Biotech 2050 Podcast

Transforming Gene Therapy: Exclusive Insights from Zandy Forbes, President & CEO of MeiraGTx

Synopsis:

Zandy Forbes, Founder, President, and CEO of MeiraGTx, joins host Rahul Chaturvedi in this compelling episode. Zandy shares her inspiring journey from academia, where she developed a deep interest in molecular biology and genetics, to her significant role in biotech investing, and eventually leading a groundbreaking gene therapy company. She elaborates on Meira’s cutting-edge approach to genetic medicines, focusing on the development of innovative therapies for non-inherited diseases. Zandy discusses the unique challenges and opportunities that arise in the biotech sector, shedding light on the strategies Meira employs to navigate this complex landscape.

Biography:

Alexandria Forbes, Ph.D. is the President and CEO of MeiraGTx (NASDAQ: MGTX). MeiraGTx is a vertically integrated gene therapy company with core capabilities in viral vector design and optimization and gene therapy manufacturing, as well as a potentially transformative gene regulation technology. The company is developing innovative gene therapy products to cost effectively treat a range of serious medical disorders, with clinical programs currently in the eye, salivary gland and CNS.

Prior to founding MeiraGTx, Dr. Forbes served as Senior Vice President of Commercial Operations at Kadmon Holdings, Inc., a biopharmaceutical company, from September 2013 to April 2015.Before joining the biotech industry, she spent 10 years as a healthcare investor at Sivik Global Partners (Argus Partners) and Meadowvale Partners. At Sivik, Dr. Forbes was responsible for investments in biotechnology, specialty pharmaceuticals and diagnostics public equities and was portfolio manager of the Sivik Global Life Science Fund, a long-biased public markets fund investing in biotechnology companies globally. During her time as a biotechnology investor, Dr. Forbes covered over 300 companies and gained expertise in biotechnology business strategies and clinical drug development as well as a wide range of disease areas. Particular areas of focus included HIV, HCV, diabetes, obesity, autoimmune disorders, cancer, Alzheimer’s disease, kidney disease and liver disease.

Before entering the hedge fund industry, Dr. Forbes was an academic scientist studying the regulation of stem cell identity and different aspects of embryogeneis. She was a Human Frontiers/Howard Hughes postdoctoral fellow at the Skirball Institute of Biomolecular Medicine at NYU Langone Medical Center, where her research focused on cytoplasmic determinants and cell signaling pathways involved in the migration, establishment and maintenance of germ line stem cells in Drosophila melanogaster. Prior to this, Dr. Forbes was a research fellow at Duke University and at the Carnegie Institute at Johns Hopkins University where she studied the role of the hedgehog gene and its signaling pathway in the Drosophila embryo and adult. Dr. Forbes received her Ph.D. in Molecular Genetics from Oxford University, UK and attained a double first degree in Natural Sciences from Cambridge University, UK.

Dr. Forbes serves on the Board of Directors of MeiraGTx, and as a Trustee and Director of the Selfridges Group Foundation, the European arm of the Weston Brain Institute, a charity supporting research into neurodegenerative diseases with the aim of speeding the time to the development of disease modifying treatments for these currently intractable diseases, particularly Alzheimer’s.

