Latest / The BioHub - by Avetix / Episode 80 - Dr. Maurits Geerlings - CEO Nanocell

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Episode 80 - Dr. Maurits Geerlings - CEO Nanocell · The BioHub - by Avetix

0:05
Welcome back to another episode of the Bio Hub and Avetics
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podcast. Today I'm joined by Doctor
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Moritz Girlings, President and CEO of Nano Cell Therapeutics.
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Moritz is a true biotech entrepreneur.
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He's Co founded and built multiple companies including
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Actinium, Formula and Marata, and now he's on a mission to
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revolutionize in vivo cell engineering.
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In this conversation, we dive into Moritz's journey, the
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unique structure of nanocell, the challenges and opportunities
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in cell therapy right now, and his bold vision for the future
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of this field. It's a pleasure to have you,
0:39
Moritz. How are you?
0:41
Thank you Max really pleasure to be on your podcast and enjoying
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very much. Yeah, honestly amazing to have
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you. Let's just start off with you.
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You've Co founded multiple companies, I just mentioned a
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few there, Actinium Formula and now Nano Cell.
1:00
What first drew you into biotech, and also what keeps you
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coming back to starting something new?
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So having studied medicine in the Netherlands, I came to the
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conclusion that for me having a physician path in career is a
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bit of a professional claustrophobia because you get
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to specialized farther and farther into a particular field.
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And my curiosity went a bit beyond just being a doctor.
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And I thought that having nonetheless great appreciation
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for the medical area, I thought probably as a life sciences
1:45
entrepreneur, I could contribute more and be more.
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Yeah, in tune with everything else around it, the, the finance
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side, the legal side, the regulatory side and the, the,
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the medical clinical side. And that brings us to life
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science entrepreneurship. Yeah, I love that.
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And it's fact. You go do something, build, then
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go suit another thing, build. What is it about the beginning
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that you like so much? It's exactly that, starting
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something that is an unchartered path.
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I'm AI guess I'm a very curious person and also eager to venture
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into an unbeaten path. And that comes also with the
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interest in bringing together people from different
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backgrounds, different disciplines, different yeah,
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skill sets and starting something de Novo that is
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beautiful to do so and that brought me to Actinium.
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It was a company that it was an idea and had a lot of hurdles to
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overcome that that's that we succeeded in then similar.
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So with Formula Pharma and now Nanocell Formula was a company
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that focused on car T therapy produced in an ex vivo
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manufacturing context. So it, it was differentiated
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with features that would make it more scalable for patients, but
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it would not answer the critical questions about how do you
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overcome patient access limitations such as cost and
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also logistical issues. And as we have seen since the
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the onset, the introduction of CAR T therapies or for that
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matter also TCRT therapies, the patient access has lagged
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tremendously and the commercial opportunity that was envisioned
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has fallen far from expectations.
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And that essentially led to the the foundation of Nanocell
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whereby we are looking to overcome these critical
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limitations such as high costs, the manufacturing logistics or
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the patient's logistics or the time it takes for a patient to
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be treated after being deemed eligible for cardiotherapy.
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And that you can in theory overcome with in vivo cardi.
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So that that brought me to found Nanocell and I have to say it
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has been the most exciting venture yet.
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That's amazing. And you talk about that those
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issues in cell and gene therapy, what what came first?
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Was it the the technology for nanocell or did you spot those
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issues and then go or how do we solve them?
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So did you look at the mistake and then or is it the opposite
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way around? So while I was running Formula
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Pharma and knowing that the company would basically be
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transitioning into an exit right, a sale to to another
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larger company, I was very inspired by a publication that
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came out by Fred Hutch Cancer Centre where they basically
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presented the concept of in vivocardi therapy using
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polymeric nanoparticles and DNA. And looking at that work, I
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realised that 22 limitations that were #1 the technology that
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was described was OK for animal studies but not really adaptable
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for human use. And the second one was that the
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technology was not protected by intellectual property.
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And in order to start a company, you need to have solid IP.
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So not being a company that is a spin out out of academia, the
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inspiration came from that article.
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And so I started looking for technology that was licensable
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and that allowed us to basically bring together the initial
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components needed for the company to launch.
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And that happened in 2021. Amazing.
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Yeah. And then this may well be what
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you, what you were talking about in essence, but but Nanocell,
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it's it's a pretty unique model, right?
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In vivo cell engineering using non viral DNA based technology.
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But can you just break down for people like me how how this
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works and why you think it could be a game changer?
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Right, OK. So for decades delivery of gene
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therapy DNA in that case has been done through viral vectors.
