How Biotech Ideas Become Real Patient Impact w/ new co-hosts Alex and Dimitri

This is the first episode in the rebranded show!

Drug and medical device breakthroughs do not reach patients because they’re clever in a lab. They reach patients when innovation, regulatory strategy, partnerships, clinical evidence and commercial reality line up at the same time, and that’s where things get messy. We’re launching Lab to Lives with a simple goal: talk honestly about what slows life sciences down and what actually helps.

We start by introducing our new co-host dynamic and mapping where we each work across the life sciences “value streams” from early R&D to compliance and commercialization. With perspectives from diagnostics, medtech and pharma, we explore why devices and drugs now overlap, why manufacturing is often the blind spot, and why modern startups can look less like research labs and more like project management teams coordinating CROs across an ecosystem.

Then we go straight into one of the biggest debates in biotech and medtech: is regulation the barrier, or is it our approach to proving safety and efficacy? We unpack risk-benefit thinking, the power of precedent, and why innovators often choose the safest regulatory path even when a different approach could unlock better products. Along the way, we talk about culture clashes between startups and big pharma, incentives that shape decisions, and how to regain agency by building a clear evidence argument regulators can assess.

If you care about drug development, medical devices, regulatory affairs, FDA and EMA expectations, and the real mechanics of translating science into patient impact, come join the conversation. Subscribe, share this with someone building in life sciences, and leave a review with the barrier you think we should tackle next.

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Transcript

Welcome And New Co-Hosts

SPEAKER_01 0:37

Welcome to this episode of Lab Two Lives. This is our very first episode and we're doing a bit of an experiment today. So a couple of things have changed on this show since it was called Transformation and Trials. One is we're trying a new format. The second thing is now there's a Wii, meaning that I have been joined by two new co-hosts that are also improvisers and that are also in the life sciences industry. So today we're going to we're going to play. We're going to figure out how we can talk about the changes that are needed in our industry in getting from the lab to making a difference in patients' lives as quickly as possible. And then we want to hear what you think. This is an ongoing conversation and we need to have it in the different sides of our industry to really understand how can we change together. So reach out, let us know what you think, join in, and we'll create this together. So getting us started on this episode, I am curious about uh Dimitri and Alex. How was your morning? What happened this morning that was noteworthy? I tried the new coffee machine in my office.

SPEAKER_02 1:41

They've installed new coffee machines, which has been a bit of a disappointment. The old coffee machines are my enemy because they produce terrible coffee. Um and the new ones, it turns out, produce slightly less terrible coffee. So I'm here with my substandard cup. But very happy to be here and talk to you both. So at least that's bringing me some joy. Dimitri, how about you?

SPEAKER_00 2:00

Morning was fun. I drop off my daughter in a nursery every morning, and today we found out that we have a gift from the Commun who printed t-shirts to our children with the logo of our nursery. Now the problem is that a nursery in Denmark you go to as a child until you're three years old, and the t-shirt is five to six year old sized. I don't know how you miss by a mile in this situation, but it was a funny thing that happened to me this morning.

SPEAKER_01 2:23

It's more like a n night dress situation.

SPEAKER_00 2:25

You know, it's it's a bit bigger than her winter jacket right now, to be honest. So I don't really know how to use it for, but I guess we'll figure out something.

SPEAKER_02 2:32

Bold marketing strategy, that to give t-shirts from the burner hero to the kids, right? It's depending on how well behaved the kid is, that could be either very good or very bad.

SPEAKER_00 2:42

True. It's always good to have an extra spare cloth. I mean, like the amount of laundry we have to do is insane, but I just wish it was a bit better sized and like it's not like Kamun knows which age children go to nurseries, right?

SPEAKER_01 2:54

That should be somewhere in their papers. This must be a specific school is for this age. Well, during my morning I've been feeling a little bit like a zombie because my youngest kid woke up at 3 a.m. And now I say youngest, but she is actually nine. She woke up and had a hard time going back to sleep, so we kind of like wandered around the apartment for an hour. I'm a little bit back to having small children. That's kind of my my feeling today. I I remember this like brain fog, and I have been very happy not to have it. But here it is, reminding me of years gone by. Nostalgia then. You're uh being brought back to those wonderful days of having young kids. Yes, yes, and so happy that those days are generally behind me. Sorry, Dimitri.

SPEAKER_00 3:32

No, no, no, it's alright. I mean you've been a bit in a time machine today, right? And uh we just we just converged. You went back in time and my my t-shirt went a bit forward in time. On average we're in present. On average we're in present.

SPEAKER_01 3:43

And that's that's it. Averages matter, especially when uh when looking at large amounts of data. Cool. Well, I would like our listeners to get to know the two of you a little bit better. So I would be curious to learn more about where in the industry is it that you fit in. I I have this uh this whole spiel about there being five major uh areas in life sciences that say either we're in the innovation stream where we're figuring out how do we develop a drug and can we find something that actually works in humans? I have a manufacturing side of things where can we actually produce this drug? There is a compliance stream where can we get the regulatory bodies to approve our drug? Then we have more the the corporate stream. Can we create a a company that can actually deliver to the product promise? And then we have the commercial side of things. Can we get governments and insurers to pay for the thing that we have developed? Kind of uh on those five scales, do you fit into some, several, none? And what has your experience been so far? I can go first on that.

