SION

PreciSION CF Phase 2a proof-of-concept trial evaluating NBD1 stabilizer SION-719 as an add-on to standard of care is on track for topline data summer of 2026 Phase 1 trial evaluating NBD1 stabilizer SION-451 in proprietary dual combinations with SION-2222 and with SION-109 also is on track for topline data summer of 2026 Maintained strong cash position with $268.3 million in cash and cash equivalents, expected to fund operations into 2028 WALTHAM, Mass., Aug. 06, 2026 (GLOBE NEWSWIRE) -- Sionna Therapeutics, Inc. (Nasdaq: SION), a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) today reported financial results for the second quarter ended June 30, 2026, and provided a business update. “We continued to advance our clinical NBD1 stabilizer programs during the second quarter as we approach two important clinical milestones this summer,” said Mike Cloonan, President and Chief Executive Officer of Sionna. “We remain focused on execution and delivering topline data from both our Phase 2a proof-of-concept trial and our Phase 1 dual combination trial. Together, these studies have the potential to further validate our core belief that directly stabilizing NBD1 is central to restoring CFTR function and transforming the treatment paradigm for people living with cystic fibrosis." Pipeline Updates PreciSION CF Phase 2a Proof-of-Concept Trial with SION-719 Is On Track: The PreciSION CF Phase 2a proof-of-concept (POC) trial (NCT07108153) is evaluating SION-719 as an add-on to standard of care (SOC) in CF participants. The trial is evaluating the safety, tolerability, and pharmacokinetics (PK) of SION-719 when administered with SOC and assessing change in CFTR function as measured by sweat chloride levels. In April 2026, Sionna announced it had completed enrollment. Topline data from this trial are on track for this summer. Phase 1 Dual Combination Trial with SION-451 and Complementary Modulators Is On Track: The Phase 1 trial (NCT07035990) is evaluating SION-451 in proprietary dual combinations with SION-2222 (galicaftor), a transmembrane domain 1 (TMD1)-directed CFTR corrector, and with SION-109, an intracellular loop 4 (ICL4)-directed CFTR corrector, in healthy volunteers. Topline data from this trial are on track for this summer. Presented Encore Data at 49th European Cystic Fibrosis Conference: In June 2026, Sionna presented encore clinical and nonclinical data at the 49th European Cystic Fibrosis Conference (ECFS) in Lisbon, Portugal. Presentations highlighted previously reported Phase 1 data for the Company's clinical-stage NBD1 stabilizers, SION-719 and SION-451, and nonclinical data demonstrating the potential of NBD1 stabilizers to increase F508del-CFTR protein half-life up to wild-type levels when used alone or in combination with complementary CFTR modulators. The same data will also be presented at the 16th Australasian Cystic Fibrosis Conference taking place August 7th-9th in Geelong, Australia. Financial Results for the Quarter Ended June 30, 2026 Research and Development Expenses: Research and development expenses were $21.9 million for the second quarter of 2026, compared to $15.4 million for the second quarter of 2025. These increases were mainly driven by development expenses to support the advancement of Sionna’s clinical pipeline and personnel-related costs, including stock-based compensation expenses, to support the Company’s continued growth and operational activities. General and Administrative Expenses: General and administrative expenses were $10.6 million for the second quarter of 2026, compared to $6.5 million for the second quarter of 2025. These increases were primarily due to personnel-related costs, including stock-based compensation expenses, to support the Company’s continued growth and operational activities. Net Loss: Net loss was $29.9 million for the second quarter of 2026, compared to a net loss of $18.1 million for the second quarter of 2025. Cash and Cash Equivalents: Cash, cash equivalents and marketable securities totaled $268.3 million as of June 30, 2026. Sionna expects its current cash position to fund operations into 2028. About Sionna Therapeutics Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide binding domain 1 (NBD1), which Sionna believes is central to potentially unlocking dramatic improvements in clinical outcomes and quality of life for people with CF. Leveraging more than a decade of the co-founders’ research on NBD1, Sionna is advancing a pipeline of small molecules engineered to correct the defects caused by the F508del genetic mutation, which occurs in NBD1. Sionna is also developing a portfolio of complementary CFTR modulators that are designed to work synergistically with its NBD1 stabilizers to improve CFTR function. For more information about Sionna, visit www.sionnatx.com. Sionna intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor Sionna’s Investor Relations website, in addition to following Sionna’s press releases, SEC filings, public conference calls, presentations, and webcasts. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Sionna’s beliefs and expectations regarding: its goal of transforming the treatment paradigm for CF and providing clinically meaningful benefit for CF participants; the potential of Sionna’s product candidates to expand therapeutic options for people with CF; the initiation, timing, progress and results of Sionna’s research and development programs, clinical trials and studies, including the timing of topline data from Sionna’s Phase 2a proof-of-concept trial and Phase 1 dual combination trial; the ability of clinical trials to demonstrate safety and efficacy of Sionna’s product candidates; the ability of Sionna’s nonclinical studies or earlier clinical trials to predict later clinical trial results; and financial projections and expectations regarding the time period in which Sionna’s capital resources will be sufficient to fund its anticipated operations, including cash runway, use of capital, expenses and other financial results. In some cases, the forward-looking statements can be identified by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by the forward-looking statements contained in this press release. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties inherent in the development of product candidates, including uncertainties concerning the initiation, timing, progress, and results of Sionna’s ongoing, planned and future clinical trials and studies; the Company’s ability to replicate positive results from earlier nonclinical studies or clinical trials in current or future clinical trials; Sionna’s ability to demonstrate that its NBD1 stabilizers, complementary CFTR modulators, and any potential future product candidates are safe and effective for their proposed indications; regulatory developments in the United States and foreign countries; the competitive landscape for CF treatments, including existing therapies; and general economic, industry and market conditions. These risks and uncertainties are described in the section entitled “Risk Factors” in Sionna’s most recent Annual Report on Form 10-K as well as any subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. In addition, any forward-looking statements represent Sionna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Sionna explicitly disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor Contact Juliet Labadorf [email protected] Media Contact Sarah [email protected]

