Therapeutic regimens and methods of treatment of NASH using mutant FGF-21 peptide conjugates

Abstract

Therapeutic regimens and uses of mutant Fibroblast Growth Factor-21 peptide conjugates in the treatment of nonalcoholic steatohepatitis are provided.

Description

[0001] Attorney Docket No.180234-011901 / PCT THERAPEUTIC REGIMENS AND METHODS OF TREATMENT OF NASH USING MUTANT FGF-21 PEPTIDE CONJUGATES CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of and priority to U.S. Provisional Application No.63 / 578,565, filed on August 24, 2023, the entire content of which is incorporated herein by reference. SEQUENCE LISTING The instant application contains a Sequence Listing which includes the file entitled 180234-011901.xml, 42,559 bytes in size, which was created August 12, 2024, the contents of which are incorporated herein by reference. FIELD OF THE INVENTION Therapeutic regimens and uses of mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugates comprising a polyethylene glycol (PEG) moiety attached to a mutant FGF-21 peptide via a glycosyl moiety thereof are provided. BACKGROUND OF THE INVENTION FGF-21 is an endocrine hormone that is naturally found as a monomeric non- glycosylated protein. Together with FGF-19 and FGF-23, FGF-21 belongs to the endocrine- acting sub-family while the remaining of the 18 mammalian FGF ligands are grouped into five paracrine-acting sub-families. SUMMARY OF THE INVENTION Provided herein are methods of treating nonalcoholic steatohepatitis (NASH) in a subject in need thereof. In some embodiments, the methods comprise administering once a month to the subject in need thereof a pharmaceutical composition comprising an effective amount of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, wherein the mutant FGF-21 peptide conjugate comprises i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine Attorney Docket No.180234-011901 / PCT at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. In some embodiments, the methods comprise administering once every two months to the subject in need thereof a pharmaceutical composition comprising an effective amount of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, wherein the mutant FGF-21 peptide conjugate comprises i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. In some embodiments, the methods comprise administering once every three months to the subject in need thereof a pharmaceutical composition comprising an effective amount of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, wherein the mutant FGF-21 peptide conjugate comprises i) a mutant FGF- 21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. In some embodiments, the administration of the pharmaceutical composition results in at least one of: a reduction of liver fat, an improvement of liver fibrosis score, resolution of NASH, ≥2 point improvement of NAFLD Activity score, improvement of VCTE score, improvement of FAST score, improvement of FIB-4 score, a reduction of the liver size as assessed by Magnetic resonance imaging – Proton density fat fraction (MRI-PDFF), a reduction of the levels of one or more biomarkers comprising Pro-C3, alanine transaminase (ALT), Enhanced LiverFibrosis (ELF) panel, CK-18, inflammation marker high-sensitivity C-reactive protein (hs-CRP), Hemoglobin A1c (HbA1c), non-HDL-c, LDL-c, and Triglycerides, and an increase of the levels of HDL-c and / or Adiponectin. Attorney Docket No.180234-011901 / PCT In some embodiments, the subject is a human subject. In some embodiments, the pharmaceutical composition is administered sub- subcutaneously. In some embodiments, the glycosyl moiety comprises at least one of an N- acetylgalactosamine (GalNAc) residue, a galactose (Gal) residue, a sialic acid (Sia) residue, a 5-amine analogue of a Sia residue, a mannose (Man) residue, mannosamine, a glucose (Glc) residue, an N-acetylglucosamine (GlcNAc) residue, a fucose residue, a xylose residue, or a combination thereof. In some embodiments, the glycosyl moiety comprises at least one N-acetylgalactosamine (GalNAc) residue, at least one galactose (Gal) residue, at least one sialic acid (Sia) residue, or a combination thereof. In some embodiments, the at least one Sia residue is a nine-carbon carboxylated sugar. In some embodiments, the at least one Sia residue is N-acetyl-neuraminic acid (2-keto-5-acetamido-3,5-dideoxy-D-glycero-D- galactononulopyranos-1-onic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), 2-keto- 3-deoxy-nonulosonic acid (KDN), or a 9-substituted sialic acid. In some embodiments, the the 9-substituted sialic acid is 9-O-lactyl-Neu5Ac, 9-O-acetyl-Neu5Ac, 9-deoxy-9-fluoro- Neu5Ac, or 9-azido-9-deoxy-Neu5Ac. In some embodiments, the glycosyl moiety comprises the structure -GalNAc-Sia-. In some embodiments, the 20 kDa PEG moiety is attached to the glycosyl moiety by a covalent bond to a linker, wherein the linker comprises at least one amino acid residue. In some embodiments, the at least one amino acid residue is a glycine (Gly). In some embodiments, the mutant FGF-21 peptide conjugate comprises the structure -GalNAc-Sia- Gly-PEG (20 kDa). In some embodiments, the mutant FGF-21 peptide conjugate comprises the structure: 21wherein n is an integer selected from 450 to 460. In some embodiments, the 20 kDa PEG is a linear PEG. In other embodiments, the 20 kDa PEG is a branched PEG. In some embodiments, the 20 kDa PEG is a 20 kDa Attorney Docket No.180234-011901 / PCT methoxy-PEG. In some embodiments, the mutant FGF-21 peptide conjugate displays an equal or higher potency than wild type FGF-21 when tested in vitro in KLB-FGFR1, KLB-FGFR2 and KLB-FGFR3 expressing cells. In some embodiments, the method comprises administering once a month to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 180 mg of the mutant FGF-21 peptide conjugate. In some embodiments, the method comprises administering once a month to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 40 mg, from about 40 mg to about 50 mg, from about 50 mg to about 60 mg, from about 60 mg to about 70 mg, from about 70 mg to about 80 mg, from about 80 mg to about 90 mg, from about 90 mg to about 100 mg, from about 100 mg to about 110 mg, from about 110 mg to about 120 mg, from about 120 mg to about 130 mg, from about 130 mg to about 140 mg, from about 140 mg to about 160 mg, from about 160 mg to about 170 mg, or from about 170 mg to about 180 mg of the mutant FGF-21 peptide conjugate. In some embodiments, the method comprises administering once every three months to the subject in need thereof the pharmaceutical composition comprising from about 90 mg to about 180 mg of the mutant FGF-21 peptide conjugate. In some embodiments, the method comprises administering once every three months to the subject in need thereof the pharmaceutical composition comprising from about 90 mg to about 100 mg, from about 100 mg to about 110 mg, from about 110 mg to about 120 mg, from about 120 mg to about 130 mg, from about 130 mg to about 140 mg, from about 140 mg to about 160 mg, from about 160 mg to about 170 mg, or from about 170 mg to about 180 mg of the mutant FGF-21 peptide conjugate. Aspects of the disclosure relate to a pharmaceutical composition comprising from 30 mg to 180 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, for use in a method of treating NASH in a subject in need thereof, wherein the pharmaceutical composition is administered subcutaneously once a month, wherein the mutant FGF-21 peptide conjugate comprises i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to Attorney Docket No.180234-011901 / PCT the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. Other aspects of the disclosure relate to pharmaceutical composition comprising from 90 mg to 180 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, for use in a method of treating NASH in a subject in need thereof, wherein the pharmaceutical composition is administered subcutaneously once every three months, wherein the mutant FGF-21 peptide conjugate comprises i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows simulated Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) change from monthly (QM) dosings of mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate described herein. Figure 2 shows simulated MRI-PDFF change from quarterly (Q3M) dosings of mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate described herein. DETAILED DESCRIPTION Nonalcoholic fatty liver disease (NAFLD) and Non-alcoholic steatohepatitis (NASH) are chronic conditions where fat is deposited in the liver with subsequent liver damage and inflammation. To date there are no specific therapies for these disorders. Among those benefits and improvements that have been disclosed, other objects and advantages of this disclosure will become apparent from the following description taken in conjunction. Detailed embodiments of the present disclosure are disclosed herein; however, it is to be understood that the disclosed embodiments are merely illustrative of the disclosure that may be embodied in various forms. In addition, each of the examples given in Attorney Docket No.180234-011901 / PCT connection with the various embodiments of the disclosure are intended to be illustrative, and not restrictive. Definitions For the sake of clarity and readability, the following definitions are provided. Any technical feature mentioned for these definitions may be read on each and every embodiment of the disclosure. Additional definitions and explanations may be specifically provided in the context of these embodiments. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Generally, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, organic chemistry, and nucleic acid chemistry and hybridization are those well-known and commonly employed in the art. Standard techniques are used for nucleic acid and peptide synthesis. The techniques and procedures are generally performed according to conventional methods in the art and various general references (e.g., Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual, 2d ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY), which are provided throughout this document. Enzyme: Enzymes are catalytically active biomolecules that perform biochemical reactions such as the transfer of glycosyl moieties or modified glycosyl moieties from the respective glycosyl donors to an amino acid of FGF-21 or to another glycosyl moiety attached to the peptide. Protein: A protein typically comprises one or more peptides or polypeptides. A protein is typically folded into a 3-dimensional form, which may be required for the protein to exert its biological function. The sequence of a protein or peptide is typically understood to be in the order, i.e. the succession of its amino acids. Recombinant protein: The term “recombinant protein” refers to proteins produced in a heterologous system, that is, in an organism that naturally does not produce such a protein, or a variant of such a protein, i.e. the protein or peptide is “recombinantly produced”. Typically, the heterologous systems used in the art to produce recombinant proteins are bacteria (e.g., Escherichia (E.) coli), yeast (e.g., Saccharomyces (S.) cerevisiae) or certain mammalian cell culture lines. Attorney Docket No.180234-011901 / PCT Expression host: An expression host denotes an organism which is used for recombinant protein production. General expression hosts are bacteria, such as E. coli, yeasts, such as Saccharomyces cerevisiae or Pichia pastoris, or also mammal cells, such as human cells. RNA, mRNA: RNA is the usual abbreviation for ribonucleic acid. It is a nucleic acid molecule, i.e. a polymer consisting of nucleotides. These nucleotides are usually adenosine- monophosphate, uridine-monophosphate, guanosine-monophosphate and cytidine- monophosphate monomers which are connected to each other along a so-called backbone. The backbone is formed by phosphodiester bonds between the sugar, i.e. ribose, of a first and a phosphate moiety of a second, adjacent monomer. The specific succession of the monomers is called the RNA sequence. DNA: DNA is the usual abbreviation for deoxyribonucleic acid. It is a nucleic acid molecule, i.e. a polymer consisting of nucleotide monomers. These nucleotides are usually deoxy-adenosine-monophosphate, deoxy-thymidine-monophosphate, deoxy-guanosine- monophosphate and deoxy-cytidine-monophosphate monomers which are – by themselves – composed of a sugar moiety (deoxyribose), a base moiety and a phosphate moiety, and polymerized by a characteristic backbone structure. The backbone structure is, typically, formed by phosphodiester bonds between the sugar moiety of the nucleotide, i.e. deoxyribose, of a first and a phosphate moiety of a second, adjacent monomer. The specific order of the monomers, i.e. the order of the bases linked to the sugar / phosphate-backbone, is called the DNA-sequence. DNA may be single-stranded or double-stranded. In the double stranded form, the nucleotides of the first strand typically hybridize with the nucleotides of the second strand, e.g. by A / T-base-pairing and G / C-base-pairing. Sequence of a nucleic acid molecule / nucleic acid sequence: The sequence of a nucleic acid molecule is typically understood to be in the particular and individual order, i.e. the succession of its nucleotides. Sequence of amino acid molecules / amino acid sequence: The sequence of a protein or peptide is typically understood to be in the order, i.e. the succession of its amino acids. Sequence identity: Two or more sequences are identical if they exhibit the same length and order of nucleotides or amino acids. The percentage of identity typically describes Attorney Docket No.180234-011901 / PCT the extent, to which two sequences are identical, i.e. it typically describes the percentage of nucleotides that correspond in their sequence position to identical nucleotides of a reference sequence, such as a native or wild type sequence. For the determination of the degree of identity, the sequences to be compared are considered to exhibit the same length, i.e. the length of the longest sequence of the sequences to be compared. This means that a first sequence consisting of 8 nucleotides / amino acids is 80% identical to a second sequence consisting of 10 nucleotides / amino acids comprising the first sequence. In other words, in the context of the present disclosure, identity of sequences particularly relates to the percentage of nucleotides / amino acids of a sequence, which have the same position in two or more sequences having the same length. Gaps are usually regarded as non-identical positions, irrespective of their actual position in an alignment. Newly introduced amino acids: “Newly introduced amino acids” denote amino acids which are newly introduced into an amino acid sequence in comparison to a native / wild type amino acid sequence. Usually by mutagenesis, the native amino acid sequence is changed in order to have a certain amino acid side chain at a desired position within the amino acid sequence. In the present disclosure, in particular the amino acid threonine is newly introduced into the amino acid sequence on the C-terminal side adjacent to a proline residue. Functional group: The term is to be understood according to the skilled person’s general understanding in the art and denotes a chemical moiety which is present on a molecule, in particular on the peptide or amino acid of the peptide or glycosyl residue attached to the peptide, and which may participate in a covalent or non-covalent bond to another chemical molecule, i.e. which allows e.g. the attachment of a glycosyl residue or PEG. Native amino acid sequence: The term is to be understood according to the skilled person’s general understanding in the art and denotes the amino acid sequence in the form of its occurrence in nature without any mutation or amino acid amendment by man. It is also called “wild-type sequence”. “Native FGF-21” or “wild-type FGF-21” denotes FGF-21 having the amino acid sequence as it occurs in nature, such as the (not mutated) amino acid sequence of human FGF-21 as depicted in SEQ ID NO: 1. The presence or absence of an N- Attorney Docket No.180234-011901 / PCT terminal methionine, which depends on the used expression host, usually does not change the status of a protein being considered as having its natural or native / wild-type sequence. Mutated: The term is to be understood according to the skilled person’s general understanding in the art. An amino acid sequence is called “mutated” if it contains at least one additional, deleted or exchanged amino acid in its amino acid sequence in comparison to its natural or native amino acid sequence, i.e. if it contains an amino acid mutation. Mutated proteins are also called mutants. In the present disclosure, a mutated FGF-21 peptide is particularly a peptide having an amino acid exchange adjacent to a proline residue on the C-terminal side of the proline residue. Thereby a consensus sequence for O-linked glycosylation is introduced into FGF-21 such that the mutant FGF-21 peptide comprises a newly introduced O-linked glycosylation side. Amino acid exchanges are typically denoted as follows: S172T which means that the amino acid serine at position 172, such as in the amino acid sequence of SEQ ID NO: 1, is exchanged by the amino acid threonine. Pharmaceutically effective amount: A pharmaceutically effective amount in the context of the disclosure is typically understood to be an amount that is sufficient to induce a pharmaceutical effect. Therapy / treatment: The term “therapy” refers to “treating” or “treatment” of a disease or condition, inhibiting the disease (slowing or arresting its development), providing relief from the symptoms or side-effects of the disease (including palliative treatment), and relieving the disease (causing regression of the disease). Therapeutically effective amount or effective amount: is an amount of a compound that is sufficient to treat a disease or condition, inhibit the disease or condition, provide relief from symptoms or side-effects of the disease, and / or cause regression of the disease or condition. Half-life: The term “half-life”, as used herein in the context of administering a mutant FGF-21 peptide and / or conjugate thereof, is defined as the time required for the plasma concentration of a drug, i.e. of the mutant FGF-21 peptide and / or conjugate, in a subject to be reduced by one half. O-linked glycosylation: “O-linked glycosylation” takes place at serine or threonine residues (Tanner et al., Biochim. Biophys. Acta. 906:81-91 (1987); and Hounsell et al, Glycoconj. J. 13:19-26 (1996)). In the present disclosure, O-linked glycosylation sites, Attorney Docket No.180234-011901 / PCT which are amino acid motifs in the amino acid sequence of a peptide which are recognized by glycosyl transferases as attachment points for glycosyl residues, include the amino acid motif proline-threonine (PT) not present in the native / wild-type amino acid sequence. In particular, the threonine residue is newly introduced adjacent to a proline and on the C- terminal side of a proline residue. The glycosyl moiety is then attached to the –OH group of the threonine residue by the glycosyl transferase. Newly introduced O-linked glycosylation side: “Newly introduced O-linked glycosylation side” denotes an O-linked glycosylation side which did not exist in the native or wild-type FGF-21 before introducing a threonine adjacent to and on the C-terminal side of a proline residue as described herein. Adjacent: Adjacent denotes the amino acid immediately next to another amino acid in the amino acid sequence, either on the N-terminal or on the C-terminal side of the respective amino acid. In the present disclosure, e.g. the newly introduced threonine residue is adjacent to a proline residue on the C-terminal side of a proline residue. Glycosyl moiety: A glycosyl moiety is a moiety consisting of one or more, identical or different glycosyl residues which links the mutant FGF-21 peptide to a polyethylene glycol (PEG), thereby forming a conjugate comprising a peptide, glycosyl moiety and PEG. The glycosyl moiety can be a mono-, di-, tri-, or oligoglycosyl moiety. The glycosyl moiety may comprise one or more sialic acid residues, one or more N-acetylgalactosamine (GalNAc) residues, one or more galactose (Gal) residues and others. The glycosyl moiety may be modified, such as with a PEG or methoxy-PEG (m-PEG), an alkyl derivative of PEG. Glycoconjugation: “Glycoconjugation”, as used herein, refers to the enzymatically mediated conjugation of a PEG-modified glycosyl moiety to an amino acid or glycosyl residue of a (poly)peptide, e.g. a mutant FGF-21 of the present disclosure. A subgenus of “glycoconjugation” is “glyco-PEGylation” in which the modifying group of the modified glycosyl moiety is PEG or m-PEG. The PEG may be linear or branched. Typically, a branched PEG has a central branch core moiety and a plurality of linear polymer chains linked to the central branch core. PEG is commonly used in branched forms that can be prepared by addition of ethylene oxide to various polyols, such as glycerol, pentaerythritol and sorbitol. The central branch moiety can also be derived from several amino acids, such Attorney Docket No.180234-011901 / PCT as lysine. The branched PEG can be represented in general form as R(-PEG-OX)min which R represents the core moiety, such as glycerol or pentaerythritol, X represents a capping group or an end group, and m represents the number of arms. The terms “glyco-PEG” and “glycosyl-PEG” are used interchangeably and denote a chemical moiety consisting of PEG or methoxy-PEG (mPEG or m-PEG), one or more glycosyl residues (or glycosyl moieties), and optionally a linker between PEG / methoxy-PEG and the glycosyl moieties, such as an amino acid, e.g. glycine. An example of a glycosyl-PEG / glyco-PEG moiety is PEG-sialic acid (PEG-Sia). It should be noted that the terms “glyco-PEG” and “glycosyl-PEG” as well as “PEG-sialic acid” and “PEG-Sia” as well as similar terms for glyco-PEG moieties may or may not include a linker between PEG and the glycosyl moiety or moieties, i.e. “PEG- sialic acid” encompasses e.g. PEG-sialic acid as well as PEG-Gly-sialic acid as well as mPEG-Gly-sialic acid. Sequence motif: A sequence motif denotes a short amino acid sequence, such as that comprising only two amino acids, which is present at any possible position in a longer amino acid sequence, such as in the amino acid sequence of human FGF-21. Sequence motifs are e.g. denoted as P172T which means that the proline at position 172 is followed C-terminally immediately by a threonine residue. Sialic acid: The term “sialic acid” or “Sia” refers to any member of a family of nine- carbon carboxylated sugars. The most common member of the sialic acid family is N-acetyl- neuraminic