Ampreloxetine hydrochloride

DUBLIN, March 3, 2026 /PRNewswire/ -- Theravance Biopharma, Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH) today announced topline results from the Phase 3 CYPRESS study evaluating the efficacy and safety of ampreloxetine in patients with symptomatic neurogenic orthostatic hypotension (nOH) due to multiple system atrophy (MSA), a rare disease. The study did not meet its primary endpoint in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score. As a result of this outcome, the Company has decided to wind down the ampreloxetine program. Phase 3 CYPRESS study did not meet the primary endpoint , the OHSA Composite Score, a patient reported outcome (PRO) "We are disappointed that ampreloxetine did not meet the primary endpoint in the CYPRESS study. These results are particularly disheartening for the patients who are suffering from this rare disease and were hoping for a new treatment option and for the employees who dedicated years of work to this program. I want to sincerely thank the patients, caregivers, investigators, and our team for their commitment and contributions to this effort," said Rick E Winningham, Chief Executive Officer of Theravance Biopharma. Phase 3 CYPRESS Topline Data Study Results In the Phase 3 CYPRESS study, the primary endpoint, the change in OHSA composite score at Week 8 during the double-blind randomized withdrawal period, was not statistically significant. Similar trends were observed in the secondary endpoints at week 8. Changes in blood pressure, heart rate and norepinephrine levels confirmed a consistent pressor effect and reaffirmed ampreloxetine's biological activity. Ampreloxetine was generally well tolerated, with safety findings consistent with prior studies, including no signal of worsening of supine hypertension. As the Company proceeds with the orderly wind down of the ampreloxetine program, it will complete additional analyses of the CYPRESS dataset and Phase 3 program, in consultation with external experts, to assess whether the data merits further regulatory discussion. This assessment is intended to provide the Committee with additional clarity regarding any remaining value in ampreloxetine for Theravance shareholders. There can be no assurance that any additional regulatory engagement will occur. About Ampreloxetine Ampreloxetine, an investigational, once-daily norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). About CYPRESS (Study 0197), a Phase 3 Study Study 0197 (NCT05696717) is a registrational Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment; the primary endpoint of the study is change in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score. Secondary endpoints include change from baseline in Orthostatic Hypotension Daily Activity Scale (OHDAS) composite score, OHDAS item 1 (activities that require standing for a short time) and OHDAS item 3 (activities that require walking for a short time). About Theravance Biopharma Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference ® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI ® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). The Company is committed to creating/driving shareholder value. For more information, please visit www.theravance.com. Forward-Looking Statements This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the Company's expectations regarding its future profitability, expenses and uses of cash, the Company's goals, designs, strategies, plans and objectives, future growth of YUPELRI sales and future royalty payments, the winddown of the Company's ampreloxetine program and R&D function and significant reduction of its G&A function, the consideration of strategic alternatives for the Company, the ability to provide value to shareholders, the Company's regulatory strategies, data regarding our investigational therapy, the status of patent infringement litigation initiated by the Company and its partner against certain generic companies in federal district courts, and contingent milestone payments due to the Company from the sale of the Company's TRELEGY royalty interests. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of this press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: factors that could increase the Company's expenses beyond its expectations and any factors that could adversely affect its profitability, whether the TRELEGY milestone thresholds will be achieved, delays or difficulties in winding down clinical studies, the potential that results from analysis of clinical or non-clinical studies indicate the Company's product candidates or product are unsafe, ineffective or not differentiated, risks of decisions from regulatory authorities that are unfavorable to the Company, delays or failure to achieve and maintain regulatory approvals for product candidates, the timing of any potential strategic transaction with respect to the Company, if at all, risks of collaborating with or relying on third parties to discover, develop, manufacture and commercialize products, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure, the ability of the Company to protect and to enforce its intellectual property rights, volatility and fluctuations in the trading price and volume of the Company's shares, and general economic and market conditions. Other risks affecting Theravance Biopharma are in the Company's Form 10-Q filed with the SEC on November 12, 2025, and other periodic reports filed with the SEC. In addition to the risks described above and in Theravance Biopharma's filings with the SEC, other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. SOURCE Theravance Biopharma, Inc.

