Harpreet Singh, CEO of Immatics

Celgene will partner with Immatics Biotechnologies to develop novel adoptive cell therapies against multiple cancers, Immatics said today, through a collaboration that could generate more than $1.5 billion for the German T-cell immunotherapy developer—and further expand Celgene’s oncology pipeline in advance of its planned $74 billion acquisition by Bristol-Myers Squibb (BMS).

Under the companies’ strategic collaboration and option agreement, Immatics plans to develop T-Cell Receptor Engineered T-cell Therapy (TCR-T) programs targeting solid tumor targets discovered through Immatics’ XPRESIDENT technology. The programs would apply proprietary T-Cell Receptors (TCRs) identified by Immatics’ XCEPTOR® TCR discovery and engineering platform.

The partnership is designed to combine Immatics’ target discovery engines, cellular manufacturing, and clinical development platforms with Celgene’s expertise in cell therapy research, development, and commercialization. For each program Immatics agrees to develop against TCR-T targets, Immatics will oversee development and validation through lead candidate stage, at which point Celgene may exercise opt-in rights and assume sole responsibility for further worldwide development, manufacturing, and commercialization.

Immatics said it would retain early-stage co-development rights or co-funding rights for selected TCR-T-cell therapies arising from the collaboration.

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.

Four-fold-plus target increase

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.

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. Immatics uses three approaches to producing those therapies:

  • ACTolog®, designed to select and expand a patient’s autologous T cells based on cancer cell targets identified by XPRESIDENT, before reinfusing back into the patient to treat their tumor.
  • ACTengine®, designed to engineering a patient’s own T cells to recognize the cancer cell targets as identified by XPRESIDENT. The cells are expanded before reinfusion back into the patient to treat their tumor.
  • ACTallo®, designed to engineer allogenic donor cells to recognize cancer cell targets as identified by XPRESIDENT, for use in development of off-the-shelf therapies.

“This alliance leverages Immatics’ excellence in developing adoptive cell therapies (ACT) and complements our proprietary clinical pipeline of ACT products and our strong portfolio of Bispecific products,” the company said.

Celgene agreed to pay Immatics $75 million upfront for access to three programs; up to $505 million per licensed product in option exercise payments plus development, regulatory, and commercial milestone payments; as well as tiered royalties on net sales.

Bolstering cancer cell therapy pipeline

The Immatics collaboration is Celgene’s latest move to bolster its cancer cell therapy pipeline. In announcing second-quarter results on July 30, Celgene said it was still on track for a fourth-quarter 2019 BLA submission for lisocabtagene maraleucel (liso-cel or JCAR017), being developed for diffuse large B-cell lymphoma and chronic lymphocytic leukemia—and inherited from Juno Therapeutics, which Celgene acquired last year for $9 billion.

Celgene also said a BLA submission is planned in the first half of 2020 for idecabtagene vicleucel (ide-cel or bb2121), an anti-B-cell maturation antigen (BCMA) CAR T cell therapy which Celgene is co-developing with bluebird bio for patients with relapsed/refractory multiple myeloma.

In May, the New England Journal of Medicine (NEJM) published interim results from the Phase I CRB-401 trial (NCT02658929). Treatment with bb2121 resulted in an 85% objective response rate with 15 of patients (45%) achieving a complete response, and an additional nine patients (27%) achieving a very good partial response.

BMS and Celgene cited liso-cel and ide-cel among six late-stage clinical candidates expected to launch over the near-term and generate more than $15 billion annually for the combined company.

In its announcement Monday of Celgene’s $13.4 billion sell-off of Otezla® (apremilast) to Amgen, BMS stated it now expects to close the Celgene acquisition by the end of 2019. Celgene is selling Otezla to address U.S. Federal Trade Commission (FTC) concerns about BMS’ planned acquisition of the biotech giant, announced January 3. The deal is subject to BMS and Celgene entering into a consent decree with the in connection with the companies’ pending merger, the closing of the merger, and other customary closing conditions.

Immatics is based in Tuebingen, Munich, Germany, with U.S. operations in Houston. Immatics’ pipeline now includes several bispecific TCR and antibody molecules, as well as T-cell therapy programs developed by its U.S. unit Immatics US with Houston-based University of Texas MD Anderson Cancer Center, and co-funded by the Cancer Prevention and Research Institute of Texas (CPRIT).

Celgene isn’t Immatics’ only multi-billion-dollar cancer immunotherapy collaboration partner. Last year, Immatics launched a potentially more-than-$2.8 billion partnership with Genmab designed to discover and develop next-generation bispecific cancer immunotherapies. Immatics also has collaborations with Amgen, MorphoSys, and Roche.

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