Compositions of a therapeutic polyene macrolide and methods of their use

Abstract

This invention relates to compositions including acid addition salt formulations including a compound of formula (I). Also disclosed are methods of their use and preparation.

Description

[0001] PATENT ATTORNEY DOCKET NO: 51336-014WO2 COMPOSITIONS OF A THERAPEUTIC POLYENE MACROLIDE AND METHODS FOR THEIR USE Field of the Invention This invention relates to compositions and their methods of use. Background of the Invention Macrolide antibiotics are overlooked in clinical applications because of their low shelf life. Moreover, macrolides may exhibit low or poor bioavailability. Compound 1 is a therapeutic polyene macrolide: Compound 1. There is a demand for new compositions that include therapeutic polyene macrolides to enhance their bioavailability and shelf-life. Summary of the Invention The present disclosure, in general, provides select acid addition salt forms and pharmaceutical compositions useful for the treatment of fungal infections. In one aspect, the invention features an acid addition salt form of a compound of formula (I): wherein the acid addition salt form is an oleate salt. PATENT ATTORNEY DOCKET NO: 51336-014WO2 In another aspect, the invention features an acid addition salt form of a compound of formula (I): wherein the acid addition salt form is a decanoate salt. In another aspect, the invention also features an acid addition salt form of a compound of formula (I): wherein the acid addition salt form is a docusate salt. In another aspect, the invention further features an acid addition salt form of a compound of formula (I): wherein the acid addition salt form is an octanoate salt. PATENT ATTORNEY DOCKET NO: 51336-014WO2 In another aspect, the invention further features an acid addition salt form of a compound of formula (I): wherein the acid addition salt form is an dodecylbenzenesulfonate salt. In any of the above aspects, the compound of formula (I) is Compound 1: Compound 1. In some embodiments, the pharmaceutical composition includes an acid addition salt form of formula (I) or Compound 1 and a carrier, a diluent, or an excipient. In still another aspect, the invention features a pharmaceutical composition including: (i) an oleate, decanoate, docusate, octanoate, or dodecylbenzenesulfonate salt form of a compound of formula (I): (ii) a carrier, a diluent, or an excipient. PATENT ATTORNEY DOCKET NO: 51336-014WO2 In particular embodiments, the compound of formula (I) in the pharmaceutical composition is Compound 1: Compound 1. In some embodiments, the pharmaceutical compositions can be in the form of a nanoparticle. In another aspect, the invention features a nanoparticle including a compound of formula (I): or a pharmaceutically acceptable salt thereof, and a TPGS compound. In another aspect, the invention features a nanoparticle including Compound 1: Compound 1, or a pharmaceutically acceptable salt thereof, and a TPGS compound. In one embodiment, the nanoparticle of the invention can include a polymeric carrier (e.g., a poly(lactic-co-glycolic acid) (PLGA)). In another aspect, the invention features an aqueous suspension including a nanoparticle of the invention and an aqueous carrier. The aqueous carrier can be a pharmaceutically acceptable carrier. For example, the aqueous carrier can be any pharmaceutically acceptable carrier described herein. PATENT ATTORNEY DOCKET NO: 51336-014WO2 In another aspect, the invention features a method of treating a fungal infection (e.g., yeast or mold) in a subject, the method including administering to the subject an oleate, decanoate, docusate, octanoate, or dodecylbenzenesulfonate salt of a compound of formula (I): in an amount that is effective for the treatment of the fungal infection. In another aspect, the invention features a method of treating a fungal infection in a subject, the method including administering to the subject a compound of formula (I): in an amount that is effective for the treatment of the fungal infection, wherein the method includes administering to the subject an acid addition salt form of the invention, a pharmaceutical composition of the invention, a nanoparticle of the invention, or an aqueous suspension of the invention. In some embodiments of the method of treating, the fungal infection is caused by a Candida species (e.g., C. albicans, C. auris, C. glabrata, C. krusei, C. parapsilosis, or C. tropicalis), by an Aspergillus species (e.g., A. niger, A. fumigatus, A. flavus, A. nidulans, or A. terreus), by a Cryptococcus species (e.g., C. neoformans var. grubii), by a Fusarium species (e.g., F. solani or F. annulatum), by a Mucorales species (e.g., M. circinelloides / ramosissimus or Rhizopus spp.), or any other strain that is susceptible to the compound. In particular embodiments, the administration is pulmonary (e.g., by inhalation), intravenous, oral, or intranasal administration. In another aspect, the invention features a method of forming nanoparticles, including the steps of: (i) providing an acid addition salt form of the invention, PLGA, and a TPGS compound in an organic solvent; (ii) adding deionized water; and (iii) quenching the solution of (ii) with aqueous saline. In particular embodiments, the nanoparticles are formed using micromixing. In some embodiments, the deionized water of step (ii) includes Pluronic F-68 or Pluronic F-127. In particular embodiments, step (i) includes: (a) the oleate salt form and alpha-tocopherol TPGS; (b) the decanoate salt form and alpha- PATENT ATTORNEY DOCKET NO: 51336-014WO2 tocopherol TPGS; (c) the docusate salt form and alpha-tocopherol TPGS; (d) the octanoate salt form and alpha-tocopherol TPGS; or (e) the dodecylbenzenesulfonate salt form and alpha-tocopherol TPGS. Definitions The term “dry (w / w)” percentage, as used herein, refers to the weight percentage of an ingredient in a composition excluding liquid pharmaceutically acceptable carriers. A dry (w / w) percentage may be measured using, e.g., liquid chromatography. The term “nanoparticles,” as used herein, represents a population of particles having a Z-average diameter of less than 1000 nm, as measured by dynamic light scattering (DLS). The term “pharmaceutical composition,” as used herein, represents a composition formulated with a pharmaceutically acceptable excipient, and having utility as part of a therapeutic regimen for the treatment of a disease in a mammal. The term “pharmaceutical dosage form,” as used herein, represents those pharmaceutical compositions intended for administration to a subject as is without further modification (e.g., without dilution with, suspension in, or dissolution in a liquid solvent). The term “pharmaceutically acceptable excipient,” as used herein, refers to any ingredient other than the active agent(s) described herein (e.g., a vehicle capable of suspending or dissolving the active agent(s)) and having the properties of being substantially non-toxic and substantially non-inflammatory in a patient. Excipients may include, e.g., antioxidants, polymeric carriers, dyes (colors), emollients, emulsifiers, preservatives, sorbents, suspending or dispersing agents, liquid solvents, and buffering agents. The term “pharmaceutically acceptable salt,” as use herein, represents those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are known in the art. For example, pharmaceutically acceptable salts are described in: Berge et al., J. Pharmaceutical Sciences 66:1-19, 1977 and in Pharmaceutical Salts: Properties, Selection, and Use, (Eds. P.H. Stahl and C.G. Wermuth), Wiley-VCH, 2008. The salts can be prepared in situ during the final isolation and purification of the compounds described herein or separately by reacting the free base group with a suitable organic acid. The term “TPGS compound,” as use herein, refers to D-α-Tocopheryl polyethylene glycol succinate (tocopheryl PEG-1000 succinate) and related TPGS compounds (e.g., a tocopherol, tocomonoenol, tocodienol, or tocotrienol) bonded to (e.g., by an ester, amide, or thioester bond) to one or more polyethylene glycol (PEG) moieties via a linker (e.g., a dicarboxylic or tricarboxylic acid). The vitamin E moiety can be any naturally occurring or synthetic form of vitamin E, including α, β, γ, and δ isoforms, and all stereoisomers of tocopherol, tocomonoenol, tocodienol, and tocotrienol. Linkers include, for example, dicarboxylic acids (e.g., succinic acid, sebacic acid, dodecanedioic acid, suberic acid, or azelaic acid, citraconic acid, methylcitraconic acid, itaconic acid, maleic acid, glutaric acid, glutaconic acid, fumaric acids, and phthalic acids). Exemplary tocopherol polyethylene glycol diesters are D-alpha- tocopheryl PEG succinate, tocopherol sebacate polyethylene glycol, tocopherol dodecanodioate polyethylene glycol, tocopherol suberate polyethylene glycol, tocopherol azelaate polyethylene glycol, tocopherol citraconate polyethylene glycol, tocopherol methylcitraconate polyethylene glycol, tocopherol PATENT ATTORNEY DOCKET NO: 51336-014WO2 itaconate polyethylene glycol, tocopherol maleate polyethylene glycol, tocopherol glutarate polyethylene glycol, tocopherol glutaconate polyethylene glycol, and tocopherol phthalate polyethylene glycol. Each of the PEG moieties of the TPGS compound can be any polyethylene glycol or any PEG derivative, and can have a molecular weight of 200-6,000 kDa (e.g., 400-4,000 kDa, 500-2,000 kDa, 750-1,500 kDa, 800- 1,200 kDa, 900-1,100 kDa, or 1,000 kDa). The PEG moieties can be polydisperse; that is, they can have a variety of molecular weights. PEG derivatives include, for example, methylated PEG, propylene glycol, PEG-NHS, PEG-aldehyde, PEG-SH, PEG-NH2, PEG-CO2H, PEG-OMe and other ethers, branched PEGs, and PEG copolymers (e.g., PEG-b-PPG-b-PEG-1100, PEG-PPG-PEG-1900, PPG-PEG-MBE- 1700, and PPG-PEG-PPG-2000). Any known source of TPGS can be used in the present disclosure. An exemplary TPGS compound is tocopheryl PEG-1000 succinate (TPGS-1000), which has a PEG moiety having a molecular weight of 1,000 kDa. A food grade TPGS-1000 is available, for example, under the trade name Eastman Vitamin E TPGS (Eastman Chemical Company, Kingsport, Tennessee). This TPGS is water-soluble form of natural-source vitamin E, which is prepared by esterification of crystalline D-α- tocopheryl acid succinate with polyethylene glycol 1000 (PEG 1000), and contains between 260 and 300 mg / g total tocopherol. Another exemplary TPGS compound is Water Soluble Natural Vitamin E (ZMC- USA, The Woodlands, Texas). Methods of preparing pegylated vitamin E are described in U.S. Patent Nos.2,680,749 and 3,102,078 and in U.S. Publication Nos.2007 / 0184117 and 2007 / 0141203, which are herein incorporated by reference. TPGS compounds also include analogs that differ in chemical composition from tocopheryl PEG succinate (e.g., TPGS-1000) by the substitution, addition, or removal of one or more atoms, methylene (CH2)n units, or