Hi everyone, welcome to episode 137 of the Cell and Gene podcast. I'm your host Erin Harris, and in today's episode we're talking about how big pharma is thinking differently about modality selection in this era of genomic medicines. My guest is Silka Pollin, PhD. She is the SVP and head of therapeutic modalities at Roche Pharma and head of the Roche Gene Therapy Center of Excellence. You'll be just as enamored and impressed by her as I am. She's a scientist by training. She's a very people-focused leader by nature. She's the former CEO of Spark Therapeutics and now she's a professor of practice at ETH Zurich, teaching science to medicines.
Silka and I talk all about why Roche starts with the disease and not the modality. And we talk about how an integrated center of excellence helps close that gap between a promising idea and then the actual medicine. She and I talk a little bit about AI and how it is already creating value in genomic medicine versus where expectations are kind of running ahead of reality. She and I talk about the milestones that would signal that genomic medicines have truly gone mainstream for common diseases. I think this episode is really important because as the genomic medicine field matures, success is going to depend more on than the advancing of the technology. It's going to depend on making smarter decisions about which modality can solve the problem and ultimately deliver that meaningful value to patients.
This is a really great episode that centers on modality strategy, that translational confidence, and the practical path to patient impact. So without further ado, here is my conversation with Roche's Dr. Silka Pollin. Enjoy.
Silka, welcome to Cell and Gene the podcast. Thank you so much for your time. What a pleasure to have you as my guest, and I'm really looking forward to our conversation today.
Happy to have you here. Thank you so much. I'm super excited about being here, Erin.
Terrific. So, let's just jump right in because I have quite a list of things I'd like to get through with you during our discussion today. First up being, tell us a little bit about your background and what being the SVP and global head of therapeutic modalities at Roche Gene Therapy Center of Excellence, excuse me, really entails.
So, I'm a biologist by training and I've spent more than 25 years in drug discovery. I grew up in a working-class family in Germany in a so-called rural region, so coal and steel country, and no one around me had ever been to university. So really there was no map for any of this. It was sheer curiosity that led me to studying biology. And then in 2000 I joined a small biotech in Munich in Germany. And this is where everything for me clicked. I realized that turning science into medicines is one of the most fascinating problems that you can try to wrap your head around. And I've been working on it ever since and I'm still completely in love with it. So today, as you said, I lead two units in Roche. One is what we call therapeutic modalities. This is our drug discovery organization and this is where we invent, discover all the molecules that may at some point become medicines. I also lead the Roche Gene Therapy Center of Excellence and there we bring together gene therapy expertise and capabilities from across Roche, the entire ecosystem in R&D, with a goal of bringing the potential of gene therapy to broader patient populations. So basically you could argue these are two very different roles. But I think the underlying question is really the same and that is how do we use the best science and the right technology to create medicines for patients.
Oh terrific, and what a backstory. And I can tell how passionate you are about what it is that you do, and I could just hear it in your voice. So, wonderful. Thank you for your time. Let's talk a little bit about the fact that you oversee modality strategy across biologics and small molecules and genomic medicines, as you're saying. So as gene editing, RNA therapeutics and cell therapies continue to grow and mature and evolve, how is Roche deciding which modality is best suited for a particular disease rather than trying to kind of fit every problem into some gene therapy solution?
That's a great question. Love the question. So I think the most important point is that we always start with the disease, not with the modality. What are we actually trying to do? What are we trying to change? Which cells, which tissues do we need to reach? Does the effect need to be temporary? Are we looking for a permanent effect? And what risk and treatment burden is acceptable to the patient? So interestingly, the modality answer to that is not always black and white, and I want to really point to one example that I think is super strong in that respect. So when we think about spinal muscular atrophy, it's a devastating disease and I always come back to this example. We have now seen where there was no treatment option available at all a few years back, we have seen three very different therapeutic modalities coming to the fore: an oligonucleotide, a gene therapy, and a small molecule splice modifier. So they work in super different ways and they give patients different options. So this is also why I feel super fortunate that Roche is a company that is not built around one specific technology or forces us to use one specific modality. Otherwise we would have to go find the problems we can solve with this. Right? But we can ask the honest question every time: what does this medicine need to do? Which modality has the best chance of doing it? Or do we even have a situation where we can imagine that different modalities could do the job? So I think biology should really guide us and tell us what the problem is that we need to solve. But then also, of course, a novel modality can completely change what we believe is solvable, and I think that's super exciting.
Yeah, it sure is. It sure is. I think starting with the disease and working your way back, you know, working backwards really makes the most sense. You're right. Okay, so a little bit more on Roche's Gene Therapy Center of Excellence. What would you say are the biggest advantages of having a centralized center of excellence? And how does that structure help reduce that technical risk and accelerate development compared with these more decentralized models?
So, I don't think of this really as a centralization. I think of it as an integration. So when we think about gene therapy, it is a complex modality as we all know, right, and it has a set of problems that I think are all interconnected and tied together. You need to understand the disease biology and then you need to write payload. You need to deliver it exactly to the right cells. You need to understand safety immunology. You need to manufacture the medicine in a reliable way and at scale. And none of these questions seem to be independently solvable for me. You can have a beautiful payload, but if you cannot deliver it to the tissue of interest, you do not have a medicine, right? You can have a promising delivery technology, but if you cannot understand its safety or how you manufacture it consistently, you also don't have a medicine. And that is what we want to do with a center of excellence: bringing the right experts from across the R&D ecosystem and from manufacturing together around the same problem instead of leaving each program to solve everything on their own. So what we do is we combine the deep gene therapy expertise with disease biology, with human model systems, computational science, safety, development and manufacturing capabilities from across the Roche universe, and this is something that you can only do at scale in a bigger company. So scale per se is important. Some of the challenges, better delivery, more predictive human models, manufacturing at scale, cannot be solved one program at a time. You need to really have a sustained investment and you need to be able to learn across different programs in your portfolio. So what we learn in one program should benefit the next one and we should not relearn the same lesson in every program. That's for me the real value of having a center of excellence: creating the best possible team around each problem and then closing the distance between the interesting scientific idea and an actual medicine for patients.
