Phase 1 Clinical Trial Ongoing for SEP-479, an Oral Small Molecule PTH1R Agonist

SEP-479 Observed Clinical Pharmacokinetic Profile Supports Once-Daily Dosing; SAD / MAD Data Expected in Q1 2027

Cash Position of $516.5 Million Expected to Support Operating Plans at Least into 2029

SOUTH SAN FRANCISCO, Calif., Aug. 10, 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 highlighted pipeline progress and anticipated milestones and reported financial results for the second quarter ended June 30, 2026.

"We continue to make meaningful progress across our portfolio as we execute on our strategy to develop differentiated oral medicines targeting GPCRs," said Jeffrey Finer, M.D., Ph.D., Chief Executive Officer and Co-founder of Septerna. "We are advancing our Phase 1 study of SEP-479 and are very pleased with the observed clinical half-life, which is at the longer end of our preclinical estimates. This finding reinforces our confidence in the potential of SEP-479 as a differentiated, once-daily oral treatment for hypoparathyroidism, and we look forward to presenting SAD/MAD data in the first quarter of 2027. We are also advancing our broader portfolio by evaluating the next phase of development for SEP-631 in mast cell-driven diseases and progressing our TSHR program toward development candidate selection."

Recent Portfolio Progress and Anticipated Milestones

   -- SEP-479 PTH1R Agonist for Hypoparathyroidism: 
 
          -- Septerna's Phase 1 clinical trial of SEP-479, a potent, selective 
             oral small molecule PTH1R agonist for the treatment of 
             hypoparathyroidism, is ongoing. The single-ascending dose (SAD) 
             and multiple-ascending dose (MAD) study is evaluating safety, 
             tolerability, pharmacokinetics and pharmacodynamics (including 
             serum calcium and endogenous serum PTH) in healthy volunteers. 
 
          -- Based on pharmacokinetic data from the ongoing Phase 1 clinical 
             trial, the observed elimination half-life of SEP-479 is 
             approximately three to four days, which the Company anticipates 
             will support once-daily dosing. To fully characterize steady-state 
             pharmacokinetics, dosing for the MAD cohorts will be extended to 
             14 days. As a result, Septerna expects to report Phase 1 data from 
             both the SAD and MAD cohorts in the first quarter of 2027. 
 
          -- During the quarter, the Company presented the first detailed 
             preclinical characterization of SEP-479 in an oral presentation at 
             ENDO 2026, highlighting data supporting its potential as a 
             differentiated, once-daily oral treatment for hypoparathyroidism. 
 
   -- SEP-631 MRGPRX2 NAM for Mast Cell-Driven Diseases: 
 
          -- As reported in March 2026, SEP-631, an oral small molecule MRGPRX2 
             negative allosteric modulator (NAM), demonstrated positive Phase 1 
             clinical results, including a well-tolerated safety profile, 
             pharmacokinetics supportive of once-daily oral dosing and robust, 
             dose-dependent suppression of icatibant-induced skin wheal 
             formation. 
 
          -- In lieu of a Phase 2b study in chronic spontaneous urticaria (CSU), 
             the Company is evaluating development strategies for 
             capital-efficient, signal-finding clinical studies in mast 
             cell-driven diseases characterized by high unmet need. 
 
   -- TSHR NAM Program: 
 
          -- Septerna continues to progress toward development candidate 
             selection for its TSHR NAM program, with the goal of delivering a 
             potential disease-modifying oral treatment for Graves' disease and 
             thyroid eye disease. 
 
   -- Additional Programs: 
 
          -- Septerna continues to advance and achieve research milestones from 
             its global collaboration with Novo Nordisk to discover, develop 
             and commercialize multiple potential oral small molecule medicines 
             for obesity, type 2 diabetes and other cardiometabolic diseases 
             based on specified GPCR targets. 
 
          -- The Company also continues to advance wholly-owned discovery-stage 
             programs utilizing its Native Complex Platform$(R)$ across multiple 
             therapeutic areas. 

Second Quarter 2026 Financial Results

   -- Cash Position: Cash, cash equivalents, and marketable securities totaled 
      $516.5 million as of June 30, 2026. Septerna expects its existing cash 
      runway to fund operations at least into 2029. 
 
   -- Revenue: Revenue from the Novo Nordisk collaboration was $26.7 million 
      for the quarter ended June 30, 2026, compared to $0.1 million from Vertex 
      for the quarter ended June 30, 2025. Revenue for the quarter ended 
      June 30, 2026, included the amortization of $14.6 million of the $195.0 
      million upfront payment and $0.9 million from the achievement of $4.0 
      million in research milestones, in addition to $11.2 million for research 
      services associated with the collaboration. 
 
   -- R&D Expenses: Research and development (R&D) expenses were $35.1 million 
      for the quarter ended June 30, 2026, compared to $22.2 million for the 
      quarter ended June 30, 2025. 
 
   -- G&A Expenses: General and administrative (G&A) expenses were $8.5 million 
      for the quarter ended June 30, 2026, compared to $6.9 million for the 
      quarter ended June 30, 2025. 
 
   -- Net Loss: Net loss was $13.0 million for the quarter ended June 30, 2026, 
      compared to $24.8 million for the quarter ended June 30, 2025. 

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(R) 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 of SEP-479 preclinical data to translate into similar clinical safety, pharmacokinetic, and pharmacodynamic findings; the estimated availability of SEP-479 Phase 1 clinical data in the first quarter of 2027; the potential for SEP-479 to be a differentiated once-daily oral therapy for patients with hypoparathyroidism; the potential of its proprietary Native Complex Platform(R) ; the continued advancement of SEP-631, including our plan to evaluate development strategies for capital-efficient, signal-finding clinical studies; the role of MRGPRX2 in mast cell-driven diseases; the potential of SEP-631 to provide a convenient oral treatment option for patients with mast cell-driven diseases; the ability of the SEP-631 Phase 1 safety and efficacy observations to successfully translate into clinical outcomes in patients; the continued development of its TSHR NAM program; the advancement of its discovery-stage programs across multiple therapeutic areas; the size and growth potential of the markets for its current and future product candidates; its expectations regarding strategic plans for its business, product candidates, and technology; its expectations regarding the Company's uses of capital, expenses and financial results, including its expected cash runway at least into 2029; and the scope of protection it is able to establish and maintain for intellectual property rights covering its Native Complex Platform(R) and its product candidates. 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: Septerna's product candidates successfully entering and advancing through clinical trials (including those for SEP-479 and SEP-631) including uncertainties related to opening INDs and obtaining other regulatory approvals; risks related to clinical development outcomes including unexpected safety or efficacy findings; the results of preclinical studies including the long-term toxicology studies for SEP-479 and SEP-631, or clinical studies not being predictive of future clinical outcomes; risks related to the timing of initiating clinical studies and future availability of clinical data; the scope of protection Septerna is able to establish and maintain for intellectual property rights covering its Native Complex Platform(R) and its product candidates; and 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 Quarterly Report on