Lisa Deschamps: CEO of AviadoBio

Lisa Deschamps, CEO of AviadoBio, shares her thoughts with BioBoss host John Simboli about leadership in biopharma and how AviadoBio is working to develop transformative medicines for patients living with debilitating and life-threatening neurodegenerative disorders.

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John Simboli: 0:06

Lisa, what led to your role as CEO of AviadoBio?

Lisa Deschamps: 0:34

I feel like I've been preparing for this role, really, for my whole career. As you probably know, I spent over 25 years at Novartis leading different therapeutic areas, started carrying the bag as a sales rep. And I feel like that foundation has really well prepared me for taking on this role as CEO. But probably the most relevant to taking on this particular role in this particular company, my last few roles at Novartis I was leading our US neuro business and then our global neuro business. And in that last role, my team did an acquisition of a gene therapy company called AveXis. And then I had the privilege, and it was a sheer privilege, to launch what is now the most widely prescribed gene therapy in the world, a product called Zolgensma, in SMA. And just being a part of that opportunity and seeing the impact, honestly, that it has on patients and families and the community at large, was just an amazing inflection point for me to say, OK, I want to be more and do more, that can contribute more widely to bringing therapies like this to patients and truly transforming care. And, of course, it's a key strategic area for Novartis. But, you know, going into a company that we're doing that all day, every day, and only focused on gene therapies is really what I had a lot of passion to go out and seek to do. So that's what led me here.

John Simboli: 2:19

The decision to launch a new company, a new biopharma company, is a significant choice. Then there's a question, of course, immediately, who should be the CEO? Did you go through a process of thinking, I wonder if I should lead this launch and identify a CEO, or I wonder if I should be the CEO as well?

Lisa Deschamps: 2:38

I felt like I was ready to be the CEO. You know, again, I had prepared many years in different roles of increasing responsibility. And I take leadership and leading teams and leading big ambitions like this very seriously. But I felt ready, I felt ready to go on and take on this role as CEO, and really just work to kind of inspire the team to get to the ultimate goal, which is the vision that the company had already set when I joined. So when I joined there was already a few managing members of the team, management team, as well as three scientific founders. And the work that they were doing just really spoke to me. It's kind of like when you are looking for a new home and you see many homes and you're critiquing each one. This one, well, if it was only a little bigger, spacious, more property, etc. And then you walk into the perfect house, and it just clicks, it just speaks to you. That's kind of how I felt when I came across AviadoBio.

John Simboli: 3:38

Having worked in a large corporation, a large pharma company, for a number of years, suggests that you actually were in many different companies within that large company, and you must have gained not only a significant depth of experience, but a breadth of experience as well, because the company is always mutating and changing and growing. And you're a part of that, right. Is that an accurate statement?,

Lisa Deschamps: 4:03

Absolutely.To your point, I mean, 25 years at Novartis felt like many, many companies all booked into one. And I also had the privilege of working across many parts of the globe. So you get that opportunity in a large pharmaceutical company with a huge global footprint. So not only did I work extensively across the US, but got to really experience different cultures, different regulatory environments, different reimbursement bodies all across the world. It pretty much worked in every continent and managed teams in every continent. So all of those things really ladder up to it feeling like many, many companies, many opportunities and the industry itself has transformed significantly. From the time I started and working across probably what we used to call large general medicines type of disease areas—hypertension, cholesterol, really large metabolic syndromes, etc., to much more—I spent probably the last 15 In years in my career in much more specialized therapeutic areas where you're dealing with rare and sometimes even ultra, ultra rare disease, and that in itself is a totally different experience as well.

John Simboli: 5:13

As you saw the opportunity, what were you anticipating that would be the satisfying part of what could be done at AviadoBio, that you might might not be able to achieve someplace else?

