A5014880230- Microscopic Colitis
- PI3K/AKT/mTOR signaling in cancer
- Inflammatory Bowel Disease
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Advanced Drug Delivery Systems
- Cardiac, Anesthesia and Surgical Outcomes
- Cancer Treatment and Pharmacology
- Chronic Lymphocytic Leukemia Research
- Gout, Hyperuricemia, Uric Acid
- Renal cell carcinoma treatment
- Protease and Inhibitor Mechanisms
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Gastrointestinal motility and disorders
- Chronic Myeloid Leukemia Treatments
- Cholinesterase and Neurodegenerative Diseases
- Lymphoma Diagnosis and Treatment
- Computational Drug Discovery Methods
- Inflammasome and immune disorders
- Cardiac Ischemia and Reperfusion
- Renal and related cancers
- Systemic Lupus Erythematosus Research
- Glioma Diagnosis and Treatment
- Kawasaki Disease and Coronary Complications
University of British Columbia
2024
Roche (United States)
2024
Inappropriate and chronic activation of the cytosolic NOD-, LRR-, pyrin domain-containing 3 (NLRP3) inflammasome, a key component innate immunity, likely underlies several inflammatory diseases, including coronary artery disease. This first-in-human phase I trial evaluated safety, pharmacokinetics (PKs), pharmacodynamics (PDs) oral, single (150-1800 mg) multiple (300 or 900 mg twice daily for 7 days) ascending doses (SADs MADs) GDC-2394, small-molecule inhibitor NLRP3, versus placebo in...
Checkpoint kinase 1 (Chk1) inhibition following chemotherapy-elicited DNA damage overrides cell cycle arrest and induces mitotic catastrophe death. GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage growth delay xenograft models. We evaluated the safety, tolerability, pharmacokinetic properties of alone combination with gemcitabine. Antitumor activity pathway modulation were assessed.In this phase I open-label study, dose escalation stage,...
GDC‐0853 is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) that highly selective and noncovalent, leading to reversible binding. In double‐blind, randomized, placebo‐controlled phase I healthy volunteer studies, was well tolerated, with no dose‐limiting adverse events (AEs) or serious AEs. The maximum tolerated dose not reached during escalation (≤600 mg, single ascending (SAD) study; ≤250 mg twice daily (b.i.d.) ≤500 once daily, 14‐day multiple (MAD) study). Plasma...
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...
Abstract Background Crenezumab, a fully humanized anti-beta-amyloid (Aβ) immunoglobulin G4 (IgG4) monoclonal antibody, binds to both monomeric and aggregated forms of Aβ. We assessed the pharmacokinetics (PK)/pharmacodynamics (PD) crenezumab its interaction with Aβ(1–40) Aβ(1–42) peptides in serum/plasma cerebrospinal fluid (CSF) samples from phase II ABBY BLAZE studies Ib GN29632 study. Methods In ABBY, BLAZE, studies, patients mild-to-moderate AD were treated either placebo or (300 mg...
Cancer remains a significant global health challenge, and despite remarkable advancements in therapeutic strategies, poor tolerability of drugs (causing dose reduction/interruptions) and/or the emergence drug resistance are major obstacles to successful treatment outcomes. Metastatic renal cell carcinoma (mRCC) accounts for 2% cancer diagnoses deaths. Despite initial success targeted therapies mRCC, challenges remain overcome that limits long-term efficacy these treatments. Our analysis aim...
Compared with intravenous formulations, subcutaneous (s.c.) formulations of therapeutic monoclonal antibodies may provide increased patient access and more convenient administration options, although historically high-volume s.c. (> 10-15 mL) has been challenging. We report results from two phase I studies in healthy participants (GP29523 GP40201) that evaluated crenezumab, an anti-Aβ antibody development for individuals at risk autosomal-dominant Alzheimer's disease. GP29523 assessed...
Etrolizumab is an IgG1-humanized monoclonal antibody that specifically targets the β7 subunit of α4β7 and α4Eβ7 integrins, it has been evaluated for treatment moderately-to-severely active ulcerative colitis (UC). Population pharmacokinetic (PK) analysis was performed to characterize etrolizumab PK properties in patients with UC evaluate covariate impacts on exposure. The population model developed based serum concentrations from enrolled six studies (one phase I, one II, four III) validated...
Etrolizumab is an IgG1-humanized monoclonal anti-β7 integrin antibody. Phase III trials with induction and/or maintenance phases were conducted in patients moderately-to-severely active ulcerative colitis (UC) who either previously treated tumor necrosis factor (TNF) inhibitors (HICKORY) or TNF inhibitor naïve (HIBISCUS I/II, LAUREL, and GARDENIA). A total of eight exposure-response analyses for two clinical outcomes (remission endoscopic improvement) at the end studies HIBISCUS I/II...
Abstract The Mayo Clinical Score is used in clinical trials to describe the status of patients with ulcerative colitis (UC). It comprises four subscores: rectal bleeding (RB), stool frequency (SF), physician's global assessment, and endoscopy (ENDO). According recent US Food Drug Administration guidelines (Ulcerative colitis: developing drugs for treatment, Guidance Document, https://www.fda.gov/regulatory‐information/s . 2022), response remission should be based on modified (mMS) relying...
Despite significant progress in biomedical research, the rate of success oncology drug development remains inferior to that other therapeutic fields. Mechanistic models provide comprehensive understanding effects drugs, which is crucial for designing effective clinical trials. This study was performed acquire a better PI3K–AKT–TOR pathway modulation and preclinical translational bridging specific compound, apitolisib (PI3K/mTOR inhibitor), by developing integrated mechanistic models....