Corticotropin releasing factor receptor 2 (CRFR2) agonists

Abstract

This disclosure provides corticotropin releasing factor receptor 2 (CRFR2) agonist peptides, pharmaceutical compositions comprising such peptides, and methods of using such peptides to treat and / or prevent, for example, cardiovascular diseases, obesity, diabetes, sarcopenia, cachexia, kidney disease, heart failure and pulmonary hypertension.

Description

Attorney Docket No.14794-010-228 / 320.WO1.PCT CORTICOTROPIN RELEASING FACTOR RECEPTOR 2 (CRFR2) AGONISTS RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Application No. 63 / 636,635, filed on April 19, 2024, the entirety of which is incorporated herein by reference. SEQUENCE LISTING

[0002] This application contains a computer readable Sequence Listing which has been submitted in XML file format with this application, the entire content of which is incorporated by reference herein in its entirety. The Sequence Listing XML file submitted with this application is entitled “14794-010-228_SEQ_LISTING.xml”, was created on April 14, 2025 and is 521,179 bytes in size. FIELD

[0003] This disclosure provides corticotropin releasing factor receptor 2 (CRFR2) agonist peptides, pharmaceutical compositions comprising such peptides, and methods of using such peptides to treat and / or prevent, for example, cardiovascular diseases, obesity, diabetes, sarcopenia, cachexia, kidney disease, heart failure and pulmonary hypertension. BACKGROUND

[0004] The urocortins (UCNs), UCN1, UCN2 and UCN3 are endogenous peptides that interact with corticotropin-releasing factor receptors 1 and 2 (CRFR1 and CRFR2). CRFR1 and CRFR2 are activated non-selectively by corticotropin releasing hormone (CRH) and UCN1, whereas UCN2 and UCN3 are CRFR2-selective agonists. UCN2 selectively activates CRFR2, including the known isoforms CRFR2-alpha (a), -beta (b) and -gamma (g).

[0005] CRFR2 agonists have demonstrated an effect preclinically in cardiovascular function via the reduction of vascular resistance, and kidney function. In clinical studies, UCN2 and UCN3 have been shown to have direct vasorelaxant actions in healthy volunteers and in patients with heart failure. Further, UCN2 has also been shown to increase cardiac output and reduce vascular resistance in patients with heart failure. However, the extremely short half-life of urocortins remains a major limitation to their therapeutic use, for example in the management patients that require treatment suitable for long-standing and home self- administration. NAI-1543420566SUMMARY

[0006] The present disclosure provides selective corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptides, or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such peptides or pharmaceutically acceptable salts thereof, and methods of using such peptides or pharmaceutically acceptable salts thereof to treat or prevent diseases associated with the abnormal or dysregulated activity of corticotropin releasing factor (CRF) signaling. Fatty acid conjugates extend the in vivo time of action of the peptides of the disclosure.

[0007] In one aspect, the present disclosure provides CRFR2 agonists suitable for subcutaneous administration for humans. In one aspect, are selective CRFR2 agonists which have high chemical and physical stability suitable for subcutaneous administration to humans.

[0008] In one aspect, the present disclosure provides a selective corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formula (I) (SEQ ID NO: 109): Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-R38-R39-R40-R41- CONH2; (I) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m- diacid, wherein: n is 0, 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)- ethoxy]-acetyl (AEEA) amine is via the nitrogen of the N-terminus (see Figures for examples); R1 is selected from pGlu, Gly, Ser, and absent; R2 is selected from pGlu, Pro, Gly, Glu, Gln, and Lys; R12is selected from Phe and D-Phe; R17is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23 is selected from Lys and Aib; R25 is selected from Glu, and K*; R26is selected from Lys and Aib; NAI-1543420566R32 is selected from Ala, Glu, Thr, E#, K#, and K*; R33is selected from Asn, Thr, Gln, and K*; R34 is selected from Asn, and Gln; R35 is selected from Ala, d-Ala, Aib, AC3C, Arg, Glu, Gln, E#, and K#; R36is selected from Arg, Glu, Gln, Ile, and K*; R37is selected from Leu, and Ile; R38 is selected from Leu, and Nle; R39is selected from Asp, and Glu; R40is selected from Thr, and Glu; R41 is selected from Ile and Val; E# and K# represent a lactam bridge between the two side chains of Glu (E) and Lys (K); K* represents Lys-(Z)0-3(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid, wherein: Z is Gly, Glu, gGlu, Lys, Ala, Gln or His; n is 0, 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue; with the proviso that n and m are not both zero; with the further proviso that one of X* and K* is present; with the further proviso that if K* is present, X* is not present and only one of R25, R32, R33, and R36 is K*; with the further proviso that if X* is present, K* is not present; and with the further proviso that when R32 is E#, R35 is K#, and when R32is K#, R35is E#.

[0009] In a further aspect of the disclosure are pharmaceutically acceptable salts of Formula (I). In some embodiments, Y is absent. In some embodiments, R1 is pGlu and in yet a further embodiment, R1is pGlu when Y is absent. In some embodiments, R1is absent. In some embodiments, R2is Gly. In some embodiments, R12is Phe. In some embodiments, R17is Lys. In some embodiments, R25 is K*, and yet in a further embodiment, K* is Lys[(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)1-(gGlu)1-C18-diacid]. In some embodiments, R26 is Lys. In some embodiments, R32is Glu or E#, and in yet a further embodiment, R32is E#. In some embodiments, R33 is Thr or Gln, and in yet a further embodiment, R33 is Thr. In some NAI-1543420566embodiments, R34 is Asn. In some embodiments, R35 is K#. In some embodiments, R36 is Arg. In some embodiments, R37is Leu. In some embodiments, R38is Nle. In some embodiments, R39 is Glu. In some embodiments R40 is Thr. In some embodiments, R41 is Ile.

[0010] In some embodiments, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein. In a further embodiment, the present disclosure provides pharmaceutically acceptable salts of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein.

[0011] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein Y is absent or X*, and in further embodiments, wherein Y is absent. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein Y is absent or X*, and in further embodiments, wherein Y is absent. In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R1 is selected from pGlu, Gly, and Ser, or in a further embodiment, wherein R1is pGlu, and yet in a further embodiment, wherein R1is pGlu when Y is absent. In some embodiments, R1is absent. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R1is selected from pGlu, Gly, and Ser, or in a further embodiment, wherein R1 is pGlu, and yet in a further embodiment, wherein R1 is pGlu when Y is absent.

[0012] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R2 is selected from pGlu, Pro, Gly, Glu, Gln, and Lys, and in a further embodiment, wherein R2is Gly. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R2 is selected from pGlu, Pro, Gly, Glu, Gln, and Lys, and in a further embodiment, wherein R2is Gly. NAI-1543420566

[0013] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R12 is selected from Phe and D-Phe, and in a further embodiment, R12 is Phe. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R12is selected from Phe and D-Phe, and in a further embodiment, R12 is Phe.

[0014] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R17 is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn, and in a further embodiment, wherein R17 is Lys. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R17 is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn, and in a further embodiment, wherein R17is Lys.

[0015] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R23is selected from Lys and Aib, and in a further embodiment, wherein R23is Lys. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R23is selected from Lys and Aib, and in a further embodiment, wherein R23is Lys.

[0016] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R25is selected from Glu, and K*, and in a further embodiment, wherein R25 is K*, and in yet a further embodiment, wherein K* is Lys[(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)1-(gGlu)1-C18-diacid]. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R25 is selected from Glu, and K*, and in a further embodiment, wherein R25is K*, and in yet a further embodiment, wherein K* is Lys[(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)1-(gGlu)1-C18-diacid]. NAI-1543420566

[0017] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R26 is selected from Lys and Aib, in a further embodiment, wherein R26 is Lys. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R26 is selected from Lys and Aib, in a further embodiment, wherein R26 is Lys.

[0018] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R32 is selected from Ala, Glu, Thr, E#, K#, and K*, and in a further embodiment, wherein R32is E#. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R32is selected from Ala, Glu, Thr, E#, K#, and K*, and in a further embodiment, wherein R32is E#.

[0019] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R33is selected from Asn, Thr, Gln, and K*, and in a further embodiment, wherein R33 is Thr or Gln, and yet in a further embodiment, wherein R33 is Thr. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R33 is selected from Asn, Thr, Gln, and K*, and in a further embodiment, wherein R33 is Thr or Gln, and yet in a further embodiment, wherein R33is Thr.

