Avacta Therapeutics (AIM: AVCT) has presented the design of its Phase 1 FOCUS-01 trial and updated preclinical data supporting AVA6103 in pancreatic ductal adenocarcinoma at the AACR Conference on Pancreatic Cancer.
AVA6103 is Avacta’s first next-generation pre|CISION peptide-drug conjugate, designed to deliver the potent topoisomerase-I inhibitor exatecan selectively within tumours while reducing systemic exposure.
The FOCUS-01 study includes a dose-dense every-two-week arm for pancreatic cancer patients, compared with the three-week dosing schedules commonly used with antibody-drug conjugates. Avacta believes the shorter interval could increase payload delivery to tumours.
Updated preclinical studies in patient-derived pancreatic cancer models showed durable complete and partial responses after AVA6103 treatment, with responses maintained for weeks after dosing stopped.
The company also reported high FAP expression in pancreatic tumours, with FAP-positive cancer-associated fibroblasts located close to blood vessels and tumour cells. Avacta said this supports the proposed mechanism whereby AVA6103 enters the tumour microenvironment, is cleaved and releases exatecan locally.
Importantly, FOCUS-01 has already produced early clinical pharmacokinetic and safety data from the first three dose levels. Avacta previously reported that these results were consistent with the intended tumour-selective delivery mechanism, while AVA6103 was tolerated at payload doses approximately 50% above the maximum tolerated dose of conventional exatecan.
Enrollment is continuing in both study arms, with patients now receiving dose level four, representing an absolute exatecan payload more than twice the conventional exatecan MTD and approaching the equivalent topoisomerase-I payload used with Enhertu in breast cancer.
For investors, the distinction is important: the AACR presentation strengthens the scientific rationale for AVA6103 in pancreatic cancer, but the decisive question is now clinical efficacy in patients rather than further preclinical validation. The planned H1 2027 initial efficacy readout should therefore be the key catalyst for determining whether tumour-selective delivery translates into meaningful anti-tumour activity.
Christina Coughlin, CEO of Avacta, commented: “The preclinical data presented at AACR underscore the significant potential of AVA6103 in addressing the challenges of pancreatic cancer, a disease with limited treatment options and poor prognosis. The robust preclinical efficacy, combined with the high FAP expression in PDAC, further strengthens our confidence in AVA6103 as a promising therapeutic candidate to improve treatment options for patients.
“This adds to the momentum of AVA6103 and highlights the potential of our unique pre|CISION® technology to bring hope to patients battling PDAC and other aggressive cancers. The first clinical data from the FOCUS-01 trial, providing clinical evidence consistent with tumor-specific delivery of exatecan by AVA6103, have further reinforced our confidence in this program and we are now moving towards an initial efficacy readout from the study in H1 2027.”
Investor takeaway: AVA6103 is moving beyond preclinical promise into early human validation, with FOCUS-01 already showing pharmacokinetic evidence consistent with tumour-selective exatecan delivery and dosing now reaching payload levels above conventional exatecan exposure. The next major value inflection point is the planned initial efficacy readout in H1 2027.
