Biotech Story Time With Tal Zaks, M.D. (Part 2, Tall Tales with Tal)

And when you last heard from us , we were testing Dr Zaks on his philosophy that it's not unmet medical need but instead curiosity that drives innovation and biotech , and more specifically in the mRNA space . And on that note , if you're tuning in today but you haven't listened yet to last week's episode , stop what you're doing right now .

Listen to last week's episode . Dive right into that one first , lest you find yourself confused even more so than you usually are trying to following along with one of my rambling- .

Instead , per your commentary , the last time we spoke , to fund and back curiosity ?

That's an academic pursuit and the basic sciences that is something that we all contribute to as citizens . That's a public health . The NIH is notable in the US for doing that . I think , when it comes to a return on investment and sort of the commercial economic sphere in which I live , what you have to do is create a vision whereby you will .

If that curiosity pans out , you ask yourself the what if ? Question , what can you do with it that's of value , and show the path that people can actually sign up to , say , yeah , we can get it . We realize it's risky , we realize you don't know anything , everything .

But if you can do this , here's what it looks like at the end and the end game is of concrete value to patients out there in the world , and I think that's what garners the investment . We're fortunate switching gears just for a second , because you asked on regulatory . The US is very unique and I'm very proud of our regulatory system .

Not many people realize this . When you go to FDA and you say , hey , I think this works , they basically tell you , show me the data and I will do my own analyses . When you go to , you know , outside the US , usually people don't have the same depth to do their own analysis . So they ask me OK , prove it .

And then they ask you questions trying to poke holes at it . Prove it , and then they ask you questions trying to poke holes at it .

But the FDA is unique in the depth of the competencies that they have and I think all of us as consumers should be really proud of it , especially in the US , and it's one of the reasons that most of the rest of the world looks to the US FDA for approvals and as a basis for making judgment .

And as a basis for making judgment , going back to sort of the curiosity angle , when somebody comes to me with an idea , back in the day when we were starting this with mRNA , the critical question was not will it work ? Can you make mRNA translate a protein in the human body ? The critical question was if it could work , what would you do with it ?

That would be of value , and I think that's where a lot of our energy went in the early days and that's where a lot of investor sentiments came in back then .

The company is famous for having raised successive rounds that were unprecedented at the time because of the potential value that we saw in it , switching gears today , when we look at investments , we look at things that are cutting edge usually and the question is always okay , what is the medicine at the end of the rainbow and is there a credible path to get

there within the financing that you're trying to raise ? The company I'm leading now , exilio , started with an idea that is based in curiosity . It basically looks at one of these elements in our genome , these genes that can go from place to place in the genome . Think of them as really early primordial viruses .

If our concept of a virus is a piece of genetic material that goes to infect somebody else , another genome , well , these primordial viruses , or parts of viruses , are sort of we call them jumping genes .

At a certain stage they actually evolved to try to jump within our own DNA and because of that they have unique ability of where they can go and what they can do . But also evolution has constrained their ability to jump , otherwise our genomes would be , you know , junk and we wouldn't be here Again for full disclosure .

You are now speaking with somebody who believes in evolution .

When the company was started , the question was well , if these indeed occur and if you map our genome and we can do that now we have been doing it for several years almost half of our genome is remnants of various kinds of these genes trying to jump about , then it's pretty clear that some of them still have that ability to jump a little bit , but evolution

has constrained that , otherwise they'd wipe us out . Can we find one of those elements and now , using modern tools of engineering , actually make them better and start to use them as a platform for fixing genes , for inserting a gene where somebody is born with an error , where they don't have the gene for that ?

That's a frequent cause of rare genetic diseases , and that was the idea . And I became excited because the team that came together actually was marrying two avenues of research . One of them is mRNA , lipid nanoparticle . We spoke about that at length . The other one was gene therapy , and we're now living .

You know , we've been , we already have some gene therapies approved and we've been using really cumbersome ways of getting these foreign genes or these fixing genes , if you will into our genome using what are called the viral vectors , so bits and bobs of viruses that are really hard to make and have a whole host of challenges associated with them .

