Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts or deuterated forms thereof, wherein R1, R2, R3, R4, L, n, m, Ra, Rb, Rc, and Rd are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, e.g., in the treatment of a disease that is treatable by administration of a DPP1 inhibitor.

Abstract: The disclosure relates to antibodies and antigen-binding fragments thereof that bind to Stem Cell Factor (SCF). The antibodies and antigen-binding fragments thereof specifically bind to SCF248. The disclosure further relates to methods for making the antibodies, and to methods of use of the antibodies including methods of treatment for inflammatory and/or fibrotic diseases and disorders.

Abstract: The disclosure relates to methods for treating atopic dermatitis with an antibody that binds to stem cell factor 248 (SCF248).

Abstract: Provided herein are methods for treating a pulmonary infection in a patient in need thereof, for example, a nontuberculous mycobacterial pulmonary infection for at least one treatment cycle. The method comprises administering to the lungs of the patient a pharmaceutical composition comprising a liposomal complexed aminoglycoside comprising a lipid component comprising electrically neutral lipids and an aminoglycoside. Administration comprises aerosolizing the pharmaceutical composition to provide an aerosolized pharmaceutical composition comprising a mixture of free aminoglycoside and liposomal complexed aminoglycoside, and administering the aerosolized pharmaceutical composition via a nebulizer to the lungs of the patient. The methods provided herein result in a change from baseline on the semi-quantitative scale for mycobacterial culture for a treated patient, and/or NTM culture conversion to negative during or after the administration period.

Abstract: Provided herein is a method for the large-scale manufacture of liposomal drug formulations containing an aminoglycoside such as amikacin having advantageous lipid/drag characteristics. The method utilizes a particular relative flow rate ratio of lipid to drug streams to obtain liposomes with a high aminoglycoside encapsulation efficiency. The resulting liposomal drug formulations advantageously comprise an overall lipid-to-drug weight ratio of less than 1:1.

Abstract: Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C18 alkyl, branched C5-C18 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-C1-C18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

Abstract: Provided is a method for treating a newly diagnosed and untreated MAC lung infection comprising administering to the lungs of a patient for an administration period of at least about 6 months, a pharmaceutical composition comprising amikacin, or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is aerosolized via a nebulizer to provide an aerosolized pharmaceutical composition comprising a mixture of free amikacin, or a pharmaceutically acceptable salt thereof, and liposomal complexed amikacin, or a pharmaceutically acceptable salt thereof, and the aerosolized pharmaceutical composition is administered via the nebulizer to the lungs of the patient once daily in a single dosing session. The treating comprises improving a respiratory symptom score as defined by one or more patient reported outcomes, during or subsequent to the administration period.

Abstract: A system for treating or providing prophylaxus against a pulmonary infection is disclosed comprising: a) a pharmaceutical formulation comprising a mixture of free antiinfective and antiinfective encapsulated in a lipid-based composition, and b) an inhalation delivery device. A method for providing prophylaxis against a pulmonary infection in a patient and a method of reducing the loss of antiinfective encapsulated in a lipid-based composition upon nebulization comprising administering an aerosolized pharmaceutical formulation comprising a mixture of free antiinfective and antiinfective encapsulated in a lipid-based composition is also disclosed.

Abstract: Provided herein are large-scale manufacturing methods for drug formulations containing an aminoglycoside such as amikacin. The method utilizes mixing a first stream comprising DPPC and cholesterol with a second stream comprising amikacin sulfate at particular flow rates to obtain a drug formulation with a superior encapsulation efficiency. The processes described herein address the need for preparing aminoglycoside drug formulations at commercial scale.

Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts or deuterated forms thereof, wherein R0, L and R1 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, e.g., in the treatment of a disease that is treatable by administration of a DPP1 inhibitor.

Abstract: Provided herein are methods for making liposomal API formulations via continuous in-line diafiltration processes. Also provided herein are liposomal API formulations manufactured by the disclosed methods.

Abstract: Provided herein are methods for treating a pulmonary infection in a patient in need thereof, for example, a nontuberculous mycobacterial pulmonary infection for at least one treatment cycle. The method comprises administering to the lungs of the patient a pharmaceutical composition comprising a liposomal complexed aminoglycoside comprising a lipid component comprising electrically neutral lipids and an aminoglycoside. Administration comprises aerosolizing the pharmaceutical composition to provide an aerosolized pharmaceutical composition comprising a mixture of free aminoglycoside and liposomal complexed aminoglycoside, and administering the aerosolized pharmaceutical composition via a nebulizer to the lungs of the patient. The methods provided herein result in a change from baseline on the semi-quantitative scale for mycobacterial culture for a treated patient, and/or NTM culture conversion to negative during or after the administration period.

