Formulations of lipidated peptide inhibitors of interleukin-23 receptor

Abstract

The present disclosure relates to oral pharmaceutical formulations comprising lipidated peptide inhibitors of the Interleukin-23 Receptor (IL-23R) or pharmaceutically acceptable salt or solvate forms thereof, and absorption enhancers, and methods and / or use thereof for increasing bioavailability of the lipidated peptides and / or for treating autoimmune inflammation and related diseases and disorders.

Description

[0001] FORMULATIONS OF LIPIDATED PEPTIDE INHIBITORS OF INTERLEUKIN-23 RECEPTOR CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 480,068 filed January 16, 2023, which is herein incorporated by reference in its entirety. INCORPORATION OF SEQUENCE LISTING The sequence listing in ST.26 XML format entitled 739658_NTT-4253PC_SL.xml, created on January 12, 2024, comprising 137,953 bytes, prepared according to 37 CFR 1.822 to 1.824, submitted concurrently with the filing of this application, is incorporated herein by reference in its entirety. FIELD The present disclosure relates to oral pharmaceutical formulations comprising lipidated peptide inhibitors of the Interleukin-23 Receptor (IL-23R) or pharmaceutically acceptable salt or solvate forms thereof, and absorption enhancers, and methods and / or use thereof for increasing bioavailability of the lipidated peptides and / or for treating autoimmune inflammation and related diseases and disorders. BACKGROUND The interleukin-23 (IL-23) cytokine has been implicated as playing a crucial role in the pathogenesis of autoimmune inflammation and related diseases and disorders, such as multiple sclerosis, asthma, rheumatoid arthritis, psoriasis, and inflammatory bowel diseases (IBDs), for example, ulcerative colitis and Crohn’s disease. Studies in acute and chronic mouse models of IBD revealed a primary role of interleukin-23 receptor (IL-23R) and downstream effector cytokines in disease pathogenesis. Efforts have been made to identify therapeutic moieties that inhibit the IL-23 pathway, for use in treating IL-23-related diseases and disorders. More recently, polypeptide inhibitors that bind to IL-23R and inhibit the binding of IL-23 to IL-23R have been identified (see, e.g., US Patent Application Publication No. US2013 / 0029907). Clinical trials in Crohn's Disease or psoriasis with briakinumab (e.g., which also target the common p40 subunit) and tildrakizumab, guselkumab, MEDI2070, and BI-655066 (e.g., which target the unique p19 subunit of IL-23) highlight the potential of IL-23 signaling blockade in treatment of human inflammatory diseases. While these findings are promising, challenges remain with respect to successful delivery of such therapeutics to their target. Effective delivery can improve the treatment of intestinal inflammation, such as intestinal bowel diseases, including Crohn's disease, ulcerative colitis, and related disorders. Lipidation of therapeutically useful polypeptides can offer advantageous physicochemical properties as compared to the corresponding unmodified polypeptides. lipidated polypeptides can exhibit improved half-life, reduced immunogenicity, enhanced intracellular uptake and / or enhanced delivery across epithelia. There remains a need in the art to develop effective pharmaceutical vehicles, such as pharmaceutical compositions, to deliver therapeutic agents to treat and prevent IL-23 and / or IL-23R associated diseases, especially those associated with autoimmune inflammation, such as in the intestinal tract, which may include, but are not limited to inflammatory bowel disease (IBD), ulcerative colitis, Crohn's Disease (CD), psoriasis, or psoriatic arthritis and the like. The present disclosure is directed to overcoming these and other problems encountered in the art. SUMMARY In general, the present disclosure relates to oral pharmaceutical compositions comprising lipidated peptide inhibitors of the interleukin-23 receptor (IL-23R) or pharmaceutically acceptable salts, solvates and / or other forms thereof, and methods and / or use thereof for increasing bioavailability of the lipidated peptides and / or for treating autoimmune inflammation and related diseases and disorders. In some embodiments, the present disclosure relates to an oral pharmaceutical formulation comprising (1) an absorption enhancer and (2) a lipidated peptide comprising 9 to 20 amino acids; wherein the lipidated peptide is cyclized to form a ring, wherein the ring comprises 4 to 14 amino acids; and wherein the ratio of the absorption enhancer to the lipidated peptide is no greater than 50:1 (w / w). The present disclosure relates to oral pharmaceutical compositions as described herein, which comprise the compounds of Formula A, Formula B, Formula I, Formula I-a, Formula I- b, Formula II, Formula III, Formula IV, or Formula V, or pharmaceutically acceptable salts, solvates, and / or other forms thereof, and the absorption enhancers as provided for herein, corresponding pharmaceutical compositions, methods and / or uses for treatment of autoimmune inflammation diseases and related disorders. The present disclosure relates to oral pharmaceutical formulations comprising an absorption enhancer as provided for herein and a lipidated peptide as provided for herein. The present disclosure relates to oral pharmaceutical compositions comprising a compound having a formula of