functional groups. TPGS compounds also include chromanol derivatives (e.g., 6-chromanol PEG-1000 succinate and 6-chromanol PEG-400 succinate), steroid derivatives (e.g., cholesteryl PEG-1000 succinate, cholic acid PEG-1000, dihydro cholic acid PEG- 1000, litho-cholic acid PEG-1000, ursodeoxycholic acid PEG-1000, chenodeoxycholic acid PEG-1000), and others (e.g., indomethacin PEG-1000, chromone-2-carboxylic acid PEG-1000, chromone-2- carboxylic acid PEG-1100-OMe, chromone-2-carboxylic acid PEG-1500, chromone-2-carboxylic acid PEG-2000, naproxen PEG-1000, probenecid PEG-1000, 7-carboxymethoxy-4-methyl-coumarin PEG- 1000, 5-(4-chlorophenyl)-2-furoic acid PEG-1000, probenecid tocopheryl PEG-1000 succinate, lithocholic acid PEG-1000, and chromone-3-carboxylic acid PEG-1000, 7-hydroxy-coumarinyl-4-acetic acid PEG- 1000). The term “subject,” as used herein, represents a human or non-human animal (e.g., a mammal) that is suffering from, or is at risk of, disease, disorder, or condition, as determined by a qualified professional (e.g., a doctor or a nurse practitioner) with or without known in the art laboratory test(s) of sample(s) from the subject. Non-limiting examples of diseases, disorders, and conditions include fungal infections caused by Candida, Aspergillus, Cryptococcus, Fusarium, or Mucorales organisms. “Treatment” and “treating,” as used herein, refer to the medical management of a subject with the intent to improve, ameliorate, stabilize, or cure a disease, disorder, or condition. This term includes active treatment (treatment directed to improve the disease, disorder, or condition); causal treatment (treatment directed to the cause of the associated disease, disorder, or condition); palliative treatment (treatment designed for the relief of symptoms of the disease, disorder, or condition); and supportive treatment (treatment employed to supplement another therapy). PATENT ATTORNEY DOCKET NO: 51336-014WO2 By “docusate” is meant a compound or mixture of compounds containing one or more stereoisomers of the following structure: , wherein the asterisks (*) indicate stereocenters. In certain embodiments, docusate is a racemic mixture of diastereomers. Detailed Description In general, the invention provides pharmaceutical compositions including acid addition salt forms of a compound of formula (I): and methods of using the same. In some embodiments, the compound of formula (I) is Compound 1: The pharmaceutical compositions of the invention include an oleate, docusate, octanoate, or decanoate salt form of a compound of formula (I) or Compound 1. The pharmaceutical compositions of the invention may be in the form of a nanoparticle. Nanoparticles described herein may include a polymeric excipient (e.g., a polymeric nanoparticle) or may include lipids (e.g., lipid nanoparticles, such as liposomes, micelles, etc.). Nanoparticles described herein may include a lipid, e.g., a phospholipid (e.g., phosphatidylcholine, phosphatidic acid, phosphatidylserine, phosphatidylethanolamine, or phosphatidylglycerol). In some embodiments, nanoparticles described herein include a phospholipid that is phosphatidylcholine (e.g., dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, egg phosphatidylcholine and soy phosphatidylcholine) or PATENT ATTORNEY DOCKET NO: 51336-014WO2 phosphatidylglycerol (e.g., dipalmitoylphosphatidylglycerol, distearoylphosphatidylglycerol, dilaurylphosphatidylglycerol, or dimyristoylphosphatidylglycerol). For example, the lipids (e.g., phospholipids) may encapsulate the compound of Formula (I) or Compound 1 in a vesicle or a micelle. Preferably, the pharmaceutical composition described herein includes a pharmaceutically acceptable polymeric excipient (e.g., poly(lactic-co-glycolic acid), poly(lactic acid), poly(alkyl cyanoacrylates), and amphiphilic polyphosphazenes. Advantageously, the pharmaceutical compositions described herein may exhibit a commercially acceptable shelf life. Without wishing to be bound by theory, encapsulation of an acid addition salt form of a compound formula (I) or Compound 1 in the pharmaceutically acceptable polymeric excipient may provide sufficient stability for a compound formula (I) or Compound 1 to have a commercially acceptable shelf life. For example, the pharmaceutical composition described herein may retain at least 80%, 85%, 90%, and 95% of the label dose of an acid addition salt form of a compound formula (I) or Compound 1 after being stored at -20 °C for 13 days. Preferably the pharmaceutical composition is stored as an aqueous solution at pH 7 (e.g., saline or phosphate buffered saline). The nanoparticulate compositions described herein may contain at least 2%, preferably at least 3%, and, in particular, at least 5% dry (w / w) of an acid addition salt form of a compound formula (I) or Compound 1, as measured by liquid chromatography. The nanoparticulate compositions described herein may contain at least 2% (e.g., 2.5 ± 0.5%, 3 ± 0.5%, 3.5 ± 0.5%, 4 ± 0.5%, 4.5 ± 0.5%, 5 ± 0.5%, 5.5 ± 0.5%, 6 ± 0.5%, 6.5 ± 0.5%, 7 ± 0.5%, 7.5 ± 0.5%, 8 ± 0.5%, 8.5 ± 0.5%, 9 ± 0.5%, or 9.5 ± 0.5%) dry (w / w) of an acid addition salt form of a compound formula (I) or Compound 1, as measured by liquid chromatography. The nanoparticulate compositions described herein may contain up to 15%, preferably, up to 12 %, and, in particular, up to 10% dry (w / w) of an acid addition salt form of a compound formula (I) or Compound 1, as measured by liquid chromatography. Non-limiting examples of ranges include 2-15%, preferably 3-10%, and, in particular, 3-6% (e.g., 3.5-15%, 4-15%, 4.5-15%, 5-15%, 5.5-15%, 6-15%, 6.5- 15%, 7-15%, 7.5-15%, 8-15%, 8.5-15%, 9-15%, 9.5-15%, 3-10%, 3.5-10%, 4-10%, 4.5-10%, 5-10%, 5.5- 10%, 6-10%, 6.5-10%, 7-10%, 7.5-10%, 8-10%, 8.5-10%, 9-10%, 9.5-10%, 3-7.5%, 3.5-7.5%, 4-7.5%, 4.5-7.5%, 5-7.5%, 5.5-7.5%, 6-7.5%, 6.5-7.5%, 7-7.5%, 3-5%, 3.5-5%, 4-5%, or 4.5-5%) dry (w / w) of an acid addition salt form of a compound formula (I) or Compound 1, as measured by liquid chromatography. The pharmaceutical compositions described herein contain a plurality of nanoparticles. The plurality of nanoparticles may have a Z-average of, e.g., 20-200 nm (preferably, the Z-average is 60-100 nm), as measured by dynamic light scattering. Preferably, the plurality of nanoparticles has a Z-average of 30-150 nm (more preferably, the Z-average is 60-100 nm), as measured by dynamic light scattering. The pharmaceutical compositions described herein include one or more pharmaceutically acceptable excipients, e.g., a pharmaceutically acceptable polymeric excipient, surfactant (e.g., a non- ionic surfactant), stabilizer, and / or carrier (e.g., an oil). In the pharmaceutical compositions described herein, polymeric excipients may be used to, e.g., encapsulate a compound of Formula (I) or Compound 1. Non-limiting examples of pharmaceutically acceptable polymeric excipients include poly(alkyl cyanoacrylates), poly(lactic-co-glycolic acid), and amphiphilic polyphosphazenes. Preferably, the pharmaceutically acceptable polymeric excipient is a poly(lactic-co-glycolic acid) (PLGA) (e.g., PEGylated PLGA, PLGA with a molecular weight ranging from 12 kDa or higher), poly(alkyl cyanoacrylate) (e.g., poly(ethylhexyl cyanoacrylate), poly(ethyl PATENT ATTORNEY DOCKET NO: 51336-014WO2 cyanoacrylate), poly(n-hexyl cyanoacrylate), poly(4-methylpentyl cyanoacrylate), poly(ethylbutyl cyanoacrylate), poly(butyl cyanoacrylate), or poly(octyl cyanoacrylate)). Nanoparticles including PLGA may be prepared in situ by micromixing a composition including an acid addition salt form of a compound formula (I) or Compound 1. In some embodiments, the pharmaceutical composition described herein include nanoparticles including a pharmaceutically acceptable polymeric excipient and an acid addition salt form of a compound formula (I) or Compound 1. The nanoparticles may be coated with polyethylene glycol (PEG). Advantageously, a PEG coating on the nanoparticles may reduce clearance, e.g., by the immune system. TPGS Compounds D-α-Tocopheryl polyethylene glycol succinate (tocopheryl PEG-1000 succinate) and related TPGS compounds can be used in the particulate formulations of the present disclosure. Tocopheryl PEG- 1000 succinate has the following structure: where n is an integer. Related TPGS compounds include additives formed using different diacid linkers, different length polyethylene glycol tails, and different isoforms (e.g., α-, β-, γ-, or δ-) of tocopherol, tocomonoenol, tocodienol, and tocotrienol. These include α-tocopherol, α-tocomonoenol, α-tocodienol, α-tocotrienol, β- tocopherol, β-tocomonoenol, β-tocodienol, β-tocotrienol, γ-tocopherol, γ-tocomonoenol, γ-tocodienol, γ- tocotrienol, δ-tocopherol, δ-tocomonoenol, δ-tocodienol, δ-tocotrienol, and any stereoisomer thereof. Suitable vitamin E compounds of the present disclosure also include desmethyl-tocopherol, desmethyl- tocomonoenol, desmethyl-tocodienol, desmethyl-tocotrienol, and any stereoisomer thereof. Furthermore, when a compound disclosed herein contains one or more chiral atoms where stereochemistry is unspecified, it will be understood that each stereoisomer of the compound is individually disclosed as if the structure of each stereoisomer were explicitly drawn. In certain embodiments of the present disclosure, the vitamin E compound may be a naturally-occurring d-stereoisomer of vitamin E. The vitamin E moieties of the present disclosure may be naturally occurring or synthetic. Certain embodiments of the present disclosure include a naturally occurring vitamin E compound such as an extract from a food source. For example, α-tocopherol, α-tocotrienol, β-tocopherol, β-tocotrienol, γ- tocopherol, γ-tocotrienol, δ-tocopherol, and δ-tocotrienol are available naturally from fortified cereals, green vegetables, nuts, seeds, and vegetable oils. Methods of extracting vitamin E from natural sources have been described, for example, in U.S. Pat. Nos.6,743,450; 6,838,104; 7,161,055; and 7,544,822, which are hereby incorporated by reference. The TGPS compound can include synthetic vitamin E moieties. An exemplary method for making α-tocopherol is the reaction of trimethylhydroquinone (TMHQ) with iso-phytol (3,7,11,15- tetramethylhexadec-1-en-3-ol) in a condensation reaction with a catalyst. It will be apparent to one skilled in the art that other tocopherol, tocomonoenol, tocodienol, and tocotrienol isoforms and their derivates PATENT ATTORNEY DOCKET NO: 51336-014WO2 can also be prepared using a similar strategy starting from appropriate precursors. For example, the starting compounds may be TMHQ and 3,7,11,15-tetramethylhexadec-2-en-1-ol. An additional method of making vitamin E with isophytol under relatively mild conditions has been described by Wehrli et al., J. Org. Chem.36:2910 (1971). Methods for synthesizing unsaturated side chains of vitamin E are described in U.S. Pat. No.4,168,271, which is hereby incorporated by reference. Additional