Avacta Group Regulatory News (AVCT)

Avacta data at AACR 2026 underline favorable profile of AVA6103 and advantages of pre|CISION® delivery platform

Presentation of additional analyses from FAP-Exd (AVA6103) study shows robust activity in PDX models with low FAP expression and more favorable kinetic profile compared to the marketed antibody-drug conjugate (ADC) Enhertu®

Dual payload capability of the pre|CISION platform showcased with first in vivo exposure and efficacy data

LONDON and PHILADELPHIA - April 21, 2026 - Avacta Therapeutics (AIM: AVCT, "the Company", "Avacta"), a clinical stage biopharmaceutical company developing pre|CISION®, a tumor-activated oncology delivery platform, is giving two presentations today at the American Association for Cancer Research (AACR) Annual Meeting 2026. These presentations include 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.

Christina Coughlin, CEO of Avacta, commented:

"The data being presented at AACR underline the potential of our pre|CISION® technology and AVA6103 to make a considerable difference to cancer patients. These observations could significantly increase the probability of success with AVA6103, given both the ability of FAP-Exd to deliver more payload selectively to the tumor in the preclinical setting, and the success of Enhertu® in the clinic. The FOCUS-01 Phase 1 clinical trial of AVA6103, now underway in the US, is designed to demonstrate the benefits of pre|CISION® in unlocking the full potential of exatecan while minimizing systemic toxicity.

Furthermore, we have shown 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 medicines. The dual delivery mechanism of pre|CISION® shows its potential to dramatically increase the therapeutic window and reduce systemic toxicities, offering improved outcomes for patients with cancer."

Details of the Two Presentations:

AVA6103 (FAP-EXd) Preclinical and Clinical Trial in Progress Highlights (Rink, C. et al.)

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[1] 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)

Abstract Number and Title: Abstract #5846, AVA6103 is a FAP-enabled pre|CISION® peptide-drug conjugate delivering sustained release of exatecan in the tumor microenvironment with potent antitumor activity.

Poster number and Location: 5846, Section 17, Board 15

Session: Tumor Microenvironment, Multi-specifics, and Immunomodulation

The pre|CISION® dual payload technology (AVA6207) update (Juskaite, V. et al.)

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®)

Abstract Number and Title: Abstract #5656, Characterization and translational development of novel pre|CISION® technology compounds delivering complementary dual payloads to the tumor microenvironment following FAP cleavage

Session: Antibody-Drug Conjugates and Linker Engineering 4

Section: Experimental and Molecular Therapeutics

(Enhertu is a registered trademark of Asta Zeneca and Daichii Sankyo)

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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 to provide unique benefits over traditional antibody drug conjugates, 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 faridoxorubicin (AVA6000), a Gen One FAP-enabled pre|CISION® version of doxorubicin that delivers the payload directly in the tumor with limited peripheral blood exposure and has demonstrated preliminary activity in tumor types sensitive to doxorubicin including salivary gland cancer and soft tissue sarcoma. 

About AVA6103 (FAP-Exd)

AVA6103 is the second clinical candidate and is based on the innovative pre|CISION® sustained 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 (FAP-Exd in Oncologic Cancers with Unmet 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. 

The FOCUS-01 Clinical Trial

The Phase 1a dose escalation portion of the FOCUS-01 clinical trial will evaluate the safety, tumor and plasma pharmacokinetics, pharmacodynamics and preliminary efficacy of AVA6103 in patients with one of six solid tumors in the advanced setting: pancreatic cancer, cervical and vulvar cancer, gastric and gastroesophageal junction cancers, small cell lung cancer, colorectal cancer and hormone receptor-positive breast cancer.

The selection of the six tumor types for the dose escalation portion of the trial was based on an AI approach investigating the co-expression of a gene that can predict sensitivity to the topoisomerase 1 inhibition mechanism (SLFN11) and FAP as part of the Company's strategic collaboration with Tempus AI. The data mining team ranked solid tumor indications based on the gene expression profiles to predict those cancer indications with the highest probability of success.

Further information on the study can be found on clinicaltrials.gov, under study number NCT07454642.