[0002] Formula I-b, or a pharmaceutically acceptable salt or solvate form thereof, wherein the variables are as defined and provided for herein. The present disclosure relates to oral pharmaceutical formulations comprising the absorption enhancer and the compound or a pharmaceutically acceptable salt or solvate form thereof in a weight ratio (w / w) from about 1 to about 200. The present disclosure relates to methods for treating a disease or disorder associated with Interleukin 23 (IL-23) / Interleukin 23 Receptor (IL-23R), which comprises administering an effective amount of an oral pharmaceutical formulation as provided for herein as provided for herein. The present disclosure relates to methods for increasing the bioavailability of a compound in the oral pharmaceutical formulation as provided for herein in a subject comprising orally administering the compound, or a pharmaceutically acceptable salt or solvate form thereof, and an absorption enhancer as provided for herein. DETAILED DESCRIPTION I. GENERAL In general, the present disclosure relates to oral pharmaceutical formulations comprising lipidated peptide inhibitors of the Interleukin-23 Receptor (IL-23R) or pharmaceutically acceptable salt or solvate forms thereof, and absorption enhancers, and methods and / or use thereof for increasing bioavailability of the lipidated peptides and / or for treating autoimmune inflammation and related diseases and disorders. II. DEFINITIONS The present disclosure relates to oral pharmaceutical formulations comprising lipidated peptide inhibitors of the Interleukin-23 Receptor (IL-23R) or pharmaceutically acceptable salt or solvate forms thereof, and absorption enhancers. Unless otherwise defined herein, scientific, and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. “About” when referring to a value includes the stated value + / - 10% of the stated value. For example, about 50% includes a range of from 45% to 55%, while about 20 molar equivalents includes a range of from 18 to 22 molar equivalents. Accordingly, when referring to a range, “about” refers to each of the stated values + / - 10% of the stated value of each end of the range. For instance, a ratio of from about 1 to about 3 (weight / weight) includes a range of from 0.9 to 3.3. “Absorption enhancer” (AE) refers to a component that improves or facilitates the mucosal absorption of a drug in the gastrointestinal tract, such as but not limited to a permeation enhancer (PE) or intestinal permeation enhancer. As conventionally understood in the art, permeation enhancers are agents aimed to improve oral delivery of therapeutic drugs and help increase bioavailability. Pes are capable of increasing the paracellular and / or transcellular passage of drugs. Pharmaceutical excipients that can increase permeation have been termed “absorption modifying excipients” (AMEs). AMEs may be used in oral compositions, for example, as wetting agents (sodium dodecyl sulfate), antioxidants (e.g., EDTA), and emulsifiers (e.g., macrogol glycerides) and may be specifically included in compositions as Pes to improve bioavailability. Pes can be categorized as to how they alter barrier integrity via paracellular or transcellular routes. In this disclosure, the term “absorption enhancer” or AE, is considered synonymous with the term “permeation enhancer” or PE. “Administering” refers to administration of the composition of the present disclosure to a subject. “Composition” as used herein is intended to encompass a product that includes the specified active product ingredient (API) and pharmaceutically acceptable excipients, carriers or diluents as described herein, such as in specified amounts defined throughout the originally filed disclosure, which results from combination of specific components, such as specified ingredients in the specified amounts as described herein. “Intestinal permeation enhancer (IPE)” refers to a component that improves the bioavailability of a component having poor bioavailability. Suitable representative IPEs for use in the present disclosure, include, but are not limited to, various surfactants, fatty acids, medium chain glycerides, steroidal detergents, acyl carnitine and alkanoylcholines, N-acetylated alpha- amino acids and N-acetylated non-alpha-amino acids, and chitosans, other mucoadhesive polymers and the like. For example, a suitable IPE for use in the present disclosure may be sodium caprate. “Joint” or “joints” refers to tissues that connect one bone to another in the human body. Examples of tissues encompassed by the term “joint” or joints” include, without limitation, sinews, cartilage, ligaments, and synovial membrane. Synovial fluid adjacent to any of the aforementioned tissues is considered herein to be part of a “joint”. “Lubricant” refers to a substance added to a formulation to reduce friction. Compounds that serve as lubricants can also have properties as glidants. Examples of lubricants may include, but are not limited to, talc, silica, and fats such as vegetable stearin, magnesium stearate or stearic acid and the like. “Patient” or “subject” refers to a living organism, which includes, but is not limited to a human subject suffering from or prone to a disease or condition that can be treated by administration of a pharmaceutical composition as provided for herein. Further non-limiting examples may include, but is not limited to humans, other mammals, bovines, rats, mice, dogs, monkeys, goat, sheep, cows, deer, horse, and other mammalian animals and the like. In some aspects, the patient is human. By “pharmaceutically acceptable” it is meant the carrier(s), diluent(s) or excipient(s) must be compatible with the other components or ingredients of the compositions of the present disclosure, i.e., that which is useful, safe, non-toxic acceptable for pharmaceutical use. In accordance with the present disclosure pharmaceutically acceptable means approved or approvable as is listed in the L.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly, in humans. Compositions or pharmaceutical compositions of the present disclosure may be in different pharmaceutically acceptable forms, including, but are not limited to a liquid composition, a tablet or matrix composition, a capsule composition, etc. and the like. “Sodium caprate” or “NaC10” refers to the IUPAC compound sodium decanoate having molecular formula C10H19NaO2and the structural formula: “Solvate” as used herein, means a physical association of the compounds of the present disclosure with one or more solvent molecules. This physical association involves varying degrees bonding, including hydrogen bonding. In certain instances, the solvate will be capable of isolation. The term “solvate” is intended to encompass both solution-phase and isolatable solvates. Non-limiting examples of suitable solvates include hydrates. “Therapeutically effective amount” refers to an amount of a compound or of a pharmaceutical composition useful for treating or ameliorating an identified disease or condition, or for exhibiting a detectable therapeutic or inhibitory effect. “Therapeutically effective amount” further includes within its meaning a non-toxic but sufficient amount of the particular drug to which it is referring to provide the desired therapeutic effect. The exact amount required will vary from subject to subject depending on factors such as the patient’s general health, the patient’s age, etc. The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20thEdition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins). “Treat”, “treating” and “treatment” is defined as the application or administration of a therapeutic agent, i.e., a compound or formulation of the present disclosure, 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 disorder or disease as described herein, a symptom thereof; or the potential to develop such disorder or disease, where the purpose of the application or administration is to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect the disorder or disease, its symptoms, or the potential to develop said disorder or disease. Such treatments may be specifically tailored or modified, based on knowledge obtained from the field of pharmacogenomics. As used herein, the term “prevent” or “prevention” means no disorder or disease development if none had occurred, or no further disorder or disease development if there had already been development of the disorder or disease. Also considered is the ability of one to prevent some or all of the symptoms associated with the disorder or disease. As used in the specification and in the claims, the “comprise(s),” “comprising,” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that require the presence of the named features, groups, ingredients, or steps and does not exclude the presence of additional features, groups, ingredients, or steps. For example, the language “a peptide of Formula (A), comprising the amino acid sequence: X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-3Pya-X16- X17(A),” means that in addition to amino acids X3through X17, the peptide may include but is not limited to additional amino acids attached to the N-terminus, additional amino acids attached to the C-terminus, N-terminal or C-terminal capping groups, chemical or biological moieties (including but not limited to, for example, lipophilic substituents, antibodies, imaging agents, etc.) conjugated to the peptide at any location, and the like. The term “comprise(s),” “comprising,” “include(s),” “having,” “has,” “can,” or “contain(s),” can include embodiments encompassed by the term "consisting essentially of" or “consisting of.” The terms “peptide,” “polypeptide,” and “protein” are used interchangeably herein and typically refer to a molecule comprising a chain of two or more amino acids (e.g., L- amino acids, D-amino acids, modified amino acids, amino acid analogs, amino acid mimetics, etc.). Naturally-occurring L-amino acids are represented by the conventional three-letter or capitalized one-letter amino acid designations of Table 1. The corresponding D-amino acids are represented by lower-case one-letter amino acid designations or by the three-letter or capitalized one letter amino acid designations of Table 1 preceded by the letter “D” (e.g., r, dR, or D-Arg). Table 1: Naturally-occurring amino acids The term “L-amino acid,” as used herein, refers to the “L” isomeric form of an amino acid, and conversely the term “D-amino acid” refers to the “D” isomeric form of an amino acid (e.g., (D)Asp or D-Asp; (D)Phe or D-Phe). D-amino acids may be indicated as customary in lower case when referred to using single-letter abbreviations. For example, D- arginine can be represented as “arg” or “r.” Alternatively, a lower case “d” in front of an amino acid can be used to indicate that it is of the D isomeric form, for example D-lysine can be represented by dK. In the case of less common or non-naturally occurring amino acids, unless they are referred to by their full name (e.g., sarcosine, ornithine, etc.), frequently employed three- or four-character codes are employed for residues thereof, including, Sar or Sarc (sarcosine, i.e., N-methylglycine), Aib (α-aminoisobutyric acid), Dab (2,4-diaminobutanoic acid), Dapa (2,3- diaminopropanoic acid), γ-Glu (γ-glutamic acid), Gaba (γ-aminobutanoic acid), β-Pro (pyrrolidine-3-carboxylic acid), and Abu (2-aminobutyric acid). Amino acids of the D-isomeric form may be located at any of the positions in the IL- 23R inhibitors set forth herein (e.g., any of X3-X17appearing in the molecule). In some embodiments, amino acids of the D-isomeric form may be located only at any one or more of X3, X5, X6, X8, X13, and optionally one additional position. In other embodiments, amino acids of the D-isomeric form may be located only at any one or more of X3, X8, X13, and optionally one additional position. In other embodiments, amino acids of the D-isomeric form may be located only at any one or more of X8, X13, and optionally one additional position. In other embodiments, amino acids of the D-isomeric form may be located only at X3and optionally one additional position. In other embodiments, amino acids of the D-isomeric form may be located only at X3, and optionally two or three additional positions. In other embodiments, amino acids of the D-isomeric form may be located at only one or two of positions X3to X17appearing in the IL-23R inhibitors set forth herein. In other embodiments, amino acids of the D-isomeric form may be located at only three or four of positions X3to X17appearing in the IL-23R inhibitors set forth herein. For example, an IL-23R inhibitor set forth herein having only positions X3to X15present may have amino acids of the D-form present in three or four of those positions. In other embodiments, amino acids of the D- isomeric form may be located at only five or six of positions X3to X17appearing in the IL- 23R inhibitors set forth herein. Peptides may be naturally occurring, synthetically produced, or recombinantly expressed. Peptides may also comprise additional groups modifying the amino acid chain, for example, functional groups added via post-translational modification. Examples of post- translation modifications include, but are not limited to, acetylation, alkylation (including, methylation), biotinylation, glutamylation, glycylation, glycosylation, isoprenylation, lipoylation, phosphopantetheinylation, phosphorylation, selenation, and C-terminal amidation. The term peptide also includes peptides comprising modifications of the amino terminus and / or the carboxy terminus. Modifications of the terminal amino group include, but are not limited to, des-amino, N-lower alkyl, N-di-lower alkyl, and N-acyl modifications. Modifications of the terminal carboxy group include, but are not limited to, amide, lower alkyl amide, dialkyl amide, and lower alkyl ester modifications (e.g., wherein lower alkyl is C1-C4 alkyl). The term peptide also includes modifications, such as but not limited to those described above, of amino acids falling between the amino and carboxy termini. As is clear to the skilled artisan, the peptide sequences disclosed herein are shown proceeding from left to right, with the left end of the sequence being the N-terminus of the peptide and the right end of the sequence being the C-terminus of the peptide. Among sequences disclosed herein are sequences incorporating either an “-OH” moiety or an “-NH2” moiety at the carboxy terminus (C-terminus) of the sequence. In such cases, and unless otherwise indicated, an “-OH” or an “-NH2” moiety at the C-terminus of the sequence indicates a hydroxy group or an amino group, corresponding to the presence of a carboxylic acid (COOH) or an amido (CONH2) group at the C-terminus, respectively. In each sequence of the disclosure, a C-terminal “-OH” moiety may be substituted for a C-terminal “-NH2” moiety, and vice-versa. The phrase “amino acid,” “amino acid residue,” or “residue” as used herein refers to an amino acid, a modified amino acid, an amino acid analog, or an amino acid mimetic that is incorporated into a peptide by an amide bond or an amide bond mimetic. Unless indicated otherwise the names of naturally occurring and non-naturally occurring aminoacyl residues used herein follow the naming conventions suggested by the IUPAC Commission on the Nomenclature of Organic Chemistry and the IUPAC-IUB Commission on Biochemical Nomenclature as set out in “Nomenclature of α-Amino Acids (Recommendations, 1974)” Biochemistry, 14(2), (1975). To the extent that the names and abbreviations of amino acids and aminoacyl residues employed in this specification and appended claims differ from those suggestions, they will be made clear to the reader. In sequences of amino acids that represent IL-23 inhibitors the individual amino acids are separated by a hyphen “-” or brackets e.g, lysine is shown as [K]. One of skill in the art will appreciate that certain amino acids and other chemical moieties are modified when bound to another molecule. For example, an amino acid side chain may be modified when it forms an intramolecular bridge with another amino acid side chain, e.g., one or more hydrogens may be removed or replaced by the bond. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly or conventionally understood by one of ordinary skill in the art. In the chemical arts a dash at the front or end of a chemical group is a matter of convenience; chemical groups may be depicted with or without one or more dashes without losing their ordinary meaning. A wavy line drawn through a line in a structure indicates a point of attachment of a group. A dashed line indicates an optional bond. Unless chemically or structurally required, no directionality is indicated or implied by the order in which a chemical group is written or the point at which it is attached to the remainder of the molecule. For instance, the group “-SO2CH2-” is equivalent to “-CH2SO2-” and both may be connected in either direction. Similarly, an “arylalkyl” group, for example, may be attached to the remainder of the molecule at either an aryl or an alkyl portion of the group. A prefix such as “Cu-v” or (Cu-Cv) indicates that the following group has from u to v carbon atoms. For example, “C1-6alkyl” and “C1-C6 alkyl” both indicate that the alkyl group has from 1 to 6 carbon atoms. The term “alkyl” Is a straight or branched saturated hydrocarbon. For example, an alkyl group can have 1 to 10 carbon atoms (i.e., (C1-C10)alkyl), 1 to 5 carbon atoms (i.e., (C1-C5)alkyl), 1 to 4 carbon atoms (i.e., (C1-C4)alkyl), or 1 to 3 carbon atoms (i.e., (C1-C3)alkyl). Examples of alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, - CH2CH3), 1-propyl (n-Pr, n-propyl, -CH2CH2CH3), isopropyl (i-Pr, i-propyl, -CH(CH3)2), 1- butyl (n-bu, n-butyl, -CH2CH2CH2CH3), 2-butyl (s-bu, s-butyl, -CH(CH3)CH2CH3), tert-butyl (t-bu, t-butyl, -CH(CH3)3), 1-pentyl (n-pentyl, -CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3) CH2CH2CH3), neopentyl (-CH2C(CH3)3), 1-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (- CH(CH3)CH2CH2CH2CH3), heptyl (-(CH2)6CH3), octyl (-(CH2)7CH3), 2,2,4-trimethylpentyl (-CH2C(CH3)2CH2CH(CH3)2), nonyl (-(CH2)8CH3), decyl (-(CH2)9CH3), undecyl (- (CH2)10CH3), and dodecyl (-(CH2)11CH3). In an embodiment, alkyl refers to C(1-6)alkyl. In another embodiment, alkyl refers to C(1-4)alkyl. In another embodiment, alkyl refers to C(1-3)alkyl. The term “alkylene” refers to a bivalent alkyl group. for example, an alkylene group can have 1 to 10 carbon atoms (i.e., (C1-C10)alkylene), 1 to 5 carbon atoms (i.e., (C1- C5)alkylene), 1 to 2 carbon atoms (i.e., (C1-C2)alkylene), or 1 carbon atom (i.e., (C1)alkylene). Examples of alkylene groups include, but are not limited to, methylene (-CH2- ), ethylene (-CH2CH2-), n-propylene (-CH2CH2CH2-), n-butylene (-CH2CH2CH2CH2-), etc. Furthermore, it is intended that within the scope of the present invention, any element, in particular when mentioned in relation to a peptide of the disclosure, or pharmaceutically acceptable salt thereof, shall comprise all isotopes and isotopic mixtures of said element, either naturally occurring or synthetically produced, either with natural abundance or in an isotopically enriched form. For example, a reference to hydrogen includes within its scope1H,2H (i.e., deuterium or D), and3H (i.e., tritium or T). In some embodiments, the compounds described herein include a2H (i.e., deuterium) isotope. By way of example, the group denoted -C(1-6)alkyl includes not only -CH3, but also CD3; not only CH2CH3, but also CD2CD3, etc. Similarly, references to carbon and oxygen include within their scope respectively12C,13C and14C and15O and16O and17O and18O. The isotopes may be radioactive or non-radioactive. Radiolabelled compounds of the disclsoure may include a radioactive isotope selected from the group comprising3H,11C,18F,35S,122I,123I,125I,131I,75Br,76Br,77Br and82Br. Preferably, the radioactive isotope is selected from the group of3H,11C and18F. As used herein, the terms “lipophilic substituent” “lipid chain” and “lipid moiety” refer to substituents comprising 4 to 40 carbon atoms, 8 to 25 carbon atoms, or 12 to 22 carbon atoms. A lipophilic substituent may be attached to an amino group of the peptide (e.g., an ε-amino group of a lysine residue) by means of a carboxyl group of the lipophilic substituent. The lipophilic substituent may optionally comprise one or more spacers (e.g., a polyethylene glycol chain having 2 or more repeating -CH2CH2O- units or gamma- glutamate). In some embodiments, the lipophilic substituent comprises a straight-chain or branched alkyl or alkylene group. In some embodiments, the lipophilic substituent is an acyl group of a straight-chain or branched fatty acid. As used herein, the term “lipidated peptide” refers to a peptide comprising one or more lipophilic substituents, as described herein. The lipophilic substituent of the lipidated peptide may, for example, be conjugated to N-terminus, the C-terminus, or to the side chain of an amino acid. The abbreviation, "(w / w)" refers to the phrase "weight for weight" or "weight by weight", i.e., the proportion of a particular substance within a mixture, as measured by weight or mass or a weight amount of a component of the composition disclosed herein relative to the total weight amount of the composition. Accordingly, the quantity is unit less or unitless and represents a weight percentage amount of a component relative to the total weight of the composition. For example, a 2% (w / w) solution means 2 grams of solute is dissolved in 100 grams of solution. Systemic routes of administration as conventionally understood in the medicinal or pharmaceutical arts, refer to or are defined as a route of administration of drug, a pharmaceutical composition or formulation, or other substance into the circulatory system so that various body tissues and organs are exposed to the drug, formulation, or other substance. As conventionally understood in the art, administration can take place orally (where drug or oral preparations are taken by mouth, and absorbed via the gastrointestinal tract), via enteral administration (absorption of the drug also occurs through the gastrointestinal tract) or parenteral administration (generally injection, infusion, or implantation, etc. "Systemically active" peptide drug therapy as it relates to the present disclosure generally refers to treatment by means of a pharmaceutical composition comprising a peptide active ingredient, wherein said peptide resists immediate metabolism and / or excretion resulting in its exposure in various body tissues and organs, such as the cardiovascular, respiratory, gastrointestinal, nervous, or immune systems. Systemic drug activity in the present disclosure also refers to treatment using substances that travel through the bloodstream, reaching and affecting cells in various body tissues and organs. Systemic active drugs are transported to their site of action and work throughout the body to attack the physiological processes that cause inflammatory diseases. Bioavailability refers to the extent and rate at which the active moiety (drug or metabolite) enters systemic circulation, thereby accessing the site of action. Bioavailability of a drug is impacted by the properties of the dosage form, which depend partly on its design and manufacture. Unless indicated otherwise the names of naturally occurring and non-naturally occurring aminoacyl residues used herein follow the naming conventions suggested by the IUPAC Commission on the Nomenclature of Organic Chemistry and the IUPAC-IUB Commission on Biochemical Nomenclature as set out in “Nomenclature of α-Amino Acids (Recommendations, 1974)” Biochemistry, 14(2), (1975). To the extent that the names and abbreviations of amino acids and aminoacyl residues employed in this specification and appended claims differ from those suggestions, they will be made clear to the reader. In sequences of amino acids that represent IL-23 inhibitors the individual amino acids are separated by a hyphen “-”. III. COMPOUNDS The present disclosure relates to oral pharmaceutical formulations comprising one or more lipidated cyclic peptide inhibitors of the interleukin-23 receptor (IL-23R) or pharmaceutically acceptable salts thereof as provided for herein and one or more enhancers as provided for herein. Some embodiments relate to an oral pharmaceutical formulation comprising: an absorption enhancer; and a lipidated peptide. In some embodiments, the present disclosure provides an oral pharmaceutical formulation comprising (1) an absorption enhancer and (2) a lipidated peptide comprising 9 to 20 amino acids; wherein the lipidated peptide is cyclized to form a ring, wherein the ring comprises 4 to 14 amino acids; and wherein the ratio of the absorption enhancer to the lipidated peptide is no greater than 50:1 (w / w). In some embodiments, the lipidated peptide comprises 12 to 16 amino acids. In some embodiments, the lipidated peptide comprises 13, 14, or 15 amino acids. In some embodiments, the lipidated peptide comprises 9 amino acids. In some embodiments, the lipidated peptide comprises 10 amino acids. In some embodiments, the lipidated peptide comprises 11 amino acids. In some embodiments, the lipidated peptide comprises 12 amino acids. In some embodiments, the lipidated peptide comprises 13 amino acids. In some embodiments, the lipidated peptide comprises 14 amino acids. In some embodiments, the lipidated peptide comprises 15 amino acids. In some embodiments, the lipidated peptide comprises 16 amino acids. In some embodiments, the lipidated peptide comprises 17 amino acids. In some embodiments, the lipidated peptide comprises 18 amino acids. In some embodiments, the lipidated peptide comprises 19 amino acids. In some embodiments, the lipidated peptide comprises 20 amino acids. In some embodiments, the lipidated peptide is an inhibitor of interleukin-23 receptor. In some embodiments, the lipidated peptide comprises a helical structure. In some embodiments, the lipidated peptide is cyclized to form a ring, wherein the ring comprises 4-11 or 14 amino acids. In some embodiments, the ring comprises 4-9 or 11 amino acids. In some embodiments, the ring comprises 4, 6, or 10 amino acids. In some embodiments, the ring comprises 4 amino acids. In some embodiments, the ring comprises 6 amino acids. In some embodiments, the ring comprises 10 amino acids. In some embodiments, the lipidated peptide comprises the amino acid sequence of Formula (A): R1a-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-3Pya-X16-X17-R2a(A), or a pharmaceutically acceptable salt thereof, wherein: R1ais an N-terminal capping group (e.g., MeCO), Zpeg, or Zlipid; X3is any amino acid or absent; X4is 4AminoPro, Abu, aG, aMeC, C, Dap, Pen, Pen(oXyl), Pen(mXyl), Pen(pXyl), or Pra; X5is any amino acid; X6is any amino acid; X7is 7MeW, W, or absent; X8is any amino acid; X9is aMeC, aG, C, D, E, hE, Pen, Dap, or Dap(N3) X10is AEF, TMAPF, AEF(d), TMAPF-Zlipid, APEG3F, or AEF-Zlipid; X11is any amino acid; X12is any amino acid; X13is any amino acid; X14is any amino acid; X16is any amino acid; X17is any amino acid or absent; R2ais a C-terminal capping group (e.g., CONH2), CONH-Zpeg, or CO-Zlipid; Zpeg, independently for each occurrence, is a polyethylene glycol chain; Zlipid, independently for each occurrence, is a lipophilic substituent; wherein the peptide comprises a linkage between the residues at X4and X9; and wherein the polypeptide comprises at least one lipophilic substituent at a position selected from R1, X3, X5, X6, X8, X10, X12, X13, X14, X16, X17, or R2. In some embodiments, the lipidated peptide comprises the amino acid sequence of Formula (A): R1a-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-3Pya-X16-X17-R2a(A), or a pharmaceutically acceptable salt thereof, wherein: R1ais MeCO, Zpeg, Zlipid, succiniccarn, 5cpaCO, or AEEP-Zlipid; X3is R, K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; X4is 4AminoPro, Abu, aG, aMeC, C, Dap, Pen, Pen(oXyl), Pen(mXyl), Pen(pXyl), or Pra; X5is N, N(NMe2), K(d), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X6is T, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid; X7is 7MeW, W, or absent; X8is K(Ac), K(d), K(NMeAc), Q, K-Zlipid, K-Zpeg, NMeK-Zlipid, Dab-Zlipid, Dab(NMecarn), or Dab-Zpeg; X9is aMeC, aG, C, D, E, hE, Pen, Dap, or Dap(N3); X10is AEF, TMAPF, AEF(d), TMAPF-Zlipid, APEG3F, or AEF- Zlipid; X11is a substituted or unsubstituted 2Nal or a substituted or unsubstituted 3Quin, X12is THP, K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X13is E, K(Ac), K(d), K-Zpeg, K(NMeAc), Dab(NMecarn), E(OAll), K-Zlipid, Dab- Zlipid, NMeK-Zlipid, or absent; X14is N, K-Zlipid, NMeK-Zlipid, or Dab-ZlipidX16is Sar, NMeK(d), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X17is K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; R2ais CONH2, CONMe2, CONH-Zpeg, or CO-Zlipid; Zpeg, independently for each occurrence, is a polyethylene glycol chain; Zlipid, independently for each occurrence, is a lipophilic substituent; wherein the peptide comprises a linkage between the residues at X4and X9. In some embodiments, for formula (A), X7is substituted or unsubstituted W. In some embodiments, X7is 7(3NacPh)W, 7BrW, 7MeW, or W. In some embodiments, X7is 7MeW. In some embodiments, R1ais MeCO, Zpeg, or Zlipid. In some embodiments, X3is r. In some embodiments, X4is Pen. In some embodiments, X5is N. In some embodiments, X6is T. In some embodiments, X8is K(Ac). In some embodiments, X9is Pen. In some embodiments, X10is AEF. In some embodiments, X10is AEF-Zlipid. In some embodiments, X11is a substituted or unsubstituted 2Nal or a substituted or unsubstituted 3Quin. In some embodiments, X11is a substituted or unsubstituted 2Nal. In some embodiments, X12is THP. In some embodiments, X12is THP-Zlipid. In some embodiments, X13is E. In some embodiments, X13is E-Zlipid. In some embodiments, X14is N. In some embodiments, X14is N-Zlipid. In some embodiments, X16is Sar. In some embodiments, X16is NMeK(d). In some embodiments, X16is K-Zlipid. In some embodiments, X16is Dab-Zlipid. In some embodiments, X16is NMeK-Zlipid. In some embodiments, X17is K-Zlipid. In some embodiments, X17is Dab-Zlipid. In some embodiments, X17is NMeK-Zlipid. In some embodiments, X17is absent. In some embodiments, R2ais CONH2. In some embodiments, R2ais CONMe2. In some embodiments, R2ais CONH-Zpeg. In some embodiments, R2ais CO-Zlipid. In some embodiments, the lipidated peptide comprises the amino acid sequence of Formula (B): R1a-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13- X14-3Pya-X16-X17-R2a(B), or a pharmaceutically acceptable salt thereof, wherein: R1ais an N-terminal capping group (e.g., MeCO), Zpeg, or Zlipid; X3is any amino acid or absent; X4is any amino acid; X5is any amino acid; X6is any amino acid; X7is 7MeW or W; X8is any amino acid; X9is any amino acid; X10is AEF, TMAPF, AEF(d), TMAPF-Zpeg, TMAPF-Zlipid, APEG3F, AEF-Zpeg, or AEF-Zlipid; X11is any amino acid; X12is any amino acid; X13is any amino acid; X14is any amino acid; X16is any amino acid; X17is any amino acid or absent; R2ais a C-terminal capping group (e.g., CONH2), CONH-Zpeg, or CO-Zlipid; Zpeg, independently for each occurrence, is a polyethylene glycol chain; Zlipid, independently for each occurrence, is a lipophilic substituent; wherein the polypeptide comprises at least one lipophilic substituent or polyethylene glycol chain at a position selected from R1a, X3, X4X5, X6, X8, X9X10, X11, X12, X13, X14, X16, X17, or R2a; and wherein the peptide is cyclized to form a first ring, wherein the first ring comprises 4- 14 amino acids. In some embodiments of the peptide of Formula (B), R1ais an N-terminal capping group (e.g., MeCO), Zpeg, or Zlipid; X3is r, k(d), k-Zlipid, dab-Zlipid, NMek-Zlipid, or absent; X4is 4AminoPro, Abu, aG, aMeC, C, Dap, Pen, Pen(oXyl), Pen(mXyl), Pen(pXyl), or Pra; X5is E, N, N(NMe2), K(d), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X6is T, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid; X7is 7MeW or W; X8is K(Ac), K(d), K(NMeAc), Q, K-Zlipid, K-Zpeg, NMeK-Zlipid, Dab-Zlipid, Dab(NMecarn), or Dab-Zpeg; X9is aMeC, aG, C, D, E, hE, Pen, Dap, or Dap(N3); X10is AEF, TMAPF, AEF(d), TMAPF-Zpeg, TMAPF-Zlipid, APEG3F, AEF-Zpeg, or AEF-Zlipid; X11is 2Nal or 6OH2Nal; X12is THP, K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X13is E, K(Ac), K(d), K-Zpeg, K(NMeAc), Dab(NMecarn), E(OAll), K-Zlipid, Dab- Zlipid, NMeK-Zlipid; X14is N, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid; X16is Sar, NMeK(d), K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; X17is K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; R2ais a C-terminal capping group (e.g., CONH2), CONH-Zpeg, or CO-Zlipid; Zpeg, independently for each occurrence, is a polyethylene glycol chain; Zlipid, independently for each occurrence, is a lipophilic substituent; wherein the peptide comprises a linkage between the residues at X4and X9; and wherein the polypeptide comprises at least one lipophilic substituent at a position selected from R1a, X3, X5, X6, X8, X10, X12, X13, X14, X16, X17, or R2a, or a polyethylene glycol chain at a position selected from R1a, X8, X10, X13, or R2a. In some embodiments of the peptide of Formula (B), R1ais an MeCO, Zpeg, Zlipid, or 5cpaCO; X3is r, k(d), k-Zlipid, dab-Zlipid, NMek-Zlipid, or absent; X4is Pen; X5is E, N, N(NMe2), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X6is T; X7is 7MeW; X8is K(Ac), K(d), K(NMeAc), K-Zlipid, K-Zpeg, NMeK-Zlipid, Dab-Zlipid, or Dab-Zpeg; X9is Pen; X10is AEF, TMAPF, APEG3F, AEF-Zpeg, or AEF-Zlipid; X11is 2Nal or 6OH2Nal; X12is THP; X13is E, K(Ac), K-Zpeg, K(NMeAc), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X14is N; X16is Sar or NMeK-Zlipid; X17is K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; R2ais CONH2, CONMe2, CONH-Zpeg, or CO-Zlipid; wherein the peptide comprises a disulfide linkage between the residues at X4and X9; and wherein the polypeptide comprises at least one lipophilic substituent at a position selected from R1a, X3, X5, X8, X10, X13, X16, X17, or R2a, or a polyethylene glycol chain at a position selected from R1a, X8, X10, X13, or R2a. In some embodiments of the peptide of Formula (B), R1ais MeCO, Zpeg, Zlipid, or 5cpaCO. In some embodiments, R1ais an N-terminal capping group. In some embodiments, R1ais MeCO. In some embodiments, R1ais 5cpaCO. In some embodiments, R1ais Zpeg. In some embodiments, R1ais Zlipid. In some embodiments of the peptide of Formula (B), X3is r, k(d), k-Zlipid, dab-Zlipid, NMek-Zlipid, or absent. In some embodiments, X3is r, k(d), or absent. In some embodiments, X3is k-Zlipid, dab-Zlipid, or NMek-Zlipid. In some embodiments, X3is r. In some embodiments, X3is k(d). In some embodiments, X3is k-Zlipid. In some embodiments, X3is dab-Zlipid. In some embodiments, X3is NMek-Zlipid. In some embodiments, X3is absent. In some embodiments of the peptide of Formula (B), X4is 4AminoPro, Abu, aG, aMeC, C, Dap, Pen, Pen(oXyl), Pen(mXyl), Pen(pXyl), or Pra. In some embodiments X4is 4AminoPro. In some embodiments X4is Abu. In some embodiments X4is aG. In some embodiments X4is aMeC. In some embodiments X4is C. In some embodiments X4is Dap. In some embodiments X4is Pen. In some embodiments X4is Pen(oXyl). In some embodiments X4is Pen(mXyl). In some embodiments X4is Pen(pXyl). In some embodiments X4is Pra. In some embodiments of the peptide of Formula (B), X5is E, N, N(NMe2), K(d), K- Zlipid, Dab-Zlipid, or NMeK-Zlipid. In some embodiments, X5is E, N, N(NMe2), or K(d). In some embodiments, X5is K-Zlipid, Dab-Zlipid, or NMeK-Zlipid. In some embodiments, X5is E. In some embodiments, X5is N. In some embodiments, X5is N(NMe2). In some embodiments, X5is K(d). In some embodiments, X5is K-Zlipid. In some embodiments, X5is Dab-Zlipid. In some embodiments, X5is NMeK-Zlipid. In some embodiments of the peptide of Formula (B), X6is T, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid. In some embodiments, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid. In some embodiments, X6is T. In some embodiments, X6is K-Zlipid. In some embodiments, X6is NMeK-Zlipid. In some embodiments, X6is Dab-Zlipid. In some embodiments of the peptide of Formula (B), X7is 7MeW or W. In some embodiments, X7is 7MeW. In some embodiments, X7is W. In some embodiments of the peptide of Formula (B), X8is K(Ac), K(d), K(NMeAc), Q, K-Zlipid, K-Zpeg, NMeK-Zlipid, Dab-Zlipid, Dab(NMecarn), or Dab-Zpeg. In some embodiments, X8is K(Ac), K(d), K(NMeAc), Q, or Dab(NMecarn). In some embodiments, X8is K-Zpeg, or Dab-Zpeg. In some embodiments, X8is K-Zlipid, NMeK-Zlipid, or Dab-Zlipid. In some embodiments, X8is K(Ac). In some embodiments, X8is K(d). In some embodiments, X8is K(NMeAc). In some embodiments, X8is Q. In some embodiments, X8is K-Zlipid. In some embodiments, X8is K-Zpeg. In some embodiments, X8is NMeK-Zlipid. In some embodiments, X8is Dab-Zlipid. In some embodiments, X8is Dab(NMecarn). In some embodiments, X8is Dab-Zpeg. In some embodiments of the peptide of Formula (B), X9is aMeC, aG, C, D, E, hE, Pen, Dap, or Dap(N3). In some embodiments, X9is aMeC. In some embodiments, X9is aG. In some embodiments, X9is C. In some embodiments, X9is D. In some embodiments, X9is E. In some embodiments, X9is hE. In some embodiments, X9is Pen. In some embodiments, X9is Dap. In some embodiments, X9is Dap(N3). In some embodiments of the peptide of Formula (B), X10is AEF, TMAPF, AEF(d), TMAPF-Zpeg, TMAPF-Zlipid, APEG3F, AEF-Zpeg, or AEF-Zlipid. In some embodiments, X10is AEF, TMAPF, AEF(d), or APEG3F. In some embodiments, X10is TMAPF-Zpeg, or AEF- Zpeg. In some embodiments, X10is TMAPF-Zlipidor AEF-Zlipid. In some embodiments, X10is AEF. In some embodiments, X10is TMAPF. In some embodiments, X10is AEF(d). In some embodiments, X10is TMAPF-Zpeg. In some embodiments, X10is TMAPF-Zlipid. In some embodiments, X10is APEG3F. In some embodiments, X10is AEF-Zpeg. In some embodiments, X10is AEF-Zlipid. In some embodiments of the peptide of Formula (B), X11is 2Nal or 6OH2Nal. In some embodiments, X11is 2Nal. In some embodiments, X11is 6OH2Nal. In some embodiments of the peptide of Formula (B), X12is THP, K-Zlipid, Dab-Zlipid, or NMeK-Zlipid. In some embodiments, X12is K-Zlipid, Dab-Zlipid, or NMeK-Zlipid. In some embodiments, X12is THP. In some embodiments, X12is K-Zlipid. In some embodiments, X12is Dab-Zlipid. In some embodiments, X12is NMeK-Zlipid. In some embodiments of the peptide of Formula (B), X13is E, K(Ac), K(d), K-Zpeg, K(NMeAc), Dab(NMecarn), E(OAll), K-Zlipid, Dab-Zlipid, NMeK-Zlipid. In some embodiments, X13is E, K(Ac), K(d), K(NMeAc), Dab(NMecarn), E(OAll). In some embodiments, X13is K-Zlipid, Dab-Zlipid, NMeK-Zlipid. In some embodiments, X13is E. In some embodiments, X13is K(Ac). In some embodiments, X13is K(d). In some embodiments, X13is K-Zpeg. In some embodiments, X13is K(NMeAc). In some embodiments, X13is Dab(NMecarn). In some embodiments, X13is E(OAll). In some embodiments, X13is K-Zlipid. In some embodiments, X13is Dab-Zlipid. In some embodiments, X13is NMeK-Zlipid. In some embodiments of the peptide of Formula (B), X14is N, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid. In some embodiments, X14is K-Zlipid, NMeK-Zlipid, or Dab-Zlipid. In some embodiments, X14is N. In some embodiments, X14is K-Zlipid. In some embodiments, X14is NMeK-Zlipid. In some embodiments, X14is Dab-Zlipid. In some embodiments of the peptide of Formula (B), X16is Sar, NMeK(d), K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent. In some embodiments, X16is Sar or NMeK(d). In some embodiments, X16is K-Zlipid, Dab-Zlipid, or NMeK-Zlipid. In some embodiments, X16is Sar. In some embodiments, X16is NMeK(d). In some embodiments, X16is K-Zlipid. In some embodiments, X16is Dab-Zlipid. In some embodiments, X16is NMeK-Zlipid. In some embodiments, X16is absent. In some embodiments of the peptide of Formula (B), X17is K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent. In some embodiments, X17is K-Zlipid, Dab-Zlipid, or NMeK-Zlipid. In some embodiments, X17is K-Zlipid. In some embodiments, X17is Dab-Zlipid. In some embodiments, X17is NMeK-Zlipid. In some embodiments, X17is absent. In some embodiments of the peptide of Formula (B), R2ais CONH2, CONMe2, CONH-Zpeg, or CO-Zlipid. In some embodiments, R2ais a C-terminal capping group. In some embodiments, R2ais CONH2, CONMe2. In some embodiments, R2ais CONH-Zpegor CO- Zlipid. In some embodiments, R2ais CONH2. In some embodiments, R2ais CONMe2. In some embodiments, R2ais CONH-Zpeg. In some embodiments, R2ais CO-Zlipid. In some embodiments, X4and X9are linked through a disulfide bond. In some embodiments, X4is Abu and X9is C. In some embodiments, X4is Abu and X9is aMeC. In some embodiments, X4is Abu and X9is Pen. In some embodiments, X4is C and X9is C. In some embodiments, X4is C and X9is aMeC. In some embodiments, X4is C and X9is Pen. In some embodiments, X4is Pen and X9is C. In some embodiments, X4is Pen and X9is aMeC. In some embodiments, X4is Pen and X9is Pen. In some embodiments, X4is aMeC and X9is C. In some embodiments, X4is aMeC and X9is aMeC. In some embodiments, X4is aMeC and X9is Pen. In some embodiments, X4is Pen(oXyl) and X9is C. In some embodiments, X4is Pen(oXyl) and X9is aMeC. In some embodiments, X4is Pen(oXyl) and X9is Pen. In some embodiments, X4is Pen(mXyl) and X9is C. In some embodiments, X4is Pen(mXyl) and X9is aMeC. In some embodiments, X4is Pen(mXyl) and X9is Pen. In some embodiments, X4is Pen(pXyl) and X9is C. In some embodiments, X4is Pen(pXyl) and X9is aMeC. In some embodiments, X4is Pen(pXyl) and X9is Pen. In some embodiments, X4is 4AminoPro and X9is D. In some embodiments, X4is 4AminoPro and X9is E. In some embodiments, X4is 4AminoPro and X9is hE. In some embodiments, X4is Dap and X9is D. In some embodiments, X4is Dap and X9is E. In some embodiments, X4is Dap and X9is hE. In some embodiments, X4is Pra and X9is Dap(N3). In some embodiments, X4is aG and X9is aG. In some embodiments, the peptide is cyclized via a linkage between two amino acid residues (e.g., at X4and X9) having a structure selected from the following:

