Crystalline forms of 5-(tetradecyloxy)furan-2-carboxylic acid and salts thereof

Abstract

Provided herein are polymorphs and their salts, methods of making these, compositions and pharmaceutical compositions containing these, kits containing these, and method of treating disease or conditions in a subject with the polymorphs, their salts, and compositions and pharmaceutical compositions containing these.

Description

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of, and priority to, U.S. Provisional Application No. 63 / 625,810, filed January 26, 2024, which is incorporated by reference in its entirety. SUMMARY Provided herein are crystalline forms of 5-(tetradecyloxy)furan-2-carboxylic acid, which has the chemical structure: , and salts thereof.

[0002] Provided herein is a crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid exhibiting X-ray lines (2-theta value

[0003] s) in a powder diffraction pattern when measured using Cu Ka radiation at 4.5, 9.0, 13.6 and 23.8.

[0004] The crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 5.6, 6.1, 10.4, 11.3, 17.9, 18.1, 19.2, 19.5, 19.7, 20.8,21.6, 22.3,22.7, 24.6, 27.3, 28.0, 28.1, 32.0, 32.5 and / or 37.0.

[0005] Further provided herein is a crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.1, 6.1, 9.2, 12.2 and 18.6.

[0006] The crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.2, 8.3. 12.2, 12.5, 15.2, 16.0, 19.1, 20.3, 21.4, 22.8, 24.9, 25.5. 27.1. 28.3, 28.9, 29.5, 30.8, 30.9, 32.9, 33.9. 34.0. 37.1. 37.2 and / or 38.0.

[0007] Additionally provided herein is crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.6, 8.6, 10.2, and 19.2.

[0008] The cry stalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate of can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 13.9, 15.6, 17.3, 23.7 and / or 28.1.

[0009] Also provided herein is a crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.4, 5.0, 7.5, 10.1 and 24.0.

[0010] The crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 8.9, 9.2, 12,4, 14.9, 17.5, 19.0, 19.1, 19.5, 20.0, 21.1, 22.5, 23.7, 25.0, 25.5, 27.0, 27.6, 29.5, 30.1, 31.8 and / or 31.9.

[0011] The crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.0, 9.0, 11.0, 12.1, 12.6, 13.6, 14.6, 15.1, 15.7, 16.9, 18.2, 19.4, 19.9, 20.3, 20.8, 21.1, 21.7, 22.1, 22.9, 23.8, 24.9, 25.8, 26.6, 27.3, 27.7, 28.9, 30.4, 33.5, 35.0, 36.7, 37.6 and / or 38.3.

[0012] Further provided herein is a solid pharmaceutical composition comprising i) a cry stalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.5, 9.0, 13.6 and 23.8 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0013] In the solid pharmaceutical composition, the crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 5.6, 6.1, 10.4, 11.3, 17.9, 18.1, 19.2, 19.5, 19.7, 20.8, 21.6, 22.3, 22.7, 24.6, 27.3, 28.0, 28.1, 32.0, 32.5 and / or 37.0.

[0014] Additionally provided herein is a solid pharmaceutical composition comprising i) a crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.1, 6.1, 9.2, 12.2 and 18.6 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0015] In the solid pharmaceutical composition the crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 can further exhibit at least one additional X-ray7 line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.2, 8.3, 12.2, 12.5, 15.2, 16.0, 19.1, 20.3, 21.4, 22.8, 24.9, 25.5. 27.1, 28.3, 28.9, 29.5, 30.8, 30.9, 32.9, 33.9, 34.0. 37.1, 37.2 and / or 38.0.

[0016] Also provided herein is a solid pharmaceutical composition comprising i) the cry stalline the Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.6, 8.6. 10.2, and 19.2 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0017] In the solid pharmaceutical composition, the crystalline the Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 13.9, 15.6, 17.3, 23.7 and / or 28.1.

[0018] Additionally provided herein is a solid pharmaceutical composition comprising i) the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.4, 5.0. 7.5, 10.1 and 24.0 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0019] In the solid pharmaceutical composition, the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 8.9, 9.2, 12,4, 14.9, 17.5, 19.0, 19.1, 19.5, 20.0, 21.1, 22.5, 23.7, 25.0, 25.5, 27.0, 27.6, 29.5, 30.1, 31.8 and / or 31.9.

[0020] Further provided herein is a solid pharmaceutical composition comprising i) the crystalline Type 1 salt of L-arginimum 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.0, 4.5, 23.5 and 24.6 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0021] In the solid pharmaceutical composition, the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.0, 9.0, 11.0, 12.1, 12.6, 13.6, 14.6, 15.1, 15.7, 16.9, 18.2, 19.4, 19.9, 20.3, 20.8, 21.1, 21.7, 22.1, 22.9, 23.8, 24.9, 25.8, 26.6, 27.3, 27.7, 28.9, 30.4, 33.5, 35.0. 36.7. 37.6 and / or 38.3.

[0022] Any solid pharmaceutical composition herein can be in unit dose form.

[0023] Any solid pharmaceutical composition can be administered concurrently or consecutively with a second therapy or a salt thereof.

[0024] In some instances, the second therapeutic or the salt thereof is a Glucagon-like peptide-1 (GLP-1) receptor agonist.

[0025] In some cases, the second therapeutic or the salt thereof is a Glucose-dependent insulinotropic polypeptide (GiP) agonist.

[0026] In some embodiments, the second therapeutic or the salt thereof is a glucagon receptor (GCGP) agonist.

[0027] In some instances, the second therapeutic or the salt thereof is a GIP-1 receptor agonist and a GiP receptor agonist.

[0028] In some cases, the second therapeutic or the salt thereof is a GIP-1 receptor agonist, a GLP receptor agonist, and a GCGP agonist.

[0029] In some cases, the second therapeutic is tirzepatide or a salt thereof.

[0030] In some embodiments, the second therapeutic is dulaglutide or a salt thereof, exenatide or a salt thereof, semaglutide or a salt thereof, liraglutide or a salt thereof, or lixisenatide or a salt thereof, or an incretin analog or a salt thereof.

[0031] Also provided herein is a kit comprising any solid pharmaceutical composition herein and a container.

[0032] Also provided herein is a method of making a crystalline Type 1 salt of Mg2+(5- (tetradecyloxy)furan-2-carboxylate)2, the method comprising: combining a 5-(tetradecyloxy)furan-2-carboxylic acid with a solvent comprising a tetrahydrofuran and a water in an about a 2:1 (volume : volume) ratio to form a first suspension; combining a magnesium hydroxide (Mg(0H)2), in a molar ratio of about 1:2 of the 5-(tetradecyloxy)furan-2-carboxylic acid to the Mg(OH)2. with the first suspension to form a second suspension at about 20 to about 22 degrees C; stirring the second suspension for about 24 hours at about 5 degrees C to form a precipitate comprising the Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2; and optionally isolating the precipitate comprising the Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2; thereby forming the crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2.

[0033] Further provided herein is a crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 made by the process(es) disclosed herein.

[0034] Also provided herein is a method of making a crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate, the method comprising: combining a 5-(tetradecyloxy)furan-2-carboxylic acid with a methyl lert-butyl ether (MTBE) to form a first suspension; combining a lysine, in a molar ratio of about 1:2 of the L-lysine to the 5-(tetradecyloxy )furan-2-carboxylic acid, with the first suspension to form a second suspension at about 20 to about 22 degrees C; stirring the second suspension for about 24 hours at about 5 degrees C to form a precipitate comprising the crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate; and optionally isolating the precipitate comprising the crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate; thereby forming the crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate.

[0035] Also provided is a crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate made by the process(es) provided herein.

[0036] Additionally provided is a method of making a crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2, the method comprising: combining a 5-(tetradecyloxy)furan-2-carboxylic acid with an ethanol to form a first suspension; combining a zinc hydrochloride, in a molar ratio of about 1:2 of the 5-(tetradecyloxy)furan-2-carboxylic acid to the zinc hydroxide, with the first suspension to form a second suspension at about 20 to about 22 degrees C; stirring the second suspension for about 24 hours at about 5 degrees C to form a precipitate comprising the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2; and optionally isolating the precipitate comprising the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2; thereby forming the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2.

[0037] Additionally provided is a cry stalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 made by the process(es) provided herein.

[0038] Further provided is a method of making a crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate, the method comprising: combining a 5-(tetradecyloxy)furan-2-carboxylic acid with a methyl tert-buty l ether (MTBE) to form a first suspension; combining L-arginine. in a molar ratio of about 1:1 of the L-arginine to the 5-(decyloxy)furan-2-carboxylic acid, with the first suspension to form a second suspension at about 20 to about 22 degrees C; stirring the second suspension for about 24 hours at about 5 degrees C to form a precipitate comprising the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate; and optionally isolating the precipitate comprising the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate; thereby forming the cry stalline Type 1 salt of L-argininium 5-(tetradecy loxy)furan-2-carboxylate.

[0039] Further provided is a crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate formed by the process(es) herein.

[0040] Additionally provided herein is a method of treating a disease of condition in a subject, which can be a subject in need thereof, the method comprising administering an effective amount of a crystalline Form A of 5-(tetradecyloxy )furan-2-carboxylic acid exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.5, 9.0, 13.6 and 23.8 to the subject, thereby treating the disease or condition in the subject.

