Tscan Therapeutics Inc. CEO David Southwell told BioWorld that his firm’s series C financing of $100 million will allow two IND filings in liquid tumors this year and three – possibly more – in solid tumors starting next year. “We’ll be filing a lot of INDs in solid tumors,” he said. The Waltham, Mass.-based firm works with T-cell receptor (TCR)-engineered T-cell therapies.
“The trouble with solid tumors is that they express multiple targets,” Southwell said. “Our approach is to use our discovery platform to discover novel shared targets,” and the company is building a bank of TCRs. Tscan is interested in medium-mutation solid tumors such as renal cell carcinoma, triple-negative breast cancer, and head and neck cancer. In those, “a relatively small bank [can] address solid tumors in quite a large proportion of patients,” he said. The situation differs with high-mutation, often environmental solid tumors such as melanoma, non-small-cell lung cancer and, to some extent, colorectal cancer. “You get really funky mutations in those cancers,” he said. In liquid tumors, the company is targeting the likes of acute myeloid leukemia, myelodysplastic syndromes and the adult form of acute lymphocytic leukemia.
Tscan inked its validating partnership in the core business with Basel, Switzerland-based Novartis AG in mid-April 2020. “We don’t plan to have any more partnerships in [oncology], and in fact we just turned one down from a major pharma company,” Southwell said. But the platform also could help make tolerizing T-cell vaccines in autoimmune disorders.
That’s not all. “I never thought we’d ever work in infectious disease – it’s just a tough area, business-wise,” Southwell said. “Then COVID-19 rolled up, and we realized we have the perfect platform to find the targets of T cells in COVID-19.” Tscan was the first company to report findings about T cells in people recovering from the virus. “We were in a race with some much larger companies,” he said. “Most interestingly, only three of the 29 targets that we found, three of the 29 epitopes, lie in the spike protein, which is where all of the vaccine development is going on today.”
What does this mean for the currently available vaccines? Southwell noted that researchers found COVID-19 structurally similar to the SARS coronavirus of 2003. “The antibodies lasted for a few months, whereas the T cells in many cases are still active 17 years later,” he said. “When they started developing the [COVID-19] vaccines, the assumption was that you go after the proteins on the spike of the virus, because the antibodies bind to that spike. The problem is that if the antibodies don’t last very long – whether they’re the antibodies in recovering patients or given in the form of a vaccine – then what you really want is a T-cell therapy. Most of the epitopes that we found weren’t the ones on the spike protein [but] in the core of the virus. They’re not really subject to mutation,” he said.
Funded for two years
“If you had a T-cell therapy that addressed the internal epitopes, the T cells would last much longer and would be more perfectly imitating the T-cell epitopes,” Southwell went on. By the time his firm published its discoveries, however, “Moderna, Pfizer and the other companies were in a race to find a vaccine that targets the spike protein,” he said. “The last thing they wanted to do is put down their pencils on their phase II or phase III studies just to add some epitopes to the vaccine.” He said he is hopeful as a citizen that the current vaccines work durably, but if adjustments must be made, “our epitopes are going to become very useful.”
Other TCR firms are taking aim at known targets (as Tscan does with its first two liquid tumor INDs); the best-known player in that space is Adaptimmune Therapeutics plc, of Oxfordshire, U.K. Some companies are busy “finding which epitopes are expressed on surface of cancer cells, which we [also] do, but they don’t focus on whether those epitopes are actually going to be immunogenic,” Southwell said.
In November of last year, Tscan signed a research license and option agreement with Qiagen NV, of Hilden, Germany, to develop T-cell-based laboratory tests for detecting prior exposure to SARS-CoV-2 using discoveries from Tscan’s high-throughput TCR/Target discovery platform, called T-Scan. In October 2020, the firm entered a research collaboration and license agreement to explore developing TCR-T cell therapies for the treatment of COVID-19 with San Diego-based Poseida Therapeutics Inc. The latter’s allogeneic T-cell platform is being used in combination with Tscan’s discovered immunodominant epitopes and TCR sequences for the development and commercialization of allogeneic TCR-T cell therapies.
New investors came aboard for the latest Tscan round, including funds and accounts managed by Blackrock, RA Capital Management, and two undisclosed health care-focused funds. Existing backers who took part include founding investor Longwood Fund, 6 Dimensions Capital, Bessemer Venture Partners, GV, Novartis Venture Fund and Pitango Healthtech. Southwell said Tscan is considering a move to go public, depending on the state of the markets. “We definitely have time to do that, because we’re now funded for at least two years,” he said.