A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

Unlabelled: Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient's own tumor cells, providing the widest cancer-specific antigen repertoire and a standardized, sustained, local delivery over days of a potent adjuvant achieved by encapsulated cell technology.

The biodistribution and clearance of AlbudAb, a novel biopharmaceutical medicine platform, assessed via PET imaging in humans.

Unlabelled: Conjugation or fusion to AlbudAbs™ (albumin-binding domain antibodies) is a novel approach to extend the half-life and alter the tissue distribution of biological and small molecule therapeutics. To understand extravasation kinetics and extravascular organ concentrations of AlbudAbs in humans, we studied tissue distribution and elimination of a non-conjugated Zr-labeled AlbudAb in healthy volunteers using positron emission tomography/computed tomography (PET/CT).

Methods: A non-conjugated AlbudAb (GSK3128349) was radiolabeled with Zr and a single 1 mg (~ 15 MBq) dose intravenously administered to eight healthy males.

Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe.

p300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. Herein, we report GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028 as an enantiomeric negative control.

Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses.

FTY720 is the first oral small molecule approved for the treatment of people suffering from relapsing-remitting multiple sclerosis. It is a potent agonist of the S1P1 receptor, but its lack of selectivity against the S1P3 receptor has been linked to most of the cardiovascular side effects observed in the clinic. These findings have triggered intensive efforts toward the identification of a second generation of S1P3-sparing S1P1 agonists.

Pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol as a triple therapy in healthy volunteers.

Objective: Two single-center, four-way, single-dose, crossover studies assessed the systemic exposure, systemic pharmacodynamics (PD), and safety profile of the closed triple fluticasone furoate/ umeclidinium/vilanterol (FF/UMEC/VI) therapy compared with dual therapies. These are the first studies where pharmacokinetic (PK) profile assessment was possible for this inhaled triple fixed-dose combination product.

Methods: Healthy volunteers were randomized to receive 4 consecutive inhalations (each administered as a single dose) via a single ELLIPT® dry powder inhaler: in study 1 (CTT116415/NCT01691547), FF/UMEC/VI at total doses of 400/500/100 μg, FF/UMEC 400/500 μg, UMEC/VI 500/100 μg, or FF/VI 400/100 μg; in study 2 (200587/NCT01894386), FF/UMEC/VI at total doses of 400/500/100 μg or 400/250/100 μg, FF/VI 400/100 μg, or UMEC/VI 250/100 μg.