LONDON and PHILADELPHIA, Sept. 25, 2026 (GLOBE NEWSWIRE) -- Avacta Therapeutics (AIM: AVCT, the "Company", "Avacta"), a life sciences company developing innovative, targeted oncology drugs, today announces the presentation of the FOCUS-01 trial design and preclinical data highlighting the potential of AVA6103 (FAP-Exd) in pancreatic ductal adenocarcinoma (PDAC).  FOCUS-01 is the Phase 1 trial of AVA6103, the Company's first Next-Generation pre|CISION^® peptide-drug conjugate (PDC) and is being presented at the American Association for Cancer Research ("AACR") Conference on Pancreatic Cancer in San Diego, California, held between 25-28 September 2026.

The presentation highlights the design of the FOCUS-01 Phase 1 study of AVA6103 and updated preclinical data supporting the assessment of AVA6103 in patients with PDAC. AVA6103 is designed to significantly increase the therapeutic window of the highly potent payload, exatecan, and the trial implements a dose-dense arm, dosing every two weeks (Q2W), to enhance the delivery of payload to the tumor over traditional dosing of ADCs at every three weeks (Q3W).  Preclinical studies using the dose-dense regimen in patient-derived xenograft (PDX) mouse models of PDAC demonstrate that AVA6103 achieved tumor-targeted delivery of exatecan with highly durable complete and partial responses in multiple models observed for weeks following cessation of dosing.

Additionally, researchers observed high FAP expression in PDAC with close proximity of FAP-expressing cancer-associated fibroblasts (CAFs) to both blood vessels and tumor cells, shown via multiplex immunofluorescence (mIF). These findings support the mechanism of action of the Next Gen pre|CISION medicines: efficient PDC delivery to the tumor, cleavage and release of payload with tumor cell uptake of released payload.

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."

FOCUS-01: Trial in Progress

The FOCUS-01 Phase 1a trial is a first in-human, multicenter dose escalation trial of AVA6103 and is enrolling patients with select tumor types predicted to be sensitive to the payload exatecan, including PDAC. Patients with PDAC are enrolled in the Q2W dosing arm, a dose-intense regimen designed to match standard of care in the indication. The ability to deliver dose intensity and flexible administration is unique to pre|CISION^® Next-Gen PDCs because:

• In contrast to antibodies, the pre|CISION^® peptide does not accumulate, enabling more frequent dosing when appropriate; and
  
  
• The pre|CISION^® Next-Gen mechanism retains and cleaves the conjugate inside the tumor, significantly limiting systemic exposure to the payload and enabling the interval between doses to be shortened, allowing delivery of higher dose intensity compared to ADCs.

Preliminary safety and pharmacokinetic (PK) data from the first three dose levels of the FOCUS-01 trial, reported earlier this month, demonstrated proof of mechanism in patients treated in the first three cohorts in the trial. AVA6103 demonstrated a favorable safety profile and was well tolerated through the first three dose levels up to a payload dose approximately 50% higher than the maximum tolerated dose (MTD) of conventional exatecan.

The pharmacokinetic data of the PDC, released peptide and released exatecan patients were remarkably consistent with predictive PK modelling based on preclinical data, greatly increasing confidence that the safety profile, tumor selectivity and antitumor efficacy observed in the preclinical studies of AVA6103 will translate into the clinic.

Enrollment is ongoing in both arms of the study with patients treated at dose level 4, which represents an absolute dose of payload that is more than double the MTD of conventional exatecan and approaches the equivalent topoisomerase I inhibitor payload dose of the approved dose of Enhertu^® in breast cancer.

Details of the poster presentation

Title:  A Phase I Trial of FAP-Exd (AVA6103), a Fibroblast Activation Protein (FAP)-enabled pre|CISION® Peptide-drug Conjugate Delivering Sustained Tumor Microenvironment (TME) Release of Exatecan in Patients with FAP-positive Solid Tumors

First Author: Alex Spira, MD

Session: New Frontiers in Biology and Therapeutic Development

Date: September 26, 2026

Enhertu^® (trastuzumab deruxtecan; T-DXd) is a protease cleavable-linker ADC, approved for both breast cancer and gastric cancer indications (an AstraZeneca/Daiichi Sankyo product). Enhertu^® is a registered trademark of Daiichi Sankyo Company, Limited and AstraZeneca.

For further information from Avacta, please contact:

About Avacta - https://avacta.com/

Avacta Therapeutics is a clinical-stage life sciences company expanding the reach of highly potent cancer therapies through its proprietary pre|CISION® platform. pre|CISION® is a payload delivery system based on a tumor-specific protease (Fibroblast Activation Protein or FAP) that is designed to concentrate highly potent payloads in the tumor microenvironment while sparing normal tissues. Avacta's innovative pre|CISION® peptide drug conjugates (PDC) are a novel entry to the XDC drug class, leveraging the success of antibody drug conjugates with alternative methods of delivery beyond antibodies.

Our pre|CISION® PDCs leverage this tumor-specific release mechanism in a small molecule format to provide unique benefits over traditional antibody drug conjugates (ADC), releasing active payload in the tumor and reducing systemic exposure and toxicity which enables dosing to be optimized to deliver the best outcomes for patients. The lead clinical program is AVA6103, a Next Generation FAP-enabled controlled release pre|CISION® version of exatecan that delivers the payload directly in the tumor with limited peripheral blood exposure and is currently in clinical development as a treatment for tumor types sensitive to exatecan including cervical cancer, HR+ breast cancer, small cell lung cancer, gastric cancer, colorectal cancer and pancreatic cancer.

About AVA6103 (FAP-Exd)

AVA6103 is the second clinical candidate and is the first asset in the pipeline based on the Next Generation innovative pre|CISION® controlled release mechanism that provides for prolonged release of payload directly in the tumor, minimizing systemic exposure. AVA6103 is being evaluated in the FOCUS-01 Phase 1 trial (F AP-Exd in O ncologic C ancers with U nmet needS). Preclinical data suggest this approach has optimized payload delivery with a high intratumoral concentration and prolonged exposure of released payload in the tumor, coupled with limited systemic exposure to the released payload.

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