Avacta’s Dual Payload Platform Data Unveiled at AACR-NCI-EORTC International Conference

Avacta Therapeutics (AIM: AVCT) has revealed encouraging preclinical data for its dual payload pre|CISION medicines at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

The company's technology allows for the simultaneous delivery of two distinct therapeutic payloads to the tumor microenvironment (TME) through a single cleavage event.

Avacta is pioneering dual payload peptide drug conjugates (PDCs), tackling resistance issues associated with single-drug therapies by using targeted combination delivery.

Avacta's dual payload pipeline features combinations of microtubule inhibition and topoisomerase I inhibition (MMAE and exatecan), and DNA damage response (DDR) agents (ATR or PARP inhibitors) combined with exatecan. These combinations aim to enhance the cytotoxic effect of exatecan by inhibiting DNA repair mechanisms.

Christina Coughlin, M.D., Ph.D., Chief Executive Officer of Avacta, commented that the dual payload peptide drug conjugate marks a significant step forward in oncology therapy, extending the potential of their pre|CISION platform by implementing combination cancer therapy in a single small molecule medicine.

The synergistic enhancement in anti-tumor activity observed with exatecan-DDR inhibitor combinations highlights the potential of targeting the tumor with a potent cytotoxic drug while attacking the known resistance mechanisms.

Key Preclinical Findings:

• Validated dual payload release mechanism: Analyses confirmed simultaneous release of two independent payloads, with tunable delivery kinetics.
• FAP-selective tumor cell killing: Dual payload compounds demonstrated potent cytotoxic activity in the presence of FAP, confirming excellent tumor selectivity.
• Confirmed dual mechanism biomarker modulation: Target-specific biomarkers for both payloads were modulated only in the presence of FAP.
• Enhanced synergistic activity: FAP-Exd/PARPi and FAP-Exd/ATRi compounds demonstrated significantly greater tumor cell killing compared to exatecan alone.
• Validated bystander mechanism: Co-culture studies confirmed that FAP-positive cancer-associated fibroblasts mediate payload release, resulting in effective killing of FAP-negative tumor cells.

Avacta's pre|CISION platform is said to offer key advantages over traditional antibody drug conjugates (ADCs), including tumor-specific payload release, small molecule manufacturing, better tumor penetration, and a large addressable market.

Avacta will hold a presentation via Investor Meet Company to review the published data.