Podcast Transcript

David Brühlmann [00:00:36]:
What if the simple act of opening an incubator to check your cells could compromise the therapy you’re developing? Today’s guest, Farlan Veraitch, Founder and Chief Scientific Officer of Ori Biotech, discovered this when he became the first to automate embryonic stem cell expansion. Primary cells demand a completely different playbook than biologics, one where pH fluctuations, temperature shifts, and shear forces converge to introduce critical variability the moment cells leave their protected environment. This precision matters because widespread patient access to life-saving cell therapies depends on manufacturing processes that deliver consistent therapeutic efficacy. Let’s dive in. Farlan, welcome. It’s great to have you on today.

Farlan Veraitch [00:02:42]:
Thank you, David. Thanks for having me.

David Brühlmann [00:02:44]:
Farlan, share something that you believe about bioprocess development that most people disagree with.

Farlan Veraitch [00:02:52]:
Most people disagree with… I don’t really think there is one. My background—I come from UCL’s Department of Biochemical Engineering, which is where the fundamentals were set in place. How do you scale up penicillin manufacturing in the 1960s? That’s where the whole department kicked off, and the people who taught me are really the founders of how you manufacture biological medicines. So yeah, I’m pretty mainstream in my thoughts. In fact, I truly believe that the work we’re doing now with cell and gene therapy, we’re not doing anything radical. We are following a tried-and-tested playbook and just applying it to a new modality that lies at the core of what Ori Biotech does.

David Brühlmann [00:03:33]:
Take us back to the beginning. As you mentioned UCL and your time at university, what sparked your passion for biotech, and what were some pivotal moments that shaped your path to becoming what I call a cell therapy automation pioneer?

Farlan Veraitch [00:03:50]:
It was a very clear moment. There was a series of talks being given really at the interface between the research going on in the Department of Biochemical Engineering and the industrial partners working with the group. And there was a presentation by the founder of the department, Professor Peter Dunnill, and his PhD student. They had started working with one of the early CDMOs that was making plasmid DNA in E. coli. They were called Cobra Biologics.

They were doing something so smart. At the end of the process, they had to disrupt the E. coli to get the plasmid DNA out, and it was contaminated with all of the other nucleic acids and intracellular components. The real challenge was the downstream processing. What they did was genetically modify the host so that when you disrupted the cell membrane, you released large amounts of RNA into suspension. The RNA essentially bound up all of the non-DNA nucleic acids before downstream processing.

That caught my attention. I was like, wow, that’s super neat. There is a lot of creativity that needs to be applied in this field, but it’s industry-focused, and there are clear commercial gains associated with brilliant scientific work. I was sold at that point.

David Brühlmann [00:05:15]:
Yeah, that sounds exciting. And then what were some other steps as you were going through undergrad and then doing your PhD? What were some highlights there?

Farlan Veraitch [00:05:23]:
Again, another talk at UCL, this time from the head of a legendary team at Lonza Biologics. They were optimizing how you manufacture monoclonal antibodies. I saw this talk from John Birch, and I knew straight away I needed to work on this challenge: how do you scale up monoclonal antibody manufacturing, and how do you drive down the cost of goods?

So I did a PhD. I moved university, but the project was in collaboration with Lonza Biologics, and that was between around 2001 and 2004. It was such an exciting time. You had this explosion in our ability to manufacture high-titer monoclonal antibodies in bioreactors. What we saw during my PhD was a tenfold increase, with people pushing titers to over 10, even up to 15 grams per liter (g/L) and beyond.

That had a tremendous impact on the entire industry. Most importantly, it had a huge impact on the business of biotech, enabling therapy producers to actually sell large volumes of product. We went from very niche products with relatively small patient populations to manufacturing at a scale that could meet worldwide demand, and doing so at a low cost of goods. These became much more broadly accessible products.

Biotech companies like Amgen and Genentech were, for the first time, able to reinvest the profits from their early wins into a vibrant pipeline of products. That really helped build the biotech industry. It’s so important not just to have a vibrant pipeline of exciting molecules and therapies, but also a manufacturing process that allows you to profit and reinvest in that pipeline—which is very expensive. The development of these medicines is extremely costly. Until those two platforms work seamlessly together, I don’t think you really have a viable business.

David Brühlmann [00:07:27]:
And this was a time when, as you said, a lot happened in biologics. We went from 1 g/L to 2 g/L, and then, as you said, to 10–15 g/L, which is massive. What did this experience teach you about gaps you were seeing in the business model or the challenges at that time in biologics?

