Septerna Announces Selection of SEP-204 as Development Candidate for Graves' Disease and TED and Reports Preclinical Data at the 2026 American Thyroid Association Annual Meeting

Animal studies showed normalization of T4 levels and reduced thyroid enlargement and eye protrusion; human dosing remains planned.

Rhea-AI Summary

Septerna (Nasdaq: SEPN) selected SEP-204 as a development candidate for Graves’ disease and thyroid eye disease and reported preclinical findings.

The oral small molecule inhibits the thyroid-stimulating hormone receptor, or TSHR. In Graves’ disease animal models, SEP-204 restored normal T4 thyroid hormone levels and reduced thyroid enlargement and eye protrusion. Human thyroid-cell assays showed inhibition of antibody-driven TSHR activation. Across preclinical species, dose-dependent increases in thyroid-stimulating hormone preceded decreases in thyroid hormones. SEP-204 was generally well tolerated in 28-day toxicology studies in rats and dogs.

Septerna anticipates that a projected human half-life of approximately 20-40 hours will support once-daily oral dosing and plans to initiate a Phase 1 trial in healthy volunteers in the first quarter of 2027.

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Positive

• Moderate pointSEP-204 selected as a development candidate for Graves’ disease and thyroid eye disease.
• Minor pointGraves’ disease animal models showed normal T4 restoration and reduced thyroid enlargement and eye protrusion.
• Minor pointHuman thyroid-cell assays showed inhibition of antibody-driven TSHR activation.
• Minor pointPreclinical testing showed selectivity over FSHR and LHR, two closely related hormone receptors.
• Minor pointPreclinical species showed dose-dependent increases in thyroid-stimulating hormone, followed by thyroid hormone decreases.

3 minor points

• Minor pointSEP-204 was generally well tolerated in 28-day toxicology studies in rats and dogs.
• Minor point. Forward-looking: it has not happened yet and may not happen.Projected human half-life of approximately 20-40 hours is anticipated to support once-daily oral dosing.
• Minor point. Forward-looking: it has not happened yet and may not happen.Septerna plans Phase 1 initiation in the first quarter of 2027 in healthy volunteers.

Negative

• None.

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Details

Market move: SEPN +9.57% in the Nov 4 session. SEP-204 preclinical data

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On Nov 4, the day this news came out, SEPN closed 9.57% above the previous close. Argus tracked a peak move of +5.8% during that session. Our momentum scanner recorded 23 alerts for this stock that day. That session’s volume was 1.6x the stock’s average daily volume.

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Key Figures

Phase 1 trial initiation: Q1 2027 Projected human half-life: Approximately 20–40 hours GLP toxicology study duration: 28 days

Phase 1 trial initiation

Q1 2027

Anticipated; healthy volunteers

Projected human half-life

Approximately 20–40 hours

Preclinical profile; anticipated to support once-daily oral dosing

GLP toxicology study duration

28 days

Studies in rats and dogs; generally well tolerated

Key Terms

negative allosteric modulator, pharmacokinetic, bioavailability, thyrocyte

4 terms

negative allosteric modulator technical

"thyroid-stimulating hormone receptor (TSHR) negative allosteric modulator (NAM)"

A negative allosteric modulator is a drug or compound that binds to a site on a biological receptor different from where the body's natural molecule binds, and reduces the receptor's activity. Think of it as turning down the volume on a signal without cutting it off entirely. For investors, this mechanism can mean more selective effects, potentially fewer side effects, and distinct commercial and regulatory prospects compared with drugs that fully block or mimic a receptor.

pharmacokinetic medical

"has pharmacokinetic properties to support once daily dosing"

Pharmacokinetic describes how a drug moves through and leaves the body — how it is absorbed, spread to tissues, broken down and excreted — like tracking a package from pickup to delivery and disposal. For investors, these properties determine effective dose, safety risks, how often a medicine must be taken, and how reliably it works, which in turn influence clinical trial success, regulatory approval chances, production complexity and a drug’s commercial value.

bioavailability medical

"High oral bioavailability and low clearance across preclinical species"

Bioavailability is the measure of how much and how quickly a substance, such as a medication or nutrient, enters the bloodstream and becomes available for use by the body. For investors, it matters because it influences how effectively a product works and how quickly results are seen, which can impact a company's success and the potential value of related investments. Think of it like how much of a medicine actually reaches your bloodstream after taking it—that determines how well it can do its job.

thyrocyte medical

"activation of TSHR in human thyrocyte cell assays"

A thyrocyte is a follicular cell in the thyroid gland that makes and secretes the thyroid hormones thyroxine (T4) and triiodothyronine (T3). Thyrocytes line spherical structures called follicles, take up iodide, synthesize the protein thyroglobulin, and convert and release T4/T3 into the bloodstream in response to thyroid-stimulating hormone; they are distinct from parafollicular (C) cells, which produce calcitonin.

