Nové Zamky, Slovakia

A Study on the Safety of TAK-279 and Whether it Can Reduce Inflammation in the Bowel of Participants With Moderately to Severely Active Crohn's Disease

The drug being tested in this study is TAK-279. TAK-279 is being tested to treat participants with moderately to severely active Crohn's disease. The study will look at the efficacy and safety of TAK-279. The study will enroll approximately 268 participants. During the Induction Period participants will be randomly assigned to one of the following treatment groups in a ratio of 1:1:1:1 to receive TAK-279 or placebo which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): 1. TAK-279 Dose 1 2. TAK-279 Dose 2 3. TAK-279 Dose 3 4. Placebo This multi-center trial will be conducted globally. The overall study duration is approximately 60 weeks including a 4-week safety follow-up period.

Multi-omics Study in Citrin Deficiency

Citrin deficiency (CD) is an inherited autosomal recessive metabolic condition that is also a secondary urea cycle disorder caused by mutations in the SLC25A13 gene, which encodes for the mitochondrial transporter, citrin. Citrin is a key component of the mitochondrial malate-aspartate shuttle (MAS) and is responsible for moving Nicotinamide Adenine Dinucleotide (NADH) from the cytosol into the mitochondria via reducing equivalents such as malate, which drives mitochondrial respiration to produce energy in the form of adenosine triphosphate (ATP). The MAS is also critical in regulating Nicotinamide Adenine Dinucleotide (NAD+/NADH) redox balance to maintain cytosolic redox-dependent metabolic pathways such as glycolysis, gluconeogenesis, amino acid metabolism, and lipid metabolism. Citrin is also required to supply cytosolic aspartate, which is the substrate of one of the urea cycle enzymes, namely argininosuccinate synthetase 1, and thus important for the proper functioning of the urea cycle. The clinical presentations of citrin deficiency often vary widely between patients but can generally be distinguished by distinct clinical phenotypes, which are neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) that affects infants, the "failure to thrive and dyslipidemia" form of CD (FTTDCD) in childhood, the adaptation or silent period, and citrullinemia type II (CTLN2), which represents the most severe form of the condition. While only a small percentage of CD patients develop CTLN2, the prognosis for these patients is typically poor. It is notable that all CD patients above 1 year old (post-NICCD) naturally develop a characteristic food preference that favors a diet rich in protein and fat while being low in carbohydrates. Other clinical findings observed in some CD patients include fatty liver, fatigue, hypoglycemia, and failure to thrive. There is currently no effective cure for CD. Before the onset of CTLN2, patients are primarily managed by diet control with a low carbohydrate, high protein and high-fat diet, as well as medium chain triglyceride (MCT) supplementation. CTLN2 patients have been treated with sodium pyruvate, arginine, and MCT with limited success, with severe cases requiring liver transplantation as the only solution. There are currently no specific biomarkers that effectively track the disease progression, making it challenging to monitor how well patients are actually doing or to measure the effectiveness of therapies. Without proper management or timely medical interventions, patients may develop CTLN2. Given the urgent and unmet need for biomarkers specific to CD, the main goal of this study is to uncover disease-specific biomarkers by analyzing blood samples collected from CD patients using both targeted and untargeted metabolomics, proteomics, lipidomics, and transcriptomics. Targeted omics will involve the analysis of cellular pathways associated with the condition, such as the MAS pathway, glycolysis, protein metabolism, de novo lipogenesis, lipolysis, gluconeogenesis, NAD+ metabolism, ureagenesis, and the glutamine synthetase pathway. Identification of such biomarkers will allow a deeper understanding of the disease pathogenesis. Importantly, these biomarkers may enable better tracking of disease progression and may help to prevent the onset of CTLN2. Finally, these biomarkers will also greatly benefit the development of effective therapeutic options for CD in clinical trials by serving as measurable endpoints. Obtaining the necessary material from patients consists of a minimally invasive venous blood sampling taken during a regular outpatient visit and after the informed consent of the patients or caretakers.

A Study to Compare the Efficacy and Safety of BMS-986489 (BMS-986012+ Nivolumab Fixed Dose Combination) in Combination With Carboplatin Plus Etoposide to That of Atezolizumab With Carboplatin Plus Etoposide as First-Line Therapy in Participants With Extensive-Stage Small Cell Lung Cancer (TIGOS).

A Study of Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer in Japanese Patients

This is a multi-center, open label Phase 2 study designed to evaluate safety and tolerability and confirm efficacy by BICR of avutometinib in combination with defactinib in Japanese patients with molecularly profiled recurrent LGSOC.