[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]

[Part I - Financial Information](index=8&type=section&id=Part%20I%20-%20Financial%20Information) [Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) The company significantly strengthened its balance sheet post-IPO, though operating losses continued to grow due to increased R&D and G&A expenses - In February 2025, the company completed its IPO, raising net proceeds of approximately **$199.6 million** and converting all outstanding redeemable convertible preferred stock to common stock[40](index=40&type=chunk) Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $82,695 | $37,788 | | Marketable securities (current & noncurrent) | $271,993 | $130,255 | | **Total Assets** | **$369,674** | **$185,752** | | Total liabilities | $17,905 | $19,097 | | Total convertible preferred stock | $0 | $330,368 | | **Total stockholders' equity (deficit)** | **$351,769** | **($163,713)** | Condensed Consolidated Statements of Operations (in thousands) | Account | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $13,668 | $10,220 | | General and administrative | $5,991 | $2,927 | | Loss from operations | ($19,659) | ($13,147) | | Interest income | $3,000 | $1,132 | | **Net loss** | **($16,482)** | **($11,847)** | Condensed Consolidated Statements of Cash Flows Highlights (in thousands) | Cash Flow Activity | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | ($16,288) | ($13,175) | | Net cash used in investing activities | ($141,194) | ($123,927) | | Net cash provided by financing activities | $202,389 | $181,333 | [Management's Discussion and Analysis of Financial Condition and Results of Operations (MD&A)](index=22&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company's net loss grew to $16.5 million in Q1 2025, but its post-IPO cash position of $354.7 million is expected to fund operations into 2028 - The company's mission is to revolutionize CF treatment by developing medicines that normalize CFTR protein function, focusing on stabilizing the **NBD1 domain**[69](index=69&type=chunk) - **Topline data** from Phase 1 trials of NBD1 stabilizers SION-719 and SION-451 are expected in Q2 2025, with a proof-of-concept trial planned for H2 2025[71](index=71&type=chunk)[72](index=72&type=chunk) - As of March 31, 2025, the company had **$354.7 million** in cash, cash equivalents, and marketable securities, sufficient to support operations into 2028[84](index=84&type=chunk)[113](index=113&type=chunk) - The **$3.4 million increase in R&D expenses** was primarily due to a $1.9 million increase in direct costs for clinical programs and a $1.2 million increase in personnel-related expenses[101](index=101&type=chunk) - The **$3.1 million increase in G&A expenses** was driven by a $2.0 million increase in personnel-related costs and a $1.0 million increase in professional services fees[102](index=102&type=chunk)[108](index=108&type=chunk) Comparison of Operating Expenses (in thousands) | Expense Category | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Research and development | $13,668 | $10,220 | $3,448 | | General and administrative | $5,991 | $2,927 | $3,064 | | **Total operating expenses** | **$19,659** | **$13,147** | **$6,512** | [Quantitative and Qualitative Disclosures About Market Risk](index=31&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is exempt from providing market risk disclosures as it qualifies as a smaller reporting company under SEC regulations - As a **"smaller reporting company,"** Sionna Therapeutics is exempt from providing the disclosures required by Item 305 of Regulation S-K[124](index=124&type=chunk) [Controls and Procedures](index=31&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2025, with no material changes to internal controls during the quarter - Management's evaluation concluded that the company's disclosure controls and procedures were **effective** at a reasonable assurance level as of the end of the period covered by the report[125](index=125&type=chunk) - **No changes** in internal control over financial reporting occurred during the quarter that have materially affected, or are reasonably likely to materially affect, these controls[126](index=126&type=chunk) [Part II - Other Information](index=32&type=section&id=Part%20II%20-%20Other%20Information) [Legal Proceedings](index=32&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any material legal proceedings, nor is management aware of any pending or threatened material legal matters - The company's management is currently not aware of any legal matters that could have a **material effect** on its financial position, results of operations, or cash flows[128](index=128&type=chunk) [Risk Factors](index=32&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant financial, developmental, competitive, and third-party dependency risks, including a history of losses and reliance on novel drug candidates - The company is a clinical-stage biopharmaceutical company with significant operating losses (**$16.5 million for Q1 2025**) and an accumulated deficit of **$197.6 million** as of March 31, 2025[130](index=130&type=chunk)[131](index=131&type=chunk) - The business is substantially dependent on the success of its **NBD1 stabilizer product candidates** (e.g., SION-719, SION-451), which target a novel protein domain, making development inherently risky[145](index=145&type=chunk)[180](index=180&type=chunk) - The company faces substantial competition from established players, with its main competitor, **Vertex**, holding a significant market share and possessing greater resources[314](index=314&type=chunk)[315](index=315&type=chunk) - Sionna is dependent on intellectual property licensed from third parties like **Sanofi and AbbVie** and relies on CROs and CDMOs for clinical trials and manufacturing[214](index=214&type=chunk)[215](index=215&type=chunk)[219](index=219&type=chunk)[223](index=223&type=chunk) - **Lock-up agreements** covering approximately 35.3 million shares of common stock from the IPO will expire in August 2025, potentially leading to significant sales and stock price volatility[357](index=357&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=88&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company's IPO in February 2025 generated net proceeds of $199.6 million, with no material change in the planned use of these funds - The company's IPO registration statement (File No. 333-284352) became effective on **February 6, 2025**[411](index=411&type=chunk) - There has been **no material change** in the planned use of the net proceeds from the IPO as described in the final prospectus[412](index=412&type=chunk) Initial Public Offering (IPO) Details | Metric | Value | | :--- | :--- | | Shares Sold (incl. underwriter option) | 12,176,467 | | Price per Share | $18.00 | | Aggregate Net Proceeds | ~$199.6 million | [Defaults Upon Senior Securities](index=89&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reports no defaults upon senior securities - None[415](index=415&type=chunk) [Mine Safety Disclosures](index=89&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[416](index=416&type=chunk) [Other Information](index=89&type=section&id=Item%205.%20Other%20Information) No directors or executive officers of the company adopted, modified, or terminated a Rule 10b5-1 trading plan during the first quarter of 2025 - During the quarter ended March 31, 2025, none of the company's directors or executive officers adopted, modified, or terminated any trading plan intended to satisfy the conditions of **Rule 10b5-1(c)**[417](index=417&type=chunk) [Exhibits](index=90&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the report, including corporate governance documents, stock plans, and required officer certifications - The report includes key corporate governance documents, such as the **Fifth Amended and Restated Certificate of Incorporation** and **Amended and Restated Bylaws**[420](index=420&type=chunk) - Compensatory plans filed as exhibits include the **2025 Stock Option and Incentive Plan**, the **2025 Employee Stock Purchase Plan**, and the **Senior Executive Cash Incentive Bonus Plan**[420](index=420&type=chunk) - **Certifications by the Principal Executive Officer and Principal Financial Officer** pursuant to Sections 302 and 906 of the Sarbanes-Oxley Act of 2002 are included as exhibits[420](index=420&type=chunk)