[0041] Also provided is a method of treating a disease or condition in a subject, which can be a subject in need thereof, the method comprising administering an effective amount of a crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.1, 6.1, 9.2, 12.2 and 18.8 to the subject, thereby treating the disease or condition in the subject.

[0042] Further provided is a method of treating a disease or condition in a subject, which can be a subject in need thereof, the method comprising administering an effective amount of a crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.6, 8.6, 10.2, and 19.2 to the subject, thereby treating the disease or condition in the subject.

[0043] Additionally provided is a method of treating a disease or condition in a subject, which can be a subject in need thereof, the method comprising administering an effective amount of a crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.4, 5.0, 7.5, 10.1 and 24.0 to the subject, thereby treating the disease or condition in the subject.

[0044] Also provided is a method of treating a disease or condition in a subject, which can be a subject in need thereof, the method comprising administering an effective amount of a crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.0, 4.5, 23.5 and 24.6 to the subject, thereby treating the disease or condition in the subject.

[0045] In some embodiments, the subject is a subject in need thereof.

[0046] In some cases, the subject or the subject in need thereof is a mammal.

[0047] In some instances, the mammal is a human.

[0048] In some embodiments, the effective amount ranges from about 0.00001 mg to about 25,000 mg.

[0049] In some instances, the administering is: once per day, twice per day, three times per day, four times per day, daily, weekly, bi-weekly, monthly, quarterly, semi-annually, annually, for life, or as needed.

[0050] In some cases, the disease or condition comprises a hepatic disease, a nonalcoholic fatty liver disease (NAFLD), a cirrhotic nonalcoholic steatohepatitis (NASH), a metabolic disorder, a -6- metabolic syndrome, an insulin resistance, a hyperglycemia, a type 2 diabetes mellitus, an obesity, a fatty liver disease, a glucose intolerance, a hyperinsulinemia, a metabolic syndrome, a hypertension, or any combination thereof.

[0051] In some embodiments, the administering is an oral administration, a nasal administration, an inhalation administration, an anal administration, an intraduodenal administration, a rectal administration, a topical administration or any combination thereof. INCORPORATION BY REFERENCE

[0052] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawing of which: FIG. 1 shows XRPD data of the crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid which has the chemical structure: FIG. 2A shows an XRPD overlay of reference freebase Type 1 (starting material) (8906062-01-A), reference magnesium hydroxide, reference magnesium salt Type 1 (6050791-04-12F), and magnesium salt Type 1 scale-up (8906062-04-Al). FIG. 2B shows a TGA / DSC of reference magnesium salt Type 1 (6050791-04-12F), and magnesium salt Type 1 scale-up (8906062-04-Al). FIG. 2C shows a PLM image of magnesium salt Type 1 scale-up (8906062-04-Al). FIG. 2D shows a DVS isotherm plot of magnesium salt Type 1 scale-up (8906062-04-Al), SO-95-0-95% RH. FIG. 2E shows an XRPD of magnesium salt Type 1 scale-up (8906062-04-Al) pre and post-DVS. FIG. 2F shows an XRPD overlay of the impact of grinding on magnesium salt Type 1 (8906062-04-A1). FIG. 3 A shows XRPD overlay of reference freebase Type 1 (starting material) (8906062-01-A), reference zinc hydroxide, reference zinc salt Type 1 (6050791-04-3A), and zinc salt Type 1 scale-up (8906062-04-A2). FIG. 3B shows a TGA / DSC of reference zinc salt Type 1 (6050791-04-4A), and zinc salt Type 1 scale-up (8906062-04-A2). FIG. 3C shows a PLM image of zinc salt Type 1 scale-up (8906062-04-A2). FIG. 3D shows a PLM image of zinc salt Type 1 scale-up (8906062-04-A2). FIG. 3E shows an XRPD of zinc salt Type 1 scale-up (8906062-04-A2) pre and post-DVS. FIG. 3F shows an XRPD overlay of the impact of grinding on zinc salt Type 1 (8906062-04- A2). FIG. 4A shows an XRPD overlay of reference freebase Type 1 (starting material) (8906062-01-A). reference arginine hydroxide, reference arginine salt Type 1 (6050791-04-12F), and arginine salt Type 1 scale-up (8906062-04-A3). FIG 4B shows a TGA / DSC of reference arginine salt Type 1 (6050791-04-12F), and arginine salt Type 1 scale-up (8906062-04-A3). FIG. 4C shows a PLM image of arginine salt Type 1 scale-up (8906062-04-A3). FIG. 4D shows a DVS isotherm plot of arginine salt Type 1 scale-up (8906062-04-A3), 50-95-095% RH. FIG. 4E shows an XRPD of arginine salt Type 1 scale-up (8906062-04-A3) pre and post-DVS. FIG. 4F shows an XRPD overlay of the impact of grinding on arginine salt Type 1 (8906062-04-A3). FIG. 5A shows an XRPD overlay of reference freebase Type 1 (starting material) (8906062-01-A), reference lysine hydroxide, reference lysine salt Type 1 (6050791-04-12F), and lysine salt Type 1 scale-up (8906062-04-A5). FIG. 5B shows a TGA / DSC of reference lysine salt Type 1 (6050791-04-10F), and lysine salt Type 1 scale-up (8906062-04-A5). FIG. 5C shows a PLM image of lysine salt Type 1 scale-up (8906062-04-A5). FIG. 5D shows a DVS isotherm plot of lysine salt Type 1 scale-up (8906062-04-A5), 50-95-095%. FIG. 5E shows an XRPD of lysine salt Type 1 scale-up (8906062-04-A5) pre and post-DVS. FIG. 5F shows an XRPD overlay of the impact of grinding on arginine salt Type 1 (8906062-04- A3). FIG. 6 shows Chromatogram and calibration curve of freebase (5-(tetradecyloxy)furan-2-carboxylic acid) Type 1 standards. DETAILED DESCRIPTION

[0054] Overview

[0055] Polymorphs and their salts herein can have advantages including at least one of: ease of formulation, increase in stability of the polymorph and / or a composition or pharmaceutical composition containing the polymorph, a more favorable dissolution profile, increased bioavailability, or any combination thereof. Provided herein are polymorphs and their salts, methods of making these, compositions and pharmaceutical compositions containing these, kits containing these, and methods of treating disease or conditions in a subject with the polymorphs, their salts, and compositions and pharmaceutical compositions containing these.

[0056] Definitions

[0057] Throughout this application, various aspects may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0058] As used herein, the term ‘about’ a number can refer to that number plus or minus 10% or plus or minus 5% of that number. The term ‘about’ a range can refer to that range minus 10% of its lowest value and plus 10% of its greatest value. The term ‘about’ a range can refer to that range minus 5% of its lowest value and plus 5% of its greatest value.

[0059] As used in the specification and claims, the singular forms “a’’, “an’’ and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a sample” includes a plurality of samples, including mixtures thereof.

[0060] Unless otherwise indicated, open terms for example “contain,” “containing,” “include,” “including,” and the like mean comprising.

[0061] The terms “determining”, “measuring”, “evaluating”, “assessing,” “assaying,” and “analyzing” are often used interchangeably herein to refer to forms of measurement and include determining if an element may be present or not (for example, detection). These terms may include quantitative and / or qualitative determinations. Assessing may be alternatively relative or absolute. “Detecting the presence of’ includes determining the amount of something present, as well as determining whether it may be present or absent.

[0062] The terms “subject,” “individual,” or “patient” are often used interchangeably herein. A “subject” may be a biological entity. The biological entity7 may be a plant, animal, or a microorganism, including, for example, a eukaryotic cell, a bacteria, a virus, a fungi, and a protozoa. The subject may be tissues, cells and their progeny of a biological entity obtained in vivo or cultured in vitro. The subject may be a mammal. The mammal may be a human. The subject may be diagnosed or suspected of being at high risk for a disease. In some cases, the subject may not be necessarily diagnosed or suspected of being at high risk for the disease. In some cases, the subject may be healthy (e.g., the subject may not have a significant disease). In some cases, a subject can be a child or an adult. In some cases, a subject can be about 1 day of age to about 18 years of age, 1 day of age to about 120 years of age, 18 years of age to about 120 years of age, 40 years to age to about 80 years of age, or 60 years of age to about 120 years of age.

[0063] The term “at least partially” may refer to a qualitative condition that exhibits a partial range or degree of a feature or characteristic of interest. For example, at least partially can comprise a partial range or degree of a feature or characteristic of interest that is at least about: 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% of the feature or characteristic.

[0064] As used herein, the terms “treatment” or “treating” are used in reference to a pharmaceutical or other intervention regimen for obtaining beneficial or desired results in the recipient. Beneficial or desired results include but are not limited to a therapeutic benefit and / or a prophylactic benefit. A therapeutic benefit may refer to eradication or amelioration of symptoms or of an underlying disorder being treated. Also, a therapeutic benefit may be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement may be observed in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. A prophylactic effect includes delaying, preventing, or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof. For a prophylactic benefit, a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease may undergo treatment, even though a diagnosis of this disease may not have been made.

[0065] A “therapeutically effective amount” refers to an amount of a composition or pharmaceutical composition as disclosed herein with or without additional agents that is effective to achieve its intended purpose, for example to treat a disease. Individual patient needs may vary. Generally, the dosage required to provide an effective amount of the composition will vary, depending on the age, health, physical condition, sex, weight, extent of the disease of the recipient, frequency of treatment and the nature and scope of the disease or condition.