[0020] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R34is selected from Asn, and Gln, and in a further embodiment, wherein R34is Asn. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R34is selected from Asn, and Gln, and in a further embodiment, wherein R34is Asn. NAI-1543420566

[0021] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R35 is selected from Ala, d-Ala, Aib, AC3C, Arg, Glu, Gln, E#, and K#, and in a further embodiment wherein R35 is K#. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R35 is selected from Ala, d-Ala, Aib, AC3C, Arg, Glu, Gln, E#, and K#, and in a further embodiment wherein R35is K#.

[0022] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R36 is selected from Arg, Glu, Gln, Ile, and K*, and in a further embodiment, wherein R36is Arg. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R36is selected from Arg, Glu, Gln, Ile, and K*, and in a further embodiment, wherein R36is Arg.

[0023] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R37is selected from Leu and Ile, and in a further embodiment, wherein R37 is Leu. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R37 is selected from Leu and Ile, and in a further embodiment, wherein R37 is Leu.

[0024] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R38 is selected from Leu and Nle, and in a further embodiment, R38is Nle. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R38 is selected from Leu and Nle, and in a further embodiment, R38 is Nle.

[0025] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other NAI-1543420566Formulae described herein, wherein R39 is selected from Asp and Glu, and in a further embodiment, R39is Glu. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R39is selected from Asp and Glu, and in a further embodiment, R39is Glu.

[0026] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R40is selected from Thr and Glu, and in a further embodiment, R40is Thr. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R40 is selected from Thr and Glu, and in a further embodiment, R40is Thr.

[0027] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R41is selected from Ile and Val, and in a further embodiment, R41is Ile. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R41is selected from Ile and Val, and in a further embodiment, R41is Ile.

[0028] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R25is K*. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R32is Glu. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R38is Nle. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R25 is K*, R32 is Glu, and R38 is Nle.

[0029] In some embodiments, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of any one of the NAI-1543420566peptides listed in Table 6. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of any one of the peptides listed in Table 6.

[0030] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 61: X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg- Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu- Nle-Glu-Thr-Ile-CONH2; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)- diacid and the diacid is a C20 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 61: X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro- Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-E#- Thr-Asn-K#-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein X* is (2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)-diacid and the diacid is a C20 diacid. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 61.

[0031] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle- Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18- diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr- Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 55.

[0032] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 64: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2- diacid, wherein the diacid is a C20 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 64: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro- Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu- Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)2-diacid, wherein the diacid is a C20 diacid. In some embodiments, NAI-1543420566the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 64.

[0033] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)- diacid, wherein the diacid is a C20 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro- Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu- Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 66.

[0034] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)- diacid, wherein the diacid is a C18 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro- Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu- Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 68.

[0035] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 69: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)- diacid, wherein the diacid is a C20 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 69: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro- Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu- Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, NAI-1543420566the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 69.

[0036] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 72: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu- Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(gGlu)-diacid and the diacid is a C20 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 72: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile- Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Glu-Val- CONH2; wherein: K* is Lys-(gGlu)-diacid and the diacid is a C20 diacid. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 72.

[0037] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 67: pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Gln-Asn-Ala-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)- diacid, wherein the diacid is a C20 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 67: pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro- Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu- Gln-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino- ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 67.

[0038] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 63: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu- Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)- diacid, wherein the diacid is a C20 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 63: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro- Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu- Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino- ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some NAI-1543420566embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 63.

[0039] In some embodiments, the peptide comprises the amino acid sequence of SEQ ID NO: 78: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys- Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)- diacid, wherein the diacid is a C20 diacid. In some embodiments, the peptide consists of the amino acid sequence of SEQ ID NO: 78: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro- Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu- Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 78.

[0040] In another aspect, the present disclosure provides a pharmaceutical composition which contains a peptide of Formula (I) in admixture with one or more suitable excipients. In another aspect, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide of Formula (I) in admixture with one or more suitable excipients.

[0041] In some embodiments, the present disclosure provides a pharmaceutical composition which contains a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein in admixture with one or more suitable excipients. In a further embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein in admixture with one or more suitable excipients.

[0042] In some embodiments, the present disclosure provides a pharmaceutical composition which contains a peptide of any one of the peptides listed in Table 6 in admixture with one or more suitable excipients. In a further embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of any one of the peptides listed in Table 6 in admixture with one or more suitable excipients.

[0043] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: NAI-154342056661: X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu-Thr- Ile-CONH2; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid and the diacid is a C20 diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 61 in admixture with one or more suitable excipients.

[0044] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr-Ile- CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 55 in admixture with one or more suitable excipients.

[0045] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: 64: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val- CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid, wherein the diacid is a C20 diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 64 in admixture with one or more suitable excipients.

[0046] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val- CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a NAI-1543420566pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 66 in admixture with one or more suitable excipients.

[0047] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val- CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 68 in admixture with one or more suitable excipients.

[0048] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: 69: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val- CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 69 in admixture with one or more suitable excipients.

[0049] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: 72: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Glu- Val-CONH2; wherein: K* is Lys-(gGlu)-diacid and the diacid is a C20 diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 72 in admixture with one or more suitable excipients.

[0050] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: 67: pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Gln-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val- NAI-1543420566CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 67 in admixture with one or more suitable excipients.

[0051] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ ID NO: 63: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Thr- Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 63 in admixture with one or more suitable excipients

[0052] In some embodiments, the present disclosure provides a pharmaceutical composition which contains the peptide comprising the amino acid sequence of SEQ the peptide comprising the amino acid sequence of SEQID NO: 78: pGlu-Gly-Gly-Pro-Pro-Ile- Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu- Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys- (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof, in admixture with one or more suitable excipients. In another embodiment, the present disclosure provides a pharmaceutical composition which contains a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 78 in admixture with one or more suitable excipients.

[0053] In another aspect, the present disclosure provides a formulation comprising a peptide disclosed herein in admixture with one or more pharmaceutically acceptable excipients. In another aspect, the present disclosure provides a formulation comprising a pharmaceutically acceptable salt of a peptide disclosed herein in admixture with one or more pharmaceutically acceptable excipients.

[0054] In another aspect, the present disclosure provides a method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of the peptide disclosed herein or the formulation disclosed herein, wherein the development or symptoms of the disease or disorder can be alleviated by the selective NAI-1543420566stimulation of CRFR2. In another aspect, the present disclosure provides a method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of the peptide disclosed herein or the formulation disclosed herein, wherein the disease or disorder is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0055] In another aspect, the present disclosure provides a method of treating a disease or disorder in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a peptide of Formula (I). In another aspect, the present disclosure provides a method of treating a disease or disorder in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide of Formula (I).

[0056] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) NAI-1543420566can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a peptide of any one of formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide of any one of formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein.

[0057] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a peptide of any one of the peptides listed in Table 6. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide of any one of the peptides listed in Table 6.

[0058] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 61: X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser- Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys- Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein X* is (2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid and the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 61. NAI-1543420566

[0059] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 55.

[0060] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 64: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid, wherein the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 64.

[0061] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- NAI-1543420566Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 66.

[0062] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 68.

[0063] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 69: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin NAI-1543420566releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 69.

[0064] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 72: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(gGlu)- diacid and the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 72.

[0065] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 67: pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Gln-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 67.

[0066] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) NAI-1543420566can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 63: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 63.

[0067] In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of the peptide comprising the amino acid sequence of SEQ ID NO: 78: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C20 diacid, or a pharmaceutically acceptable salt thereof. In some embodiments, the present disclosure provides a method of treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease, which method comprises administering to a patient a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 78.

[0068] In another aspect, the present disclosure provides the use of a peptide of Formula (I) in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease. In another aspect, the present disclosure provides a peptide of Formula (I) or any Formulae described herein, for use in therapy. In another aspect, the present disclosure provides a peptide of Formula (I) or any Formulae described herein, for use in the treatment of a disease in a patient in which activation of NAI-1543420566corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease. In another aspect, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide of Formula (I) in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a peptide of Formula (I) or any Formulae described herein, for use in therapy. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a peptide of Formula (I) or any Formulae described herein, for use in the treatment of a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease.

