Company Overview - Sionna Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing novel medicines to treat cystic fibrosis (CF) by normalizing 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 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 synergistically [3] Upcoming Events - Management will present at the Guggenheim Securities Emerging Outlook: Biotech Summit 2026 on February 11, 2026, at 2:00 p.m. ET [1] - A live webcast of the presentation will be available on Sionna's Investor Relations website, with a replay accessible after the event [2]

PresentationGood morning, everybody. Thank you so much for joining us here on Day 2 of the JPMorgan Healthcare Conference. My name is Bhavana Balakrishnan. I am an associate with the Healthcare Investment Banking team. Thank you for joining us here for the presentation of Sionna Therapeutics. With us, we have Mike Cloonan, President and Chief Executive Officer; Elena Ridloff, Chief Financial Officer; and Charlotte McKee, Chief Medical Officer. Over to you, Mike.Michael CloonanPresident, CEO & Director Thank ...

Summary of Sionna Therapeutics FY Conference Call Company Overview - **Company**: Sionna Therapeutics (NasdaqGM:SION) - **Industry**: Cystic Fibrosis (CF) Treatment - **Founded**: Late 2019, as a spinout from Sanofi - **Mission**: To revolutionize CF treatment using first-in-class NBD1 stabilizers Key Points and Arguments Unmet Need in Cystic Fibrosis - Despite advancements, a significant unmet need remains in CF treatment, particularly in achieving normal CFTR protein function - Only one-third of patients on standard care reach normal CFTR function, indicating a large opportunity for improvement [4][26] Market Opportunity - The CF market is currently valued at $12 billion and is projected to exceed $15 billion by 2030 [4] - Sionna aims to disrupt this market with novel therapies targeting NBD1, which has been historically considered an undruggable target [5][9] NBD1 Target - NBD1 is crucial for correcting CFTR protein function, and Sionna's approach is to stabilize NBD1, which no approved modulators currently do [5][8] - The company has multiple clinical assets targeting NBD1, with promising preclinical data suggesting potential for significant efficacy improvements [9][10] Pipeline Development - **Lead Compounds**: SION-719 and SION-451, both NBD1 stabilizers, have shown positive Phase 1 data and are advancing to Phase 2A studies [10][12] - SION-719 is in a Phase 2A proof-of-concept study called the Precision CF Study, with expected data by mid-2026 [11][19] - SION-451 is being tested in a dual combination study with complementary mechanisms, also expected to yield data in mid-2026 [20][21] Clinical Strategy - The Precision CF Study aims for a clinically meaningful improvement of at least 10 millimoles in sweat chloride, which correlates with a 3% improvement in FEV1 [22][24] - The study design is efficient, requiring fewer than 20 patients, and each patient acts as their own control [22] Competitive Landscape - Current standard of care, Trikafta, has shown significant improvements but still leaves many patients below normal CFTR function [26] - Sionna's approach aims to provide additional options for the two-thirds of patients not achieving normal function, thus addressing a critical gap in treatment [26] Financial Position - Sionna ended Q3 with $325 million in cash, providing a runway into 2028, which supports ongoing development and upcoming milestones [42] Future Outlook - The company is well-positioned to transform CF treatment with its innovative approach and has a strong team and capital to support its strategy [27][45] - Upcoming data releases in mid-2026 are anticipated to validate the efficacy of NBD1 stabilization and its potential impact on CF treatment [44][45] Additional Important Content - The company emphasizes the importance of patient feedback in determining what constitutes a clinically meaningful improvement in CF treatment [24] - Sionna's strategy includes the potential to co-position both the add-on and dual combination therapies in the market, maximizing commercial opportunities [31][32] - The historical challenges in targeting NBD1 are acknowledged, with Sionna leveraging extensive research and development to overcome these hurdles [39][40]

Company Overview - Sionna Therapeutics has a market capitalization of $1.62 billion and a net income of -$70.68 million for the trailing twelve months (TTM) [4] - The company's stock has experienced a 1-year price change of 45.36%, calculated using January 12, 2025, as the reference date [4] Insider Transactions - On December 5, 2025, Chief Legal Officer Jennifer Fitzpatrick exercised 10,250 options and sold the resulting shares for a total transaction value of $415,330, with a weighted average purchase price of $40.52 per share [1][2] - Following this transaction, Fitzpatrick holds no directly owned shares but retains 61,185 outstanding options, which may provide future exposure contingent on vesting and exercise conditions [6] Market Performance - The shares were sold at a price modestly above the market close of $40.29 on December 5, 2025, and the current price as of January 12, 2026, is $36.34 [6] - The company has been active in insider transactions, with at least five different insiders conducting transactions recently [8] Business Focus - Sionna Therapeutics specializes in researching and developing pharmaceutical medicine targeting cystic fibrosis, with no current revenue but potential revenue from future product commercialization or licensing [7] - The company is optimistic about its clinical strategies to combat cystic fibrosis and claims to have strong financial support for development through 2028 [9]

