BioBoss

#36 - Koen De Witte: Managing Director, ReMYND

May 30, 2021 John Simboli Season 3 Episode 6
BioBoss
#36 - Koen De Witte: Managing Director, ReMYND
Show Notes Transcript

Koen De Witte, managing director of reMYND NV, headquartered in Leuven, Belgium, shares his thoughts with BioBoss host John Simboli about leadership and how reMYND is advancing treatments for Alzheimer’s, diabetes and other diseases caused by cellular dysfunction. 


Koen De Witte
"We just decided which mountaintop we wanted to be standing on."

John Simboli
That’s the voice of Koen De Witte, managing director of reMYND NV, headquartered in Leuven, Belgium. Listen in now to hear Koen’s thoughts about leadership, and how reMYND  is advancing treatments for Alzheimer’s, diabetes and other diseases caused by cellular dysfunction. 

I’m John Simboli.
You’re listening to BioBoss.



John Simboli  
Today I'm speaking with Koen De Witte, Managing Director of reMYND, headquartered in Leuven, Belgium. Welcome to BioBoss, Koen.

Koen De Witte  
Thank you,

John Simboli  
What led you to your role as managing director at reMYND?

Koen De Witte  
There's been a bit of long path traveling there. I think if I look back, I'm actually by training a  mechanical engineer. So it's already not a very obvious jump from there all the way to running a biotech company. And then I mean, definitely, as a kid, I always wanted to create things, and always was sure I wanted to do something that would create my own thing, whatever that might mean, I also realized very early on, that often I might come in to the same solutions, but often thinking a bit differently. And therefore, I think it's better just to do it my own way. And that's what I wanted to do. And if you'd asked me as a kid, it probably would have been really a mechanical thing, it would be a car, it would be something around that. That's why I studied mechanical engineering. And lots of different things. In the end I also went into consultancy, did a lot in health care, after having worked in medical devices, where I leveraged my mechanical engineering background. But at a certain point in time, I wanted to do something where, rather than just advising from the sidelines, really do something, really build something. And that's when I started looking around. Given I was already a bit more advanced in my career when I have something where there's at least already a bit of a kernel of things that I could build from. And that's where I started looking around at lots of different opportunities in Europe. And I ended up at reMYND, which, back in 2007, we're still primarily very close to an academic lab providing services, they were kind of first science have some own products, and some great people around. And that's basically what convinced me to make the jump.

John Simboli  
What was that process like for you to decide, I want to go out and build something?

Koen De Witte  
Honestly, I really wanted to do something, create something. And I did very, very many different things to do that. And so it was never my idea to really kind of found a biopharma, but it's more I think what I did in consultancy. I worked at McKinsey, they do a lot of stuff very a lot of nice stuff, everything I did, the red thread was always innovation. And at that point in time, I said, like, look, now I want to do something where I can really build something. But I didn't think it was the best idea for me to kind of really, go and sit in a room, think from scratch of something but rather than like, Is there something that I can already have something like a little basis I can start from and then take that further,

John Simboli  
When you first came on board at reMYND with these hopes of creating something and you had a picture of what it might be like, how did that picture match up with the reality of the work that you would be doing over the next number of years compared to what you thought it might be?

Koen De Witte  
Honestly, the picture is a lot bigger and more exciting than I thought it would be back then. But at the same time, it's a lot later. Honestly, if you would have told me, I joined basically in 2008, if you would have told me look, it's going to take you 13 years to get where you are now. And actually, we're just now into the clinic, probably, definitely I would not have done it. I would definitely not have done it. So it took a lot longer. But honestly, where we stand now is so much larger than I ever could have imagined. Even though of course you are thinking of these things, and you're dreaming of these things. And to be fair, I think we still stand absolutely nowhere. But at least we're now at a point that I could see that, guys, I mean, this could be real. And in a couple of years time, we really could have proven something. And let's hope it materializes. I mean once you're in the clinic, and we I mean the path forward is a lot cleaner than if you're still in discovery, and so on. So, yes, I think the potential for it could be so much bigger than I could ever have imagined.

