Design and discovery of a bispecific conditional TNF-R agonist

Tumor Necrosis Factor (TNF) receptor agonist antibodies represent a promising frontier in cancer treatment. These antibodies bind specifically to TNFRs, mimicking the action of a natural TNF and induce receptor trimerization, which is essential for downstream signaling. However, activation of  TNF receptors via bivalent bispecific antibody in isolation is ineffective. Similarly, activation via Fc gamma receptors can lead to systemic inflammation and potential toxicity, leading to a low maximum tolerated dose and compromising treatment efficacy. Hence, trimerization must occur via multivalent bispecific antibodies. This requires expertise in developing multivalent bispecific antibodies from design to lead optimization and selection. In this talk, we discuss the various steps involved in bispecific antibody discovery and a brief overview of Syngene’s capabilities in this space.  

DMPK and non-clinical safety considerations in the assessment of developability in drug discovery

Present-day drug design strategies allow the identification of drug candidates with remarkable drug-like properties. Understanding the drug candidate’s target product profile and establishing a correlation with DMPK and safety assessment is essential to any program’s clinical and commercial success. This helps adapt candidate screening strategies and predict better dosages. In this talk, we present case studies to show how a drug candidate’s safety assessment against the target product profile impacts a drug program. We also demonstrate PK/PD correlation using in vivo and in vitro tests to predict the most efficacious human dose.