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.

Summary of Septerna Conference Call Company Overview - **Company**: Septerna (NasdaqGM:SEPN) - **Focus**: Drug discovery targeting G protein-coupled receptors (GPCRs) using the Native Complex Platform - **Financial Position**: Cash runway into at least 2029 [4][4][4] Key Programs SEP631 - **Type**: MRGPRX2 inhibitor, currently in Phase 1 clinical trials - **Indication**: Mast cell-driven diseases - **Expected Readouts**: First half of the upcoming year [3][4][5] - **Mechanism**: Targets MRGPRX2, leading to mast cell degranulation through an IgE-independent pathway [5][6] - **Profile**: - High potency (single-digit nanomolar to high picomolar) - Excellent oral bioavailability with once-daily dosing projected - Good preclinical safety profile [6][6][11] - **Phase 1 Trial Design**: Randomized placebo-controlled, includes skin challenge with Icatibant [8][9][17] SEP479 - **Type**: PTH1 receptor agonist for hypoparathyroidism, expected to enter the clinic in the first half of next year [3][28] - **Challenges**: Historically difficult target for small molecules; previous candidate (SEP786) faced issues with bilirubin increases [29][30] - **Current Status**: - New compound shows no UGT1A1 inhibition or bilirubin increase - Predicted human half-life of 40-80 hours, aiming for once-daily oral dosing [30][31] - **Clinical Goals**: - Aim for serum calcium increases of about 1 mg/dL in Phase 1 trials - Final IND enabling studies wrapping up, including a 28-day GLP-tox study in monkeys [33][34][40] Future Directions - **Phase 2 Strategy**: Plans to move into chronic spontaneous urticaria (CSU) trials post-Phase 1 [22][26] - **Exploration of Other Indications**: Potential for expansion into asthma and pain-related conditions involving mast cells [26][26] - **Collaboration with Novo**: Developing a TSH receptor negative allosteric modulator, with hopes for a development candidate next year [41][42] Additional Insights - **Safety Profile**: SEP631 has shown no liver involvement in preclinical studies, distinguishing it from other X2 agonists [11][12] - **Market Opportunities**: Significant market potential for both SEP631 and SEP479 due to their targeted mechanisms and the unmet medical needs in their respective indications [4][4][28]

Summary of Septurna (SEPN) 2025 Conference Call Company Overview - **Company**: Septurna - **Event**: 2025 Cantor Healthcare Conference - **CEO**: Jeff Feiner introduced the company and its updates on drug discovery platforms and lead programs [1][2] Industry and Market Context - **Industry**: Biopharmaceuticals focusing on G protein-coupled receptors (GPCRs) - **Market Opportunity**: GPCRs are a significant target class in drug discovery, with over 70% of approved GPCR drugs targeting just six subfamilies [6] Key Programs and Developments 1. Lead Programs - **SEP-479**: Next-generation parathyroid hormone receptor small molecule agonist for hyperparathyroidism, announced as a new development candidate [4][20] - **SEP-631**: Focused on MRGPRAX2 for mast cell-driven diseases, recently started Phase 1 trials [5][33] 2. Drug Discovery Platform - **Native Complex Platform**: A novel approach to drug discovery that allows for the isolation of fully functional GPCRs, enhancing the ability to design effective small molecules [3][7] - **Structural Biology**: Utilizes cryo-electron microscopy for rapid structure determination, enabling efficient structure-based design [9][10] 3. Therapeutic Areas - **Focus Areas**: Endocrinology, immunology, inflammation, metabolic diseases, and early-stage efforts in neurology [11][12] Clinical Insights SEP-479 - **Mechanism**: Aims to replace traditional injectable therapies for hypoparathyroidism with an oral small molecule [17] - **Efficacy**: Demonstrated effectiveness in animal models at significantly lower doses compared to previous compounds [25][26] - **Safety Profile**: No observed UGT1A1 inhibition, which was a concern with the previous candidate SEP-786 [32] SEP-631 - **Target**: MRGPRAX2, involved in mast cell activation pathways, with a focus on chronic spontaneous urticaria [34] - **Profile**: Designed as a negative allosteric modulator with a slow off-rate, showing promise in preclinical models [35][38] Collaborations and Financials - **Novo Nordisk Collaboration**: Involves five targets with an upfront payment of $195 million, significantly reducing Septurna's R&D costs [46] - **Financial Position**: Well-capitalized with operating capital projected to last until at least 2029 [4][48] Management and Governance - **Experienced Team**: Led by a seasoned management team and supported by a strong board of directors and advisory board [47] Conclusion - **Outlook**: Septurna is positioned for growth with a robust pipeline and strategic collaborations, focusing on innovative therapies for significant unmet medical needs [48]