SPEAKER_02 4:43

I'm gonna complicate your diagram slightly. I am very much leaning towards the more medical device diagnostic side of things than drugs. So I guess there's a parallel five streams there alongside your own. But I work mostly in that innovation piece. So how you go from an idea promising new way of treating patients or diagnosing patients that exists in a lab to something that's actually in patient hands and on market. Particularly, that's a complex journey with a lot of pieces that need to be brought together. Uh, we talk about the commercial, regulatory, and technical elements of that. So that puts me in your innovation, compliance, and commercial boxes. In the past, I've also done some work on the corporate side. So, how to approach innovation in general, how to build innovative teams, how to structure companies and development plans. So manufacturing is the pillar that I don't do. Design for manufacturers and things like that, setting up production lines is is less my field, but uh everything else I cover, though, more on the device side than the drugs. Though, of course, our other big thing is those two aren't very separate anymore, right? If you've got biologics or cell and gene therapies, then you need to be worrying about your device just as much as your drugs nowadays.

SPEAKER_01 6:02

Absolutely agree. And I kinda like the like the this visual of there being a uh like a parallel reality in the medical device space that has the same tracks but also that intermingles with the the drug side. Maybe there's like a multidimensional model we need to build here.

SPEAKER_02 6:18

Well, and similar but not the same, right? Because talking about labs to lives, one of the things that we find is that farmers often struggle with devices. And that's because there's similar stages, there's different cultures and different approaches you need to get something through. And that's often a sticking point for companies who are excellent at at drugs, but then struggle with devices because it's a bit of a different world, but looks very similar, so it can really trick you and trip you up sometimes.

SPEAKER_01 6:44

Dimitri, where are you?

SPEAKER_00 6:45

I'm definitely just placed on the innovation box, I would say. That that's much closer to me. I work in uh doing tech solutions that help companies to innovate, to do their RD, to develop new drugs, to develop new uh diagnostic methods. Very often, diagnostics is very much my passion, and it's very much the innovation part, the RD part. So I can normally when I work, it's often even a startups or scale-up, so very early stage companies who don't even have the phase two done yet, get along phase three, and they don't even have a drug on the market yet, but they're going towards there. Or if you're talking about diagnostic, they have a proof of concept device, the one that they already have partnerships with the hospitals that they can try, but not the ones where it's already manufactured on mask. So that's very much my focus. Of course, there's always some tapping into compliance, corporate, commercial manufacturing, just like in Alex's case, is very much my blind spot. But the innovation is the part where I focus, I would say. It's a funny one because I feel a little bit like in a quantum mechanics. You know, you have this 11 dimensions that we live in, apparently. But then when you go in the real world, seven of them folds together, and then it's only four dimensions you're left with. And that's how I feel about my work often that we have to work in this eleven dimensions, but before we can move on to compliance and to manufacturing and to real world implementation, we have to fold seven of them so that we can focus on something that actually matters for the real world.

SPEAKER_01 8:00

I love that comparison. And also it makes me feel better about my model because I did uh take like the complexity of our whole industry and collapse it into five things.

SPEAKER_00 8:08

Yeah, yeah, exactly. Right. And also it's a bit about parallel universes, it's just this uh the non-Copenhagen interpretation, the parallel universe interpretation.

SPEAKER_01 8:15

Yeah, yeah, that's funny. I also find it very funny because uh just as Alex and Dimitri, on all those five value streams, the one that I know least about, and that least is almost nothing, is manufacturing. So perhaps this podcast should be called We Don't Know Anything About Manufacturing.

SPEAKER_02 8:31

Until I've ignore manufacturing.

SPEAKER_01 8:33

Yeah, great.

SPEAKER_02 8:33

It's a bit of a wordier title. Maybe we should also ask the same question of you. What areas do you cover? Because I'm sure that some of your listeners, it's been a while since they listened to the first episode, right? So maybe an overall refresh is useful.

SPEAKER_01 8:45

That is that is a fair point. There's this whole uh theory of mind thing, and the things that I know, I assume everybody else knows. But that might not be uh the case. Most of my career in in life sciences I have spent in in that innovation value stream, either in late stage research or in the clinical trial space, medical affairs with investigator trials and pharmacovigilance. And then I have also been in the commercial track. My frustration with the commercial track is that a lot of the problems we have once a drug reaches commercial stage are actually like drug problems. They're problems about the product itself, and then you have to kind of like push it into the market. So I prefer being in the innovation space where it seems like we have more freedom.

SPEAKER_00 9:24

Prefer doing better drugs than selling them better.

Designing For Commercial Reality Early

SPEAKER_01 9:26

Yes, yes, that is that is my general preference. Sorry, my commercial colleagues, you're doing an awesome job. But your job is tough.

SPEAKER_02 9:33

Well, I I I think it comes back to what a lot of this discussion is about, right? What do we see as barriers from labs to lives? And I think that's definitely one also in medical devices as well, which is you certainly need to integrate your commercial stream very early in the development process and understand what organizations or patients or hospitals are going to buy as a drug product, what features it's gonna need, and and design around those features. Because being kind to your commercial colleagues, if those problems are emerging at the commercial state, that's also a a little bit too late to be doing anything about it. Uh I think also the FDA had a nice stat for a long time, which I can never find the reference to now, but they had a thing on devices, which was 75% of approval failures for devices once you traced back the cause. It was actually in scoping what the product should do uh at that very early phase and how it needed to serve the needs of patients and health systems. So it's a huge challenge and something that's very difficult to get right, about something very important to get right.

