Resilience in Neurodegeneration: Prilenia’s Journey in Huntington’s Disease Drug Development

Thank you, Kieran. It's such a pleasure to finally do this conversation together. As you mentioned, I really remember when we started working together, back in the early days of 2020 — the crazy 2020, which we may come back to. I'm really looking forward to this conversation, and how it turns out.

Kieran @ Seuss+ (02:12)
Great. So my first question is actually — we talk a lot about the journey of developing an asset in the biotech world, right, and about getting a product from inflection point to inflection point, to market. But there's always a journey that got you there, that got all of us in this industry to where we are. So I think it's really interesting to hear — what was your journey up until the point you joined Prilenia?

That's a great question — partly because my background really isn't the typical way people get into biotech or the life sciences. I started my career in a very different field — foreign policy, national security, and government. What I loved about that was the ability to work on strategy, on planning and operations, figuring out what needs to be done, and then driving it through. At some point I decided to look at where else I could apply those kinds of activities, those passions of mine. And, completely serendipitously, I ended up at Teva Pharmaceuticals — that's back in 2013.

The Teva team at the time included Michael Hayden, who's now CEO of Prilenia Therapeutics — we'll mention him again later — and they took a chance on someone coming from government, on the idea that some of those learnings could actually apply to big pharma. I ended up in a business operations role within Teva R&D, which was a pretty large organization, and I fell in love with the team, the field, the passion it involves — the ability to actually drive toward making real impact on people who really need it. That whole notion, which sometimes becomes too much of a cliché in our industry, of real unmet need in patients' lives — I really fell in love with that, and with what I could do to help move things forward. I spent about five years at Teva.

We worked on many things, went through ups and downs on a larger pipeline, and other difficulties. Teva itself ran into financial difficulties, which is no secret to anybody, in 2017, and at that point had to shelve a few products. At the time I was Chief of Staff of the R&D organization — a global organization of about 2,000 people — and we had to shelve a few pipeline products we were still very excited about. One of the things Teva did that I think was very respectful was staying open to finding new homes for these drug candidates, rather than just letting them sit in the doghouse. Three companies actually started out of that: 89bio, Clexio Biosciences, and Prilenia Therapeutics.

I had the privilege of taking the drug candidate pridopidine — which is what Prilenia has been built around — and developing it further, taking it to the next steps of clinical development, first for Huntington's disease, and later for ALS as well, and building a company around it. That's really what we're talking about today.

Kieran @ Seuss+ (05:51)
Yeah, I think that's so interesting, in an industry — especially small biotech, small pharma — where a lot of strength gets visualized through a very specific background: a medical background, a scientific background. We definitely love our key opinion leaders, our in-depth experts. And I think what you're describing is really what, in this case, Michael — but also you — recognized by coming from a completely different industry: how to get through an executional phase. Clinical development, in essence, is defining a strategy and then executing on it as focused and rigidly as you can. That doesn't always require a specific pedigree. And I think that's been visible over the last five years — that Prilenia, originally, but also more recently, has shown that bringing in different expertise brings a different kind of strength, a different focus too. I'm sure you have your own stories of things that surprised you in clinical development, in drug development generally.

But now we're in 2025 — and this year you announced a partnership with Ferrer, which is very exciting, a really positive development and milestone. That's one of the highs, right — one of the ones we talked about. But I know over the last five years many different things have happened, and you, as COO of Prilenia, have had to make adaptations — in the company, in your strategies — and take action. So I'm going to read this next question, because I think it's a good one and I'm afraid I'll botch it otherwise: we know the neurodegenerative disease area is challenging — every disease area has its own challenges, to be fair, recognizing I'm agnostic here — but neurodegenerative is a minefield for R&D. So I was curious — what actions have you and the team taken specifically, over the past few years, to navigate this space?

That's again a great question. I think one of the things that drives us is a real adamance in the neurodegenerative space, and the passion to actually tackle what feels like an insurmountable problem, working on these rare diseases — in our case, first Huntington's disease, then ALS — and just driving through, dealing with all the difficulties. I think we've been trying to find the best way to overcome the challenges of running effective clinical trials in this space. We face the same challenges everybody else faces, and we always try to get through and overcome them — with the science, with our passion, by involving both the experts and the community, and by involving the patient voice and the patient community, trying to find the best way to drive things forward.

You mentioned that we're at a point of a high right now, and I think it's important to say — it hasn't always been like that. When we started, it was a very different situation. We had to take this product — it was five of us — and build the company almost from scratch, with a lot of help. Teva supported and helped in the beginning, with the handoff and throughout with things we needed. But it was us, along with our initial seed investor, Talisman Capital, back in the US. We embarked, relatively quickly, within a few months, on a fundraising process — and that actually took a very, very long time. Initially, when we met with potential investors — and we met with a lot of them — that was right in the biggest hype of gene therapy and ASOs. People looked at us and said, why would you continue developing small molecules? There's no future for small molecules in this space, in Huntington's disease. We had to hear a lot of no's — meetings with investors where you feel like everything's going great, and then the no comes really quickly. But we got through that, and kept going, because we really believed in the potential of this drug to make an impact, and in the need to do it. It took a lot. And then we secured our first Series A funding, with Forbion — who's had its own journey too, I think, since 2020 — as the lead investor, and built a syndicate around that with really great investors, which also allowed us to build a good board.

