149 Bio announces nomination of integrin a3b1 as a target for its unique agonist antibodies as therapeutics for kidney disease


integrin a3b1 agonists are therapeutics for renal diseases

149 Bio, LLC has announced its therapeutic target for kidney diseases as integrin heterodimer alpha3beta1 (a3b1) that is highly expressed on kidney podocytes and is essential for podocyte attachment and health. The company also disclosed identification of novel allosteric agonist antibodies that target integrin a3b1 and enhance integrin-dependent ligand binding and cell adhesion.

Human kidney is a bean-shaped organ in the body that filters blood, by removing waste and excess fluids from the body via urine. Each of the body’s two kidneys is made up of a million tiny filters called nephrons, with a glomerulus as its main filtration apparatus. In turn, each glomerulus is composed of thousands of unique cells, called podocytes, that stick to the outside of tiny blood vessels and form an inter-digitating meshwork that forms the kidney’s molecular filter. a3b1 is the key integrin on the surface of podocytes that mediates podocyte attachment to the outside of blood vessels and form a healthy glomerulus. Progressive loss of podocytes in disease, via de-adhesion and injury, is a hallmark of multiple glomerular diseases, such as Focal Segmental Glomerulosclerosis (FSGS).

Since the integrin a3b1 mediates podocyte adhesion, activating integrin a3b1 may act as a compensatory mechanism in glomerular diseases, by helping stabilize podocyte attachment, preventing cell loss in the urine, and thereby providing protection from loss in kidney function. Indeed, prior research from the laboratory of 149 Bio’s co-founder, Vineet Gupta, PhD, has shown that certain integrin agonists help protect the podocytes and the kidney from injury and disease. Thus, the company developed an assay platform to discover agonist antibodies targeting a3b1 and has identified several novel antibodies.

The company expects to present some of the initial findings from this research at an upcoming international conference. The company anticipates moving its lead a3b1 allosteric agonist antibody candidate into clinical trials in 2023.

About 149 Bio, LLC

149 Bio is a privately held biopharmaceutical company focused on targeting integrin receptors with a highly differentiation mechanism of action – allosteric agonism. The company is leveraging pioneering discoveries of its co-founder Vineet Gupta, PhD, who was among the first to develop allosteric agonists as novel therapeutics for integrins. Dr. Gupta’s research has shown that allosteric agonism is a highly differentiated modality to develop therapeutics targeting integrins. The company has also developed a proprietary CellStaple platform that enables discovery and validation of novel candidates. The company is using this platform for rapid identification and development of allosteric agonists against multiple different integrin targets and has a pipeline of four different therapeutic programs in various stages of development.

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