SPEAKER_00 10:35

Right. I think I come from a startup world, so it's a bit different perspective, but the problem is the same. What I see in companies often is that the way you treat technology, AI, data science, etc., is often differs between what's commonly called as a cost center versus benefit center. And if you start with saying, oh, we have a wet product, we have a drug to develop, we have a molecule to push, and then you often perceive tech as a cost center. And as a result, you don't integrate it into your like value, you don't integrate into your commercial future benefit, you like you don't see how it generates money for you, and then you become like a second-class citizen, which is treated more like a necessary expense. Then there's other companies who start kind of, if not tech first, then at least tech equal drug value, and they just act differently and they hire differently and they and they behave differently. So it's kind of the same thing. How do you plan to commercialize your product? Do you see yourself just developing a drug based on some AP you have? Then it's one strategy. If you do see yourself like, oh, we actually gonna be becoming a platform, then often you want to talk about closed loops, how you generate mass data screening that goes back into your drug design so the next iteration of your platform works better. And that can often be like even though it's in the startup world, it's kind of the same thinking. Do you put the thinking into how you use technology, a software, AI, in the design of your startup basically, in like in the foundation of your startup, or do you just start with a single drug and then you usually end up with a single drug?

SPEAKER_02 11:51

Well, it's the core challenge, right? We could equally call this podcast everything, everywhere, all at once. Because that's what this journey is, right? You need to take care of all of these little bits at the same time throughout the process, and that's not easy. And I have huge respect for anyone embarking on this journey because it's a real challenge, actually. And really it's hard because it's hard.

SPEAKER_01 12:14

It's an ecosystem of different kinds of players, both like within the large pharmaceutical companies, but also as an industry in general. We have the early stage startups who may have the technology, also the the wet stuff that we need for uh actual commercialization. We we have the different partners that are necessary for us to be able to actually deliver on a drug, and like the whole ecosystem has to work together to actually get uh towards making a difference in in patients' lives. It's a it's a complex and adaptive ecosystem.

SPEAKER_02 12:45

Well, and increasingly so nowadays, right? Since the costs of that final stage to market, your final clinical trials, your manufacture, which we know so much about, you know, it's more than most companies are ever going to be able to get in investment. So increasingly you're looking at partnership with big pharma players, big medical device players to bridge that final gap to market. I think very few companies IPOing nowadays. Whereas, you know, 20, 30 years ago that was much more the norm because people could still afford to do that. So it partnership's the key here at every stage.

SPEAKER_00 13:18

In earlier stages too, I think it's very interesting because modern-day startups are effectively just project group and then they fundamentally outsource everything to CROs because CRO has certification, CRO has the capacity, CRO has the labs and everything, the know-hows. And why would you spend like millions of investor money trying to build internal labs when there's a CRO next door that can do the same for 10,000? It's very much an ecosystem where you have to sort of rely on the part of the ecosystem around you. And fundamentally you become just a project management team that coordinates 20, 30 different CROs doing all the different experiments for you, much more than you do research yourself. So even though we have the separation between like innovation and like corporate, uh in a sense, a research group, a research startup today is is the project management startup.

SPEAKER_01 14:01

I find that interesting. And and here we're kind of getting into what are some of the key barriers or maybe enablers in our industry. Because for me, the the partnership piece, being able to work towards a common goal, even though you're working potentially five different legal entities together on creating a drug and like creating that coherence even though you're not the same legal entity. In my experience, that is tricky to pull off and often falls apart in one way or another. So figuring out how can we do that, like that would be such a game changer.

Partnerships And The CRO Ecosystem

SPEAKER_02 14:32

Also, the cultural end in this is so important. The outlook practices, focus areas of a startup are not the same as a large corporate. And we we've done a lot of work actually in in trying to bridge those two. And and that's one of the biggest challenges is first of all, having a common goal. Uh, but secondly, understanding each other and how each organization works and the dominant culture, and even companies using the same language to mean completely different things. That's also a challenge, right? Helping the big companies understand the small companies and the small companies understand the big companies so you can even begin to work together and produce something.

SPEAKER_00 15:08

Can you elaborate more, Alex? Do you have a small company or a big company? The small company wants to develop a drug, put it on a market, earn money. The big company wants to develop a drug, put it on a market, earn money. How's their goals different? Like why are they different?

SPEAKER_02 15:19

I think it's about different focus areas. So a startup, for instance, is very focused on the new, right? They're generally trying to bring something new to market. A new way of creating a treatment, a new way of delivering something. Whereas big companies tend to be very much more about risk management. How do you de-risk this product? How do you make sure that all of the little bits and pieces are taken care of? And so where a conflict has emerged in the past that I've seen is between a startup company that's trying to push this bold new idea out and a corporate that's saying, whoa, well, we want this little bit of it, but all of this other bigger vision is too much. You need to shrink that down, you need to take all of the risk out of this, and we need to put it in this safe little box that we can then actually engage with and take out to market. And that's caused conflict and and projects to fail. And it's it's not that any side of that is necessarily right or wrong either, but in the combination of the two, you can reach a position where you end up with something, yes, on market, but that doesn't reach its full potential, or something that's very much promising in a lot of areas, but has tried to be too big in one go and just fallen over because of that. And and and both both outcomes under the liver for patience. So it's a very careful balance needed between the two.

SPEAKER_00 16:40

It sounds to me very much similar to, you know, the way customer rights work in a sense. I'll try to explain in a minute. What I mean here is that, you know, as a producer, let's say I produce a washing machine and I want to push more washing machines that are out there that are cooler and cheaper and more innovative, and then I'm really like incentivized to push them out. And if they break in half a year afterwards, oh well, it's sort of a customer problem. Whereas as a customer, I don't want a washing machine that breaks every half a year. I want it to be reliable, so I push for like warranty laws and for the warranty regulations, and they have to give me like two years of warranty and the right to repair and all the other things, right? And there's just this kind of a thing because as a as a user, I want to I like they made the machine and they and they want to make it as cool and as fast as possible. And if coolness comes with some unreliability and unpredictability because it's a new experimental technology, oh well, but it's cool, right? It's cool. Whereas the customer, I just want a washing machine that washes laundry every day and doesn't flood me and my neighbors downstairs every other week. And in a sense, as a customer, I want the risk management of the washing machine because I'm to live with whatever these guys have produced. And in this partnership that you described, it feels very much like startups kind of often produce the IP and produce the product that a bigger company ends up adopting or even just altogether buying the IP rights for that or licensing rights for that, and so they become the users of the washing machine that actually gets to process the stuff and they really don't want to flood the people living downstairs.

