Insmed Incorporated

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.

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.

Provided herein are novel DPP1 inhibitor compounds having the general structure of Formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof. Also provided are certain methods of treatment, e.g., a method for treating an obstructive disease of the airway or a method of treating an inflammatory condition with a composition comprising an effective amount of one of the compounds provided herein.

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts or deuterated forms thereof, wherein R 0 , L and R 1 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.

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C 5 -C 18 alkyl, branched C 5 -C 18 alkyl, linear C 2 -C 18 alkenyl, branched C 3 -C 18 alkenyl, aryl, aryl-C 1 -C 18 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.

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.

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.

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.

Provided herein are compounds of formulae (I)-(IX), or pharmaceutically acceptable salts or deuterated forms thereof as defined herein. Also provided herein are pharmaceutical compositions comprising a compound of formula (I)-(IX) or pharmaceutically acceptable salt or deuterated form thereof, and methods of using a compound of formula (I)-(IX) 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.

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts or deuterated forms thereof, wherein R 1 , R 2 , R 3 , R 4 , L, n, m, R a , R b , R c , and R d 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.