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So that has been very well known and that is also essentially how
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the initial clinical experience as we have now seen from other
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companies resides in in the field of of viral vector
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delivery of DNA. ESO biotech is, is an example
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and but there are limitations with regards to viral vector
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delivery of DNA at the manufacturing level.
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There is a a well known scalability and manufacturing
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capacity limitation potentially also some safety aspects where
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the the viral vector integrates and also potentially
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immunogenicity. So in order to overcome mostly
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the the the the manufacturing cost and scalability issues, you
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would want to focus on lipid nanoparticles because those are
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the most, I would say well known non viral delivery vectors.
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The the experience with LMPS lipid nanoparticles resides a
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lot in COVID experience with the delivery of RNA.
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Now when you want to deliver DNA with lipid nanoparticles, there
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is a long known challenge in getting the DNA into the nucleus
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of primary T cells, right. So somehow the immune, these
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immune cells have complexities and and mechanisms that make it
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difficult for non viral DLA to be deposited, you know into the
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nucleus. We have spent four years with
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the nano cell to overcome those limitations of hurdles and what
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we have developed is a nanoparticle, A lipid
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nanoparticle that contains the therapeutic GNA, sorry DNA in
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the form of a mini circle DNA. So that they say a a gene of
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interest that codes for the CAR therapy or the TCR therapy and
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that is loaded in that LMP also. What we do is we load RNA in the
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same particle and that RNA prescribed for a transposease
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technology. What that means is that the
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transposease takes the DNA and integrates that into the genome
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of the targeted T cell. So we have these two nucleic
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acid components. Then we coat the lip
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nanoparticle with a protein that is a form of a of an antibody
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type protein that directs the LMP specifically to T cells and
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we can also target NK cells, natural killer cells.
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What that then does is provides that specificity of the
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targeting of your LMP to your immune cells of interest.
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And then the T cell takes up the particle.
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And then one last hurdle that we need to overcome is the
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delivery, the transportation of DNA from cytoplasm into the
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nucleus of the T cell. And that requires T cell
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activation. And we activate these T cells by
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way of a fusion protein that combines the targeting of the T
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cell with the activation of the T cell of the T cell.
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The activation is done through CD3 or to say AT cell specific
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antigen that helps activate these T cells and the targeting
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occurs via ACD 7 binding. So that's whole mechanism.
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It's, it sounds maybe simple by describing the components, but
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it is not exactly straightforward because it
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requires the combination of a variety of specific compositions
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of matter, the proportionality, the functionality, the force
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formulation and all that makes it, you know, really A4
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dimensional Rubik's Cube effort to to resolve these hurdles
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associated with non viral delivery.
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But we succeeded. We have been able to transact T
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cells in vivo and turn them into CAR T cells with high
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efficiency. We get 60 to 90% circulating CAR
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T cells in the blood, very long lasting.
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We have data going beyond 140 days.
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We have shown tumor control in mice that carry a high burden of
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highly aggressive leukemia and formal cells and we have been
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able to show elimination of that.
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So we are very excited now to transition to the development of
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our clinical candidate and get to the clinic as soon as
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possible. Yeah, it's awesome, super
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exciting what you guys are doing.
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But I suppose like there's also this, this this aspect of the
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cell therapy space being really exciting, but also at the moment
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at least notoriously challenging.
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How do you see the market and what keeps you so, so optimistic
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on about what you guys are doing?
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The market has been really negatively affected by the lack
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of patients access, right. So we have a very promising CAR
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T mechanism and for the for that matter, it is also TCRT therapy
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that is the same, same approach, but overcoming those patient
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access issues such as cost and logistics that requires really
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the in vivo approach. And why I'm so optimistic is
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that the vast majority of patients that are eligible for
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cardiotherapy are actually available, right.
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They are in the periphery of the highly specialised hospitals.
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And that is exactly where we envision in vivocar T to be
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prescribable and and and administrable in community
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settings where patients can be treated nearby, where they live
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as A and under control of their oncologist as opposed to being
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reliant on a very far geographically distant
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specialised hospital with a limited bed capacity under the
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care of a different team. And so the vast majority of
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patients that actually could benefit from criteria are yet to
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get access to it. And I think that in vivo
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criteria really has that promise that this become mainstream as
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opposed to, you know, a treatment for the few.
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And my personal definition for success for this is actually
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being able to see this treatment prescribed, widely prescribed in
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countries that are typically left out, South America, Africa,
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Middle East, Asian countries, right, that don't have that
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healthcare insurance infrastructure like what we
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have. Yeah.