[0066] As used herein, a “dose” can refer to a measured quantity of a therapeutic agent to be taken at one time.

[0067] As used herein, the term “unit dose” or “dosage form” may be used interchangeably and may be meant to refer to pharmaceutical drug products in the form in which they are marketed for use. with a specific mixture of active ingredients and inactive components or excipients, in a particular configuration, and apportioned into a particular dose to be delivered. The term “unit dose” may also sometimes encompass non-reusable packaging. More than one unit dose may refer to distinct pharmaceutical drug products packaged together, or to a single pharmaceutical drug product containing multiple drugs and / or doses. Types of unit doses may vary with the route of administration for drug delivery, and the substance(s) being delivered. A solid unit dose may be the solid form of a dose of a chemical compound used as a pharmaceutically acceptable drug or medication intended for administration or consumption.

[0068] The term “substantially” or “essentially” can refer to a qualitative condition that exhibits an entire or nearly total range or degree of a feature or characteristic of interest. In some cases, substantially can refer to a total range or degree of a feature or characteristic of interest by about plus or minus: 1%, 2%, 3%, 4%, 5%, 6%. 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%. 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%. 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%. 44%, 45%. 46%. 47%. 48%. 49%. 50%. 51%. 52%. 53%. 54%. 55%. 56%. 57%. 58%. 59%. 60%. 61%. 62%. 63%. 64%, 65%, 66%, 67%, 68%, 69%. 70%, 71%, 72%, 73%, 74%, 75%, 76%. 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. In some cases, substantially can refer to at least about: 70%, 75%. 80%. 85%. 90%. 95%. 99%. or 100% of the total range or degree of a feature or characteristic of interest.

[0069] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0070] As used herein, reference to a therapy, a compound, or a composition, includes reference to any salt, solvate, ester, or polymorph of the therapy, the compound, or the composition. A “salt” can include a pharmaceutically acceptable salt. -11-

[0071] In some embodiments, the pharmaceutically acceptable salts include, but are not limited to, metal salts such as sodium salt, potassium salt, cesium salt and the like; alkaline earth metals such as calcium salt, magnesium salt and the like; organic amine salts such as triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt and the like; inorganic acid salts such as hydrochloride, hydrobromide, phosphate, sulphate and the like; organic acid salts such as citrate, lactate, tartrate, maleate, fumarate, mandelate, acetate, dichloroacetate, trifluoroacetate, oxalate, formate and the like; sulfonates such as methanesulfonate, benzenesulfonate, p- toluenesulfonate and the like; and amino acid salts such as arginate, asparginate, glutamate and the like. In some instances, a salt of a polypeptide or derivative thereof or a compound can be a Zwitterionic salt.

[0072] In some embodiments, a pharmaceutical composition comprising the salt of the pharmaceutically active ingredient can comprise an organic salt or an inorganic salt. In some cases, an organic salt may comprise a phosphinate (e.g., sodium hypophosphite), a hydrazinium salt, a urate, a diazonium salt, an oxalate salt, a tartrate, a choline chloride. An example of an inorganic salt may be sodium chloride, calcium chloride, magnesium chloride, sodium bicarbonate, potassium chloride, sodium sulfate, calcium carbonate, calcium phosphate, or any combination thereof. In some cases, a salt comprises an HC1 salt, an ascorbic acid salt, a mandelic acid salt, an aspartic acid salt, a carbonic acid salt, a citric acid salt, a formic acid salt, a glutamic acid salt, a lactic acid salt, a lauric acid salt, a maleic acid salt, a borate salt, a bitartrate salt, a palmitic acid salt, a phosphoric acid salt, or any combination thereof.

[0073] In some embodiments, a composition can comprise an excipient, a carrier, and / or a diluent. In some embodiments, an excipient, a carrier, and / or a diluent can be a pharmaceutically acceptable excipient, carrier, and / or diluent. In some embodiments, a composition herein can comprise one or more of the following excipients: acacia, acesulfame potassium, acetic acidglacial. acetone, acetyltributyl citrate, acetyltriethyl citrate, adipic acid, agar, albumin, alcohol, alginic acid, aliphatic polyesters, alitame, almond oil, alpha tocopherol, aluminum hydroxide adjuvant, aluminum monostearate, aluminum oxide, aluminum phosphate adjuvant, ammonia solution, ammonium alginate, ammonium chloride, ascorbic acid, ascorbyl palmitate, aspartame, attapulgite, bentonite, benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, benzyl benzoate, boric acid, bronopol, butylated hydroxyanisole, butylated hydroxytoluene, butylene glycol, butylparaben, calcium acetate, calcium alginate, calcium carbonate, calcium chloride, calcium hydroxide, calcium lactate, calcium phosphate-dibasic anhydrous, calcium phosphate-dibasic dihydrate, calcium phosphate-tribasic. calcium silicate, calcium stearate, calcium sulfate, canola oil. carbomer, carbon dioxide, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carrageenan, castor oil, castor oil-hydrogenated, cellulose-microcrystalline, cellulose-microcrystalline and carboxymethylcellulose sodium, cellulose-powdered, cellulose-silicified microcrystalline, cellulose acetate, cellulose acetate phthalate, ceratonia, ceresin, cetostearyl alcohol, cetrimide. cetyl alcohol, cetylpyridinium chloride, chitosan, chlorhexidine, chlorobutanol, chlorocresol, chlorodifluoroethane (hcfc), chlorofluorocarbons (cfc), chloroxylenol, cholesterol, citric acid monohydrate, coconut oil, colloidal silicon dioxide, coloring agents, copovidone, com oil, com starch and pregelatinized starch, cottonseed oil, cresol, croscarmellose sodium, crospovidone, cyclodextrins, cyclomethicone, denatonium benzoate, dextrates, dextrin, dextrose, dibutyl phthalate, dibutyl sebacate, diethanolamine, diethyl phthalate, difluoroethane (hfc), dimethicone, dimethyl ether, dimethyl phthalate, dimethyl sulfoxide, dimethylacetamide, disodium edetate, docusate sodium, edetic acid, erythorbic acid, erythritol, ethyl acetate, ethyl lactate, ethyl maltol, ethyl oleate, ethyl vanillin, ethylcellulose, ethylene glycol stearates, ethylene vinyl acetate, ethylparaben, fructose, fumaric acid, gelatin, glucose—liquid, glycerin, glyceryl behenate, glyceryl monooleate, glyceryl monostearate, glycetyl palmitostearate, glycine, glycofurol, guar gum, hectorite, heptafluoropropane (hfc), hexetidine, hydrocarbons (he), hydrochloric acid, hydrophobic colloidal silica, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl betadex, hydroxypropyl cellulose, hydroxypropyl cellulose-low-substituted, hydroxypropyl starch, hypromellose, hypromellose acetate succinate, hypromellose phthalate, imidurea, inulin, iron oxides, isomalt, isopropyl alcohol, isopropyl myristate, isopropyl palmitate, kaolin, lactic acid, lactitol, lactose-anhydrous, lactose-inhalation. lactose-monohydrate, lactose-monohydrate and com starch, lactose-monohydrate and microcrystalline cellulose, lactose-monohydrate and povidone, lactose-monohydrate and powdered cellulose, lactose-spray-dried, lanolin, lanolin-hydrous, lanolin alcohols, lauric acid, lecithin, leucine, linoleic acid, macrogol 15 hydroxy stearate, magnesium aluminum silicate, magnesium carbonate, magnesium oxide, magnesium silicate, magnesium stearate, magnesium trisilicate, maleic acid, malic acid, maltitol, maltitol solution, maltodextrin, maltol, maltose, mannitol, medium-chain triglycerides, meglumine, menthol, methionine, methylcellulose, methylparaben, mineral oil, mineral oil-light, mineral oil and lanolin alcohols, monoethanolamine, monosodium glutamate, monothioglycerol, myristic acid, myristyl alcohol, neohesperidin dihydrochalcone, neotame, nitrogen, nitrous oxide, octyldodecanol, oleic acid, oleyl alcohol, olive oil, palmitic acid, paraffin, peanut oil, pectin, pentetic acid, petrolatum, petrolatum and lanolin alcohols, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, phospholipids, phosphoric acid, polacrilin potassium, poloxamer. polycarbophil, polydextrose, poly (dl-lactic acid), polyethylene glycol, polyethylene oxide, polymethacrylates, poly(methyl vinylether / maleic anhydride), polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, polyoxylglycerides, polyvinyl acetate phthalate, polyvinyl alcohol, potassium alginate, potassium alum, potassium benzoate, potassium bicarbonate, potassium chloride, potassium citrate, potassium hydroxide, potassium metabisulfite, potassium sorbate, povidone, propionic acid, propyl gallate, propylene carbonate, propylene glycol, propylene glycol alginate, propylparaben, propylparaben sodium, pyrrolidone, raffinose, saccharin, saccharin sodium, safflower oil, saponite, sesame oil, shellac, simethicone, sodium acetate, sodium alginate, sodium ascorbate, sodium benzoate, sodium bicarbonate, sodium borate, sodium carbonate, sodium chloride, sodium citrate dihydrate, sodium cyclamate, sodium formaldehyde sulfoxylate, sodium hyaluronate, sodium hydroxide, sodium lactate, sodium laury l sulfate, sodium metabisulfite, sodium phosphate—dibasic, sodium phosphate—monobasic, sodium propionate, sodium starch glycolate, sodium stearyl fumarate, sodium sulfite, sodium thiosulfate, sorbic acid, sorbitan esters (sorbitan fatty acid esters), sorbitol, soybean oil, starch, starch-pregelatinized, starch—sterilizable maize, stearic acid, stearyl alcohol, sucralose, sucrose, sucrose octaacetate, sugar-compressible, sugar-confectioner's, sugar spheres, sulfobutylether b-cyclodextrin, sulfur dioxide, sulfuric acid, sunflower oil, suppository' bases—hard fat, tagatose, talc, tartaric acid, tetrafluoroethane (hfc). thaumatin, thimerosal. thymol, titanium dioxide, tragacanth, trehalose, triacetin, tributyl citrate, tricaprylin, triethanolamine, triethyl citrate, triolein, vanillin, vegetable oil-hydrogenated, vitamin e polyethylene glycol succinate, water, wax-anionic emulsifying, wax-camauba, wax-cetyl esters, wax-microcrystalline, wax-nonionic emulsifying, wax-white, wax-yellow, xanthan gum, xylitol, zein, zinc acetate, or zinc stearate.

