[FORM 10-Q Filing Information](index=1&type=section&id=FORM%2010-Q) This section provides basic identification details for Sionna Therapeutics, Inc.'s Form 10-Q filing for the quarterly period ended June 30, 2025 [Registrant Information](index=1&type=section&id=Registrant%20Information) This section provides the basic identification details for Sionna Therapeutics, Inc.'s Form 10-Q filing for the quarterly period ended June 30, 2025, including its address, telephone number, and Nasdaq Global Market trading symbol 'SION', classifying the company as a non-accelerated filer, a smaller reporting company, and an emerging growth company - Sionna Therapeutics, Inc. is filing its Quarterly Report on Form 10-Q for the period ended June 30, 2025[2](index=2&type=chunk) - The number of shares of registrant's common stock outstanding as of August 1, 2025, was **44,139,823**[5](index=5&type=chunk) Trading Symbol Information | Title of each class | Trading Symbol(s) | Name of each exchange on which registered | | :------------------ | :---------------- | :---------------------------------------- | | Common Stock, $0.001 par value per share | SION | The Nasdaq Global Market | Filer Status | Filer Status | | | :---------------------- | :--- | | Large accelerated filer | o | | Accelerated filer | o | | Non-accelerated filer | x | | Smaller reporting company | x | | Emerging growth company | x | [Cautionary Note Regarding Forward-Looking Statements](index=2&type=section&id=CAUTIONARY%20NOTE%20REGARDING%20FORWARD-LOOKING%20STATEMENTS) This section cautions readers about forward-looking statements in the report, which involve substantial risks and uncertainties [Nature of Forward-Looking Statements](index=2&type=section&id=Nature%20of%20Forward-Looking%20Statements) This section highlights that the report contains forward-looking statements involving substantial risks and uncertainties, cautioning that actual results may differ materially - The Quarterly Report contains forward-looking statements about the company and its industry, involving substantial risks and uncertainties, made pursuant to safe harbor provisions[8](index=8&type=chunk) - Statements cover future results of operations, financial position, business strategy, product candidates, preclinical studies, clinical trials, research and development costs, regulatory approvals, commercial strategy, timing and likelihood of success, and management plans[8](index=8&type=chunk) - Actual results, performance, or achievements may be materially different from those expressed or implied by forward-looking statements due to known and unknown risks, uncertainties, and other important factors beyond the company's control[8](index=8&type=chunk) [Key Areas of Forward-Looking Statements](index=2&type=section&id=Key%20Areas%20of%20Forward-Looking%20Statements) This section details specific forward-looking statements regarding R&D, clinical trials, regulatory approvals, funding, market potential, and intellectual property - Initiation, timing, progress, and results of research and development programs, preclinical studies, and clinical trials[10](index=10&type=chunk) - Ability of clinical trials to demonstrate safety and efficacy of product candidates[10](index=10&type=chunk) - Timing, scope, and likelihood of regulatory filings and approvals[10](index=10&type=chunk) - Implementation of business model and strategic plans for product candidates[10](index=10&type=chunk) - Ability to obtain additional cash and sufficiency of existing cash to fund operations[10](index=10&type=chunk) - Accuracy of estimates regarding expenses, future revenue, capital requirements, and financing needs[10](index=10&type=chunk) - Size and growth potential of markets for product candidates and manufacturing capabilities[10](index=10&type=chunk) - Scope of intellectual property protection[10](index=10&type=chunk) - Developments relating to competitors and industry[10](index=10&type=chunk) - Existing regulations and regulatory developments, including changes in U.S. federal policy[10](index=10&type=chunk) - Expectations regarding future events under collaboration and licensing agreements[10](index=10&type=chunk) - General economic, industry, and market conditions, including elevated interest rates and inflation[10](index=10&type=chunk) - Ability to attract and retain key personnel[10](index=10&type=chunk) - Expectations regarding emerging growth company status[10](index=10&type=chunk) - Anticipated use of existing cash, cash equivalents, and marketable securities[10](index=10&type=chunk) - These statements are based on current expectations and projections but are not guarantees of future performance and are subject to risks described in the 'Risk Factors' section[9](index=9&type=chunk)[11](index=11&type=chunk) [Note Regarding Trademarks](index=4&type=section&id=NOTE%20REGARDING%20TRADEMARKS) This section clarifies the ownership and usage of trademarks within the report, including company and third-party marks [Trademark Ownership and Usage](index=4&type=section&id=Trademark%20Ownership%20and%20Usage) This section clarifies Sionna Therapeutics, Inc.'s trademark ownership and usage, noting that other trademarks belong to third parties - Sionna Therapeutics, Inc. owns the trademarks SIONNA and SIONNA THERAPEUTICS, and other design trademarks[15](index=15&type=chunk) - The absence of ™ and ® symbols does not indicate a lack of trademark rights[15](index=15&type=chunk) - References to 'Sionna,' 'Company,' 'we,' 'us,' and 'our' refer to Sionna Therapeutics, Inc. and its subsidiary[16](index=16&type=chunk) [Summary of Material Risks Associated with Our Business](index=5&type=section&id=SUMMARY%20OF%20MATERIAL%20RISKS%20ASSOCIATED%20WITH%20OUR%20BUSINESS) This section provides a high-level overview of the significant risks inherent in the company's business operations and financial outlook [Key Business Risks](index=5&type=section&id=Key%20Business%20Risks) This section summarizes key risks including operating losses, funding needs, dependence on NBD1 stabilizers, regulatory uncertainties, competition, and stock volatility - Incurred significant operating losses since inception, with net losses of **$34.6 million** and **$20.4 million** for the six months ended June 30, 2025, and 2024, respectively, and an accumulated deficit of **$215.6 million** as of June 30, 2025[18](index=18&type=chunk) - Requires substantial additional funding for product development and commercialization, with potential inability to raise capital on acceptable terms[19](index=19&type=chunk) - Substantially dependent on the success of NBD1 stabilizers; failure or delays would materially harm the business[19](index=19&type=chunk) - Developing combination treatments increases complexity and risk, including drug-drug interactions and unforeseen side effects[19](index=19&type=chunk) - Regulatory approval processes are lengthy, time-consuming, and unpredictable; failure to obtain approval would substantially harm the business[19](index=19&type=chunk) - Preclinical and interim clinical trial results are not necessarily predictive of later clinical trial outcomes[19](index=19&type=chunk) - Targeting the NBD1 domain of CFTR protein is novel, with no guarantee of successful product development[19](index=19&type=chunk) - Clinical trials may fail to demonstrate safety and efficacy, or identify serious adverse side effects[19](index=19&type=chunk) - Must prioritize development of certain product candidates due to limited resources, potentially missing more profitable opportunities[19](index=19&type=chunk) - Dependent on licensed intellectual property; loss of rights or breach of agreements could prevent development/commercialization[19](index=19&type=chunk) - Relies on third parties for manufacturing, increasing risks of insufficient quantities, unacceptable cost, or quality[19](index=19&type=chunk) - Inability to obtain, maintain, and enforce intellectual property rights could allow competitors to commercialize similar products[19](index=19&type=chunk) - Faces substantial competition, particularly from Vertex, which holds significant market share and greater resources[21](index=21&type=chunk) - The trading price of common stock may be volatile, leading to potential investment loss[21](index=21&type=chunk) [Part I - Financial Information](index=8&type=section&id=Part%20I%20-%20Financial%20Information) This section presents the unaudited interim condensed consolidated financial statements and management's discussion and analysis [Item 1. Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) This section presents the unaudited interim condensed consolidated financial statements, including balance sheets, statements of operations, equity, and cash flows [Condensed Consolidated Balance Sheets](index=9&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section provides a snapshot of the company's assets, liabilities, and equity at specific points in time Condensed Consolidated Balance Sheets (in thousands) | Assets (June 30, 2025) | Amount ($) | Assets (December 31, 2024) | Amount ($) | | :----------------------- | :--------- | :--------------------------- | :--------- | | Cash and cash equivalents | 40,985 | Cash and cash equivalents | 37,788 | | Marketable securities, current | 221,586 | Marketable securities, current | 109,750 | | Prepaid expenses and other current assets | 4,175 | Prepaid expenses and other current assets | 3,455 | | **Total current assets** | **266,746** | **Total current assets** | **150,993** | | Property and equipment, net | 2,246 | Property and equipment, net | 2,466 | | Marketable securities, noncurrent | 74,699 | Marketable securities, noncurrent | 20,505 | | Restricted cash | 962 | Restricted cash | 962 | | Operating lease right-of-use asset | 7,395 | Operating lease right-of-use asset | 7,832 | | Other assets | — | Other assets | 2,994 | | **Total assets** | **352,048** | **Total assets** | **185,752** | | Liabilities (June 30, 2025) | Amount ($) | Liabilities (December 31, 2024) | Amount ($) | | Accounts payable | 914 | Accounts payable | 1,186 | | Accrued expenses | 5,468 | Accrued expenses | 8,162 | | Operating lease liability, current | 1,168 | Operating lease liability, current | 1,072 | | **Total current liabilities** | **7,550** | **Total current liabilities** | **10,420** | | Operating lease liability, noncurrent | 8,069 | Operating lease liability, noncurrent | 8,677 | | **Total liabilities** | **15,619** | **Total liabilities** | **19,097** | | Total convertible preferred stock | — | Total convertible preferred stock | 330,368 | | Stockholders' equity (deficit) | 336,429 | Stockholders' equity (deficit) | (163,713) | | **Total liabilities, convertible preferred stock and stockholders' equity (deficit)** | **352,048** | **Total