics that give them absurdly high LDL cholesterol levels, that makes the most sense to go after those patients first because they are at extremely high risk of heart attacks and strokes. If the treatment proves to be efficacious and safe, then I think it's tempting to speculate that a larger and larger population of people who would benefit from having lower LDL cholesterol levels, which is probably most people, that they would also be candidates for this kind of therapy.Eric Topol (17:22):Yeah, no, it's actually pretty striking how that could be achieved. And I know in the primates that were done prior to the people in New Zealand, there was a very durable effect that went on well over I think a year or even two years. So yeah, that's right. Really promising. So now that gets us to a couple of things. One of them is the potential for off-target effects. As you've gotten more and more with these tools to be so precise, is the concern that you could have off-target effects just completely, of course inadvertent, but potential for other downstream in time known unknowns, if you will. What are your thoughts about that?David Liu (18:15):Yeah, I have many thoughts on this issue. It's very important the FDA and regulatory bodies are right to be very conservative about off-target editing because we anticipate those off targets will be permanent, those off-target edits will be permanent. And so we definitely have a responsibility to minimize adding to the mutational burden that all humans have as a function of existing on this planet, eating what we eat, being bombarded by cosmic rays and sunlight and everything else. But I think it's also important to put off-target editing into some context. One context is I think virtually every substance we've ever put into a person, including just about every medicine we've ever put into a person, has off-target effects, meaning modulates the function of biological molecules other than the intended target. Of course, the stakes are higher when those are gene editing agents because those modifications can be permanent.(19:18):I think most off-target edits are very likely to have no consequence because most of our genome, if you mutate in the kinds of small ways like making an individual base pair change for a base editor are likely to have no consequence. We sort of already know this because we can measure the mutational burden that we all face as a function of living and it's measurable, it's low, but measurable. I've read some papers that estimate that of the roughly 27 trillion [should be ~37] cells in an adult person, that there are billions and possibly hundreds of billions of mutations that accumulate every day in those 27 [37] trillion cells. So our genomes are not quite the static vaults that we'd like to think that they are. And of course, we have already purposefully given life extending medicines to patients that work primarily by randomly mutating their genomes. These are chemotherapeutic agents that we give to cancer patients.(20:24):So I think that history of giving chemotherapeutic agents, even though we know those agents will mess up the genomes of these patients and potentially cause cancer far later down the road, demonstrates that there are risk benefit situations where the calculus favors treatment, even if you know you are causing mutations in the genome, if the condition that the patient faces and their prognosis is sufficiently grave. All that said, as I mentioned, we don't want to add to the mutational burden of these patients in any clinically relevant way. So I think it is appropriate that the early gene editing clinical candidates that are in trials or approved now are undergoing lots and lots of scrutiny. Of course, doing an off-target analysis in an animal is of limited value because the animal's genome is quite different than the human genome. So the off targets won't align, but doing off-target analysis in human cells and then following up these patients for a long time to confirm hopefully that there isn't clinical evidence of quality of life or lifespan deterioration caused by off-target editing, that's all very, very important.(21:55):I also think that people may not fully appreciate that on target editing consequences also need to be examined and arguably examined with even more urgency than off-target edits. Because when you are cutting a chromosome at a target site with a nucleus, for example, you generate a complex mixture of different products of different DNA sequences that come out, and the more sequences you sequence, the more different products you realize are generated. And I don't think it's become routine to try to force the companies, the clinical groups that are running these trials to characterize the top 1000 on target products for their biological consequence. That would be sort of impractical to do and would probably slow down greatly the benefit of these early nuclease clinical trials for patients. But those are actually the products that are generated with much higher frequency typically than the off-target edits. And that's part of why I think it makes more sense from a clinical safety perspective to use more precise gene editing methods like base editing and prime editing where we know the products that are generated are mostly the products that we want are not uncontrolled mixtures of different deletion and insertion products.(23:27):So I think paying special attention to the on-target products, which are generated typically 70 to 100% of the time as opposed to the off targets which may be generated at a 0.1 to 1% level and usually not that many at that level once it reaches a clinical candidate. I think that's all important to do.Eric Topol (23:51):You've made a lot of great points there and thanks for putting that in perspective. Well, let's go on to the delivery issue. You mentioned nanoparticles, viral vectors, and then you've come up with small virus-like neutered viruses if you will. I think a company Nvelop that you've created to push on that potential. What are your thoughts about where we stand since you've become a force for coming up with much better editing, how about much better and more diverse delivery throughout the body? What are your thoughts about that?David Liu (24:37):Yeah, great. Great question. I think one of the legacies of gene editing is and will be that it inspired many more scientists to work hard on macromolecular delivery technologies. All of these gene editing agents are macromolecules, meaning they're proteins and or nucleic acids. None of them are small molecules that you can just pop a pill and swallow. So they all require special technologies to transfer the gene editing agent from outside of the cell into the cell. And the fact that taking control of our genetic features has become such a popular aspiration of medicine means that there's a lot of scientists as measured, most importantly by the young scientists, by the graduate students and the postdocs and the young professors of which I'm no longer one sadly, who have decided that they're going to devote a big part of their program to delivery. So you summarized many of the clinically relevant, clinically validated delivery technologies already, somewhat sadly, because if there were a hundred of these technologies, you probably wouldn't need to ask this question. But we have lipid nanoparticles that are particularly good at delivering messenger RNA, that was used to deliver the covid vaccine into billions of people. Now also used to deliver, for example, the adenine base editor mRNA into the livers of those hypercholesterolemia patients in the Verve/Beam clinical trial.(26:20):So those lipid nanoparticles are very well matched for gene editing delivery as long as it's liver. And they also are particularly well matched because their effect is transient. They cause a burst of gene editing agents to be produced in the liver and then they go away. The gene editing agents can't persist, they can't integrate into the genome despite what some conspiracy theorists might worry about. Not that you've had any encounter with any of those people. I'm sure that's actually what you want for a gene editing agent. You ideally want a delivery method that exposes the cell only for the shortest amount of time needed to make the on-target edit at the desired level. And then you want the gene editing agent to disappear and never come back because it shouldn't need to. DNA edits to our genome for durable cells should be permanent. So that's one method.(27:25):And then there are a variety of other methods that researchers have used to deliver to other cells, but they each carry some trade-offs. So if you're trying to edit hematopoietic stem cells, you can take them out of the body. Once they're out of the body, you have many more methods you can use to deliver efficiently into them. You can electroporated messenger, RNA or even ribonuclear proteins. You can treat with lipids or viruses, you can edit and then put them back into the body. But as you already mentioned, that's sort of a unique feature of blood cells that isn't applicable to the heart or the brain, for example, or the eyes. So then that brings us to viral vectors. There are a variety of clinically validated viral methods for delivery. AAV— adeno associated virus— is probably the most diverse, most relevant, and one of the best tolerated viral delivery methods. The beauty of AAV is that it can deliver to a variety of tissues. AAV can deliver into spinal cord neurons, for example, into retinal cells, into the heart, into the liver, into a few other tissues as well.(28:48):And that diversity of being able to choose AAV capsids that are known to get into the types of tissues that you're trying to target is a great strength of that approach. One of the downsides of AAV for gene editing agents is that their delivery tends to be fairly durable. You can engineer AAVs into next generation capsids that sort of get rid of themselves or the gene editing agents get rid of themselves. But classic AAV tends to stay around in patients for a long time, at least months, for example, and possibly years. And we also don't yet have a good way, clinically validated way of re-dosing AAV. And once you administer high doses of AAV in a patient that tends to provoke high-titer, neutralizing antibodies against those AAVs making it difficult to then come back six months or a year later and dose again with an AAV.(29:57):So researchers are on the bright side, have become very good at engineering and evolving in the laboratory next generation AAVs that can go to greater diversity issues that can be more potent. Potency is important because if you can back off the dose, maybe you can get around some of these immunogenicity issues. And I think we will see a renaissance with AAV that will further broaden its clinical scope. Even though I appreciate that the decisions by a couple large pharma companies to sort of pull out of using AAV for gene therapy seemed to cause people to, I think prematurely conclude that AAV has fallen out of favor. I think for gene therapy, it's quite different than gene editing. Gene therapy, meaning you are delivering a healthy copy of the gene, and you need to keep that healthy copy of the gene in the patient for the rest of the patient's life.(30:59):That's quite different than gene editing where you just need the edit to take place over days to weeks, and then you want the editing agent to actually go away and you never want to come back. I think AAV will used to deliver gene editing agents will avoid some of the clinical challenges like how do we redose? Because you shouldn't need to redose if the gene editing clinical trial proceeds as you hope. And then you mentioned these virus-like particles. So we became interested in virus-like particles as other labs have because they offer some of the best strengths of non-viral and viral approaches like non-viral approaches such as LMPs. They deliver the transient form of a gene editing agent. In fact, they can deliver the fully assembled protein RNA complex of a base editor or a prime editor or a CRISPR nuclease. So in its final form, and that means the exposure of the cell to the editing agent is minimized.(32:15):You can treat with these virus-like particles, deliver the protein form of these gene editing agents, allow the on-target site to get edited. And then since the half-life of these proteins tends to be very small, roughly 24 hours for example, by a week later, there should be very little of the material left in the animal or prospectively in the patient virus-like particles, as you call them, neutered viruses, they lack viral DNA or RNA. They don't have the ability to integrate a virus's genome into the human genome, which can cause some undesired consequences. They don't randomly introduce DNA into our genomes, therefore, and they disappear more transiently than viruses like AAV or adenoviruses or other kinds of lentiviruses that have been used in the clinic. So these virus-like particles or VLP offer really some of the best strengths on paper at least of both viral and non-viral delivery.(33:30):Their limitation thus far has been that there really haven't been examples of potent in vivo delivery of cargoes like gene editing agents using virus-like particles. And so we recently set out to figure out why, and we identified several bottlenecks, molecular bottlenecks that seemed to be standing in the way of virus-like particles, doing a much more efficient job at delivering inside of an animal. (Figure from that paper below.) And we engineered solutions to each of these first three molecular bottlenecks, and we've identified a couple more since. And that resulted in what we call VLPs engineered virus-like particles. And as you pointed out, Keith Joung and myself, co-founded a company called Nvelop to try to bring these technologies and other kinds of molecular delivery technologies, next generation delivery technologies to patients.Eric Topol (34:28):Well, that gets me to the near wrapping up, and that is the almost imagination you could use about where all this can go in the future. Recently, I spoke to a mutual friend Fyodor Urnov, who talked about wouldn't it be amazing if for people with chronic pain you could just genome edit neurons their spinal cord? As you already touched on recently, Jennifer Doudna, who we both know talked about editing to prevent Alzheimer's disease. Well, that may be a little far off in time, but at least people are talking about these things that is not, we're not talking about germline editing, we're just talking about somatic cell and being able to approach conditions that have previously been either unapproachable or of limited success and potential of curing. So this field continues to evolve and you and all your colleagues are a big part of how this has evolved as quickly as it has. What are your thoughts about, are there any bounds to the potential in the longer term for genome editing? Right.David Liu (35:42):It's a great question because all of the early uses of gene editing in people are appropriately focused on people who are at dire risk of having shorter lives or very poor quality of life as it should be for a new kind of therapeutic because the risks are high until we continue to validate the clinical benefit of these gene editing treatments. And therefore we want to choose patients the highest that face the poorest prognosis where the risk benefit ratio favors treatment as strongly as possible. But your question, I think very accurately highlights that our genome and changes to it determine far more than whether you have a serious genetic disorder like Sickle Cell Disease or Progeria or Cystic Fibrosis or Familial Hypercholesterolemia or Tay-Sachs disease. And being able to not just correct mutations that are associated with devastating genetic disorders, but perhaps take control of our genomes in more sophisticated way that you pointed out two examples that I think are very thought provoking to treat chronic pain permanently to lower the risk of horrible diseases that affect so many families devastating to economies worldwide as well, like Alzheimer's disease, Parkinson's disease, the genetic risk factors that are the strongest genetic determinants of diseases like Alzheimer's disease are actually, there are several that are known already.(37:36):And an interesting possibility for the future, it isn't going to happen in the next few years, but it might happen within the next 10 or 20 years, might be to use gene editing to precisely change some of those most grievous alleles that are risk factors for Alzheimer's disease like a apoE4, to change them to the genetic forms that have normal or even reduced risk for Alzheimer's disease. That's a very tough clinical trial to run, but I'd say not any tougher than the dozens of most predominantly failed Alzheimer's clinical trials that have probably collectively accounted for hundreds of billions of dollars of investmentEric Topol (38:28):Easily.David Liu (38:31):And all of that speaks to the fact that Alzheimer's disease, for example, is enormous burden on society by every measure. So it's worth investing and major resources and taking major risks to try to create perhaps preventative treatments that just lower our risk globally. Getting there will require that these pioneering early clinical trials for gene editing are smashing successes. I'm optimistic that they will be, there will be bumps in the road because there always are bumps in the road. There will be patients who have downturns in their health and everyone will wonder whether those patients had a downturn because of a gene editing treatment they received. And ascertaining whether that's the case will be very important. But as these trials continue to progress, and as they continue hopefully on this quite positive trajectory to date, it's tempting to imagine a future where we can use precise gene editing methods. For example, you can install a variety using prime editing, a variety of alleles that naturally occur in people that reduce the risk of Alzheimer's disease or Parkinson's disease like the mutation that 0.1% of Icelandic people and almost nobody else has in amyloid precursor protein changing alanine 673 to threonine (A673T).(40:09):It is very thought provoking, and I don't think society is ready now to take that step, but I think if things continue to proceed on this promising trajectory, it's inevitable because arguably, the defining trait of our species is that we use every ounce of our talents and our gifts and our resources and our creativity to try to improve our lives and those of our children. And I don't think if we have ways of treating genetic diseases or even of reducing grievous genetic disease risk, that we will be able to sit on our hands and not take steps towards that kind of future solon as those technologies continue to be validated in the clinic as being safe and efficacious. It's, I teach a gene editing class and I walk them through a slippery slope at the end of five ethics cases, starting with progeria, where most people would say having a single C of T mutation in one gene that you, by definition didn't inherit from mom or dad.(41:17):It just happened spontaneously. That gives you an average lifespan of 14 and a half years and strongly affects other aspects of the quality of your life and your family's life that if you can change as we did in animals that T back into a C and correct the disease and rescue many of the phenotypes and extend lifespan, that that's an ethical use of gene editing. Treating genetic deafness is the second case. It's a little bit more complicated because many people in the deaf community don't view deafness as a disability. It's at least a more subjective situation than progeria. But then there are other cases like changing apoE4 to apoE3 or even apoE2 with the lower than normal risk of Alzheimer's disease, or installing that Icelandic mutation and amyloid precursor protein that substantially lowers risk of Alzheimer's disease. And then finally, you can, I always provoke a healthy debate in the class at the end by pointing out that in the 1960s, one of the long distance cross country alpine skiing records was set by a man who had a naturally occurring mutation in his EPO receptor, his erythropoietin receptor, so that his body always thought he was on EPO as if he were dosing on EPO, although that was of course before the era of EPO dosing was really possible, but it was just a naturally occurring mutation in this case, in his family.(42:48):And when I first started teaching this class, most students could accept using gene editing to treat progeria, but very few were willing to go even past that, even to genetic deafness, certainly not to changing a ApoE risk factors for Alzheimer's. Nowadays, I'd say the 50% vote point is somewhere between case three and case four, most people are actually say, yeah, especially since they have family members who've been through Alzheimer's disease. If they are a apoE4, some of them are a apoE4/apoE4 [homozygotes], why not change that to a apoE3 or even an ApoE2 or as one student challenged the class this year, if you were born with a apoE2, would you want to change it to a ApoE3 so you could be more normal? Most people would say, no, there's no way I would do that.(43:49):And for the first time this year, there were one or two students who actually even defended the idea of putting in a mutation in erythropoietin receptor to increased increase their endurance under low oxygen conditions. Of course, it's also presumably useful if you ever, God forbid, are treated with a cancer chemotherapeutic. Normally you get erythropoietin to try to restore some, treat some of the anemia that can result, and this student was making a case, well, why wouldn't we? If this is a naturally occurring mutation that's been shown to benefit certain people doing certain things. I don't think that's a general societal view. And I am a little bit skeptical we'll ever get widespread acceptance of case number five. But I think all of it is healthy stimulates a healthy discussion around the surprisingly gentle continuum between disease treatment, disease prevention, and what some would call human improvement.And it used to be that even the word human improvement was sort of an anathema. I think now at least the students in my class are starting to rethink what does that really mean? We improving ourselves a number of ways genetically and otherwise by virtue of our lifestyles, by virtue of who we choose to procreate with. So it's a really interesting debate, and I think the rapid development and now clinical progression and now approval, regulatory approval of gene editing drugs will play a central role in this discussion.Eric Topol (45:38):No question. I mean, also just to touch on the switch from a apoE4 to apoE2, you would get a potential 2-fer of lesser risk for Alzheimer's and a longer lifespan. So I mean, there's a lot of things here. The thing that got me years ago, I mean, this is many years ago at a meeting with George Church and he says, we're going to just edit 60 genes and then we can do all sorts of xeno-pig transplants and forget the problem of donors. And it's happening now.David Liu (46:11):Yeah, I mean, he used a base editor to edit hundreds of genes at once, if not thousands ofEric Topol (46:16):That's why it's just, yeah, no, it's just extraordinary. And I think people need to be aware that opportunities here, as you say, with potential bumps along the way, unquestionably, is almost limitless. So this has been a masterclass thanks to you, David, in where we are, where we're headed in genome editing at a very extraordinary time where we've really seeing things click. And I just want to also add that you're going to be here with a conference in La Jolla in January, I think, on base and prime editing. Is that right? So for those who are listeners who are into this topic, maybe they can also hear the latest, I'm sure there'll be more between now and next. Well, several weeks from now at your, it's aDavid Liu (47:12):Conference on, it's the fifth international conference on base and prime editing and associated enzymes, the somewhat baroque name. And I will at least be giving a virtual talk there. It actually overlaps with the talk I'm giving at Rockefeller that time. Ah, okay, cool. But I'm speaking at the conference either in person or virtually.Eric Topol (47:34):Yeah. Well, anytime we get to hear from you and the field, of course it's enlightening. So thanks so much for joining. Thank youDavid Liu (47:42):For having me. And thank you also for all of your, I think, really important public service in connecting appropriately the ground truths about science and vaccines and other things to people. I think that's very much appreciated by scientists like myself.Eric Topol (48:00):Oh, thanks David.Thanks for listening, reading, and subscribing to Ground Truths. To be clear, this is a hybrid format, roughly alternating between analytical newsletters/essays and podcasts with exceptional people, attempting to achieve about 2 posts per week. It's all related to cutting-edge advances in life science, medicine, and information tech (A.I.)All content is free. If you wish to become a paid subscriber know that all proceeds go to Scripps Research. Get full access to Ground Truths at erictopol.substack.com/subscribe

Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in the Pharma and Biotech world. Today, we have some interesting news to share with you. Let's get started.## Artificial Intelligence Revolutionizing Regulatory Approval ProcessesArtificial intelligence (AI) is making advancements in regulatory approval processes in the life sciences industry. It has the potential to revolutionize these processes by accelerating and improving consistency and confidence. AI can significantly speed up the regulatory approval process, which currently takes an average of 10 years for drug development. Embracing new technologies like AI is crucial for the industry to move forward.## Abzena: A Leader in Biologics and BioconjugatesAbzena, a contract development and manufacturing organization (CDMO), specializes in biologics and bioconjugates. They have a proven track record of helping clients discover lead candidates, create production cell lines, and deliver programs for investigational new drug (IND) applications. Their effectiveness at getting things done has led to 85% of clients returning to work with them again.## Sarepta Therapeutics Shares Drop After Failed StudySarepta Therapeutics' shares dropped by more than 40% after the results of the Embark study failed to meet its main goal. The study aimed to confirm the approval of its gene therapy Elevidys for treating Duchenne muscular dystrophy. However, there is still hope for gene editing technology as the FDA reviews Vertex Pharmaceuticals and CRISPR Therapeutics' case for approval of a sickle cell therapy.## Eli Lilly Acquires Beam TherapeuticsEli Lilly has acquired Beam Therapeutics in a deal worth $200 million upfront and an additional $50 million investment. This acquisition gives Lilly option rights to several gene editing programs. It is an exciting move that showcases the company's commitment to advancements in gene therapy.## Pfizer's RSV Vaccine Sees Strong SalesPfizer's respiratory syncytial virus (RSV) vaccine, Abrysvo, has seen over $300 million in sales during its first few months on the market. This success is expected to help offset declining sales of COVID-19 vaccines. It is a positive development in the fight against respiratory diseases.## Promising Results for Novartis' Kidney Disease DrugNovartis' bet on a kidney disease drug has yielded positive results in a phase 3 trial. The therapy, acquired through the acquisition of Chinook Therapeutics, met its goals in the trial. This success highlights the potential for advancements in treating kidney diseases.## Neuroscience Drug Development Shows PromiseIn the field of neuroscience drug development, there are promising new drugs for conditions such as Alzheimer's, ALS, and depression. These developments show that neuroscience is becoming a priority again in the biopharmaceutical industry. It is an exciting time for advancements in treating neurological disorders.## Philips Recalls Sleep Apnea Devices, GE Healthcare Remains ResilientPhilips has issued multiple recalls of its sleep apnea devices and ventilators due to problems with soundproofing foam. Despite these recalls, GE Healthcare's sales have remained resilient. The company has raised its earnings forecast for 2023 and plans to expand margins. They are navigating challenges such as China's anti-corruption campaign.## Amgen Takes Write-down, Sarepta Fails Phase III TrialAmgen has announced a $650 million write-down after discontinuing its prostate cancer drug candidate. Sarepta Therapeutics has also failed to meet the primary endpoint in a Phase III trial of its gene therapy for Duchenne

Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in the Pharma and Biotech world. In today's episode, we'll be discussing the importance of crystallization process development in drug development and manufacturing. Crystallization plays a crucial role in ensuring the quality and effectiveness of a final drug product. It helps control the physical form of a compound, which is directly linked to its biological activity. Drug manufacturers must demonstrate that they understand and can control the physical properties and chemical purity of a drug substance.Cambrex, a pharmaceutical services company, specializes in bridging the gap between bench-scale development and manufacturing. They provide controlled crystallization processes to help their clients achieve clinical delivery timelines. By leveraging their expertise, Cambrex assists clients in developing robust crystallization processes that meet regulatory requirements and ensure the quality of the drug product.Healthcare insurer Humana has filed a lawsuit against the US Department of Health and Human Services (HHS) over Medicare Advantage (MA) audits. Humana relies heavily on revenue from Medicare and is challenging a rule implemented earlier this year that aims to recover overpayments in the MA program. The rule allows the HHS to retroactively audit MA organizations and recoup any overpayments made.Moving on, Beam Therapeutics has begun testing its first-of-its-kind cancer drug that utilizes base editing technology. This marks progress for the company after facing trial delays, and it is the first time in the US that a patient has received a base editing treatment.In other news, Jacob Thaysen, a former executive at Agilent Technologies, has been appointed as the new CEO of Illumina, replacing Francis deSouza who stepped down in June following a proxy fight with activist investor Carl Icahn. Thaysen's experience in the life sciences industry, particularly in the diagnostics sector, makes him well-suited to lead Illumina during this critical time.Roche has recently experienced success in the field of oncology with the approval of the subcutaneous administration of its cancer drug Tecentriq in the UK. This approval gives Roche an advantage over its competitors in the race to bring subcutaneous versions of their drugs to market. Roche also had positive news with its ALK inhibitor Alecensa, which showed promising results in reducing disease recurrence in patients with early-stage non-small cell lung cancer.Lastly, the text discusses how new technology trends, such as AI, virtual reality, and robotics, have the potential to address long-standing challenges in the healthcare industry. Hospitals, payers, and other healthcare companies are using these tech trends to navigate workforce shortages, economic pressures, and consumer demands.And that's it for today's episode. Stay tuned for more updates in the Pharma and Biotech world.

James Dahlman is a biomedical engineer who works at the intersection of nanotechnology, molecular biology, and genomics. He is an associate professor at Georgia Institute of Technology and Emory School of Medicine, and the director of the Lab for Precision Therapies. His lab designs drug delivery vehicles that target RNA and other nucleic acids to cells in the body, and uses DNA barcodes to screen thousands of nanoparticles in vivo. He has applied his technology to treat diseases such as heart disease, cancer, inflammation, and pulmonary hypertension. He has also developed new tools for gene editing using CRISPR-Cas9. James has received numerous awards for his research, including the McCamish Foundation Early Career Professorship. His work has been translated via Guide Therapeutics, which was spun out of Georgia Tech and acquired by Beam Therapeutics. He is also a passionate educator and mentor who loves to share his enthusiasm for science with students and the public.

Dr. David R. Liu is the Richard Merkin Professor and Director of the Merkin Institute of Transformative Technologies in Healthcare, vice-chair of the faculty at the Broad Institute of MIT and Harvard, the Thomas Dudley Cabot Professor of the Natural Sciences at Harvard University, and a Howard Hughes Medical Institute (HHMI) investigator. In addition, he is the founder or co-founder of several biotechnology and therapeutics companies, including Beam Therapeutics, Prime Medicine, Editas Medicine, Pairwise Plants, Exo Therapeutics, Chroma Medicine, Resonance Medicine, and Nvelop Therapeutics. David's research integrates components of biological evolution with chemistry to enable the development of new types of therapeutics and to better study biology. Through chemistry, they can change the structure of a molecule in order to change its function in anticipated ways. They also harness the power of cycles of natural selection to evolve molecules with desired tailor-made properties. Outside of science, David's hobbies include photography, making wooden vessels using a wood lathe, growing bonsai trees, and exploring electronic art and other homemade art projects. He enjoys blending creativity and intellectual pursuits to create something surprising and beautiful. He completed his undergraduate education at Harvard College, majoring in chemistry. He was awarded his PhD in organic chemistry from UC Berkeley, and he joined the faculty at Harvard University afterwards. He has been an HHMI investigator since 2005. Over the course of his career, David has received numerous awards and accolades, including being named the 2022 King Faisal Prize Laureate in Medicine and receipt of the Ronald Breslow Award for Biomimetic Chemistry, the American Chemical Society David Perlman Award, ACS Chemical Biology Award, the American Chemical Society Pure Chemistry Award, the Arthur Cope Young Scholar Award, and other prestigious awards for his research and teaching. In 2016 and 2020, he was named one of the Top 20 Translational Researchers in the world by Nature Biotechnology, and he was named one of Nature's 10 researchers in 2022. In addition, he is an elected Member of the U.S. National Academy of Sciences, the U.S. National Academy of Medicine, and the American Association for the Advancement of Science. In this interview, David shares more about his life and science.