[0074] In some cases, a composition herein can comprise a carrier and / or a diluent. In some cases, a carrier or a diluent can be a pharmaceutically acceptable carrier and / or diluent. In some instances, a carrier or diluent can comprise a water, an alcohol, a salt solution (e.g., saline), or a mixture thereof. In some instances, a carrier can comprise a carbohydrate (e.g.. a sugar), a buffer, a salt, a pH adjuster, or any combination thereof. In some cases, sodium phosphate, citric acid, acetic acid, tromethamine, histidine, gluconic, lactic acid, tartaric acid, aspartic acid, glutamic acid, a citric acid cycle intermediate, or any combination thereof can be a buffer. In some cases, citrate can be used as a buffer. In some cases, a carrier can be a substrate used in the process of drug delivery. In some cases, a carrier can contribute a product’s attributes such as stability, biopharmaceutical profile, and / or appearance. In some cases, a carrier can be an organic excipient.

[0075] In some instances: XRPD can mean X-ray powder diffraction, TGA can mean thermogravimetric analysis, DSC can mean differential scanning calorimetry, PLM can mean polarized light microscopy, DVS can mean dynamic vapor sorption, RH can mean relative humidity, and KF can mean Karl fisher titration.

[0076] In some instances, a compound or a polymorph herein can be a hydrate, for example, a monohydrate, a dihydrate, a trihydrate, tetrahydrate, a sesquihydrate, or a hemi-hydrate. In some instances, a compound or a polymorph herein and be anhydrous or substantially anhydrous.

[0077] Polymorphs

[0078] In some instances, the terms polymorph and crystalline polymorph can be used interchangeably.

[0079] Provided herein is a crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.5, 9.0, 13.6 and 23.8.

[0080] The crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 5.6, 6.1, 10.4, 11.3, 17.9, 18.1, 19.2, 19.5, 19.7,20.8,21.6,22.3,22.7, 24.6, 27.3, 28.0, 28.1, 32.0, 32.5 and / or 37.0.

[0081] Further provided herein is a crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.1, 6.1, 9.2, 12.2 and 18.6.

[0082] The cry stalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.2.8.3.12.2.12.5. 15.2. 16.0. 19.1,20.3,21.4,22.8,24.9, 25.5, 27.1, 28.3, 28.9, 29.5, 30.8, 30.9, 32.9, 33.9, 34.0, 37.1, 37.2 and / or 38.0.

[0083] Additionally provided herein is cry stalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.6, 8.6, 10.2, and 19.2.

[0084] The crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate of can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 13.9, 15.6, 17.3, 23.7 and / or 28.1.

[0085] Also provided herein is a crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.4, 5.0, 7.5, 10.1 and 24.0.

[0086] The cry stalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate )2 can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 8.9, 9.2. 12.4. 14.9. 17.5, 19.0, 19.1, 19.5, 20.0,21.1, 22.5, 23.7, 25.0, 25.5, 27.0, 27.6, 29.5, 30.1, 31.8 and / or 31.9.

[0087] The cry stalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.0, 9.0. 11.0, 12.1, 12.6, 13.6, 14.6, 15.1, 15.7, 16.9. 18.2, 19.4, 19.9, 20.3, 20.8, 21.1, 21.7, 22.1, 22.9, 23.8, 24.9, 25.8, 26.6, 27.3, 27.7, 28.9, 30.4, 33.5, 35.0, 36.7, 37.6 and / or 38.3.

[0088] Pharmaceutical Compositions

[0089] Further provided herein is a solid pharmaceutical composition comprising i) a cry stalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.5, 9.0, 13.6 and 23.8 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0090] In the solid pharmaceutical composition, the crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 5.6, 6.1, 10.4, 11.3, 17.9, 18.1, 19.2, 19.5, 19.7, 20.8, 21.6, 22.3, 22.7, 24.6, 27.3, 28.0, 28.1, 32.0, 32.5 and / or 37.0.

[0091] Additionally provided herein is a solid pharmaceutical composition comprising i) a crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.1, 6.1, 9.2, 12.2 and 18.6 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0092] In the solid pharmaceutical composition the crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 can further exhibit at least one additional X-ray7 line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.2, 8.3, 12.2, 12.5, 15.2, 16.0, 19.1, 20.3, 21.4, 22.8, 24.9, 25.5. 27.1, 28.3, 28.9, 29.5, 30.8, 30.9, 32.9, 33.9, 34.0, 37.1, 37.2 and / or 38.0.

[0093] Also provided herein is a solid pharmaceutical composition comprising i) the crystalline the Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.6, 8.6, 10.2, and 19.2 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0094] In the solid pharmaceutical composition, the cry stalline the Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 13.9, 15.6, 17.3. 23.7 and / or 28.1.

[0095] Additionally provided herein is a solid pharmaceutical composition comprising i) the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.4, 5.0. 7.5, 10.1 and 24.0 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0096] In the solid pharmaceutical composition, the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 8.9, 9.2, 12,4, 14.9, 17.5, 19.0, 19.1, 19.5, 20.0, 21.1, 22.5, 23.7, 25.0, 25.5, 27.0, 27.6, 29.5, 30.1, 31.8 and / or 31.9.

[0097] Further provided herein is a solid pharmaceutical composition comprising i) the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.0, 4.5, 23.5 and 24.6 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

[0098] In the solid pharmaceutical composition, the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate can further exhibit at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.0, 9.0, 11.0, 12.1, 12.6, 13.6, 14.6, 15.1, 15.7, 16.9, 18.2, 19.4, 19.9, 20.3, 20.8, 21.1, 21.7, 22.1, 22.9, 23.8, 24.9, 25.8, 26.6, 27.3, 27.7, 28.9, 30.4, 33.5, 35.0. 36.7, 37.6 and / or 38.3.

[0099] Unit Dose Form

[0100] Any solid pharmaceutical composition herein can be in unit dose form.

[0101] Kits

[0102] Also provided herein are kits comprising a polymorph or salt thereof herein and a container. The polymorph or salt thereof can be in the container, which can be open, or can be sealed, with for example, a screw top, or a stopper. In some cases, a container can be a metal container, a plastic container, a glass container, or any combination thereof.

[0103] Diseases and Conditions

[0104] In some embodiments, in the method(s) herein, the disease or condition comprises a hepatic disease, a nonalcoholic fatty liver disease (NAFLD), a cirrhotic nonalcoholic steatohepatitis (NASH), a metabolic disorder, a metabolic syndrome, an insulin resistance, a hyperglycemia, a ty pe 2 diabetes mellitus, an obesity7, a fatty7 liver disease, a glucose intolerance, a hyperinsulinemia, a metabolic syndrome, a hypertension, or any combination thereof.

[0105] Additional Therapies

[0106] In some instances, the additional or second therapeutic or the salt thereof is a Glucagon-like peptide-1 (GLP-1) receptor agonist. In some cases, the additional or second therapeutic or the salt thereof is a Glucose-dependent insulinotropic polypeptide (GiP) agonist. In some embodiments, the additional or second therapeutic or the salt thereof is a glucagon receptor (GCGP) agonist. In some instances, the additional or second therapeutic or the salt thereof is a GIP-1 receptor agonist and a GiP receptor agonist. In some cases, the additional or second therapeutic or the salt thereof is a GIP-1 receptor agonist, a GLP receptor agonist, and a GCGP agonist. In some cases, the additional or second therapeutic is tirzepatide or a salt thereof. In some embodiments, the additional or second therapeutic is dulaglutide or a salt thereof, exenatide or a salt thereof, semaglutide or a salt thereof, liraglutide or a salt thereof, or lixisenatide or a salt thereof.

[0107] In some cases, an additional or second therapy or a salt thereof can be administered to a subject to treat a disease or condition. In some embodiments, an additional therapy or a salt thereof (e.g., a second therapy) can be administered to a subject in a unit dose. In some cases, 1, 2, 3, 4, 5 or more therapies or salt thereof can be administered to a subject in need thereof. In some cases, the additional therapy or salt thereof can be administered consecutively or concurrently to a first therapy.

