Avacta Showcases Promising Preclinical Results for AVA6103 and AVA7100 at 2024 EORTC-NCI-AACR Symposium

Highlights

• Targeted Tumor Therapy: AVA6103 and AVA7100 demonstrated strong preclinical results, focusing on tumor-specific drug delivery through FAP cleavage.
• Reduced Toxicity: Both therapies show promise in minimizing off-target effects and optimizing the bystander effect, crucial for treating diverse tumor types.
• Clinical Progress: AVA6103 is expected to enter IND-enabling studies in late 2024, with AVA7100 following in the second half of 2025.

Avacta Therapeutics (LSE:AVCT), a life sciences company focused on developing next-generation peptide drug conjugates (PDCs) for cancer treatment, presented promising preclinical data on two novel oncology assets, AVA6103 and AVA7100, at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. These presentations highlighted advancements in Avacta's pre|CISION® technology, which enables targeted delivery of anti-tumor therapies with reduced systemic toxicity.

The data were presented in the Antibody Drug Conjugate (ADC) poster session, showcasing Avacta's innovative approach to overcoming key limitations of traditional ADCs by using peptide drug conjugates that specifically target the tumor microenvironment (TME).

AVA6103: Enhanced Therapeutic Index and Tumor-Specific Action

AVA6103, a pre|CISION-enabled PDC, links the potent topoisomerase I inhibitor, exatecan, to a pre|CISION peptide that is cleaved only by Fibroblast Activation Protein (FAP) in the TME. This mechanism ensures that the active drug is released only in the tumor, reducing off-target effects.

Key findings presented in the poster, "The novel peptide drug conjugate AVA6103 is a FAP-enabled pre|CISION® medicine which targets Topoisomerase I to the tumor microenvironment via FAP cleavage," included:

• Increased Therapeutic Index: AVA6103 demonstrated a significantly higher maximum tolerated dose—75 times that of conventional exatecan—thanks to its tumor-specific activation.
• Bystander Effect Optimization: The FAP-specific cleavage mechanism allows released exatecan to penetrate FAP-negative cancer cells, enhancing its anti-tumor effect.
• High Tumor Accumulation: Preclinical data showed up to 50-fold higher concentrations of the active warhead in tumors compared to plasma, resulting in tumor growth inhibition and complete responses in engineered models expressing human FAP. Additionally, survival was improved in models treated with AVA6103.

AVA6103 is slated to enter Investigational New Drug (IND)-enabling studies later this year, moving it closer to potential clinical trials.

AVA7100: Advancing Affimer® Drug Conjugates for Broader Tumor Applications

AVA7100 is part of a new class of pre|CISION-enabled Affimer® drug conjugates (AffDCs), which are designed to deliver potent anti-tumor warheads to tumors with lower levels of FAP expression. AVA7100 leverages Affimer proteins that bind to FAP and release the warhead directly in the TME, enhancing the bystander effect to target both antigen-positive and antigen-negative tumor cells.

The poster, "Affimer® Drug Conjugates (AffDC) targeting Fibroblast Activation Protein-α deliver highly toxic warheads to the tumor microenvironment by leveraging the pre|CISION® release mechanism," presented the following key findings:

• Optimized Bystander Effect: By releasing the warhead extracellularly through FAP cleavage, AffDCs effectively kill both FAP-positive and FAP-negative tumor cells.
• Superior Tumor Penetration: Affimer proteins, being 10-20% the size of traditional antibodies, improve tumor penetration and can be engineered for optimal performance.
• High Potency: AffDC molecules demonstrated single-digit picomolar potency in binding to FAP, ensuring efficient targeting and tumor-specific warhead release, even in tumors with low FAP expression.

AVA7100 is expected to enter IND-enabling studies in the second half of 2025, expanding its potential application across various cancer types.