In this interview, we spoke to Andy about Cellistic’s recent acquisition of a GMP facility and how their newly increased capabilities will help them make a bigger difference in bringing iPSC-based allogeneic cell therapies to patients faster. Plus, Andy gave us a sneak peek into some of Cellistic’s upcoming projects and his predictions for how the iPSC landscape will evolve in the next five years.
Cellistic specializes in induced pluripotent stem cell (iPSC) technology. Can you give us a brief overview of what your company provides in this field?
We think we can offer something impactful and useful to cell therapy developers. The technology of reaching targets for regenerative medicine with cell therapies has shown to be promising and effective. They have provided borderline miracle cures and certainly a revolution for how liquid cancers are treated and hopefully cell therapies could be the future of solid cancer treatments as well. But there are logistical and modality limitations of the one-patient-one-dose autologous system.
If you are looking to move into an allogeneic, batch-driven, efficient platform, we believe iPSCs are the way to achieve that. But iPSCs for allogeneic therapies come with some challenges. You've got to figure out how to do several complex gene edits. You've got to stabilize and control a cell line that is trying to differentiate into any and every other cell type. Along with that, the differentiation protocols necessary to reach a therapeutically relevant cell type are their own beast.
We have real expertise in the control and scalability of differentiating iPSCs. We also believe strongly that this should be done in suspension environments, and chemically defined environments as much as possible. Those sorts of principles and precepts drive the value of trying to simplify, accelerate and de-risk moving to an allogeneic iPSC platform. We have deep expertise on differentiation and expansion protocols and processes in biomanufacturing-friendly environments that help scale. It’s that expertise that will help realize that vision of the future of cell therapy.
In 2022, you acquired a GMP facility. How will this enable Cellistic to make a bigger difference in bringing iPSC-based allogeneic cell therapies to patients faster?
I think there are two pieces to that. Firstly, we now have a GMP facility. We can't reach patients without clinically and commercially safe materials. We have to be operating in a patient safe environment and that's not a research bench top. That's not an R&D or even a process development lab. That's a GMP facility. Since Cellistic began we knew that we needed GMP capacity to allow us to be manufacturing batches and helping patients and releasing clinical and commercial materials. The manufacturing unit of Celyad Oncology that we purchased was an incredible opportunity and the facility itself is exciting. We're going to work to refresh the facility and optimize it for allogeneic cell therapy. We could have made that investment in capacity in several ways, but we see this as a huge opportunity because the facility already does exist and has carried GMP certification.
But the facility is probably 30% of the value. It's the staff that were able to bring on as well. And they are the second piece. For us it’s not just about capacity, it’s about capability. And so the opportunity to have 35 people who have made hundreds of batches of cell therapies was unmissable. They've not only made cell therapies, but they made them in GMP, and they've fed clinical trials. They've got huge amounts of experience. There was even an allogeneic phase 3 trial that was fed and supplied by this facility and this team. All of that is a promise fulfilled as well as a huge opportunity to bring in expertise for where we want to go.
What are the challenges in developing allogeneic therapies in comparison to their autologous counterparts and how can Cellistic help address these issues?
For autologous therapies, you’re not particularly worried about scale. You also don’t have to worry much about immune reactions, or the challenges posed by taking something from one person and transplanting it into a lot of people, which of course is at the heart of allogeneic cell therapy.
The challenges of autologous therapies are the variability of the starting material and logistics. You are under immense time pressure to try and force a patient’s cells to expand and grow, while also being genetically modified, all in 14 days or less. Then you must keep that therapy fresh and get it back to the patient.
The challenges on the allogeneic side are also numerous. Are you starting with the right stuff? Are you doing the right characterization? Are you characterizing it the right way? Do you have a full understanding of your starting cell before you reprogram? Are you using the right reprogramming technique for the safest possible iPSC? Do you have control of off-target effects for your gene edits? How do you demonstrate your process is under control when you are driving a very specific endpoint out of a very powerful kind of multiverse? Each of those questions is in some way a very separate and deep challenge.
You heard at the beginning, our focus is on controlling that differentiation and expansion. That expertise of knowing how many passages to do and what subpopulations of the intermediate cells lead to the most potent cells at the end. I could go on and on. We spent a lot of time thinking about that stuff and really only that stuff.
Additionally, doing all this in a six-well dish is great but for allogeneic therapies, it doesn’t accomplish much unless you can produce ten, 80, 100 and 1000 doses out of a single batch. Without scalability, you're not unlocking any promise. You might as well stay with autologous if you can't scale allogeneic. But we have thought about this. We have thought about moving away from feeder layers, moving away from adherent systems, moving to methods that allow us to go from one liter to 50 liters of culture and say we are truly scaling up.
We have really, really smart cell biologists and really, really smart bioengineers. Those two jobs together are what we do. And those challenges, and frankly only those challenges are what we're trying to help solve. I mean, that's enough challenge for anybody.
How do you see the iPSC landscape evolving in the next five years?
We are evangelists for iPSC being the way of the future in cell therapy, and we don't think we're alone in that. We're certainly not the first ones to say that, but we're early on that list, and that group is getting more and more crowded every day, which is exciting for us. It's neat to see even more growth this year, with approved INDs for iPSC-derived therapeutics happening. That's a huge milestone and really promising.
Our history is pretty deep. We’ve been working in iPSC, first in drug discovery and now in cell therapy, for a decade and we're focused and passionate about what iPSCs can do. Right now, we're trying to be enablers and we’re trying to simplify and de-risk the choice to move to iPSC. We can help make it a little bit easier. If you have a great idea that is inhibited by modality, maybe we can un-inhibit it.
I think iPSC is going to grow a lot as we and others succeed in this. It will unlock swathes of the market that right now are waiting on the sidelines for the first adopters to learn all these lessons. A lot of our team deserves that credit for being early adopters and path blazers. We’re happy to be lesson learners in the field of iPSC so we can be a part of a truly transformative time in medicine.
What will be the next big developments in the pipeline for Cellistic?
We have a couple of projects that by the end of the year, we'll have some exciting data on. In terms of platform development, we're excited by what we are seeing with the Quell Therapeutics (London, UK) partnership that we signed in 2022 and potentially reaching regulatory T cells, as well as other immune cells that we are seeing exciting data on.
We are also starting to bring in the first few customers outside of Quell. We have a few partnership announcements planned and we are just so excited about every single one of those. They are the right kind of believers in this modality and the future of the iPSC landscape, so we are humbled to be working with them.
Editor’s Note: This interview previously appeared on www.regmednet.com.