The funny thing that happened is that when we were about to close that financing, it was March of 2020. Michael Hayden, our CEO, and I were basically about to fly to the Netherlands when the quarantine started across Europe. So we cancelled the flight at the last minute, and did our last piece of due diligence from home instead — which was, in some ways, our first step into doing things virtually, because until then, all those meetings, all the meetings with investors, had been in person.

And then we had to go through closing the financing during the outbreak, starting a trial during the outbreak, dealing with all of that — figuring out how you start a trial in a completely unknown situation, and handling that risk, and running through it. Then, going through all of that, we also ran into some of the difficulties everybody in drug development goes through — things that come up in clinical trials that you need to deal with, interactions you didn't think you'd need to handle. And then even our results — our initial results, actually, in ALS, as part of the ALS Healey Platform Trial, which was also a great project, though we probably don't have time to talk about it much today — those results came in, and you have to figure out: what do you see, what does it mean, what can you take from it? Is there enough there to take the drug forward? I think it's been persistence, and the ability to just focus, dig deep, and not give up at the first piece of bad news on anything, that's helped us look at things methodically, and, through the science, find explanations for what we're seeing, and figure out what learnings we can apply and move forward with. So yeah — we've had to go through a lot of that, throughout the years. I have countless examples.

Kieran @ Seuss+ (13:33)
Yeah. So it's the intersection, right — of the financial, the scientific, and, in your case, and really all of our cases, the political too — and how all of that intersects to allow you to continue developing your organization, and get an asset to the patients and loved ones you're trying to serve. It can be a minefield, and outside of driving focus, excellence, execution, and not being deterred, there are moments in those last five years where you're constantly being asked, so what's the new direction, what are we doing with strategy — and these shifts, because of environmental changes, and this intersection of things that were, in some cases, unexpected — COVID, and the financial landscape's evolution over the last few years has been interesting too. So how have you adapted your strategy — organizational or clinical development — to the changing biotech, political, or commercial landscape? How have you done that over the last five years, through some pretty significant changes?

Yeah. So I think it's a strength of ours, as a company and as a team, to identify the moments where we need to adapt, and to actually do that pretty quickly — our ability to remain agile. We're small and mighty, as we said at the beginning — well, not as small anymore, we've grown to about 45 now, so 9x over the years — but it's still that mindset: you see something, you go through it, right, you go through the tension in order to overcome it.

I think our focus on analyzing the situation, figuring it out, and then adapting, is part of our deep culture, and we've been able to build a team that has those capabilities too — able to handle uncertainty, actually embrace it, and not be deterred by it, or by the need to change. It's something we put an emphasis on in the hiring process too, which I think is really critical. You have to adapt all the time — I think that's true in every field, but definitely in biotech, which is a whole different level of a rollercoaster that we all need to go through. It's the ability to say, okay, now we're in a high, now we're in a low, and you just go through it, and adapt.

I think we've been fortunate to have the team we have, to be able to do that. In our field, people often say — in high-tech it's mostly people and a little bit of technology, and in biotech it's all the technology and a little bit of the people. I don't think that's exactly the case — I think people really make the difference. Without our team, a lot of other teams would have given up, might not have been able to withstand all the shifts, the changes, all the challenges. Sometimes you just have to face the adversity and deal with it. We have a strong team that, as you mentioned, has had to face challenging situations. We have a team in Israel — myself included — where, on October 7th, we were working on very important elements of our regulatory strategy at the time, on Huntington's disease, when the war started, and we never missed a beat. It's a crazy thing to even think about — that we have a team dealing with a lot of both anxiety and tragedy all around them, and still so determined and passionate about what we do, and what we're trying to do for the community we're trying to serve.

Kieran @ Seuss+ (17:57)
Yeah, I would completely agree with that. As I said, I've had the privilege of being a partner on that journey, so I know quite a bit of the insight, and quite a bit of the passion and the drive of the individuals involved. What I'd also say is the respect for different expertise, and the lack of fear to run into friction — to say, "but I don't agree." Being focused on the humans, the people, the patients and their loved ones, doesn't mean you avoid the things that are difficult or uncomfortable. The environment makes things uncomfortable enough on its own, and part of resilience is also going through difficult situations together — that doesn't always mean agreeing. We've had the same, right? And I think some of it is: we're going to get through this, this is what needs to be done, because there's a laser focus on why you're doing something together. I'd a hundred percent agree with that — the resilience and grit has been beautiful to watch, because you were right, it's not just one thing — not just the data, not just the science — it's a complex interaction of multiple things, and I'd agree that the people in it are just as crucial. Maybe not a 50-50 balance, but pretty close, in order to find success — not just to find a valuation.