Farlan Veraitch [00:07:50]:
Very much so. As I said before, the ability to increase the titer meant that you didn’t have to build huge new manufacturing facilities. I don’t know if many people remember, but at the time there was a real panic—people were building 20,000-liter bioreactors as quickly as they possibly could to meet demand for these amazing new therapies.

But there’s a huge cost and a massive amount of time required for that, and then you have technology transfer on top of it, which is extremely challenging. Increasing capacity through large infrastructure projects was really holding the industry back. Once you started pushing titers higher, you could meet global demand using existing manufacturing facilities. That greatly reduced the time needed to reach the market.

Time is an incredibly important metric in the development of medicines, and scaling up your manufacturing process is something that needs to happen quickly.

David Brühlmann [00:08:55]:
Following your experience in biologics, how did you transition into cell and gene therapy? Draw us into that twist.

Farlan Veraitch [00:09:04]:
It was really two things happening simultaneously. Watching the work at Lonza, part of me was thinking, these guys have nailed it. I could see the trajectory they were on, and I knew they were going to make it even better. You were starting to see the biotech industry truly blossom as a result.

So as a young scientist–engineer, I was looking around and thinking, what’s the next class of medicine that’s going to have to go through this same challenge? At the same time, in the lab next to us at the University of Birmingham, where my academic group was based, people were starting to grow embryonic stem cells. I became good friends with the group in that lab, and it was incredible to see the potential. They were taking embryonic stem cells and creating seemingly any cell type they wanted.
Immediately—in the pub, in the student union afterwards—we were getting incredibly excited about the therapeutic potential. Everything from Parkinson’s to diabetes, heart disease, forms of blindness—the list went on and on. But it was also very clear to me that there was no way cell-based therapies would be able to scale as they were.

The fundamentals of what I saw when I went into those labs were all about variability and control. You had these innovative teams, but within a group there would be individuals who were exceptionally good at controlling the cells, and others who simply didn’t have the knack. When they published their work, other labs around the world couldn’t reproduce the results. They would literally have to send individuals from one lab to another to replicate the experiments.

The human influence on these manufacturing processes was tremendous. On top of that, the cells coming from each patient were radically different. So you had two massive sources of variability stacked on top of each other, which was really stopping the field from progressing at the rate it wanted to.

David Brühlmann [00:11:05]:
What are the reasons that stem cells, in particular, are so sensitive? And can you tell us a bit about the main factors that influence these cells?

Farlan Veraitch [00:11:16]:
It’s not just stem cells—I think it’s all primary cells. We’re seeing that variability in CAR-T just as much as we saw going from one embryonic stem cell line to the next, or one iPS line to another. You have inherent biological differences—differences between your biology and mine, differences with age, for example.

With CAR-T cells, there’s also a lot of variability driven by the treatment regimens patients have already been through. These are major sources of inherent variability from one patient to the next, and I don’t think we’re ever going to escape that. That’s a fundamental part of this field and something we have to embrace. The fact that the cells come from each individual patient is exactly what makes this area so exciting.

You can clearly see differences in efficacy. We now have data comparing autologous and allogeneic approaches, and you can really sit down and appreciate the power of autologous cellular therapies. So we have to deal with patient-to-patient variability. But what that means is that we must absolutely minimize every other source of variability.

That realization came to me very early on—back in 2005—watching people culture these cells. I realized immediately that if we were going to have so much variability from one cell line to the next, from one patient to the next, then we needed to automate. We needed to replace reliance on highly skilled individuals, understand what they were manipulating in the environment during cell culture, and begin to standardize the manufacturing process.

David Brühlmann [00:12:59]:
Yeah, so in other words, we need to take out the human variability because it’s not only in stem cells or primary cells—we’ve all seen that. You’re listening, smart biotech scientists: you’ve seen in the lab that there’s variability between operators. That’s part of the game. But what I’m hearing so far is that this becomes much more critical when we manipulate these highly sensitive cells, where suddenly a slight variability results in a huge difference at the end of the day.

So tell us a bit more: what are the main parameters you need to carefully control, what is the solution, and how did this lead you to developing automation for these cells?

Farlan Veraitch [00:13:47]:
As I emerged from my PhD, I went back to UCL and did a postdoc there. During that time, we built the first-ever automation platform for embryonic stem cell culture, as well as the directed differentiation of embryonic stem cells. That was around 2006–2007.

Before building the automation platform, I carried out a fundamental study in collaboration with one of the leading stem cell groups in the world—Austin Smith’s lab in Cambridge. I was incredibly lucky. I spent weeks there just watching the best cell culture scientists in the field at work. I came in with a whole set of hypotheses, but what struck me immediately was how quickly they worked and the very high level of skill they demonstrated. They didn’t appear to be exposing the cells to any harsh conditions—it was actually beautiful to watch.

