LONDON, UK, 10 OCT 2024, Avacta Group plc (AIM: AVCT), a life sciences company developing innovative, targeted cancer treatments, today announced that the Company will present new preclinical data on two breakthroughs in the pre|CISION™ platform in poster sessions at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain from 23-25 October 2024. Together, the presentations advance the utility of our pre|CISION™ drug delivery platform technology, which delivers highly potent warheads directly to the tumor microenvironment while minimizing exposure in normal tissues, thus allowing dosing to be optimized to deliver the best outcomes for patients.
The first advance in the pre|CISION™ platform is the design and preclinical analysis of the Company’s newest development candidate, AVA6103, a novel, potent peptide drug conjugate (PDC) that FAP-enables the most potent Topoisomerase I inhibitor in clinical testing, via the pre|CISION™ technology with tumor-specific delivery of the warhead to induce DNA damage and drive cancer cell death. AVA6103 is a Generation Two pre|CISION™ PDC in the Avacta pipeline.
The second advance in the pre|CISION™ platform is the first description of a novel class of engineered biotherapeutics, called Affimer® Drug Conjugates, that are dual-targeting and have the potential to offer a delivery mechanism with greater specificity than the PDC, thus potentially unlocking the patient populations with low expression of FAP in the tumor. This program is a Generation Three pre|CISION™ medicine and utilizes the same release mechanism in the pre|CISION™ platform. Based on this, the Affimer drug conjugates have the potential to not only increase the specificity of delivery but to also minimize systemic exposure to the warhead.
AVA6103: FAP-enabled PDC Targeting Topoisomerase I to the Tumor Microenvironment
Avacta discovered AVA6103 using its pre|CISION™ platform technology and structure-based drug design. AVA6103 incorporates a dipeptide that is specifically cleaved by Fibroblast Activation Protein α (FAP), which is overexpressed on the surface of cancer associated fibroblasts. AVA6103 consists of a highly potent Topoisomerase I warhead that is covalently linked to a dipeptide containing a cleaving sequence susceptible to hydrolysis by FAP, but which is resistant to hydrolysis by mammalian peptidases. The high selectivity of the pre|CISION™ substrate to FAP results in release of the topoisomerase inhibitor warhead only in the tumor microenvironment, which could potentially reduce systemic exposure and enable greater tolerability. Avacta will present in vivo data that demonstrates the ability to target and accumulate the active warhead in the tumor microenvironment, resulting in tumor growth inhibition with AVA6103.
Details of the poster are as follows:
- Abstract Title: The novel peptide drug conjugate AVA6103 is a FAP-enabled pre|CISION™ medicine which targets Topoisomerase I to the tumor microenvironment via FAP cleavage
- Session Title: Antibody Drug Conjugate Therapeutics
- Session Date: October 24, 2024
Affimer® Drug Conjugates: New Class of Engineered Biotherapeutics Targeting FAP to Deliver Powerful Warheads to the Tumor Microenvironment
Avacta has created Affimer® Drug Conjugates (AFFDCs) as a novel class of engineering biotherapeutics that incorporate a topoisomerase inhibitor for delivery specifically in the tumor microenvironment. AFFDCs are designed with several key advantages over monoclonal antibodies, including significant smaller size, tumor penetration, tunable binding affinity to specific cancer targets and the ability to be dimerized. Avacta will present data supporting that exposure of tumor cell line or fibroblast cell co-cultures to AFFDCs results in drug cleavage, release of the warhead and tumor cell kill as a bystander function.
Details of the poster presentations are as follows:
- Abstract Title: Affimer® Drug Conjugates targeting Fibroblast Activation Protein α deliver highly toxic warheads to the tumor microenvironment by leveraging the pre|CISION™ release mechanism
- Session Title: Antibody Drug Conjugate Therapeutics
- Session Date and Time: October 24, 2024