Simplifying Progress Advancements and Technologies Driving Peptide Drug Design and Development Peptides are small intrinsic signaling molecules associated with numerous physiological functions. Since the introduction of insulin in the clinic in the 1920s, and the advent of peptide synthesis in the 1950s, dozens of therapeutic peptides have been developed. Peptides offer several advantages over other therapeutics, and ongoing research and development is aimed at enhancing their stability and efficacy. Advantages Challenges Discovery and Development ▪ high selectivity and potency ▪ chemical and physical ▪ new peptides and protein instability fragments ▪ safety and tolerability hydrolysis and oxidation focused libraries ▪ predictable metabolism ▪ ▪ aggregation new formulations ▪ easily synthesized ▪ ▪ short half-life multifunctional peptides ▪ shorter time to market ▪ ▪ and conjugates ▪ few are orally available (Fosgerau & Hoffmann, 2015) Types of Therapeutic Peptides Cell surface peptides Cell-penetrating peptides Peptide-drug conjugates Peptide CPP + macromolecule Membrane receptor Peptide-drug conjugate Intracellular signaling cascade Drug released Key Technologies that Accelerate Discovery Key solutions for Advanced Flow Live-Cell Biolayer concentration Cytometry Analysis Interferometry buffer exchange and diafiltration ▪ Assess phenotype ▪ Quantitative ▪ Label-free ▪ Rapid and function post live-cell imaging detection concentration of peptide treatment and analysis peptides in times ▪ Insights into as quick as under ▪ Rapid access to ▪ Visualize biomolecular multiple cellular and quantify interactions and ten minutes parameters cytotoxicity mechanism ▪ PES and RC using time-lapse of action membranes to ▪ Fewer cells and imaging optimize molecule less reagent ▪ Rapid, real-time Continuous results to membrane ▪ High throughput ▪ kinetic compatibility processing and ▪ Crude sample analysis measurements compatibility ▪ Desalting samples over days or and exchange ▪ Deeper, more months buffer in efficient insights concentrators ▪ Real-time insights into biological instead of lengthy processes overnight dialysis Approved Therapeutic Peptides CENTRAL NERVOUS Corticotropin Glatiramer Taltirelin SYSTEM inflammatory diseases Multiple sclerosis Spinocerebellar West syndrome degeneration Melanocortin MHC II TRH receptor receptors Created by popcornarts from the Noun Project UROLOGY Vasopressin Desmopressin Buserelin Leuprorelin Triptorelin Vasodilatory shock Diabetes insipidus Prostate cancer Prostate cancer Prostate cancer Bleeding esophogeal Nocturia Endometriosis Endometriosis Endometriosis Breast varices Assisted reproduction Uterine fibroids cancer Precocious puberty Precocious puberty Created by Prettycons from the Noun Project AVP1 receptor V2 receptor GnRH receptor GnRH receptor GnRH receptor Goserelin Aviptadil Abarelix Degarelix Breast cancer Erectile dysfunction Prostate cancer Prostate cancer Endometriosis Prostate cancer GnRH receptor VIP1 receptor GnRH receptor GnRH receptor Stem Cell Biology INFERTILITY & Oxytocin Gonadorelin Nafarelin Histrelin Cetrorelix OB-GYN Labor induction Assisted reproduction Precocious puberty Prostate cancer Assisted Postpartum Primary amenorrhea Endometriosis Precocious puberty reproduction hemorrhage Lactation OT receptor GnRH receptor GnRH receptor GnRH receptor GnRH receptor Created by libertetstudio from the Noun Project Ganirelix Atosiban Carbetocin Assisted reproduction Preterm labor Postpartum hemorrhage GnRH receptor OT receptor OT receptor ENDOCRINOLOGY Lanreotide Pasireotide Etelcalcetide Tetracosactide Octreotide Acromegaly Acromegaly Cushing’s Secondary Multiple inflammatory Acromegaly Neuroendocrine disease hyperparathyroidism diseases Neuroendocrine tumors tumor