SOUTH SAN FRANCISCO, Calif., Aug. 27, 2025 (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 that management will participate in the following upcoming investor conferences in September: Cantor Global Healthcare Conference 2025 Presentation on Wednesday, September 3, 2025, at 11:30 a.m. ET 2025 Wells Fargo Healthcare ConferenceFireside chat on Friday, September 5, 2025, at 8:45 a ...

"Mast cell-driven diseases represent significant unmet medical needs worldwide, affecting millions of patients who often struggle with inadequate symptom relief with current therapies," said Jae Kim, M.D., chief medical officer of Septerna. "We are excited to initiate the first-in-human trial for SEP-631, a small molecule NAM that aims to inhibit mast cell activation by selectively blocking MRGPRX2, a GPCR that plays a critical role in mast cell activation and degranulation. SEP-631 has the potential to pro ...

PART I. FINANCIAL INFORMATION [Item 1. Financial Statements (unaudited)](index=7&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) Unaudited H1 2025 financials reveal decreased assets to $415.2 million, a widened net loss of $46.3 million, and increased operating cash outflow [Condensed Balance Sheets](index=7&type=section&id=Condensed%20Balance%20Sheets) As of June 30, 2025, total assets decreased to $415.2 million from $456.6 million, primarily due to a drop in cash, while equity declined Condensed Balance Sheet Summary (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $189,311 | $238,196 | | Total current assets | $334,141 | $356,824 | | **Total assets** | **$415,231** | **$456,554** | | **Liabilities & Equity** | | | | Total current liabilities | $15,127 | $12,849 | | **Total liabilities** | **$37,674** | **$36,507** | | **Total stockholders' equity** | **$377,557** | **$420,047** | | Accumulated deficit | $(164,688) | $(118,374) | [Condensed Statements of Operations and Comprehensive Loss](index=8&type=section&id=Condensed%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Net loss for H1 2025 widened to $46.3 million from $30.6 million, driven by increased R&D and G&A expenses Statement of Operations Summary (in thousands, except per share data) | Metric | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Revenue | $338 | $687 | | Research and development | $41,459 | $28,188 | | General and administrative | $13,767 | $6,054 | | **Total operating expenses** | **$55,226** | **$34,242** | | Loss from operations | $(54,888) | $(33,555) | | **Net loss** | **$(46,314)** | **$(30,607)** | | Net loss per share | $(1.05) | $(13.40) | [Condensed Statements of Cash Flows](index=10&type=section&id=Condensed%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased to $43.6 million in H1 2025, with minimal financing cash compared to prior year Cash Flow Summary (in thousands) | Activity | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(43,630) | $(29,698) | | Net cash used in investing activities | $(5,660) | $(2,565) | | Net cash provided by financing activities | $405 | $74,952 | | **Net (decrease) increase in cash** | **$(48,885)** | **$42,689** | [Notes to Unaudited Condensed Financial Statements](index=12&type=section&id=Notes%20to%20Unaudited%20Condensed%20Financial%20Statements) Notes detail the company's IPO, a major collaboration with Novo Nordisk, and confirm sufficient capital for 12 months - The company is a biotechnology firm focused on GPCR oral small molecule drug discovery using its proprietary Native Complex Platform™[31](index=31&type=chunk) - In October 2024, the company completed its IPO, raising net proceeds of **$302.8 million**[35](index=35&type=chunk) - The company believes its cash, cash equivalents, and marketable securities of **$379.2 million** as of June 30, 2025, are sufficient to fund operations for at least **12 months**[40](index=40&type=chunk) - In May 2025, the company entered into a collaboration with Novo Nordisk, effective July 1, 2025, receiving a **$195.0 million** upfront payment in July 2025 and eligible for up to **$498.0 million** in milestones per R&D program, plus tiered royalties[52](index=52&type=chunk)[54](index=54&type=chunk) - A milestone related to the 2023 asset purchase agreement with Vertex was achieved in July 2025, resulting in a **$12.5 million** payment received in August 2025[57](index=57&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=29&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the GPCR platform, increased H1 2025 operating losses, and the Novo Nordisk collaboration, projecting funding into 2029 [Overview and Pipeline](index=29&type=section&id=Overview%20and%20Pipeline) Septerna, a biotechnology company, pioneers GPCR oral small molecule drug discovery with its Native Complex Platform™ and a pipeline in endocrinology, immunology, and metabolic diseases - The company's proprietary Native Complex Platform™ replicates the natural structure and function of GPCRs, enabling an industrialized, structure-based drug design approach[100](index=100&type=chunk) Development Pipeline Summary | Program / Target | Therapeutic Area | Development Status | | :--- | :--- | :--- | | **Wholly-Owned Programs** | | | | PTH1R Program | Endocrinology | Discovery | | SEP-631 (MRGPRX2) | Immunology and Inflammation | Discovery | | TSHR Program | Endocrinology | Discovery | | **Partnered Programs** | | | | Metabolic Programs (GLP-1R, etc.) | Obesity & Cardiometabolic | Partnered (Novo) | [Results of Operations](index=39&type=section&id=Results%20of%20Operations) Net loss increased to $46.3 million in H1 2025, driven by a $13.3 million rise in R&D expenses and a $7.7 million increase in G&A expenses Comparison of Results of Operations (in thousands) | Line Item | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Change | | :--- | :--- | :--- | :--- | | Revenue | $338 | $687 | $(349) | | Research and development | $41,459 | $28,188 | $13,271 | | General and