Archive For: News

Comprehensive mathematical model of the alternative complement pathway describing in vitro experimental- and clinical-data

We recently published a comprehensive mathematical model of the alternative complement pathway in the PLOS Computational Biology journal. The model includes all known positive and negative regulators of the pathway and has been tested on a comprehensive set of in vitro experimental data and clinical data. As such its an exciting tool to probe the pathway model to predict the outcome of different pharmaceutical interventions on key bio- and pharmacodynamic markers.… Read the rest


Population PK/PD Modeling of Glenzocimab (ACT017) a Glycoprotein VI Inhibitor of Collagen‐Induced Platelet Aggregation

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.

We developed a model to understand the PK/PD properties of this compound and to help with the dose selection. Read more details in the following paper.… Read the rest


Pharmacokinetics-pharmacodynamics of enmetazobactam combined with cefepime in a neutropenic murine thigh infection model

Fabian Bernhard, Rajesh Odedra, Sylvie Sordello, Rossella Cardin, Samantha Franzoni, Cédric Charrier, Adam Belley, Peter Warn, Matthias Machacek, Philipp Knechtle

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 ESBL inhibitor developed in combination with cefepime for empiric treatment of serious Gram-negative infections in settings where ESBLs are prevalent. Cefepime-enmetazobactam has been investigated in a phase 3 trial in patients with complicated urinary tract infections or acute pyelonephritis.… Read the rest


The Exposure Response Relationship of Enmetazobactam, Combined with Cefepime, is Best Described by f T > C T in a Murine Thigh Infection Model

F. Berhard 1, M. Machacek 1, P. Warn 2, R. Odedra 2, S. Sordello 2, A. Belley 3, P. Knechtle 3

1 LYO-X Allschwil CH; 2 Evotec Cheshire UK; 3 Allecra Therapeutics Saint-Louis FR

ASM-ESCMID Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance • September 3-6, 2019 • Boston, MA.… Read the rest


Pharmacodynamic Targets of Enmetazobactam, Combined with Cefepime, against ESBL Producing Isolates of K. pneumoniae in a Murine Thigh Infection Model

P. Warn 1 , R. Odedra 1 , S. Sordello 1 , F. Berhard 2 , M. Machacek 2 , A. Belley 3 , P. Knechtle 3

1 Evotec Cheshire UK; 2 LYO-X Allschwil CH; 3 Allecra Therapeutics Saint Louis FR.  

ASM-ESCMID Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance • September 3-6, 2019 • Boston, MA.… Read the rest


Half-life extension and non-human primate pharmacokinetic safety studies of i-body AD-114 targeting human CXCR4

Katherine Griffiths, Uli Binder, William McDowell, Rita Tommasi, Mark Frigerio, William G. Darby, Chris G. Hosking, Lionel Renaud, Matthias Machacek, Peter Lloyd, Arne Skerra & Michael Foley. mAbs, 2019

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 therapeutic single domain antibodies. Here, we describe and evaluate the conjugation of a single domain i-body, AD-114, which targets CXCR4, to a panel of half-life extension technologies including a human serum albumin-binding peptide, linear and branched PEG, and PASylation (PA600).… Read the rest


ECCMID 2019 in Amsterdam

We will be at ECCMID 2019 with a poster contribution and as an exhibitor. The poster is on a novel cUTI mouse model and the application of PK/PD modelling to derive the required effect in the mouse model that translates to clinical response. We used historical Levofloxacin data to establish this animal-human translation. Visit us at our booth to learn more how we can support your preclinical, translational and clinical program with PK/PD modelling. … Read the rest


LYO-X joint BEAM to Fight Antimicrobial Resistance

LYO-X joint the BEAM (Biotech companies in Europe combating AntiMicrobial Resistance) alliance, a strong Network of ~ 50 European biopharmaceutical companies committed to developing innovative products to fend-off antibiotic-resistant pathogens.

We have continuously expanded our support of biotech companies with PK/PD modelling and SystemsPharmacology to translate their antibiotics more effectively to patients. Helping biotechnology companies to succeed and bringing new antibiotics to patients is something we feel really committed to.

By joining BEAM we hope to help even more biotechs to bring their drugs to patients and to increase the awareness of PK/PD modelling as a tool for efficient antibiotics drug development.… Read the rest