And when you can do that , you can only do that once , because the immune system then immediately recognizes that you can never give that gene again . So you got to get it right on the first shot , and the whole gene therapy industry has evolved to this mantra of a one-time dose right , once and done .

Well , it turns out that once and done is actually a bug , it's not a feature . We can't do it more than once , even if we needed to . And what this team that formed Xilio actually came up with ?

The notion that if we could get this to work , if we could leverage what's already in nature but improve upon it , we can then use mRNA and lipid nanoparticle technology to deliver it . And the beauty is that mRNA and LNP technology is not immunogenic . You can give it with repeat dosing .

And so now I don't have to be once and done , I can actually repeat dose and get to the exact gene level I need to get a therapeutic benefit and potentially even a cure . That's what got me excited , and so this is early stage . The team is super curious .

They're engineering there , you know , they've got these structures up using machine learning , ai , all the usual buzzwords but the critical piece is at the end of it . You can paint a path to actually curing somebody of their disease , and that's where you get rewarded .

But at the end of the day , I think that one of the value propositions that hasn't really been seized upon yet by the mRNA space is that ability to redose and that can really , I think , open up the space to a whole host of advantages , both especially with patients too , that are probably more familiar with that level of treatment right , chronic treatments in the

biologic space , for example , it's a risk versus benefit profile right that they're more familiar with per se than one and done . But you know , I'm really curious too in terms of you know , as you're looking at all of this curiosity in the space and in the mRNA world , how the funding journey has been .

Have you had to sort of reiterate this story of overcome that sort of allure of the one-and-done treatment in the gene therapy space as you're working in the mRNA world , treatment right in the gene therapy space , as you're working in the mRNA world , and what are you finding is being more rewarded in terms of curiosity in the mRNA space today ?

safe . And so a lot of things that would have probably taken us , you know , a decade or two to get to were actually accelerated to the benefit of this technology by the utilization of these vaccines . I think , where you see the conversation today , many companies and many investors are looking to invest in sort of next gen .

Okay , what can we do with this technology ?

And , of course , the space that I'm in and there are competing companies like CRISPR , beam , et cetera , that are also trying similar approaches , trying to get away from traditional viral vectors for gene therapy but actually leverage what the capabilities that have been demonstrated mRNA and LNP can do and bring them into the gene therapy world .

It's going to take some time but between know the new technologies that are emerging , I'm very optimistic that we will see new medicines come about that leverage sort of both , both streams coming together recognize that actually progress is not really the Archimedes in the bathtub moment of aha , but it's more like people taking things that have matured to a certain

point from different fields and bringing them together , and that's where you get sort of true innovation . You know , one example for me that I'm super always happy to discuss and proud of is the journey of the cancer vaccines . I started my career as a postdoc working on that eons ago when I joined Moderna .

I sort of realized that between what we now understood about cancer and what the immune system recognizes , between our ability to do sequencing that we never had before of every person's tumor our ability to do sequencing that we never had before of every person's tumor and our ability now to use mRNA technology to create a very particular type of vaccine that

stimulates just the right part of the immune system to go after cancer , we should be able to put together a personalized cancer vaccine , and we did .

We started it back towards the end of 2015 when I was at Moderna , and the results of a randomized controlled trial have recently shown that it looks like that that personalized vaccine can actually prevent recurrence of melanoma almost half the time if given in the right setting . So it's these strands that all come together .

For Xilio , it is the understanding of sequencing evolutions , these jumping genes and what you can do with modern protein engineering tools , and then what you can bring from mRNA and lipid nanoparticle .

And you know , everybody talks about AI and machine learning as the next enabler , and we're starting to see how that's accelerating our ability to do discovery in almost every place . You look as well . So it's these pulling on different strands where curiosity has given us new tools and how you put them together to actually create new medicines .

That's what's fundable .

We're looking into protein replacement , gene editing , with mRNA and LNPs predominantly . Have you found right that that narrative , that education , that awareness , is needed in certain areas more so than others , or are people pretty up to speed ?

