Matthias Macháček
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View article: Prediction of Cardiac <scp>ATTR</scp> Depletion by <scp>NI006</scp> (<scp>ALXN2220</scp>) Using Mechanistic <scp>PK</scp>/<scp>PD</scp> Modeling
Prediction of Cardiac <span>ATTR</span> Depletion by <span>NI006</span> (<span>ALXN2220</span>) Using Mechanistic <span>PK</span>/<span>PD</span> Modeling Open
NI006 (aka ALXN2220) is a therapeutic antibody candidate in phase III clinical development for the depletion of amyloid transthyretin (ATTR) in patients with ATTR cardiomyopathy, an infiltrative cardiomyopathy leading to increased left ven…
View article: NfL concentration in CSF is a quantitative marker of the rate of neurodegeneration in aging and Huntington's disease: a semi-mechanistic model-based analysis
NfL concentration in CSF is a quantitative marker of the rate of neurodegeneration in aging and Huntington's disease: a semi-mechanistic model-based analysis Open
The concentrations of neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and plasma have become key biomarkers of many neurodegenerative diseases, including Huntington's Disease (HD). However, the relationship between the dynamic…
View article: Neutralizing GDF-15 can overcome anti-PD-(L)1 resistance in late-stage cancer
Neutralizing GDF-15 can overcome anti-PD-(L)1 resistance in late-stage cancer Open
Cancer immunotherapies with antibodies blocking immune checkpoint molecules are active treatments across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumor progression com…
View article: Re‐estimation of drug‐specific amyloid removal parameters and the rate constant for pathogenic tau turnover brings the Q‐ATN model into better alignment with recent phase 3 data from gantenerumab and lecanemab
Re‐estimation of drug‐specific amyloid removal parameters and the rate constant for pathogenic tau turnover brings the Q‐ATN model into better alignment with recent phase 3 data from gantenerumab and lecanemab Open
Background The Q‐ATN model (Mazer et al., Alzheimer’s & Dementia. 2022; https://doi.org/10.1002/alz/12877 ) is a quantitative semi‐mechanistic representation of the A (amyloid)/T (tau)/N (neurodegeneration) framework for simulating the nat…
View article: 2529. Population pharmacokinetic models for cefepime and enmetazobactam derived from pooled Phase 1 to Phase 3 clinical studies
2529. Population pharmacokinetic models for cefepime and enmetazobactam derived from pooled Phase 1 to Phase 3 clinical studies Open
Background The investigational β-lactam/β-lactamase inhibitor combination of cefepime (FEP)/enmetazobactam (ENM) met criteria for non-inferiority and superiority compared to piperacillin/tazobactam in a phase 3 clinical trial of adult pati…
View article: Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide, a Glucagon-Like Peptide-2 Analog, in Healthy Volunteers
Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide, a Glucagon-Like Peptide-2 Analog, in Healthy Volunteers Open
Apraglutide (FE 203799) is a glucagon-like peptide-2 (GLP-2) analog under development for the treatment of intestinal failure associated with short bowel syndrome (SBS-IF) and graft-versus-host disease (GvHD). Compared with native GLP-2, a…
View article: Coordination of Rho GTPase activities during cell protrusion
Coordination of Rho GTPase activities during cell protrusion Open
The GTPases Rac1, RhoA and Cdc42 act in concert to control cytoskeleton dynamics1-3. Recent biosensor studies have shown that all three GTPases are activated at the front of migrating cells4-7 and biochemical evidence suggests that they ma…
View article: Modeling the activation of the alternative complement pathway and its effects on hemolysis in health and disease
Modeling the activation of the alternative complement pathway and its effects on hemolysis in health and disease Open
The complement system is a powerful mechanism of innate immunity poised to eliminate foreign cells and pathogens. It is an intricate network of >35 proteins, which, once activated, leads to the tagging of the surface to be eliminated, prod…
View article: Population Pharmacokinetic/Pharmacodynamic Modeling of Glenzocimab (ACT017) a Glycoprotein VI Inhibitor of Collagen‐Induced Platelet Aggregation
Population Pharmacokinetic/Pharmacodynamic Modeling of Glenzocimab (ACT017) a Glycoprotein VI Inhibitor of Collagen‐Induced Platelet Aggregation Open
Glenzocimab (ACT017) is a humanized monoclonal antigen‐binding fragment (Fab) directed against the human platelet glycoprotein VI, a key receptor for collagen and fibrin that plays a major role in thrombus growth and stability. Glenzocimab…
View article: Pharmacokinetics-Pharmacodynamics of Enmetazobactam Combined with Cefepime in a Neutropenic Murine Thigh Infection Model
Pharmacokinetics-Pharmacodynamics of Enmetazobactam Combined with Cefepime in a Neutropenic Murine Thigh Infection Model Open
Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum β-lactamases (ESBLs) as principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel …
View article: Half-life extension and non-human primate pharmacokinetic safety studies of i-body AD-114 targeting human CXCR4
Half-life extension and non-human primate pharmacokinetic safety studies of i-body AD-114 targeting human CXCR4 Open
Single domain antibodies that combine antigen specificity with high tissue penetration are an attractive alternative to conventional antibodies. However, rapid clearance from the bloodstream owing to their small size can be a limitation of…
View article: Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab
Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab Open
Objective— ACT017 is a novel, first in class, therapeutic antibody to platelet GPVI (glycoprotein VI) with potent and selective antiplatelet effects. This first-in-human, randomized, placebo-controlled phase 1 study was conducted to evalua…
View article: Population Modeling of Selexipag Pharmacokinetics and Clinical Response Parameters in Patients With Pulmonary Arterial Hypertension
Population Modeling of Selexipag Pharmacokinetics and Clinical Response Parameters in Patients With Pulmonary Arterial Hypertension Open
Selexipag (Uptravi) is an oral selective IP prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension (PAH). The pivotal GRIPHON study was the largest clinical study ever conducted in PAH patients, providi…