David Liu is the Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare, vice-chair of the faculty at the Broad Institute of MIT and Harvard, the Thomas Dudley Cabot Professor of the Natural Sciences at Harvard University, and a Howard Hughes Medical Institute (HHMI) investigator. Liu's research integrates chemistry and evolution to illuminate biology and enable next-generation therapeutics. His major research interests include the engineering, evolution, and in vivo delivery of genome editing proteins such as base editors and prime editors to study and treat genetic diseases; the evolution of proteins with novel therapeutic potential using phage-assisted continuous evolution (PACE); and the discovery of bioactive synthetic small molecules and synthetic polymers using DNA-templated organic synthesis and DNA-encoded libraries. Base editing—the first general method to perform precision gene editing without double-stranded breaks, and a Science 2017 Breakthrough of the Year finalist—as well as prime editing, PACE, and DNA-templated synthesis are four examples of technologies pioneered in his laboratory. These technologies are used by thousands of labs around the world and have enabled the study and potential treatment of many genetic diseases. Four base editing clinical trials are already underway to treat leukemia, hypercholesterolemia, beta-thalassemia, and sickle-cell disease, with the first base editing clinical readout occuring last December, when it was announced that Alyssa, a 13-year-old girl in the UK, was cleared of T-cell leukemia by receiving triply base-edited CAR-T cells.Liu graduated first in his class at Harvard College in 1994. During his doctoral research at UC Berkeley, Liu initiated the first general effort to expand the genetic code in living cells. He earned his PhD in 1999 and became assistant professor of chemistry and chemical biology at Harvard University in the same year. He was promoted to associate professor in 2003 and to full professor in 2005.Liu became a Howard Hughes Medical Institute investigator in 2005 and joined the JASONs, academic science advisors to the U.S. government, in 2009. In 2016 he became a Core Institute Member and Vice-Chair of the Faculty at the Broad Institute of MIT and Harvard, and Director of the Chemical Biology and Therapeutics Science Program. Liu has been elected to the U.S. National Academy of Sciences, the U.S. National Academy of Medicine, and the American Association for the Advancement of Science. He is the 2022 King Faisal Prize Laureate in Medicine.He is the founder or co-founder of several biotechnology and therapeutics companies, including Prime Medicine, Beam Therapeutics, Editas Medicine, Pairwise Plants, Exo Therapeutics, Chroma Medicine, Resonance Medicine, and Nvelop Therapeutics.Alix Ventures, by way of BIOS Community, is providing this content for general information purposes only. Reference to any specific product or entity does not constitute an endorsement nor recommendation by Alix Ventures, BIOS Community, or its affiliates. The views & opinions expressed by guests are their own & their appearance on the program does not imply an endorsement of them nor any entity they represent. Views & opinions expressed by Alix Ventures employees are those of the employees & do not necessarily reflect the view of Alix Ventures, BIOS Community, affiliates, nor its content sponsors.Thank you for listening!BIOS (@BIOS_Community) unites a community of Life Science innovators dedicated to driving patient impact. Alix Ventures (@AlixVentures) is a San Francisco based venture capital firm supporting early stage Life Science startups engineering biology to create radical advances in human health.Music: Danger Storm by Kevin MacLeod (link & license)

Please note: as of 6/30/22, ARK's clients own greater than 1% of the shares outstanding of Beam Therapeutics Inc. On today's episode, ARK analyst Ali Urman hosts the inventors of the adenine base editor (ABE) and the cytosine base editor (CBE) Nicole Gaudelli and Alexis Komor, respectively. Nicole is the Senior Director and Head of Gene Editing Platform Technologies at Beam Therapeutics, and Alexis is an Assistant Professor of Chemistry and Biochemistry DNA damage and repair and Genome editing at the University of California, San Diego. Alexis and Nicole worked together to develop a pair of CRISPR base editors, capable of engineering precise single-base substitutions. In today's conversation, Alexis and Nicole discuss their discovery of base editing, what base editing is, how they grew interested in the space and what the future applications of this discovery might be! Key Points From This Episode Alexis and Nicole on the discovery of base editing What exactly base editing is How Alexis and Nicole grew interested in base editing Alexis' interest in directed evolution How CRISPR and antibiotics integrate What itwas like working with Dr. David Liu The potential disease curing applications of base editing Why Alexis decided to go into academia rather than corporate Why Nicole decided to go into industry instead of academia

Bob Gantzer, Director of Lab Automation at Beam Therapeutics joins us to talk about his trials and tribulations across his lab automation journey. Here are some of the many golden threads of wisdom he speaks to: How he became a lab automation guru by being a “flunky scientist” Taking the hard lessons of automating in a large company and raising it to a fledgling biotech company Why you must prioritize automation in your R&D Lab automation is not a technical problem, it's a people problem, and you have to sell the dream to scientists who aren't trained with highly integrated robotics. There's a ton of helpful things Bob said about lab automation and how he learned to be successful at implementing it. Listen to the podcast to follow the conversation. If you have any questions about this podcast - hello@synthace.com is only an email away!

Let's understand the business from a company that wants to provide life-long cures to patients suffering from serious diseases.(00:00) Intro (00:13) Business Description(03:32) Industry Landscape(06:11) Annual Financial PerformanceIndustry: Biotechnology

Hitha Palepu:  Hitha Palepu is a consummate multi-hyphenate. She is an entrepreneur, investor, author, and speaker. She is the CEO of Rhoshan Pharmaceuticals and a partner in Adama Ventures, focused on investments in women-founded and women-focused companies. She is the author of We're Speaking: The Life Lessons of Kamala Harris(Little, Brown Spark) and How To Pack: Travel Smart for Any Trip (Clarkson Potter). #5SmartReads is her Webby-honored news curation that reaches over 82,000 accounts. Her Instagram content uplifts and informs her community of over 57,000 followers. Hitha is a sought-after speaker on the topics of entrepreneurship, investing, parenting-work juggle, and on diversity and inclusion. In 2021, she has delivered the keynote address to the ILPA's W.E.L.L. Summit and been a panelist at events hosted by Beam Therapeutics, Everywomen in Tech, HelloNeighbor, and The 4th Floor. Hitha's 2022 speaking engagements include serving as emcee and moderator of three Thread Count Summits hosted for Taco Bell executives & franchisees, delivering a keynote address at WNORTH's 2022 Summit, and speaking on the closing keynote panel for the Female Founders Collective Summit. Her upcoming engagements include the WIN Summit, and Black Tech Week. Hitha is an experienced moderator for book launches and author events. Events included the book launch for the New York Times Bestseller *HRH: So Many Thoughts on Royal Style* by Elizabeth Holmes, *Meet You In The Middle* by Devon Daniels, *She's Unlikeable* by Aparna Shewakramani, and *The Modern Loss Handbook* by Rebecca Soffer. Hollie Harper is a comedy nerd from South Jersey. She is currently the creator and co-exec producer of Hella Late! with Hollie Harper on BRIC TV and a co-host of the nationally trending Twitter Storytelling Chat “BlerdDating.” Hella Late! with Hollie Harper was recently in the 2021 NYC Web Fest where she was nominated as Best Actress.Hollie was a semi-finalist in the 2019 NBC Standup Competition and has been featured on NY1, and in Black Enterprise Magazine, Thrive Global, Confessional Magazine and Black San Diego Magazine. Her popular sketch comedy show AMERICAN CANDY has played the Comic Strip, Gotham Comedy Club, BAM Café as well as the Chicago Sketch Comedy Festival. Time Out Chicago named them one of the five groups to watch. Hollie is a regular host for West Side Comedy Club in NYC and works with Gold Comedy and Stand Up Girls, two programs that empower young women by teaching them standup comedy. She was recently the talent coordinator and casting for “Blood Lassi” on Spotify, written by Pratima Mani, and moderated the panel for the Emmy Award winning, WOC editing team of Black Lady Sketch Show for The Black TV and Film Collective. She is also the Creative Consultant for the very successful Black Women in Comedy Laff Fest. Always hosted by Marina Franklin - One Hour Comedy Special: Single Black Female ( Amazon Prime, CW Network), TBS's The Last O.G, Last Week Tonight with John Oliver, Hysterical on FX, The Movie Trainwreck, Louie Season V, The Jim Gaffigan Show, Conan O'Brien, Stephen Colbert, HBO's Crashing, and The Breaks with Michelle Wolf  

In our final episode of our first season, we chatted with John Evans, CEO of Beam Therapeutics. Our conversation spans lessons in commercializing therapies across the development life cycle, programmable gene editing platforms, evaluating biopharma partnerships, future trends in gene therapy accessibility, and more.Beam Therapeutics is a leader in the nascent gene editing space, pioneering proprietary base editing to develop precision genetic medicines. In January 2022, Beam entered a $300M+ research collaboration with Pfizer. Beam Therapeutics is based in Cambridge, MA.

Dr. Agnieszka Czechowicz is driven by her passion for making an impact and changing the way that care is provided. Throughout her career she has taken science and translated it into medicines, many of which are having helping patients. Agnieszka has worked with a wide range of companies, from those that do gene editing to those that focus on hearing and balance disorders. However, her main area of research is in the field of hematopoietic stem cells. In today's episode, Agnieszka explains the importance of these cells, and the benefits of the hematopoietic stem cells transplants. Agnieszka's interest in transplant medicine began at a young age, and her passion for the field continues to grow year after year. Tune in today to hear about how Agnieska is contributing to the transformation of the medical field! “We showed that your own stem cells compete for space with the transplanted stem cells in a hematopoietic stem cell transplantation process.” — @aneeshka Key Points from this Episode An overview of Dr. Agnieszka Czechowicz's incredible career. Where Agnieszka's interest in transplant medicine originated. What keeps Agnieszka motivated, despite the challenges of being a physician scientist. The power of hematopoietic stem cells. An explanation of the two bone marrow failure syndromes that Agnieszka specializes in. Discoveries that Agnieszka made many years ago when conducting research into hematopoietic stem cell transplantation. Problems with the genotoxic conditioning that is used prior to bone marrow and hematopoietic stem cell transplants. The mission of Magenta Therapeutics, of which Agnieszka is a co-founder. Feedback on progress that Magenta Therapeutics is making. The potentially transformative power of agent CD117 ADC. How agents developed by Magenta Therapeutics can be used in gene editing and gene therapy. Agnieszka's involvement with Jasper Therapeutics, and the therapy that they are currently working on. Interventions that Agnieszka believes will cause a profound reduction in graft versus host diseases. Work that Agnieszka has done for Third Rock Ventures. Some of bluebird bio's achievements and setbacks. Agnieszka's involvement with Editas, Decibel Therapeutics, and Beam Therapeutics (and where the name Beam came from). Ex vivo versus in vivo manipulation techniques. What drives Agnieskza to do the work that she does. Agnieszka's passion for women's health.

Please note: as of 12/31/21, ARK's clients own greater than 1% of the shares outstanding of Beam Therapeutics. Base editing, and gene editing as a broader industry, are a major focus of our research at ARK, and a major piece of DNA Sequencing, one of our 5 technology platforms. To dive deeper into the world of base editing, Analyst Ali Urman sits down with industry expert, Beam Therapeutics CEO John Evans. Evans was previously a Venture Partner with ARCH Venture Partners and an early employee and member of the leadership team at Agios Pharmaceuticals. At Agios, he helped develop IDHIFA and TIBSOVO, two IDH inhibitors for the treatment of acute myeloid leukemia (AML), helped initiate and lead Agios' landmark alliance with Celgene, and co-led Agios's expansion into rare genetic diseases. On this episode, Ali and John discuss the falling costs of medicine, the convergence of 3D Printing and Base Editing, Base Editing's applications for chronic illness, the total opportunity of the gene editing space and much more! “Every base in the genome can be toggled, and, so, every base that has function, we can change that function” – @john_evans3 Key Points From This Episode: John's favorite poet, Wallace Stevens Medicine's cost declines and what that means for patients The efficiency of of Multiplex Gene Editing (MGE) The convergence between and potential of 3D Printing and Gene Editing The many colors of CRISPR Gene Editing Base editing applications for chronic illnesses The intersection between Base Editing and Prime Editing Beam Therapeutic's partnerships with Pfizer and Verve Measuring the opportunity in the Base Editing space The potential total market opportunity in the gene editing space The CRISPR patent ruling and its impact on the genomics field What John finds interesting about Twitter and why he is so active on the platform

Beam Therapeutics is pioneering the use of base editing, a new class of precision genetic medicines with a vision of providing life-long cures to patients suffering from serious diseases.

