Avacta Therapeutics, a clinical-stage biopharmaceutical firm, has announced the unveiling of preclinical data related to its pioneering dual payload pre|CISION® technology (AVA6207) at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held in Boston, Massachusetts, on October 25, 2025. This technology represents a significant advancement in cancer therapy, as it allows for the simultaneous delivery of two distinct therapeutic payloads to the tumor microenvironment (TME) through a single cleavage event mediated by fibroblast activation protein (FAP).
As the first company to introduce dual payload peptide drug conjugates (PDCs), Avacta aims to overcome resistance mechanisms that cancer cells have developed against conventional single-drug therapies while enhancing the therapeutic effect by delivering a targeted combination. This innovative approach could potentially tackle several pressing challenges faced in cancer treatment.
The dual payload pipeline from the Company encompasses two strategic tactics: the combination of microtubule inhibition and topoisomerase I inhibition (MMAE and exatecan), which represent two different anti-cancer mechanisms with proven clinical efficacy; and the pairing of DNA damage response (DDR) agents, such as ATR or PARP inhibitors, with exatecan to amplify its cytotoxic effect.
Dr. Christina Coughlin, CEO of Avacta, expressed enthusiasm regarding this development, stating, “The first dual payload peptide drug conjugate marks an important step forward in oncology therapy, significantly extending the potential of our pre|CISION® platform by implementing combination cancer therapy in a single small molecule medicine. The synergistic enhancement in anti-tumor activity observed with our exatecan-DDR inhibitor combinations highlights the potential of targeting the tumor with a potent cytotoxic drug while attacking the known resistance mechanisms. We believe this technology has the potential to markedly improve outcomes for cancer patients, particularly those with highly-resistant tumors.”
The pre|CISION® platform has demonstrated its effectiveness with compelling clinical results from faridoxorubicin (AVA6000, FAP-Dox), which showcased a remarkable tumor-to-plasma payload concentration ratio of 100:1, alongside a significant decrease in off-target toxicities, even when administered at doses approximately four times higher than conventional doxorubicin.
Key Findings from Preclinical Studies
The pre|CISION® dual payload technology exhibited strong FAP-selective delivery and significant anti-tumor activity across various complementary payload combinations. The poster presentation (Abstract #C123), which is accessible on the Company”s website, detailed the discovery and characterization of these novel pre|CISION® technology compounds.
Key preclinical findings include the validation of a dual payload release mechanism, where biologic and biochemical analyses confirmed the simultaneous release of two independent payloads from a single FAP cleavage event. The study also demonstrated that modifications to the self-immolative linkers allowed for tunable payload delivery kinetics, optimizing therapeutic profiles for different combinations.
In particular, dual payload compounds achieved potent cytotoxic activity comparable to free payloads in the presence of FAP, indicating excellent tumor selectivity. The compounds significantly modulated target-specific biomarkers only in the presence of FAP, confirming that both mechanisms of action were operational.
Furthermore, the study revealed an enhanced synergistic activity that effectively addressed resistance mechanisms, showing that FAP-Exd/PARPi and FAP-Exd/ATRi compounds resulted in significantly greater tumor cell killing compared to exatecan alone.
The Avacta team will present a detailed analysis of the published data via Investor Meet Company on October 29, 2025. The webinar details will be updated on the Avacta homepage and available through the Investor Meet Company platform.
For more information, please visit Avacta”s website.