SPEAKER_02 17:59

Yeah, yeah, exactly. And this also brings in the regulatory piece, right? Because we quite often see regulation as this tick box exercise that you maybe do at the end and hopefully get something past the regulators and on to market. But really it's it's this exercise in managing and controlling risk. I mean to to probably go too far in this metaphor of of these products being products that we know well, you know, startups tend to deliver race cars, and uh, big companies tend to want to deliver sensible family cars. And in there, the patients need something. They might need a race race car, they might need a family car, but what you're doing as a company in releasing one of those is taking on more or less levels of risk. And so you need to do a more or less complete job in demonstrating the safety and efficacy and controllability of of all of that. And there's always a push to either direction, right? But the optimal is often somewhere in the middle.

SPEAKER_01 18:58

There's also the patient piece, depending on the stage and progression of one's disease and the like treatment availabilities, you might be willing to take a lot of risk, or you might not be willing to take any risk at all if it's something that doesn't impact your life too much.

SPEAKER_00 19:12

And I think from terms of corporate and commercial perspective, there's also the point that race cars are cool, of course, and you can sell them very expensive, but then you're probably gonna be 200 people company, mostly focusing on design and engineering, outsourcing manufacturing to someone as well, very often, or doing it hands-on, whereas from a bigger company perspective, it's more convenient to sell Ford Model T because there's like hundreds of millions who will buy the Ford Model T because they want Ford Model T unlike a race car that's ten times more expensive and not that much more useful, actually. And so there's also this commercial perspective coming into play that on top of the regulatory and on top of the race cars versus normal cars, and on top of the perspective is that there's just more people who want an average generic hatchback where they can put all the groceries than the people who want a fancy racing car where they can't even put a child seat anymore because it's only two people.

SPEAKER_01 19:59

Yeah, and then we come back to kids. Yes, back to the kids.

SPEAKER_00 20:02

Back to the kids.

Is Regulation Blocking Innovation

SPEAKER_01 20:03

I think I would be curious, are are there any other barriers in in our industry that the two of you are particularly interested in today? Is there something that's uh fresh in mind and should be different as of this?

SPEAKER_00 20:15

I can go on right away because I have a I have a very opinionated position here. So my my problem here is that I can think uh of all of us here guys, I come from the most like tech background and least life science background, and that's why I'm so frustrated by the regulation we have in life science all the time. I think that's a very interesting situation because the tech industry is under regulated, but then the life sciences industry is overregulated. I genuinely think we could benefit from making the market easier and more accessible because the easier it is to access the market, the more competition it produces, and the more competition produces better products as an outcome to the to the end customer, to the end patient. Right? I'm gonna go back to the cars we just talked about, right? Tesla as a company has many problems today, but the fact is that before Tesla, nobody was doing electric cars because fancy schmancy thing, why would we do it so hard to do? Then Tesla came, brought a really good brand, and even though today they have a lot of challenges with Cybertruck and everything, the fact is other companies sell a lot of electric cars. I heard I read today that some classical and traditional company, I forgot which one it was, sold a lot a lot of electric cars more than some of their diesel models that they sell. And like just the presence of competition pushed other companies to move. Or think airplanes. Boing was sitting very comfortably and an Airbus came and it pushes it a little bit, and now Boeing has to do a better job. Whereas if it was only Boeing accessible on the market, then 737 Max would crash and people would be like, well, we don't really have a better plane anyway, so what can we do? But the fact that there is an alternative makes even just one alternative, makes the perspective completely different, in my opinion. And I feel, and like again, aviation is extremely regulated, car manufacturing is also quite regulated, but there is a degrees of regulation, there's a spectrum, if you please. And uh I personally think that one of the biggest problems we have is uh suffocation of the market innovation by all the regulatory challenges it has. The barrier is already pretty high. You need a lot of talented PhDs to build a lab who can come up with a relevant IP, who can be a cohesive team that pushes it to some meaningful product, who can cooperate with a lot of CROs to make the corporate and commercial parts of it to fulfill compliance requirements. We could be we could be more lenient on that to allow more people to come on the market and develop more drugs, develop more medical devices, understand better the mechanisms we have out there.

SPEAKER_01 22:24

Yeah, it's it's it's hard if you are if you have never done it before, it is very hard uh to get a drug through all the stages. You essentially need someone who has done it before on your team uh to guide the team through. And that kinda is a a bottleneck problem because it Then we can only reproduce uh drugs at the scale of the people that we can harvest from the industry and repurpose in other companies.

SPEAKER_00 22:45

Maybe we just replace those people with AI. How about that? We take these people, we put them into the AI, and then they do it for us. But actually, I think it's a very point, right, Ivana? I work with startups and there's a thing about serial serial entrepreneurship. If you work specifically, let's say in therapeutics and you have successfully made a startup that brought a drug to the market, you basically have a playbook. You have the same CROs, and for the next time you make your drug, you use the same CROs, the same contractors, the same partners. You do a different drug for a different target. You need like two or three new CROs that can do experiments that you didn't need in your last iteration. But the playbook of how you do step by step and what money you raise at each stage and which results you show is there. You fundamentally get a lot of benefit by doing a second drug startup because you've already been there. You know a lot about how to do it.

