Summary of Septerna's Conference Call Company Overview - **Company**: Septerna - **Focus**: G protein-coupled receptors (GPCRs) and small molecule discovery using the Native Complex platform - **Financial Position**: Well-capitalized with an operating cash runway into at least 2029 [2][2][2] Key Programs 1. **SEP479 Program** - **Target**: Parathyroid hormone receptor agonist for hyperparathyroidism - **Clinical Development**: Anticipated entry into the clinic in the first half of next year [3][3][9] - **Pharmacodynamics**: Demonstrated ability to normalize serum calcium and phosphate levels in preclinical studies with low dosing (0.15 mg/kg) [7][7][8] - **Safety Profile**: Improved pharmaceutical properties compared to previous candidate SEP786, which was discontinued due to safety issues related to bilirubin levels [6][14][15] - **Half-Life**: Predicted human half-life of 40-80 hours, supporting once-daily dosing [7][17][17] 2. **SEP631 Program** - **Target**: MRGPRX2 negative allosteric modulator for mast cell-driven diseases, including chronic spontaneous urticaria - **Clinical Development**: Currently in phase one trial, with data expected in early 2026 [9][12][25] - **Pharmacodynamics**: Demonstrated complete inhibition of extravasation in preclinical models [11][11] - **Differentiation**: Unique profile as an insurmountable negative allosteric modulator, potentially offering a long duration of action [10][19] 3. **Thyroid-Stimulating Hormone Receptor Program** - **Target**: Graves' disease and thyroid eye disease - **Market Opportunity**: Significant unmet need with a large market size; current treatments are outdated [26][26][27] - **Mechanism**: Utilizing an insurmountable negative allosteric modulator approach to inhibit receptor activation by various antibodies [27][28] Collaborations and Financials - **Collaboration with Novo Nordisk**: Announced a significant collaboration in May, including $195 million upfront and full support for R&D costs [4][4] Market Context and Competitive Landscape - **Mast Cell Indications**: Potential to target multiple mast cell-driven diseases, with chronic spontaneous urticaria as the initial focus [21][21] - **Competitive Landscape**: Acknowledgment of a crowded market for chronic spontaneous urticaria treatments, with a focus on differentiating SEP631 from existing therapies [22][22][19] Future Outlook - **Pipeline Expansion**: The platform has broader applications for GPCRs, with potential for a deep pipeline of products targeting various therapeutic areas [29][30] - **Clinical Trials**: Plans to initiate trials for SEP631 in chronic spontaneous urticaria following successful phase one results [25][25] Conclusion - **Overall Sentiment**: Positive outlook on the progress of Septerna's programs, with a focus on advancing clinical development and addressing significant market needs in the biopharma space [30][30]