EP4622997A2 - Melanocortin and glp-1 receptor agonists and methods of use - Google Patents

Description

Attorney Docket No.371255-7003WO1 (00011) TITLE OF THE INVENTION Melanocortin and GLP-1 Receptor Agonists and Methods of Use CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to U.S. Provisional Patent Application No. 63/427,555 entitled "MELANOCORTIN AND GLP-1 RECEPTOR AGONISTS AND METHODS OF USE," filed November 23, 2022, the disclosure of which is incorporated herein by reference in its entirety. INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED AS A TEXT FILE This invention contains one or more sequences in a computer readable format in an accompanying text file titled "371255-7003WO1_Sequence_ST26.xml," which was created on November 21, 2023 and is 44.7 KB in size, the contents of which are incorporated herein by reference in its entirety. BACKGROUND Despite public health education and other initiatives, obesity and type 2 diabetes (T2D) are among the greatest health challenges facing not only the U.S, but the entire world. Weight loss significantly improves morbidity and mortality associated with obesity and associated metabolic disease, such as T2D. However, rigid dietary intervention increases the risk for disinhibited eating and weight regain. In recent years it became clear that hypothalamic dysfunction plays a major role in many forms of severe obesity, such as common obesity, monogenic obesity, and hypothalamic obesity. While therapies based on endogenous gut peptides such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP- 1RAs) have been compelling therapeutic agents for obesity and T2D, only a few have achieved partial long-term weight loss (≥5-15% in adults at 1 year), and all have shown significant side-effects, including nausea/malaise and gastrointestinal ailments. In recent years, melanocortin receptor agonists have been developed and tested in forms of obesity caused by deficient hypothalamic melanocortin signaling as in patients with pro-opiomelanocortin or leptin receptor deficiency. To reduce the burden and risk of obesity- associated diseases, there is dire unmet clinical need for new anti-obesity agents with increased efficacy, safety and patient tolerance. The present disclosure addresses this unmet need. - 1 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) BRIEF SUMMARY OF THE INVENTION In various aspects, provided herein is a dual melanocortin receptor (MCR) and glucagon like peptide (GLP-1) agonist peptide, or a pharmaceutically acceptable salt thereof, comprising the amino acid sequence: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13- X14-X15-X16-X17-X18-X19-X20-X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31- X32-X33-X34-X35-X36-X37-X38-X39-X40-X41-X42-X43-X44-X45-X46-X46-X47-X48- X49-X50-X51-X52-X53-X54-X55-X56-X57-X58-X59-X60-NH2 (SEQ ID NO.1) is provided. Amino acid residues X1-X60 are defined as follows: Position Definition in SEQ ID NO: 1 X1 H h h l i i i h i n - 2 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X21 E, e, or any other analog or derivative described herein X22 F, f, α-methyl-Phe, or any other analog or derivative described herein n n , - - 3 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X46 Absent, A, R, N, D, C, E, Q, G, H, I, L, K, M, F, P, S, T, W, Y, V, a, r, n, d, c, e, q, g, h, i, l, k, m, f, p, s, t, w, y, v, Nle, Nva, α-methyl-Phe, α-methyl-Ala, α- thlS thlL K* K^a th l d i ti d ibd , - , - , - , - , - , - , - , - , - - 4 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X56 Absent, A, R, N, D, C, E, Q, G, H, I, L, K, M, F, P, S, T, W, Y, V, a, r, n, d, c, e, q, g, h, i, l, k, m, f, p, s, t, w, y, v, Nle, Nva, α-methyl-Phe, α-methyl-Ala, α- th l S th l L K* K^a th l d i ti d ib d , - , - , - , - n var ous aspects, met o s o treat ng, ame orat ng, an or prevent ng a meta o c disease or disorder using the peptides of SEQ ID NO.1-6 and 10-16 are also provided. Non- limiting examples of metabolic diseases or disorders include type 2 diabetes, obesity, nonalcoholic fatty liver disease, hypothalamic obesity, prediabetes, and/or nonalcoholic steatohepatitis. BRIEF DESCRIPTION OF THE FIGURES The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments of the present application. FIGs.1A-1D show confirmation of synthesis and purity of non-limiting chimeric peptides, according to various embodiments. (FIG.1A) KSCEM01 (5016.52 g/mol; 15.244 min T_R; 96.4% pure), (FIG.1B) KSCEM02 (5097.61 g/mol; 17.447 min T_R; 95.6% pure), (FIG.1C) KSCEM03 (4716.14 g/mol; 16.863 min TR; 99.9% pure), (FIG.1D) KSCEM04 (4223.62 g/mol; 15.817 min T_R; 98.8% pure). FIG.2 shows a non-limiting competitive binding assay at hGLP-1R. KSCEM01 (KD = 9.9 nM) binding at the human GLP-1R, as measured via SPR vs. an Ex-4 (KD = 5.9 nM) control. Ex-4 is Exendin-4, His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met- - 5 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly- Ala-Pro-Pro-Pro-Ser-NH₂ (SEQ ID NO: 9). FIG.3 shows non-limiting in vitro evaluation of KSCEM01 at the hGLP-1R. Dose- dependent agonism (% change in FRET ratio tracking levels of cAMP) of KSCEM01 (EC₅₀ = 4.08 nM) at the human GLP-1R vs. an Ex-4 (EC50 = 0.29 pM) control. FIG.4 illustrates the MALDI mass spectrum of KSCEM01. FIG.5 illustrates the reduction in food intake as a result of once-daily KSCEM01 administered for 3-days at each dose to male diet-induced obese Sprague Dawley Rats in a dose escalation experiment. FIG.6 illustrates the reduction in food intake as a result of once-daily KSCEM01 administration to male diet-induced obese Sprague Dawley Rats. FIGs.7A-7C illustrates the comparative metabolic as a result of once-daily KSCEM01, liraglutide, and control administration to male diet-induced obese Wistar Rats in 16-day treatment experiments. Shown are changes in body weight (FIG.7A), cumulative food intake (FIG.7B), and calorie intake (FIG.7C). DETAILED DESCRIPTION OF THE INVENTION Reference will now be made in detail to certain embodiments of the disclosed subject. While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the exemplified subject matter is not intended to limit the claims to the disclosed subject matter. Throughout this document, values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement "about X to Y" has the same meaning as "about X to about Y," unless indicated otherwise. Likewise, the statement "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z," unless indicated otherwise. In this document, the terms "a," "an," or "the" are used to include one or more than one unless the context clearly dictates otherwise. The term "or" is used to refer to a nonexclusive "or" unless otherwise indicated. The statement "at least one of A and B" or "at - 6 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) least one of A or B" has the same meaning as "A, B, or A and B." In addition, it is to be understood that the phraseology or terminology employed herein, and not otherwise defined, is for the purpose of description only and not of limitation. Any use of section headings is intended to aid reading of the document and is not to be interpreted as limiting; information that is relevant to a section heading may occur within or outside of that particular section. All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the methods described herein, the acts can be carried out in any order, except when a temporal or operational sequence is explicitly recited. Furthermore, specified acts can be carried out concurrently unless explicit claim language recites that they be carried out separately. For example, a claimed act of doing X and a claimed act of doing Y can be conducted simultaneously within a single operation, and the resulting process will fall within the literal scope of the claimed process. Definitions The term "about" as used herein can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range, and includes the exact stated value or range. A disease or disorder is "alleviated" if the severity of a symptom of the disease or disorder, the frequency with which such a symptom is experienced by a patient, or both, is reduced. As used herein, the terms "alteration," "defect," "variation," or "mutation" refer to a mutation in a gene in a cell that affects the function, activity, expression (transcription or translation) or conformation of the polypeptide it encodes, including missense and nonsense mutations, insertions, deletions, frameshifts and premature terminations. As used herein, the term "composition" or "pharmaceutical composition" refers to a mixture of at least one peptide described herein with a pharmaceutically acceptable carrier. The pharmaceutical composition facilitates administration of the peptide to a patient or subject. Multiple techniques of administering a peptide exist in the art including, but not limited to, intravenous, oral, aerosol, parenteral, ophthalmic, pulmonary and topical administration. As used herein, the terms “conservative variation” or “conservative substitution” as used herein refers to the replacement of an amino acid residue by another, biologically similar residue. Conservative variations or substitutions are not likely to change the shape of - 7 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) the peptide chain. Examples of conservative variations, or substitutions, include the replacement of one hydrophobic residue such as isoleucine, valine, leucine or methionine for another, or the substitution of one polar residue for another, such as the substitution of arginine for lysine, glutamic for aspartic acid, or glutamine for asparagine. Additional examples include swaps within groups such as Gly / Ala; Val / Ile / Leu; Asp / Glu; Asn / Gln; Ser / Thr; Lys / Arg; and Phe / Tyr. The degree of identity between two polypeptides is determined using computer algorithms and methods that are widely known for the persons skilled in the art. The identity between two amino acid sequences is preferably determined by using the BLASTP algorithm (BLAST Manual, Altschul et al., NCBI NLM NIH Bethesda, Md.20894, Altschul et al., J. Mol. Biol.215: 403-410 (1990)), though other similar algorithms can also be used. BLAST and BLAST 2.0 are used, with the parameters described herein, to determine percent sequence identity. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. A "disease" is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal's health continues to deteriorate. In contrast, a "disorder" in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal's state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal's state of health. As used herein, the terms "effective amount," "pharmaceutically effective amount" and "therapeutically effective amount" refer to a nontoxic but sufficient amount of an agent to provide the desired biological result. That result may be reduction and/or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. An appropriate therapeutic amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation. As used herein, the term "efficacy" refers to the maximal effect (Emax) achieved within an assay. The term "independently selected from" as used herein refers to referenced groups being the same, different, or a mixture thereof, unless the context clearly indicates otherwise. Thus, under this definition, the phrase "X¹, X², and X³ are independently selected from noble gases" would include the scenario where, for example, X¹, X², and X³ are all the same, where X¹, X², and X³ are all different, where X¹ and X² are the same but X³ is different, and other - 8 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) analogous permutations. "Isolated" means altered or removed from the natural state. For example, a nucleic acid or a polypeptide naturally present in a living animal is not "isolated," but the same nucleic acid or polypeptide partially or completely separated from the coexisting materials of its natural state is "isolated." An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell. The terms "patient," "subject," or "individual" are used interchangeably herein, and refer to any animal, or cells thereof whether in vitro or in situ, amenable to the methods described herein. In a non-limiting embodiment, the patient, subject or individual is a human. As used herein, the term "peptide(s)" and "peptide(s)" are used interchangeably. As used herein, the term "pharmaceutically acceptable" refers to a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the peptide, and is relatively non-toxic, i.e., the material may be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained. As used herein, the language "pharmaceutically acceptable salt" refers to a salt of the administered peptides prepared from pharmaceutically acceptable non-toxic acids or bases, including inorganic acids or bases, organic acids or bases, solvates, hydrates, or clathrates thereof. Suitable pharmaceutically acceptable acid addition salts may be prepared from an inorganic acid or from an organic acid. Examples of inorganic acids include hydrochloric, hydrobromic, hydriodic, nitric, carbonic, sulfuric (including sulfate and hydrogen sulfate), and phosphoric acids (including hydrogen phosphate and dihydrogen phosphate). Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which include formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, malonic, saccharin, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, 4-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, trifluoromethanesulfonic, 2- hydroxyethanesulfonic, p-toluenesulfonic, sulfanilic, cyclohexylaminosulfonic, stearic, alginic, β-hydroxybutyric, salicylic, galactaric and galacturonic acid. Suitable pharmaceutically acceptable base addition salts of peptides described herein include, for example, ammonium salts, metallic salts including alkali metal, alkaline earth metal and transition metal salts such as, for example, calcium, magnesium, potassium, - 9 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) sodium and zinc salts. Pharmaceutically acceptable base addition salts also include organic salts made from basic amines such as, for example, N,N'-dibenzylethylene-diamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All of these salts may be prepared from the corresponding peptide by reacting, for example, the appropriate acid or base with the peptide. As used herein, the term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" means a pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, stabilizer, dispersing agent, suspending agent, diluent, excipient, thickening agent, solvent or encapsulating material, involved in carrying or transporting a peptide described herein within or to the patient such that it may perform its intended function. Typically, such constructs are carried or transported from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation, including the peptide(s) described herein, and not injurious to the patient. Some examples of materials that may serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; surface active agents; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. As used herein, "pharmaceutically acceptable carrier" also includes any and all coatings, antibacterial and antifungal agents, and absorption delaying agents, and the like that are compatible with the activity of the peptide(s) described herein, and are physiologically acceptable to the patient. Supplementary active peptides may also be incorporated into the compositions. The "pharmaceutically acceptable carrier" may further include a pharmaceutically acceptable salt of the peptide(s) described herein. Other additional ingredients that may be included in the pharmaceutical compositions used with the methods or peptides described herein are known in the art and described, for example in Remington's Pharmaceutical Sciences (Genaro, Ed., Mack Publishing Co., 1985, Easton, PA), which is incorporated herein by reference. - 10 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) As used herein, the term "potency" refers to the dose needed to produce half the maximal response (ED₅₀). The terms "prevent," "preventing," and "prevention", as used herein, refer to inhibiting the inception or decreasing the occurrence of a disease in a subject. Prevention may be complete (e.g. the total absence of pathological cells in a subject) or partial. Prevention also refers to a reduced susceptibility to a clinical condition. In certain embodiments, "preventing" comprises preventing onset of a disease or disorder. The term "room temperature" as used herein refers to a temperature of about 15 °C to 28 °C. The term "solvent" as used herein refers to a liquid that can dissolve a solid, liquid, or gas. Non-limiting examples of solvents are silicones, organic peptides, water, alcohols, ionic liquids, and supercritical fluids. The term "standard temperature and pressure" as used herein refers to 20 °C and 101 kPa. As used herein, "substantially purified" refers to being essentially free of other components. For example, a substantially purified polypeptide is a polypeptide that has been separated from other components with which it is normally associated in its naturally occurring state. Non-limiting embodiments include 95% purity, 99% purity, 99.5% purity, 99.9% purity and 100% purity. The term "substantially" as used herein refers to a majority of, or mostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%. The term "substantially free of" as used herein can mean having none or having a trivial amount of, such that the amount of material present does not affect the material properties of the composition including the material, such that the composition is about 0 wt% to about 5 wt% of the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less. The term "substantially free of" can mean having a trivial amount of, such that a composition is about 0 wt% to about 5 wt% of the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less, or about 0 wt%. The term "substituted" as used herein in conjunction with a molecule or an organic group as defined herein refers to the state in which one or more hydrogen atoms contained therein are replaced by one or more non-hydrogen atoms. The substitution can be direct - 11 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) substitution, whereby the hydrogen atom is replaced by a functional group or substituent, or an indirect substitution, whereby an intervening linker group replaces the hydrogen atom, and the substituent or functional group is bonded to the intervening linker group. A non-limiting example of direct substitution is: RR-H ^ RR-Cl, wherein RR is an organic moiety/fragment/molecule. A non-limiting example of indirect substitution is: RR-H ^ RR- (LL)_zz-Cl, wherein RR is an organic moiety/fragment/molecule, LL is an intervening linker group, and 'zz' is an integer from 0 to 100 inclusive. When zz is 0, LL is direct substitution results. The intervening linker group LL is at each occurrence independently selected from the group consisting of -H, -O-, -OR, -S-, -S(=O)-, -S(=O)2-, -SR, -N(R)-, - NR2, -CR=, -C ^ ^ ^-CH2-, -CHR-, -CR2-, -CH3, -C(=O)-, -C(=NR)-, and combinations thereof. (LL)zz can be linear, branched, cyclic, acyclic, and combinations thereof. The term "substituent" or "functional group" as used herein refers to a group that can be or is substituted onto a molecule or onto an organic group. Examples of substituents or functional groups include, but are not limited to, a halogen (e.g., F, Cl, Br, and I); an oxygen atom in groups such as hydroxy groups, alkoxy groups, aryloxy groups, aralkyloxy groups, oxo(carbonyl) groups, carboxyl groups including carboxylic acids, carboxylates, and carboxylate esters; a sulfur atom in groups such as thiol groups, alkyl and aryl sulfide groups, sulfoxide groups, sulfone groups, sulfonyl groups, and sulfonamide groups; a nitrogen atom in groups such as amines, hydroxyamines, nitriles, nitro groups, N-oxides, hydrazides, azides, and enamines; and other heteroatoms in various other groups. Non-limiting examples of substituents that can be bonded to a substituted carbon (or other) atom include F, Cl, Br, I, OR, OC(O)N(R)₂, CN, NO, NO₂, ONO₂, azido, CF₃, OCF₃, R, O (oxo), S (thiono), C(O), S(O), methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, SO2R, SO2N(R)2, SO3R, C(O)R, C(O)C(O)R, C(O)CH₂C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)₂, OC(O)N(R)₂, C(S)N(R)2, (CH2)0-2N(R)C(O)R, (CH2)0-2N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)₂, N(R)SO₂R, N(R)SO₂N(R)₂, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(=NH)N(R)2, C(O)N(OR)R, and C(=NOR)R, wherein R can be hydrogen or a carbon-based moiety; for example, R can be hydrogen, (C₁-C₁₀₀)hydrocarbyl, alkyl, acyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, or heteroarylalkyl; or wherein two R groups bonded to a nitrogen atom or to adjacent nitrogen atoms can together with the nitrogen atom or atoms form a heterocyclyl. A "therapeutic" treatment is a treatment administered to a subject who exhibits signs of pathology, for the purpose of diminishing or eliminating those signs. - 12 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) As used herein, the term "treatment" or "treating" is defined as the application or administration of a therapeutic agent, i.e., a peptide or peptides as described herein (alone or in combination with another pharmaceutical agent), to a patient, or application or administration of a therapeutic agent to an isolated tissue or cell line from a patient (e.g., for diagnosis or ex vivo applications), who has a condition contemplated herein or a symptom of a condition contemplated herein, with the purpose to alleviate, relieve, alter, remedy, ameliorate, improve or affect a condition contemplated herein, or the symptoms of a condition contemplated herein. Such treatments may be specifically tailored or modified, based on knowledge obtained from the field of pharmacogenomics. GLP-1 and MCR Dual Agonist Peptides Peptides (peptides) described herein can be prepared by the general schemes described herein, using the synthetic method known by those skilled in the art. The following examples illustrate non-limiting embodiments of the peptide(s) described herein and their preparation. In various embodiments, provided herein are chimeric dual-agonist peptides having agonistic function at both GLP-1 (glucagon like peptide) and MCR (melanocortin) receptors. In various embodiments, the dual agonist peptide is less than or equal to 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 amino acids in length. In various embodiments, the dual agonist peptide has the sequence: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17- X18-X19-X20-X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-X32- X33-X34-X35-X36-X37-X38-X39-X40-X41-X42-X43-X44-X45-X46-X46- X47-X48-X49-X50-X51-X52-X53-X54-X55-X56-X57-X58-X59-X60-NH₂ (SEQ ID NO: 1), wherein the amino acid residues X1-X60 have the definitions listed in Table 1. Table 1: Definitions for residues in SEQ ID NO.1. Position Definition in SEQ ID NO: 1 - 13 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X4 G X5 T, t, or any other analog or derivative described herein n n - 14 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X32 S, s, α-methyl-Ser, or any other analog or derivative described herein X33 H, h, Y, y, or any other analog or derivative described herein n , - , - , - , - , - - 15 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X50 Absent, A, R, N, D, C, E, Q, G, H, I, L, K, M, F, P, S, T, W, Y, V, a, r, n, d, c, e, q, g, h, i, l, k, m, f, p, s, t, w, y, v, Nle, Nva, α-methyl-Phe, α-methyl-Ala, α- thlS thlL K* K^a th l d i ti d ibd , - , - , - , - , - , - , - , - , - - 16 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X60 Absent, A, R, N, D, C, E, Q, G, H, I, L, K, M, F, P, S, T, W, Y, V, a, r, n, d, c, e, q, g, h, i, l, k, m, f, p, s, t, w, y, v, Nle, Nva, α-methyl-Phe, α-methyl-Ala, α- th l S th l L K* K^a th l d i ti d ib d other analog described herein of the naturally occurring amino acid as defined for a given position, and any derivatives as described herein of the naturally occurring amino acid as defined for a given position. In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSKYLEEEAVREFIAWLKNGGPSYSMEHFRWGKPV-NH₂ (SEQ ID NO.2). In various embodiments, the dual agonist peptide has the sequence: HSQGTFTSDLSKYLEEEAVREFIAWLKNGGPSYSMEHFRWGKPV-NH₂ (SEQ ID NO.3). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSKYLEEEAVREFIAWLKNGGPSYS(Nle)EHfRWGKPV-NH₂ (SEQ NO.4). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSKYLEEEAVREFIAWLKNGGPSYS(Nle)EHfRW-NH₂ (SEQ ID NO.5). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSKYLEEEAVREFIAWLKNGGPSHfRW-NH₂ (SEQ ID NO: 6). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSKYLEEEAVREFIAWLK*NGGPSYSMEHFRWGKPV-NH₂ (SEQ ID NO.10). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSKYLEEEAVREFIAWLKNGGPSYSMEHFRWGK*PV-NH₂ (SEQ ID NO.11). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSKYLEEEAVREFIAWLK*NGGPSYSMEHFRWGK*PV-NH₂ (SEQ ID NO.12). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSK*YLEEEAVREFIAWLKNGGPSYSMEHFRWGKPV-NH₂ (SEQ ID NO.13). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSK*YLEEEAVREFIAWLK*NGGPSYSMEHFRWGKPV-NH₂ (SEQ ID NO.14). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSK*YLEEEAVREFIAWLKNGGPSYSMEHFRWGK*PV-NH₂ (SEQ ID NO.15). In various embodiments, the dual agonist peptide has the sequence: HsQGTFTSDLSK*YLEEEAVREFIAWLK*NGGPSYSMEHFRWGK*PV-NH₂ (SEQ ID NO. 16). - Attorney Docket No.371255-7003WO1 (00011) In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.2. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.3. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.4. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.5. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.6. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.10. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.11. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.12. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.13. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.14. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.15. In various embodiments, the dual agonist peptide has a sequence that is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to the dual agonist peptide of SEQ ID NO.16. In various embodiments, peptides of SEQ ID NO.1-6 and 10-16 are dual agonists of GLP-1 and MCR3. In various embodiments, peptides of SEQ ID NO.1-6 and 10-16 are dual agonists of GLP-1 and MCR4. In various embodiments, peptides of SEQ ID NO.1-6 and 10- 16 are dual agonists of GLP-1 and MCR3/4. In various embodiments, a dual agonist of GLP-1 and MCR3 independently has an in vitro or in vivo potency (as measured by IC50 or EC50) against each of GLP-1 and MCR3 that is less than, at least, or equal to about 100, 90, 80, 70, 60, 50, 40, 3020, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.1, 0.05, or about 0.01 nM. The potency of the dual agonist peptide of SEQ ID NO.1-6 and 10-16 against GLP-1 is independent of the potency of the dual agonist peptide of SEQ ID NO.1-6 and 10-16 against MCR3, although each potency is about 0.01 to about 100 - 18 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) nM as set forth herein. In various embodiments, a dual agonist of GLP-1 and MCR4 independently has an in vitro or in vivo potency (as measured by IC50 or EC50) against each of GLP-1 and MCR3 that is less than, at least, or equal to about 100, 90, 80, 70, 60, 50, 40, 3020, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.1, 0.05, or about 0.01 nM. The potency of the dual agonist peptide of SEQ ID NO.1-6 and 10-16 against GLP-1 is independent of the potency of the dual agonist peptide of SEQ ID NO.1-6 and 10-16 against MCR4, although each potency is about 0.01 to about 100 nM as set forth herein. In various embodiments, a dual agonist of GLP-1 and MCR3/4 independently has an in vitro or in vivo potency (as measured by IC₅₀ or EC₅₀) against each of GLP-1, MCR3, and MCR4 that is less than, at least, or equal to about 100, 90, 80, 70, 60, 50, 40, 3020, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.1, 0.05, or about 0.01 nM. The potency of the dual agonist peptide of SEQ ID NO.1-6 and 10-16 against GLP-1 is independent of the potency of the dual agonist peptide of SEQ ID NO.1-6 and 10-16 against each of MCR3 and MCR4, although each potency is about 0.01 to about 100 nM as set forth herein. In various embodiments, the agonist potencies against GLP-1, MCR3, and/or MCR4 are in murine receptors. In various embodiments, the agonist potencies against GLP-1, MCR3, and/or MCR4 are in human receptors. Agonist potencies against GLP-1, MCR3, and/or MCR4 can be measured according to the methods described herein, or similar methods known in the art. Analogs and Derivatives of Naturally Occurring Amino Acids in SEQ ID NOs.1-6 and 10-16 In the peptides described herein, an amino acid single-letter code in lower-case represents the corresponding D-amino acid. For example, in SEQ ID NO.1, the lower-case "s" represents D-serine. The peptides described herein can include L-amino acids, D-amino acids, or a combination of both. In various embodiments, the peptides are D retro-inverso peptides. The term “retro-inverso isomer” refers to an isomer of a linear peptide in which the direction of the sequence is reversed and the chirality of each amino acid residue is inverted. See, e.g., Jameson et al., Nature, 368, 744-746 (1994); Brady et al., Nature, 368, 692-693 (1994), which is incorporated herein in its entirety by reference. The net result of combining D-enantiomers and reverse synthesis is that the positions of carbonyl and amino groups in each amide bond are exchanged, while the position of the side-chain groups at each alpha carbon is preserved. Unless specifically stated otherwise, it is presumed that any given L- amino acid sequence of the invention may be made into a D retro-inverso peptide by - 19 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) synthesizing a reverse of the sequence for the corresponding native L-amino acid sequence. In various embodiments, one or more amino acids in the peptides described herein can be replaced by a non-naturally occurring amino acid or a naturally or non-naturally occurring amino acid analog. For example, an aromatic amino acid can be replaced by 3,4-dihydroxy- L-phenylalanine, 3-iodo-L-tyrosine, triiodothyronine, L-thyroxine, phenylglycine (Phg) or nor-tyrosine (norTyr). Phg and norTyr and other amino acids including Phe and Tyr can be substituted by, e.g., a halogen, -CH3, -OH, -CH2NH3, -C(O)H, -CH2CH3, - CN, - CH₂CH₂CH₃, -SH, or another group. With regard to non-naturally occurring amino acids or naturally and non-naturally occurring amino acid analogs, a number of substitutions in dual agonist peptides described herein are possible alone or in combination. For example, glutamine residues can be substituted with gamma-hydroxy-Glu or gamma-carboxy-Glu. Tyrosine residues can be substituted with an alpha substituted amino acid such as L-alpha-methylphenylalanine or by analogues such as: 3-amino-Tyr; Tyr(CH₃); Tyr(PO₃(CH₃)₂); Tyr(SO₃H); β-cyclohexyl-Ala; β -(l-cyclopentenyl)-Ala; β - cyclopentyl-Ala; β -cyclopropyl-Ala; β -quinolyl-Ala; β -(2- thiazolyl)-Ala; β- (triazole-l-yl)-Ala; β -(2-pyridyl)-Ala; β -(3-pyridyl)-Ala; amino-Phe; fluoro-Phe; cyclohexyl-Gly; t-Bu-Gly; β -(3-benzothienyl)-Ala; beta-(2-thienyl)-Ala; 5- methyl-Trp; and α-methyl-Trp. Proline residues can be substituted with homo-Pro (L-pipecolic acid); hydroxy-Pro; 3,4-Dehydro-Pro; 4-fluoro-Pro; or α-methyl-Pro. Alanine residues can be substituted with alpha-substituted or N-methylated amino acid such as alpha-amino isobutyric acid (aib), L/D- alpha-ethylalanine (L/D-isovaline), L/D-methylvaline, or L/D-alpha-methylleucine or a non- natural amino acid such as beta-fluoro-Ala. Alanine can also be substituted with: n = 0, 1, 2, 3 Glycine residues can be substituted with alpha-amino iso-butyric acid (aib) or L/D-alpha- ethylalanine (L/D-isovaline). Other non-standard amino acid residues that can, in various embodiments, replace one or more standard amino acid residues in the dual agonist peptides described herein include, norleucine (Nle), norvaline (Nva), citrulline (Cit), ornithine (Orn), Naphthylalanine (Nal), α-aminobutryic acid (Abu), 2,4-diaminobutyric acid (Dab), methionine sulfoxide, methionine sulfone, and the like. The peptides described herein can be modified using standard modifications. Modifications may occur at the amino (N-), carboxy (C-) terminus, internally or a combination of any of the preceding. In various embodiments, there may be more than one type of modification in the dual agonist peptide. Modifications include, but are not limited to: acetylation, amidation, biotinylation, cinnamoylation, farnesylation, formylation, - 20 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) myristoylation, palmitoylation, phosphorylation (Ser, Tyr or Thr), stearoylation, succinylation, sulfurylation and cyclisation (via disulfide bridges or amide cyclisation). The dual agonist peptides described herein may also be modified by 2, 4-dinitrophenyl (DNP), DNP-lysine, modification by 7-amino-4-methyl- coumarin (AMC), flourescein, NBD (7- nitrobenz-2-oxa-l,3-diazole), p-nitro-anilide, rhodamine B, EDANS (5-((2- aminoethyl)amino)naphthalene-1-sulfonic acid), dabcyl, dabsyl, dansyl, Texas red, FMOC, and Tamra (tetramethylrhodamine). The dual agonist peptides described herein may also be conjugated to, for example, polyethylene glycol (PEG); alkyl groups (e.g., C1-C30 straight or branched alkyl groups); fatty acid radicals (e.g., C₁-C₃₀ straight or branched fatty acid radicals); as well as combinations of PEG, alkyl groups and fatty acid radicals. In various embodiments, PEG groups, (-CH2CH2- O)_m, can have m equal to 1 to 50. The conjugation can be at any suitable amino acid side chain, such as at a side chain containing a carboxyl group (Asp or Glu), an amine (His, Lys, Arg), or an alcohol (Ser, Thr). Contemplated herein is a dual-agonist peptide sequence having a D-amino acid, α- amino acid, β-amino acid, methylated amino acid, acetylated amino acid, amidated amino acid, biotinylated amino acid, cinnamoylated amino acid, farnesylated amino acid, formylated amino acid, myristoylated amino acid, palmitoylated amino acid, phosphorylated (Ser, Tyr or Thr), stearoylated amino acid, succinylated amino acid, a sulfurylated amino acid, or any other non-standard/non-natural amino acid analog described herein at any one residue position in the peptides of SEQ ID NO.1-6 and 10-16. Contemplated herein is a dual-agonist peptide sequence having a D-amino acid, α- amino acid, β-amino acid, methylated amino acid, acetylated amino acid, amidated amino acid, biotinylated amino acid, cinnamoylated amino acid, farnesylated amino acid, formylated amino acid, myristoylated amino acid, palmitoylated amino acid, phosphorylated (Ser, Tyr or Thr), stearoylated amino acid, succinylated amino acid, a sulfurylated amino acid, or any other non-standard/non-natural amino acid analog described herein at any two residue positions in the peptides of SEQ ID NO.1-6 and 10-16, wherein any of the preceding unnatural amino acids can be independently present. Contemplated herein is a dual-agonist peptide sequence having a D-amino acid, α- amino acid, β-amino acid, methylated amino acid, acetylated amino acid, amidated amino acid, biotinylated amino acid, cinnamoylated amino acid, farnesylated amino acid, formylated amino acid, myristoylated amino acid, palmitoylated amino acid, phosphorylated (Ser, Tyr or Thr), stearoylated amino acid, succinylated amino acid, a sulfurylated amino acid, or any - 21 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) other non-standard/non-natural amino acid analog described herein at any three residue positions in the peptides of SEQ ID NO.1-6 and 10-16, wherein any of the preceding unnatural amino acids can be independently present. Contemplated herein is a dual-agonist peptide sequence having a D-amino acid, α- amino acid, β-amino acid, methylated amino acid, acetylated amino acid, amidated amino acid, biotinylated amino acid, cinnamoylated amino acid, farnesylated amino acid, formylated amino acid, myristoylated amino acid, palmitoylated amino acid, phosphorylated (Ser, Tyr or Thr), stearoylated amino acid, succinylated amino acid, a sulfurylated amino acid, or any other non-standard/non-natural amino acid analog described herein at any four, five, six, seven, eight, nine, or ten residue positions in the peptides of SEQ ID NO.1-6 and 10-16, wherein any of the preceding unnatural amino acids can be independently present. In various embodiments, K* is a lysine residue in which the amino side chain is substituted according to the structure: , wherein n is 9, 10, 11, or 12; PEG is a moiety that contains one or more ethylene glycol units; and A is independently at each occurrence a linear or branched C_4-18 alkyl, linear or branched C4-18 alkenyl, or linear or branched C4-18 alkynyl. In various embodiments, K* is a lysine residue in which the amino side chain is substituted according to the structure: . In linear or branched C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, or C18 alkyl. In various embodiments, A is independently at each occurrence a linear or branched C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, or C18 alkenyl. In various