Financial Data and Key Metrics Changes - The company has identified a new development candidate for its parathyroid hormone receptor program, moving forward after unexpected findings with a previous compound [3][5] - The new compound, SEP-479, shows significantly improved pharmaceutical properties compared to the discontinued SEP-786, with a lower effective dose in preclinical models [9][10] Business Line Data and Key Metrics Changes - The parathyroid hormone receptor program has transitioned to SEP-479, which has demonstrated the ability to normalize serum calcium levels in preclinical models [9][10] - The MRGPRX2 program has initiated a phase one trial with a randomized, placebo-controlled design, focusing on skin-based indications [14][15] Market Data and Key Metrics Changes - The company has formed a collaboration with Novo Nordisk, which includes a $195 million upfront payment and covers all R&D costs going forward, allowing the company to expand its programs without increasing its burn rate [46][47] Company Strategy and Development Direction - The company is focused on GPCR drug discovery, utilizing its Native Complex Platform to optimize compounds quickly and effectively [2][4] - The strategic partnership with Novo Nordisk aims to leverage their expertise in the metabolic space while pursuing multiple programs in parallel [46][47] - The company is exploring additional opportunities in areas such as osteoporosis, neurology, cardiovascular diseases, and respiratory diseases [50][51] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the connection between preclinical data and eventual patient data for PTH peptides, indicating a strong potential for the new compound [21][22] - The company aims to gather safety and pharmacokinetic data in phase one trials to inform future patient dosing strategies [23][24] Other Important Information - The company has completed additional studies on SEP-786 to understand its effects better, particularly regarding bilirubin metabolism [7][8] - The company is optimistic about the potential for once-daily dosing with SEP-479, which could significantly improve patient compliance [31][32] Q&A Session Summary Question: When did the company start to see issues with bilirubin in the SINOS study for SEP-786? - The company observed bilirubin issues within a couple of days in the SINOS study, similar to findings in patients [18] Question: What is the development plan for SEP-479? - The company plans to conduct a phase one study with hopes of seeing safety and pharmacokinetic properties that will inform patient dosing [20][22] Question: How does SEP-479 differ from SEP-786? - SEP-479 is a completely different structural series with no observed functional differences in assays, but it is expected to have a lower risk of off-target effects [29][30] Question: What is the expected timeline for the phase one trial? - The company anticipates starting the phase one trial in the first half of next year, with more precise timing to be communicated later [34] Question: What is the opportunity within mast cell diseases for the MRGPRX2 program? - The company sees potential in various mast cell-driven diseases, including chronic spontaneous urticaria and atopic dermatitis, and plans to pursue multiple lead indications [35][40]

Summary of Septerna (SEPN) 2025 Conference Call Company Overview - **Company**: Septerna (SEPN) - **Focus**: Development of drugs targeting G protein-coupled receptors (GPCRs) using a proprietary platform called the native complex platform [1][2] Portfolio Strategy - **Target Selection**: Focus on biologically and clinically validated targets with significant unmet needs and market opportunities [2] - **Current Programs**: Discussion of four main programs, including a parathyroid hormone receptor agonist, MRGPRX2, thyroid stimulating hormone receptor negative allosteric modulator, and an incretin receptor agonist [3][4] Financial Position - **Capitalization**: Well-capitalized following an IPO in October and a recent collaboration with Novo Nordisk, providing a strong financial position for ongoing research and development [3][54] Key Programs 1. **Parathyroid Hormone Receptor Agonist Program** - **Target**: Oral small molecules for hypoparathyroidism [16] - **Challenges**: Discontinued trial of first compound (SEP-786) due to unanticipated bilirubin levels, but ongoing investigation into next-generation compounds [23][24][26] - **Animal Model Results**: Promising results in normalizing calcium levels in hypoparathyroid rat models with new compounds showing lower dosing requirements compared to SEP-786 [29][31][34] 2. **MRGPRX2 Program** - **Target**: Mast cell diseases, including chronic spontaneous urticaria and allergic asthma [35][37] - **Compound**: SEP-631, a negative allosteric modulator showing potent inhibition of receptor activation and promising preclinical results [38][42] - **Clinical Timeline**: Expected to enter Phase 1 trials in Q3 [43] 3. **Thyroid Stimulating Hormone Receptor Program** - **Focus**: Treating Graves' disease and thyroid eye disease with a negative allosteric modulator [44] - **Mechanism**: Aiming for a universal approach to target multiple autoantibodies in patients [45][46] 4. **Incretin Receptor Agonist Program** - **Innovation**: Discovery of a novel binding pocket allowing for the development of multi-incretin receptor agonists [50] - **Preclinical Results**: Early-stage molecules showing weight loss effects comparable to existing treatments [52] Collaboration with Novo Nordisk - **Details**: Collaboration includes three known targets and two undisclosed targets, with an upfront payment of $195 million and Novo responsible for all R&D costs [53][54] Leadership and Future Outlook - **Team**: Experienced leadership with decades of industry experience and a strong advisory board [55] - **Market Potential**: Each program represents a significant market opportunity, with ongoing efforts to extend financial runway into early 2028 and beyond [56] Conclusion - **Overall Position**: Septerna is well-positioned in the GPCR drug discovery space with a robust pipeline and strategic collaborations, aiming to address significant unmet medical needs across various therapeutic areas [56]