UCB (Union Chimique Belge) is a multinational biopharmaceutical company headquartered in Brussels, Belgium. UCB is an international company with a revenue of €4.178 billion in 2016 which focuses primarily on research and development, specifically involving medications centered on epilepsy, Parkinson's, and Crohn's diseases. The company's efforts are focused on treatments for severe diseases treated by specialists, particularly in the fields of central nervous system (CNS) disorders (including epilepsy), inflammatory disorders (including allergy), and oncology. Every three years, the company presents the UCB Award under the patronage of the Queen Elisabeth Medical Foundation to promote neuroscience research. The winner of this award is selected by an independent scientific committee.
Identifying how drugs interact with proteins is fundamental to understanding their therapeutic effects and side effects. While numerous chemical proteomics methods exist for determining protein targets of drugs, each exhibits “blind spots,” necessitating complementary approaches. We introduce Above-Filter Digestion Proteomics (AFDIP), which monitors trypsin digestion rates that decrease at ligand-binding sites, while potentially increasing elsewhere. Molecular dynamics simulations showed that these changes relate to backbone flexibility. Using AFDIP, we identified targets of various drugs and metabolites, allowing two-dimensional analysis with the drug concentration as the second dimension. The method identifies binding sites within ≤10 Å of crystallography-determined locations with improved resolution (≤5 Å) for larger proteins. Compared with existing proteolysis approaches, AFDIP offers simpler sample preparation, deeper proteome analysis, and broader sequence coverage. AFDIP addresses the blind spots of current techniques and provides structural insights, enhancing the chemical proteomics toolkit.
The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52 weeks (Wk52) using matching-adjusted indirect comparisons (MAIC). Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons. In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95
Staccato alprazolam (STAP) is a hand-held device that can provide rapid systemic delivery of alprazolam via pulmonary inhalation. UP0099/NCT04802746, a phase 1, randomized, double-blind, placebo-controlled trial, evaluated pulmonary safety of two consecutive doses of STAP administered 72 h apart (days 1, 4). Part A evaluated STAP 1 mg and 2 mg vs. placebo in a three-way crossover design in healthy adults. Part B evaluated STAP 2 mg vs. placebo in a two-arm parallel-group design in adults with mild asthma. In Part A (n = 30 randomized) on day 1, mean change from baseline in forced expiratory volume in 1 s (FEV1) showed a statistically significant decrease vs. placebo at 5 min postdose for STAP 1 mg and 5/20 min for STAP 2 mg. On day 4, there were no statistically significant negative changes from baseline in FEV1. Respiratory treatment-emergent adverse events (TEAEs) were reported by 8/29 and 12/29 participants on STAP 1 mg/2 mg, respectively (day 1), and 8/29 and 9/28 (day 4) (placebo: 0). In Part B (n = 25 placebo, n = 23 STAP) on days 1 and 4, mean change from baseline in FEV1 showed a statistically significant decrease for STAP 2 mg vs. placebo at 5/20 min and 6 h postdose. Respiratory TEAEs were reported by 16/23 participants on STAP 2 mg on day 1, 15/22 on day 4 (placebo: 0). Most respiratory TEAEs were mild in intensity. No evidence of clinically relevant airway obstruction or respiratory TEAEs indicative of bronchospasm with STAP were observed. Two doses of STAP (1 mg/2 mg) administered 72 h apart were well tolerated in healthy participants and those with mild asthma.
Objectives The HIPPOCRATES project is a 5-year, international research partnership dedicated to studying and treating psoriatic disease. Integrating Patient Research Partners (PRPs) into large scientific groups, particularly those heavily focused on preclinical or laboratory-based science, is challenging. This paper details a midterm evaluation of how effectively PRPs have been engaged in the HIPPOCRATES project. Methods Our evaluation used a mixed-method approach comprising 7 dedicated reflective PRP meetings, 2 midterm surveys among PRPs and researchers, a modified World Café discussion, and 5 structured dialogue meetings. We used descriptive statistics and pragmatic constant comparative analysis. Results Substantial PRP input occurred early during the project’s presubmission phase, which resulted in a formal strategy for patient involvement. However, 3 years after approval, significant differences emerged between researcher and PRP perspectives. Compared with researchers, PRPs reported more challenges, had differing expectations, and perceived a lower overall impact. Although PRPs were highly motivated at the start and contributed significantly to clinical components, motivation decreased for some regarding the laboratory components. This was attributed to highly technical language, long contract negotiations, and a lack of clear opportunities for input or tangible results. Consortium members collaboratively agreed upon a set of specific changes during the 5 dialogue sessions. Conclusions Despite the early and substantial involvement of PRPs in the initial study design, the PRPs themselves rated their influence on HIPPOCRATES lower than the researchers did. Further evaluation over the next 2 years will show whether the jointly developed solutions successfully enhance their impact on future research outcomes.
