Elexacaftor/Ivacaftor/Tezacaftor

Post hoc analyses of SION-719 PreciSION CF subset showed a mean placebo-adjusted sweat chloride reduction of up to -8.6 mmol/L consistent with NBD1 biological activity Dual combination Phase 2a trial expected to initiate in first quarter of 2027 46% workforce reduction and other cost-saving measures prioritize advancing the dual combination program and extend cash runway into the second half of 2029 Sionna to host conference call today at 4:30 p.m. ET WALTHAM, Mass., Sept. 14, 2026 (GLOBE NEWSWIRE) -- Sionna Therapeutics, Inc. (Nasdaq: SION), a clinical-stage biopharmaceutical company on a mission to develop novel medicines for cystic fibrosis (CF), today announced plans to advance SION-451 + SION-2222, its preferred proprietary dual combination, into the AscenSION CF Phase 2a proof-of-concept (POC) trial, and results from the company’s post hoc analysis of the PreciSION CF Phase 2a trial. The decision to advance SION-451 + SION-2222 follows an extensive review of clinical, pharmacokinetic (PK) and nonclinical data from PreciSION CF. Learnings from that trial and the previous Phase 1 dual combination trial will inform the development strategy for the dual combination. “It was important for us to take the time to complete a comprehensive post hoc data analysis to better understand the SION-719 PreciSION CF trial results and their potential implications before determining the right path forward for our dual combination,” said Mike Cloonan, President and Chief Executive Officer of Sionna. “The analysis identified important factors that we believe complicated interpretation of the trial and may have blunted the impact of NBD1 stabilization. The post hoc findings, together with the favorable Phase 1 results for SION-451 + SION-2222, support advancing the dual combination into Phase 2a. We have been inspired by the CF community, whose voices continue to reinforce the need for new treatment options.” “Despite the substantial progress made, there remains a significant need for new options for people with CF,” said Gregory S. Sawicki, M.D., M.P.H., Director of the Cystic Fibrosis Center at Boston Children's Hospital and Associate Professor of Pediatrics at Harvard Medical School. “Directly stabilizing NBD1 continues to represent a differentiated approach to addressing the underlying biology of CF. I’m excited to see Sionna proceed with a Phase 2a trial of SION-451 + SION-2222, which will be an important next step in further exploring whether the NBD1 biology can translate into meaningful benefit for people with CF.” Post Hoc Analysis of SION-719 PreciSION CF Phase 2a Clinical Trial PreciSION CF Phase 2a ( NCT07108153 ) was a randomized, double-blind, placebo-controlled, crossover trial that evaluated the safety and tolerability of SION-719 when added to Trikafta ® in 15 adult participants with CF homozygous for F508del. Change in sweat chloride, an important measure of CFTR function, was the key activity endpoint. As previously announced , the trial did not achieve its key activity endpoint, and