Twist Bioscience Functional GLP-1R Antibodies Identified From Its Proprietary Synthetic DNA GPCR Libraries Demonstrate Potent Blood Glucose Control

Twist Bioscience Corporation (Nasdaq: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, today announced positive preclinical data demonstrating that GLP-1R antibodies identified from its proprietary G-protein coupled receptor (GPCR) libraries showed potent blood glucose control. Glucagon-like peptide-1 receptor (GLP-1R) is a class B GPCR that acts as the receptor for the incretin GLP-1, a peptide released to regulate insulin levels in response to food intake. The data were published online in mAbs detailing the work of researchers at Twist Biopharma, the biologics division of Twist Bioscience.

“These data demonstrate the power of our antibody libraries. The panel of antibodies generated showed excellent results in these preclinical studies, with one antibody possessing a half-life needed to achieve once-weekly dosing in treating the Type-2 diabetes patients. GLP-1R agonists and antagonists are widely used to control blood glucose levels to treat multiple diseases, which suggests our potent antibodies could have multiple clinical indications,” said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. “We continue to advance these antibody leads and in parallel, work with a wide variety of partners to discover and optimize their antibodies across modalities and disease areas.”

As published in mAbs, researchers discovered a panel of 13 high-affinity GLP-1R-targeting antibodies by mining Twist Biopharma’s proprietary GPCR-focused phage display library with 1 × 10¹⁰ diversity created using Twist’s precision synthetic DNA writing technologies. In the resulting antibodies, the heavy chain complementarity-determining region 3 (HCDR3), which confers most of the binding activity and specificity, was found to include either a GLP-1 motif, a GLP-2 motif, or an unknown/unique sequence. Many of the GLP-1R antibodies discovered were GLP-1R antagonists, which have the ability to prevent hypoglycemia incidents in congenital hyperinsulinism and post-bariatric hyperinsulinism.

In addition, Twist Biopharma created an agonist antibody by fusing GLP-1 peptide to the light chain of a non-functional GLP-1R-specific antibody. The resulting peptide antibody fusion, TB59-2, had a comparable binding affinity to the free peptide to GLP-1R-expressing CHO cells, comparable function in the agonistic format of the cAMP activity assay and a 2-day half-life in preclinical model studies using 10 mg/kg dosing and based on the measurement of the full GLP-1 peptide presence in the blood samples. In vivo studies indicate that TB59-2 has potential to be used to treat type 2 diabetes with a once-weekly dose.