Harnessing Natural Mosaics: Antibody-Instructed, Multi-Envelope HIV-1 Vaccine Design.

The year 2021 marks the 40th anniversary since physicians recognized symptoms of the acquired immunodeficiency syndrome (AIDS), a disease that has since caused more than 30 million deaths worldwide. Despite the passing of four decades, there remains no licensed vaccine for the human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS. Despite the development of outstanding anti-retroviral drugs, there are currently more than one-half million deaths each year due to AIDS.

Development and validation of bioanalytical methods to support investigations of AZD9496 in the clinic.

AZD9496 is an oral nonsteroidal, potent and selective antagonist and degrader of ER-α. Two major active metabolites (M3 and M5 as diastereomers) were identified in humans. Multianalyte, sensitive LC-MS/MS method in human plasma was developed and validated that overcame the challenges encountered.

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects.

Purpose: Fixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR.

Methods: This randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18-55 years.

Incurred sample reanalysis in AstraZeneca small molecule portfolio - what have we learned and where do we go next?

In this paper, experiences and learnings are shared from the 10-year application of incurred sample reanalysis (ISR) in support of the AstraZeneca small molecule portfolio. The conclusions from including ISR in every clinical bioanalysis study for a period of 5 years, generating ISR data from 550 studies, are shared. Our preclinical ISR approach is described and data generated using capillary microsampling demonstrate confidence in its routine application.

Bioequivalence of Dapagliflozin/Metformin Extended-release Fixed-combination Drug Product and Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Russian Subjects.

Purpose: Fixed-combination drug products (FCDPs) combining dapagliflozin and metformin extended release (XR) may provide patients with type 2 diabetes mellitus with an alternative antihyperglycemic treatment, which could improve adherence by reducing tablet burden. This study evaluated the bioequivalence of dapagliflozin/metformin XR FCDP versus the co-administration of the individual monotherapy tablets currently available for use in the Russian Federation.

Methods: Healthy subjects aged 18 to 45 years were enrolled in this randomized, open-label, 2-period crossover study, conducted in a single Russian center.