Enrollment completed in the PreciSION CF Phase 2a proof-of-concept trial evaluating NBD1 stabilizer SION-719 as an add-on to standard of care in participants with cystic fibrosis; topline data on track for the summer of 2026 Ongoing Phase 1 trial evaluating NBD1 stabilizer SION-451 in proprietary dual combinations with SION-2222 and with SION-109 in healthy volunteers is also on track for topline data in the summer of 2026 Maintained strong cash position with approximately $289.9 million in cash and cash equivalents, expected to fund operations into 2028 WALTHAM, Mass., May 12, 2026 (GLOBE NEWSWIRE) -- Sionna Therapeutics, Inc. (Nasdaq: SION), a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) today reported financial results for the first quarter ended March 31, 2026, and provided a business update. “We entered 2026 with strong execution across our programs, highlighted by the recent completion of enrollment in our proof-of-concept Phase 2a trial of SION-719, an important milestone for Sionna,” said Mike Cloonan, President and Chief Executive Officer of Sionna. “With both of our clinical stage NBD1 stabilizer programs on track for topline readouts this summer, we remain focused on advancing these first-in-class product candidates that could expand therapeutic options for people with CF.” Pipeline Updates NBD1 Stabilizers Enrollment Completed in PreciSION CF Phase 2a Proof-of-Concept Trial with SION-719; Topline Data On Track: In April 2026, Sionna announced it had completed enrollment in the PreciSION CF Phase 2a proof-of-concept (POC) trial (NCT07108153) evaluating SION-719 as an add-on to standard of care (SOC) in CF patients. The trial is evaluating the safety, tolerability, and pharmacokinetics (PK) of SION-719 when administered with SOC and assessing change in CFTR function as measured by sweat chloride levels. Topline data from this trial are anticipated in the summer of this year. Ongoing Phase 1 Dual Combination Trial with SION-451 and Complementary Modulators; Topline Data On Track: The Phase 1 trial (NCT07035990) is evaluating SION-451 in proprietary dual combinations with SION-2222 (galicaftor), a transmembrane domain 1 (TMD1)-directed CFTR corrector, and with SION-109, an intracellular loop 4 (ICL4)-directed CFTR corrector, in healthy volunteers. Topline data from this trial are anticipated in the summer of this year. Encore Data to be Presented at 49th European Cystic Fibrosis Conference: Encore data previously presented at the 2025 North American Cystic Fibrosis Conference (NACFC) will be featured in an oral and ePoster presentation at the European Cystic Fibrosis Society’s (ECFS) 49th European Cystic Fibrosis Conference, being held June 3-6, 2026, in Lisbon, Portugal. Details of the presentations are as follows: Abstract Title: Safety, tolerability, and pharmacokinetics of novel NBD1 stabilizers SION-719 and SION-451 from two Phase 1 first-in-human studies Abstract number: EPS07.01 Presenting Author: Jason H. Maley, MD, MS, Senior Director, Clinical Development, Sionna Therapeutics Oral ePoster Session Title: Old and new – exploring the portfolio for CF treatment Date and Time: Friday, June 5, 2026, 2:00-2:06 p.m. CEST/9:00-9:06 a.m. ET Abstract Title: Clinical-stage NBD1 stabilizers can increase F508del-CFTR protein half-life to wild-type levels when used alone or in combination with other CFTR modulators Abstract ID: WS15.3 Presenting Author: Greg Hurlbut, Ph.D., Co-Founder and Senior Vice President, Discovery Research, Sionna Therapeutics Session Title: Workshop 15: Novel approaches, future therapies Date and Time: Friday, June 5, 2026, 5:30-5:45 p.m. CEST/11:30-11:45 a.m. ET Financial Results for the Quarter Ended March 31, 2026 Research and Development Expenses: Research and development expenses were $19.0 million for the first quarter of 2026, compared to $13.7 million for the first quarter of 2025. These increases were mainly driven by development expenses to support the advancement of Sionna’s clinical pipeline and personnel-related costs, including stock-based compensation expenses, to support the Company’s continued growth and operational activities. General and Administrative Expenses: General and administrative expenses were $10.6 million for the first quarter of 2026, compared to $6.0 million for the first quarter of 2025. These increases were primarily due to personnel-related costs, including stock-based compensation expenses, to support the Company’s continued growth and operational activities. Net Loss: Net loss was $26.8 million for the first quarter of 2026, compared to a net loss of $16.5 million for the first quarter of 2025. Cash and Cash Equivalents: Cash, cash equivalents and marketable securities totaled $289.9 million as of March 31, 2026. Sionna expects its current cash position to fund operations into 2028. About Sionna Therapeutics Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide binding domain 1 (NBD1), which Sionna believes is central to potentially unlocking dramatic improvements in clinical outcomes and quality of life for people with CF. Leveraging more than a decade of the co-founders’ research on NBD1, Sionna is advancing a pipeline of small molecules engineered to correct the defects caused by the F508del genetic mutation, which occurs in NBD1. Sionna is also developing a portfolio of complementary CFTR modulators that are designed to work synergistically with its NBD1 stabilizers to improve CFTR function. For more information about Sionna, visit www.sionnatx.com. Sionna intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor Sionna’s Investor Relations website, in addition to following Sionna’s press releases, SEC filings, public conference calls, presentations, and webcasts. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Sionna’s beliefs and expectations regarding: its goal of transforming the treatment paradigm for CF and providing clinically meaningful benefit for CF patients; the potential of Sionna’s product candidates to expand therapeutic options for people with CF; the initiation, timing, progress and results of Sionna’s research and development programs, clinical trials and studies, including the timing of topline data from Sionna’s Phase 2a proof-of-concept trial and Phase 1 dual combination trial; the ability of clinical trials to demonstrate safety and efficacy of Sionna’s product candidates; the ability of Sionna’s preclinical studies or earlier clinical trials to predict later clinical trial results; and financial projections and expectations regarding the time period in which Sionna’s capital resources will be sufficient to fund its anticipated operations, including cash runway, use of capital, expenses and other financial results. In some cases, the forward-looking statements can be identified by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by the forward-looking statements contained in this press release. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties inherent in the development of product candidates, including uncertainties concerning the initiation, timing, progress, and results of Sionna’s ongoing, planned and future clinical trials and studies; the Company’s ability to replicate positive results from earlier preclinical studies or clinical trials in current or future clinical trials; Sionna’s ability to demonstrate that its NBD1 stabilizers, complementary CFTR modulators, and any potential future product candidates are safe and effective for their proposed indications; regulatory developments in the United States and foreign countries; and general economic, industry and market conditions. These risks and uncertainties are described in the section entitled “Risk Factors” in Sionna’s most recent Annual Report on Form 10-K as well as any subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. In addition, any forward-looking statements represent Sionna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Sionna explicitly disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Media Contact Sarah Spencer [email protected] Investor Contact Juliet Labadorf [email protected]

