Charles River [NYSE: CRL]

Matthew (Matt) Hewitt, a leader in the cell and gene therapy field, joined Charles River in 2021 as Senior Director, Scientific Solutions in the C and GT,  space. Later, Hewitt was promoted to his current position as the Executive Director, Scientific Solutions C and GT. He started his journey 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 allergy and asthma. His post-doctoral training at Johns Hopkins was focused on neural control of airway diseases.                

Prior to Charles River Matt led R&D 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. Another feather on Hewitt’s cap is that he was the Associate Director of Immunology group within the Gene Therapy Program at the University of Pennsylvania.

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

What are the existing challenges in the C and GT, space?

In the in vivo gene therapy space, I think we're still working to understand how to translate the science to the clinic. There are limitations to using 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 redose patients if the need arises. 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 technology improvements to bring costs down to increase patient access to these therapeutics. There are now multiple C and GT,  commercially approved products and a constant concern is price but I believe we need promising new therapeutics before we worry about cost. This field has a habit of innovating our way out of problems and this doesn’t seem to be any different. C and GT,  therapeutics are potentially curative and don’t just treat symptoms.

The C and 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”

I will say this again because I believe it’s important, we can 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.

Tell us about 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 and GT. If you want to make a CAR-T therapy 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 and GT programs (both autologous and allogeneic). We have also added RUO through GMP CDMO capabilities for plasmid, vector, and cell products.

Testing is key component in the portfolio. All product release testing as well as analytical development is performed in-house at Charles River. This is critical for all therapies but especially important 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 and GT,  space and will continue doing this.

What are the pieces of advice that you want to impart to your colleagues?

The C and 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.