administrative | $13,767 | $6,054 | $7,713 | | **Net loss** | **$(46,314)** | **$(30,607)** | **$(15,707)** | Research and Development Expense Breakdown (in thousands) | Program | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Change | | :--- | :--- | :--- | :--- | | PTH1R | $6,733 | $4,746 | $1,987 | | SEP-631 (MRGPRX2) | $3,765 | $874 | $2,891 | | Other programs | $9,996 | $2,153 | $7,843 | | Unallocated costs | $20,965 | $20,415 | $550 | | **Total R&D Expense** | **$41,459** | **$28,188** | **$13,271** | [Liquidity and Capital Resources](index=42&type=section&id=Liquidity%20and%20Capital%20Resources) With $379.2 million in cash as of June 30, 2025, bolstered by $195.0 million from Novo and $12.5 million from Vertex, the company projects funding into 2029 - The company historically financed operations through convertible notes, preferred stock, and its October 2024 IPO, which raised **$302.8 million** in net proceeds[143](index=143&type=chunk) - Management projects that its cash position of **$379.2 million** as of June 30, 2025, combined with the **$195.0 million** from Novo and **$12.5 million** from Vertex, will fund operations into **2029**[144](index=144&type=chunk) Summary of Cash Flows (in thousands) | Cash Flow Activity | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(43,630) | $(29,698) | | Net cash used in investing activities | $(5,660) | $(2,565) | | Net cash provided by financing activities | $405 | $74,952 | [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=28&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Septerna, Inc. is not required to provide the information requested under this item - The company is a smaller reporting company as defined by Rule 12b-2 of the Exchange Act and is not required to provide quantitative and qualitative disclosures about market risk[161](index=161&type=chunk) [Item 4. Controls and Procedures](index=28&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls were effective as of June 30, 2025, with no material changes in internal control over financial reporting - Based on an evaluation as of the end of the period, the Principal Executive Officer and Principal Financial Officer concluded that the company's disclosure controls and procedures were effective at a reasonable assurance level[163](index=163&type=chunk) - No changes in internal control over financial reporting occurred during the quarter ended June 30, 2025, that have materially affected, or are reasonably likely to materially affect, internal controls[164](index=164&type=chunk) PART II. OTHER INFORMATION [Item 1. Legal Proceedings](index=29&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any legal proceedings deemed probable to have a material adverse effect on its business - The company is not currently involved in any litigation or legal proceedings expected to have a material adverse effect on its business, financial condition, or results of operations[168](index=168&type=chunk) [Item 1A. Risk Factors](index=29&type=section&id=Item%201A.%20Risk%20Factors) Updated risk factors include potential FDA disruptions, unfavorable global economic conditions, geopolitical instability, and healthcare legislative reforms impacting drug pricing - Risks include potential disruptions at the FDA and other agencies due to staffing reductions, funding shortages, or government shutdowns, which could delay product development and approval[170](index=170&type=chunk)[171](index=171&type=chunk) - Unfavorable global economic conditions, political instability, and geopolitical events such as military conflicts and trade tariffs could adversely affect the business, financial condition, and stock price[172](index=172&type=chunk)[173](index=173&type=chunk) - Healthcare legislative reforms, including the Inflation Reduction Act (IRA) and recent Executive Orders, may negatively impact the business by containing healthcare costs and affecting drug pricing and reimbursement[176](index=176&type=chunk)[179](index=179&type=chunk)[180](index=180&type=chunk) - Recent changes to U.S. tax law, such as the One Big Beautiful Bill Act (H.R.1), could materially affect the company's business and cash flow, particularly regarding the capitalization and amortization of R&D expenses[186](index=186&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=32&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered sales occurred; IPO proceeds of $302.8 million are reallocated to advance other pipeline candidates after discontinuing the SEP-786 program - The company's October 2024 IPO generated net proceeds of **$302.8 million**[189](index=189&type=chunk) - The planned use of IPO proceeds has changed due to the discontinuation of the SEP-786 product candidate; funds will now advance other programs, including a next-generation PTH1R agonist and SEP-631[190](index=190&type=chunk) [Item 3. Defaults Upon Senior Securities](index=33&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) Not applicable - No defaults upon senior securities were reported[192](index=192&type=chunk) [Item 4. Mine Safety Disclosures](index=33&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Not applicable - No mine safety disclosures were required[193](index=193&type=chunk) [Item 5. Other Information](index=33&type=section&id=Item%205.%20Other%20Information) No directors or officers adopted or terminated Rule 10b5-1 trading plans during the fiscal quarter ended June 30, 2025 - No directors or officers adopted or terminated a Rule 10b5-1 trading plan or other similar trading arrangement during the quarter[194](index=194&type=chunk) [Item 6. Exhibits](index=34&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Form 10-Q, including corporate governance documents, the Novo Collaboration Agreement, and certifications - The list of exhibits includes the Novo Collaboration Agreement, CEO/CFO certifications, and XBRL data files[196](index=196&type=chunk)

