Summary of Septerna's Presentation at the J.P. Morgan Healthcare Conference Company Overview - **Company Name**: Septerna - **Focus**: Development of drugs targeting G-Protein Coupled Receptors (GPCRs) using the Native Complex Platform for drug discovery [2][5] Key Programs 1. **SCP479**: - **Target**: Parathyroid hormone receptor agonist for hypoparathyroidism - **Status**: Wrapping up IND-enabling studies, expected to enter phase one trials in the first half of 2025 [3][25] - **Market Opportunity**: Significant unmet need; current standard of care involves high doses of calcium and vitamin D [46] - **Clinical Data**: Early studies show normalization of serum calcium levels in animal models [19][24] - **Pharmaceutical Properties**: Projected human half-life of 40-80 hours, supporting once-daily oral dosing [23] 2. **SCP631**: - **Target**: MRGPRX2 for mast cell-driven diseases, including chronic spontaneous urticaria - **Status**: Phase one trial wrapping up, with data expected to be shared at the Quad AI meeting in March [4][31] - **Mechanism**: Insurmountable negative allosteric modulator, effectively turning off the receptor [28][48] - **Market Need**: Significant unmet need for second-line treatment options for patients refractory to high-dose antihistamines [27] 3. **Other Programs**: - **Thyroid-Stimulating Hormone Receptor (TSHR)**: Targeting Graves' disease and thyroid eye disease with a negative allosteric modulator [34][35] - **Incretin Receptor Agonist Program**: Collaboration with Novo Nordisk focusing on multiple receptors [39] Market Insights - **Hypoparathyroidism Market**: Approximately 70,000-80,000 patients in the U.S.; current treatments are not fully effective, creating demand for oral options [46][47] - **Mast Cell Disorders**: Growing evidence of mast cell involvement in various conditions, indicating a broad opportunity for SCP631 [50] Platform and Technology - **Native Complex Platform**: Allows for the isolation of GPCRs in a functional form, enabling high-resolution structure determination and screening of billions of compounds [7][9] - **Drug Discovery Efficiency**: Rapid optimization of compounds, with timelines from medicinal chemistry to active compounds in animals being less than a year [10] Financial Position - **Capitalization**: Well-capitalized with cash runway into at least 2029 following IPO and collaboration deals [3] - **Collaboration with Novo Nordisk**: Includes three receptors and undisclosed targets, with Novo covering all R&D costs going forward [39] Regulatory and Development Strategy - **Phase One Trials**: Focus on safety, tolerability, and pharmacokinetics, with plans to pivot quickly to patient studies based on promising results [45] - **IP Strategy**: Protecting novel binding pockets and chemical structures identified through the platform [52] Conclusion - **Future Focus**: Execution on the current pipeline while remaining opportunistic for business development and partnerships [53]