Duration:: 50m
Broadcast on:: 24 Jul 2024
Audio Format:: mp3

(upbeat music) - Hello and welcome to the biotech 2050 podcast. Biotech 2050 is a think tank chronicling the disruptions changing the biotech sector over the next several decades. Check out our website at biotech 2050.com or on your favorite podcast listening platform. I'm Rahul Chuttervedi, co-founder of this podcast and today's host, I'm also the founder and CEO of Chlora. Chlora is a platform that enables biotechs to build on-demand fractional teams. You can check us out at Chlora.com. I'm very excited to welcome Zandy Forbes, founder, president and CEO at Mira Therapeutics. Wonderful to finally have you on today, Zandy. - Thank you so much for inviting me. I'm happy to be here. - Great, so Zandy to kick us off and to set the context for the rest of the conversation, would love if you could talk to us about your initial interest in biotech and then the arc of your career from there on out. - Yeah, thank you. So I was educated in the UK, where one focuses early on either science or art. So my university education was at Cambridge and I was lucky enough there to do the one science subject they have, which is natural sciences. And at that point, I really gained an interest in the molecular biology side of life, how cells work. After leaving Cambridge, I went and did a PhD, Oxford, and that introduced me to really the world of genetics, real genetics, because I chose to work on the model organism, the fruit fly is really the master organism for studying genetics. And the topic I chose to do, this is quite some years ago, was an idea that was really interesting to me. And this was when a cell is fertilized and egg is fertilized and it divides into the ultimately trillions of cells that make a embryo and then a body, every single one of those cells has identical genes. And what is it that tells every single cell where it is in the body, and therefore how to use just that tiny subset of genes that are required for that particular cell. I only get life by tightly controlling which genes are on in which place. And that was really the foundation of my understanding in biology. And I went on to be visiting professor and work in the US at Hopkins and Duke and a number of places. And in the area of fruit fly genetics, I studied a group of genes, which ended up being very important in telling the body in mammals, what was front and back, what were neurons, what were not neurons. And my gene that I studied, the signaling pathway of in my PhD was a gene called hedgehog. And that led me into a number of areas, including stem cells. And so I worked for a decade as an academic, after my education, I worked at universities in the US and I was actually starting a stem cell lab back in England when I was introduced to a man who at that time was one of the best performing hedge fund managers. In the world, he ran a healthcare fund at a fund called Gallian, a very large fund at the time. And he asked me to go and work for him. So I put my stem cell lab on hold for a year and I went to work for Christian Sude. We set up a separate healthcare fund and I actually didn't go back to science after a year. I went on to manage biotech investments in public markets long short. And what I will say about my decade in or more as a public markets investor is that while academia allows you to focus on any problem you like and your imagination and mind can fly, I was in a position where I had access to information and teaching about anything in healthcare that I thought would inform me as to making the best decisions and investment. So during that time, I was able to learn not just about drugs or therapeutic areas or particular diseases, but also about people and incentives and how companies work. I watched so many FDA panels, I saw things fail. And when you're invested in something that fails, you learn from it. So I have a massive respect for the extensive knowledge of public market investors and for their decision-making ability because every second you have to be using every piece of knowledge within yourself to make a decision then. You can't say call a friend, maybe you can, but you can't just decide later, you have to decide every minute. And so I learned so much in that over a decade about how companies are, how people work. And within myself, how to actually get conviction in the absence of sufficient information and make a decision based on what you have in front of you. And I think that was hugely valuable. I'm incredibly grateful that I had that opportunity. I was later on a board of a private company that actually went public and then was sold to Snowfee. That introduced me to some of the technology that we were thinking about at Mira. And from that, I was one of the founders of the company that I'm now the CEO of, which is a genetic medicines company. And we have actually developed technology to be able to control genes with oral small molecules, which means that as Moderna uses RNA to deliver proteins, we use DNA sequences to deliver message, to make any protein, peptide, antibody, and that's triggered by a small molecule. That's the technology that we've built in building that company over the last eight years. We have developed a number of non-controlled genetic medicines. We target non inherited diseases with currently three phase three programs. One, two of them in diseases which are highly prevalent, complete unmet need, where it's more tissue engineering or circuit engineering. One's in Parkinson's and one's in zero stomia. The company has late stage clinical and we're advancing to the clinic in peptide in vivo