Summary of Septerna FY Conference Call Company Overview - **Company**: Septerna (NasdaqGM:SEPN) - **Focus**: G-protein coupled receptors (GPCRs) and drug discovery through the Native Complex Platform - **Financial Position**: Well-capitalized with cash runway into at least 2029 [2][3] Key Programs and Developments SEP-479 - **Indication**: Hyperparathyroidism - **Type**: Second-generation PTH1 receptor agonist - **Clinical Status**: Preparing to enter the clinic in the first half of next year - **Dosing**: Active at 0.15 mg/kg once daily, significantly lower than previous candidate SEP-786 [5][6] - **Pharmacokinetics**: Projected human half-life of 40-80 hours, supporting once-daily oral dosing [6][24] - **Preclinical Data**: Demonstrated normalization of calcium and phosphate levels in a rat model of hyperparathyroidism [5][6] - **Comparison with Peptides**: Aims to achieve similar receptor occupancy to peptide therapies, with effective doses requiring only 2-3% receptor occupancy [25][26] SEP-631 - **Indication**: Mast cell-driven diseases - **Type**: Negative allosteric modulator for MRGPRX2 - **Clinical Status**: Currently in phase I trials with a standard SAD-MAD design - **Preclinical Data**: Demonstrated ability to inhibit extravasation in a mouse model, indicating potential efficacy [10][11] TSHR Program - **Indication**: Graves' disease and thyroid eye disease - **Development Focus**: Optimizing both potency and pharmaceutical properties, aiming for selectivity against closely related receptors [34][35] - **Future Plans**: Targeting Graves' disease first, with potential expansion to prevent thyroid eye disease [36] Market Opportunities - **SEP-479**: Represents a significant market opportunity in treating hyperparathyroidism, with a focus on achieving effective calcium levels in patients [8][31] - **SEP-631**: Addresses unmet needs in mast cell-driven diseases, with a strong preclinical profile [10][11] - **TSHR Program**: Targets a large patient population with Graves' disease, aiming to improve treatment outcomes [36] Additional Insights - **Challenges**: Previous candidate SEP-786 faced issues in phase I due to unconjugated bilirubin increases, leading to its discontinuation [4][5] - **Regulatory Considerations**: Emphasis on ensuring safety in healthy volunteers before advancing to patient studies [32] - **Collaboration**: Notable collaboration with Novo Nordisk on the incretin receptor agonist program [3] Conclusion - Septerna is advancing multiple promising drug candidates with significant market potential, focusing on innovative approaches to GPCR-targeted therapies. The company is well-positioned for future growth with a solid financial foundation and a clear development strategy.