Abstract: Described herein are techniques to regulate the treatment of a culture of cells having cells corresponding to different cell categories. Some techniques may be used together with a cell imaging and incubation system including an imaging sensor configured to obtain an image of the culture and an incubator configured to incubate the culture. Regulation of treatment of the culture may be based on the processing of an image of the culture obtained by the imaging sensor of the system. The processing may include segmenting the image of the culture into multiple image segments by assigning individual pixels of the image to corresponding cell categories. According to some embodiments, the techniques include determining, based on the image segments, an amount of the culture corresponding to a particular cell category. The amount of the culture corresponding to the particular cell category may inform regulation of the treatment of the culture.

Abstract: The present invention relates to RNAi constructs for reducing expression of the LPA gene, which encodes apolipoprotein(a), a component of lipoprotein(a)(Lp(a)) particles. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease, peripheral artery disease, stroke, and myocardial infarction, and to reduce serum Lp(a) levels are also described.

Abstract: Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

Abstract: Provided herein are amorphous solid dispersions comprising sotorasib in an amorphous form and a matrix polymer. Also provided herein are processes for preparing the disclosed amorphous solid dispersions and pharmaceutical compositions comprising and methods of using the disclosed amorphous solid dispersions.

Abstract: Provided herein are KRAS G12C and KRAS G12D inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

Abstract: Provided herein are processes for synthesizing Mcl-1 inhibitors and intermediates such as compound Y that can be used to prepare them where the variable R1 is as defined herein. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof, compound A2, and salts and solvates thereof, and compound A3 and salts and solvates thereof.

Abstract: A biologics manufacturing process that connects the drug substance and drug product processes into an integrated, continuous process.

Abstract: The present disclosure provides novel 15-hydroxy-prostaglandin dehydrogenase inhibitors, pharmaceutical compositions comprising such compounds, and methods of using such compounds and compositions in treating 15-hydroxy-prostaglandin dehydrogenase-mediated disease. Also provided are methods of making such compounds and intermediates thereof. The compounds have a structure of Formula (I): or a pharmaceutically acceptable salt thereof; wherein is Formula (i) or Formula (ii) Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

Abstract: The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung cancer, pancreatic cancer, colorectal cancer, and solid tumors. In particular, the disclosure provides compounds of Formula (II):, and pharmaceutically acceptable salts thereof, wherein the substituents are as described.

Abstract: Formulations of compounds of Formula I are provided as are doses and dosing regimens useful in methods of treating cancer including hematological malignances such as acute myelogenous leukemia, multiple myeloma, and non-Hodgkin's lymphoma.

Abstract: Drug delivery devices and related methods of assembly are disclosed. The drug delivery device may include a housing and a container disposed therein. The container may include a reservoir containing a drug and a movable stopper. A first seal member may be connected to the container at a distal end of the reservoir. A first removable membrane may cover an exterior surface of the first seal member to maintain sterility of that surface prior to operation of the device. A fluid pathway assembly may be configured to establish fluid communication with the reservoir during operation of the device. A second seal member may be connected to a first end of the fluid pathway assembly. A second removable membrane may cover an exterior surface of the second seal member to maintain sterility of that surface prior to operation of the device.

Abstract: A method of aligning images for 3D imaging of a sample includes, for each of multiple cameras located around a vessel, activating a respective light source that provides backlighting for the vessel, and capturing a respective 2D calibration image of the vessel. The method also includes, for each 2D calibration image, measuring a respective vertical position, horizontal position, and rotation of the image, in part by detecting edges of the vessel as depicted in the image. The method also includes generating calibration data based on the measured vertical positions, horizontal positions, and rotations for the respective 2D calibration images, capturing, by each camera, a respective set of 2D images of the sample in the vessel, and digitally resampling, using the calibration data, at least one of the respective sets of 2D images to correct for vertical offset, horizontal offset, and rotational offset of the set(s) of 2D images.

Abstract: The present disclosure provides novel 15-hydroxy-prostaglandin dehydrogenase inhibitors, pharmaceutical compositions comprising such compounds, and methods of using such compounds and compositions in treating 15-hydroxy-prostaglandin dehydrogenase-mediated disease. Also provided are methods of making such compounds and intermediates thereof. The compounds have a structure of Formula (I). Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

Abstract: Disclosed herein are compounds useful for the inhibition of IGF-1R. The compounds have a general Formula (I): or a pharmaceutically acceptable salt thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, an IGF-1R mediated disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

Abstract: Provided herein are IL-2 muteins and IL-2 mutein Fc-fusion molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are methods of making and using the compositions of the present invention.

Abstract: The present disclosure provides combination therapy with GDF15 molecules. In some embodiments, the GDF15 molecule is a GDF15-Fc fusion, in which a GDF15 region is fused to an Fc region, optionally via a linker. In one embodiment, combination therapy comprises administration of a GDF15 molecule with a GLP-1R agonist. In another embodiment, combination therapy comprises administration of a GDF15 molecule with a GIPR antagonist.

Abstract: Automated systems and methods for low-pH viral inactivation include adding an elution pool to a first vessel with an acid. Once first vessel pH probes measure sufficiently low pH, the pool is transferred to a second vessel, where the pH is checked again, and the pool is held for a time sufficient to reduce virus concentration to a safe level, and neutralized, filtered, and transferred to a third vessel. Meanwhile, the first vessel is filled with a known-pH buffer, which is checked against readings from first vessel pH probes to determine whether recalibration is needed. After the pool is transferred to the third vessel, the second vessel is filled with a known-pH buffer, which is checked against readings from second vessel pH probes to determine whether recalibration is needed. The process repeats when the known-pH buffer is dumped and a new elution pool is added to the first vessel.

Abstract: The present invention relates to methods for purifying nucleic acids. In particular, the present invention relates to methods for purifying carbohydrate-conjugated oligonucleotides using a mixed-mode stationary phase and a mobile phase comprising a dual salt/organic solvent gradient. Methods for purifying carbohydrate-conjugated oligonucleotides using an anion exchange stationary phase and a mobile phase comprising a dual pH/salt gradient are also described.

Abstract: A drug delivery device is provided comprising a housing having a first opening, a drug storage device including a delivery member having an insertion end configured to extend at least partially through the first opening in the housing, a plunger, a drive mechanism activatable to drive the plunger in a distal direction to expel a drug from the drug storage container, and a needle guard moveably disposed adjacent to the first opening. The needle guard has an extended position where the needle guard extends at least partially through the first opening and a retracted position where the needle guard is positioned away from the extended position. The needle guard has a base surface configured to contact an injection site and having an inner diameter defining a second opening and an outer diameter. A ratio of the outer diameter to the inner diameter is between about 3:1 and about 2:1.