102861Improving the Therapeutic Index of Antibody Drug Conjugates through precision conjugate designClosedCollaborative R&DInnovate UKAntibody Drug Conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over traditional chemotherapy. By combining the targeting power of antibodies with the cell killing capability of potent cytotoxic molecules, it is possible to kill cancer cells more effectively whilst reducing debilitating side effects. Broadly, anti-cancer activity is driven by toxicity of the toxin, whilst tolerability is governed by stability of the conjugation chemistry and tissue distribution of the antigen (i.e. whether the target is present in healthy tissue or not). The project will exploit Glythera's innovative, highly specific and stable PermaLink technology in combination with its portfolio of novel toxins and antibodies to develop safer and more efficacious ADCs for the treatment of hard to treat tumours including pancreatic, lung or ovarian cancers to name but three. Antibodies that are assessed as suitable for ADC application according to pre-determined criteria will be combined with a range of novel, ultra-potent toxin molecules via Glythera’s PermaLink conjugation chemistry. Data from the in vitro and in vivo studies of these conjugates will be used to prioritise the most promising candidate for a pre-clinical development program leading up to ‘first in man studies’.