delivery. - Wonderful, thank you, Sandy, for that wonderful background. We're recording this in the second quarter of 2024 and the life sciences sector has been on quite a journey over the last several years. I'm curious from your vantage point as a former investor in publicly traded companies within the sector. What are some of the stark differences that you've observed in how the sector is behaving or how capital markets are behaving compared to let's say 10 to 15 years ago when you were quite active on the investment side? - That's a really interesting question. And first, I'll start with my experience as the CEO of a public company compared to the CEO of a private company. And I would say that for me, the ability to talk to and understand public investors is hugely helpful. And I found it a lot more difficult to negotiate with the way of being of a private investor. Really, there is a language that you can use. There are real confines around how you speak. And I think that being able to speak that language is incredibly helpful. When you're running a public company and we went public very quickly, partly because of that dynamic and a greater comfort with public investors. Now, having said that during the time I was investing from 2000 to say 2013 or 2011, 2012, I've never seen this sort of long term, I would say, this sort of capital markets environment. There are today a number of things that were very different from when I was investing. I will say there were certainly many challenging years and many challenging stocks. Today, one of the things that we started seeing before the downturn, before increasing interest rates was huge numbers of biotech companies. So in 2018, 2019, there were maybe multiple IPAs a week. So this notion of share of voice, the notion of pre-IPO investors and crossover investors, that was relatively new compared to when in the early 2000s. So that was one thing. And as we get to today, which is three years into a very interest rate driven environment, it's with a huge amount, more machines trading as opposed to people and with a real focus on interest rates, that large number of companies and that difficulty in getting share of voice, I think is reflected in the illiquidity in many stocks companies, biotech companies that are under a billion dollars. And it is challenging in an illiquid environment to encourage people to buy stocks publicly, which feeds through to things being less liquid. There's huge short pressure from interest rates. And so sellers are really what happens in the market. So we are very much as public CEOs, looking into a world where stocks are very unrelated with respect to actual value, may be completely correlated, where you can have potentially an event bringing in 50 million of cash and your stock will be down 10% because the CPI number is disappointing. So volume, it's very different. And even some of the investors that I respect the most to some of our holders, it's really difficult for healthcare investors to negotiate that huge pressure of macro selling in super liquid stocks. And that's difficult for everyone. It doesn't stop us managing and running our business successfully them. I would say that when I look at our business today, even compared to three years ago, let alone compared to the IPO, the company has grown and matured. We now have three late stage programs. We have one of the best manufacturing infrastructures in the world. We now have a technology that's unprecedented to deliver peptides that appears to be a solution to one of the problems the farmer industry is most obsessed by. And that is delivery of metabolic peptides. So from a reality perspective, we've got a really valuable company today. Manufacturing is real. We've got a valuable company in the next several months with late stage clinical programs. And we look to a future where we're not addressing rare diseases, but it appears like Moderna had the solution to COVID out of the blue. It appears that we have a solution to many of the problems that we're now seeing in this massive market of metabolic disease, but interestingly very related, homeostasis and aging, and in a really scientific way. So how do we deal with that? Continue talking to our investors, continue running the business, continue to really focus. We were probably doing too many things. Now we're focusing on what I just told you about, focusing on the things that will be most valuable to the industry in the shortest possible time. - Yeah, and Denny, before we jump into all the exciting work that you're pursuing at Mira, I'd love to just hear your perspective on the gene therapy landscape as a whole, and what have been historically some of the challenges that several companies have gone through. And then obviously then where you saw the opportunity as it relates to your delivery model. - Yeah, another very interesting question. So over the last five or six, 10 years, the words gene therapy have come to me in something a little bit more specific than they meant colloquially five, 10 years ago. When you mentioned gene therapy today, it tends to bring to mind and actually mean to people, even the FDA, whoever it might be in our world, you're taking a perfect gene and replacing a damaged gene, addressing an inherited disorder. Those inherited disorders are by their nature rare, and they're actually hard to treat because you are hooting correct genes into cells which are already damaged. Number one, number two, you need to get that correct gene into every cell that needs it. So targeting is really difficult. And one of the issues has been you've had to deliver very large