John Simboli  
At any point between joining the company and becoming its leader and getting to a point where you're in the clinic now did you ever think, this is just too long, I don't have the patience for this?

Koen De Witte  
The way we always looked at it the imagery always had, look, I mean, we just decided which mountain top we want to be standing on. We said like that's the top we want to be standing on. And then there's just many different ways to get there. And we went always up. I cannot say that I think Okay, look, I mean, there's a year we went up and then we were sliding down and you need to come back up again. I mean, then that I think would have been tough, right? If you kind of need to start up again. But no, it was never like a Sisyphus type of ordeal. I think we always went up and we always got closer and and so it's always every little step was a little victory, I think, that we passed. And that I think made it exciting and fun. Okay, it all took a lot longer but I can tell you I think every week I think we went a bit closer. Sometimes, frankly, it's also good, right, not to know everything. And not to know what's coming at you. Because frankly, if I would also realize everything else would be coming at me. Also, I don't think I would have seen this. And sometimes maybe go to almost, I wouldn't call it naive, but just, yeah, just go for it. And so, where I definitely think the demand that we always kind of set for us, I think we might be setting ourselves a little bit apart is that I think the way we define aspirations, we would not define this s IRR. in financial terms, we would really define this what we kind of call it as global qualities, right, I think, what's the global impact we could have? And that almost falls out into two elements, right, it's how many people could we touch? And how big an impact are we going to have per person that we touch? And then if you look at that, I don't think there's a lot better you can go after than I think what we do, and our aim in the end is really curing Alzheimer's. And I'm not going to say that our next treatment is going to cure Alzheimer's. But at least I think we're on the way and we're going to hopefully learn enough from it. Right? To be fair, it could also be dead next week, if something goes wrong, but there's at least from it. And so in that one, I think the Alzheimer, it's a very large thing as you touch upon a lot of people. And honestly, if you kind of see the aspirations we set, for us it was not, Oh, let's try to slow things down a bit. I think our aspiration was always as a start base, let's stop it right, let's make sure it doesn't progress. Actually, if you look at the preclinical data in the mouse, we found actually we curing Alzheimer's. And and I want to be very careful with that word, curing, because it has a bit this notion, you take this one magical pill, and it's all over. And that's not going to be the case. But we honestly do believe that Alzheimer's is curable. And I should at least explain that a little bit before, I think you think it's completely unrealistic. And maybe I'm like a donkey trying to go after windmills. Now Honestly, while it might be strange for me, if you look at all the others I think we have been looking at have been spending billions on things, actually, if you look at the data, at best it's slowed down by 30%. And I think it's meaningful 30%. But that is not the aspiration we're after. And why do we think we can do it still, I think it's 50 people make a difference and and try to cure while others have been able to barely slow things down is that, as is often the case, I think we have, there is one problem, but you often have very different ways of looking at the same problem. And often, if you look at the problem from a different angle, probably a solution might be a lot easier. And so in the case of Alzheimer's, if you look at it, I think it also has had people close to you. What you definitely must have noticed is actually they have no issue with retrieving memory. They don't have an issue with retrieving what they did 10 years ago. So it is not in a way literally, actually, it's not an even though I would sometimes call it a memory loss disease is not a memory loss disease. It's a disease of memory formation, people can no longer form new memory. It's not about preventing the loss of memory from the past. It's, can you form again, memory today? I mean, where did you leave the keys of your car? Did you already get your breakfast? Did you get your pill? How can you get these things, get that into memory? So it's very much a memory formation. Of course, I think we will never, I think if some memories of 10 years ago are gone, we will never be able to retrieve them. And honestly, I don't think it would be good anyway. I think we would have a very hard time surviving, if you would remember everything 100%.

Koen De Witte  
It's good. I mean, there's a reason why we forget. I mean, there is a reason why memory is being cleared. And so that is not the issue. The issue is how you can form it. If you have a neuron that is still there, but it's too much compromised that it can no longer form synapses because that's the way they form memory. That's a neuron we can probably save again. And that's exactly what we see in mice. So that's what we see in mice that this whole capacity, which is basically gone. As, for instance, in the minds of of the age of about four months, if you didn't customize it eight months, which are kind of very advanced in it. You basically see that we can recover about 80% of this synapse-forming potential. And in doing so, yes, I think it's not that you need to recover the whole brain. I mean, if you just, part of it and have enough neurons that we can get functional again. Then we can allow people again to form memories. As it's a very different way of just looking at the same problem, so we're very much focused on synaptic plasticity and restoring synaptic plasticity.