[0108] In some embodiments, a therapy or polymorph or salt or composition or pharmaceutical composition herein can be administered to a subject in a unit dose. A unit dose that is administered to a patient may comprise from about 0.0001 g - 500 g, 0.001 g - 250 g, 0.01 g -100 g, 0.1 g - 50 g. 10 g - 25 g, 0.1 g - 5 g, 0.1 g - 1 g, or 1 g - 10 g of a pharmaceutical composition of the current disclosure. In some embodiments, polymorph or a salt thereof or a composition a pharmaceutical composition comprises an amount of at least about, or equal to about: 0.0001 g, 0.001 g, 0.01 g, 0.1 g, 0.5 g, 1 g, 2 g, 3 g, 4 g, 5 g, 6 g, 7 g, 8 g, 9 g, 10 g, 11 g, 12 g, 13 g, 14 g, 15 g, 16 g, 17 g, 18 g, 19 g, 20 g. 21 g. 22 g. 23 g, 24 g, 25 g, 26 g, 27 g, 28 g, 29 g, 30 g, 31 g, 32 g, 33 g, 34 g, 35 g, 36 g, 37 g, 38 g, 39 g, 40 g, 41 g, 42 g, 43 g, 44 g, 45 g, 46 g, 47 g, 48 g, 49 g, 50 g, 51 g, 52 g, 53 g, 54 g, 55 g, 56 g, 57 g, 58 g, 59 g, 60 g, 61 g, 62 g, 63 g, 64 g, 65 g, 66 g, 67 g, 68 g, 69 g, 70 g, 71 g, 72 g, 73 g, 74 g, 75 g, 76 g, 77 g, 78 g, 79 g, 80 g, 81 g, 82 g, 83 g, 84 g, 85 g, 86 g, 87 g, 88 g. 89 g. 90 g, 91 g, 92 g, 93 g, 94 g, 95 g, 96 g, 97 g, 98 g, 99 g, 100 g, 125 g, 150 g, 175 g, 200 g, 250 g, 300 g, 350 g, 400 g, 450 g, 500 g, or more of an active ingredient of the current disclosure. In some embodiments, a treatment herein can comprise from 0.001 g - 2 g of an active ingredient of the current disclosure in a single dose. In some embodiments, an additional therapy comprises an amount between about 1 g - 15 g of an active ingredient of the current disclosure of the current disclosure. In some embodiments, an additional therapy or salt thereof can be an amount from about 0.1 g - 5 g of a therapeutic composition, a compound, or a salt thereof of the current disclosure.

[0109] Administration

[0110] A therapy or a salt thereof or a composition or pharmaceutical composition or a polymorph or a salt thereof can be administered by any method. In some embodiments, administration can be orally, for example, in the form of a liquid, a tablet, a pill, or a capsule. In some cases, a composition can be delivered by parenchymal injection, intra-thecal injection, intra-ventricular injection, intra-tumoral injection, intra-cistemal injection, or any combination thereof. In some cases, a method of administration can be by inhalation, intraarterial injection, intracerebroventricular injection, intracistemal injection, intramuscular injection, intraorbital injection, intraparenchymal injection, intraperitoneal injection, intraspinal injection, intrathecal injection, intravenous injection, intraventricular injection, stereotactic injection, subcutaneous injection, or any combination thereof. In some cases, delivery can comprise buccal administration, by infusion administration, nasal administration, otic administration, ophthalmic administration, sublingual administration, or transdermal administration. Delivery can include parenteral administration (including intravenous, subcutaneous, intrathecal, intraperitoneal, intramuscular, intravascular or infusion), oral administration, nasal administration, inhalation administration, anal administration, intraduodenal administration, rectal administration. In some cases, delivery can include delivery7 of a composition by a surgery7, or by an injection. Delivery can include topical administration to an external surface of a surface, such as a skin. In some cases, a therapy or a salt thereof disclosed herein can be administered consecutively or concurrently to an additional therapy. [OlH] In some instances, a composition or pharmaceutical composition may be in the form of a capsule, a solid, a tablet, a gummy, an oil, a syrup, a liquid, a tincture, a lotion, a cream, a balm, a food, a beverage, an oil, a suppository, a liquid for injection (which can be. for example, an intra venous liquid, an intra muscular liquid, a subcutaneous liquid), or any combination thereof

[0112] In some embodiments, administering of a therapy and / or composition can be performed at least about: 1 time per day, 2 times per day, 3 times per day, 4 times per day, 5 times per day, 6 times per day, 7 times per day. or more than 7 times per day. In some cases, administering can be performed daily, weekly, monthly, or as needed. In some cases, administration can be performed at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 times a week. In some cases, administration can be performed at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29. 30. 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43. 44. 45. 46, 47, 48, 49, 50, 51, 52, 53, 54, 55. 56. 57. 58. 59. 60. 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, or 90 times a month.

[0113] Administration of a composition or a therapy disclosed herein can be performed for a treatment duration of at least about: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84. 85. 86. 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 days consecutive or nonconsecutive days. In some cases, a treatment duration can be from about: 1 to about 30 days, 1 to about 60 days, 1 to about 90 days, 30 days to about 90 days, 60 days to about 90 days, 30 days to about 180 days, from 90 days to about 180 days, or from 180 days to about 360 days.

[0114] In some aspects, the composition may be administered as needed. In some embodiments, administration of a composition or a therapy disclosed herein can be performed for a treatment duration of at least about 1 week, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, at least about 6 years, at least about 7 years, at least about 8 years, at least about 9 years, at least about 10 years, at least about 15 years, at least about 20 years, or for life. In some cases, administration can be performed repeatedly over a lifetime of a subject, such as once a month, once a week, or once a year for the lifetime of a subject. Administration can be performed repeatedly over a substantial portion of a subject’s life, such as once a month, once a week, or once a year for at least about 1 year. 5 years, 10 years, 15 years, 20 years, 25 years, 30 years, or more.

[0115] Product by Process

[0116] Also provided are crystalline polymorphs and their salts made by any process herein.

[0117] Examples

[0118] XRPD

[0119] XRPD was performed with a Panalytical X’Pert Powder XRPD on a Si zerobackground holder. The 20 position was calibrated against a Panalytical Si reference standard disc. The parameters used were: Parameters Reflection Made Cu, ka X-Ray wavelength Kal (A): 1.540598, Ko? (A): 1.544426. Ka2 / Kal intensity ratio: 0.50 X-Ray tube setting 45 kV, 40 mA Divergence slit Fixed 1 / 8° S can mode Continuous Scan. range 3 Aft CZUD J -49- Scan, step time [s] 18.87 Step size a m Test Time 4 min 15 s

[0120] TGA and DSC

[0121] TGA data was collected using a TA Discovery 550 TGA from TA Instrument. TGA was calibrated using nickel reference standard. DSC was performed using a TA D2500 DSC from TA Instrument. DSC was calibrated with an Indium reference standard. Detailed parameters used were: Parameters TGA DSC Method Ramp Ramp Sample pan Platinum, open Aluminum, crimped Temperature RT - desired temperature 25 ®C - desired temperature Heating rate 10 10 CC m m Purge gas A;

[0122] PLM

[0123] Polarized light microscopic picture was captured on Nikon DS-Fi2 upright microscope at room temperature.

[0124] KF

[0125] Karl fisher titration (KF) was collected on V30 volumetric KF titrator (Mettler Toledo) to determine the content of water in the sample (mg / g). Water standard 10 mg / g was used to calibrate the Karl fisher titration with the Titer of HYDRANAL-composite 5 in the range of 4.55.5 mg / ml.

[0126] DVS

[0127] DVS was measured via an SMS (Surface Measurement Systems) DVS Resolution (CPNJ-E44). The relative humidity at 25 °C were calibrated against deliquescence point of LiCl. Mg(NO3)2 and KC1. Actual parameters for DVS test were: Item Value Temperature 25 CC Sample size 10 ~ 20 mg Gas and flow rate 200 mL / mm dm / dt 0.002% / snia Mm. dm / dt stability duration 10 min Max. equilibrium time 180 min RH range             Ambient % RH - 95% RH - 0% RH - 95% RH RH step size                                 10%

[0128] ------------------------------------------------------------------------------------------

[0129] Example 1: Crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 Approximately 30 mg of 5-(tetradecyloxy)furan-2-carboxylic acid free acid form (6060791-01-A) was added to 0.2 mL of a solvent consisting of THF:H2O = 2:1 (v:v) in a 2 mL glass vial to form a suspension. 10.8 mg magnesium hydroxide (molar ratio API: Mg(0H)2 = 1:2) was then added to the suspension and stirred at about 20 to about 22 degrees C and then stirring was continued at about 5 degrees C for about 24 hours. The precipitate was centrifuged and isolated from the mother liquor without additional purification, and characterized by XRPD (X-ray Powder Diffraction), TGA (Thermogravimetric analysis). DSC (Differential Scanning Calorimetry) and PLM (Polorized light microscopy). X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation for the Type 1 salt of Mg2+(5-(tetradecyloxy )furan-2-carboxylate)2 was: Relative Intensity 2-Theta 100 3.1 38.77 6.1 25.75 9.2 6.79 18.6 1.94 12.2 1.89 21.4 1.3 22.8 1.14 4.2 1.1 15.2 0.75 30.8 0.69 30.9 0.67 25.5 0.65 38.0 0.45 37.1 0.42 34.0 0.4 20.3 0.37 37.2 0.35 33.9 0.29 19.1 0.17 24.9 0.14 28.3 0.13 27.1 0.08 8.3 0.07 16.0 0.06 12.5 0.03 28.9 0.03 29.5 0.02 32.9

