Barely a year after pulling in $125 million to advance a pair of T-cell therapies, TCR2 Therapeutics is looking to raise up to $80 million in an IPO.
The Cambridge, Massachusetts-based biotech plans to sell 5 million shares at a price between $14 and $16 apiece, putting the IPO range between $70 million and $80 million. TCR2’s lead treatment, TC-210, targets mesothelin, what CEO Garry Menzel calls an “ideal” cancer target. Mesothelin is a tumor antigen expressed in high levels in several cancers but in low levels in healthy tissue.
TCR2 is developing TC-210 for a number of cancers—including those that have the highest expression of mesothelin—such as cholangiocarcinoma, or bile duct cancer, and mesothelioma, a cancer of the mesothelium, the thin tissue that lines the lung, chest wall and abdomen. Just last week, TC-210 earned orphan drug designation for mesothelioma, which has a five-year survival rate of 1% to 16%, depending on how advanced the cancer is.
The company is also hoping to target ovarian cancer and non-small cell lung cancer with TC-210, as mesothelin is expressed in more than half of these cancers. It filed the IND for TC-210 in December and expects data in the second half of the year.
TCR2 has two more solid tumor programs underway—its ovarian cancer treatment, TC-220 targets MUC16 and is in IND-enabling studies, and its TC-410 targets both MUC16 and mesothelioma, and is being developed for ovarian and pancreatic cancers. It expects to file an IND for TCR-220 in early 2020.
In an interview earlier this year, Menzel said that TCR2 had decided to focus on solid tumors but that he believes there is plenty of room in the hematological market, particularly on the safety side. TCR2 is developing TC-10, which targets CD19, and TC-310, which targets both CD19 and CD22. Both are in development for adult acute lymphoblastic leukemia, diffuse large B-cell lymphoma and follicular lymphoma.
The company’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.
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 not has faced difficulties in solid tumors.
As for engineered TCR treatments, 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. 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, in a previous interview.
To avoid these problems, 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.