Abstract: Provided, inter alia, are macrocyclic compounds.

Abstract: Described herein are methods of treating PIK3CA-mutant cancer patients by administering metformin and a PI3K inhibitor, GDC-0077.

Abstract: The present disclosure relates to benzothiazole compounds and to methods of using such compounds. The present disclosure further relates to the use of the compounds described herein, or pharmaceutical compositions thereof, to prevent and/or treat a range of diseases, disorders, and conditions.

Abstract: Particular embodiments provide a method for anomaly detection in images of tissue. An image processing system may receive an image of a tissue sample. A set of tiles may be generated from the image of the tissue sample. The set of tiles may be input into an anomaly detection model comprising a generator model comprising functional skip-connections and a Markovian discriminator model. The anomaly detection model may be trained to isolate a feature space of normal tissue samples. Anomaly scores may be computed for the set of tiles, and an assessment may be generated for the image of the tissue sample based on the anomaly scores for the set of tiles. The assessment may include a reconstructed heatmap of the image of the tissue sample, wherein colors of the heatmap are selected based on the anomaly scores.

Abstract: The invention provides anti-B7-H4 antibodies and immunoconjugates and methods of using the same.

Abstract: The invention provides novel compounds having the general formula I: wherein R1, X, Z1, L, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds.

Abstract: The invention provides antibodies that bind mixed-topology polyubiquitin and multispecific anti-polyubiquitin antibodies, and methods of using the same.

Abstract: The invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof wherein A, X, R1, R4 and n are as defined herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

Abstract: The present invention is directed to a combination therapy involving an anti-HER2 antibody-drug conjugate and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a HER2-expressing cancer.

Abstract: The invention provides anti-Ly6E antibodies and immunoconjugates, and methods of using the same.

Abstract: The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. ?,?-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

Abstract: An apparatus and method for direct drug infusion from a vial to a patient are provided. A movable hanger label is provided to adhere to and support the vial to facilitate direct infusion of a drug, such as one or more pharmaceuticals, biopharmaceuticals, and/or biologics, from the vial to the patient. Additionally, a process is provided in which the drug, contained in the vial with the movable hanger label, may be directly infused through a primed infusion line with a rapid infusion rate. A saline flush is incorporated at the end of the administration to flush the infusion line, resulting in a reduced amount of the drug remaining in the line.

Abstract: This disclosure relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.

Abstract: Described herein are tetrahydro-pyrido[3,4-b]indol-1-yl compounds with estrogen receptor modulation activity or function having the Formula I structure: and stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such estrogen receptor modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

Abstract: The invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein the variables Y1-Y6, X, Z, Z1, Z2, R2-R3, and R6 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

Abstract: The present disclosure relates to novel sulfonimidamide compounds and related compounds and their use in treating a disorder responsive to modulation of cytokines such as IL-1? and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process.

Abstract: A data set can be provided that includes an input data element and one or more label data portion definitions that each identify a feature of interest within the input data element. A machine-learning model can generate model-identified portions definitions that identify predicted feature of interests within the input data element. At least one false negative (where a feature of interest is identified without a corresponding predicted feature of interest) and at least one false positive (where a predicted feature of interest is identified without a corresponding feature of interest) can be a identified. A class-disparate loss function can be provided that is configured to penalize false negatives more than at least some false positives. A loss can be calculated using the class-disparate loss function. A set of parameter values of the machine-learning model can be determined based on the loss.

Abstract: The invention provides for methods of viral inactivation using high temperature short time (HTST) treatment and adjustment of various parameters such that generation of precipitate and depositions of precipitate are reduced and/or minimized.

Abstract: The invention provides a compound of formula (I): or a prodrug thereof, or a pharmaceutically acceptable salt thereof, wherein R1 and R2 have any of the values described in the specification, as well as compositions comprising a compound of formula (I) or a prodrug thereof, or a pharmaceutically acceptable salt thereof. The compounds are agonists of glycolytic enzyme phosphofructokinase-1 liver type and are useful for treating diseases associated with the activity of glycolytic enzyme phosphofructokinase-1 liver type, such as cancer, diabetes, sepsis, and septic shock.

Abstract: The invention relates generally crystalline mesylate salts, crystalline chloride salts and crystalline sulfate salts of the compound(S)-2-(3?-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino) -6-oxo-1,6-dihydro-[3,4?-bipyridin]-2?-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one that is an inhibitor of Bruton's tyrosine kinase. In some aspects, the crystalline salts are single polymorphs.