Oct. 10 Preclinical Quick Takes: Merck-Prokaryotics Inc.-Princeton ID new antibiotic class; plus NIH, Owkin, Genentech and ICR

Merck, Prokaryotics, Princeton ID new class of antibiotic
Merck & Co. Inc. (NYSE:MRK), Prokaryotics Inc. and Princeton University researchers reported in a Proceedings of the National Academy of Sciences paper the identification of MRL-494, a small molecule representing a new antibiotics class that acts against Gram-negative and Gram-positive bacteria, but through different mechanisms. It blocks Gram-negative growth by impairing outer membrane protein biogenesis via inhibition of the β-barrel assembly complex protein BamA, which is required for assembly and integration of proteins into the outer membrane. It kills Gram-positive bacteria by permeabilizing the cell membrane.

NIH outlines program for molecular, cellular atlas of human body

The Human Biomolecular Atlas Program (HuBMAP) outlined its framework to establish, via methods including single-cell techniques, a 3D molecular and cellular atlas of the human body in health and various diseases. Reported in a Nature paper, the NIH program will generate multi-omic profiles from single cells and single nuclei; and determine the spatial distribution of up to hundreds of molecules within tissues through methods including fluorescent microscopy and mass cytometry. The project will advance the technologies, for example by developing approaches to improve resolution and sensitivity and speed up data processing; and provide funding to expand the range of tissues and technologies studied.

Owkin AI model predicts mesothelioma prognosis
In a study published in Nature Medicine, Owkin Inc. showed that its MesoNet algorithm could predict the prognoses of mesothelioma patients. The deep neural network model was trained on digitized histology slides from 2,300 patients, and identified novel stromal biomarkers of patient outcome. The researchers validated MesoNet's predictive power using slides from an additional 737 patients, and is using the biomarkers to enrich patient selection in clinical trials.

Genentech reveals clinical allosteric anti-tryptase mAb for asthma

Genentech Inc. published preclinical data in Cell showing that an allosteric inhibitor mAb against β-tryptase reduced anaphylaxis in a mouse model of asthma, and lowered tryptase activity levels in the lungs of mice and of non-human primates. The mAb breaks the active tetrameric form of tryptase into inactive monomers. While elevated tryptase levels in mast cells has long been associated with asthma, the tetrameric structure makes it difficult for small molecules to bind with the potency and specificity needed for a therapeutic. Genentech told BioCentury the antibody is in a Phase I trial; a Phase II is planned.

ICR announces preclinical data, trial launch for TTK inhibitor
Scientists from the Institute of Cancer Research published data showing BOS172722, an inhibitor of the spindle assembly checkpoint kinase TTK, sensitized triple-negative breast cancer (TNBC) cells to paclitaxel in cell culture and xenograft models. The compound, which originated at ICR, is in Phase I testing for advanced solid tumors by Boston Pharmaceuticals Inc. and will be a focus of study at ICR’s planned Centre for Evolution and Cancer (see "Targeting Cancer Evolution Offers a Way to Foil Drug Resistance").

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