[0003] In some embodiments, the peptide is cyclized via a linkage between the residues at X4and X9having a structure selected from the following: In some embodiments, the peptide is cyclized via a linkage between the residues at X4and X9having the following structure: Pen – Pen. In some embodiments, the peptide comprises a linkage between X5and X10having the following structure: E – AEF. In some embodiments, the peptide is cyclized to form a first ring, wherein the first ring comprises 4-11 or 14 amino acids. In some embodiments, the first ring comprises 4-9 or 11 amino acids. In some embodiments, the first ring comprises 4, 6, or 10 amino acids. In some embodiments, the first ring comprises 4 amino acids. In some embodiments, the first ring comprises 5 amino acids. In some embodiments, the first ring comprises 6 amino acids. In some embodiments, the first ring comprises 7 amino acids. In some embodiments, the first ring comprises 8 amino acids. In some embodiments, the first ring comprises 9 amino acids. In some embodiments, the first ring comprises 10 amino acids. In some embodiments, the first ring comprises 11 amino acids. In some embodiments, the first ring comprises 14 amino acids. In some embodiments, the first ring comprises a linkage between two amino acids having a structure selected from the following:

[0004] In some embodiments, the first ring comprises a linkage between the N-terminus of the peptide and an amino acid and has a structure selected from the following: In some embodiments, the first ring is formed between X4and X9, X4and X13, X5and X10, X3and X13, or X6and X9. In some embodiments, the first ring is formed between X4and X9, X4and X13, X5and X10, X3and X13, or X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X4and X9, X4and X13, X5and X10, X3and X13, or X6and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X4and X9, X4and X13, or X6and X9. In some embodiments, the first ring is formed between X4and X9, X4and X13, or X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X4and X9, X4and X13, or X6and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X4and X9. In some embodiments, the first ring is formed between X4and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X4and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X4and X13. In some embodiments, the first ring is formed between X4and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X4and X13via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X5and X10. In some embodiments, the first ring is formed between X5and X10via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X5and X10via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X3and X13. In some embodiments, the first ring is formed between X3and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X3and X13via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X6and X9. In some embodiments, the first ring is formed between X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X6and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the peptide is further cyclized to form a second ring, wherein the second ring comprises 4-14 amino acids. In some embodiments, the peptide is further cyclized to form a second ring, wherein the second ring comprises 4-11 or 14 amino acids. In some embodiments, the second ring comprises 4-9 or 11 amino acids. In some embodiments, the second ring comprises 4, 6, 10 or 11 amino acids. In some embodiments, the second ring comprises 4 amino acids. In some embodiments, the second ring comprises 5 amino acids. In some embodiments, the second ring comprises 6 amino acids. In some embodiments, the second ring comprises 7 amino acids. In some embodiments, the second ring comprises 8 amino acids. In some embodiments, the second ring comprises 9 amino acids. In some embodiments, the second ring comprises 10 amino acids. In some embodiments, the second ring comprises 11 amino acids. In some embodiments, the second ring comprises 14 amino acids. In some embodiments, the second ring comprises a linkage between two amino acids having a structure selected from the following:

[0005] In some embodiments, the second ring comprises a linkage between the N-terminus of the peptide and an amino acid and has a structure selected from the following: In some embodiments, the second ring is formed between X4and X9, X4and X13, X5and X10, X3and X13, or X6and X9. In some embodiments, the second ring is formed between X4and X9, X4and X13, X5and X10, X3and X13, or X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the second ring is formed between X4and X9, X4and X13, X5and X10, X3and X13, or X6and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the second ring is formed between X5and X10or X3and X13. In some embodiments, the second ring is formed between X5and X10or X3and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the second ring is formed between X5and X10or X3and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the second ring is formed between X5and X10or X3and X13via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the second ring is formed between X4and X9. In some embodiments, the second ring is formed between X4and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the second ring is formed between X4and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the second ring is formed between X4and X13. In some embodiments, the second ring is formed between X4and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the second ring is formed between X4and X13via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the second ring is formed between X5and X10. In some embodiments, the second ring is formed between X5and X10via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the second ring is formed between X5and X10via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the second ring is formed between X3and X13. In some embodiments, the second ring is formed between X3and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the second ring is formed between X3and X13via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the second ring is formed between X6and X9. In some embodiments, the second ring is formed between X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the second ring is formed between X6and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the second ring is formed between X13and the N-terminus of the peptide. In some embodiments, the second ring is formed between X13and the N-terminus of the peptide via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the second ring is formed between X13and the N-terminus of the peptide via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X4and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; and the second ring is formed between X3and X13, between X5and X10, between X10and X13, or between X13and the N-terminus of the peptide via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X4and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole; and the second ring is formed between X3and X13, between X5and X10, between X10and X13, or between X13and the N-terminus of the peptide via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X4and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; and the second ring is formed between X5and X10or between X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X4and X13via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole; and the second ring is formed between X5and X10or between X6and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the first ring is formed between X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; and the second ring is formed between X3and X13, between X4and X13, between X5and X10, between X10and X13, or between X13and the N-terminus of the peptide via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole. In some embodiments, the first ring is formed between X6and X9via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole; and the second ring is formed between X3and X13, between X4and X13, between X5and X10, between X10and X13, or between X13and the N-terminus of the peptide via a linker selected from the group consisting of a disulfide, thioether, amide, olefin, and triazole. In some embodiments, the peptide comprises at least one polyethylene glycol chain. In some embodiments, the peptide comprises no more than five, no more than four, no more than three, no more than two, or no more than one polyethylene glycol chain. In some embodiments, each polyethylene glycol chain, independently, terminates in an ammonium group of a methyl group. In some embodiments, the polyethylene glycol chain terminates in an ammonium group. In some embodiments, the polyethylene glycol chain terminates in a methyl group. In some embodiments, the peptide comprises a polyethylene glycol chain having the following structure: , wherein: n is an integer from 2 to 24. In some embodiments, the peptide comprises a polyethylene glycol chain having the following structure: . In some embodiments, the peptide comprises a polyethylene glycol chain having the following structure: wherein: ZA is -N+(CH3)3; and n is an integer from 2 to 24. In some embodiments, n is an integer from 2 to 15. In some embodiments, n is an integer from 2 to 5.2. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10. In some embodiments, n is 11. In some embodiments, n is 12. In some embodiments, n is 14. In some embodiments, n is 14. In some embodiments, n is 15. In some embodiments, R1, R2, or any amino acid of the peptide is conjugated to a polyethylene glycol chain. Non-limiting examples of polyethylene glycol chains are provided in Table A. Table A. Example polyethylene glycol chains

[0006] In some embodiments, the peptide comprises at least one lipophilic substituent. In some embodiments, the peptide comprises one lipophilic substituent. In some embodiments, the peptide comprises no more than three, no more than two, or no more than one lipophilic substituent. In some embodiments, the peptide comprises no more than one lipophilic substituent. In some embodiments, the peptide comprises a lipophilic substituent having the following structure: , wherein:

[0007] ZEis -H, -COOH, or tetrazolyl; ZF is -H or -CH3; Xaa is, independently for each occurrence, , p, independently for each occurrence, is 0, 1, 2, 3, 4, 5, or 6; q is 1, 2, 3, 4, 5, or 6; r is an integer from 6 to 24; v is 0 or 1; and w, independently for each occurrence, is 0 or 1. In some embodiments, the peptide comprises a lipophilic substituent having the following structure: , wherein: p, independently for each occurrence, is 1, 2, 3, 4, 5, or 6; q is 1, 2, 3, 4, 5, or 6; r is an integer from 6 to 24; and w, independently for each occurrence, is 0 or 1. In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: , wherein:

[0008] p, independently for each occurrence, is 1, 2, 3, 4, 5, or 6; q is 1, 2, 3, 4, 5, or 6; r is an integer from 6 to 24; v is 0 or 1; and w, independently for each occurrence, is 0 or 1. In some embodiments, the peptide comprises a lipophilic substituent having the following structure: , wherein: p, independently for each occurrence, is 1, 2, 3, 4, 5, or 6; q is 1, 2, 3, 4, 5, or 6; r is an integer from 6 to 24; and w, independently for each occurrence, is 0 or 1. In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, the peptide comprises a lipophilic substituent having the following structure: . In some embodiments, . In some embodiments, . In some embodiments, . In some embodiments, ZEis -H. In some embodiments, ZEis -COOH. In some embodiments, ZE is tetrazolyl. In some embodiments, ZF is -H. In some embodiments, ZF is -CH3. In some embodiments, Xaa is, independently for each occurrence, , . In some embodiments, p is 1, 2, 3, or 4. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 5. In some embodiments, p is 6. In some embodiments, q is 1, 2, 3, or 4. In some embodiments, q is 1. In some embodiments, q is 2. In some embodiments, q is 3. In some embodiments, q is 4. In some embodiments, q is 5. In some embodiments, q is 6. In some embodiments, r is an integer between 10 and 20. In some embodiments, r is 10. In some embodiments, r is 11. In some embodiments, r is 12. In some embodiments, r is 13. In some embodiments, r is 14. In some embodiments, r is 15. In some embodiments, r is 16. In some embodiments, r is 17. In some embodiments, r is 18. In some embodiments, r is 19. In some embodiments, r is 20. In some embodiments, w is 0. In some embodiments, w is 1. In some embodiments, R1, R2, or any amino acid of the peptide is conjugated to a lipophilic substituent. In some embodiments, the lipophilic substituent is selected from Table B1. Table B1. Exemplary lipophilic substituents

[0009] Further non-limiting examples of lipophilic substituents are provided in Table B2. Table B2. Example lipophilic substituents In some embodiments, the lipophilic substituent is selected from PEG2PEG2GolAC18OH, PEG2PEG2SP6gEC18OH, PEG2PEG6gEC18OH, PEG2PEG2gE(c)C18OH, PEG2PEG2gEC18OH, or PEG12gEC18OH. In particular, the present disclosure relates to oral pharmaceutical formulations comprising lipidated cyclic peptide inhibitors of the interleukin-23 receptor (IL-23R) or pharmaceutically acceptable salts thereof, wherein each lipidated cyclic peptide is a compound with a formula as identified in Table 1.