Core Insights - Sionna Therapeutics, Inc. 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 at the 44th Annual J.P. Morgan Healthcare Conference on January 13, 2026 [1] 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 advancing a pipeline of small molecules designed to correct defects caused by the F508del genetic mutation, which affects NBD1 [3] - Sionna is also developing complementary CFTR modulators to work synergistically with its NBD1 stabilizers to enhance CFTR function [3] Investor Relations - Sionna plans to use its Investor Relations website for disclosing material nonpublic information and complying with Regulation FD [4] - Investors are encouraged to monitor the Investor Relations website along with press releases, SEC filings, public conference calls, presentations, and webcasts for updates [4]

Core Insights - The transaction involving Advisors LLC Orbimed's sale of 33,356 shares of Sionna Therapeutics was primarily driven by the remaining share capacity, as their indirect holdings have significantly decreased in 2025, limiting further large-scale disposals [1][5]. Company Overview - Sionna Therapeutics is a clinical-stage biotechnology company focused on developing innovative treatments for cystic fibrosis, utilizing a specialized approach to CFTR modulation to address unmet medical needs in this patient population [7]. Transaction Details - The sale of 33,356 shares was valued at $1,486,009.80 and was executed on December 24, 2025, through indirect holdings attributed to OrbiMed Private Investments VIII, LP, with no direct ownership involved [5][6]. - This transaction represented 0.93% of Advisors LLC Orbimed's indirect holdings, indicating a structured approach to selling as their holdings near exhaustion [4][5]. Market Context - The size of the sale aligns with the median size of recent open-market sales, suggesting a continued pattern of structured, incremental block sales [3][5]. - Despite the sale, Advisors LLC Orbimed retains over 3.5 million shares, indicating that this transaction does not reflect a lack of confidence in Sionna Therapeutics [9]. Clinical Progress - Sionna Therapeutics raised approximately $191 million in its initial public offering in February and has made progress with its experimental treatments, including positive phase 1 results for lead candidates SION-719 and SION-451 [9][10]. - The company has initiated a phase 2 trial with SION-719 involving cystic fibrosis patients, with top-line results expected around mid-year [10].

Upgrades - CFRA upgraded Pool Corp. (POOL) to Buy from Hold with a price target of $304 [2] - Piper Sandler upgraded SEI Investments (SEIC) to Overweight from Neutral with a price target of $102, increased from $93, citing SEI as a "clear beneficiary" of the expanding alternatives landscape [2] - TD Cowen upgraded Ametek (AME) to Buy from Hold with a price target of $230, up from $180, noting that backlog remains near highs and is expected to grow [3] Downgrades - TD Cowen downgraded Janus Henderson (JHG) to Hold from Buy with a price target of $49 after the company agreed to be acquired for $7.4 billion or $49.00 per share [4] - Piper Sandler downgraded Clearwater Analytics (CWAN) to Neutral from Overweight with a price target of $24.55, down from $27, following its agreement to be acquired for $24.55 per share in cash [4] - BMO Capital downgraded Brown & Brown (BRO) to Market Perform from Outperform with a price target of $88, down from $90, due to lower consensus organic growth estimates for 2026 [5] - Evercore ISI downgraded Coty (COTY) to In Line from Outperform with a price target of $7, citing a lack of visibility on timing and catalysts for potential value unlock [6] Initiations - Oppenheimer initiated coverage of Spruce Biosciences (SPRB) with an Outperform rating and a price target of $283, supported by FDA confirmation of compelling clinical biomarker data [7] - LifeSci Capital initiated coverage of Sionna Therapeutics (SION) with an Outperform rating and a price target of $60, highlighting multiple quality shots on goal with its therapies [7] - Oppenheimer initiated coverage of Aardvark Therapeutics (AARD) with an Outperform rating and a price target of $35, noting the company's differentiated obesity franchise [7] - JonesResearch initiated coverage of Septerna (SEPN) with a Buy rating and a price target of $43, forecasting $2.5 billion in unadjusted U.S. peak sales in 2035 [7] - Loop Capital initiated coverage of Malibu Boats (MBUU) with a Buy rating and a price target of $34, indicating the marine industry is in the late stages of inventory rationalization [7]

Core Insights - The company, Sionna, is focused on developing treatments for cystic fibrosis (CF) by targeting a differentiated and previously considered undruggable target known as NBD1 [3] Company Overview - Sionna aims to transform the standard of care in cystic fibrosis, with NBD1 as the central element of its strategy [3] - The company has recently initiated a Phase IIa proof-of-concept study for its NBD1 stabilizer, SION-719, which will be tested in conjunction with TRIKAFTA, the current standard of care [4]