Sionna is not advancing SION-719 as an add-on to SOC. Following the announcement of topline results, Sionna conducted a comprehensive analysis of the clinical, PK, and nonclinical data to better understand the PreciSION CF outcome, including implications for the NBD1 mechanism and the SION-451 + SION-2222 dual combination. The primary analysis in the trial assessed placebo-adjusted sweat chloride change using Day 1 as baseline. A prespecified secondary analysis assessed placebo-adjusted sweat chloride change using the baseline measured at the start of each treatment period. Across the 14 evaluable participants, results were similar under both methodologies, with placebo-adjusted sweat chloride changes of -1.0 mmol/L in the primary analysis and -1.1 mmol/L in the secondary analysis. The post hoc analysis identified three factors that may have confounded the observed treatment effect: PK outliers: Three participants had drug exposures (one with SION-719 and two with the components of Trikafta (elexacaftor/tezacaftor/ivacaftor; ETI) at key timepoints consistent with non-adherence. Excluding these confounded participants resulted in mean placebo-adjusted sweat chloride change of -8.6 mmol/L using the secondary analysis of baseline measured at the start of each treatment period. The Company believes the secondary analysis to assess sweat chloride best accounts for variability observed between treatment periods. Trikafta Exposure Levels: ETI exposures were lower during SION-719 treatment periods, with mean exposures of all three components declining by approximately 25-30% on average while remaining relatively stable during placebo periods. CFTR Channel Biology: Post hoc analysis of preclinical CFHBE assay data suggests that the interaction between an NBD1 stabilizer, like SION-719, and a potentiator, like ivacaftor, may have blunted the additional benefit of NBD1 stabilization. This interaction is not observed when an NBD1 stabilizer is combined with complementary correctors targeting TMD1 or ICL4. Sionna believes these analyses suggest that SION-719 was biologically active in the trial, but that PK outliers and complex interactions between SION-719 and Trikafta may have affected the observed outcome and blunted a potential treatment signal. SION-451 + SION-2222 Dual Combination Phase 2 Development Plan Sionna plans to advance SION-451 + SION-2222 into the AscenSION CF Phase 2a POC trial. The Company continues to believe that directly stabilizing NBD1 in combination with a complementary CFTR modulator has the potential to meaningfully improve CFTR function. The AscenSION CF POC will be an open-label trial evaluating adults with CF homozygous for F508del treated with SION-451 + SION-2222 for 28 days. Participants will switch from Trikafta to SION-451 + SION-2222, and the trial will assess sweat chloride, safety, and PK. The design will incorporate key learnings from PreciSION CF with respect to dosing adherence and sweat chloride variability, and the trial is expected to initiate in the first quarter of 2027. The decision