[0130] Example 2: Crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate Approximately 30 mg of 5-(tetradecyloxy)furan-2-carboxylic acid free acid form (6060791-01-A) was added to 0.2 mL of MTBE in a 2 mL glass vial to form a suspension. 27.0 mg L-lysine (molar ratio API: L-lysine= 1:2) was then added to the suspension and stirred at about 20 to about 22 degrees C and then stirring was continued for 24 hours at 5°C. The precipitate was centrifuged and isolated from the mother liquor without additional purification, and characterized by XRPD, TGA. DSC and PLM. X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation for the Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 was: Relative Intensity’ 2-Theta 100 8.6 45.14 3.6 27.26 19.2 7.79 10.2 6.73 15.6 6.65 6.8 5.39 17.3 5.34 23.7 5.15 13.9 2.78 28.1

[0131] Example 3:

[0132] Crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid

[0133] 5-(tetradecyloxy)furan-2-carboxylic acid was crystallized with stirring at about 25 degrees C for about 3 days, or about 7 days, in various solvents and solvent combinations to yield the crystalline Form A (Table 1) and at about 5 degrees C for about 3 days, or about 7 days, in various solvents and solvent combinations, to yield the crystalline Form A (Table 2). All yielded cry stalline form A of 5-(tetradecyloxy)furan-2-carboxylic acid. Exp.ID solvent (v / v) solid form (Day 3) solid form (Day 7) Al MIBK Form A Form A A2 EtOAc Form A Form A A3 EtOH Form A Form A A4 Toluene Form A Form A A5 MeOH Form A Form A A6 H2O Form A Form A A7 MEK Form A Form A A8 Hexane Form A Form A A9 Acetone Form A Form A A10 H2O / DMF (El) Form A Form A All H2O / 2-MeTHF (1:1) Form A Form A A12 H2O / THF(1:1) Form A Form A A13 H2O / Dioxane (1:1) Form A Form A A14 Dioxane / Heptane (1:1) Form A Form A A15 ACN Form A Form A

[0134] Table 1.

[0135] In Tables 1 and 2, MEK is methyl ethyl ketone, 2-MeTHF is 2-methyl tetrahydrofuran, ACN is acetonitrile, EtOH is ethanol, and MIBK is methyl isobutyl ketone. DCM is dichloromethane, IPA is isopropyl alcohol and v / v is volume to volume, while the Experimental ID for each of Table 1 and 2 is is unique to Table 1 and Table 2. Exp.ID solvent (v / v) solid form (Day 3) solid form (Day 7) Al Acetone Form A FormA A2 MEK Form A FormA A3 THF Form A FormA A4 DCM Form A FormA A5 MTBE Form A FormA A6 THF / MeOH (1:1) Form A FormA A7 THF / IPA (1:1) FormA Fonn A A8 THF / ACN(1:1) Form A FormA A9 THF / Toluene (1:1) FormA Form A A10 H2O / DMF(1:1) FormA FormA All H2O / 2-MeTHF (1:1) FormA FormA A12 HjO / THF (1:2) Form A Form A A13 ACN FormA Form A

[0137] Table 2.

[0138] The crystalline form A of 5-(tetradecyloxy)furan-2-carboxylic acid was analyzed using XRPD yielding X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation of: Relative Intensity' 2-Theta 100 4.5 9.66 9.0 5.37 23.8 3.7 23.8 2.47 13.6 0.84 28.0 0.53 28.1 0.45 18.1 0.35 27.3 0.25 5.6 Hyl 0.25 6.1 0.24 19.5 0.21 32.5 0.2 24.6 0.12 19.7 0.08 11.3 0.08 19.2 0.08 22.7 0.07 10.4 0.07 17.9 0.06 21.6 0.04 22.3 0.04 37.0 0.03 20.8 0.02 32.0

[0139] Example 4:

[0140] Crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2

[0141] Approximately 30 mg of 5-(tetradecyloxy)furan-2-carboxylic acid free acid form (6060791-01-A) was added to 0.2 mL of ethanol (EtOH) in a 2 mL glass vial to form a suspension. 18.4 mg zinc hydroxide (molar ratio API: Zn(OH)2 = 1:2) was then added to the suspension at about 20 to about 22 degrees C and then stirring was continued at about 5 degrees C for about 24 hours. The precipitate was centrifuged and isolated from the mother liquor without additional purification, and characterized by XRPD, TGA, DSC and PLM. X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation for crystalline the Crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2was: Relative Intensity7 2-Theta 100 5.0 59.2 7.5 21.72 3.4 17.82 10.1 12.14 24.0 8.07 19.0 7.41 19.1 7.01 23.7 6.72 17.5 6.54 6.8 5.85 22.5 4.23 12.4 3.31 19.5 3.22 31.8 3.2 25.5 3.07 20.0 2.91 27.0 2.81 31.9 2.72 8.9 2.18 27.6 1.88 22.1 1.55 25.0 1.52 21.1 1.34 9.2 0.98 29.5 0.58 30.1 0.44 14.9

[0142] Example 5: Crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate

[0143] Approximately 30 mg of 5-(tetradecyloxy)furan-2-carboxylic acid free acid form (6060791-01-A) was added to 0.2 rnL of methyl tert-butyl ether (MTBE) in a 2 mL glass vial to form a suspension. 16.1 mg L-arginine (molar ratio API : L-arginine = 1:1) was then added to the suspension at about 20 to about 22 degrees C with stirring, and stirring was continued for about 24 hours at 5°C. The precipitate was centrifuged and isolated from the mother liquor without additional purification, and characterized by XRPD, TGA, DSC and PLM. PLM. X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation for crystalline the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate was: Relative Intensity’ 2-Theta 100 3.0 98.31 4.5 19.42 23.5 19.26 23.5 13 24.6 7.95 11.0 7.88 19.4 7.1 23.8 7.08 9.0 6.9 19.9 6.53 22.1 5.21 6.0 4.76 24.9 3.31 21.7 3.04 20.8 3.01 16.9 2.77 15.1 2.73 22.9 2.37 20.3 1.98 13.6 1.77 25.8 1.58 21.1 1.46 27.7 1.42 33.5 1.17 15.7 1.04 14.6 0.94 27.3 0.91 35.0 0.86 36.7 0.85 30.4 0.7 26.6 0.57 18.2 0.57 38.3 0.45 28.9 0.43 12.6 0.42 12.1 0.26 37.6

[0144] Example 6:

[0145] Scale up of the Type 1 salt Mg2+(5-(tetradecyloxy)furan-2-carboxylate

[0146] An experiment was performed to scale up magnesium salt Type 1 (Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 to a 150 mg scale. Starting with freebase (5-(tetradecyloxy)furan-2-carboxylic acid) Type 1, the crystalline starting material, 150 mg, was dissolved in 5 ml. The suspension was magnetically stirred at 5 °C for approximately 10 minutes. Then, 13.5 mg of magnesium hydroxide was added to the slurry. The slurry was then set to stir at 5 °C and analyzed periodically by XRPD until solids were isolated and dried on Day 5. The dried solids were analyzed by XRPD, TGA. DSC. PLM, KF, and DVS.

[0147] XRPD indicated that magnesium salt Type 1 scale up matched the reference pattern of the smaller scale experiment from the previous project (Figure 2a). TGA of the scaled-up sample showed 8.961% up to 137.38 °C and DSC showed a broad endothenn with peaks at 79.74 °C and 93.43 °C likely associated with the concurrent desolvation and melting (Figure 2 2b). PLM showed irregularly shaped birefringent particles (Figure 2c). KF indicated 10.37% water content. HPLC-CAD showed API : Magnesium (counter-ion) stoichiometry of 1:0.37.

[0148] Magnesium salt Type 1 showed a water absorption of 0.198% at 25°C / 80% RH by DVS when analyzed by a 50-95-0-95% RH method, indicating that the sample is not hygroscopic in nature (Figure 2d). XRPD post-DVS indicated minimal changes in crystallinity (Figure 2e).

[0149] The impact of grinding on magnesium salt Type 1 was analyzed by XRPD and KF. A mortar and pestle were used to apply a first round of grinding to the material for approximately 5 seconds. The sample was then analyzed by XRPD and KF. The same material left in the mortar and pestle was then ground a second time more aggressively for approximately 15-20 seconds and analyzed by XRPD and KF. Results are summarized in Figure 2f. The Mg2+(5-(tetradecyloxy)furan-2-carboxylate Type 1 compound was found to be a trihydrate.

[0150] Example 7: Scale up of the Type 1 saltZn2+(5-(tetradecyloxy)furan-2-carboxylate)2

[0151] An experiment to scale up at a 150 mg scale was run. Starting with freebase (5-(tetradecyloxy)furan-2-carboxylic acid) Type 1, the crystalline starting material, 150 mg was dissolved in 2 rnL of MTBE (methyl tert-butyl ether) and 20 pL H2O. The suspension was magnetically stirred at 5 °C for approximately 10 minutes. Then, 23.0 mg of zinc hydroxide was -29- added to the slurry7. The slurry7 was then set to stir at 5 °C and analyzed periodically by XRPD until solids were isolated and dried on Day 5. The dried solids were analyzed by XRPD, TGA, DSC.PLM, KF, and DVS.

