Abstract: Described herein are methods of treating a proliferative disorder (e.g., cancer) in a patient by administering a DNA damaging agent and between about 12 and about 48 hours later administering to the subject a compound that inhibits ATR protein kinase. Methods of treating a proliferative disorder (e.g., cancer) in a patient by administering a compound that inhibits ATR protein kinase are also described. Exemplary ATR inhibitors are represented by Formulae A-I and A-II or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

Abstract: Provided herein are methods of producing ? cells and precursors thereof utilizing a Wnt signaling inhibitor or PKC activator, or both. Also provided herein are in vitro cultures comprising said cells, methods of treating a subject with a disease characterized by high blood sugar levels over a prolonged period of time by administering said cells, and devices for encapsulating said cells.

Abstract: The present application provides materials and methods for treating a patient with one or more conditions associated with SCN9A whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of SCN9A gene in a cell by genome editing.

Abstract: Compounds of Formula (I): pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed. Also disclosed are solid state forms of Compound 1 and salts and solvates thereof.

Abstract: The present invention provides compounds of Formula I?, or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof for treating cellular proliferative disorders (e.g., cancer).

Abstract: Processes for preparing 5,5-dimethyl-3-methylenepyrrolidin-2-one, (S)-3,5,5-trimethylpyrrolidine-2-one, (R)-3,5,5-trimethylpyrrolidine-2-one, (S)-2,4,4-trimethylpyrrolidine, and (R)-2,4,4-trimethylpyrrolidine, and their salt forms are disclosed.

Abstract: The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R1, R2, R3, W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

Abstract: The present application provides materials and methods for treating a patient with one or more conditions associated with DMPK whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of DMPK gene in a cell by genome editing.

Abstract: Materials and methods for treating a patient with hemoglobinopathy, both ex vivo and in vivo and materials and methods for deleting at least a portion of a human beta globin locus on chromosome 11 in a human cell by genome editing and thereby increasing the production of fetal hemoglobin (HbF).

Abstract: A pharmaceutical composition comprising Compound I: Methods of treating cystic fibrosis comprising administering one or more of such pharmaceutical compositions to a patient.

Abstract: This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis by administering such modulators and pharmaceutical compositions, and processes for making such modulators.

Abstract: The present invention relates to pharmaceutical compositions containing a solid dispersion of N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide including formulations of the solid dispersions into powders, granules and mini-tablets, methods for manufacturing and processing the powders, granules and mini-tablets, and methods for treating cystic fibrosis employing the pharmaceutical composition.

Abstract: The present invention provides crystalline forms of a compound of formula (I): Also provided are pharmaceutical compositions that include the provided crystalline forms and methods of using the provided crystalline forms and pharmaceutical compositions for the treatment of cancer.

Abstract: Materials and methods for treating a patient with a hemoglobinopathy, both ex vivo and in vivo, and materials and methods for deleting, modulating, or inactivating a transcriptional control sequence of a BCL11A gene in a cell by genome editing.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: or a pharmaceutically acceptable salt, wherein the variables are as devined herein. Moreover, The compounds of this invention have formula I-A: or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

Abstract: The present application provides materials and methods for treating a patient with Duchenne Muscular Dystrophy (DMD) both ex vivo and in vivo. In addition, the present application provides materials and methods for editing a dystrophin gene in a cell by genome editing.

Abstract: Compositions and methods for treating excising trinucleotide repeats, as well as for treating diseases and disorders associated with trinucleotide repeats are encompassed.

Abstract: Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. The compounds have the formula (I) wherein R is H or CH2OPO(OH)2. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.

Abstract: The present disclosure relates to macroencapsulation devices and related methods of manufacture where the membranes of a device may be mounted to an associated frame in a relaxed, or slack, configuration prior to filling with a desired material.

Abstract: A method of preparing Compound (1) or a pharmaceutically acceptable salt thereof: comprises: (a) reacting Compound (X): or a pharmaceutically acceptable salt thereof with Compound (Y): in the presence of a palladium catalyst and a carbonate or phosphate base to form compound (Z): or a pharmaceutically acceptable salt thereof; and (b) deprotecting the Ts group of Compound (Z) to form Compound (1) or a pharmaceutically acceptable salt thereof.