SPEAKER_01 23:29

And then that builds rigidity into the system because then you reuse what you have, and it's hard to introduce uh introduce new players because it's a it's a formula that you run.

SPEAKER_00 23:37

And I can't argue with that, right? I I'm very glad that Boeing and Airbus have engineers who work there for twenty years and know what they're doing. Yeah. Instead of just bringing random fresh graduates to build an airplane. I would prefer the first kind of plane fly other than the second one. But it doesn't mean there has to be I don't know. I would love it to see scaling. And uh I don't think it's a bad thing per se that we bring the people with experience and we want to see them on a team. I think it's a very valid thing. But I think the point of regulation is to prevent dangerous things coming out. And I think since we introduced these regulations in the 20th century, a lot of time has passed, a lot of technology has developed, a lot of understanding from inside of us has developed. The reason we don't need 15 years of flying a plane in a test mode before putting it on the market is because we have a really good physics model that allows us to simulate out 90% of effects. And then we have aerodynamic tubes where we can put a prototype where we can eliminate another 5%, it's 5%, we eliminate 4%, we eliminate by some few test flights we take and a thorough protocols of that. And that's it. We don't need three years of clinical testing in a real world, flying the airplane all over different hubs in the world to see how it reacts in jungles and in rain and in hail and in sunny weather, because we just have a better understanding of how things are and we can do this testing much quicker and much simpler. And why don't bring this attitude to the to the drug development world?

Risk Benefit And Defining Safety

SPEAKER_02 24:53

I think this is why this is gonna be such an interesting group of people to get together and discuss these things with. Because we all have very come from different places and different positions. I mean, I'm much more skeptical of the idea that regulatory in and of itself is a huge barrier to innovation in this space. I like to do a little thought exercise here, which is to take out the word regulatory and demonstrate and instead show that our device or drug is safe and effective. So what I like to hear then when someone says, oh well, we need less regulation, it's oh we need less focus on demonstrating that things are safe, safe and effective. My experience of regulatory so far is that we have a lot more freedom than we think we do. Most authorities will accept an argument, a well-founded argument, about why something is safe and effective. But it's on us to develop that argument, put it together, produce the convincing evidence, and convince them. I think the limitation is much more frequently not the regulations and how they're written, but our imagination and ability to convincingly, demonstrably prove in a short and effective way whether something is safe and effective. And yes, different perspectives we can discuss on the show and always easier to discuss with specific examples as well, but that's just my point of view. The other concept that we should jump on here is risk-benefit, right? Because actually, it's also not that our drugs or devices should have no risk of harm to patients at all. We should, of course, avoid extreme risk. If it looks like you're gonna kill anybody, that's that's automatically out. But a lot of what we're doing when we're talking to regulatory authorities is also demonstrating that the benefit that we're delivering to patients outweighs the risk of the intervention that we're putting in place, because interventions always carry some risk of harm. So the other switch we could do there is showing that our drug gives more benefit to patients than risk.

SPEAKER_00 26:56

I think I can jump on that and do another new choice in that it's not only in drug, but it's also in financial. I read an interesting blog article recently which is titled The Most Optimal Fraud Level in Financial System is not zero. And it comes with the same kind of idea that you cannot make things function if you want people to never ever commit a fraud. But you need to demonstrate that the systems you implement, as you Alex say, benefit more than the risks they introduce. Because somebody will always try to fraud people, somebody always try to money launder, but if we make people show a passport every time they have to buy groceries in a supermarket, the system is gonna collapse. So it's about risk benefit. We need to allow some level of risk as long as it benefits society and as long as it benefits the people, just like in pharma, but it's also in financial.

SPEAKER_02 27:38

Well, and it reminds me actually of have you heard the story of why US parks have so much trouble making bins that bears can't get into? No. Why? Tell us. Well, so because you know, bears are attracted to food, and when you put things in a bin in a park, they'll come and they'll try and forage. But I think the actual statement was the problem with making a bearproof bin is that there's a significant amount of overlap between the intelligence of the smartest bear and the tele intelligence of the least smart human. And so does this grey zone, right? Where some bears will be able to open it and some humans won't. And it's it's the same with risk, right? Anything that we do is gonna introduce some risk or some difficulty for people to use it, and there's no optimum solution. We're working in this grey area. And I that's actually the point where regulation becomes onerous because we're in this grey area, because we're in this uncertainty where there's overlap between, you know, the smartest bear and the and the stupidest human. And that's where we need so much more justification and so much care in what we're doing, and to really be able to write down this is why we know it's safe, this is why we've had to test all of these different situations to demonstrate that it's safe. I'm really stretching the analogy here, I'm sorry.

Agency With Regulators And Evidence

SPEAKER_00 28:58

I think it's really a good one. And I thought, but for me, it's an interesting one because I think it's also this gray area is now something I want to jump on, is that I think it allows us to move into the domain of what do we consider safe. Our idea of what is safe has progressed throughout the years. Fifty years ago, you let your children run around on the street and do whatever because it was considered safe. To do it, nobody would do that because cars, because serial killers, because everything, right? And children are now like four times more likely to stay at home than they used to be in in 30, 40 years ago. And I think that's an interesting question where does this gray area spans and how it goes, because if we say we need to prove it's safe, but who defines what's safe? Like who watched the watchman and who decides what is safe? We decided six five years ago that it's better to keep people at home because coronavirus has come and it was safe, and the benefit was outweighing the risk that it hurts social connections, it hurts people, personalities because they feel lonely, it hurts social development of children next generation because they don't get to mingle with their peers and critical formative years. And somebody made this decision, and how do we know it's the right one? And often there may be no good choice, there could may be no good solution because there's always a risk, as you say, and there's always a benefit. And from a point of a person who's dying from a disease, the risk in three months and they would like a drug now, the risk-benefit proportion is very different from a person who's afraid that the their less intelligent relative is going to buy this generic off-the-shelf, hoard it, and then poison themselves because that's the thing they're afraid of, because that's the intelligence overlap we're talking to about.