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Potent, selective TSHR NAM with pre-clinical activity demonstrated across biochemical, thyroid and ocular endpoints

Favorable PK profile anticipated to support once-daily oral dosing in humans

Phase 1 clinical trial initiation planned for the first quarter of 2027

SOUTH SAN FRANCISCO, Calif., Nov. 04, 2026 (GLOBE NEWSWIRE) -- Septerna, Inc. (Nasdaq: SEPN), a clinical-stage biotechnology company pioneering a new era of G protein-coupled receptor (GPCR) drug discovery, today announced the selection of SEP-204 as its potential first-in-class development candidate for the treatment of Graves’ disease and thyroid eye disease (TED) and reported initial preclinical data ahead of a poster presentation at the 2026 American Thyroid Association (ATA) Annual Meeting on November 5.

SEP-204 is a potent and selective oral small molecule thyroid-stimulating hormone receptor (TSHR) negative allosteric modulator (NAM). SEP-204 inhibited TSHR activation in Graves’ disease animal models and has pharmacokinetic properties to support once daily dosing. A Phase 1 trial in healthy volunteers is anticipated to initiate in the first quarter of 2027.

“Based on the pre-clinical data we have generated to date, we believe SEP-204 has the potential to change the treatment paradigm for Graves’ disease and TED, two serious autoimmune endocrine diseases that can profoundly affect patients’ health and quality of life,” said Rajiv Patni, chief medical officer of Septerna. “We look forward to working closely with disease experts and the patient community to advance SEP-204 into clinical development and build upon these promising preclinical findings with clinical results.”

Preclinical studies of SEP-204 demonstrated the following key findings:

• Potent TSHR inhibition with desirable drug-like properties and a high level of selectivity over the closely related follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR).
• Inhibition of thyroid-stimulating antibody (TSAb) activation of TSHR in human thyrocyte cell assays.
• In Graves’ disease animal models, findings included restoration of normal thyroid hormone T4 levels and reductions in thyroid enlargement and orbital proptosis.
• Dose-dependent increases in TSH levels followed by decreases in thyroid hormone levels were observed across preclinical species.
• Generally well tolerated in 28-day GLP toxicology studies in rats and dogs.
• High oral bioavailability and low clearance across preclinical species, with a projected human half-life of approximately 20-40 hours, which is anticipated to support once-daily oral dosing in humans.
  
  

About SEP-204, Graves’ Disease and Thyroid Eye Disease

SEP-204 is an investigational oral small molecule thyroid-stimulating hormone receptor (TSHR) negative allosteric modulator (NAM) being developed as a potential disease-modifying treatment for Graves’ disease and thyroid eye disease (TED). It is designed to block the overactivation of TSHR caused by patients’ autoantibodies in thyroid cells and orbital fibroblasts and has the potential to address both conditions. Graves’ disease is an autoimmune condition in which antibodies activate TSHR, stimulating excess thyroid hormone production and causing hyperthyroidism. Some patients also develop TED, a serious, potentially vision-threatening autoimmune condition affecting tissues behind the eyes that can cause eye bulging, swelling, pain and blurred or double vision. Current standard-of-care treatments do not address the shared underlying cause of both Graves’ disease and TED.

About Septerna
Septerna, Inc. is a clinical-stage biotechnology company with a world-class team of GPCR experts and drug developers advancing cutting-edge science to unlock the full potential of GPCR therapies for patients with significant unmet needs. The company’s proprietary Native Complex Platform^® is designed to enable new approaches to GPCR drug discovery and has led to the development of a diverse pipeline of novel oral small molecule drug candidates. Septerna is advancing programs in endocrinology, immunology and inflammation, metabolic diseases and additional therapeutic areas, both independently and with partners. 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 potential translation of preclinical findings to clinical outcomes in patients; the potential of SEP-204 to be a first-in-class, disease-modifying treatment for Graves’ disease and TED; advancing SEP-204 into a Phase 1 clinical study and the timing thereof; SEP-204’s potential for once daily dosing; the potential of its proprietary Native Complex Platform^®; and the scope of protection it is able to establish and maintain for intellectual property rights covering its Native Complex Platform^® and its product candidates; among others. 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: SEP-204 successfully entering and advancing through clinical trials including uncertainties related to opening investigational new drug applications and obtaining other regulatory approvals; risks related to clinical development outcomes including unexpected safety or efficacy findings; the results of preclinical studies not being predictive of future clinical outcomes; risks related to the timing of initiating clinical studies; and the scope of protection Septerna is able to establish and maintain for intellectual property rights covering its Native Complex Platform^® and its product candidates; among others. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Septerna’s Quarterly Report on Form 10-Q for the three months ended June 30, 2026, 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.

Investor Contact:
Renee Leck, THRUST
renee@thrustsc.com

Media Contact:
Carly Scaduto, THRUST
carly@thrustsc.com

FAQ

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What did Septerna report from SEP-204 preclinical studies?

SEP-204 restored normal T4 thyroid hormone levels and reduced thyroid enlargement and eye protrusion in Graves’ disease animal models. Human thyroid-cell assays also showed inhibition of antibody-driven activation of the thyroid-stimulating hormone receptor. SEP-204 was generally well tolerated in 28-day toxicology studies in rats and dogs.

When does Septerna plan to begin the SEP-204 Phase 1 trial?

Septerna anticipates initiating a Phase 1 trial in healthy volunteers in the first quarter of 2027. The trial is planned, not underway.