amounts of systemic doses and that has both delivery implications, but also safety implications and really important cost of goods. So when we started this company, all of those things were still true. And yet there were very obviously success stories, zulgensma, right? A great drug that saved the lives of many babies and a very clear example of gene therapy. And there are many others, potentially fiducians, potentially for other indications where gene therapy is useful. Also supporting the interest in gene therapy was a notion which has got, I would say, less and less popular is this idea that if the disease is rare enough, you can charge whatever you like. And it started with Genzyme, right? Genzyme was a company that Saturdays was like this first realization that, wow, we can make billions of dollars selling to very few patients because there are so few of them globally, right? No one insurance company is gonna worry about it. And that was a paradigm for investing for quite some time. I think that has lost favor. And we can see the complete antithesis today when we look at the metabolic disease market. It's the biggest number of people out there or Alzheimer's, the second biggest number of people or maybe vice versa. So gene therapy really has the opportunity to be successful, but there are those issues with delivery and dosing. And as we have increasing concern about overall cost of healthcare, that model of build a company to treat as two people as possible and charge as much, just is flying less and less. Clearly there has to be a mechanism for paying to treat patients who have severe inherited disorders and we have multiple organizations and FDA and companies, by the way, who are focused on that. But as an overall thought pattern, it's just a little bit less in favor. Now, when we started Mira, I explained that our aim was to invent a technology for controlling genes with small molecules, but we just had an idea. And we also wanted to build a pipeline using the best technology available that we were optimizing for using DNA to treat different diseases. And we circumvented some of the issues I've just mentioned. We thought were a problem and other people were braver and actually face those issues and have been very successful. But we decided to, number one, only use local delivery, use delivery of very small doses to somewhat immune protected areas and really not focus on only inherited diseases, but rather larger indications, like zerostomia or Parkinson's disease, where you, not just randomly, but where you can have a really differentiated approach to an unmet need in that large disease. And that is quite unusual to be a genetic medicines business that has always had a focus on non-inherited diseases, small doses, and a small dose means low cost of goods. So you can treat a large number of patients at a reasonable price. In order to address the cost of goods issue even more, which is a big one when you're going to be treating large numbers of people, we built our own manufacturing and reduced our cost of goods significantly. And what we found in the vector optimization aspect of developing these drugs is that if we could optimize capsids and promoters and translational machinery, if we could optimize all of that, we could increase the potency of our vectors, not just 10%, but two, three logs. And if you increase potency, two or three logs, you're not just doing the best things for your patient in having efficacy at greater safety at lower doses. A three log improvement in potency is a three log reduction in cost of goods. So I think that a lot of what we have done in this company, tiny local delivery and doing everything from manufacturing across the board to optimization to reduce cost of goods has actually addressed many of the concerns that we had when we started that others have addressed in different ways. But that's really what we saw then and we've seen today. - Great Sandy, there's a lot to unpack there. Seems like you've done something quite remarkable in terms of threading that needle of driving down the cost of goods while increasing potency and maybe one has to do with the other it sounds like. How does that inform your strategic approach? So what I mean by that is as a result of being able to increase potency and driving down the cost of goods, what does that mean for you as a company from an R&D perspective? - It's really about price, right? If you are giving a massive systemic dose to a young kid who has a genetic disorder of some kind, it is going to be really hard for you even if you improve the potency tenfold. Even if you can fit your vector into the capsid even if you get it delivered right with whatever vector you use, it's going to be really hard for you to price in the normal range of an antibody or a drug while having a good margin. So for a business. And that in fact will drive investment, right? potency and manufacturing is really important and it's not only important for cost of goods which is important. But what we found is we actually had a collaboration with Johnson & Johnson. We sold the drug back to them last year but we remain the commercial manufacturer for them. And in that collaboration, we actually worked and really built our manufacturing infrastructure so that it's deemed today to be one of the most comprehensive and leading end-to-end manufacturing for viral vectors in the world. Why do we care about that? Really nice, really valuable, we could be a CDMO. Why it matters to us is we are able for any product to reduce the development timeline probably by two to three years. That gives you huge advantage with your