methods of synthesizing vitamin E side chains have been reviewed by Stalla-Bourdillon, Ind. Chim. Belg.35, 13 (1970). Additional methods of synthesizing tocopherols are described in U.S. Pat. Nos.5,523,420, and 6,005,122, each of which is incorporated herein by reference. Additional methods of synthesizing tocotrienols are described in U.S. Pat. No.7,038,067, which is hereby incorporated by reference. The TGPS compounds can include different linkers, for example, dicarboxylic acids (e.g., succinic acid, sebacic acid, dodecanedioic acid, suberic acid, or azelaic acid, citraconic acid, methylcitraconic acid, itaconic acid, maleic acid, glutaric acid, glutaconic acid, fumaric acids and phthalic acids). Exemplary tocopherol polyethylene glycol diesters are TPGS, tocopherol sebacate polyethylene glycol, tocopherol dodecanodioate polyethylene glycol, tocopherol suberate polyethylene glycol, tocopherol azelaate polyethylene glycol, tocopherol citraconate polyethylene glycol, tocopherol methylcitraconate polyethylene glycol, tocopherol itaconate polyethylene glycol, tocopherol maleate polyethylene glycol, tocopherol glutarate polyethylene glycol, tocopherol glutaconate polyethylene glycol, and tocopherol phthalate polyethylene glycol. The PEG moiety of the TPGS compound can be any polyethylene glycol or derivative thereof, and can have a molecular weight of 200-6000 kDa (e.g., 400-4000 kDa, 500-2000 kDa, 750-1500 kDa, 800-1200 kDa, 900-1100 kDa, or 1000 kDa). PEG derivatives include, for example, methylated PEG, polypropylene glycol (PPG), PEG-NHS, PEG-aldehyde, PEG-SH, PEG-NH2, PEG-CO2H, PEG-OMe and other ethers, branched PEGs, and PEG copolymers (e.g., PEG-b-PPG-b-PEG-1100, PEG-PPG-PEG- 1900, PPG-PEG-MBE-1700, and PPG-PEG-PPG-2000). Any known source of TPGS compound can be used in the present disclosure. TPGS typically has an HLB value between 13 and 18. An exemplary TPGS compound is tocopheryl PEG-1000 succinate (also referred to herein as “TPGS 1000”), which has a PEG moiety having a molecular weight of 1000 kDa. A food grade TPGS 1000 is available, for example, under the trade name Eastman Vitamin E TPGS (Eastman Chemical Company, Kingsport, Tenn.). This TPGS is water-soluble form of natural-source vitamin E, which is prepared by esterification of crystalline D-α-tocopheryl acid succinate with polyethylene glycol 1000 (PEG 1000), and contains between 260 and 300 mg / g total tocopherol. Another exemplary TPGS compound is Water Soluble Natural Vitamin E (ZMC-USA, The Woodlands, Tex.). Methods of preparing TPGS are described in U.S. Pat. Nos.2,680,749 and 3,102,078 and in U.S. Publication Nos.2007 / 0184117 and 2007 / 0141203, which are herein incorporated by reference. TPGS analogs also include chromanol derivatives (e.g., 6-chromanol PEG-1000 succinate and 6- chromanol PEG-400 succinate), steroid derivatives (e.g., cholesteryl PEG-1000 succinate, cholic acid PEG-1000, dihydro cholic acid PEG-1000, litho-cholic acid PEG-1000, ursodeoxycholic acid PEG-1000, chenodeoxycholic acid PEG-1000), and others (e.g., indomethacin PEG-1000, chromone-2-carboxylic acid PEG-1000, chromone-2-carboxylic acid PEG-1100-OMe, chromone-2-carboxylic acid PEG-1500, chromone-2-carboxylic acid PEG-2000, naproxen PEG-1000, probenecid PEG-1000, 7-carboxymethoxy- 4-methyl-coumarin PEG-1000, 5-(4-chlorophenyl)-2-furoic acid PEG-1000, probenecid tocopheryl PEG- PATENT ATTORNEY DOCKET NO: 51336-014WO2 1000 succinate, lithocholic acid PEG-1000, and chromone-3-carboxylic acid PEG-1000, 7-hydroxy- coumarinyl-4-acetic acid PEG-1000). Surfactants may be used to stabilize pharmaceutical compositions against, e.g., crystallization and mechanical stresses, such as agitation and / or shearing. A surfactant may be non-ionic or ionic. Non-limiting examples of non-ionic surfactants include Pluronic (e.g., Pluronic F-68 or Pluronic F-127), polyoxyethylene ether, polyoxyethylene ester (e.g., polyoxyethylene fatty acid ester), sorbitan ester, polysorbate, sorbitol, ethoxylated phenol, ethoxylated diphenol, polyethoxylated castor oil, polyoxyethylene / polyoxypropylene block copolymer (e.g., poloxamer), poloxamine, fatty acid monoglyceride, fatty acid diglyceride, polysaccharide (e.g., hyaluronic acid or sialic acid), protein (e.g., albumin or casein), and combinations thereof. Preferably, the surfactant is a Pluronic surfactant. More preferably, the surfactant is Pluronic F-68 or Pluronic F-127. Non-limiting examples of ionic surfactants include, e.g., sodium dodecyl sulfate, sodium lauryl sulfate, a sulfosuccinate salt, and a fatty acid addition salt. A surfactant may be covalently linked to a polymeric excipient. In a non-limiting example, the surfactant described herein may be included in the mixture of the solvent, active agent, and monomers of a polymeric excipient. Stabilizers may be incorporated in the nanoparticles to stabilize pharmaceutical compositions against, e.g., oxidative stress. Non-limiting examples of stabilizers include vanillin, butylated hydroxytoluene, butylated hydroxyanisole, vitamin E, TPGS, and 6-O-palmitoyl-L-ascorbic acid. Preferably, the stabilizer is a TPGS compound. A pharmaceutical composition may include, e.g., 0.1- 10%, preferably, 0.5-8%, and, in particular, 1-5% (e.g., 0.1-9%, 0.1-8%, 0.1-7%, 0.1-6%, 0.1-5%, 0.1-4%, 0.1-3%, 0.1-2%, 0.1-1%, 0.1-0.5%, 0.2-10%, 0.2-9%, 0.2-8%, 0.2-7%, 0.2-6%, 0.2-5%, 0.2-4%, 0.2-3%, 0.2-2%, 0.2-1%, 0.2-0.5%, 0.5-10%, 0.5-9%, 0.5-8%, 0.5-7%, 0.5-6%, 0.5-5%, 0.5-4%, 0.5-3%, 0.5-2%, 0.5-1%, 1-10%, 1-9%, 1-8%,1-7%, 1-6%, 1-5%, 1-4%, 1-3%, 1-2%, 2-10%, 2-9%, 2-8%, 2-7%, 2-6%, 2- 5%, 2-4%, 2-3%, 3-10%, 3-9%, 3-8%, 3-7%, 3-6%, 3-5%, 3-4%, 4-10%, 4-9%, 4-8%, 4-7%, 4-6%, 4-5%, 5-10%, 5-9%, 5-8%, 5-7%, 5-6%, or 5%) (w / w) of the stabilizer relative to the particle mass. Carriers may be used to suspend the nanoparticles in the pharmaceutical composition. Carriers may also be used to prevent Ostwald ripening during the formulation preparation. A suspending or solubilizing carrier may be an aqueous carrier, e.g., water or saline (e.g., isotonic saline). Non-limiting examples of further pharmaceutically acceptable carriers include a pharmaceutically acceptable oil, e.g., medium chain triglycerides, long chain triglycerides, or a combination thereof. Preferably, the pharmaceutically acceptable oil is one or more medium chain triglycerides (e.g., Miglyol, Captex, and Kollisolv). A pharmaceutical composition may include, e.g., 0.5-5%, preferably, 1-5%, and, in particular, 2-3% (e.g., 0.5-5%, 0.5-4.5%, 0.5-4%, 0.5-3.5%, 0.5-3%, 0.5-2.5%, 0.5-2%, 0.5-1.5%, 0.5-1%, 1-5%, 1- 4.5%, 1-4%, 1-3.5%, 1-3%, 1-2.5%, 1-2%, 1-1.5%, 1.5-5%, 1.5-4.5%, 1.5-4%, 1.5-3.5%, 1.5-3%, 1.5- 2.5%, 1.5-2%, 2-5%, 2-4.5%, 2-4%, 2-3.5%, 2-3%, 2-2.5%, 2.5-5%, 2.5-4.5%, 2.5-4%, 2.5-3.5%, 2.5-3%, 3-5%, 3-4.5%, 3-4%, 3-3.5%, 3.5-5%, 3.5-4.5%, 3.5-4%, 4-5%, 4-4.5%, or 4.5-5%) (w / w) of the pharmaceutically acceptable oil in the liquid carrier. The pharmaceutical compositions described herein may be aqueous compositions (e.g., suspensions). The pH of the pharmaceutical composition may be, e.g., 4.0 to 8.0 (preferably 5.0 to 7.0). PATENT ATTORNEY DOCKET NO: 51336-014WO2 Alternatively, the pharmaceutical composition may be a lyophilized composition. A lyophilized composition may be reconstituted to produce an aqueous composition prior to use. The pharmaceutical compositions described herein may be used to treat a subject in need thereof. The method of treating the subject includes administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein. The subject may be suffering from a fungal infection (e.g., an invasive fungal infection), e.g., caused by Candida, Aspergillus, Cryptococcus, Fusarium, or Mucorales organisms. The pharmaceutical compositions described herein may be administered to the subject in a single dose or in multiple doses. When multiple doses are administered, the doses may be separated from one another by, for example, 1-12 hours, 1-24 hours, 1-7 days, or 1-4 weeks. The pharmaceutical composition may be administered according to a schedule, or the pharmaceutical composition may be administered without a predetermined schedule. It is to be understood that, for any particular subject, specific dosage regimes should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the pharmaceutical compositions. An effective amount of a compound of the invention may be, for example, a total daily dosage of, e.g., between 0.02 mg and 3000 mg of a compound of Formula (I) or Compound 1. Alternatively, the dosage amount can be calculated using the body weight of the patient. For example, the compounds of the invention can be dosed at 0.02 mg / kg body weight. In some embodiments, doses of the pharmaceutical composition are administered to a subject on a daily basis, as needed. In some embodiments, the pharmaceutical compositions are administered to a subject at the onset of symptoms. When a pharmaceutical composition is administered daily, administration may occur, for example, 1-4 times per day. The pharmaceutical compositions described herein include those formulated for pulmonary (e.g., by inhalation), intravenous, oral or intranasal administration. The pharmaceutical compositions described herein may include nanoparticles described herein. Advantageously, pharmaceutical compositions nanoparticles described herein may facilitate targeted delivery of a compound of formula (I) or Compound 1 to a target tissue (e.g., kidney, lungs, liver, brain, intestines, eyes, sinuses and / or heart). Pharmaceutical compositions nanoparticles described herein may be prepared, e.g., according to a method described herein. For example, nanoparticles may be in a solution. The nanoparticles may be prepared in situ as described herein, or may be reconstituted from a dry composition. The pharmaceutical compositions described herein may be prepared using techniques and methods described herein and those known in the art. The invention further features a method of forming nanoparticles including an acid addition salt form of a compound of formula (I) or Compound 1. In particular, the nanoparticles may include, e.g., a pharmaceutically acceptable polymeric excipient. The method may include the following steps: (i) providing an acid addition salt form of a compound of formula (I) or Compound 1 and a TPGS compound in an organic solvent; (ii) adding deionized water; and (iii) quenching the solution of (ii) with aqueous saline. The nanoparticles may be found by micromixing. PATENT ATTORNEY DOCKET NO: 51336-014WO2 In the formation methods described herein, the aqueous solution of (ii) may further include a pharmaceutically acceptable surfactant (e.g., non-ionic surfactant, such as Pluronic (e.g., Pluronic F-68 or Pluronic F-127), polyoxyethylene ether, polyoxyethylene fatty acid ester, sorbitan ester, polysorbate, polyethoxylated castor oil, polyoxyethylene / polyoxypropylene block copolymer, or a combination thereof). Preferably, the