$TheravanceBiopharma(TBPH)$摘要TheravanceBiopharmaInc.(NASDAQ:TBPH)是一家战略高度聚焦、已实现商业化盈利的生物制药公司。公司构建了极具韧性的“双支柱”商业模式：支柱一是成熟呼吸产品YUPELRI®，作为美国市场首个且唯一的每日一次雾化LAMA，为公司提供稳定增长的现金流与利润，专利保护至2039年；支柱二是临近爆发的神经管线核心资产Ampreloxetine，其针对多系统萎缩（MSA）所致神经源性直立性低血压（nOH）的III期关键数据（CYPRESS研究）将于2026年第一季度揭晓，有望成为该领域重磅首创疗法。公司财务基础异常稳固：截至2025年Q3，持有现金及等价物约3.33亿美元，零负债，并于当季实现非GAAP盈亏平衡。近期还有高达1.75亿美元高概率里程碑付款即将触发。公司正处在一个明确的“现金流+催化剂”价值拐点，Ampreloxetine的成功与否将决定其能否从单一产品公司跃升为双领域并重的领先者。第一部分：公司战略与核心竞争力分析1.1“精研型”商业模式解析TheravanceBiopharma摒弃了大型药企的广泛布局模式，采用了典型的“精研型”策略：疾病领域聚焦：深度专注于呼吸系统与神经系统两大领域，积累了深厚的专业知识与研发经验。管理层及研发团队均在这些领域拥有数十年成功经验。“内部研发+外部合作”双轮驱动：核心资产如YUPELRI®和Ampreloxetine均为内部自主研发，确保了公司对核心知识产权和开发节奏的完全掌控。同时，在商业化（如与Viatris合作推广YUPELRI®）及部分资产货币化（如向RoyaltyPharma出售TRELEGYroyaltyinterest）上灵活借助外部力量，优化资本效率。从“科研概念”到“商业验证”的全周期能力：公司官网与资料中强调“DemonstratedSuccessinAdvancingIn-HouseDevelopedAssetsthroughApprovalandSuccessfulCommercialization”，证明了其具备从早期发现、临床开发到最终成功商业化的完整能力闭环。第二部分：核心产品线深度剖析2.1现金流支柱：YUPELRI®(revefenacin)–雾化COPD治疗的基石2.1.1产品定位与临床价值YUPELRI是一种长效毒蕈碱受体拮抗剂，对多种毒蕈碱受体亚型（M1至M5）具有相似的亲和力，可抑制肺部气道周围的M3受体，从而产生药理作用，引起支气管扩张。该药由TheravanceBiopharma和Mylan联合研发，最初于2018年11月在美国获准用于治疗成人慢性阻塞性肺病，是首款获得美国FDA批准的每日一次雾化型长效毒蕈碱受体拮抗剂。其临床价值在于解决了COPD治疗中的一个关键痛点：患者依从性与器械使用能力。目标患者画像：约28%的MedicareCOPD患者使用雾化器。YUPELRI®精准定位于那些因认知障碍、手部灵活性下降、吸气流速不足或手-呼吸协调困难而无法有效使用手持吸入器的患者。市场调研显示，约150万美国患者属于此列。差异化优势：每日一次的雾化治疗无需复杂操作，护理人员可协助，确保了给药的有效性。临床数据显示，其能提供持续24小时的支气管扩张作用，且安全性良好。2.1.2商业表现与增长动力YUPELRI®自2019年上市以来，净销售额持续增长，2025年Q3美国净销售额达7140万美元，同比增长15%。增长驱动力来自：1.医院市场渗透：作为关键起点，超过80%在医院使用YUPELRI®的患者在出院时获得处方。公司在医院市场份额已达21%。2.患者转换：大多数新患者来自从手持吸入器转换过来的患者，他们主要因灵活性和认知问题而转换。3.市场教育：在CHEST2025等学术会议上发布的新证据，进一步强化了其临床地位。2.1.3专利护城河与竞争格局公司为YUPELRI®构建了坚实的专利壁垒：化合物专利：2028年到期。晶型专利：2030-2031年到期。关键方法专利：将市场独占期保护至2039年。尽管面临仿制药挑战，但公司已与8家ANDA申报者中的7家达成和解，授权其最早在2039年4月进入市场。这实质上将YUPELRI®的商业独占期延长了超过8年，提供了罕见的长周期收入可见性。2.2价值增长引擎：Ampreloxetine–瞄准罕见神经疾病未满足需求2.2.1疾病基础：高负担的MSA与nOH多系统萎缩症（MSA）是一种快速进展、致命的神经退行性疾病。约80%的MSA患者受神经源性直立性低血压（nOH）困扰，导致站立时头晕、眩晕甚至晕厥，严重损害日常生活能力与生活质量。