[0010] Table 1. Compounds

[0011] 2 O OH NH2O O ONNHNO O NH2HO HN NH O O OH NH HN HN O O O O NH2NH O O HN O O HN O HN O NH NH O H N O N H O O HN O S S O O HN H H N N OH N O H O HN O NH2O O MeCO-k(PEG2PEG2GolAC18OH)-Pen(3)-N-T-7MeW-K(Ac)-Pen(3)-AEF-2Nal- THP-K(Ac)-N-3Pya-Sar-CONH2

[0012] 739658: NTT-4253PC 3 4 MeCO-k(PEG2PEG2gEC18OH)-Pen(3)-N-T-7MeW-K(Ac)-Pen(3)-AEF-2Nal- THP-K(Ac)-N-3Pya-Sar-CONH2 5 MeCO-k(PEG2PEG6gEC18OH)-Pen(3)-N-T-7MeW-K(Ac)-Pen(3)-AEF-2Nal- THP-K(Ac)-N-3Pya-Sar-CONH2

[0013] 6 MeCO-k(PEG2PEG2gE(c)C18OH)-Pen(3)-N-T-7MeW-K(Ac)-Pen(3)-AEF-2Nal- THP-K(Ac)-N-3Pya-Sar-CONH2

[0014] 7 MeCO-r-Pen(3)-N-T-7MeW-K(Ac)-Pen(3)-AEF-2Nal-THP-E-N-3Pya-Sar- K(PEG2PEG2gEC18OH)-CONH2

[0015]

[0016]

[0017]

[0018]

[0019]

[0020] 17 cPEG5aCO-Pen(3)-N(N(Me)2)-T-7MeW-Dab(NMecPEG5a)-Pen(3)-AEF-2Nal- THP-E-N-3Pya-Sar-CON(Me)2

[0021]

[0022]

[0023]

[0024] 22

[0025]

[0026] 26 O OONHO ONHO O O HN HN HO O OH H O OHNNH O NH HN NH O O OH O N NH H NH OSSHO O HN O O NH O O HN O OH2NH HN N O O NH O N HN H2N OO N O NH2MeCO-Pen(3)-K(PEG2PEG2gEC20OH)-T-7MeW-K(Ac)-Pen(3)-AEF-6OH2Nal- THP-K(Ac)-N-3Pya-Sar-CONH2

[0027]

[0028] 32 OH O HO O H H2NO OHNNH O NH HN NH O O O O O N NH H NH HN SSOH HO O HN O O NH O NH O O O HN O O O H2N H HN N O O O NH O O N HN H2N O O O N O O O HN NH2O O HN O O O O O MeCO-Pen(3)-N-T-7MeW-K(Ac)-Pen(3)-AEF-6OH2Nal-THP-K(Ac)-N-3Pya-Sar- K(PEG12gEC20OH)-CONH2 33 HOC20gEPEG2PEG2CO-k(d)-Pen(3)-N-T-7MeW-K(Ac)-Pen(3)-AEF-6OH2Nal- THP-E-N-3Pya-Sar-CONH2 35 HO O H H2NO OHNNH O NH HN NH O H O O O N O O O N NH H N O O NHSSHO O H O O N O O O NH O O O O HN N+O O O H2N HN N O O O NH O O HN N H2N O O O N O O NH2HN O HO NH O O O OH cPEG3aCO-k(PEG12gEC18OH)-Pen(3)-N-T-7MeW-K(NMeAc)-Pen(3)-AEF- 6OH2Nal-THP-K(NMeAc)-N-3Pya-Sar-CONH2 36 HOC18gEPEG12CO-Pen(3)-N-T-7MeW-K(NMeAc)-Pen(3)-AEF-6OH2Nal-THP- K(NMeAc)-N-3Pya-Sar-CONH2

[0029] 38 5cpaCO-Pen(3)-E(2)-T-7MeW-K(Ac)-Pen(3)-AEF(2)-6OH2Nal-THP- K(PEG2PEG2gEC18OH)-N-3Pya-Sar-CONH2 39 O H HO N O NH O O HHNNH H O HN NH O O N+ OO O O N O N H H SNHOHN S H O NHOHO NH2O O O H O HN N N HNNH2O O N HNOO O OONOH HNOHO NH O O O HO cPEG3aCO-Pen(3)-E(2)-T-7MeW-K(Ac)-Pen(3)-AEF(2)-6OH2Nal-THP- K(PEG2PEG2gEC18OH)-N-3Pya-Sar-CONH2 In the peptide sequences shown above, where a number in parenthesis follows a particular residue, that residue is linked to another residue in the sequence that is denoted with the same number. For example, in the sequence MeCO-r-Pen(3)-N-T-7MeW-K(Ac)- Pen(3)-AEF-6OH2Nal-THP-E-N-3Pya-Sar-K(PEG12NMegENMeC18OH)-CONH2 (SEQ ID NO: 40), the two Pen(3) residues are linked to one another. SYNTHESIS The compounds or lipidated peptide as described herein may be synthesized by many techniques that are known to those skilled in the art. In certain aspects, monomer subunits are synthesized and purified using the techniques described in the accompanying Examples. In some aspects, the present disclosure provides a method of producing a compound (or monomer subunit thereof) of the disclosure, comprising chemically synthesizing a peptide having an amino acid sequence described herein, including but not limited to any of the amino acid sequences set forth in the compounds of Formula I to Formula V or Table 1 herein. In some aspects, a portion of the peptide is recombinantly synthesized, instead of being chemically synthesized. In some aspects, methods of producing a compound further include cyclizing the compound precursor after the constituent subunits have been attached. In particular aspects, cyclization is accomplished via any of the various methods described herein. The present disclosure may include, but is not limited to, polynucleotides and vectors (e.g., expression vectors) that encode a portion of the amino acid sequence of a compound described herein, for instance, in the accompanying Examples or Table 1. The present disclosure further describes synthesis of lipidated compounds described herein, such as the compounds of Formula I to Formula V, and the compounds of Table 1. In some aspects, one or more of the amino acid residues or amino acid monomers are lipidated and then covalently attached to one another to form a compound of the disclosure. In some aspects, one or more of the amino acid residues or amino acid monomers are covalently attached to one another and lipidated at an intermediate oligomer stage before attaching additional amino acids and cyclization to form a compound of the disclosure. In some aspects, a cyclic peptide is synthesized and then lipidated to form a compound of the disclosure. Illustrative synthetic methods are described in the Examples. The present disclosure further describes synthesis of compounds described herein, such as the compounds of Formulas I to V and the compounds of Table 1. Illustrative synthetic methods are described in the Examples. IV. PHARMACEUTICAL COMPOSITIONS In general, the present disclosure relates to oral pharmaceutical formulations comprising lipidated peptide inhibitors of the Interleukin-23 Receptor (IL-23R) or pharmaceutically acceptable salt or solvate forms thereof, and absorption enhancers, and methods and / or use thereof for increasing bioavailability of the lipidated peptides and / or for treating autoimmune inflammation and related diseases and disorders . In one aspect, the present disclosure provides oral pharmaceutical formulations comprising one or more inhibitors of the present disclosure and one or more absorption enhancers as provided for herein and a pharmaceutically acceptable carrier, diluent, or excipient. The pharmaceutically acceptable carrier, diluent or excipient may be a solid, semi- solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like. The lipidated peptides of the present disclosure as provided for herein may be prepared and / or formulated as pharmaceutically acceptable salts or when appropriate in neutral form. Pharmaceutically acceptable salts are non-toxic salts of a neutral form of a compound that possess the desired pharmacological activity of the neutral form. These salts may be derived from inorganic or organic acids or bases. For example, a compound that contains a basic nitrogen may be prepared as a pharmaceutically acceptable salt by contacting the compound with an inorganic or organic acid. Non-limiting examples of pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen-phosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-1,4-dioates, hexyne-1,6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, methylsulfonates, propylsulfonates, besylates, xylenesulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, γ-hydroxybutyrates, glycolates, tartrates, and mandelates. Lists of other suitable pharmaceutically acceptable salts are found in Remington: The Science and Practice of Pharmacy, 21st Edition, Lippincott Wiliams and Wilkins, Philadelphia, Pa., 2006. Examples of “pharmaceutically acceptable salts” of the compounds disclosed herein also include salts derived from an appropriate base, such as an alkali metal (for example, sodium, potassium), an alkaline earth metal (for example, magnesium), ammonium and NX4+(wherein X is C1-C4alkyl). Also included are base addition salts, such as sodium or potassium salts. The present disclosure relates to oral pharmaceutical compositions comprisng an IL- 23R inhibitor of the present disclosure or pharmaceutically acceptable salts, isomers, or a mixture thereof, in which from 1 to n hydrogen atoms attached to a carbon atom may be replaced by a deuterium atom or D, in which n is the number of hydrogen atoms in the molecule. As known in the art, the deuterium atom is a non-radioactive isotope of the hydrogen atom. Such compounds may increase resistance to metabolism, and thus may be useful for increasing the half-life of the compounds described herein or pharmaceutically acceptable salts, isomer, or a mixture thereof when administered to a mammal. See, e.g., Foster, “Deuterium Isotope Effects in Studies of Drug Metabolism,” Trends Pharmacol. Sci., 5(12):524-527 (1984). Such compounds are synthesized by means well known in the art, for example by employing starting materials in which one or more hydrogen atoms have been replaced by deuterium. Examples of isotopes that can be incorporated into the disclosed compounds also include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine, and iodine, such as 2H, 3H, 11C, 13C, 14C, 13N, 15N, 15O, 17O, 18O, 31P, 32P, 35S, 18F, 36Cl, 123I, and 125I, respectively. Substitution with positron emitting isotopes, such as 11C, 18F, 15O and 13N, can be useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds of Formula (I), can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the Examples as set out below using an appropriate isotopically labeled reagent in place of the non-labeled reagent previously employed. In some embodiments, the present disclosure provides oral pharmaceutical formulations comprising an absorption enhancer as provided for herein and a lipidated peptide as provided for herein. In some embodiments, the peptide in the oral pharmaceutical formulation as provided for herein comprises the amino acid sequence of Formula (A). In some embodiments, the peptide in the oral pharmaceutical formulation as provided for herein comprises the amino acid sequence of Formula (B). In some embodiments, the peptide in the oral pharmaceutical formulation as provided for herein is a compound having a formula of ,

[0030] or a pharmaceutically acceptable salt or solvate form thereof, wherein: L is -O-, -S-, or -S-S-; R1, R2, R3, R4, R5, R6, R8, R9, and R10are each independently H, CH3, -C(=O)CH3, -C(=O)NHR11, R14,-(CH2)nNHR12, -(CH2)nC(=O)NHR12, -(CH2)nC(=O)OR12, -C(=O)(CH2)nNHR12, or -C(=O)(CH2)nOR12; R7 is -(CH2)pNHR13or -(CH2)qNHC(=NH)NH2; each m, n, p, and q are independently 1, 2, 3, 4, or 5; each R11, R12, R13, and R14are independently H or a lipid moiety. In some embodiments, the peptide in the oral pharmaceutical formulation as provided for herein the peptide is a compound having a formula of . In some embodiments, the peptide in the oral pharmaceutical formulation as provided for herein is a compound having a formula of

[0031] Formula I-a. In some embodiments, the peptide in the oral pharmaceutical formulation as provided for herein is a compound having a formula of Formula I-b. In some embodiments, each lipid moiety is selected independently from a Z1to Z5group: Z1 is wherein: PEG is –OCH2CH2-;n’ is 0 or 2-24, when n’ is 0 the group is absent and replaced by a bond;m’ is 0 or 2-24, when m’ is 0 the group is absent and replaced by a bond;v’ is independently selected from the range of 1-4 for each occurrence;v’’ is independently selected from the range of 0-4 for each occurrence, whenv'’’ is 0 the group is replaced by a bond;X is gE, dgE, 4SB, P, PPP, gE-(c), gE-(C), sp6, gDab, eK, Trx, or absent;o’ is 6-18;Y is gE, sp6, GolA, Pro, D-Pro, meG, Dab, Trx, or absent;Uis hydrogen or methyl;Vis -COOH, tetrazole, GolB, mXOH, pXOH, OPhenyl, carnitine, d-carnitine, or hydrogen; Z2is wherein: PEG is –OCH2CH2-; n’ is 0 or 2-24, when n’ is 0 the group is absent and replaced by a bond; m’ is independently selected from 0 or the range of 2-24 for each occurrence, when m’ is 0 the group is replaced by a bond;v’ is independently selected from the range of 1-4 for each occurrence;v’’ is independently selected from the range of 0-4 for each occurrence,when ^^’’ is 0 the group is replaced by a bond;p’ is 1-3;V’is sp6 or gEgE; X is gE, dgE, 4SB, P, PPP, gE-(c), gE-(C), sp6, gDab, eK, Trx, or absent; Y is gE, sp6, GolA, Pro, D-Pro, meG, Dab, Trx, or absent; X is Trx; U is hydrogen or methyl; o’ is 6-18; V is -COOH, tetrazole, GolB, mXOH, pXOH, OPhenyl, carnitine, d- carnitine, or hydrogen; Z3is -gE-C(O)(CH2)6-10CH3, or -gE-C(O)(CH2)11-18CH3; Z4 is -C(O)(CH2)6-18COOH or -C(O)(CH2)6-18COO(C1-4 alkyl); Z5 is wherein: n’’ and m’’ are independently selected from the range of 0 to 24; X is absent or is selected from the group consising of E, dgE, 4SB, gE- (c), gE-(C), sp6, gDab, eK, or Trx; Y is absent or is selected from the group consising of E, dgE, 4SB, gE- (c), gE-(C), sp6, gDab, eK, or Trx; and Xaa is a diamino-carboxylic acid. In some embodiments, each lipid moiety of the peptide in the oral pharmaceutical formulation as provided for herein is , ZEis -H, -COOH, phenoxy, or tetrazolyl; ZF is -H or -CH3; Xaaais, independently for each occurrence, pa, independently for each occurrence, is 0, 1, 2, 3, 4, 5, or 6; qais 1, 2, 3, 4, 5, or 6; rais an integer from 6 to 24; vais 0 or 1; and wa, independently for each occurrence, is 0 or 1. In some embodiments, the lipid moiety is one of the Peg Moieties and Peg Modified Monomers as shown in Table 2D. In some embodiments, R2is methyl. In some embodiments, R3is H. In some embodiments, R4 is H. In some embodiments, R5 is H. In some embodiments, R8is H. In some embodiments, R4 is H. In some embodiments, R9 is H. In some embodiments, R10is -C(=O)CH3. In some embodiments, the compound, or a pharmaceutically acceptable salt thereof, . In some embodiments, R7 is -(CH2)qC(=O)NH)NH2. In some embodiments, q is 3. In some embodiments, the compound has a formula of Formula III. In some embodiments, the compound, or a pharmaceutically acceptable salt thereof, has a formula of

[0032] (SEQ ID NO: 1). In some embodiments, the compound, or a pharmaceutically acceptable salt thereof, has a formula of Formula II, wherein R6 is -C(=O)CH3. In some embodiments, R7is -(CH2)pNHR12. In some embodiments, p is 4. In some embodiments, the compound, or a pharmaceutically acceptable salt thereof, has a formula of Formula IV. In some embodiments, the compound, or a pharmaceutically acceptable salt thereof, has a formula of (SEQ ID NO: 2),

[0033]

[0034] ĨSEQ ID NO: 4),

[0035]

[0036] (SEQ ID NO: 8). In some embodiments, the compound, or a pharmaceutically acceptable salt thereof, has a formula of

[0037] Formula V. In some embodiments, wherein R1is .In some embodiments, m is 4. In some embodiments, the compound, or a pharmaceutically acceptable salt thereof, has a formula of (SEQ ID NO: 7). In some embodiments, the compound, or a pharmaceutically acceptable salt thereof, has a formula of (SEQ ID NO: 2),

[0038]

