Septerna (NasdaqGM:SEPN) FY Conference Transcript

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.