Lisa Deschamps: 5:24

I had to first believe in the science. It had to be in an area that had a high unmet need, which for me, just personally, is where my passion and purpose comes from. And it had to be, then, the scientific premise, if you will, had to be compelling. I had to believe in it and learn more about it. And then at the end of the day, the last part, which is not the least part, by any means, is all about the people. I had to Can you recall, how was it similar to what you pictured?, believe that I aligned to the values of the people that I would be leading, such as scientific founders at the beginning, as well as a number of the founding management team. Also the investors, were they really committed, or was it people who were just looking to make quick turn. And those were just some of my key criteria where it had to speak to me. I had to feel like, personally, in my core, it was the right, opportunity. As you say, we spend a lot of time at work. And it's not always, Monday through Friday, nine to five, in fact, very rarely it is. And so you have to believe in what you're doing and have a passion around it. And so for me, when I started looking for a new home it had to it had to fit and had Any things that were similar or different? The things that I found most inspiring and maybe very to be able to kind of align to my core values and what I felt was worthy of being a part of. And this team has a very compelling scientific premise. And, most importantly, is coming from an inspiration of really rallying around making a refreshing was, in a sense, the courage of the people. And you difference in patient care. don't think about it maybe as much when you're in a big organization. But certainly, when you get out into the startup world and you think about the courage it takes of scientific founders of investors, people who join as employee number one and two, to come together and do something. And many times that has an uncharted path and is huge risk. Often they lead something they were very comfortable in whether it was a high academic position or a position at an industry, and just come together because they align to that purpose. And then they hold hands and they take the risk together. To me, that is the most inspiring part of of what I've seen so far. You know it, but until you experience it and become a part of it, I think it's not as tangible.

John Simboli: 8:07

If you're talking with someone from outside the biopharma industry, and, perhaps you get introduced to them through a family connection, maybe and they say, Lisa, what do you do for a living? How do you like to answer that?

Lisa Deschamps: 8:18

We are transforming the lives of a patient or we're striving, we're chasing the opportunity to transform the life of a patient. And the impact that that can have is not just on that one patient or the in that one disease area. But truly, if we can solve some of these key challenges, the utility of that is so massive and so great. And it's hard to make that sound tangible for people.. And sometimes it can even sound corny—making a difference in the world or transforming care. But it is so true, right? We get up every day and work so hard because of the opportunity to do that. Not because of titles or money or any of that. It has to do with the opportunity to really make a difference. And, pretty much, it's a common thread. When you meet people across industries, certainly across functions and different team members, regardless of the level, there's that kind of anchor around the purpose of why we do. The most important part of my job is about being able and having the ability to inspire greatness out of my team to achieve the extraordinary together. That is the first and foremost most important thing. If I can do that, successfully, we can achieve so much. A lot of times, people just need to believe. They want to feel inspired. I believe that my role and the role of the entire leadership team is to do that, is to inspire the teams. Anchor people, of course around our common purpose and our vision, mission as a company, but if we can inspire greatness out of our teams, to achieve the extraordinary, we can have such a massive impact on society,

John Simboli: 10:06

In a typical day, how much of your time is thinking about how you want to implement this strategy? I know it's going to be different every day, obviously, and how much of it is meeting with the team and seeing where people are and reaching consensus and making decisions? What that balance, like?

Lisa Deschamps: 10:23

My style is to be very inclusive, and I feel like we get the best out, of whether we're solving a challenge or just discussing a strategy or etc. You know, it's not just me sitting in my office by myself with my two St. Bernard's here, discussing it. It's really about discussing it with the people who are part of that journey and debating. And debating is not something that people are always comfortable with. And I feel like every time I've taken on, and worked in a new team, you see different levels of comfort around that. But my style is to get people around the table. And if you're around the table, you have a core responsibility, which is to contribute to the conversation. I don't care which swim lane you're in, when you're at the table, you can swim in any lane. When you leave the table, you go back to your own swim lanes, and you execute, of course, and we all have our role, depending on the roles we play and the functions we lead. But my passion is to bring people around the table, and to really strategize and debate and really provoke those discussions to get to a better outcome.

John Simboli: 11:28

And then there are those days when you're helping to tell a story, like what we're doing today, whether it's in a media environment, or perhaps an investor conference. It could be lots of different places, but how does the storytelling part fall into the priorities for a CEO for you, as a CEO?

Lisa Deschamps: 11:45

The storytelling part is so important. And I think it's one that people underestimate, because if you don't know what you're focused on, as a company ond how you're going to achieve that, and be able to tell it in a very simple way, it's hard to bring people along with you. And that's true internally, as well as externally. The storytelling part is just as important to your teams, internally, and to the organization and helping people, themselves, tell that story to others. And if you think about the impact that can have, if we're all telling this story, and communicating how we're set out on this mission and how we're going to do it together. And then from an external environment perspective, people are simple in nature, including myself, and we need to know simply, what are we set out to do? And how will we do it? And it has to be in a way that's concise and memorable and clear.

