Core Insights - Sionna Therapeutics has completed Phase 1 dosing for its NBD1 stabilizers SION-719 and SION-451, with topline data expected this quarter [1][6] - The company is financially strong following an upsized IPO, with approximately $354.7 million in cash and cash equivalents, which is projected to fund operations into 2028 [1][9] - Sionna plans to initiate a Phase 2a proof-of-concept trial and at least one dual combination MAD trial in the second half of 2025, with topline data anticipated in mid-2026 [1][6] Pipeline Updates - The Phase 1 trials for SION-719 and SION-451 have been completed, and both compounds have shown to be generally well tolerated [1][6] - Target exposures achieved in the trials suggest potential clinical benefits when combined with Sionna's complementary modulators or as an add-on to current standard of care [6] - The upcoming Phase 2a trial will evaluate an NBD1 stabilizer in combination with the current standard of care in cystic fibrosis patients [6] Business Highlights - Sionna completed an upsized IPO in February 2025, raising approximately $219 million in gross proceeds [4] - The company issued 12,176,467 shares at a public offering price of $18.00 per share, with trading commencing on February 7, 2025 [4] - Research and development expenses for Q1 2025 were $13.7 million, up from $10.2 million in Q1 2024, reflecting increased spending to support the clinical pipeline [7][8] Financial Results - General and administrative expenses for Q1 2025 were $6.0 million, compared to $2.9 million in Q1 2024, primarily due to personnel-related costs [8] - The net loss for Q1 2025 was $16.5 million, an increase from a net loss of $11.8 million in Q1 2024 [8] - As of March 31, 2025, cash, cash equivalents, and marketable securities totaled $354.7 million, including net proceeds from the IPO of $199.6 million [9][17]

Summary of Sionna Therapeutics (SION) 2025 Conference Call Company Overview - **Company**: Sionna Therapeutics - **CEO**: Mike Clunan - **Founded**: 2019 as a spin-out from Sanofi, with historical ties to Genzyme [5][6] Industry Focus - **Industry**: Life Sciences, specifically targeting cystic fibrosis (CF) [2][4] - **Market Opportunity**: The current market for CF treatments is valued at $11 billion and is expected to grow [7] Core Points and Arguments 1. **Unmet Need in Cystic Fibrosis**: - Despite advancements by Vertex Pharmaceuticals, a significant unmet need remains in CF treatment [6] - Only one-third of patients on the standard of care, TRIKAFTA, achieve normal CFTR function, indicating a large opportunity for Sionna [6][48] 2. **Targeting NBD1**: - Sionna is focusing on NBD1, a previously considered "undruggable" target, to enhance CFTR correction [7][8] - NBD1 stabilization could potentially deliver clinical benefits comparable to the triple combination therapy of Trikafta [13][23] 3. **Predictive CF HBE Assay**: - The CF HBE assay is a gold standard in vitro assay that is highly predictive of clinical outcomes [8][9] - This assay is used for early screening of compounds and determining exposure targets for clinical trials [9] 4. **Pipeline Development**: - Two NBD1 compounds, 719 and 451, are in Phase 1 trials, with encouraging interim data expected soon [14][15] - Sionna has licensed three complementary mechanisms from AbbVie to enhance their portfolio [10][20] 5. **Combination Strategies**: - The company plans to prioritize two combination assets, Galacaftor and ICL4 corrector (109), to work alongside NBD1 [16][39] - The goal is to create a dual combination that provides meaningful clinical benefits over existing treatments [18][19] 6. **Financial Position**: - Sionna raised $219 million in its IPO, providing financial flexibility and a runway into 2028 [20][46] 7. **Upcoming Milestones**: - Top-line data from Phase 1 studies is expected soon, followed by a Phase 2a proof of concept study to demonstrate the efficacy of NBD1 as an add-on to Trikafta [41][44] - Combination studies with healthy volunteers are also planned to assess tolerability and pharmacokinetics [45] Additional Important Content - **Clinical Endpoint Correlation**: - There is a strong correlation (0.96) between chloride transport and FEV1, with a target of at least a 10 millimole improvement in sweat chloride to demonstrate clinical benefit [53] - **Strategic Flexibility**: - Sionna's unique approach to targeting NBD1 allows for multiple strategies in the market, including layering NBD1 on top of existing therapies [17][18] - **Patient Impact**: - The company aims to shift the treatment paradigm in CF by providing more options and improving patient outcomes [50][49] This summary encapsulates the key points discussed during the conference call, highlighting Sionna Therapeutics' strategic focus, market opportunities, and upcoming milestones in the development of its cystic fibrosis treatments.

Company Overview - Sionna Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on revolutionizing the treatment of cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein [3] - The company aims to deliver differentiated medicines that restore CFTR function to near-normal levels by directly stabilizing CFTR's nucleotide-binding domain 1 (NBD1), which is believed to be crucial for improving clinical outcomes and quality of life for CF patients [3] Pipeline and Research Focus - Sionna is advancing a pipeline of small molecules engineered to correct defects caused by the F508del genetic mutation located in NBD1 [3] - The company is also developing a portfolio of complementary CFTR modulators designed to work synergistically with its NBD1 stabilizers to enhance CFTR function [3] Upcoming Events - Management will present at The Citizens Life Sciences Conference on May 7, 2025, at 12:30 p.m. ET [1] - A live webcast of the presentation will be available on the company's Investor Relations website, with a replay accessible for 90 days post-event [2]

Company Overview - Sionna Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on revolutionizing the treatment of cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein [3] - The company aims to deliver differentiated medicines that restore CFTR function to near-normal levels by directly stabilizing CFTR's nucleotide-binding domain 1 (NBD1), which is believed to be crucial for improving clinical outcomes and quality of life for CF patients [3] - Sionna is advancing a pipeline of small molecules designed to correct defects caused by the F508del genetic mutation in NBD1 and is also developing complementary CFTR modulators to enhance CFTR function [3] Upcoming Events - Management will present at The Citizens Life Sciences Conference on May 7, 2025, at 12:30 p.m. ET [1] - A live webcast of the presentation will be available on the company's Investor Relations website, with a replay accessible for 90 days post-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, encouraging investors to monitor the website along with press releases, SEC filings, and public conference calls [4]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K __________________________ (Mark One) x ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM____ to Commission file number 001-42504 _________________________________________________ SIONNA THERAPEUTICS, INC. (E ...

Exhibit 99.1 Sionna Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results Phase 1 MAD dosing completed for SION-451 and final MAD cohort of SION-719 planned; Interim data in healthy volunteers show potential to provide clinically meaningful benefit to CF patients. Topline data anticipated in first half of 2025 On track to initiate NBD1 Phase 2a proof-of-concept trial in combination with SOC in CF patients and combination MAD trials of an NBD1 stabilizer with a complementary modulator in h ...