CAR-T therapies are heating up, with two new approvals in the past year, but the drug class has been limited to blood cancers and can run into resistance issues. Mnemo Therapeutics thinks it has a solution, and a new funding round of €75 million ($90 million) will help get that plan rolling.
The $90 million, drawn from Mnemo’s seed investor Sofinnova Partners along with Casdin Capital, Redmile, Emerson Collective and Alexandria Venture Investments, will bankroll the development of Mnemo’s CAR-T discovery and development technology as well as propel at least two candidates into clinical trials in early 2024, said Mnemo CEO Alain Maiore.
The company will also invest in its autologous and allogeneic manufacturing power to make sure the reagents used in discovery work are the same ones that will later be used in development, Maiore said.
Mnemo’s pipeline is based on technology licensed from its scientific founders: Sebastian Amigorena, Ph.D., of the Institut Curie in Paris and Michel Sadelain, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center. Known as EnfiniT, the platform is built around a discovery engine aimed at identifying epigenetic antigens as targets for CAR-T treatments.
“You want to identify antigens that are very, very specific for your tumor. For solid tumors, it has been particularly difficult to find those because they tend to be expressed in other tissues, as well,” said François Gaudet, Ph.D., chief scientific officer of Mnemo.
Targets that are overexpressed in solid tumors can be expressed in lower levels elsewhere, making heathy tissues vulnerable to attack by the CAR-T. Epigenetic antigens are the result of DNA sequences called transposable elements that can change their position within the genome and create mutations. This leads to the production of proteins that are found in the tumor cells, but not healthy cells.
As for tired T cells and tumor resistance, Mnemo is working on those, too. Its technology could boost CAR-T cell memory and persistence, which are required “to be able to see efficacy in the clinic.” And another piece of the platform addresses antigen escape, the process by which a cancer stops addressing the antigen that a CAR-T is designed to hunt down.
“We have a technology that can recognize and kill tumor cells with very, very low levels of antigen, almost on par with the sensitivity of a natural T cell,” Gaudet said. “It’s different than the traditional CAR design and it leads to greater activity and less resistance.”
Though Mnemo will eventually develop CAR-T therapies against epigenetic targets, the initial programs will aim at known targets in solid and blood cancers.
“We know there are 15 or 20 targets out there that people are using either in liquid or solid tumors. In order to validate our technology platform and also tackle the first commercial opportunities to the patient benefit, we picked up some of these targets,” Maiore said.
Mnemo is working toward applying to move the first two programs into the clinic in early 2024. Meanwhile, the company will carry on discovering and developing treatments against epigenetic targets with hopes to get two programs into the clinic by late 2024 or early 2025, Maiore said.
Mnemo will keep some of those programs and license others out to partners, Maiore said.
“Eventually, with the accumulation of compelling preclinical data we will raise more money and do business development alliances,” he added.
Some companies, such as Allogene and Cellectis, view allogeneic, or off-the-shelf, CAR-T treatments as the future, replacements for today’s autologous treatments, which are made from a patient’s own cells. But Mnemo believes the two approaches, as well as in vivo CAR-T, where a medicine generates CAR-T cells within the body, will all be part of a cancer-fighting toolbox.
“In our mind, they are going to be used together … The condition, the patient situation will dictate which of the three technologies you want to use,” Maiore said.