Twist Bioscience (NASDAQ:TWST) Corporation (TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, today announced publication of preclinical data supporting the potential use of the highly potent and optimized GLP-1R antagonist antibody, TB-222-023, as a treatment for congenital hyperinsulinism (CHI). This pediatric genetic disorder has estimates of prevalence ranging from 1 in 25,000 to 1 in 50,000 live births in the U.S., which could translate into a steady-state treatable population of up to 2,500 cases in the U.S. It is caused by excessive pancreatic beta cell insulin secretion, resulting in hypoglycemia that can cause brain damage or death without treatment.
The Diabetes publication entitled, “Optimization of a glucagon-like peptide 1 receptor antagonist antibody for treatment of hyperinsulinism”, presents the results from several preclinical experiments using TB-222-023 as part of a research collaboration between Twist and the laboratory of Diva D. De León-Crutchlow, MD, Chief of the Division of Endocrinology and Diabetes and Director of the Congenital Hyperinsulinism Center at Children's Hospital of Philadelphia.
“Patients with congenital hyperinsulinism have few treatment options. The promising results from our studies described in the Diabetes paper demonstrate that targeting GLP-1R with an antibody antagonist, such as TB-222-023, could be an effective strategy for the treatment of this very serious condition,” said De León-Crutchlow.
Twist researchers had previously identified a highly potent and specific GLP-1R antagonist antibody, TB-001-003, from synthetic antibody libraries designed to target G protein-coupled receptors. Subsequently, this lead was optimized further for greater activity against GLP-1R using the Twist Antibody Optimization (TAO) library platform. One antagonist, TB-222-023, was identified and shown to be more potent than exendin-(9-39), a clinical stage GLP-1R antagonist peptide. The results of the studies conducted at Children's Hospital of Philadelphia showed that TB-222-023 effectively decreased insulin secretion in primary isolated pancreatic islets from a mouse model of hyperinsulinism, Sur1-/- mice, and in islets from an infant with hyperinsulinism. TB-222-023 also increased plasma glucose and decreased the insulin to glucose ratio in Sur1-/- mice.
“GLP-1R is very high profile within the industry and targeting this receptor with potent therapeutic candidates has potential in several medical conditions in addition to CHI, such as post-bariatric hypoglycemia (PBH),” said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. “This paper describes the power of Twist’s highly specific and potent antibody libraries as well as our ability to then optimize and improve on resulting candidates. The fact that TB-222-023 showed potency higher than a Phase 3 ready clinical candidate peptide is very promising. TB-222-023 has the potential to be a first-in-class antibody, a modality with advantages over peptides. We are now looking for partners to help take TB-222-023 and related antibodies forward in development.”
About Twist Biopharma Solutions (The Biologics Discovery and Optimization Division of Twist Bioscience)
Twist Biopharma Solutions combines high-throughput DNA synthesis technology, deep expertise in antibody engineering and in vivo, in vitro and in silico discovery methods to provide end-to-end antibody discovery solutions across the preclinical continuum and tailored to our partner’s specific needs. By leveraging our unique ability to manufacture DNA at scale, we can construct proprietary antibody libraries with discovery beginning with either in vivo or in vitro diversity. Our Library of Libraries gives our partners an integral and unbiased resource for antibody therapeutic discovery and optimization. This precise and rational approach to library fabrication combined with sophisticated bioinformatics and software expertise expedites antibody discovery by decreasing risk, increasing speed, and lowering the failure rate for antibody therapeutic development. Additionally, in vivo discovery approaches including single B cell screening and hybridoma discovery enable parallel paths where multiple technology methods can be leveraged to create a panel of highly diverse antibody leads. Our automated screening and panning processes enable us to identify high affinity leads that our partners can move forward into the clinic. We also offer supporting development capabilities, including IgG conversion, expression, purification, biophysical characterization, and functional characterization.
For more information visit: https://www.twistbioscience.com/products/antibody-discovery/twist-bioscience-and-abveris