Using structure- and ligand-based design principles, a novel series of piperidyl chromane arylsulfonamide Nav1.7 inhibitors was discovered. Early optimization focused on improvement of potency through refinement of the low energy ligand conformation and mitigation of high in vivo clearance. An in vitro hepatotoxicity hazard was identified and resolved through optimization of lipophilicity and lipophilic ligand efficiency to arrive at GNE-616 (24), a highly potent, metabolically stable, subtype selective inhibitor of Nav1.7. Compound 24 showed a robust PK/PD response in a Nav1.7-dependent mouse model, and site-directed mutagenesis was used to identify residues critical for the isoform selectivity profile of 24.

Since the Coronavirus Disease 2019 (COVID‐19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much‐shortened timeline of 3–6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS‐CoV‐2‐neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization  approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late‐stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next‐generation sequencing‐based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID‐19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic‐related biologics development may innovate typical biologics development timelines and become a new standard in the industry.

The aim of this study was to investigate the survival, distribution and reaction of different cell types on a monolayer disk, as well as their behavior under bioreactor treatment. Specifically, porcine EEC and porcine fibroblasts (PCF) were labeled with GFT and Texas Red, respectively, to track their viability and distribution. The experiments involved monitoring the cells using various microscopy techniques and comparing the results with controls. These findings have important implications for understanding cell behavior and potential applications for Discrete Subaortic Stenosis. This paper aims to discuss the implications of the findings in the context of existing literature and future research directions.