liabilities, convertible preferred stock and stockholders' equity (deficit)** | **185,752** | - Total assets increased significantly from **$185.8 million** at December 31, 2024, to **$352.0 million** at June 30, 2025, primarily driven by an increase in marketable securities[29](index=29&type=chunk) - Total liabilities decreased from **$19.1 million** to **$15.6 million**, while stockholders' equity shifted from a deficit of **$163.7 million** to a positive **$336.4 million**, largely due to the IPO and conversion of preferred stock[29](index=29&type=chunk) [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) This section details the company's revenues, expenses, and net loss over specific reporting periods Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :----------------------------------- | :------------------------------- | :------------------------------- | :------------------------------- | :------------------------------- | | Research and development | $15,383 | $8,233 | $29,051 | $18,453 | | General and administrative | $6,523 | $3,059 | $12,514 | $5,986 | | **Total operating expenses** | **$21,906** | **$11,292** | **$41,565** | **$24,439** | | Loss from operations | $(21,906) | $(11,292) | $(41,565) | $(24,439) | | Interest income | $3,667 | $2,566 | $6,667 | $3,698 | | Other income | $171 | $174 | $348 | $342 | | **Total other income** | **$3,838** | **$2,740** | **$7,015** | **$4,040** | | **Net loss** | **$(18,068)** | **$(8,552)** | **$(34,550)** | **$(20,399)** | | Net loss per share, basic and diluted | $(0.41) | $(2.71) | $(0.98) | $(6.54) | | Weighted-average common shares outstanding | 44,116,997 | 3,159,815 | 35,404,928 | 3,121,225 | | Unrealized loss on marketable securities | $(118) | $(148) | $(185) | $(156) | | **Comprehensive loss** | **$(18,186)** | **$(8,700)** | **$(34,735)** | **$(20,555)** | - Net loss for the six months ended June 30, 2025, increased to **$34.6 million** from **$20.4 million** in the prior year, driven by higher operating expenses[31](index=31&type=chunk) - Research and development expenses increased by **$10.6 million (57.4%)** and general and administrative expenses increased by **$6.5 million (109.0%)** for the six months ended June 30, 2025, compared to the same period in 2024[31](index=31&type=chunk) - Interest income significantly increased to **$6.7 million** for the six months ended June 30, 2025, from **$3.7 million** in 2024, due to increased investment in debt securities following the IPO[31](index=31&type=chunk) [Condensed Consolidated Statements of Convertible Preferred Stock and Stockholders' Equity (Deficit)](index=12&type=section&id=Condensed%20Consolidated%20Statements%20of%20Convertible%20Preferred%20Stock%20and%20Stockholders'%20Equity%20(Deficit)) This section outlines changes in the company's equity structure, including preferred stock conversion and IPO impact - Upon the closing of the initial public offering in February 2025, all outstanding convertible preferred stock (Series Seed, A, B, C) automatically converted into **27,149,206** shares of common stock[36](index=36&type=chunk)[42](index=42&type=chunk) - The IPO also resulted in the issuance of **12,176,467** shares of common stock, generating net proceeds of approximately **$199.6 million**[36](index=36&type=chunk)[42](index=42&type=chunk) - Total stockholders' equity (deficit) dramatically improved from a deficit of **$(163.7 million)** at December 31, 2024, to a positive **$336.4 million** at June 30, 2025[36](index=36&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=14&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This section presents the inflows and outflows of cash from operating, investing, and financing activities Condensed Consolidated Statements 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 | $(34,441) | $(23,320) | | Net cash used in investing activities | $(164,439) | $(152,548) | | Net cash provided by financing activities | $202,077 | $181,371 | | **Net increase in cash, cash equivalents and restricted cash** | **$3,197** | **$5,503** | - Net cash used in operating activities increased to **$34.4 million** for the six months ended June 30, 2025, from **$23.3 million** in the prior year, primarily due to increased net loss[38](index=38&type=chunk)[118](index=118&type=chunk)[119](index=119&type=chunk) - Net cash provided by financing activities was **$202.1 million** in 2025, mainly from the IPO, compared to **$181.4 million** in 2024 from Series C convertible preferred stock issuance[38](index=38&type=chunk)[121](index=121&type=chunk) - Cash, cash equivalents, and restricted cash at the end of the period were **$41.9 million** in 2025, a slight decrease from **$45.0 million** in 2024[38](index=38&type=chunk) [Notes to Condensed Consolidated Financial Statements](index=15&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed explanations and additional information supporting the condensed consolidated financial statements [1. Nature of the Business](index=15&type=section&id=1.%20Nature%20of%20the%20Business) This note describes Sionna Therapeutics, Inc.'s core focus, recent corporate actions, and financial viability - Sionna Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing novel medicines to normalize CFTR protein function for cystic fibrosis patients[39](index=39&type=chunk) - The company completed a **1-for-1.4611** reverse stock split on January 31, 2025, and an Initial Public Offering (IPO) in February 2025, raising approximately **$199.6 million** net proceeds[41](index=41&type=chunk)[42](index=42&type=chunk) - As of June 30, 2025, the company had an accumulated deficit of **$215.6 million** but believes its existing cash, cash equivalents, and marketable securities of **$337.3 million** will fund operations beyond twelve months[44](index=44&type=chunk)[45](index=45&type=chunk) [2. Summary of Significant Accounting Policies](index=16&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) This note outlines the key accounting principles and recent pronouncements relevant to the financial statements - No material changes to significant accounting policies since the Annual Report on Form 10-K for the year ended December 31, 2024[46](index=46&type=chunk) - The interim financial statements are unaudited and prepared on the same basis as audited annual statements, reflecting normal recurring adjustments[47](index=47&type=chunk) - ASU 2023-09 (Income Taxes): Effective for annual periods after December 15, 2024; not expected to have a material impact[48](index=48&type=chunk) - ASU 2024-03 (Income Statement Expenses): Effective for annual periods after December 15, 2026; currently evaluating the effect[49](index=49&type=chunk) [3. Marketable Securities](index=17&type=section&id=3.%20Marketable%20Securities) This note details the composition and fair value of the company's marketable securities portfolio Marketable Securities (in thousands) | Category | June 30, 2025 Fair Value ($) | December 31, 2024 Fair Value ($) | | :----------------------------- | :----------------------------- | :----------------------------- | | U.S. Treasury securities | 183,705 | 70,679 | | Commercial paper | 61,638 | 5,934 | | Government agency securities | 37,870 | 36,415 | | Corporate debt | 13,072 | 17,227 | | **Total marketable securities** | **296,285** | **130,255** | - Total marketable securities increased significantly from **$130.3 million** at December 31, 2024, to **$296.3 million** at June 30, 2025[50](index=50&type=chunk) - As of June 30, 2025, **$74.7 million** of marketable securities had remaining maturities between one and two years; all others matured in less than a year. No realized gains or losses were recorded in either period[50](index=50&type=chunk) [4. Fair Value Measurements](index=18&type=section&id=4.%20Fair%20Value%20Measurements) This note describes the fair value hierarchy and measurements applied to the company's financial assets Fair Value Measurements of Financial Assets (in thousands) | Asset Category | June 30, 2025 Total Fair Value ($) | December 31, 2024 Total Fair Value ($) | | :----------------------- | :--------------------------------- | :--------------------------------- | | Money market funds | 40,485 | 37,288 | | U.S. Treasury securities | 183,705 | 70,679 | | Commercial paper | 61,638 | 5,934 | | Government agency securities | 37,870 | 36,415 | | Corporate debt | 13,072 | 17,227 | | **Total financial assets** | **336,770** | **167,543** | - Total financial assets measured at fair value increased from **$167.5 million** at December 31, 2024, to **$336.8 million** at June 30, 2025[52](index=52&type=chunk) - The majority of assets are classified as Level 1 (money market funds, U.S. Treasury securities) or Level 2 (commercial paper, government agency securities, corporate debt) in the fair value hierarchy[52](index=52&type=chunk) [5. Property and Equipment, net](index=18&type=section&id=5.%20Property%20and%20Equipment,%20net) This note provides details on the company's property and equipment, including depreciation Property and Equipment, net (in thousands) | Category | June 30, 2025 ($) | December 31, 2024 ($) | | :----------------------- | :---------------- | :-------------------- | | Leasehold improvements | 1,854 | 1,854 | | Laboratory equipment | 1,547 | 1,461 | | Furniture & fixtures | 722 | 722 | | **Total property and equipment** | **4,123** | **4,037** | | Less: accumulated depreciation | (1,877) | (1,571) | | **Property and equipment, net** | **2,246** | **2,466** | - Net property and equipment decreased from **$2.47 million** at December 31, 2024, to **$2.25 million** at June 30, 2025[53](index=53&type=chunk) - Depreciation expense was **$0.3 million** for both the six months ended June 30, 2025, and 2024[53](index=53&type=chunk) [6. Accrued Expenses](index=19&type=section&id=6.%20Accrued%20Expenses) This note details the composition and changes in the company's accrued expenses Accrued Expenses (in thousands) | Category | June 30, 2025 ($) | December 31, 2024 ($) | | :----------------------------- | :---------------- | :-------------------- | | Accrued research and development | 2,660 | 3,961 | | Accrued compensation and benefits | 1,991 | 2,972 | | Accrued professional fees | 782 | 737 | | Accrued other | 35 | — | | Accrued offering costs | — | 492 | | **Total accrued expenses** | **5,468** | **8,162** | - Total accrued expenses decreased from **$8.16 million** at December 31, 2024, to **$5.47 million** at June 30, 2025, primarily due to decreases in accrued research and development and compensation and benefits, and the payment of accrued offering costs[54](index=54&type=chunk) [7. Commitments and Contingencies](index=19&type=section&id=7.