With $125M in the bag, TCR2 advances lead T-cell programs

TCR2 Therapeutics raised an oversubscribed series B round from the likes of 6 Dimensions Capital, Curative Ventures, Sirona Capital, Alexandria Venture Investments and MPM Capital. (NikolayFrolochkin)

Immuno-oncology biotech TCR2 Therapeutics reeled in $125 million in an oversubscribed series B, which will propel two programs through clinical proof of concept.

The company now has runway into 2021, allowing it to generate the first clinical data for its lead solid tumor asset, TC-210, and one other program, CEO Garry Menzel said. TC-210 targets mesothelin, an “ideal” cancer target. It’s a tumor antigen expressed in high levels in several cancers but in low levels in normal tissue.

“You don’t find it at all in the brain, so neurotoxicity is not an issue,” Menzel said.

Mesothelin is expressed in more than half of ovarian pancreatic and lung cancers, large patient populations that TCR2 hopes to target. The company will also go after mesothelioma and cholangiocarcinoma, the cancers with the highest expression of the mesothelin antigen, Menzel said.

TCR2’s programs use its TRuC technology, which is designed to go where other engineered T-cell approaches, such as CAR-T or T-cell receptor (TCR) therapies, cannot.

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CAR-T, which involves engineering T cells taken from a patient’s blood and then re-infusing them back into the patient, has seen success in blood cancers but has run into trouble against solid tumors.

As for engineered TCRs, they have shown activity in solid tumors but rely on the antigen HLA, to which they bind. HLA is downregulated in many cancers, making them invisible to T cells. And some TCR treatments only work with certain subtypes of HLA, which limits the addressable market. Finding treatable patients requires lots of screening, and even then these patients are still at risk of relapse due to subsequent downregulation of HLA, said Alfonso Quintás Cardama, M.D., TCR2’s chief medical officer.

TCR2’s tech, designed by Patrick Baeuerle, tethers a tumor antigen-binding domain directly to the TCR complex, creating a TRuC construct that is able to recognize highly expressed tumor antigens without HLA. The full TCR is activated, which stimulates the T cell to kill the cancer cell, Menzel said.

The company has a program combining TC-210 with a PD1 switch, which it will investigate in lung cancer. If all goes well, it will use the series B funding to move this candidate into the clinic. And it’s got a second solid tumor program, dubbed Program X, which is in the works for a number of different targets. Menzel did not disclose what these targets are, saying we’ll know more once TCR2 is ready to nominate a candidate.

Finally, TCR2 also has a blood cancer candidate in the pipeline, a dual CD19/22 treatment. While it has decided that solid tumors are where it should put its money, Menzel believes there is plenty of room in the hematological market, particularly on the safety side. It's a timely concern—earlier this month, another T-cell player, Unum Therapeutics, disclosed in an SEC filing that a phase 1 trial of its lead candidate is under an FDA hold due to patient deaths related to cytokine release syndrome, a frequent side effect of CAR-T therapies that can be fatal.