acid (2-keto-5-acetamido-3,5-dideoxy-D-glycero-D-galactononulopyranos-1- onic acid (often abbreviated as Neu5Ac, NeuAc, or NANA). A second member of the family is N-glycolylneuraminic acid (Neu5Gc or NeuGc), in which the N-acetyl group of NeuAc is hydroxylated. A third sialic acid family member is 2-keto-3-deoxy-nonulosonic acid (KDN) (Nadano et al. (1986) J. Biol. Chem. 261:11550-11557). Also included are 9-substituted sialic acids such as a 9-0-C1-C6acyl-Neu5Ac like 9-O-lactyl-Neu5Ac or 9-O-acetyl- Neu5Ac, 9-deoxy-9-fluoro-Neu5Ac and 9-azido-9-deoxy-Neu5Ac. For review of the sialic acid family, see e.g. Varki, Glycobiology 2:25-40 (1992)). Pharmaceutically acceptable excipient: “Pharmaceutically acceptable” excipient includes any material, which when combined with the mutant FGF-21 peptide conjugate of the disclosure retains the conjugates’ activity and is non-reactive with a subject’s immune systems. Examples include, but are not limited to, any of the standard pharmaceutical Attorney Docket No.180234-011901 / PCT excipients such as a phosphate buffered saline solution, water, salts, emulsions such as oil / water emulsion, and various types of wetting agents. Pharmaceutical container: A “pharmaceutical container” is a container which is suitable for carrying a pharmaceutical composition and typically made of an inert material and sterile. Administering: The term “administering” means oral administration, inhalation, administration as a suppository, topical contact, intravenous, intraperitoneal, intramuscular, intralesional, intranasal or subcutaneous administration, or the implantation of a slow-release device e.g., a mini-osmotic pump, to the subject. Administration is by any route including parenteral, and transmucosal (e.g. oral, nasal, vaginal, rectal, or transdermal). Parenteral administration includes e.g. intravenous, intramuscular, intraarteriole, intradermal, subcutaneous, intraperitoneal, intraventricular and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc. Diabetes and diabetes related diseases: “Diabetes” is a well-known and well- characterized disease often referred to as diabetes mellitus. The term describes a group of metabolic diseases in which the person has high blood glucose levels (blood sugar), either because insulin production is inadequate, or because the body's cells do not respond properly to insulin, or both. Patients with high blood sugar will typically experience polyuria (frequent urination), they will become increasingly thirsty (polydipsia) and hungry (polyphagia). “Diabetes related diseases” are diseases characterized by the same symptoms such as obesity, polyuria, polydipsia and polyphagia. Diabetes type 2: “Diabetes type 2” is the most common form of diabetes / diabetes mellitus. Diabetes type 2 most commonly develops in adulthood and is more likely to occur in people who are overweight and physically inactive. Unlike type 1 diabetes, which currently cannot be prevented, many of the risk factors for type 2 diabetes can be modified. The International Diabetes Foundation lists four symptoms that signal the need for diabetes testing: a) frequent urination, b) weight loss, c) lack of energy and d) excessive thirst. Insulin resistance is usually the precursor to diabetes type 2 a condition in which more insulin than usual is needed for glucose to enter the cells. Insulin resistance in the liver results in more glucose production while resistance in peripheral tissues means glucose uptake is impaired. Attorney Docket No.180234-011901 / PCT Nonalcoholic fatty liver disease (NAFLD) and Non-alcoholic steatohepatitis (NASH): are a condition where fat is deposited in the liver with subsequent liver damage and inflammation. Metabolic syndrome: a defined cluster of risk factors (biochemical and physiological changes) that are associated with the development of type 2 diabetes and cardiovascular disease. Natural FGF-21 has a comparatively short half-life in vivo, with a reported circulating half-life ranging from 0.5 to 4 hours in rodents and non-human primates, which limits its clinical applicability. The half-life of recombinant human FGF-21 is 1–2 hours. To improve pharmacokinetic properties of FGF-21, various half-life extension strategies have been developed. See also WO2019 / 043457 and PCT / US23 / 72811, the entire content of each of which which is incorporated herein in its entirety. Abbreviations used herein include: PEG, poly(ethyleneglycol); PPG, poly(propyleneglycol); Ara, arabinosyl; Fru, fructosyl; Fuc, fucosyl; Gal, galactosyl; GalNAc, N-acetylgalactosaminyl; Glc, glucosyl; GlcNAc, N-acetylglucosaminyl; Man, mannosyl; ManAc, mannosaminyl acetate; Xyl, xylosyl; NeuAc, sialyl or N- acetylneuraminyl; Sia, sialyl or N-acetylneuraminyl; and derivatives and analogues thereof. PEGylation In glycoPEGylation, a PEG moiety may be transferred to an amino acid or glycosyl residue attached to an amino acid of the protein or peptide using a glycosyltransferase. The general final structure is protein – glycosyl moiety – optional further linker – PEG. A more particular final structure is protein – (N-, C- or internal) amino acid of the protein – one or more glycosyl residues – optional linker (e.g., amino acid linker) – linear or branched PEG moiety of various lengths, wherein the glycosyl moiety may comprise one or more glycosyl residues. The one or more glycosyl residues comprising at least part of the structure linking the protein to the PEG moiety may be any possible glycosyl residue. A diverse array of methods for glycoPEGylating proteins are known in the art and are described in detail herein below. In some embodiments, Fibroblast Growth Factor-21 (FGF-21) peptide conjugates comprise: Attorney Docket No.180234-011901 / PCT i) a mutant FGF-21 peptide comprising at least one threonine (T) residue adjacent to at least one proline (P) residue on the C-terminal side of said at least one proline residue, thereby forming at least one O-linked glycosylation site which does not exist in the corresponding native FGF-21, wherein the corresponding native FGF-21 has an amino acid sequence that is at least 95% identical to SEQ ID NO: 1, and ii) a 20 kDa polyethylene glycol (PEG), wherein said 20 kDa PEG is covalently attached to said mutant FGF-21 peptide at said at least one threonine residue via at least one glycosyl moiety. In some embodiments, the mutant FGF-21 peptide conjugate comprises a mutant FGF-21 peptide comprising the amino acid sequence PT. In some embodiments, the mutant FGF-21 peptide comprises at least one amino acid sequence selected from the group consisting of P172T, P156T, P5T, P3T, P9T, P50T, P61T, P79T, P91T, P116T, P129T, P131T, P134T, P139T, P141T, P144T, P145T, P148T, P150T, P151T, P158T, P159T, P166T, P178T and combinations thereof, wherein the positions of proline and threonine are based on the amino acid sequence as depicted in SEQ ID NO: 1. In some embodiments, the mutant FGF-21 peptide comprises at least one amino acid sequence selected from the group consisting of P172T, P156T, P5T and combinations thereof, particularly consisting of P172T, P156T and combinations thereof, wherein the positions of proline and threonine are based on the amino acid sequence as depicted in SEQ ID NO: 1. In some embodiments, the proline residue is located between amino acid 145 and the C-terminus of the mutant FGF- 21 peptide, wherein the position of amino acid 145 is based on the amino acid sequence as depicted in SEQ ID NO: 1. In some embodiments, the mutant FGF-21 peptide comprises the amino acid sequence P172T, wherein the positions of proline and threonine are based on the amino acid sequence as depicted in SEQ ID NO: 1. In some embodiments, the mutant FGF-21 peptide comprises the mutations S173T and R176A, wherein the positions of the amino acids S and R are based on the amino acid sequence as depicted in SEQ ID NO: 1, particularly the mutant FGF-21 peptide comprises the amino acid sequence as depicted in SEQ ID NO: 2. In some embodiments, the mutant FGF-21 peptide comprises the mutation Q157T, wherein the position of the amino acid Q is based on the amino acid sequence as depicted in Attorney Docket No.180234-011901 / PCT SEQ ID NO: 1, particularly the mutant FGF-21 peptide comprises the amino acid sequence as depicted in SEQ ID NO: 4. In some embodiments, the mutant FGF-21 peptide comprises the mutation D6T, wherein the position of the amino acid D is based on the amino acid sequence as depicted in SEQ ID NO: 1, particularly the mutant FGF-21 peptide comprises the amino acid sequence as depicted in SEQ ID NO: 5. In some embodiments, the mutant FGF-21 peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 to 28. In some embodiments, the mutant FGF-21 peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 to 5. In some embodiments, the mutant FGF-21 peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 to 4. In some embodiments, the mutant FGF-21 peptide comprises an amino acid sequence consisting of SEQ ID NO: 2. In some embodiments, the mutant FGF-21 peptide conjugate comprises at least one glycosyl moiety comprising N-acetylgalactosamine (GalNAc), galactose (Gal) and / or sialic acid (Sia). In a particular embodiment thereof, the at least one glycosyl moiety comprises the structure -GalNAc-Sia-. In some embodiments, the mutant FGF-21 peptide conjugate comprises a 20 kDa PEG moiety which is attached to the at least one glycosyl moiety via an amino acid residue, particularly glycine (Gly). In an even more particular embodiment, the mutant FGF-21 peptide conjugate comprises the structure -GalNAc-Sia-Gly-PEG(20kDa). Still more particularly, the mutant FGF-21 peptide conjugate comprises the structure: , wherein n is an integer selected from 450 to 460. Attorney Docket No.180234-011901 / PCT In some embodiments, the mutant FGF-21 peptide conjugate comprises a 20 kDa PEG which is a linear or branched PEG. In some embodiments, the mutant FGF-21 peptide conjugate comprises a 20 kDa PEG which is a linear PEG. In some embodiments, the 20 kDa PEG is a 20 kDa methoxy-PEG. In some embodiments, the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG (also referred herein as mutant FGF-21 peptide conjugate having SEQ ID NO: 2). In some embodiments, encompassed herein is a pharmaceutical composition comprising at least one mutant FGF-21 peptide conjugate described herein and a pharmaceutically acceptable carrier. In some embodiments, the mutant FGF-21 peptide conjugate comprises a 20 kDa PEG which is linear. In some embodiments, the mutant FGF- 21 peptide conjugate comprises a 20 kDa PEG which is a mutant FGF-21 peptide conjugate having SEQ ID NO: 2. In some embodiments, the mutant FGF-21 peptide conjugate is present in a concentration in the range from 0.1 mg / mL to 50 mg / mL, from 1 mg / mL to 45 mg / mL, more from 10 mg / mL to 40 mg / mL, for example in a concentration of 26±4 mg / mL. The buffering agent may be a Tris buffer. The buffering agent may be present in a concentration from 1 mM to 100 mM, from 2 mM to 75 mM, from 5 mM to 50 mM, from 10 mM to 25 mM, for example 16±2 mM. The pH may be in the range from 6.0 to 8.5, from 6.5 to 8.0, from 6.75 to 8.0, for example 7.5±0.3. The pharmaceutical composition may further comprise a salt, for example an inorganic salt, e,g, NaCl. The pharmaceutical composition may comprise a salt which is present in a concentration from 30 mM to 200 mM, from 40 mM to 150 mM, from 50 mM to 100 mM, for example 56±2 mM. The pharmaceutical composition may further comprise a tonicity modifying agent. Suitable tonicity modifying agents include glycerol, amino acids, sodium chloride, proteins, or sugars and sugar alcohols. In some embodiments, the tonicity modifying agent is a sugar, In some embodiments, the tonicity modifying agent is sucrose. The tonicity modifying agent is Attorney Docket No.180234-011901 / PCT present in a concentration of 50 mM to 200 mM, of 100 mM to 175 mM, of 135 mM to 160 mM, for example 150±2 mM. The pharmaceutical composition may further comprise a surfactant, for example a non-ionic surfactant. The surfactant or non-ionic surfactant may be a polysorbate-based non-ionic surfactant, particularly polysorbate 20 or polysorbate 80. The surfactant or non-ionic surfactant may be present in a concentration of 0.01 mg / mL to 1 mg / mL, 0.05 to 0.5 mg / mL, for example 0.2±0.02 mg / mL. In some embodiments, the pharmaceutical composition comprises 0.1 mg / mL to 50 mg / mL of mutant FGF-21 peptide conjugate, 1 mM to 100 mM buffering agent, such as Tris buffer, 30 mM to 200 mM salt, such as NaCl, 50 mM to 200 mM tonicity modifying agent, such as sucrose, and 0.01 mg / mL to 1 mg / mL surfactant or non-ionic surfactant, such as polysorbate 20, and has a pH of 6.0 to 8.5. A pharmaceutical container comprising at least one of the mutant FGF-21 peptide conjugates described herein and / or a pharmaceutical composition comprising same are also encompassed herein. Suitable pharmaceutical containers include, without limitation, a syringe, vial, infusion bottle, ampoule, carpoule, a syringe equipped with a needle protection system, and a carpoule within an injection pen. FGF-21 Conjugates In some embodiments, exemplary conjugates of a modified sugar and a mutant FGF- 21 peptide are presented. In some embodiments, mutant FGF-21 peptide conjugates were made comprising a mutant FGF peptide and at least one modified sugar, wherein a first of the at least one modified sugar is linked to an amino acid of the peptide through a glycosyl linking group. As described herein, the amino acid to which the glycosyl linking group is attached is mutated to create a site recognized by the glycosyltransferase. In another exemplary embodiment, a mutant FGF-21 peptide conjugate can comprise a mutant FGF-21 peptide and a glycosyl group attached to the mutated amino acid residue of the mutant FGF-21 peptide. In an exemplary embodiment, the glycosyl group is an intact glycosyl linking group. In another exemplary embodiment, the glycosyl group further comprises a modifying group. In another exemplary embodiment, the modifying group is a non-glycosidic modifying group. In another exemplary embodiment, the modifying group does not include a naturally occurring saccharide moiety. Attorney Docket No.180234-011901 / PCT In some embodiments, the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. In some embodiments, the mutant FGF-21 peptide conjugate comprises the structure: 21wherein n is an integer selected from 450 to 460. Modified Sugars In an exemplary embodiment, mutant FGF-21 peptides are reacted with a modified sugar, thus forming a peptide conjugate. A modified sugar comprises a “sugar donor moiety” as well as a “sugar transfer moiety”. The sugar donor moiety is any portion of the modified sugar that will be attached to the peptide, either through a glycosyl moiety or amino acid moiety, as a conjugate described herein. The sugar donor moiety includes those atoms that are chemically altered during their conversion from the modified sugar to the glycosyl linking group of the mutant FGF-21 peptide conjugate. For modified sugars described herein, the saccharyl moiety may be a saccharide, a deoxy-saccharide, an amino-saccharide, or an N-acyl saccharide. The term “saccharide” and its equivalents, “saccharyl,” “sugar,” and “glycosyl” refer to monomers, dimers, oligomers and polymers. The sugar moiety is also functionalized with a modifying group. The modifying group is conjugated to the saccharyl moiety, typically, through conjugation with an amine, sulfhydryl or hydroxyl, e.g., primary hydroxyl, moiety on the sugar. In an exemplary embodiment, the modifying group is attached through an amine moiety on the Attorney Docket No.180234-011901 / PCT sugar, e.g., through an amide, a urethane or a urea that is formed through the reaction of the amine with a reactive derivative of the modifying group. Any saccharyl moiety can be utilized as the sugar donor moiety of the modified sugar. The saccharyl moiety can be a known sugar, such as mannose, galactose or glucose, or a species having the stereochemistry of a known sugar. The general formulae of these modified sugars are: Other saccharyl moieties that are useful in methods described herein include, but are not limited to fucose and sialic acid, as well as amino sugars such as glucosamine, galactosamine, mannosamine, the 5-amine analogue of sialic acid and the like. The saccharyl moiety can be a structure found in nature or it can be modified to provide a site for conjugating the modifying group. For example, in one embodiment, the modified sugar provides a sialic acid derivative in which the 9-hydroxy moiety is replaced with an amine. The amine is readily derivatized with an activated analogue of a selected modifying group. Examples of modified sugars useful in methods described herein are presented in PCT Patent Application No. PCT / US05 / 002522, which is incorporated herein by reference in its entirety. In a further exemplary embodiment, the disclosure utilizes modified sugars in which the 6-hydroxyl position is converted to the corresponding amine moiety, which bears a linker-modifying group cassette such as those set forth above. Exemplary glycosyl groups that can be used as the core of these modified sugars include Gal, GalNAc, Glc, GlcNAc, Attorney Docket No.180234-011901 / PCT Fuc, Xyl, Man, and the like. A representative modified sugar according to this embodiment is set forth below: in which R11-R14are members independently selected from H, OH, C(O)CH3, NH, and NH C(O)CH3. R10is a link to, e.g., another glycosyl residue (—O-glycosyl). R14is OR1, NHR1or NH-L-R1. R1and NH-L-R1are as described herein. In a still further exemplary embodiment, the glycosyl groups used as the core of modified sugars in which the 6-hydroxyl position is converted to the corresponding amine moiety include Gal and / or GalNAc. Glycosyl Linking Groups In an exemplary embodiment, mutant FGF-21 peptide conjugates comprising a modified sugar described herein and a mutant FGF peptide are presented. In this embodiment, the sugar donor moiety (such as the saccharyl moiety and the modifying group) of the modified sugar becomes a “glycosyl linking group”. The “glycosyl linking group” can alternatively refer to the glycosyl moiety which is interposed between the peptide and the modifying group. In the exemplary embodiments that follow, the disclosure is illustrated by reference to the use of selected derivatives of furanose and pyranose. Those of skill in the art will appreciate that the structures and compositions set forth are generally applicable across the genus of glycosyl linking groups and modified sugars. The glycosyl linking group can, therefore, comprise virtually any mono- or oligo-saccharide. In an exemplary embodiment, methods described herein utilize a glycosyl linking group that has the formula: Attorney Docket No.180234-011901 / PCT in which J is a glycosyl moiety, L is a bond or a linker and R1is a modifying group, e.g., a polymeric modifying group. Exemplary bonds are those that are formed between an NH2moiety on the glycosyl moiety and a group of complementary reactivity on the modifying group. For example, when R1includes a carboxylic acid moiety, this moiety may be activated and coupled with the NH2moiety on the glycosyl residue affording a bond having the structure NHC(O)R1. J in some embodiments is a glycosyl moiety that is “intact”, not having been degraded by exposure to conditions that cleave the pyranose or furanose structure, e.g. oxidative conditions, e.g., sodium periodate. Exemplary linkers include alkyl and heteroalkyl moieties. The linkers include linking groups, for example acyl-based linking groups, e.g., —C(O)NH—, —OC(O)NH—, and the like. The linking groups are bonds formed between components of the conjugates, e.g., between the glycosyl moiety and the linker (L), or between the linker and the modifying group (R1). Other exemplary linking groups are ethers, thioethers and amines. For example, in one embodiment, the linker is an amino acid residue, such as a glycine residue. The carboxylic acid moiety of the glycine is converted to the corresponding amide by reaction with an amine on the glycosyl residue, and the amine of the glycine is converted to the corresponding amide or urethane by reaction with an activated carboxylic acid or carbonate of the modifying group. An exemplary species of NH-L-R1has the formula: — NH{C(O)(CH2)aNH}s{C(O)(CH2)b(OCH2CH2)cO(CH2)dNH}tR1, in which the indices s and t are independently 0 or 1. The indices a, b and d are independently integers from 0 to 20, and c is an integer from 1 to 2500. Other similar linkers are based on species in which an — NH moiety is replaced by another group, for example, —S, —O or —CH2. As is understood in the art, one or more of the bracketed moieties corresponding to indices s and t can be replaced with a substituted or unsubstituted alkyl or heteroalkyl moiety. In some embodiments, compounds described herein may comprise NH-L-R′, wherein NH-L-R′ is: NHC(O)(CH2)aNHC(O)(CH2)b(OCH2CH2)cO(CH2)dNHR1, NH(CH2)aNHR1, and NHR1. In these formulae, the indices a, b and d are independently Attorney Docket No.180234-011901 / PCT selected from the integers from 0 to 20, for example from 1 to 5. The index c is an integer from 1 to about 2500. In an exemplary embodiment, c is selected such that the PEG moiety is approximately 1 kD, 5 kD, 10, kD, 15 kD, 20 kD, 25 kD, 30 kD, 35 kD, 40 kD, 45 kD, 50 kD, 55 kD, 60 kD or 65 kD. In some embodiments, the c is selected such that the PEG moiety ranges from 15-25 kD, 16-25 kD, 17-25 kD, 18-25 kD, 19-25 kD, 20-25 kD, 21-25 kD, 22-25 kD, 23-25 kD, 24-25 kD, 15-20 kD, 16-20 kD, 17-20 kD, 18-20 kD, 19-20 kD, 20-30 kD, 21-30 kD, 22-30 kD, 23-30 kD, 24-30 kD, 25-30 kD, 26-30 kD, 27-30 kD, 28-30 kD, 29-30 kD. In some embodiments, the c is selected such that the PEG moiety is 20 kD, 22 kD, 23 kD, 24 kD, 25 kD, 26 kD, 27 kD, 28 kD, 29 kD, or 30 kD. For the purposes of clarity, the glycosyl linking groups in the remainder of this section are based on a sialyl moiety. However, one of skill in the art will recognize that another glycosyl moiety, such as mannosyl, galactosyl, glucosyl, or fucosyl, could be used in place of the sialyl moiety. In an exemplary embodiment, the glycosyl linking group is an intact glycosyl linking group, in which the glycosyl moiety or moieties forming the linking group are not degraded by chemical (e.g., sodium metaperiodate) or enzymatic (e.g., oxidase) processes. Selected conjugates of the disclosure include a modifying group that is attached to the amine moiety of an amino-saccharide, e.g., mannosamine, glucosamine, galactosamine, sialic acid etc. In an exemplary embodiment, the disclosure provides a peptide conjugate comprising an intact glycosyl linking group having a formula that is selected from:

[0002] Attorney Docket No.180234-011901 / PCT In Formulae I R2is H, CH2OR7, COOR7or OR7, in which R7represents H, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl. When COOR7is a carboxylic acid or carboxylate, both forms are represented by the designation of the single structure COO−or COOH. In Formulae I and II, the symbols R3, R4, R5, R6and R6′independently represent H, substituted or unsubstituted alkyl, OR8, NHC(O)R9. The index d is 0 or 1. R8and R9are independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, sialic acid or polysialic acid. At least one of R3, R4, R5, R6or R6′includes a modifying group. This modifying group can be a polymeric modifying moiety e.g., PEG, linked through a bond or a linking group. In an exemplary embodiment, R6and R6′, together with the carbon to which they are attached are components of the pyruvyl side chain of sialic acid. In a further exemplary embodiment, the pyruvyl side chain is functionalized with the polymeric modifying group. In another exemplary embodiment, R6and R6′, together with the carbon to which they are attached are components of the side chain of sialic acid and the polymeric modifying group is a component of R5. Attorney Docket No.180234-011901 / PCT Exemplary modifying group-intact glycosyl linking group cassettes according to this motif are based on a sialic acid structure, such as those having the formulae: In the formulae above, R1and L are as described above. Further detail about the structure of exemplary R1groups is provided below. In still a further exemplary embodiment, the conjugate is formed between a peptide and a modified sugar in which the modifying group is attached through a linker at the 6- carbon position of the modified sugar. Thus, illustrative glycosyl linking groups according to this embodiment have the formula: ^ in which the radicals are as discussed above. Glycosyl linking groups include, without Attorney Docket No.180234-011901 / PCT limitation, glucose, glucosamine, N-acetyl-glucosamine, galactose, galactosamine, N- acetylgalactosamine, mannose, mannosamine, N-acetyl-mannosamine, and the like. In some embodiments, the present disclosure provides a mutant FGF-21 peptide conjugate comprising the following glycosyl linking group: wherein D is a member selected from —OH and R1-L-HN—; G is a member selected from H and R1-L- and —C(O)(C1-C6)alkyl; R1is a moiety comprising a straight-chain or branched poly(ethylene glycol) residue; and L is a linker, e.g., a bond (“zero order”), substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl. In exemplary embodiments, when D is OH, G is and when G is —C(O)(C1-C6)alkyl, D is R1-L-NH—. In some embodiments, the peptide conjugate includes a glycosyl linking group having the formula: ^ In some embodiments, the glycosyl linking group has the formula: Attorney Docket No.180234-011901 / PCT in which the index t is 0 or 1. In some embodiments, the glycosyl linking group has the formula: in which the index t is 0 or 1. In some embodiments, the glycosyl linking group has the formula: in which the index p represents and integer from 1 to 10; and a is either 0 or 1. In some embodiments, a glycoPEGylated peptide conjugate is selected from the formulae set forth below: Attorney Docket No.180234-011901 / PCT In the formulae above, the index t is an integer from 0 to 1 and the index p is an integer from 1 to 10. The symbol R15′represents H, OH (e.g., Gal-OH), a sialyl moiety, a sialyl linking group (i.e., sialyl linking group-polymeric modifying group (Sia-L-R1), or a Attorney Docket No.180234-011901 / PCT sialyl moiety to which is bound a polymer modified sialyl moiety (e.g., Sia-Sia-L-R1) (“Sia- Siap”)). Exemplary polymer modified saccharyl moieties have a structure according to Formulae I and II. An exemplary peptide conjugate of the disclosure will include at least one glycan having a R15′that includes a structure according to Formulae I or II. The oxygen, with the open valence, of Formulae I and II is, in some embodiments, attached through a glycosidic linkage to a carbon of a Gal or GalNAc moiety. In a further exemplary embodiment, the oxygen is attached to the carbon at position 3 of a galactose residue. In an exemplary embodiment, the modified sialic acid is linked α2,3-to the galactose residue. In another exemplary embodiment, the sialic acid is linked α2,6-to the galactose residue. In an exemplary embodiment, the sialyl linking group is a sialyl moiety to which is bound a polymer modified sialyl moiety (e.g., Sia-Sia-L-R1) (“Sia-Siap”). Here, the glycosyl linking group is linked to a galactosyl moiety through a sialyl moiety: An exemplary species according to this motif is prepared by conjugating Sia-L-R1to a terminal sialic acid of a glycan using an enzyme that forms Sia-Sia bonds, e.g., CST-11, ST8Sia-II, ST8Sia-III and ST8Sia-IV. In another exemplary embodiment, the glycans on the peptide conjugates have a formula that is selected from the group:

[0003] Attorney Docket No.180234-011901 / PCT and combinations thereof. In each of the formulae above, R15′is as discussed above. Moreover, an exemplary mutant FGF-21 peptide conjugate described herein will include at least one glycan with an R15moiety having a structure according to Formulae I or II. In another exemplary embodiment, the glycosyl linking group comprises at least one glycosyl linking group having the formula: wherein R15is said sialyl linking group; and the index p is an integer selected from 1 to 10. In an exemplary embodiment, the glycosyl linking moiety has the formula:

[0004] Attorney Docket No.180234-011901 / PCT in which b is an integer from 0 to 1. The index s represents an integer from 1 to 10; and the index f represents an integer from 1 to 2500. In an exemplary embodiment, the polymeric modifying group is PEG. In another exemplary embodiment, the PEG moiety has a molecular weight of 20-30 kDa. In exemplary embodiments, the PEG moiety has a molecular weight of 17 kDa, 18 kDa, 19 kDa, 20 kDa, 21 kDa, 22 kDa, 23 kDa, 24 kDa, 25 kDa, 26 kDa, 27 kDa, 28 kDa, 29 kDa, 30 kDa, 31 kDa, 32 kDa, or 33 kDa. In another exemplary embodiment, the PEG moiety has a molecular weight of 20 kDa. In another exemplary embodiment, the PEG moiety has a molecular weight of 30 kDa. In another exemplary embodiment, the PEG moiety has a molecular weight of about 5 kDa. In another exemplary embodiment, the PEG moiety has a molecular weight of about 10 kDa. In another exemplary embodiment, the PEG moiety has a molecular weight of about 40 kDa. In an exemplary embodiment, the glycosyl linking group is a linear 10 kDa-PEG- sialyl, and one or two of these glycosyl linking groups are covalently attached to the peptide. In an exemplary embodiment, the glycosyl linking group is a linear 20 kDa-PEG- sialyl, and one or two of these glycosyl linking groups are covalently attached to the peptide. In an exemplary embodiment, the glycosyl linking group is a linear 30 kDa-PEG-sialyl, and one or two of these glycosyl linking groups are covalently attached to the peptide. In an exemplary embodiment, the glycosyl linking group is a linear 5 kDa-PEG-sialyl, and one, two or three of these glycosyl linking groups are covalently attached to the peptide. In an exemplary embodiment, the glycosyl linking group is a linear 40 kDa-PEG-sialyl, and one or two of these glycosyl linking groups are covalently attached to the peptide. In a still further exemplary embodiment, a mutant FGF-21 peptide is pegylated in accordance with methods described herein. In some embodiments, the mutant FGF-21 peptide comprises the mutations S172T and R176A, wherein the positions of the amino acids S and R are based on the amino acid sequence as depicted in SEQ ID NO: 1. In some embodiments, the mutant FGF-21 peptide comprises the amino acid sequence as depicted in SEQ ID NO: 2. As detailed herein above, the at least one glycosyl moiety attached to the threonine residue and linking the newly introduced threonine residue to the PEG moiety may virtually be any possible glycosyl moiety. The only limitation is that it should be able to attach to threonine and that it should be able to be attached to PEG or m-PEG, more Attorney Docket No.180234-011901 / PCT particularly via a linker, e.g. an amino acid residue, for example glycine. In some embodiments, the at least one glycosyl moiety comprises N-acetylgalactosamine (GalNAc), galactose (Gal) and / or sialic acid (Sia). In a more particular embodiment, the at least one glycosyl moiety comprises the structure -GalNAc-Sia-, i.e. two glycosyl moieties, namely GalNAc and Sia, wherein the PEG residue may be attached to GalNAc or Sia, for example to Sia. The glycosyl moiety which is not attached to the PEG moiety may be attached to the newly introduced threonine residue. In some embodiments, the 20 kDa PEG moiety is attached to the at least one glycosyl linker via a linker, e.g. an amino acid residue, particularly a small amino acid, such as alanine or glycine, more particularly via glycine (Gly). Hence, the PEG or m-PEG moiety is attached to the amino acid and the amino acid is attached to a glycosyl moiety, such as Sia. The glycosyl moiety is attached to the amino acid linker, if present, and to the newly introduced threonine residue in the mutant FGF-21 amino acid sequence. The amino acid residue is attached to PEG and the glycosyl residue via a method described in WO 03 / 031464 which is incorporated herein by reference. In some embodiments, the mutant FGF-21 peptide (e.g., SEQ ID NO: 2) conjugate comprises the structure -GalNAc-Sia-Gly-PEG(20kDa), wherein GalNAc is attached, e.g. to a newly introduced threonine residue and to Sia. Sia is further attached via a glycine residue to a PEG of 17 kDa, 18 kDa, 19 kDa, 20 kDa, 21 kDa, 22 kDa, 23 kDa, 24 kDa, 25 kDa, 26 kDa, 27 kDa, 28 kDa, 29 kDa, 30 kDa, 31 kDa, 32 kDa, or 33 kDa. In some embodiments, the mutant FGF-21 peptide (e.g., SEQ ID NO: 2) conjugate comprises the structure -GalNAc-Sia-Gly-PEG(20kDa), wherein GalNAc is attached, e.g. to a newly introduced threonine residue and to Sia. Sia is further attached via a glycine residue to a PEG of 20 kDa, 21 kDa, 22 kDa, 23 kDa, 24 kDa, 25 kDa, 26 kDa, 27 kDa, 28 kDa, 29 kDa, or 30 kDa. In some embodiments, the mutant FGF-21 peptide (e.g., SEQ ID NO: 2) conjugate comprises the structure -GalNAc-Sia-Gly-PEG(20kDa), wherein GalNAc is attached, e.g. to a newly introduced threonine residue and to Sia. Sia is further attached via a glycine residue to a PEG of 20 kDa, 25 kDa, or 30 kDa. In some embodiments, the mutant FGF-21 peptide (e.g., SEQ ID NO: 2) conjugate comprises the structure -GalNAc-Sia-Gly-PEG(20kDa), wherein GalNAc is attached, e.g. to Attorney Docket No.180234-011901 / PCT a newly introduced threonine residue and to Sia. Sia is further attached via a glycine residue to a PEG of 20 kDa or 30 kDa. In some embodiments, the mutant FGF-21 peptide (e.g., SEQ ID NO: 2) conjugate comprises the structure -GalNAc-Sia-Gly-PEG(20kDa), wherein GalNAc is attached, e.g. to a newly introduced threonine residue and to Sia. Sia is further attached via a glycine residue to a PEG of 20 kDa. In some embodiments, the mutant FGF-21 peptide conjugate comprises the structure: , wherein n is an integer selected from 450 to 460. The 20 kDa PEG may be linear or branched. In some embodiments, the 20 kDa PEG, is a linear 20 kDa PEG. In some embodiments, the 20 kDa PEG is a 20 kDa methoxy-PEG (mPEG, m-PEG). PEG and mPEG of different molecular weight can be obtained from various suppliers, such as from JenKem Technology USA, Plano, TX, USA, or Merckle Biotec, Ulm, Germany. It is understood in the art that PEG 20kDa means that the size of the PEG residues is 20 kDa in average and that the majority of the PEG residues are 20 kDa in size. Mutant FGF-21 peptides and conjugates thereof As described herein, variants of Fibroblast Growth Factor-21 (FGF-21) having surprising properties, including variants having exceptionally long half-lives are produced, which variants are peptide conjugates comprising: i) a mutant FGF-21 peptide comprising at least one threonine (T) residue adjacent to at least one proline (P) residue on the C-terminal side of the at least one proline residue, thereby forming at least one O-linked glycosylation site which does not exist in the corresponding native FGF-21, wherein the corresponding native FGF-21 has an amino acid sequence that is at least 95% identical to SEQ ID NO: 1, and Attorney Docket No.180234-011901 / PCT ii) a 20-30 kDa polyethylene glycol (PEG), wherein said 20-30 kDa PEG is covalently attached to said mutant FGF-21 peptide at the at least one threonine residue via at least one glycosyl moiety. For the attachment of the 20-30 kDa PEG residue, a threonine residue is introduced into the amino acid sequence of native FGF-21 adjacent to and on the C-terminal side of a proline residue which is already present in the amino acid sequence of native FGF-21, i.e. is a native proline residue. For this purpose, either (i) an additional threonine may be introduced immediately next to the native proline residue or (ii) the native amino acid which is present in the native amino acid sequence of FGF-21 adjacent to and located on the C- terminal side of a native proline residue is exchanged for a threonine residue. In the present disclosure, option (ii) is an exemplary embodiment. As described herein, more than one threonine residue may be introduced adjacent and C-terminal to a proline residue which is already present. A mutant FGF-21 of the present disclosure may thus comprise both threonine residues which have been additionally introduced and threonine residues which have been introduced instead of a native amino acid. By the introduction of a new threonine residue on the C-terminal side and adjacent to a proline residue, a consensus sequence for O-glycosylation enzyme is formed. Because proline residues are typically found on the surface of proteins (in, e.g., turns, kinks, and / or loops), a design that calls for O-glycosylation and PEGylation thereto using a PEG-glycosyl moiety in close proximity to a proline residue benefits from the relative accessibility of the target attachment site for the glycosyl transferase that transfers the glycosyl or glycol-PEG moiety and the potential to accommodate the conjugated glycosyl and / or PEG structure without disruption of protein structure. For introduction of the threonine residues into the native amino acid sequence of FGF-21, the general methods include Sambrook and Russell, Molecular Cloning, A Laboratory Manual (3rd ed. 2001); Kriegler, Gene Transfer and Expression: A Laboratory Manual (1990); and Ausubel et al., eds., Current Protocols in Molecular Biology (1994). In some embodiments, the native FGF-21 amino acid sequence corresponds to the native amino acid sequence of human FGF-21 depicted in SEQ ID NO: 1. Attorney Docket No.180234-011901 / PCT In some embodiments, the mutant FGF-21 peptide comprises the amino acid sequence PT, i.e. a threonine residue C-terminally adjacent to a proline residue. The sequence PT is not present in the native FGF-21 amino acid sequence. Optionally, the mutant FGF-21 peptide comprises at least one amino acid sequence selected from the group consisting of P172T (e.g. SEQ ID NO: 2 or 3), P156T (e.g. SEQ ID NO: 4), P5T (e.g. SEQ ID NO: 5), P3T (e.g. SEQ ID NO: 6), P9T (e.g. SEQ ID NO: 7), P50T (e.g. SEQ ID NO: 8), P61T (e.g. SEQ ID NO: 9), P79T (e.g. SEQ ID NO: 10), P91T (e.g. SEQ ID NO: 11), P116T (e.g. SEQ ID NO: 12), P120T (e.g. SEQ ID NO: 13), P125T (e.g. SEQ ID NO: 14), P129T (e.g. SEQ ID NO: 15), P131T (e.g. SEQ ID NO: 16), P134T (e.g. SEQ ID NO: 17), P139T (e.g. SEQ ID NO: 18), P141T (e.g. SEQ ID NO: 19), P144T (e.g. SEQ ID NO: 20, P145T (e.g. SEQ ID NO: 21), P148T (e.g. SEQ ID NO: 22), P150T (e.g. SEQ ID NO: 23), P151T (e.g. SEQ ID NO: 24), P158T (e.g. SEQ ID NO: 25), P159T (e.g. SEQ ID NO: 26), P166T (e.g. SEQ ID NO: 27), P178T (e.g. SEQ ID NO: 28), and combinations thereof, wherein the positions of proline and threonine are based on the native amino acid sequence of FGF-21 as depicted in SEQ ID NO: 1, particularly the mutant FGF-21 peptide comprises at least one amino acid sequence selected from the group consisting of P172T, P156T, P5T and combinations thereof, more particularly consisting of P172T, P156T and combinations thereof, and even more particularly the mutant FGF-21 peptide comprises the sequence motif P172T, based on the amino acid sequence as depicted in SEQ ID NO: 1, wherein the positions of proline and threonine are based on the amino acid sequence as depicted in SEQ ID NO: 1. In some embodiments, the proline residue is located between amino acid 145 and the C-terminus of the mutant FGF-21 peptide, wherein the position of amino acid 145 is based on the amino acid sequence as depicted in SEQ ID NO: 1. As demonstrated by results presented herein, the C-terminus of FGF-21 surprisingly tolerates attachment of PEG and in particular of glycosyl-PEG moieties. This was unexpected since the literature reports that the intact C-terminus is necessary for β-Klotho binding of FGF-21. In some embodiments, the mutant FGF-21 peptide comprises the mutations S172T and R176A, wherein the positions of the amino acids S and R are based on the amino acid sequence as depicted in SEQ ID NO: 1, particularly the mutant FGF-21 peptide comprises the amino acid sequence as depicted in SEQ ID NO: 2. The mutation R176A has been found beneficial to the protein´s overall stability after introducing the O-linked glycosylation site Attorney Docket No.180234-011901 / PCT at threonine 173. By this mutation, the relatively large arginine side chain was removed and replaced by the small side chain of alanine. It is assumed that the smaller side chain of alanine interferes less with the voluminous glycosyl-PEG moiety to be attached to thindicae mutated FGF-21 peptide. In an alternative embodiment, the mutant FGF-21 peptide comprises the mutation Q157T, wherein the position of the amino acid Q is based on the amino acid sequence as depicted in SEQ ID NO: 1, particularly the mutant FGF-21 peptide comprises the amino acid sequence as depicted in SEQ ID NO: 4, or the mutation D6T, wherein the position of the amino acid D is based on the amino acid sequence as depicted in SEQ ID NO: 1, particularly the mutant FGF-21 peptide comprises the amino acid sequence as depicted in SEQ ID NO: 5. In some embodiments, the mutant FGF-21 peptide conjugate comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 to 28, more particularly an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 to 5, even more particularly an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 to 4, and most particularly the mutant FGF-21 peptide comprises the amino acid sequence as depicted in SEQ ID NO: 2. In some embodiments, the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG (also referred herein as mutant FGF-21 peptide conjugate having SEQ ID NO: 2). In some embodiments, the mutant FGF-21 peptide conjugate comprises the structure: 21 Attorney Docket No.180234-011901 / PCT wherein n is an integer selected from 450 to 460. Pharmaceutical compositions and methods of treatment In some embodiments, the pharmaceutical compositions comprise the mutant FGF- 21 peptide conjugate and a pharmaceutically acceptable carrier, such as water or a physiologically compatible buffer. The pharmaceutical compositions typically comprise a therapeutically effective or pharmaceutically active amount of the mutant FGF-21 peptide conjugate as active agent. In some embodiments, the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG (also referred herein as mutant FGF- 21 peptide conjugate having SEQ ID NO: 2). In some embodiments, the mutant FGF-21 peptide conjugate comprises the structure: 21wherein n is an integer selected from 450 to 460. In some embodiments, the pharmaceutical compositions are suitable for use in a variety of drug delivery systems. Suitable formulations for use in the present disclosure are found in Remington's Pharmaceutical Sciences, Mack Publishing Company, Philadelphia, PA, 17thed. (1985). The pharmaceutical compositions are intended for parenteral, intranasal, topical, oral, or local administration, such as by subcutaneous injection, aerosol inhalation, or transdermal adsorption, for prophylactic and / or therapeutic treatment. Commonly, the pharmaceutical compositions are administered parenterally, e.g., subcutaneously or intravenously. Attorney Docket No.180234-011901 / PCT In some embodiments, the disclosure provides compositions for parenteral administration which comprise the mutant FGF-21 peptide conjugate dissolved or suspended in an acceptable carrier, particularly an aqueous carrier, e.g., water, buffered water, saline, phosphate buffered saline (PBS) and the like. The compositions may also contain detergents such as Tween 20 and Tween 80; stabilizers such as mannitol, sorbitol, sucrose, and trehalose; and preservatives such as EDTA and m-cresol. The compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions, such as pH adjusting and buffering agents, tonicity adjusting agents, wetting agents, detergents and the like. In some embodiments, the pharmaceutical compositions may be sterilized by conventional sterilization techniques or may be sterile filtered. The resulting aqueous solutions may be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous carrier prior to administration. The compositions containing the FGF peptide conjugates can be administered for prophylactic and / or therapeutic treatments, in particular for the treatment of diabetes or diabetes related diseases, particularly for the treatment of diabetes type 2, NASH and metabolic syndrome. In therapeutic applications, compositions are administered to a subject already suffering from a disease or condition related to diabetes, in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications. An amount adequate to accomplish this is defined as a “therapeutically effective amount” and usually depends the patient´s state of health and weight. Efficacious doses range from 0.1 mg / kg to 6 mg / kg when tested in various animal models of NASH and type 2 diabetes. In some embodiments, the methods for treating a disease and / or a disorder or symptoms thereof comprise administering a therapeutically effective amount of a compound (a mutant FGF-21 peptide conjugate described herein) or a pharmaceutical composition comprising same to a subject (e.g., a mammal such as a human). Thus, one embodiment is a method for treating a subject suffering from diabetes or a diabetes related disease (e.g., diabetes type 2, NAFLD, NASH or metabolic syndrome) or a symptom thereof. The method includes the step of administering to the mammal an amount of a compound described herein in an amount sufficient to treat the disease or disorder or symptom thereof or a composition Attorney Docket No.180234-011901 / PCT comprising same, under conditions such that the disease or disorder is treated. In some embodiments, the composition is administered subcutaneously. In some embodiments, the therapeutic dosing regimen comprises a range of from about 60 mg to about 150 mg. In some embodiments, the therapeutic dosing regimen comprises a range of from about 60 mg to about 70 mg, from about 70 mg to about 80 mg, from about 80 mg to about 90 mg, from about 90 mg to about 100 mg, from about 100 mg to about 110 mg, from about 110 mg to about 120 mg, from about 120 mg to about 130 mg, from about 130 mg to about 140 mg or from about 140 mg to about 150 mg. In some embodiments, the therapeutic dosing regimen comprises a range of from about 60 mg to about 65 mg, from about 65 mg to about 70 mg, from about 70 mg to about 75 mg, from about 75 mg to about 80 mg, from about 80 mg to about 85 mg, from about 85 mg to about 90 mg, from about 90 mg to about 95 mg, from about 95 mg to about 100 mg, from about 100 mg to about 105 mg, from about 105 mg to about 110 mg, from about 110 mg to about 115 mg, from about 115 mg to about 120 mg, from about 120 mg to about 125 mg, from about 125 mg to about 130 mg, from about 130 mg to about 135 mg, from about 135 mg to about 140 mg, from about 140 mg to about 145 mg, from about 145 mg to about 150 mg. In some embodiments, the therapeutic dosing regimen comprises a range of from about 50 mg to about 60 mg. In some embodiments, the method comprises administering once a month to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every two months to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every three months to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 3 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 4 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 5 weeks to the subject in need thereof the therapeutically effective amount of the Attorney Docket No.180234-011901 / PCT pharmaceutical composition. In some embodiments, the method comprises administering once every 6 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 7 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 8 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 9 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 10 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 11 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 12 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. In some embodiments, the method comprises administering once every 13 weeks to the subject in need thereof the therapeutically effective amount of the pharmaceutical composition. The term “about” as used herein refers to an amount equal to 10% more or 10% less of the particularly indicated amount. The aforementioned therapeutic dosing regimens may be administered to a human in need thereof to treat at least one of diabetes (e.g., diabetes type 2), NAFLD, NASH, or metabolic syndrome. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to reduce triglyceride levels. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human to reduce triglyceride levels. The aforementioned therapeutic dosing regimens may be administered to a human in need thereof to treat NASH. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to reduce liver fat. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to reduce ALT. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to reduce NAFLD Activity Attorney Docket No.180234-011901 / PCT scores. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to reduce improve fibrosis. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to improve HbA1c levels. In some embodiments, the aforementioned therapeutic dosing regimens result in an increase of Adiponectin levels. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to reduce weight. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to improve lipid parameters. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human in need thereof to reduce triglyceride levels. In some embodiments, the aforementioned therapeutic dosing regimens are administered to a human to reduce triglyceride levels. The aforementioned therapeutic dosing regimens may also be administered to a human in need thereof to reduce cravings for sugary foods and / or beverages. In some embodiments, a pharmaceutical composition comprising any one of or at least one of the mutant FGF-21 peptide conjugates described herein and a pharmaceutically acceptable carrier is presented. The mutant FGF-21 peptide conjugate may be present in the pharmaceutical composition in a concentration in a range from 0.1 mg / mL to 100 mg / mL, 0.1 mg / mL to 90 mg / mL, 0.1 mg / mL to 80 mg / mL, 0.1 mg / mL to 70 mg / mL, 0.1 mg / mL to 60 mg / mL, 0.1 mg / mL to 50 mg / mL, 0.1 mg / mL to 40 mg / mL, 0.1 mg / mL to 30 mg / mL. or 0.1 mg / mL to 20 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 1 mg / mL to 100 mg / mL, 1 mg / mL to 90 mg / mL, 1 mg / mL to 80 mg / mL, 1 mg / mL to 70 mg / mL, 1 mg / mL to 60 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 40 mg / mL, 1 mg / mL to 30 mg / mL. or 1 mg / mL to 20 mg / mL.. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 10 mg / mL to 100 mg / mL, 10 mg / mL to 90 mg / mL, 10 mg / mL to 80 mg / mL, 10 mg / mL to 70 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 40 mg / mL. 10 mg / mL to 30 mg / mL. or mg / mL to 20 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 20 mg / mL to 100 mg / mL, 20 mg / mL to 90 mg / mL, 20 mg / mL to 80 mg / mL, 20 mg / mL to 70 mg / mL, 20 mg / mL to 60 mg / mL, 20 mg / mL to 50 mg / mL, 20 mg / mL to 40 mg / mL. or Attorney Docket No.180234-011901 / PCT 20 mg / mL to 30 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 30 mg / mL to 100 mg / mL, 30 mg / mL to 90 mg / mL, 30 mg / mL to 80 mg / mL, 30 mg / mL to 70 mg / mL, 30 mg / mL to 60 mg / mL, 30 mg / mL to 50 mg / mL, or 30 mg / mL to 40 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 40 mg / mL to 100 mg / mL, 40 mg / mL to 90 mg / mL, 40 mg / mL to 80 mg / mL, 40 mg / mL to 70 mg / mL, 40 mg / mL to 60 mg / mL, or 40 mg / mL to 50 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 50 mg / mL to 100 mg / mL, 50 mg / mL to 90 mg / mL, 50 mg / mL to 80 mg / mL, 50 mg / mL to 70 mg / mL, or 50 mg / mL to 60 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 60 mg / mL to 100 mg / mL, 60 mg / mL to 90 mg / mL, 60 mg / mL to 80 mg / mL, or 60 mg / mL to 70 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 70 mg / mL to 100 mg / mL, 70 mg / mL to 90 mg / mL, or 70 mg / mL to 80 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in the pharmaceutical composition in a concentration in a range from 80 mg / mL to 100 mg / mL, or 80 mg / mL to 90 mg / mL, or 90 mg / mL to 100 mg / mL. In some embodiments, the pharmaceutical composition further comprises a buffering agent, particularly a Tris buffer. In another embodiment, the buffering agent is present in a concentration from 1 mM to 100 mM, for example from 2 mM to 75 mM, from 5 mM to 50 mM, from 10 mM to 25 mM, or of 16±2 mM. In some embodiments, the pH is in the range from 6.0 to 8.5, for example from 6.5 to 8.0 from 6.75 to 8.0, or 7.5±0.3. In some embodiments, the pharmaceutical composition further comprises a salt, for example an inorganic salt, including but not limited to NaCl. In some embodiments, the salt is present in a concentration from 30 mM to 200 mM, for example from 40 mM to 150 mM, 50 mM to 100 mM, or of 56±2 mM. The pharmaceutical composition may further comprise a tonicity modifying agent. Such tonicity modifying agents include, without limitation, glycerol, amino acids, sodium chloride, proteins, sugars and sugar alcohols. In some embodiments, the tonicity modifying agent is a sugar. In some embodiments, the tonicity modifying agent is sucrose. In some embodiments, the tonicity modifying agent is present Attorney Docket No.180234-011901 / PCT in a concentration of 50 mM to 200 mM, for example in a concentration of 100 mM to 175 mM, in a concentration of 135 mM to 160 mM, or in a concentration of 150±2 mM. In some embodiments, the pharmaceutical composition further comprises a surfactant, for example a non-ionic surfactant. In some embodiments, the surfactant or non-ionic surfactant is a polysorbate-based non-ionic surfactant, for example polysorbate 20 or polysorbate 80. In some embodiments, the surfactant or non-ionic surfactant is present in a concentration of 0.01 mg / mL to 1 mg / mL, for example in a concentration of 0.05 to 0.5 mg / mL or in a concentration of 0.2±0.02 mg / mL. In some embodiments, the pharmaceutical composition comprises 0.1 mg / mL to 100 mg / mL of mutant FGF-21 peptide conjugate, 1 mM to 100 mM buffering agent, particularly Tris buffer, 30 mM to 200 mM salt, particularly NaCl, 50 mM to 200 mM tonicity modifying agent, particularly sucrose, and 0.01 mg / mL to 1 mg / mL surfactant or non-ionic surfactant, particularly polysorbate 20, and has a pH of 6.0 to 8.5. In some embodiments, the pharmaceutical composition is a liquid pharmaceutical composition comprising at least one mutant FGF-21 peptide conjugate and a pharmaceutically acceptable carrier. In some embodiments, the mutant FGF-21 peptide conjugate is present in a concentration in the range from 0.1 mg / mL to 100 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in a concentration in the range from 10 mg / mL to 50 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in a concentration in the range from 40 mg / mL to 50 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in a concentration in the range from 10 mg / mL to 48 mg / mL. In some embodiments the mutant FGF-21 peptide conjugate is present in a concentration of 26±4 mg / mL. For example, the FGF-21 peptide conjugate is present at a concentration of about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36 mg / mL. In some embodiments, the mutant FGF-21 peptide conjugate is present in a 36±6 mg / mL. For example, the FGF-21 peptide conjugate is present at a concentration of about 30, 32, 34, 36, 38, 40, 42 mg / mL. In some embodiments, the liquid pharmaceutical composition comprises 10-48 mg / mL FGF-21 peptide conjugate, for example about 15 mg / mL, 18 mg / mL, 20 mg / mL, 22 mg / mL, 24 mg / mL, 26 mg / mL, 28 mg / mL, 30 mg / mL, 32 mg / mL, 34 mg / mL, 36 mg / mL, 38 mg / mL, 40 mg / mL, 42 mg / mL, 44 mg / mL, 46 mg / mL, 48 mg / mL. Attorney Docket No.180234-011901 / PCT In some embodiments, the liquid pharmaceutical composition comprises 49-70 mg / mL FGF-21 peptide conjugate, for example about 49 mg / mL, 50 mg / mL, 52 mg / mL, 54 mg / mL, 56 mg / mL, 60 mg / mL, 62 mg / mL, 64 mg / mL, 66 mg / mL, 68 mg / mL, 70 mg / mL. In some embodiments, the liquid pharmaceutical composition comprises 71-100 mg / mL FGF-21 peptide conjugate, for example about 72 mg / mL, 74 mg / mL, 76 mg / mL, 78 mg / mL, 80 mg / mL, 82 mg / mL, 84 mg / mL, 86 mg / mL, 88 mg / mL, 90 mg / mL, 92 mg / mL, 94 mg / mL, 96 mg / m, 98 mg / mL, 100 mg / mL. In some embodiments, liquid pharmaceutical composition comprises or consists of from about 10 mg / mL to about 100 mg / mL (e.g.10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate, from about 50 mM to about 500 mM arginine; from about 0.01 to about 0.1% (w / v) Polysorbate 80 (PS-80) or Polysorbate 20 (PS-20); about 20 mM buffer, pH 7-8; and a pharmaceutically acceptable carrier. In some embodiments, liquid pharmaceutical composition comprises or consists of from about 10 mg / mL to about 100 mg / mL (e.g. 10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate, from about 150 mM to about 500 mM arginine; from about 0.01 to about 0.1% (w / v) Polysorbate 80 (PS-80) or Polysorbate 20 (PS-20); about 20 mM buffer, pH 7-8; and a pharmaceutically acceptable carrier. In some embodiments, the formulation has an osmolality between about 250 mOsmol / kg to about 510 mOsmol / kg. In some embodiments, the liquid formulation comprises or consists of from 10 mg / mL to about 100 mg / mL (e.g.10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate comprising a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, a glycosyl moiety, and a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG; from 50 mM to 500 mM Arginine; from 0.01 to 0.1% (w / v) Polysorbate 80 (PS- 80) or Polysorbate 20 (PS-20); 20 mM buffer, pH 7-8; and a pharmaceutically acceptable carrier. In some embodiments, the liquid formulation comprises or consists of from 10 mg / mL to about 100 mg / mL (e.g. 10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate comprising a mutant FGF-21 peptide Attorney Docket No.180234-011901 / PCT comprising the amino acid sequence of SEQ ID NO: 2, a glycosyl moiety, and a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG; from 150 mM to 500 mM Arginine; from 0.01 to 0.1% (w / v) Polysorbate 80 (PS- 80) or Polysorbate 20 (PS-20); 20 mM buffer, pH 7-8; and a pharmaceutically acceptable carrier. In some embodiments, the formulation has an osmolality between about 250 mOsmol / kg to about 550 mOsmol / kg. In some embodiments, the liquid pharmaceutical composition comprising or consisting of from about 10 mg / mL to about 100 mg / mL (e.g.10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate comprising a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, a glycosyl moiety, and a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG; from about 50 mM to about 500 mM arginine, from about 50 mM to about 250 mM alanine, about 50 mM to about 250 mM proline, about 50 mM to about 250 mM glycine, about 50 mM to about 250 mM MgCl2, about 1% to about 5% (v / v) glycerol, about 1% to 5% (v / v) PEG 400, or combination thereof; from about 0.01 to about 0.1% (w / v) Polysorbate 80 (PS-80) or Polysorbate 20 (PS-20); about 20 mM buffer at pH 7-8; and a pharmaceutically acceptable carrier. In some embodiments, the liquid pharmaceutical composition comprising or consisting of from about 10 mg / mL to about 100 mg / mL (e.g.10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate comprising a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, a glycosyl moiety, and a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG; from about 150 mM to about 500 mM arginine, from about 50 mM to about 250 Attorney Docket No.180234-011901 / PCT mM alanine, about 50 mM to about 250 mM proline, about 50 mM to about 250 mM glycine, about 50 mM to about 250 mM MgCl2, about 1% to about 5% (v / v) glycerol, about 1% to 5% (v / v) PEG 400, or combination thereof; from about 0.01 to about 0.1% (w / v) Polysorbate 80 (PS-80) or Polysorbate 20 (PS-20); about 20 mM buffer at pH 7-8; and a pharmaceutically acceptable carrier. In some embodiments, the weight ratio of mutant FGF-21 to arginine is from about 0.6 to about 0.7, from about 0.6 to about 0.8, about 0.6 to about 0.9, from about 0.6 to about 1, e.g. about 0.6, 0.7, 0.8, 0.9, 0.1. In some embodiments, the molar ratio of mutant FGF-21 to arginine is from about from about 0.006 to about 0.008, 0.006 to about 0.009, 0.006 to about 0.010, from about 0.007 to about 0.008, from about 0.007 to about 0.009, from about 0.007 to about 0.010, e.g about 0.006, 0.007, 0.008, 0.009. In some embodiments, the liquid formulation has an osmolality of about 250 mOsmol / kg to about 550 mOsmol / kg. Liquid pharmaceutical compositions in some embodiments comprise 20 mg / mL of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate comprising a mutant FGF- 21 peptide comprising the amino acid sequence of SEQ ID NO: 2, a glycosyl moiety, and a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG (also referred herein as PEG-FGF21) in 20 mM Tris, 150 mM Arginine, 0.02% (w / v) PS-80, pH 7.5. Liquid pharmaceutical formulations in some embodiments comprise 20 mg / mL PEG-FGF21 in 20 mM Phosphate, 150 mM Arginine, 0.02% (w / v) PS-80, pH 7.5. In some embodiments, the composition has an osmolality between about 250 mOsm / kg to about 380 mOsm / kg. In some embodiments, the composition has an osmolality of about 300 mOsm / kg. Liquid pharmaceutical compositions in some embodiments comprise 28 mg / mL PEG-FGF21 in 20 mM Tris, 275 mM Arginine, 0.02% (w / v) PS-80, pH 7-8. In some embodiments, the composition has an osmolality of about 505 mOsm / kg. Liquid pharmaceutical formulations in some embodiments comprise 18-44 mg / mL PEG-FGF21 in 20 mM Tris, 200-350 mM Arginine, 0.02% (w / v) PS-80, pH 7.0-pH 7.5. In some embodiments, the liquid pharmaceutical composition comprises about 20 mg / mL PEG- FGF21, about 150 mM arginine HCl, about 20 mM Tris, 0.02 % (w / v) PS-80, wherein pH Attorney Docket No.180234-011901 / PCT is about 7.5 and has an osmolality is about 300 mOsm / kg. In some embodiments, the liquid pharmaceutical composition comprises about 28mg / mL PEG-FGF21, about 260 mM Arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80, wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises about 28mg / mL PEG- FGF21, about 260 mM Arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80, wherein pH is about 7.1 and has an osmolality of about 505 mOsm / kg. In some embodiments, the liquid pharmaceutical composition comprises about 36mg / mL PEG-FGF21, about 270 mM Arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80, wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises about 36 mg / mL PEG- FGF21, about 270 mM Arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80, wherein pH is about 7.1 and has a osmolality is about 530 mOsm / kg. In some embodiments, the liquid pharmaceutical composition comprises 36mg / mL PEG-FGF21, 200 mM Arginine HCl, 20mM Tris, 0.02% (w / v) PS80, wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises 36mg / mL PEG-FGF21, 200 mM Arginine HCl, 20mM Tris, 0.02% (w / v) PS80, wherein pH is about 7.1 and has an osmolality is about 421 mOsm / kg. In some embodiments, the liquid pharmaceutical composition comprises about 42mg / mL PEG-FGF21, about 270 mM Arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80, wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises about 42mg / mL PEG-FGF21, about 270 mM Arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80, wherein pH is about 7.1 and has an osmolality is about 528 mOsm / kg. In some embodiments, the liquid pharmaceutical composition comprises 44 mg / mL mutant FGF21, 200 mM Arginine HCl, 20mM Tris, 0.02% (w / v) PS80, wherein pH is 7.1. In some embodiments, the liquid pharmaceutical composition comprises 44 mg / mL PEG-FGF21, 200 mM Arginine HCl, 20mM Tris, 0.02% (w / v) PS80, wherein pH is 7.1 and has an osmolality is about 455 mOsm / kg. In some embodiments, the liquid pharmaceutical composition comprises 44 mg / mL PEG-FGF21, 230 mM Arginine HCl, 20mM Tris, 0.02% (w / v) PS80, wherein pH is 7.1. In some embodiments, the liquid pharmaceutical composition comprises 44 mg / mL PEG-FGF21, 230 mM Arginine HCl, 20mM Tris, 0.02% (w / v) PS80, wherein pH is 7.1 and has an osmolality is about 485 mOsm / kg. In some embodiments, the liquid composition further comprises a surfactant. In some embodiments, the surfactant comprises cetrimonium bromide, sodium gluconate or Attorney Docket No.180234-011901 / PCT combination thereof. In some embodiments, the liquid formulation comprises from about 0.05% to about 0.1% (w / v) cetrimonium bromide, from about 0.05% to about 0.1% (w / v) sodium gluconate or combination thereof. In some embodiments, the liquid pharmaceutical composition further comprising one or more active agent. In some embodiments, the PEG-FGF21 is co-formulated with one or more active agent. In some embodiments, the one or more active agent can comprise a peptide, a small molecule or combinations thereof. In some embodiments, the one or more active agent can comprise an hormone. For example, the one or more agents can comprise oxyntomodulin, insulin, leptin, glucagon. eroxisome proliferator-activated receptor (PPAR) agonists, FXR (Farnesoid X receptor) agonists, Thyroid Hormone Receptor-Beta (TRβ) Agonists, Sodium glucose co-transporter 2 (SGLT2) Inhibitors, analogs thereof, or combinations thereof. As used herein an “analog” is a molecule having a modification including one or more amino acid substitutions, deletions, inversions or additions when compared with wild type peptide sequence. The buffering agent may be present in a concentration from 1 mM to 100 mM. In some embodiments, the buffering agent is present at a concentration ranging from 2 mM to 75 mM, 5 mM to 50 mM, 10 mM to 25 mM, 14 to 22 mM. In some embodiments, the buffering agent is present at a concentration of about 14, 16, 18, 20, 22, 24, 26, 30, 32, 34, 36, 38, 40 mM or more. For example, the buffering agent is present at a concentration of about 20 mM. The pH may be in the range from 6.0 to 8.5, from 6.5 to 8.0, from 6.75 to 8.0, from 7.1 to 8. The buffering agent may be a Tris phosphate buffer. For example, the buffering agent can have a pH of 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9 or 8. The liquid pharmaceutical composition may further comprise a tonicity modifying agent. Suitable tonicity modifying agents include glycerol, amino acids, sodium chloride, proteins, or sugars and sugar alcohols. For example, the modifying agent comprise arginine, such as arginine HCl or arginine sulfate. The tonicity modifying agent is present in a concentration of 50 mM to 500 mM. For example, the modifying agent (e.g. arginine HCL) comprises from 150 mM to 500 mM arginine, 150 to 275 mM or 245 to 275 mM. In some embodiments, modifying agent comprise arginine, such as arginine HCl or arginine sulfate is present at a concentration between 31.6 mg / ml (150 mM) and 54.8 mg / ml (260 mM). The liquid pharmaceutical composition may further comprise a non-ionic surfactant. Attorney Docket No.180234-011901 / PCT The non-ionic surfactant may be a polysorbate-based non-ionic surfactant, for example polysorbate 20 or polysorbate 80, for example polysorbate 80. The non-ionic surfactant may be present in a concentration of 0.01% (w / v) to 1% (w / v). For example, the non-ionic surfactant may be present in a concentration of 0.01%, 0.02%.0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1% (w / v). In some embodiments, the liquid pharmaceutical composition may further comprise cetrimonium bromide, sodium gluconate or combination thereof. For example, the composition may comprise from 0.05% to 0.1% (w / v) cetrimonium bromide, from 0.05% to 0.1% (w / v) sodium gluconate or combination thereof. In an embodiment, the liquid pharmaceutical composition comprises 10 mg / mL to 50 mg / mL of mutant FGF-21 peptide conjugate, 1 mM to 100 mM buffering agent, for example Tris buffer, 150 mM to 500 mM tonicity arginine, and 0.02% to 1% (w / v) polysorbate-based non-ionic surfactant, particularly polysorbate 80, and has a pH of 7.0 to 8.0. In some embodiments, the liquid formulation comprises 0.02% (w / v) PS80 (0.2 mg / ml). In some embodiments, the buffer is Tris or phosphate buffer. In some embodiments, the liquid formulation comprises 20 mM Tris buffer. In some embodiments, the liquid formulation comprises 15 mg / ml of mutant FGF-21. In some embodiments, the liquid formulation comprises 28 mg / ml of mutant FGF-21. In some embodiments, the liquid formulation comprises 30 mg / ml of mutant FGF-21. In some embodiments, the liquid formulation comprises 36 mg / ml of mutant FGF-21. In some embodiments, the liquid formulation comprises 44 mg / ml of mutant FGF-21. In some embodiments, the liquid formulation comprises from 150 mM to 275 mM arginine. In some embodiments, arginine is arginine HCl or arginine sulfate. In some embodiments, the pH is 7.1. In some embodiments, the liquid pharmaceutical composition comprises about 20 mg / mL mutant FGF-21 peptide conjugate having SEQ ID NO: 2, about 150 mM arginine HCl, about 20 mM Tris, 0.02 % (w / v) PS-80 and wherein pH is about 7.5. In some embodiments, the liquid pharmaceutical composition comprises about 28mg / mL mutant FGF-21 peptide conjugate having SEQ ID NO: 2, about 260 mM arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80 and wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises about 36mg / mL mutant FGF-21 peptide conjugate Attorney Docket No.180234-011901 / PCT having SEQ ID NO: 2, about 270 mM arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80 and wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises 36mg / mL mutant FGF-21 peptide conjugate having SEQ ID NO: 2, 200 mM arginine HCl, 20mM Tris, 0.02% (w / v) PS80 and wherein pH is about 7.1 In some embodiments, the liquid pharmaceutical composition comprises about 42mg / mL mutant FGF-21 peptide conjugate having SEQ ID NO: 2, about 270 mM arginine HCl, about 20mM Tris, about 0.02% (w / v) PS80 and wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises 44 mg / mL mutant FGF-21 peptide conjugate having SEQ ID NO: 2, 200 mM arginine HCl, 20mM Tris, 0.02% (w / v) PS80 and wherein pH is 7.1. In some embodiments, the liquid pharmaceutical composition comprises 44 mg / mL mutant FGF-21 peptide conjugate having SEQ ID NO: 2, 230 mM arginine HCl, 20mM Tris, 0.02% (w / v) PS80 and wherein pH is 7.1. In some embodiments, the pharmaceutical composition is a liquid pharmaceutical composition comprising: (a) from 10 mg / mL to about 100 mg / mL (e.g.10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate comprising a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, a glycosyl moiety, and a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG; (b) from 50 mM to 500 mM arginine; (c) from 0.01% to 0.1% (w / v) Polysorbate 80 (PS-80) or Polysorbate 20 (PS-20); (d) from 5 to 25 mM buffer, pH 7-8; and (e) a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition is a liquid pharmaceutical composition comprising: (a) from 10 mg / mL to about 100 mg / mL (e.g.10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate comprising a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, a glycosyl moiety, and a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the Attorney Docket No.180234-011901 / PCT glycosyl moiety and the 20 kDa PEG; (b) from 150 mM to 500 mM arginine; (c) from 0.01% to 0.1% (w / v) Polysorbate 80 (PS-80) or Polysorbate 20 (PS-20); (d) from 5 to 25 mM buffer, pH 7-8; and (e) a pharmaceutically acceptable carrier. In some embodiments, the liquid pharmaceutical composition comprises: (a) from 10 mg / mL to about 100 mg / mL (e.g.10 mg / mL to about 50 mg / mL) of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate comprising a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, a glycosyl moiety, and a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG; (b) from 150 mM to 500 mM arginine, from 50 mM to 250 mM alanine, 50 mM to 250 mM proline, 50 mM to 250 mM glycine, 50 mM to 250 mM MgCl2, 1 to 5% (v / v) glycerol, 1 to 5% (v / v) PEG 400, or combination thereof; (c) from 0.01% to 0.1% (w / v) Polysorbate 80 (PS-80) or Polysorbate 20 (PS-20); (d) a buffer having a pH of 7-8; and (e) a pharmaceutically acceptable carrier. In some embodiments, the liquid formulation, further comprises a surfactant. In some embodiments, the surfactant comprises cetrimonium bromide, sodium gluconate or combination thereof. In some embodiments, the liquid formulation comprises from 0.05% to 0.1% (w / v) cetrimonium bromide, from 0.05% to 0.1% (w / v) sodium gluconate or combination thereof. In some embodiments, the buffer is Tris or phosphate buffer. In some embodiments, the liquid formulation comprises 20 mM Tris buffer. In some embodiments, the pH of the liquid formulation is from 7.0 to 7.5. In some embodiments, the liquid pharmaceutical composition comprises from 20 to 44 mg / ml of the mutant FGF-21 peptide conjugate. In some embodiments, the liquid pharmaceutical composition comprises from 150 mM to 275 mM arginine. In some embodiments, the arginine in the liquid pharmaceutical composition comprises arginine HCl, arginine sulfate or combination thereof. In some embodiments, the weight ratio of mutant FGF-21 peptide conjugate to arginine is from 0.6 Attorney Docket No.180234-011901 / PCT to 0.9. In some embodiments, the molar ratio of mutant FGF-21 peptide conjugate to arginine is from about 0.006 to about 0.009. In some embodiments, the liquid pharmaceutical composition comprises about 28 mg / mL mutant FGF-21 peptide conjugate, about 260 mM arginine HCl, about 20 mM Tris, 0.02 % (w / v) PS-80 and wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises about 20 mg / mL mutant FGF-21 peptide conjugate, about 150 mM arginine HCl, about 20 mM Tris, 0.02 % (w / v) PS-80 and wherein pH is about 7.5. In some embodiments, the liquid pharmaceutical composition comprises about 36 mg / mL mutant FGF-21 peptide conjugate, about 200 mM arginine HCl, about 20 mM Tris, 0.02 % (w / v) PS-80 and wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises about 44 mg / mL mutant FGF-21 peptide conjugate, about 200 mM arginine HCl, about 20 mM Tris, 0.02 % (w / v) PS-80 and wherein pH is about 7.1. In some embodiments, the liquid pharmaceutical composition comprises about 44 mg / mL mutant FGF-21 peptide conjugate, about 230 mM arginine HCl, about 20 mM Tris, 0.02 % (w / v) PS-80 and wherein pH is about 7.1. In some embodiments, the liquid formulation has an osmolality of about 250 mOsmol / kg to about 550 mOsmol / kg. In some embodiments, the liquid formulation is a liquid formulation as described in U.S. Patent No.: 11,596,669 which is incorporated by reference in its entirety. In some embodiments, also encompassed herein is a pharmaceutical container comprising any one of or at least one of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising same. Exemplary such pharmaceutical containers include, without limitation, a syringe, vial, infusion bottle, ampoule, carpoule, a syringe equipped with a needle protection system, or a carpoule within an injection pen. Method of treatment In some embodiments, methods for treating (e.g., controlling, relieving, ameliorating, alleviating, or slowing the progression of) or methods for preventing (e.g., delaying the onset of or reducing the risk of developing) diabetes and related diseases, Attorney Docket No.180234-011901 / PCT particularly diabetes type 2, NAFLD, non-alcoholic steatohepatitis (NASH) and / or metabolic syndrome in a subject in need thereof are disclosed. In some embodiments, a method for treating diabetes and related diseases, particularly diabetes type 2, NAFLD, non-alcoholic steatohepatitis (NASH) and / or metabolic syndrome is presented, the method comprising administering to a subject in need thereof a therapeutically effective amount of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising at least one of the mutant FGF-21 peptide conjugates described herein. In some embodiments, the subject in need thereof is a human subject. In some embodiments, a method for treating diabetes or a diabetes related disease is disclosed, comprising administering to a subject in need thereof an amount of a mutant FGF- 21 peptide conjugate