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Septerna TSHR NAM program
- Development stage
- Preclinical
- Lead developer
- Septerna
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Septerna is developing an oral small molecule thyroid-stimulating hormone receptor (TSHR) negative allosteric modulator (NAM) program for the treatment of Graves' disease and thyroid eye disease (TED). The program targets TSHR, a G protein-coupled receptor (GPCR) that is pathologically activated by autoantibodies in these conditions, leading to hyperthyroidism and orbital complications like proptosis. By binding to an allosteric site on the receptor, these NAMs are designed to inhibit autoantibody-induced signaling. Preclinical lead compounds, including SP-1351, have demonstrated the ability to reverse hyperthyroidism and eye bulging in mouse models and have shown inhibition of patient-derived TSHR autoantibodies in human cell assays. As of late 2024, the program is in the lead optimization stage, progressing toward the selection of a formal development candidate for IND-enabling studies.
- Other names
- TSHR Program
02
Targets
TSHR (Thyroid-stimulating hormone receptor)
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