A First-in-Class Treatment For Hypoxia

GB-001 is a tissue-targeted, engineered protein that produces red blood cells and protects tissues against hypoxia

Therapeutic Effects and Side Effects of Erythropoietin (EPO)

Erythropoietin is a mammalian hormone that mediates the body’s response to hemorrhage – massive blood loss.  As part of this response, EPO stimulates production of red blood cells, to replace the cells that were lost and to improve oxygen delivery. EPO also tells tissues not to die in spite of the hypoxia that they experience during blood loss. Finally, EPO upregulates blood clotting, which is important if there is a major wound that is in the process of healing.

If a patient suffers from hypoxia due to COPD, cystic fibrosis, or COVID-19, it would be useful to increase red blood cells and to tell cells to not die in the face of low oxygen.  It is NOT useful to increase blood clotting, which may increase the chances of a heart attack or stroke.  

General Biologics is developing a form of erythropoietin, GB-001, in which the red blood cell-producing activity and tissue-protective activity of EPO are retained, but the blood-clotting activity is significantly reduced.  The protein engineering uses new principles inspired by natural hormones that signal through complex receptor systems.

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GB-001 is fabricated from protein modules that direct EPO activity to the right cells.

GB-001: Cell Targeting of Hormone Activity

GB-001 contains an EPO protein module that sends hormonal signals, and an antibody element that directs this protein to red blood cell precursors.  These are connected by a short peptide linker, so that GB-001 is a single protein chain and can be manufactured by the same, well-established methods used to make monoclonal antibodies.

GB-001 also contains a mutation (X) in the EPO module that reduces its activity.  The mutation is on the surface of the EPO protein and is at a point of contact with the EPO receptor.  The effect of this mutation is to reduce (but not eliminate) binding to the EPO receptors that stimulate production of red blood cells and platelets.  However, GB-001 will first bind to red blood cell precursors via its antibody module (blue diamond), and this places the EPO module (red ellipse) in a very high concentration on the cell surface, so that binding to EPO receptors occurs in spite of the weakening mutation.  Production of red blood cells results.  However, binding to EPO receptors on platelet precursors is significantly reduced, and production of platelets is also reduced.

Tissue-protective signaling by EPO occurs through a receptor system that is different from the system that signals to red blood cells and platelets.  The mutation in the EPO element does not affect signaling through this system, so GB-001 should help protect tissues against damage.

Note:  Statements about receptor systems used for EPO signaling and properties of GB-001 represent current scientific consensus and working hypotheses, but are subject to the usual limitations of statements about cutting-edge scientific research.

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