[0069] In some embodiments, the present disclosure provides the use of a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated NAI-1543420566steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0070] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity- induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0071] In some embodiments, the present disclosure provides a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein for use in therapy. In some embodiments, the present disclosure provides a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein for use in the treatment of a disease in a patient in which activation of NAI-1543420566corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0072] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein for use in the treatment of a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from NAI-1543420566heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0073] In some embodiments, the present disclosure provides the use of a peptide of any one of the peptides listed in Table 6 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. NAI-1543420566

[0074] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide of any one of the peptides listed in Table 6 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a peptide of any one of the peptides listed in Table 6 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide of any one of the peptides listed in Table 6 for use in therapy. In some embodiments, the present disclosure provides a peptide of any one of the peptides listed in Table 6, or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and NAI-1543420566sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0075] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide of any one of the peptides listed in Table 6, or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker NAI-1543420566Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0076] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 61: X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser- Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys- Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein X* is (2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid and the diacid is a C20 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0077] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid NAI-1543420566sequence of SEQ ID NO: 61 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0078] In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 61 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 61 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 61 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight NAI-1543420566selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0079] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 61 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, NAI-1543420566depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0080] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity- induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0081] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 55 in the manufacture of a medicament for treating a disease in a NAI-1543420566patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0082] In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 55 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 55 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 55 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity NAI-1543420566linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0083] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 55 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention NAI-1543420566from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0084] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 64: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid, wherein the diacid is a C20 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0085] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 64 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, NAI-1543420566inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0086] In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 64 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 64 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 64 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) a disease associated with excess body weight (defined by standard body mass index calculations), including but not limited to obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (ii) a skeletal muscle wasting disease including but not limited to age-related muscle loss (sarcopenia), or preserving skeletal muscle during, for example, cancer cachexia; (iii) a combination of weight management and the preservation or building of muscle mass; (iv) a cardiovascular NAI-1543420566disease wherein the cardiovascular disease is selected from heart failure, hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (v) chronic kidney disease; (vi) myalgic encephalomyelitis; (vii) nicotine withdrawal; and (viii) acute pancreatitis.

[0087] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 64 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) a disease associated with excess body weight (defined by standard body mass index calculations), including but not limited to obesity-linked inflammation, obesity linked sarcopenia, obesity- linked gallbladder disease, and obesity-induced sleep apnea; (ii) a skeletal muscle wasting disease including but not limited to age-related muscle loss (sarcopenia), or preserving skeletal muscle during, for example, cancer cachexia; (iii) a combination of weight management and the preservation or building of muscle mass; (iv) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure, hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (v) chronic kidney disease; (vi) myalgic encephalomyelitis; (vii) nicotine withdrawal; and (viii) acute pancreatitis.

[0088] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer NAI-1543420566cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0089] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 66 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or NAI-1543420566metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0090] In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 66 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 66 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 66for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0091] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 66 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory NAI-1543420566disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0092] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from NAI-1543420566heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0093] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 68 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or NAI-1543420566metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0094] In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 68 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 68 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 68 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0095] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 68 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory NAI-1543420566disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0096] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 69: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from NAI-1543420566heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0097] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 69 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or NAI-1543420566metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0098] In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 69 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 69 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 69 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 69 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in NAI-1543420566the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0099] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 72: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(gGlu)- diacid and the diacid is a C20 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic NAI-1543420566kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 72 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 72 for use in therapy. In some embodiments, the NAI-1543420566present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 72 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 72 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 72 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease NAI-1543420566selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0100] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 67: pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Gln-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker NAI-1543420566Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 67 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 67 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 67 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 67 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or NAI-1543420566ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 67 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic NAI-1543420566encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0101] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 63: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); NAI-1543420566and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 63 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 63 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 63 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 63 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), NAI-1543420566gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 63 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, NAI-1543420566depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0102] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 78: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C20 diacid in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 78 in the manufacture of a medicament for treating a disease in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can NAI-1543420566prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 72 for use in therapy. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 72 for use in therapy. In some embodiments, the present disclosure provides a peptide comprising the amino acid sequence of SEQ ID NO: 72 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of NAI-1543420566skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a peptide comprising a pharmaceutically acceptable salt of SEQ ID NO: 72 for use in the treatment of a disease in which activation of corticotropin releasing factor receptor 2 (CRFR2) can prevent, inhibit, or ameliorate pathology and / or symptoms of a disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or NAI-1543420566metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0103] In another aspect, the present disclosure provides a peptide of Formula (I) for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) contributes to the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0104] In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a peptide of Formula (I) for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) contributes to the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder NAI-1543420566disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0105] In some embodiments, the present disclosure provides the use of a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, NAI-1543420566ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, NAI-1543420566obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of a peptide of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, NAI-1543420566ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0106] In some embodiments, the present disclosure provides the use of a peptide of any one of the peptides listed in Table 6 in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of any one of the peptides listed in Table 6 in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity NAI-1543420566linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a peptide of any one of the peptides listed in Table 6 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or NAI-1543420566metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0107] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of any one of the peptides listed in Table 6 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0108] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 61: X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser- Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys- Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein X* is (2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid and the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- NAI-1543420566negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 61 in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular NAI-1543420566dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 61 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0109] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 61 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, NAI-1543420566sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0110] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type- 2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) NAI-1543420566addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0111] In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib- Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)-(gGlu)-C18-diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or NAI-1543420566metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0112] In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 55 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 55 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease NAI-1543420566selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0113] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 64: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid, wherein the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and NAI-1543420566Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 64 in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 64 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; NAI-1543420566(ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 64 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, NAI-1543420566ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0114] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- NAI-1543420566acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 66 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, NAI-1543420566arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 66 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0115] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- NAI-1543420566Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and NAI-1543420566sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 68 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention NAI-1543420566from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising a pharmaceutically acceptable salt of SEQ ID NO: 68 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0116] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 69: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or NAI-1543420566inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 69 in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; NAI-1543420566(xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 69 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 69 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, NAI-1543420566sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0117] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 72: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(gGlu)- diacid and the diacid is a C20 diacid, in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) NAI-1543420566addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 72 in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 72 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 NAI-1543420566diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 72 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular NAI-1543420566dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0118] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 67: pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Gln-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid NAI-1543420566sequence of SEQ ID NO: 67 in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 67 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary NAI-1543420566heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 67 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0119] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 63: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- NAI-1543420566Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 63: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn- AC3C-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and NAI-1543420566sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 63 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention NAI-1543420566from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 63 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity- linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0120] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 78: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C20 diacid in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- NAI-1543420566negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the use of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 78 in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular NAI-1543420566dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides the peptide comprising the amino acid sequence of SEQ ID NO: 78 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder. In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of SEQ ID NO: 78 for use in therapy in a patient in which activation of corticotropin releasing factor receptor 2 (CRFR2) can be beneficial for the pathology and / or symptoms of the disease wherein the disease is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; NAI-1543420566(ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

[0121] In another aspect, the present disclosure provides processes for preparing peptides of Formula (I). In another aspect, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of Formula (I).

[0122] In some embodiments, the present disclosure provides processes for preparing peptides of any one of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of a peptide of Formulae (Ia), (Ib), (Ic), (Id), or (Ie), or any other Formulae disclosed herein.

[0123] In some embodiments, the present disclosure provides processes for preparing a peptide of any one of the peptides listed in Table 6. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of any one of the peptides listed in Table 6.

[0124] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 61: X*-Gly-Pro- Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys- Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid and the diacid is a C20 NAI-1543420566diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 61.

[0125] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 55.

[0126] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 64: pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 64.

[0127] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 66.

[0128] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 68.

[0129] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 69: pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- NAI-1543420566K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 69.

[0130] In some embodiments, the present disclosure provides the use of the peptide comprising the amino acid sequence of SEQ ID NO: 72: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile- Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln- Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(gGlu)- diacid and the diacid is a C20 diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 72.

[0131] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 67: pGlu-Gln-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Gln-Asn-Ala-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 67.

[0132] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 63: pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 63.

[0133] In some embodiments, the present disclosure provides processes for preparing the peptide comprising the amino acid sequence of SEQ ID NO: 78: pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid, wherein the diacid is a C20 diacid. In some embodiments, the present disclosure provides processes for preparing a pharmaceutically acceptable salt of SEQ ID NO: 78. NAI-1543420566

[0134] For a better understanding of the present disclosure, together with other and further aspects thereof, reference is made to the accompanying drawings, detailed description, and claims. BRIEF DESCRIPTION OF FIGURES

[0135] FIG.1 Structure of peptide of SEQ ID NO: 1, Example A1, where X* is (2- [2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-C18-diacid.

