Avacta Group Regulatory News (AVCT)

Avacta's pre|CISION Mechanism for Payload Delivery Shows Key Advantages Compared to an Antibody Drug Conjugate in Innovative AI-Driven Analysis

Experimental data from FAP-Exd (AVA6103) demonstrates a more favorable profile compared to the marketed Antibody Drug Conjugate (ADC) Enhertu®

Clinical trial with AVA6103 is expected to be initiated in Q1 2026

LONDON and PHILADELPHIA - February 24, 2026 - Avacta Therapeutics (AIM: AVCT, "the Company", "Avacta"), a clinical stage biopharmaceutical company developing pre|CISION®, a tumor-activated oncology delivery platform, today 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 protease cleavable-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 Q1 2026.

Christina Coughlin, CEO of Avacta commented,

"Our analysis demonstrates three potential advantages of our proprietary pre|CISION delivery mechanism when compared to the marketed ADC, Enhertu®: more rapid drug penetration into the tumor, a one log higher absolute maximum drug concentration in the tumor and the Tumor Selectivity Index (a critical safety and effectiveness measure) being nearly three-fold higher.

"This data analysis supports our belief that our pre|CISION payload delivery mechanism has many key advantages over the ADC mechanism, currently one of the most successful drug classes in oncology.

"This innovative use of AI to recreate a synthetic comparator arm also demonstrated the creativity and expertise of our team. This synthetic comparator allows a direct comparison of the FAP-Exd data with the data published by the Enhertu® team, rather than repeating their experiments in-house.

"We believe the observations in this dataset have significantly increased the probability of success with FAP-Exd, given both the ability of FAP-Exd to deliver more payload selectively to the tumor in the preclinical setting and success of Enhertu® in the clinic. We look forward to the start of the clinical trial."

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:

1. 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;

2. 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

3. 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-Exd in tumor models having the lowest observed expression 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.

1Vasalou C, et al. Quantitative evaluation of trastuzumab deruxtecan pharmacokinetics and pharmacodynamics in mouse models of varying degrees of HER2 expression. CPT Pharmacometrics Syst Pharmacol. 2024 (6):994-1005. doi: 10.1002/psp4.13133 (AZ nonclinical data)

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About Avacta - https://avacta.com/

Avacta Therapeutics is a clinical-stage life sciences company expanding the reach of highly potent cancer therapies with the pre|CISION® platform. pre|CISION® is a proprietary 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.

Our innovative pipeline consists of pre|CISION® peptide drug conjugates (PDC) or Affimer® drug conjugates (AffDC) that leverage the tumor-specific release mechanism, providing unique benefits over traditional antibody drug conjugates.

The pre|CISION® platform comprises an anticancer payload conjugated to a proprietary peptide that is a highly specific substrate for fibroblast activation protein (FAP) which is upregulated in most solid tumors compared with healthy tissues. The pre|CISION® platform harnesses this tumor specific protease to cleave pre|CISION® peptide drug conjugates and pre|CISION® antibody/Affimer® drug conjugates in the tumor microenvironment, thus releasing active payload in the tumor and reducing systemic exposure and toxicity, allowing dosing to be optimized to deliver the best outcomes for patients.