Financial Data and Key Metrics Changes - The company raised $219 million in its IPO in February, providing financial flexibility to execute its strategy through 2028 [7] - The company entered Q3 with $325 million in cash, ensuring a cash runway into 2028 [47] Business Line Data and Key Metrics Changes - The company is focused on cystic fibrosis (CF) and is developing two NBD1 stabilizers: SION-719 for an add-on approach and SION-451 for a dual combination strategy [5][6] - The goal is to improve CFTR function in patients, with a target of achieving at least a 10 millimole per liter change in sweat chloride as a primary endpoint in clinical studies [30][69] Market Data and Key Metrics Changes - The CF market is currently valued at $12 billion and is expected to grow to $15 billion [12] - The company aims to create more treatment options for the approximately 85%-90% of CF patients with the F508del mutation, as two-thirds of patients on standard care do not achieve normal CFTR function [16][19] Company Strategy and Development Direction - The company is pursuing a differentiated approach to CF treatment by targeting the NBD1 protein, which has been considered undruggable [4][10] - The strategy includes a dual combination approach to potentially provide meaningful clinical benefits above the current standard of care, which is a triple combination therapy [6][12] - The company is open to exploring new therapeutic areas in the future but is currently focused solely on CF [50][51] Management's Comments on Operating Environment and Future Outlook - Management believes that the current modulators have not fully addressed the unmet needs in CF, as many patients still do not achieve normal CFTR function [16] - The company is confident in its ability to leverage its historical research and partnerships, particularly with the Cystic Fibrosis Foundation, to advance its clinical studies [65][66] - Management emphasized the importance of patient access in pricing strategies, aiming to ensure that new therapies are accessible to patients [60] Other Important Information - The company has licensed three compounds from AbbVie, enhancing its portfolio with clinical data and complementary mechanisms [42][44] - The company is conducting a healthy volunteer phase 1 study for its dual combination strategy, which is expected to inform future development [38][40] Q&A Session Summary Question: What is the company's approach to addressing unmet needs in CF? - The company aims to improve CFTR function and believes that NBD1 stabilization is key to moving more patients to normal CFTR function [16][19] Question: How does the company plan to differentiate its products in the market? - The company is focused on improving efficacy through its dual combination strategy and leveraging historical data to predict clinical outcomes [67][70] Question: What is the expected timeline for clinical data? - The company anticipates data from its phase 2a proof of concept study in mid-2026, which will be crucial for future development decisions [5][30]

Financial Data and Key Metrics Changes - The company raised $219 million in its IPO in February 2025, providing financial flexibility to execute its strategy through 2028 [7] - As of Q3, the company reported having $325 million in cash, ensuring a cash runway into 2028 [46] Business Line Data and Key Metrics Changes - The company is focused on developing two NBD1 stabilizers: SION-719 for an add-on approach to the standard of care and SION-451 for a dual combination strategy [5][6] - The company aims to demonstrate a clinically meaningful improvement of at least 10 millimoles per liter in sweat chloride, which is expected to correlate with a 3-point improvement in FEV1 [34][35] Market Data and Key Metrics Changes - The cystic fibrosis market is currently valued at $12 billion and is projected to grow to $15 billion [12] - The company targets the same patient population as the standard of care, focusing on the F508del mutation, which affects 85%-90% of cystic fibrosis patients [19] Company Strategy and Development Direction - The company aims to transform the standard of care in cystic fibrosis by focusing on the NBD1 target, which has been historically considered undruggable [4][10] - The dual combination strategy is prioritized, with the goal of raising the efficacy bar through innovative combinations of therapies [6][12] Management's Comments on Operating Environment and Future Outlook - Management believes that there is a significant unmet need in the cystic fibrosis community, as two-thirds of patients on standard care do not achieve normal CFTR function [16] - The company is optimistic about its clinical development strategy and the potential to improve patient outcomes significantly [70] Other Important Information - The company has licensed three compounds from AbbVie, enhancing its portfolio with clinical data and complementary mechanisms [41][42] - The Therapeutics Development Network (TDN) of the Cystic Fibrosis Foundation is a key partner, providing access to a well-organized research network [65][66] Q&A Session Summary Question: What is the company's strategy for addressing the unmet needs in cystic fibrosis? - The company aims to improve CFTR function in patients who are currently on standard care but do not achieve normal function, focusing on the NBD1 stabilization approach [16][19] Question: How does the company plan to differentiate its products in the market? - The company plans to leverage its unique dual combination strategy and the historical data from its assays to demonstrate improved efficacy compared to existing therapies [6][70] Question: What are the expected timelines for clinical data? - The company anticipates data from its phase 2a proof of concept study in mid-2026, which will be crucial for informing future development and capital raising decisions [5][29]