competitors in a timing perspective. And to anyone who's even thinking about the value of a drug huge ROI improvement. So the value of things like manufacturing where we actually bought the land and built the facilities has a physical flaw to the valuation of your company but for every product because when we manufacture, we manufacture for commercial, when we file an IND that product can go all the way through to a BLA. Small changes. In addition, when you hear about viral vector manufacturing you think it's about capacity. How big is your bioreactor? That isn't the issue in manufacturing today. There's quite a lot of capacity. However, what lacks in the world today, particularly amongst CDMOs and even large pharma or other biotechs is the end-to-end nature. So we have plasmid, we have viral vector and we have QC. And we've got a commercial license for QC 'cause we couldn't get time to QC from the market so we can release material. But it's the process. Now, we developed our process. We're lucky enough to be a product company with a pipeline. Our process is leading in its full ratio and its yield, not just for one product but we've developed over 20 different viral vectors. So we now eight years later have massive data lakes that inform us if we have any vector, how we make it optimally. And that process is something that if you're a CDMO you don't have the opportunity to develop 'cause you don't have a pipeline. And if you are a pipeline company and you haven't developed manufacturing, you haven't had the opportunity to develop manufacturing. So we are in an unusual position and having that process not only gives us quality but again, gives us speed and we've got global regulatory interactions, we cross-reference everything with all the different filings we make and we're in a position where we're actually quite well-known for the quality of the material we make and we don't have issues taking into the clinic, can we don't have to do further bridging on the whole to get it to commercial? So from a strategic point of view, did we know when we started the company how valuable manufacturing would be? No, we built a facility 'cause we knew we went everywhere in the world and no one could make stuff. So we built it. Did we intend to do plasmid, intend to do QC? No, we had to because we're the commercial manufacturer for J&J and we have to be able to launch their product. But has it put us in a position where we're probably five years ahead of anyone who was to start that today? Yes, that speeds everything we do, increases the value of everything we do and increases the quality of the product and the patient's treatment. So that being the most interesting thing, it's tangible in a way because it's actual facilities, actual throughput that you can charge for, but really the true value is more in the improvement in your development of your drugs. - If you're an HR or hiring manager in biotech, you know all too well that the pool of experts seeking full-time employment is shrinking. Filling key full-time positions can be a long, drawn out ordeal. It can slow the pace of execution and growth. Throw away the old hiring playbook. Now you can build a biotech dream team in a fraction of that time. Find out how. Visit chlora.com. Chlora, talent optimized. - It seems like that your approach is driving pretty significant capital efficiency and also enabling you to have multiple shots on goal while remaining quite focused on obviously the underlying technology. When you do have such a powerful process, it seems like you can go after many different disease areas. Talk to us about how you decide when you could potentially boil the ocean or get into that mindset of, hey, we can do everything. How you think about indication selection perhaps a couple of years ago and then how that thinking has evolved now. - Really be interesting because our indication selection in our initial programs was very much about our clinical data, low doses, locally delivered and we looked at the market, right? In our zerostomia, one of the reasons we moved forward with that was because for a genetic medicine while being a rare, it's orphaned disease. 170,000 target patients in the US alone, 15,000 a year, a low dose, low cost of goods and we could price well below the hundreds of thousands or whatever the gene therapies are being charged in a market where there was no other treatment. These people can't produce saliva after they've been treated for head and neck cancer. They are with their physicians at least once a year and this was their number one complaint. So we looked at this market and we thought to ourselves with this cost of goods, we can really benefit this completely unmet need and it can be a financial success for us. We've gone to payers, we can support a very good pricing and it's also unlike genetic disorders which is one vector, one disease, this is much more like an antibody in that it's qua pore and gene that makes salivary glands permeable to water and we looked at this market and go, okay, your first indication, radiation-ducerostomia, right? And that's our pivotal study is in that indication but we've got great preclinical data in showgrounds. We've got great data in showgrounds from biopsies, from humans. So identical vector, identical manufacturing, in fact, the same batches can be used for showgrounds. If you get it approved for one indication, you can do another phase three. You don't start phase one again. And then you are obviously seeing the radiotherapies for prostate cancer at the moment. We hear every week about the issue of zerostomia and so there is the identical