In this interview, Matthew Hewitt, VP, CTO CGT & Biologics at Charles River Laboratories discusses the key highlights from his session at Advanced Therapies Week and explains the importance of the ‘Concept to Cure’ solution.
Could you start by introducing yourself?
My name is Matt Hewitt, I am the Vice President and Chief Technical Officer for Cell and Gene Therapy and Biologics at Charles River Laboratories. I oversee our CDMO operations from a technical perspective as well as providing insight to clients, as well as internally to our senior management, about advanced therapeutics and biologics, the way to bring them through development into manufacturing and ultimately into the market. I’ve been doing this for almost 10 years, having started life as a PhD immunologist focused on T cell biology.
What are the key highlights you’d like the audience to take away from your session, ‘The Future of Cell and Gene Therapy Manufacturing, Development, and Commercialization’?
The title of my presentation inside that session is called, ‘The End of the Beginning: The Next Frontier or the Next Phase of Advanced Therapeutics Development’, because I think the past 7 or so years – I typically gate it from when we saw the first approval in this space – we’ve seen a tremendous amount of therapy development.
We have 16 products commercialized here in the US, around 8–10 on deck for 2024, and so now we’re entering a period where we need to start operationalizing the manufacturing and distribution of these therapies. We’re entering a period where we should start to see between 10–20 being approved each year.
So, my presentation is going to be about how we’re going to be seeing that, and then coupled with the learnings that we’ve obtained over the last several decades, but really in the last 10–15 years, and how to better streamline the development process for these advanced therapeutics so we can get them to patients quicker.
Could you tell us about Charles River Laboratories’ ‘Concept to Cure’ solution, and how this initiative relates to advanced therapies commercialization strategies, to patient delivery?
The ‘Concept to Cure’ motto came to be when I first joined, and I was asked ‘how do you see this portfolio?’ I said that this is a ‘concept to cure’.
You can really struggle to say end-to-end, because a lot of people say they have end-to-end portfolios, but it’s hard to know where they consider that ‘start’ to ‘end’.
In the case of Charles River, because of all the different business units we have, we have the ability to take things from an idea or a concept, develop them in our discovery business – which can range from things like target identification, target discovery, through looking at immunogenicity of various targets – move it into in vitro and in vivo testing, which we’ve been doing for quite some time. At the same time, we can also couple those activities with our CDMOs.
When we do that, as an example, we do a lot of the analytical development early in the space so that the analytics that you’re using, and the discovery part of your program can then be seamlessly transitioned to a CDMO where it then goes from being used as a research assay to something that’s used for product release and GMP.
This provides immense value, we believe, to a lot of our clients, because it eliminates the need for multiple relationships externally, from multiple different stakeholders.
One of the key things in this space is that we’re moving very quickly, and so that’s what we aim to do, and the overall aim of Charles River with these types of structures within our organization is to eliminate up to 12 months from the development timeline by bringing everything in-house.
We have had a very good response from our clients on this, and this is because a lot of companies now are – I wouldn’t say ‘capitally constrained’, but let’s just say that capital is not as free flowing as it once was – they’re looking to be more efficient in the way that they’re administering their capital. They already use us generally for a lot of pre-clinical activities, so it’s a very natural progression to bring us this clinical work as well.
They need to focus less on managing capital and multiple exterior relationships, and focus more on their core mission, which is therapeutic development.
Why is it important that we’re talking about this?
The reason it’s important that we’re talking about this is that in the advanced therapeutic space, it’s one that enables us to have a direct impact on patients very quickly, and I think that’s something that draws a lot of people to this space – the ability to see your work progress to the point where it actually gets into the patients and has a direct therapeutic effect.
In the case of cell therapy, we generally say that we have a literal poster child for this that was treated over 11–12 years ago and is still cancer-free. We’re seeing people have significant outcomes that were heavily pre-treated coming in, in the case of oncology.
In the case of the gene therapy space, a lot of these rare and ultra rare indications are in children, and there are little to no other treatment options for a lot of these diseases and disorders.
So, we want to make sure that we are working with not only the therapeutic developers, but also the patient advocacy groups and the foundations to bring these therapies into the clinic, and hopefully the commercial, to provide these patients with a new therapeutic option, and that’s really important to us.
At the end of the day, yes of course we talk a lot about business units and we’re a publicly traded company, but at our core, what we are and what really sustains us is that mission to help patients.
What key topic do you anticipate will be the focal point of our discussion?
There’ll be multiple points – a lot of it will be talking about what we saw in the last year as it relates to therapeutic approvals in this space, what we’re looking at on deck – so to speak – for 2024. We’ll be looking at the reasons why various companies make decisions around manufacturing, whether that’s keeping it internal or using a partner CDMO to do it, the different considerations when you’re looking at manufacturing in this space.
Most traditional therapeutics, whether we’re talking about small or large molecule, are what we typically call ‘maintenance therapies’. We’re using chemistry or pieces of biology to transiently change biology, where in advanced therapeutics, we’re using biology to, in many cases, permanently change biology. It’s somewhat of a different paradigm, and because of that, the manufacturing considerations are different.
I’m also going to talk about some of the key pain points that we’re dealing with around transferring manufacturing from site to site, looking at the people considerations because ‘people’ is always concerning in this space.
I’ll then be settling down a little bit on some of the new concepts that the FDA and others are thinking about in the regulatory space, focusing primarily on decentralized manufacturing, and then end with a little bit of an inspirational note on the fact that we have a lot of new options coming to the market in this space to help us bring down pricing and costs, and then talk about the fact that while manufacturing is our current problem because it’s sitting right in front of us, it won’t be our last, and that we should start thinking about some of those down the line problems that we should proactively start thinking about how we might want to solve.
How do events such as Advanced Therapies Week contribute to addressing specific challenges or opportunities currently faced by the Cell and Gene Therapy Industry?
I think we have maybe three primary things.
So, the first one is that we have a lot of ideas internally and we do interact with the field quite a bit, but I think it’s always good to bring folks together in a conference setting where we can have more off-the-cuff conversations that may lead to better solutions, and ones that are more collaborative. Certainly since the pandemic, we’ve all enjoyed getting back in together in person, and it’s far more effective than trying to do something on Teams, on Zoom, or whatever.
I think secondly, it brings us together with our current clients, as well as prospective clients that we can talk with, and we can understand our abilities to work together in those synergies. Again, the in-person aspect, I think is quite important.
I think the last is that we are but one solutions provider in this space. Now, we certainly have a very comprehensive portfolio, but I won’t pretend that we are the experts around everything. So, the other thing that gives us an opportunity to do is meet with some of the other solutions providers in the space, talk about how we can work together, where those synergies are, and we can ultimately be collaborative.
That’s something that our clients want us to do. Our clients want us to be collaborative with other solutions providers where possible, so that they can have a better, more seamless experience in translating their programs from pre-clinical into clinical, and hopefully commercial.
Xavier De Mollerat Du Jeu, Senior Director R&D at Thermo Fisher Scientific is accompanied by Gianluca Pettiti, Executive Vice President and President, Life Sciences Group at Thermo Fisher Scientific and Fred Parietti, Co-Founder and CEO at Multiply Labs for this Workshop at Advanced Therapies Week 2024.
Manufacturing capacity, complexity and cost are core constraints that limit commercialization of cell and gene therapies, and ultimately patient access. In this Fireside Chat series, join Georgi Makin, VP of Digital & Editorial at Phacilitate and the Germfree team as we discuss the challenges and opportunities associated with delivering cell therapies in a decentralized manufacturing model.