Peptide drugs are capable of affecting a range of therapeutic targets with high specificity. Innovation in Peptide Design & Delivery is needed to make this class of drugs an important player. a _peptide therapeutic_ as a chain of amino acids (the building blocks of proteins) containing [40 amino acids or less](http://weeklycms.biotechprimer.com/t/t-l-ukottt-uljrddkyd-t/), and regulates them as small molecules.  Peptide therapeutics are *similar to small molecule drugs* in that they can be synthesized in the lab using a **peptide synthesis machine** — a machine that links amino acids together in a specified order. Peptides also *share key characteristics with large molecule drugs* which include sensitivity to digestive enzymes, delivery by injection, and high specificity for their target ## Examples Examples of peptide drugs on the market today include - glucagon-like peptide-1 (GLP-1) receptor activators, such as: - Byetta (**AstraZeneca**; Cambridge, England), - Victoza (**Novo Nordisk**; Bagsvaerd, Denmark), - Trulicity (**Eli Lilly**; Indianapolis, Indiana). - These peptide drugs work by interacting with a receptor on the surface of pancreatic beta cells and stimulate the release of insulin for diabetes ## Innovation Opportunity Most peptide therapeutics do not penetrate cell membranes. Design peptides that could enter cells would endow them with the best characteristics of both large and small molecule therapies. ![[Pasted image 20210910105809.png]] #### Stapled Peptides Aileron Therapeutics - Peptides are synthesized according to an optimized amino acid sequence - Next, a chemical linker is used to connect two amino acids within the chain, creating a folded or “stapled” version of the peptide.  - These stapled peptides still recognize their target protein, are more stable, and better able to penetrate cell membranes than the linear versions. Aileron’s leading stapled peptide candidate, ALRN-6924, activates [p53](http://weeklycms.biotechprimer.com/t/t-l-ukottt-uljrddkyd-h/), a protein that triggers cell death in cancer cells but is inactivated in a range of malignancies. ALRN-6924 is in Phase II clinical studies for lymphoma. The company is pursuing the development of stapled peptides in a range of therapeutic areas, including *inflammation and endocrine and metabolic diseases.* #### Bicycle Peptides Bicycle Therapeutics - Bicycle Therapeutics also uses chemically-linked peptides to i**ncrease stability, target interaction, and penetrate cells**. Their peptides are formed — using a chemical linker — into the shape of a bicycle. - Bicycle’s lead candidate, BT1718, is a “bicycle drug conjugate” — a bicyclic peptide with a toxic drug attached. The peptide targets a protein called “membrane type 1 matrix metalloproteinase” (MT1-MMP) which is overexpressed in many tumors. - BT1718 delivers its toxic payload to tumors overexpressing MT1-MMP. BT1718 is now in Phase I clinical studies for solid tumors.