We report pharmacokinetics, pharmacodynamics, and safety of a novel anti‐CD28 domain antibody antagonist (lulizumab pegol) in healthy subjects following single‐ or multiple‐dose administration. A minimal anticipated biological effect level approach was used to select a 0.01 mg starting dose for a single‐ascending‐dose (SAD), double‐blind, first‐in‐human study. Part 1 included 9 intravenous (IV; 0.01‐100 mg) and 3 subcutaneous (SC; 9‐50 mg) doses or placebo. In part 2, a keyhole limpet hemocyanin (KLH) immunization was performed in 16 subjects/panel, who received 1 of 3 IV doses (9‐100 mg) or placebo. In a double‐blind, multiple‐ascending‐dose (MAD) study, subjects received SC lulizumab 6.25 mg every 2 weeks, 12.5 mg weekly, 37.5 mg weekly, or placebo. Among 180 treated subjects, 169 completed the studies. Peak concentrations and areas under the curve from time 0 to infinity increased dose proportionally. Estimated SC bioavailability was 68.2%. Receptor occupancy of approximately ≥80% was maintained for ≥2 weeks at ≥9‐mg doses (SAD) and throughout the dosing interval (MAD). IV doses ≥9 mg inhibited antibody production against KLH for 2 weeks. No significant cytokine or immune cell changes were observed. No immunogenicity responses persisted, and there was no correlation to adverse events. Headache occurred in 21 SAD and 4 MAD subjects receiving lulizumab; in the MAD study 5 lulizumab subjects experienced infections. Lulizumab IV or SC was safe at all doses studied, without evidence of cytokine release.

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In many areas of drug discovery and development, scientists are in a constant search for methods and platforms to reduce assay time and cost. The Gyrolab™ microfluidics platform that we describe here promises to deliver faster ligand-binding assays with lower reagent and sample consumption, while maintaining good accuracy and precision. Due to its limited track record, we evaluated its performance on assays currently used to support pharmacokinetic and immunogenicity studies, and detection of host cell protein impurities in samples from biotechnology processes. This article summarizes our preliminary conclusions about the utility of the Gyrolab microfluidics platform from Gyros AB.

Gene expression analysis has facilitated a more complete understanding of the molecular biology of cellular processes and how variations of RNA expression are useful for the classification of various diseases. Furthermore, recent analysis of a variety of noncoding RNAs, such as microRNAs, has demonstrated that these RNAs play an important role in many cellular events, including cell differentiation and death, and may also serve as biological markers for disease. Besides helping in the understanding of diseases, RNA analysis is used in drug discovery, patient prognosis and treatment evaluation. One obstacle left to overcome is the amount of material required for the analysis, particularly when trying to extract information from precious, limited, clinical samples. Here we review the many approaches scientists take to either amplify the amount of RNA or amplify the signal generated from small amounts of RNA.

Abstract. The purpose of this manuscript is to provide a summary of the evaluation done by the Throughput and Multiplexing subteam on five emerging technologies: Single molecule array (Simoa™), Optimiser™, CyTOF® (Mass cytometry), SQIDLite™, and iLite™. Most of the information is presented with a minimum amount of published data and much is based on discussions with users and the vendor, to help provide the reader with an unbiased assessment of where the subteam sees each technology fitting best in the bioanalysis of large molecules. The evaluation focuses on technologies with advantages in throughput and multiplexing, but is wide enough to capture their strengths in other areas. While all platforms may be suited to support bioanalysis in the discovery space, because of their emergent nature, only Optimiser and SQIDLite are currently ready to be used in the regulated space. With the exception of Optimiser, each instrument/technology requires an up-front investment from the bioanalytical lab that will need justification during capital budget discussions. Ultimately, the platform choice should be driven by the quality of data, project needs, and the intended use of the data generated. In a time-and resourceconstrained environment, it is not possible to evaluate all emergent technologies available in the market; we hope that this review gives the reader some of the information needed to decide which technology he/ she may want to consider evaluating to support their drug development program in comparison to the options they already have in their hands.