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Key Points:
- AVA6103, a new peptide drug conjugate (PDC), targets Topoisomerase I inhibitors to tumor cells, reducing toxicity to healthy tissues and showing promising tumor inhibition.
- Affirmer® Drug Conjugates, a new class of biotherapeutics, offer dual-targeting capabilities, expanding treatment options for tumors with low FAP expression.
- Avacta’s pre|CISION™ platform advances cancer treatment by enhancing drug specificity, reducing systemic exposure, and improving patient outcomes.
Avacta Group plc (LSE:AVCT), a life sciences company focused on developing innovative cancer treatments, has announced new preclinical data on two advancements in its proprietary pre|CISION™ platform. The company will present these findings in poster sessions at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place in Barcelona, Spain from October 23-25, 2024. These presentations highlight the platform's potential in improving the targeting of potent anti-cancer drugs to tumor sites while minimizing harmful exposure to healthy tissues, thus optimizing dosing and improving outcomes for patients.
Key Developments in the Pre|CISION™ Platform
- AVA6103 – A Novel Peptide Drug Conjugate (PDC): Avacta's first preclinical breakthrough involves AVA6103, a Generation Two PDC that targets the tumor microenvironment through Fibroblast Activation Protein α (FAP) activity. This candidate is designed to deliver a highly potent Topoisomerase I inhibitor directly to tumors. Topoisomerase I inhibitors are known to induce DNA damage, leading to cancer cell death. However, their potency has traditionally been limited by systemic toxicity. By using Avacta’s pre|CISION™ platform, which facilitates tumor-specific delivery, AVA6103 allows for the precise release of the inhibitor within the tumor, minimizing exposure to healthy tissues.
AVA6103 utilizes a dipeptide that is cleaved by FAP, a protein overexpressed in cancer-associated fibroblasts, to release the drug only within the tumor. Preclinical data to be presented at the symposium shows the compound’s ability to effectively accumulate the active drug in the tumor microenvironment, leading to tumor growth inhibition. This targeting capability could reduce systemic side effects and enhance the tolerability of the drug, a significant advantage in cancer therapies.
- Affirmer® Drug Conjugates – Generation Three Biotherapeutics: The second major advancement comes from a novel class of engineered biotherapeutics known as Affirmer® Drug Conjugates. These dual-targeting drug conjugates represent a new frontier in Avacta’s pre|CISION™ pipeline. While peptide drug conjugates (PDCs) like AVA6103 are highly effective in tumors with high FAP expression, Affirmer® Drug Conjugates aim to expand the range of treatable cancers, including those with low FAP expression.
Utilizing the same release mechanism as other pre|CISION™ platform drugs, Affirmer® Drug Conjugates provide greater specificity in targeting tumors. This could unlock treatment options for a broader range of patients while further minimizing systemic exposure to the warhead, reducing unwanted side effects. The technology also holds the potential for improved therapeutic efficacy by delivering the drug directly to the tumor with greater precision than traditional PDCs.
AVA6103 – Targeting Topoisomerase I with Tumor-Specific Precision
AVA6103 is designed through a combination of pre|CISION™ technology and structure-based drug design. This therapeutic includes a dipeptide sequence cleaved by FAP, allowing selective activation of its Topoisomerase I inhibitor only within the tumor microenvironment. Since FAP is overexpressed on cancer-associated fibroblasts, the drug remains inactive in normal tissues but becomes active in tumor cells, limiting systemic toxicity and improving tolerability.
The novel approach taken by AVA6103 reflects Avacta's strategy of using the pre|CISION™ platform to focus on cancer-selective targeting. In vivo preclinical data to be presented at the symposium demonstrates the ability of AVA6103 to inhibit tumor growth effectively, further solidifying its potential as a targeted cancer therapeutic.
Future Potential of the Pre|CISION™ Platform
Both AVA6103 and Affirmer® Drug Conjugates exemplify Avacta’s commitment to developing highly specific cancer treatments. By improving drug delivery precision, these advancements aim to enhance efficacy while reducing the harmful side effects often associated with chemotherapy and other potent cancer drugs. The platform could pave the way for the next generation of cancer treatments, addressing previously untreatable patient populations and offering new hope for those with aggressive forms of cancer.