SOUTH SAN FRANCISCO, Calif. – August 11, 2025 – Septerna, Inc. (Nasdaq: SEPN), a biotechnology company pioneering a new era of G protein-coupled receptor (GPCR) drug discovery, today highlighted key business updates and upcoming milestones and reported financial results for the second quarter ended June 30, 2025. "We are executing effectively across our portfolio, with each program nearing important milestones," said Jeffrey Finer, M.D., Ph.D., chief executive officer and co-founder of Septerna. "Our next-g ...

Core Insights - Septerna, Inc. is advancing its next-generation oral small molecule PTH1R agonist program for hypoparathyroidism, with plans to select a development candidate in Q3 2025 and initiate a Phase 1 clinical trial in H1 2026 [2][3] - The company is also initiating a Phase 1 clinical trial for SEP-631, an oral small molecule for mast cell diseases, in Q3 2025 [7] - Septerna's cash position is strong, with $379.2 million in cash and equivalents as of June 30, 2025, and an expected cash runway extending into 2029 following a $195 million upfront payment from Novo Nordisk [12][15] PTH1R Agonist Program - The PTH1R agonist program aims to provide full-day calcium control for patients with hypoparathyroidism, with a development candidate selection expected in Q3 2025 [3] - A Phase 1 clinical trial is planned to commence in the first half of 2026 after successful preclinical development [3] SEP-631 MRGPRX2 NAM Program - SEP-631 is a selective oral small molecule MRGPRX2 negative allosteric modulator for mast cell diseases, with a Phase 1 trial to assess safety and tolerability in healthy volunteers starting in Q3 2025 [7] Collaboration with Novo Nordisk - A global collaboration and license agreement with Novo Nordisk became effective on July 1, 2025, focusing on the discovery and development of oral small molecule therapies for obesity, type 2 diabetes, and other cardiometabolic diseases [7] - Septerna received a $195 million upfront payment as part of this collaboration [7] Business Highlights - The company continues to progress its TSHR NAM program, moving multiple lead compounds closer to development candidate selection for treating Graves' disease and thyroid eye disease [7] - Septerna's discovery-stage programs are advancing across various therapeutic areas utilizing its Native Complex Platform™ [7] Financial Results - For Q2 2025, Septerna reported R&D expenses of $22.2 million, up from $15.0 million in Q2 2024, and G&A expenses of $6.9 million, compared to $3.4 million in the same period [12] - The net loss for Q2 2025 was $24.8 million, compared to a net loss of $16.4 million in Q2 2024 [12][14]