%20Commitments%20and%20Contingencies) This note outlines the company's operating lease commitments, legal proceedings, and indemnification obligations - No material changes to operating lease commitments during the six months ended June 30, 2025[55](index=55&type=chunk) - The company was not subject to any material legal proceedings as of June 30, 2025, and is not aware of any pending or threatened[56](index=56&type=chunk) - The company provides indemnification to vendors, lessors, business partners, directors, and senior management, with potential unlimited future payments, but has not incurred material costs to date[59](index=59&type=chunk) [8. License Agreements](index=19&type=section&id=8.%20License%20Agreements) This note describes the company's various third-party license agreements and their financial implications - The company has various license agreements with third parties involving upfront, milestone, and royalty payments[60](index=60&type=chunk) - No material changes to the terms, conditions, or accounting conclusions of these license agreements since the Annual Report[60](index=60&type=chunk) [9. Stock-Based Compensation](index=20&type=section&id=9.%20Stock-Based%20Compensation) This note details the company's stock option plans and the associated compensation expense - The 2020 Stock Option and Grant Plan has no shares remaining for future issuance as of June 30, 2025[61](index=61&type=chunk) - The 2025 Stock Option and Incentive Plan became effective in February 2025, initially reserving **5,060,000** shares, subject to evergreen provisions[62](index=62&type=chunk) Stock Option Activity (Six Months Ended June 30, 2025) | Metric | Number of Common Stock Options | Weighted-Average Exercise Price ($) | | :----------------------------- | :----------------------------- | :---------------------------------- | | Outstanding as of Dec 31, 2024 | 3,700,335 | 5.87 | | Granted | 2,305,760 | 17.40 | | Exercised | (7,944) | 0.76 | | Cancelled or forfeited | (24,000) | 10.16 | | **Outstanding as of June 30, 2025** | **5,974,151** | **10.31** | | Exercisable as of June 30, 2025 | 2,097,556 | 6.39 | Stock-Based Compensation Expense (in thousands) | Expense Category | Three Months Ended June 30, 2025 ($) | Three Months Ended June 30, 2024 ($) | Six Months Ended June 30, 2025 ($) | Six Months Ended June 30, 2024 ($) | | :----------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | | Research and development | 1,084 | 396 | 1,888 | 675 | | General and administrative | 1,756 | 575 | 3,046 | 943 | | **Total** | **2,840** | **971** | **4,934** | **1,618** | - Total stock-based compensation expense increased to **$4.9 million** for the six months ended June 30, 2025, from **$1.6 million** in the prior year[66](index=66&type=chunk) [10. Segment Information](index=21&type=section&id=10.%20Segment%20Information) This note provides a breakdown of the company's net loss and expenses by operational categories Segment Net Loss and Expenses (in thousands) | Category | Three Months Ended June 30, 2025 ($) | Three Months Ended June 30, 2024 ($) | Six Months Ended June 30, 2025 ($) | Six Months Ended June 30, 2024 ($) | | :---------------------------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | | External research and development expenses | 11,291 | 5,485 | 21,269 | 13,204 | | Personnel-related R&D (excl. stock-based comp) | 2,494 | 1,821 | 4,877 | 3,508 | | Facility and IT allocated R&D expenses | 464 | 460 | 904 | 924 | | Personnel-related G&A (excl. stock-based comp) | 2,417 | 1,267 | 4,649 | 2,467 | | General corporate and facility expenses | 1,902 | 876 | 3,845 | 1,971 | | Other segment items | (500) | (1,357) | (994) | (1,675) | | **Net loss** | **18,068** | **8,552** | **34,550** | **20,399** | - External research and development expenses increased significantly, reflecting increased clinical programs and combination development activities[67](index=67&type=chunk) - Personnel-related expenses for both R&D and G&A functions increased due to workforce expansion[67](index=67&type=chunk) [11. Net Loss Per Share](index=22&type=section&id=11.%20Net%20Loss%20Per%20Share) This note explains the calculation of net loss per share and the impact of anti-dilutive securities Shares Excluded from Diluted Net Loss Per Share Calculation | Category | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :----------------------------- | :----------------------------- | :----------------------------- | | Convertible Preferred Stock | — | 27,149,206 | | Options to purchase common stock | 5,974,151 | 3,434,751 | | Unvested restricted common stock | — | 165,301 | | **Total** | **5,974,151** | **30,749,258** | - All convertible preferred stock converted to common stock upon the IPO in 2025, hence no preferred stock was excluded from diluted EPS calculation for the 2025 period[68](index=68&type=chunk) - Options to purchase common stock and unvested restricted common stock were excluded due to their anti-dilutive effect[68](index=68&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=23&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's perspective on financial condition, operations, product candidate progress, liquidity, and future funding needs [Overview](index=23&type=section&id=Overview) This section provides a high-level summary of the company's mission and recent clinical development milestones - Sionna Therapeutics is a clinical-stage biopharmaceutical company developing novel medicines to normalize CFTR protein function for cystic fibrosis patients[71](index=71&type=chunk) - The company announced positive topline data from two Phase 1 clinical trials for lead NBD1 stabilizer product candidates, SION-719 and SION-451, in June 2025[73](index=73&type=chunk) - Both SION-719 and SION-451 were well tolerated, with no serious adverse events, and met exposure thresholds predictive of clinically meaningful benefit in preclinical models[74](index=74&type=chunk) - SION-719 will advance into a Phase 2a proof-of-concept trial in CF patients as an add-on to standard of care, anticipated in H2 2025[75](index=75&type=chunk) - SION-451 will advance to a Phase 1 dual combination trial in healthy volunteers with galicaftor (SION-2222) and SION-109, anticipated in H2 2025[76](index=76&type=chunk) [Strategic In-Licensing & Complementary Modulators](index=24&type=section&id=Strategic%20In-Licensing%20%26%20Complementary%20Modulators) This section describes the company's strategy to expand its product pipeline through in-licensing and complementary modulators - The company in-licensed three clinical-stage compounds from AbbVie Global Enterprises Ltd. in 2024 to expand its portfolio of combination product opportunities[77](index=77&type=chunk) - This includes galicaftor (SION-2222), a complementary modulator targeting CFTR's TMD1, which has completed Phase 2 clinical trials[77](index=77&type=chunk) - A Phase 1 clinical trial for another complementary modulator, SION-109 (targeting CFTR's ICL4 region), was completed in December 2024[77](index=77&type=chunk) [Sources of Liquidity and Financing History](index=24&type=section&id=Sources%20of%20Liquidity%20and%20Financing%20History) This section reviews the company's funding sources, historical capital raises, and future liquidity outlook - Since inception in 2019, the company has not generated revenue and has funded operations primarily through preferred stock sales, raising **$330.4 million**[79](index=79&type=chunk) - In February 2025, the company completed its IPO, raising **$199.6 million** net proceeds from the sale of **12,176,467** common shares[79](index=79&type=chunk) - Net losses were **$34.6 million** and **$20.4 million** for the six months ended June 30, 2025, and 2024, respectively, with an accumulated deficit of **$215.6 million** as of June 30, 2025[80](index=80&type=chunk) - Expenses and operating losses are expected to increase substantially due to advancing clinical development, research, regulatory approvals, manufacturing, intellectual property, personnel, and public company costs[81](index=81&type=chunk) - The company expects to finance operations through equity offerings, debt financings, or strategic arrangements, as it does not have approved products for sale[82](index=82&type=chunk) - As of June 30, 2025, cash, cash equivalents, and marketable securities totaled **$337.3 million**, projected to fund operations into 2028[83](index=83&type=chunk)[85](index=85&type=chunk) [Components of Results of Operations](index=25&type=section&id=Components%20of%20Results%20of%20Operations) This section explains the key revenue and expense categories contributing to the company's financial performance - The company has not generated any revenue to date and does not expect to for several years, if ever, relying on product sales from approved products or collaboration/license agreements in the future[87](index=87&type=chunk) - Research and development expenses include personnel, external costs (CROs, CDMOs, consultants), manufacturing, facility costs, and intellectual property protection[89](index=89&type=chunk)[90](index=90&type=chunk) - R&D expenses are expected to increase substantially as product candidates advance to later stages[91](index=91&type=chunk)[92](index=92&type=chunk) - General and administrative expenses include personnel, legal, professional fees, office, IT, and insurance costs, expected to increase with public company operations and pre-commercial activities[94](index=94&type=chunk)[95](index=95&type=chunk) - Interest income is from cash equivalents and marketable securities, while other income primarily consists of sublease income[97](index=97&type=chunk)[98](index=98&type=chunk)[99](index=99&type=chunk)[100](index=100&type=chunk) [Results of Operations](index=28&type=section&id=Results%20of%20Operations) This section provides a comparative analysis of the company's financial performance over different reporting periods [Comparison of the Three Months Ended June 30, 2025 and 2024](index=28&type=section&id=Comparison%20of%20the%20Three%20Months%20Ended%20June%2030,%202025%20and%202024) This section compares the company's financial performance for the second quarter of 2025 against the same period in 2024 Results of Operations (Three Months Ended June 30, in thousands) | Metric | 2025 ($) | 2024 ($) | Change ($) | | :-------------------------- | :------- | :------- | :--------- | | Research and development | 15,383 | 8,233 | 7,150 | | General and administrative | 6,523 | 3,059 | 3,464 | | **Total operating expenses** | **21,906** | **11,292** | **10,614** | | Loss from operations | (21,906) | (11,292) | (10,614) | | Interest income | 3,667 | 2,566 | 1,101 | | Other income | 171 | 174 | (3) | | **Net loss** | **(18,068)** | **(8,552)** | **(9,516)** | - Net loss increased by **$9.5 million** to **$18.1 million** for Q2 2025, compared to **$8.6 million** for Q2 2024[102](index=102&type=chunk) - Research and development expenses increased by **$7.2 million**, primarily due to increased clinical programs and combination development activities, and a **$1.4 million** increase in personnel-related expenses[103](index=103&type=chunk) - General and administrative expenses increased by **$3.5 million**, driven by a **$2.3 million** increase in personnel-related expenses and a **$1.0 million** increase in professional services fees[104](index=104&type=chunk)[108](index=108&type=chunk) - Interest income increased by **$1.1 million** due to increased investment in debt securities from IPO proceeds[105](index=105&type=chunk) [Comparison of the Six Months Ended June 30, 2025 and 2024](index=29&type=section&id=Comparison%20of%20the%20Six%20Months%20Ended%20June%2030,%202025%20and%202024) This section compares the company's financial performance for the first half of 2025 against the same period in 2024 Results of Operations (Six Months Ended June 30, in thousands) | Metric | 2025 ($) | 2024 ($) | Change ($) | | :-------------------------- | :------- | :------- | :--------- | | Research and development | 29,051 | 18,453 | 10,598 | | General and administrative | 12,514 | 5,986 | 6,528 | | **Total operating expenses** | **41,565** | **24,439** | **17,126** | | Loss from operations | (41,565) | (24,439) | (17,126) | | Interest income | 6,667 | 3,698 | 2,969 | | Other income | 348 | 342 | 6 | | **Net loss** | **(34,550)** | **(20,399)** | **(14,151)** | - Net loss increased by **$14.2 million** to **$34.6 million** for the six months ended June 30, 2025, compared to **$20.4 million** for the same period in 2024[107](index=107&type=chunk) - Research and development expenses increased by **$10.6 million**, primarily due to a **$7.3 million** increase in direct R&D for clinical programs and combination development, and a **$2.6 million** increase in personnel-related expenses[109](index=109&type=chunk)[112](index=112&type=chunk) - General and administrative expenses increased by **$6.5 million**, mainly from a **$4.3 million** increase in personnel-related expenses and a **$2.1 million** increase in professional services fees[110](index=110&type=chunk)[113](index=113&type=chunk) - Interest income increased by **$3.0 million** due to higher investment in debt securities following the IPO[111](index=111&type=chunk) [Liquidity and Capital Resources](index=31&type=section&id=Liquidity%20and%20Capital%20Resources) This section discusses the company's current cash position, cash flow activities, and future funding requirements - As of June 30, 2025, the company had **$337.3 million** in cash, cash equivalents, and marketable securities[116](index=116&type=chunk) - Existing capital is believed to be sufficient to fund operations into 2028, but this is a forward-looking estimate subject to risks[122](index=122&type=chunk) - Net cash used in operating activities was **$34.4 million** for the six months ended June 30, 2025, primarily due to net loss[117](index=117&type=chunk)[118](index=118&type=chunk) - Net cash used in investing activities was **$164.4 million**, mainly from purchases of marketable securities[120](index=120&type=chunk) - Net cash provided by financing activities was **$202.1 million**, primarily from the IPO proceeds[121](index=121&type=chunk) - Future funding requirements depend on clinical trial progress, manufacturing costs, regulatory review, intellectual property, personnel, and commercialization efforts[123](index=123&type=chunk) [Contractual Obligations and Commitments](index=33&type=section&id=Contractual%20Obligations%20and%20Commitments) This section addresses the company's contractual obligations and commitments, noting no material changes - No material changes to contractual obligations and commitments during the six months ended June 30, 2025, as described in the Annual Report[126](index=126&type=chunk) [Critical Accounting Estimates](index=33&type=section&id=Critical%20Accounting%20Estimates) This section discusses the significant judgments and assumptions used in preparing the financial statements - No material changes to critical accounting estimates during the six months ended June 30, 2025, as described in the Annual Report[128](index=128&type=chunk) - The preparation of financial statements requires estimates and assumptions affecting reported amounts, based on historical experience and reasonable factors[127](index=127&type=chunk) [Recent Accounting Pronouncements](index=33&type=section&id=Recent%20Accounting%20Pronouncements) This section refers to disclosures regarding recently issued accounting standards and their potential impact - Information on recently issued accounting pronouncements is disclosed in Note 2, 'Summary of Significant Accounting Policies,' within the consolidated financial statements[129](index=129&type=chunk) [Emerging Growth Company and Smaller Reporting Company Status](index=33&type=section&id=Emerging%20Growth%20Company%20and%20Smaller%20Reporting%20Company%20Status) This section explains the company's status as an emerging growth and smaller reporting company, and associated regulatory benefits - The company qualifies as an 'emerging growth company' and 'smaller reporting company,' allowing it to take advantage of reduced disclosure and governance requirements[130](index=130&type=chunk)[131](index=131&type=chunk) - The company has elected to use the extended transition period for complying with new or revised accounting standards[130](index=130&type=chunk) - Emerging growth company status will be maintained until the earlier of five years post-IPO, **$1.235 billion** in annual gross revenue, becoming a large accelerated filer, or issuing over **$1.0 billion** in non-convertible debt[130](index=130&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=34&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a 'smaller reporting company,' Sionna Therapeutics, Inc. is not required to provide quantitative and qualitative disclosures about market risk under Item 305 of Regulation S-K - The company is exempt from providing quantitative and qualitative disclosures about market risk due to its 'smaller reporting company' status[132](index=132&type=chunk) [Item 4. Controls and Procedures](index=34&type=section&id=Item%204.%20Controls%20and%20Procedures) This section details the company's disclosure controls and procedures and internal control over financial reporting, concluding that disclosure controls were effective as of June 30, 2025, with no material changes in internal control - Management concluded that disclosure controls and procedures were effective at the reasonable assurance level as of June 30, 2025[133](index=133&type=chunk) - No material changes in internal control over financial reporting occurred during the six months ended June 30, 2025[134](index=134&type=chunk) [Part II - Other Information](index=35&type=section&id=Part%20II%20-%20Other%20Information) This section provides additional information not covered in the financial statements, including legal, risk factors, and equity sales [Item 1. Legal Proceedings](index=35&type=section&id=Item%201.%20Legal%20Proceedings) This section states that Sionna Therapeutics, Inc. is not currently involved in any material legal proceedings that could significantly impact its financial position, results of operations, or cash flows as of June 30, 2025, and records liabilities for probable and estimable future losses from legal matters - The company is not aware of any material legal proceedings currently pending or threatened as of June 30, 2025[136](index=136&type=chunk) - Liabilities for legal matters are recorded when probable and reasonably estimable[136](index=136&type=chunk) [Item 1A. Risk Factors](index=35&type=section&id=Item%201A.%20Risk%20Factors) This section comprehensively outlines various risks impacting the business, including financial, development, third-party dependence, intellectual property, regulatory, commercial, operational, and stock ownership factors [Risks Related to Our Limited Operating History, Financial Condition and Need for Additional Capital](index=35&type=section&id=Risks%20Related%20to%20Our%20Limited%20Operating%20History,%20Financial%20Condition%20and%20Need%20for%20Additional%20Capital) This section details risks stemming from the company's limited operational history, significant losses, and ongoing need for substantial capital - The company is a clinical-stage biopharmaceutical company with a limited operating history, incurring significant operating losses since inception (**$34.6 million** net loss for H1 2025, **$215.6 million** accumulated deficit as of June 30, 2025)[138](index=138&type=chunk)[139](index=139&type=chunk) - Substantial additional funding is required to develop and commercialize product candidates, with no guarantee of raising capital on acceptable terms, potentially leading to delays or elimination of development programs[146](index=146&type=chunk)[148](index=148&type=chunk) - Raising additional capital may dilute stockholders' ownership, restrict operations, or require relinquishing rights to product candidates[149](index=149&type=chunk)[150](index=150&type=chunk) [Risks Related to the Discovery and Development of Our Product Candidates](index=38&type=section&id=Risks%20Related%20to%20the%20Discovery%20and%20Development%20of%20Our%20Product%20Candidates) This section outlines risks associated with the R&D of product candidates, including clinical trial failures and regulatory hurdles - The company is substantially dependent on the success of its NBD1 stabilizers (SION-719 and SION-451); failure to advance or obtain regulatory approval would materially harm the business[152](index=152&type=chunk)[153](index=153&type=chunk) - Developing combination treatments increases complexity and risk, including potential drug-drug interactions, unforeseen side effects, or clinical trial failures[161](index=161&type=chunk)[162](index=162&type=chunk) - Regulatory approval processes are lengthy, time-consuming, and unpredictable, with no assurance of obtaining approval for any product candidate[164](index=164&type=chunk) - Preclinical, interim, topline, and preliminary results are not necessarily predictive of later clinical trial outcomes, and positive results may not be replicated[179](index=179&type=chunk)[181](index=181&type=chunk)[182](index=182&type=chunk) - Targeting the NBD1 domain of the CFTR protein is novel, introducing uncertainty regarding successful product development and potential regulatory challenges[185](index=185&type=chunk)[186](index=186&type=chunk) - Clinical trials may fail to demonstrate safety and efficacy, or identify serious adverse side effects, potentially leading to abandonment, delays, or