described herein or obtainable by a method described herein or a pharmaceutical composition comprising same. The diabetes or the diabetes related disease may comprise at least one of diabetes type 2, NAFLD, NASH, or metabolic syndrome. In some embodiments, a method for treating NASH is disclosed, comprising administering to a subject in need thereof an amount of a mutant FGF-21 peptide conjugate described herein or obtainable by a method described herein or a pharmaceutical composition comprising same. In some embodiments, a method for treating NAFLD is disclosed, comprising administering to a subject in need thereof an amount of a mutant FGF-21 peptide conjugate described herein or obtainable by a method described herein or a pharmaceutical composition comprising same. In some embodiments, a method for preventing the progression of NASH is disclosed, comprising administering to a subject in need thereof an amount of a mutant FGF-21 peptide conjugate described herein or obtainable by a method described herein or a pharmaceutical composition comprising same. In some embodiments, a method for preventing the progression of NAFLD is disclosed, comprising administering to a subject in need thereof an amount of a mutant FGF-21 peptide conjugate described herein or obtainable by a method described herein or a pharmaceutical composition comprising same. In some embodiments, the subject is a human subject. In some embodiments, the mutant FGF-21 peptide conjugate is mutant FGF-21 peptide conjugate having SEQ ID NO: 2. In some embodiments, the administering reduces HbA1C levels, wherein reducing HbA1C levels is indicative of a durable reduction in blood glucose levels Attorney Docket No.180234-011901 / PCT over time. A variety of exemplary indicators are known in the art and described herein including, without limitation, a reduction in glucose, insulin, body weight, serum lipids (total cholesterol, LDL, Triglycerides), liver enzymes (ALT, AST), liver weight, relative liver weight (% body weight), NAFLD Activity Score (NAS), fibrosis score (e.g., liver fibrosis), pro-inflammatory cytokines (e.g., IL1β, MCP-1), fibrosis biomarkers (αSMA, Collagen 1 alpha), hepatic cholesterol, hepatic triglycerides, and hepatic fatty acids. Increases in at least one of adiponectin (e.g. high molecular weight (HMW)) or HDL are also indicators of clinical efficacy of compounds and compositions described herein. In some embodiments, the method of treatment of the method for preventing the progression of the disease is assessed by Magnetic resonance imaging – Proton density fat fraction (MRI-PDFF) to determine the liver size (e.g. reduction of liver size). The NAFLD fibrosis score is used to distinguish between patients with nonalcoholic fatty liver disease who have (F3-F4) and do not have (F0-F2) advanced fibrosis. A fibrosis score of F0 to F1 (2 to 7 kPa) means there is little or no scarring on the liver. A fibrosis score of F2 (7.5 to 10 kPa) indicates moderate scarring that has spread outside the liver. A fibrosis score of F3 (10 to 14 kPa) indicates severe scarring which has spread and disrupts normal blood flow. A fibrosis score of F4 (14 kPa or higher) means late-stage scarring or cirrhosis, where the scarring is permanent and the damage is irreversible. Methods of treatment of NASH In some embodiments, methods for treating (e.g., controlling, relieving, ameliorating, alleviating, or slowing the progression of) or methods for preventing (e.g., delaying the onset of or reducing the risk of developing) non-alcoholic steatohepatitis (NASH) in a subject in need thereof are disclosed. In some embodiments, a method for treating non-alcoholic steatohepatitis (NASH) is presented, the method comprising administering to a subject in need thereof a therapeutically effective amount of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising at least one of the mutant FGF-21 peptide conjugates described herein. In some embodiments, the subject in need thereof is a human subject. Attorney Docket No.180234-011901 / PCT In some embodiments, the step of administering comprises administering an effective dose of the composition that results in NASH resolution (NAS score of 0–1 for inflammation, 0 for ballooning). In some embodiments, the step of administering comprises administering an effective dose of the composition that results in at least one of the following: reduction of at the level of markers of NASH (e.g. serum markers), reduction of symptoms associated with NASH, reduction of liver fibrosis, reduction in NAS score. In some embodiments, a method for treating NASH is disclosed, comprising administering to a subject in need thereof an amount of a mutant FGF-21 peptide conjugate described herein or obtainable by a method described herein or a pharmaceutical composition comprising same. In some embodiments, a method for preventing the progression of NASH is disclosed, comprising administering to a subject in need thereof an amount of a mutant FGF-21 peptide conjugate described herein or obtainable by a method described herein or a pharmaceutical composition comprising same. In some embodiments, the subject is a human subject. In some embodiments, the administering reduces HbA1C levels, wherein reducing HbA1C levels is indicative of a durable reduction in blood glucose levels over time. A variety of exemplary indicators are known in the art and described herein including, without limitation, a reduction in glucose, insulin, body weight, serum lipids (total cholesterol, LDL, Triglycerides), liver enzymes (ALT, AST), liver weight, relative liver weight (% body weight), NAFLD Activity Score (NAS), fibrosis score (e.g., liver fibrosis), FIB-4 score, FAST score, pro-inflammatory cytokines (e.g., IL1β, MCP-1), fibrosis biomarkers (αSMA, Collagen 1 alpha), hepatic cholesterol, hepatic triglycerides, and hepatic fatty acids. Increases in at least one of adiponectin (e.g. high molecular weight (HMW)) or HDL are also indicators of clinical efficacy of compounds and compositions described herein. In some embodiments, the method of treatment of the method for preventing the progression of the disease is assessed by Magnetic resonance imaging – Proton density fat fraction (MRI-PDFF) to determine the liver size (e.g. reduction of liver size). In some embodiments, the indicators or endpoints used to determine the efficacy of the treatment include one or more of the following: NAS score NASH resolution Attorney Docket No.180234-011901 / PCT Fibrosis improvement. In some embodiments, the biomarkers used to determine the efficacy of the treatment include one or more of the following: Fibrosis-4 (FIB-4) score FibroScan-AST (FAST) score Vibration-Controlled Transient Elastography (VCTE) to assess fibrosis and steatosis Triglycerides Non-high density lipoprotein (Non-HDL) cholesterol High density lipoprotein (HDL-c) Low density lipoprotein (LDL-c) Hemoglobin A1c (HbA1c) Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Liver function tests: alanine transaminase (ALT), aspartate transaminase (AST) Adiponectin N-Terminal Propeptide of Type III Collagen (Pro-C3) Free fatty acids and Adipo-IR (fasting free fatty acids x fasting insulin) Inflammation marker high-sensitivity C-reactive protein (hs-CRP) Total cholesterol OGTT including C-peptide, glucose, and insulin IGF-1, total CK-18 Enhanced LiverFibrosis (ELF) panel. In some embodiments, encompassed herein is any one of the mutant FGF-21 peptide conjugates described herein or a pharmaceutical composition comprising same for use in a method for treating diabetes or a diabetes related disease. In some embodiments, the mutant FGF-21 peptide conjugate is mutant FGF-21 peptide conjugate having SEQ ID NO: 2. The diabetes or the diabetes related disease may comprise at least one of diabetes type 2, NAFLD, NASH, or metabolic syndrome. In some embodiments, the diabetes or the diabetes related disease afflicts a human subject. In some embodiments, the use reduces HbA1C levels, wherein reducing HbA1C levels is indicative of a durable reduction in blood glucose levels over time. A variety of exemplary indicators are known in the art and described herein Attorney Docket No.180234-011901 / PCT including, without limitation, a reduction in glucose, insulin, body weight, serum lipids (total cholesterol, LDL, Triglycerides), liver enzymes (ALT, AST), liver weight, relative liver weight (% body weight), NAFLD Activity Score (NAS), fibrosis score (e.g., liver fibrosis), pro-inflammatory cytokines (e.g., IL1β, MCP-1), fibrosis biomarkers (αSMA, Collagen 1 alpha), hepatic cholesterol, hepatic triglycerides, and hepatic fatty acids. Increases in at least one of high molecular weight (HMW) adiponectin (e.g. high molecular weight (HMW)) or HDL are also indicators of clinical efficacy of compounds and compositions described herein. In some embodiments, use of a mutant FGF-21 peptide conjugate described herein in the preparation of a medicament for use in a method for treating diabetes or a diabetes related disease is presented. The diabetes or the diabetes related disease may comprise at least one of diabetes type 2, NAFLD, NASH, or metabolic syndrome. In some embodiments, the diabetes or the diabetes related disease afflicts a human subject. In some embodiments, the use reduces HbA1C levels, wherein reducing HbA1C levels is indicative of a durable reduction in blood glucose levels over time. A variety of exemplary indicators are known in the art and described herein including, without limitation, a reduction in glucose, insulin, body weight, serum lipids (total cholesterol, LDL, Triglycerides), liver enzymes (ALT, AST), liver weight, relative liver weight (% body weight), NAFLD Activity Score (NAS), fibrosis score (e.g., liver fibrosis), pro-inflammatory cytokines (e.g., IL1β, MCP-1), fibrosis biomarkers (αSMA, Collagen 1 alpha), hepatic cholesterol, hepatic triglycerides, and hepatic fatty acids. Increases in at least one of adiponectin (e.g. high molecular weight (HMW)) or HDL are also indicators of clinical efficacy of compounds and compositions described herein. In some embodiments, a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate is presented comprising i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, wherein the glycosyl moiety comprises the structure -GalNAc-Sia-, and iii) a 30 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the Attorney Docket No.180234-011901 / PCT glycosyl moiety and wherein the glycosyl moiety is attached to the 30 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 30 kDa PEG. In some embodiments, the 30 kDa PEG moiety is attached to the glycosyl moiety by a covalent bond to a linker, wherein the linker comprises at least one amino acid residue. Exemplary amino acids include: polar, but neutral amino acids (e.g., serine, threonine, cysteine, tyrosine, asparagine, and glutamine) and non-polar amino acids with relatively simple side chains (e.g. glycine, alanine, valine, leucine). In some embodiments, the at least one amino acid residue is at least one glycine (Gly). In some embodiments, the mutant FGF-21 peptide conjugate comprises the structure -GalNAc-Sia-Gly-PEG(30kDa). A mutant FGF-21 peptide conjugate described herein may comprise a 30 kDa PEG which is a linear or branched PEG. In some embodiments, the 30 kDa PEG is a linear PEG. In some embodiments, the 30 kDa PEG is a 30 kDa methoxy-PEG.In some embodiments, single or multiple administrations of the compositions can be carried out with dose levels and pattern being selected by the treating physician. In any event, the pharmaceutical compositions should provide a quantity of the mutant FGF-21 peptide conjugate of the disclosure sufficient for an effective treatment of the subject in need of such treatment. In the pharmaceutical composition, in some embodiments, the mutant FGF-21 peptide conjugate is present in a concentration in the range from 0.1 mg / mL to 100 mg / mL. All components of the pharmaceutical composition as well as the specific concentrations of the components have carefully selected after testing very many different conditions, compounds and concentrations thereof. Hence, the pharmaceutical composition disclosed herein is not an arbitrary selection of compounds and compound concentrations but a specific and rational selection of conditions which have been found to be most optimal for an aqueous pharmaceutical composition containing the mutant FGF-21 peptide conjugate or mutant FGF-21 peptide according to the disclosure for use as a medicament. In some embodiments, the pharmaceutical composition comprises a buffering agent, such as a phosphate or Tris buffer, for example a Tris buffer, e.g. Tris(hydroxymethyl)aminomethane (THAM). Optionally, the buffering agent is present in a concentration from 1 mM to 100 mM, from 2 mM to 75 mM, from 5 mM to 50 mM, from 10 mM to 25 mM, for example 16±2 mM. Tris buffer was selected since solubility of the protein was found to be better than for other buffer systems and it is suitable to keep the pH Attorney Docket No.180234-011901 / PCT at pH 7.5. This pH seems the most optimal one for prolonged storage of the PEGylated mutant FGF-21 peptide conjugate. Moreover, probability of Tris crystallization at lower temperatures is lower than that of phosphate based buffering agents. In some embodiments, the mutant FGF-21 peptide conjugate may undergo precipitation of the pH is below 6.0. Optionally, the pH of the pharmaceutical composition is in the range from 6.0 to 8.5, from 6.5 to 8.0, from 6.75 to 8.0, from 7.0 to 8.0, for example 7.5±0.3 as lowest fragmentation in SDS-PAGE and least aggregation in SEC was observed if the pH is in the range of 7 – 8. This pH has also been identified to be optional with respect to viscosity. As the pH of a solution may depend on the temperature of the solution, the pH should be adapted and measured at 25±2 °C. The pH is adjusted with HCl. The pharmaceutical composition may further comprise a salt, such as an inorganic salt, for example NaCl. Optionally, the salt is present in a concentration from 30 mM to 200 mM, from 40 mM to 150 mM, from 50 mM to 100 mM, for example 56±2 mM. The presence of a salt, for example NaCl, is beneficial to reduce viscosity which is increased in PEG containing samples. For the same reason, it is also beneficial to include sorbitol and / or glycine. In some embodiments, the pharmaceutical composition may further comprise a tonicity modifying agent. The tonicity modifying agent may be selected from the group consisting of glycerol, amino acids, sodium chloride, proteins, sugars and sugar alcohols. In some embodiments, the tonicity modifying agent is a sugar. In some embodiments, the tonicity modifying agent is sucrose. A tonicity modifying agent, in particular sucrose, was found to have an advantageous effect on the pharmaceutical composition as it reduces aggregation of the active agent, namely the mutant FGF-21 peptide (conjugate). The tonicity modifying agent, for example sucrose, may be present in a concentration of 50 mM to 200 mM, 100 mM to 175 mM, 135 mM to 160 mM, for example 150±2 mM. Further, the pharmaceutical composition, in some embodiments, may comprise a surfactant, for example a non-ionic surfactant. The surfactant or non-ionic surfactant particularly is a polysorbate-based non-ionic surfactant, for example polysorbate 20 or polysorbate 80. A surfactant, in particular polysorbate 20 or polysorbate 80, was found to reduce sub-visible particles below 10 μm and thus seems to have a stabilizing effect on the pharmaceutical composition. Attorney Docket No.180234-011901 / PCT The surfactant or non-ionic surfactant, for example polysorbate 20 or 80, is optionally present in a concentration of 0.01 mg / mL to 1 mg / mL, 0.05 to 0.5 mg / mL, for example 0.2±0.02 mg / mL. Polysorbate 20 or 80 were found to stabilize the formulation to aggregation. In some embodiments, a pharmaceutical composition comprises 0.1 to 100 mg / mL, for example 10 to 50 mg / mL, e.g. 33±7 mg / mL of mutant FGF-21 peptide conjugate; 1 mM to 100 mM, particularly 20±2 mM, buffering agent, particularly a Tris buffer; 30 mM to 200 mM, particularly 70±2 mM, salt, particularly NaCl; and has a pH of 7.5 ± 0.3 (measured at 25 ± 2 °C). In some embodiments, thepharmaceutical composition 0.1 to 100 mg / mL, for example 10 to 50 mg / mL, e.g. 26±4 mg / mL of mutant FGF-21 peptide conjugate; 1 mM to 100 mM, for example 16±2 mM, buffering agent, such as a Tris buffer; 30 mM to 200 mM, for example 56±2 mM, salt, such as NaCl; 50 mM – 200 mM tonicity modifying agent, for example sucrose; and 0.01 to 1 mg / mL, for example 0.2±0.02 mg / mL, surfactant or non- ionic surfactant, for example polysorbate 20; and has a pH of 7.5 ± 0.3 (measured at 25 ± 2 °C). In some embodiments, a pharmaceutical container comprising the mutant FGF-21 peptide conjugate of the disclosure and as described herein or the pharmaceutical composition of the disclosure and as described herein. In some embodiments, the pharmaceutical container is a syringe, vial, infusion bottle, ampoule, carpoule, a syringe equipped with a needle protection system, or a carpoule within an injection pen. After protein expression, optional purification, the PEG residue is attached to the mutant FGF-21 peptide, specifically at the newly introduced threonine residue via at least one glycosyl moiety and optionally via at least one amino acid residue which is present between the PEG and the glycosyl residue. To obtain high yield expression of a nucleic acid encoding a mutant FGF-21 as described herein, one typically subclones a polynucleotide encoding the mutant Fibroblast Growth Factor into an expression vector that contains a strong promoter to direct transcription, a transcription / translation terminator and a ribosome binding site for translational initiation. Suitable bacterial promoters are described, e.g., in Sambrook and Russell, supra, and Ausubel et al, supra. Bacterial expression systems for expressing the native or mutant FGF- Attorney Docket No.180234-011901 / PCT 21 are available in, e.g., Escherichia coli (E. coli), Bacillus sp., Salmonella, and Caulobacter. Kits for such expression systems are commercially available. Eukaryotic expression systems for mammalian cells, yeast, and insect cells are commercially available. In one embodiment, the eukaryotic expression vector is an adenoviral vector, an adeno- associated vector, or a retroviral vector. In some embodiments, the mutant FGF-21 peptide is recombinantly produced in E. coli cells, i.e. the expression host is E. coli. In some embodiments, the present disclosure also provides the mutant FGF-21 peptide conjugate and / or the pharmaceutical composition for use as a medicament and for use in the treatment of diabetes and related diseases, particularly diabetes type 2, nonalcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and / or metabolic syndrome. For example, some embodiments also provide the use of the mutant FGF-21 peptide conjugate of the disclosure and / or the use of the pharmaceutical composition of the disclosure for the treatment of diabetes and related diseases, particularly diabetes type 2, NAFLD, NASH and / or metabolic syndrome. In some embodiments is provided a method of treating diabetes and related diseases, particularly diabetes type 2, NASH, nonalcoholic fatty liver disease (NAFLD), and / or metabolic syndrome comprising administering to a subject in need thereof an amount of the mutant FGF-21 peptide conjugate according to the disclosure or the pharmaceutical composition according to the disclosure. In some embodiments, the subject is a human subject. NASH is a chronic liver disease, characterized histologically by hepatic steatosis in ≥5% of hepatocytes, injury (ballooning). It is part of the spectrum of NAFLD that includes NASH, and cirrhosis resultant from fatty liver. NAFLD is a common chronic liver disease in Western countries, which can progress to cirrhosis and is associated with an increased mortality risk in general and an increased cardiovascular disease mortality risk in particular. In North America, the prevalence of NAFLD is estimated at ~24%. NAFLD patients tend to be obese, with insulin resistance and / or type 2 diabetes mellitus (T2DM), dyslipidemia, hypertriglyceridemia, and hypertension, and NAFLD is increasingly recognized as the liver disease component of the metabolic syndrome (MetS) (Chalasani, 2018). NAFLD is usually asymptomatic, unless progression to cirrhosis has occurred. It is often diagnosed by demonstration of hepatic steatosis on liver imaging (e.g., ultrasound or Attorney Docket No.180234-011901 / PCT magnetic resonance imaging (MRI)) in subjects, commonly with features of the metabolic syndrome, in whom no alternative etiology for liver fat accumulation can be identified (e.g., alcoholic liver disease, medications). Validated noninvasive tests for diagnosis of steatohepatitis are not currently available, and a liver biopsy is still needed to diagnose the inflammation and cellular ballooning features of NASH (Torres, 2012). Current pharmacological treatment of NAFLD has limited efficacy and therefore, there is a pressing need to develop more effective and safe agents for this common and life- threatening disease. Obeticholic acid (OCA), a selective agonist of the farnesoid X receptors, appears to have promise as a therapeutic agent for the management of NAFLD. The Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment (FLINT) trial in patients with NASH, revealed that OCA administration is associated with improvements in liver histology, as well as weight loss and reduction in blood pressure. Although its adverse effects on lipid profile and insulin sensitivity are noteworthy, OCA might be considered in selected patients with NAFLD / NASH, particularly those with adequately controlled glucose and lipid levels. With respect to indicators demonstrating clinical efficacy of compounds and compositions described herein, a variety of exemplary indicators are known in the art and described herein including, without limitation, a reduction in HbA1c, glucose and Insulin, body weight, serum lipids (total cholesterol, LDL, Triglycerides), liver enzymes (ALT, AST), liver weight, relative liver weight (% body weight), NAFLD Activity Score (NAS), fibrosis score (e.g., liver fibrosis), pro-inflammatory cytokines (e.g., IL1β, MCP-1), fibrosis biomarkers (αSMA, Collagen 1 alpha), hepatic cholesterol, hepatic triglycerides, and hepatic fatty acids. Increases in at least one of adiponectin (e.g. high molecular weight (HMW)) or HDL are also indicators of clinical efficacy of compounds and compositions described herein. Accordingly, a change (as indicated above) in at least one of the indicators reflects clinical efficacy of a compound or composition described herein. In some embodiments, the therapeutic efficacy of a compound or composition described herein is determined based on a reduction in at least one of serum triglyceride levels or serum insulin levels. HOMA-IR is, for example, is an indicator of the presence and extent of insulin resistance in a subject. It is an accurate indicator of the dynamic between baseline (fasting) blood sugar Attorney Docket No.180234-011901 / PCT and insulin levels responsive thereto. It is referred to as an insulin resistance calculator. For humans, a healthy range is 1.0 (0.5-1.4). Less than 1.0 indicates that a subject is insulin- sensitive, which is ideal; above 1.9 indicates that a subject is exhibiting early insulin resistance; above 2.9 indicates that a subject is exhibiting significant insulin resistance. HOMA-IR blood code calculation is determined as follows: insulin uIU / mL (mU / L) X glucose (mg / dL) = HOMA-IR. The calculation requires U.S. standard units. To convert from international SI units: for insulin: pmol / L to uIU / mL, divide (÷) by 6; for glucose: mmol / L to mg / dL, multiply (X) by 8. Some embodiments relate to dosage regimen whereby an effective amount of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising a therapeutically effective amount of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof. In some embodiments, the