Septerna, Inc. · NASDAQ:SEPN
Septerna — J.P. Morgan Healthcare Conference 2026
30 slides from Septerna's conference presentation, Jan 12, 2026
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 2026 January 2026 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 cont
Slide 3: Septerna: Pioneering a New Era of GPCR Drug Discovery
Septerna: Pioneering a New Era Lead Programs of GPCR Drug Discovery with SEP-479 PTH1R Agonist: Potential first-in-class oral small molecule for hypoparathyroidism; Phase 1 Oral Small Molecules clinical trial initiation anticipated in 1H 2026 Native Complex Platform designed to SEP-631 MRGPRX2 NAM:
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: Advancing a Deep Portfolio of Oral Small Molecule GPCR-Targeted Programs
Advancing a Deep Portfolio of Oral Small Molecule GPCR-Targeted Programs Wholly-Owned Programs Development Status Program / Target Therapeutic Area Discovery IND-enabling Phase 1 Phase 2 Mode of Action Indications / US Patient Population * Phase 1 initiation Anticipate Phase 1 Endocrinology SEP-479
Slide 7: SEP-479: Oral Small Molecule PTH1R Agonist
SEP-479: Oral Small Molecule PTH1R Agonist Targeting PTH1R for Hypoparathyroidism © 2026 SEPTERNA
Slide 8: 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 PTH: Master Regulator of Blood Calcium • ~70K patients in US; ~140K patients in EU Challenging patient symptoms • Muscle cramps, tingling, brain fog • Life-threatening compli
Slide 9: Native Complex Platform Identified Portfolio of PTH1R Agonists
Native Complex Platform Identified Portfolio of PTH1R Agonists with Potential to Address Significant Unmet Need in Hypoparathyroidism Native Complex Hit Native Complex Structure-Based Identification Design and Optimization Multiple PTH1R agonists Multiple PTH1R agonist with distinct binding sites se
Slide 10: SEP-479 Normalized Serum Calcium and Phosphate in Hypoparathyroidism Animal Model
SEP-479: A Potent, Selective PTH1R Agonist Normalized Serum Calcium and Phosphate in Hypoparathyroidism Animal Model Rat surgical model of SEP-479: 28-day Oral QD Dosing hypoparathyroidism Sustained Normalization of Sustained Normalization of 2+ Serum Ca Levels Serum Phosphate Levels Rat Surgery to
Slide 11: SEP-479: Preclinical Studies Demonstrated Favorable Oral Small Molecule Candidate Profile
SEP-479: Preclinical Studies Demonstrated Favorable Oral Small Molecule Candidate Profile SEP-479: 7-day Healthy Cynomolgus Monkey Pharmacodynamic Study 2+ Serum PTH Levels Serum Ca Levels • Demonstrated robust dose-dependent decreases in endogenous PTH levels and increases in serum calcium • Lesson
Slide 12: SEP-479: On Track to Initiate Phase 1 in 1H 2026
SEP-479: On Track to Initiate Phase 1 in 1H 2026 Non-clinical safety studies have completed • 28-day GLP toxicology studies completed in rats, dogs, and cynomolgus monkeys • SEP-479 was generally well tolerated in all non-clinical safety studies • Dose-limiting effect in each species was on-target h
Slide 13: SEP-631: Oral Small Molecule MRGPRX2 NAM
SEP-631: Oral Small Molecule MRGPRX2 NAM Targeting MRGPRX2 for Mast Cell-Driven Diseases, Including CSU © 2026 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 cells are potentially drivers of several chronic allergic and inflammatory diseases • CSU, CIndU, prurigo nodularis,
Slide 15: SEP-631: Clinical-Stage MRGPRX2 NAM with Potentially Differentiated Profile
SEP-631: Clinical-Stage MRGPRX2 NAM with Potentially Differentiated Profile for Mast Cell-Driven Diseases Preclinical Profile: Key Criteria for Advancement SEP-631 Complete High Potency High potency observed in multiple functional and binding assays Insurmountable inhibition of multiple endogenous a
