Getting Ahead of the Pack in the CAR-T Field

Celyad is one of many companies in the immuno-oncology field seeking to take the lead in the development of a new generation of CAR-T cell therapy that outperforms its predecessors Yescarta and Kymriah in both efficacy and safety. Filippo Petti, CEO of Celyad, shares the company’s strategy to get ahead in such a crowded field.

Filippo Petti joined Celyad last August as CFO, and became CEO in March. He started his scientific career in the biotech industry at OSI Pharmaceuticals, a US cancer drug discovery company. Petti was there during the time the company signed major partnerships with pharma and commercialized its first cancer drug, eventually being sold to Astellas for $4B. He then moved to investment banking, where he stayed close to the biotech industry.

“Oncology therapeutics have been a major focus of mine,” Petti told me. “When I was on Wall Street, the majority of the companies I focused on were cell therapy companies and oncology companies.”

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“Celyad presented itself as a fantastic opportunity to reenter the biotech industry, to push on the development and discovery of oncology products, while also taking some of the benefits and learnings of Wall Street over the last decade about how strategic investors think about opportunities within oncology.”

Petti has been around long enough to see multiple experimental cancer therapies come and go. “It’s funny, I see that many of the targets I was working on 15 or 20 years ago in the lab resurfaced and given a new spin,” he said. But the cancer target that is now getting most of his attention in his new role at Celyad stands out.

Called NKG2D, this target is a receptor protein found on the surface of natural killer cells — a type of immune cell involved in the innate response against infected and cancerous cells.

“The reason why we’re really in love with this receptor is because it targets stress ligands that are both on hematological and solid tumors, so we’re not restricted to a specific type of cancer,” he explained. “We can go very broad.”

Indeed, NKG2D is able to recognize 8 different molecules produced by cancer cells, which allows it to target over 80% of cancers. Including, unlike current CAR-T cell therapies, solid tumors.

Celyad has been working on this cancer target since 2015, after acquiring a technology developed at Dartmouth College in the US, back when the company was called Cardio3 Biosciences. While at first the company was alone, a few other companies have shown interest in this target. One is Nkarta, a young US biotech company. Another is bluebird bio, a major player in the cell therapy field.

“For the last few years, we’ve been really focused on a receptor that many were not familiar with, so we had to go out and educate many of the investors, and it’s been a big focus of ours to describe the biology behind NKG2D. Now, we find that it’s very validating that companies like Nkarta and leaders like bluebird are looking at programs with NKG2D because it helps validate the target.”

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Making the best of a technology

Celyad is now running several clinical trials with its lead cell therapy candidate against the NKG2D cancer target. The company’s current strategy is to test this treatment under different conditions with the goal to find the right dose, schedule and treatment combination to take its technology to its first phase II trial by year end.

One remarkable finding in this exploratory phase is that Celyad’s cell therapy has been shown to have an effect on some patients that had not received preparatory chemo as part of the treatment. “That is very different from anyone else who is looking at CAR-T development and our peers because they all follow preconditioning,” explained Petti.

Removing the chemo step could be a big advantage, but Celyad is now testing the treatment in both liquid and solid tumors in combination with different chemo courses. The goal is to evaluate which option can have the biggest effect on cancer patients without causing unwanted toxicity.

The company has seen some levels of cytokine release syndrome — an inflammatory reaction that has been known to cause some deaths in clinical trials of approved CAR-T therapies. Petti assures the levels are so far not as strong, though.

“The cytokine release syndrome is something that some of the other modalities, such as bispecifics, are seeing as well,” he said. “I think it’s a challenge for the field in general when we’re looking at these immunotherapies, to be able to assess and tackle.”

Moving to the next generation

While Celyad awaits the results for its lead cell therapy, the company is already working on a new generation of CAR-T therapy that has an edge over other players in the field. The company’s ultimate goal, according to Petti, is to lead a next-generation wave of allogeneic CAR-T cell therapy that is derived from donors rather than the patient’s own cells. Thus making the therapy available off the shelf and rendering the manufacturing easier, faster and more cost-effective.

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“We’re the first company globally to have a program for allogeneic therapy for the treatment of solid tumors,” Petti told me. “This year we’ll get a comparison between an autologous and an allogeneic modality in CAR-T looking at the same target for the same patient population. I think that’s going to be beneficial because we want to be leaders in this space within CAR-T.”

One of Celyad’s differentiating features in this area is that the company does not use gene editing to create its cancer-fighting cells, but rather an “all-in-one vector” that carries genetic instructions where different elements can be introduced and removed using a ‘plug and play’ approach.

This might be a key advantage in manufacturing — one of the main challenges to the success of cell therapies. In addition, Celyad has seen that cells derived from donors using this approach continued to fight tumors in mice for longer compared with those created using gene editing approaches.

“Our strategy is ‘can we marry NKG2D with the best-in-class approach for allogeneic CAR-T development?’” said Petti. “We think ours can be the best-in-class approach to the field. That’s really the long-term goal.”

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