John Simboli  
When you were in that moment of thinking about leading a biopharma company and making this transition, how did you decide that this was the area that you wanted to focus on, this particular company? This particular science among the many of them, I'm sure, that you investigated?

Koen De Witte  
That's a very good question. And to be fair, it was never my decision, when I decided I wanted to get into the field to select, I'm going to go for Alzheimer's, and I'm going to solve that issue. What I did, I just very extensively looked at lots of different biotech companies, I started talking to different people. And that's basically I think, the way it went, I just kind of from talking to one person, because for me, it was a very different world within McKinsey, that's not the world I know. And then very quickly, I talk to you to people like Rudy Dekeyser, who was one of the persons who founded VIB, Advanced Institute for Biotech. It's basically it's a bit kind of like a spreading thing. I talked to two three people and each of them give me another two or three people to talk to. And in that way, I've just spoken to a lot of people. And then in the end, there were different ones. Honestly, McKenzie also had been helpful, actually, because I never worked in Alzheimer's in McKinsey, but then there were some experts. And when I told him, Look, I'll be leaving, but would like to have a chat with you on, for instance, Alzheimer's, can we have a chat? I mean, people were always available; it was quite impressive, because they were all so busy. And then I could almost think of it as a bit as a mini project for myself, and then figure it out, I think, where to go. And actually, I kind of did three things that, I think, while all undecided for reMYND, is one, of course, I mean, this whole idea about Alzheimer, and then it was only Alzheimer's and Parkinson's and actually was more Parkinson's than Alzheimer's. Back then, I mean, that definitely is something there, then a couple of people that I really got along with very well and felt that I think it just worked out great, like with our CSO, Gerard Griffioen, I think very similar things in the way we think about things and so on. And so that's definitely the second thing. The third thing, which I think was quite equally important, having been in the whole, of course, visiting McKinsey over in the financing front, also realized that I think what we wanted to do there, and it's going to take a long time to get there. And that is not the type of story that really fits very well in a typical VC approach. And also the way we're going to finance the company, we kind of needed to completely reinvent it in our way. And so when I was at reMYND, one of the earliest things I've been able to do is negotiate a nice licensing deal on one of the animal models. And it was just on an animal model for one company, I think we got a very nice deal out of that one. And that allowed us at least to kind of jump start a lot of other things and then together with with some grants, and then basically from there basically jump from one to the other in all non-diluted funding because the VC world, I mean definitely has its benefits, but it was not the best fit for what we wanted to accomplish. It was a high risk. First of all, in Alzheimer's, we were extremely early. Honestly, all science was fully developed in house. I mean, the IP that came at the start of reMYND was IP on the mouse models, but it was for the fee for service business, was not for the pipeline. So there were many things that you said like look anyway, I think there is just no fit with what we want and how to fund ourselves in the VC world. And that's why these three elements made me jump to reMYND.

John Simboli  
What have you learned about your management style over the years? What works best for you? What makes you, you?

Koen De Witte  
Really in-depth problem solving. And so I try to combine it with kind of giving people freedom, creating an atmosphere, but on the issues that I do think are key, I really really go in depth and I really go very deep on these things. And so that's a bit of what I've tried to be in my management style, I hope, is kind of provide people the opportunity, be very supportive, help them to develop, but also really intervene and really kind of try to pull things together and often sometimes really collecting the data myself and then saying like, look, I think should we do this or that. And, yes, I mean it's these these these two things, right? But this general scene-setting but then on certain topics really go into depth.

John Simboli  
How do you know when you're going to dig in deep? How do you know when you're going to back off and let that be something someone on your team is handling? Is that intuition? Is that a clear signal? How do you know?

