Less than a year after backing Tscan Therapeutics Inc.'s $48 million series B round, Novartis AG is tapping the Waltham, Mass.-based company to discover and develop new T-cell receptor (TCR)-engineered T-cell therapies for up to three new solid tumor targets.

David Southwell, CEO, Tscan
The collaboration includes an up-front technology access fee and research funding totaling $30 million, as well as potential clinical, regulatory and sales-based milestone payments that could total hundreds of millions of dollars, Tscan said.

The partnership, essentially in the making ever since Novartis' Global Head of Immuno-oncology, Glenn Dranoff, took an observer seat on Tscan's board as part of the series B, is the result of "a really good relationship with them," Tscan CEO David Southwell told BioWorld.

Under terms of the agreement, Tscan will identify and characterize TCRs – group of proteins found on T cells that bind to certain antigens on abnormal cells, like cancer cells. Novartis will then have the option to license and develop up to three TCRs for novel targets. The Basel, Switzerland-based big pharma also gained rights of first negotiation for additional targets and TCRs that arise from the collaboration. In addition to the milestones, Tscan stands to earn mid-single to low double-digit royalties on net sales for any product Novartis markets from the work and is free to develop TCRs against targets not licensed by Novartis.

A multiplexing approach

Gavin MacBeath, CSO, Tscan

Tscan's approach is methodical and multipronged, starting with the isolation of T cells from the tumors of patients who are responding to checkpoint therapy, followed by figuring out what their T cells recognized. Its researchers then build up a collection of TCRs that recognize various targets of interest, Chief Scientific Officer Gavin MacBeath told BioWorld.

Over the last year, the company has built the capacity to process "thousands to tens of thousands of T cells to really industrialize this whole discovery process," MacBeath said. "Now that we've set that up, we anticipate that from the day you get a tumor sample to the day you discover a target is about a six-week process," he said.

The Novartis deal covers sourcing tissues from a prespecified number of cancer patients, then fully studying the T cells from those patients' tumors to pick the best targets. Including that part of the process, Southwell said he expects it will probably take a year or two for Tscan's team to do all the work required to characterize the potential targets before packaging them up for selection by Novartis.

Well-funded and looking at COVID-19

Meanwhile, Tscan will continue advancing its in-house pipeline, which already includes a liquid tumor program and efforts to identify additional solid tumor targets to advance. The goal for TSC-100, the company's lead program, is to prevent relapse following hematopoietic stem cell transplant and chemotherapy – an issue for about 20% to 30% of patients who relapse after myeloablative, or high-dose chemotherapy that kills cells in the bone marrow, including cancer cells. Current plans at the company call for filing two INDs in the liquid tumor program during 2021.

Because tumors are heterogeneous and wily, often becoming resistant to therapy by eliminating the target of the drug, Tscan is also expecting its internal programs to end up delivering not just a single TCR that hits one target, but ultimately pulling two or three TCRs together for treatment.

The company has already identified five novel targets on its own in solid tumors. It will likely continue to establish new collaborations like the Novartis one since its platform is capable of yielding more targets than it can pursue on its own. However, there's unlikely to be pressure to establish those ties as a support for its internal work. Southwell said the company is in strong financial shape, with enough funding to get it into 2022. Though he still feels it's possible for companies to raise new funds despite current pressures, "it's nice to not have to raise money for the next couple years," he said.

In addition to its cancer-focused work, Tscan's team is in the early stages of applying its expertise to help with the current coronavirus pandemic with a coronavirus library that spans every peptide coding variant in all of the roughly 100 viral isolates of SARS-CoV-2 sequenced so far, it said in March.

Working with cancer centers it was already working with in New Jersey and New Orleans, both COVID-19 hot spots, it's seeking out blood from patients who've already had and recovered from COVID-19. "Those patients presumably have T cells which constitute their immunity," Southwell said. "We're going to take that blood and figure out which antigens the T cells are attacking and take those to develop them into vaccines," he said.