Novartis, TScan unite on TCR treatments for solid tumors

While it works on certain targets with Novartis, TScan is developing its own pipeline, which includes programs in blood cancers and solid tumors. (TScan Therapeutics)

Last summer, Novartis pitched in to a $48 million venture round for a cell therapy startup called TScan Therapeutics. Now, the Swiss pharma is back for more: In a deal worth $30 million upfront, the duo is on the hunt for targets that could lead to new T-cell receptor (TCR) therapies for solid cancers.

Although the deal focuses specifically on kidney cancer, the partners’ goal is to find new antigens that are shared between tumor types, which could lead to treatments for multiple cancers. TScan will identify the targets, as well as the TCRs that recognize them. Novartis has the right to license and develop up to three TCR treatments for three of those targets and has first dibs on any other targets and TCRs that come out of the collaboration.

All told, TScan could rake in hundreds of millions in clinical, regulatory and sales milestones.

Like chimeric antigen receptor T-cell (CAR-T) therapy, TCR treatments are based on giving patients immune cells that have been modified to attack cancer cells. But unlike CAR-Ts, which recognize targets on the surface of cancer cells, TCRs can zero in on proteins within the cells. It’s an approach that could work in solid tumors, an area where CAR-Ts have struggled.

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While its peers are developing TCRs against 15 or so known antigens, TScan is using technology out of Harvard University to find completely new ones, TScan President and CEO David Southwell said.

TScan Chief Scientific Officer
Gavin MacBeath, Ph.D. (TScan)

“There hasn’t been technology that enables you to, on a completely genome-wide basis, discover what the natural target of a T-cell receptor is,” added TScan Chief Scientific Officer Gavin MacBeath, Ph.D. “Previously there have been limited efforts at this, where people had a small collection of targets they could look at to see if a T-cell receptor is recognizing them. But there was no path forward to finding a natural target.”

TScan’s technology, developed by Stephen Elledge, Ph.D., a professor of genetics and medicine at Harvard Medical School, starts with the immune system itself. It looks at T cells and what they recognize in tumor cells in a cancer patient.

“When we discover a new target, we simultaneously discover the TCR that recognizes that target, so we lump target discovery and therapeutic discovery into one process,” MacBeath said. With each hit, the company immediately has leads that can be pushed toward the clinic—“an aspect that really captured Novartis’ attention.”

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While it works on certain targets with Novartis, TScan is developing its own pipeline, which is led by a blood cancer program, although it includes solid tumor assets, too. Although other cell therapies, like Novartis’ CAR-T Kymriah, have transformed treatment for some blood cancers, there’s still room for improvement.

“The partnership gives us complete freedom on our liquid tumor program, the goal for which is to prevent relapse after hematopoietic stem cell transplant in diseases like acute myeloid leukemia that have a 30% to 40% relapse rate,” Southwell said.

As for solid tumors, TScan thinks there are plenty of targets to go around. It’s free to pursue any targets and TCRs that Novartis doesn’t pick up.

“It’s possible we’re going to discover a lot more common antigens than Novartis actually licenses,” Southwell said. So, in addition to extending TScan’s runway from 2021 to 2022, the deal will also turn up a number of new targets it can file away in its repository, he said.

Eventually, TScan wants to match targets in a given patient’s tumor to a TCR in that repository that can be pulled out and quickly developed into a treatment—“much more quickly than if we had to identify all of these things from the beginning,” Southwell said.

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