Koen De Witte  
I always prioritize, is it an important thing? Is it something that's really going to bring us a step closer to our goal or not? And how important is this? I mean, that's always my first thing, I only have so many hours I can spend. So we need to devote where it is. And that's, what I think intuitively, am quite good at figuring out what's important. And on the things that are important I honestly do believe that, two things, things that are important and things where I would say like, if you would just do your first reflex, it's probably wrong. That you can select, look, this is important. And it's not going to be the obvious solution. Let's think a bit about that.

John Simboli  
Koen, what's new at  reMYND?

Koen De Witte  
What's new, new, at reMYND, is that we're clinical stage. We were founded in 2001, we went into phase one at the end of 2020. And then we're on track to get things assessed in 2022. 

John Simboli  
How did it  feel when you crossed over that threshold, and you realized, we're in the clinic? After all this work, we're in the clinic?

Koen De Witte  
You do the studies in dogs and rats, and you see, it's all safe, and you wait for all the data to come in. And every time you get new data, you get a bit more excited and then  you put all the file together, now you submit the file, and then you get the questions back and you say this all looks all very good. And they're all small steps. The one that's definitely going to be of course a big step, that's going to be a big bang, and that's going to be really from one mode to the other is the moment that we got the first data on the phase 2. And that's going to be normally next year, hopefully middle of next year. And that is indeed the one thing where you could say, like, wow. That's a big bang. That's indeed going to be kind of a moment I'm really looking forward to but I'm also wondering how that's actually going to play out, right? Because it's going to be moment that you know that this is the moment we're going to open the envelope and then you're going to know it. But that's good. Everything else, honestly, have been just always steps from one to the other.

John Simboli  
How would you describe the mechanism of action?

Koen De Witte  
We always start from certain proteins that through genetic defects start misfolding and then cause cell dysfunction and cell loss. And this is kind of tau, in the case of Alzheimer's, huntingtin in the case of Huntington, IAPP in the case of diabetes. And so basically what we do is we kind of make cells sick, put in small molecules, and then we can see whether they rescue basically survival. And if you do that, then we know we have something that modifies the disease. But then honestly, we don't know how the compound does that. And then we have a second part of our platform that to figure out what's the target and then the mechanism. And so it is very common in the platform that we have and to be specific, it's all about protein misfolding through genetic defects, and that causes cellular dysfunction. So that's the link between all of them. But that's it. So the way the Alzheimer's program works, actually, it's not that hard to explain, actually, maybe contrary to what people might expect is, in the case of Alzheimer's, actually cells are over-activated. Neurons are over-activated and you have more plaques, more tangles because certain neurons start failing, others take it over to get over activated. And everything actually is getting, these neurons start working too hard and are working so hard that they're no longer functional, no longer can actually really make synapses. And in all these things there's one element that's very pivotal, and that's calcium. And that's not new, that was new in the 80s, that you have elevated calcium levels. And if you look at it, all these risk factors that we know like a-beta, tau, traumatic brain injury, actually the number one risk factor in Alzheimer is aging. And so all these risk factors, all of them lead to elevated calcium levels. And that's already known quite a long time, now. Calcium is such a pivotal process, that if you intervene with that, you're very quickly going to get toxicity. I mean, either you're going to get into it, you're going to lower it, you see effect, you get it too low. And you see tox.

Koen De Witte  
That is something we did not design to go for calcium homeostasis, it's just that it came out of the screen. And it is kind of an indirect modulator of a calcium channel, of an orai channel. And in that way, it only intervenes if it's over activated. And once the neuron is back to normal, the target kind of disappears and isn't there anymore. It's propriety target that we do not disclose. But that's basically the mechanism, the mechanism that we bring calcium back to normal levels. And if you bring calcium back to normal levels, again, it's such a central process that actually is downstream from all these risk factors. It automatically also improves everything at the same time. Like with the economy, I mean, often you have an economy going well and you have increasing productivity and then people feel confident and because they're confident, they buy more and they grow and so on. And everything goes together, up. And then you have something that goes down, right, a big event. And suddenly the confidence drops, people buy less, less produced and everything goes down. And to me, that's the very same thing that happens here, right? I mean, everything's interacting with everything. And so if you then act quite centrally and bring things back to normal, everything's good. 