Core Viewpoint - HC Wainwright has initiated coverage on Septerna, Inc., highlighting its innovative drug design platform targeting previously undruggable G protein-coupled receptors (GPCRs) [1][3] Company Overview - Septerna is focused on GPCR drug discovery through its proprietary Native Complex Platform, aiming to maximize the potential of GPCR therapies [1] - The company has a deep pipeline of oral small molecule product candidates targeting endocrinology, immunology and inflammation, and metabolic diseases [2] Financial Insights - Analyst Raghuram Selvaraju noted that Septerna trades at a discount to its cash position and recent partnership cash, presenting a risk-mitigated investment opportunity with multiple catalysts expected in the next 6 to 12 months [3][7] - HC Wainwright has set a Buy rating for Septerna with a price target of $26 [3] Drug Development - The leading drug candidate, SEP-631, is a selective oral small molecule MRGPRX2 negative allosteric modulator for mast cell diseases, including chronic spontaneous urticaria (CSU) [4] - SEP-631 could provide a unique treatment option for CSU patients due to its selective mast cell inhibition and potential for combination therapy [4] Market Potential - If SEP-631 can match the efficacy of Novartis and Roche's Xolair, which generated nearly $3.9 billion in sales in 2023, it could achieve blockbuster status [5] - Septerna has entered an exclusive global collaboration with Novo Nordisk for the development of oral small-molecule medicines for obesity, type 2 diabetes, and other cardiometabolic diseases, starting with four development programs [6] Valuation Perspective - HC Wainwright emphasized that the financial implications of the partnership suggest Septerna's implied enterprise value may be negligible or negative, indicating the company is undervalued [7]

Summary of Septerna (SEPN) 2025 Conference Call Company Overview - **Company**: Septerna (SEPN) - **Focus**: Development of drugs targeting G protein-coupled receptors (GPCRs) using a proprietary platform called the native complex platform [1][2] Portfolio Strategy - **Target Selection**: Focus on biologically and clinically validated targets with significant unmet needs and market opportunities [2] - **Current Programs**: Discussion of four main programs, including a parathyroid hormone receptor agonist, MRGPRX2, thyroid stimulating hormone receptor negative allosteric modulator, and an incretin receptor agonist [3][4] Financial Position - **Capitalization**: Well-capitalized following an IPO in October and a recent collaboration with Novo Nordisk, providing a strong financial position for ongoing research and development [3][54] Key Programs 1. **Parathyroid Hormone Receptor Agonist Program** - **Target**: Oral small molecules for hypoparathyroidism [16] - **Challenges**: Discontinued trial of first compound (SEP-786) due to unanticipated bilirubin levels, but ongoing investigation into next-generation compounds [23][24][26] - **Animal Model Results**: Promising results in normalizing calcium levels in hypoparathyroid rat models with new compounds showing lower dosing requirements compared to SEP-786 [29][31][34] 2. **MRGPRX2 Program** - **Target**: Mast cell diseases, including chronic spontaneous urticaria and allergic asthma [35][37] - **Compound**: SEP-631, a negative allosteric modulator showing potent inhibition of receptor activation and promising preclinical results [38][42] - **Clinical Timeline**: Expected to enter Phase 1 trials in Q3 [43] 3. **Thyroid Stimulating Hormone Receptor Program** - **Focus**: Treating Graves' disease and thyroid eye disease with a negative allosteric modulator [44] - **Mechanism**: Aiming for a universal approach to target multiple autoantibodies in patients [45][46] 4. **Incretin Receptor Agonist Program** - **Innovation**: Discovery of a novel binding pocket allowing for the development of multi-incretin receptor agonists [50] - **Preclinical Results**: Early-stage molecules showing weight loss effects comparable to existing treatments [52] Collaboration with Novo Nordisk - **Details**: Collaboration includes three known targets and two undisclosed targets, with an upfront payment of $195 million and Novo responsible for all R&D costs [53][54] Leadership and Future Outlook - **Team**: Experienced leadership with decades of industry experience and a strong advisory board [55] - **Market Potential**: Each program represents a significant market opportunity, with ongoing efforts to extend financial runway into early 2028 and beyond [56] Conclusion - **Overall Position**: Septerna is well-positioned in the GPCR drug discovery space with a robust pipeline and strategic collaborations, aiming to address significant unmet medical needs across various therapeutic areas [56]