John Simboli: 12:41

Let me look at the other side of being an entrepreneur or being at the early stages of building a new company. There's also the unpredictable aspect of it. It's the nature of biopharma that data change, and it's in the nature of science that what we think we know turns out to be not something that we know, down the road. But there's also those moments I'm thinking about, when we have to deal with the immediate thing. I'm thinking about a founder I spoke with who said, well, their days, John, when I feel like I'm at the bottom floor of a building with faulty electrical engineering or something like that, and things are falling down through. It's my job to catch them, and sort of put them back in place so that we can go back to doing our jobs. That's not a pleasant part of being a CEO, but I imagine that is a part of it.

Lisa Deschamps: 13:32

Absolutely. So I always say the science is the science and all we can do is set ourselves best up to to execute the science, but the science will be the science, the rest of it is an art. And the art of being able to lead, weather any storm, it's really about how you're able to manage that. And the role that I feel I play in that is keeping ourselves and the teams anchored on the purpose and our mission at hand. And being calm and cool and collected, I guess, in a sense, to help the teams continue forward. And not everybody takes those twists and turns with the same level of comfort. You do see, depending on the experience levels, more anxiety or less or things like that. My role is to make sure we continue to be the purveyor of hope, if you will, and stay true to our mission. And again, not everything will go right. In fact, it's quite the opposite. And we have to be willing to continue on because we believe, we relentlessly believe in what we're doing. When opportunities arise, you have to take them right and sometimes it's a totally different path than than you expected. Actually, I've found in leading teams, sometimes the worst thing that happens is we think we know it all., We're not even open to what we don't know. This is why, also, I love the idea of bringing cross-functional teams around the table, even if it's something that's very specific to one group, because the less people know, the more value I think they bring to the conversation, sometimes. And, and I think, the same is true in a sense of serendipity. as you're bringing it up, we often have things that come along, that could be opportunistic, but sometimes you see teams saying, well, that's not what we're doing, which is maybe OK. You know, focus is knowing what you're not doing. But sometimes it's so opportunistic, that you may have to change what you thought was true yesterday to be able to kind of springboard forward. So, absolutely, I think it's being able to just balance all those things, weather the storm, know that you have a place you're headed, a destination, but along the way you may encounter—whether it's turbulence or smooth, smooth sailing and be able to capitalize on certain opportunities and weather the storms. A nd that's just the reality of the work we need to do. You're coming across one of the things that, actually, I find most energizing about being a leader, and is one of my biggest areas I feel like it's important to lead teams— is when people don't even think something is possible, and rallying them together. Inspiring that greatness is the most rewarding role as a leader. When you see people go from extreme doubt, to believing something's possible, to the light goes off in their head, and they're fighting for it every step of the way. And I've seen that along my career. And it is so rewarding, not only for the ultimate outcome, which can, again, hopefully make a difference in a person's life, but also just from the personal growth that you see. And the excitement and inspiration that you see the team, themselves, go along. And so, I think some of the best pivots come from those opportunities. But again, often you have to break through that clutter of people like, No, no, no, no, that's not the plan, or no, no, that's not possible.. And if you could break through that clutter, as a leader, is really so rewarding.

John Simboli: 17:32

In order to do that, is there an aspect of visualizing? Do you find sometimes that you can help someone on a team picture something they haven't pictured before? Or is that their job to picture that?

Lisa Deschamps: 17:45

Oh, no, I definitely think it's my job to help them picture that. Not to fully picture it for them, but to help facilitate the visualization, as you say, of that. I do think it depends on the team. I've been in situations in the past where maybe you have a highly analytical group. And so, the numbers may not add up to thinking this is could be a reality, so you have to tailor your style to, sometimes, using examples where quantitative answers are not going to help us get there. And other times, it could just be a story or an analog or something like that. And sometimes, you may have to be even a bit more directive: this is the expectation, so go and find a way to do it, and then send them off. And the stress that you can see on people's face, but then you see that transition where they come back, maybe it's not the first time, the second time, but the third time where they themselves now believe, like they found an opportunity, and they get so energized by going on that path. And again, I think that's truly when you can achieve greatness and extraordinary things together, is in those moments.