[0152] XRPD indicated that zinc salt Type 1 scale up matched the reference pattern of the smaller scale experiment from the previous project (Figure 3a). TGA of the scaled-up sample showed 4.39% up to 107.10 °C and the DSC showed an endotherm with a peak at 29.10 °C followed by a desolvation / melting endotherm at 83.81 °C (Figure 3b). PLM showed irregularly shaped birefringent particles (Figure 3c). KF indicated 5.29% water content. HPLC-CAD showed API : Zinc (counter-ion) stoichiometry of 1:0.84.

[0153] Zinc salt Type 1 showed a water absorption of 1.75% at 25°C / 80% RH by DVS when analyzed by a 50-95-0-95% RH method, indicating that the sample is slightly hygroscopic in nature (Figure 3d). XRPD post-DVS indicated minimal changes in crystallinity (Figure 3e).

[0154] The impact of grinding on zinc salt Type 1 was analyzed by XRPD and KF. A mortar and pestle was used to apply a first round of grinding to the material for approximately 5 seconds. The sample was then analyzed by XRPD and KF. The same material left in the mortar and pestle was then ground a second time more aggressively for approximately 15-20 seconds and analyzed by XRPD and KF. Results are summarized in Figure 3f. The resulting polymorph was a sesquihydrate.

[0155] Example 8:

[0156] Scale up of the Type 1 salt L-argininium 5-(tetradecyloxy)furan-2-carboxylate

[0157] An experiment was performed to scale up arginine salt Type 1 to a 150 mg scale. Starting with freebase (5-(tetradecyloxy)furan-2-carboxylic acid) Type 1 crystalline starting material, 150 mg was dissolved in 2 mb of MTBE and 20 pL H2O. The suspension was magnetically stirred at 5 °C for approximately 10 minutes. Then, 80.5 mg of arginine hydroxide was added to the slurry. The slurry was then set to stir at 5 °C and analyzed periodically by XRPD until solids were isolated and dried on Day 18. The dried solids were analyzed by XRPD, TGA, DSC, PLM, KF, and DVS.

[0158] XRPD indicated that arginine salt Type 1 scale up matched the reference pattern of the smaller scale experiment from the previous project (Figure 4a). TGA of the scaled-up sample showed negligible weight loss up to 130.6 °C and the DSC showed a melt at onset of 144.87 °C. (Figure 4b). PLM showed irregularly shaped birefringent particles (Figure 4c). KF indicated 0.41% water content. HPLC-CAD showed API: Arginine (counter-ion) stoichiometry of 1:0.98.

[0159] Arginine salt Type 1 showed a water absorption of 0.638% at 25°C / 80% RH by DVS when analyzed by a 50-95-0-95% RH method, indicating that the sample is not hygroscopic in nature (Figure 4d). XRPD post-DVS indicated minimal changes in crystallinity (Figure 4e).

[0160] The impact of grinding on arginine salt Type 1 was analyzed by XRPD and KF. A mortar and pestle were used to apply a first round of grinding to the material for approximately 5 seconds. The sample was then analyzed by XRPD and KF. The same material left in the mortar and pestle was then ground a second time more aggressively for approximately 15-20 seconds and analyzed by XRPD and KF. Results are summarized in Figure 4f. The resulting polymorph was anhydrous.

[0161] Example 9:

[0162] Scale up of the Type 1 Salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate

[0163] An experiment was performed to scale up lysine salt Type 1 to a 150 mg scale. Starting with freebase (5-(tetradecyloxy)furan-2-carboxylic acid) Type 1, the crystalline starting material. 148.8 mg was dissolved in 2 mL of dioxane. The suspension was magnetically stirred at 5 °C for approximately 10 minutes. Then, 139.2 mg of lysine hydroxide was added to the slurry. The slurry was then set to stir at 5 °C and analyzed periodically by XRPD. The solids did not match the XRPD pattern of the reference pattern, so the slurry was dried completely and resuspended in a 2:1 ratio of THF:H2O. Solids were analyzed each day by XRPD and were isolated and dried on Day 7. The fully dried solids were analyzed by XRPD, TGA, DSC, PLM, KF, and DVS.

[0164] XRPD indicated that ly sine salt Type 1 scale up matched the reference pattern of the smaller scale experiment from the previous project (Figure 5a). TGA of the scaled-up sample showed a weight loss of 3.26% up to 125.06 °C. The DSC showed a broad desolvation endotherm at 62.28 °C, accompanied by two smaller endotherms at 105.71 °C and 129.42 °C (peaks) followed by decomposition starting at 178 °C (Figure 5b). PLM showed irregularly shaped birefringent particles (Figure 5c). KF indicated 2.28% water content. HPLC-CAD showed API: lysine (counter-ion) stoichiometry- of 1:2.04.

[0165] Lysine salt Type 1 showed a water absorption of 7.32% at 25°C / 80% RH by DVS when analyzed by a 40-95-0-95% RH method, indicating that the sample is hygroscopic in nature (Figure 5d). XRPD post-DVS indicated a slight decrease in crystallinity but still demonstrating the same pattern (Figure 5e).

[0166] The impact of grinding on lysine salt Type 1 was analyzed by XRPD and KF. A mortar and pestle were used to apply a first round of grinding to the material for approximately 5 seconds. The sample w as then analy zed by XRPD and KF. The same material left in the mortar and pestle was then ground a second time more aggressively for approximately 15-20 seconds and analyzed by XRPD and KF. Results are summarized in Figure 5f. the Type 1 Salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate was in the form of a hemi-hydrate. -31-

[0167] Example 10:

[0168] HPLC (High Performance Liquid Chromatography) Method

[0169] To develop and optimize a method for freebase (5-(tetradecyloxy)furan-2-carboxylic acid) Type 1, the HPLC method was optimized by varying parameters such as flow rate, gradient conditions, and injection volume. The column that was explored for this project: Agilent Poroshell 120 C18 ( 4.6 x 100 mm, 2.7 pm) and was used for conducting the solubility experiments in this project.

[0170] The final optimized HPLC method used for solubility studies is outlined below. An overlay of standards analyzed using this method and the resulting calibration curve is shown in Figure 3 1. Using a 5 pL injection volume, a calibration curve was established at the concentration ranging from 0.02907 to 0.5814 mg / mL to determine the sensitivity of the method. HPLC Me&od Parameters Instrument Agilent 1290 Infinity II Mobile Phase A 59 mM Ammonium Acetate Buffer (v / v) Mobile Phase B 100% MeOH (v / v) Column Agilent         120    (2.7 pm, 4.6 x 100 mm) Column Temperature 35 °C Injector Volume 5 pL Detector Wavelength 220. 235.254,273,280 am Flaw Rate 0.80 mUmin Diluent EfOH Gradient Program Time (min) % Mobile Phase A % Mobile Phase B 0.0 41.0 59.0 3.0 41.0 59.0 12.0 10 90 16.0 10 90 16.1 90 10 17.0 41.0 59.0 20.0 41.0 59.0

[0171] Figure 6 displays Chromatogram and calibration curve of freebase (5-(tetradecyloxy)furan-2-carboxylic acid) Type 1 standards.

[0172] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. A crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.5, 9.0, 13.6 and 23.8.

2. The crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid of claim 1, further exhibiting at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 5.6, 6.1, 10.4, 11.3, 17.9, 18.1, 19.2, 19.5, 19.7, 20.8, 21.6, 22.3, 22.7, 24.6, 27.3, 28.0, 28.1, 32.0, 32.5 and / or 37.0.

3. A crystalline Type 1 salt of Mg2+(5-(tetradecyloxy )furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.1, 6.1, 9.2, 12.2 and 18.6.

4. The crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 of claim 3, further exhibiting at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.2, 8.3, 12.2, 12.5, 15.2, 16.0, 19.1, 20.3, 21.4, 22.8, 24.9, 25.5, 27.1, 28.3, 28.9, 29.5, 30.8, 30.9, 32.9, 33.9, 34.0, 37.1, 37.2 and / or 38.0.

5. A crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.6, 8.6, 10.2, and 19.2.

6. The crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate of claim 5, further exhibiting at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 13.9, 15.6, 17.3, 23.7 and / or 28.1.

7. A crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.4, 5.0, 7.5, 10.1 and 24.0.

8. The cry stalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate )2 of claim 7, further exhibiting at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 8.9, 9.2, 12,4, 14.9, 17.5, 19.0, 19.1, 19.5, 20.0, 21.1, 22.5, 23.7, 25.0, 25.5, 27.0, 27.6, 29.5, 30.1, 31.8 and / or 31.9.

9. A crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.0, 4.5, 23.5 and 24.6.

10. The cry stalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate of claim 9, further exhibiting at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.0, 9.0, 11.0, 12.1, 12.6, 13.6, 14.

6. 15.1, 15.7, 16.9, 18.2, 19.4, 19.9, 20.3, 20.8, 21.1, 21.7, 22.1, 22.9, 23.8, 24.9, 25.8, 26.6, 27.3, 27.7, 28.9, 30.4, 33.5, 35.0, 36.7, 37.6 and / or 38.3.