to advance SION-451 + SION-2222 is supported by results from the Phase 1 healthy volunteer trial of SION-451-based dual combinations, for which the Company announced topline results on August 10, 2026. The trial achieved its safety, tolerability, and PK objectives. SION-451 + SION-2222 was identified as the preferred dual combination based on target exposure coverage, and the go-forward SION-451 twice daily (BID) + SION-2222 once daily (QD) regimen demonstrated a favorable tolerability profile. Phase 1 exposures of the planned doses were within the range associated with meaningful improvement in CFTR function in Sionna’s CFHBE assay. Corporate Update Following the completion of a comprehensive review of its operations, Sionna’s Board of Directors has approved a workforce reduction of approximately 46% and the Company has implemented other cost-saving measures to focus its resources on advancing SION-451 + SION-2222 and extend its operating runway. Sionna expects to retain the core clinical, scientific, regulatory, technical, and corporate capabilities required to advance the dual combination program. The Company currently estimates it will incur aggregate restructuring and related charges of approximately $6.4 million. Sionna ended Q2 2026 with approximately $268.3 million in cash, cash equivalents, and marketable securities. The Company estimates that the workforce reduction, discontinuation of investment in SION-719 as an add-on to standard of care, and other cost-saving measures will extend its cash runway into the second half of 2029. Webcast Details Sionna Therapeutics’ live webcast will begin at 4:30 p.m. ET today, September 14th, 2026, and can be accessed via this link . Participants who prefer to listen via telephone, or ask a question, may register on Sionna’s Investor Relations website or by clicking here . A replay will be available on the “Events” page in the “Investors” section of Sionna's website at . 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 meaningful improvements in clinical outcomes and quality of life for people with CF. For more information about Sionna, visit . 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; its interpretation of the results of the PreciSION CF trial and the impact of potential confounding factors on the interpretation of those results; the potential for NBD1 stabilization to improve CFTR function and produce clinical benefit, including beliefs about biological activity of SION-719 in PreciSION CF and the translatability of preclinical and in vitro assay data to clinical outcomes; the objectives, design, timing, initiation and conduct of a planned Phase 2a proof-of-concept trial of SION-451 + SION-2222; the therapeutic potential, clinical benefits and safety of SION-451 + SION-2222; the expected timing, scope, costs and benefits of the workforce reduction and other cost-saving measures; the Company’s ability to retain the capabilities and personnel needed to advance SION-451 + SION-2222 and operate as a public company; the Company’s expected cash runway; and