limitations on development[187](index=187&type=chunk) [Risks Related to Our Dependence on Third Parties](index=53&type=section&id=Risks%20Related%20to%20Our%20Dependence%20on%20Third%20Parties) This section addresses risks arising from reliance on third parties for intellectual property, clinical trials, manufacturing, and collaborations - The company is dependent on licensed intellectual property from third parties (e.g., Sanofi, AbbVie); loss of these rights or breach of agreements could prevent development or commercialization[219](index=219&type=chunk)[220](index=220&type=chunk) - Reliance on CROs and other vendors for clinical trials means limited control over their performance, potentially leading to delays or compromised data quality[224](index=224&type=chunk)[225](index=225&type=chunk) - Reliance on CDMOs for manufacturing increases the risk of insufficient quantities, unacceptable cost/quality, or supply disruptions, potentially delaying development or commercialization[228](index=228&type=chunk)[229](index=229&type=chunk) - Establishing collaborations for development or commercialization is challenging; failure to secure favorable terms or unsuccessful arrangements could alter development plans[233](index=233&type=chunk)[234](index=234&type=chunk)[235](index=235&type=chunk) [Risks Related to Our Intellectual Property](index=58&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) This section covers risks concerning the company's ability to obtain, maintain, enforce, and protect its intellectual property rights - Inability to obtain, maintain, and enforce intellectual property rights (patents, trade secrets) could allow competitors to commercialize similar products, adversely affecting commercialization efforts[239](index=239&type=chunk)[240](index=240&type=chunk)[241](index=241&type=chunk) - Patent terms may be inadequate to protect competitive position, and failure to obtain patent term extensions could shorten exclusivity and reduce revenue[250](index=250&type=chunk)[251](index=251&type=chunk)[252](index=252&type=chunk) - Failure to comply with obligations in third-party intellectual property licenses could result in loss of material rights, impacting development and commercialization[253](index=253&type=chunk)[255](index=255&type=chunk) - Patent reform legislation (e.g., Leahy-Smith Act) and changes in patent laws could increase uncertainties and costs for patent prosecution and enforcement[260](index=260&type=chunk)[261](index=261&type=chunk)[262](index=262&type=chunk) - Involvement in lawsuits to protect or enforce patents could be expensive, time-consuming, and unsuccessful, potentially leading to invalidation of patents or licensing requirements[263](index=263&type=chunk)[264](index=264&type=chunk)[265](index=265&type=chunk) - Third parties may allege infringement of their intellectual property rights, leading to litigation, substantial damages, or the need to obtain costly licenses[267](index=267&type=chunk)[268](index=268&type=chunk) - Reliance on third parties necessitates sharing trade secrets, increasing the risk of misappropriation or unauthorized disclosure, which could harm competitive position[273](index=273&type=chunk)[275](index=275&type=chunk) - Limited geographical patent protection and varying enforceability of intellectual property rights in different countries could hinder global commercialization efforts[277](index=277&type=chunk)[278](index=278&type=chunk)[279](index=279&type=chunk) [Risks Related to Legal and Regulatory Compliance Matters](index=69&type=section&id=Risks%20Related%20to%20Legal%20and%20Regulatory%20Compliance%20Matters) This section details risks associated with healthcare laws, regulatory oversight, reform initiatives, and potential misconduct - Business operations are subject to extensive healthcare laws (e.g., fraud and abuse laws); non-compliance could lead to substantial penalties, reputational harm, and significant defense costs[303](index=303&type=chunk)[304](index=304&type=chunk)[307](index=307&type=chunk) - Approved products remain subject to ongoing regulatory oversight, including manufacturing, labeling, promotion, and post-marketing requirements; failure to comply could result in restrictions or withdrawal from the market[308](index=308&type=chunk)[309](index=309&type=chunk)[311](index=311&type=chunk) - Healthcare reform initiatives in the U.S. and foreign jurisdictions could adversely impact business, leading to more rigorous coverage criteria, downward pressure on pricing, or other negative consequences[313](index=313&type=chunk)[314](index=314&type=chunk)[318](index=318&type=chunk) - Inadequate funding or disruptions at government agencies (FDA, SEC) could delay product development, regulatory approvals, or normal business functions[344](index=344&type=chunk)[345](index=345&type=chunk) - Misconduct by employees, contractors, or collaborators, including non-compliance with regulatory standards or healthcare laws, could lead to significant penalties and reputational damage[346](index=346&type=chunk)[348](index=348&type=chunk) [Risks Related to the Commercialization of Our Product Candidates](index=72&type=section&id=Risks%20Related%20to%20the%20Commercialization%20of%20Our%20Product%20Candidates) This section addresses risks concerning market competition, product acceptance, reimbursement, market size, and product liability - The company faces substantial competition, particularly from Vertex Pharmaceuticals, which holds significant market share and greater resources in the CF market[321](index=321&type=chunk)[324](index=324&type=chunk) - Even if approved, product candidates may fail to achieve sufficient market acceptance by physicians, patients, and third-party payors, especially against established standard-of-care therapies like Trikafta[326](index=326&type=chunk)[327](index=327&type=chunk) - Commercial success depends significantly on obtaining and maintaining coverage and adequate reimbursement from third-party payors; cost containment trends could adversely affect profitability[329](index=329&type=chunk)[330](index=330&type=chunk) - Estimates of the potential market for product candidates may be smaller than anticipated, limiting revenues and hindering profitability[333](index=333&type=chunk) - Clinical trial and product liability lawsuits could divert resources, incur substantial liabilities, and limit commercialization, with insurance potentially inadequate to cover all costs[334](index=334&type=chunk)[335](index=335&type=chunk) [Risks Related to Our Business Operations, Employee Matters and Managing Our Growth](index=76&type=section&id=Risks%20Related%20to%20Our%20Business%20Operations,%20Employee%20Matters%20and%20Managing%20Our%20Growth) This section covers risks related to personnel retention, managing organizational growth, potential litigation, and business disruptions - Future success depends on retaining key executives and attracting/retaining qualified personnel; loss of key individuals could impede objectives[337](index=337&type=chunk)[338](index=338&type=chunk) - Expected expansion in clinical development, regulatory, and commercial capabilities may lead to difficulties in managing growth, disrupting operations and increasing costs[340](index=340&type=chunk) - The company could be affected by litigation, government investigations, and enforcement actions, leading to significant damages, fines, reputational harm, and diversion of resources[341](index=341&type=chunk)[343](index=343&type=chunk) - Business disruptions (e.g., natural disasters, cybersecurity incidents) affecting operations or those of suppliers/CROs could harm revenue, financial condition, and increase costs[354](index=354&type=chunk) [Risks Related to Ownership of Our Common Stock](index=79&type=section&id=Risks%20Related%20to%20Ownership%20of%20Our%20Common%20Stock) This section addresses risks concerning stock price volatility, potential dilution, corporate governance, and dividend policy - Operating results may fluctuate significantly due to various factors (e.g., clinical trial outcomes, competition, regulatory changes), making future results difficult to predict and potentially causing stock price decline[355](index=355&type=chunk)[356](index=356&type=chunk)[357](index=357&type=chunk) - The trading price of common stock may be highly volatile due to industry-specific and general market factors, leading to potential loss of investment[358](index=358&type=chunk)[359](index=359&type=chunk) - Sales of a substantial number of common stock shares by stockholders (e.g., after lock-up expiry) could significantly drop the market price[366](index=366&type=chunk) - Provisions in corporate charter documents and Delaware law may prevent or frustrate attempts to change management or acquire a controlling interest, potentially lowering stock price[367](index=367&type=chunk)[368](index=368&type=chunk)[369](index=369&type=chunk) - Executive officers, directors, and principal stockholders own a significant percentage of stock, allowing them to exert substantial control over stockholder-approved matters[370](index=370&type=chunk) - The company does not anticipate paying cash dividends in the foreseeable future, making capital appreciation the sole source of gain for stockholders[372](index=372&type=chunk) [General Risk Factors](index=84&type=section&id=General%20Risk%20Factors) This section covers broad risks including cybersecurity, data privacy, compliance, internal controls, tax laws, and global economic conditions - Compromised information technology systems or data, or those of third parties, could lead to regulatory actions, litigation, fines, business disruptions, and reputational harm[375](index=375&type=chunk)[376](index=376&type=chunk)[386](index=386&type=chunk) - The company is subject to stringent and evolving data privacy and security laws (e.g., GDPR, HIPAA); non-compliance could result in investigations, fines, litigation, and operational disruptions[389](index=389&type=chunk)[390](index=390&type=chunk)[392](index=392&type=chunk)[397](index=397&type=chunk) - Compliance with governmental export/import controls, economic sanctions, and anti-corruption laws is required; violations could lead to criminal liability and severe consequences[399](index=399&type=chunk)[400](index=400&type=chunk) - Failure to maintain an effective system of internal controls over financial reporting could impair the ability to produce accurate financial statements, leading to stock price decline and sanctions[401](index=401&type=chunk)[404](index=404&type=chunk) - The company may not be able to utilize a significant portion of its net operating loss (NOL) carryforwards due to limitations under Section 382 of the IRC or future regulatory changes[406](index=406&type=chunk)[407](index=407&type=chunk) - New