The disruptive potential of gene editing could have huge implications for health care. Suddenly, several chronic diseases -- which may have required patients to be treated for decades -- have a potential to be fundamentally cured at the genomic level. This is unlocking publicly-tradable investment opportunities. Companies are utilizing the power of CRISPR gene editing, base editing, and prime editing to directly modify patient DNA. Larger pharmaceutical companies are partnering with these smaller drug developers and are building commercial programs that could be worth billions of dollars. Genetic sequencing companies are reducing costs and unlocking broader market adoption, which is rewarding them with greater volumes and higher profits. These opportunities are what has led Kelly ETFs to launch its newest investment product, the CRISPR & Gene Editing Technology ETF (Nasdaq: XDNA). In this exclusive conversation with 7investing CEO Simon Erickson, Kelly ETFs founder Kevin Kelly describes why he brought the ETF to market and how it is less-correlated with other health care funds that are available. He describes his allocation approach and why he isn't afraid to take large stakes in smaller companies. The two also dig into several of the ETF's largest positions, including Beam Therapeutics (Nasdaq: BEAM), Intellia Therapeutics (Nasdaq: NTLA), and Illumina (Nasdaq: ILMN). Publicly-traded companies mentioned in this interview include Abbott Laboratories, Beam Therapeutics, CRISPR Therapeutics, Editas Medicine, Illumina, Intellia Therapeutics, Regeneron, and Thermo Fisher. 7investing's advisors or its guests may have positions in the companies mentioned. Welcome to 7investing. We are here to empower you to invest in your future! We publish our 7 best ideas in the stock market to our subscribers for just $49 per month or $399 per year. Start your journey toward's financial independence: https://www.7investing.com/subscribe Stop by our website to level-up your investing education: https://www.7investing.com Join the 7investing Community Forum: https://discord.gg/6YvazDf9sw Follow us: ► https://www.facebook.com/7investing ► https://twitter.com/7investing ► https://instagram.com/7investing --- Send in a voice message: https://anchor.fm/7investing/message Support this podcast: https://anchor.fm/7investing/support

There aren't many single events that bring together a Who's Who list of the leading private and public companies in biotech and synthetic biology. The JP Morgan Healthcare Conference is one of the rare exceptions. The annual event, held every January, is one of the biggest stages for companies to reveal innovative new products in development, announce acquisitions, and form landscape-shifting collaborations. Investors were left wanting more after the 2021 meeting, which was relatively subdued due to the coronavirus pandemic. The first few days of the 2022 event seemed to live up to historical expectations, with a handful of companies making splashy announcements so far. In this episode of the podcast, 7investing Lead Advisors Simon Erickson and Maxx Chatsko sit down to provide quick takeaways on some of the biggest reveals from the beginning of the 2022 JP Morgan Healthcare Conference. These include: The unveiling of a long-read DNA sequencing technology from Illumina (NASDAQ: ILMN) and an enzymatic DNA synthesis technology from Twist Bioscience (NASDAQ: TWST). Molecular testing leader Exact Sciences (NASDAQ: EXAS) used the stage to reveal that it comfortably beat full-year 2021 guidance and jump into hereditary cancer testing. Meanwhile, Beam Therapeutics (NASDAQ: BEAM) announced a research collaboration with Pfizer (NYSE: PFE) that had an unusual structure. Simon and Maxx also share their thoughts on the slow pace of merger and acquisitions (M&A) in drug development in the last two years — and why record cash balances and a constant need for innovation at the largest companies suggest that could change in 2022. Publicly-traded companies mentioned or alluded to in this podcast include Beam Therapeutics, CRISPR Therapeutics, Eli Lilly, Exact Sciences, Illumina, Intellia Therapeutics, Novo Nordisk, Pacific Biosciences, and Twist Bioscience. 7investing's advisors may own positions in the companies that are mentioned. Welcome to 7investing. We are here to empower you to invest in your future! We publish our 7 best ideas in the stock market to our subscribers for just $49 per month or $399 per year. Start your journey toward's financial independence: https://www.7investing.com/subscribe Stop by our website to level-up your investing education: https://www.7investing.com Follow us: ► https://www.facebook.com/7investing ► https://twitter.com/7investing ► https://instagram.com/7investing --- Send in a voice message: https://anchor.fm/7investing/message Support this podcast: https://anchor.fm/7investing/support

El fabricante de videojuegos Take-Two Interactive comprará Zynga en un trato de $12.7 mil millones de dólares. Pfizer Inc firmó tres acuerdos para ampliar el uso de la tecnología de ARN mensajero en la que se basó su vacuna COVID-19, incluido un pacto valorado en $1.35 mil millones de dólares con el especialista en edición de genes Beam Therapeutics. Tilray informa un aumento del 20% en los ingresos debido a una mayor demanda.

Gene therapy holds the promise to permanently cure diseases that have been considered life-long challenges. But the complexity of rewriting DNA is truly huge and lives in its own special kind of big-data world. On this episode, you'll meet David Born, a computational biologist who uses Python to help automate genetics research and helps move that work to production. Links from the show David on Twitter: @Hypostulate Beam Therapeutics: beamtx.com AWS Cloud Development Kit: aws.amazon.com/cdk Jupyter: jupyter.org $1,279-per-hour, 30,000-core cluster built on Amazon EC2 cloud: arstechnica.com Luigi data pipelines: luigi.readthedocs.io AWS Batch: aws.amazon.com/batch What is CRISPR?: wikipedia.org SUMMIT supercomputer: olcf.ornl.gov/summit Watch YouTube live stream edition: youtube.com Episode transcripts: talkpython.fm ---------- Stay in touch with us ---------- Subscribe on YouTube (for live streams): youtube.com Follow Talk Python on Twitter: @talkpython Follow Michael on Twitter: @mkennedy Sponsors Shortcut Talk Python Training AssemblyAI

John Evans, CEO of Beam Therapeutics, on base editing technology for therapeutics.

