Avacta Therapeutics, a biopharmaceutical company focused on clinical-stage development, has unveiled significant preclinical findings regarding its groundbreaking dual payload pre|CISION® technology at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held in Boston, Massachusetts, on October 25, 2025.
The company”s innovative approach involves concurrently delivering two distinct therapeutic agents to the tumor microenvironment (TME) through a single cleavage event mediated by fibroblast activation protein (FAP). This technology, known as AVA6207, positions Avacta as a pioneer in the realm of dual payload peptide drug conjugates (PDCs), which are designed to counteract the resistance mechanisms that cancer cells often develop against traditional single-drug therapies.
According to Christina Coughlin, M.D., Ph.D., CEO of Avacta, the introduction of the first dual payload peptide drug conjugate represents a significant advancement in cancer treatment. The combination therapy facilitated by this technology aims to enhance anti-tumor efficacy while overcoming established resistance pathways. Coughlin emphasized that this approach could substantially improve outcomes for patients, particularly those battling highly resistant tumors.
The pre|CISION® platform has already demonstrated its potential through compelling clinical data with faridoxorubicin (AVA6000, FAP-Dox), which indicated a remarkable tumor-to-plasma payload concentration of 100:1. This demonstrates a significant reduction in off-target toxicities, even at doses that are approximately four times higher than those of standard doxorubicin.
Key findings from the preclinical studies indicate that the dual payload technology allows for effective FAP-selective delivery and potent anti-tumor activity with various complementary payload combinations. The dual payload compounds achieved notable cytotoxic effects comparable to free payloads in the presence of FAP, while showing minimal activity without it, confirming great tumor selectivity.
In particular, the research confirmed that the dual payload compounds not only release both therapeutic agents from a single FAP cleavage event but also successfully modulate target-specific biomarkers. This modulation was evident only in the presence of FAP, demonstrating the specificity and efficacy of the delivery mechanism.
Moreover, the combination of payloads has shown enhanced synergistic activity, effectively addressing known resistance mechanisms in cancer treatment. For instance, compounds combining FAP-Exd with DNA damage response (DDR) inhibitors exhibited four to five times greater cytotoxicity compared to exatecan alone, underscoring the technology”s potential to confront DNA repair-mediated resistance pathways.
The presentation, titled “Discovery and characterization of novel pre|CISION® technology compounds delivering complementary dual payloads to the tumor microenvironment following FAP cleavage,” is available on the company”s website. Following the conference, the Avacta team will host a presentation via Investor Meet Company to discuss the findings further.
Avacta continues to innovate in the field of oncology by developing its proprietary drug delivery platform designed to enhance the efficacy and tolerability of cancer treatments. The dual payload approach represents a promising frontier in the fight against cancer, potentially benefiting a significant portion of patients suffering from solid tumors.