mutant FGF-21 peptide conjugate is mutant FGF-21 peptide conjugate having SEQ ID NO: 2. In some embodiments, the method comprises administering once a month, once every two months, or once every three months to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 180 mg of the mutant FGF-21 peptide conjugate. In some embodiments, from about 30 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 30 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three weeks, once a month, or once every four weeks. In some embodiments, from about 60 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 60 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three weeks, once a month, or once every four weeks. In some embodiments, from about 90 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 90 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three weeks, once a month, or once every four weeks. In some embodiments, from about 120 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 120 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three weeks, once a Attorney Docket No.180234-011901 / PCT month, or once every four weeks. In some embodiments, from about 150 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 150 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three weeks, once a month, or once every four weeks. In some embodiments, from about 60 mg to about 90 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 60 mg to about 90 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three weeks, once a month, or once every four weeks. In some embodiments, from about 90 mg to about 120 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 90 mg to about 120 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three weeks, once a month, or once every four weeks. In some embodiments, from about 120 mg to about 150 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 120 mg to about 150 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three weeks, once a month, or once every four weeks. In some embodiments, the method comprises administering once a month to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 180 mg of the mutant FGF-21 peptide conjugate. In some embodiments, the method comprises administering once a month to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 40 mg, from about 40 mg to about 50 mg, from about 50 mg to about 60 mg, from about 60 mg to about 70 mg, from about 70 mg to about 80 mg, from about 80 mg to about 90 mg, from about 90 mg to about 100 mg, from about 100 mg to about 110 mg, from about 110 mg to about 120 mg, from about 120 mg to about 130 mg, from about 130 mg to about 140 mg, from about 140 mg to about 150 mg, from about 150 mg to about 160 mg, from about 160 mg to about 170 mg, from about 170 mg to about 180 mg. In some embodiments, the method comprises administering once a month to the subject in need thereof the pharmaceutical composition comprising about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg of a mutant FGF-21 peptide conjugate described herein (e.g. mutant FGF-21 peptide Attorney Docket No.180234-011901 / PCT conjugate having SEQ ID NO: 2). In some embodiments, from about 30 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 30 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every two months. In some embodiments, from about 60 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 60 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every two months. In some embodiments, from about 90 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 90 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every two months. In some embodiments, from about 120 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 120 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every two months. In some embodiments, from about 150 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 150 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every two months. In some embodiments, from about 60 mg to about 90 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 60 mg to about 90 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every two months. In some embodiments, from about 90 mg to about 120 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 90 mg to about 120 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every two months. In some embodiments, from about 120 mg to about 150 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 120 mg to about 150 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every two months. In some embodiments, the method comprises administering once every two months to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 180 mg of the mutant FGF-21 peptide conjugate. In some Attorney Docket No.180234-011901 / PCT embodiments, the method comprises administering once every two months to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 40 mg, from about 40 mg to about 50 mg, from about 50 mg to about 60 mg, from about 60 mg to about 70 mg, from about 70 mg to about 80 mg, from about 80 mg to about 90 mg, from about 90 mg to about 100 mg, from about 100 mg to about 110 mg, from about 110 mg to about 120 mg, from about 120 mg to about 130 mg, from about 130 mg to about 140 mg, from about 140 mg to about 150 mg, from about 150 mg to about 160 mg, from about 160 mg to about 170 mg, from about 170 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein (e.g. mutant FGF-21 peptide conjugate having SEQ ID NO: 2). In some embodiments, the method comprises administering once every two months to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 180 mg of the mutant FGF-21 peptide conjugate. In some embodiments, the method comprises administering once every two month to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 40 mg, from about 40 mg to about 50 mg, from about 50 mg to about 60 mg, from about 60 mg to about 70 mg, from about 70 mg to about 80 mg, from about 80 mg to about 90 mg, from about 90 mg to about 100 mg, from about 100 mg to about 110 mg, from about 110 mg to about 120 mg, from about 120 mg to about 130 mg, from about 130 mg to about 140 mg, from about 140 mg to about 150 mg, from about 150 mg to about 160 mg, from about 160 mg to about 170 mg, from about 170 mg to about 180 mg. In some embodiments, the method comprises administering once every two month to the subject in need thereof the pharmaceutical composition comprising about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg of a mutant FGF-21 peptide conjugate described herein. In some embodiments, from about 60 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 60 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three months. In some embodiments, from about 90 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 90 mg to about 180 mg of a mutant FGF-21 peptide Attorney Docket No.180234-011901 / PCT conjugate is administered to the subject in need thereof once every three months. In some embodiments, from about 120 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 120 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three months. In some embodiments, from about 150 mg to about 180 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 150 mg to about 180 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three months. In some embodiments, from about 60 mg to about 90 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 60 mg to about 90 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three months. In some embodiments, from about 90 mg to about 120 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 90 mg to about 120 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three months. In some embodiments, from about 120 mg to about 150 mg of a mutant FGF-21 peptide conjugate described herein or a pharmaceutical composition comprising from about 120 mg to about 150 mg of a mutant FGF-21 peptide conjugate is administered to the subject in need thereof once every three months. In some embodiments, the method comprises administering once every three months to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 180 mg of the mutant FGF-21 peptide conjugate. In some embodiments, the method comprises administering once every three months to the subject in need thereof the pharmaceutical composition comprising from about 30 mg to about 40 mg, from about 40 mg to about 50 mg, from about 50 mg to about 60 mg, from about 60 mg to about 70 mg, from about 70 mg to about 80 mg, from about 80 mg to about 90 mg, from about 90 mg to about 100 mg, from about 100 mg to about 110 mg, from about 110 mg to about 120 mg, from about 120 mg to about 130 mg, from about 130 mg to about 140 mg, from about 140 mg to about 150 mg, from about 150 mg to about 160 mg, from about 160 mg to about 170 mg, from about 170 mg to about 180 mg. In some embodiments, the method comprises administering once every three month to the subject in need thereof the pharmaceutical composition comprising about about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, 110 mg, about 120 Attorney Docket No.180234-011901 / PCT mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg of a mutant FGF-21 peptide conjugate described herein (e.g. mutant FGF-21 peptide conjugate having SEQ ID NO: 2). In some embodiments, the administration of the mutant FGF-21 peptide conjugate is effective in reducing hepatic fat fraction by at least 30%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60% for a time period of at least 3 months. In some embodiments, the administration of the mutant FGF-21 peptide conjugate is effective in improving liver fibrosis (e.g by ≥1 stage) without NASH worsening. In some embodiments, the administration of the mutant FGF-21 peptide conjugate is effective in NASH resolution without worsening of fibrosis. Without being bound to the theory, once a month, once every two month, once every three month dosing regimen of the mutant FGF-21 peptide conjugate described herein may greatly enhance compliance with dosing. Long duration efficacy of mutant FGF-21 peptide conjugates described herein is evidenced by the surprisingly long half-life (between about 55 to about 100 hours) determined for these conjugates in animal model systems. Native FGF21 has a short life (~2 hours), limiting the potential to use it as a therapeutic agent. In humans, the effects of pegbelfermin (Pegylated FGF-21 having a half-life of 19-24 hours) showed a lower efficacy in the lipid measurements (% change vs. baseline) when dosed weekly vs daily. Long duration efficacy of mutant FGF-21 peptide conjugates described herein, in turn, makes it possible to administer the mutant FGF-21 peptide conjugates less frequently, for example once every three weeks, once every four weeks, once every 5 weeks, once every 6 weeks, once every 7 weeks, once every 8 weeks, once every 9 weeks, once every 10 weeks, once every 11 weeks, once every 12 weeks or once every 13 weeks. Accordingly, in some embodiments, a mutant FGF-21 peptide conjugate described herein or a composition comprising same is administered to a subject in need thereof at a frequency of equal to once every three weeks, once every four weeks, once every 5 weeks, once every 6 weeks, once every 7 weeks, once every 8 weeks, once every 9 weeks, once every 10 weeks, once every 11 weeks, once every 12 weeks or once every 13 weeks. For example, the mutant FGF-21 peptide conjugate described herein or a composition comprising same may be administered to a subject in need thereof once every once every 21 days, once every 22 days, once every Attorney Docket No.180234-011901 / PCT 22 days, once every 23 days, once every 24 days, once every 25 days, once every 26 days, once every 27 days, once every 28 days, once every 29 days, once every 30 days, or once every 31 days. In an exemplary embodiment, the compounds described herein and compositions comprising same is administered to a subject in need thereof at a frequency of once a month. In an exemplary embodiment, the compounds described herein and compositions comprising same is administered to a subject in need thereof at a frequency of once every two months. In an exemplary embodiment, the compounds described herein and compositions comprising same is administered to a subject in need thereof at a frequency of once every three months. In another exemplary therapeutic regimen, compounds described herein and compositions comprising same are following a course of “induction” therapy, which calls for more frequent administration such as twice a week or weekly at the onset of the treatment regimen followed by maintenance therapy, which may involve weekly, once every two weeks, once a month, once every two months, once every three months administration. Such regimen is effective in that the initial induction therapy improves the subject’s condition to a manageable level that is acceptable with regard to achieving a clinical state that is acceptable for maintenance of the disease / condition. Thereafter, the maintenance therapy is used to preserve the level of wellness at the maintenance level. Therapeutic efficacy of a compound and / or composition for treating diabetes and related diseases, particularly diabetes type 2, nonalcoholic fatty liver disease (NAFLD), non- alcoholic steatohepatitis (NASH) and / or metabolic syndrome may be evaluated using a variety of parameters and assays known by persons of skill in the art. Therapeutic efficacy of a compound and / or composition for treating non-alcoholic steatohepatitis (NASH) may be evaluated using a variety of parameters and assays known by persons of skill in the art. MRI-PDFF is a non-invasive, quantitative biomarker to assess liver fat content. There is a strong correlation between the measurements of hepatic fat by MRI-PDFF and histological evaluation and early-phase NASH trials have employed MRI-PDFF as an endpoint to evaluate therapeutic efficacy (Brown et al. JHEP Rep 2023 Jan 7;5(4):100661). For example, A 30% relative reduction in hepatic fat fraction measured by MRI-PDFF has been associated with histological NASH improvement (Loomba et al., Hepatology.2020;72:1219–1229.) Attorney Docket No.180234-011901 / PCT Measuring HbA1C is considered a standard assay for measuring glycemic index of a subject over a long duration. It is, therefore, a stable indicator of glycemic index, reflecting glucose levels over the course of approximately the last 3-4 months. Accordingly, a subject who has diabetes (e.g., diabetes type 2) may be defined by the percent HbA1C determined in a suitable assay. For a healthy person without diabetes, the normal range for the hemoglobin A1c level is between 4% and 5.6%. Hemoglobin A1c levels between 5.7% and 6.4% indicate that a person has a higher chance of developing diabetes. Levels of 6.5% or higher indicate that a person has diabetes. In some embodiments, HbA1C is measured with HPLC by using the Glycated hemoglobin test system (BIO-RAD, Hercules, CA, USA). Blood samples (e.g., 1.0 mL / per time) may be collected from the cephalic or saphenous vein into BD Vacutainer® K2-EDTA tubes. Samples may be stored immediately at 4 degrees C or maintained on wet ice and analyzed on the same day the blood was collected. HbA1c levels in the blood may be measured by persons skilled in the art with HPLC by using the Glycated hemoglobin test system (BIO-RAD, Hercules, CA, USA). With regard to NASH, this condition is currently diagnosed by biopsy. There are some surrogate biomarkers however, that are considered predictive of NASH, such as liver fat (determined by MRI), liver enzymes (ALT and ALT / AST ratio), and fibrosis biomarkers, such as pro-C3, non-invasive tests (NITs), such as VCTE, FAST, FIB-4. Specific examples of methods and kits have been described herein for purposes of illustration. These are only examples. The technology provided herein can be applied to systems other than the example systems described above. Many alterations, modifications, additions, omissions, and permutations are possible within the practice of this disclosure. This disclosure includes variations on described embodiments that would be apparent to the skilled addressee, including variations obtained by: replacing features, elements and / or acts with equivalent features, elements and / or acts; mixing and matching of features, elements and / or acts from different embodiments; combining features, elements and / or acts from embodiments as described herein with features, elements and / or acts of other technology; and / or omitting combining features, elements and / or acts from described embodiments. The embodiments of the disclosure described above are intended to be exemplary only. Attorney Docket No.180234-011901 / PCT Those skilled in this art will understand that various modifications of detail may be made to these embodiments, all of which come within the scope of the disclosure. Additional Embodiments Embodiment 1: A method of treating nonalcoholic steatohepatitis (NASH) in a subject in need thereof, comprising administering once a month to once every three months to the subject in need thereof a pharmaceutical composition comprising from 60 mg to 150 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, wherein the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. Embodiment 2: The method of embodiment 1, wherein the subject is a human subject. Embodiment 3: The method of embodiment 1, wherein the pharmaceutical composition is administered sub-subcutaneously. Embodiment 4: The method of embodiment 1, wherein administration of the pharmaceutical composition results in at least one of: a reduction of liver fat, an improvement of liver fibrosis score, resolution of NASH, ≥2 point improvement of NAFLD Activity score, improvement of VCTE score, improvement of FAST score, improvement of FIB-4 score, a reduction of liver size as assessed by Magnetic resonance imaging – Proton density fat fraction, a reduction of levels of one or more biomarkers comprising Pro-C3, alanine transaminase (ALT), Enhanced LiverFibrosis (ELF) panel, CK-18, inflammation marker high-sensitivity C-reactive protein (hs-CRP), Hemoglobin A1c (HbA1c), non-HDL-c, LDL-c, and Triglycerides, and an increase of the levels of HDL-c and / or Adiponectin. Embodiment 5: The method of claim 1, wherein the mutant FGF-21 peptide conjugate comprises the structure: Attorney Docket No.180234-011901 / PCT 21wherein n is an integer selected from 450 to 460. Embodiment 6: The method of embodiment 1, wherein the 20 kDa PEG is a linear or branched PEG. Embodiment 7: The method of embodiment 1, wherein the pharmaceutical composition is administered once a month. Embodiment 8: The method of embodiment 1, wherein the pharmaceutical composition is administered once every two months. Embodiment 9: The method of embodiment 1, wherein the pharmaceutical composition is administered once every three months. Embodiment 10: A pharmaceutical composition comprising from 30 mg to 180 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, for use in a method of treating NASH in a subject in need thereof, wherein the pharmaceutical composition is administered subcutaneously once a month, wherein the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. Embodiment 11: A pharmaceutical composition comprising from 90 mg to 180 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, for use in a method of treating NASH in a subject in need thereof, wherein the pharmaceutical composition is administered subcutaneously once every three months, Attorney Docket No.180234-011901 / PCT wherein the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG. EXAMPLES Example 1: Simulation MRI-PDFF Change from QM Dosings The Pharmacokinetic / Pharmacodynamic (PK / PD) modeling of data from the Pegozafermin phase Ib / IIa study (Tseng et al. Clin Pharmacol Ther.2023 Dec;114(6):1323- 1331) was used to predict the efficacy of 30 mg QM, 60 mg QM, 90 mg QM, 120 mg QM, 150 mg QM, and 180 mg QM dosing regimen. Pegozafermin is a long-acting glycoPEGylated analog of fibroblast growth factor 21 (FGF21) in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. In a phase Ib / IIa placebo-controlled, double-blind, multiple ascending dose study in patients with NASH (NCT04048135), administration of pegozafermin resulted in clinically meaningful reductions in hepatic fat fraction (HFF), with a favorable safety and tolerability profile. The model adequately describes a relationship between PK (i.e., kinetics of drug concentrations) and PD response (i.e., hepatic fat reduction as measured by MRI-PDFF at Month 3) for Phase Ib / IIa data. The model then predicted that the dosing regimen 30 mg, weekly (QW) and 44 mg every other week (Q2W) in humans were efficacious. Consequently, the doses including 30mg QW and 44 mg Q2W dosage regimen were tested in Phase 2 ENLIVEN study (NCT04929483) and the ENLIVEN data confirmed the model prediction. The data showed that the 30 mg QW dose approximated the full PD effect and almost all patients benefit from a greater than or equal to 30% HFF reduction, suggesting liver histological improvement (Loomba et al., Hepatology. 2020;72:1219–1229.) Furthermore, 44 mg Q2W dosing was shown to also be an effective regimen for HFF reduction. ENLIVEN data (Loomba et al. N Engl J Med. 2023 Sep Attorney Docket No.180234-011901 / PCT 14;389(11):998-1008) show 7%, 26% and 27%, respectively in the pooled placebo, 30 mg QW and 44 mg Q2W group had fibrosis improvement by ≥1 stage without NASH worsening. 2%, 23% and 26%, respectively in the placebo, 30 mg QW and 44 mg Q2W group had NASH resolution without worsening of fibrosis. These data confirm the robustness of the PK / PD model to guide dose selection for mutant FGF-21 peptide conjugate comprising the amino acid sequence of SEQ ID NO: 2 described herein. The PK / PD model was used to predict how drug concentrations resulting from 30 mg QM, 60 mg 90 mg QM, 120 mg QM, 150 mg QM, and 180 mg QM dosing regimen elicit desired MRI-PDFF response. See Figure 1. Figure 1 shows simulated MRI-PDFF change from QM dosing regimen. QM regimen over the examined doses from about 30 mg to about 180 mg QM elicits MRI-PDFF reduction. Figure 1 shows that 30 mg QM, 60 mg QM, 90 mg QM, 120 mg QM, 150 mg QM, and 180 mg QM dosing regimen result in relative reduction in hepatic fat fraction measured by MRI-PDFF greater than 30%. A 30% relative reduction in hepatic fat fraction measured by MRI-PDFF has been associated with histological NASH improvement (Loomba et al., Hepatology. 2020;72:1219–1229.) Figure 1 shows that dosing regimen 30 mg QM, 60 mg QM, 90 mg QM, 120 mg QM, 150 mg QM, and 180 mg QM result in relative reduction in hepatic fat fraction measured by MRI-PDFF greater than 30%. Figure 1 shows that the results obtained with dosing regimen 60 mg QM, 90 mg QM, 120 mg QM, 150 mg QM, and 180 mg QM are comparable the results obtained 30 mg QW and 44 mg Q2W dosing regimen, with more than 50% relative reduction in hepatic fat fraction. Example 2 Simulation MRI-PDFF Change from Q3M Dosings The PK / PD modeling was used to predict the efficacy of 30 mg Q3M, 60 mg Q3M, 90 mg Q3M, 120 mg Q3M, 150 mg Q3M, and 180 mg Q3M dosing regimen. Figure 2 shows simulated MRI-PDFF change from Q3M dosing regimen. Q3M regimen over the examined doses from about 30 mg to about 180 mg QM elicits MRI-PDFF reduction. Figure 2 shows that 90 mg Q3M, 120 mg Q3M, 150 mg Q3M, and 180 mg Q3M dosing regimen result in relative reduction in hepatic fat fraction measured by MRI-PDFF greater than 30%. A 30% relative reduction in hepatic fat fraction measured by MRI-PDFF has been associated with histological NASH improvement (Loomba et al., Hepatology.2020;72:1219–1229.) Attorney Docket No.180234-011901 / PCT All publications mentioned herein are hereby incorporated by reference in their entireties. While the foregoing disclosure has been described in some detail for purposes of clarity and understanding, it will be appreciated by one skilled in the art from a reading of the disclosure that various changes in form and detail can be made without departing from the true scope of the disclosure in the appended claims.