pharmaceutically acceptable surfactant is Pluronic (e.g., Pluronic F-68 or Pluronic F-127). In the production methods described herein, the solution of (i) may further include a pharmaceutically acceptable stabilizer (e.g., vitamin E, TPGS, vanillin, butylated hydroxytoluene, or butylated hydroxyanisole). Preferably, the pharmaceutically acceptable stabilizer is TPGS. In the production methods described herein, the polymeric carrier may be, e.g., PLGA. In the production methods described herein, the plurality of nanoparticles may have a Z-average of 20-200 nm (e.g., 60-100 nm), as measured by dynamic light scattering. In the production methods described herein, the plurality of nanoparticles may have a Z-average of 30-150 nm (e.g., 60-100 nm), as measured by nanoparticle tracking analysis. The liquid may be, e.g., an aqueous composition (e.g., an aqueous composition having the pH of 0.5 to 8.0 (e.g., pH of 0.5 to 3.0, 2.0 to 8.0, or 3.0 to 7.0)). The formation method may further include the step of lyophilizing the plurality of nanoparticles. Additionally or alternatively, the production method may further include the step of dialyzing the nanoparticles using aqueous saline. In the production methods described herein, pH of the liquid may be adjusted as desired. For example, the pH of the liquid may be adjusted to be in the range 4.0 to 8.0 (e.g., 5.0 to 7.0). Examples The following examples are merely illustrative and should not be construed as limiting the scope of this disclosure in any way as many variations and equivalents will become apparent to those skilled in the art upon reading the present disclosure. The contents of all references, patents, and patent applications cited throughout this application are expressly incorporated herein by reference. Example 1: Preparation of the docusate salt of Compound 1 To prepare docusic acid, 6.2 mmol sodium docusate was dissolved in 50 mL tetrahydrofuran (THF), and 6.0 mmol methanolic HCl (3.0 M) was added to the solution. The solution was cooled to 0 °C and the precipitated NaCl was removed by filtration (0.45 µm filter). The solution was dried in vacuo, redissolved in THF, and dried 3 times to remove any access HCl. To prepare the docusate salt of Compound 1, Compound 1 (0.224 mmol) was dissolved in 5 mL of 1:1 chloroform / methanol (2.5) mL. To this solution, 0.202 mmol sodium docusate (898 µL, dissolved in chloroform) and 0.064 mmol docusic acid (284 µL, dissolved in chloroform) was added and stirred for 10 minutes. The sample was dried in vacuo at 25 °C. The salts of Compound 1 were dissolved in DMSO to 0.05 mg / mL, and these DMSO solutions were analyzed by HPLC-DAD to quantify the ratio of Compound 1 and potential degradation of these salts. Minimal degradation of Compound 1 was detected. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Example 2: Preparation of the oleate salt of Compound 1 0.028 mmol of Compound 1 was dissolved in 3 mL of 1:1 chloroform / methanol. To this solution, either 1.1 eq of oleic acid or 1.1 eq of sodium oleate, or 1.3 eq of oleic acid / sodium oleate dissolved in 2 mL of chloroform was added. The solution was stirred for 10 minutes. The sample was dried in vacuo at 25 °C. The salts of Compound 1 were dissolved in DMSO to 0.05 mg / mL, and these DMSO solutions were analyzed by HPLC-DAD to quantify the ratio of Compound 1 and potential degradation of these salts. Minimal degradation of Compound 1 was detected. Example 3: Preparation of the octanoate salt of Compound 1 0.028 mmol of Compound 1 was dissolved in 3 mL of 1:1 chloroform / methanol. To this solution, 1.1 eq of octanoic acid dissolved in 2 mL of chloroform was added. The solution was stirred for 10 minutes. The sample was dried in vacuo at 25 °C. The salts of Compound 1 were dissolved in DMSO to 0.05 mg / mL, and these DMSO solutions were analyzed by HPLC-DAD to quantify the ratio of Compound 1 and potential degradation of these salts. Minimal degradation of Compound 1 was detected. Example 4: Preparation of the decanoate salt of Compound 1 0.028 mmol of Compound 1 was dissolved in 3 mL of 1:1 chloroform / methanol. To this solution, 1.1 eq of decanoic acid dissolved in 2 mL of chloroform was added. The solution was stirred for 10 minutes. The sample was dried in vacuo at 25 °C. The salts of Compound 1 were dissolved in DMSO to 0.05 mg / mL, and these DMSO solutions were analyzed by HPLC-DAD to quantify the ratio of Compound 1 and potential degradation of these salts, and minimal degradation of Compound 1 was detected. Example 5: Preparation of the benzoate salt of Compound 1 0.028 mmol of Compound 1 was dissolved in 3 mL of 1:1 chloroform / methanol. To this solution, 1.1 eq of benzoic acid dissolved in 2 mL chloroform was added. The solution was stirred for 10 minutes. The sample was dried in vacuo at 25 °C. The salts of Compound 1 were dissolved in DMSO to 0.05 mg / mL, and these DMSO solutions were analyzed by HPLC-DAD to quantify the ratio of Compound 1 and potential degradation of these salts. Minimal degradation of Compound 1 was detected. Example 6: Preparation of the pamoate salt of Compound 1 0.028 mmol of Compound 1 was dissolved in 3 mL of 1:1 chloroform / methanol. To this solution, 1.1 eq of pamoic acid dissolved in 2 mL chloroform was added. The solution was stirred for 10 minutes. The sample was dried in vacuo at 25 °C. The salts of Compound 1 were dissolved in DMSO to 0.05 mg / mL, and these DMSO solutions were analyzed by HPLC-DAD to quantify the ratio of Compound 1 and potential degradation of these salts, and minimal degradation of Compound 1 was detected. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Example 7: Preparation of Compound 1 with alpha-tocopherol 0.028 mmol of Compound 1 was dissolved in 3 mL of 1:1 chloroform / methanol. To this solution, 1.1 eq of alpha-tocopherol dissolved in 2 mL of chloroform was added. The solution was stirred for 10 minutes. The sample was dried in vacuo at 25 °C. Example 8: Preparation poly(lactic-co-glycolic acid) (PLGA) nanoparticulate formulations including lipophilic salts of Compound 1 or Compound 1 and alpha-tocopherol To produce a suspension of PLGA nanoparticles encapsulated with a salt of Compound 1, three solutions are prepared: an organic phase, an aqueous phase, and a quench solution. To prepare the organic phase, 1.3 mg of the desired Compound 1 salt produced from any one of Examples 1-7, 15 mg of PLGA (Resomer RG504, Merck), and 15 mg of TPGS are dissolved in 3 mL of THF. To prepare the aqueous phase, 3.15 mL of deionized water is optionally combined with either 12 mg of Pluronic F-68 or 6 mg of Pluronic F-127. The quench solution was prepared using 15 mL of aqueous 0.9% saline. A ratio of 0.087:1 or 0.15:1 of Compound 1 salt / Vitamin E TPGS was used to prepare the nanoparticulate formulations. The nanoparticles are made using jet impingement micromixing. A syringe containing the organic phase and another syringe containing the aqueous phase are mounted on a T-mixer. The syringes are plunged rapidly, and the resulting suspension is collected in the quench solution. The suspension is dialyzed against 0.9% saline for injection twice for 3 hours each time, before it is concentrated. Residual THF from the mixture was removed in-vacuo and the mixture was subjected to tangential flow filtration (TFF) to diafiltrate and concentrate the mixture. The concentrated nanoparticulate formulation was sterile filtered and stored in a freezer. The nanoparticulate formulation was removed from the freezer and allowed to thaw to room temperature to be used in experiments, e.g., MIC assays. Example 9: Preparation poly(lactic-co-glycolic acid) (PLGA) nanoparticulate formulations including in situ formation of lipophilic salts of Compound 1 To produce a suspension of PLGA nanoparticles encapsulated with Compound 1, three solutions are prepared: an organic phase, an aqueous phase, and a quench solution. To prepare the organic phase, 1-3 mg of Compound 1 and the desired lipophilic acid (0.5-2.0 molar equivalent chosen from oleic acid, decanoic acid, docusic acid, benzoic acid, pamoic acid, sodium docusate alpha-D-tocopherol, sodium dodecylbenzenesulfonate (SDBS)), or 0.5-2.0 molar equivalent of alpha-tocopherol, 12-18 mg of PLGA (Resomer RG504, Merck), and 12-18 mg of TPGS are dissolved in 3 mL of THF. To prepare the aqueous phase, 3.15 mL of deionized water (3.15 mL) is optionally combined with either 12 mg of Pluronic F-68 or 6 mg of Pluronic F-127. The quench solution was prepared using 15 mL of aqueous 0.9% saline. The nanoparticles are made using jet impingement micromixing. A syringe containing the organic phase and another syringe containing the aqueous phase are mounted on a T-mixer. The syringes are plunged rapidly, and the resulting suspension is collected in the quench solution. The suspension is dialyzed against 0.9% saline for injection twice for 3 hours each time, before it is concentrated. Residual THF from the mixture was removed in-vacuo and the mixture was subjected to tangential flow filtration (TFF) to diafiltrate and concentrate the mixture. The concentrated nanoparticulate formulation was sterile PATENT ATTORNEY DOCKET NO: 51336-014WO2 filtered and stored in a freezer. The nanoparticulate formulation was removed from the freezer and allowed to thaw to room temperature to be used in experiments, e.g., MIC assays. Example 10: Measurement of Compound 1 concentration and stability in nanoparticulate formulations including lipophilic salts of Compound 1 To calculate the amount of encapsulated Compound 1 in the nanoparticulate formulations, 100 µL of the nanoparticle suspension was dissolved in 400 µL DMSO. The concentration of extracted Compound 1 is quantified using an Agilent 1260 HPLC system coupled to a diode array detector (DAD). The configuration of the HPLC system is summarized in Table 1. Table 1. Summary of the configuration of the HPLC system. 20 mM ammonium acetate buffer at pH=5 adjusted with acetic acid [A] Mobile phases and 30:70 Tetrahydrofuran : acetonitrile [B] HPLC system Agilent 1260 HPLC system with a 1260 DAD Column Luna 3 µm C18(2) 100 Å, 150x2 mm (Phenomenex) Temp autosampler 18 °C Column thermostat 25 °C Flow rate 0.25 mL / min Injection volume 5 µL Wavelength 385 nm for measuring Compound 1, Scan 190-600 nm Software Agilent 1100 Chemstation Up to 95% of Compound 1 was recovered after the extraction of the nanoparticle formulation and no degradation of Compound 1 was observed during the formulation process. Example 11: HPLC purity and Compound 1 (w / w) percent of lipophilic salts of Compound 1 Lipophilic salts of Compound 1 were prepared according to Examples 1-3, 5, and 6 using Compound 1 having 89% purity as determined with the HPLC method given in Example 10. Analyses of the lipophilic salts of Compound 1 showed that there was no significant degradation of Compound 1 during the salt formation process for any of these excipients (Table 2).

