TMAC Cancer Therapy Platform Demonstrates Successful Proof-of-concept

Avacta, the developer of Affimer® biotherapeutics and reagents, has announced that it has demonstrated initial proof-of-concept for its proprietary new class of drug conjugate, TMAC™, in a pre-clinical animal model of cancer. The study showed that AVA04-VbP outperformed Bavencio (Avelumab), a marketed anti-PD-L1 immunotherapy.

Avacta’s tumor microenvironment activated drug conjugates (TMAC) are a new form of cancer immunotherapy, combining its Affimer biotherapeutics with chemotherapies in a single drug, using a linker (incorporating its proprietary pre|CISION™ substrate) that is designed to only release the chemotherapy in the tumor microenvironment through the action of an extracellular enzyme called FAPα. This mechanism is designed to overcome the need to target an internalizing cancer marker, as with conventional antibody drug conjugates (ADCs), and allows extremely potent chemotherapies to be combined with Affimer immune-checkpoint therapies.

AVA04-VbP combines an Affimer PD-L1 checkpoint inhibitor with an I-DASH chemotherapy warhead, addressing the acute systemic toxicity associated with I-DASH inhibitors by targeting the release of the drug warhead in the tumor microenvironment. The drug warhead induces a highly pro-inflammatory cell death, which in turn stimulates an immune response in the tumor, which is supported by the Affimer PD-L1/PD-1 signaling pathway blockade.

In a mouse syngeneic tumor model study, Avacta has shown that AVA04-VbP outperforms Bavencio; animals treated with AVA04-VbP showed a significant reduction in the rate of tumor growth with respect to those treated with Bavencio. A considerably higher level of the released I-DASH warhead was measured in the tumors compared with very low levels in the blood, indicating that healthy tissues are less exposed to the highly toxic warhead. This tumor targeting is central to the TMAC mechanism of action, and permits the use of the highly potent cancer-killing warheads.