This week Harry is joined by Kevin Davies, author of the 2020 book Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing. CRISPR—an acronym for Clustered Regularly Interspaced Short Palindromic Repeats—consists of DNA sequences that evolved to help bacteria recognize and defend against viral invaders, as a kind of primitive immune system. Thanks to its ability to precisely detect and cut other DNA sequences, CRISPR has spread to labs across the world in the nine years since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking 2012 Science paper describing how the process works. The Nobel Prize committee recognized the two scientists for the achievement in 2020, one day after Davies' book came out. The book explains how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused. Today's interview covers all of that ground and more.Davies is a PhD geneticist who has spent most of his career in life sciences publishing. After his postdoc with Harvey Lodish at the Whitehead Institute, Davies worked as an assistant editor at Nature, the founding editor of Nature Genetics (Nature's first spinoff journal), editor-in-chief at Cell Press, founding editor-in-chief of the Boston-based publication Bio-IT World, and publisher of Chemical & Engineering News. In 2018 he helped to launch The CRISPR Journal, where he is the executive editor. Davies' previous books include Breakthrough (1995) about the race to understand the BRCA1 breast cancer gene, Cracking the Genome (2001) about the Human Genome Project, The $1,000 Genome (2010) about next-generation sequencing companies, and DNA (2017), an updated version of James Watson's 2004 book, co-authored with Watson and Andrew Berry.Please rate and review MoneyBall Medicine on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to the page of the MoneyBall Medicine podcast. You can find it by searching for it or selecting it from your library. 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Your review may not be immediately visible.Full TranscriptHarry Glorikian: I'm Harry Glorikian, and this is MoneyBall Medicine, the interview podcast where we meet researchers, entrepreneurs, and physicians who are using the power of data to improve patient health and make healthcare delivery more efficient. You can think of each episode as a new chapter in the never-ending audio version of my 2017 book, “MoneyBall Medicine: Thriving in the New Data-Driven Healthcare Market.” If you like the show, please do us a favor and leave a rating and review at Apple Podcasts.Harry Glorikian: We talk a lot on the show about how computation and data are changing the way we develop new medicines and the way we deliver healthcare. Some executives in the drug discovery business speak of the computing and software side of the business as the “dry lab” —to set it apart from the “wet labs” where scientists get their hands dirty working with actual cells, tissues, and reagents.But the thing is, recent progress on the wet lab side of biotech has been just as amazing as progress in areas like machine learning. And this week, my friend Kevin Davies is here to talk about the most powerful tool to come along in the last decade, namely, precise gene editing using CRISPR.Of course, CRISPR-based gene editing has been all over the news since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking Science paper in 2012 describing how the process works in the lab. That work earned them a Nobel Prize in medicine just eight years later, in 2020.But what's not as well-known is the story of how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused.Kevin put that whole fascinating story together in his 2020 book Editing Humanity. And as the executive editor of The CRISPR Journal, the former editor-in-chief of Bio-IT World, the founding editor at Nature Genetics, and the author of several other important books about genomics, Kevin is one of the best-placed people in the world to tell that story. Here's our conversation.Harry Glorikian: Kevin, welcome to the show. Kevin Davies: Great to see you again, Harry. Thanks for having me on.Harry Glorikian: Yeah, no, I mean, I seem to be saying this a lot lately, it's been such a long time since, because of this whole pandemic, nobody's really seeing anybody on a regular basis. I want to give everybody a chance to hear about, you had written this book called Editing Humanity, which is, you know, beautifully placed behind you for, for product placement here. But I want to hear, can you give everybody sort of an overview of the book and why you feel that this fairly technical laboratory tool called CRISPR is so important that you needed to write a book about it?Kevin Davies: Thank you. Yes. As you may know, from some of my previous “bestsellers” or not, I've written about big stories in genetics because that's the only thing I'm remotely qualified to write about. I trained as a human geneticist in London and came over to do actually a pair of post-docs in the Boston area before realizing my talents, whatever they might be, certainly weren't as a bench researcher. So I had to find another way to stay in science but get away from the bench and hang up the lab coats.So moving into science publishing and getting a job with Nature and then launching Nature Genetics was the route for me. And over the last 30 years, I've written four or five books that have all been about, a) something big happening in genomics, b) something really big that will have both medical and societal significance, like the mapping and discovery of the BRCA1 breast cancer gene in the mid-90s, the Human Genome Project at the turn of the century, and then the birth and the dawn of consumer genetics and personalized medicine with The $1,000 Genome. And the third ingredient I really look for if I'm trying to reach a moderately, significantly large audience is for the human elements. Who are they, the heroes and the anti heroes to propel the story? Where is the human drama? Because, you know, we all love a good juicy, gossipy piece of story and rating the good guys and the bad guys. And CRISPR, when it first really took off in 2012, 2013 as a gene editing tool a lot of scientists knew about this. I mean, these papers are being published in Science in particular, not exactly a specialized journal, but I was off doing other things and really missed the initial excitement, I'm embarrassed to say. It was only a couple of years later, working on a sequel to Jim Watson's DNA, where I was tasked with trying to find and summarize the big advances in genomic technology over the previous decade or whatever, that I thought, well, this CRISPR thing seems to be taking off and the Doudnas and the Charpentiers are, you know, winning Breakthrough Prizes and being feted by celebrities. And it's going on 60 Minutes. They're going to make a film with the Rock, Dwayne Johnson. What the heck is going on. And it took very little time after that, for me to think, you know, this is such an exciting, game-changing disruptive technology that I've got to do two things. I've gotta, a) write a book and b) launch a journal, and that's what I did. And started planning at any rate in sort of 2016 and 17. We launched the CRISPR Journal at the beginning of 2018. And the book Editing Humanity came out towards the end of 2020. So 2020, literally one day before the Nobel Prize—how about that for timing?—for Doudna and Charpentier for chemistry last year. Harry Glorikian: When I think about it, I remember working with different companies that had different types of gene editing technology you know, working with some particularly in the sort of agriculture space, cause it a little bit easier to run faster than in the human space. And you could see what was happening, but CRISPR now is still very new. But from the news and different advances that are happening, especially here in the Boston area, you know, it's having some real world impacts. If you had to point to the best or the most exciting example of CRISPR technology helping an actual patient, would you say, and I've heard you say it, Victoria Gray, I think, would be the person that comes to mind. I've even, I think in one of your last interviews, you said something about her being, you know, her name will go down in history. Can you explain the technology that is helping her and what some of the similar uses of CRISPR might be?Kevin Davies: So the first half of Editing Humanity is about the heroes of CRISPR, how we, how scientists turned it from this bizarre under-appreciated bacterial antiviral defense system and leveraged it and got to grips with it, and then figured out ways to turn it into a programmable gene editing technology. And within a year or two of that happening that the classic Doudna-Charpentier paper came out in the summer of 2012. Of course the first wave of biotech companies were launched by some of the big names, indeed most of the big names in CRISPR gene editing hierarchies. So Emmanuel Charpentier, Nobel Laureate, launched CRISPR Therapeutics, Jennifer Doudna co-founded Editas Medicine with several other luminaries. That didn't go well for, for reasons of intellectual property. So she withdrew from Editas and became a co-founder of Intellia Therapeutics as well as her own company, Caribou, which just went public, and Feng Zhang and others launched Editas Medicine. So we had this sort of three-way race, if you will, by three CRISPR empowered gene editing companies who all went public within the next two or three years and all set their sights on various different genetic Mendelian disorders with a view to trying to produce clinical success for this very powerful gene editing tool. And so, yes, Victoria Gray is the first patient, the first American patient with sickle cell anemia in a trial that is being run by CRISPR Therapeutics in close association with Vertex Pharmaceuticals. And that breakthrough paper, as I think many of your listeners will know, came out right at the end of 2020 published in the New England Journal of Medicine. Doesn't get much more prestigious than that. And in the first handful of patients that CRISPR Therapeutics have edited with a view to raising the levels of fetal hemoglobin, fetal globin, to compensate for the defective beta globin that these patients have inherited, the results were truly spectacular.And if we fast forward now to about two years after the initial administration, the initial procedures for Victoria Gray and some of her other volunteer patients, the results still look as spectacular. Earlier this year CRISPR Therapeutics put out of sort of an update where they are saying that the first 20 or 24 patients that they have dosed with sickle cell and beta thallasemia are all doing well. There've been little or no adverse events. And the idea of this being a once and done therapy appears very well founded. Now it's not a trivial therapy. This is ex-vivo gene editing as obviously rounds of chemotherapy to provide the room for the gene edited stem cells to be reimplanted into the patient. So this is not an easily scalable or affordable or ideal system, but when did we, when will we ever able to say we've pretty much got a cure for sickle cell disease? This is an absolutely spectacular moment, not just for CRISPR, but for medicine, I think, overall. And Victoria Gray, who's been brilliantly profiled in a long running series on National Public Radio, led by the science broadcaster Rob Stein, she is, you know, we, we can call her Queen Victoria, we can call it many things, but I really hope that ,it's not just my idea, that she will be one of those names like Louise Brown and other heroes of modern medicine, that we look and celebrate for decades to come.So the sickle cell results have been great, and then much more recently, also in the New England Journal, we have work led by Intellia Therapeutics, one of the other three companies that I named, where they've been also using CRISPR gene editing, but they've been looking at a rare liver disease, a form of amyloidosis where a toxic protein builds up and looking to find ways to knock out the production of that abnormal gene.And so they've been doing in vivo gene editing, really using CRISPR for the first time. It's been attempted using other gene editing platforms like zinc fingers, but this is the first time that I think we can really say and the New England Journal results prove it. In the first six patients that have been reported remarkable reductions in the level of this toxic protein far, not far better, but certainly better than any approved drugs that are currently on the market. So again, this is a very, very exciting proof of principle for in vivo gene editing, which is important, not just for patients with this rare liver disorder, but it really gives I think the whole field and the whole industry enormous confidence that CRISPR is safe and can be used for a growing list of Mendelian disorders, it's 6,000 or 7,000 diseases about which we know the root genetic cause, and we're not going to tackle all of them anytime soon, but there's a list of ones that now are within reach. And more and more companies are being launched all the time to try and get at some of these diseases.So as we stand here in the summer of 2021, it's a really exciting time. The future looks very bright, but there's so much more to be done. Harry Glorikian: No, we're just at the beginning. I mean, I remember when I first saw this, my first question was off target effects, right? How are we going to manage that? How are they going to get it to that place that they need to get it to, to have it to that cell at that time, in the right way to get it to do what it needs to do. And you know, all these sorts of technical questions, but at the same time, I remember I'm going to, trying to explain this to my friends. I'm like, “You don't understand, this can change everything.” And now a high school student, I say this to people and they look at me strangely, a high school student can order it and it shows up at your house.Kevin Davies: Yeah, well, this is why I think, and this is why one reason why CRISPR has become such an exciting story and receives the Nobel Prize eight years after the sort of launch publication or the first demonstration of it as a gene editing tool. It is so relatively easy to get to work. It's truly become a democratized or democratizing technology. You don't need a million-dollar Illumina sequencer or anything. And so labs literally all around the world can do basic CRISPR experiments. Not everyone is going to be able to launch a clinical trial. But the technology is so universally used, and that means that advances in our understanding of the mechanisms, new tools for the CRISPR toolbox new pathways, new targets, new oftware, new programs, they're all coming from all corners of the globe to help not just medicine, but many other applications of CRISPR as well.Harry Glorikian: Yeah. I always joke about like, there, there are things going on in high school biology classes now that weren't, available, when I was in college and even when we were in industry and now what used to take an entire room, you can do on a corner of a lab bench.Kevin Davies: Yeah. Yeah. As far as the industry goes we mentioned three companies. But you know, today there's probably a dozen or more CRISPR based or gene editing based biotech companies. More undoubtedly are going to be launched before the end of this year. I'm sure we'll spend a bit of time talking about CRISPR 2.0, it seems too soon to be even thinking about a new and improved version of CRISPR, but I think there's a lot of excitement around also two other Boston-based companies, Beam Therapeutics in Cambridge and Verve Therapeutics both of which are launching or commercializing base editing. So base editing is a tool developed from the lab of David Lu of the Broad Institute [of MIT and Harvard]. And the early signs, again, this technology is only five or six years old, but the early signs of this are incredibly promising. David's team, academic team, had a paper in Nature earlier this year, really reporting successful base editing treatment of sickle cell disease in an animal model, not by raising the fetal globin levels, which was sort of a more indirect method that is working very well in the clinic, but by going right at the point mutation that results in sickle cell disease and using given the chemical repertoire of base editing.Base editing is able to make specific single base changes. It can't do the full repertoire of single base changes. So there are some limitations on researchers' flexibility. So they were unable to flip the sickle cell variant back to the quote unquote wild type variants, but the change they were able to make is one that they can live with, we can live with because it's a known benign variant, a very rare variant that has been observed in other, in rare people around the world. So that's completely fine. It's the next best thing. And so that looks very promising. Beam Therapeutics, which is the company that David founded or co-founded is trying a related approach, also going right at the sickle cell mutation. And there are other companies, including one that Matthew Porteus has recently founded and has gone public called Graphite Bio.So this is an exciting time for a disease sickle cell disease that has been woefully neglected, I think you would agree, both in terms of basic research, funding, medical prioritization, and medical education. Now we have many, many shots on goal and it doesn't really, it's not a matter of one's going to win and the others are going to fall by the wayside. Just like we have many COVID vaccines. We'll hopefully have many strategies for tackling sickle cell disease, but they are going to be expensive. And I think you know the economics better than I do. But I think that is the worry, that by analogy with gene therapies that have been recently approved, it's all, it's really exciting that we can now see the first quote, unquote cures in the clinic. That's amazingly exciting. But if the price tag is going to be $1 million or $2 million when these things are finally approved, if and when, that's going to be a rather deflating moment. But given the extraordinary research resources that the CRISPRs and Intellias and Beams and Graphites are pouring into this research, obviously they've got to get some return back on their investment so that they can plow it back into the company to develop the next wave of of gene editing therapies. So you know, it's a predicament Harry Glorikian: One of these days maybe I have to have a show based on the financial parts of it. Because there's a number of different ways to look at it. But just for the benefit of the listeners, right, who may not be experts, how would you explain CRISPR is different from say traditional gene therapies. And is CRISPR going to replace older methods of, of gene therapy or, or will they both have their place? Kevin Davies: No, I think they'll both have their place. CRISPR and, and these newer gene editing tools, base editing and another one called prime editing, which has a company behind it now called Prime Medicine, are able to affect specific DNA changes in the human genome.So if you can target CRISPR, which is an enzyme that cuts DNA together with a little program, the GPS signal is provided in the form of a short RNA molecule that tells the enzyme where to go, where to go in the genome. And then you have a couple of strategies. You can either cut the DNA at the appropriate target site, because you want to inactivate that gene, or you just want to scramble the sequence because you want to completely squash the expression of that gene. Or particularly using the newer forms of gene editing, like base editing, you can make a specific, a more nuanced, specific precision edit without, with one big potential advantage in the safety profile, which is, you're not completely cutting the DNA, you're just making a nick and then coaxing the cell's natural repair systems to make the change that you sort of you're able to prime.So there are many diseases where this is the way you want to go, but that does not in any way invalidate the great progress that we're making in traditional gene therapy. So for example today earlier today I was recording an interview or for one of my own programs with Laurence Reid, the CEO of Decibel Therapeutics, which is looking at therapies for hearing loss both genetic and other, other types of hearing disorders.And I pushed him on this. Aren't you actually joinomg with the gene editing wave? And he was very circumspect and said, no, we're very pleased, very happy with the results that we're getting using old fashioned gene replacement therapy. These are recessive loss of function disorders. And all we need to do is get the expression of some of the gene back. So you don't necessarily need the fancy gene editing tools. If you can just use a an AAV vector and put the healthy gene back into the key cells in the inner ear. So they're complimentary approaches which is great.Harry Glorikian: So, you know, in, in this podcast, I try to have a central theme when I'm talking to people. The relationships of big data, computation, advances in new drugs, and other ways to keep people healthy. So, you know, like question-wise, there's no question in my mind that the whole genomics revolution that started in the ‘90s, and I was happy to be at Applied Biosystems when we were doing that, would have been impossible in the absence of the advances in computing speed and storage in the last three decades. I think computing was the thing that held up the whole human genome, which gave us the book of life that CRISPR is now allowing us to really edit. But I wonder if you could bring us sort of up-to-date and talk about the way CRISPR and computation are intertwined. What happens when you combine precision of an editing tool like CRISPR with the power of machine learning and AI tools to find meaning and patterns in that huge genetic ball? Kevin Davies: Yeah. Well, yeah. I'm got to tread carefully here, but I think we are seeing papers from some really brilliant labs that are using some of the tools that you mentioned. AI and machine learning with a view to better understanding and characterizing some of the properties and selection criteria of some of these gene editing tools. So you mentioned earlier Harry, the need to look out for safety and minimize the concern of off-target effects. So I think by using some of these some algorithms and AI tools, researchers have made enormous strides in being able to design the programmable parts of the gene editing constructs in such a way that you increase the chances that they're going to go to the site that you want them to go to, and nnot get hung up latching onto a very similar sequence that's just randomly cropped up on the dark side of the genome, across the nucleus over there. You don't want that to happen. And I don't know that anybody would claim that they have a failsafe way to guarantee that that could never happen. But the you know, the clinical results that we've seen and all the preclinical results are showing in more and more diseases that we've got the tools and learned enough now to almost completely minimize these safety concerns. But I think everyone, I think while they're excited and they're moving as fast as they can, they're also doing this responsibly. I mean, they, they have to because no field, gene therapy or gene editing really wants to revisit the Jesse Gelsinger tragedy in 1999, when a teenage volunteer died in volunteering for a gene therapy trial at Penn of, with somebody with a rare liver disease. And of course that, that setback set back the, entire field of gene therapy for a decade. And it's really remarkable that you know, many of the sort of pioneers in the field refuse to throw in the towel, they realized that they had to kind of go back to the drawing board, look at the vectors again, and throw it out. Not completely but most, a lot of the work with adenoviruses has now gone by the wayside. AAV is the new virus that we hear about. It's got a much better safety profile. It's got a smaller cargo hold, so that's one drawback, but there are ways around that. And the, the explosion of gene therapy trials that we're seeing now largely on the back of AAV and now increasingly with, with non-viral delivery systems as well is, is very, very gratifying. And it's really delivery. I think that is now the pain point. Digressing from your question a little bit, but delivery, I think is now the big challenge. It's one thing to contemplate a gene therapy for the eye for rare hereditary form of blindness or the ear. Indeed those are very attractive sites and targets for some of these early trials because of the quantities that you need to produce. And the localization, the, the physical localization, those are good things. Those help you hit the target that you want to. But if you're contemplating trying something for Duchenne muscular dystrophy or spinal muscular atrophy, or some of the diseases of the brain, then you're going to need much higher quantities particularly for muscular disorders where, you run into now other challenges, including, production and manufacturing, challenges, and potentially safeguarding and making sure that there isn't an immune response as well. That's another, another issue that is always percolating in the background.But given where we were a few years ago and the clinical progress that we've talked about earlier on in the show it, I think you can safely assume that we've collectively made enormous progress in, in negating most, if not all of these potential safety issues.Harry Glorikian: No, you know, it's funny, I know that people will say like, you know, there was a problem in this and that. And I look at like, we're going into uncharted territories and it has to be expected that you just…you've got people that knew what they were doing. All of these people are new at what they are doing. And so you have to expect that along the way everything's not going to go perfectly. But I don't look at it as a negative. I look at it as, they're the new graduating class that's going to go on and understand what they did right. Or wrong, and then be able to modify it and make an improvement. And, you know, that's what we do in science. Kevin Davies: Well, and forget gene editing—in any area of drug development and, and pharmaceutical delivery, things don't always go according to plan. I'm sure many guests on Moneyball Medicine who have had to deal with clinical trial failures and withdrawing drugs that they had all kinds of high hopes for because we didn't understand the biology or there was some other reaction within, we didn't understand the dosing. You can't just extrapolate from an animal model to humans and on and on and on. And so gene editing, I don't think, necessarily, should be held to any higher standard. I think the CRISPR field has already in terms of the sort of market performance, some of the companies that we've mentioned, oh my God, it's been a real roller coaster surprisingly, because every time there's been a paper published in a prominent journal that says, oh my God, there's, there's a deletion pattern that we're seeing that we didn't anticipate, or we're seeing some immune responses or we're seeing unusual off target effects, or we're seeing P53 activation and you know, those are at least four off the top of my head. I'm sure there've been others. And all had big transient impact on the financial health of these companies. But I think that was to be expected. And the companies knew that this was just an overreaction. They've worked and demonstrated through peer review publications and preclinical and other reports that these challenges have been identified, when known about, pretty much completely have been overcome or are in the process of being overcome.So, you know, and we're still seeing in just traditional gene therapy technologies that have been around for 15, 20 years. We're still seeing reports of adverse events on some of those trials. So for gene editing to have come as far as it's common, to be able to look at these two big New England Journal success stories in sickle cell and ATTR amyloidosis, I don't think any very few, except the most ardent evangelists would have predicted we'd be where we are just a few years ago. [musical transition]Harry Glorikian: I want to pause the conversation for a minute to make a quick request. If you're a fan of MoneyBall Medicine, you know that we've published dozens of interviews with leading scientists and entrepreneurs exploring the boundaries of data-driven healthcare and research. And you can listen to all of those episodes for free at Apple Podcasts, or at my website glorikian.com, or wherever you get your podcasts.There's one small thing you can do in return, and that's to leave a rating and a review of the show on Apple Podcasts. It's one of the best ways to help other listeners find and follow the show.If you've never posted a review or a rating, it's easy. All you have to do is open the Apple Podcasts app on your smartphone, search for MoneyBall Medicine, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but it'll help us out immensely. Thank you! And now back to the show.[musical transition]Harry Glorikian:One of your previous books was called The $1,000 Genome. And when you published that back in 2010, it was still pretty much science fiction that it might be possible to sequence someone's entire genome for $1,000. But companies like Illumina blew past that barrier pretty quickly, and now people are talking about sequencing individual genome for just a few hundred dollars or less. My question is, how did computing contribute to the exponential trends here. And do you wish you'd called your book The $100 Genome?Kevin Davies: I've thought about putting out a sequel to the book, scratching out the 0's and hoping nobody would notice. Computing was yes, of course, a massive [deal] for the very first human genome. Remember the struggle to put that first assembly together. It's not just about the wet lab and pulling the DNA sequences off the machines, but then you know, the rapid growth of the data exposure and the ability to store and share and send across to collaborators and put the assemblies together has been critical, absolutely critical to the development of genomics.I remember people were expressing shock at the $1,000 genome. I called the book that because I heard Craig Venter use that phrase in public for the first time in 2002. And I had just recently published Cracking the Genome. And we were all still recoiling at the billions of dollars it took to put that first reference genome sequence together. And then here's Craig Venter, chairing a scientific conference in Boston saying what we need is the $1,000 genome. And I almost fell off my chair. “what are you? What are you must you're in, you're on Fantasy Island. This is, there's no way we're going to get, we're still doing automated Sanger sequencing. God bless Fred Sanger. But how on earth are you going to take that technology and go from billions of dollars to a couple of thousand dollars. This is insanity.” And that session we had in 2002 in Boston. He had a local, a little episode of America's Got Talent and he invited half a dozen scientists to come up and show what they had. And George Church was one of them. I think Applied Biosystems may have given some sort of talk during that session. And then a guy, a young British guy from a company we'd never heard of called Celexa showed up and showed a couple of pretty PowerPoint slides with colored beads, representing the budding DNA sequence on some sort of chip. I don't know that he showed any data. It was all very pretty and all very fanciful. Well guess what? They had the last laugh. Illumina bought that company in 2006. And as you said, Harry you know, I think when, when they first professed to have cracked the $1,000 dollar genome barrier, a few people felt they needed a pinch of salt to go along with that. But I think now, yeah, we're, we're, we're well past that. And there are definitely outfits like BGI, the Beijing Genomics Institute being one of them, that are touting new technologies that can get us down to a couple of hundred. And those were such fun times because for a while there Illumina had enormous competition from companies like 454 and Helicose and PacBio. And those were fun heady times with lots and lots of competition. And in a way, Illumina's had it a little easy, I think over the last few years, but with PacBio and Oxford Nanopore gaining maturity both, both in terms of the technology platforms and their business strategy and growth, I think Illumina' gonna start to feel a little bit more competition in the long read sequence space. And one is always hearing whispers of new companies that may potentially disrupt next-gen sequencing. And that would be exciting because then we'd have an excuse to write another book. Harry Glorikian: Well, Kevin, start writing because I actually think we're there. I think there are a number of things there and you're right, I think Illumina has not had to bring the price down as quickly because there hasn't been competition. And you know, when I think about the space is, if you could do a $60 genome, right, it starts to become a rounding error. Like what other business models and opportunities now come alive? And those are the things that excite me. All right. But so, but you have a unique position as editor of the journal of CRISPR and the former editor of a lot of prominent, you know, publications, Nature Genetics, Bio-IT World, Chemical & Engineering News. Do you think that there's adequate coverage of the biological versus the computing side of it? Because I, I have this feeling that the computing side still gets a little overlooked and underappreciated. Kevin Davies: I think you're right. I mean I think at my own company Genetic Engineering News, we still have such deep roots in the wet lab vision and version of biotechnology that it takes a conscious effort to look and say, you know, that's not where all the innovation is happening. Bio-IT World, which you mentioned is interesting because we launched that in 2002. It was launched by the publisher IDG, best-known from MacWorld and ComputerWorld and this, this whole family of high-tech publications.And we launched in 2002 was a very thick glossy print magazine. And ironically, you know, we just couldn't find the advertising to sustain that effort, at least in the way that we'd envisioned it. And in 2006 and 2007, your friend and mine Phillips Kuhl, the proprietor of Cambridge Healthtech Institute, kind of put us out of our misery and said, you know what I'll, take the franchise because IDG just didn't know what to do with it anymore. But what he really wanted was the trade show, the production. And even though at the magazine eventually we fell on our sword and eventually put it out of its misery, the trade show went from strength to strength and it'll be back in Boston very soon because he had the vision to realize there is a big need here as sort of supercomputing for life sciences.And it's not just about the raw high-performance computing, but it's about the software, the software tools and data sharing and management. And it's great to go back to that show and see the, you know, the Googles and Amazons and yeah, all the big household names. They're all looking at this because genome technology, as we've discussed earlier has been one of the big growth boom areas for, for their services and their products.Harry Glorikian: Right. I mean, well, if you look at companies like Tempus, right. When I talked to Joel Dudley over there on the show it's, they want to be the Amazon AWS piping for all things genomic analysis. Right. So instead of creating it on your own and building a, just use their platform, basically, so it's definitely a growth area. And at some point, if you have certain disease states, I don't see how you don't get you know, genomic sequencing done, how a physician even today in oncology, how anybody can truly prescribe with all the drugs that are being approved that have, you know, genomic biomarkers associated with them and not use that data.Kevin Davies: On a much lower, lo-fi scale, as I've been doing a lot of reading about sickle cell disease lately, it's clear that a lot of patients who are, of course, as you, as you know, as your listeners know, are mostly African-American because the disease arose in Africa and the carrier status gives carriers a huge health advantage in warding off malaria. So the gene continues to stay, stay high in in frequency. Many African-American patients would benefit from some generic drugs that are available in this country that provide some relief, but aren't aware of it and maybe their physicians aren't completely aware of it either. Which is very sad. And we've neglected the funding of this disease over many decades, whereas a disease like cystic fibrosis, which affects primarily white people of Northern European descent that receives far more funding per capita, per head, than than a disease like sickle cell does. But hopefully that will begin to change as we see the, the potential of some of these more advanced therapies.I think as far as your previous comment. I think one of the big challenges now is how we tackle common diseases. I think we're making so much progress in treating rare Mendelian diseases and we know thousands of them. But it's mental illness and asthma and diabetes you know, diseases that affect millions of people, which have a much more complicated genetic and in part environmental basis.And what can we learn, to your point about having a full genome sequence, what can we glean from that that will help the medical establishment diagnose and treat much more common diseases, not quite as simple as just treating a rare Mendelian version of those diseases? So that's, I think going to be an important frontier over the next decade.Harry Glorikian: Yeah. It's complicated. I think you're going to see as we get more real-world data that's organized and managed well, along with genomic data, I think you'll be able to make more sense of it. But some of these diseases are quite complicated. It's not going to be find one gene, and it's going to give you that answer.But I want to go back to, you can't really talk about CRISPR without talking about this specter of germline editing. And a big part of your book is about this firestorm of criticism and condemnation around, you know, the 2018 when the Chinese researcher He Jankui, I think I said it correctly.Yep.Kevin Davies: He Jankui is how I say it. Close. Harry Glorikian: He announced that he had created twin baby girls with edits to their genomes that were intended to make them immune to HIV, which sort of like—that already made me go, what? But the experiment was, it seems, unauthorized. It seems that, from what I remember, the edits were sloppy and the case spurred a huge global discussion about the ethics of using CRISPR to make edits that would be inherited by future generations. Now, where are we in that debate now? I mean, I know the National Academy of Sciences published a list of criteria, which said, don't do that. Kevin Davies: It was a little more nuanced than that. It wasn't don't do that. It was, there is a very small window through which we could move through if a whole raft of criteria are met. So they, they refuse to say hereditary genome editing should be banned or there should be a moratorium. But they said it should not proceed until we do many things. One was to make sure it is safe. We can't run before we can walk. And by that, I mean, we've got to first demonstrate—because shockingly, this hasn't been done yet—that genome editing can be done safely in human embryos. And in the last 18 months there've been at least three groups, arguably the three leading groups in terms of looking at genetic changes in early human embryos, Kathy Niakan in London, Shoukhrat Mitalipov in Oregon, and Dieter Egli in New York, who all at roughly the same time published and reports that said, or posted preprints at least that said, when we attempt to do CRISPR editing experiments in very early human embryos, we're seeing a mess. We're seeing a slew of off-target and even on-target undesirable edits.And I think that says to me, we don't completely understand the molecular biology of DNA repair in the early human embryo. It may be that there are other factors that are used in embryogenesis that are not used after we're born. That's speculation on my part. I may be wrong. But the point is we still have a lot to do to understand, even if we wanted to.And even if everybody said, “Here's a good case where we should pursue germline editing,” we've gotta be convinced that we can do it safely. And at the moment, I don't think anybody can say that. So that's a huge red flag.But let's assume, because I believe in the power of research, let's assume that we're going to figure out ways to do this safely, or maybe we say CRISPR isn't the right tool for human embryos, but other tools such as those that we've touched on earlier in the show base editing or prime editing, or maybe CRISPR 3.0 or whatever that is right now to be published somewhere. [Let's say ] those are more safe, more precise tools. Then we've got to figure out well, under what circumstances would we even want to go down this road? And the pushback was quite rightly that, well, we already have technologies that can safeguard against families having children with genetic diseases. It's called IVF and pre-implantation genetic diagnosis. So we can select from a pool of IVF embryos. The embryos that we can see by biopsy are safe and can therefore be transplanted back into the mother, taken to term and you know, a healthy baby will emerge.So why talk about gene editing when we have that proven technology? And I think that's a very strong case, but there are a small number of circumstances in which pre-implantation genetic diagnosis will simply not work. And those are those rare instances where a couple who want to have a biological child, but have both of them have a serious recessive genetic disease. Sickle cell would be an obvious case in point. So two sickle cell patients who by definition carry two copies of the sickle cell gene, once I have a healthy biological child preimplantation genetic diagnosis, it's not going to help them because there are no healthy embryos from whatever pool that they produce that they can select. So gene editing would be their only hope in that circumstance. Now the National Academy's report that you cited, Harry, did say for serious diseases, such as sickle cell and maybe a few others they could down the road potentially see and condone the use of germline gene editing in those rare cases.But they're going to be very rare, I think. It's not impossible that in an authorized approved setting that we will see the return of genome editing, but that's okay. Of course you can can issue no end of blue ribbon reports from all the world's experts, and that's not going to necessarily prevent some entrepreneur whose ethical values don't align with yours or mine to say, “You know what, there's big money to be made here. I'm going offshore and I'm going to launch a CRISPR clinic and you know, who's going to stop me because I'll be out of the clutches of the authorities.” And I think a lot of people are potentially worried that that scenario might happen. Although if anyone did try to do that, the scientific establishment would come down on them like a ton of bricks. And there'll be a lot of pressure brought to bear, I think, to make sure that they didn't cause any harm.Harry Glorikian: Yeah. It's funny. I would like to not call them entrepreneurs. I like entrepreneurs. I'd like to call them a rogue scientist. Kevin Davies: So as you say, there's the third section of four in Editing Humanity was all about the He Jankui debacle or saga. I had flown to Hong Kong. It's a funny story. I had a little bit of money left in my travel budget and there were two conferences, one in Hong Kong and one in China coming up in the last quarter of 2018. So I thought, well, okay, I'll go to one of them. And I just narrowed, almost a flip of a coin, I think. Okay, let's go to the Hong Kong meeting.It's a bioethics conference since I don't expect it to be wildly exciting, but there are some big speakers and this is an important field for the CRISPR Journal to monitor. So I flew there literally, you know, trying to get some sleep on the long flights from New York and then on landing, turn on the phone, wait for the new wireless signal provider to kick in. And then Twitter just explode on my feed as this very, very astute journalists at MIT Technology Review, Antonio Regalado, had really got the scoop of the century by identifying a registration on a Chinese clinical trial website that he and only he had the foresight and intelligence to sort of see. He had met He Jankui in an off the record meeting, as I described in the book, about a month earlier. A spider sense was tingling. He knew something was up and this was the final clue. He didn't know at that time that the Lulu and Nana, the CRISPR babies that you mentioned, had actually been born, but he knew that there was a pregnancy, at least one pregnancy, from some of the records that he'd seen attached to this registration document. So it was a brilliant piece of sleuthing. And what he didn't know is that the Asociated Press chief medical writer Marilynm Marchion had confidentially been alerted to the potential upcoming birth of these twins by an American PR professional who was working with He Jankui in Shenzhen. So she had been working on an embargoed big feature story that He Jankui and his associates hoped would be the definitive story that would tell the world, we did this quote unquote, “responsibly and accurately, and this is the story that you can believe.” So that story was posted within hours.And of course the famous YouTube videos that He Jankui had recorded announcing with some paternal pride that he had ushered into the world these two gene edited, children, screaming and crying into the world as beautiful babies I think was [the phrase]. And he thought that he was going to become famous and celebrated and lauded by not just the Chinese scientific community, but by the world community for having the ability and the bravery to go ahead and do this work after Chinese researchers spent the previous few years editing human embryos. And he was persuaded that he had to present his work in Hong Kong, because he'd set off such a such an extraordinary firestorm. And I think you've all seen now you're the clips of the videos of him nervously walking onto stage the muffled, the silence, or the only sound in the front row, the only sound in the big auditorium at Hong Kong university—[which] was absolutely packed to the rim, one side of the auditorium was packed with press photographers, hundreds of journalists and cameras clicking—and the shutters clattering was the only, that was the applause that he got as he walked on stage.And to his credit, he tried to answer the questions directly in the face of great skepticism from the audience. The first question, which was posed by David Liu, who had traveled all the way there, who just asked him simply, “What was the unmet medical need that you are trying to solve with this reckless experiment? There are medical steps that you can do, even if the couple that you're trying to help has HIV and you're trying to prevent this from being passed on. There are techniques that you can use sperm washing being one of them. That is a key element of the IVF process to ensure that the no HIV is transmitted.”But he was unable to answer the question in terms of I'm trying to help a family. He'd already moved out and was thinking far, far bigger. Right? And his naiveté was shown in the manuscript that he'd written up and by that point submitted to Nature, excerpts of which were leaked out sometime later.So he went back to Shenzhen and he was put under house arrest after he gave that talk in Hong Kong. And about a year later was sentenced to three years in jail. And so he's, to the best of my knowledge that's where he is. But I often get asked what about the children? As far as we know, there was a third child born about six months later, also gene-edited. We don't even know a name for that child, let alone anything about their health. So one hopes that somebody in the Chinese medical establishment is looking after these kids and monitoring them and doing appropriate tests. The editing, as you said, was very shoddily performed. He knocked out the gene in question, but he did not mimic the natural 32-base deletion in this gene CCR5 that exists in many members of the population that confers, essentially, HIV resistance. So Lulu and Nana on the third child are walking human experiments, sad to say. This should never have been done. Never should have been attempted. And so we hope that he hasn't condemned them to a life of, you know, cancer checkups and that there were no off-target effects. They'll be able to live, hopefully, with this inactivated CCR5 gene, but it's been inactivated in a way that I don't think any, no other humans have ever been recorded with such modifications. So we, we really hope and pray that no other damage has been done. Harry Glorikian: So before we end, I'd love to give you the chance to speculate on the future of medicine in light of CRISPR. Easy, fast, inexpensive genome sequencing, give us access to everybody's genetic code, if they so choose. Machine learning and other forms of AI are helping understand the code and trace interactions between our 20,000 genes. And now CRISPR gives us a way to modify it. So, you know, it feels like [we have] almost everything we need to create, you know, precise, targeted, custom cures for people with genetic conditions. What might be possible soon, in your view? What remaining problems need to be solved to get to this new area of medicine? Kevin Davies: If you know the sequence that has been mutated to give rise to a particular disease then in principle, we can devise a, some sort of gene edit to repair that sequence. It may be flipping the actual base or bases directly, or maybe as we saw with the first sickle cell trial, it's because we understand the bigger genetic pathway. We don't have to necessarily go after the gene mutation directly, but there may be other ways that we can compensate boost the level of a compensating gene.But I think we, we should be careful not to get too carried away. As excited as I am—and hopefully my excitement comes through in Editing Humanity—but for every company that we've just mentioned, you know, you can go on their website and look at their pipeline. And so Editas might have maybe 10 diseases in its cross hairs. And CRISPR [Therapeutics] might have 12 diseases. And Intellia might have 14 diseases and Graphite has got maybe a couple. And Beam Therapeutics has got maybe 10 or 12. And Prime Medicine will hasn't listed any yet, but we'll hopefully have a few announced soon. And so I just reeled off 50, 60, less than a hundred. And some of these are gonna work really, really well. And some are going to be either proven, ineffective or unviable economically because the patient pool is too small. And we've got, how many did we say, 6,000 known genetic diseases. So one of the companies that is particularly interesting, although they would admit they're in very early days yet, is Verve Therapeutics. I touched on them earlier because they're looking at to modify a gene called PCSK9 that is relevant to heart disease and could be a gene modification that many people might undergo because the PCSK9 gene may be perfectly fine and the sequence could be perfectly normal, but we know that if we re remove this gene, levels of the bad cholesterol plummet, and that's usually a good thing as far as heart management goes. So that's an interesting, very interesting study case study, I think, to monitor over the coming years, because there's a company looking at a much larger patient pool potentially than just some of these rare syndromes with unpronounceable names. So the future of CRISPR and gene editing is very bright. I think one of the lessons I took away from CRISPR in Editing Humanity is, looking at the full story, is how this technology, this game-changing gene-editing technology, developed because 25 years ago, a handful of European microbiologists got really interested in why certain microbes were thriving in a salt lake in Southeastern Spain. This is not exactly high-profile, NIH-must-fund-this research. There was a biological question that they wanted to answer. And the CRISPR repeats and the function of those repeats fell out of that pure curiosity, just science for science's sake. And so it's the value of basic investigator-driven, hypothesis-driven research that led to CRISPR being described and then the function of the repeats.And then the story shifted to a yogurt company in Europe that was able to experimentally show how having the right sequence within the CRISPR array could safeguard their cultures against viral infection. And then five years of work people in various groups started to see, were drawn to this like moths to a flame. Jennifer Doudna was intrigued by this from a tip-off from a coffee morning discussion with a Berkeley faculty colleagues, Jill Banfield, a brilliant microbiologist in her own. And then she met meets Emmanuelle Charpentier in Puerto Rico at a conference, and they struck up a friendship and collaboration over the course of an afternoon. And that, why should that have worked? Well, it did, because a year later they're publishing in Science. So it's serendipity and basic research. And if that can work for CRISPR, then I know that there's another technology beginning to emerge from somewhere that may, yet trump CRISPR.And I think the beauty of CRISPR is its universal appeal. And the fact is, it's drawn in so many people, it could be in Japan or China or South Korea or parts of Europe or Canada or the U.S. or South America. Somebody is taking the elements of CRISPR and thinking well, how can we improve it? How can we tweak it?And so this CRISPR toolbox is being expanded and modified and updated all the time. So there's a hugely exciting future for genome medicine. And you know, whether it's a new form of sequencing or a new form of synthetic biology, you know, hopefully your show is going to be filled for many years to come with cool, talented, young energetic entrepreneurs who've developed more cool gadgets to work with our genome and other genomes as well. We haven't even had time to talk about what this could do for rescuing the wooly mammoth from extinction. So fun things, but maybe, maybe another time. Harry Glorikian: Excellent. Well, great to have you on the show. Really appreciate the time. I hope everybody got a flavor for the enormous impact this technology can have. Like you said, we talked about human genome, but there's so many other genomic applications of CRISPR that we didn't even touch. Kevin Davies: Yup. Yup. So you have to read the book. Harry Glorikian: Yeah. I will look forward to the next book. So, great. Thank you so much. Kevin Davies: Thanks for having me on the show, Harry. All the best.Harry Glorikian: Take care.Harry Glorikian: That's it for this week's show. You can find past episodes of MoneyBall Medicine at my website, glorikian.com, under the tab “Podcast.” And you can follow me on Twitter at hglorikian.  Thanks for listening, and we'll be back soon with our next interview.

ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. The American Cancer Society reports that at least 42% of newly diagnosed cancers in the United States, excluding non-melanoma skin cancer, are potentially avoidable because they are attributable to lifestyle factors. Today we will discuss strategies and resources to help the oncology community focus on health promotion as a key component of cancer risk reduction as well as in survivorship care. Joining me for this discussion are Dr. Amy Comander, the director of breast oncology and cancer survivorship at the MGH Cancer Center in Waltham and at Newton-Wellesley Hospital, and Dr. Poorvi Desai, a hematologist-oncologist at Comprehensive Hematology Oncology in Tampa Bay, Florida. Both Dr. Comander and Dr. Desai are board certified in lifestyle medicine. My guests report no conflicts of interest relating to our topic today. And their full disclosures and those relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Comander and Dr. Desai, it's great to have you on the podcast today. Dr. Amy Comander: Thank you so much for the invitation. Dr. Poorvi Desai: Thank you, it's really great to be here. ASCO Daily News: Dr. Comander and Dr. Desai, you recently co-wrote an interesting editorial featured in the ASCO Daily News that raises concerns about newly diagnosed cancers in the United States that are potentially avoidable because they are attributable to lifestyle factors. You also note that as the population of cancer survivors in the U.S. continues to grow, risk factors for cancer development are becoming more prevalent. So the obesity epidemic in the United States is a huge concern. This is just one risk factor for cancer. Dr. Comander, can you tell us about this and other risk factors and why oncologists should be addressing these risk factors sooner rather than later? Dr. Amy Comander: As you clearly stated, there's increasing prevalence of obesity in this country. And this has troubling consequences in terms of cancer risk and outcomes for specific types of cancer. Interestingly, just this week, we learned data from the annual report to the nation on the status of cancer that, overall, cancer death rates in the United States are declining, especially for lung cancer and melanoma. And this is amazing. And that is due to the incredible advances in treatments that we've witnessed over these past few years. But interestingly, for prostate cancer, colorectal cancer, and female breast cancers, death rates continue to increase or these declines have slowed or even leveled off. And in terms of understanding why that may be the case, it seems that lifestyle factors, such as obesity, lack of physical activity, [and] increased alcohol use, may be risk factors for why we are seeing these results. And therefore, further research will certainly need to be done in this area, but attention to these factors is very important. ASCO Daily News: Well, Dr. Desai, I'd like to ask you about your interest in lifestyle medicine. I understand you became interested in lifestyle medicine during your fellowship training. Can you tell us about this? Dr. Poorvi Desai: Yes, I recently just graduated from my hem-onc fellowship at USF and Moffitt Cancer Center. And I was really impressed during my fellowship looking into all of the data very particularly when it comes to every single different type of cancer. But one thing I thought was lacking was just the overall picture of lifestyle factors, and especially modifiable risk factors, when it comes to pre-survivorship along with things that patients can do during active treatment and in the survivorship phase. And I think that there are structures that are starting to appear to help guide us with more evidence-based data. And so I became very interested, as I had an attending in my internal medicine residency who was a part of lifestyle medicine. And through the American College of Lifestyle Medicine, I met several people around the country who had been working with organizations such as AICR, as well as the World Health Organization, [and] American Cancer Society. And there was a very big push on these lifestyle factors to look at them in a way that is actually studied through evidence and actual guidelines that I was never really taught about throughout my fellowship. So I made it a point to kind of self-teach a lot of this. But I definitely think that there's a role moving forward in bringing this to not just fellowship education but just all of oncology care, whether it's medical oncology, surgical, radiation, but just any oncology care team. ASCO Daily News: Well, you make a really great point. Evidence-based guidelines do exist to help facilitate lifestyle modification in cancer care, but there are barriers to health promotion in cancer care. Dr. Comander, what are the major barriers? Dr. Amy Comander: That's an excellent question because we know this is an important issue. And actually, it was an issue studied recently by ASCO. Dr. Ligibel and colleagues published a paper in 2013 that was a survey of oncologists and their understanding of obesity and other lifestyle factors and how they address these issues in clinic (DOI: 10.14694/EdBook_AM.2013.33.52).  And I think we can all say that our colleagues are well aware that obesity and lifestyle factors play an important role in cancer outcome. But in terms of the practical steps of how to address these issues with our patients, how to get our patients to lose weight, how to get our patient to exercise, how to help our patient cut back on alcohol use--those are just some examples--there really are limitations. And in that paper, they really outlined some of the reasons for that. Some of it is lack of education, as Dr. Desai just noted. She sought out teachings and lifestyle medicine as part of her fellowship training. She had to go elsewhere to look for that because it really wasn't part of the standard curriculum. So a lack of education, lack of resources. I'm fortunate to work in a cancer center with excellent oncology colleagues with expertise in nutrition, exercise, et cetera. But we know, in the rest of the country, not every doctor has access to these resources. And the third reason is really lack of clinician time. Our visits are very focused. And often the priority, of course, is discussing the patient's treatment, how is--I'm a breast cancer doctor. How is my patient doing on her endocrine therapy? What kind of side effects is she experiencing? How can I ensure she's complying with her medication? So there really isn't a lot of time to address these issues in a visit. So these are all factors we need to work on. ASCO Daily News: Well, how about solutions? How tough is it to convince patients who are grappling with the physical and emotional toll of cancer treatment to prioritize their nutrition and exercise? Dr. Desai, what do you think are the next steps? What would you say to oncologists who really do need to pay more attention to this? Dr. Poorvi Desai: So I think that one of the biggest things to take out of our article is that oncologists don't need to carry the burden of doing this by themselves. I think that while it does take a lot of resources, which is a big constraint, especially financially, I do think that there is a lot of worth in building a care team that's dedicated towards this. Or if that's not possible, then seeking out community, local, or national resources and kind of bringing together any other structure that's already in place and having a good referral to those areas, so that patients do understand that it is important to continue physical activity and working on nutrition. And I definitely think that it's something that patients feel they can have some control over. I think a lot of oncologists don't feel qualified to talk about these things because they are not very well taught in our education. And so I think then a lot of patients in this realm of lifestyle feel on their own in trying to figure out what's good for them, what's not good for them. There's a lot of misinformation online and unsolicited advice that can be given to our patients. There's a lot of fear around foods and what the right type of activity is. And I think that the more evidence-based information that we have to provide to our patients, we can be more confident in making these suggestions. And again, we don't--as oncologists, we don't need to be the ones who are actually doing all the counseling, doing all of this, making sure that they have their exercise prescriptions or whatever it may be, but at least acknowledging that this should be a part of the care team and seeking out resources that the care team can then take over. So that in conjunction with active treatment or in conjunction with survivorship care, this then becomes something that patients feel they have some kind of control over. And I also think that it's important that we don't over-promise and under-deliver as well. I think that it's important to show patients that these are things that are as important as their active treatment to pay attention to, but also as oncologists start becoming more comfortable with the idea of risk reduction and having the information to back up our claims that lifestyle is of the utmost important in cancer. ASCO Daily News: Absolutely. Dr. Comander, do you have any thoughts on this? Is it more difficult to do what Dr. Desai has described in a community practice than where you are in a larger institution? Dr. Amy Comander: I think Dr. Desai answered that question beautifully. I will add that, as an oncologist, what we say makes such an impression on our patients. Often our patients are recording what we say, or they have a family member with them writing down everything we say. So if we just tell our patient, it's really important for you to exercise--and that might just mean a 10 minute walk each day or walking to the mailbox to get the mail, starting with something very basic in terms of exercise counseling--can make a big difference. And so I think just the fact that, as Dr. Desai just stated, a doctor acknowledging that exercise has a role, nutrition has a role, stress management has a role, I think just that simple act has a big impact on our patients. And it's very important. ASCO Daily News: Indeed. Well, patients and survivors often grapple with depression, anxiety, fear of recurrence, financial issues, and more. Sleep disorders and insomnia can interfere with adherence to a nutrition plan or an exercise regime. Are there helpful tools available, or what are the helpful tools available to oncology practices to help them address these issues with their patients? Dr. Amy Comander: I think that's a really important question. We know that distress screening is actually incorporated into each visit. And that's recommended through the NCCN guidelines really to assess these issues you just inquired about--coping skills, anxiety, depression, financial issues, et cetera. So certainly, it's very important to ask our patients about these issues and refer them to appropriate colleagues, whether that's a mental health provider or social worker, to help address these concerns. I will also acknowledge ASCO has a number of great resources to help guide patients to. The website Cancer.Net has many resources that help patients find perhaps something in the community that could help them address these specific concerns. Dr. Desai, I'm interested in your comments as well. Dr. Poorvi Desai: I absolutely agree with you. I think that the NCCN is doing a really great job in compiling a comprehensive set of resources in their survivorship guidelines. There is that distress assessment thermometer that we had addressed in our article. We definitely understand that these psychosocial evaluations are pretty much of utmost importance. There's a lot of anxiety and distress that comes with a cancer diagnosis. And we know that it lasts. It has an impact that's lifelong. And so definitely one of the big pillars of lifestyle medicine is stress and social connectivity. And so we definitely are an advocate for having mental health professionals as a part of the care team and looking at mental and physical well-being going hand-in-hand. And I think one of the biggest things to understand is that we have to meet our patients where they are. And so we don't want to advocate for anybody saying, OK, now you have to exercise five times a day strenuously, and you have to eat perfectly, and all of these things that can be extremely overwhelming. And so I think that there are great guidelines. And I think the NCCN Survivorship Panel has put together a good amount of resources for us to show patients how to work on mindfulness strategies and sort of systematically work them through a very difficult diagnosis in order to slowly, but surely, result in those healthy lifestyle changes. I like to tell my patients that it's a marathon, not a sprint. Any progress is good progress. You don't have to be perfect. And I think that's definitely something that we should be mindful of when we talk about changing lifestyle behaviors. ASCO Daily News: Right. Dr. Comander, do you think there is a role for increased collaboration between oncology providers and primary care providers in the context of cancer survivorship, for example? Survivors might see their oncologists every few months, every 6 months, every year, but who is monitoring the hypertension, the weight gain? Who should own that responsibility, or is it a collaboration? Dr. Amy Comander: That's a great question. And as you stated at the beginning, thankfully due to advances in treatment and screening, the number of cancer survivors in this country is increasing greatly each year. And therefore, it is very important that we have a strong collaboration with our primary care colleagues in terms of providing excellent care for our patients following completion of primary treatment. So in my practice, it definitely is a collaboration. I'm fortunate to work with so many wonderful primary care physicians [and] we work together in terms of monitoring our patients' blood pressure, risk for cardiovascular disease, risk for diabetes and other chronic diseases, and certainly when it comes to other lifestyle interventions, such as weight management, management of substance abuse, et cetera. So that collaboration is really key. And I see primary care providers already playing a huge role in survivorship care. And I think that will continue to grow in time to come. ASCO Daily News: Well, as you said, the number of cancer survivors continues to grow. It's projected to increase to 22 million in the United States by 2030. So do you think the focus on lifestyle medicine will increase in the future? Let's start with Dr. Desai. Dr. Poorvi Desai: Yeah, I think that this has to become one of the major things that we regard. I think that most oncologists are very aware that our treatments are--they have long term consequences. We had mentioned in our article that there are two major themes to look at when it comes to survivorship care. One is infection-related mortality. But the other big one, which is what we focused on, was lifestyle--cardiovascular disease, cerebrovascular disease, accelerated aging with telomere shortening and metabolic changes that happen after cancer diagnosis and the treatments that patients receive. So a lot of what we are subjecting our patients to is truly aging in nature. And we have evidence to suggest that we can work on these lifestyle modifications as the forefront way to really help them overcome the fact that we have given them radiation to their chest or cardiotoxic medications, or whatever it may be. And that when they are overweight or obese, this can then further accelerate that process of metabolic aging. I think one of the things that's really important to talk about is assessing metabolic health. And so not just looking at their BMI, but how does their BMI actually break down into metabolic patterns? How much of this is bone density or muscle weight? We put patients a lot on hormonal treatments, which can then affect their fracture risk moving forward. And I think that we are very well aware of that. And so these are the things that should really be assessed because, like we've mentioned, one of the biggest reasons for, I guess, moving forward with the number of cancer survivors that we're going to have, a lot of it--the focus needs to shift, basically, to long term chronic disease management, in which lifestyle really does play a huge role. ASCO Daily News: Absolutely. Dr. Comander, is there anything else that you'd like to share before we wrap up the podcast today? I certainly do think your article pointed out the importance of using evidence-based guidelines to strive for the best possible outcomes for survivors and patients to prevent newly diagnosed cancers. Dr. Amy Comander: Yes, I think, as summarized in our article, we did provide resources that can help our colleagues address these concerns with our patients, since, again, some of us have not been educated about these topics during our medical training. So in addition to the excellent resources provided by ASCO, I would really refer our listeners to the AICR website, American Institute for Cancer Research. In addition, the American Cancer Society is playing a role in helping provide further education about the role of nutrition and physical activity in cancer survivorship. So the American Cancer Society is a great resource, as is the American College of Sports Medicine when it comes to exercise recommendations. And on their website, they have some great graphics that really illustrate what the recommendations are for exercise and what the benefits are for cancer survivors as well. And finally, we referred to the NCCN during this podcast. And of course, their guidelines are excellent and address these lifestyle behaviors as well. So I would just highlight those resources for our listeners in case they want to get more information. ASCO Daily News: Absolutely, some great resources there. Well, thank you, Dr. Comander and Dr. Desai, very much for sharing your valuable insight with us today on the ASCO Daily News podcast. Our listeners will find a link to your article in our show notes. Thank you very much. Dr. Amy Comander: Thank you so much for the invitation. Dr. Poorvi Desai: Thank you so much. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Amy Comander: Consulting or Advisory Role: Advance Medical, Applied Genetic Technologies Corporation, Beam Therapeutics, Biogen, Inc., Blue Cross Blue Shield Association, CRICO Harvard Risk Management Foundation, Editas Medicine, GenSight Biologics, Harvard University, infiniteMD, RBC Investments, Sanofi SA, Vedere 1, WAVE Life Sciences Dr. Poorvi Desai: None disclosed.  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