Abstract: Provided herein are methods for treating a pulmonary infection in a patient in need thereof, for example, a nontuberculous mycobacterial pulmonary infection for at least one treatment cycle. The method comprises administering to the lungs of the patient a pharmaceutical composition comprising a liposomal complexed aminoglycoside comprising a lipid component comprising electrically neutral lipids and an aminoglycoside. Administration comprises aerosolizing the pharmaceutical composition to provide an aerosolized pharmaceutical composition comprising a mixture of free aminoglycoside and liposomal complexed aminoglycoside, and administering the aerosolized pharmaceutical composition via a nebulizer to the lungs of the patient. The methods provided herein result in a change from baseline on the semi-quantitative scale for mycobacterial culture for a treated patient, and/or NTM culture conversion to negative during or after the administration period.

Abstract: The present disclosure relates to methods for treating bronchiectasis, for example, non-cystic fibrosis bronchiectasis with compositions comprising an effective amount of certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds of Formula (I), including pharmaceutically acceptable salts thereof, that inhibit dipeptidyl peptidase 1 (DPP1) activity. Methods provided herein are useful for prophylaxis, increasing the lung function in a patient, and/or decreasing the rate of pulmonary exacerbation in a patient. In one embodiment, the compound of Formula (I) is (2S)-N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide.

Abstract: The present disclosure provides a dry powder composition of treprostinil prodrugs and a method of treating pulmonary hypertension (e.g., pulmonary arterial hypertension), portopulmonary hypertension, or pulmonary fibrosis in a patient in need thereof. The dry powder composition includes (a) from about 0.1 wt % to about 3 wt % of a compound of Formula (I): or an enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof, (b) from about 0.01 wt % to about 3 wt % of DSPE-PEG2000, (c) from about 10 wt % to about 50 wt % of leucine, and the balance being (d) a sugar selected from the group consisting of trehalose and mannitol. The entirety of (a), (b), (c), and (d) is 100 wt %, and R1 is tetradecyl, pentadecyl, hexadecyl, heptadecyl, or octadecyl. The method includes administering an effective amount of the dry powder composition to the lungs of the patient by inhalation via a dry powder inhaler. In certain compositions and methods provided herein, R1 is hexadecyl, e.g., linear hexadecyl.

Abstract: Methods for making prodrugs of treprostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C18 alkyl, branched C5-C18 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-C1-C18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.

Abstract: The present disclosure relates to methods for treating hidradenritis suppurativa with a composition comprising an effective amount of a N-(1-cyano-2-phenylethyl)-1, 4-oxazepane-2-carboxamide DPP1 inhibitor compound of Formula (1) or a pharmaceutically acceptable salt thereof. In one embodiment, the compound of Formula (I) is (2S)—N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1, 3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide (brensocatib).

Abstract: Provided herein are methods for making liposomal API formulations via continuous in-line diafiltration processes. Also provided herein are liposomal API formulations manufactured by the disclosed methods.

Abstract: Provided herein are methods for treating a pulmonary infection in a patient in need thereof, for example, a nontuberculous mycobacterial pulmonary infection for at least one treatment cycle. The method comprises administering to the lungs of the patient a pharmaceutical composition comprising a liposomal complexed aminoglycoside comprising a lipid component comprising electrically neutral lipids and an aminoglycoside. Administration comprises aerosolizing the pharmaceutical composition to provide an aerosolized pharmaceutical composition comprising a mixture of free aminoglycoside and liposomal complexed aminoglycoside, and administering the aerosolized pharmaceutical composition via a nebulizer to the lungs of the patient. The methods provided herein result in a change from baseline on the semi-quantitative scale for mycobacterial culture for a treated patient, and/or NTM culture conversion to negative during or after the administration period.

Abstract: Provided herein are systems for treating a subject with a pulmonary infection, for example, a nontuberculous mycobacterial pulmonary infection, a Burkholderia pulmonary infection, a pulmonary infection associated with bronchiectasis, or a Pseudomonas pulmonary infection. The system includes a pharmaceutical formulation comprising a liposomal aminoglycoside dispersion, and the lipid component of the liposomes consist essentially of electrically neutral lipids. The system also includes a nebulizer which generates an aerosol of the pharmaceutical formulation at a rate greater than about 0.53 gram per minute. The aerosol is delivered to the subject via inhalation for the treatment of the pulmonary infection.