other statements that are not historical facts. In some cases, 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 are based on management’s current expectations and beliefs and are subject to risks, uncertainties and important factors that may cause actual events or results to differ materially, including uncertainties inherent in developing product candidates; interpreting the PreciSION CF results and potential confounding factors; the inherent limitations of post hoc analyses, which are exploratory and may not reliably predict future outcomes; the risk that in vitro and preclinical data may not translate to clinical benefit; the risk that results observed with one compound may not be predictive of results with a different compound or combination; and designing and conducting the planned Phase 2a trial. Additional risks include the Company’s ability to demonstrate that its candidates are safe and effective; obtain regulatory feedback or approvals; achieve anticipated restructuring savings and runway extension; retain key personnel and capabilities following the workforce reduction; secure sufficient funding; and respond to general economic, industry and market conditions. These risks and uncertainties are described in “Risk Factors” in Sionna’s most recent Quarterly Report on Form 10-Q and subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. 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 disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties, express or implied, are made about the accuracy of any such forward-looking statements. Media Contact Sarah Spencer media@sionnatx.com Investor Contact Juliet Labadorf ir@sionnatx.com

如果不卖股权，不借利息，还能怎么融资？一家成立近30年、累计部署资本超300亿美元的公司，用“药品特许权”给出了答案。 在生物医药这个高投入、长周期、高风险的领域，传统的股权融资和债务融资往往难以兼顾研发者的利益与资金需求。而一家名为Royalty Pharma的公司，通过“收入分成融资”的独特模式，在过去近30年里悄然成为全球生物制药行业最重要的资本力量之一。什么是Royalty Pharma？ Royalty Pharma成立于1996年，由Pablo Legorreta在纽约创立，是全球最大的生物制药特许权买家，也是生命科学领域创新的主要投资者。2020年6月，它在纳斯达克上市，股票代码为RPRX。 简单来说，Royalty Pharma的业务模式是：向生物制药公司、学术机构、研究医院等提供前期资金，以换取其药品未来销售收入的“特许权”（royalty）。 截至2026年，Royalty Pharma已累计投入超过300亿美元资本，完成了超过80项特许权收购交易，占全球生物制药特许权交易市场的50%以上，拥有超过60%的全球市场份额。商业模式：如何运作“药品特许权”融资？ Royalty Pharma的商业模式可以理解为一种基于收入的融资（Revenue-Based Financing, RBF），但它的特殊之处在于，投资的标的物是已上市或接近上市的生物医药产品。 两种主要方式： 直接合作：与生物制药公司合作，共同资助晚期临床试验和新药上市项目，以换取未来的特许权收入。 间接收购：从原始创新者（如大学、研究医院、非营利组织）手中购买现有的特许权权益。 关键区别：与传统风投或私募股权不同，Royalty Pharma不寻求控制被投资公司的运营，也不稀释创始团队的股权。它只是获得未来销售收入的一部分作为回报，与被投资方形成“利益共同体”。 一个生动的比喻：如果新药研发是一部电影，传统融资是投资人买下整个电影公司；而Royalty Pharma的模式是，电影拍完后，它只购买“票房分成”的权利，不干预电影制作本身。 创始人与团队 Royalty Pharma的创始人、董事长兼CEO Pablo Legorreta出生于1963年，毕业于墨西哥伊比利亚美洲大学。 公司拥有一支经验丰富的管理团队，核心成员包括：执行副总裁兼CFO Terrance P. Coyne、负责合作与投资事务的执行副总裁Greg Butz、研究与投资执行副总裁Marshall Jonathan Urist博士、以及投资与首席科学官James Folmar Reddoch博士等。里程碑事件：从小众到主流 Royalty Pharma的发展历程，就是药品特许权融资从小众走向主流的过程： 1996年，Pablo Legorreta在纽约创立Royalty Pharma，开创了药品特许权融资市场。 2004年，以2.63亿美元收购纪念斯隆凯特琳癌症中心在安进公司Neupogen/Neulasta上的特许权，标志着其大规模交易的开始。 2007年，以7亿美元从西北大学收购辉瑞Lyrica（乐瑞卡）的全球特许权，这是当时规模最大的药品特许权交易之一。 2014年，以33亿美元收购囊性纤维化基金会（CFF）在Vertex公司囊性纤维化药物组合上的特许权。