Claims

Attorney Docket No.180234-011901 / PCT CLAIMS 1. A method of treating nonalcoholic steatohepatitis (NASH) in a subject in need thereof, comprising: administering once a month to the subject in need thereof a pharmaceutical composition comprising from 30 mg to 180 mg of a mutant Fibroblast Growth Factor- 21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, wherein the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG.

2. The method of claim 1, wherein the subject is a human subject.

3. The method of claim 1, wherein the pharmaceutical composition is administered sub- subcutaneously.

4. The method of claim 1, wherein administration of the pharmaceutical composition results in at least one of: a reduction of liver fat, an improvement of liver fibrosis score, resolution of NASH, ≥2 point improvement of NAFLD Activity score, improvement of VCTE score, improvement of FAST score, improvement of FIB-4 score, a reduction of liver size as assessed by Magnetic resonance imaging – Proton density fat fraction, a reduction of levels of one or more biomarkers comprising Pro-C3, alanineAttorney Docket No.180234-011901 / PCT transaminase (ALT), Enhanced LiverFibrosis (ELF) panel, CK-18, inflammation marker high-sensitivity C-reactive protein (hs-CRP), Hemoglobin A1c (HbA1c), non-HDL-c, LDL-c, and Triglycerides, and an increase of the levels of HDL-c and / or Adiponectin.

5. The method of claim 1, wherein the mutant FGF-21 peptide conjugate comprises the structure: OH21wherein n is an integer selected from 450 to 460.

6. The method of claim 1, wherein the 20 kDa PEG is a linear or branched PEG.

7. A method of treating nonalcoholic steatohepatitis (NASH) in a subject in need thereof, comprising: administering once every three months to the subject in need thereof a pharmaceutical composition comprising from 90 mg to 180 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, wherein the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG.

8. The method of claim 7, wherein the subject is a human subject.

9. The method of claim 7, wherein the pharmaceutical composition is administered sub- subcutaneously.Attorney Docket No.180234-011901 / PCT 10. The method of claim 7, wherein administration of the pharmaceutical composition results in at least one of: a reduction of liver fat, an improvement of liver fibrosis score, resolution of NASH, ≥2 point improvement of NAFLD Activity score, improvement of VCTE score, improvement of FAST score, improvement of FIB-4 score, a reduction of liver size as assessed by Magnetic resonance imaging – Proton density fat fraction, a reduction of levels of one or more biomarkers comprising Pro-C3, alanine transaminase (ALT), Enhanced LiverFibrosis (ELF) panel, CK-18, inflammation marker high-sensitivity C-reactive protein (hs-CRP), Hemoglobin A1c (HbA1c), non-HDL-c, LDL-c, and Triglycerides, and an increase of the levels of HDL-c and / or Adiponectin.

11. The method of claim 7, wherein the mutant FGF-21 peptide conjugate comprises the structure: OOFGF-21wherein n is an integer selected from 450 to 460.

12. The method of claim 7, wherein the 20 kDa PEG is a linear or branched PEG.

13. A pharmaceutical composition comprising from 30 mg to 180 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, for use in a method of treating NASH in a subject in need thereof, wherein the pharmaceutical composition is administered subcutaneously once a month, wherein the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ IDAttorney Docket No.180234-011901 / PCT NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG.

14. A pharmaceutical composition comprising from 90 mg to 180 mg of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate and a pharmaceutically acceptable carrier, for use in a method of treating NASH in a subject in need thereof, wherein the pharmaceutical composition is administered subcutaneously once every three months, wherein the mutant FGF-21 peptide conjugate comprises: i) a mutant FGF-21 peptide comprising the amino acid sequence of SEQ ID NO: 2, ii) a glycosyl moiety, and iii) a 20 kDa polyethylene glycol (PEG), wherein the mutant FGF-21 peptide is attached to the glycosyl moiety by a covalent bond between a threonine at amino acid position 173 of SEQ ID NO: 2 and a first site of the glycosyl moiety and wherein the glycosyl moiety is attached to the 20 kDa PEG by a covalent bond between a second site of the glycosyl moiety and the 20 kDa PEG.

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