Next generation warheads in antibody drug conjugates

Spirogen, a leading oncology-focused company developing DNA sequence targeted agents, and BioAtla LLC, a San Diego headquartered antibody therapeutics developer, have announced new data on the use of pyrrolobenzodiazepine (PBD) dimers as warheads in antibody drug conjugates (ADCs) at the annual meeting of the American Association for Cancer Research (AACR) in Washington, DC.
 
The study evaluated the efficacy of five ADCs against solid and hematological cancer targets.  The hematological target antibody was engineered using BioAtla’s proprietary CIAO™ and BioAcceleration™ technologies and conjugated to Spirogen’s cytotoxic PBD dimers. Trastuzumab ADCs were tested against Her2-expressing human breast cancer in vivo.
 
For both tumour types data showed that the ADCs achieved durable complete regression and tumor free survival. The PBD dimers were not found to be cross-resistant with widely-used chemotherapeutic agents.
 
Professor John Hartley, lead author of the study and Director of Pre-clinical Development at Spirogen, said: “Significant activity at remarkably low doses and at low drug-antibody ratios was seen in all tumor types we studied. Antibody-PBD conjugates are the most promising next-generation oncology compounds for clinical development.”
 
Dr Jay M Short, Chairman and CEO of BioAtla, said: “By pairing our technologies with Spirogen’s warheads, we have achieved affinity and efficient internationalisation of these exciting novel ADCs.”
 
The AACR study, Abstract #2856, titled ‘Pyrrolobenzodiazepine (PBD) dimers - potent next generation warheads in antibody drug conjugates (ADCs) targeted at both solid and hematological tumors’, was authored by scientists from Spirogen, BioAtla, ADC Therapeutics, and UCL Cancer Institute, in London.

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