John Simboli: 19:01

Let me ask one more question about the getting to know Lisa part, and then we'll talk a little bit about getting to know AviadoBio. Can you recall when you were a young person, maybe eight or nine or 10, or whatever is the appropriate age and you're trying to picture, I know my parents would like me to be this when I grew up. Was there anything you can recall thrilling you or making you think, Ah, this is something that gets a hold of me? And if so, if you can remember that, does that have anything to do with your professional life?

Lisa Deschamps: 19:30

I did used to want to be a journalist, kind of an investigative reporter. I'm very inquisitive. And I think the foundation of who I am is to ask tons of questions. My team will, for sure tell you that. Maybe I wouldn't have thought of that to here, but maybe in the in the transition, the factfinding nature and inquisitive nature of a child who wants to know it all or to find the answers, in a sense, does, of course, nicely translate to science. And the hypothesis of me trying to find the answers and prove them. Later on I had other interests, I was very interested in fashion and other things.. So my own career has taken some twists and turns, of where I thought I would go to pivoting to where I ended up. And I'm forever grateful, because I don't think I could have found a more rewarding field to be in and certainly career where you can actually touch so many people's lives. But it didn't start out in that. But I do think the inquisitive nature is very relevant.

John Simboli: 20:44

When you were at Novartis, did you find experiences along the way there where you got close to seeing what patients and families were dealing with that also directed where you want to go with your professional life?

Lisa Deschamps: 20:56

Absolutely. Novartis, is a very patient-centric organization. And I've had the privilege to launch,, prior to the gene therapy launch, 14 other products in my career, in different capacities, as I moved through the organization in different roles, of increasing responsibility. And in every one of those, I had the opportunity to meet patients, families, advocacy groups, physicians, of course, that were treating loved ones of families. When that comes to life, you can never go back, you can never do anything else, because it's so contagious. And you feel like, there's such purpose in what you do. And maybe it starts out very transactional. But, you know, shortly it transitions to really understanding the magnitude of the work we're doing. One of the things I tell my teams, because, in my organization today, obviously, there's a lot of people in the labs every day working on very early parts of the discovery. So it feels far from them, from the patient. And one of the things I say is, every person plays a role. So whether you're looking at something in the very early discovery phase, and you're processing tissues, and creating assays, or you're doing clinical operations and getting ready to execute a clinical trial, if that person who was doing the tissue processing and assays didn't do their role, we would have never got to regulatory enabling studies to then start a clinical trial. And I constantly kind of educate people on every role, and how every role ladders up to that end result of truly impacting a patient. Because otherwise, people don't have that connectivity. And also that sense of purpose. And no matter what role you play in an organization like mine, or others that I've worked in the past, it really does ladder up to that, and I feel very fortunate. And certainly the role in launching a gene therapy and meeting, in this case, kids, and family, parents–their kids may not have lived past two years old—was like nothing I had ever experienced. It was very hard, emotionally, ethically, you just think about wanting to bring so much more to so many more families and the role that you and your team plays in that. You take it very seriously.

John Simboli: 23:19

Lisa, what do you say when people ask who is AviadoBio?

