Septerna, Inc. · NASDAQ:SEPN
Septerna — TD Cowen 45th Annual Health Care Conference 2025
27 slides from Septerna's conference presentation, Mar 3, 2025
Slide 1: Pioneering a New Era of GPCR Drug Discovery
Nasdaq: SEPN Pioneering a New Era of GPCR Drug Discovery March 2025 TD Cowen 45th Annual Health Care Conference Exhibit 99.1
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains express or implied forward‐looking statements of Septerna, Inc. (the “Company,” “we,” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. All statements other than statements of historical facts conta
Slide 3: Septerna: Pioneering a New Era of GPCR Drug Discovery with Oral Small Molecules
Septerna: Pioneering a New Era of GPCR Drug Discovery with Oral Small Molecules Native Complex Platform™ designed to unlock the full potential of GPCR therapies Iterative structure-based drug design to rapidly optimize and validate programs in animal models Portfolio strategy to drive value creation
Slide 4: GPCR Drug Discovery Success Has Been Highly Concentrated to a Small Fraction of GPCRs
GPCR Drug Discovery Success Has Been Highly Concentrated to a Small Fraction of GPCRs Historically productive target class, yet substantial untapped opportunity to expand the number of druggable GPCRs >70% of GPCR drugs target 6 small subfamilies of GPCRs ~1/3 of all FDA-approved drugs (~500 approve
Slide 5: Proprietary Native Complex Platform
Proprietary Native Complex Platform™ Today’s GPCR Drug Discovery Challenge Several new small molecule drug discovery technologies have largely been inaccessible to GPCRs Inability to isolate fully functional GPCR proteins significantly limits use of modern discovery tools G protein Lipid Bilayer Lig
Slide 6: Native Complex Platform is a Highly Efficient Platform for GPCR Structure-based Drug Design
Native Complex Platform™ is a Highly Efficient Platform for GPCR Structure-based Drug Design New Small Molecule Ligand New Ligand-Bound GPCR Structure ~1-2 weeks Native Complex Cryo-EM Structure-Based Design Rapid Iterative Cycle Apo (no ligand) Agonist Positive Allosteric Modulator Antagonist Negat
Slide 7: Advancing a Deep Portfolio of Oral Small Molecule GPCR-Targeted Programs
Advancing a Deep Portfolio of Oral Small Molecule GPCR-Targeted Programs Programs Development Status a Program / Target Mode of Action Therapeutic Area Indications / US Patient Population Discovery IND-enabling Phase 1 PTH1R Agonist Endocrinology Hypoparathyroidism: ~70k SEP-631 (MRGPRX2) Negative A
Slide 8: PTH1R Agonist Program
PTH1R Agonist Program Oral Small Molecule Targeting PTH1R for Hypoparathyroidism
Slide 9: Hypoparathyroidism: Significant Unmet Need for an Oral PTH Replacement
Hypoparathyroidism: Significant Unmet Need for an Oral PTH Replacement Hypoparathyroidism: Low PTH leads to low blood calcium ~70K patients in US; ~140K patients in EU Challenging patient symptoms Muscle cramps, tingling, brain fog Life-threatening complications: cardiac arrhythmias, seizures Inadeq
Slide 10: Discontinuation of SEP-786 Development to Focus on Next-Generation PTH1R Agonist
Discontinuation of SEP-786 Development to Focus on Advancing Next-Generation Oral Small Molecule PTH1R Agonist Decision to discontinue SEP-786 Phase 1 SAD/MAD trial in healthy volunteers No Serious Adverse Events across all participants 2 unanticipated severe (Grade 3) events of elevated unconjugate
Slide 11: Native Complex Platform Identified Broad Portfolio of Chemically Distinct PTH1R Agonists
Native Complex Platform™ Identified Broad Portfolio of Chemically Distinct PTH1R Agonists Structurally unrelated to SEP-786 Potent, selective, oral small molecule Normalizes serum calcium in preclinical animal models PK/PD projects full-day calcium control in hypoparathyroidism patients with QD or B
Slide 12: Next-Generation PTH1R Agonists Normalize Serum Calcium and Phosphate in Animal Model
Potent, Selective Next-Generation PTH1R Agonists Normalize Serum Calcium and Phosphate in Hypoparathyroidism Animal Model Surgery to remove parathyroid glands Rat Decreased serum calcium (hypocalcemia) Oral small molecule PTH1R agonist Normalize serum calcium Rat surgical model of hypoparathyroidism
Slide 13: Multiple Next-Generation PTH1R Agonists with Favorable Pharmacokinetics Profiles
