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]

Core Insights - Septerna, Inc. has appointed Mark A. Wilson as Chief Legal Officer, bringing over 25 years of experience in pharmaceutical and biotech sectors [1][2] - The company aims to enhance its governance framework and maximize the value of its proprietary Native Complex Platform™ under Mr. Wilson's leadership [2] - Septerna is focused on transforming GPCR drug discovery and developing innovative therapies for patients with significant unmet needs [4] Company Overview - Septerna, Inc. is a clinical-stage biotechnology company specializing in G protein-coupled receptor (GPCR) drug discovery [1][4] - The company has developed a diverse pipeline of novel oral small molecule drug candidates targeting areas such as endocrinology, immunology, inflammation, and metabolic diseases [4] - Septerna operates both independently and in collaboration with partners to advance its therapeutic programs [4] Leadership Background - Mark A. Wilson previously served as Senior Vice President and Chief Legal Officer at Nektar Therapeutics, where he managed legal, human resources, and IT departments [2] - He has extensive experience in global development, commercialization collaborations, and patent strategy, having joined Nektar in 2002 [2] - Mr. Wilson holds a J.D. from Seton Hall University School of Law and a B.S. in Pharmacy from Rutgers University College of Pharmacy [3]

Upgrades - CFRA upgraded Pool Corp. (POOL) to Buy from Hold with a price target of $304 [2] - Piper Sandler upgraded SEI Investments (SEIC) to Overweight from Neutral with a price target of $102, increased from $93, citing SEI as a "clear beneficiary" of the expanding alternatives landscape [2] - TD Cowen upgraded Ametek (AME) to Buy from Hold with a price target of $230, up from $180, noting that backlog remains near highs and is expected to grow [3] Downgrades - TD Cowen downgraded Janus Henderson (JHG) to Hold from Buy with a price target of $49 after the company agreed to be acquired for $7.4 billion or $49.00 per share [4] - Piper Sandler downgraded Clearwater Analytics (CWAN) to Neutral from Overweight with a price target of $24.55, down from $27, following its agreement to be acquired for $24.55 per share in cash [4] - BMO Capital downgraded Brown & Brown (BRO) to Market Perform from Outperform with a price target of $88, down from $90, due to lower consensus organic growth estimates for 2026 [5] - Evercore ISI downgraded Coty (COTY) to In Line from Outperform with a price target of $7, citing a lack of visibility on timing and catalysts for potential value unlock [6] Initiations - Oppenheimer initiated coverage of Spruce Biosciences (SPRB) with an Outperform rating and a price target of $283, supported by FDA confirmation of compelling clinical biomarker data [7] - LifeSci Capital initiated coverage of Sionna Therapeutics (SION) with an Outperform rating and a price target of $60, highlighting multiple quality shots on goal with its therapies [7] - Oppenheimer initiated coverage of Aardvark Therapeutics (AARD) with an Outperform rating and a price target of $35, noting the company's differentiated obesity franchise [7] - JonesResearch initiated coverage of Septerna (SEPN) with a Buy rating and a price target of $43, forecasting $2.5 billion in unadjusted U.S. peak sales in 2035 [7] - Loop Capital initiated coverage of Malibu Boats (MBUU) with a Buy rating and a price target of $34, indicating the marine industry is in the late stages of inventory rationalization [7]

Core Insights - Septerna, Inc. is a clinical-stage biotechnology company focused on G protein-coupled receptor (GPCR) drug discovery [1][3] - The company will present at the 44th Annual J.P. Morgan Healthcare Conference on January 13, 2026 [1] - Septerna's proprietary Native Complex Platform™ is aimed at advancing GPCR therapies for patients with significant unmet medical needs [3] Company Overview - Septerna is developing a diverse pipeline of novel oral small molecule drug candidates targeting various therapeutic areas including endocrinology, immunology, inflammation, and metabolic diseases [3] - The company is led by a team of GPCR experts and drug developers [3] - Septerna collaborates with partners to enhance its drug discovery efforts [3] Presentation Details - Jeffrey Finer, M.D., Ph.D., CEO and co-founder of Septerna, will present at 3:45 p.m. PT [1] - A live webcast of the presentation will be available on the company's website and archived for at least 30 days [2]

Core Insights - Septerna, Inc. is a clinical-stage biotechnology company focused on G protein-coupled receptor (GPCR) drug discovery [1][3] - The company will present at the 44th Annual J.P. Morgan Healthcare Conference on January 13, 2026 [1] - Septerna's proprietary Native Complex Platform™ is aimed at advancing GPCR therapies for patients with significant unmet medical needs [3] Company Overview - Septerna is developing a diverse pipeline of novel oral small molecule drug candidates targeting various therapeutic areas including endocrinology, immunology, inflammation, and metabolic diseases [3] - The company is led by a team of GPCR experts and drug developers [3] - Septerna collaborates with partners to enhance its drug discovery efforts [3] Presentation Details - Jeffrey Finer, M.D., Ph.D., CEO and co-founder of Septerna, will present at the conference [1] - A live webcast of the presentation will be available on the company's website and archived for at least 30 days [2]

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.

Core Viewpoint - Septerna, Inc. is participating in the 8th Annual Evercore Healthcare Conference, highlighting its focus on G protein-coupled receptor (GPCR) drug discovery and its innovative approach in the biotechnology sector [1]. Company Overview - Septerna, Inc. is a clinical-stage biotechnology company specializing in GPCR drug discovery, aiming to address significant unmet medical needs through its proprietary Native Complex Platform™ [3]. - The company has developed a diverse pipeline of novel oral small molecule drug candidates targeting various therapeutic areas, including endocrinology, immunology, inflammation, and metabolic diseases [3]. Event Participation - Management will engage in a fireside chat at the conference on December 2, 2025, at 10:25 a.m. ET, indicating the company's commitment to investor relations and transparency [1]. - A live webcast of the presentation will be available on the company's website, ensuring accessibility for investors and stakeholders [2].

Group 1 - Septerna, Inc. reported a 3Q25 GAAP EPS of $0.18, indicating a significant improvement from previous losses, primarily driven by partnership-related revenue [1] - The company has a focus on biotechnology, emphasizing innovative approaches in drug development, including novel mechanisms of action and first-in-class therapies [1] - The analysis aims to evaluate the science behind drug candidates, the competitive landscape, clinical trial design, and potential market opportunities while balancing financial fundamentals and valuation [1]

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 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]