And the fascinating thing about it for me at least , and it goes back to my root as a physician you know , the biggest challenge every physician has , and the one that we most often fail at , is our ability or the need we have to explain similar pathophysiology processes of what the disease is to different people in different language , coming at us from a different

viewpoint . And everybody has the experiment of going to a physician and not understanding , well , what is it that they are actually saying ? And , trust me , the physician understood what they were saying , but the problem is they didn't figure out how to relate it to the patient . And it's on us to learn how to explain things in different language and and it .

You know it's true in in , in pharma as well , you have people with different expertises . You have the engineering folks , the research folks , the clinical folks , even the finance folks , and they all kind of have their own language and and and the fascinating thing is it turns out , it's actually inbred into how we and into our culture .

When I was a medical student , I read a fascinating book .

There's a Canadian philosopher called John Ralston Soule and he wrote a book called Voltaire's Bastard , and the subtitle is the Tyranny of Reason in Western Civilization , and basically he sort of claims that you know , reason doesn't lead you necessarily to morally correct choices , which is fair , and one of the subplots there that caught my attention is this notion that

ever since the Middle Ages , when we started to specialize , every specialty started to sort of enshroud their knowledge in their own language , and that was a barrier to other people , because your power was your knowledge and so you wouldn't share it except with you know , the cognoscente of your trade .

And so you started to speak in lingo that nobody else could perceive . And boy do we still have it . By the way , physicians are the absolute worst offenders to this , and I'll give you a simple example . A patient can come to the office and their platelet counts are low .

I have no idea why , but because they're low they will have a certain type of skin rash , and the patient sits there and the next thing you do is you tell them well , sir , you've got idiopathic thrombocytopenia , purpura .

Well , I just told them that you've got a low platelet , skin rash , for reasons that I don't know , except I said it in Latin Idiopathic , I don't know . Purpura , skin rash , thrombocytopenia .

Your platelets are low , right , and so every profession sort of has that , and the fun for me has been to sort of try to decipher what the other guys actually mean when they use that and that's within pharma . But when you're speaking about what it is you do .

You know , my PhD mentor , the late Shraga Segal , pulled me aside once and said Tom , if you can't explain what you're doing to somebody in kindergarten , you don't really understand what it is you're doing .

And so I think on all of us it's incumbent those of us who are fortunate enough to be doing the cool stuff that we are , you know we have to be able to translate that to everybody to a language that everybody can understand , otherwise what we do will be for none .

And that's , frankly where you guys come in as well , and I'm so happy to be here , because for me it's an opportunity to share with you , and with you , with the rest of the public , what's so cool about the stuff that we do .

And the strand that says I can do something with a moron and looping down a particle and I can insert a whole gene doing gene therapy based on these primordial elements if I can engineer them better .

And so he went and talked to some academics who were working in the space and he managed to get a few to kind of talk to him and start to kick the idea back and forth . And then they hired a few people . Ordinary Venture firm backed him in this idea and gave them some initial seed funding to go hire some folks .

And we initially hired somebody who does this bioinformatics thing where they go and look at genomes of various species .

The interesting thing about these elements is that they evolve in different species but because they're limited to a species and they don't jump between species , then they will look very different if they're in a fish or in a bird or in a mammal or in a human being , but if they exist in areas that are conserved in our genome .

Then you can actually take an element from a butterfly or from a fish and you can actually put them in our genome and it's going to work , because the landing pad of the sequences are actually the same .

And so he started to put these folks together , hired some very creative and talented team , started up a lab and started to explore can I find these sequences , can I improve upon them ? And I was about 18 months into or , yeah , about 18 months after the company was formed .

I was visiting the area area and they said you know , you're a partner , why don't you come and hear the pitch ? And I'm thinking to myself well , this is great , right , I can just go around . Why don't I hear the pitch ?

And then we'll go out for lunch , I'll make some new friends , I'll say my curiosity and that'd be the end of it , because 99% of the pitches I hear , you know , most of the time I don't even get lunch , but at least I get my curiosity .

But I'm thinking to myself this is , this is really a neat idea , because you're taking something that you find in evolution , you figure out what is it that you can tweak about it to actually make it better and get it to a level of potency that you can now use it as a therapeutic . Okay , tell me more .

And then they keep going and an hour turns into two . At a certain point Part of it I said you know , forget lunch , we're not going to get to the restaurant , let's just keep talking . They get the scientific founder on the phone and by hour three I was hooked because I realized they'd actually reduced it a practice .