or changed tax laws (e.g., OBBBA) could materially adversely affect business, cash flows, financial condition, or results of operations[408](index=408&type=chunk)[409](index=409&type=chunk)[410](index=410&type=chunk) - Unstable global economic and geopolitical conditions (e.g., inflation, conflicts, tariffs) could adversely affect business, financial condition, stock price, and ability to raise capital[418](index=418&type=chunk)[419](index=419&type=chunk)[420](index=420&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=92&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) This section reports on the company's initial public offering (IPO) completed on February 6, 2025, detailing the shares issued, net proceeds, and the current use of these funds - On February 6, 2025, the company completed its IPO, issuing and selling **12,176,467** shares of common stock at **$18.00** per share[422](index=422&type=chunk) - The IPO generated aggregate net proceeds of **$199.6 million**, after deducting underwriter discounts, commissions, and other offering expenses[422](index=422&type=chunk) - A significant portion of the net proceeds is held in money market funds, with no material change in the planned use of proceeds[423](index=423&type=chunk) [Item 3. Defaults Upon Senior Securities](index=92&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This section states that there were no defaults upon senior securities during the reporting period - No defaults upon senior securities were reported[425](index=425&type=chunk) [Item 4. Mine Safety Disclosures](index=92&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to Sionna Therapeutics, Inc - This item is not applicable[426](index=426&type=chunk) [Item 5. Other Information](index=92&type=section&id=Item%205.%20Other%20Information) This section discloses Rule 10b5-1 trading arrangements adopted by the company's executive officers during the three months ended June 30, 2025, specifying plans for common stock sales with expiration dates in 2026 Rule 10b5-1 Trading Arrangements Adopted by Executive Officers (Three Months Ended June 30, 2025) | Name (Title) | Action Taken (Date of Action) | Type of Trading Arrangement | Nature of Trading Arrangement | Expiration Date of Trading Arrangement | Aggregate Number of Securities | | :--------------------------------------- | :---------------------------- | :-------------------------- | :---------------------------- | :------------------------------------- | :----------------------------- | | Michael Cloonan (President and CEO) | Adoption (May 21, 2025) | Rule 10b5-1 trading arrangement | Sale | August 17, 2026 | Up to 200,000 | | Elena Ridloff (CFO and Head of Corporate Development) | Adoption (May 20, 2025) | Rule 10b5-1 trading arrangement | Sale | August 6, 2026 | Up to 85,000 | | Jennifer Fitzpatrick (Chief Legal Officer) | Adoption (June 5, 2025) | Rule 10b5-1 trading arrangement | Sale | September 15, 2026 | Up to 41,000 | [Item 6. Exhibits](index=94&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including corporate charter documents, stock certificates, officer certifications, and Inline XBRL documents - Exhibit 3.1: Fifth Amended and Restated Certificate of Incorporation[430](index=430&type=chunk) - Exhibit 3.2: Amended and Restated Bylaws[430](index=430&type=chunk) - Exhibit 4.1: Specimen Common Stock Certificate[430](index=430&type=chunk) - Exhibit 31.1*: Certification of Principal Executive Officer (Section 302)[430](index=430&type=chunk) - Exhibit 31.2*: Certification of Principal Financial Officer (Section 302)[430](index=430&type=chunk) - Exhibit 32.1*+: Certification of Principal Executive Officer and Principal Financial Officer (Section 906)[430](index=430&type=chunk) - Exhibit 101.INS: Inline XBRL Instance Document[430](index=430&type=chunk) - Exhibit 101.SCH: Inline XBRL Taxonomy Extension Schema With Embedded Linkbase Documents[430](index=430&type=chunk) - Exhibit 104: Cover Page Interactive Data File[430](index=430&type=chunk) [Signatures](index=95&type=section&id=SIGNATURES) This section contains the authorized signatures confirming the submission of the Form 10-Q report [Authorized Signatures](index=95&type=section&id=Authorized%20Signatures) This section contains the authorized signatures for the Form 10-Q report, confirming its submission on behalf of Sionna Therapeutics, Inc. by its President and Chief Executive Officer, Michael Cloonan, and its Chief Financial Officer and Head of Corporate Development, Elena Ridloff, both dated August 11, 2025 - The report is signed by Michael Cloonan, President and Chief Executive Officer (Principal Executive Officer), and Elena Ridloff, Chief Financial Officer and Head of Corporate Development (Principal Financial Officer and Principal Accounting Officer)[436](index=436&type=chunk) - The signing date for the report is August 11, 2025[436](index=436&type=chunk)

[Executive Summary](index=1&type=section&id=Executive%20Summary) [Key Highlights](index=1&type=section&id=Key%20Highlights) Sionna Therapeutics reported positive Phase 1 data for NBD1 stabilizers, is advancing to Phase 2a and dual combination trials in H2 2025, and holds $337.3 million in cash to fund operations into 2028 - Positive Phase 1 data for SION-719 and SION-451 demonstrated both **NBD1 stabilizers were generally well tolerated and exceeded pharmacokinetic targets**[1](index=1&type=chunk) - Initiation of Phase 2a proof-of-concept trial of SION-719 and advancement of Phase 1 healthy volunteer trial of SION-451 in two proprietary dual combinations are **on track for the second half of 2025, with topline data expected in mid-2026**[1](index=1&type=chunk) Cash Position and Funding Outlook | Metric | Amount (Millions) | | :----- | :---------------- | | Cash, cash equivalents, and marketable securities (as of June 30, 2025) | $337.3 | | Expected to fund operations | Into 2028 | [Business Update](index=1&type=section&id=Business%20Update) [CEO Commentary](index=1&type=section&id=CEO%20Commentary) CEO Mike Cloonan expressed satisfaction with positive Phase 1 data for SION-719 and SION-451, reinforcing confidence in advancing NBD1 stabilizers to Phase 2a and dual combination trials this year with mid-2026 topline results - CEO Mike Cloonan expressed pleasure with progress, citing **encouraging tolerability and PK data from Phase 1 trials of SION-719 and SION-451**[2](index=2&type=chunk) - Confidence in advancing both NBD1 stabilizers into next development stages, with **Phase 2a SION-719 and Phase 1 SION-451 dual combination trials planned for initiation this year and topline results in mid-2026**[2](index=2&type=chunk) [Pipeline Updates](index=1&type=section&id=Pipeline%20Updates) Sionna provided updates on NBD1 stabilizers SION-719 and SION-451, including positive Phase 1 results, plans for Phase 2a and Phase 1 dual combination trials, and preclinical data showing full F508del-CFTR correction with dual combinations [NBD1 Stabilizers (SION-719 & SION-451)](index=1&type=section&id=NBD1%20Stabilizers%20(SION-719%20%26%20SION-451)) Positive Phase 1 results for SION-719 and SION-451, announced in June 2025, demonstrated general tolerability and exceeded target exposure levels in healthy volunteers, suggesting potential for clinically meaningful benefit as add-on or dual combination therapies - Positive Phase 1 data for SION-719 and SION-451 announced in June 2025, demonstrating **general tolerability and exceeding target exposure levels in over 200 healthy volunteers**[3](index=3&type=chunk) - Data reinforces Sionna's decision to progress SION-719 and SION-451, believing they have the **potential for clinically meaningful benefit as add-on therapies or in proprietary dual combinations**[3](index=3&type=chunk) [Phase 2a Proof-of-Concept Trial with SION-719](index=1&type=section&id=Phase%202a%20Proof-of-Concept%20Trial%20with%20SION-719) Sionna is on track to initiate a Phase 2a proof-of-concept trial for SION-719 in H2 2025, with topline data anticipated in mid-2026, following completion of a midazolam drug-drug interaction study - Phase 2a proof-of-concept trial for SION-719 as an add-on to standard of care in CF patients is **on track for H2 2025, with topline data expected in mid-2026**[3](index=3&type=chunk) - The trial aims to demonstrate the **unique mechanism of NBD1 stabilization and potential to improve CFTR function beyond current SOC**, as defined by sweat chloride[3](index=3&type=chunk) - Midazolam drug-drug interaction study for SION-719 initiated and **on track for completion prior to Phase 2a trial**[4](index=4&type=chunk) [Phase 1 Dual Combination Trial with SION-451 and Complementary Modulators](index=2&type=section&id=Phase%201%20Dual%20Combination%20Trial%20with%20SION-451%20and%20Complementary%20Modulators) Sionna plans to advance a Phase 1 healthy volunteer trial for SION-451 in dual combination with SION-2222 and SION-109 in H2 2025, with topline data expected in mid-2026 - Phase 1 healthy volunteer trial evaluating SION-451 in combination with SION-2222 (TMD1-directed CFTR corrector) and SION-109 (ICL4-directed CFTR corrector) is **on track for H2 2025**[9](index=9&type=chunk) - Topline data from the SION-451 dual combination trial is **anticipated in mid-2026**[9](index=9&type=chunk) [Preclinical Data Presented at 48th European Cystic Fibrosis Conference](index=2&type=section&id=Preclinical%20Data%20Presented%20at%2048th%20European%20Cystic%20Fibrosis%20Conference) Sionna presented preclinical data at the 48th ECFS Annual Conference in June 2025, demonstrating full correction of F508del-CFTR in CF models using NBD1 stabilizers in dual combinations with complementary modulators - Preclinical data presented at 48th ECFS Annual Conference in June 2025 demonstrated **full correction of F508del-CFTR in CF models using Sionna's NBD1 stabilizers in dual combinations with proprietary complementary modulators**[9](index=9&type=chunk) - These findings highlight the **strong mechanistic rationale and synergy of Sionna's dual combination approach to restoring CFTR function**[9](index=9&type=chunk) [Financial Results](index=2&type=section&id=Financial%20Results) [Second Quarter 2025 Financial Performance](index=2&type=section&id=Financial%20Results%20for%20the%20Quarter%20Ended%20June%2030,%202025) Sionna Therapeutics reported increased Q2 2025 operating expenses, driven by higher R&D and G&A costs, resulting in a widened net loss of $18.1 million compared to $8.6 million in Q2 2024 [Research and Development Expenses](index=2&type=section&id=Research%20and%20Development%20Expenses) Research and development expenses significantly increased to $15.4 million in Q2 2025 from $8.2 million in Q2 2024, primarily due to direct program spend supporting Sionna's clinical pipeline Research