CAR-T cell therapy: biopharma is betting allogeneic is next-generation – Business Insider

Wendy Fullem, a 54-year-old administrator at a New Jersey college, hadn’t been feeling well for some time when, in fall 2016, she was diagnosed with leukemia.

Leukemia is a type of blood cancer that comes in many forms. There were about 60,000 new cases in the US last year, and one treatment option is a bone marrow transplant, a decades-old scientific procedure that has potential to treat upwards of 70 different diseases, including many types of cancer.

Doctors quickly shuttled Fullem into an intense, weeks-long process of chemotherapy, followed by the transplant.

Doctors had warned Fullem that the post-transplant process would be “like hell,” and they were right, she said. She had “almost every side effect in the book,” including one potentially deadly one that can accompany these transplants. But Fullem eventually made a full recovery.

“It blows my mind,” Fullem told Business Insider. “I am grateful for my life. When people say it’s nice to see you, I say, ‘It’s nice to be seen.'”

Today, companies are working to improve on the process Fullem went through, in hopes of supercharging this science and making what is currently a highly individualized treatment more widely available.

The new approach is called allogeneic CAR-T and is a variant of a cutting-edge treatment that some patients with cancer are today receiving. Called CAR-T cell therapy, the current approach consists of collecting a patient’s blood, reengineering their disease-fighting T-cells to better kill cancer tumors, and then putting the cells back in the body.

You can think of the new experimental approach, allogeneic CAR-T, as a next-generation version. Instead of using a patient’s own cells, the experimental tech uses immune cells from a healthy donor to treat diseases like cancer. It’s named “allogeneic” after the cells it employs, which don’t come from the patient’s body.

Roughly 30 individual allogeneic CAR-Ts are being developed today by biopharma companies for many different types of cancer, according to an analysis done for Business Insider by Informa Pharma Intelligence.

Just a quarter, though, are far enough along to be tested in humans, the analysis shows, with drugmakers like Allogene Therapeutics and Cellectis SA working on the most programs. All of the about 30 allogeneic CAR-Ts are experimental, meaning the tech isn’t currently approved for use or to be sold.

Shayanne Gal / Business Insider

And at least $8.5 billion has been poured into licensing deals for this tech since 2014, according to the Informa Pharma Intelligence analysis.

“We’re waiting to see if that approach goes prime time,” Jay Feinberg, the founder and CEO of the Gift of Life Marrow Registry told Business Insider.

Shayanne Gal / Business Insider

New tech would be more convenient for patients, but faces technical challenges

Allogeneic CAR-T therapies “may well be the future,” Jill O’Donnell-Tormey, CEO of the nonprofit Cancer Research Institute, told Business Insider.

That’s because they should be easier and faster to make and deliver to patients, at least in theory.

Today’s CAR-T cell therapies take about three weeks to collect from the patient, engineer, and then infuse back into the patient. CAR-T products already approved and sold today are autologous, meaning they use the patient’s own cells. In the US they include Gilead Sciences’ Yescarta and Novartis’ Kymriah.

The donor cells employed by allogeneic CAR-T, by contrast, can be held on standby, ready for patients in a matter of mere days.

But to get there, drugmakers must first confront major technical challenges. Allogeneic CAR-T hinges on using the immune system against cancer cells, but it also runs the risk of triggering the immune system in potentially deadly ways.

“Your body naturally, because you have an immune system, is going to try to reject anything you put into it,” said Mizuho analyst Salim Syed. “This is why we don’t have [allogeneic CAR-T therapies] right now.”

Companies like Atara Biotherapeutics are trying to get around that by better matching immune cells with a patient’s cells, to avoid an attack. Another approach, employed by companies like Allogene, involves reengineering cells and also knocking out receptors on the surface of a T-cell that play a key role in these rejections, Syed said.

Others are turning to a different type of “natural killer” immune cell, in hopes of avoiding this issue entirely.

Crucially, the experimental tech still has to be proven out. But big pharma companies are all starting to talk about it, especially if they sell or are developing other similar cell therapies, Syed said.

That list includes Gilead, Novartis, and Celgene, which is in the process of being bought by Bristol-Myers Squibb.

“Is it a threat to the autologous version? It can be. We don’t know yet,” Mizuho’s Syed said. “Anyone who has an autologous CAR-T needs to think about allo.”

Source: https://www.businessinsider.com/investors-are-betting-on-new-type-of-car-t-for-bone-marrow-transplants-2019-3

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