So, I have one more question. We were just talking about the why, right. And one of the things that can be — I don't know if I can call it irritating, but it is kind of irritating — is that in this industry we spend a lot of time talking about things, but not always acting that way. Patient-centricity is a great example. I really think there's been a big evolution over the last few years — I see the dedication, the determination — but with the complexity of financial, political, and regulatory challenges, we sometimes forget the why: the patients, the loved ones. Last week, another client of ours posted something about their cystic fibrosis study, and it reminded me that what we're doing is helping patients breathe. And then I thought, god, it's helping a mother hug her children. It's just a big reminder that sometimes we forget, in the daily grind. So what I think would be great for our listeners is to hear about the engagement of patients, families, and their loved ones in the R&D process — because I've seen your uniqueness, your strength, the dedication, the reminders, pulling this group closer, understanding why this matters and what's needed. What impact has that had on Prilenia's development path — your strategy, your approach? What was the impact of this patient- and loved-one-centric approach?

Yeah, so I think this probably starts before Prilenia. I mentioned Michael, our CEO — he's been working on Huntington's disease for so many years, starting back in his medical school days, in South Africa, working with families affected by Huntington's disease, which is a devastating disease that affects whole families — sometimes called the worst disease known to man, because of the many ways it impacts individuals and their families — children who are no longer children, having to take care of parents, knowing they may have the same fate as their parents.

When I joined, in the Teva days, Michael had first brought Huntington's disease to Teva — and by the way, there's another drug Teva later marketed for Huntington's disease, Austedo, which was also part of that journey. That sentiment was so ingrained in our team, that's what we built on — and when the initial Prilenia team came out of that Teva R&D group, that's what brought us together, and kept us going. I think we've always stayed close to the patient community — to the Huntington's community, and later the ALS community too, and we continue to do that. It's so much a part of how we are that it's tough to say what impact it had, because—

Kieran @ Seuss+ (22:27)
Yeah, I don't—

—well, all that we are is that. So I feel it's such a big part of who we are that it's hard to separate.

Kieran @ Seuss+ (22:36)
Yeah, it is, right — it just is.

Yeah, yeah.

Kieran @ Seuss+ (22:40)
It's part of your guiding light. It leads — not every, but a lot of — decisions, and that makes it even more worth fighting for. It's almost one of the reasons the resilience, the strength, the ability to get back up and move forward, is so powerful within Prilenia. You see a bit less of the volatility you might see with other companies who have a great career, or an interest in the science, but perhaps don't have that strong why, that connection to the patients, that comes from Michael, but is really throughout your whole company — and something I've seen you remind your colleagues of as well. It's good to see.

So — but one of the funny things about resilience is that in the moment you need it most, you feel it least, right? The scraped knees, the broken teeth, getting up again — the "we're fine" feeling of leadership when it may not actually be fine. This is a setback, this is painful. The lockdown, in that moment, wasn't just painful — the anxiety was huge. Dealing with the data, the top-line results, the path forward from there, the moment you and your colleagues are asking, how safe are we, how much are we even going to be able to continue — because of a really significant political issue, that also becomes very personal. And now we're seeing it with the political changes in the US too, creating a lot of that sense of lack of safety, or lack of predictability. So — if you could go back to any moment in the last five years, any moment when you needed the most resilience, for whatever reason, what would that moment be — if you could go back to yourself for five minutes, what would you say? So, what moment, and what would you say?

Hmm. Yeah, that's a great, and a tough, question — because on our journey, you know, we're never the same, and I think our experiences, in general, shape us. Typically, when people ask, "would you go back to any point," I'd say no, because then I wouldn't be who I am. But I think, as you mentioned — yes. Even though, looking back, we can see how we overcame the challenges, that doesn't take away from how hard they were — and in some cases, still are.

I think there are maybe two points, personally, I'd go back to. Yes, the COVID days — at some point it was just, are we even going to get this through, is there going to be a clinical trial that starts. It was a crazy world, it just was crazy. But usually, when there's a crisis, you do get through to some new equilibrium in the end — but we can get through it.

I think if you go to October 7th, or to the results, or now, with everything going on — I'd say, on the global level, or at the industry level — when you're in the middle of it, in the middle of the storm, it's very tough. But at some point, we're humans, so we adapt to everything, that's how we're built. I think it's just a reminder, even to myself, that at every step of the way, we'll find a way, and we'll get through it, and do it together. All those points where we faced those difficulties, we just have to remind ourselves of that — because every time, in the moment, it feels like, this is really bad, and it's tough to see how you get to the light. It's more about knowing that we will.

Kieran @ Seuss+ (27:08)
So — not sugarcoating the fact that it's difficult, that it's going to take, in your words, a hard day's work. I'd add — embrace the friction if needed, respect the expertise you have around you, and keep going, all along with a focus on the why you're doing it. Thank you so much, Limor — it's been a huge pleasure to have this podcast together. I look forward to many more of these conversations in the future. And for all of our listeners, please do subscribe — feel free to listen to all of our other podcasts as well. Thank you again, Limor, and I hope you have a great day.

Thank you, Kieran. It was a pleasure.