SPEAKER_02 30:23

I really like that because actually that's clarified for me my main point about regulation is that we often we often talk about regulation as something that's imposed upon us, right? We it we have this very victim mindset, you know, it's there's too much of it, there's too much to do, they're asking us to do this and that. Also, what we get is why can't the regulators just tell us what they want, right? But we should feel empowered in this space. If we move to this mindset of what we are trying to do is prove that our our product is safe and effective, we should feel empowered to go to regulators and say, hey, we've done X, Y, and Z for this reason, and we believe that this demonstrates sufficient safety and efficacy for this reason, they might still say no. In general, though, our experience is as long as that's well founded, as long as there's good science in there, they will at least consider it, if not say yes. And so actually, if I had one key message to come back to your point, Navana, is we should feel empowered in this space. But we've got to take on that responsibility for ourselves to be confident and capable in determining what safety and efficacy looks like and proving it out.

SPEAKER_01 31:30

Yeah. And it's a it's a great point, but also requires that competency and having done it before to be able to say, you know what? No, even though this is kind of outside of what we usually do, we believe that demonstrating safety and efficacy in this way is sufficient, even though it may be different. That does take some chest here to be able to say that to the regulatory authorities.

SPEAKER_00 31:49

I like your point about it, like not bravery, but agency in a sense, to be like, yeah, okay, actually, we we should go in and be empowered to do that. It's important because I think there is always a narrative, and uh even probably even regulatory bodies themselves would like a narrative where there's super strong, omnipowerful entities that decide who to approve and not to approve. Because if they don't present this energy out to the world, nobody fears them and nobody does a good job of proving safety and efficacy. So then we need to project this kind of image out there. But on the other hand, we should remember that it's actually about us. And uh there's also can be a lot of in in-industry regulation. Like many industries just agree to do something voluntarily just so that governments wouldn't regulate them. And I think we don't really see it in farm, unfortunately. But that's I'm very happy, Alex, we managed to in our distillation lab here, we managed to distill your idea and uh and down to the to its main point of uh being brave of agency.

SPEAKER_02 32:43

And I mean regulators, if I kind of also humanize regulators for for an instant as well, they have the same issues, right? There's a shortage of expertise also for regulators, and they're trying to get ahead of so many new advances in the space, selling gene therapies and all sorts of different things. And actually, quite often what their starting point for a new space is to actually understand from companies how they're approaching demonstrating safety and efficacy to set that benchmark. And so, actually, also by us coming to regulatory authorities and saying we think that safety and efficacy can and should be demonstrated in this way, we're helping them out, we're giving them new ways of thinking about things and and basis for for new ways of regulating things in the future. We live in a complex world. In reality, you know, this gray area is our whole lives, particularly in pharma, particularly in medtech. And so, yeah, it's it's about navigating that, right? And uh giving ourselves the tool to navigate that well.

Precedent Versus Flexibility In Approval

SPEAKER_00 33:41

I must say, talking with you, Alex, make it sound that the regulatory market you made it appear more democratic to me in a sense, because like imagine you have a society and then like your politician, a king or whoever is like 200 years ago and it's like, well, I decide you have these taxes now, and I decide you need to report this thing, and you also need to provide food to my court. And people are like, okay, what can we do? And it's very agentless, and it's very like, okay, what can we do? And that's kind of, I feel a narrative sometimes fluctuating around the regulatory topics because we need this big guy to protect us from the god or from our own smartness, choose your fighter, right? Whereas with the way you present it makes it much more democratic. People are like, no, we go on a protest, we go on and do something, and we cannot elect people at FDA, right? But we can, as a community, as an ecosystem, if you please, we can bring our points upstairs, we can do public advocacy, we can go on TV channels and say no, king should be no more. We can go and like some sort of threaten a boycott in a sense, just like an employee can threaten a boycott and to their to their employer through the union. We have this kind of other power and the w where we can nudge the regulators in a direction of doing the good things for everyone. Actually, if we bring arguments that it is good for everyone, it is good for individual people, and why specifically John sitting in Texas will benefit from this thing being regulated differently, uh we may get a lot of support and we make a world a better place, which makes it sound extremely democratic, even though technically we don't elect officials at the FDA, which is probably a good thing.

SPEAKER_02 35:10

Where a company has some new drug products and they wrote to the EMA saying, hey, we want to get some new secondary endpoints here. Because the primary endpoint is well established, but we don't think it gives as early indication or as as good of indication as these secondary endpoints. So we want to include these secondary endpoints in our phase two and phase three trials. Actually, they were running a phase two, but can we use the evidence gathered from the phase two trials to include this in the phase three trials? The reply from the EMA was actually no. But what they said was no because you haven't given given sufficient evidence that these endpoints are clinically relevant, and you haven't given sufficient evidence that the device you're using to measure these endpoints is sufficiently accurate and repeatable. They didn't say, hey, so you need to go out and do this experiment and that experiment and the other experiment and fulfill all of these regulations and da-da-da, and then we'll consider it. It's completely open to this company how they do this. All the EMA are saying, we need you to demonstrably show to us that these endpoints are clinically relevant and that you're measuring them well. And that's quite often the case, actually, in the in the regulatory space.

