Avacta Group plc provided detailed pre-clinical, clinical and pharmacokinetic data from the Phase 1a dose escalation study of its lead pre|CISIONTM programme, AVA6000, a tumour activated form of doxorubicin. The key conclusions drawn from the data for AVA6000 to date are: The pre|CISIONTM platform targets the release of a chemotherapy to the tumour as intended. The data show that the pre|CISIONTM modification is cleaved specifically by Fibroblast Activation Protein (FAP), an enzyme present in high concentrations in many solid tumours compared with healthy tissue.

In the case of AVA6000, this targets the release of doxorubicin to the tumour microenvironment,concentrating the active cytotoxic drug within the tumor micro-environmentand limiting systemic exposure to the chemotherapy. AVA6000 has significantly improved the safety and tolerability of doxorubicin. A significant reduction in the frequency and severity of the known doxorubicin toxicities has been observed across the dosing range.

A maximum tolerated dose has not been reached in the three-weekly dose escalation study despite dosing approximately 3.5x the normal level of doxorubicin in the highest and final dose cohort in this part of the Phase 1a study. AVA6000 has shown encouraging preliminary clinical signs of anti-tumour activity. Preliminary results in the Phase 1a trial demonstrate activity of AVA6000 in patients with tumours with high FAP activity, validating the mechanism of action of AVA6000.

For example, a 59-year-old male patient with Undifferentiated Pleomorphic Sarcoma (UPS) has shown a reduction in tumour volume of 65% with a duration of response >6 months and ongoing. A number of other patients with different cancer types have shown smaller ongoing reductions in tumour volume or stable disease. The next steps with AVA6000 involve optimising the patient population, dose and schedule in order to increase efficacy and tolerability of doxorubicin treatment via pre|CISIONTM targeting.

Given the favourable safety data from the three-weekly dosing study, a fortnightly dosing study, which is now screening patients with high FAP levels in the United States, will assist in optimising the schedule and dose for a potentially pivotal Phase 2 study in 2024.