Ongoing PreciSION CF Phase 2a proof-of-concept trial evaluating NBD1 stabilizer SION-719 as an add-on to standard of care in participants with cystic fibrosis is on track with topline data anticipated in mid-2026 Ongoing Phase 1 trial evaluating NBD1 stabilizer SION-451 in proprietary dual combinations with SION-2222 and with SION-109 in healthy volunteers is on track with topline data anticipated in mid-2026 Maintained strong cash position with approximately $310.3 million in cash and cash equivalents, expected to fund operations into 2028 WALTHAM, Mass., March 02, 2026 (GLOBE NEWSWIRE) -- Sionna Therapeutics, Inc. (Nasdaq: SION), a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, today reported financial results for the fourth quarter and full year ended December 31, 2025, and provided a business update. “2025 was a remarkable and transformative year for Sionna. Propelled by the momentum of our upsized IPO in February, we have been steadily executing across our pipeline and strengthening the capabilities of our team. We delivered positive results from the two Phase 1 trials of our first-in-class NBD1 stabilizers SION-719 and SION-451 and expeditiously advanced these candidates into the next stages of development,” said Mike Cloonan, President and Chief Executive Officer of Sionna. “With topline readouts from both of our ongoing trials anticipated this year, along with the capital to support us into 2028, Sionna is making meaningful progress toward our goal to deliver additional options for those living with CF.” Pipeline Updates NBD1 Stabilizers Ongoing PreciSION CF Phase 2a Proof-of-Concept Trial with SION-719 On Track: In October 2025, Sionna announced the initiation of the PreciSION CF Phase 2a proof-of-concept (POC) trial (NCT07108153) evaluating SION-719 as an add-on to standard of care (SOC) in CF patients. The trial is evaluating the safety, tolerability, and pharmacokinetics (PK) of SION-719 when administered with SOC and assessing change in CFTR function as measured by sweat chloride levels. Topline data from this trial are anticipated in mid-2026. Ongoing Phase 1 Dual Combination Trial with SION-451 and Complementary Modulators On Track: In August 2025, Sionna announced the initiation of the Phase 1 trial (NCT07035990) evaluating SION-451 in proprietary dual combinations with SION-2222 (galicaftor), a transmembrane domain 1 (TMD1)-directed CFTR corrector, and with SION-109, an intracellular loop 4 (ICL4)-directed CFTR corrector, in healthy volunteers. The trial is ongoing, with topline data anticipated in mid-2026. Data Presented at 2025 North American Cystic Fibrosis Conference: In October 2025, Sionna presented data at the 2025 North American Cystic Fibrosis Conference (NACFC). An oral presentation highlighted data from the two single agent healthy volunteer Phase 1 clinical trials of novel NBD1 stabilizers, SION-719 and SION-451. As previously disclosed, in these Phase 1 trials, both SION-719 and SION-451 were generally well tolerated and exceeded target exposure levels. A poster presentation included new preclinical data that show the impact of SION-719 and SION-451 on the half-life of F508del-CFTR protein. In preclinical studies, NBD1 stabilizers SION-719 and SION-451 increased the half-life of mature F508del-CFTR protein up to levels seen in wild-type. This effect was apparent when NBD1 stabilizers were used as single agents or when combined with complementary modulators. These data reinforce the differentiation of the NBD1 mechanism of action. Financial Results for the Quarter and Year Ended December 31, 2025 Research and Development Expenses: Research and development expenses were $15.2 million for the fourth quarter of 2025 and $60.3 million for the year ended December 31, 2025, compared to $14.3 million and $57.3 million, respectively, for the same periods of 2024. These increases were mainly driven by development expenses to support the advancement of Sionna’s clinical pipeline. General and Administrative Expenses: General and administrative expenses were $8.4 million for the fourth quarter of 2025 and $28.7 million for the year ended December 31, 2025, compared to $3.9 million and $13.3 million, respectively, for the same periods of 2024. These increases were primarily due to personnel-related costs, professional fees, and stock-based compensation expenses to support the Company’s continued growth and operational activities. Net Loss: Net loss was $20.4 million for the fourth quarter of 2025 and $75.3 million for the year ended December 31, 2025, compared to a net loss of $15.8 million and $61.7 million, respectively, for the same periods of 2024. Cash and Cash Equivalents: Cash, cash equivalents and marketable securities totaled $310.3 million as of December 31, 2025. Sionna expects its current cash position to fund operations into 2028. About Sionna Therapeutics Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide binding domain 1 (NBD1), which Sionna believes is central to potentially unlocking dramatic improvements in clinical outcomes and quality of life for people with CF. Leveraging more than a decade of the co-founders’ research on NBD1, Sionna is advancing a pipeline of small molecules engineered to correct the defects caused by the F508del genetic mutation, which occurs in NBD1. Sionna is also developing a portfolio of complementary CFTR modulators that are designed to work synergistically with its NBD1 stabilizers to improve CFTR function. For more information about Sionna, visit www.sionnatx.com. Sionna intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor Sionna’s Investor Relations website, in addition to following Sionna’s press releases, SEC filings, public conference calls, presentations, and webcasts. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Sionna’s beliefs and expectations regarding: its goal of transforming the treatment paradigm for CF and providing clinically meaningful benefit to CF patients; the initiation, timing, progress and results of Sionna’s research and development programs, clinical trials and studies, including the timing of topline data from Sionna’s Phase 2a proof-of-concept trial and Phase 1 dual combination trial; the ability of clinical trials to demonstrate safety and efficacy of Sionna’s product candidates, including the potential of an NBD1 stabilizer added to the standard of care or used in a proprietary dual combination to provide clinically meaningful benefit; the ability of Sionna’s preclinical studies or earlier clinical trials to predict later clinical trial results; and financial projections and expectations regarding the time period in which Sionna’s capital resources will be sufficient to fund its anticipated operations, including cash runway, use of capital, expenses and other financial results. In some cases, the forward-looking statements can be identified by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by the forward-looking statements contained in this press release. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties inherent in the development of product candidates, including uncertainties concerning the initiation, timing, progress, and results of Sionna’s ongoing, planned and future clinical trials and studies; the company’s ability to replicate positive results from earlier preclinical studies or clinical trials in current or future clinical trials; Sionna’s ability to demonstrate that its NBD1 stabilizers, complementary CFTR modulators, and any potential future product candidates are safe and effective for their proposed indications; regulatory developments in the United States and foreign countries; and general economic, industry and market conditions. These risks and uncertainties are described in the section entitled “Risk Factors” in Sionna’s most recent Annual Report on Form 10-K as well as any subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. In addition, any forward-looking statements represent Sionna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Sionna explicitly disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Media Contact Adam Daley CG Life 212.253.8881 [email protected] Investor Contact Juliet Labadorf [email protected]