Lisa Deschamps: 23:23

AviadoBio is a drug and delivery company. So that's in its simplest form, what I say. But our mission is to develop and deliver transformative gene therapies to those living with neurological conditions. And our focus on being able to pay that off is being able to deliver these medications in a way that can maximize therapeutic benefit for a patient without any of the negative safety baggage that can come along with it. So we are basically taking things that we know a lot about, like AAV9 or micro-RNA and changing something big about it. So we're taking what we know, even things that have regulatory paths already approved and things like that, but changing the way we deliver it into the person. So in our lead program, let's take that as an example, which is in frontotemporal dementia, in patients who have a specific mutation. Basically, we are going directly into their brain. So instead of delivering it systemically like an infusion, we're going directly into the brain, into a part of the brain, which is the thalamus that in a sense is the central relay hub. It delivers through billions of sets and synapses to other parts of the brain. And by doing it this way, we can be very targeted and efficient, give very small doses to patients. And hopefully, ultimately, what we've seen so far in three different animal species is minimize any negative safety effects. And this has been a key challenge. In CNS disease today, not specific to gene therapies, but in CNS overall, crossing the blood brain barrier is very difficult. And our body's defense is to protect our brain. So the the blood brain barrier develops when you're only a couple of years old, fully, and its role is to allow nutrients into the body, but protect from any harmful toxicities. So any pharmaceutical or drug therapeutic gene therapy, etc, will face the same challenge, which is it goes on the defense to protect the brain. And this is why treating CNS diseases is so challenging. Where we feel differentiated from what other gene therapies are doing is that we're going direct into the brain through the thalamus to be able to deliver very small doses without any of the negative safety potential side effects. So we're very excited. It's bold, it's a very bold approach. But again, we're taking something that we know a lot about, which is AAV9, which has already an approved regulatory path, etc, we know a lot of its positives, as well as limitations, and we're changing the delivery approach which we feel will get the best of both. We'll get something that we know a lot about therapeutically, and we'll deliver it in a way that has been a big challenge for others. We are, in our lead program and our first program, we are a gene supplementation. So the mechanism of action is basically taking a gene, in this case, it's called GRN gene that is not working or functioning and replacing that with a functioning copy of the gene. So it replaces the functioning and the the goal of the mechanism of action, in a sense, is to restore a person's progranulin levels in the body. For a healthy individual, you have a certain level of progranulin in your body, which protects your body and helps it to work, cognitively and function normally. For someone who has a frontotemporal dementia, they may have only about 30% of the progranulin levels that you have in your own body. The mechanism and the approach that we're taking is to restore tthe patient's progranulin levels to as close to normal as possible, to what a healthy individual has. And we're doing that in a way, again, with the focus on delivery, which is a very direct, into the brain, approach. People who have frontotemporal dementia have their frontal and temporal areas of their brain, cortical areas of their brain is where it starts, it becomes a global disease in nature as it progresses. So we want to go into the thalamus and not only hit those frontal and temporal areas, but also have broad distribution into the brain. So as the disease progresses, it prevents it from further progression and we can maximize the biodistribution across the board. So again, the mechanism is to restore progranulin levels in a patient who has frontotemporal dementia to healthy and normal levels of a person who doesn't. And the approach, delivery approach, to do it is to go very direct into a part of the brain that we feel can maximize the distribution and be able to have the best therapeutic benefit.

John Simboli: 28:27

If Aviado Bio progresses, where you hope it will, and if the restoc ration becomes a reality someday, how incremental or transformational? Where will you fall on that as you try to picture the life life of a particular person who's had the treatment?

Lisa Deschamps: 28:43

Like in all gene therapies, depending on how early you get the patient, in a perfect world, we prove this in patients who are symptomatic than in patients who are not even symptomatic, yet, pre-symptomatic. They could still be dosed and prevent the disease from ever starting. So obviously, there's genetic testing and all the things that would need to go along with it. But if you think about that, you could eradicate disease, in a sense, if you can get it before it even starts. So that's the big picture, prize at the end of the day. But also, it's not just specific to this program in frontotemporal dementia, if we could truly solve the delivery challenges that are seen in neurological conditions today and are preventing progress in neurological conditions today, the utility of that is so much even broader than frontotemporal dementia.

John Simboli: 29:43

So let me talk about this from an investor viewpoint for a moment I can picture and have witnessed presentations where the CEO describes a bit of what you're describing and then a certain percentage of the people say, I'm interested, let's talk more. A certain percentage say, Oh, I understand, just not a good match. And then there's the interesting group, somewhere in there, that says, Oh, I think I understand it. And then you realize, by the nature of their questions, they've heard something different than what you've intended. They filtered out something or they've, there's something else going on. When that happens, is there any kind of pattern? I know that it may be too early to know this? But is there a pattern where people say, Oh, I think I see what you're doing, Lisa? And then you say, well, actually, we're doing this, let me help you understand what we're really doing.

