GSK partners with Lyell to bring gene, cell therapies into solid tumors

As GSK looks to expand its cell and gene therapy pipeline, the pharma has partnered with Lyell to take the modalities into solid tumors by improving T cell functionality and manufacturing.

Lyell Immunopharma Inc. is focused on delaying T cell exhaustion to enhance initial response rates in solid tumor cancers and prevent relapses due to loss of T cell functionality.

GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) and Lyell will collaborate for five years on T cell receptor therapies and for two years on CAR therapies. GSK and Lyell declined to disclose financial terms.

GSK said it will initially use Lyell’s platform to improve the efficacy of its TCR therapy, GSK3377794, before applying it to other assets in its cell and gene therapy pipeline.

GSK3377794, an autologous therapy targeting NY-ESO-1, is in a Phase II trial in patients with advanced or recurrent non-small cell lung cancer who are positive for NY-ESO-1- or CTAG2.

Lyell was co-founded by David Baker, the director of the University of Washington’s Institute for Protein Design (IPD). He is also a professor of biochemistry at the University of Washington and a Howard Hughes Medical Institute investigator.

While Lyell declined to disclose the details of its T cell platform, a Nature paper published by IPD researchers in July describes a de novo protein switch platform that could be applied to create programmable biologics and cell therapies. The system, dubbed latching orthogonal cage-key proteins (LOCKR), can modulate a range of biological functions such as controlling binding, tuning gene expression and amplifying or suppressing signaling pathways (see “Institute for Protein Design’s de Novo Revolution”).

Work by EVP, Research Nick Restifo, who was a researcher at NIH’s National Cancer Institute (NCI) for 31 years, could provide a glimpse of how Lyell’s platform may improve manufacturing. An NCI team led by Restifo published a Science paper in March showing that raising potassium levels or adding a citrate derivative when manufacturing adoptive T cell therapies can help the cells maintain characteristics associated with stem cells, such as persistence, self-renewal and multipotency. The characteristics have been linked with successful treatment outcomes with checkpoint inhibitors and adoptive T cell therapies (see “NCI Team Details Method to Improve T Cell Therapies”).

Lyell’s other co-founders include Crystal Mackall, a professor of pediatrics and internal medicine at Stanford University; and CEO Rick Klausner, a serial entrepreneur who previously founded Juno Therapeutics Inc. and Grail Inc., and directed NCI.

Other cancer veterans on Lyell’s executive team include Restifo and CSO Margo Roberts, who held the same position at Kite Pharma Inc., where she helped develop CAR T therapy Yescarta axicabtagene ciloleucel.

Lyell’s board includes Arch Venture Partners’ Robert Nelson and ex-Juno CEO Hans Bishop, who is now Grail’s CEO.

Targets: CTAG2 (LAGE1; NY-ESO-2) - Cancer/testis antigen 2; NY-ESO-1 (CTAG1B) - Cancer/testis antigen 1B

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