[0039] ĨSEQ ID NO: 4),

[0040] ĨSEQ ID NO: 5),

[0041] ĨSEQ ID NO: 6),

[0042] ĨSEQ ID NO: 8),

[0043] ĨSEQ ID NO: 1), or

[0044] (SEQ ID NO: 7). In some embodiments, the peptide in the oral pharmaceutical formulation as provided for herein is selected from the group consisting of SEQ ID NOs:1-40. In some embodiments, the compound or a pharmaceutically acceptable salt or solvate form thereof is present in the oral pharmaceutical composition as provided for herein in an amount of from about 0.1% to about 15% (w / w) of the oral pharmaceutical formulation. In some embodiments, the weight ratio (w / w) of the absorption enhancer to the compound or a pharmaceutically acceptable salt or solvate form thereof in the oral pharmaceutical composition as provided for herein is in a range from about 1 to about 200. In some embodiments, the weight ratio (w / w) of the absorption enhancer to the compound or a pharmaceutically acceptable salt or solvate form thereof is in a range from about 1 to about 100. In some embodiments, the weight ratio (w / w) of the absorption enhancer to the compound or a pharmaceutically acceptable salt or solvate form thereof is in a range from about 1 to about 20. In some embodiments, the weight ratio (w / w) of the absorption enhancer to the compound or a pharmaceutically acceptable salt or solvate form thereof is in a range from about 1 to about 10. In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is no more than 50:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is no more than 40:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is no more than 30:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is no more than 20:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is no less than 3:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is no less than 5:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is no less than 7:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is no less than 9:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 3:1 (w / w) and 50:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 3:1 (w / w) and 30:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 4:1 (w / w) and 40:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 5:1 (w / w) and 50:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 3:1 (w / w) and 15:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 15:1 (w / w) and 30:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 30:1 (w / w) and 50:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 5:1 (w / w) and 15:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is between 9:1 (w / w) and 11:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is about 10:1 (w / w). In some embodiments, the ratio of the absorption enhancer to the lipidated peptide is about 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, or 50:1 (w / w). In some embodiments, the absorption enhancer is present in the formulation in an amount greater than 200 mg. In some embodiments, the absorption enhancer is present in the formulation in an amount greater than 250 mg. In some embodiments, the absorption enhancer is present in the formulation in an amount less than 1000 mg. In some embodiments, the absorption enhancer is present in the formulation in an amount less than 700 mg. In some embodiments, the absorption enhancer is present in the formulation in an amount between 200 mg and 1000 mg. In some embodiments, the absorption enhancer is present in the formulation in an amount between 250 mg and 700 mg. In some embodiments, the absorption enhancer in the oral pharmaceutical composition as provided for herein comprises one or more of sodium caprate, sodium caprylate, sodium palmitate, sodium stearate, sodium citrate, sodium salicylate, sodium salcaprozate (SNAC), a polyethylene glycol (PEG)-modified medium chain fatty acid triglyceride of capric and caprylic acid, sucrose laurate, sodium octanoate, labrasol, and lauroyl-L-carnitine (LC). In some embodiments, the absorption enhancer comprises sodium salcaprozate (SNAC). In some embodiments, the absorption enhancer comprises lauroyl-L- carnitine (LC). In some embodiments, the absorption enhancer comprises sodium octanoate. In some embodiments, the absorption enhancer comprises sodium labrasol. In some embodiments, the absorption enhancer comprises sodium caprate. In some embodiments, the sodium caprate is present in an amount of from about 1% to about 99% (w / w). In some embodiments, the sodium caprate has a purity of at least 98%. In some embodiments, the oral pharmaceutical formulation further comprises one or more pharmaceutically acceptable excipients. In some embodiments, the oral pharmaceutical formulation improves oral bioavailability of the compound. In some embodiments, the oral pharmaceutical formulation improves oral bioavailability of the compound by about 2 to about 500 folds. In some embodiments, the oral pharmaceutical formulation improves oral bioavailability of the compound by about 2 to about 250 folds. The present disclosure also provides methods of increasing the bioavailability of a compound in the oral pharmaceutical formulation as provided for herein in a subject comprising orally administering the compound, or a pharmaceutically acceptable salt or solvate form thereof, and an absorption enhancer. In some embodiments, the method comprises the absorption enhancer which comprises one or more of sodium caprate, sodium caprylate, sodium palmitate, sodium stearate, sodium citrate, sodium salicylate, sodium salcaprozate (SNAC), a polyethylene glycol (PEG)-modified medium chain fatty acid triglyceride of capric and caprylic acid, sucrose laurate, sodium octanoate, labrasol, and lauroyl-L-carnitine (LC). In some embodiments, the compound or a pharmaceutically acceptable salt or solvate form thereof, and the absorption enhancer are co-administered. In some embodiments, the compound or a pharmaceutically acceptable salt or solvate form thereof, and the enhancer are co-administered in a pharmaceutically acceptable formulation as provided for herein. The present disclosure also provides methods of use of an oral pharmaceutical formulation as provided for herein for the preparation of a medicament for the treatment of an inflammatory disorder or autoimmune inflammatory disorder. In some embodiments, an oral pharmaceutical formulation as provided for herein was used for the preparation of a medicament for the treatment of autoimmune inflammation and related diseases and disorders including, but not limited to: multiple sclerosis, asthma, rheumatoid arthritis, inflammation of the gut, inflammatory bowel diseases (IBDs), juvenile IBD, adolescent IBD, Crohn’ s disease, ulcerative colitis, Celiac disease (nontropical Sprue), microscopic colitis, collagenous colitis, eosinophilic gastroenteritis / esophagitis, colitis associated with radio- or chemo-therapy, colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1, sarcoidosis, Systemic Lupus Erythematosus, ankylosing spondylitis (axial spondyloarthritis), psoriatic arthritis, psoriasis (e.g., plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, Palmo-Plantar Pustulosis, psoriasis vulgaris, or erythrodermic psoriasis), atopic dermatitis, acne ectopica, enteropathy associated with seronegative arthropathies, chronic granulomatous disease, glycogen storage disease type 1b, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Wiskott-Aldrich Syndrome, pouchitis, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin- dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, primary biliary cirrhosis, viral-associated enteropathy, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, uveitis, or graft versus host disease. In some embodiments, the disease or disorder is selected from Inflammatory Bowel Disease (IBD), Ulcerative colitis (UC), Crohn’ s Disease (CD), psoriasis (PsO), and psoriatic arthritis (PsA). The present disclosure also provides methods of methods for treating a disease or disorder associated with Interleukin 23 (IL-23) / Interleukin 23 Receptor (IL-23R), which comprises administering an effective amount of an oral pharmaceutical formulation as provided for herein. In some embodiments, the disease or disorder is associated with autoimmune inflammation. In some embodiments, the disease or disorder is multiple sclerosis, asthma, rheumatoid arthritis, inflammation of the gut, inflammatory bowel diseases (IBDs), juvenile IBD, adolescent IBD, Crohn’ s disease, ulcerative colitis, Celiac disease (nontropical Sprue), microscopic colitis, collagenous colitis, eosinophilic gastroenteritis / esophagitis, colitis associated with radio- or chemo-therapy, colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1, sarcoidosis, Systemic Lupus Erythematosus, ankylosing spondylitis (axial spondyloarthritis), psoriatic arthritis, psoriasis (e.g., plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, Palmo-Plantar Pustulosis, psoriasis vulgaris, or erythrodermic psoriasis), atopic dermatitis, acne ectopica, enteropathy associated with seronegative arthropathies, chronic granulomatous disease, glycogen storage disease type 1b, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Wiskott-Aldrich Syndrome, pouchitis, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin- dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, primary biliary cirrhosis, viral-associated enteropathy, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, uveitis, or graft versus host disease. In some embodiments, the disease or disorder is associated with Ulcerative colitis (UC), Crohn’s Disease (CD), psoriasis (PsO), or psoriatic arthritis (PsA). In general, oral pharmaceutical compositions of the present disclosure may be formed into different dosage forms prepared using conventional materials and techniques known in the pharmaceutical and formulary arts, which may include, but is not limited to techniques, such as mixing, blending and the like and as set forth throughout the instant disclosure. Moreover, pharmaceutical composition used to form dosage forms may also include, but are not limited to, suitable adjuvants, carriers, excipients, or stabilizers, etc. and can be in solid or liquid form such as, solid, or liquid dosage forms, which may include, but are not limited to tablets, capsules, powders, solutions, suspensions, or emulsions and the like, etc. In accordance with the present disclosure, solid unit dosage forms may be other conventional types known in the art. Further, suitable for use in the present disclosure are solutions, which may, but are not limited to, such as in water, saline, aqueous dextrose and related sugar solutions, and glycols such as, propylene glycol or polyethylene glycol, buffered solutions and the like, etc., are preferred liquid carriers, particularly for injectable solutions. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The oral pharmaceutical compositions of the present disclosure may include a variety of other pharmaceutically acceptable components or excipients, such as, including, but not limited to, a glidant, a lubricant, a disintegrant, a binder, a desiccant, a filler, and other components or excipients and the like. These components are described within. In some aspects, oral pharmaceutical compositions of the present disclosure may not include or may exclude use of an absorption enhancer depending on the intended delivery or use thereof and / or for treatment of specific indications as defined in the present disclosure. In other aspects, suitable oral pharmaceutical compositions of the present disclosure may exhibit improved bioavailability when administered in conjunction with an absorption enhancer, such as but not limited to an intestinal permeation enhancer. In some aspects, oral pharmaceutical compositions of the present disclosure may include an absorption or permeation enhancer. When present, the absorption or permeation enhancer may be, but not limited to the following forms: zwitterionic, cationic, anionic, or non-ionic. In one aspect, the absorption or permeation enhancer is an intestinal permeation or absorption enhancer. In some aspects, the absorption enhancer may be selected from, but is not limited to medium-chain saturated fatty acids, such as a caprate, a caprylate, a myristate, a palmitate, or a stearate, including salt forms, such as sodium caprate, sodium caprylate, sodium myristate, sodium palmitate, or sodium stearate) and the like. Other absorption or permeation enhancer(s) may include, but is / are not limited to a citric acid or citrate salt, such as sodium citrate, tartaric acid or tartrate salt, a salicylic acid or a derivative thereof, or a salicylate salt, a fatty acid acylated amino acid, an alkylsaccharide, a C8-o alkylpolysaccharide, n-octyl-beta-D-glucopyranoside, n-dodecyl-beta-D-maltoside, n- tetradecyl-beta-D-maltoside, tridecylbeta-D-maltoside, sucrose laurate, sucrose myristate, sucrose palmitate, sucrose cocoate, sucrose mono-dodecanoate, sucrose mono-tridecanoate, sucrose monotetradecanoate, a coco-glucoside, a cyclodextrins, alkanoyl carnitine such as lauroyl carnitine, myristoyl carnitine or palmitoyl carnitine, lauroyl carnitine chloride, myristoyl carnitine chloride or palmitoyl carnitine chloride, fatty acid acylated amino acids, including, without limitation, sodium lauroyl alaninate, N-dodecanoyl-L-alanine, sodium lauroyl asparaginate, N-dodecanoyl-L-asparagine, sodium lauroyl aspartic acid, N- dodecanoyl-L-aspartic acid, sodium lauroyl cysteinate, N-dodecanoyl-L-cysteine, sodium lauroyl glutamic acid, N-dodecanoyl-L-giutamic acid, sodium lauroyl glutaminate, N- dodecanoyl-L-glutamine, sodium lauroyl glycinate, N-dodecanoyl-L-glycine, sodium lauroyl histidinate, N-dodecanoyl-L-histidine, sodium lauroyl isoleucinate, N-dodecanoyl-L- isoleucine, sodium lauroyl leucinate, N-dodecanoyl-L-leucine, sodium lauroyl methioninate, N-dodecanoyl-L-methionine, sodium lauroyl phenylalaninate, N-dodecanoyl-L- phenylalanine, sodium lauroyl propionate, N-dodecanoyl-L-proline, sodium lauroyl serinate, N-dodecanoyl-L-serine, sodium lauroyl threoninate, N-dodecanoyl-L-threonine, sodium lauroyl tryptophanate, N-dodecanoyl-L-tryptophan, sodium lauroyl tyrosinate, N-dodecanoyl- L-tyrosine, sodium lauroyl valinate, N-dodecanoyl-L-valine, sodium lauroyl sarcosinate, N- dodecanoyl-L-sarcosine, sodium capric alaninate, N-decanoyl-L-alanine, sodium capric asparaginate, N-decanoyl-L-asparagine, sodium capric aspartic acid, N-decanoyl-L-aspartic acid, sodium capric cysteinate, N-decanoyl-L-cysteine, sodium capric glutamic acid, N- decanoyl-L-glutamic acid, sodium capric glutaminate, N-decanoyl-L-glutamine, sodium capric glycinate, N-decanoyl-L-glycine, sodium capric histidinate, N-decanoyl-L-histidine, sodium capric isoleucinate, N-decanoyl-L-isoleucine, sodium capric leucinate, N-decanoyl-L- leucine, sodium capric methioninate, N-decanoyl-Lmethionine, sodium capric phenylalaninate, N-decanoyl-L-phenylalanine, sodium capric propionate, N-decanoyl-L- proline, sodium capric serinate, N-decanoyl-L-serine, sodium capric threoninate, N-decanoyl- L-threonine, sodium capric tryptophanate, N-decanoyl-L-tryptophan, sodium capric tyrosinate, N-decanoyl-L-tyrosine, sodium capric valinate, N-decanoyl-L-valine, sodium capric sarcosinate, N-decanoyl-L-sarcosine, sodium oleoyl sarcosinate, sodium N- decylleucine, sodium stearoyl glutamate (e.g., Amisoft HS-11 P), sodium myristoyl glutamate (e.g., Amisoft MS-11), sodium lauroyl glutamate (e.g., Amisoft LS-11), sodium cocoyl glutamate (e.g., Amisoft CS-11), sodium cocoyl glycinate (e.g., Am lite GCS-11), sodium N-decyl leucine, sodium cocoyl glycine, sodium cocoyl glutamate, sodium lauroyl alaninate, N-dodecanoyl-L-alanine, sodium lauroyl asparaginate, N-dodecanoyl-L- asparagine, sodium lauroyl aspartic acid, N-dodecanoyl-L-aspartic acid, sodium lauroyl cysteinate, N-dodecanoyl-L-cysteine, sodium lauroyl glutamic acid, N-dodecanoyl-L- glutamic acid, sodium lauroyl giutaminate, N-dodecanoyl-L-glutamine, sodium lauroyl glycinate, N-dodecanoyl-L-glycine, sodium lauroyl histidinate, N-dodecanoyl-L-histidine, sodium lauroyl isoleucinate, N-dodecanoyl-L-isoleucine, sodium lauroyl leucinate, N- dodecanoyl-L-leucine, sodium lauroyl methinoninate, N-dodecanoyl-L-methionine, sodium lauroyl phenylalaninate, N-dodecanoyl-L-phenylalanine, sodium lauroyl propionate, N- dodecanoyl-L-proline, sodium lauroyl serinate, N-dodecanoyl-L-serine, sodium lauroyl threoninate, N-dodecanoyl-L-threonine, sodium lauroyl tryptophanate, N-dodecanoyl-L- tryptophan, sodium lauroyl tyrosinate, N-dodecanoyl-L-tyrosine, sodium lauroyl valinate, N- dodecanoyl-L-valine, N-dodecanoyl-L-sarcosine, sodium capric alaninate, N-decanoyl-L- alanine, sodium capric asparaginate, N-decanoyl-L-asparagine, sodium capric aspartic acid, N-decanoyl-L-aspartic acid, sodium capric cysteinate, N-decanoyl-L-cysteine, sodium capric glutamic acid, N-decanoyl-L-glutamic acid, sodium capric glutaminate, N-decanoyl-L- glutamine, sodium capric glycinate, N-decanoyl-L-glycine, sodium capric histidinate, N- decanoyl-L-histidine, sodium capric isoleucinate, N-decanoyl-Lisoleucine, sodium capric leucinate, N-decanoyl-L-leucine, sodium capric methioninate, N-decanoyl-L-methionine, sodium capric phenylalaninate, N-decanoyl-L-phenylalanine, sodium capric prolinate, N- decanoyl-L-proline, sodium capric serinate, N-decanoyl-L-serine, sodium capric threoninate, N-decanoyl-L-threonine, sodium capric tryptophanate, N-decanoyl-Ltryptophan, sodium capric tyrosinate, N-decanoyl-L-tyrosine, sodium capric valinate, N-decanoyl-L-valine, sodium capric sarcosinate, sodium oleoyl sarcosinate, and pharmaceutically acceptable salts of any of the aforementioned compounds; or an alkanoyl sarcosinate (e.g., a lauroyl sarcosinate, such as sodium lauroyl sarcosinate) or one of the 20 standard proteinogenic alpha-amino acids that is acylated with a C8-C20 alkanoic acid), an alkylsaccharide (e.g., a C1-C20 alkylsaccharide, such as, MultitropeTM 1620-LQ-(MV); or, n-octyl-beta-D- glucopyranoside, n-dodecyl-beta-D-maltoside, n-tetradecyl-beta-D-maltoside, tridecyl-beta- D-maltoside, sucrose laurate, sucrose myristate, sucrose palmitate, sucrose cocoate, sucrose mono-dodecanoate, sucrose monotridecanoate, sucrose mono-tetradecanoate, a coco- glucoside, alkylsaccharides, a cyclodextrin (e.g., alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, methyl-beta-cyclodextrin, hydroxypropyl beta-cyclodextrin), N-[8-(2- hydroxybenzoyl)amino]caprylic acid, a N-[8-(2-hydroxybenzoyl)amino]caprylate, sodium N- [8-(2-hydroxybenzoyl)amino]caprylate, also referred to as "SNAC"), a calcium chelating compound (e.g., ethylenediaminetetraacetic acid (EDTA), cremophor EL (also referred to as "Kolliphor EL"; CAS no.61791-12-6), chitosan, N,N,N-trimethyl chitosan, benzalkonium chloride, bestatin, or alkanols (e.g., ethanol, decanol), caprylocaproyl polyoxylglycerides (such as caprylocaproyl polyoxyl-8 glycerides; available as LABRASOL®or ACCONON®MC8-2), ethyl caprylate, glyceryl monolaurate, lysophosphatidylcholine, menthol, a C -2o alkylamine, a C8-C20 alkenylamine (e.g oleylamine), phosphatidylcholine, a poloxamer, polyethylene glycol monolaurate, polyoxyethylene, polypropylene glycol monolaurate, a polysorbate (e.g., polysorbate 80), cholic acid (or a cholate salt, e.g., sodium chlolate), a deoxycholate (e.g ., sodium deoxycholate), sodium glycocholate, sodium glycodeoxycholate, sodium lauryl sulfate (SDS), sodium decyl sulfate, sodium octyl sulfate, sodium laureth sulfate, N-lauryl sarcosinate, decyltrimethyl ammonium bromide, benzyldimethyl dodecyl ammonium chloride, myristyltrimethyl ammonium chloride, dodecyl pyridinium chloride, or decyldimethyl ammonio propane sulfonate and the like. In some aspects, the absorption or permeation enhancer may include, but is not limited to sodium caprate, sodium caprylate, sodium palmitate, sodium stearate, sodium citrate, sodium salicylate, sodium salcaprozate (SNAC), a polyethylene glycol (PEG)- modified medium chain fatty acid triglyceride of capric and caprylic acid (such as LABRASOL®, available from Gattefosse, USA), sucrose laurate, or lauroyl-L-carnitine (LC, such as PEPTELLIGENCE®, available from Enteris BioPharma, NJ, USA) and the like. In some aspects, the absorption enhancer is sodium caprate, sodium caprylate, sodium palmitate, sodium stearate, sodium citrate, sodium salicylate, sodium salcaprozate (SNAC), a polyethylene glycol (PEG)-modified medium chain fatty acid triglyceride of capric and caprylic acid, sucrose laurate, or lauroyl-L-carnitine (LC). In some aspects, the absorption or permeation enhancer can be a polyethylene glycol (PEG)-modified medium chain fatty acid triglyceride of capric and caprylic acid. In other aspects, the absorption or permeation enhancer used may be sodium salcaprozate. In some aspects, the absorption or permeation enhancer used may include, but is not limited to a polyethylene glycol (PEG)-modified medium chain fatty acid triglyceride of capric and caprylic acid and the like. In some aspects, the absorption or permeation enhancer used in a composition of the present disclosure may be, but is not limited to sodium caprate. In another aspect, the present disclosure provides oral pharmaceutical compositions which comprise an IL-23R inhibitor of the present disclosure or a pharmaceutically acceptable salt or solvate form thereof in an amount of from about 0.1% to about 15% (w / w) of the composition. In some aspects, the sodium caprate can be present in a composition in an amount of from about 1% to about 99% (w / w) of the composition. In one aspect, for use in oral pharmaceutical compositions of the present disclosure, sodium caprate may have a purity of at least 98%, 98.2%, 98.4%.98.6%, 98.8%, 99.0%, 99.5%, or at least 99.9%. Without being bound by any theory, the higher degree of purity of the sodium caprate can provide improved bioavailability compared to lower technical grade sodium caprate, such 90% or 95% pure sodium caprate. In some aspects, sodium caprate has a purity of at least 98% for use in the present disclosure. In another aspect, sodium caprate may be present in any form to be adapted for use in oral pharmaceutical compositions of the present disclosure. In some aspects, the sodium caprate can be in crystalline form, amorphous form, or semi-crystalline form. In some aspects, the use of crystalline sodium caprate can enhance bioavailability of an IL-23R inhibitor of the present disclosure. In some aspects, the use of amorphous sodium caprate can enhance bioavailability of an IL-23R inhibitor of the present disclosure. In some aspects, the use of semi-crystalline sodium caprate can enhance bioavailability of an IL-23R inhibitor of the present disclosure. In some aspects, the use of crystalline sodium caprate may enhance bioavailability of an IL-23R inhibitor of the present disclosure or a pharmaceutically acceptable salt or solvate form thereof. In some aspects, the use of amorphous sodium caprate may enhance bioavailability of an IL-23R inhibitor of the present disclosure or a pharmaceutically acceptable salt or solvate form thereof. In some aspects, the use of semi-crystalline sodium caprate may enhance bioavailability of an IL-23R inhibitor of the present disclosure or a pharmaceutically acceptable salt or solvate form thereof. In some embodiments, the peptide has SEQ ID NO:1. In some embodiments, the peptide has SEQ ID NO:2. In some embodiments, the peptide has SEQ ID NO:3. In some embodiments, the peptide has SEQ ID NO:4. In some embodiments, the peptide has SEQ ID NO:5. In some embodiments, the peptide has SEQ ID NO:6. In some embodiments, the peptide has SEQ ID NO:7. In some embodiments, the peptide has SEQ ID NO:8. V. METHODS OF TREATMENTS AND / OR USES In one aspect, the present disclosure relates to a method or use for treating inflammatory disease in a subject which comprises administering to the subject a therapeutically effective amount of a composition disclosed herein. In some aspects, the present disclosure provides a method of treating inflammatory disease in a subject which comprises administering to the subject a therapeutically effective amount of a composition of the present disclosure. Suitable inflammatory diseases for treatment with formulations or compositions of the present disclosure, may include, but is not limited to inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO), or psoriatic arthritis (PsA) and the like. In some aspects, the present disclosure provides methods or uses for treating a subject afflicted with a condition or indication associated with IL-23 or IL-23R (e.g., activation of the IL-23 / IL-23R signaling pathway), where the method or use comprises administering to the subject the compositions of the present disclosure. In some aspects, a method or use is provided for treating a subject afflicted with a condition or indication characterized by inappropriate, deregulated, or increased IL-23 or IL-23R activity or signaling, which comprises administering to the individual a composition of the present disclosure in an amount sufficient to inhibit (partially or fully) binding of IL-23 to IL-23R in the subject. In some aspects, the inhibition of IL-23 binding to IL-23R occurs in particular organs or tissues of the subject, e.g., which includes, but is not limited to organs such as the stomach, small intestine, large intestine / colon, intestinal mucosa, lamina propria, Peyer's Patches, mesenteric lymph nodes, or lymphatic ducts. In some aspects, methods or uses of the present disclosure can comprise providing a composition of the present disclosure to a subject in need thereof. In some aspects, the subject in need thereof has been diagnosed with or has been determined to be at risk of developing a disease or disorder associated with IL-23 / IL-23R. Each aspect of the present disclosure defined in this or in any other section may incorporate definitions and limitations, such as those set forth in Sections I to V herein and throughout the originally filed disclosure, specification, and claims. VI. EXAMPLES The following examples illustrate the invention. These examples are not intended to limit the scope of the present disclosure, but rather to provide guidance to the skilled artisan to prepare and use the compounds, compositions, and methods of the present disclosure. While particular aspects of the present disclosure are described, the skilled artisan will appreciate that various changes and modifications can be made without departing from the spirit and scope of the invention. Some abbreviations useful in describing the invention are defined below in the following Tables 2A-2G. Table 2A. Amino Acid Abbreviations

