Bellicum pins its next cell therapy hope on Her2

While Bellicum tries to get its lead cell therapy, Rivo-Cel, across the regulatory finish line it is continuing to talk up the early-stage pipeline. This week it revealed that a fifth pipeline asset, a CAR-T therapy called BPX-603, will target the Her2 antigen and enter the clinic this year. This might seem puzzling: Her2 is known to be expressed on healthy as well as cancerous cells, and the risk of on-target/off-tumour toxicity with a therapy as powerful as CAR-T is considerable. Indeed, an NCI study of a Her2-directed CAR that caused a patient death has been well documented. Nevertheless, several such trials are ongoing, including one at Bellicum’s academic parent, Baylor College. And Bellicum reckons it can overcome problems by using in BPX-603 a humanised binding domain that is more selective for Her2 than Baylor’s murine binder, as well as employing dual “on” and “off” switch domains. Still, there is little to suggest that an adverse event that occurs as fast as cytokine storm can be counteracted by this type of off switch, and in any case this technology does not appear to be proprietary to Bellicum.

Selected Her2-directed CAR-T therapies
Sponsor Project Cancer types Trial ID
Mustang Bio/NCI HER2-CAR Brain or leptomeningeal metastases NCT03696030
Baylor College HER2-CAR Sarcoma NCT00902044
Baylor College HER2-CAR Her2 +ve CNS tumors NCT02442297
Seattle Children's Hospital HER2-specific CAR Her2 +ve CNS tumors NCT03500991
Leucid Bio/King's College  T1E28z* Head & neck cancer NCT01818323
NCI Anti-Her-2 cells Colon cancer NCT00924287**
Bellicum BPX-603 Gastric & endometrial cancers TBA
Source:; *targets Erb dimers including Her2; **study terminated owing to patient death.

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