Created by Line Icons Pro from the Noun Project Created by IcoLabs SST receptors SST receptors CasR MC receptors SST 2 receptor from the Noun Project Created by Eucalyp from the Noun Project OPHTHALMOLOGY Eledoisin Dry eye NK1 receptor Created by sumhi_icon from the Noun Project HEPATOLOGY/ Somatostatin Terlipressin CRITICAL CARE Bleeding esophogeal Bleeding esophageal varices varices SST receptor AVP1 receptor Created by fauzan akbar from the Noun Project PAIN Felypressin Ziconotide Dental anesthesia Pain adjunct AVP1 receptor N-type calcium Created by IYIKON from the Noun Project channels BONES & Calcitonin (salmon) Elcatonin Calcitonin (human) Aloparatide Teriparatide CONNECTIVE TISSUES Hypercalcemia Osteoporosis Hypercalcemia Paget’s Osteoporosis Osteoporosis Paget’s disease disease Osteoporosis Osteoporosis Calcitonin receptor Calcitonin receptor Calcitonin receptor PTH1 receptor PTH1 receptor Created by libertetstudio from the Noun Project HEMATOLOGY Ornipressin Bivalirudin Peginesatide Romiplostim Bleeding esophageal Acute coronary Anemia associated Immune varices syndrome with chronic kidney thrombocytopenic Heparin-induced disease purpura thrombocytopeni Thrombosis Created by Eucalyp AVP1 receptor Thrombin EPO receptor Thrombopoietin from the Noun Project receptor ONCOLOGY Mifamurtide Carfilzomib Osteosarcoma Multiple myeloma NOD2 protein Chymotrypsin-like active site in 20S proteasome Created by Vectorstall from the Noun Project ALLERGY & Thymopentin IMMUNOLOGY Autoimmune and infectious diseases HLA-DR Created by LINECTOR from the Noun Project CARDIOVASCULAR Enalapril Lisinopril Carperitide Eptifbatide Nesiritide Heart failure Acute myocardial Acute decompensated Acute coronary Acute Hypertension infarction heart failure syndrome (medical decompensated Heart failure management or heart failure Hypertension percutaneous coronary intervention) Angiotensin- Angiotensin NPR-A GP IIb IIIa NPR-A Created by Nick Bluth from the Noun Project converting enzyme converting enzyme Icatibant Heriditary angioedema in C1-esterase- inhibitor deficiency B2 receptor METABOLIC Glucagon Pramlintide Exenatide Liraglutide Tesamorelin Hypoglycemia Type 1 and 2 diabetes Type 2 diabetes Type 2 diabetes HIV lipodystrophy Glucagon receptor Calcitonin receptor GLP-1 receptor GLP-1 receptor GHRH receptor Created by Turkkub from the Noun Project Lixisenatide Albiglutide Dulaglutide Type 2 diabetes Type 2 diabetes Type 2 diabetes GLP-1 receptor GLP-1 receptor GLP-1 receptor ORTHOPEDICS P-15 Bone grafting α2β1 Created by Line Icons Pro from the Noun Project ANTIMICROBIAL/ Enfuvirtide ANTIVIRAL HIV infection gp41 Created by ProSymbols from the Noun Project RESPIRATORY Lucinactant Neonatal respiratory distress syndrome Surfactant replacement Created by karina from the Noun Project GASTROENTEROLOGY Linaclotide Teduglutide Plecanatide Irritable bowel Short bowel syndrome Chronic idiopathic syndrome constipation Chronic idiopathic constipation Created by DailyPM from the Noun Project GC-C receptor GLP-2 receptor GC-C receptor DERMATOLOGY Afamelanotide Erythropoietic protoporphyria MC1 receptor (Adapted from Lau & Dunn, 2017) Learn about groundbreaking solutions to advance therapeutic peptide development, using novel development strategies focused on the improvement of pharmaceutical properties. Discover our solutions at www.sartorius.com/therapeutic-peptides References 1. Fosgerau, K., & Hoffmann, T. (2015). Peptide therapeutics: Current status and future directions. Drug Discovery Today, 20(1), 122–128. https://doi.org/10.1016/j. drudis.2014.10.003 2. Lau, J., & Dunn, M. (2017). Therapeutic peptides: historical perspectives, current development trends, and future directions. Bioorg Med Chem, 61(16), 5985–5991. https://doi.org/10.1038/nature.