TCR2 IPO hits midpoint, setting stage for trials of CAR-T rivals

TCR2 thinks its T cell therapies will have superior durability and safety than CAR-Ts. (Nasdaq)

TCR2 Therapeutics has priced its IPO at the midpoint of the target range. The offering stands to net TCR2 $67 million, setting it up to move cell therapies designed to better CAR-Ts through early-phase development. 

Massachusetts-based TCR2 has reached the cusp of clinical development fueled by $125 million in series B funds it raised last year. TCR2 still had $131 million in the bank as of the end of September but, with aspirations to test several autologous T cell therapies in humans in the coming years, has turned to public markets for more money to see it through to 2022.

Investors have proved to be receptive to the pitch. Having set out to sell 5 million shares at $14 to $16 a piece, TCR2 has landed in the middle of the range, setting it up to gross $75 million. Minus fees, TCR2 stands to pocket $67.3 million.

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By hitting its fundraising target, TCR2 has positioned itself to move three candidates into and through early-phase development. TCR2 plans to start testing TC-210 in patients with mesothelin-positive solid tumors imminently and get therapies against CD19-positive B-cell hematological malignancies and MUC16-positive solid tumors into the clinic by early next year.

The flurry of INDs will lay the groundwork for a series of readouts in the coming years, starting with early data on TC-210 in the second half of 2019. TCR2 expects to generate data on the other drugs in 2020 and 2021.

Those readouts will provide early pointers as to whether TCR2’s cell therapies work as hoped. TCR2 thinks its T cell therapies will have superior durability and safety than CAR-Ts, while also performing better in solid tumors. That view is underpinned by TCR2’s analysis of the shortcomings of CAR-Ts and preclinical data on its candidates.

As TCR2 sees it, CAR-T therapies are held back by their use of just one subunit of the TCR2 signaling complex and independence from normal T cell signaling mechanisms, leading them to overproduce cytokines.

TCR2 makes its cell therapies by fusing a cancer antigen recognition domain to a subunit of the T cell receptor (TCR). A lentiviral vector then transfers genetic information for TCR2’s TCR Fusion Construct into a patient’s own T cells. This results in T cells that zero in an a specific antigen. When the T cells find the antigen, TCR2 thinks they will harness the entire TCR, triggering a strong yet safe attack.

That idea has held up in preclinical tests but could come unstuck in a number of ways in the clinic. One theoretical concern is that the production process will expand a T cell that recognizes a patient’s own cells as invaders. Such a cell therapy could attack healthy tissues, potentially killing the patient.

TCR2 plans to exclude people with a history of severe autoimmune disease from its trials to mitigate the risk, but even then there is a slim chance it will produce autoreactive T cell therapies. 


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