“Endowing Cells with Super-Physical Properties” to Better Treat Patient Populations
For this interview, Phacilitate’s Ryan Leahy speaks with David Sourdive Ph.D., Executive Vice President of CMC and Manufacturing, Cellectis, about what to expect from his session, ‘Is cGMP Enough? Operational Excellence for Advanced Medicines’ at Advanced Therapies Week 2023.
As we get started, could you please introduce yourself?
Hello, my name is David Sourdive. I am one of the two founders of Cellectis, and today I am more specifically in charge of CMC and manufacturing, especially for our gene editing tools, as well as for the process analytical development of our off-the-shelf allogeneic CAR-T cell products.
What have you and the Cellectis team been working on recently?
Cellectis was created almost 23 years ago and since inception, Cellectis has been working on gene editing. This field has become very popular, but it wasn’t so when Cellectis was founded. We’ve been first working on gene editing technologies and tools making meganucleases, homing endoonucleases, TALEN®, MegaTAL, recently CRISPR, but I would say that almost 10 years ago we decided to focus on one class of nucleases, the most accurate and precise one, TALEN, and to deploy it into clinical applications, and especially in adoptive T cell immunotherapies.
We invented the concept of allogeneic off-the-shelf CAR-T cell products, breaking the donor/receiver barrier and allowing the use of T cells from healthy donors in any patient. The platform was then developed to take this technology to the clinic. Today, it is the technology that has the broadest data set with more than 200 patients treated through the clinical trials we run or that are run by our partners, because the very first products we made were licensed out to our partners, Servier and Allogene. Today, we have 4 products in the clinic that are wholly owned: UCART22 in acute lymphoblastic leukemia; UCART123 in acute myeloid leukemia, UCARTCS1 in multiple myeloma; and quite recently a fourth one entered the clinic, UCART20x22 in non-Hodgkin’s lymphoma. The very first product, UCART19 today called ALLO501 and ALLO501a is about to enter pivotal phase, as recently announced by our partners at Allogene and Servier.
So this is essentially what we’ve been working on, as well as the industrialization of these new products, setting up manufacturing capabilities both for the gene editing components, DNA, RNA for TALEN®, vectors, and for the off-the-shelf final cellular products.
Excellent, thank you. Quite importantly, the UCART20 by 22 is the first product with fully integrated in-house development, marking Cellectis as an end-to-end cell therapy company. Can you talk a little bit more about that?
UCART20x22 is very exciting – it is the first allogeneic dual CAR-T product ever. It is recognizing both CD20 and CD22. These two targets are quite well validated in non-Hodgkin’s lymphoma and we believe that it is a great opportunity for patients. It is something that captures a better makeup for the targets. It is also not targeting CD19, which is a very crowded target with a lot of product candidates.
We are also very excited about this product because we made it from end-to-end. It was conceived, developed, manufactured completely internally – we even selected the gene editing components of the product itself. We’re very excited because it’s also the beginning of this new generation of products with more sophistication, more powerful edits and features engineered into the cells.
What are you particularly excited about in the cell and gene therapy space?
What excites us in the cell and gene therapy space is this transition that we see now and at the very forefront of which we are. Cell therapy has been growing in the world of ‘grafts’ for decades, and is now transitioning to the world of off-the-shelf pharmaceutical products. We think that is essentially driven by gene editing, but it’s just the beginning. The game is now shifting and there are new concepts of products that are coming.
The products within this new generation will undergo much more sophisticated genomic design. We are literally programming scenarios into the genome of these cells that they will then be able to execute once they’re infused into patients. We are endowing these cells with supra-physiological properties so that they will succeed where the patient’s own cells fail, especially when confronted with more difficult diseases such as solid tumors, for example, that are already visible to the immune system, but defend themselves by choking the immune responses, using checkpoint inhibition, or blocking cytokines or even developing a protective micro-environment to evade immune attacks.
We’ve already made public some of the candidate products we’re working on: UCARTMUC1, UCARTFAP, UCARTMESO directed at different targets. But we think this is just the beginning of this new era, that of “smart cells”, that are genetically designed to actually execute these sophisticated clinical scenarios with, we hope, much more favorable outcomes for patients, and that are capable of better addressing these high unmet medical needs in these big indications and complicated diseases.
This is really something that excites us very much, and at the same time, it’s also the systematic industrialization of cells, like antibodies that used to be drawn from donors and are now completely made by industrial manufacturing. So engineered cells are becoming another tool in the therapeutic arsenal and that’s also quite exciting because we are very much at the forefront of that revolution.
What are you most looking forward to at Phacilitate’s Advanced Therapies Week this year?
I’m very much looking forward to Phacilitate’s Advanced Therapies Week because it is a venue where we can meet other people who are in the field, understand where the state-of-the-art is, what are the big elements that are shifting, or moving, also get a feel for the trends, understand where the regulatory doctrine and perspective of different aspects are shifting, moving, getting precise and sometimes evolving.
It is also a venue where we can meet all these players that support our activities by providing us technologies, reagents, tools, machines and so forth, that make our endeavor possible and the industrialization of cell therapy a reality.
It is a great moment in the year, a moment where we can have all these conversations and also better understand where the entire field is going, what’s important, and to also get the contacts with the people we would love to work with.
Don’t miss David’s session, ‘Is cGMP Enough? Operational Excellence for Advanced Medicines’ on Thursday January, 19 2023.
Join us at Advanced Therapies Week >>