embodiments, A is independently at each occurrence a linear or branched C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, or C18 alkynyl. - 22 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) In various embodiments, n is 1. In various embodiments, n is 2. In various embodiments, n is 3. In various embodiments, n is 3. In various embodiments, n is 4. In various embodiments, n is 5. In various embodiments, n is 6. In various embodiments, n is 7. In various embodiments, n is 8. In various embodiments, n is 9. In various embodiments, n is 10. In various embodiments, n is 11. In various embodiments, n is 12. In various embodiments, A is C6 alkyl. In various embodiments, A is C6 alkenyl. In various embodiments, A is C6 alkynyl. In various embodiments, A is C7 alkyl. In various embodiments, A is C7 alkenyl. In various embodiments, A is C7 alkynyl. In various embodiments, A is C8 alkyl. In various embodiments, A is C8 alkenyl. In various embodiments, A is C8 alkynyl. In various embodiments, A is C9 alkyl. In various embodiments, A is C9 alkenyl. In various embodiments, A is C9 alkynyl. In various embodiments, A is C10 alkyl. In various embodiments, A is C10 alkenyl. In various embodiments, A is C10 alkynyl. In various embodiments, A is C11 alkyl. In various embodiments, A is C11 alkenyl. In various embodiments, A is C11 alkynyl. In various embodiments, A is C12 alkyl. In various embodiments, A is C12 alkenyl. In various embodiments, A is C12 alkynyl. In various embodiments, A is C13 alkyl. In various embodiments, A is C13 alkenyl. In various embodiments, A is C13 alkynyl. In various embodiments, A is C14 alkyl. In various embodiments, A is C14 alkenyl. In various embodiments, A is C14 alkynyl. In various embodiments, A is C15 alkyl. In various embodiments, A is C15 alkenyl. In various embodiments, A is C15 alkynyl. In various embodiments, A is C16 alkyl. In various embodiments, A is C16 alkenyl. In various embodiments, A is C16 alkynyl. In various embodiments, A is C17 alkyl. In various embodiments, A is C17 alkenyl. In various embodiments, A is C17 alkynyl. In various embodiments, A is C18 alkyl. In various embodiments, A is C18 alkenyl. In various embodiments, A is C18 alkynyl. In various embodiments, in SEQ ID NO:14 each A is a C12 alkyl. In various embodiments, K^a is a lysine residue in which the amino side chain is substituted according to the structure: - 23 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) . Lysine residue derivatives K^a can be further reacted or bio- conjugated to other chemical or vitro or in vivo), in various embodiments, using copper-free or copper-mediated click-chemistry. In various embodiments, the dual agonist peptide of SEQ ID NO: 1 does not contain any of the following amino acid sequences: HAEGTFTSDVSSYLEGQAAKEFIAWLVRGR (SEQ ID NO.7), HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR (SEQ ID NO.8), or any continuous sequence of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids starting with the first amino acid in either SEQ ID NO.7 or 8 (His1), or any sequence that has at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence homology to SEQ ID NO.7 or SEQ ID NO.8. Table 2. Sequences of GLP-1R/MC4R chimeric dual agonists. Peptide Sequence ID KSCEM01, KSCEM02, KS thesized and purified to >95% purity. Lowercase letters den o e -a o ac s; e o eucine. The peptides described herein can possess one or more stereocenters, and each stereocenter can exist independently in either the (R) or (S) configuration. In certain embodiments, peptides described herein are present in optically active or racemic forms. It is to be understood that the peptides described herein encompass racemic, optically-active, regioisomeric and stereoisomeric forms, or combinations thereof that possess the therapeutically useful properties described herein. Preparation of optically active forms is achieved in any suitable manner, including by way of non-limiting example, by resolution of the racemic form with recrystallization techniques, synthesis from optically-active starting materials, chiral synthesis, or chromatographic separation using a chiral stationary phase. In - 24 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) certain embodiments, a mixture of one or more isomer is utilized as the therapeutic peptide described herein. In other embodiments, peptides described herein contain one or more chiral centers. These peptides are prepared by any means, including stereoselective synthesis, enantioselective synthesis and/or separation of a mixture of enantiomers and/ or diastereomers. Resolution of peptides and isomers thereof is achieved by any means including, by way of non-limiting example, chemical processes, enzymatic processes, fractional crystallization, distillation, and chromatography. The methods and formulations described herein include the use of N-oxides (if appropriate), crystalline forms (also known as polymorphs), solvates, amorphous phases, and/or pharmaceutically acceptable salts of peptides having the structure of any peptide(s) described herein, as well as metabolites and active metabolites of these peptides having the same type of activity. Solvates include water, ether (e.g., tetrahydrofuran, methyl tert-butyl ether) or alcohol (e.g., ethanol) solvates, acetates and the like. In certain embodiments, the peptides described herein exist in solvated forms with pharmaceutically acceptable solvents such as water, and ethanol. In other embodiments, the peptides described herein exist in unsolvated form. In certain embodiments, the peptides(s) described herein can exist as tautomers. All tautomers are included within the scope of the peptides presented herein. In certain embodiments, peptides described herein are prepared as prodrugs. A “prodrug“ refers to an agent that is converted into the parent drug in vivo. In certain embodiments, upon in vivo administration, a prodrug is chemically converted to the biologically, pharmaceutically or therapeutically active form of the peptide. In other embodiments, a prodrug is enzymatically metabolized by one or more steps or processes to the biologically, pharmaceutically or therapeutically active form of the peptide. In certain embodiments, sites on, for example, the aromatic ring portion of peptide(s) described herein are susceptible to various metabolic reactions. Incorporation of appropriate substituents on the aromatic ring structures may reduce, minimize or eliminate this metabolic pathway. In certain embodiments, the appropriate substituent to decrease or eliminate the susceptibility of the aromatic ring to metabolic reactions is, by way of example only, a deuterium, a halogen, or an alkyl group. Peptides described herein also include isotopically-labeled peptides wherein one or more atoms is replaced by an atom having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes suitable for inclusion in the peptides described herein include and are - 25 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) not limited to ²H, ³H, ¹¹C, ¹³C, ¹⁴C, ³⁶Cl, ¹⁸F, ¹²³I, ¹²⁵I, ¹³N, ¹⁵N, ¹⁵O, ¹⁷O, ¹⁸O, ³²P, and ³⁵S. In certain embodiments, isotopically-labeled peptides are useful in drug and/or substrate tissue distribution studies. In other embodiments, substitution with heavier isotopes such as deuterium affords greater metabolic stability (for example, increased in vivo half-life or reduced dosage requirements). In yet other embodiments, substitution with positron emitting isotopes, such as ¹¹C, ¹⁸F, ¹⁵O and ¹³N, is useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically-labeled peptides are prepared by any suitable method or by processes using an appropriate isotopically-labeled reagent in place of the non-labeled reagent otherwise employed. In certain embodiments, the peptides described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels. The peptides described herein, and other related peptides having different substituents are synthesized using techniques and materials described herein and as described, for example, in Fieser & Fieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Peptides, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989), March, Advanced Organic Chemistry 4^th Ed., (Wiley 1992); Carey & Sundberg, Advanced Organic Chemistry 4th Ed., Vols. A and B (Plenum 2000,2001), and Green & Wuts, Protective Groups in Organic Synthesis 3rd Ed., (Wiley 1999) (all of which are incorporated by reference for such disclosure). General methods for the preparation of peptide as described herein are modified by the use of appropriate reagents and conditions, for the introduction of the various moieties found in the formula as provided herein. Peptides described herein are synthesized using any suitable procedures starting from peptides that are available from commercial sources, or are prepared using procedures described herein. In certain embodiments, reactive functional groups, such as hydroxyl, amino, imino, thio or carboxy groups, are protected in order to avoid their unwanted participation in reactions. Protecting groups are used to block some or all of the reactive moieties and prevent such groups from participating in chemical reactions until the protective group is removed. In other embodiments, each protective group is removable by a different means. Protective groups that are cleaved under totally disparate reaction conditions fulfill the requirement of differential removal. - 26 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) In certain embodiments, protective groups are removed by acid, base, reducing conditions (such as, for example, hydrogenolysis), and/or oxidative conditions. Groups such as trityl, dimethoxytrityl, acetal and t-butyldimethylsilyl are acid labile and are used to protect carboxy and hydroxy reactive moieties in the presence of amino groups protected with Cbz groups, which are removable by hydrogenolysis, and Fmoc groups, which are base labile. Carboxylic acid and hydroxy reactive moieties are blocked with base labile groups such as, but not limited to, methyl, ethyl, and acetyl, in the presence of amines that are blocked with acid labile groups, such as t-butyl carbamate, or with carbamates that are both acid and base stable but hydrolytically removable. In certain embodiments, carboxylic acid and hydroxy reactive moieties are blocked with hydrolytically removable protective groups such as the benzyl group, while amine groups capable of hydrogen bonding with acids are blocked with base labile groups such as Fmoc. Carboxylic acid reactive moieties are protected by conversion to simple ester peptides as exemplified herein, which include conversion to alkyl esters, or are blocked with oxidatively-removable protective groups such as 2,4-dimethoxybenzyl, while co-existing amino groups are blocked with fluoride labile silyl carbamates. Allyl blocking groups are useful in the presence of acid- and base- protecting groups since the former are stable and are subsequently removed by metal or pi-acid catalysts. For example, an allyl-blocked carboxylic acid is deprotected with a palladium-catalyzed reaction in the presence of acid labile t-butyl carbamate or base-labile acetate amine protecting groups. Yet another form of protecting group is a resin to which a peptide or intermediate is attached. As long as the residue is attached to the resin, that functional group is blocked and does not react. Once released from the resin, the functional group is available to react. Typically blocking/protecting groups may be selected from: - 27 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) H H H H H C H H C C H H H C . to the creation of protecting groups and their removal are described in Greene & Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, NY, 1999, and Kocienski, Protective Groups, Thieme Verlag, New York, NY, 1994, which are incorporated herein by reference for such disclosure. Pharmacology In various embodiments, the peptide(s) described herein can be administered to a subject in an amount ranging from about 0.01 mg/kg to about 200 mg/kg, or about 0.5 mg/kg to about 190 mg/kg, or about 0.75 mg/kg to about 180 mg/kg, or about 1 mg/kg to about 170 mg/kg, or about 1.5 mg/kg to about 160 mg/kg, or about 2 mg/kg to about 150 mg/kg, or about 2.5 mg/kg to about 140 mg/kg, or about 3 mg/kg to about 130 mg/kg, or about 3.5 mg/kg to about 120 mg/kg, or about 4 mg/kg to about 110 mg/kg, or about 4.5 mg/kg to about 100 mg/kg, or about 5 mg/kg to about 95 mg/kg, or about 5.5 mg/kg