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