Septerna Reports Third Quarter 2024 Financial Results and Recent Business Highlights Deep Pipeline of GPCR Programs Focused Initially on Indications in Endocrinology, Immunology and Inflammation, and Metabolic Diseases P

Septerna Reports Third Quarter 2024 Financial Results and Recent Business Highlights

Deep Pipeline of GPCR Programs Focused Initially on Indications in Endocrinology, Immunology and Inflammation, and Metabolic Diseases

Phase 1 Clinical Trial Ongoing for SEP-786, Oral Small Molecule for Hypoparathyroidism,

with Data Expected in Mid-2025

Well-Capitalized with Balance Sheet to Support a Planned

Operating Runway into Second Half of 2027

SOUTH SAN FRANCISCO, Calif. November 20, 2024 Septerna, Inc.

(Nasdaq: SEPN), a clinical-stage biotechnology company pioneering a new era of G protein-coupled receptor (GPCR) drug discovery, today reported financial results for the third quarter ended September 30, 2024 and provided a portfolio overview

and business highlights.

At Septerna, we recently celebrated two major milestones: our transition to a clinical-stage company with the initiation

of our Phase 1 clinical trial for SEP-786, and our debut as a public company following a successful IPO, said Jeffrey Finer, M.D., Ph.D., chief executive officer and

co-founder of Septerna. Our Native Complex Platform has yielded a deep pipeline of oral small molecule programs, each offering a unique product

profile, early clinical biomarker readouts, and substantial market potential. Leading our pipeline is SEP-786, which we believe could transform hypoparathyroidism treatment by providing full-day calcium control with a convenient, disease-modifying oral therapy. With a talented team, a pioneering platform, a robust pipeline, and a strong balance sheet, we believe we are well positioned to deliver

multiple novel GPCR medicines with the potential to meaningfully improve patients lives.

Septerna s proprietary Native Complex PlatformTM is uniquely designed to enable targeting of GPCRs with a wide spectrum of pharmacologies to affect GPCR signaling in different ways to achieve desired therapeutic effects. Using this platform,

Septerna aims to discover and develop a portfolio of oral small molecule GPCR-targeted medicines with novel mechanisms to treat diseases across multiple therapeutic areas.

SEP-786 PTH1R Agonist Advancing in Phase 1 Clinical Trial:

SEP-631 MRGPRX2 Negative Allosteric Modulator (NAM) in IND-Enabling Studies:

TSHR NAM Program for Endocrine

Incretin Receptor (GLP-1R, GIPR,

GCGR) Program for Metabolic Diseases:

Third Quarter 2024 Financial Results

a clinical-stage biotechnology company pioneering a new era of GPCR oral small molecule drug discovery powered by its proprietary Native Complex Platform . Its industrial-scale platform aims

to unlock the full potential of GPCR therapies and has led to the discovery and development of its deep pipeline of product candidates focused initially on treating patients in three therapeutic areas: endocrinology, immunology and inflammation, and

metabolic diseases. Septerna was launched by preeminent drug discovery company builders and scientific leaders in the biochemistry, structural biology, and pharmacology of GPCRs. For more information, please visit www.septerna.com.

Forward-Looking Statements

This press release contains

forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Septerna s beliefs and expectations regarding: the continued

development and advancement of Septerna s oral small molecule GPCR-targeted programs, including the ongoing clinical trial of SEP-786 and the timing of clinical updates for

SEP-786 in mid-2025; the initiation, timing, progress, and results of conducting its research and development programs and its current and future preclinical studies and

anticipated clinical trials, and the release of data related thereto; its ability to demonstrate, and the timing of, preclinical proof-of-concept in vivo and

ex vivo for multiple programs; its ability to advance any product candidates that it may identify and successfully complete any clinical studies; the potential of its proprietary Native Complex Platform ; its expectations regarding the implementation of its business model, and strategic plans for its business, product candidates, and technology; and the accuracy of its estimates regarding

expenses and capital requirements, including its expected cash runway through the second half of 2027. The words anticipate, believe, continue, could, estimate, expect,

intend, may, might, objective, ongoing, plan, predict, project, potential, should, or would, or the negative of these

terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

Any forward-looking statements in this press release are based on management s current expectations and beliefs and are subject to a number of risks,

uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with:

uncertainties related to Septerna s product candidates entering clinical trials; the authorization, initiation, and conduct of preclinical and IND-enabling studies and other development requirements for

potential product candidates, including uncertainties related to opening INDs and obtaining regulatory approvals; risks related to the development and optimization of new technologies, the

results of preclinical studies, or clinical studies not being predictive of future results in connection with future studies; the scope of protection Septerna is able to establish and maintain for intellectual property rights covering its Native

Complex Platform ; Septerna s ability to identify and enter into future license agreements and collaborations; and general economic, industry and market conditions. These and other risks

and uncertainties are described in greater detail in the section entitled Risk Factors in Septerna s most recent Quarterly Report on Form 10-Q, as well as any subsequent filings with the

Securities and Exchange Commission. In addition, any forward-looking statements represent Septerna s views only as of today and should not be relied upon as representing its views as of any subsequent date. Septerna explicitly disclaims any

obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.

Condensed Statements of Operations

(In thousands, except for share and per share data)

Condensed Balance Sheets

(In thousands, except for share and per share data)