They had some initial data to show that they can indeed do this . They can find such an element , they can improve it to the point that I could see a path to a medicine . And they tell me don't worry , just give me funding for another year and I'll keep improving it . And I'm thinking to myself yeah , you can .

You know you can go keep improving it , but can we please make a medicine out of this ? This is , this is good enough , let's get started down the road and making medicines . And so they all looked at me and said , yeah , okay , what do we do ? These are , you know , a bunch of early research guys , and .

And so I basically joined and took it upon myself to raise more money and start to build the what we call development , so to take the research and translate it into what could be development candidates , so that we can see a path to making medicines . And we're now well into that journey .

We still need to hire , still need to build a team , still need to find a CEO that's better than me . We'll get there . But in the meantime , the companies continue to make progress .

Like they said when I joined them , they indeed have continued to improve on that potency , while in the meantime , we've hired a couple of people who can start to do the experiments and animals to start to show what this thing can actually look like .

You have this really unique perch at OrbitMed where you've got the lay of the land and access to all sorts of companies mRNA and otherwise right , you would more than likely be anointed the leader of any mRNA company that chose to have you given your experience and yet you choose . Maybe you answer the question and sort of your .

You know your description of how things came together and you're intrigued by the curiosity . And you're intrigued by the curiosity , but why , like , take me through the thought process , like , why join this company and choose to lead it ? That is starting so early stage , you know ?

So , when you could probably step into a super cushy position with a company that's far closer to you know , commercial viability and perhaps putting a product on the market . Just take me , I'm just curious to get inside your brain , like when you're making this decision .

You know , at this stage in life to kind of learn by doing , you know , with full immersion in a place and a team that has this phenomenal track record of success success of successful investment in life sciences companies , I take it as a privilege . I'm not that long into the tenure here , I don't know .

I don't think any leadership of any company is a cushy position , no matter what stage the company . I think being an operator is always challenging , and especially being a CEO . This wasn't , if you will , a choice that I did because I thought , uh-huh , the next thing in my career , I need to go tick that box . As I alluded to in our previous conversation .

I'm sort of done with a box ticking part of my life and now it's about OK , where can I add value by virtue of what I know ?

I think what happened , honestly , is that I just saw an opportunity to translate what I thought was a fascinating bit in science and to push it along outside of the research slash curiosity domain into the let's put it on a path to making medicines domain , the path that is fundable , the path that should align with a return on investment .

And I felt that I was sort of uniquely qualified , given my experiences , to go help this company in that next leg of its journey . And you know , with that experience and the privilege of having done what I've done and the luck to have been able to do what I've done , I feel comes a certain responsibility to actually make good on that .

So if you see something like this and you think okay , you think you believe you've got some experiences that are relevant , uniquely relevant here and you can help this group of folks in this bit of science to go on the next leg of journey towards making medicine , well , that also carries an obligation to do that and I sort of felt compelled .

Again , my goal , neither for the short run nor the long run , frankly , is necessarily to be the CEO of this company . But this company right now , in this bit of science , has the potential to translate into medicine and I'm in a position , I think , to contribute to support doing that . So I'm obligated .

And so that story being on the record , I want to push you a little bit more on that story and maybe extract what that experience , because here Xelio is in a position where there is no stated pipeline but there is IP .

So , coming off of that experience and , I'm sure , other experiences like it , how is it informing what you're doing now in terms of your management of an early stage company that has IP but doesn't have a quote , unquote publishable pipeline ?

healthy volunteers , you don't need to , my personal philosophy is you have to publish everything you do in mankind , full stop .

You have to publish it in peer review journals , and if you agree with that logic , then actually , it also means you have to publish the preclinical basis for any clinical experiment , so if I want to treat another human being with a medicine , then the science behind that , why that is credible needs to be published in a peer-reviewed journal .

That's my personal belief . It's not written . I don't think in any regulation , and you can get regulatory approval without publishing your papers , but I think it's incumbent upon you to have that sort of public scrutiny and what it is you're doing .