Koen De Witte  
And so we see indeed there are no longer, we rescue 80% of the capacity to form cognition, we have no longer buildup of plaques, we reduce tar, we reduce inflammation. So basically, everything goes in the right direction. So the objective when we started 15 years ago, was really disease modification. I think that's the end, let's try to slow down or let's even stop the disease progression. That was the the hope. What we have realized, actually that we do a lot better. It's not only that we kind of stop disease progression. But we actually also have fast symptomatic relief. And so we basically have the two; it is disease modifying and relieving the symptoms. But what we see in mice is that if you treat after one day, we already see that their capacity to form synapses improves significantly. And if you do it after one week, we always see restore about 80%. And that is what we call immediate. So it's not that we need to wait a long, long time for that. Now, the question is, of course going to be if we have this whole function going back up on synaptic plasticity, how long is it going to take before you're going to have an impact on cognition, and that might take a bit longer, because it might take some time to really get there. And so we do not know yet how fast that is. But again, it's a very fast process. I think we also have done all the clinical proof of concept, have that fully designed, and we're going to look at certain biomarkers. You can look at biomarkers that reflect quite well the synaptic plasticity, synaptic functioning, or phospho-tau, and so on. And that's going to be the key one.Where we're now is so much more exciting than I ever could have imagined. 

Koen De Witte  
What's happening in diabetes? How are we not managing glucose well? Basically, because a lot for diet induced elements. And so what happens there, also your pancreas, the human body is really fantastic, because you have all these beta cells that produce insulin, they put too much stress on a certain cell, starts failing, that's why all the cells take over. But because you get more stress on them, they start failing later. And actually, it's once that 70-80% has failed, it's only then that you're going to have an impact on glucose, and you're going to see it. And also there, it's about cells being over activated and too much oxidative stress species in there. What we do is we prevent the formation of oxidative stress. And in that way, we allow the the beta cells basically kind of to breathe again, and to kind of be productive again. And it's not that they're more better cells coming, but the better cells that are there become more functional. And so they're to our big surprise, what we were hoping, indeed, is just a treatment that would kind of delay the disease and select, you know what, you bring it now. And if you treat for four weeks, and at least after four weeks, if you would stop, then it would go up, the rate would have gone up today. To our surprise, treatment, actually remains stable. We were really puzzled by that. How is it possible, it's the same because the compound is gone after four hours and so on. And it's only done when we did another study and then sacrificed the mice, and then took out the the pancreas we saw versus study start, imagine that they have like an insulin producing capacity of 100. If you don't treat them, they go down to 50. We were hoping we would keep them at 100. What we saw, to our surprise, actually, went up to 200. And so there it's not that we just stopped the disease; in a way we almost turn back the disease, we kind of make them functional again, which is weird, right? I mean, if I will just tell you that I mean, that's not possible. But if you think like hey, I mean, there are lots of beta cells in there where they do something but not as well, if you take away the stress they kind of can produce again. Yeah, of course, it's possible that you, again, make it better. And that that's actually what we seen. And that's why we see like it's this combination between disease modifying plus fast symptomatic relief. If you want to do the thing, we wanted to do it. Yeah, we need to figure out a way to find out the target, we needed to find our way of financing the company because with VCs, it would not have worked. We also need to find our logic. And our logic is for instance, on this thing is, I'm not sure if you're very familiar with that, you have this frequentist approach and the Bayesian logic. And so a lot of the things that we do is actually based on Bayesian logic, and then of course, everything we communicate outside I mean, we don't communicate Bayesian logic outside; it's always just on the frequentist approach under standard t-test, and these type of things. But there's so many things if you look at from a Bayesian logic perspective, then it's very obvious is staring you in the eyes, if you would look at all these beta antibodies that failed. If you look at each of them at a frequentist approach, yeah. And is there something is there not something? If you look at all of them and integrate them in a Bayesian logic, it's very obvious that actually a beta does work. But at best, it gives you an impact of 30%. And you need to treat early, it's not something you can deduct from just looking at one of the studies, which if you integrate them already, in 2012, actually, you could start coming up to this conclusion. And so there's so many different things in the kind of whole approach that I think just sets us apart.