Company Overview - Septerna, Inc. is a biotechnology company focused on G protein-coupled receptor (GPCR) drug discovery, utilizing its proprietary Native Complex Platform™ to enhance GPCR therapies [3] - The company has developed a deep pipeline of oral small molecule product candidates targeting three therapeutic areas: endocrinology, immunology and inflammation, and metabolic diseases [3] Upcoming Event - Jeffrey Finer, M.D., Ph.D., CEO and Co-founder of Septerna, will present at the Jefferies Global Healthcare Conference on June 5, 2025, at 3:45 p.m. ET in New York [1] - A live webcast of the presentation will be available on the company's website and will be archived for at least 30 days [2]

Core Viewpoint - The S&P 500 has experienced persistent volatility in 2025, leading to cautious investor sentiment, but this environment may present opportunities for significant gains for those willing to take moderate risks [1]. Group 1: Septerna Inc. - Septerna Inc. is a clinical-stage biotechnology firm focused on developing G protein-coupled receptor (GPCR) oral small molecule drug candidates for various diseases [4][6]. - The company has secured a major partnership with Novo Nordisk, which could enhance its growth potential, with an immediate payment of approximately $200 million and a deal potentially worth over $2 billion [5][6]. - Analysts have a consensus price target of $27 per share for Septerna, indicating a potential upside of 184.81% from the current price of $9.48, despite the stock having fallen by about 58% year-to-date [7][4]. Group 2: Intellia Therapeutics Inc. - Intellia Therapeutics is a genome editing firm developing therapies for conditions such as hemophilia and cancers, with promising trial data reported for its ongoing Phase 1 trial [9][10]. - The company has a strong cash position of $707 million as of March 31, 2025, which is expected to fund operations through early 2027 [10]. - The consensus price target for Intellia shares is $36.90, suggesting a potential quadrupling of the stock's current price, with 14 out of 21 analysts rating the stock as a Buy [11]. Group 3: Novavax Inc. - Novavax has received full FDA approval for its protein-based COVID-19 vaccine, unlocking a $175 million milestone payment from Sanofi, positioning it as a non-mRNA option [12][13]. - Despite the approval, the FDA has imposed significant restrictions that may limit the vaccine's availability, contributing to mixed market reactions [13]. - The consensus price target for Novavax shares is $19, indicating a potential upside of 160.63%, with four out of seven analysts rating the stock as a Buy [12][13].

Group 1 - Septerna, Inc. (SEPN) shares have increased by 57.8% over the past four weeks, closing at $9.42, with a mean price target of $23.67 indicating a potential upside of 151.3% [1] - The average price targets range from a low of $18 to a high of $28, with a standard deviation of $5.13, suggesting a high degree of agreement among analysts [2] - Analysts show strong optimism regarding SEPN's earnings prospects, as indicated by a 63.2% increase in the Zacks Consensus Estimate for the current year, with no negative revisions [12][11] Group 2 - SEPN holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] - The consensus price target may not be a reliable indicator of the stock's potential gain, but the direction of price movement implied by it appears to be a good guide [13][10]