I went back to UCL and started to systematically uncover what happens when you take cells out of an incubator, pipette them, centrifuge them, and then culture them. What I realized was that skilled human operators were getting the cells out of the incubator and back in very quickly, and that was tremendously important. The reason is that when you take cells out of an incubator, you expose them to ambient CO₂ and ambient temperature, which leads to changes in pH and temperature.

I started investigating this further and realized that both the expansion and differentiation of stem cells were influenced by transient shifts in pH and temperature that occur during these handling steps. I then went a bit deeper and started thinking: the really skilled operators also don’t look like they’re being harsh with the cells. So I began exposing stem cells to transient shear forces. That turned out to be fascinating.

What we observed was a very clear relationship between how much transient shear force the cells were exposed to and their proliferation once they were returned to the incubator. This ultimately resulted in a landmark paper, where I deconstructed how the cell microenvironment is manipulated by human operators and identified what we needed to be extremely careful about when designing automation for this field.

David Brühlmann [00:16:23]:
And how did these observations—that pH, temperature, and shear forces have such a strong impact on cell cultures—lead you to design the first automation system? Because, as I imagine, what you were seeing in cell therapy is quite different from what we typically see in biologics.

Farlan Veraitch [00:16:47]:
Absolutely. There was nothing available to solve this problem, so I had to build it. As a young engineer, you have to start by pulling together some off-the-shelf components—you can’t make everything from scratch. So I bought an automated incubator, cut a hole in the liquid-handling deck, and put a centrifuge underneath it.

But the key thing I did was place the entire system inside an environmentally controlled hood, where the temperature and CO₂ levels did not change during cell manipulation compared to when the cells were being cultured. Immediately, you saw very clear benefits in terms of reproducibility once that level of control was implemented.

One of my favorite papers from that period was when we started working under hypoxic conditions. Hypoxia is a very important tool for enhancing the differentiation of stem cells. One of my favorite results was performing low-oxygen differentiation without exposing the cells to ambient oxygen every time the media was changed. That had a radical impact on neuronal yield. We were making neurons back then, and the yield went up dramatically just by eliminating exposure to ambient oxygen during routine media changes every couple of days.

It’s a great example of how we need to think much more carefully about environmental control in cellular therapy manufacturing processes.

David Brühlmann [00:18:14]:
You’re making an excellent point here, Farlan, and I want to highlight it once again. The needs and requirements for cell and gene therapy are fundamentally different from what we typically see in biologics. This requires us, as scientists and engineers, to completely rethink established systems and adapt them to the specific environments we see in cell and gene therapy.

This brings me to the system you developed at Ori Biotech. Tell us about the strategic choices you made. When I look at the system, it appears very flexible and modular. Given all the learnings you’ve accumulated across different labs and many years, how did those insights influence your development approach?

Farlan Veraitch [00:19:04]:
Let’s go back to that original automation platform. I built it, published the work—and nobody ever used it again. It literally sat there collecting dust. Fundamentally, the automation wasn’t suitable for early process development (early PD). I realized very quickly that what I had built needed to be something that could be placed into any lab. That was critically important.

I needed a system that provided all the required functionality, but that teams around the world could use to develop new therapies and test them in mouse models long before they ever thought about scaling up—while already working on a platform that controlled environmental shifts.

That realization led me to conclude that we had to take a modular approach when building the infrastructure—but a modular approach that also eliminated exposure to ambient conditions. This ultimately led us to split Ori’s platform into two core modules.

Ori has one module that is fully controlled at 37 °C and 5% CO₂, where all cell culture steps can be completed without ever removing the cells from the module. That’s IRO®, which we’ve brought to market. The second module, which is currently under development, is designed for upstream and downstream processing—including washing, cell selection, preparation for freezing and shipping, final formulation, electroporation, and potentially other unit operations as the field continues to evolve.

David Brühlmann [00:20:50]:
This wraps up part one of our conversation, in which we’ve explored Farlan Veraitch’s journey—from pushing mAb titers to pioneering cell therapy automation. We’ve also discussed why cells demand exponentially tighter specifications than traditional biologics, and the critical moments during manual processing when pH, temperature, and shear forces introduce process variability.

In part two, we’ll discover how Farlan translated these insights into IRO®, a modular automation platform designed to eliminate human variability and enable point-of-care manufacturing. If you’re finding value in these conversations, please leave a review on Apple Podcasts and share the episode with a colleague. Thank you so much for tuning in, and I’ll see you in part two.