Earlier than that , though , you have to contend with the competitive nature of our business and wanting to actually give your investors a return on their investment , which means you , if you're ahead of the competition , then you can't enable them and so you publish , really when you need to be credible .

And the question is well , okay , why do you need to be credible ? And you need to be credible because you want to attract talent , you want to attract capital . Well , if you can do that in a confidential manner which as a private company you can you can attract capital as a private company . Then you don't necessarily need to publish and you can hire people .

If you have them sign CDAs and you show them data and confidence . That's common , and so you don't actually need that public sort of imprint that what you do is actually holds up Now . Imprint that what you do actually holds up Now . That being said , it does mean that investors and potential employees who need to join you need to do their due diligence .

They can't rely on proxies in the public domain to say , yeah , some two peers , who shall remain anonymous , have vetted this , even though we know often that doesn't necessarily replicate .

I think this ecosystem is stringent enough and the good venture capital firms , the ones that are known , have a reputation and they're also careful to vet their investments and not put their money behind things that are nonsense . I think where Exilio is today , there is no immediate need to publish and probably a hindrance to publish when Exilio will be .

Hopefully , tomorrow we will start to have a need to publish to justify the clinical experiment that we're about to undertake , and at that point we absolutely will .

But you know , in the meantime , as you are about to embark into the clinic tomorrow , you know there's a lot of challenges , I'm sure , ahead of you . Where are you looking that you think you're going to be spending most of your time in the next year right in terms of leading this company ?

What are you expecting to be challenged by the most , and keeping in mind too that this is a nascent scientific space , as we're moving mRNA into the therapeutic world ?

The challenges , you know . I think they're sort of in three buckets . The first is , as any young company , our science is nascent and we need to continue the balance between exploring our curiosity and doing the stuff that will get us the actual product , if you will .

Because any time you hit sort of a roadblock when something doesn't work as expected and every young company has those then it takes a bunch of curious , smart people to start to poke around the edges and figure out , well , how do we get around this right ? And so there's always that balance , and getting that balance right is always challenging .

If this were to follow a logical step of progression oh , to solve that you do this it wouldn't be what it is . You know it . Actually it takes me back .

My late father was a mathematician and I never fully understood everything he did , but I understood enough to know that for every you know , the greatest mathematicians are known not necessarily by the answers they gave , but by the questions they posed , and so they were able to pose a question . How do you prove this ? I think this is right .

Can anybody prove it ? And you know , the better the mathematician , the longer it took for somebody to actually answer that question . And if you think about it , even in mathematics which is the epitome of logical thinking , proving something new , writing a new paper actually takes some sort of associative thinking that comes out of left field .

Because if it were just a logical progression , it wouldn't be tough to do . Because if it were just a logical progression , it wouldn't be tough to do .

I think the corollary in our space and I'm taking you back to the challenges that we face it is making sure that we get the balance right within the company as we navigate our way forward from this nascent science and technology into actual products that we think can work for people . There's a lot of work for us ahead on that .

The second challenge is finding the right people . There's a lot of work for us ahead on that . The second challenge is finding the right people . This is a team sport and every time I'm in a meeting , if I'm the one giving the answer to the question , I know that I've got a problem .

We're not in a good place if I'm the one giving the questions , giving the answers . My answers may be okay . Most of the time they won't be . The problem is I won't know if they are or not right .

So building up the team with the right level of experience and the right competencies to take this company forward is absolutely my number one challenge these days as we continue to grow the team and make progress . And the final one , which kind of goes back to the investment thesis .

You know , balancing the books in the sense that balancing the spend on a monthly basis versus what you have in the bank , versus what is actually creating value that you can show investors . You're one step further down the path . No , I'm still not in that clinical experiment that I promised Anna Rose . I'll be tomorrow , but I'm one step closer to it .

Therefore , the value is increased . Therefore , it's time for another funding round . How do you manage that with ? The is increased . Therefore , it's time for another funding round . How do you manage that ? With the actual burn , if you will ? Your financing strategy is absolutely critical for success and that's part of the equation here .

With the macroeconomic changes that we face , you realize that people who invest in us can invest anywhere . They don't need to invest with us . So we're competing for those investment dollars with tech , with biotech , with other investment opportunities at some level with treasuries . When interest rates go up , then a long-term investment suddenly becomes less palatable .