to about 90 mg/kg, or about 6 mg/kg to about 85 mg/kg, or about 6.5 mg/kg to about 80 mg/kg, or about 7 mg/kg to about 75 mg/kg, or about 7.5 mg/kg to about 70 mg/kg, or about 8 mg/kg to about 65 mg/kg, or about 8.5 mg/kg to about 60 mg/kg, or about 9 mg/kg to about 55 mg/kg or about 9.5 mg/kg to about 50 mg/kg, or about 10 mg/kg to about 45 mg/kg. In various embodiments, the peptide(s) described herein can be administered to a subject in an amount that is less than, equal to, or greater than about 0.01 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 0.75 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 2.5 mg/kg, 3 mg/kg, 3.5 mg/kg, 4 mg/kg, 4.5 mg/kg, 5 mg/kg, 5.5 mg/kg, 6 mg/kg, 6.5 mg/kg, 7 mg/kg, - 28 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) 7.5 mg/kg, 8 mg/kg, 8.5 mg/kg, 9 mg/kg, 9.5 mg/kg, 10 mg/kg, 12 mg/kg, 14 mg/kg, 16 mg/kg, 18 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg, 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg, 130 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155 mg/kg, 160 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 185 mg/kg, 190 mg/kg, 195 mg/kg, or 200 mg/kg. Compositions The compositions containing the peptide(s) described herein include a pharmaceutical composition comprising at least one peptide as described herein and at least one pharmaceutically acceptable carrier. In certain embodiments, the composition is formulated for an administration route such as oral or parenteral, for example, transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal and (trans)rectal, intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. Methods of Treatment, Amelioration, and/or Prevention The disclosure includes a method of treating, ameliorating, and/or preventing a metabolic disease or disorder using the peptides of SEQ ID NO.1-6 and 10-16. Non-limiting examples of metabolic diseases or disorders include type 2 diabetes, obesity, nonalcoholic fatty liver disease, hypothalamic obesity, prediabetes, and nonalcoholic steatohepatitis. In various embodiments, a method of treating, preventing, and/or ameliorating a metabolic condition in the subject includes administering to the subject a therapeutically effective amount of any peptide of the disclosure, thereby treating, preventing, and/or ameliorating the metabolic condition. Surprisingly and unexpectedly, administering peptides of SEQ ID NO.1-6 and 10-16 results in fewer or no significant side-effects, including nausea/malaise and gastrointestinal ailments and/or discomfort as compared to administration of endogenous gut peptides such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP- 1RAs). Surprisingly and unexpectedly, in various embodiments, administration of peptides of the disclosure (such as but not limited to any one of SEQ ID NOs.1-6 and 10-16) results in synergistic effects such that the therapeutic benefits and/or reduction in side effects as a result of their administrations is superior to the administration of a combination of a GLP-1 agonist and a MCR agonist as individual therapeutic agents. In various embodiments, the methods of - 29 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) treating, preventing, and/or ameliorating a metabolic condition in the subject includes reduction of energy intake in the subject (reduced food intake and/or reduced appetite), stimulation of energy expenditure (e.g. increased metabolic rate), reduction or elimination of hypothalamic dysfunction, and improvement of gluco-regulation. In various embodiments, the metabolic condition is selected from the group consisting of type 2 diabetes, obesity, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis. In various embodiments, the administration is by a route selected from the group consisting of oral, transdermal, transmucosal, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. In various embodiments, the subject is a mammal. In various embodiments, the mammal is a human. The methods described herein include administering to the subject a therapeutically effective amount of at least one peptide described herein, which is optionally formulated in a pharmaceutical composition. In various embodiments, a therapeutically effective amount of at least one peptide described herein present in a pharmaceutical composition is the only therapeutically active peptide in a pharmaceutical composition. In certain embodiments, the method further comprises administering to the subject an additional therapeutic agent that treats metabolic diseases or disorders. In certain embodiments, administering the peptide(s) described herein to the subject allows for administering a lower dose of the additional therapeutic agent as compared to the dose of the additional therapeutic agent alone that is required to achieve similar results in treating a metabolic disease or disorder in the subject. For example, in certain embodiments, the peptide(s) described herein enhance(s) the activity of the additional therapeutic peptide, thereby allowing for a lower dose of the additional therapeutic peptide to provide the same effect. In certain embodiments, the peptide(s) described herein and the therapeutic agent are co-administered to the subject. In other embodiments, the peptide(s) described herein and the therapeutic agent are coformulated and co-administered to the subject. In certain embodiments, the subject is a mammal. In other embodiments, the mammal is a human. Combination Therapies The peptides useful within the methods described herein can be used in combination - 30 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) with one or more additional therapeutic agents useful for treating metabolic diseases or disorders. These additional therapeutic agents may comprise peptides that are commercially available or synthetically accessible to those skilled in the art. These additional therapeutic agents are known to treat or reduce the symptoms, of a metabolic disease or disorder. In various embodiments, a synergistic effect is observed when a peptide as described herein is administered with one or more additional therapeutic agents or peptides. A synergistic effect may be calculated, for example, using suitable methods such as, for example, the Sigmoid-E_max equation (Holford & Scheiner, 1981, Clin. Pharmacokinet.6:429- 453), the equation of Loewe additivity (Loewe & Muischnek, 1926, Arch. Exp. Pathol Pharmacol.114:313-326) and the median-effect equation (Chou & Talalay, 1984, Adv. Enzyme Regul.22:27-55). Each equation referred to above may be applied to experimental data to generate a corresponding graph to aid in assessing the effects of the drug combination. The corresponding graphs associated with the equations referred to above are the concentration-effect curve, isobologram curve and combination index curve, respectively. Administration/Dosage/Formulations The regimen of administration may affect what constitutes an effective amount. The therapeutic formulations may be administered to the subject either prior to or after the onset of a metabolic disease or disorder. Further, several divided dosages, as well as staggered dosages may be administered daily or sequentially, or the dose may be continuously infused, or may be a bolus injection. Further, the dosages of the therapeutic formulations may be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation. Administration of the compositions described herein to a patient, preferably a mammal, more preferably a human, may be carried out using known procedures, at dosages and for periods of time effective to treat a metabolic disease or disorder in the patient. An effective amount of the therapeutic peptide necessary to achieve a therapeutic effect may vary according to factors such as the state of the disease or disorder in the patient; the age, sex, and weight of the patient; and the ability of the therapeutic peptide to treat a metabolic disease or disorder in the patient. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. A non- limiting example of an effective dose range for a therapeutic peptide described herein is from about 1 and 5,000 mg/kg of body weight/per day. One of ordinary skill in the art would be - 31 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) able to study the relevant factors and make the determination regarding the effective amount of the therapeutic peptide without undue experimentation. Actual dosage levels of the active ingredients in the pharmaceutical compositions described herein may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. In particular, the selected dosage level depends upon a variety of factors including the activity of the particular peptide employed, the time of administration, the rate of excretion of the peptide, the duration of the treatment, other drugs, peptides or materials used in combination with the peptide, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well, known in the medical arts. A medical doctor, e.g., physician or veterinarian, having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the peptides described herein employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In certain embodiments, it is especially advantageous to formulate the peptide in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the patients to be treated; each unit containing a predetermined quantity of therapeutic peptide calculated to produce the desired therapeutic effect in association with the required pharmaceutical vehicle. The dosage unit forms of the peptide(s) described herein are dictated by and directly dependent on (a) the unique characteristics of the therapeutic peptide and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of peptideing/formulating such a therapeutic peptide. In certain embodiments, the compositions described herein are formulated using one or more pharmaceutically acceptable excipients or carriers. In certain embodiments, the pharmaceutical compositions described herein comprise a therapeutically effective amount of a peptide described herein and a pharmaceutically acceptable carrier. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity may be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the - 32 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms may be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it is preferable to include isotonic agents, for example, sugars, sodium chloride, or polyalcohols such as mannitol and sorbitol, in the composition. Prolonged absorption of the injectable compositions may be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate or gelatin. In certain embodiments, the compositions described herein are administered to the patient in dosages that range from one to five times per day or more. In other embodiments, the compositions described herein are administered to the patient in range of dosages that include, but are not limited to, once every day, every two, days, every three days to once a week, and once every two weeks. It is readily apparent to one skilled in the art that the frequency of administration of the various combination compositions described herein varies from individual to individual depending on many factors including, but not limited to, age, disease or disorder to be treated, gender, overall health, and other factors. Thus, administration of the peptides and compositions described herein should not be construed to be limited to any particular dosage regime and the precise dosage and composition to be administered to any patient is determined by the attending physician taking all other factors about the patient into account. The peptide(s) described herein for administration may be in the range of from about 1 µg to about 10,000 mg, about 20 µg to about 9,500 mg, about 40 µg to about 9,000 mg, about 75 µg to about 8,500 mg, about 150 µg to about 7,500 mg, about 200 µg to about 7,000 mg, about 350 µg to about 6,000 mg, about 500 µg to about 5,000 mg, about 750 µg to about 4,000 mg, about 1 mg to about 3,000 mg, about 10 mg to about 2,500 mg, about 20 mg to about 2,000 mg, about 25 mg to about 1,500 mg, about 30 mg to about 1,000 mg, about 40 mg to about 900 mg, about 50 mg to about 800 mg, about 60 mg to about 750 mg, about 70 mg to about 600 mg, about 80 mg to about 500 mg, and any and all whole or partial increments therebetween. In some embodiments, the dose of a peptide described herein is from about 1 mg and about 2,500 mg. In some embodiments, a dose of a peptide described herein used in