Optimizing Cell and Gene Therapy Development: Tackling Challenges, Learning from Vaccines, and the Power of Strategic Partnerships

To start with, please could you introduce yourself and tell us a little about your role?

I am Peter Abbink, I’m the Managing Director of Batavia Biosciences, Inc. in Massachusetts. I manage the operations in the US, we are part of a global CDMO, but I’m responsible for the US portions of it.

In supporting drug development from process development to commercial manufacturing, what specific challenges do therapeutic developers face in these stages?

There are lot of challenges along the way. It starts with early process development where you want to get higher titers and understand the basics of your process pretty well.

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But you have to have the end product in mind – you want to think about what you are going to do in clinical management later, and how this is going to impact your cost of goods, your titers, the quality of the product you’re making, and how it is logistically going to be executed.

So, the people in the lab need to have a process that is doable, and when you think even further about commercial, cost of goods is a major player, of course, in drugs and treatments. So that comes early on – what materials are you going to use, how long do you incubate processes for – those are all important things to think about.

How can these challenges be addressed?

While addressing the challenges that you occur during process development can be done in different ways, it depends a little bit on the challenges that you have.

If you think about maybe just a biological challenge, maybe your virus or product doesn’t reach the titers that you anticipated, you might want to look at how can you increase those titers, such as by using different medias, harvesting at different times, maybe using different pHs or different settings of your bioreactors.

If that helps you do that, obviously if you fix the problem you can move on, but there could also be other challenges such as availability of materials, and you have to make choices based on where you are going to get your material from that are not always under your control. You’ll rely a lot on vendors, you’ll rely a lot on partnerships that you have formed over the years that that will hopefully help you overcome those challenges.

What lessons can be learned from vaccine development, and potentially applied to the development and manufacturing of cell and gene therapies?

Well, a lot of lessons can be learned from vaccine development and applied to viral vectors for gene therapy applications.

Vaccine development has been ongoing for a very long time and actually, Batavia Biosciences is, by origin, a vaccine developer. We have a lot of experience in vaccine development, a lot of hurdles overcome, a lot of challenges that we incurred. I think those lessons are similar because viral vectors for gene therapy, they’re also viral vectors that grow in cells in similar ways. There might be nuanced differences, but I think you can apply these lessons with the team that you have gone through those challenges with.

Batavia is lucky enough to have people who have been there for a long time, so we can use that experience.

There are some unique challenges with gene therapy. Titers for doses are often higher than a vaccine, so those are challenges that the field occurs in general, and that is something that everybody is working on.

How could higher titers help reduce the cost per dose for cell and gene therapies?

That’s an easy question. So, higher titers to reduce cost of goods sort of goes hand-in-hand. As I just mentioned, the high titers seen for gene therapies are really the major cost drivers because you need a lot more process development, a lot more work, a lot of consumables, much larger volumes to grow your virus in, and those are all directly linked to your cost of goods.

If you can reduce those volumes, reduce the consumables because you’re making much higher titers, then that will have an immediate impact. How to do that is not as easy. Process development to optimize your titers is really where it all starts.

How can process development optimize and enhance upstream processing, for higher impact production?

There are many components to process development or to a manufacturing process in the upstream part that can impact the titers.

It’s sometimes as simple as incubating a little bit longer and harvesting at a later time so that your cells have more time to produce virus. But not always, because the longer you incubate it, there might also be more residuals that come in to play and that may impact your downstream processing, losing a lot more virus. So, you may have gained a lot in the beginning, but you’re losing it all in the end.

You have to really fine tune all the different steps, as one change in the beginning might have an impact at the end, so there’s a lot of development that you should be doing that Batavia does as well, with a lot of experience in that. DOEs (design of experiments) also play a big role in this so this you can really fine tune each of those parameters and the impact that they have on each other.

Partnerships have been highlighted as a mechanism for developing solutions to address the cost per dose challenge in the CGT space. What should developers look for in a partner?

There’s a lot to think about when you’re choosing a partner. From building a relationship with a vendor, for instance.

I think we all rely on each other. I think during the Covid-19 pandemic it was abundantly clear that partnerships are needed, otherwise we would have never had a Covid-19 vaccine that fast.

CDMOs, vendors, academic developers should be working together, even in early stages, to have the most impact later on, and to be able to provide treatments to people.

Looking towards impact, how could addressing these challenges with these approaches support developers in developing mature therapeutics, manufacturing them effectively, and ultimately contributing to the goal of seeing treatments delivered to patients as soon as possible?

Addressing the challenges to get treatments to people is indeed on the forefront of everybody’s mind. I think that is – in the end – what we all do it for.

Biotech is an exciting place to be, but really what we’re doing is helping people. If we’re not addressing challenges that we see along the way to make therapies available for people, then what is the point of it?

There’s so much advancement now in gene therapy. You can do all of this, but if it doesn’t make it to the people, then we’re not doing it for anything.

The prices or the cost of goods, again, is really the biggest hurdle. If you look at what treatments have come out and that are approved now, they cost $1 million+ for a single treatment for a person, which is not sustainable, and everybody’s aware of that.

Advancements to reduce those cost of goods through addressing hurdles, addressing challenges together in partnerships, collaborations early on will be key.

This is what Batavia does as well through a lot of partnerships. We really look forward to working with people to address those challenges head-on. It’s not always easy – there are a lot of unexpected hurdles that come along the way. Some of them you can predict pretty easily, some of them not. But together, addressing and having honest reviews of the data that comes out with good communication with your clients/partners/collaborators – because everybody knows more about one thing or another – collectively utilizing all those brains, that’s really where I see the most benefit and how most advancements will be made.

Eventually, we can actually treat people.

This interview has been produced in partnership with Batavia Biosciences.