Slide 16: SEP-631 Inhibited MRGPRX2 Activation in Translational Models
SEP-631 Inhibited MRGPRX2 Activation in Translational Models SEP-631 Potently Inhibited Skin Extravasation in MRGPRX2 Knock-in SEP-631 Potently Inhibited Primary Mouse Model Human Skin Mast Cell Degranulation Knock-in Mouse Complete Inhibition of Skin mMRGPRB2 KO Extravasation with SEP-631 hMRGPRX2
Slide 17: SEP-631 Phase 1 Trial On Track – SAD/MAD Results Planned for AAAAI
SEP-631 Phase 1 Trial is on Track – Presentation of SAD / MAD Results Planned for AAAAI Annual Meeting in March 2026 Phase 1 Goal: Evaluate the safety, tolerability, PK and PD of oral SEP-631 in healthy adult volunteers Study design: • Randomized, placebo-controlled, single ascending dose (SAD) and
Slide 18: TSHR NAM Program
TSHR NAM Program Oral Small Molecule Targeting TSHR for Graves’ Disease and TED © 2026 SEPTERNA
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 i
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 TSHR Activating TSHR Activating Ab Selective TSHR NAMs Antibody +TSHR NAM ↑ Thyroid Hormone Levels Reversal of Thyroid and ↑ Thyroid Size Eye Manifestations • Blocked activation of TSHR by patient- ↑ Eye Proptosis (bulgin
Slide 21: Metabolic Programs
Metabolic Programs Oral Small Molecule Programs Targeting GLP-1R, GIPR, GCGR and Other Targets for Obesity, Diabetes, and Other Cardiometabolic Diseases © 2026 SEPTERNA
Slide 22: Collaboration with Novo Nordisk for Oral Small Molecules for Metabolic Diseases
Collaboration with Novo Nordisk for Oral Small Molecules for Metabolic Diseases Septerna and Novo commenced four initial R&D programs targeting five GPCRs • Includes GLP-1, GIP and glucagon receptors • Collaboration includes Septerna’s preclinical, selective, oral, small molecule GIP receptor agonis
Slide 23: Building a World-Class GPCR-Focused Biotechnology Company
Building a World-Class GPCR-Focused Biotechnology Company © 2026 SEPTERNA
Slide 24: Proven Leaders in GPCR Drug Development and Company Building
Proven Leaders in GPCR Drug Development and Company Building Senior Leadership Dan Long, DPhil Jeff Finer, MD PhD Liz Bhatt, MS MBA Jae Kim, MD Gil Labrucherie, CFA JD Uwe Klein, PhD Samira Shaikhly Mark Wilson, JD CEO President & COO CMO CFO SVP Biological Sciences SVP Drug Discovery CPO CLO Board
Slide 25: Septerna: Pioneering a New Era of GPCR Drug Discovery
Septerna: Pioneering a New Era of GPCR Drug Discovery Wholly-Owned Programs Development Status • Portfolio of oral small molecule Program / Target Discovery IND-enabling Phase 1 Phase 2 GPCR-targeted programs Mode of Action * Phase 1 initiation Anticipate Phase 1 SEP-479 (PTH1R) anticipated in topli
Slide 26: Pioneering a New Era of GPCR Drug Discovery
Pioneering a New Era of GPCR Drug Discovery © 2026 SEPTERNA
Slide 27: Appendix
Appendix © 2026 SEPTERNA
Slide 28: 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 29: SEP-786: First Clinical PTH1R Agonist Discontinued in Phase 1 in February 2025
SEP-786: First Clinical PTH1R Agonist Discontinued in Phase 1 in February 2025 Due to Unanticipated Events SEP-786 Phase 1 SAD/MAD trial in healthy Investigation into the mechanism of volunteers discontinued unconjugated hyperbilirubinemia • 2 unanticipated severe (Grade 3) events of elevated SEP-78
Slide 30: SEP-479: Preclinical Studies Demonstrated a Favorable Pharmacokinetic Profile
SEP-479: Preclinical Studies Demonstrated a Favorable Pharmacokinetic Profile • SEP-479 demonstrated higher oral bioavailability across preclinical species and longer projected human half-life than SEP-786 • Human PK projections are anticipated to support QD oral dosing for SEP-479 SEP-479 SEP-786 P