compositions described herein is less than about 10,000 mg, or less than about 8,000 mg, or less than about 6,000 mg, or less than about 5,000 mg, or less than about 3,000 mg, or less than about 2,000 mg, or less than about 1,000 mg, or less than about 500 mg, or less than about 200 mg, or less than about 50 mg. Similarly, in some embodiments, a dose of a second - 33 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) peptide as described herein is less than about 1,000 mg, or less than about 800 mg, or less than about 600 mg, or less than about 500 mg, or less than about 400 mg, or less than about 300 mg, or less than about 200 mg, or less than about 100 mg, or less than about 50 mg, or less than about 40 mg, or less than about 30 mg, or less than about 25 mg, or less than about 20 mg, or less than about 15 mg, or less than about 10 mg, or less than about 5 mg, or less than about 2 mg, or less than about 1 mg, or less than about 0.5 mg, and any and all whole or partial increments thereof. In certain embodiments, a composition as described herein is a packaged pharmaceutical composition comprising a container holding a therapeutically effective amount of a peptide described herein, alone or in combination with a second pharmaceutical agent; and instructions for using the peptide to treat, prevent, or reduce one or more symptoms of a metabolic disease or disorder in a patient. Formulations may be employed in admixtures with conventional excipients, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for oral, parenteral, nasal, intravenous, subcutaneous, enteral, or any other suitable mode of administration, known to the art. The pharmaceutical preparations may be sterilized and if desired mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure buffers, coloring, flavoring and/or aromatic substances and the like. They may also be combined where desired with other active agents, e.g., other analgesic agents. Routes of administration of any of the compositions described herein include oral, nasal, rectal, intravaginal, parenteral, buccal, sublingual or topical. The peptides for use in the compositions described herein can be formulated for administration by any suitable route, such as for oral or parenteral, for example, transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal and (trans)rectal), intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. Suitable compositions and dosage forms include, for example, tablets, capsules, caplets, pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, transdermal patches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs, suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolized formulations for inhalation, compositions and formulations for intravesical administration and the like. It should be understood that the formulations and compositions - 34 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) described herein are not limited to the particular formulations and compositions that are described herein. Oral Administration For oral application, particularly suitable are tablets, dragees, liquids, drops, suppositories, or capsules, caplets and gelcaps. The compositions intended for oral use may be prepared according to any method known in the art and such compositions may contain one or more agents selected from the group consisting of inert, non-toxic pharmaceutically excipients that are suitable for the manufacture of tablets. Such excipients include, for example an inert diluent such as lactose; granulating and disintegrating agents such as cornstarch; binding agents such as starch; and lubricating agents such as magnesium stearate. The tablets may be uncoated or they may be coated by known techniques for elegance or to delay the release of the active ingredients. Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert diluent. For oral administration, the peptide(s) described herein can be in the form of tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., polyvinylpyrrolidone, hydroxypropylcellulose or hydroxypropyl methylcellulose); fillers (e.g., cornstarch, lactose, microcrystalline cellulose or calcium phosphate); lubricants (e.g., magnesium stearate, talc, or silica); disintegrates (e.g., sodium starch glycollate); or wetting agents (e.g., sodium lauryl sulphate). If desired, the tablets may be coated using suitable methods and coating materials such as OPADRY™ film coating systems available from Colorcon, West Point, Pa. (e.g., OPADRY™ OY Type, OYC Type, Organic Enteric OY-P Type, Aqueous Enteric OY-A Type, OY-PM Type and OPADRY™ White, 32K18400). Liquid preparation for oral administration may be in the form of solutions, syrups or suspensions. The liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, methyl cellulose or hydrogenated edible fats); emulsifying agent (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters or ethyl alcohol); and preservatives (e.g., methyl or propyl p-hydroxy benzoates or sorbic acid). Compositions as described herein can be prepared, packaged, or sold in a formulation suitable for oral or buccal administration. A tablet that includes a peptide as described herein can, for example, be made by compressing or molding the active ingredient, optionally with one or more additional ingredients. Compressed tablets may be prepared by compressing, in a suitable device, the active ingredient in a free-flowing form such as a powder or granular preparation, optionally mixed with one or more of a binder, a lubricant, an excipient, a - 35 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) surface active agent, and a dispersing agent. Molded tablets may be made by molding, in a suitable device, a mixture of the active ingredient, a pharmaceutically acceptable carrier, and at least sufficient liquid to moisten the mixture. Pharmaceutically acceptable excipients used in the manufacture of tablets include, but are not limited to, inert diluents, granulating and disintegrating agents, dispersing agents, surface-active agents, disintegrating agents, binding agents, and lubricating agents. Suitable dispersing agents include, but are not limited to, potato starch, sodium starch glycollate, poloxamer 407, or poloxamer 188. One or more dispersing agents can each be individually present in the composition in an amount of about 0.01% w/w to about 90% w/w relative to weight of the dosage form. One or more dispersing agents can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w/w relative to weight of the dosage form. Surface-active agents (surfactants) include cationic, anionic, or non-ionic surfactants, or combinations thereof. Suitable surfactants include, but are not limited to, behentrimonium chloride, benzalkonium chloride, benzethonium chloride, benzododecinium bromide, carbethopendecinium bromide, cetalkonium chloride, cetrimonium bromide, cetrimonium chloride, cetylpyridine chloride, didecyldimethylammonium chloride, dimethyldioctadecylammonium bromide, dimethyldioctadecylammonium chloride, domiphen bromide, lauryl methyl gluceth-10 hydroxypropyl dimonium chloride, tetramethylammonium hydroxide, thonzonium bromide, stearalkonium chloride, octenidine dihydrochloride, olaflur, N-oleyl-1,3-propanediamine, 2-acrylamido-2-methylpropane sulfonic acid, alkylbenzene sulfonates, ammonium lauryl sulfate, ammonium perfluorononanoate, docusate, disodium cocoamphodiacetate, magnesium laureth sulfate, perfluorobutanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluorooctanoic acid, potassium lauryl sulfate, sodium alkyl sulfate, sodium dodecyl sulfate, sodium laurate, sodium laureth sulfate, sodium lauroyl sarcosinate, sodium myreth sulfate, sodium nonanoyloxybenzenesulfonate, sodium pareth sulfate, sodium stearate, sodium sulfosuccinate esters, cetomacrogol 1000, cetostearyl alcohol, cetyl alcohol, cocamide diethanolamine, cocamide monoethanolamine, decyl glucoside, decyl polyglucose, glycerol monostearate, octylphenoxypolyethoxyethanol CA-630, isoceteth-20, lauryl glucoside, octylphenoxypolyethoxyethanol P-40, Nonoxynol-9, Nonoxynols, nonyl phenoxypolyethoxylethanol (NP-40), octaethylene glycol monododecyl ether, N-octyl beta- - 36 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) D-thioglucopyranoside, octyl glucoside, oleyl alcohol, PEG-10 sunflower glycerides, pentaethylene glycol monododecyl ether, polidocanol, poloxamer, poloxamer 407, polyethoxylated tallow amine, polyglycerol polyricinoleate, polysorbate, polysorbate 20, polysorbate 80, sorbitan, sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, stearyl alcohol, surfactin, Triton X-100, and Tween 80. One or more surfactants can each be individually present in the composition in an amount of about 0.01% w/w to about 90% w/w relative to weight of the dosage form. One or more surfactants can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w/w relative to weight of the dosage form. Suitable diluents include, but are not limited to, calcium carbonate, magnesium carbonate, magnesium oxide, sodium carbonate, lactose, microcrystalline cellulose, calcium phosphate, calcium hydrogen phosphate, and sodium phosphate, Cellactose ® 80 (75 % ^- lactose monohydrate and 25 % cellulose powder), mannitol, pre-gelatinized starch, starch, sucrose, sodium chloride, talc, anhydrous lactose, and granulated lactose. One or more diluents can each be individually present in the composition in an amount of about 0.01% w/w to about 90% w/w relative to weight of the dosage form. One or more diluents can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w/w relative to weight of the dosage form. Suitable granulating and disintegrating agents include, but are not limited to, sucrose, copovidone, corn starch, microcrystalline cellulose, methyl cellulose, sodium starch glycollate, pregelatinized starch, povidone, sodium carboxy methyl cellulose, sodium alginate, citric acid, croscarmellose sodium, cellulose, carboxymethylcellulose calcium, colloidal silicone dioxide, crosspovidone and alginic acid. One or more granulating or disintegrating agents can each be individually present in the composition in an amount of about 0.01% w/w to about 90% w/w relative to weight of the dosage form. One or more granulating or disintegrating agents can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w/w relative to weight of the dosage form. - 37 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) Suitable binding agents include, but are not limited to, gelatin, acacia, pre-gelatinized maize starch, polyvinylpyrrolidone, anhydrous lactose, lactose monohydrate, hydroxypropyl methylcellulose, methylcellulose, povidone, polyacrylamides, sucrose, dextrose, maltose, gelatin, polyethylene glycol. One or more binding agents can each be individually present in the composition in an amount of about 0.01% w/w to about 90% w/w relative to weight of the dosage form. One or more binding agents can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w/w relative to weight of the dosage form. Suitable lubricating agents include, but are not limited to, magnesium stearate, calcium stearate, hydrogenated castor oil, glyceryl monostearate, glyceryl behenate, mineral oil, polyethylene glycol, poloxamer 407, poloxamer 188, sodium laureth sulfate, sodium benzoate, stearic acid, sodium stearyl fumarate, silica, and talc. One or more lubricating agents can each be individually present in the composition in an amount of about 0.01% w/w to about 90% w/w relative to weight of the dosage form. One or more lubricating agents can each be individually present in the composition in an amount of at least, greater than, or less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% w/w relative to weight of the dosage form. Tablets can be non-coated or they may be coated using known methods to achieve delayed disintegration in the gastrointestinal tract of a subject, thereby providing sustained release and absorption of the active ingredient. By way of example, a material such as glyceryl monostearate or glyceryl distearate may be used to coat tablets. Further by way of example, tablets may be coated using methods described in U.S. Patent Nos.4,256,108; 4,160,452; and 4,265,874 to form osmotically controlled release tablets. Tablets may further comprise a sweetening agent, a flavoring agent, a coloring agent, a preservative, or some combination of these in order to provide for pharmaceutically elegant and palatable preparation. Tablets can also be enterically coated such that the coating begins to dissolve at a certain