Avacta Therapeutics published new data which demonstrates the favorable delivery profile and advantages of its proprietary pre|CISION platform's compared to a marketed antibody drug conjugate (ADC). The data analysis compares pre|CISION FAP-cleavable payload delivery with that of Enhertu, a proteasecleavable-linker ADC, approved for both breast cancer and gastric cancer indications (an AstraZeneca/Daiichi Sankyo product, trastuzumab-deruxtecan (T-Dxd), an exatecan-derivative ADC). Avacta expects to initiate the Phase 1 clinical trial of its FAP-Exd (AVA6103) program in first quarter 2026.

The analysis uses a synthetic comparator arm that was generated using AI to recreate a published AstraZeneca data set1 and compare to experimental data generated with FAP-Exd (AVA6103) in a similar experimental design using a FAP-high animal model with two drugs using similar payloads (exatecan and deruxtecan). The analysis demonstrates three key pharmacokinetic (PK) advantages in the kinetics of the release of payload, specifically: AVA6103 results in more rapid drug penetration into the tumor, with the maximal concentration (Cmax) in tumor tissue occurring within minutes of dosing compared with T-Dxd maximum concentration observed at 24 hours; The observed absolute maximum concentration (Cmax) observed with FAP-Exd in the tumor was more than a log higher than the Cmax observed with T-Dxd; and The Tumor Selectivity Index (TSI, ratio of the area under the curve (AUC) observed over 14 days in the tumor v. plasma) was nearly three-fold higher with pre|CISION®? delivery (FAP-Exd) versus ADC delivery (T-Dxd).

Avacta's scientists have also described two key impacts of these PK differences in animal efficacy models, including (1) higher activity of FAP compared with variable activity of T-Dxd at low expression levels of HER2 and (2) deep, durable responses that are observed to persist for many weeks after the 3 dose regimen with FAP-Exd. Avacta scientists plan to present these data at an upcoming scientific congress and submit to a peer-reviewed journal in the near future. Enhertu is a registered trademark of AstraZeneca and Daiichi Sankyo product, an exatecan-deruxtecan, an exatecan-d.