[0002] PATENT ATTORNEY DOCKET NO: 51336-014WO2 Table 2. The (w / w) percent of Compound 1 and HPLC purity (ratio of Compound 1 / total polyene absorbing at 385 nm) of five lipophilic salts of Compound 1. Compound 1 is stable during the salt forming process. Description of test Compound 1 HPLC Name Excipient articles (w / w)% purity Docusate salt of Docusic acid Example 1 44% 83% Compound 1 Benzoate salt of Benzoic acid Example 5 59% 88% Compound 1 Octanoate salt of Octanoic Example 3 64% 87% Compound 1 acid Oleate salt of Compound Oleic acid Example 2 55% 89% 1 Oleate salt of Compound Sodium Example 2 58% 86% 1 oleate Pamoate salt of Pamoic acid Example 6 55% 86% Compound 1 Example 12: General procedure for Minimum inhibitory concentration (MIC) assays using nanoparticulate formulations including lipophilic salts of Compound 1 Minimum inhibitory concentration (MIC) assays are performed according to the EUCAST protocol (E. DEF 7.3.2 April 2020) to determine the MIC50 and MIC90 values of all test articles against C. albicans (ATCC 10231). Stock solutions of each test article are used to prepare working solutions for the MIC assay. The medium used in the MIC assay was RPMI-1640 with 2 mM L-Glutamine without Sodium Bicarbonate (Sigma, R6504-10L) supplemented with 18 g / L extra glucose (Sigma 49161) and 34.5 g / L MOPS (Sigma M1254). Polypropylene deep well plates with 2-mL well volumes were used to prepare the 2x dilution series. From the deep well plates, 70 µL of diluted test article was transferred to four cultivation plates (Greiner 655163 flat bottom) to prepare three parallel plats for cultivation and one vehicle control. The plates were inoculated with 30 µL of medium added C. albicans ATCC 10231. The concentrations of active compounds in each row in the cultivation plates are given in Table 3. The colony forming units (CFU) of the cultivation plates were between 1.8 × 104CFU / mL and 2.1 × 104CFU / mL. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Table 3. Concentrations of formulations in the cultivation plates after addition of 30 µL inoculum. The highest concentration of Amphotericin B (AmpB) was 8 µg / mL and the highest concentration of nanoparticulate formulations were 2 µg / mL. 1 2 3 4 5 6 7 8 9 10 11 12 Concentration of AmpB / Compound 8.0 4.0 2.0 1.0 0.5 0.3 0.125 0.063 0.031 0.016 0.008 0.000 1-Docusate (µg / mL) Concentration of nanoparticulate 2.0 1.0 0.5 0.3 0.1 0.1 0.031 0.016 0.008 0.004 0.002 0.000 formulations (µg / mL) The cultivation plates were packed in plastic bags to prevent media evaporation and incubated at 34 ⁰C without shaking at 85 % humidity. The incubator was covered with aluminum foil to prevent possible degradation of Compound 1 due to light exposure. The OD600 was measured using a plate reader from Tecan (Tecan WS2) controlled by Tecan i-control. Prior to reading, the plates were subject to robotic controlled shaking for 30 seconds at 1000 rpm. OD600 was measured after 17 h, 24 h, and 42 h after inoculation. The MIC50 and MIC90 were determined from curves of growth versus concentration of test article. For the assays with the lowest CFU at inoculation, the yeast growth (measured as OD600) did not reach the maximum value after 24 hours and the MIC50 and MIC90 values were therefore determined after 42 hours. Example 13: Minimum inhibitory concentration (MIC) assays using nanoparticulate formulations including lipophilic salts of Compound 1 The MIC50 values of the Compound 1 nanoparticulate formulations were determined using the method described in Example 12. The assays tested the nanoparticulate formulations Nano-1, Nano-2, Nano-3, Nano-4, Nano-5, Nano-6, Nano-7, Nano-8, Nano-9, Nano-10, Nano-11, Nano-12, and Nano-13 were tested in the MIC assay. The descriptions of the test articles are given in Table 4. The MIC values of the nanoparticulate formulations are significantly lower than that of amphotericin B dissolved in DMSO. The MIC values are approximately the same for all nanoparticulate formulations. The Nano-14, Nano-15, Nano-16, and Nano-17 formulations were not suitable for the MIC assay. Specifically, the Nano-14, Nano-15, and Nano-16 formulations comprised of particles that were too large for z-average and PDI measurements, while the Nano-17 formulations were simply not compatible with the MIC assay (i.e., the Nano-17 formulations did not form pharmaceutically appropriate nanoparticles). In general, nanoparticles with large Z-average and PDI measurements are not viable for use in subjects. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Table 4. Test articles used in the MIC assay, with their corresponding concentrations and dilutions, the particle sizes (z-average given as nm), size distributions (PDI given as nm), and MIC50and MIC90values. The MIC50and MIC90values were determined using the method described in Example 12. Method of Z-average MIC50 MIC90 Test articles Description dilution for and PDI (µg / mL) (µg / mL) MIC assay A 2.5 mg / mL DMSO stock Amphotericin B solution (assay Amphotericin B (AmpB, USP corrected) was N / A 0.5 0.65 1032007). diluted in RPMI medium to 11.4 µg / mL. A 2.5 mg / mL DMSO stock solution (assay Docusate salt Example 1. corrected) was N / A 1.2 1.4 of Compound 1 diluted in RPMI medium to 4.29 µg / mL. The formulation Example 8 with the (110 µg / mL) in Z-avg: 118 Nano-1 docusate salt of 0.15 0.22 saline was PDI: 0.20 Compound 1. diluted in RPMI to 2.86 µg / mL. The Example 8 with the formulation docusate salt of (100 µg / mL) in Z-avg: 127 Nano-2 0.07 0.12 Compound 1 and saline was PDI: 0.14 pluronic F-68. diluted in RPMI to 2.86 µg / mL. The Example 9 with the formulation (99 docusate salt of µg / mL) in Z-avg: 75 Nano-3 Compound 1 from 0.1 0.12 saline was PDI: 0.15 sodium docusate and diluted in RPMI docusic acid. to 2.86 µg / mL. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Method of Z-average MIC50 MIC90 Test articles Description dilution for and PDI (µg / mL) (µg / mL) MIC assay Example 9 with the The docusate salt of formulation (74 Compound 1 (from µg / mL) in Z-avg: 101, Nano-4 0.08 0.1 sodium docusate and saline was PDI: 0.19 docusic acid) and diluted in RPMI pluronic F-68. to 2.86 µg / mL. The Example 9 with the formulation docusate salt of (128 µg / mL) in Z-avg: 83, Nano-5 0.1 0.12 Compound 1 from saline was PDI: 0.17 sodium docusate. diluted in RPMI to 2.86 µg / mL. The Example 9 with the formulation (56 docusate salt of µg / mL) in Z-avg: 88, Nano-6 Compound 1 (from 0.06 0.075 saline was PDI: 0.14 sodium docusate) diluted in RPMI and pluronic F-68. to 2.86 µg / mL. The Example 9 with the formulation (22 octanoate salt of µg / mL) in Z-avg: 97, Nano-7 0.03 0.05 Compound 1 and saline was PDI: 0.13 pluronic F-68. diluted in RPMI to 2.86 µg / mL. The formulation (36 Example 9 with the µg / mL) in oleate salt of saline was Z-avg: 99, Nano-8 0.05 0.06 Compound 1 and diluted in RPMI PDI: 0.14 pluronic F-68. to 2.86 µg / mL. The Example 9 with formulation (23 Compound 1, alpha- µg / mL) in Z-avg: 84, Nano-9 0.03 0.03 tocopherol, and saline was PDI: 0.15 pluronic F-68. diluted in RPMI to 2.86 µg / mL. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Method of Z-average MIC50 MIC90 Test articles Description dilution for and PDI (µg / mL) (µg / mL) MIC assay The formulation (70 Example 9 with the µg / mL) in Z-avg: 81.8 Nano-10 oleate salt of 0.1 0.12 saline was PDI: 0.18 Compound 1. diluted in RPMI to 2.86 µg / mL. The formulation (87 Example 9 with the Z-avg: µg / mL) in Nano-11 octanoate salt of 144.8 PDI: 0.1 0.12 saline was Compound 1. 0.16 diluted in RPMI to 2.86 µg / mL. The formulation Example 9 with the Z-avg: (139 µg / mL) in Nano-12 docusate salt of 194.3 PDI: 0.11 0.12 saline was Compound 1. 0.245 diluted in RPMI to 2.86 µg / mL. The formulation Example 9 with the Z-avg: (114 µg / mL) in Nano-13 decanoate salt of 108.0 PDI: 0.1 0.11 saline was Compound 1. 0.18 diluted in RPMI to 2.86 µg / mL. Example 9 with the Z-avg: N / A1Nano-14 oleate salt of N / A N / A2N / A2PDI: N / A Compound 1. Example 9 with the Z-avg: N / A1Nano-15 pamoate salt of N / A N / A2N / A2PDI: N / A Compound 1. Example 9 with N / A Z-avg: N / A1Nano-16 Compound 1 and N / A2N / A2PDI: N / A SDBS. Example 9 with the Z-avg: Nano-17 benzoate salt of N / A 223.4 PDI: N / A2N / A2Compound 1. 0.202 PATENT ATTORNEY DOCKET NO: 51336-014WO2 Method of Z-average MIC50 MIC90 Test articles Description dilution for and PDI (µg / mL) (µg / mL) MIC assay Example 9 with oleate The salt of Compound 1. formulation (58 Z-avg: 78.5 Nano-18 Addition of mannitol is µg / mL) was 0.065 0.07 PDI: 0.126 described in Example diluted in RPMI 14. to 0.41 µg / mL. Example 9 with the The oleate salt of formulation (75 Compound 1. Z-avg: 67.3 Nano-19 µg / mL) was 0.07 0.09 Addition of sucrose is PDI: 0.051 diluted in RPMI described in Example to 0.52 µg / mL 14. The Example 8 with the formulation (79 docusate salt of Z-avg: 111 Nano-20 µg / mL) was 0.031 0.035 Compound 1 and PDI: 0.18 diluted in RPMI pluronic F-127. to 0.21 µg / mL.1Particles not suitable for measurement of size and PDI2Particles not suitable for MIC measurements Example 14: Physical stability and minimum inhibitory concentration (MIC) of nanoparticulate formulations including the oleate salt of Compound 1 after freezing at -20 °C Freeze-thaw experiments of the nanoparticulate formulations of the oleate salt of Compound 1 were evaluated to determine if the formulations suspended in saline could withstand freezing at -20 °C followed by thawing. The formulations tested included Nano-10, Nano-18, and Nano-19. Each tested formulation was divided into six separate test samples: two samples contained 100 mg / mL mannitol, two samples contained 100 mg / mL sucrose, and two samples lacked a cryoprotectant, serving as a negative control. The six samples were stored at -20 °C for 13 days. After 13 days, the formulations were thawed and the MIC, Z-average, and PDI values were measured for each test sample, summarized in Table 5. The data show that the Nano-10, Nano-18, and Nano-19 can be frozen and thawed and still retain the same antifungal and physical properties as fresh formulations such as Nano- 10. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Table 5. The MIC50, MIC90, size (Z-average), and size distribution (PDI) of the nanoparticulate formulations including the oleate salt of Compound 1 (Nano-10, Nano-18, and Nano-19) after freezing followed by thawing. Z-average PDI MIC90 Formulation Description MIC50(µg / mL) (before / after (before / after (µg / mL) freezing) freezing) AmpB N / A 0.12 0.175 After freezing, Nano-10 followed by 0.09 0.11 80.6 / 80.0 0.201 / 0.241 thawing After freezing, Nano-10 with followed by 0.065 0.07 100.0 / 125.9 0.213 / 0.357 mannitol thawing After freezing, Nano-10 with followed by 0.07 0.09 100.8 / 86.2 0.198 / 0.212 sucrose thawing Example 15: Minimum fungicidal concentration (MFC) assays using nanoparticulate formulations of lipophilic salts of Compound 1 After incubating the MIC cultivation plates from Example 13 for 42 hours, the plates were removed from the incubator, and clear wells were detected by measuring the OD600 values of each well. Minimum fungicidal concentration (MFC) was determined for one parallel run of each formulation. For all clear wells, 100 µL of culture from the plate was streaked onto potato dextrose agar plates. The plates were incubated at 34 °C for three days. The colonies on the plates were subsequently counted and the reduction in CFU relative to the initial CFU of 2.1 × 105CFU / mL was measured. The concentration of active compound where the CFU was less than 0.05 % (> 99.95% killed) of the initial CFU is given in Table 6. Table 6. Minimum fungicidal concentration (MFC) values of the Nano-10 nanoparticulate formulation after storage at -80 ⁰C for 13 days, with and without cryoprotectant. Concentration of Formulation name formulation at which >99.95% are killed AmpB 0.95 Nano-10 0.23 Nano-18 0.14 Nano-19 0.18 PATENT ATTORNEY DOCKET NO: 51336-014WO2 Example 16: Freeze-thawing analysis of nanoparticulate formulations including lipophilic salts of Compound 1 Freeze-thawing of the nanoparticulate formulation including the oleate salt of Compound 1, Nano- 10, was evaluated to determine if the liquid formulation could withstand several freeze-thaw cycles. Nano-10 was included in six test samples, each containing 1 mL of sample. Three of the test samples contained 5% mannitol, while the remaining three samples lacked a cryoprotectant. The six samples were stored at -20 °C, then thawed to room temperature. When the temperature in the samples reached room temperature, the size and size distributions (Z-average and PDI) were measured by DLS. The test samples were subjected to three cycles, and the nanoparticles were characterized by DLS after each cycle. A slight apparent increase in size was observed for the nanoparticulate formulations stored in 5% aqueous mannitol, indicating an increased viscosity in the sample, and these samples collapsed after the second cycle. In contrast, the nanoparticulate formulations stored in saline remained stable over three cycles. Thus, the data from this experiment demonstrate that Nano-10 is most stable in saline, compared to mannitol, after freeze-thawing. Example 17: Compound 1 stability in nanoparticulate formulations including lipophilic salts of Compound 1 determined by HPLC analysis The nanoparticulate formulations including lipophilic salts of Compound 1 were stored at 4 °C and analyzed by HPLC to determine the chemical stability of Compound 1 in the nanoparticulate formulations. It is assumed that the extinction coefficients of the impurities of Compound 1 are the same as that of Compound 1. The data in Table 7 demonstrate that the formulations can be stored at 4 °C over 50 days without significant loss in Compound 1 purity. Table 7. Compound 1 stability in nanoparticulate formulations determined by HPLC. Compound 1 percent Test Article purity determined by HPLC 0 days: 90% Nano-20 51 days: 89% 0 days: 90% Nano-2 51 days: 88% Example 18: Administration of nanoparticulate formulations for treating candidemia or invasive candidiasis The nanoparticles of the invention are suspended in an aqueous solution and administered by inhalation, intravenously, orally, or intranasally to a subject for the treatment of candidemia or invasive candidiasis. Each administration delivers 0.05 mg to 1000 mg of the compound of formula (I) or Compound 1. The subject is treated once, twice, or three times daily for a period of 1 to 12 weeks. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Example 19: Minimum inhibitory concentration (MIC) assays using nanoparticulate formulations of lipophilic salts of Compound 1 against a panel of fungal strains The minimum inhibitory concentration (MIC) activities of Compound 1, AmpB, and three nanoparticulate formulations (Nano-10, Nano-19, and Nano-13) were evaluated against a panel of yeast and mold clinical isolates using the CLSI reference broth microdilution (BMD) method. Organisms Twenty-seven clinical yeast and mold isolates collected between 2016 and 2022 from geographically diverse hospitals that have been identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and / or DNA-based methods. All isolates were collected in 2022, except the 2 Mucorales spp. isolates which were collected in 2016 and 2019 due to their rare incidence. The tested isolates include: • Two isolates each of Candida albicans, Candida auris, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis (including QC strains C. krusei ATCC 6258 and C. parapsilosis ATCC 22019) • Two isolates of Cryptococcus neoformans var. grubii • Two isolates each of Aspergillus flavus species complex, Aspergillus fumigatus, Aspergillus nidulans species complex, Aspergillus niger species complex, and Aspergillus terreus. • Two Aspergillus QC strains (A. flavus ATCC 204304 and A. fumigatus ATCC MYA-3626) • Two Fusarium spp. isolates (1 Fusarium solani species complex, and 1 Fusarium annulatum) • Two Mucorales isolates (1 Mucor circinelloides / ramosissimus, 1 Rhizopus spp.) Susceptibility testing All testing was performed by the broth microdilution method as described by Clinical and Laboratory Standards Institute (CLSI) documents M38-A3 (CLSI, 2017). Fresh panels were prepared using RPMI 1640 broth supplemented with morpholinepropanesulfonic acid (MOPS) buffer and 0.2% glucose. Test articles and concentrations tested were Compound 1, Nano-10, Nano-19, and Nano-13 (ranges 0.008 – 16 mg / L), and amphotericin B (range 0.03 – 16 mg / L). The test articles were prepared in glass containers whenever possible. Panels were inoculated with approximately 1 to 5 x 103CFU / mL suspensions for yeast and 0.4 to 5 x 104CFU / mL for mold isolates. MIC values were determined visually after 24 and 48 hours or 48 and 72 hours of incubation at 35ºC. These MIC values were read at the lowest antifungal concentration that resulted in ≥50% inhibition of growth relative to the growth control and complete (100%) inhibition of growth for all investigational compounds. Amphotericin B MIC values were read at 100% inhibition for yeast and mold isolates. MIC results were read at 24 and 48 hours for all isolates, except for the Cryptococcus isolates which were read at 48 and 72 hours. However, the 24-hour reading MIC results for Candida spp. and Mucorales were used for analysis. The 48-hour MIC results were used for analysis for Aspergillus spp. and Fusarium spp. isolates. Finally, the 72-hour MIC results were used in analysis for Cryptococcus, as recommended by CLSI M38 (2017). PATENT ATTORNEY DOCKET NO: 51336-014WO2 Test Articles Table 8 summarizes the test articles and their corresponding concentration ranges that were tested in the MIC assay. Table 8. Summary of test articles used in the MIC assays. Test Article Concentration Ranges Used (mg / L) Amphotericin B 0.03 – 16 mg / L Compound 1 0.008 – 16 mg / L Nano-10 0.008 – 16 mg / L Nano-19 0.008 – 16 mg / L Nano-13 0.008 – 16 mg / L Quality control Quality control (QC) strains were tested concomitantly with clinical isolates, and inoculum density was monitored by colony counts. QC ranges and interpretive criteria followed the CLSI M27M44SEd3E (2022) guidelines for yeast testing and M38M51SEd3E (2022) guidelines for mold testing. The following QC and reference strains were used: Candida krusei ATCC 6258; Candida parapsilosis ATCC 22019; A. flavus ATCC 204304, and A. fumigatus ATCC MYA-3626. Quality control results All amphotericin B MIC values were within the CLSI published range against the four quality control ATCC strains tested after 24- and 48-hour incubation periods for Candida spp. and 48-hour incubation period for Aspergillus spp. MIC50and MIC assay results The MIC50 and MIC values were determined for all the antifungal agents in RPMI 1640 broth buffered with MOPS and 0.2% glucose after 24 and 48 hours of incubation at 35 °C, except for Cryptococcus spp., where 48 and 72 hours incubation periods were recorded. The MIC data of various fungus genera is summarized in Table 9. The data show the three nanoparticulate formulations (Nano-10, Nano-19, and Nano-13) are superior at inhibiting the growth of the tested fungus genera compared to AmpB and Compound 1. For example, the Nano-10, Nano-19, and Nano-13 were 2-8 fold more potent at inhibiting the growth of the tested fungi, compared to AmpB and Compound 1. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Table 9. Summary of MIC50 and MIC values (in mg / L) of antifungal agents against various fungus genera. Fungus genera (number of MIC Compound AmpB Nano-10 Nano-19 Nano-13 isolates (mg / mL) 1 tested in parentheses) Candida spp. MIC50 0.5 1 0.03 0.06 0.03 (12) MIC1002 1 0.12 0.25 0.12 Cryptococcus MIC500.5 1 0.03 0.06 0.03 spp. (2) MIC100 NA NA NA NA NA Aspergillus MIC50 0.5 1 0.12 0.25 0.06 spp. (12) MIC1002 1 0.5 0.5 0.5 Fusarium spp. MIC500.5 0.25 0.12 0.12 0.12 (2) MIC100 NA NA NA NA NA Mucorales MIC50 0.25 0.5 0.06 0.06 0.06 group (2) MIC100NA NA NA NA NA The MIC data of various fungus species is summarized in Table 10. The data show the three nanoparticulate formulations (Nano-10, Nano-19, and Nano-13) are superior at inhibiting the growth of the tested fungus species compared to AmpB and Compound 1. For example, the Nano-10, Nano-19, and Nano-13 were 2-16 fold more potent at inhibiting the growth of the tested fungi, compared to AmpB and Compound 1, with the exception of: A. terreus, in which Nano-10, Nano-19, and Nano-13 all had comparable MIC activity to AmpB; and A. nidulans, in which Nano-10, Nano-19, and Nano-13 all had comparable MIC activity to both AmpB and Compound 1. Table 10. Summary of MIC values (in mg / L) of antifungal agents against various fungus species. Compound Isolate AmpB Nano-10 Nano-19 Nano-13 1 C. albicans 0.5 1 0.03 0.06 0.03 C. glabrata 1 0.5 0.06 0.06 0.06 C. parapsilosis 0.5 1 0.06 0.06 0.06 C. tropicalis 0.5 0.5 0.03 0.06 0.03 C. krusei 1 1 0.06 0.06 0.06 PATENT ATTORNEY DOCKET NO: 51336-014WO2 Compound Isolate AmpB Nano-10 Nano-19 Nano-13 1 C. auris 1 1 0.06 0.06 0.06 A. fumigatus 1 1 0.12 0.25 0.12 A. flavus 1 1 0.12 0.25 0.12 A. niger 0.12 0.25 0.06 0.06 0.06 A. terreus 0.5 1 0.5 0.5 0.5 A. nidulans 0.12 0.25 0.12 0.25 0.06 Example 20: Minimum fungicidal concentration (MFC) assays using nanoparticulate formulations of lipophilic salts of Compound 1 against a panel of fungal strains The minimum fungicidal concentration (MFC) activities of Compound 1, AmpB, and three nanoparticulate formulations of lipophilic salts of Compound 1 (Nano-21, Nano-22, and Nano-23) were evaluated against a panel of yeast and mold clinical isolates using the CLSI reference broth microdilution (BMD) method. Organisms Twenty-seven clinical yeast and mold isolates collected between 2016 and 2022 from geographically diverse hospitals that have been identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and / or DNA-based methods. All isolates were collected in 2022, except the 2 Mucorales spp. isolates which were collected in 2016 and 2019 due to their rare incidence. The tested isolates include: • Two isolates each of Candida albicans, Candida auris, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis (including QC strains C. krusei ATCC 6258 and C. parapsilosis ATCC 22019) • Two isolates of Cryptococcus neoformans var. grubii • Two isolates each of Aspergillus flavus species complex, Aspergillus fumigatus, Aspergillus nidulans species complex, Aspergillus niger species complex, and Aspergillus terreus. • Two Aspergillus QC strains (A. flavus ATCC 204304 and A. fumigatus ATCC MYA-3626) • Two Fusarium spp. isolates (1 Fusarium solani species complex, and 1 Fusarium annulatum) • Two Mucorales isolates (1 Mucor circinelloides / ramosissimus, 1 Rhizopus spp.) PATENT ATTORNEY DOCKET NO: 51336-014WO2 Susceptibility testing Isolates were susceptibility tested using the CLSI broth microdilution method as described in the reference CLSI documents M27 (2017) for yeasts and M38 (2017) for filamentous fungi. Fresh frozen- form panels were prepared on the day of testing. MFC values were assessed by plating 100 µL of the broth content from the MIC well and those five log2 dilutions above the MIC (100% inhibition) for each organism (including the four QC strains) onto appropriate agar growth media. Negative well sampling was performed after 24 hours incubation for Candida spp., and Mucorales, after 48 hours incubation for Aspergillus spp. and Fusarium, and after 72 hours incubation for Cryptococcus. Quantitative colony counts were performed on the initial inoculum. The lowest concentration of each compound that kills ≥99.9% of the starting test inoculum is defined as the MFC endpoint (Moody and Knapp, 2004). Antifungal agents tested Table 11 summarizes the test articles and their corresponding concentration ranges that were tested in the MFC assay. Table 11. Summary of test articles used in the MFC assays. Test Article Concentration Ranges Used (mg / L) Amphotericin B 0.03 – 16 mg / L Compound 1 0.008 – 16 mg / L Nano-10 0.008 – 16 mg / L Nano-19 0.008 – 16 mg / L Nano-13 0.008 – 16 mg / L Quality control Quality control (QC) was performed as recommended in M27M44S and M38M51S CLSI documents using the following strains and inoculum density monitored by colony counts: C. parapsilosis ATCC 22019, C. krusei ATCC 6258, A. flavus ATCC 204304 (mold testing only), A. fumigatus ATCC MYA-3626 (mold testing only). MFC assay results The MFC values were determined for all the antifungal agents in the appropriate agar growth media after 24 hours of incubation at 35°C and re-incubated for additional 24 hours if no growth is observed. The MFC data is summarized in Table 12. The data show the three nanoparticulate formulations (Nano-10, Nano-19, and Nano-13) are generally superior at killing the tested fungus species compared to AmpB and Compound 1, with the exception of Nano-13 against A. niger, Nano-10 and Nano-19 against A. terreus, and Nano-10 and Nano-19 against A. nidulans, which all had comparable or equivalent MFC values with respect to AmpB and Compound 1. PATENT ATTORNEY DOCKET NO: 51336-014WO2 Table 12. Summary of MFC values (in mg / L) of antifungal agents against various fungal species. Compound Isolate AmpB Nano-10 Nano-19 Nano-13 1 C. albicans 1 1 0.06 0.06 0.06 C. glabrata 1 1 0.12 0.12 0.06 C. parapsilosis 1 1 0.12 0.12 0.06 C. tropicalis 1 1 0.03 0.06 0.06 C. krusei 1 1 0.12 0.25 0.12 C. auris 1 1 0.06 0.12 0.06 A. fumigatus 2 1 0.25 0.5 0.25 A. flavus 1 1 0.25 0.25 0.12 A. niger 0.25 0.25 0.12 0.12 0.25 A. terreus >16 8 8 16 4 A. nidulans 0.12 0.25 0.12 0.25 0.06