11. A solid pharmaceutical composition comprising i) the crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.5, 9.0, 13.6 and 23.8 of claim 1 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

12. The solid pharmaceutical composition of claim 11, wherein the crystalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid further exhibits at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 5.6, 6.1, 10.4, 11.3, 17.9, 18.1, 19.2, 19.5, 19.7, 20.8,21.6,22.3,22.7, 24.6, 27.3, 28.0, 28.1,32.0, 32.5 and / or 37.0.

13. A solid pharmaceutical composition comprising i) the crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.1, 6.1, 9.2, 12.2 and 18.6 of claim 3 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

14. The solid pharmaceutical composition of claim 13, wherein the crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 further exhibits at least one additional X-rayline (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.2,8.3, 12.2, 12.5, 15.2, 16.0, 19.1, 20.3, 21.4, 22.8, 24.9, 25.5, 27.1, 28.3, 28.9, 29.5, 30.8, 30.9, 32.9, 33.9, 34.0, 37.1, 37.2 and / or 38.0.

15. A solid pharmaceutical composition comprising i) the crystalline the Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.6, 8.6, 10.2, and 19.2 of claim 5 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

16. The solid pharmaceutical composition of claim 15, wherein the crystalline the Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate further exhibits at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 13.9, 15.6, 17.3, 23.7 and / or 28.1.

17. A solid pharmaceutical composition comprising i) the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.4, 5.0, 7.5, 10.1 and 24.0 of claim 7 and ii) a pharmaceutically acceptable: excipient, diluent, carrier, or any combination thereof.

18. The solid pharmaceutical composition of claim 17, wherein the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 further exhibits at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 6.8, 8.9, 9.2, 12,4, 14.9, 17.5, 19.0, 19.1, 19.5, 20.0, 21.1, 22.5, 23.7, 25.0, 25.5, 27.0, 27.6, 29.5, 30.1, 31.8 and / or 31.9.

19. A solid pharmaceutical composition comprising i) the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.0, 4.5, 23.5 and 24.6 of claim 9 and ii) a pharmaceutically acceptable: excipient, diluent, earner, or any combination thereof.

20. The solid pharmaceutical composition of claim 19, wherein the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate further exhibits at least one additional X-ray line (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiationat 6.0, 9.0, 11.0, 12.1, 12.6, 13.6, 14.6, 15.1, 15.7, 16.9, 18.2, 19.4, 19.9, 20.3, 20.8, 21.1, 21.7,22.1, 22.9, 23.8, 24.9, 25.8, 26.6, 27.3, 27.7, 28.

9. 30.4, 33.5, 35.0, 36.7, 37.6 and / or 38.3.

21. The solid pharmaceutical composition of any one of claims 11-20, that is in unit dose form.

22. A kit comprising the solid pharmaceutical composition of any one of claims 11-20 and a container.

23. A kit comprising the solid pharmaceutical composition in unit dose form of claim 21 and a container.

24. A method of making a crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2, the method comprising:combining a 5-(tetradecyloxy)furan-2-carboxylic acid with a solvent comprising a tetrahydrofuran and a water in an about a 2:1 (volume : volume) ratio to form a first suspension:combining a magnesium hydroxide (Mg(OH)2), in a molar ratio of about 1:2 of the 5-(tetradecyloxy)furan-2-carboxylic acidto the Mg(OH)2, with the first suspension to form a second suspension at 20-22 degrees C;stirring the second suspension for about 24 hours at about 5 degrees C to form a precipitate comprising the Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2; andoptionally isolating the precipitate comprising the Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2;thereby forming the crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2.

25. A crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 made by the process of claim 24.

26. A method of making a crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate, the method comprising:combining a 5-(tetradecyloxy)furan-2-carboxylic acid with a methyl tert-buty l ether (MTBE) to form a first suspension;combining a lysine, in a molar ratio of about 1:2 of the L-lysine to the 5-(decyloxy)furan-2-carboxylic acid, with the first suspension to form a second suspension at 20-22 degrees C;stirring the second suspension for about 24 hours at about 5 degrees C to form a precipitate comprising the crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate; andoptionally isolating the precipitate comprising the crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate;thereby forming the crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate.

27. A crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate made by the process of claim 26.

28. A method of making a crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2, the method comprising:combining a 5-(tetradecyloxy)furan-2-carboxylic acid with an ethanol to form a first suspension;combining a zinc hydrochloride, in a molar ratio of about 1:2 of the 5-(tetradecyloxy)furan-2-carboxylic acid to the zinc hydroxide, with the first suspension to form a second suspension at 20-22 degrees C;stirring the second suspension for about 24 hours at about 5 degrees C to form a precipitate comprising the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2; andoptionally isolating the precipitate comprising the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2;thereby forming the crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxyiale)2.

29. A crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 made by the process of claim 28.

30. A method of making a crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate, the method comprising:combining a 5-(tetradecyloxy)furan-2-carboxylic acid with a methyl tert-butylether (MTBE) to form a first suspension:combining L-arginine, in a molar ratio of about 1:1 of the L-arginine to the 5-(decyloxy)furan-2-carboxylic acid, with the first suspension to form a second suspension;stirring the second suspension for about 24 hours at about 5 degrees C to form a precipitate comprising the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate; andoptionally isolating the precipitate comprising the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate;thereby forming the crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate.

31. A crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate formed by the method of claim 30.

32. A method of treating a disease of condition in a subject, the method comprising administering an effective amount of a cry stalline Form A of 5-(tetradecyloxy)furan-2-carboxylic acid exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 4.5, 9.0, 13.6 and 23.8 to the subject, thereby treating the disease or condition in the subject.

33. A method of treating a disease or condition in a subject, the method comprising administering an effective amount of a crystalline Type 1 salt of Mg2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.1, 6.1, 9.2, 12.2 and 18.8 to the subject, thereby treating the disease or condition in the subject.

34. A method of treating a disease or condition in a subject, the method comprising administering an effective amount of a crystalline Type 1 salt of L-lysinium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.6, 8.6, 10.2, and 19.2 to the subject, thereby treating the disease or condition in the subject.

35. A method of treating a disease or condition in a subject, the method comprising administering an effective amount of a crystalline Type 1 salt of Zn2+(5-(tetradecyloxy)furan-2-carboxylate)2 exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.4, 5.0, 7.5, 10.1 and 24.0 to the subject, thereby treating the disease or condition in the subject.

36. A method of treating a disease or condition in a subject, the method comprising administering an effective amount of a crystalline Type 1 salt of L-argininium 5-(tetradecyloxy)furan-2-carboxylate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Ka radiation at 3.0, 4.5, 23.5 and 24.6 to the subject, thereby treating the disease or condition in the subject.

37. The method of any one of claims 32-36, wherein the subject is a subject in need thereof.

38. The method of any one of claims 32-37, wherein the subject or the subject in need thereof is a mammal.

39. The method of claim 38, wherein the mammal is a human.

40. The method of any one of claims 32-39, wherein the effective amount ranges fromabout 0.00001 mg to about 25.000 mg.

41. The method of any one of claims 32-40, wherein the administering is: once per day, twice per day, three times per day, four times per day, daily, weekly, bi-weekly, monthly, quarterly, semi-annually, annually, for life, or as needed.

42. The method of any one of claims 32-41, wherein the disease or condition comprises a hepatic disease, a nonalcoholic fatty liver disease (NAFLD), a cirrhotic nonalcoholic steatohepatitis (NASH), a metabolic disorder, a metabolic syndrome, an insulin resistance, a hyperglycemia, a type 2 diabetes mellitus, an obesity, a fatty liver disease, a glucose intolerance, a hyperinsulinemia, a metabolic syndrome, a hypertension, or any combination thereof.

43. The method of any one of claims 32-42, wherein the administering is an oral administration, a nasal administration, an inhalation administration, an anal administration, an intraduodenal administration, a rectal administration, a topical administration or any combination thereof.

44. The method of any one of claims 32-43, further comprising administering a second therapeutic or a salt thereof.

45. The method of claim 44, wherein the second therapeutic or the salt thereof is administered concurrently or consecutively.

46. The method of anyone of claims 44-45, wherein the second therapeutic or the salt thereof is a Glucagon-like peptide-1 (GLP-1) receptor agonist.

47. The method of any one of claims 44-45, wherein the second therapeutic or the salt thereof is a glucose-dependent insulinotropic polypeptide (GiP) agonist.

48. The method of any one of claims 44-45, the second therapeutic or the salt thereof is a glucagon receptor (GCGP) agonist.

49. The method of any one of claims 44-45, wherein the second therapeutic or the salt thereof is a GIP-1 receptor agonist and a GiP receptor agonist.

50. The method of any one of claims 44-45, wherein the second therapeutic or the salt thereof is a GIP-1 receptor agonist, a GLP receptor agonist, and a GCGP agonist.

51. The method of any one of claims 44-45, wherein the second therapeutic istirzepatide or a salt thereof.

52. The method of any one of claims 44-45, wherein the second therapeutic is dulaglutide or a salt thereof, exenatide or a salt thereof, semaglutide or a salt thereof, liraglutide or a salt thereof, or lixisenatide or a salt thereof, or an incretin analog or a salt thereof.

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