Immatics CEO Harpreet Singh, PhD

GlaxoSmithKline (GSK) will partner with Immatics Biotechnologies to develop novel adoptive cell therapies targeting multiple cancers, Immatics said today, through a collaboration that could generate more than $1 billion for the German/American developer of T-cell redirecting cancer immunotherapies.

GSK and Immatics have agreed to partner on identifying, researching, and developing next-generation T-cell receptor (TCR) therapeutics, with a focus on solid tumors. The companies will initially develop autologous T-cell therapies, with the option to add allogeneic cell therapies using Immatics’ ACTallo® approach.

ACTallo is one of three Immatics proprietary approaches designed to produce Adoptive Cell Therapies; the other two are ACTolog® and ACTengine®.

Those approaches have been developed to produce T-cell therapy programs in collaboration through Immatics US with The University of Texas MD Anderson Cancer Center and co-funded by the Cancer Prevention and Research Institute of Texas (CPRIT), a $3 billion fund created by the Lone Star State through a 2007 state constitutional amendment, and renewed last year by Texas voters when they agreed to double, to $6 billion, the amount of bonds that can be issued to support the agency.

Billion-dollar partners

GSK joins several other biopharma giants in partnering with Immatics on T-cell immunotherapies. Celgene, now a subsidiary of Bristol-Myers Squibb, launched a potentially more than $1.5 billion collaboration with Immatics in August 2019, while Genmab inked a potentially more than $1.8 billion alliance with Immatics in July 2018 focused on developing bispecific cancer immunotherapy treatments.

ACTallo is based on genetically engineering allogeneic gamma delta donor T cells to recognize cancer cell targets as identified by Immatics’ XPRESIDENT® target discovery platform technology.

Immatics and GSK said they plan to use proprietary TCRs identified by Immatics’ TCR discovery platform XCEPTOR®, directed against two proprietary targets that were discovered and validated by XPRESIDENT.

XCEPTOR is Immatics’ TCR technology platform designed to enable the fast and efficient discovery and qualification of a large number of high-affinity and high-specificity TCRs for use in the company’s adoptive cell therapies.

XPRESIDENT is a high-throughput technology platform designed to identify targets in virtually any type of cancer, for use in developing a range of immunotherapies. According to Immatics, the cancer targets identified by XPRESIDENT are all peptides detected at an attomolar concentration and presented by human leucocyte antigen (HLA) receptors on the surface of tumor cells, but absent in normal tissue.

The peptides are then analyzed and identified through a combination of quantitative transcriptomics (mRNA sequencing) and quantitative HLA-peptidomics (mass spectrometry). That data, Immatics said, is further analyzed to examine the differential expression and presentation of these potential peptidic drug targets between tumor and normal tissue.

XPRESIDENT is designed to unlock all intracellular antigens, increasing the target space by more than four-fold. By contrast, according to Immatics, classical antibody and CAR-T therapies are restricted to cell surface proteins which constitute about 20–25% of all available targets on a solid tumor.

Commitment to TCR-T

“By combining Immatics’ world-leading target and TCR discovery platforms with GSK’s advanced manufacturing, development capabilities and a commitment to next-generation TCR-T technologies, both companies are joining forces to enable the development of effective novel therapies for cancer patients with high unmet medical need,” Immatics CEO Harpreet Singh, PhD, said in a statement.

Immatics has agreed to assume primary oversight for the development and validation of the TCR therapeutics up to designation of a clinical candidate. At that point, GSK has agreed to take sole responsibility for further worldwide development, manufacturing, and commercialization of the TCR therapeutics, with the possibility for Immatics to co-develop one or more TCR therapeutics—including conducting the first-in-human clinical trial at GSK’s request.

GSK agreed to pay Immatics $50 million upfront for two initial programs, and potentially more than $550 million in per-product payments tied to achieving development, regulatory, and commercial milestone, plus additional royalties.

GSK also obtained an option to select additional target programs to be developed through the collaboration. For each additional program selected, GSK has agreed to pay Immatics additional option, milestone, and royalty payments.

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