Compelling Phase 1 Data for SEP-631 (MRGPRX2 NAM) in Healthy Volunteers Support Phase 2b Development, Initially in Chronic Spontaneous Urticaria (CSU) in Second Half of 2026

Advancing SEP-479 (PTH1R Agonist) Toward Phase 1 Initiation in First Half of 2026

Cash Runway Expected to Support Operating Plans at Least into 2029

SOUTH SAN FRANCISCO, Calif., March 09, 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 fourth quarter and full year ended December 31, 2025.

"We made significant strides advancing our pipeline in the past year, and 2026 has already delivered a meaningful milestone with positive Phase 1 results for SEP-631," said Jeffrey Finer, M.D., Ph.D., chief executive officer and co-founder of Septerna. "These results demonstrate clinical proof-of-mechanism and validate the ability of our Native Complex Platform$(R)$ to uncover novel mechanisms of action and rapidly generate differentiated oral small molecules for historically challenging GPCRs. With SEP-479 approaching Phase 1 initiation in the coming months, SEP-631 poised for Phase 2 development in the second half of the year, and additional programs progressing behind them, we believe 2026 will be a year of strong progress for Septerna and for the patients we are committed to serving."

Recent Pipeline Progress and Anticipated Milestones

   -- SEP-631 MRGPRX2 NAM for Mast Cell Diseases: 
 
          -- In March 2026, Septerna presented positive results from its Phase 
             1 clinical trial evaluating SEP-631, its potent, selective and 
             insurmountable oral small molecule MRGPRX2 negative allosteric 
             modulator (NAM) and outlined its initial Phase 2 development 
             strategy. Key findings include: 
 
                 -- Safety: SEP-631 was well-tolerated at all doses studied 
                    with an adverse event profile comparable to placebo. 
 
                 -- Pharmacokinetics $(PK)$: SEP-631 demonstrated a PK profile 
                    supportive of convenient once-daily oral dosing without 
                    food restrictions. 
 
                 -- Pharmacodynamics $(PD)$: SEP-631 produced robust suppression 
                    of wheal formation across evaluated dose levels, with 
                    complete inhibition observed at doses as low as 10 mg once 
                    daily following the 10 ug/mL icatibant challenge. Following 
                    the 100 ug/mL icatibant challenge, inhibition was 
                    dose-dependent, with progressively greater suppression 
                    observed at increasing SEP-631 doses with near to complete 
                    inhibition achieved at 90 and 200 mg once daily. 
 
          -- Septerna plans to initiate a Phase 2b trial of SEP-631 in CSU in 
             the second half of 2026 following completion of long-term 
             toxicology studies, with an open-label study in chronic inducible 
             urticaria (CIndU) patients with symptomatic dermatographism to 
             follow. Septerna is also evaluating additional mast cell-driven 
             diseases with high unmet need and MRGPRX2 expression on 
             tissue-resident mast cells. 
 
   -- SEP-479 PTH1R Agonist for Hypoparathyroidism: 
 
          -- Septerna has completed IND-enabling studies for SEP-479, its 
             potent and selective oral small molecule PTH1R agonist, and is on 
             track to initiate a Phase 1 clinical trial in the first half of 
             2026. 
 
   -- 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. 
 
   -- Discovery Programs: 
 
          -- Septerna also continues to advance discovery-stage programs 
             utilizing its Native Complex Platform(R) across multiple 
             therapeutic areas. 

Business Highlights

   -- In January 2026, Septerna appointed Mark A. Wilson as chief legal 
      officer. Mr. Wilson is an accomplished pharmaceutical and biotech 
      executive with more than 25 years of experience across intellectual 
      property, corporate legal, strategic collaborations and corporate 
      governance matters. 

Fourth Quarter and Full Year 2025 Financial Results

   -- Cash Position: Cash, cash equivalents, and marketable securities totaled 
      $548.7 million as of December 31, 2025, compared to $420.8 million as of 
      December 31, 2024. During 2025, Septerna received a $195.0 million 
      upfront payment from Novo Nordisk and a $12.5 million milestone payment 
      from Vertex. Septerna expects its existing cash runway to fund operations 
      at least into 2029. 
 
   -- Revenue: Revenue was $24.1 million for the fourth quarter of 2025 and 
      $46.0 million for the full year ended December 31, 2025, compared to $0.2 
      million for the fourth quarter of 2024 and $1.1 million for the full year 
      ended December 31, 2024. 
 
          -- Revenue for the fourth quarter of 2025 included the amortization 
             of $14.0 million of the $195.0 million upfront payment received 
             from Novo Nordisk in July 2025, as well as $10.1 million for 
             research services associated with the collaboration. 
 
          -- Revenue for the full year ended December 31, 2025, included the 
             amortization of $26.8 million of the $195.0 million upfront 
             payment received from Novo Nordisk in July 2025, as well as $18.6 
             million for research services associated with the collaboration. 
 
   -- R&D Expenses: Research and development (R&D) expenses were $31.9 million 
      for the fourth quarter of 2025 and $97.6 million for the full year ended 
      December 31, 2025, compared to $19.3 million for the fourth quarter of 
      2024 and $65.3 million for the full year ended December 31, 2024. 
 
   -- G&A Expenses: General and administrative (G&A) expenses were $8.3 million 
      for the fourth quarter of 2025 and $29.2 million for the full year ended 
      December 31, 2025, compared to $5.6 million for the fourth quarter of 
      2024 and $16.6 million for the full year ended December 31, 2024. 
 
   -- Net Loss: Net loss was $10.7 million for the fourth quarter of 2025 and 
      $48.9 million for the full year ended December 31, 2025, compared to net 
      losses of $20.7 million for the fourth quarter of 2024 and $71.8 million 
      for the full year ended December 31, 2024. 

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 continued advancement of SEP-631, including the plan to initiate a Phase 2b clinical study in CSU in the second half of 2026 subject to the successful completion of long-term preclinical toxicology 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 CSU and other mast cell-driven diseases; expectations regarding the anticipated once-daily dosing frequency of SEP-631; the ability of the SEP-631 Phase 1 safety and efficacy observations to successfully translate into clinical outcomes in patients; the continued advancement of SEP-479, including the plan to initiate a Phase 1 clinical study in the first half of 2026; the continued development of its TSHR NAM program; the advancement of its discovery-stage programs across multiple therapeutic areas; the potential of its proprietary Native Complex Platform(R) ; 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.

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