[0136] FIG.2 Structure of peptide of SEQ ID NO: 62, Example A2, where K* is Lys-(gGlu)-C20-diacid.

[0137] FIG.3 Structure of peptide of SEQ ID NO: 59, Example A3, where K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-C20-diacid.

[0138] FIG.4 Structure of peptide of SEQ ID NO: 64, Example A4, where K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-C20-diacid.

[0139] FIG.5 Structure of peptide of SEQ ID NO: 66, Example A5, where K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-C20-diacid.

[0140] FIG.6 Structure of peptide of SEQ ID NO: 68, Example A6, where K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid.

[0141] FIG.7 Structure of peptide of SEQ ID NO: 69, Example A7, where K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-C20-diacid.

[0142] FIG.8 Structure of peptide of SEQ ID NO: 67, Example A8, where K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-C20-diacid.

[0143] FIG.9 Structure of peptide of SEQ ID NO: 78, Example A9, where K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C20-diacid.

[0144] FIG.10 Structure of peptide of SEQ ID NO: 55, Example A10, where K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid.

[0145] FIG.11 Structure of peptide of SEQ ID NO: 72, Example A11, where K* is Lys-(gGlu)-C20-diacid. DETAILED DESCRIPTION

[0146] Urocortins (UCNs), UCN1, UCN2 and UCN3 are endogenous peptides that interact with corticotropin-releasing factor receptors 1 and 2 (CRFR1 and CRFR2).

[0147] Studies in mice have demonstrated that UCN2 and / or UCN3 gene transfer in mice improves not only cardiac function but also glucose disposal. In addition, subcutaneous NAI-1543420566delivery of pegylated UCN2 has been shown to improve glucose tolerance and increase glucose uptake in skeletal muscle while reducing body weight. These findings demonstrate that urocortins can be useful not only in the treatment of cardiovascular diseases but also in the treatment of diseases or conditions such as diabetes and obesity.

[0148] The extremely short half-life of urocortins remains a major limitation to their therapeutic use. Specifically, treatment with urocortins cannot be sustained without continuous intravenous infusion. However, the management of chronic diabetic or heart failure patients or treatment of conditions such as obesity require treatment suitable for long- standing and home self-administration.

[0149] To overcome these limitations, there remains a need for improved CRFR2 agonists which are useful as therapeutic agents in the treatment and prevention of diseases. There is a need for selective CRFR2 agonists having desirable efficacy, pharmacokinetic properties (e.g., improved half-life) and / or physicochemical properties (e.g., improved stability and / or solubility), for the treatment of disease or disorders selected from, but not limited to, cardiovascular diseases, obesity, diabetes, sarcopenia, kidney disease, cachexia, heart failure and pulmonary hypertension. Provided herein are CRFR2 agonist peptides or salts thereof, pharmaceutical compositions comprising such peptides or salts thereof, and methods of using such peptides or salts thereof that meet such needs.

[0150] The CRFR2 agonist fatty acid conjugated peptides of the present disclosure have various superior results as compared to other CRFR2 agonist peptides in the art, such as potent CRFR2 agonist activity, high physical and chemical stability, high solubility, low aggregation, low viscosity, and low or no CRFR1 agonist activity, and superior pharmacokinetic properties. In some embodiments, the peptides of the present disclosure demonstrate substantial improvement in in vivo functional effects, including body weight reduction, fat mass reduction, and muscle mass retention, for example as described in the Examples below. In certain embodiments, without being bound by the theory, the fatty acid conjugates extend the in vivo time of action of the peptides of the disclosure.

[0151] In certain embodiments, without being bound by the theory, the amino-acid- sequence features of the peptides provided herein lead to superior results in comparison to known reference peptides. Such features include but are not limited to K* at R25. In addition to K* at R25, features include Nle at R38 and / or Glu at R32, in the formulae provided herein, such as: SEQ ID NO: 55; SEQ ID NO: 63; SEQ ID NO: 64; SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68; SEQ ID NO: 69; SEQ ID NO: 72; and SEQ ID NO: 78. The superior NAI-1543420566results associated with such features include but are not limited to potent in vitro CRFR2 agonist activity, high physical and chemical stability, high solubility, low aggregation, low viscosity, low or no CRFR1 agonist activity, high in vivo CRFR2 activity, high target selectivity, and superior pharmacokinetic properties, for example, as described in the Examples below. In certain embodiments, the provided CRFR2 agonist peptides and the associated sequence features have demonstrated improved in vivo therapeutic effects in body weight reduction, fat mass reduction, and muscle mass retention, for example, as described in the Examples below. Definitions

[0152] The nomenclature used to define the peptides disclosed herein is that specified by Schroder & Lubke, "The Peptides", Academic Press (1965) wherein, in accordance with conventional representation, the peptide sequence is written left-to-right from the N-terminus at the left to the C-terminus at the right. The standard 3-letter abbreviations are used to identify the alpha-amino acid residues, and where the amino acid residue has isomeric forms, it is the L-form of the amino acid that is represented unless otherwise expressly indicated, e.g., Ser=L-serine, Orn=L-ornithine, Aad=L-2-aminoadipic acid, Nle=L-norleucine, etc. The D-form of an amino acid may be represented using a lowercase standard 1-letter abbreviation for that amino acid, e.g., s = D-serine, g = D-glycine, etc. In addition, Table 1 describes the amino acids and corresponding abbreviations used in the present disclosure. Table 1. Amino acids and corresponding abbreviations.NAI-1543420566NAI-1543420566NAI-1543420566

[0153] “CRF Receptor” means corticotropin-releasing hormone receptors or corticotropin-releasing factor (CRF) receptors belonging to the superfamily of G-protein- coupled receptors. Two CRF receptor subtypes have been identified, CRFR1 (or CRF1R or CRF1 receptor, also known as corticotropin-releasing hormone 1 receptor (CRH1R or CRHR1)) and CRFR2 (or CRF2R or CRF2 receptor, also known as corticotropin-releasing hormone 2 receptor (CRH2R or CRHR2)). CRFR1 receptors are widely distributed throughout neocortical, limbic and brainstem regions of the central nervous system while CRFR2 receptors are limited to discrete brain regions. CRFR2 has three major functional isoforms, alpha, beta, and gamma. In humans, CRFR2-beta is primarily expressed in the brain, while CRFR2-alpha is more broadly expressed in the brain and found in additional peripheral tissues.

[0154] The terms “effective amount” or “therapeutically effective amount” refer to an amount of a therapeutic (e.g., a composition provided herein) which is sufficient to treat, prevent, delay the onset of, reduce and / or ameliorate the severity and / or duration of a given condition, disorder or disease and / or a symptom related thereto. These terms also encompass an amount necessary for the reduction, slowing, or amelioration of the advancement or progression of a given disease, reduction, slowing, or amelioration of the recurrence, development or onset of a given disease, and / or to improve or enhance the prophylactic or therapeutic effect(s) of another therapy or to serve as a bridge to another therapy. In some embodiments, “effective amount” as used herein also refers to the amount of a composition described herein to achieve a specified result. As used herein, the terms “subject” and “patient” are used interchangeably.

