A5052765300- Erythrocyte Function and Pathophysiology
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- Lipid metabolism and disorders
- Angiogenesis and VEGF in Cancer
- Hemoglobinopathies and Related Disorders
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Erythropoietin and Anemia Treatment
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Neonatal Health and Biochemistry
- Toxin Mechanisms and Immunotoxins
- Pregnancy-related medical research
- Cancer, Lipids, and Metabolism
- Lymphoma Diagnosis and Treatment
- biodegradable polymer synthesis and properties
- CAR-T cell therapy research
- Blood groups and transfusion
- Renal Diseases and Glomerulopathies
- Occupational Health and Performance
- Biomedical Text Mining and Ontologies
- Graphene and Nanomaterials Applications
- RNA Interference and Gene Delivery
- Chemotherapy-related skin toxicity
AstraZeneca (United States)
2020-2022
NGM Biopharmaceuticals (United States)
2022
University of Iowa
2012-2019
Serimmune (United States)
2019
Translational Therapeutics (United States)
2019
Abstract Pralsetinib, a potent and selective inhibitor of oncogenic RET fusion mutant proteins, is substrate the drug metabolizing enzyme CYP3A4 efflux transporter P‐gp based on in vitro data. Therefore, its pharmacokinetics (PKs) may be affected by co‐administration inhibitors inducers, inhibitors, combined inhibitors. With frequent overlap between substrates/inhibitors, pralsetinib challenging representative example need to more quantitatively characterize transporter‐enzyme interplay. A...
Purpose: This first-in-human study aimed to determine the MTD and safety of MEDI3617, a selective anti-angiopoietin-2 (Ang2) mAb, alone combined with bevacizumab or cytotoxic chemotherapy.Patients Methods: phase I/Ib, multicenter, open-label, dose-escalation dose-expansion evaluated patients advanced solid tumors. Patients received intravenous MEDI3617 as monotherapy [5-1,500 mg every 3 weeks (Q3W)] 2 (Q2W) Q3W, weekly paclitaxel, carboplatin plus paclitaxel Q3W. Dose expansions included...
OBJECTIVES: Fenebrutinib (FEN) is a potent orally administered CNS penetrant Bruton's tyrosine kinase inhibitor that highly selective and noncovalent, leading to reversible binding [1]. FEN inhibits both B-cell proliferation microglia activation are drivers of acute chronic inflammation in relapsing multiple sclerosis (RMS) [2]. FENopta study (NCT05119569) Phase 2 evaluating the efficacy, safety, pharmacokinetics (PK) patients with RMS receiving 200 mg twice-a-day oral fenebrutinib or...
Background Heart failure is one of the leading causes death in Western countries, and there a need for new therapeutic approaches. Relaxin‐2 peptide hormone that mediates pleiotropic cardiovascular effects, including antifibrotic, angiogenic, vasodilatory, antiapoptotic, anti‐inflammatory effects vitro vivo. Methods Results We developed RELAX 10, fusion protein composed human relaxin‐2 Fc antibody, to test hypothesis extended exposure could reduce cardiac hypertrophy fibrosis. 10...
Although numerous small molecules have been synthesized with sulfenamide bonds (R(2)N-SR), this is the first report of synthesis polysulfenamides. These polymers are readily at room temperature using secondary diamines and dithiosuccinimides. The dithiosuccinimides were in one step by reaction dithiols such as HS(CH(2))(6)SH N-chlorosuccinimide. resulting either recrystallized or purified chromatography on silica gel required no special handling. conversions polymerization ranged from 95 to...
The randomized, double-blind, phase 2 b MUSE study evaluated the efficacy and safety of type I IFN receptor antibody anifrolumab (300 mg or 1000 every 4 weeks) compared with placebo for 52 weeks in patients chronic, moderate to severe SLE. Characterizing exposure-response relationship will enable selection its optimal dosage regimen two 3 studies SLE.The relationship, pharmacokinetics (PK) SLE Responder Index (SRI(4)) data were analysed using a population approach. A dropout hazard function...
Abstract Pralsetinib is a highly potent oral kinase inhibitor of oncogenic RET (rearranged during transfection) fusions and mutations. received approval from the United States Food Drug Administration for treatment patients with metastatic fusion‐positive non‐small cell lung cancer (NSCLC), accelerated thyroid cancer. Exposure–response (ER) analyses efficacy were performed separately in NSCLC, but data all pooled safety analysis. ER models developed time‐varying exposure; effect covariates...
We characterized the population pharmacokinetics of anifrolumab, a type I interferon receptor-blocking antibody. Pharmacokinetic data were analyzed from anifrolumab (intravenous [IV], every 4 weeks) arms 5 clinical trials in patients with systemic lupus erythematosus (SLE) (n = 664) and healthy volunteers 6). Population pharmacokinetic modeling was performed using 2-compartment model parallel linear nonlinear elimination pathways. The impact covariates (demographics, gene signature [IFNGS,...
The quality of transfused red blood cells (RBCs) to treat anemia depends on its potential for oxygen delivery, governed by two properties: 1) initial posttransfusion recovery and 2) life span initially surviving RBCs. latter property is poorly evaluated the traditional mean (MPL) or cell age (MA), because these parameters do not evaluate how long RBCs remain in circulation. Furthermore, evaluation MPL based problematic assumptions regarding RBCs: they were produced at a constant steady-state...
Aims To characterize the pharmacokinetics (PK) of moxetumomab pasudotox, an anti‐CD22 recombinant immunotoxin, in adults with relapsed or refractory hairy cell leukaemia, we examined data from a phase 1 study (Study 1001; n = 49) and pivotal clinical 1053; 74). Methods Data both studies were pooled ( 123) to develop population PK model. Covariates included demographics, disease state, liver kidney function, prior treatment, antidrug antibodies (ADAs). Exposure–response exposure–safety...
Abstract Recently, biotechnology and pharmaceutical industries have made strides to adopt implement Natural Language Processing (NLP) address challenges faced when extracting synthesizing high volumes of information found in unstructured semistructured text. Here we present, provide a summary the findings from, use case where NLP text mining methodologies were used extract clinical trial data from ClinicalTrials.gov for mRNA cancer vaccines.
To evaluate the effects of fenebrutinib on MRI outcomes and ability to enter cerebrospinal fluid (CSF) in ongoing Phase II study FENopta (NCT05119569).
To evaluate the safety, tolerability and pharmacokinetics of fenebrutinib its effect on cardiac repolarization in healthy participants.
In oncology drug development, tumor dynamics modeling is widely applied to predict patients' overall survival (OS) via parametric models. However, the current paradigm, which assumes a disease-specific link between and survival, has its limitations. This particularly evident in development scenarios where clinical trial under consideration contains patients with types for there little no prior institutional data. this work, we propose use of pan-indication solid machine learning (ML)...
In this brief report, we provide insights into current practices in preclinical messenger RNA (mRNA) cancer vaccine characterization. To enable a more automated and thorough survey of mRNA data the literature, implemented natural language processing to mine abstracts from PubMed followed by annotation selected articles. Through analysis identified gap literature wherein pharmacokinetic (PK) characterization is not reported vaccine-focused As result, field unable evaluate discuss cross-study...