Avacta Therapeutics gave two presentations at the American Association for Cancer Research (AACR) Annual Meeting 2026. These presentations included the first in vivo efficacy and exposure pharmacology for the pre|CISION dual payload technology program and updated pharmacology and preclinical exposure data analyses highlighting the favorable delivery profile of AVA6103 (FAP-EXd), its second clinical candidate, which has recently entered Phase 1 development. Updates to the ongoing Phase 1 clinical trial are also being presented.
This presentation includes updated preclinical data from the Company's second clinical candidate, AVA6103, a novel FAP-activated pre|CISION peptide-drug conjugate (PDC) delivering the topoisomerase I inhibitor (TOP1i) exatecan directly to the tumor-stroma interface, as well as details of the ongoing FOCUS-01 Phase 1 trial of this agent. The data demonstrate that AVA6103 has robust activity in multiple patient-derived xenograft (PDX) models with FAP levels ranging from very low to high, suggesting excellent antitumor effects even at the lowest levels of FAP expression in stromal cells only. This presentation also includes a data analysis comparing pre|CISION FAP-cleavable payload delivery with that of the leading marketed ADC Enhertu (an AstraZeneca/Daiichi Sankyo product).
The data analysis used a synthetic comparator arm that was generated using AI to recreate a published AstraZeneca data set and compare to experimental data generated with AVA6103 in a similar experimental design using a FAP-high animal model with two drugs using similar payloads (exatecan and deruxtecan). It demonstrated three key differences in the pharmacokinetics (PK) of the payload: more rapid tumor penetration and payload release with AVA6103, tumor Cmax of more than one log higher with AVA6103, and Tumor Selectivity Index (TSI: AUCtumor /AUCplasma) three times higher with AVA6103. AVA6103 has recently entered the clinic, with the first patient receiving treatment in the FOCUS-01 study in March.
FOCUS-01 (NCT07454642) is a multicenter, open-label Phase 1 clinical trial of AVA6103 in adults with selected advanced cancers, and the initial clinical data readout from the study is anticipated later this year. Based on favorable preclinical activity and biomarker readouts from the strategic collaboration with Tempus, two indications have been added to the trial: colorectal cancer (CRC) and hormone receptor-positive breast cancer (HR+ BC). This presentation includes the description of how pre|CISION delivers a therapeutically relevant combination of payloads specifically to the tumor microenvironment while reducing systemic dose-limiting toxicities, broadening its utility in the delivery of novel combinations of medicines.
The AVA6207 dual payload is designed to simultaneously release a TOP1i and a DNA Damage Repair (DDR) inhibitor by FAP cleavage, resulting in synthetic lethality in two genetic models of TOP1i resistance: tumor cells harboring either (1) ATM-deficiency or (2) loss of SLFN11. These studies demonstrate the ability of AVA6207 to overcome key mechanisms of TOP1i resistance and mediate synergistic tumor cell killing. The first in vivo data with this novel combination mechanism are presented, with tumor and plasma pharmacokinetic studies demonstrating the robust tumor-selective release of both payloads with a highly potent TSI.
In addition to the robust exposure data, antitumor efficacy is demonstrated in a patient-derived xenograft (PDX) model of HER2+ gastric cancer with low FAP expression with optimal activity of AVA6207 over the HER2-targeted TOP1i ADC (Enhertu).
