Septerna, Inc. · NASDAQ:SEPN
Septerna — J.P. Morgan Healthcare Conference 2025
26 slides from Septerna's conference presentation, Jan 13, 2025
Slide 1: Pioneering a New Era of GPCR Drug Discovery
Exhibit 99.1 Pioneering a New Era of GPCR Drug Discovery J.P. Morgan Healthcare Conference 2025 January 2025 Nasdaq: SEPN
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
Septerna: Pioneering a New Era Lead Candidates of GPCR Drug Discovery with SEP-786 PTH1R Agonist: Potential first-in-class oral Oral Small Molecules small molecule for hypoparathyroidism; Phase 1 underway with SAD/MAD data expected in mid-2025 SEP-631 MRGPRX2 NAM: Pipeline-in-a-product Native Comple
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 ~1/3 of all FDA-approved drugs (~500 approved products) target GPCRs >70% of GPCR drugs target 6 sm
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 Native Complex Platform
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 GPCR cryo-EM now achieving resolutions relevant for structure-based drug design Native Complex cryo-EM enables rapid and iterative lead optimization • Applies to a broad range of lead candidate modes of actio
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 Program / Target Therapeutic Area Discovery IND-enabling Phase 1 Phase 2 Phase 3 Mode of Action Indications / US Patient Population Endocrinology SEP-786 (PTH1R) Hypoparathyroidism: ~70k Agonist Immu
Slide 8: SEP-786: Oral Small Molecule PTH1R Agonist
SEP-786: Oral Small Molecule PTH1R Agonist Targeting PTH1R for Hypoparathyroidism © 2025 SEPTERNA
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 PTH: Master Regulator of Blood Calcium calcium • ~70K patients in US; ~140K patients in EU Challenging patient symptoms • Muscle cramps, tingling, brain fog • Life-threatening compli
Slide 10: SEP-786: Product of Our Native Complex Platform
SEP-786: Product of Our Native Complex Platform Drug Discovery Native Complex Native Complex Native Complex Hit Identification Structure-Based Design Lead Optimization Led to SEP-786 Multiple PTH1R agonists Multiple PTH1R agonist with distinct binding sites series optimized in parallel SEP-786 • Pot
Slide 11: SEP-786 Demonstrated Potent, Selective Activation of PTH1R and Dose-dependent Serum Calcium Increases
SEP-786 Demonstrated Potent, Selective Activation of PTH1R and Dose-dependent Serum Calcium Increases Rat surgical model of hypoparathyroidism Single-dose 28-day dosing 2+ Matches efficacy of peptide Sustained Ca control 4 4 Vehicle (PO) Rat Vehicle (PO) SEP-786 (PO, 3 mg/kg BID) 3 3 SEP-786 (PO, 3
Slide 12: SEP-786: Phase 1 Trial Underway, Data Expected Mid-2025
SEP-786: Phase 1 Trial Underway, Data Expected Mid-2025 Preclinical data supports clinical development • PK studies in mice, rats, dogs, and monkeys support predicted human PK for QD or BID dosing • 28-day GLP toxicology studies in rats and dogs: generally well-tolerated • Effects of exaggerated o
Slide 13: SEP-631: Oral Small Molecule MRGPRX2 NAM
SEP-631: Oral Small Molecule MRGPRX2 NAM Targeting MRGPRX2 for Mast Cell Disorders, Including CSU © 2025 SEPTERNA
Slide 14: 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 millio
Slide 15: SEP-631: Oral Small Molecule 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: Selective MRGPRX2 NAM Knock-in Mouse mMRGPRB2 KO hMRGPRX2 KI • Potent oral small molecule SEP-631 Potently Inhibited Skin Treat with oral MRGPRX2 • Blocked activation of all endogenous Extrava
Slide 16: 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 Excellent oral bioavailability; PK profile across s
Slide 17: TSHR NAM Program
TSHR NAM Program Targeting TSHR for Graves’ Disease and TED © 2025 SEPTERNA
Slide 18: No Disease-Modifying Therapies for Graves' Disease and Thyroid Eye Disease (TED)
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 i
Slide 19: Oral Small Molecule TSHR NAMs Reversed Symptoms in Novel Graves' Disease Model
Oral Small Molecule TSHR NAMs Reversed Symptoms in Novel Graves’ Disease Model Selective TSHR NAMs TSHR Activating TSHR Activating Ab • Blocked activation of TSHR by Antibody +TSHR NAM Thyroid Hormone Levels patient-derived autoantibodies Reversal of Thyroid and Thyroid Size Eye Manifestations 6
Slide 20: Oral Small Molecule Incretin Receptor Agonist Programs
Oral Small Molecule Incretin Receptor Agonist Programs Single- and Multi-GLP-1R, GIPR, and GCGR Agonists for Metabolic Disorders, Including Obesity and Type 2 Diabetes © 2025 SEPTERNA
Slide 21: Next-Generation Oral Incretin Receptor Agonists
Next-Generation Oral Incretin Receptor Agonists Incretin peptide therapeutics have been transformative Our Strategy: Next-generation treatments for obesity and diabetes incretin receptor agonists • Marketed GLP-1 and GLP-1/GIP products generated ~$36B in global Oral small molecule single- and multi-
Slide 22: 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 Identified Multiple Incretin Receptor alone and with additive activity in combination with a GLP-1 peptide Agonist Chemical Series • Diet-induced obese (D
Slide 23: Building a World-Class GPCR-Focused Biotechnology Company
Building a World-Class GPCR-Focused Biotechnology Company © 2025 SEPTERNA
Slide 24: Proven Leaders in GPCR Drug Development and Company Building
Proven Leaders in GPCR Drug Development and Company Building Senior Leadership Jeff Finer, MD PhD Liz Bhatt, MS MBA Jae Kim, MD Gil Labrucherie, CFA JD Uwe Klein, PhD Dan Long, DPhil Samira Shaikhly CEO COO CMO CFO SVP Biological Sciences SVP Drug Discovery CPO Board of Directors Academic Co-Founder
Slide 25: Septerna: Pioneering a New Era of GPCR Drug Discovery
Septerna: Pioneering a New Era of GPCR Drug Discovery Wholly-owned pipeline of programs, each with a multi-billion $ market opportunity • Clinical-stage lead program Program / Target Therapeutic Area IND- with data expected mid-2025 Discovery Phase 1 Phase 2 Phase 3 Mode of Action Indications enabli
Slide 26: Pioneering a New Era of GPCR Drug Discovery
Pioneering a New Era of GPCR Drug Discovery © 2025 SEPTERNA