vector. Could we do a study to expand the label there? So when we're looking at indications, even for some of our non-regulated products, it's much more like the way you look at a market for another type of drug, right? And when we think about what we charge for one-time treatment that lasts five to 10 years. And when you do that, you actually get to something really cost-effective where no drugs work. And very similar for our Parkinson's program. So that's how we thought about our late stage programs. Now, as we look to the future with our in vivo delivery, that's been really interesting. And we have been really shocked by the incredible precision of the platform we've created, such that the ability to control RNA production from any DNA template, whether it's knocked into a cell delivered by lenti or AV or even naked DNA, any DNA template, really remarkable. So we can literally give a small molecule orally and any protein, antibody. We've done every big pharma's largest antibody from dupixin, PD-R1, herceptin, all of them. We can precisely, with a pill, control how much antibody is produced and maintained in the body. And we were really pleased with our fantastic, we can dose antibodies with a pill. And then we thought, let's just look at the standard things that you'd like to dose orally and really control those genes. And so we looked at EPO, PTH, growth hormone and indeed we can, with the dose of a pill, precisely control hematocrit. We can rescue little mice. We have oral pill that delivers natural growth hormone that works really well. So we did all of those things and we can regulate, you know, nucleases and gene editing super, super precisely and very tightly, 10,000-fold dynamic range. But we were really looking for something that solved a problem in a really big indicator, really differentiating. And prior to the approval of GLP1's for obesity, I had been struck in 2004 by data that Amelin showed at the diabetes meeting before Exenitide was approved. They showed data that they had the Exenitide data that was going to come out. And they showed data on combination that had Amelin and PYY and maybe GLP1 in it. And it was extraordinary. These, I think they were rats, but they lost weight, they were no longer diabetic, they looked young. And we're all the analysts sitting there going, that's your drug. Why on your earth are you doing GLP1 by itself? And they said something which went into my brain and his 20 years later resulted in the program today, which resulted in the data which showed us why we were differentiated. And they said, Amelin, it's going to be a three or four times a day injection. PYY, you've basically got to infuse it. We can't make these long acting. But we can make GLP1 a twice day injection and that's a drug you can use in diabetes. And that is the genesis of the use of agonist peptides as drugs really. I mean, there's EPO and the ones I've described already, but these are short-lived. And I stress short-lived because these are peptides that are involved in responding to the environment. They're agonists and they're responsive. And when you have responsive agonists, when they switch their receptor on, there are systems to come in and switch the receptor off. And it transpires that having agonists persistently on is a problem because the body, the cell, the signaling pathways try and switch them off. And we approach metabolic peptides going to ourselves, oh, we're going to beat GLP1 because we can give you by giving the template, Amelin, PYY, GLP1, so we can give you a better combination that will work better at lower doses. And we did that and we made loads of combinations and they're fantastic and they work. But what we suddenly saw in the data is that we can take GLP1, for example, and deliver it so the receptors on all the time and you lose weight. We all know that we've got multiple approved drugs, GLP1, GIP on all the time, animals lose weight, people lose weight. And what we then did is, okay, let's instead of giving it so the receptors are on all the time, are you making it long-acting? What we'll do is we'll give those animals a pill every day and activate the short-acting peptides just once a day. And what was so amazing is when we did that, those animals lost one way more weight with very little peptide expressed. And it suddenly told us, oh, wow, if you give fast-acting peptides in a physiological timeframe controlled by a pill, you don't just improve tolerability. You massively improve efficacy. And this was light bulb moment because we've now done that with multiple combinations. We've done GLP1, GIP, glucagon, okay? And just like I've described for GLP or GLP1, GIP, when we do that and we give that triple combination in the fast-acting native form, the animals lose weight, they go to the edge of the limit of the model, their lean, just like Amlen showed us 20 years ago. But what's so interesting is when you talk to physicians about the super-triple G with glucagon in it, what do they say to you? They say, we're really worried about gluconeogenesis. We're worried that you might exacerbate diabetes and glucose control. So we looked at that and what we found is that when you have GLP1, GIP, glucagon, activating its receptor persistently, indeed, like a long-acting peptide combination, indeed, you lose weight, not as much weight, but you look 16, 18 weeks later, you don't get postprandial glucose control. However, if you've treated those animals once a day, wick disappearing peptide, not only do you get massive weight loss, you get perfect postprandial glucose control in a DIO mouse. So it's really this notion that for the