John Simboli  
Koen, what aspect of thought leadership in biopharma is especially engaging for you?

Koen De Witte  
I think, relatively general, I think thought leadership element that's more broadly applicable. And maybe just first of all about biopharma. I mean, if you look at the current times, it is quite impressive. Have you suddenly gained acceptance on new ideas so fast, right, normally probably should have taken at least another 10 years before mRNA technology would be accepted, it's now accepted within a year, you're going to see massive benefits of that. But I also do believe in these times probably would allow us kind of fast acceptance of an idea that's also a very old idea, that's been around for 10-20 years, but got more prominence back in 2019, in the discussion of the Business Roundtable, when 200 top CEOs announced kind of a redefinition of the purpose of a corporation, and where I think Milton Friedman in the 70s, has always said kind of the purpose of the corporation is maximize shareholder value, they kind of feel like, actually, we need to kind of now go more into stakeholder value. And I think for me a big misconception on that one is, if you focus on stakeholder value, it doesn't mean that you're going to give more value to the stakeholders at the detriment of the shareholders. Actually, what you do is, you basically create just more more value for everyone, by focusing on the right thing. And so if you were to define a company as the key focus is IRR to shareholders, it's very difficult to rally people behind that. But if you do it, it's really about creating things for the stakeholders and creating a difference for patients, it is a lot easier to rally people around it. And it actually gives superior returns to shareholders other than what people often think. 

Koen De Witte  
And kind of one of the nice examples from completely different thing that often reminds me of that is somebody you might know, Kim Clijsters, I think she's one of the top Belgian tennis players. And she was always very good. But actually, she didn't win a lot of finals. And then suddenly, actually, it was more after she became a mom. And she started again, that it became a lot more easier for her to win finals. And what she said is that a mistake I made in the past that I focused too much on winning the final. And if you're focusing too much on winning the final, you start making mistakes. And while if I just focus on my next hit, and 100% of my focus is on the next hit that I'll do, then I mean things go by itself, I think it's very similar here, of course, IRR to shareholders is important. But that should not be the primary purpose. I mean, if you have a slightly different purpose, it will be better for everyone. And so I'll see that also in discussions I have now with with different stakeholders, my experience is kind of the more somebody has accomplished and really realized, the more that automatically always thinks more in focusing on the stakeholder value. Of course, what's happening now in the biopharma industry, it's a lot about technology and a lot about new technologies. And that definitely is a major, I think, benefit for me the biggest benefit is still coming more from this mindset. And this mindset is I think, where do you put your mind on and what's really the purpose you have in mind, as well as the purpose more about, I mean shareholder value or more about stakeholder value, and I don't think you present to choose I think it's more the sequence right, which one do you put first, and also I do believe if you put in the stakeholder first, then actually also shareholder will follow and will be even better.

John Simboli  
Thanks for taking the time to speak with me today.

Koen De Witte  
Thank you for giving this opportunity and for having this discussion.


John Simboli
Near the start of my conversation with Koen, I heard two thoughts that resonated throughout our discussion:  new ways to approach challenges, and building a company.

For Koen, finding his own way and building reMYND  began with,“Choosing which mountaintop to stand on.” It also meant considering new pathways to climb the mountain—and his understanding that an initial reflex for solving a problem is often wrong and must be reconsidered with a combination of creativity and determination.

For Koen this meant finding new approaches to funding the company, choosing an appropriate logic framework, and defining the goal as rallying all stakeholders around making a difference for patients.

What I heard during our conversation is the tale of a dramatic journey from the early days at reMYND, when the company’s research focused on slowing the progression of Alzheimer’s, to the present, with reMYND now in the clinic. While Koen cautions that the solution for millions of people living with Alzheimer’s, diabetes, or other diseases caused by cellular dysfunction won’t be one magical pill, it’s heartening to hear him say, “Where we stand now is so much larger than I ever could have imagined. I do believe that Alzheimer’s is curable.” 


I’m John Simboli

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