Multiple Next-Generation PTH1R Agonists with Distinct Chemical Structures and Favorable Pharmacokinetics Profiles Example Next-Generation PTH1R Agonist PK Profiles PK studies in mice, rats, dogs, and cynomolgus monkeys support predicted human PK for QD or BID dosing Next-Gen PTH1R Agonist #1 Next-Ge
Slide 14: SEP-631: Oral Small Molecule MRGPRX2 NAM
SEP-631: Oral Small Molecule MRGPRX2 NAM Targeting MRGPRX2 for Mast Cell Disorders, Including CSU
Slide 15: MRGPRX2: Emerging Target for Mast Cell-Driven Diseases
MRGPRX2: Emerging Target for Mast Cell-Driven Diseases MRGPRX2 Highly and uniquely expressed on mast cells Distinct from IgE / allergen pathway Multiple endogenous agonists Mast Cell-Driven Diseases CSU, atopic dermatitis, allergic asthma, and others CSU: Significant Unmet Need ~1.5 million patients
Slide 16: SEP-631: Oral MRGPRX2 NAM Designed to Stop Mast Cell Degranulation
SEP-631: Oral Small Molecule MRGPRX2 NAM Designed to Stop MRGPRX2-Mediated Mast Cell Degranulation SEP-631 Potently Inhibited Skin Extravasation in MRGPRX2 Knock-in Mouse Model Treat with oral MRGPRX2 NAM (SEP-631) or vehicle Administer Evans Blue dye Measure extravasation of dye into skin Extravasa
Slide 17: SEP-631: MRGPRX2 NAM with Potentially Differentiated Profile
SEP-631: MRGPRX2 NAM with Potentially Differentiated Profile Key Criteria SEP-631 High Potency Demonstrated in multiple functional and binding assays Broad Inhibition Long residence time and insurmountable inhibition of multiple endogenous agonists Good Oral PK Excellent oral bioavailability; PK pro
Slide 18: TSHR NAM Program
TSHR NAM Program Oral Small Molecule Targeting TSHR for Graves’ Disease and TED
Slide 19: No Disease-Modifying Therapies for Graves' Disease and Thyroid Eye Disease
No Disease-Modifying Therapies for Graves’ Disease and Thyroid Eye Disease (TED) Graves’ Disease & TED Pathophysiology: Autoantibodies activate TSHR in thyroid gland and in orbital fibroblasts behind the eyes Graves’ Disease >2M patients in US Standard-of-care: antithyroid drugs, radioactive iodine,
Slide 20: Oral Small Molecule TSHR NAMs Reversed Symptoms in Novel Graves' Disease Model
Oral Small Molecule TSHR NAMs Reversed Symptoms in Novel Graves’ Disease Model Agonist mAb + Vehicle Agonist mAb + SP-1351 Isotype mAb control + Vehicle TSHR Activating Antibody Mouse Thyroid Hormone Levels Thyroid Size Eye Proptosis (bulging) TSHR Activating Ab +TSHR NAM Reversal of Thyroid a
Slide 21: Incretin Receptor Agonist Programs
Incretin Receptor Agonist Programs Oral Small Molecule Single- and Multi-GLP-1R, GIPR, and GCGR Agonists for Metabolic Disorders, Including Obesity and Type 2 Diabetes
Slide 22: Next-Generation Oral Incretin Receptor Agonists
Next-Generation Oral Incretin Receptor Agonists Incretin peptide therapeutics have been transformative treatments for obesity and diabetes Marketed GLP-1 and GLP-1/GIP products generated ~$36B in global sales in 2023 Limitations: tolerability, injection administration, prolonged titration schemes Ou
Slide 23: Discovery of Oral Small Molecule Single- and Multi-Incretin Receptor Agonists
Discovery of Oral Small Molecule Single- and Multi-Incretin Receptor Agonists Example: Selective mono-GIPR agonists demonstrated weight loss both alone and with additive activity in combination with a GLP-1 peptide Diet-induced obese (DIO) mouse model +/- semaglutide Identified Multiple Incretin Rec
Slide 24: Building a World-Class GPCR-Focused Biotechnology Company
Building a World-Class GPCR-Focused Biotechnology Company
Slide 25: Proven Leaders in GPCR Drug Development and Company Building
Proven Leaders in GPCR Drug Development and Company Building Senior Leadership Jeff Finer, MD PhD CEO Liz Bhatt, MS MBA COO Gil Labrucherie, CFA JD CFO Samira Shaikhly CPO Jae Kim, MD CMO Uwe Klein, PhD SVP Biological Sciences Dan Long, DPhil SVP Drug Discovery Board of Directors Jeff Finer, MD, PhD
Slide 26: Septerna: Pioneering a New Era of GPCR Drug Discovery
Septerna: Pioneering a New Era of GPCR Drug Discovery Program / Target Mode of Action Therapeutic Area Indications Discovery IND-enabling Phase 1 PTH1R Agonist Endocrinology Hypoparathyroidism SEP-631 (MRGPRX2) Negative Allosteric Modulator Immunology and Inflammation CSU and other mast cells diseas
Slide 27: Pioneering a New Era of GPCR Drug Discovery
Pioneering a New Era of GPCR Drug Discovery
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