这是Royalty Pharma史上最大的一笔交易，也是慈善组织获得的最大单笔财务回报之一。 2017年，以28.5亿美元收购百健（Biogen）Tysabri的特许权收益。 2020年6月，在纳斯达克上市，IPO发行价28美元，首日开盘价即飙升至44.24美元，涨幅达58%，市值达268亿美元。为什么是“收入分成融资”的典范？ Royalty Pharma的模式完美诠释了RBF的核心优势： 风险偏好与收益匹配 Royalty Pharma主要投资于已上市或晚期临床阶段的药品，而非早期研发。这意味着它投资的产品已经通过了最关键的审批风险，收入可预测性更高。截至2026年，其投资组合涵盖超过35个已上市产品和20个在研产品候选药物。 非稀释性融资 对于生物制药公司而言，与Royalty Pharma合作意味着无需放弃股权，可以在不稀释现有股东权益的情况下获得急需的资金，用于推进研发或商业化。 利益高度一致 Royalty Pharma的收入完全取决于药品的顶层销售（top-line sales）。这意味着投资方与被投资方目标完全一致：都希望药品卖得越好。这种“一条船上的蚂蚱”机制，避免了传统融资中可能出现的短期博弈。 独创的“合成特许权” Royalty Pharma还不断创新，开发了“合成特许权”等新型融资方案，为合作伙伴提供更灵活的定制化资金解决方案。投资组合：王牌产品一览 Royalty Pharma的投资组合涵盖了多个治疗领域的重磅炸弹级药物： 囊性纤维化领域：代表性产品包括Trikafta、Alyftrek、Kalydeco、Symdeko，合作方为Vertex。 免疫学领域：代表性产品为Tremfya（古塞奇尤单抗），合作方为强生（J&J）。 呼吸系统领域：代表性产品为Trelegy（氟替美维），合作方为GSK。 神经系统领域：代表性产品包括Tysabri（那他珠单抗）、Spinraza（诺西那生钠），合作方为Biogen。 血液肿瘤领域：代表性产品为Imbruvica（伊布替尼），合作方为AbbVie、强生。 前列腺癌领域：代表性产品为Xtandi（恩杂鲁胺），合作方为Astellas、辉瑞。 偏头痛领域：代表性产品为Nurtec ODT（瑞美吉泮），合作方为辉瑞。 乳腺癌领域：代表性产品为Trodelvy（戈沙妥珠单抗），合作方为吉利德（Gilead）。 脊髓性肌萎缩症领域：代表性产品为Evrysdi（利司扑兰），合作方为罗氏（Roche）。 这些产品在2024年及之后的销售额均超过10亿美元，部分甚至超过30亿美元。最新动态：持续扩张与风险管控 Royalty Pharma并未满足于现有成就。最新的动态显示，它正在积极拓展全球版图，尤其是亚洲市场： 2026年5月，任命Kenneth Sun为高级副总裁兼亚洲区负责人，常驻香港，以开拓亚洲生物医药创新者的特许权融资需求。 2026年7月，与Neurimmune达成协议，以最高4.25亿美元收购阿斯利康cliramitug的特许权权益，该药是一种针对ATTR-CM（转甲状腺素蛋白淀粉样变性心肌病）的潜在first-in-class药物。 2026年，与Zymeworks达成2.5亿美元融资协议，获得其HER2靶向药物Ziihera的特许权。 2026年，与Denali Therapeutics达成最高2.75亿美元的协议，收购其Hunter综合征药物tividenofusp alfa的特许权。 2026年8月，与Zealand Pharma达成1亿美元的rusfertide融资协议，该药用于真性红细胞增多症。 风险管控的典范案例：2026年9月，Royalty Pharma公布了诺华pelacarsen三期临床未达主要终点的消息。但Royalty Pharma此前与Ionis的5亿美元融资协议采用保护性结构设计——将资金分配到Spinraza（确定性较高的已上市产品）和pelacarsen（高风险高回报的在研产品）两部分。因此，即使pelacarsen失败，Royalty Pharma预计仍能收回总投资并获得适度正回报，同时重申了2030年投资组合收入目标为47亿美元或以上。风险与挑战 当然，Royalty Pharma的模式并非没有风险： 核心产品集中度风险：其投资组合高度依赖少数“重磅炸弹”药物，如Trikafta等。如果这些药物面临专利悬崖、竞争加剧或安全性问题，将对公司收入产生重大影响。 竞争加剧：随着药品特许权市场的成熟，越来越多的资本进入这一领域，可能导致交易价格上升、回报率下降。 利率风险：作为一家以长期现金流为核心的公司，其估值和融资成本受利率环境变化影响较大。 临床失败风险：尽管Royalty Pharma主要投资晚期或已上市产品，但仍需面对在研产品临床试验失败的风险，如pelacarsen案例所示。对RBF的启示 Royalty Pharma的成功，向整个收入分成融资领域传递了明确的信号： 标的物的确定性是RBF的核心 Royalty Pharma专注投资于“已上市”或“接近上市”的产品，这大幅降低了收入的波动性和不确定性。对于RBF行业而言，评估标的收入的可预测性远比追求高回报重要。 非稀释性是RBF的最大卖点 在生物医药这样一个需要大量资金但创始人又极度珍视控制权的领域，RBF的“非稀释性”优势被发挥到了极致。Royalty Pharma证明了，不拿股权，依然可以成为企业最重要的合作伙伴。 行业深耕胜过广撒网 Royalty Pharma专注于生物医药领域，积累了深厚的行业知识和评估能力。其拥有一支具备深厚科学背景的长期任职专家团队，并建立了覆盖临床试验分析和市场评估的独特平台。这种专业化、深耕化的策略，是其能够持续发现价值、定价风险的基础。 保护性结构设计是风控关键 Royalty Pharma在交易结构设计上极为讲究，如与Ionis的协议中将资金分配到确定性资产和风险资产两部分，确保即使高风险项目失败，整体投资仍能获得正回报。结语 Royalty Pharma用近30年的实践证明，收入分成融资（RBF）不仅是一种可行的金融创新，更是一个能够创造巨大价值的投资范式。它让生物医药公司获得了“不稀释股权”的资本，让高校和医院获得了“可立即变现”的研发资金，让投资者获得了“与药品销量挂钩”的长期回报。 对于正在探索RBF的创业者和投资者而言，Royalty Pharma的故事值得反复品味：真正的创新融资，不是简单地借钱或卖股，而是找到一种让所有参与者利益一致的交易结构，并用精妙的风险设计来守护这份信任。 发送信息到RBFA@qq.com可以获取Royalty Pharma公司20页PDF市场报告。 关于RBF商业联盟    精彩纷呈RBF商业联盟（Colorful and Wonderful RBF Association.）成立于2024年9月，发起成员涵盖学者、律师、会计师、投资机构、科技企业等，致力于搭建一个从业机构与专业人士共同交流合作的平台，推动RBF在中国的创新与发展，构建“资本-产业-数据”联动的创新生态。       欢迎RBF投资机构、专业融资顾问、生态服务机构、品牌运营方及会计、律师等专业人士加入，一起交流合作。 联盟服务： 专业交流 投融资信息发布 专业RBF方案咨询与设计 滴灌通澳交所SPAC、SPV挂牌联系方式：RBFA@qq.com/www.RBF.fund