When you live in a zero interest rate world , then somebody's got a hundred bucks and they need to figure out what to do with it . Well , if nobody gives them any interest on it , then they can sit on a hundred bucks and in 10 years that hundred bucks will be a hundred bucks .

And if they come to me and I say , look , I'm going to , I'm going to make you three times that money , but it's going to take me 10 years , then they say great , because now I can make 100 into 300 . And it's OK because time doesn't cost me .

But if we're in a world of 5% interest rates , then in 10 years that $100 is already $200 if I do nothing else with it but buy treasuries .

So our hurdle rate what we call the level that we need to justify as a return on the investment has suddenly become challenging , and that's had an effect on a lot of very early stage kind of platform biotechs , and so managing the time to value creation is critical , while managing how much investment you absolutely need and don't get more money than you absolutely

need to get to the next step . And that's a little bit different than what it used to be . It used to be that well , as soon as you can get money , go get money . Now you're going to have to justify a higher valuation for getting more money , and that's becoming more and more challenging .

And so you've seen the effects in the ecosystem , and I think one of the jobs I have is to thread that needle , is to make sure that the capital that the investors have given me is deployed wisely , deployed efficiently and meeting the milestones required to demonstrate progress on that path to making the medicine .

I'm not sure how you can impact it more , except to say that you watch very carefully what it is you're spending money on . You try to give people some freedom , but I'll give you a concrete example .

At Exilio , we've made the decision to outsource the messenger RNA and lipid nanoparticle for the animal work that we need , because we thought it would be more capital efficient . I've very much constrained the size of the team because you know , as we move things further along , the guys who are doing the early discovery well , you know , guess what ?

They want to keep doing early discovery and at a certain point I have to say , yeah , no , you know , if you keep doing what you were doing yesterday and I need to do new stuff , that means I need to go hire more people . Well , we're actually going to constrain the size of the organization until we get to , sort of , our next milestone .

So I need you to do less of that and go over here and help your buddies who are kind of trying to move the ball down the field .

understand all of the work that you're doing at Auxilio and that the entire industry is doing today to bring mRNA therapeutics to market is going to be for naught , right , if people don't understand what they're doing . So you know , kind of leaping from that commercial return of investment concept into the world of commercializing an mRNA therapeutic right .

You've emphasized the importance of that . Education and publications are one way to do that . But we've also seen a couple of things happen in the past couple of weeks . We saw Moderna just released , I think , kind of the first of its kind right a free course on mRNA medicines to start educating the public about what these products are and what mRNA can do .

But you know , as someone that's now heading up a company in the mRNA therapeutic space , how do you think we should , as an industry and individual companies , company leaders , be educating the public today about what these medicines are and , even more importantly , what they are not , what they do versus what they do not do ?

I think Stefan's been a visionary from the get-go in educating the public and speaking about it in terms that are easy to understand , in making sure that Moderna invested in those resources and , frankly , if you look at the history of Moderna starting with educating the Moderna workforce about everything that they're doing and I have a lot of admiration for his

leadership in those regards I think that there's not a one size fit all here . You know , I've tried to do it in whatever academic opportunities I've had . When I think one of the one of the things that scare people when it comes to nucleic acid technology , mrna , dna , gene therapy is , you know , are we messing with creation ?

That's sort of a slippery slope , because everything you do around us is not as found by nature . I think what's important to explain to people is why we believe what we're doing is safe and why do we think it's got a benefit to people .

And that's why we who are at the forefront of developing novel medicines feel we have a moral imperative to develop novel treatments that are safe and effective . This is probably particularly relevant for gene therapy .

This is probably particularly relevant for gene therapy and I can tell you , for many years when I was at Moderna , you know , I looked at a lot of the approaches and I was on record as saying , you know , as a medical oncologist , some of those things scare me .

And mRNA the beauty of mRNA as opposed to gene therapy is that mRNA is very transient , does not integrate with the genome , you know the effects are gone in a day or two at least as far as protein production , and there's no longstanding effect .

