Living on the edge: the challenge of doing things differently in cell therapy

July 17, 2019 Sponsored BioVox

Belgian company Celyad is a trailblazer in oncology: its T cell therapies based on NK receptors are cutting edge even for CAR-T. At the Science for health event in September the visionary Christian Homsy, former Celyad CEO, will be presenting one of the keynote talks. In this BioVox interview, we asked him to share his thoughts on the challenges faced by a company that’s pushing boundaries in the oncology space.

By Amy LeBlanc. Read this previous BioVox article for more on the Science for health event.

CAR-T is a relatively new field; only a couple of products have already hit the market, with most still under development. Of the 150 odd companies working on CAR-T therapies around the world, the vast majority are working on products very similar to the treatments already available to patients.

In Belgium, Celyad is developing a next-generation CAR-T, using a unique approach to cell therapy. We spoke with Christian Homsy, former CEO of Celyad. He shared with us his thoughts on what sets Celyad apart and the challenges the company has had to face because of the originality of their technology.

What makes Celyad’s CAR-T next-gen?

Celyad’s T-cell immunotherapy approach is unique because it draws on receptors used by Natural Killer cells (NK cells). NK cells form an important part of our immune systems, as these blood cells are part of the body’s first line of defense against pathogens and cancer.

The NK receptor CAR-T therapy that we are developing is capable, in theory, of targeting 80% of all cancers. – Christian Homsy, Celyad

Unlike traditional CAR-T approaches, which modify T cells by inserting a gene coding for an antibody, Celyad instead engineers their T cells to express NK activating receptors. These receptors don’t bind with specific antigens, but instead bind with the ligands expressed by stressed cells. Homsy explains:

“Celyad are developing a set of CAR-T therapies that are much broader in terms of their targeting potential than traditional methods. The Celyad T cells are engineered to target stress ligands and cancer cells are, by definition, stressed. This means that the NK receptor CAR-T therapy that we are developing is capable, in theory, of targeting 80% of all cancers.”

Because the ligands recognized by the engineered T cells are also expressed by the tumor’s blood vessels, Celyad’s T cells target and kill tumor cells while also eliminating the cancer’s micro-environment. The modified T cells also attract other immune cells to the cancer site and establish long term cell memory.

Notably, Celyad’s therapy is one of the first CAR-T treatments that can target solid tumors, not just blood cancers. When asked about specific indications, Homsy explained that the company is currently diving in the deep end with their clinical trials:

“We’re a small company and we cannot test everything, so, we’ve chosen to focus our clinical trials on a selection of particularly challenging indications. We’ve chosen Acute myeloid leukemia (AML) as a model for hematological malignancy, because it’s one of the toughest blood-borne cancers that exist. For solid tumors, we’re using colorectal cancer as a model, because it is a very tough cancer to treat once it has relapsed and is refractory. Using those two indications, we’re finetuning the effectiveness of our treatments for both hematological and solid cancers.”

The challenges of trailblazing

The Celyad approach to cell therapy has the potential to be revolutionary, but the company is still relatively young. Their lead candidate, CYAD-01, has been successfully undergoing a number of Phase I clinical trials. The company are also conducting Phase 1 trials for CYAD-101, which is the allogeneic version of CYAD-01.

I think success drives success. I’m confident that Celyad will get there and once you’ve opened the door many more will come. – Christian Homsy, Celyad

Celyad has recently announced that the Phase I trials for both CYAD-01 and CYAD-101 are going well, but it hasn’t all been smooth sailing. It is hard to develop any new product in the pharmaceutical industry and Celyad has the dual challenge of both a new field and a novel approach. Are there specific challenges associated with developing such cutting-edge therapies? Homsy thinks there are four main hurdles:

“It is challenging to be in such a new field. I’d say one of the first hurdles is educating investors. There is always a bit of reluctance to back a new concept; making people believe in your technology when they’ve never heard of it before it is always going to take more time and effort.

Finding the right talent is also particularly challenging. To develop a new therapy, you need to find people that are very forward-looking; visionary people who are leaders in their field. People possessing the experience necessary to develop CAR-T therapies are simply very scarce. At Celyad, we are very fortunate to have one of the pioneers of CAR-T, David Gilham, heading our R&D department. We’ve built and incredible R&D team but finding that talent was not easy.

Concerning regulatory aspects: you have to approach things in a novel way when dealing with a new therapy. Agencies are very willing to help, but you need to communicate with them well and invent new ways of doing things.

Finally, most large pharmaceutical companies have yet to fully embrace CAR-T therapies; a lot of major players are currently still sitting on the sidelines. Progress will be easier when they put their weight behind cell therapies. This all being said; I’ve never encountered a new breakthrough that wasn’t confronted with the same types of challenges.”

Does Homsy think that Celyad’s success could open doors for other companies to try their hand at alternative CAR-T therapies?

“Yes, I think success drives success. I’m confident that Celyad will get there and once you’ve opened the door many more will come. That’s a good thing, as far as I’m concerned, because ultimately what continues to drive our research and our leadership in the field is making progress in the fight against deadly diseases.”

For more information or to register, please visit the Science for health website.

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