RARE Daily

Atara Biotherapeutics: Off-the Shelf Allogeneic Cell Therapies for Rare Disease and Beyond

July 16, 2020

Pascal Touchon, who led the Novartis’ cell and gene therapy efforts in oncology that resulted in the first approved CAR-T Kymriah, left the company in 2019 to become president and CEO of Atara Biotherapeutics, a reflection of his belief in the clinical-stage company’s cell therapy technology.

Atara in 2015 entered into an agreement with Memorial Sloan Kettering to develop a new type of therapy to address an ultra-rare type of cancer that occurs in a small number of transplant patients known as post-transplant lymphoproliferative disorder (PTLD).

PTLD is a specific lymphoma linked with the proliferation of B-cells that are infected by Epstein-Barr virus (EBV). Most people are infected with EBV, but they are usually asymptomatic. Immune-suppressants administered to avoid transplant rejection can cause T-cells from controlling B-cells, causing them to run amok and lead to lymphoma. About half of patients with PTLD die within two years.

Atara’s experimental PTLD therapy, Tab-cel is derived from blood cells from healthy donors in which the B-cells are separated from the T-cells. The T-cells are activated to be responsive to EBV antigens. The final product is a population of T-cells that are specific and selective for EBV that targets only EBV-infected cells. It could soon become the first ever allogeneic T cell therapy to be submitted to the U.S. Food and Drug Administration for approval.

Because it is allogeneic, Touchon said it will be safe to use in patients in different diseases since the T cells will not attack other cell in the body, only those infected with EBV.

“It is potentially a totally transformative therapy,” said Touchon.

In a phase 2 study that Memorial Sloan Kettering conducted, the response rate was between 50 and 82 percent, and overall survival after two years in responders was more than 80 percent.

Tab-cel is currently in a phase 3 study for relapsed refractory EBV-PTLD with interim data expected during the third quarter of 2020 and plans to apply for regulatory approval in the United States by the end of the year.

While the patient population for this ultra-rare indication is small, Atara is pursuing many other indications for Tab-cel, including a phase 2 study of it in other EBV-expressed cancers and the use of the therapy as a first-line treatment for PTLD.

But Tab-cel is not the only potential therapeutic in Atara’s pipeline, which has grown through partnerships with academic institutions. Its pipeline includes a mesothelin CAR-T therapy with Memorial Sloan Kettering, a partnership with Moffitt Cancer Center in CAR-T, and a partnership with Queensland Institute of Medical Research in Australia in EBV-linked multiple sclerosis.

Atara plans to file an application with the FDA by the end of the year to begin human clinical trials for its CAR-T cell therapy targeting mesothelioma. Its partner Memorial Sloan Kettering will conduct the first-in-human trials. Touchon believes Atara’s CAR-T will work in other cancers with over-expressed mesothelin cells or CD-19 over-expressed tumor cells.

“Our experimental treatment for multiple sclerosis has the potential to change the treatment paradigm, and we are now starting to see other companies looking at the connection between EBV and multiple sclerosis. We already have an investigational treatment for that, said Touchon. “And we have a platform for allogeneic CAR-T that relies on the EBV T cell, which we see as the most efficient platform for safety and efficacy and persistence with durable remission.”

Photo: Pascal Touchon, president and CEO of Atara Biotherapeutics

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