Initiated PreciSION CF Phase 2a proof-of-concept trial evaluating NBD1 stabilizer SION-719 as an add-on to standard of care in participants with cystic fibrosis Successfully completed drug-drug interaction study to support initiation of PreciSION CF Phase 2a Initiated Phase 1 trial evaluating NBD1 stabilizer SION-451 in proprietary dual combinations with SION-2222 and with SION-109 in healthy volunteers Topline data from both trials anticipated in mid-2026 Maintained strong cash position with approximately $325.0 million in cash and cash equivalents, expected to fund operations into 2028 WALTHAM, Mass., Nov. 05, 2025 (GLOBE NEWSWIRE) -- Sionna Therapeutics, Inc. (Nasdaq: SION), a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, today reported financial results for the quarter ended September 30, 2025, and provided a business update. “We maintain our track record of strong execution, achieving substantial progress across our pipeline in the third quarter. Following the positive data from the two Phase 1 clinical trials evaluating our first-in-class NBD1 stabilizers SION-719 and SION-451, we have initiated both the PreciSION CF Phase 2a proof-of-concept trial of SION-719 as an add-on to standard of care and the Phase 1 trial of SION-451 in proprietary dual combinations. We are looking forward to sharing results from both trials in mid-2026,” said Mike Cloonan, President and Chief Executive Officer of Sionna. “Our recent engagement with the CF community at the North American Cystic Fibrosis Conference in October has reinforced the importance of our science and our mission to revolutionize the treatment paradigm for people living with CF.” Pipeline Updates NBD1 Stabilizers Initiated PreciSION CF Phase 2a Proof-of-Concept Trial with SION-719: In October 2025, Sionna announced initiation of the PreciSION CF Phase 2a proof-of-concept (POC) trial (NCT07108153) evaluating nucleotide binding domain 1 (NBD1) stabilizer SION-719 as an add-on to the current standard of care (SOC) in CF participants. The trial will evaluate the safety, tolerability, and pharmacokinetics (PK) of SION-719 when administered with SOC and assess change in CFTR function as measured by sweat chloride levels. Topline data from this trial are anticipated in mid-2026. Sionna also completed a successful drug-drug interaction study with midazolam, a sensitive CYP3A4 substrate, which confirmed that SION-719 can be dosed in combination with Trikafta®, the current SOC, according to its label. Initiated Phase 1 Dual Combination Trial with SION-451 and Complementary Modulators: In August 2025, Sionna announced initiation of the Phase 1 trial (NCT07035990) evaluating SION-451 in proprietary dual combinations with SION-2222 (galicaftor), a transmembrane domain 1 (TMD1)-directed CFTR corrector, and with SION-109, an intracellular loop 4 (ICL4)-directed CFTR corrector, in healthy volunteers. Topline data from this trial are anticipated in mid-2026. Investigational New Drug (IND) Application Cleared for SION-451: The U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application to support the advancement of SION-451 to later-stage development. Data Presented at 2025 North American Cystic Fibrosis Conference: In October 2025, Sionna presented data at the 2025 North American Cystic Fibrosis Conference (NACFC) in Seattle, Washington. An oral presentation highlighted data from the two single agent healthy volunteer Phase 1 clinical trials of novel NBD1 stabilizers, SION-719 and SION-451. As previously disclosed, in these Phase 1 trials, both SION-719 and SION-451 were generally well tolerated and exceeded target exposure levels. Based on these data and its cystic fibrosis human bronchial epithelial (CFHBE) model, Sionna believes that its NBD1 stabilizers have the potential to deliver clinically meaningful benefit including up to wild-type levels of CFTR function with SION-719 as an add-on to SOC or with SION-451 in proprietary dual combinations. A poster with new preclinical data showed the impact of NBD1 stabilizers SION-719 and SION-451 on the half-life of F508del-CFTR protein. In preclinical studies, NBD1 stabilizers SION-719 and SION-451 increased the half-life of mature F508del-CFTR protein up to levels seen in wild-type. This effect was apparent when NBD1 stabilizers were used as single agents or when combined with complementary modulators. These data highlight the further differentiation of the NBD1 mechanism of action, which has the potential to improve both the function of CFTR and CFTR half-life up to wild-type levels. Business Highlights Strengthened Leadership: In September 2025, Sionna appointed Caroline Stark Beer, MBA, as Chief Business Officer. Caroline brings over 20 years of experience in the life science industry to her role at Sionna, most recently as Chief Business Officer at Jnana Therapeutics until Jnana’s sale to Otsuka Pharmaceutical. Financial Results for the Quarter Ended September 30, 2025 Research and Development Expenses: Research and development expenses were $16.0 million for the third quarter of 2025, compared to $24.6 million for the third quarter of 2024. This decrease was mainly driven by one-time in-process research and development charges recognized in connection with a license agreement executed in the prior year, partially offset by an increase in development expenses to support the advancement of Sionna’s clinical pipeline. General and Administrative Expenses: General and administrative expenses were $7.8 million for the third quarter of 2025, compared to $3.4 million for the third quarter of 2024. This increase was primarily due to personnel-related costs, professional fees, and stock-based compensation expenses to support the Company’s continued growth and operational activities. Net Loss: Net loss was $20.3 million for the third quarter of 2025, compared to a net loss of $25.4 million for the third quarter of 2024. Cash and Cash Equivalents: Cash, cash equivalents and marketable securities totaled $325.0 million as of September 30, 2025. Sionna expects its current cash position to fund operations into 2028. About Sionna Therapeutics Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide binding domain 1 (NBD1), which Sionna believes is central to potentially unlocking dramatic improvements in clinical outcomes and quality of life for people with CF. Leveraging more than a decade of the co-founders’ research on NBD1, Sionna is advancing a pipeline of small molecules engineered to correct the defects caused by the F508del genetic mutation, which resides in NBD1. Sionna is also developing a portfolio of complementary CFTR modulators that are designed to work synergistically with its NBD1 stabilizers to improve CFTR function. For more information about Sionna, visit www.sionnatx.com. Sionna intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor Sionna’s Investor Relations website, in addition to following Sionna’s press releases, SEC filings, public conference calls, presentations, and webcasts. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Sionna’s beliefs and expectations regarding: its goal of transforming the treatment paradigm for CF and providing clinically meaningful benefit to CF patients; the initiation, timing, progress and results of Sionna’s research and development programs, clinical trials and studies, including the timing of topline data from Sionna’s Phase 2a proof-of-concept trial and Phase 1 dual combination trial; the ability of clinical trials to demonstrate safety and efficacy of Sionna’s product candidates, including the potential of an NBD1 stabilizer added to the standard of care or used in a proprietary dual combination to provide clinically meaningful benefit, including up to wild-type levels of CFTR function; the differentiation of the NBD1 mechanism of action and the potential to improve both the function of CFTR and CFTR half-life up to wild-type levels; the ability of Sionna’s preclinical studies to predict later clinical trial results; and financial projections and expectations regarding the time period in which Sionna’s capital resources will be sufficient to fund its anticipated operations, including cash runway, use of capital, expenses and other financial results. In some cases, the forward-looking statements can be identified by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by the forward-looking statements contained in this press release. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties inherent in the development of product candidates, including uncertainties concerning the initiation, timing, progress, and results of Sionna’s ongoing, planned and future clinical trials and studies; the company’s ability to replicate positive results from earlier preclinical studies or clinical trials in current or future clinical trials; Sionna’s ability to demonstrate that its NBD1 stabilizers, complementary CFTR modulators, and any potential future product candidates are safe and effective for their proposed indications; regulatory developments in the United States and foreign countries; and general economic, industry and market conditions. These risks and uncertainties are described in the section entitled “Risk Factors” in Sionna’s most recent Quarterly Report on Form 10-Q as well as any subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. In addition, any forward-looking statements represent Sionna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Sionna explicitly disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Media Contact Adam Daley CG Life 212.253.8881 [email protected] Investor Contact Juliet Labadorf [email protected]

Announced positive Phase 1 data for SION-719 and SION-451 demonstrating both first-in-class NBD1 stabilizers were generally well tolerated and exceeded pharmacokinetic targets Initiation of Phase 2a proof-of-concept trial of SION-719 as an add-on to standard of care in cystic fibrosis patients is on track for the second half of 2025 with topline data expected in mid-2026 Advancement of Phase 1 healthy volunteer trial of SION-451 in two proprietary dual combinations is on track for the second half of 2025 with topline data expected in mid-2026 Maintained strong cash position with approximately $337.3 million in cash and cash equivalents, expected to fund operations into 2028 WALTHAM, Mass., Aug. 11, 2025 (GLOBE NEWSWIRE) -- Sionna Therapeutics, Inc. (Nasdaq: SION), a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, today reported financial results for the quarter ended June 30, 2025, and provided a business update. “We are pleased with the progress we’ve made this past quarter, underscored by the encouraging tolerability and PK data from the Phase 1 trials of our first-in-class NBD1 stabilizers, SION-719 and SION-451,” said Mike Cloonan, President and Chief Executive Officer of Sionna. “These data reinforce our confidence in advancing both NBD1 stabilizers into the next stages of development. We are preparing to initiate the Phase 2a proof-of-concept trial of SION-719 as an add-on to standard of care and the Phase 1 trial of SION-451 in dual combinations this year and look forward to sharing topline results from both studies in mid-2026. Supported by a clear development plan and a strong financial position, we are excited to be advancing CF therapies that have the potential to make a meaningful difference for people affected by the disease.” Pipeline Updates NBD1 Stabilizers Positive Phase 1 Results for SION-719 and SION-451: In June 2025, Sionna announced positive Phase 1 data for its first-in-class nucleotide binding domain 1 (NBD1) stabilizers, SION-719 and SION-451. The randomized, double-blind, placebo-controlled trials enrolled over 200 healthy volunteers and evaluated each compound’s safety, tolerability, and pharmacokinetics (PK) across single and multiple ascending dose cohorts. Both NBD1 stabilizers were generally well tolerated and exceeded target exposure levels that Sionna believes, based on its cystic fibrosis human bronchial epithelial (CFHBE) model, have the potential to deliver clinically meaningful benefit as add-on therapies to standard of care (SOC) or in proprietary dual combinations with complementary modulators. These data reinforce Sionna’s decision to progress SION-719 and SION-451 to the next phases of development. Phase 2a Proof-of-Concept Trial with SION-719: Sionna is on track to progress SION-719 into a proof-of-concept (POC) trial in the second half of 2025 evaluating the compound as an add-on to SOC in CF patients, with topline data anticipated in mid-2026. The trial is designed to demonstrate the unique mechanism of NBD1 stabilization and the potential opportunity to drive improved CFTR function beyond the current SOC, as defined by sweat chloride. The midazolam drug-drug interaction study to confirm SION-719 can be dosed in combination with the SOC according to its label has initiated and is on track to be completed prior to initiation of the Phase 2a trial. Phase 1 Dual Combination Trial with SION-451 and Complementary Modulators: Sionna is on track to advance a Phase 1 healthy volunteer trial evaluating SION-451 in combination with SION-2222 (galicaftor), a transmembrane domain 1 (TMD1)-directed CFTR corrector, and with SION-109, an intracellular loop 4 (ICL4)-directed CFTR corrector, in the second half of 2025. Topline data are anticipated in mid-2026. Preclinical Data Presented at 48th European Cystic Fibrosis Conference: In June 2025, Sionna presented preclinical data at the European Cystic Fibrosis Society’s (ECFS) 48th Annual Conference demonstrating that Sionna’s NBD1 stabilizers, in dual combinations with proprietary complementary modulators, enable full correction of F508del-CFTR in CF models. Sionna believes that these findings highlight the strong mechanistic rationale and the synergy of its dual combination approach to restoring CFTR function, suggesting the potential for these dual combinations to produce meaningful clinical outcomes and improved quality of life for