pH, such as at about pH 5.0 to about pH 7.5, thereby releasing a peptide as described herein. The coating can contain, for example, EUDRAGIT ® L, S, FS, and/or E polymers with acidic or alkaline groups to allow release of a peptide as described herein in a particular location, including in any desired section(s) of the intestine. The coating can also contain, for example, EUDRAGIT ® RL and/or RS polymers with cationic or neutral groups to allow for - 38 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) time controlled release of a peptide as described herein by pH-independent swelling. Parenteral Administration For parenteral administration, the peptides as described herein may be formulated for injection or infusion, for example, intravenous, intramuscular or subcutaneous injection or infusion, or for administration in a bolus dose and/or continuous infusion. Suspensions, solutions or emulsions in an oily or aqueous vehicle, optionally containing other formulatory agents such as suspending, stabilizing and/or dispersing agents may be used. Sterile injectable forms of the compositions described herein may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non- toxic parenterally-acceptable diluent or solvent, for example as a solution in 1, 3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or di-glycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as such as lauryl, stearyl, or oleyl alcohols, or similar alcohol. Additional Administration Forms Additional dosage forms suitable for use with the peptide(s) and compositions described herein include dosage forms as described in U.S. Patents Nos.6,340,475; 6,488,962; 6,451,808; 5,972,389; 5,582,837; and 5,007,790. Additional dosage forms suitable for use with the peptide(s) and compositions described herein also include dosage forms as described in U.S. Patent Applications Nos.20030147952; 20030104062; 20030104053; 20030044466; 20030039688; and 20020051820. Additional dosage forms suitable for use with the peptide(s) and compositions described herein also include dosage forms as described in PCT Applications Nos. WO 03/35041; WO 03/35040; WO 03/35029; WO 03/35177; WO 03/35039; WO 02/96404; WO 02/32416; WO 01/97783; WO 01/56544; WO 01/32217; WO 98/55107; WO 98/11879; WO 97/47285; WO 93/18755; and WO 90/11757. - 39 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) Controlled Release Formulations and Drug Delivery Systems In certain embodiments, the formulations described herein can be, but are not limited to, short-term, rapid-offset, as well as controlled, for example, sustained release, delayed release and pulsatile release formulations. The term sustained release is used in its conventional sense to refer to a drug formulation that provides for gradual release of a drug over an extended period of time, and that may, although not necessarily, result in substantially constant blood levels of a drug over an extended time period. The period of time may be as long as a month or more and should be a release which is longer that the same amount of agent administered in bolus form. For sustained release, the peptides may be formulated with a suitable polymer or hydrophobic material which provides sustained release properties to the peptides. As such, the peptides for use with the method(s) described herein may be administered in the form of microparticles, for example, by injection or in the form of wafers or discs by implantation. In some cases, the dosage forms to be used can be provided as slow or controlled- release of one or more active ingredients therein using, for example, hydropropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, or microspheres or a combination thereof to provide the desired release profile in varying proportions. Suitable controlled-release formulations known to those of ordinary skill in the art, including those described herein, can be readily selected for use with the pharmaceutical compositions described herein. Thus, single unit dosage forms suitable for oral administration, such as tablets, capsules, gelcaps, and caplets, that are adapted for controlled-release are encompassed by the compositions and dosage forms described herein. Most controlled-release pharmaceutical products have a common goal of improving drug therapy over that achieved by their non-controlled counterparts. Ideally, the use of an optimally designed controlled-release preparation in medical treatment is characterized by a minimum of drug substance being employed to cure or control the condition in a minimum amount of time. Advantages of controlled-release formulations include extended activity of the drug, reduced dosage frequency, and increased patient compliance. In addition, controlled-release formulations can be used to affect the time of onset of action or other characteristics, such as blood level of the drug, and thus can affect the occurrence of side effects. Most controlled-release formulations are designed to initially release an amount of drug that promptly produces the desired therapeutic effect, and gradually and continually - 40 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) release of other amounts of drug to maintain this level of therapeutic effect over an extended period of time. In order to maintain this constant level of drug in the body, the drug must be released from the dosage form at a rate that will replace the amount of drug being metabolized and excreted from the body. Controlled-release of an active ingredient can be stimulated by various inducers, for example pH, temperature, enzymes, water, or other physiological conditions or peptides. The term "controlled-release component" is defined herein as a peptide or peptides, including, but not limited to, polymers, polymer matrices, gels, permeable membranes, liposomes, or microspheres or a combination thereof that facilitates the controlled-release of the active ingredient. In certain embodiments, the peptide(s) described herein are administered to a patient, alone or in combination with another pharmaceutical agent, using a sustained release formulation. In certain embodiments, the peptide(s) described herein are administered to a patient, alone or in combination with another pharmaceutical agent, using a sustained release formulation. The term delayed release is used herein in its conventional sense to refer to a drug formulation that provides for an initial release of the drug after some delay following drug administration and that mat, although not necessarily, includes a delay of from about 10 minutes up to about 12 hours. The term pulsatile release is used herein in its conventional sense to refer to a drug formulation that provides release of the drug in such a way as to produce pulsed plasma profiles of the drug after drug administration. The term immediate release is used in its conventional sense to refer to a drug formulation that provides for release of the drug immediately after drug administration. As used herein, short-term refers to any period of time up to and including about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes and any or all whole or partial increments thereof after drug administration after drug administration. As used herein, rapid-offset refers to any period of time up to and including about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes, and any and all whole or partial increments thereof after drug administration. Dosing The therapeutically effective amount or dose of a peptide described herein depends on - 41 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) the age, sex and weight of the patient, the current medical condition of the patient and the progression of a metabolic disease or disorder in the patient being treated. The skilled artisan is able to determine appropriate dosages depending on these and other factors. A suitable dose of a peptide described herein can be in the range of from about 0.01 mg to about 5,000 mg per day, such as from about 0.1 mg to about 1,000 mg, for example, from about 1 mg to about 500 mg, such as about 5 mg to about 250 mg per day. The dose may be administered in a single dosage or in multiple dosages, for example from 1 to 4 or more times per day. When multiple dosages are used, the amount of each dosage may be the same or different. For example, a dose of 1 mg per day may be administered as two 0.5 mg doses, with about a 12-hour interval between doses. It is understood that the amount of peptide dosed per day may be administered, in non-limiting examples, every day, every other day, every 2 days, every 3 days, every 4 days, or every 5 days. For example, with every other day administration, a 5 mg per day dose may be initiated on Monday with a first subsequent 5 mg per day dose administered on Wednesday, a second subsequent 5 mg per day dose administered on Friday, and so on. In the case wherein the patient's status does improve, upon the doctor's discretion the administration of the peptide(s) described herein is optionally given continuously; alternatively, the dose of drug being administered is temporarily reduced or temporarily suspended for a certain length of time (i.e., a “drug holiday“). The length of the drug holiday optionally varies between 2 days and 1 year, including by way of example only, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, 20 days, 28 days, 35 days, 50 days, 70 days, 100 days, 120 days, 150 days, 180 days, 200 days, 250 days, 280 days, 300 days, 320 days, 350 days, or 365 days. The dose reduction during a drug holiday includes from 10%-100%, including, by way of example only, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%. Once improvement of the patient's conditions has occurred, a maintenance dose is administered if necessary. Subsequently, the dosage or the frequency of administration, or both, is reduced to a level at which the improved disease is retained. In certain embodiments, patients require intermittent treatment on a long-term basis upon any recurrence of symptoms and/or infection. The peptides described herein can be formulated in unit dosage form. The term “unit dosage form“ refers to physically discrete units suitable as unitary dosage for patients undergoing treatment, with each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, optionally in association with a suitable - 42 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) pharmaceutical carrier. The unit dosage form may be for a single daily dose or one of multiple daily doses (e.g., about 1 to 4 or more times per day). When multiple daily doses are used, the unit dosage form may be the same or different for each dose. Toxicity and therapeutic efficacy of such therapeutic regimens are optionally determined in cell cultures or experimental animals, including, but not limited to, the determination of the LD₅₀ (the dose lethal to 50% of the population) and the ED₅₀ (the dose therapeutically effective in 50% of the population). The dose ratio between the toxic and therapeutic effects is the therapeutic index, which is expressed as the ratio between LD₅₀ and ED50. The data obtained from cell culture assays and animal studies are optionally used in formulating a range of dosage for use in human. The dosage of such peptides lies preferably within a range of circulating concentrations that include the ED50 with minimal toxicity. The dosage optionally varies within this range depending upon the dosage form employed and the route of administration utilized. Examples Various embodiments of the present application can be better understood by reference to the following Examples which are offered by way of illustration. The scope of the present application is not limited to the Examples given herein. Methods Peptide Syntheses and Purification Solid-Phase Peptide Synthesis was performed on ProTide Rink amide resin using a microwave-assisted CEM Liberty Blue peptide synthesizer (Matthews, NC). Fmoc-protected amino acids were coupled to the resin using Oxyma Pure (0.25 M) and N, N’- diisopropylcarbodiimide (0.125 M) as the activator and activator base, respectively. Fmoc was removed between couplings with 20% Piperidine. Global deprotection and cleavage of the peptides from the solid-support resin achieved using a CEM Razor instrument over a 40- minute incubation period at 40°C in a mixture of 95% TFA, 2.5% TIPS, and 2.5% water. Peptides were purified on an Agilent 1200 series High-Performance Liquid Chromatography (HPLC) instrument (10-75% HPLC-grade acetonitrile