T2 Protect AD: Achieving a rapid recruitment timeline in a multisite clinical trial for individuals with mild to moderate Alzheimer's disease.

Introduction: The reporting of approaches facilitating the most efficient and timely recruitment of Alzheimer's disease (AD) patients into pharmacologic trials is fundamental to much-needed therapeutic progress.

Methods: T2 Protect AD (T2), a phase 2 randomized placebo-controlled trial of troriluzole in mild to moderate AD, used multiple recruitment strategies.

Results: T2 exceeded its recruitment target, enrolling 350 participants between July 2018 and December 2019 (randomization rate: 0.

Enriching the design of Alzheimer's disease clinical trials: Application of the polygenic hazard score and composite outcome measures.

Introduction: Selecting individuals at high risk of Alzheimer's disease (AD) dementia and using the most sensitive outcome measures are important aspects of trial design.

Methods: We divided participants from Alzheimer's Disease Neuroimaging Initiative at the 50th percentile of the predicted absolute risk of the polygenic hazard score (PHS). Outcome measures were the Alzheimer's Disease Assessment Schedule-Cognitive Subscale (ADAS-Cog), ADNI-Mem, Clinical Dementia Rating-Sum of Boxes (CDR SB), and Cognitive Function Composite 2 (CFC2).

Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases.

Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. However, further refinement is needed to this class of agents, particularly in terms of adverse events (potentially driven by kinase promiscuity), which preclude their evaluation in nononcology indications. Here, we report the discovery and preclinical characterization of evobrutinib, a potent, obligate covalent inhibitor with high kinase selectivity.

Ocular Distribution and Pharmacodynamics of SF0166, a Topically Administered Integrin Antagonist, for the Treatment of Retinal Diseases.

SF0166, a small-molecule antagonist, has physiochemical properties that allow distribution to the posterior segment of the eye after topical administration in an ophthalmic solution. The pharmacodynamics and ocular distribution of SF0166 were evaluated in several cell lines, chick chorioallantoic membrane assays, and models of ocular neovascularization in mice and pigmented rabbits. SF0166 inhibited cellular adhesion to vitronectin across human, rat, rabbit, and dog cell lines with IC values of 7.

Maximum levels of hepatitis C virus lipoviral particles are associated with early and persistent infection.

Background & Aims: Hepatitis C virus (HCV) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle (LVP). Experimental evidence indicates that LVPs have decreased susceptibility to antibody-mediated neutralisation and higher infectivity. This study tested the hypothesis that LVPs are required to establish persistent infection, and conversely, low levels of LVP in recent HCV infection increase the probability of spontaneous HCV clearance.