[0003] PATENT ATTORNEY DOCKET NO: 51336-014WO2 Other Embodiments While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure come within known or customary practice within the art to which the invention pertains and may be applied to the essential features hereinbefore set forth. All publications, patents, and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference in its entirety. Some embodiments are within the following numbered paragraphs. 1. An acid addition salt form of a compound of formula (I): wherein the acid addition salt form is an oleate salt. 2. An acid addition salt form of a compound of formula (I): wherein the acid addition salt form is a decanoate salt. PATENT ATTORNEY DOCKET NO: 51336-014WO2 3. An acid addition salt form of a compound of formula (I): wherein the acid addition salt form is a docusate salt. 4. An acid addition salt form of a compound of formula (I): wherein the acid addition salt form is an octanoate salt. 5. An acid addition salt form of a compound of formula (I): wherein the acid addition salt form is a dodecylbenzenesulfonate salt. PATENT ATTORNEY DOCKET NO: 51336-014WO2 6. An acid addition salt form of Compound 1: Compound 1, wherein the acid addition salt form is an oleate salt. 7. An acid addition salt form of Compound 1: Compound 1, wherein the acid addition salt form is a decanoate salt. 8. An acid addition salt form of Compound 1: Compound 1, wherein the acid addition salt form is a docusate salt. PATENT ATTORNEY DOCKET NO: 51336-014WO2 9. An acid addition salt form of Compound 1: Compound 1, wherein the acid addition salt form is an octanoate salt. 10. An acid addition salt form of Compound 1: Compound 1, wherein the acid addition salt form is a dodecylbenzenesulfonate salt. 11. A pharmaceutical composition including an acid addition salt form of any one of paragraphs 1-10 and a carrier, a diluent, or an excipient. 12. A pharmaceutical composition including: (i) an oleate salt form of a compound of formula (I): (ii) a carrier, a diluent, or an excipient. PATENT ATTORNEY DOCKET NO: 51336-014WO2 13. A pharmaceutical composition including: (i) a decanoate salt form of a compound of formula (I): (ii) a carrier, a diluent, or an excipient. 14. A pharmaceutical composition including: (i) a docusate salt form of a compound of formula (I): (ii) a carrier, a diluent, or an excipient. 15. A pharmaceutical composition including: (i) an octanoate salt form of a compound of formula (I): (ii) a carrier, a diluent, or an excipient. PATENT ATTORNEY DOCKET NO: 51336-014WO2 16. A pharmaceutical composition including: (i) a dodecylbenzenesulfonate salt form of a compound of formula (I): (ii) a carrier, a diluent, or an excipient. 17. A pharmaceutical composition including: (i) an oleate salt form of Compound 1: Compound 1, and (ii) a carrier, a diluent, or an excipient. 18. A pharmaceutical composition including: (i) a decanoate salt form of Compound 1: Compound 1, and (ii) a carrier, a diluent, or an excipient. PATENT ATTORNEY DOCKET NO: 51336-014WO2 19. A pharmaceutical composition including: (i) a docusate salt form of Compound 1: Compound 1, and (ii) a carrier, a diluent, or an excipient. 20. A pharmaceutical composition including: (i) an octanoate salt form of Compound 1: Compound 1, and (ii) a carrier, a diluent, or an excipient. 21. A pharmaceutical composition including: (i) a dodecylbenzenesulfonate salt form of Compound 1: Compound 1, and (ii) a carrier, a diluent, or an excipient. PATENT ATTORNEY DOCKET NO: 51336-014WO2 22. The pharmaceutical composition of any one of paragraphs 11-21, wherein the pharmaceutical composition is in the form of a nanoparticle. 23. A nanoparticle including a compound of formula (I): or a pharmaceutically acceptable salt thereof, and a TPGS compound. 24. A nanoparticle including Compound 1: Compound 1, or a pharmaceutically acceptable salt thereof, and a TPGS compound. 25. The nanoparticle of paragraphs 22-24, further including a polymeric carrier. 26. The nanoparticle of paragraph 25, wherein the polymeric carrier is a poly(lactic-co-glycolic acid) (PLGA). 27. An aqueous suspension including a nanoparticle of any one of paragraphs 22-26 and an aqueous carrier. 28. The aqueous suspension of paragraph 27, wherein the aqueous carrier is a pharmaceutically acceptable carrier. PATENT ATTORNEY DOCKET NO: 51336-014WO2 29. A method of treating a fungal infection in a subject, the method including administering to the subject an oleate salt of a compound of formula (I): in an amount that is effective for the treatment of the fungal infection. 30. A method of treating a fungal infection in a subject, the method including administering to the subject a decanoate salt of a compound of formula (I): in an amount that is effective for the treatment of the fungal infection. 31. A method of treating a fungal infection in a subject, the method including administering to the subject a docusate salt of a compound of formula (I): in an amount that is effective for the treatment of the fungal infection. PATENT ATTORNEY DOCKET NO: 51336-014WO2 32. A method of treating a fungal infection in a subject, the method including administering to the subject an octanoate salt of a compound of formula (I): in an amount that is effective for the treatment of the fungal infection. 33. A method of treating a fungal infection in a subject, the method including administering to the subject a dodecylbenzenesulfonate salt of a compound of formula (I): in an amount that is effective for the treatment of the fungal infection. 34. The method of any one of paragraphs 29-33, wherein the compound of formula (I) is Compound 1: PATENT ATTORNEY DOCKET NO: 51336-014WO2 35. A method of treating a fungal infection in a subject, the method including administering to the subject a compound of formula (I): in an amount that is effective for the treatment of the fungal infection, wherein the method includes administering to the subject an acid addition salt form of any one of paragraphs 1-10, a pharmaceutical composition of any one of paragraphs 11-22, a nanoparticle of any one of paragraphs 23-26, or an aqueous suspension of paragraph 27 or 28. 36. The method of paragraph 35, wherein the compound of formula (I) is Compound 1: Compound 1. 37. The method of any one of paragraphs 29-36, wherein the administration is pulmonary (e.g., by inhalation), intravenous, oral, or intranasal administration. 38. A method of forming nanoparticles, including the steps of: (i) providing an acid addition salt form from any one of paragraphs 1-10, PLGA, and a TPGS compound in an organic solvent; (ii) adding deionized water; and (iii) quenching the solution of (ii) with aqueous saline. 39. The method of paragraph 38, wherein the TPGS compound in step (i) is alpha-tocopherol TPGS. 40. The method of paragraph 38 or 39, wherein the nanoparticles are formed using micromixing. PATENT ATTORNEY DOCKET NO: 51336-014WO2 41. The method of any one of paragraphs 38-40, wherein the deionized water of step (ii) includes Pluronic F-68. 42. The method of any one of paragraphs 38-40, wherein the deionized water of step (ii) includes Pluronic F-127. 43. The method of any one of paragraphs 38-40, wherein step (i) includes the oleate salt form and alpha-tocopherol TPGS. 44. The method of any one of paragraphs 38-40, wherein step (i) includes the decanoate salt form and alpha-tocopherol TPGS. 45. The method of any one of paragraphs 38-40, wherein step (i) includes the docusate salt form and alpha-tocopherol TPGS. 46. The method of any one of paragraphs 38-40, wherein step (i) includes the octanoate salt form and alpha-tocopherol TPGS. 47. The method of any one of paragraphs 38-40, wherein step (i) includes the dodecylbenzenesulfonate salt form and alpha-tocopherol TPGS. Other embodiments are within the following claims. What is claimed is:

Claims

PATENT ATTORNEY DOCKET NO: 51336-014WO2 CLAIMS 1. An acid addition salt form of a compound of formula (I):wherein the acid addition salt form is an oleate salt.

2. An acid addition salt form of a compound of formula (I):wherein the acid addition salt form is a decanoate salt.

3. An acid addition salt form of a compound of formula (I):wherein the acid addition salt form is a docusate salt.PATENT ATTORNEY DOCKET NO: 51336-014WO2 4. An acid addition salt form of a compound of formula (I):wherein the acid addition salt form is an octanoate salt.

5. An acid addition salt form of a compound of formula (I):wherein the acid addition salt form is a dodecylbenzenesulfonate salt.

6. The acid addition salt form of any one of claims 1-5, wherein the compound of formula (I) is Compound 1:Compound 1.

7. A pharmaceutical composition comprising an acid addition salt form of any one of claims 1-6 and a carrier, a diluent, or an excipient.PATENT ATTORNEY DOCKET NO: 51336-014WO2 8. A pharmaceutical composition comprising: (i) an oleate, decanoate, docusate, octanoate, or dodecylbenzenesulfonate salt form of a compound of formula (I):(ii) a carrier, a diluent, or an excipient.

9. The pharmaceutical composition of claim 8, wherein the compound of formula (I) is Compound 1:Compound 1.

10. A pharmaceutical composition of any one of claims 7-9, wherein the pharmaceutical composition is in the form of a nanoparticle.

11. A nanoparticle comprising a compound of formula (I):or a pharmaceutically acceptable salt thereof, and a TPGS compound.PATENT ATTORNEY DOCKET NO: 51336-014WO2 12. A nanoparticle comprising Compound 1:Compound 1, or a pharmaceutically acceptable salt thereof, and a TPGS compound.

13. The nanoparticle of claim 11 or 12, further comprising a polymeric carrier.

14. The nanoparticle of claim 13, wherein the polymeric carrier is a poly(lactic-co-glycolic acid) (PLGA).

15. An aqueous suspension comprising a nanoparticle of any one of claims 11-14 and an aqueous carrier.

16. The aqueous suspension of claim 15, wherein the aqueous carrier is a pharmaceutically acceptable carrier.

17. A method of treating a fungal infection in a subject, the method comprising administering to the subject an oleate, decanoate, docusate, octanoate, or dodecylbenzenesulfonate salt of a compound of formula (I):in an amount that is effective for the treatment of the fungal infection.PATENT ATTORNEY DOCKET NO: 51336-014WO2 18. A method of treating a fungal infection in a subject, the method comprising administering to the subject a compound of formula (I):in an amount that is effective for the treatment of the fungal infection, wherein the method comprises administering to the subject an acid addition salt form of any one of claims 1-6, a pharmaceutical composition of any one of claims 7-10, a nanoparticle of any one of claims 11-14, or an aqueous suspension of claim 15 or 16.

19. The method of claim 17 or 18, wherein the administration is pulmonary, intravenous, oral, or intranasal administration.

20. A method of forming nanoparticles, comprising the steps of: (i) providing an acid addition salt form from any one of claims 1-6, PLGA, and a TPGS compound in an organic solvent; (ii) adding deionized water; and (iii) quenching the solution of (ii) with aqueous saline.

21. The method of claim 20, wherein the nanoparticles are formed using micromixing.

22. The method of claim 21, wherein the deionized water of step (ii) comprises Pluronic F-68 or Pluronic F-127.

23. The method of claim 20, wherein step (i) comprises the oleate salt form and alpha-tocopherol TPGS.

24. The method of claim 20, wherein step (i) comprises the decanoate salt form and alpha-tocopherol TPGS.

25. The method of claim 20, wherein step (i) comprises the docusate salt form and alpha-tocopherol TPGS.

26. The method of claim 20, wherein step (i) comprises the octanoate salt form and alpha-tocopherol TPGS.PATENT ATTORNEY DOCKET NO: 51336-014WO2 27. The method of claim 20, wherein step (i) comprises the dodecylbenzenesulfonate salt form and alpha-tocopherol TPGS.

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