Avacta Therapeutics is a clinical stage biopharmaceutical company challenging current drug delivery methods to expand the utility of highly potent cancer therapeutics.
The Company benefits from a world class research and development facility, team of exceptionally talented scientists and a highly experienced management team with members located in both the London headquarters and the US.
Our proprietary pre|CISION® platform masks toxic warheads by binding them to a short, engineered peptide that is cleavable only by the tumor-specific protease, fibroblast activation protein (FAP). The peptide is designed to disable the warhead before the cleavage step releases it directly in the tumor microenvironment.
Our innovative pipeline consists of pre|CISION® peptide drug conjugates (PDC) or Affimer® drug conjugates (AffDC) that leverage the tumor-specific release mechanism. The tumor-specificity of the warhead release and bystander effect optimization of our medicines provide unique benefits over traditional antibody drug conjugates.
Our lead pre|CISION® program AVA6000, a Gen One peptide drug conjugate form of doxorubicin, recently completed Phase 1a studies and is currently moving into indication-specific expansion cohorts in three diseases. AVA6000 has shown a dramatic improvement in safety and tolerability compared with conventional doxorubicin and multiple ongoing and durable RECIST responses have been observed in patients with FAPhigh and doxorubicin sensitive diseases. A significant concentration of released doxorubicin is observed in all patients with post-treatment biopsies, even in patients whose tumors have lower levels of FAP activity. In addition, multiple responses have occurred in patients with expression of FAP only noted in stromal cells (cancer-associated fibroblasts, or CAFs). This indicates that tumor cell expression of FAP is not required for the release of doxorubicin, with even lower levels of stroma-only expression being sufficient.
In the AVA6000 Phase 1 trial, we have observed multiple favorable changes in the pharmacokinetic profile of released doxorubicin, including a dramatic reduction in the maximal concentrations of released doxorubicin, reduction in exposure (AUC) and reduction in volume of distribution, essentially recapitulating the preclinical findings. The changes in the kinetics in patients underscore the mechanism of action of the pre|CISION platform provide a framework for platform improvements in the PK of additional warheads.
The pre|CISION® chemistry has been optimized in our Gen Two PDC in the pipeline, whereby the conjugations are optimized to (1) significantly extend half-life of the conjugated drug and thus the released warhead and (2) modulate the rate of cleavage (kcat/Km). Both of these developments are anticipated to significantly alter the pharmacokinetic profile of a released warhead and enables our scientists to tune the delivery of warheads directly to the tumor with minimal peripheral exposure in normal tissues. Our first Gen Two pre|CISION medicine is AVA6103, a PDC containing the most potent topoisomerase 1 inhibitor in clinical testing, exatecan.
Our Gen 3 pre|CISION® pipeline leverages the highly specific binder proteins, the Affimer® proteins to create an entirely novel class of drug, the Affimer-DC (AffDC) which have 3 key advantages over traditional ADC. These antibody mimetics have applicability as biologics to oncology therapeutics and are currently being used in the development of pre|CISION® drug conjugates, that both significantly extend half-life and deliver the drug warhead intratumorally in a sustained release mechanism. Our first Gen Three candidate is a FAP-binding Affimer drug conjugate (AffDC) designed to enable this platform to treat patients with cancers considered FAP low and extend the reach of the pre|CISION platform.
Avacta Group also contains a Diagnostics Division that comprises two business units – Launch Diagnostics and Coris Bioconcept. Launch Diagnostics has well-established sales channels in the professional, centralised hospital laboratory testing markets in the UK and France. Coris, based in Gembloux, Belgium, develops, manufactures and markets rapid diagnostic test kits, mainly lateral flow tests, for use by healthcare professionals.
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