[0155] The carbonyl group of “-CONH2” as recited in the Formulae and amino acid sequences provided herein is the carbonyl group of the respective C-terminal amino acid residue. The structures shown in the figures provide examples showing that the carbonyl group of “-CONH2” is the carbonyl group of the C-terminal amino acid residue. Embodiments

[0156] The present disclosure relates to corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptides of Formula (I). The present disclosure further relates to pharmaceutically acceptable salts of corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptides of Formula (I). The peptides of Formula I can activate CRFR2 to prevent, inhibit, or ameliorate the pathology and / or symptoms of a NAI-1543420566disease associated with aberrant corticotropin releasing factor (CRF) signaling. Further, pharmaceutically acceptable salts of the peptides of Formula I can activate CRFR2 to prevent, inhibit, or ameliorate the pathology and / or symptoms of a disease associated with aberrant corticotropin releasing factor (CRF) signaling. In some embodiments, the peptides of Formula (I), are selected from Formulae (I-1), (I-2), (I-3), (I-4), (I-5), or any combination thereof. In further embodiments, pharmaceutically acceptable salts of the peptides of Formula (I), are selected from Formulae (I-1), (I-2), (I-3), (I-4), (I-5), or any combination thereof: Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-K#-R36-R37-R38-R39-R40-R41-CONH2 (SEQ ID NO: 110) Formula (I-1); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-R35-R36-R37-R38-R39-R40-R41-CONH2(SEQ ID NO: 111) Formula (I-2); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-R38-R39-R40-R41-CONH2 (SEQ ID NO: 112) Formula (I-3); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle-R39-R40-R41- CONH2 (SEQ ID NO: 113) Formula (I-4); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-R38-Glu-R40-R41- CONH2(SEQ ID NO: 114) Formula (I-5). NAI-1543420566

[0157] In one aspect, with respect to peptides of Formula (I), are peptides of Formula (Ia). In a further aspect, pharmaceutically acceptable salts of the peptides of Formula (I), are selected from Formulae (I-1), (I-2), (I-3), (I-4), (I-5), or any combination thereof: Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu- Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-R40- R41-CONH2(SEQ ID NO: 115) (Ia) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n- (gGlu)m-diacid, wherein: n is 0, 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)- ethoxy]-acetyl (AEEA) amine is via the nitrogen of the N-terminus; R1 is selected from pGlu, Gly, and Ser; R2is selected from pGlu, Pro, Gly, Glu, Gln, and Lys; R12is selected from Phe and D-Phe; R17 is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23 is selected from Lys and Aib; R25is selected from Glu, and K*; R26 is selected from Lys and Aib; R33 is selected from Asn, Thr, Gln, and K*; R34is selected from Asn, and Gln; R36is selected from Arg, Glu, Gln, Ile, and K*; R37 is selected from Leu, and Ile; R38is selected from Leu, and Nle; R39is selected from Asp, and Glu; R40 is selected from Thr, and Glu; R41 is selected from Ile and Val; NAI-1543420566E# and K# represent a lactam bridge between the two side chains of Glu (E) and Lys (K); K* represents Lys-(Z)0-1(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid, wherein: Z is Glu, gGlu, Lys, Ala, Gln or His; n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue; with the proviso that n and m are not both zero; with the further proviso that one of X* and K* is present; with the further proviso that if K* is present, X* is not present and only one of R25,R33,and R36is K*; with the further proviso that if X* is present, K* is not present. In some embodiments, the peptides of Formula (Ia) are selected from Formula (Ia-1), Formula (Ia-2), Formula (Ia-3), Formula (Ia-4), Formula (Ia-5), Formula (Ia-6), Formula (Ia- 7), Formula (Ia-8), or any combination thereof. In some embodiments, pharmaceutically acceptable salts of the peptides of Formula (Ia) are selected from Formula (Ia-1), Formula (Ia-2), Formula (Ia-3), Formula (Ia-4), Formula (Ia-5), Formula (Ia-6), Formula (Ia-7), Formula (Ia-8), or any combination thereof: Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-R40-R41-CONH2 (SEQ ID NO: 116) Formula (Ia-1); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-R40-R41-CONH2(SEQ ID NO: 117) Formula (Ia-2); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-Lys-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-R40-R41-CONH2 (SEQ ID NO: 118) Formula (Ia-3); NAI-1543420566Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-K*-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-R40-R41-CONH2 (SEQ ID NO: 119) Formula (Ia-4); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-Lys-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-R40-R41-CONH2(SEQ ID NO: 120) Formula (Ia-5); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-Asn-K#-R36-R37-R38-R39-R40-R41-CONH2 (SEQ ID NO: 121) Formula (Ia-6); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-Thr-R41-CONH2(SEQ ID NO: 122) Formula (Ia-7); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu-Ile- Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-R40-Ile-CONH2 (SEQ ID NO: 123) Formula (Ia-8).

[0158] In another aspect, with respect to peptides of Formula (Ia), are peptides of Formula (Ib). In a further aspect are pharmaceutically acceptable salts of Formula (Ib): Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile- Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-E#-R33-Asn-K#-Arg-R37-R38-R39-Thr-Ile- CONH2(SEQ ID NO: 124); (Ib) NAI-1543420566wherein: Y is absent; R1 is selected from pGlu, and Gly; R2 is selected from pGlu, Pro, and Gly; R33is selected from Asn, Thr, and Gln; R37is selected from Leu and Ile; R38 is selected from Leu, and Nle; R39is selected from Asp, and Glu; E# and K# represent a lactam bridge between the two side chains of Glu I and Lys (K); K* represents Lys-(Z)0-1(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys- (PEG12)-(gGlu)1-2-diacid, wherein: Z is Glu, gGlu, Lys, Ala, Gln or His; n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue.

[0159] In a further aspect are peptides of Formula Ib, wherein K* is selected from Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid and the diacid is a C18 diacid, Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)1-(gGlu)1-diacid and the diacid is a C18 diacid, and Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid and the diacid is a C20 diacid; and X* is selected from (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)1-diacid and the diacid is a C18 diacid, and (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)1-diacid and the diacid is a C20 diacid; with the proviso that if K* is present, X* is not present.

[0160] In a further aspect is a peptide of Formula Ib, comprising the amino acid sequence pGlu-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu- Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-E#-Asn-Asn-K#-Arg-Leu-Leu-Asp-Thr-Ile- CONH2and K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid and the diacid is a C18 diacid (SEQ ID NO: 30).

[0161] In a further aspect is a peptide of Formula Ib, comprising the amino acid sequence pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu-Thr- NAI-1543420566Ile-CONH2 and K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-diacid and the diacid is a C18 diacid (SEQ ID NO 58).

[0162] In a further aspect is a peptide of Formula Ib, comprising the amino acid sequence pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu-Thr- Ile-CONH2and K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid and the diacid is a C20 diacid (SEQ ID NO: 59).

[0163] In a further aspect is a peptide of Formula Ib, comprising the amino acid sequence X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val- Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu- Thr-Ile-CONH2 and X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid and the diacid is a C18 diacid (SEQ ID NO: 60).

[0164] In a further aspect is a peptide of Formula Ib, comprising the amino acid sequence X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val- Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle-Glu- Thr-Ile-CONH2and X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid and the diacid is a C20 diacid (SEQ ID NO: 61).

[0165] In another aspect are peptides of Formula (Ic). In a further aspect are pharmaceutically acceptable salts of peptides of Formula (Ic): Y-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu- Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-Asn-Ala-R36-R37-R38-Asp- Thr-Ile-CONH2 (SEQ ID NO: 125); (Ic) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n- (gGlu)m-diacid, wherein: n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)- ethoxy]-acetyl (AEEA) amine is via the nitrogen of the N-terminus; R2is selected from pGlu, and Pro; R12 is selected from Phe and D-Phe; NAI-1543420566R17 is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23is selected from Lys and Aib; R25 is selected from Glu, and K*; R26 is selected from Lys and Aib; R32is selected from Ala, and K*; R33is selected from Asn and K*; R36 is selected from Arg, and K*; R37is selected from Leu, Ile, and K*; R38is selected from Leu, and Nle; K* represents Lys-(Z)0-1(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid, wherein: Z is Glu, gGlu, Lys, Ala, Gln or His; n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue; with the proviso if K* is present, X* is not present and only one of R25, R32, R33, R36 and R37is K*.

[0166] In a further aspect are peptides of Formula (Ic). In a further aspect are pharmaceutically acceptable salts of peptides of Formula (Ic), selected from the peptides in Table 2. Table 2. Exemplary fatty acid conjugated peptides of Formula (Ic).NAI-1543420566NAI-1543420566

[0167] In a further aspect are peptides of Formula (Ic). In a further aspect are pharmaceutically acceptable salts of peptides of Formula (Ic), selected from the peptides in Table 3. Table 3. Exemplary fatty acid conjugated peptides of Formula (Ic).NAI-1543420566NAI-1543420566

[0168] In another aspect, with respect to peptides of Formula (I), are peptides of Formula (Id). In a further aspect are pharmaceutically acceptable salts of peptides of Formula (Id): Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2 (SEQ ID NO: 126); (Id) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n- (gGlu)m-diacid, wherein: n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)- ethoxy]-acetyl (AEEA) amine is via the nitrogen of the N-terminus; R1is selected from pGlu, Gly, and Ser; R2is selected from pGlu, Pro, Gly, Glu, Gln, and Lys; R17 is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23is selected from Lys and Aib; R25is selected from Glu, and K*; R26 is selected from Lys and Aib; R32 is selected from Ala, Glu, and Thr; R33is selected from Asn, Thr, and Gln; R34 is selected from Asn, and Gln; R35 is selected from Ala, d-Ala, Aib, Arg, AC3C, Glu, and Gln; R37is selected from Leu and Ile; R36is selected from Arg, Glu, Gln, and Ile; R40 is selected from Thr, and Glu; R41is selected from Ile and Val; K* represents Lys-(Z)0-1(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid, wherein: Z is Glu, gGlu, Lys, Ala, Gln or His; n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via NAI-1543420566the gamma carboxylate of the gGlu residue; with the proviso that one of X* and K* is present; with the further proviso that if K* is present, X* is not present.