Lisa Deschamps: 30:28

One of the most common times that that happens is we have competitors in the space. progranulin is a big area of interest, not only in frontotemporal dementia, but could be broadly in neurodegenerative disease. And so, when people hear, okay, we have a program, focused on restoring progranulin levels and understand the role progranulin plays, sometimes they lose that we're delivering it in a very different way, piece of it. And so they'll kind of lump everything together. Okay, yeah, I get it. It's a competitive space, there's others doing it, Why should we care about what you're doing, versus what others are doing, or is everyone just the same? How will you know, even, that the way you're delivering it has a differentiating benefit, and even potentially a higher probability of success versus the others. And that's when we have to pause and almost rewind again and say, OK, let's talk about our delivery approach and why we feel it's different. And in fact, we've even looked at other constructs and delivering it in similar ways to others. And we firsthand can tell you, it may not work or it may not deliver the best benefit for patients in the safest way possible. And so, we have to really hone in on that, because the way we are going about our focus, the way we are going about our pipeline in general, not only from the lead program, but all the way through, is everything has that hyper-focus on delivery, and overcoming that key challenge, whether it's in the brain for blood brain barrier for diseases that are more, cortical in nature, or in the spinal cord and diseases that have more spinal cord involvement. So that is really the essence of what differentiates us as a company. And if an investor or a stakeholder misses that we must go back, and I don't want to say correct, but re-educate on on the core essence.

John Simboli: 32:17

How does the pipeline of AviadoBio express your vision for the company?

Lisa Deschamps: 32:21

it's very much focused on being able to overcome some of the biggest challenges in neurological conditions today and forms of dementia. So in FTD, I don't even know if you know this, but it's the most common form of dementia in patients under the age of 60. So it hits people so young. So part of this is an educational piece and getting people to realize. I mean, you probably have seen Bruce Willis, unfortunately, his recent diagnosis is in frontotemporal dimension, probably most people have never even heard of that. And then our pipeline, currently, the rest of the other four programs that we have in development, a little bit earlier in the discovery phase, are in ALS. And we all know ALS is another huge area of unmet need. And while there's some potential new therapies coming, they're still not going to be as transformative as a gene therapy can be, truly with a one time administration, hopefully provide a lifelong benefit. Of course, we have to prove all those things. But we believe in ALS, just as well as in frontotemporal dementia, the best opportunity a patient can have will be to deliver it in a very different way. And so in our pipeline programs, we are taking another bold delivery approach, which is called sub-pial. Basically, we've licensed exclusively in across all CNS disease, in gene therapy, from a company called Neurgain, in California, a sub-pial delivery platform, let's call it, which includes the approach as well as the actual delivery technology to enable that delivery. And so, for diseases like ALS, where it goes right into the spinal cord, we believe we can have truly a transformative and differentiating effect, and no one else is doing that in ALS today.

John Simboli: 34:11

What kind of partners are a good fit to AviadoBio?

Lisa Deschamps: 34:14

It's kind of multidisciplinary. So, of course, we have the academic partnerships which are critical to not only sometimes where the concepts are born, as as it was here, AviadoBio is a spin out of Professor Chris Shaw's lab, you know, King's College London, so the science was born in the academic institution, but also remain to be partners in executing the development as we go along. We often partner to do some of the animal work and things like that, as well as explore together some other potential areas of innovation. And so academia is extremely important. Also, big pharma, as they call it, is very important to be able to potentially partner whether that's today or in the future to co-develop and or co-commercialize over over time. And so those are key stakeholders. And then of course, and this is certainly not in this order, but you know, the community at large. So the patient advocacy groups, caregivers themselves, clinicians who treat patients. I mean, these are other important partnerships. We need to be informed and guided by what we hear from the community and where the needs are, and how we can best tailor our programs to meet those needs. And in addition to that, even other biotech startups or companies who you could say are competitors, in a sense, but we actually are all small together, but we create a large force as one. And so we need to learn to collaborate. And we often do that. I talk to many other peer CEOs, where we're collaborating or taking learnings and sharing them. Because at the end of the day, we can only really advance our cause and our mission together if we if we share and collaborate and learn from one another, and at times, work even more directly with each other.

John Simboli: 36:16

As you look towards the future of where biopharma is going, and where what you can contribute, and what AviadoBio can contribute, are there any particular areas of it that catch your attention that make you think this is where I can fit in, where I can really contribute, where I want to contribute?