first time, we have technology to deliver this whole world of potential therapeutics, not just GLP1, GIP, which are being studied in multiple different companies, but there are others of them, right? So we started looking at the big concerns in weight loss, one of them being muscle. And so we're really driven in our choices by what the data shows us and what the big problems appear to be. So when you lose weight, you lose fat and you lose muscle. And you've got companies like Regeneron who are looking at my start in the active inhibitors to release the inhibition on muscle strength on the metabolism, in fact, that results along with muscle strength on exercise. So we thought that's inhibitors of inhibitors and what if we just deliver the actual peptides that drive muscle strength, the peptides that drive white fat browning, that drive bone strength. And we did that. And now, just like we can deliver GLP1 with a pill, we can deliver the short-acting natural peptides that are downstream of these antibodies. And we can actually give the body the efficacious, fast-acting activator of muscle strength, activator of white fat, activator of bone strength. And what's super important about this that we have recently found is that those same muscle-derived factors actually drive BDNF expression in local spots in the brain. One of the spots actually controls appetite. But as one gets older, the source of cognitive flexibility, which is one of the most important aspects of psychiatric disorder, Alzheimer's and Parkinson's, as you get older, the source of cognitive flexibility is BDNF expression. BDNF expression is largely activated locally by some of the peptides. And it's revealed to us that the industry today is looking at this weight loss issue, the muscle loss issue, as making people thin but feeble, worrying about people falling, all of which are really important concerns. However, unless you deliver what comes out of the muscle on strength and exercise to the brain, i.e., you give the actual signaling peptides, you will not only be thin and frail, you will be losing your cognition, enhancing Alzheimer's, making neurodegenerative disease worse. So what has led us to our focus on muscle peptides and the incretins, the duct peptides, to be delivered in their natural form, physiologically, so they disappear, is not only that the improved efficacy, there is also the factor that you don't have to manufacture them in giant manufacturing facilities that Novo spent 15, 20 billion on or whatever, the body manufactures them. And which brings us back to our cuts of goods, right? So we deliver the DNA, okay? It solves a lot of those problems, but it's also revealed that the problem is more than just weakness and frailty as one gets on. It's also revealing neurodegenerative problems that we're now in our preclinical studies addressing with some of these peptides because metabolism, BDNF, strength, and cognition, as you get to be over 60, are highly linked. Bit too long, a discussion. So we're really focusing on metabolic disease because it's responsive, and that's where short-acting things are important. - Yeah, and when you have a technology and platform as powerful as the one that you've developed, you obviously have the ability to prosecute several therapeutic areas as you are pursuing, building a cross-functional team that can operate across multiple therapeutic areas and have the ability to contact shift, if you will, from program to program, can be quite challenging. I'm curious if there's any advice or lessons learned about being able to pursue multiple therapeutic areas or building a team that is, let's say, somewhat therapeutic area agnostic for the most part that you can share. - So, really good question because most companies are focused on therapeutic areas, right? They may be focused on Alzheimer's, they may be focused on Parkinson's, they may be focused on liver disease. And we, from our foundation, have been a technology-focused company. And as we develop technology, we saw the power of that technology and then focused on where we thought that power could be most applied at this moment in history. And that has taken us to metabolic disease. And frankly, that's really our pre-clinical to get into the clinic next year focus. I would say that the second place that this technology was most interesting is in cell therapy. Where we found, if you control a car in CAR-T, you massively improve the phenotype of those cells, you totally normalize them, you don't have car during manufacturing, you can manufacture them, they have no exhaustion markers, they have the phenotype of a naive T cell, they are four times more potent in vitro and in vivo, as the currently-approved identical car. And this has huge applications for autoimmune disease, for oncology, for solid tumors. Now, are we a CAR-T company? No. So rather than bringing in experts, what we've done is create little businesses, subs, you could call them, in Mira, where we will be seeking, we are discussing separate expert management, collaborations just in that area, and that's where we will get the expertise in T cells, NK cells, cell therapy. Because you're absolutely right, we can't be doing every single indication that our technology could be used for. We can partner with people who have a target and regulate, and that's fine, we'll do that for them and they develop it. But where we see really extraordinary data, like the CAR-T, it goes into a separate silo, which can be its own company separately financed with separate management, because you can't have so many different companies, all under one team, I would call