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And that that's all part of this big bold vision for making cell
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therapy more scalable and accessible that you talk about.
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What? What does that big picture
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success look like for you in say, the the next 5-10 years?
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Well, that's essentially means that multiple clinical
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indications are pursued both in oncology as well as in
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autoimmune disease because CAR T has shown its benefits in
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autoimmune as well. But really to see this type of
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treatment being administered, tested and then commercialized
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in countries that now are left out that I think is the litmus
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test. Are you able to commercialize
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this in India, in Africa, in Middle East, in South America,
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right, those countries that for me would be absolutely a
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celebration for for this field. Yeah, because that's the that's
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the issue at the moment, right? Like this, the cost, the
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scalability, like I see the passion as well in like it, it
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seems like a a problem everyone should be looking at, right.
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But like maybe there's times in the market, it's like, is this
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the right time to be doing something so ambitious?
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But I love like the way you think, the way you guys are
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going about it. I I just think it's awesome.
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This is truly democratising therapy, right?
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There's a lot of words about that, how to democratise, but I
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think that in Vivocaty has that promise.
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But you also want to be most scalable and not have the
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manufacturing limitations, right?
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So that is, that is another factor that weighs in in
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practice, in whether or not you truly can deliver to patients.
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And that is why Nanocell has been able to to stand out as a
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company delivering non viral DNA.
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Yeah, 100 percent, 100%. I mean you, you personally as
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well. You've navigated fundraising,
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partnerships and multiple exits. What advice would you give to
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other biotech founders trying to build something transformative
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today? So what is important is to C to
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keep in mind that that nothing is a straight line and that
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while you keep very focus on a vision and your objectives,
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right, very important to to measure what matters is a great
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book that came out of that that also applied to to biotech.
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But you always need to keep in mind that you might have to
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pivot. And so having a Plan B and plan
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C in mind and being able to adapt to circumstances that
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needs to be part of your, of your tool set and your mindset
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in order to succeed as an entrepreneur.
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And that also applied to to Nano Cell because we started as a
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company working with polymeric nano particle technology.
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And nine months in, we absolutely broke our heads.
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And it goes like, why can't we get this to work right?
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And so we pivot it. So rather than take a a major
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defeat, we said, well, let's take what we learned and put it
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into, into a lipid formulation. And what was important there is
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that with polymeric nanoparticles, we couldn't get
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it to be a stable product, so it fell apart in the process of, of
18:57
producing it. With lipids, you have the type
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of chemistry that actually keeps the, the drug, you know, stable
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and, and, and, but before you realise it, because you go off
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of what you read in, in literature, it takes a while,
19:15
but you can learn much along the way.
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And, and, and that flexibility was very important for for nano
19:24
cell and the the persistence also is very infective for your
19:32
investors, because the investors love to support a team that that
19:40
knows how to overcome and whether through the biggest
19:44
crisis is right because you can that's.
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Interesting. How?
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How does that conversation go when you you go to the invest
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investors who were originally invested in that idea and you go
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actually like, you know, we've got this wrong, we think we
19:57
should take this route. Is that a positive conversation
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in your eyes or? It depends on how you how you
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prepare your investors right. If there's hope and there is
20:11
very clear commitment from the team to to continue because also
20:16
the team you need to keep together, then then investors
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are are really supportive of that, at least ours and we were
20:26
able to that particular crisis year raised twice as much as we
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started only because we actually overcome, overcame a big
20:36
problem. Right.
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Is there an element of that? Because you actually just
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attended it as well? Is there an element of getting
20:44
the right investors as well that are invested in you and that
20:49
journey rather than specifically that that that idea?
20:54
Very much so you you would want to start with investors who
21:00
share a motivation that is not primarily driven by by an exit
21:08
right by money. So the investors that we
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assembled were which you can call visionary investors, right?
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They share the vision of developing an in vivo Cartis
21:23
platform for the benefit for patients because also the
21:27
opportunity is grand, the opportunity for patients for,
21:32
for, for the field of medicine. That is the that's a very
21:37
important mindset that you need to have among your investors.
21:40
Secondarily, of course, there are the financial parameters,
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but our investors were also prepared to accept a set back,
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right, even a material set back. But then it comes back to the
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team, how strong is the team, how committed is the team and
22:03
capable in actually overcoming issues.
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And as we were experiencing already the, the, the critical
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difficulties, we started already working with the pivot.
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And so it was not like, oh, investor, we are completely in
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the blank. We don't know yet what to do.
