Pharma, BioPharma

Adaptimmune, TCR2 Therapeutics to Combine in Marriage of Cell Therapy Developers

Adaptimmune and TCR2 Therapeutics have complementary technologies and an aligned strategy of developing cell therapies for solid tumors, but this marriage is preceded by divorce. Before consummating the TCR2 deal, Adaptimmune ended an alliance with a larger pharmaceutical company.

Adaptimmune and TCR2 Therapeutics, two clinical-stage biotechs that have recently cut staff to conserve capital, are coming together in a deal that aligns their cell therapy strategies. The business combination also extends the new company’s cash runway during a difficult time for publicly traded firms to raise money, which Adaptimmune will need as it looks ahead to the regulatory review and potential commercialization of its first cancer cell therapy.

The transaction announced Monday is framed as a merger, but it amounts to an Adaptimmune acquisition. The all-stock deal will result in shareholders of Oxford, U.K.-based Adaptimmune owning 75% of the combined company, which will retain the Adaptimmune name and be run by that company’s CEO, Adrian Rawcliffe.

Both Adaptimmune and Cambridge, Massachusetts-based TCR2 are developing therapies made by the engineering of a patient’s own immune cells. The first cell therapies that have reached the market all address blood cancers. Adaptimmune and TCR2 are among the companies aiming to bring cell therapy to solid tumors, which account for about 90% of cancer deaths in the U.S., Adaptimmune said in an investor presentation.

Adaptimmune’s T cell platform tech platform, called Spear, addresses targets inside of a cell. This technology identifies T cell receptors (TCRs) that can bind a target peptide or protein. Those TCRs, which are further engineered to improve their ability to recognize and bind to cancer targets, become the homing mechanism for an Adaptimmune cell therapy.

The most advanced program for the combined company will be Adaptimmune’s cell therapy candidate targeting MAGE-A4. While this cancer protein is found on many types of solid tumors, the first indication the company aims to treat is synovial sarcoma, a rare cancer that affects soft tissue such as muscle and ligaments. In its pivotal clinical trial, the Adaptimmune cell therapy, afamitregene-autoleucel (“afami-cel” for short), led to a 39% overall response rate in patients who had previously been treated for the cancer. The median duration of the response to the Adaptimmune therapy was 12 months. A rolling submission initiated with the FDA at the end of last year is expected to be complete in mid-2023.

“The combined company will drive forward its pipeline of cell therapies aimed at treating multiple cancers with high unmet medical needs,” Rawcliffe said in a prepared statement. “This includes gaining approval for the first engineered TCR T-cell therapy for a solid tumor—afami-cel for the treatment of synovial sarcoma.”

Adaptimmune is also looking to address MAGE-A4 to treat other types of cancer. This year, the company plans to begin clinical trials testing the MAGE-A4 cell therapy in ovarian cancer, head and neck cancer, and urothelial cancer. To keep its MAGE-A4 plans on track, Adaptimmune announced last November it would shift resources away from “non-core programs” as part of a corporate restructuring that would cut its headcount by up to 30%.

Meanwhile, TCR2’s T cell receptor fusion constructs (TRuC) platform addresses targets on the surface of a cell. That company’s most advanced program is gavocabtagene autoleucel (gavo-cel). This cell therapy, engineered with a TCR that targets a cancer antigen called mesothelin, is in a Phase 1/2 clinical trial enrolling patients with non-small cell lung cancer, ovarian cancer, mesothelioma, or cholangiocarcinoma. In January, TCR2 announced a restructuring resulting in the layoff of about 40% of its staff.

Adaptimmune’s marriage announcement with TCR2 and its mesothelin-targeting lead program coincides with the end of an alliance with an Astellas Pharma subsidiary called Universal Cells. Under a deal struck in 2020, Universal Cells paid Adaptimmune $50 million up front and pledged up to $897.5 million more in milestones in a research partnership developing allogeneic, or “off-the-shelf,” cell therapies. The first target of the alliance was an allogeneic cell therapy addressing mesothelin.

According to a Monday regulatory filing, Adaptimmune and Universal Cells mutually agreed on March 2 to terminate their collaboration agreement effective March 6. The termination means that each party must return all confidential information to the other party within 30 days. Also, all cell lines developed under the partnership must be destroyed within the same time frame. No financial penalties were incurred by either party as a result of the termination of the agreement, the filing said.

The end of the alliance means Adaptimmune gives up the opportunity to work with a larger company in Astellas, which has been active lately in cell and gene therapy deals. But in TCR2, it gets a more advanced, albeit autologous, mesothelin-targeting program. Adaptimmune also gets more immediate access to cash. As of the end of the third quarter of last year, TCR2 reported having $176 million in cash, which it estimated would last for at least the next 12 months. Adaptimmune’s cash position at the end of 2022 was $204.6 million. When the merger closes, the combined company expects its cash will support operations into 2026. Adaptimmune still has an active partnership with Genentech developing allogeneic cell therapies for cancer. But last October, Adaptimmune announced that GSK gave notice it was terminating its alliance and returning the partnered assets to the biotech.

The shareholders of both Adaptimmune and TCR2 still need to approve the deal, which is expected to close in the second quarter of this year.

Photo: nespix, Getty Images

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