Sanofi pays $160M for mRNA tech to reprogram T cells in vivo

Sanofi has paid $160 million upfront to buy a preclinical biotech that is using mRNA to reprogram immune cells inside the human body. The technology could enable patients to make their own CAR-T cells, eliminating the complex cell therapy supply chain while improving safety and dosing.

The biotech, LabCentral-based Tidal Therapeutics, has kept a low public profile since spinning out of the Fred Hutchinson Cancer Research Center but still quickly attracted attention. Mission BioCapital seeded the biotech with assists from investors including RA Capital, New Enterprise Associates and AbbVie Ventures. Now, Sanofi has given those investors an early exit.

Much of what is known about Tidal comes from papers published by Fred Hutch’s Matthias Stephan, M.D., Ph.D. In 2019, Stephan and his colleagues described the use of nanocarriers to deliver mRNA encoding for transcription factors that reprogram tumor-associated macrophages to reverse immunosuppression. 

In mice, the nanocarriers delayed tumor progression, leading collaborators to outline a role for the macrophage-modifying treatment in combination therapies in populations refractory to other drugs. The collaborators identified ovarian cancer as a targeted indication. 

Fred Hutch disclosed that the technology was exclusively licensed to Tidal. Stephan is a scientific founder of the biotech. Ulrik Nielsen, Ph.D., the co-founder of Merrimack, is CEO.

Last year, Stephan co-authored another paper describing the use of mRNA to cause in vivo creation of T cells expressing tumor-specific CARs or virus-specific TCRs. The study suggested the approach may be as effective as the adoptive transfer of engineered T cells while providing greater control over the pharmacokinetic properties of the therapy.

In a statement, Frank Nestle, M.D., chief scientific officer at Sanofi, said the “next generation, off-the-shelf approach has the potential to bring CAR-T cell therapy to a much broader patient population.” 

Other biotechs see bispecific antibodies as a way to deliver CAR-T-level efficacy without taking on the complexity, costs and risks of cell therapies. However, Stephan and his collaborators said the need to give bispecifics by continuous infusion can cause systemic toxicities. The researchers also identified the ability of their system to “generate de novo tumor-specific T cells, which as a ‘living drug actively localize to the target, increase in number and serially destroy cancer cells” as an advantage.

The technology has applications in infectious diseases as well—the Fred Hutch team has engineered T cells to recognize hepatitis B—inflammatory diseases and other therapeutic areas. Sanofi valued the big, broad potential of the platform at $160 million upfront and up to $310 million in milestones.

If the technology lives up to its potential, it could give Sanofi products that generate sales that dwarf the outlay on Tidal, but the novel, early-stage nature of the approach means there are pitfalls. The Fred Hutch team identified the nanoparticles as a source of risk in the 2020 paper, explaining that “minor variations in many parameters” can affect safety and efficacy and that “only a few facilities with the requisite degree of expertise are currently operational in the United States.”