[0045] Table 2B. Abbreviations for Substituents, Reagents, and Solvents

[0046] Table 2C. Amino Acid Monomers 165 166 167 168 169 196 197 198 199 200 201 202 203 204 205

[0047] In some embodiments, naturally-occurring L-amino acids and D-amino acids are both represented by either conventional three-letter, or capitalized one-letter, amino acid designations of Table 2C-a. In some embodiments, D-amino acids, are represented by lower- case one-letter amino acid designations corresponding to one-letter designations of Table Table 2C or Table 2C-a, i.e., g, a, l, m, f, w, k, q, e, s, p, v, i, c, y, h, r, n, d, and t. Table 2C-a: Naturally-occurring amino acids GGlycine Gly P Proline ProA Alanine Ala V Valine ValL Leucine Leu I Isoleucine IleM Methionine Met C Cysteine CysF Phenylalanine Phe Y Tyrosine TyrW Tryptophan Trp H Histidine HisK Lysine Lys R Arginine ArgQ Glutamine Gln N Asparagine AsnE Glutamic Acid Glu D Aspartic Acid AspS Serine Ser T Threonine ThrThe term “L-amino acid,” as used herein, refers to the “L” isomeric form of an amino acid, and conversely the term “D-amino acid” refers to the “D” isomeric form of an amino acid (e.g., (D)Asp or D-Asp; (D)Phe or D-Phe). Amino acid residues in the D isomeric form can be substituted for any L-amino acid residue, as long as the desired function is retained by the peptide. D-amino acids may be indicated as customary in lower case when referred to using single-letter abbreviations. For example, D-arginine can be represented as “arg” or “r.” Alternatively, a lower case “d” in front of an amino acid can be used to indicate that it is of the D isomeric form, for example D-lysine can be represented by dK. In the case of less common or non-naturally occurring amino acids, unless they are referred to by their full name (e.g., sarcosine, ornithine, etc.), frequently employed three- or four-character codes are employed for residues thereof, including, Sar or Sarc (sarcosine, i.e., N-methylglycine), Aib (α-aminoisobutyric acid), Dab (2,4-diaminobutanoic acid), Dapa (2,3- diaminopropanoic acid), γ-Glu (γ-glutamic acid), Gaba (γ-aminobutanoic acid), β-Pro (pyrrolidine-3-carboxylic acid), and Abu (2-aminobutyric acid). Peptides may be naturally occurring, synthetically produced, or recombinantly expressed. Peptides may also comprise additional groups modifying the amino acid chain, for example, functional groups added via post-translational modification. Examples of post- translation modifications include, but are not limited to, acetylation, alkylation (including, methylation), biotinylation, glutamylation, glycylation, glycosylation, isoprenylation, lipoylation, phosphopantetheinylation, phosphorylation, selenation, and C-terminal amidation. The term peptide also includes peptides comprising modifications of the amino terminus and / or the carboxy terminus. Modifications of the terminal amino group include, but are not limited to, des-amino, N-lower alkyl, N-di-lower alkyl, and N-acyl modifications. Modifications of the terminal carboxy group include, but are not limited to, amide, lower alkyl amide, dialkyl amide, and lower alkyl ester modifications (e.g., wherein lower alkyl is C1-C4 alkyl). The term peptide also includes modifications, such as but not limited to those described above, of amino acids falling between the amino and carboxy termini. Table 2D. Peg Moieties and Peg Modified Monomers

[0048]

[0049]

[0050]

[0051]

[0052] Table 2E. Non-limiting N-Terminal Modifications

[0053] Table 2F. Non-limiting C-Terminal Modifications The amino acid structures provided in Table 2G, below, are presented without stereochemical indicators at the alpha carbon; however, it is to be understood that these amino acids occur as either the L-amino acid or the D-amino acid. For example, “Dap” may be present in the peptides of the instant disclosure as the L-stereoisomer: , or as the D-stereoisomer (e.g., when referred to as “dap,” “dDap,” or “D-Dap”): . Table 2G. Monomer Abbreviations

[0054] Example 1. Synthesis of HOC18gEPEG2PEG2-r-Pen*-N-T-7MeW-K(Ac)-Pen*-AEF- 2Nal-THP-K(Ac)-N-3Pya-Sar-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 1)

[0055] Intermediate 1-1 Synthesis of Intermediate 1-1 The peptide was synthesized by standard Solid-phase Peptide Synthesis (SPPS) using Fmoc / t-Bu chemistry. The assembly was performed on a Rink-amide AM resin (110 μmol, 100-200Mesh; loading 0.33 mmol / g) on the Cem Liberty Blue microwave peptide synthesizer (CEM Inc.). During peptide assembly on solid phase, the side chain protecting groups were: tert-butyl for Thr and Glu; trityl for Pen and Asn; tert-butoxy-carbonyl for AEF, Pbf (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl) for Arg. All the amino acids were dissolved at a 0.4 M concentration in DMF. The acylation reactions were performed for 3 min at 90°C under MW irradiation with 5 folds excess of activated amino acids over the resin free amino groups. The amino acids were activated with equimolar amounts of 0.5M solution of DIC in DMF and Oxyma solution 1M in DMF. Double acylation reactions were performed for 3Pya and 2Nal. Fmoc deprotections were performed using 20%(V / V) piperidine in DMF. Capping of the free amino group was performed manually (PEG2, PEG2 and the gE (Fmoc- Glu-OtBu) residues) using DIC-HOAT (6Eq, 1:1:1) at room temperature. C18OH (18-(tert- butoxy)-18-oxooctadecanoic acid) was coupled using DIC-HOAT (6Eq, 1:1:1) at room temperature and complete acylation was monitored by ninhydrin test. At the end of the assembly the resin was washed with DMF, MeOH, DCM, Et2O. The peptide was cleaved from solid support using 15 ml of TFA solution (v / v) (87.5% TFA, 5% H2O, 2.5% TIPS, 5%Phenol) for approximately 1.5 hours, at room temperature. The resin was then filtered and precipitated in cold MTBE (135mL). After centrifugation, the peptide pellets were washed with fresh cold diethyl-ether to remove the organic scavengers. The process was repeated twice. Final pellets were dried, re-suspended in H2O and acetonitrile 1:1 + 0.1% TFA and stirred overnight. The mixture was then lyophilized to afford the desired Intermediate 1-1 (78.1 % yield). LCMS anal. calc. For C132H200N28O33S22771.32; found: 924.7 (M+3)3+. Synthesis of HOC18gEPEG2PEG2-r-Pen*-N-T-7MeW-K(Ac)-Pen*-AEF-2Nal-THP-K(Ac)-N- 3Pya-Sar-CONH2(SEQ ID NO: 1) Intermediate 1-1 was dissolved in ACN / H2O (1mg / ml). Saturated Iodine in acetic acid was then added dropwise under stirring until yellow color persisted. Reaction was completed in 30 min (monitored by UPLC-MS). Solid ascorbic acid was added until the solution became clear. After lyophilization the cyclized peptide was purified by reverse-phase HPLC using preparative Waters DeltaPak C4 (200x40mm, 300Å, 15µm). Mobile phase A: + 0.1% TFA, mobile phase B: Acetonitrile (ACN) + 0.1% TFA. The following gradient of eluent B was used: 25%B to 25%B over 5min, to 40%B over 25min, flow rate 80 mL / min, wavelength 214 nm. Collected fractions were lyophilized to afford the desired compound (22% yield). LCMS anal. calc. For C132H198N28O33S22769.32; found: 1386.1 (M+2)2+. Example 2. Synthesis of MeCO-k(PEG2PEG2GolAC18OH)-Pen*-N-T-7MeW-K(Ac)- Pen*-AEF-2Nal-THP-K(Ac)-N-3Pya-Sar-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 2) Intermediate 2-1 The compound of was prepared according to similar procedures to prepare Example 1 or the like. The compound of SEQ ID NO: 2 was prepared. LCMS anal. calc. For C141H217N28O35S2+:2771.33; found: 1386.55 (M+2)2+. Example 3. Synthesis of MeCO-k(PEG2PEG2SP6gEC18OH)-Pen*-N-T-7MeW-K(Ac)- Pen*-AEF-2Nal-THP-K(Ac)-N-3Pya-Sar-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 3) Synthesis of Intermediate 3-1 The peptide was synthesized by standard Solid-phase Peptide Synthesis (SPPS) using Fmoc / t-Bu chemistry. The assembly was performed on a Rink-amide AM resin (110 μmol, 100-200Mesh; loading 0.34 mmol / g) on the Cem Liberty Blue microwave peptide synthesizer (CEM Inc.). During peptide assembly on solid phase, the side chain protecting groups were: tert-butyl for Thr and Glu; trityl for Pen and Asn; tert-butoxy-carbonyl for AEF. The N- terminal D-Lys was protected by the orthogonal DDe protecting group. All the amino acids were dissolved at a 0.4 M concentration in DMF. The acylation reactions were performed for 3 min at 90°C under MW irradiation with 5 folds excess of activated amino acids over the resin free amino groups. The amino acids were activated with equimolar amounts of 0.5M solution of DIC in DMF and Oxyma solution 1M in DMF. Double acylation reactions were performed for 3Pya and 2Nal. Fmoc deprotections were performed using 20%(V / V) piperidine in DMF. Capping of the free amino group was performed manually using 10eq of acetic anhydride in DMF. At the end of the peptide assembly on solid phase, the resin was treated with 100 ml of 3% hydrazine solution in DMF. The solution was drained, and the resin washed with DCM (3 × 5 mL) and DMF (5 × 5 mL). Further side chain derivatization was performed manually (PEG2, PEG2, Fmoc-SP6 ((2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-N- (carboxymethyl)-N,N-dimethylethan-1-aminium) and the gE (Fmoc-Glu-OtBu) residues) using DIC-HOAT (3Eq, 1:1:1) at room temperature. C18OH (18-(tert-butoxy)-18- oxooctadecanoic acid) was coupled using DIC-HOAT (6Eq, 1:1:1) at room temperature and complete acylation was monitored by ninhydrin test. At the end of the assembly the resin was washed with DMF, MeOH, DCM, Et2O. The peptide was cleaved from solid support using 15 ml of TFA solution (v / v) (87.5% TFA, 5% H2O, 2.5% TIPS, 5%Phenol) for approximately 1.5 hours, at room temperature. The resin was then filtered and precipitated in cold MTBE (135mL). After centrifugation, the peptide pellets were washed with fresh cold diethyl-ether to remove the organic scavengers. The process was repeated twice. Final pellets were dried, re-suspended in H2O and acetonitrile 1:1 + 0.1% TFA and stirred overnight. The mixture was then lyophilized to afford the desired Intermediate 3-1 (80% yield). LCMS anal. calc. C140H215N28O35S2+: 2914.52; found: 972.5 (M+3)3+. Synthesis of MeCO-k(PEG2PEG2SP6gEC18OH)-Pen*-N-T-7MeW-K(Ac)-Pen*-AEF-2Nal- THP-K(Ac)-N-3Pya-Sar-CONH2 (SEQ ID NO: 3) Intermediate 3-1 was dissolved in ACN / H2O (1mg / ml). Saturated iodine in acetic acid was then added dropwise under stirring until yellow color persisted. Reaction was completed in 30 min (monitored by UPLC-MS). Solid ascorbic acid was added until the solution became clear. After lyophilization the cyclized peptide was purified by reverse-phase HPLC using preparative Waters DeltaPak C4 (200x40mm, 300Å, 15µm). Mobile phase A: + 0.1% TFA, mobile phase B: Acetonitrile (ACN) + 0.1% TFA. The following gradient of eluent B was used: 25%B to 25%B over 5min, to 40%B over 25min, flow rate 80 mL / min, wavelength 214 nm. Collected fractions were lyophilized to afford the desired compound (35% yield). LCMS anal. calc. For C140H213N28O35S2+: 2912.52; found: 1456.6(M+2)2+. Example 4. Synthesis of MeCO-k(PEG2PEG2gEC18OH)-Pen*-N-T-7MeW-K(Ac)-Pen*- AEF-2Nal-THP- K(Ac)-N-3Pya-Sar-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 4)

[0056] Intermediate 4-1 Synthesis of Intermediate 4-1 The peptide was synthesized by standard Solid-phase Peptide Synthesis (SPPS) using Fmoc / t-Bu chemistry. The assembly was performed on a Rink-amide AM resin (110 μmol, 100-200Mesh; loading 0.33 mmol / g) on the Cem Liberty Blue microwave peptide synthesizer (CEM Inc.). During peptide assembly on solid phase, the side chain protecting groups were: tert-butyl for Thr; trityl for Pen and Asn; tert-butoxy-carbonyl for AEF. The N-terminal D- Lys was protected by the orthogonal DDe protecting group. All the amino acids were dissolved at a 0.4 M concentration in DMF. The acylation reactions were performed for 3 min at 90°C under MW irradiation with 5 folds excess of activated amino acids over the resin free amino groups. The amino acids were activated with equimolar amounts of 0.5M solution of DIC in DMF and Oxyma solution 1M in DMF. Double acylation reactions were performed for 3Pya and 2Nal. Fmoc deprotections were performed using 20%(V / V) piperidine in DMF. Capping of the free amino group was performed manually using 10eq of acetic anhydride in DMF. At the end of the peptide assembly on solid phase, the resin was treated with 100 ml of 3% hydrazine solution in DMF. The solution was drained, and the resin washed with DCM (3 × 5 mL). The deprotection step was repeated, and then the resin was washed with DCM (5 × 5 mL), DMF (5 × 5 mL). Further side chain derivatization was performed manually (PEG2, PEG2 and the gE (Fmoc- Glu-OtBu) residues) using DIC-HOAT (3Eq, 1:1:1) at room temperature. C18OH (18-(tert- butoxy)-18-oxooctadecanoic acid) was coupled using DIC-HOAT (6Eq, 1:1:1) at room temperature and complete acylation was monitored by ninhydrin test. At the end of the assembly the resin was washed with DMF, MeOH, DCM, and Et2O. The peptide was cleaved from solid support using 15 ml of TFA solution (v / v) (87.5% TFA, 5% H2O, 2.5% TIPS, 5%Phenol) for approximately 1.5 hours, at room temperature. The resin was then filtered and precipitated in cold MTBE (135mL). After centrifugation, the peptide pellets were washed with fresh cold diethyl-ether to remove the organic scavengers. The process was repeated twice. Final pellets were dried, re-suspended in H2O and acetonitrile 1:1 + 0.1% TFA and stirred overnight. The mixture was then lyophilized to afford the desired Intermediate 4-1 (89% yield). LCMS anal. calc. For C134H202N26O34S2: 2785.3; found: 1393.4 (M+2)2+. Synthesis of MeCO-k(PEG2PEG2gEC18OH)-Pen*-N-T-7MeW-K(Ac)-Pen*-AEF-2Nal-THP-K(Ac)-N-3Pya-Sar-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 4)Intermediate 4-1 was dissolved in ACN / H2O (5mg / ml). Saturated iodine in acetic acid was then added dropwise under stirring until yellow color persisted. Reaction was completed in 30 min (monitored by UPLC-MS). Solid ascorbic acid was added until the solution became clear. After lyophilization the cyclized peptide was purified by reverse-phase HPLC using preparative Waters DeltaPak C4 (200x40mm, 300Å, 15µm). Mobile phase A: + 0.1% TFA, mobile phase B: Acetonitrile (ACN) + 0.1% TFA. The following gradient of eluent B was used: 25%B to 25%B over 5min, to 40%B over 25min, flow rate 80 mL / min, wavelength 214 nm. Collected fractions were lyophilized to afford desired compound (28% yield): LCMS anal. calc. For C134H200N26O34S2: 2783.34; found: 1392.4 (M+2)2+. Example 5. Synthesis of MeCO-k(PEG2PEG6gEC18OH)-Pen*-N-T-7MeW-K(Ac)- Pen*-AEF-2Nal-THP-K(Ac)-N-3Pya-Sar-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 5)

[0057] Intermediate 5-1 The compound of SEQ ID NO: 5 was prepared according to similar procedures to prepare Example 1 or the like. The compound of SEQ ID NO: 5 was prepared in 13% yield. LCMS anal. calc. For C141H217N28O35S2+:2973.58; found: 1487.5 (M+2)2+. Example 6. Synthesis of MeCO-k(PEG2PEG2gE(c)C18OH)-Pen*-N-T-7MeW-K(Ac)- Pen*-AEF-2Nal-THP-K(Ac)-N-3Pya-Sar-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 6)