people with CF. Financial Results for the Quarter Ended June 30, 2025 Research and Development Expenses: Research and development expenses were $15.4 million for the second quarter of 2025, compared to $8.2 million for the second quarter of 2024. This increase was mainly driven by direct program spend to support Sionna’s clinical pipeline. General and Administrative Expenses: General and administrative expenses were $6.5 million for the second quarter of 2025, compared to $3.1 million for the second quarter of 2024. This increase was primarily due to personnel-related costs, including stock-based compensation, and professional fees. Net Loss: Net loss was $18.1 million for the second quarter of 2025, compared to a net loss of $8.6 million for the second quarter of 2024. Cash and Cash Equivalents: Cash, cash equivalents and marketable securities totaled $337.3 million as of June 30, 2025. Sionna continues to expect its current cash position to fund operations into 2028. About Sionna Therapeutics Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide-binding domain 1 (NBD1), which Sionna believes is central to potentially unlocking dramatic improvements in clinical outcomes and quality of life for people with CF. Leveraging more than a decade of the co-founders’ research on NBD1, Sionna is advancing a pipeline of small molecules engineered to correct the defects caused by the F508del genetic mutation, which resides in NBD1. Sionna is also developing a portfolio of complementary CFTR modulators that are designed to work synergistically with its NBD1 stabilizers to improve CFTR function. For information about Sionna, visit www.sionnatx.com. Sionna intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor Sionna’s Investor Relations website, in addition to following Sionna’s press releases, SEC filings, public conference calls, presentations, and webcasts. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Sionna’s beliefs and expectations regarding: its goal of transforming the treatment paradigm for CF and providing clinically meaningful benefit to CF patients; the initiation, timing, progress and results of Sionna’s research and development programs, preclinical studies and clinical trials and studies, including the timing of the planned initiation of a Phase 2a proof-of-concept trial and Phase 1 healthy volunteer dual combination trial and the timing of topline data from these trials; the ability of clinical trials to demonstrate safety and efficacy of Sionna’s product candidates; the ability of Sionna’s preclinical studies to predict later clinical trial results and support Sionna’s dual combination approach to restoring CFTR function; and financial projections and expectations regarding the time period in which Sionna’s capital resources will be sufficient to fund its anticipated operations, including cash runway, use of capital, expenses and other financial results. In some cases, the forward-looking statements can be identified by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by the forward-looking statements contained in this press release. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties inherent in the development of product candidates, including uncertainties concerning the initiation, timing, progress, and results of Sionna’s planned and future clinical trials and studies; the company’s ability to replicate positive results from earlier preclinical studies or clinical trials in current or future clinical trials; Sionna’s ability to demonstrate that its NBD1 stabilizers, complementary CFTR modulators, and any potential future product candidates are safe and effective for their proposed indications; regulatory developments in the United States and foreign countries; and general economic, industry and market conditions. These risks and uncertainties are described in the section entitled “Risk Factors” in Sionna’s most recent Quarterly Report on Form 10-Q as well as any subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. In addition, any forward-looking statements represent Sionna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Sionna explicitly disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Media Contact Adam Daley CG Life 212.253.8881 [email protected] Investor Contact Juliet Labadorf [email protected]

Phase 1 dosing completed for NBD1 stabilizers SION-719 & SION-451; both compounds continue to be generally well tolerated Phase 1 topline data anticipated this quarter On track to initiate Phase 2a proof-of-concept trial and at least one dual combination MAD trial in the second half of 2025; topline data for both anticipated in mid-2026 Strong cash position following completed upsized IPO, with approximately $354.7 million in cash and cash equivalents, expected to fund operations into 2028 WALTHAM, Mass., May 12, 2025 (GLOBE NEWSWIRE) -- Sionna Therapeutics, Inc. (Nasdaq: SION), a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, today reported financial results for the quarter ended March 31, 2025, and provided a business update. “Following our upsized IPO in February, we are in a strong financial position to advance our mission to transform the treatment paradigm for patients with CF,” said Mike Cloonan, President and Chief Executive Officer of Sionna. “We continue to execute across our pipeline and have completed dosing in our Phase 1 trials for both SION-719 and SION-451. We look forward to announcing topline data from these trials this quarter, and to initiating our Phase 2a POC trial and the combination MAD Phase 1 program later this year. With multiple meaningful milestones on the horizon, we are focused on execution and building on our strong momentum throughout 2025.” Pipeline Updates NBD1 Stabilizers Phase 1 Dosing Completed: Sionna has completed dosing in the single ascending dose (SAD), multiple ascending dose (MAD), and food effect and tablet bioequivalence parts of the Phase 1 healthy volunteer trials of SION-719 and SION-451. Both compounds continue to be generally well tolerated, and their safety profiles remain consistent with prior disclosures. Full topline data are on schedule to be reported the second quarter of 2025. As previously reported in interim data, target exposures were achieved that have the potential, based on Sionna’s preclinical cystic fibrosis human bronchial epithelial (CFHBE) model, to provide clinically meaningful benefit to patients if SION-719 or SION-451 were administered as part of a dual combination with one of Sionna’s complementary modulators or as an add-on to the current standard of care (SOC). Phase 2a Proof-of-Concept Trial: Sionna remains on track to initiate a Phase 2a proof-of-concept (POC) trial in the second half of 2025, after completion of a drug-drug interaction trial, to evaluate an NBD1 stabilizer in combination with the current SOC in CF patients. Topline data from this trial are anticipated in mid-2026. Dual Combination MAD Trials: Sionna remains on track to initiate at least one combination MAD trial in the second half of 2025, evaluating a dual combination of an NBD1 stabilizer with a complementary modulator in healthy subjects. Topline data are expected in mid-2026. Business Highlights Completion of Upsized IPO: In February 2025, Sionna completed its upsized initial public offering (IPO), raising approximately $219 million gross proceeds before deducting underwriting discounts and commissions and other expenses. Sionna issued 12,176,467 shares of its common stock at a public offering price of $18.00 per share, which included 1,588,234 