for 20 minutes at 2 mL/min flow rate using an Agilent Zorbax C18 column (5 µm, 9.4 x 250 mm) tracked at 280 nm. Peptides were purified to >95%. Competitive Binding Assay at GLP-1R KSCEM01 binding at the human GLP-1R was measured via a Nicoya Open SPR - 43 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) instrument in-house using His-tagged GLP-1R bound to an NTA sensor. The Ex-4 was run in a duplicate, dose response manner (0.1 nM-150 nM) and the KSCEM01 was ran once in a dose-response manner (0.1 nM-150 nM). In vitro Receptor Agonism at hGLP-1R H188 virally transduced HEK293 cells stably expressing human GLP-1R were obtained from Novo Nordisk A/S for use in FRET assays. HEK293 C24 cells stably expressing the H188 FRET reporter were obtained by G418 selection and grown in monolayers to ∼70% confluency in 100 cm² tissue culture dishes and were then transfected with plasmids (11 μg/dish) encoding human GLP-1R. Transfected cells were then incubated for 48 h in fresh culture media. For real-time FRET kinetic assays, cells were harvested, resuspended in 21 mL of SES buffer, and plated at 196 μL per well. Plated cells were pretreated with 4 μL of agonist at a given target concentration and incubated for 20 min before performing the assay. For these assays, increased levels of cAMP were measured as an increase of the 485/535 nm FRET ratio serving as a readout for binding of cAMP to the H188 biosensor that is based on the exchange protein activated by cAMP. Dose Escalation Experiment Referring to FIG.5, male Sprague Dawley rats (n=4) were fed a 60% HF diet for 48 weeks before the start of the study. Rats were then housed singly and allowed to acclimate to their new environment for 10 days. A dose escalation study was performed consisting of three days of baseline measures, followed by KSCEM01 administered via subcutaneous injection at 2 nmol/kg/day for 3 days, 5 nmol/kg/day for 3 days, and 10 nmol/kg/day for 3 days; treatments were administered 30 minutes prior to the start of the dark cycle. Rats averaged 947 ± 145 g at start of treatment. Food intake was recorded daily by hopper weighs and body weight was measured daily immediately before the start of the dark cycle. KSCEM01 treatment resulted in a 54.7% reduction in food intake at 2 nmol/kg/day, a 64.8% reduction in food intake at 5 nmol/kg/day, and a 62.9% reduction in food intake at 10 nmol/kg/day. 11-Day Treatment Experiment at Stable Daily Dosing (10 nmol/kg/day) Referring to FIG.6, male Sprague Dawley rats (n=4) were fed a 60% HF diet for 48 weeks before the start of the study. Rats were then housed singly and allowed to acclimate to their new environment for 10 days. Baseline measures of body weight and food intake were collected for five days, and rats averaged 969 ± 227 g at start of treatment. KSCEM01 was administered via subcutaneous injection just prior to the start of the dark cycle at 10 nmol/kg/day for eleven days. Food intake was recorded daily by hopper weighs and body - 44 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) weight was measured daily immediately before the start of the dark cycle. Eleven-day KSCEM01 treatment at 10 nmol/kg/day resulted in a 5.4% reduction in body weight and an average 40.9% reduction in food intake. 16-Day Treatment Experiment with Increasing Doses Referring to FIGs.7A-7C, male Wistar rats (n=5) were fed a 60% HF diet for 40 weeks before the start of the study. Rats were then housed singly in BioDAQ cages and allowed to acclimate to their new environment for 10 days. Baseline measures of body weight and food intake were collected for four days, and rats averaged 850 ± 41 g at start of treatment. KSCEM01 was administered via subcutaneous injection just prior to the start of the dark cycle on the following dosing schedule: 5 nmol/kg/day for 4 days, 10 nmol/kg/day for 4 days, and 25 nmol/kg/day for 8 days. Food intake was monitored continuously throughout the experiment. Body weights were measured daily immediately before the start of the dark cycle. Outcomes for Liraglutide and vehicle treated groups from a prior experiment using the same study design were included for reference. At start of treatment, rats treated with Liraglutide weighed 658 ± 68 g and rats treated with vehicle weighed 661 ± 96 g; animals from both groups were on 60% HF diet for 20 weeks before the start of the study. Sixteen-day KSCEM01 treatment resulted in a 4.7% reduction in body weight relative to pre-treatment and >30% reduction in calorie intake. Enumerated Embodiments The following exemplary embodiments are provided, the numbering of which is not to be construed as designating levels of importance: Embodiment 1 provides a dual melanocortin receptor (MCR) and glucagon like peptide (GLP-1) agonist peptide, or a pharmaceutically acceptable salt thereof, comprising the amino acid sequence: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20- X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37-X38- X39-X40-X41-X42-X43-X44-X45-X46-X46-X47-X48-X49-X50-X51-X52-X53-X54-X55- X56-X57-X58-X59-X60-NH₂ (SEQ ID NO.1), wherein the residues X1-X60 are as defined in Table 1. Embodiment 2 provides the peptide of embodiment 1, wherein the amino acid sequence is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to a peptide of SEQ ID NO.2. Embodiment 3 provides the peptide of any one of embodiments 1-2, wherein residues - 45 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X51-X60 are absent. Embodiment 4 provides the peptide of any one of embodiments 1-3, having an amino acid sequence selected from the group consisting of SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO. 4, SEQ ID NO.5, SEQ ID NO.6, SEQ ID NO.10, SEQ ID NO.11, SEQ ID NO.12, SEQ ID NO.13, SEQ ID NO.14, SEQ ID NO.15, and SEQ ID NO.16. Embodiment 5 provides the peptide of any one of embodiments 1-4, wherein the peptide has the amino acid sequence of SEQ ID NO.2. Embodiment 6 provides the peptide of any one of embodiments 1-5, wherein X12 and X27 are each independently selected from the group consisting of K, k, α-methyl-Lys, K*, and K^a, wherein K* has the , wherein: n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or more ethylene glycol units; and A is a linear or branched C4-18 alkyl, linear or branched C4-18 alkenyl, or linear or branched C_4-18 alkynyl; and wherein K^a has the structure: . 7 provides the peptide of any one of embodiments 1-6, having the sequence of SEQ ID NO.14. Embodiment 8 provides a pharmaceutical composition comprising the peptide of any one of embodiments 1-7 and at least one pharmaceutically acceptable carrier or excipient. Embodiment 9 provides a method of treating, preventing, and/or ameliorating a metabolic condition in the subject, the method comprising administering to the subject a therapeutically effective amount of the peptide of any one of embodiments 1-7 and/or the pharmaceutical composition of claim 8. Embodiment 10 provides the method of embodiment 9, wherein the metabolic condition is selected from the group consisting of type 2 diabetes, obesity, nonalcoholic fatty liver disease, hypothalamic obesity, prediabetes, and nonalcoholic steatohepatitis. Embodiment 11 provides the method of any one of embodiments 9-10, wherein the peptide is selected from the group consisting of SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO. 4, SEQ ID NO.5, SEQ ID NO.6, SEQ ID NO.10, SEQ ID NO.11, SEQ ID NO.12, SEQ - 46 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) ID NO.13, SEQ ID NO.14, SEQ ID NO.15, and SEQ ID NO.16. Embodiment 12 provides the method of any one of embodiments 9-11, wherein the peptide has the sequence of SEQ ID NO: 2 or SEQ ID NO: 14. Embodiment 13 provides the method of any one of embodiments 9-12, wherein the administration is by a route selected from the group consisting of oral, transdermal, transmucosal, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. Embodiment 14 provides the method of any one of embodiments 9-13, wherein the subject is a mammal. Embodiment 15 provides the method of embodiment 14, wherein the mammal is a human. The terms and expressions employed herein are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the embodiments of the present application. Thus, it should be understood that although the present application describes specific embodiments and optional features, modification and variation of the compositions, methods, and concepts herein disclosed may be resorted to by those of ordinary skill in the art, and that such modifications and variations are considered to be within the scope of embodiments of the present application. - 47 - 51296505.1

Claims

Attorney Docket No.371255-7003WO1 (00011) CLAIMS What is claimed is: 1. A dual melanocortin receptor (MCR) and glucagon like peptide (GLP-1) agonist peptide, or a pharmaceutically acceptable salt thereof, comprising the amino acid sequence: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20- X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37-X38- X39-X40-X41-X42-X43-X44-X45-X46-X46-X47-X48-X49-X50-X51-X52-X53-X54-X55- X56-X57-X58-X59-X60-NH2 (SEQ ID NO.1), wherein residues X1-X60 are as defined in Table 1: Position Definition in SEQ ID NO: 1 n - 48 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X20 R, r, or any other analog or derivative described herein X21 E, e, or any other analog or derivative described herein n n - 49 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X45 Absent, A, R, N, D, C, E, Q, G, H, I, L, K, M, F, P, S, T, W, Y, V, a, r, n, d, c, e, q, g, h, i, l, k, m, f, p, s, t, w, y, v, Nle, Nva, α-methyl-Phe, α-methyl-Ala, α- thlS thlL K* K^a th l d i ti d ibd , - , - , - , - , - , - , - , - , - - 50 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) X55 Absent, A, R, N, D, C, E, Q, G, H, I, L, K, M, F, P, S, T, W, Y, V, a, r, n, d, c, e, q, g, h, i, l, k, m, f, p, s, t, w, y, v, Nle, Nva, α-methyl-Phe, α-methyl-Ala, α- th l S th l L K* K^a th l d i ti d ib d , - , - , - , - , - 2. The peptide of claim 1, wherein the amino acid sequence is at least 80, 85, 90, 95, 96, 97, 98, or 99% homologous to a peptide of SEQ ID NO.2. 3. The peptide of claim 1, wherein residues X51-X60 are absent. 4. The peptide of claim 1, comprising an amino acid sequence selected from the group consisting of SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5, SEQ ID NO.6, SEQ ID NO.10, SEQ ID NO.11, SEQ ID NO.12, SEQ ID NO.13, SEQ ID NO.14, SEQ ID NO.15, and SEQ ID NO.16. 5. The peptide of claim 4, comprising the amino acid sequence of SEQ ID NO.2. 6. The peptide of claim 1, wherein X12 and X27 are each independently selected from - 51 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) the group consisting of K, k, α-methyl-Lys, K*, and K^a, wherein K* has the structure: , wherein: n is at occurrence 8, 9, 10, 11, or 12; PEG is a moiety comprising one or more ethylene glycol units; and A is independently at each occurrence a linear or branched C4-18 alkyl, linear or branched C_4-18 alkenyl, or linear or branched C_4-18 alkynyl; and wherein K^a has the structure: . 7. The peptide of claim 6, comprising the sequence of SEQ ID NO.14. 8. A pharmaceutical composition comprising the peptide of any one of claims 1-7 and at least one pharmaceutically acceptable carrier or excipient. 9. A method of treating, preventing, and/or ameliorating a metabolic condition in a subject, the method comprising administering to the subject a therapeutically effective amount of the peptide of any one of claims 1-7 and/or the pharmaceutical composition of claim 8. 10. The method of claim 9, wherein the metabolic condition is selected from the group consisting of type 2 diabetes, obesity, nonalcoholic fatty liver disease, hypothalamic obesity, prediabetes, and nonalcoholic steatohepatitis. 11. The method of claim 10, wherein the peptide is selected from the group consisting of SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5, SEQ ID NO.6, SEQ ID NO. 10, SEQ ID NO.11, SEQ ID NO.12, SEQ ID NO.13, SEQ ID NO.14, SEQ ID NO.15, and - 52 - 51296505.1 Attorney Docket No.371255-7003WO1 (00011) SEQ ID NO.16. 12. The method of claim 11, wherein the peptide has the sequence of SEQ ID NO: 2 or SEQ ID NO: 14. 13. The method of claim 9, wherein the administering is by a route selected from the group consisting of oral, transdermal, transmucosal, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. 14. The method of claim 9, wherein the subject is a mammal. 15. The method of claim 14, wherein the mammal is a human. - 53 - 51296505.1