[0058] Synthesis of Intermediate 6-1 The peptide was synthesized by standard Solid-phase Peptide Synthesis (SPPS) using Fmoc / t-Bu chemistry. The assembly was performed on a Rink-amide AM resin (110 μmol, 100-200Mesh; loading 0.33 mmol / g) on the Cem Liberty Blue microwave peptide synthesizer (CEM Inc.). During peptide assembly on solid phase, the side chain protecting groups were: tert-butyl for Thr and Glu; trityl for Pen and Asn; tert-butoxy-carbonyl for AEF. The D-Lys was protected by the orthogonal DDe protecting group. All the amino acids were dissolved at a 0.4 M concentration in DMF. The acylation reactions were performed for 3 min at 90°C under MW irradiation with 5 folds excess of activated amino acids over the resin free amino groups. The amino acids were activated with equimolar amounts of 0.5M solution of DIC in DMF and Oxyma solution 1M in DMF. Double acylation reactions were performed for 3Pya and 2Nal. Fmoc deprotections were performed using 20%(V / V) piperidine in DMF. Capping of the free amino group was performed manually using 10eq of acetic anhydride in DMF. At the end of the peptide assembly on solid phase, the resin was treated with 100 ml of 3% hydrazine solution in DMF. The solution was drained, and the resin washed with DCM (5 × 5 mL) and DMF (5 × 5 mL). Further side chain derivatization was performed manually (PEG2, PEG2 and the gE ((S,E)-4- ((Fmoc)amino)-5-oxo-5-(prop-1-en-1-yloxy)pentanoic acid) residues) using DIC-HOAT (3Eq, 1:1:1) at room temperature. C18OH (18-(tert-butoxy)-18-oxooctadecanoic acid) was coupled using DIC-HOAT (6Eq, 1:1:1) at room temperature and complete acylation was monitored by ninhydrin test. The resin was then treated with 0.25Eq of Pd Tetrakis, 24 Eq of Phenylsilane in 5ml of DCM Dry under N2 atmosphere for 30 min (process repeated 2 times); washed with DCM, DMF and a solution of 0.5% sodium dimethyldithiocarbamate (0.5%) and DIPEA (0.5%) in DMF. The resin was then manually preactivated with HATU (1.2Eq) and dipea (2Eq) and was left under stirring for 10 minutes. Amino-carnitine (2 Eq; (R)-2-amino-4-(tert-butoxy)-N,N,N-trimethyl-4-oxobutan-1-aminium) was added. Reaction was completed after 2hr (monitored by test cleavage). At the end of the assembly the resin was washed with DMF, MeOH, DCM, Et2O. The peptide was cleaved from solid support using 15 ml of TFA solution (v / v) (87.5% TFA, 5% H2O, 2.5% TIPS, 5%Phenol) for approximately 1.5 hours, at room temperature. The resin was then filtered and precipitated in cold MTBE (135mL). After centrifugation, the peptide pellets were washed with fresh cold diethyl-ether to remove the organic scavengers. The process was repeated twice. Final pellets were dried, re-suspended in H2O and acetonitrile 1:1 + 0.1% TFA and stirred overnight. The mixture was then lyophilized to afford the Intermediate 6-1 (73.6% yield). LCMS anal. calc. For C141H217N28O35S2+: 2928.55; found: 1464.74 (M+2)2+. Synthesis of MeCO-k(PEG2PEG2gE(c)C18OH)-Pen*-N-T-7MeW-K(Ac)-Pen*-AEF-2Nal- THP-K(Ac)-N-3Pya-Sar-CONH2(SEQ ID NO:6) Intermediate 6-1 was dissolved in ACN / H2O (1mg / ml). Saturated Iodine in acetic acid was then added dropwise under stirring until yellow color persisted. Reaction was completed in 30 min (monitored by UPLC-MS). Solid ascorbic acid was added until the solution became clear. After lyophilization the cyclized peptide was purified by reverse-phase HPLC using preparative Waters DeltaPak C4 (200x40mm, 300Å, 15µm). Mobile phase A: + 0.1% TFA, mobile phase B: Acetonitrile (ACN) + 0.1% TFA. The following gradient of eluent B was used: 20%B to 20%B over 5min, to 35%B over 25min, flow rate 80 mL / min, wavelength 214 nm. Collected fractions were lyophilized to afford the desired compound (20% yield). LCMS anal. calc. For C141H215N28O35S2+: 2926.55; found 1463.9 (M+2)2+. Example 7. Synthesis of MeCO-r-Pen*-N-T-7MeW-K(Ac)-Pen*-AEF-2Nal-THP-E-N- 3Pya-Sar-K(PEG2PEG2gEC18OH)-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 7)

[0059] Intermediate 7-1 Synthesis of Intermediate 7-1 Intermediate 7-1 was synthesized by standard Solid-phase Peptide Synthesis (SPPS) using Fmoc / t-Bu chemistry. The assembly was performed on a Rink-amide AM resin (110 μmol, 100-200Mesh; loading 0.33 mmol / g) on the Cem Liberty Blue microwave peptide synthesizer (CEM Inc.). During peptide assembly on solid phase, the side chain protecting groups were: tert-butyl for Thr and Glu; trityl for Pen and Asn; tert-butoxy-carbonyl for AEF, Pbf (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl) for Arg. The C-terminal Lys was protected by the orthogonal DDe protecting group. All the amino acids were dissolved at a 0.4 M concentration in DMF. The acylation reactions were performed for 3 min at 90 °C under microwave (MW) irradiation with 5 folds excess of activated amino acids over the resin free amino groups. The amino acids were activated with equimolar amounts of 0.5M solution of DIC in DMF and Oxyma solution 1M in DMF. Double acylation reactions were performed for 3Pya and 2Nal. Fmoc deprotections were performed using 20% (V / V) piperidine in DMF. Capping of the free amino group was performed manually using 10eq of acetic anhydride in DMF. At the end of the peptide assembly on solid phase, the resin was treated with 100 ml of 3% hydrazine solution in DMF. The solution was drained, and the resin washed with DCM (3 × 5 mL). The deprotection step was repeated, and then the resin was washed with DCM (5 × 5 mL) and DMF (5 × 5 mL). Further side chain derivatization was performed on Cem Liberty Blue microwave peptide synthesizer using standard coupling conditions with 5 folds excess of activated building blocks (Fmoc-PEG2, Fmoc-PEG2 and the Fmoc-gE (Fmoc-Glu-OtBu) and equimolar amounts of 0.5M solution of DIC in DMF and Oxyma solution 1M in DMF. C18OH (18- (tert-butoxy)-18-oxooctadecanoic acid) was coupled manually using DIC-HOAT (3Eq, 1:1:1) at room temperature and complete acylation was monitored by ninhydrin test. At the end of the assembly the resin was washed with DMF, MeOH, DCM, and Et2O. The peptide was cleaved from solid support using 15 ml of TFA solution (v / v) (87.5% TFA, 5% H2O, 2.5% TIPS, 5% Phenol) for approximately 1.5 hours, at room temperature. The resin was then filtered and precipitated in cold MTBE (135mL). After centrifugation, the peptide pellets were washed with fresh cold diethyl-ether to remove the organic scavengers. The process was repeated twice. Final pellets were dried, re-suspended in H2O and acetonitrile 1:1 + 0.1% TFA and stirred overnight. The mixture was then lyophilized to afford the desired Intermediate 7-1 (50% yield). LCMS anal. calc. for C137H207N29O36S2: 2900.45; found: 967.8 (M+3)3+. Synthesis of MeCO-r-Pen*-N-T-7MeW-K(Ac)-Pen*-AEF-2Nal-THP-E-N-3Pya-Sar- K(PEG2PEG2gEC18OH)-CONH2(*Pen-Pen form disulfide bond) (SEQ ID NO: 7) Intermediate 7-1 was dissolved in ACN / H2O (1mg / ml). Saturated iodine in acetic acid was then added dropwise under stirring until yellow color persisted. Reaction was completed in 30 min (monitored by UPLC-MS). Solid ascorbic acid was added until the solution became clear. After lyophilization the cyclized peptide was purified by reverse-phase HPLC using preparative Waters DeltaPak C4 (200x40mm, 300Å, 15µm). Mobile phase A: + 0.1% TFA, mobile phase B: Acetonitrile (ACN) + 0.1% TFA. The following gradient of eluent B was used: 25%B to 25%B over 5min, to 40%B over 25min, flow rate 80 mL / min, wavelength 214 nm. Collected fractions were lyophilized to afford the desired compound (5% yield). LCMS anal. calc. for C137H205N29O36S2: 2898.43; found; 1450.0 (M+2)2+. Example 8. Synthesis of MeCO-k(PEG12gEC18OH)-Pen*-N-T-7MeW-K(Ac)-Pen*- AEF-2Nal-THP-K(Ac)-N-3Pya-Sar-CONH2(SEQ ID NO: 8)

[0060] Peptide Assembly: The peptide was synthesized by solid-phase peptide synthesis (SPPS) using Fmoc chemistry. Peptide assembly was performed on Rink Amide MBHA resin (0.15 mmol, 0.65 mmol / g) on a Biotage Syro II parallel peptide synthesizer. Side chain protecting groups used were: tert-butyl (tBu) for Thr and Glu; trityl (Trt) for Pen and Asn; tert-butoxy-carbonyl (Boc) for AEF, Pbf (2,2,4,6,7-pentamethyldihydrobenzofuran-5- sulfonyl) for Arg, and Dde for the N-terminal Lys. Fmoc-protected amino acids (5 eq, 0.75 mmol, 5 mL, 0.5 M in DMF) were coupled using HATU (5 eq, 0.75 mmol, 1.56 mL, 0.48 M in DMF) and NMM (10 eq, 1.5 mmol, 0.75 mL, 2 M in DMF) at room temperature for 1 hr. Fmoc deprotections were carried out by treating the resin with 40% piperidine in DMF for 3 min, followed by another treatment with 20% piperidine in DMF for 9 min. Capping of the free terminal amino group was performed by treating the resin with a solution of acetic anhydride:NMM:DMF (2:2:6, 5 mL) at rt for 20 min. The Dde group was then deprotected by treating the resin with 2% hydrazine in DMF (5 mL) at rt for 10 min. The solution was drained, followed by addition of a fresh solution for 10 min. The resin was drained and washed with DMF and DCM. Side-chain derivatization was performed in the Biotage Syro II peptide synthesizer using the conditions described above. Disulfide Formation: After assembly, resin-bound peptide was treated with a solution of iodine (4 eq) in DMF and allowed to mix at rt for 1 hr. The resin was washed with 1 M sodium ascorbate in DMF, DMF, and DCM and dried. Cleavage and Purification: The peptide was cleaved from solid support and deprotected by treating the resin with cleavage cocktail (5 mL, 92.5% TFA, 2.5% water, 2.5% TIPS, 2.5% DODT) at 42 °C on a CEM Razor cleavage station for 30 min. The resin was filtered and washed with cleavage cocktail (2 mL). To the filtrate was added cold MTBE to precipitate the peptide. After centrifugation, the peptide pellets were washed with fresh cold MTBE twice. The dried pellets were dissolved in water and acetonitrile (1:1 + 0.1% TFA) and lyophilized. The crude peptide was then purified by reverse-phase HPLC using a Waters Xbridge CSH C18 OBD 19x150mm column. Mobile phase A: water + 0.1% TFA, mobile phase B: acetonitrile + 0.1% TFA. Gradient: 35% B to 40% B over 10 min, flow rate 25 mL / min. Pure fractions were combined and lyophilized to afford the desired product (12% yield). LCMS anal. calc. for C149H231N25O41S2: 3090.62, observed 1546.6 (M+2H)2+, 1031.6 (M+3H)3+, 774.0 (M+4H)4+. Example 9: Pharmacokinetic Study of the compositions as described and provided for herein Following Single Intravenous, Oral (PO), Intraduodenal (ID) or Intracolonic Administration (IC) to Rats. The compositions were administered by intravenous, oral, or intracolonic administration routes to male Sprague-Dawley rats. The compositions were administered as follows: Dose: 0.5 mg / kg (IV), 5 mg / kg (ID), or 10 mg / kg (PO or IC) in a dose volume: 1 mL / kg (IV), 5 mg / kg (ID), or 10 mg / mL (PO or IC). Plasma is collected and treated with 5% (volume%) protease inhibitor. Samples were collected as follows: IV sampling time points: 0.08, 0.25, 0.5, 1, 3, 6, 8, 12, 24 hours post-dose and PO, ID, and IC sampling time points: 0.25, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose. Plasma was analyzed by LC-MS / MS for concentrations (ng / mL) of parent compound and concentration data and pharmacokinetic parameters were calculated. The table below illustrates the data. PK Data of the compound of SEQ ID NO:7 on Rat with Intraduodenal (ID) dosing at 5 mg / kg along with absorption enhancers at 100 mg / kg as shown below.

[0061] SNAC, Sodium caprate powder, Labrasol oil, Lauroyl-Lcarnitine, and Sodium octanoate significantly increased the AUClast.of SEQ ID NO:7 visa intraduodenal (ID) dosing with rats as the results are shown in the table below. Unexpectedly and surprisingly, Sodium caprate powder and Labrasol oil increased the AUClast.of SEQ ID NO:7 by about 7 and 10 folds respectively. The following table illustrates the bioavailability data of the compounds of SEQ ID NOs:1-8 on Rat with Intracolonic Administration (IC) and Oral (PO) dosing at 10 mg / kg with and without sodium caprate at 100 mg / kg

[0062] F%: bioavailability IC / C10: Intracolonic Administration of the peptide at 10 mg / kg along with Sodium caprate at 100 mg / kg. PO / C10: Oral Administration of the peptide at 10 mg / kg along with Sodium caprate at 100 mg / kg. Unexpectedly and surprisingly, sodium caprate powder significantly increased the bioavailability of all the compounds of SEQ ID NOs:1-8 in a range from about 2 to about 20 folds when it was co-administrated with Sodium caprate at 100 mg / kg. The compounds of SEQ ID NO: 9-40 also exhibited high bioavailability when co-administered with Sodium caprate. All references cited herein are incorporated by reference to the same extent as if each individual publication, database entry (e.g., Genbank sequences or GeneID entries), patent application, or patent, was specifically and individually indicated to be incorporated by reference. This statement of incorporation by reference is intended by Applicants, pursuant to 37 C.F.R. § 1.57(b)(1), to relate to each and every individual publication, database entry (e.g., Genbank sequences or GeneID entries), patent application, or patent, each of which is clearly identified in compliance with 37 C.F.R. § 1.57(b)(2), even if such citation is not immediately adjacent to a dedicated statement of incorporation by reference. The inclusion of dedicated statements of incorporation by reference, if any, within the specification does not in any way weaken this general statement of incorporation by reference. Citation of the references herein is not intended as an admission that the reference is pertinent prior art, nor does it constitute any admission as to the contents or date of these publications or documents. The present embodiments are not to be limited in scope by the specific embodiments described herein. Indeed, various modifications in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the embodiments and any appended claims. The present specification is considered to be sufficient to enable one skilled in the art to practice the embodiments. Various modifications in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description and fall within the scope of the present disclosure and any appended claims.

Claims

What is claimed is:

1. An oral pharmaceutical formulation comprising: an absorption enhancer; and a lipidated peptide comprising 9 to 20 amino acids; wherein the lipidated peptide is cyclized to form a ring, wherein the ring comprises 4 to 14 amino acids; and wherein the ratio of the absorption enhancer to the lipidated peptide is no greater than 50:1 (w / w).

2. The oral pharmaceutical formulation of claim 1, wherein the lipidated peptide comprises the amino acid sequence of Formula (A): R1a-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-3Pya-X16-X17-R2a(A), or a pharmaceutically acceptable salt thereof, wherein: R1ais an N-terminal capping group (e.g., MeCO), Zpeg, or Zlipid; X3is any amino acid or absent; X4is 4AminoPro, Abu, aG, aMeC, C, Dap, Pen, Pen(oXyl), Pen(mXyl), Pen(pXyl), or Pra; X5is any amino acid; X6is any amino acid; X7is 7MeW, W, or absent; X8is any amino acid; X9is aMeC, aG, C, D, E, hE, Pen, Dap, or Dap(N3) X10is AEF, TMAPF, AEF(d), TMAPF-Zlipid, APEG3F, or AEF-Zlipid; X11is any amino acid; X12is any amino acid; X13is any amino acid; X14is any amino acid; X16is any amino acid; X17is any amino acid or absent; R2ais a C-terminal capping group (e.g., CONH2), CONH-Zpeg, or CO-Zlipid; Zpeg, independently for each occurrence, is a polyethylene glycol chain; Zlipid, independently for each occurrence, is a lipophilic substituent; wherein the peptide comprises a linkage between the residues at X4and X9; andwherein the polypeptide comprises at least one lipophilic substituent at a position selected from R1, X3, X5, X6, X8, X10, X12, X13, X14, X16, X17, or R2.

3. The oral pharmaceutical formulation of claim 2, wherein: R1ais MeCO, Zpeg, Zlipid, succiniccarn, 5cpaCO, or AEEP-Zlipid; X3is R, K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; X4is 4AminoPro, Abu, aG, aMeC, C, Dap, Pen, Pen(oXyl), Pen(mXyl), Pen(pXyl), or Pra; X5is N, N(NMe2), K(d), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X6is T, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid; X7is 7MeW, W, or absent; X8is K(Ac), K(d), K(NMeAc), Q, K-Zlipid, K-Zpeg, NMeK-Zlipid, Dab-Zlipid, Dab(NMecarn), or Dab-Zpeg; X9is aMeC, aG, C, D, E, hE, Pen, Dap, or Dap(N3); X10is AEF, TMAPF, AEF(d), TMAPF-Zlipid, APEG3F, or AEF-Zlipid; X11is a substituted or unsubstituted 2Nal or a substituted or unsubstituted 3Quin, X12is THP, K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X13is E, K(Ac), K(d), K-Zpeg, K(NMeAc), Dab(NMecarn), E(OAll), K-Zlipid, Dab- Zlipid, NMeK-Zlipid, or absent; X14is N, K-Zlipid, NMeK-Zlipid, or Dab-ZlipidX16is Sar, NMeK(d), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X17is K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; and R2 is CONH2, CONMe2, CONH-Zpeg, or CO-Zlipid.

4. The oral pharmaceutical composition of claim 1, wherein the lipidated peptide comprises the amino acid sequence of Formula (B): R1a-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-3Pya-X16-X17-R2a(B), or a pharmaceutically acceptable salt thereof, wherein: R1ais an N-terminal capping group (e.g., MeCO), Zpeg, or Zlipid; X3is any amino acid or absent; X4is any amino acid; X5is any amino acid; X6is any amino acid; X7is 7MeW or W;X8is any amino acid; X9is any amino acid; X10is AEF, TMAPF, AEF(d), TMAPF-Zpeg, TMAPF-Zlipid, APEG3F, AEF-Zpeg, or AEF-Zlipid; X11is any amino acid; X12is any amino acid; X13is any amino acid; X14is any amino acid; X16is any amino acid; X17is any amino acid or absent; R2ais a C-terminal capping group (e.g., CONH2), CONH-Zpeg, or CO-Zlipid; Zpeg, independently for each occurrence, is a polyethylene glycol chain; Zlipid, independently for each occurrence, is a lipophilic substituent; wherein the polypeptide comprises at least one lipophilic substituent or polyethylene glycol chain at a position selected from R1a, X3, X4X5, X6, X8, X9X10, X11, X12, X13, X14, X16, X17, or R2a; and wherein the peptide is cyclized to form a first ring, wherein the first ring comprises 4- 14 amino acids.