SPEAKER_01 36:29

It's a great example.

SPEAKER_00 36:30

I don't know. I personally feel a bit reluctant here to accept that point. I think when you get into the world of vague criteria, it sparks a lot of feeling of unfairness and also potential for corruption and other things. And that's that's a classical problem, right? It's not like I have a solution, but there is a problem between having keeping two strict rules and standardized points that will completely suffocate innovation and no secondary endpoint will be approved ever anymore. And also allows the players to game the system versus keeping the system completely open, completely prone to interpretation, and then creating situations where good things get rejected because somebody's right foot didn't like them. And I think there's always like a challenge between the two, and like in general, there is no good answer between the two.

SPEAKER_02 37:15

No, but and and this is why we should feel empowered because we're navigating this ourselves. I mean, uh another example it makes to pick up some injectors. You're developing an auto injector, you want to take it to the US. What we hear a lot from people is well, the regulations say that if you've got an auto-injector, it needs to deliver the fluid into the patient within nine or ten seconds. Because there's this huge body of evidence that says beyond that, you know, patients have trouble, particularly if they've got comorbidities in keeping the auto injector in place, and or they stop before the injection is right, or or things like that. Actually, there is not anywhere any rule that says it has to be nine or ten seconds. There's a huge body of precedent in that there's so many products on the market that have this approval on this basis that that is just what most people do because it's so well established. But there's no reason that you couldn't go to a regulatory authority and argue for 20 seconds, 30 seconds. However, what you need to do that is a very good reason why you're doing it, a very good evidence that it's still safe, very good evidence that you've mitigated the extra risk involved through the design of your auto injector. And again, it it comes back to this risk-effort balance. Actually, it's much, much easier to do a 9 or 10 second injection period. But it's not that this other period's impossible, it's that the standard of evidence that you need to deliver to upturn this convention is that much higher. And do you as a company want to take on that risk, or do you just want to implement nine or ten seconds?

SPEAKER_00 38:47

I think that kind of proves that it's exactly how you suffocate the innovation, Alex. Here I'm gonna jump just to what you said because I think you basically exactly explain it. It's like it's about incentives. You could take a simple path and don't innovate, or you could do innovation, which is risky in its own, very risky, and then hope that this innovation gets approved later, but you need to provide an extra evidence for that, right? I'll bring here an example from Denmark. You know, in Denmark, if you are a third world foreigner, you need to get a permanent residency, you can apply, and then there is like some criteria you need to fulfill. And one of them is demonstrating knowledge of Danish culture and involvement in Danish culture. There's different ways you can fulfill this criteria. You can be like a member of a school council for like a year, and then you provide papers and you provide like a proof and evidence that you actually did a lot of active work. Or you can just go and pass an exam, which takes you two hours. And the exam is a yes or no. If you pass it, you automatically qualify. And with the paperwork around your school council, it's up to interpretation and you convincing a particular guy who maybe woke up that day in a bad mood and just don't want to approve any evidence whatsoever that day. And as a result, 99% just go and do the exam. Even though the exam, objectively, if you ask me, proves much less involvement in the culture, proves less involvement in the democratic values. But it's just a standardized process that everybody does. And even though you have theoretically the second path, nobody takes the second path because the risk of waiting for a year to get a residence permit and then being rejected because some particular guy decided it wasn't good enough and you can't even object it, is very painful and very heavy on people. In the same way, it's why should we expect the company to act different? In the same way, like a person waiting for a residence permit would say, I'm just gonna do the test. The company will say, Yes, there is no formal rules. And I love it. I think it's really good that there is no strict rules about nine seconds, it's just current evidence shows and that's why we do it. You really, really need to have an extraordinary evidence to move this flag post, which is kind of what's suffocating the problems here, like where the suffocation problem comes from in the first place. You really you already need extraordinary innovation to come up with something new, and then you need a second extraordinary innovation to happen to be able to prove that you can approve that.

SPEAKER_01 40:49

It's the same situation exists uh when we look at uh computerized system validation in pharma, where uh an inexperienced validation manager will prolong your process significantly and create way more documentation overhead. Whereas a very skilled validation manager will show you you only need to do these five things, and then you have actually proven uh all the things you need about the validity of the software. Okay, can you tell more how that works? It's experience and maturity and that risk willingness, like understanding why do we do certain things enables you to also understand, well, when are these steps unnecessary, or when uh could we do something that is an alternative route that's in essence is the same thing. It's kind of like the the letter of the law versus the the spirit of the law. Like what is the intention versus what is the standard documentation provided?

SPEAKER_02 41:39

Well, and this is where for me it gets to a question of are our barriers regulation or not. And to take this scenario, right? You've got an easy route that requires not a lot of evidence, and you've got a hard route that requires an awful lot of evidence. Is the large number of people taking the easy route really a regulatory challenge or is it a risk tolerance challenge? I tend to see it much more as a risk tolerance challenge, to be honest. I also think it's about incentives because to pick the needle delivery time example itself, there are incentives where I have seen companies wanting to take this more difficult route. For example, there's a trend right now in monoclonal antibodies to want to increase the dose size as a bolus because you can reduce the dose frequency or you can get a some some monoclonal antibodies are needing much higher doses to get efficacy. And the problem there is that as you increase that dose, you're increasing the viscosity of your fluid. If you're delivering it in a short period of time, then you are increasing the risk of, for example, agglomeration of the antibodies and you know immunological responses. And so there, what you're in a position of is well, we could do an auto-injector that's an easy device route, but doesn't open up a multi-billion dollar market for us. Or there's a very difficult regulatory route that does open up a multi-billion dollar market for us if we can do this. And so I think then that puts this not in the realm of a regulatory challenge, but in a innovation risk-benefit challenge. And I think that's much more commonly the case. I see that as much more commonly the case in the market than a traditional sort of regulatory barrier. But again, that's just my experience. I know you two have had different experiences, and I'm sure listeners will have also had a very different experience as well.