[0169] In some embodiments, the peptides, or the pharmaceutically acceptable salt thereof, are selected from Formula (Id-1), Formula (Id-2), Formula (Id-3), Formula (Id-4), Formula (Id-5), Formula (Id-6), Formula (Id-7), Formula (Id-8), Formula (Id-9), Formula (Id- 10), Formula (Id-11), or any combination thereof: Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2, wherein Y is absent (SEQ ID NO: 127) Formula (Id-1); Y-pGlu-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2(SEQ ID NO: 128) Formula (Id-2); Y-R1-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2 (SEQ ID NO: 129) Formula (Id-3); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2(SEQ ID NO: 130) Formula (Id-4); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-Lys-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle- Glu-R40-R41-CONH2 (SEQ ID NO: 131) Formula (Id-5); NAI-1543420566Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-K*-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2 (SEQ ID NO: 132) Formula (Id-6); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-Lys-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle- Glu-R40-R41-CONH2(SEQ ID NO: 133) Formula (Id-7); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-Glu-R33-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2 (SEQ ID NO: 134) Formula (Id-8); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-Thr-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2(SEQ ID NO: 135) Formula (Id-9); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-Asn-R35-R36-R37-Nle- Glu-R40-R41-CONH2 (SEQ ID NO: 136) Formula (Id-10); Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-Arg-R37-Nle- Glu-R40-R41-CONH2(SEQ ID NO: 137) Formula (Id-11).

[0170] In a further aspect of the disclosure are peptides of Formula (Id). In a further aspect are pharmaceutically acceptable salts of peptides of Formula (Id), selected from the peptides in Table 4. NAI-1543420566Table 4. Exemplary fatty acid conjugated peptides of Formula (Id).NAI-1543420566NAI-1543420566NAI-1543420566NAI-1543420566NAI-1543420566NAI-1543420566

[0171] In a further aspect is a peptide of Formula Id, comprising the amino acid sequence (SEQ ID NO: 55) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib- Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)-(gGlu)-C18-diacid. In a further aspect is a pharmaceutically acceptable salt of a peptide of Formula Id, comprising the amino acid sequence (SEQ ID NO: 55) pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid.

[0172] In another aspect, with respect to peptides of Formula (Id), are peptides of Formula (Ie). In a further aspect are pharmaceutically acceptable salts of peptides of Formula (Ie): pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-R35-Arg-R37-Nle- Glu-R40-R41-CONH2 (SEQ ID NO: 138); (Ie) wherein: R35 is selected from Ala, AC3C, and Aib; R37is selected from Leu and Ile; R40 is selected from Thr and Glu; R41 is selected from Val and Ile; and NAI-1543420566K* represents Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid wherein: n is 0, 1, or 2; m is 1, or 2; and wherein the diacid is a C18, or C20 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue.

[0173] In a further aspect of Formula (Id), K* is selected from: Lys-(2-[2-(2-amino- ethoxy)-ethoxy]-acetyl)2-(gGlu)-diacid; Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)- diacid; Lys-(gGlu)-diacid; and Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid; wherein the diacid in each instance is independently selected from a C18 and C20 diacid.

[0174] In a further aspect is a peptide of formula (Ie), comprising the amino acid sequence (SEQ ID NO: 64) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)2-diacid, wherein the diacid is a C20 diacid. In a further aspect is a pharmaceutically acceptable salt of a peptide of formula (Ie), comprising the amino acid sequence (SEQ ID NO: 64) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)2-diacid, wherein the diacid is a C20 diacid.

[0175] In a further aspect is a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 66) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In a further aspect is pharmaceutically acceptable salt of a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 66) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid.

[0176] In a further aspect is a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 68) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid. In a further aspect is a NAI-1543420566pharmaceutically acceptable salt of a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 68) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)-(gGlu)-diacid, wherein the diacid is a C18 diacid.

[0177] In a further aspect is a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 69) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In a further aspect is a pharmaceutically acceptable salt of a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 69) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid.

[0178] In a further aspect is a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 72) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn- AC3C-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(gGlu)-diacid, wherein the diacid is a C20 diacid. In a further aspect is a pharmaceutically acceptable salt of a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 72) pGlu-Gly-Gly-Pro-Pro- Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys- Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(gGlu)-diacid, wherein the diacid is a C20 diacid.

[0179] In a further aspect is a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 67) pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Gln-Asn-Ala- Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In a further aspect is a pharmaceutically acceptable salt of a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 67) pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Gln-Asn-Ala- NAI-1543420566Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid.

[0180] In a further aspect is a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 63) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn- AC3C-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid. In a further aspect is a pharmaceutically acceptable salt of a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 63) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn- AC3C-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid.

[0181] In a further aspect is peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 62) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala- Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein: K* is Lys-(gGlu)-C20-diacid. In a further aspect is a pharmaceutically acceptable salt of a peptide of Formula (Ie), comprising the amino acid sequence (SEQ ID NO: 62) pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu- Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala- Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein: K* is Lys-(gGlu)-C20-diacid.

[0182] In a further aspect is peptide of Formula (Ie), or a pharmaceutically acceptable salt thereof, comprising the amino acid sequence (SEQ ID NO: 78) pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C20-diacid. In a further aspect is a pharmaceutically acceptable salt of a peptide of Formula (Ie), or a pharmaceutically acceptable salt thereof, comprising the amino acid sequence (SEQ ID NO: 78) pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C20-diacid.

[0183] In a further aspect is peptide of Formula (Ie), or a pharmaceutically acceptable salt thereof, comprising the amino acid sequence (SEQ ID NO: 55) pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- NAI-1543420566K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid. In a further aspect is pharmaceutically acceptable salt of a peptide of Formula (Ie), or a pharmaceutically acceptable salt thereof, comprising the amino acid sequence (SEQ ID NO: 55) pGlu-Gly-Gly- Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile-Glu-Ile-Glu-Lys-Gln- K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle-Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-C18-diacid.

[0184] In a further aspect are peptides selected from the peptides in Table 5. Table 5. Exemplary fatty acid conjugated peptides.

[0185] In a further aspect are pharmaceutically acceptable salts of SEQ ID NO: 1 and SEQ ID NO: 2.

[0186] In some aspects, the present disclosure provides a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R25 is K*. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other Formulae described herein, wherein R32 is Glu. In another aspect, the present disclosure provides a pharmaceutically acceptable salt of a corticotropin releasing factor receptor 2 (CRFR2) agonist fatty acid conjugated peptide of Formulae (I), or any other ...

Claims

What is claimed is:

1. A peptide of Formula (I) comprising the following amino acid sequence: Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu- Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-R38-R39-R40- R41-CONH2(SEQ ID NO: 109); (I) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m- diacid, wherein n is 0, 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)- ethoxy]-acetyl (AEEA) amine is via the nitrogen of the N-terminus; R1is selected from pGlu, Gly, Ser, and absent; R2is selected from pGlu, Pro, Gly, Glu, Gln, and Lys; R12 is selected from Phe and D-Phe; R17is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23is selected from Lys and Aib; R25 is selected from Glu, and K*; R26 is selected from Lys and Aib; R32is selected from Ala, Glu, Thr, E#, K#, and K*; R33 is selected from Asn, Thr, Gln, and K*; R34 is selected from Asn, and Gln; R35is selected from Ala, d-Ala, Aib, AC3C, Arg, Glu, Gln, E#, and K#; R36is selected from Arg, Glu, Gln, Ile, and K*; R37 is selected from Leu, and Ile; R38is selected from Leu, and Nle; R39is selected from Asp, and Glu; R40 is selected from Thr, and Glu; R41 is selected from Ile and Val; NAI-1543420566E# and K# represent a lactam bridge between the two side chains of Glu (E) and Lys (K); K* represents Lys-(Z)0-3(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid; wherein: Z is Gly, Glu, gGlu, Lys, Ala, Gln or His; n is 0, 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue; with the proviso that n and m are not both zero; with the further proviso that one of X* and K* is present; with the further proviso that if K* is present, X* is not present and only one of R25,R32,R33,and R36is K*; with the further proviso that if X* is present, K* is not present; and with the further proviso that when R32 is E#, R35 is K#, and when R32 is K#, R35 is E#; or a pharmaceutically acceptable salt thereof.

