THEY HAVE A PROBLEM WITH LINKERS...3 Feb 2025 12:21
Thinking on linkers for antibody-drug conjugates
.’But Jackson has seen many ADCs fail once they reach clinical trials. “Right now, we’re at the height of the ADC hype,” he says. The roller coaster will descend again, he says, unless there are some new linker-payload chemistries, new conjugation approaches, new targets, or new antibody formats. “I hope there will be some novel innovations in the field that can move it forward.”
https://cen.acs.org/pharmaceuticals/Thinking-linkers-antibody-drug-conjugates/102/i28#:~:text=Exatecan%20recently%20came%20off%20patent,which%20are%20usually%20PEG%20based.
Avacta doesn't have a problem with linkers...‘Our Mission is to improve patients’ lives and grow shareholder value by developing novel cancer therapies and powerful diagnostics using our proprietary Affimer® and pre|CISION™ platforms.’
‘Partnering is key to Avacta’s strategy as we continue to expand our pipeline of innovative treatments for cancer.
Our partnering strategy includes teaming up with pharmaceutical partners to help advance our pipeline products through to market, as well as combining our proprietary platforms with novel warheads to develop next generation cancer therapies.’
‘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..
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