shares issued upon the full exercise by the underwriters of their option to purchase additional shares of common stock in the offering. Shares began trading on the Nasdaq Global Market on February 7, 2025, under the symbol “SION.” Upcoming Events and Presentations Presentation at 48th European Cystic Fibrosis Conference: Preclinical data assessing combinations of Sionna’s NBD1 stabilizers, SION-451 and SION-719, with complementary Sionna CFTR modulators, galifactor (SION-2222) and SION-109, will be featured in an oral presentation at the European Cystic Fibrosis Society’s (ECFS) 48th European Cystic Fibrosis Conference, being held June 4-7, 2025 in Milan, Italy. The abstract is entitled, “Stabilizers of CFTR NBD1 synergize with galicaftor (SION-2222) or SION-109 to enable full correction of ΔF508-CFTR.” Financial Results for the Quarter Ended March 31, 2025 Research and Development Expenses: Research and development expenses were $13.7 million for the first quarter of 2025, compared to $10.2 million for the first quarter of 2024. This increase was mainly driven by direct program spend to support Sionna’s clinical pipeline. General and Administrative Expenses: General and administrative expenses were $6.0 million for the first quarter of 2025, compared to $2.9 million for the first quarter of 2024. This increase was primarily due to personnel-related costs, including stock-based compensation, and professional fees. Net Loss: Net loss was $16.5 million for the first quarter of 2025, compared to a net loss of $11.8 million for the first quarter of 2024. Cash and Cash Equivalents: Cash, cash equivalents and marketable securities totaled $354.7 million as of March 31, 2025, which includes net proceeds from Sionna’s IPO of $199.6 million, after deducting underwriting discounts and commissions and other offering costs. Sionna expects its current cash position to fund operations into 2028. About Sionna Therapeutics Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for CF by developing novel medicines that normalize the function of the CFTR protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide-binding domain 1 (NBD1), which Sionna believes is central to potentially unlocking dramatic improvements in clinical outcomes and quality of life for people with CF. Leveraging more than a decade of the co-founders’ research on NBD1, Sionna is advancing a pipeline of small molecules engineered to correct the defects caused by the F508del genetic mutation, which resides in NBD1. Sionna is also developing a portfolio of complementary CFTR modulators that are designed to work synergistically with its NBD1 stabilizers to improve CFTR function. For information about Sionna, visit www.sionnatx.com. Sionna intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Sionna’s beliefs and expectations regarding: the initiation, timing, progress and results of Sionna’s research and development programs, preclinical studies and clinical trials, including the timing of Phase 1 topline data for SION-719 and SION-451, and the planned initiation of combination MAD trials and a Phase 2a POC trial and the timing of topline data from these trials; the ability of clinical trials to demonstrate safety and efficacy of Sionna’s product candidates; the ability of Sionna’s preclinical studies to predict later clinical trial results; financial projections and expectations regarding the time period in which Sionna’s capital resources will be sufficient to fund its anticipated operations, including cash runway, use of capital, expenses and other financial results; and other statements that are not historical facts. In some cases, the forward-looking statements can be identified by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by the forward-looking statements contained in this press release. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties inherent in the development of product candidates, including uncertainties concerning the initiation, timing, progress, and results of our planned and future clinical trials and studies; our ability to replicate positive results from earlier preclinical studies or clinical trials in current or future clinical trials; our ability to demonstrate that our NBD1 stabilizers, complementary CFTR modulators, and any potential future product candidates are safe and effective for their proposed indications; regulatory developments in the United States and foreign countries; and general economic, industry and market conditions. These risks and uncertainties are described in the section entitled “Risk Factors” in Sionna’s most recent Annual Report on Form 10-K as well as any subsequent filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. In addition, any forward-looking statements represent Sionna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Sionna explicitly disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Media Contact Adam Daley CG Life 212.253.8881 [email protected] Investor Contact Juliet Labadorf [email protected]

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 healthy volunteers in the second half of 2025, with topline data for both anticipated in mid-2026 Completed upsized IPO with gross proceeds of approximately $219 million, extending runway into 2028 WALTHAM, Mass., March 20, 2025 (GLOBE NEWSWIRE) -- Sionna Therapeutics, Inc. (Nasdaq: SION), a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, today reported financial results for the fourth quarter and full year ended December 31, 2024, and provided a business update. “2024 was an excellent year for Sionna including strong clinical execution across multiple programs. Encouraging interim Phase 1 data for SION-719 and SION-451, our highly potent nucleotide-binding domain 1 (NBD1) stabilizers, showed that both candidates were generally well tolerated and achieved target exposures—reinforcing their potential to deliver meaningful clinical benefits for people with CF,” said Mike Cloonan, President and Chief Executive Officer of Sionna. “Building on this momentum, we successfully completed an upsized IPO, a significant milestone that extends our cash runway into 2028 and provides financial and strategic flexibility. 2025 is off to a strong start with the consummation of the IPO and the progression of the Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) trials for SION-719 and SION-451. We look forward to announcing topline data in the first half of this year and initiating our Phase 2a proof-of-concept (POC) trial and the combination MAD Phase 1 program later this year.” Pipeline Updates NBD1 Stabilizers Phase 1 MAD advancement: Sionna has completed dosing in the MAD part of the Phase 1 healthy volunteer trial of SION-451 and the final MAD cohort of SION-719 is planned. The additional completed cohorts since Sionna reported interim Phase 1 data evaluated 225 mg and 25 mg (fed) of SION-451 and 160 mg of SION-719, dosed twice daily (BID) over 10 days. The final MAD cohort for SION-719 will evaluate 120 mg BID. All MAD data, including from the recently completed cohorts, remain blinded to individual subject treatment assignment. Both compounds were generally well tolerated in these additional completed cohorts. There were no serious adverse events (SAEs), and most treatment emergent adverse events (TEAEs) were mild to moderate. There were no TEAEs related to liver function tests and no TEAEs that led to discontinuation of trial drug. Part C of both trials, in which Sionna is evaluating the effect of food on the pharmacokinetics (PK) of each product candidate and