2. The peptide of claim 1, comprising or consisting of the following amino acid sequence: Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu- Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-R38-R39-R40- R41-CONH2(SEQ ID NO: 109); (I) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m- diacid, wherein n is 0, 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)- ethoxy]-acetyl (AEEA) amine is via the nitrogen of the N-terminus; R1 is selected from pGlu, Gly, Ser, and absent; R2is selected from pGlu, Pro, Gly, Glu, Gln, and Lys; R12 is selected from Phe and D-Phe; NAI-1543420566R17 is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23is selected from Lys and Aib; R25 is selected from Glu, and K*; R26 is selected from Lys and Aib; R32is selected from Ala, Glu, Thr, E#, K#, and K*; R33is selected from Asn, Thr, Gln, and K*; R34 is selected from Asn, and Gln; R35is selected from Ala, d-Ala, Aib, AC3C, Arg, Glu, Gln, E#, and K#; R36is selected from Arg, Glu, Gln, Ile, and K*; R37 is selected from Leu, and Ile; R38 is selected from Leu, and Nle; R39is selected from Asp, and Glu; R40 is selected from Thr, and Glu; R41 is selected from Ile and Val; E# and K# represent a lactam bridge between the two side chains of Glu (E) and Lys (K); K* represents Lys-(Z)0-3(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid; wherein: Z is Gly, Glu, gGlu, Lys, Ala, Gln or His; n is 0, 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue; with the proviso that n and m are not both zero; with the further proviso that one of X* and K* is present; with the further proviso that if K* is present, X* is not present and only one of R25, R32, R33, and R36 is K*; with the further proviso that if X* is present, K* is not present; and with the further proviso that when R32is E#, R35is K#, and when R32is K#, R35is E# (Formula I).

3. The peptide of claim 1 of Formula (Ia) comprising the following amino acid sequence: NAI-1543420566Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu- Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-E#-R33-R34-K#-R36-R37-R38-R39-R40- R41-CONH2 (SEQ ID NO: 115); (Ia) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m- diacid, wherein: n is 0, 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)- ethoxy]-acetyl (AEEA) amine is via the nitrogen of the N-terminus; R1is selected from pGlu, Gly, and Ser; R2 is selected from pGlu, Pro, Gly, Glu, Gln, and Lys; R12 is selected from Phe and D-Phe; R17is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23is selected from Lys and Aib; R25 is selected from Glu, and K*; R26is selected from Lys and Aib; R33is selected from Asn, Thr, Gln, and K*; R34 is selected from Asn, and Gln; R36 is selected from Arg, Glu, Gln, Ile, and K*; R37is selected from Leu, and Ile; R38 is selected from Leu, and Nle; R39 is selected from Asp, and Glu; R40is selected from Thr, and Glu; R41is selected from Ile and Val; E# and K# represent a lactam bridge between the two side chains of Glu (E) and Lys (K); K* represents Lys-(Z)0-1(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid, wherein: Z is Glu, gGlu, Lys, Ala, Gln or His; n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and NAI-1543420566wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue; with the proviso that n and m are not both zero; with the further proviso that one of X* and K* is present; with the further proviso that if K* is present, X* is not present and only one of R25,R33,and R36is K*; with the further proviso that if X* is present, K* is not present.

4. The peptide of claim 1 of Formula (Ib) comprising the following amino acid sequence: Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-E#-R33-Asn-K#-Arg-R37-R38-R39- Thr-Ile-CONH2(SEQ ID NO: 124); (Ib) wherein: Y is absent; R1is selected from pGlu, and Gly; R2is selected from pGlu, Pro, and Gly; R33 is selected from Asn, Thr, and Gln; R37is selected from Leu and Ile; R38is selected from Leu, and Nle; R39 is selected from Asp, and Glu; E# and K# represent a lactam bridge between the two side chains of Glu (E) and Lys (K); K* represents Lys-(Z)0-1(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid, wherein: Z is Glu, gGlu, Lys, Ala, Gln or His; n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue. NAI-15434205665. The peptide of claim 4, wherein K* is selected from Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)2-diacid and the diacid is a C18 diacid, Lys-(2-[2-(2-amino- ethoxy)-ethoxy]-acetyl)1-(gGlu)1-diacid and the diacid is a C18 diacid, and Lys-(2-[2- (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-diacid and the diacid is a C20 diacid.

6. The peptide of claim 4 comprising the amino acid sequence of SEQ ID NO 58: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle- Glu-Thr-Ile-CONH2, wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)- (gGlu)-diacid and the diacid is a C18 diacid.

7. The peptide of claim 4 comprising the amino acid sequence of SEQ ID NO: 59: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle- Glu-Thr-Ile-CONH2, wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2- (gGlu)2-diacid and the diacid is a C20 diacid.

8. The peptide of claim 4 comprising the amino acid sequence of SEQ ID NO: 60: X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle- Glu-Thr-Ile-CONH2, wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)- diacid and the diacid is a C18 diacid.

9. The peptide of claim 4 comprising the amino acid sequence of SEQ ID NO: 61: X*-Gly-Pro-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-E#-Thr-Asn-K#-Arg-Leu-Nle- Glu-Thr-Ile-CONH2, wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)- diacid and the diacid is a C20 diacid.

10. The peptide of claim 1 of Formula (Ic) comprising the following amino acid sequence: NAI-1543420566Y-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-R12-Gln-Leu-Leu-Arg-R17-Val-Ile-Glu- Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-Asn-Ala-R36-R37-R38-Asp- Thr-Ile-CONH2 (SEQ ID NO: 125); (Ic) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m- diacid, wherein: n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]- acetyl (AEEA) amine is via the nitrogen of the N-terminus; R2is selected from pGlu, and Pro; R12 is selected from Phe and D-Phe; R17 is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23is selected from Lys and Aib; R25is selected from Glu, and K*; R26 is selected from Lys and Aib; R32is selected from Ala, and K*; R33is selected from Asn and K*; R36 is selected from Arg, and K*; R37 is selected from Leu, Ile, and K*; R38is selected from Leu, and Nle; K* represents Lys-(Z)0-1(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid, wherein: Z is Glu, gGlu, Lys, Ala, Gln or His; n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue; with the proviso if K* is present, X* is not present and only one of R25,R32,R33,R36and R37is K*.

11. The peptide of claim 10 comprising the amino acid sequence selected from: NAI-1543420566NAI-1543420566NAI-154342056612. The peptide of claim 10 comprising the amino acid sequence selected from:NAI-154342056613. The peptide of claim 1 of Formula (Id) comprising the following amino acid sequence: Y-R1-R2-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-R17-Val-Ile- Glu-Ile-Glu-R23-Gln-R25-R26-Glu-Lys-Gln-Gln-Ala-R32-R33-R34-R35-R36-R37-Nle-Glu- R40-R41-CONH2(SEQ ID NO: 126); (Id) wherein: Y is absent or X*; wherein X* is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m- diacid, wherein: n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]- acetyl (AEEA) amine is via the nitrogen of the N-terminus; R1is selected from pGlu, Gly, and Ser; R2is selected from pGlu, Pro, Gly, Glu, Gln, and Lys; R17 is selected from Lys, N-Me-K, a-Me-K, Glu, and Orn; R23 is selected from Lys and Aib; R25is selected from Glu, and K*; R26 is selected from Lys and Aib; R32 is selected from Ala, Glu, and Thr; R33is selected from Asn, Thr, and Gln; R34 is selected from Asn, and Gln; R35 is selected from Ala, d-Ala, Aib, Arg, AC3C, Glu, and Gln; R36is selected from Arg, Glu, Gln, and Ile; NAI-1543420566R37 is selected from Leu and Ile; R40is selected from Thr, and Glu; R41 is selected from Ile and Val; K* represents Lys-(Z)0-1(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid or Lys-(PEG12)-(gGlu)1-2-diacid, wherein: Z is Glu, gGlu, Lys, Ala, Gln or His; n is 1, 2 or 3; m is 0, 1, 2, or 3; and wherein the diacid is a C16, C18, C20, or C22 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue; with the proviso that one of X* and K* is present; with the further proviso that if K* is present, X* is not present.

