Regeneron’s second cell therapy foray

Regeneron, best known for effectively serving as Sanofi’s R&D division, seems an unlikely cell therapy player. But the discovery deal it signed yesterday with Bluebird Bio marks its second in the field of engineered T-cell receptor (TCR) therapeutics. The Bluebird tie-up saw Regeneron take a $100m premium-priced equity stake in its partner, and will focus on six undisclosed targets. It came after Regeneron, two years ago, revealed an allogeneic CAR-T and engineered TCR alliance with the private group Adicet Bio – at the time famous for being run by the former chief executive of Kite Pharma, Aya Jakobovits. In development terms engineered TCRs have seriously lagged behind CARs; because TCRs only recognise antigens presented on a target cell’s major histocompatibility complex they are limited by the fact that in humans many different haplotypes of this complex exist, and therefore each product has to be matched appropriately. All the current TCR work is at the early clinical stage, and Bluebird itself already has a separate discovery alliance, with Germany’s Medigene.

Selected engineered TCR projects
Company/group Project Target Status Trial ID
Adaptimmune MAGE-A10 TCR MAGE A10 Phase I NCT02592577
  MAGE-A4 TCR MAGE A4 Phase I NCT03132922
  AFP TCR Alpha-fetoprotein Phase I NCT03132792
Gilead KITE-718 MAGE A3/A6 Phase I NCT03139370
  KITE-439 HPV-16 E7 Phase I NCT02858310
  KRAS TCR G12V variant of mutated RAS Phase I NCT03190941
  SSX2 TCR SSX2 Preclinical NA
NCI (NIH) HPV-16 E6 TCR HPV-16 E6 Phase I NCT03197025
  MAGE A3 TCR MAGE A3 Phase I NCT02153905
Glaxosmithkline GSK3377794  NY-ESO-1  Phase I NCT02992743
  PRAME TCR PRAME Preclinical NA
Celgene JTCR016 WT-1 Phase I NCT02408016 
Bellicum BPX-701 PRAME (rimiducid-activated suicide switch) Phase I NCT02743611
Cell Medica CMD-602 WT-1 Phase I NCT02550535 
  CMD-601 Survivin Preclinical NA
Tmunity NYCE T cells NY-ESO-1 (Crispr-edited, TCR-deleted, PD-1-deleted) Phase I NCT03399448
Immatics IMA201 Undisclosed Phase I NCT03247309
Medigene MDG1011 PRAME Phase I NCT03503968
  TCR-IIT MAGE A1 Preclinical NA
Medigene/Bluebird None Four undisclosed targets Preclinical NA
Regeneron/Adicet Bio None Undisclosed targets for allogeneic use Preclinical NA
Regeneron/Bluebird None Six undisclosed targets Preclinical NA
Source: company filings & clinicaltrials.gov.

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