Charles River Laboratories

Matthew Hewitt

Matthew (Matt) Hewitt, a leader in the cell and gene therapy field, joined Charles River in 2021 as Senior Director, Scientific Solutions in the cell and gene therapy (C & GT) space. Later, Hewitt was promoted to his current position as executive director, Scientific Solutions C & GT. He began as an immunologist with an undergraduate degree in molecular biology and a Ph.D. in immunology. His Ph.D. dissertation focused on understanding adaptive immune responses in airway diseases, specifically in allergies and asthma. His post-doctoral training at Johns Hopkins was focused on neural control of airway diseases.

Before joining Charles River, Matt led research and development and clinical development for a multinational manufacturing company’s personalized medicine business unit. He was also responsible for building and leading the tumor immunology and microenvironment program for a leading biotech company. Hewitt was also the Associate Director of the Immunology group within the Gene Therapy Program at the University of Pennsylvania.

At Charles River, Hewitt plays a vital role in driving C & GT strategic vision and leading one of the company's C & GT contract developments and manufacturing organization (CDMO) sites. Under his strategic leadership, Charles River works with innovative labs, start-ups, and established pharma companies.

What are the Existing Challenges in the C & GT Space?

In the in-vivo gene therapy space, we're still working to understand how to translate the science to the clinic. There are limitations to using Adeno[1]associated virus (AAV) viral vectors in humans.

The AAV viral vector doses administered to patients are generating an immune response. When patients build immunity against a particular viral vector it limits the ability to re-dose patients if needed. This has driven researchers to seek additional gene delivery options, such as liquid-lipid nanoparticle technology (LNPs). Another concern in the field is the high cost of AAV therapies, and there is considerable focus on technological improvements to bring down costs to increase patient access to these therapeutics. There are now multiple C & GT commercially approved products and a constant concern is price but we need promising new therapeutics before we worry about cost. This field has a habit of innovating a way out of problems, and this doesn't seem to be any different. C & GT therapeutics are potentially curative and don't just treat symptoms.

I will say this again that it's important to find a way through these problems via continuous innovation. Even a few years back, no one could imagine the commercialization of cell or gene therapy, but smart scientists are always finding ways to solve difficult problems.

What Are Some of the Recent Trends in This Space and the Position of Charles River in the Market?

We have a truly end-to-end portfolio when it comes to C & GT. If you want to make a chimeric antigen receptor T-cell therapy (CAR-T) for oncology, bring us a target sequence that we can use to generate an antibody. Then using additional protein engineering we can generate a single-chain variable fragment (scFv) used to target specific antigens. Once this is complete, we move to in-vitro assessment studies. Following this, in-vivo safety studies are required; safety assessment is an area where Charles River Laboratories is a world leader. In the past 2-3 years, Charles River has added several other pieces, including our Cell Solutions business which provides cellular starting material for C & GT programs (both autologous and allogeneic). We have also added research use only (RUO) through good manufacturing practice (GMP) CDMO capabilities for plasmid, vector, and cell products.

Testing is a key component in the portfolio. All product release testing and analytical development is performed in-house at Charles River. This is critical for all therapies but especially for autologous cell therapies in oncology.

We are starting to see some growth in the in vivo cell therapy space using LNP technology. Keeping these trends in mind, we are continuously striving to ensure we have the latest technologies in place to support clients’ diverse needs.

We are aligning with the changes in the C & GT space and will continue doing this.

What Are the Pieces of Advice That You Want to Impart to Your Colleagues?

The C & GT space is undergoing rapid evolution, so scientists should never be afraid of making mistakes, sometimes getting a "no" result is just as important as a "yes." Another piece of advice is many of us spend many years accumulating knowledge in a specific space. I typically call this knowing way too much about way too little but because we have this knowledge we have a responsibility to pass on our knowledge and know-how to the next generation of scientists.