Avacta Group (AVCT) Status Update summary

Innovative drug delivery platforms and approach

• FAP-targeted peptide drug conjugates and Affimer technology enable precise delivery of potent therapeutics to the tumor microenvironment, minimizing off-target toxicity and enhancing efficacy, with clinical proof of concept achieved for AVA-6000 in 2024.

• The pre|CISION technology links peptides cleaved by FAP to warheads, preventing cellular entry until release in the tumor, and can be combined with Affimer technology for next-generation ADCs.

• FAP expression is highest at the tumor-stroma interface, optimizing warhead delivery in cancers with high unmet need.

• Affimers, engineered antigen-binding proteins, offer superior tissue penetration, high stability, and efficient bacterial production, enhancing tumor penetration and manufacturing efficiency over monoclonal antibodies.

• The modular Affimer system allows flexible drug conjugation, rapid, cost-effective production, and supports development of multispecific and multimeric formats.

Clinical trial progress and results

• AVA-6000, a FAP-enabled doxorubicin, demonstrated high tumor-specific drug concentration, significant anti-tumor activity, and a widened therapeutic index in phase I trials, with reduced toxicity compared to standard doxorubicin.

• Tumor responses, including shrinkage and partial responses, were observed in patients with FAP-positive tumors, including soft tissue sarcoma, GI cancers, and treatment-resistant disease.

• Clinical data confirm that warhead concentration in tumors is significantly higher than in plasma, validating the platform's mechanism.

• PK/PD modeling supports ongoing exploration of dosing schedules, including every-two-week regimens, to define the recommended phase II dose.

• Ongoing phase I trials are enrolling for new regimens, with expansion cohorts planned for the second half of 2024.

Manufacturing and platform advantages

• Peptide drug conjugates and Affimers allow for cost-effective, rapid manufacturing due to their small molecule nature, 1:1 drug-to-peptide ratio, and efficient E. coli production.

• Affimers are thermally stable, low molecular weight, and enable efficient conjugation and lower costs compared to traditional ADCs.

• The modularity of Affimers allows for flexible drug design, including multispecific and multimeric formats, with rapid discovery and unencumbered IP.

• Manufacturing advantages of Affimers support scalability and cost efficiency for future clinical development.