the bioequivalence of a tablet formulation is ongoing. Topline data from both trials are expected in the first half of 2025. Encouraging Phase 1 Interim Data: Sionna previously reported encouraging Phase 1 interim data from the completed SAD part and three cohorts of the MAD part of each Phase 1 trial of SION-719 and SION-451 in healthy subjects. As of the data cutoff date of January 14, 2025, both SION-719 and SION-451 were generally well tolerated at all administered dose levels, achieving target exposures that have the potential, based on Sionna’s preclinical cystic fibrosis human bronchial epithelial (CFHBE) model, to provide clinically meaningful benefit to patients if SION-719 or SION-451 were administered as part of a dual combination with one of Sionna’s complementary modulators or as an add-on to the current standard of care (SOC). Phase 2a Proof-of-Concept Trial: Sionna plans to initiate a Phase 2a POC trial in the second half of 2025, after completion of a drug-drug interaction trial, to evaluate an NBD1 stabilizer in combination with the current SOC in CF patients. Topline data from this trial are anticipated in mid-2026. Combination MAD Trials: Sionna plans to initiate combination MAD trials in the second half of 2025, evaluating dual combinations of an NBD1 stabilizer with galifactor (SION-2222), a transmembrane domain 1 (TMD1)-directed CFTR corrector and/or SION-109, an intracellular loop 4 (ICL4)-directed CFTR corrector, in healthy subjects. Topline data are expected in mid-2026. Complementary Modulators Successful Completion of Phase 1 Trial for SION-109: In December 2024, Sionna completed a Phase 1 clinical trial of SION-109 in healthy subjects. SION-109 was generally well tolerated at all dose levels administered and its target exposure as part of a dual combination with SION-451 or SION-719 was achieved with both single and multiple doses. Business Highlights Completion of Upsized IPO: In February 2025, Sionna completed its upsized IPO, raising approximately $219 million gross proceeds before deducting underwriting discounts and commissions and other expenses. Sionna issued 12,176,467 shares of its common stock at a public offering price of $18.00 per share, which included 1,588,234 shares issued upon the full exercise by the underwriters of their option to purchase additional shares of common stock in the offering. Shares began trading on the Nasdaq Global Market on February 7, 2025, under the symbol “SION.” Strengthened Leadership: Sionna enhanced its Board of Directors with the appointments of Laurie Stelzer, Marcella Kuhlman Ruddy, M.D., and Jo Viney, Ph.D., who collectively bring decades of leadership experience in the biopharmaceutical industry, further supporting Sionna’s strategic growth and innovation. Financial Results for the Quarter and Year Ended December 31, 2024 Research and Development Expenses: Research and development expenses were $14.3 million for the fourth quarter of 2024 and $57.3 million for the year ended December 31, 2024, compared to $9.9 million and $40.6 million, respectively, for the same periods of 2023. These increases were mainly driven by direct program spend to support Sionna’s clinical pipeline. In 2024, Sionna licensed three clinical-stage assets, galicaftor (SION-2222), navocaftor (SION-3067) and SION-2851, from AbbVie Global Enterprises LTD, which resulted in the recognition of in-process research and development expenses of $13.6 million, which consisted of a $5.0 million upfront payment and $8.6 million of non-cash expense. General and Administrative Expenses: General and administrative expenses were $3.9 million for the fourth quarter of 2024 and $13.3 million for the year ended December 31, 2024, compared to $2.7 million and $9.7 million, respectively, for the same periods of 2023. The increase was primarily due to personnel-related costs, including stock-based compensation, and professional fees. Net Loss: Net loss was $15.8 million for the fourth quarter of 2024 and $61.7 million for the year ended December 31, 2024, compared to a net loss of $11.9 million and $47.3 million, respectively, for the same periods of 2023. Cash and Cash Equivalents: Cash, cash equivalents and marketable securities totaled $168.0 million as of December 31, 2024. This balance excludes net proceeds from our IPO of $199.6 million after deducting underwriting discounts and commissions and other offering costs. With the net IPO proceeds, Sionna expects its current cash position to fund operations into 2028. About Sionna Therapeutics Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for CF by developing novel medicines that normalize the function of the CFTR protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide-binding domain 1 (NBD1), which Sionna believes is central to potentially unlocking dramatic improvements in clinical outcomes and quality of life for people with CF. Leveraging more than a decade of the co-founders’ research on NBD1, Sionna is advancing a pipeline of small molecules engineered to correct the defects caused by the F508del genetic mutation, which resides in NBD1. Sionna is also developing a portfolio of complementary CFTR modulators that are designed to work synergistically with its NBD1 stabilizers to improve CFTR function. For more information about Sionna, visit www.sionnatx.com. Sionna intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Sionna’s beliefs and expectations regarding: the initiation, timing, progress and results of Sionna’s research and development programs, preclinical studies and clinical trials, including the timing of Phase 1 topline data for SION-719 and SION-451, and the planned initiation of combination MAD trials and a Phase 2a POC trial; the ability of clinical trials to demonstrate safety and efficacy of Sionna’s product candidates; the ability of Sionna’s preclinical studies to predict later clinical trial results; financial projections and expectations regarding the time period in which Sionna’s capital resources will be sufficient to fund its anticipated operations, including cash runway, use of capital, expenses and other financial results; and other statements that are not historical facts. In some cases, the forward-looking statements can be identified by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by the forward-looking statements contained in this press release. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties inherent in the development of product candidates, including uncertainties concerning the initiation, timing, progress, and results of our planned and future clinical trials and studies; our ability to replicate positive results from earlier preclinical studies or clinical trials in current or future clinical trials; our ability to demonstrate that our NBD1 stabilizers, complementary CFTR modulators, and any potential future product candidates are safe and effective for their proposed indications; regulatory developments in the United States and foreign countries; and general economic, industry and market conditions. These risks and uncertainties are described in the section entitled “Risk Factors” in Sionna’s most recent Annual Report on Form 10-K as well as any subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. In addition, any forward-looking statements represent Sionna’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Sionna explicitly disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Media Contact Adam Daley CG Life 212.253.8881 [email protected] Investor Contact Juliet Labadorf [email protected]