WO-2026096203-A1 - PEPTIDE ANALOGS AND METHODS OF USING THE SAME

Abstract

Provided herein are peptide analogs of gastrin releasing peptide (GRP), corresponding pharmaceutical compositions, and methods of using such peptide analogs of GRP in the treatment of a disease or disorder.

Inventors

• NEELAMKAVIL, Santhosh F.
• MOYES, CHRISTOPHER

Assignees

• KALLYOPE, INC.

Dates

Publication Date

20260507

Application Date

20251015

Priority Date

20241029

Claims (20)

1. CLAIMS
2. WHAT IS CLAIMED IS:
3. 1. A peptide comprising the amino acid sequence of Formula (I):
4. X0-Xl-X2-X3-7MeTrp-X5-X6-P-Ala-X8-X9-Nle
5. or a pharmaceutically acceptable salt, solvate, or isomer thereof, wherein:
6. XO is absent or a natural or non-natural amino acid or amino acid analog;
7. XI, X2, X3, X5, X6, X8, and X9 are each independently a natural or non-natural amino acid or amino acid analog;
8. X3 is not Leu; and
9. when XO is a natural or non-natural amino acid or amino acid analog, X2 is not Leu;
10. 7MeTrp is 7-methyltryptophan;
11. Nle is norleucine; and
12. wherein the peptide is conjugated to one or more lipid moieties.
13. 2. A peptide comprising the amino acid sequence of Formula (II):
14. X0-Xl-X2-X3-7MeTrp-X5-X6-P-Ala-X8-X9-Nle
15. or a pharmaceutically acceptable salt, solvate, or isomer thereof, wherein:
16. XO is absent or a natural or non-natural amino acid or amino acid analog;
17. XI, X2, X3, X5, X6, X8, and X9 are each independently a natural or non-natural amino acid or amino acid analog;
18. X6 is not Thr; and
19. when XO is a natural or non-natural amino acid or amino acid analog, X5 is not Thr;
20. 7MeTrp is 7-methyltryptophan;

Description

PEPTIDE ANALOGS AND METHODS OF USING THE SAME CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U. S. Provisional Application No. 63/713,191, filed on October 29, 2024, U. S. Provisional Application No. 63/757,920, filed on February 13, 2025, and U. S. Provisional Application No. 63/784,599, filed on April 7, 2025, each of which is hereby incorporated by reference in its entirety. SEQUENCE LISTING [0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on September 30, 2025, is named 50339-761_601_SL.xml and is 517,117 bytes in size. BACKGROUND [0003] Gastrin releasing peptide (GRP) is a 27 amino acid peptide that stimulates release of gastrin and regulates gastric acid secretion. GRP1-27 can be further processed to give GRP18-27, also known as GRP-10 or neuromedin C. GRP receptors are widely distributed in mammals, especially in the central nervous system (CNS) and peripheral nervous system. GRP receptors regulate several functions including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation. SUMMARY [0004] Described herein are peptide analogs of gastrin releasing peptide (GRP). In some embodiments, a peptide described herein is conjugated to a lipid. In some embodiments, a peptide described herein is a gastrin releasing peptide receptor (GRPR) agonist. In some embodiments, a peptide described herein is useful in the treatment of a disease or disorder. In some embodiments, the disease or disorder is gastrointestinal disease or a weight-related condition. [0005] In one aspect, provided herein is a peptide comprising the amino acid sequence of Formula (I): X0-Xl-X2-X3-7MeTrp-X5-X6-P-Ala-X8-X9-Nle wherein: XO is absent or a natural or non-natural amino acid or amino acid analog; XI, X2, X3, X5, X6, X8, and X9 are each independently a natural or non-natural amino acid or amino acid analog; X3 is not Leu; and when XO is a natural or non-natural amino acid or amino acid analog, X2 is not Leu; 7MeTrp is 7-methyltryptophan; Nle is norleucine; and wherein the peptide is conjugated to one or more lipid moieties. [0006] In some embodiments, the peptide of Formula (I) is a peptide of Formula (XI): X(-1)-X0-X1-X2-X3-7MeTrp-X5-X6-β-Ala-X8-X9-Nle, wherein X0 and X(-1) are each independently a natural or non-natural amino acid or amino acid analog; wherein X2 and X3 are not Leu. [0007] In one aspect, provided herein is a peptide comprising the amino acid sequence of Formula (II): X0-Xl-X2-X3-7MeTrp-X5-X6-P-Ala-X8-X9-Nle wherein: X0 is absent or a natural or non-natural amino acid or amino acid analog; XI, X2, X3, X5, X6, X8, and X9 are each independently a natural or non-natural amino acid or amino acid analog; X6 is not Thr; and when X0 is a natural or non-natural amino acid or amino acid analog, X5 is not Thr; 7MeTrp is 7-methyltryptophan; Nle is norleucine; and wherein the peptide is conjugated to one or more lipid moieties. [0008] In some embodiments, the peptide of Formula (II) is a peptide of Formula (XII): X(-1)-X0-X1-X2-X3-7MeTrp-X5-X6-β-Ala-X8-X9-Nle, wherein X0 and X(-1) are each independently a natural or non-natural amino acid or amino acid analog; and wherein X5 and X6 are not Thr. [0009] In one aspect, provided herein is a peptide comprising the amino acid sequence of Formula (III): X0-Xl-X2-X3-7MeTrp-X5-X6-P-Ala-X8-X9-Nle wherein: X0 is absent or a natural or non-natural amino acid or amino acid analog; X1, X2, X3, X5, X6, X8, and X9 are each independently a natural or non-natural amino acid or amino acid analog; X9 is not Phe; and when X0 is a natural or non-natural amino acid or amino acid analog, X8 is not Phe; 7MeTrp is 7-methyltryptophan; Nle is norleucine; and wherein the peptide is conjugated to one or more lipid moieties. [0010] In some embodiments, the peptide of Formula (III) is a peptide of Formula (XIII): X(-l)-X0-Xl-X2-X3-7MeTrp-X5-X6-P-Ala-X8-X9-Nle, wherein XO and X(-l) are each independently a natural or non-natural amino acid or amino acid analog; and wherein X8 and X9 are not Phe. [0011] Other objects, features and advantages of the compounds, methods and compositions described herein will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments, are given by way of illustration only, since various changes and modifications within the spirit and scope of the instant disclosure will become apparent to those skilled in the art from this detailed description. INCORPORATION BY REFERENCE [0012] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indica