The founding CEO of Beam Therapeutics, John Evans explains the new world of precision genome editing (Base Editing). Beam Therapeutics is the base editing company co-founded by David Liu, Feng Zhang and Keith JoungClose to the Edge | Ep. 5 | John Evans, CEO Beam Therapeuticshttps://www.youtube.com/watch?v=ydU-l...Welcome back, tribe members! Today I'm discussing "My Next 4X Stock - Buy Now". If you enjoy this video feel free to SUBSCRIBE! Make sure to follow me on social media for even more coverage of the stock market.The Power of a Tribe: https://www.amazon.com/dp/B096TWBDM3/...Get Surfshark VPN at  https://surfshark.deals/INVESTORS and enter promo code INVESTORS for 83% off and 3 extra months for free!  Facebook: https://www.facebook.com/BestofUSLLC/Instagram: https://www.instagram.com/bestofusinv...Twitter: https://twitter.com/BestOfUsInvestHelp Kerry and Nita win the race against Childhood Cancer and keep their daughter Shay's memory alive. Your support makes a direct impact in the fight against Pediatric Cancer at Children's of Alabama by helping advance research in finding a cure for cancer http://give.childrensal.org/bestofusWe have Up-Graded Our Discord: Kerry's Portfolio, Trades and InsightsThis is the new link: https://discord.io/bestofus. It is now organized by topics and will be easier to navigate and communicate