Lisa Deschamps: 36:33

I've spent my career in being part of, in a sense commercialized drugs and bringing pipeline to commercialization, whether it was 10 years before, etc. And so, I think the opportunity that I have, or the experience that I have that can really help this company, and hopefully the industry at large, is just really thinking about what does that end goal look like? And how do we really make it a reality? Because, again, each part of the journey plays a critical role to get there. But you have to also have a vision about what that destination looks like. And you have to think of practically, OK, how does every decision we make and every step practically ladder up to making that a reality. I'll give you an example, bringing genetic medicines to patients is something that there's lots of people rallied around doing right now. And we truly all know that if we can, in diseases that are monogenic, and that mutation is known, and you can truly address the root cause of the disease, you can have a major preventative and transformative impact, and potentially even the opportunity to eradicate disease as we were just talking about. But what is it going to take to actually make that a reality? Part of that is the drugs, of course, and the clinical and regulatory path they will face. But the other part of that is everything else that needs to be enabled to make that a reality for patients. And sometimes those things get lost in the science focus and the regulatory focus. And, again, each part of it is so important. And so as I think about genetic medicines, and having launched a genetic medicine, gene therapy prior, you know, all the other stuff becomes a huge reality, once the science part is is finished,, and the regulatory part. And if you hadn't planned for it along the journey, you won't be successful, and patients won't get the therapy. And so things like implementing genetic testing, and if you think about in the disease areas that we're focused on, they're affecting people older in life. And so, as part of our normal routine care as healthy individuals today, we're not getting normal cognitive tests. We may get mammograms or colonoscopies or other things that we have been established now for decades. But when you think about dementia, or ALS, or some of these other neurological conditions, unless you have symptoms, or there's a genetic known defect in your family, you're not getting anything proactively by your physician. I'm obsessed about this. So if you think about this, how do we make sure that with all of those companies like ours, developing gene therapies, cell and gene therapies, how do we make sure that at the end of the day, people can really benefit from them? 1ot just the people who are already symptomatic, where the magnitude of benefit will be important, but not as great as it could be for those that aren't even symptomatic yet or don't even know that they may have this potential issue. So that's where I feel like, from my very executional experience in launching therapies, I can bring that value to think about, OK, what needs to be true for the future that assuming success of these programs at large, what would need to be true to ensure we could have the greatest potential impact as possible for patients?

John Simboli: 39:58

What you're talking about is a pragmatic possibility for something on a huge scale. How do you move forward without getting stuck, immmobilized?

Lisa Deschamps: 40:08

It's a great question. And it's one that the answer will evolve, as you say, over time. But it goes back to the to the comment you made earlier around the importance of partnerships. This will take partnerships, there's no question about it, it will take partnership with the community, it will take partnerships across the industry. And we can't see ourselves as competitors, here, we have to see ourselves as all working together for the common good. And it will take, I always say, it takes a village to do these things. And ther's village, usually, surrounding just one particular patient, because that's what it takes. And so it will require partnerships, it will require passion and perseverance. You're changing, potentially, policy in the future to enable these things to happen. Having had the experience with Zolgensma, we did a lot of that, but it takes time effort, and it takes that vision, and then it takes the collaboration across the community. As gene therapies become more of the standard of care, versus the one-offs policy, will need to change. Policy as it relates to when a patient turns maybe 40 years old, what is normal practice for assessing some of these things that might be related to CNS or neurological conditions overall. They're not currently part of medical practice, proactively. They're more reactive, if you will. So we'll need to shift from reactive to proactive in some of these areas where now we do have treatments for and we should be looking. In addition, policy will play a role in collaboration and partnerships. So policy makers, you have to understand, with anywith any stakeholder, you have to understand what's important for them. So as it relates to policymakers, and where is the common thread and the mutual area of interest, and certainly will be on societal burden, health care utilization, cost, effectiveness and all of those things. So you have to think about, okay, if we were to change policy or advocate to change policy in any way, why would that make sense? What would need to be true for each of the individual stakeholders, the policymaker, the physician, the caregivers, all of us at large, because finding the mutual interest, and then finding what's important to each stakeholder and how that can pay off is critical. To bring people together to make something which seems so far off and so big, almost intangible. But to be able to break it up into small bits and make it angible enough to become a reality takes takes vision, takes understanding what's important to each stakeholder and certainly takes bringing people around the table together to align on the common area of interest. And then I truly believe we can get there, but it will take effort, planning and real thought around it. But you do it because the the the possibility is so great. We're providing possibilities where there may not have been any in the past and I couldn't think of a greater inspiration than that.

John Simboli: 43:22

Lisa, thanks for speaking with me today. I enjoyed our conversation.

Lisa Deschamps: 43:26

Thank you, John. It has been such a pleasure.