14. The peptide of claim 13 comprising the amino acid sequence selected from:NAI-1543420566NAI-1543420566NAI-1543420566NAI-1543420566NAI-154342056615. The peptide of claim 1 of Formula (Ie) comprising the following amino acid sequence: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-R35-Arg-R37-Nle- Glu-R40-R41-CONH2 (SEQ ID NO: 138); (Ie) wherein: NAI-1543420566R35is selected from Ala, AC3C, and Aib; R37 is selected from Leu and Ile; R40 is selected from Thr and Glu; R41is selected from Val and Ile; and K* represents Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)n-(gGlu)m-diacid wherein: n is 0, 1, or 2; m is 1, or 2; and wherein the diacid is a C18, or C20 diacid, and wherein the linkage to the 2-[2-(2-amino-ethoxy)-ethoxy]-acetyl (AEEA) amine is via the gamma carboxylate of the gGlu residue.

16. The peptide of claim 15 wherein K* is selected from: Lys-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)2-(gGlu)-diacid; Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)- diacid; Lys-(gGlu)-diacid; and Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2- diacid; wherein the diacid in each instance is independently selected from a C18 and C20 diacid.

17. The peptide of any one of claims 1-4, and 13, wherein R25is K*.

18. The peptide of any one of claims 1, 2, 13, and 17, wherein R32is Glu.

19. The peptide of any one of claims 1-5, 17, and 18, wherein R38 is Nle.

20. The peptide of any one of claims 1, 2, 13, and 17-19, wherein: R25 is K*; R32 is Glu; and R38is Nle.

21. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 64: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2- (gGlu)2-diacid, wherein the diacid is a C20 diacid. NAI-154342056622. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 66: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2- (gGlu)-diacid, wherein the diacid is a C20 diacid.

23. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 68: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)- (gGlu)-diacid, wherein the diacid is a C18 diacid.

24. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 69: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2- (gGlu)-diacid, wherein the diacid is a C20 diacid.

25. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 67: pGlu-Gln-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Gln-Asn-Ala-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2- (gGlu)-diacid, wherein the diacid is a C20 diacid.

26. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO 63: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu- Nle-Glu-Thr-Ile-CONH2; wherein: K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)-diacid, wherein the diacid is a C20 diacid.

27. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 62: NAI-1543420566pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Ala-Arg-Leu-Nle- Glu-Thr-Ile-CONH2; wherein: K* is Lys-(gGlu)-C20-diacid.

28. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 72: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-AC3C-Arg-Leu- Nle-Glu-Glu-Val-CONH2; wherein: K* is Lys-(gGlu)-C20-diacid.

29. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 78 pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle- Glu-Glu-Val-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)- (gGlu)-C20-diacid.

30. The peptide of claim 15 comprising the amino acid sequence of SEQ ID NO: 55: pGlu-Gly-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Pro-Phe-Gln-Leu-Leu-Arg-Lys-Val-Ile- Glu-Ile-Glu-Lys-Gln-K*-Lys-Glu-Lys-Gln-Gln-Ala-Glu-Thr-Asn-Aib-Arg-Leu-Nle- Glu-Thr-Ile-CONH2; wherein K* is Lys-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)- (gGlu)-C18-diacid.

31. A pharmaceutically acceptable salt of the peptide of any one of claims 1-30.

32. A formulation comprising the peptide of any one of claims 1-30, in admixture with one or more pharmaceutically acceptable excipients.

33. A formulation comprising a pharmaceutically acceptable salt of the peptide of any one of claims 1-30, in admixture with one or more pharmaceutically acceptable excipients.

34. A method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of the peptide of any one of claims 1- 30, the pharmaceutically acceptable salt of claim 31, or the formulation of any one of NAI-1543420566claims 32-33, wherein the development or symptoms of the disease or disorder can be alleviated by the selective stimulation of CRFR2.

35. The peptide of any one of claims 1-30, the pharmaceutically acceptable salt of claim 31, or the formulation of any one of claims 32-33 for use in treating a disease or disorder selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity- linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

36. The use of the peptide of any one of claims 1-30, the pharmaceutically acceptable salt of claim 31, or the formulation of any one of claims 32-33 in the manufacture of a medicament for the treatment of a disease or disorder selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess NAI-1543420566body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age- related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

37. A method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of the peptide of any one of claims 1-30, the pharmaceutically acceptable salt of claim 31, or the formulation of any one of claims 32-33, wherein the disease or disorder is selected from: (i) type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram-negative bacteria in the colon, sarcopenia (including related to chronic kidney disease), gallbladder disease, and sleep apnea; (ii) a disease associated with excess body weight selected from obesity, obesity-linked type 2 diabetes, obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea; (iii) a skeletal muscle wasting disease selected from age-related muscle loss; (iv) the preservation of skeletal muscle during cancer cachexia; (v) a cardiovascular disease wherein the cardiovascular disease is selected from heart failure (for example, HFpEF), hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke; (vi) chronic kidney disease; (vii) myalgic encephalomyelitis; (viii) addiction / nicotine withdrawal syndrome; (ix) acute pancreatitis; (x) Prader-Willi syndrome; (xi) rare genetic causes of obesity such as NAI-1543420566Bardet-Biedl syndrome (BBS); (xii) muscular dystrophies in autoinflammatory and genetic diseases such as Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD); (xiii) anxiety, depression, and stress relief; (xiv) chronic fatigue syndrome; (xv) muscle atrophy prevention from, for example, ICU / hospitalization; (xvi) metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD); and (xvii) alcohol use disorder.

38. The method of claim 37 wherein the disease or disorder is selected from a disease associated with excess body weight selected from obesity-linked inflammation, obesity linked sarcopenia, obesity-linked gallbladder disease, and obesity-induced sleep apnea.

39. The method of claim 37 wherein the disease or disorder is age-related muscle loss.

40. The method of claim 37 wherein the disease or disorder is the preservation of skeletal muscle during cancer cachexia.

41. The method of claim 37 wherein the disease or disorder is a combination of weight management and the preservation or building of muscle mass.

42. The method of claim 37 wherein the disease or disorder is a cardiovascular disease selected from heart failure, HFpEF, hypertension, dyslipidemia, atherosclerosis, arteriosclerosis, coronary heart disease and stroke.

43. The method of claim 37 wherein the disease or disorder is selected from chronic kidney disease, myalgic encephalomyelitis, and addiction / nicotine withdrawal syndrome.

44. The method of claim 37 wherein the disease or disorder is acute pancreatitis.

45. The method of claim 37 wherein the disease or disorder is selected from type 2 diabetes, type-2 diabetes associated with insulin resistance, rheumatologic or inflammatory disorders, skin inflammation, acute inflammatory response due to gram- NAI-1543420566negative bacteria in the colon, sarcopenia, sarcopenia related to chronic kidney disease, gallbladder disease, and sleep apnea.

46. The method of claim 37 wherein the disease or disorder is selected from Prader-Willi syndrome and Bardet-Biedl syndrome (BBS).

47. The method of claim 37 wherein the disease or disorder is selected from muscular dystrophies in autoinflammatory and genetic diseases, Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD).

48. The method of claim 37 wherein the disease or disorder is selected from anxiety, depression, stress relief, chronic fatigue syndrome, and muscle atrophy prevention from ICU / hospitalization.

49. The method of claim 37 wherein the disease or disorder is selected from metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction–associated fatty liver disease (MAFLD).

50. The method of claim 37 wherein the disease or disorder is alcohol use disorder.

51. A method of reducing body fat in a subject comprising administering to the subject an effective amount of the peptide of any one of claims 1-30, the pharmaceutically acceptable salt of claim 31, or the formulation of any one of claims 32-33.

52. A method of reducing body weight and / or increasing weight loss in a subject comprising administering to the subject an effective amount of the peptide of any one of claims 1-30, the pharmaceutically acceptable salt of claim 31, or the formulation of any one of claims 32-33. NAI-1543420566

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