Avacta Expands its Pipeline with Two Novel Assets Developed Using its pre|CISION Platform

Avacta Group plc recently announced the addition of two novel preclinical oncology assets, AVA6103 and AVA7100, to its pipeline of pre|CISION-enabled drug conjugates.

Avacta is developing a portfolio of pre|CISION product candidates that are designed to be activated specifically in the tumor microenvironment, thereby enabling improved antitumor activity while reducing systemic toxicities. The Company has developed a pipeline of peptide drug conjugates, each of which is comprised of an active antitumor drug (known as a payload) linked to the pre|CISION peptide, which is cleaved only within the tumor by the action of Fibroblast Activation Protein, or FAP.

The first of the two new programs is AVA6103, a novel pre|CISION-enabled peptide drug conjugate comprised of the pre|CISION peptide linked to exatecan, the most potent topoisomerase I inhibitor in clinical development. This PDC is designed to deliver the exatecan payload directly to tumors while limiting the exposure of the released payload in normal tissues. Exatecan has demonstrated clinical activity in breast, gastric, lung and pancreatic cancers; however, it is associated with severe dose-limiting toxicities and a short half-life in patients that led to discontinuation of its monotherapy development. More recently, this payload has been adapted for use in antibody drug conjugates and other approaches. AVA6103 is designed to enable patients to obtain the therapeutic benefit associated with exatecan, while limiting the systemic exposure associated with its poor tolerability.

The second program is AVA7100, a pre|CISION-enabled Affimer drug conjugate, a new class of therapies being developed by Avacta with potential applications in a variety of cancer types, including those with lower levels of FAP in the tumor. Affimer molecules are small proteins that are engineered to bind to a target molecule in the same way that an antibody does, but with several advantages, including smaller molecule size and greater binding affinity. AVA7100 consists of a novel FAP-Affimer conjugated to a pre|CISION-peptide linker with multiple options for the payload.

Christina Coughlin, MD, PhD, Chief Executive Officer of Avacta, said “The expansion of our pipeline highlights the broad potential of our proprietary pre|CISION technology to deliver multiple potent oncology therapeutics directly into difficult-to-treat tumors, while sparing healthy tissues. These novel assets have been carefully selected to complement our existing portfolio, by targeting cancers with high unmet need and having clear development strategies. We look forward to sharing data across our programs in the near future.”

Further details of these programs will be released in conjunction with the company’s two presentations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics being held in Barcelona from October 23-25, 2024. The platform and the pipeline will be presented at the investor and analyst R&D Spotlight Event: Focus on pre|CISION, in London on October 30, 2024.

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.

The lead pre|CISION program AVA6000, a peptide drug conjugate form of doxorubicin, is in Phase 1 studies. It has shown an improvement in safety and tolerability in clinical trials to date compared with standard doxorubicin and preliminary signs of clinical activity in multiple patients.

Avacta Group is a UK-based life sciences company focused on improving healthcare outcomes through targeted cancer treatments and diagnostics. Its clinical stage oncology biotech division Avacta Therapeutics is harnessing the proprietary pre|CISION platform technology to develop novel, highly targeted cancer drugs. Avacta Diagnostics focuses on supporting healthcare professionals and broadening access to diagnostics. For more information, visit https://avacta.com.