5. The oral pharmaceutical composition of claim 4, wherein the first ring comprises 4-9 or 11 amino acids.

6. The oral pharmaceutical composition of claim 4, wherein the first ring is formed between X4and X9, X4and X13, X5and X10, X3and X13, or X6and X9.

7. The oral pharmaceutical composition of claim 4, wherein the first ring is formed between X4and X9, X4and X13, or X6and X9.

8. The oral pharmaceutical composition of claim 7, wherein the first ring is formed between X4and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole.

9. The peptide of claim 7, wherein the first ring is formed between X4and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole.

10. The peptide of claim 7, wherein the first ring is formed between X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole.

11. The peptide of any one of claims 4-10, wherein the peptide is further cyclized to form a second ring comprising 4-14 amino acids.

12. The peptide of claim 11, wherein the second ring comprises 4, 6, 10, or 11 amino acids.

13. The peptide of claim 8, wherein the peptide is further cyclized to form a second ring, wherein: the second ring is formed between X3and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; the second ring is formed between X5and X10via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; the second ring is formed between X10and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; or the second ring is formed between X13and the N-terminus of the peptide via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole.

14. The peptide of claim 9, wherein the peptide is further cyclized to form a second ring, wherein: the second ring is formed between X5and X10via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; orthe second ring is formed between X6and X9via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole.

15. The peptide of claim 10, wherein the peptide is further cyclized to form a second ring, wherein: the second ring is formed between X3and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; the second ring is formed between X4and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; the second ring is formed between X5and X10via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; the second ring is formed between X10and X13via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole; or the second ring is formed between X13and the N-terminus of the peptide via a linker having one or more groups selected from the group consisting of a disulfide, thioether, amide, olefin, ether, alkylene, and triazole.

16. The oral pharmaceutical composition of claim 4, or a pharmaceutically acceptable salt thereof, wherein: R1ais an N-terminal capping group (e.g., MeCO), Zpeg, or Zlipid; X3is r, k(d), k-Zlipid, dab-Zlipid, NMek-Zlipid, or absent; X4is 4AminoPro, Abu, aG, aMeC, C, Dap, Pen, Pen(oXyl), Pen(mXyl), Pen(pXyl), or Pra; X5is E, N, N(NMe2), K(d), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X6is T, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid; X7is 7MeW or W; X8is K(Ac), K(d), K(NMeAc), Q, K-Zlipid, K-Zpeg, NMeK-Zlipid, Dab-Zlipid, Dab(NMecarn), or Dab-Zpeg; X9is aMeC, aG, C, D, E, hE, Pen, Dap, or Dap(N3);X10is AEF, TMAPF, AEF(d), TMAPF-Zpeg, TMAPF-Zlipid, APEG3F, AEF-Zpeg, or AEF-Zlipid; X11is 2Nal or 6OH2Nal; X12is THP, K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X13is E, K(Ac), K(d), K-Zpeg, K(NMeAc), Dab(NMecarn), E(OAll), K-Zlipid, Dab- Zlipid, NMeK-Zlipid; X14is N, K-Zlipid, NMeK-Zlipid, or Dab-Zlipid; X16is Sar, NMeK(d), K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; X17is K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; R2ais a C-terminal capping group (e.g., CONH2), CONH-Zpeg, or CO-Zlipid; Zpeg, independently for each occurrence, is a polyethylene glycol chain; Zlipid, independently for each occurrence, is a lipophilic substituent; wherein the peptide comprises a linkage between the residues at X4and X9; and wherein the polypeptide comprises at least one lipophilic substituent at a position selected from R1a, X3, X5, X6, X8, X10, X12, X13, X14, X16, X17, or R2a, or a polyethylene glycol chain at a position selected from R1a, X8, X10, X13, or R2a.

17. The oral pharmaceutical composition of claim 4 or claim 16, wherein: R1ais an MeCO, Zpeg, Zlipid, or 5cpaCO; X3is r, k(d), k-Zlipid, dab-Zlipid, NMek-Zlipid, or absent; X4is Pen; X5is E, N, N(NMe2), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X6is T; X7is 7MeW; X8is K(Ac), K(d), K(NMeAc), K-Zlipid, K-Zpeg, NMeK-Zlipid, Dab-Zlipid, or Dab-Zpeg; X9is Pen; X10is AEF, TMAPF, APEG3F, AEF-Zpeg, or AEF-Zlipid; X11is 2Nal or 6OH2Nal; X12is THP; X13is E, K(Ac), K-Zpeg, K(NMeAc), K-Zlipid, Dab-Zlipid, or NMeK-Zlipid; X14is N; X16is Sar or NMeK-Zlipid; X17is K-Zlipid, Dab-Zlipid, NMeK-Zlipid, or absent; R2ais CONH2, CONMe2, CONH-Zpeg, or CO-Zlipid;wherein the peptide comprises a disulfide linkage between the residues at X4and X9; and wherein the polypeptide comprises at least one lipophilic substituent at a position selected from R1a, X3, X5, X8, X10, X13, X16, X17, or R2a, or a polyethylene glycol chain at a position selected from R1a, X8, X10, X13, or R2a.

18. The oral pharmaceutical formulation of claim 1, wherein the lipidated peptide is a compound having a formula of,or a pharmaceutically acceptable salt or solvate form thereof, wherein: L is -O-, -S-, or -S-S-; R1, R2, R3, R4, R5, R6, R8, R9, and R10are each independently H,R14,-(CH2)nNHR12, -(CH2)nC(=O)NHR12, -(CH2)nC(=O)OR12, -C(=O)(CH2)nNHR12, or -C(=O)(CH2)nOR12; R7 is -(CH2)pNHR13or -(CH2)qNHC(=NH)NH2; each m, n, p, and q are independently 1, 2, 3, 4, or 5; each R11, R12, R13, and R14are independently H or a lipid moiety.

19. The oral pharmaceutical formulation of claim 18, wherein the lipidated peptide is a compound having a formula of.

20. The oral pharmaceutical formulation of claim 18, wherein the compound is a compound having a formula of.

21. The oral pharmaceutical formulation of claim 18, wherein the compound is a compound having a formula of.

22. The oral pharmaceutical formulation of claims 18-21, wherein each lipid moiety or lipophilic substituent is independently selected from a Z1to Z5group: Z1iswherein: each PEG is independently –OCH2CH2-; each n’ is independently 0 or the range of 2-24, when n’ is 0 the group is absent and replaced by a bond; each m’is independently selected from 0 or the range of 2-24 for each occurrence, when m’ is 0 the group is replaced by a bond; each v’ is independently selected from the range of 1-4 for each occurrence; each v’’ is independently selected from the range of 0-4 for each occurrence, when v’’ is 0 the group is replaced by a bond; p’ is 1-3; V’ is sp6 or gEgE; each X is independently gE, dgE, 4SB, P, PPP, gE-(c), gE-(C), sp6, gDab, eK, Trx, or absent; each Y is independently gE, sp6, GolA, Pro, D-Pro, meG, Dab, Trx, or absent; T is Trx; each U is independently hydrogen or methyl; each o’ is independently 6-18; each V is independently -COOH, tetrazole, GolB, mXOH, pXOH, OPhenyl, carnitine, d-carnitine, or hydrogen; Z3is -gE-C(O)(CH2)6-10CH3, or -gE-C(O)(CH2)11-18CH3; Z4is -C(O)(CH2)6-18COOH or -C(O)(CH2)6-18COO(C1-4alkyl); Z5iswherein: n’’ and m’’ are independently selected from the range of 0 to 24; X’ is absent or is selected from the group consising of E, dgE, 4SB, gE- (c), gE-(C), sp6, gDab, eK, or Trx; Y’ is absent or is selected from the group consisting of E, dgE, 4SB, gE- (c), gE-(C), sp6, gDab, eK, or Trx; and Xaa is a diamino-carboxylic acid.

23. The oral pharmaceutical formulation of claims 18-21, wherein each lipid moiety or lipophilic substituent is ,ZEis -H, -COOH, phenoxy, or tetrazolyl; ZFis -H or -CH3; Xaaais, independently for each occurrence,,pa, independently for each occurrence, is 0, 1, 2, 3, 4, 5, or 6; qais 1, 2, 3, 4, 5, or 6; rais an integer from 6 to 24; vais 0 or 1; and wa, independently for each occurrence, is 0 or 1.

24. The oral pharmaceutical formulation of any one of claims 18-23, wherein R2is methyl.

25. The oral pharmaceutical formulation of any one of claims 18-24, wherein R3is H.

26. The oral pharmaceutical formulation of any one of claims 18-25, wherein R4is H.

27. The oral pharmaceutical formulation of any one of claims 18-26, wherein R5is H.

28. The oral pharmaceutical formulation of any one of claims 18-27, wherein R8is H.

29. The oral pharmaceutical formulation of any one of claims 18-28, wherein R4is H.

30. The oral pharmaceutical formulation of any one of claims 18-29, wherein R9is H.

31. The oral pharmaceutical formulation of any one of claims 18-30, wherein R10is -C(=O)CH3.

32. The oral pharmaceutical formulation of any one of claims 18-23, wherein the compound, or a pharmaceutically acceptable salt thereof, has a formula of.

33. The oral pharmaceutical formulation of claim 32, wherein R7is -(CH2)qC(=O)NH)NH2.

34. The oral pharmaceutical formulation of claim 33, wherein q is 3.

35. The oral pharmaceutical formulation of claim 34, wherein the compound has a formula ofFormula III.

36. The oral pharmaceutical formulation of claim 35, wherein the compound, or a pharmaceutically acceptable salt thereof, has a formula of(SEQ ID NO: 1).

37. The oral pharmaceutical formulation of claim 32, wherein R6is -C(=O)CH3.

38. The oral pharmaceutical formulation of claim 37, wherein R7is -(CH2)pNHR12.

39. The oral pharmaceutical formulation of claim 38, wherein p is 4.

40. The oral pharmaceutical formulation of claim 39, wherein the compound, or a pharmaceutically acceptable salt thereof, has a formula ofFormula IV.

41. The oral pharmaceutical formulation of claim 40, wherein the compound, or a pharmaceutically acceptable salt thereof, has a formula of(SEQ ID NO: 2),ĨSEQ ID NO: 4),(SEQ ID NO: 8).

42. The oral pharmaceutical formulation of any one of claims 18-23, wherein the compound, or a pharmaceutically acceptable salt thereof, has a formula ofFormula V.

43. The oral pharmaceutical formulation of claim 42, wherein R1is.

44. The oral pharmaceutical formulation of claim 43, wherein m is 4.

45. The oral pharmaceutical formulation of claim 44, wherein the compound, or a pharmaceutically acceptable salt thereof, has a formula ofĨSEQ ID NO: 7).

46. The oral pharmaceutical formulation of claim 19, wherein the compound, or a pharmaceutically acceptable salt thereof, has a formula ofĨSEQ ID NO: 2),ĨSEQ ID NO: 4),ĨSEQ ID NO: 6),ĨSEQ ID NO: 8),ĨSEQ ID NO: 1), or(SEQ ID NO: 7).

47. The oral pharmaceutical formulation of claim 1, wherein the lipidated peptide is selected from the group consisting of SEQ ID NOS: 1-40.

48. The oral pharmaceutical formulation of any one of claims 1-47, wherein the weight ratio (w / w) of the absorption enhancer to the lipidated peptide or a pharmaceutically acceptable salt or solvate form thereof is in a range from about 1 to about 200.

49. The oral pharmaceutical formulation of any one of claims 1-47, wherein the weight ratio (w / w) of the absorption enhancer to the lipidated peptide or a pharmaceutically acceptable salt or solvate form thereof is in a range from about 1 to about 100.

50. The oral pharmaceutical formulation of any one of claims 1-47, wherein the weight ratio (w / w) of the absorption enhancer to the lipidated peptide or a pharmaceutically acceptable salt or solvate form thereof is in a range from about 1 to about 20.

51. The oral pharmaceutical formulation of any one of claims 1-47, wherein the weight ratio (w / w) of the absorption enhancer to the lipidated peptide or a pharmaceutically acceptable salt or solvate form thereof is in an range from about 1 to about 10.

52. The oral pharmaceutical formulation of any one of claims 1-47, wherein the ratio of the absorption enhancer to the lipidated peptide is no less than 3:1 (w / w).

53. The oral pharmaceutical formulation of any one of claims 1-47, wherein the ratio of the absorption enhancer to the lipidated peptide is between 3:1 (w / w) and 30:1 (w / w).

54. The oral pharmaceutical formulation of claim 4 of any one of claims 1-47, wherein the ratio of the absorption enhancer to the lipidated peptide is between 5:1 (w / w) and 50:1 (w / w).

55. The oral pharmaceutical formulation of any one of claims 1-47, wherein the ratio of the absorption enhancer to the lipidated peptide is about 10:1 (w / w).

56. The oral pharmaceutical formulation of any one of claims 1-55, wherein the absorption enhancer is present in an amount greater than 250 mg.

57. The oral pharmaceutical formulation of any one of claims 1-56, wherein the absorption enhancer is present in an amount less than 700 mg.

58. The oral pharmaceutical formulation of any one of claims 1-57, wherein the absorption enhancer comprises one or more of sodium caprate, sodium caprylate, sodium palmitate, sodium stearate, sodium citrate, sodium salicylate, sodium salcaprozate (SNAC), a polyethylene glycol (PEG)-modified medium chain fatty acid triglyceride of capric and caprylic acid, sucrose laurate, sodium octanoate, labrasol, and lauroyl-L-carnitine (LC).

59. The oral pharmaceutical formulation of any one of claims 1-58, wherein the absorption enhancer comprises sodium salcaprozate (SNAC).

60. The oral pharmaceutical formulation of any one of claims 1-58, wherein the absorption enhancer comprises lauroyl-L-carnitine (LC).

61. The oral pharmaceutical formulation of any one of claims 1-58, wherein the absorption enhancer comprises sodium octanoate.

62. The oral pharmaceutical formulation of any one of claims 1-58, wherein the absorption enhancer comprises sodium labrasol.

63. The oral pharmaceutical formulation of any one of claims 1-58, wherein the absorption enhancer comprises sodium caprate.

64. The oral pharmaceutical formulation of any one of claims 63, wherein the sodium caprate has a purity of at least 98%.

65. The oral pharmaceutical formulation of any one of claims 1-64, wherein the oral pharmaceutical formulation further comprises one or more pharmaceutically acceptable excipients.

66. The oral pharmaceutical formulation of any one of claims 1-65, wherein the oral pharmaceutical formulation improves oral bioavailability of the compound.

67. The oral pharmaceutical formulation of any one of claims 1-65, wherein the oral pharmaceutical formulation improves oral bioavailability of the compound by about 2 to about 500 fold.

68. The oral pharmaceutical formulation of any one of claims 1-65, wherein the oral pharmaceutical formulation improves oral bioavailability of the compound by about 2 to about 250 fold.

69. A method of increasing the bioavailability of a lipidated peptide as described in any one of claims 1-47 in a subject comprising orally administering the compound, or a pharmaceutically acceptable salt or solvate form thereof, and an absorption enhancer.

70. The method of claim 69, wherein the absorption enhancer comprises one or more of sodium caprate, sodium caprylate, sodium palmitate, sodium stearate, sodium citrate, sodium salicylate, sodium salcaprozate (SNAC), a polyethylene glycol (PEG)- modified medium chain fatty acid triglyceride of capric and caprylic acid, sucrose laurate, sodium octanoate, labrasol, and lauroyl-L-carnitine (LC).

71. The method of claims 69 or 70, wherein the compound or a pharmaceutically acceptable salt or solvate form thereof, and the absorption enhancer are co- administered.

72. The method of any one of claims 69-71, wherein the compound or a pharmaceutically acceptable salt or solvate form thereof, and the enhancer are co-administered in a pharmaceutically acceptable formulation.

73. Use of an oral pharmaceutical formulation according to any of claims 1-68 for the preparation of a medicament for the treatment of an inflammatory disorder or autoimmune inflammatory disorder.

74. The use of claim 73 for the preparation of a medicament for the treatment of autoimmune inflammation and related diseases and disorders including, but not limited to: multiple sclerosis, asthma, rheumatoid arthritis, inflammation of the gut, inflammatory bowel diseases (IBDs), juvenile IBD, adolescent IBD, Crohn’s disease, ulcerative colitis, Celiac disease (nontropical Sprue), microscopic colitis, collagenous colitis, eosinophilic gastroenteritis / esophagitis, colitis associated with radio- or chemo-therapy, colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1, sarcoidosis, Systemic Lupus Erythematosus, ankylosing spondylitis (axial spondyloarthritis), psoriatic arthritis, psoriasis (e.g., plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, Palmo-Plantar Pustulosis, psoriasis vulgaris, or erythrodermic psoriasis), atopic dermatitis, acne ectopica, enteropathy associated with seronegative arthropathies, chronicgranulomatous disease, glycogen storage disease type 1b, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Wiskott-Aldrich Syndrome, pouchitis, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, primary biliary cirrhosis, viral-associated enteropathy, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, uveitis, or graft versus host disease.

75. The use of claim 73 for the preparation of a medicament for the treatment of a disease or disorder selected from Inflammatory Bowel Disease (IBD), Ulcerative colitis (UC), Crohn’ s Disease (CD), psoriasis (PsO), and psoriatic arthritis (PsA).

76. A method for treating a disease or disorder associated with Interleukin 23 (IL- 23) / Interleukin 23 Receptor (IL-23R), which comprises administering an effective amount of a pharmaceutical formulation according to any of claims 1-68 to a patient in need thereof.

77. The method of claim 76, wherein the disease or disorder is associated with autoimmune inflammation.

78. The method of claim 77, wherein the disease or disorder is multiple sclerosis, asthma, rheumatoid arthritis, inflammation of the gut, inflammatory bowel diseases (IBDs), juvenile IBD, adolescent IBD, Crohn’ s disease, ulcerative colitis, Celiac disease (nontropical Sprue), microscopic colitis, collagenous colitis, eosinophilic gastroenteritis / esophagitis, colitis associated with radio- or chemo-therapy, colitis associated with disorders of innate immunity as in leukocyte adhesion deficiency-1, sarcoidosis, Systemic Lupus Erythematosus, ankylosing spondylitis (axial spondyloarthritis), psoriatic arthritis, psoriasis (e.g., plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, Palmo-Plantar Pustulosis, psoriasis vulgaris, or erythrodermic psoriasis), atopic dermatitis, acne ectopica, enteropathy associated with seronegative arthropathies, chronic granulomatous disease, glycogen storage disease type 1b, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Wiskott-Aldrich Syndrome, pouchitis, pouchitis resulting after proctocolectomy and ileoanal anastomosis, gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, primary biliary cirrhosis, viral-associatedenteropathy, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, uveitis, or graft versus host disease.

79. The method of claim 78, wherein the disease or disorder is associated with Ulcerative colitis (UC), Crohn’s Disease (CD), psoriasis (PsO), or psoriatic arthritis (PsA).

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