And I have to tell you , accelio is the first company that I'm sort of personally investing both time and capital , and the primary reason for me to get involved here personally , beyond the curiosity and the path to medicine , is the sense that there's a potential for differentiating safety .

The specific elements that the folks described and discovered and are engineering are elements that live within our genome in places that are very safe .

We have hundreds of repeat elements and they're nowhere near any cancer-causing gene and so if our elements can really live specifically only in those places , then I'm much more comfortable as a medical oncologist that I can go and put a new gene in one of those places and it'll be fine .

And so far the specificity , that exquisite ability to only be there , is maintained .

And what got me confident is not sort of because we engineered it to be that way , but because when the team started looking at these elements , they looked at nature across the tree of life and they could only find them in that very specific area that's not close to any cancer-causing gene .

And that gave me the confidence that these elements are indeed within a safe harbor location and therefore , if we go make a gene medicine based on this , it should indeed be safe . Now , you know , we have to prove that and we're developing the tools to prove it , and the onus of proof is , of course , on us .

But if that holds true , then I feel very comfortable , as a medical oncologist to say that I believe this should be both efficacious and safe to develop for patients . It's the same framework that the FDA uses . It has to do with safety and efficacy , right , and the bar is probably different , if you're Well for sure .

It's different if you're talking about a cancer patient or you're talking about a healthy person trying to get vaccinated against an infectious disease that they might not even get , and I think one of the things I've enjoyed most and learned most was the stark difference between the two and how it makes you think about medicine as a whole .

You know it's interesting , and people much smarter than me have spoken about this . The medicine , as I practiced it , as I learned it is treatment of sick people . Few people are as sick as cancer patients with late-stage disease , and so my goal is to take a person who's sick and cure them right , make them better .

Okay , my vision for that patient is actually their past . The best I can hope for them is that they will be a few days before when they didn't have cancer . We , as physicians , don't try to take healthy people or people who are clinically well and think about how do we make them healthier , how do we make them better ? That is something that we leave for .

You know that's an engineering mindset of continuous improvement . Physicians , we don't think about it . I'm a medical oncologist . I'm a serious physician . I treat with serious illness . I don't make healthy people healthier . I mean , if you come to my office and you're healthy , well , get out of my office . What am I going to do for you , right ?

The people who make healthy people healthier . Oh , we leave that to the yoga instructionist and the nutritionist . And you know Well , really , the nutritionist , and you know well , really , yeah , I mean , what did I do ? I developed a vaccine that took healthy people and made them healthier , yeah , when you think about it right .

And so it kind of made me step back and think about what is it that we're trying to do as physicians ? And I think that concept of benefit risk has to be put in the context of your health and what the benefit is that you anticipate getting .

But I don't want to let you off the hook without giving you an opportunity to share with us a little bit about what is next on the immediate horizon , besides finding a new CEO to replace you when you're ready when you're ready , when your contributions are to the future your contributions are waning . No , but seriously , what are , what are sort of the next ?

I guess inflection points for Exilio .

For me it's to build a company and to continue my journey at OrbiMed , I think , as a field and we didn't touch on this watching new technologies start to abut and make inroads into our industry . Ai is the buzzword that everybody's using . There's several stories I can share on where that stands today .

That's been a fascinating thing for me to watch and learn and start to be part of and , as I said , we're using some of those tools already at Exelio .

But we're just in a very fortunate moment of time from a translating science into medicine perspective , given all the progress that's happening and accelerating in the world of science , and I'm just super jazzed to be able to be part of translating all that into actually people feeling better and living longer .

I think the most in-depth and convincing conversations I've had with companies that are playing with AI have come from AI companies who just happen to be working in our industry or perhaps developing a , you know , demonstrable pipeline based on that technology . But when I talk to the hardcore folks , you know it's like there's all sorts of skepticism .

So I would like to open up that conversation with you sometime , but again , we need to wrap things up here today .

There you'll find this and hundreds of other videos of our interviews with biotech builders . And while you're at it , subscribe to the Business of Biotech newsletter at bioprocessonlinecom . Backslash B-O-B . Go visit Anna Rose at Advancing RNA as well . In the meantime , we'll see you next week and thanks for listening .