When Caribou Biosciences (NASDAQ: CRBU) became the seventh publicly-traded CRISPR stock in July 2021, I saw an exchange on social media. One person asked why the company sported a market valuation of $900 million when another newly-public CRISPR stock, Verve Therapeutics (NASDAQ: VERV), was valued near $2.3 billion. "Is there any reason for this other than the timing of the IPOs?", asked the individual. The thread received multiple responses confirming the seemingly large valuation difference between the two companies, with others "agreeing" or responding that they were buying Caribou Biosciences because of it. That was 100% the wrong take. I've observed similar arguments among individual investors within the gene editing space. However, it's important to acknowledge that there are significant differences between gene editing approaches and technology platforms. Caribou Biosciences and Verve Therapeutics might both be using CRISPR systems, but that's where the overlap ends. They're developing completely different tools that have almost nothing in common. Individual investors don't necessarily need to have a deep technical understanding of gene editing tools, but I would argue that there's a minimum level of information required to responsibly invest in the field. Unfortunately, the way the internet works means most investors aren't provided with the information they need. Let's fix that. In this episode of the podcast, 7investing Lead Advisors Maxx Chatsko (me) and Dan Kline introduce simple frameworks for evaluating opportunities and challenges in gene editing. These can be summarized as follows: The Emerging Approaches: There's first-generation tools (gene editing), second-generation tools (base editing), and third-generation tools (prime editing). These approaches are not limited to any specific system. For example, there are CRISPR, TALEN, ARCUS, and other tools capable of performing base editing. The Major Applications: There are knock outs, insertions, activations, precise corrections, knock ins, and other uses of gene editing tools. Each has advantages and disadvantages. The Major Administration Routes: This primarily comes down to in vivo (inside the body) and ex vivo (outside the body). Each has advantages and disadvantages. In addition to this podcast introducing the three frameworks, 7investing Lead Advisor Maxx Chatsko has written an in-depth article explaining these frameworks and how each gene editing stock fits into each -- and it's free to read! Publicly-traded companies mentioned in this podcast include Alnylam Pharmaceuticals, Beam Therapeutics, Caribou Biosciences, Cellectis, CRISPR Therapeutics, Editas Medicine, Graphite Bio, Intellia Therapeutics, Precision BioSciences, Sana Biotechnology, and Verve Therapeutics. 7investing Lead Advisors may have positions in the companies that are mentioned. This interview was originally recorded on August 2nd, 2021 and was first published on August 3rd, 2021. --- Send in a voice message: https://anchor.fm/7investing/message Support this podcast: https://anchor.fm/7investing/support

Intellia Therapeutics (NTLA) stock jumped more than 50% after the biotech, along with Regeneron Pharmaceuticals (REGN), reported positive results from its first clinical trial using a new, Nobel Prize-winning Crispr technology to treat Transthyretin Amyloidosis, a rare condition characterized by an abnormal buildup of a protein called amyloid in the body's organs and tissues. Other Crispr-related companies saw gains on Monday as well. Crispr Therapeutics has increased by 6.39 percent, while Beam Therapeutics has increased by 15.98 percent.