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Give us some time. We already were able to to
22:28
overlap with data and say, you know, well, this has not shown
22:34
successes far. We are starting to make some
22:38
very interesting breakthrough with another approach, right.
22:44
So let if we can elaborate on that within a certain period of
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time, we expect to to have reached a certain data set data
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point that really is worthy supporting further.
22:57
Yeah. So on a.
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Personal note how do you how stressful is that?
23:03
Like is not really or. It, it is, but you're also as an
23:12
entrepreneur, you need to be willing to look death in the
23:14
eye, right? And to fly on in an airplane
23:18
that has two clipped wings and and have a propeller, I mean,
23:22
and then and then face a big mountain, right?
23:26
That's about right. I mean, how do you think that
23:30
the James Bond's movies were invented with those scenes where
23:34
the last seconds you see that the airplane just go over the
23:37
mountain, right? That's.
23:40
What it feels like. Right.
23:44
Those are the most exciting ones, right?
23:46
These movies, Yeah. Exactly, exactly.
23:49
I love that. And look, wait, it's my final
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question and it's when I ask every guest that comes on the
23:55
Bio hub. I don't know if you've had a
23:58
chance to think about this as well, Maris, but if you could
24:01
have dinner with any scientist or innovator, past or present,
24:06
who would it be and why? Yeah, well, there are a number
24:10
of great, great scientists to to pick out from.
24:14
But I would say one of them, a contemporary 1 is actually Elon
24:21
Musk, right? He is a, a, a controversial
24:26
person, but he definitely has the the status of a clear
24:32
visionary innovator, right. So he can transcend what many
24:36
people believe is is impossible. And that is hugely inspiring.
24:43
And I would love to have a conversation with him because I
24:47
think that Namasal has a bit of that flavor as well.
24:51
Like we are trying to achieve something that has been long
24:54
believed. It's impossible and yet there
24:57
are so many hurdles to overcome. And so I have, I would have a
25:00
lot of questions for him in, in, in that regard, but beyond just,
25:07
you know, being being an entrepreneur and I would love to
25:11
tell him about what Nanosole does and maybe he would support
25:14
it, right? As a good side bonus, 100%.
25:18
I agree with you approach. I think I think you're right,
25:22
Like Elon Musk is, is without doubt like one of the best
25:25
innovators around. And what I like about him
25:27
personally is that he comes up with an idea and then he thinks
25:32
about how he can make it profitable in a business later.
25:35
It's like, well, how do we execute this idea?
25:37
And then money comes after, which I really like, which is in
25:41
in a way like similar to what what you're talking about with
25:43
Dano Cell. Right, Yeah, absolutely.
25:47
And, and also, I would say, you know, comes with in the back of
25:52
the mind is who else would be very influential as, as mentors,
25:57
right, people that that, that you would have a cross path
26:01
with. And on that note, for me, Frank
26:04
Baldino at Cephalon was a very important person.
26:07
You know, I worked at Cephalon and I saw him being a a
26:12
calculated visionary risk taker as an entrepreneur.
26:16
And he built a company from scratch to, to a very meaningful
26:21
enterprise. And what I saw in him is, is how
26:25
he gave autonomy to the teams that were left free in resolving
26:34
the problems and having that freedom of communication and to
26:38
very large extent A lateral form of management.
26:43
And that is so important also for Nanocell because that's
26:46
exactly how we were actually able to overcome the continuous
26:50
flow of hurdles, right? Because when you talk about T
26:53
cell complexity and LMB complexities, you have
26:58
constantly, you know, roads to take that are uncharted and, and
27:02
it comes with hurdles that you need to overcome.
27:04
So complete open communication and freedom to solve issues and
27:11
having the responsibility is also part of our corporate
27:14
culture. And, and so as we started, it
27:20
was like, OK, here we are, we're six people, We are SEAL team 6,
27:24
right? We do everything together.
27:26
We we celebrate together, we fight together.
27:28
Nobody is left behind in what they do.
27:31
And now we have Seal Team 12 and I hope that this is also
27:35
scalable as much as the DLMP technology is.
27:39
Yeah, amazing. Honestly.
27:42
Thank you so much for coming on Moritz.
27:43
It's it's pleasure finance. It like fascinating in
27:47
everything you're saying in terms of the business
27:49
personality, like thank you so much for coming on.
27:52
Thank you, Max great pleasure and look forward to seeing each
27:56
other again. Yeah, absolutely.
27:58
And please everyone like and subscribe to the Bio Hub and
28:02
thank you again, Maris. Thank you, Max.
28:04
Bye bye.