SPEAKER_00 43:22

Um, but I agree. I think it's a really good point to make. And I think in general, you know, they say if nobody complains about your work, you're not doing anything important. So in that sense, relatory is obviously doing a very important work. But I think also what you point out kind of segues us into the next episode's topic, maybe, because it feels organic now to talk either about corporate or commercial because it talks about incentives, right?

SPEAKER_01 43:41

Yes.

SPEAKER_00 43:42

What kind of incentives we have there and how do we make things, right? Ivana raised the point that we train people to be extremely cautious, overly cautious and paranoidly cautious, only for the best of them to actually not be cautious too much and know exactly which shortcuts to take and how not shortcuts, but like how to actually reasonably sense your logic so you don't have to be overly cautious. In the same sense, what you raised right now, Alexis, I feel a little bit is that what are the incentives there? If we train our managers and our investors and our everyone that they need a short-term return and they need to put this particular drug on the market next five years or bust, then we discourage the long term thinking, right? But actually, the long term thinking and the idea that it opens the multi-billion dollar market can be a better way for innovation and for the better health care in the future and medical devices and medical drugs in the future. And that kind of talks about incentives and a corporate structure and commercialization potential.

Drug Name Or Pokemon Game

SPEAKER_01 44:33

I think that's a good point. And we're back to bringing the innovation value stream to Together with the commercial value stream and to be able to succeed in the commercial value stream, you need to be able to develop your drug so that you can reap the benefits of the commercial value stream. And uh you gotta you gotta tie those uh value streams together to get good results and get to those patients whose lives you're trying to impact. Everything all the time, all at once, yeah. Yeah Great.

SPEAKER_00 45:00

I mean aga if it wasn't such a simple project it wouldn't cost a billion to develop a drug.

SPEAKER_01 45:04

Exactly. No, we're here because this is interesting. I would like us to play a game now. That's it. We are going to try playing the game of is this a drug name or is this a Pokemon? Yeah, okay. That sounds fun. Alex and Dimitri, I am going to throw a couple of words at you, and then I would be curious to hear if uh this is a drug or a Pokemon. And the winner gets the glory. Excellent. Let's let's try this. Let's do it. Okay, first up, Baraskeuda. Drug name or Pokemon?

SPEAKER_00 45:37

I'm pretty confident it sounds like a Pokemon. I don't know why. It just vibe vibes like a Pokemon war to me.

SPEAKER_02 45:43

I'm saying drug because I don't think Pokemons often have two-word names, but what's that one word? I'll be uh the the naysayer. I'll say I'll say uh what did you say, Dimitri, Pokemon?

SPEAKER_00 45:53

I said it's a Pokemon because it's also you know it's like a Barracuda, like the animal.

SPEAKER_01 45:57

I'll say drug. Very good. It is in fact a fish-looking Pokemon. A barracuda, then, yeah. Very good. Okay, let's uh let's move on here. Next word. Key truder.

SPEAKER_00 46:09

Keytruder.

SPEAKER_02 46:10

That sounds like our Pokemon. Beavery-based Pokemon to me. Uh what based? Beavery-based. Like intruder, but key truder, because it's shaped like a key. I don't know, Pokemon away.

SPEAKER_00 46:19

Yeah, but it also sounds like a fancy, fancy uh marketing name, so I'll go with the drug this time.

SPEAKER_01 46:24

Okay. It is a cancer drug.

SPEAKER_00 46:28

Like it's a very aggressive marketing. Imagine like an American startup sitting there at their at the board meeting and be like, what do we call our drug so that people know that we like intrude into the tissue of the cancer and like we like pow pow pow everywhere.

SPEAKER_02 46:42

I like the idea that people name drugs and Pokemon in the same way. What does it do? How can we make that into a word that sounds kind of cool?

SPEAKER_00 46:49

That would be fashion much more fun, you know. You come to a pharmacy and you say, gonna have some uh hexagonal shooter and something like that, because it releases some benzo somewhere that's very valuable to your body.

SPEAKER_01 47:01

Yeah. Last, last one, more pico.

SPEAKER_00 47:04

That sounds like a thing I would say in a baker's shop. What do you want on top? Oh, I want more pico.

SPEAKER_02 47:08

Just more drink. I'm wondering whether the pico in there is a red herring around Pikachu, so I'm gonna go drug. Let's let's swing for the fences.

SPEAKER_00 47:17

I'll go for the for the Pokemon because it ends with an O and I feel it's more Pokemon thing than the drug thing.

SPEAKER_01 47:23

It is a Pokemon. I'm so mad at this game.

SPEAKER_00 47:28

That's because you work in medical devices, Alex. Next time we play, is it an IKEA furniture or a medical device?

SPEAKER_01 47:35

Yeah, we should do that. Well, speaking of next time, this was our first show. We are super curious to hear what you think, what you would have liked to see more of, and which other topics you're curious about. Next time, perhaps we shall dive into the incentive model and commercialization of drugs. That would be a fun, fun topic. Otherwise, reach out to us on LinkedIn. You'll find all of our profiles in the show notes, and we are looking forward to the recording content for you again. See you soon. See you all.