Immatics and Adaptimmune show that T-cell receptor deals aren't dead

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Two deals in as many days featuring engineered T-cell receptors (TCRs) show that interest in this approach is alive and well, with companies able to command respectable sums for a technology that has yet to deliver any notable clinical breakthroughs. Immatics announced today that Celgene had handed over $75m up front for options over three research projects; the targets were not disclosed, though solid tumours are the focus. Celgene's cell therapy focus, via its Juno acquisition, has mainly been on CAR-T, though it has one TCR project in the clinic; Bristol-Myers Squibb has said that a key reason why it wanted to buy Celgene was to gain a foothold in cell therapy, and the big pharma group has presumably signed off on this transaction, though Immatics declined to confirm that. Yesterday, the UK’s Adaptimmune unveiled a collaboration with Noile-Immune Biotech to develop TCRs that co-express IL-7 and CCL19, also aiming at solid tumours; the deal is worth up to $312m to the Japanese company. Adaptimmune is arguably one of the leaders in this field, but its work has been blighted by patient deaths; perhaps this deal is an acknowledgement that its technology needs a tweak.

Selected engineered TCR projects
Company/group Project Target Status Trial ID
Adaptimmune MAGE-A10 TCR MAGE A10 (deprioritised Aug 2019) Phase I NCT02592577
  MAGE-A4 TCR MAGE A4 (linked to one patient death) 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
  H3.3K27M TCR H3.3K27M Preclinical  NA
Immatics IMA201 Undisclosed Phase I NCT03247309
  IMA202 Undisclosed Phase I NCT03441100
Medigene MDG1011 PRAME Phase I NCT03503968
  TCR-IIT MAGE A1 Preclinical NA
Medigene/Bluebird None Six undisclosed targets Preclinical NA
Regeneron/Adicet Bio None Undisclosed targets for allogeneic use Preclinical NA
Regeneron/Bluebird None Six undisclosed targets Preclinical NA
Zelluna TCR-CRC-001 TGFβII Preclinical NCT03431311
*Licensed from Adaptimmune. Source: company filings & clinicaltrials.gov.

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