and Development Expenses (QoQ) | Period | 2025 Q2 (in thousands) | 2024 Q2 (in thousands) | Change (YoY) | | :----- | :--------------------- | :--------------------- | :----------- | | R&D Expenses | $15,383 | $8,233 | +86.8% | - Increase mainly driven by **direct program spend to support Sionna's clinical pipeline**[5](index=5&type=chunk) [General and Administrative Expenses](index=2&type=section&id=General%20and%20Administrative%20Expenses) General and administrative expenses rose to $6.5 million in Q2 2025 from $3.1 million in Q2 2024, primarily due to personnel-related costs and professional fees General and Administrative Expenses (QoQ) | Period | 2025 Q2 (in thousands) | 2024 Q2 (in thousands) | Change (YoY) | | :----- | :--------------------- | :--------------------- | :----------- | | G&A Expenses | $6,523 | $3,059 | +113.2% | - Increase primarily due to **personnel-related costs, including stock-based compensation, and professional fees**[6](index=6&type=chunk) [Net Loss](index=2&type=section&id=Net%20Loss) The net loss for Q2 2025 was $18.1 million, significantly higher than the $8.6 million net loss in Q2 2024, reflecting increased operating expenses Net Loss (QoQ) | Period | 2025 Q2 (in thousands) | 2024 Q2 (in thousands) | Change (YoY) | | :----- | :--------------------- | :--------------------- | :----------- | | Net Loss | $(18,068) | $(8,552) | +111.3% | [Cash Position and Outlook](index=2&type=section&id=Cash%20and%20Cash%20Equivalents) As of June 30, 2025, Sionna held $337.3 million in cash, cash equivalents, and marketable securities, anticipated to fund operations into 2028 Cash Position and Funding Outlook | Metric | Amount (Millions) | Funding Outlook | | :----- | :---------------- | :-------------- | | Cash, cash equivalents, and marketable securities (as of June 30, 2025) | $337.3 | Into 2028 | [Company Overview](index=2&type=section&id=Company%20Overview) [About Sionna Therapeutics](index=2&type=section&id=About%20Sionna%20Therapeutics_detail) Sionna Therapeutics is a clinical-stage biopharmaceutical company focused on revolutionizing cystic fibrosis treatment by developing novel medicines that normalize CFTR protein function through NBD1 stabilization and complementary modulators - Sionna Therapeutics is a clinical-stage biopharmaceutical company focused on **normalizing CFTR protein function to revolutionize cystic fibrosis treatment**[8](index=8&type=chunk) - The company's goal is to **restore CFTR function by directly stabilizing its NBD1 domain and developing complementary CFTR modulators to work synergistically**[8](index=8&type=chunk) - Leveraging over a decade of NBD1 research, Sionna is **advancing small molecules engineered to correct defects caused by the F508del genetic mutation**[8](index=8&type=chunk) [Additional Information](index=2&type=section&id=Additional%20Information) [Investor Relations and Disclosure](index=2&type=section&id=Investor%20Relations%20and%20Disclosure) Sionna intends to use its Investor Relations website for disclosing material nonpublic information and fulfilling Regulation FD obligations, advising investors to monitor it alongside other public communications - Sionna intends to use its **Investor Relations website for disclosing material nonpublic information and complying with Regulation FD**[9](index=9&type=chunk)[10](index=10&type=chunk) - Investors should **monitor the Investor Relations website in addition to press releases, SEC filings, public conference calls, presentations, and webcasts**[10](index=10&type=chunk) [Cautionary Note Regarding Forward-Looking Statements](index=3&type=section&id=Cautionary%20Note%20Regarding%20Forward-Looking%20Statements) This section highlights forward-looking statements subject to risks and uncertainties regarding clinical trial timing, results, safety, efficacy, and financial projections, advising that actual results may differ materially and disclaiming any obligation to update these statements except as required by law - The press release contains **forward-looking statements regarding Sionna's goals, R&D programs, clinical trials (initiation, timing, results), product candidate safety/efficacy, preclinical study predictability, and financial projections**[11](index=11&type=chunk) - These statements are subject to **risks and uncertainties inherent in product development, regulatory developments, and economic conditions, which may cause actual results to differ materially**[11](index=11&type=chunk) - Sionna explicitly **disclaims any obligation to update forward-looking statements except as required by law**[11](index=11&type=chunk) [Media and Investor Contacts](index=3&type=section&id=Media%20Contact) Contact information for media inquiries (Adam Daley, CG Life) and investor relations (Juliet Labadorf) is provided - Media contact: **Adam Daley, CG Life (adaley@cglife.com, 212.253.8881)**[12](index=12&type=chunk) - Investor contact: **Juliet Labadorf (ir@sionnatx.com)**[12](index=12&type=chunk) [Consolidated Financial Statements](index=4&type=section&id=Consolidated%20Financial%20Statements) [Consolidated Statements of Operations](index=4&type=section&id=Consolidated%20Statements%20of%20Operations) The Consolidated Statements of Operations show a significant increase in operating expenses and net loss for both the three and six months ended June 30, 2025, compared to 2024, primarily driven by research and development and general and administrative expenses Consolidated Statements of Operations (Selected Data, in thousands) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :---------------------------------- | :------------------------------- | :------------------------------- | :------------------------------- | :------------------------------- | | Research and development | $15,383 | $8,233 | $29,051 | $18,453 | | General and administrative | $6,523 | $3,059 | $12,514 | $5,986 | | Total operating expenses | $21,906 | $11,292 | $41,565 | $24,439 | | Loss from operations | $(21,906) | $(11,292) | $(41,565) | $(24,439) | | Interest income | $3,667 | $2,566 | $6,667 | $3,698 | | Net loss | $(18,068) | $(8,552) | $(34,550) | $(20,399) | | Net loss per share, basic and diluted | $(0.41) | $(2.71) | $(0.98) | $(6.54) | | Weighted-average common shares outstanding | 44,116,997 | 3,159,815 | 35,404,928 | 3,121,225 | [Selected Consolidated Balance Sheet Data](index=5&type=section&id=Selected%20Consolidated%20Balance%20Sheet%20Data) Sionna's balance sheet data as of June 30, 2025, shows a significant increase in cash, cash equivalents, and marketable securities to $337.3 million from $168.0 million, with total assets and stockholders' equity also increasing substantially Selected Consolidated Balance Sheet Data (in thousands) | Metric | June 30, 2025 | December 31, 2024 | Change | | :---------------------------------- | :-------------- | :---------------- | :----- | | Cash, cash equivalents, and marketable securities | $337,270 | $168,043 | +$169,227 | | Working capital | $259,196 | $140,573 | +$118,623 | | Total assets | $352,048 | $185,752 | +$166,296 | | Total stockholders' equity (deficit) | $336,429 | $(163,713) | +$500,142 | - Working capital is defined as **current assets minus current liabilities**[16](index=16&type=chunk)

Core Insights - Sionna Therapeutics announced positive Phase 1 data for its first-in-class NBD1 stabilizers, SION-719 and SION-451, which were well tolerated and exceeded pharmacokinetic targets [1][2][3] - The company is on track to initiate a Phase 2a proof-of-concept trial for SION-719 in cystic fibrosis patients in the second half of 2025, with topline data expected in mid-2026 [1][3] - Sionna maintains a strong cash position of approximately $337.3 million, which is expected to fund operations into 2028 [1][6] Pipeline Updates - Positive Phase 1 results for SION-719 and SION-451 were reported, with over 200 healthy volunteers participating in trials that evaluated safety, tolerability, and pharmacokinetics [3] - The Phase 2a trial for SION-719 aims to demonstrate its potential as an add-on therapy to standard of care in cystic fibrosis, with a focus on improving CFTR function [3] - A Phase 1 trial for SION-451 in dual combinations with other CFTR modulators is also set to begin in the second half of 2025, with topline data anticipated in mid-2026 [1][3] Financial Results - Research and development expenses for Q2 2025 were $15.4 million, up from $8.2 million in Q2 2024, primarily due to increased spending on clinical programs [4] - General and administrative expenses rose to $6.5 million in Q2 2025 from $3.1 million in Q2 2024, attributed to personnel-related costs and professional fees [5] - The net loss for Q2 2025 was $18.1 million, compared to a net loss of $8.6 million in Q2 2024 [5][12]

Financial Data and Key Metrics Changes - The company raised $219 million from its IPO in February 2025, providing significant financial flexibility and a cash runway extending into 2028 [54][55] - The market for cystic fibrosis treatments is currently valued at $11 billion and is projected to grow to $15 billion in the near term [53] Business Line Data and Key Metrics Changes - The company has concluded Phase I trials for both CYON719 and CYON451R2, reporting positive data indicating both compounds were well tolerated and exceeded pharmacokinetic (PK) targets [8][9] - CYON719 will advance into Phase IIa as an add-on to standard care, while CYON451 will be used in a dual combination study [11][12] Market Data and Key Metrics Changes - The company aims to drive incremental clinical benefits above the standard of care, specifically targeting a 10 millimole improvement in sweat chloride levels compared to Trikafta [27][40] - The company is focused on stabilizing the NBD1 region of the CFTR protein, which is critical for correcting cystic fibrosis [18][22] Company Strategy and Development Direction - The company's mission is to transform the standard of care in cystic fibrosis through differentiated NBD1 stabilizers [5][6] - The strategy includes a dual combination approach with NPD-one as the anchor, aiming to achieve fully normal CFTR function for more patients [7][21] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of NPD-one to deliver clinically meaningful benefits, emphasizing the need for further data to guide future decisions [44][52] - The company is optimistic about the upcoming Phase IIa data and its implications for both the add-on and dual combination strategies [42][45] Other Important Information - The company has prioritized two complementary mechanisms, Cyon2222 and Cyon109, for future studies based on their favorable profiles [46][48] - The company plans to conduct a drug-drug interaction (DDI) study to ensure that the addition of CYON719 does not affect the components of Trikafta [34][36] Q&A Session Summary Question: Can you provide an overview of Ciona's story and strategy? - Ciona was formed as a spinout from Sanofi in late 2019, with a mission to transform cystic fibrosis care through innovative therapies [3][4] Question: What are the key milestones for the company in the next 12-18 months? - Key milestones include the initiation of Phase IIa for CYON719 and a healthy volunteer study for CYON451, both expected to yield data by mid-2026 [14][16] Question: How does the company plan to ensure the efficacy of its treatments? - The company aims for a 10 millimole improvement in sweat chloride levels, which has been shown to correlate with meaningful improvements in FEV1 [27][40] Question: What is the rationale behind the dual combination strategy? - The dual combination strategy is expected to provide a differentiated treatment option that could lead to fully normal CFTR function, addressing the limitations of current therapies [21][52] Question: How does the company view the commercial opportunity in the cystic fibrosis market? - The company believes that its dual combination approach could become the new standard of care, with significant commercial potential given the size of the market [52][53]