it. And, Sandy, earlier you had mentioned from your time as an investor, you've had the opportunity to see failures along the way, as is the right of passage in biotech, right? I'm curious, what are some of the common pitfalls that you've observed when private company CEOs are making that transition to becoming a public company CEO? You mentioned one, which is effectively around, I think, understanding the lexicon and how to talk to public investors. Curious if there's any others that you've carried with you into your current role? - I don't know. I didn't really focus on private investments or how CEOs behave from private to public or what mistakes they have. So the mistakes that I witnessed were much more and that really hurt me, where I had positions in companies and I saw how a panel didn't work or I owned a company and a clinical trial failed because they hadn't duplicated the entry criteria, rookie stuff, the entry criteria the phase two and the phase three. So it's more that kind of rookie stuff you learn because it really hurts you. You think you've got everything buttoned up and then you're really wrong. You remember that. And I remember the Avastin panel for Avastin in breast cancer, like I remember understanding how political things can be. I remember many things because things went wrong, which I never imagined would go wrong. So it's much more general what I learned as an investor and there are lots of failures and you feel it, right? - Yeah. - You feel it maybe more even when you're focused on a drug over the long term you're doing. So it's a real intense learning experience of multiple aspects of drug development. - Yeah. And Zandy, I imagine you have just based on having chatted with you now a couple of times, you've seen a lot more than your typical first time biotech CEO, given all the different hats that you've worn. Curious if you could reflect with us for a minute about what were some of the things that you perhaps hadn't expected, sitting in that seat for the first time that you'd be willing to share? - I would say that I am, as a personality, I'm not a sales person and I'm probably too literal and straightforward and like data driven. Look at this, it's right. I would say that there are probably better CEOs of worse companies that are able to at the same time as be really honest, be really charismaticly promotional. And I don't know that I've learned how to communicate in the most effective way to investors. I definitely can communicate in a way that is really clear and really honest and I really understand regulations from being on the buy side. I see CEOs of biotech companies that I look at them and all pharma companies. I look at them, I watch them present and I go back and I go so interesting how they structured what they say and how they say it. I'm gonna do that because it's way better than how I do it. I don't know because I haven't seen really in the last 10 years, many CEOs of biotech companies, but it's also you're asking me at a time following three years of persistent daily rejections and criticism. I'm not that pleased with myself, frankly. I would say if you were to do a poll of how I am, I don't think anyone would question my honesty or my intelligence and some might hope that I was a little bit more promotional. - Yeah, and Zendy on that topic before we let you run, given all that you have now experienced across several different careers now, what's one piece of advice you wish you could provide your younger self? I'm just pulling on kind of the same thread, but if anything new comes to mind. - I think that it's really hard to do, but all success that I've ever had of any kind is because I don't give up and that I recognized many years ago as essential, just looking at the data of how people were successful. If you do something for long enough and you stick with it and you really try, that's really hard. You remember that you will, if you do things right, just keep going. Don't, I know that's for re-advice every week on GIMS. - No, in residence. - And in thought of an environment, but do things as well as you can be imaginative, be creative, always try and find the next solution, always look at the next thing around the corner. How are you gonna make this right? How are you going to make this opportunity the most optimal situation? Always just try really hard to do the best you can. - Yeah. - Pretty obvious, right? - Yeah, no, it's a wonderful point. - We're talking today, remember you said the date of the previous performance of the across this sector. - Yeah, yeah. - First of all, weeks and maybe some understand where I'm coming from. - Yeah, absolutely. We'll have to have you back on, in a year or two, ones biotech bounces back, hopefully. - Yeah, it's really hard for a whole 'nother 12 months. - Well, Andy, on that salient piece of advice, thank you so much for joining us today for the thoughtful discussion. Congrats on all the exciting progress at Mira and also for just being vulnerable with us and talking about all the ups and downs and everything that CEOs have to deal with being in the biotech sector. Really appreciate the conversation. - Thank you so much for having me. It's been really interesting, thank you. (upbeat music) - Thank you for listening to this episode of biotech 2050. This episode is hosted by me, Rahul Chaturvedi and Alok Taiyi. If you enjoyed this episode of biotech 2050, please subscribe to our podcast and leave us a review. Also follow us on Twitter and Instagram and biotech 2050 pod. Again, that's biotech 2050 POD. Until next time. (upbeat music) (upbeat music) (upbeat music) [BLANK_AUDIO]