Core Insights - Sionna Therapeutics is focused on developing novel medicines to normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, aiming to revolutionize the treatment paradigm for cystic fibrosis (CF) [1][4] Company Overview - Sionna Therapeutics is a clinical-stage biopharmaceutical company dedicated to creating therapies that restore CFTR function, particularly targeting the nucleotide-binding domain 1 (NBD1) [4] - The company has a pipeline of small molecules designed to correct defects caused by the F508del genetic mutation, which is prevalent in CF patients [4] Research and Development - Sionna has developed NBD1 stabilizers, SION-719 and SION-451, which have shown the ability to increase the stability of isolated ΔF508-NBD1 by 16°C, surpassing wild-type NBD1 levels [5] - Preclinical data indicate that SION-719 and SION-451 can correct F508del-CFTR maturation to wild-type levels when combined with other modulators, SION-2222 and SION-109 [5] - The company plans to advance SION-719 into a Phase 2a proof-of-concept trial and SION-451 into a Phase 1 trial, both expected to start in the second half of 2025 [3] Conference Presentation - Sionna presented preclinical data at the 48th European Cystic Fibrosis Conference, showcasing the effectiveness of dual combinations of NBD1 stabilizers with proprietary modulators [1][3]

Sionna Therapeutics Overview - Sionna's approach to stabilizing NBD1 has the potential to revolutionize CF treatment, addressing the unmet need for >66% of patients who lack normal CFTR function[7] - The CFTR modulator market is currently >$11 billion and is projected to reach $15 billion by 2029[7] - Sionna has a robust clinical-stage pipeline of NBD1 stabilizers and complementary modulators, offering multiple paths to transform CF patient care[7] Phase 1 Clinical Trial Results - Both NBD1 stabilizers, SION-719 and SION-451, exceeded desired PK targets and were generally well-tolerated in Phase 1 trials[13] - SION-719 is advancing to a Phase 2a proof-of-concept trial as an add-on to standard of care (SOC), based on its high potency at low doses[13] - SION-451 is advancing as an anchor in proprietary dual combinations, based on higher exposure achieved[13] Clinical Development Strategy - A Phase 2a proof-of-concept trial for SION-719 in CF patients is planned for the second half of 2025[14] - A Phase 1 healthy volunteer dual combination trial for SION-451 is also planned for the second half of 2025[14] - Sionna's cash runway extends into 2028, supporting the execution of its clinical development plans[14, 61] Market Opportunity - Approximately 106,000 patients worldwide have CF, with ~90% having at least one F508del-CFTR mutation[55] - >66% of patients on SOC do not have normal CFTR function, highlighting the significant unmet need[55, 59]

Summary of Ciona Therapeutics Conference Call Company Overview - **Company**: Ciona Therapeutics - **Focus**: Development of novel therapies for cystic fibrosis (CF) targeting CFTR function Key Industry Insights - **Cystic Fibrosis Market**: - Current market size exceeds $11 billion and is expected to grow - Approximately two-thirds of CF patients do not achieve normal CFTR function despite existing treatments [6][34] - The most common mutation, F508L, affects about 90% of CF patients [9] Core Points and Arguments - **Phase I Data**: - Positive results for compounds CYON-seven 19 and CYON-four 51, indicating potential for significant clinical benefits [4][11] - Both compounds exceeded pharmacokinetic targets and demonstrated favorable tolerability profiles [11][20] - **Targeting NDD1**: - NDD1 is identified as a key target for normalizing CFTR function, which has been historically considered undruggable [6][7] - Ciona aims to provide a unique and clinically meaningful option for CF patients by stabilizing NDD1 [5][10] - **Clinical Strategy**: - Plans to advance CYON-seven 19 into a Phase 2a trial as an add-on to standard care (Trikafta) [12][28] - CYON-four 51 will be evaluated in a dual combination trial with complementary modulators [12][32] - Both trials are expected to initiate in the second half of 2025, with data anticipated by mid-2026 [14][28] - **Clinical Assays**: - The CF human bronchial epithelial (CFHBE) assay is critical for predicting clinical outcomes and guiding development [21][22] - Data from the CFHBE assay indicates that both compounds are positioned to deliver meaningful clinical benefits [23][27] Additional Important Information - **Safety and Tolerability**: - No serious adverse events reported in Phase I trials for both compounds, supporting their advancement to further studies [20][26] - Mild to moderate treatment-emergent adverse events were observed, with no dose-limiting toxicities [20][26] - **Market Opportunity**: - Ciona is focused on the unmet needs of CF patients, particularly those with the F508del mutation, and aims to improve CFTR function significantly [34][36] - The company is well-funded through 2028, allowing for the execution of its clinical goals [36] - **Strategic Optionality**: - The decision to pursue both add-on and dual combination strategies provides flexibility in development paths [59][60] - The company emphasizes a data-driven approach to determine the best path forward based on clinical outcomes [60] Conclusion - Ciona Therapeutics is positioned to potentially transform the treatment landscape for cystic fibrosis with its innovative approach targeting CFTR function through NDD1 stabilization. The promising Phase I data and strategic clinical plans highlight the company's commitment to addressing significant unmet needs in the CF patient population.

Core Insights - Sionna Therapeutics announced positive Phase 1 clinical trial results for SION-719 and SION-451, which are first-in-class NBD1 stabilizers aimed at treating cystic fibrosis (CF) [2][3] - Both compounds were well tolerated in trials, achieving pharmacokinetic targets that suggest potential clinical benefits for CF patients [4][5][6] - The company plans to advance SION-719 to a Phase 2a proof-of-concept trial and SION-451 to a Phase 1 dual combination trial, with both trials expected to start in the second half of 2025 and topline data anticipated in mid-2026 [8][9] Company Development Plans - Sionna plans to initiate a Phase 2a trial for SION-719 as an add-on to standard of care in CF patients, focusing on improving CFTR function and demonstrating its unique mechanism [8] - SION-451 will enter a Phase 1 trial evaluating its combination with other CFTR modulators, aiming to inform future Phase 2b trials [9] Clinical Trial Details - The Phase 1 trials were randomized, double-blind, and placebo-controlled, involving 100 subjects for SION-719 and 110 subjects for SION-451 [4] - No serious adverse events were reported, and most treatment-emergent adverse events were mild to moderate [5] Market Context - The development of NBD1 stabilizers addresses a significant unmet need in CF treatment, as many patients on existing therapies do not achieve normal CFTR function [7] - Sionna's approach aims to restore CFTR function, potentially improving clinical outcomes and quality of life for CF patients [11]

Company Overview - Sionna Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing novel medicines to normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein [3] - The company's mission is to revolutionize the treatment paradigm for cystic fibrosis (CF) by delivering differentiated medicines that restore CFTR function as close to normal as possible [3] - Sionna is advancing a pipeline of small molecules engineered to correct defects caused by the F508del genetic mutation, which is located in the nucleotide-binding domain 1 (NBD1) of the CFTR protein [3] Upcoming Events - Management will participate in a fireside chat at the Goldman Sachs 46th Annual Healthcare Conference in Miami, Florida on June 11, 2025, at 8:00 a.m. ET [1] - A live webcast of the presentation will be available on the "Events" page within the Investors section of Sionna's website, with a replay accessible after the event [2] Investor Relations - Sionna intends to use its Investor Relations website to disclose material nonpublic information and comply with disclosure obligations under Regulation FD [4] - Investors are encouraged to monitor the company's Investor Relations website, press releases, SEC filings, public conference calls, presentations, and webcasts for updates [4]

Core Insights - Sionna Therapeutics is focused on developing novel medicines to treat cystic fibrosis (CF) by normalizing the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein [1][3] - The company will present preclinical data on its NBD1 stabilizers, SION-451 and SION-719, in combination with CFTR modulators, galicaftor (SION-2222) and SION-109, at the European Cystic Fibrosis Conference [1][2] Company Overview - Sionna Therapeutics is a clinical-stage biopharmaceutical company aiming to revolutionize CF treatment through innovative medicines that stabilize CFTR's nucleotide-binding domain 1 (NBD1) [3] - The company is developing a pipeline of small molecules targeting the F508del genetic mutation and complementary CFTR modulators to enhance CFTR function [3] Presentation Details - The oral presentation titled "Stabilizers of CFTR NBD1 synergize with galicaftor (SION-2222) or SION-109 to enable full correction of ΔF508-CFTR" will take place on June 6, 2025 [2] - The presentation will be available on Sionna's website under the "Scientific Presentations" section [2]