当前疗法（米多君、屈昔多巴）存在疗效不持久、有卧位高血压黑框警告、需每日多次服药等局限，存在巨大未满足需求。2.2.2药物机制与开发逻辑Ampreloxetine是一种高选择性、高亲和力的去甲肾上腺素再摄取抑制剂（NRI）（PDF第56页）。其开发基于精妙的病理生理学洞见：MSA患者的中枢自主神经元受损，但外周交感神经末梢相对保留。通过抑制去甲肾上腺素的再摄取，Ampreloxetine可增强外周交感神经信号，精准提升站立血压，而对卧位血压影响较小，从而避免了现有疗法的主要安全隐患。2.2.3临床开发路径与关键数据分析早期临床验证：在早期的REDWOOD研究（Study0170）中，针对MSA患者亚组的预设分析显示，Ampreloxetine在主要终点OHSA综合评分上产生了具有临床意义的1.6分改善（p<0.05）。同时，站立收缩压显著改善（提高约15.7mmHg），且未观察到卧位高血压恶化的信号。关键III期CYPRESS研究设计：这是一项针对纯MSA患者的随机撤药研究。设计上充分吸取了前期经验，优化了成功概率：人群精准：仅纳入MSA患者，确保同质性。终点明确：采用FDA认可的OHSA综合评分作为主要终点。设计灵敏：采用随机撤药设计，先进行开放标签治疗，对有效的患者进行随机化，能更灵敏地检测药物维持疗效的能力。监管路径：已获得FDA孤儿药认定，并与FDA就III期试验设计和注册路径达成一致，降低了监管不确定性。2.2.4市场潜力与商业化准备市场规模：公司通过详尽的索赔数据分析，估算美国约有4万名MSA患者受nOH困扰。这些患者集中于少数自体神经和运动障碍诊疗中心，便于高效商业化。定价潜力：参考近年罕见病慢性疗法年均治疗费用，Ampreloxetine有望定位于高端。支付方访谈显示，其对能解决nOH所致跌倒、住院等重大负担的创新疗法持开放态度。商业化策略：计划采用精简的、针对罕见病的“靶向”营销模式，聚焦约100-200个高诊疗量的核心医疗中心和专科医生，以极低的销售费用实现快速渗透。第三部分：财务现状与前景建模3.1历史财务表现深度解读公司已成功转型为盈利实体：收入增长：2025年Q3总收入1999万美元，主要来自Viatris合作。YUPELRI®销售增长是驱动力。费用控制：2025年Q3，剔除股权激励的研发和SG&A费用合计2187万美元，同比保持稳定，显示了严格的成本控制。盈利转折点：2025年Q3，按GAAP准则实现净利润362万美元（去年同期亏损1270万美元）；按非GAAP准则实现净利润226万美元（去年同期亏损290万美元）。这标志着公司跨过了关键的盈亏平衡门槛。3.2资产负债表与现金流分析强劲的现金状况：截至2025年Q3末，现金及等价物3.327亿美元，无任何债务。这为公司运营和潜在业务发展提供了至少数年的安全垫。高确定性未来现金流：1.近期里程碑：来自TRELEGY的1.5亿美元和YUPELRI®的2500万美元里程碑付款，在2025/2026年触发的可能性极高。2.持续经营现金流：来自YUPELRI®的35%美国利润分成，预计将持续增长并产生稳定现金流。3.3未来财务预测与情景分析基于公开信息，我们可以构建一个简化的财务前景框架：第四部分：风险因素与综合评估4.1主要风险量化分析1.Ampreloxetine临床失败风险（高风险）：III期临床试验本身具有不确定性。尽管设计优化，但若主要终点未达到统计学显著性，将导致该资产价值归零，是公司面临的最大风险。2.商业化执行风险（中等风险）：即使获批，Ampreloxetine在罕见病市场的定价、医保准入和医生采纳速度可能不及预期。公司需证明其精简团队能有效触达分散的专科医生。3.YUPELRI®竞争与专利风险（中低风险）：长期看，2039年后将面临仿制药冲击。短期看，需应对其他新型COPD疗法（如生物制剂、双靶点抑制剂）的竞争，但其在特定患者群体中的优势地位预计可维持。4.财务与运营风险（低风险）：当前现金充裕，但若Ampreloxetine开发费用超预期或YUPELRI®增长放缓，可能影响其实现持续盈利的时间表。5.合作方依赖风险（低风险）：YUPELRI®的美国利润依赖于与Viatris的合作关系，虽然协议稳固，但任何合作波动都可能影响收入。4.2投资亮点总结1.清晰的“现金流+催化剂”模型：稳健的YUPELRI®业务为高风险、高回报的Ampreloxetine提供了财务保障和时间窗口。2.临近的重磅催化剂：2026年Q1的III期数据读出是明确的股价催化事件，可能带来巨大的上行空间。3.强大的财务安全垫：巨额现金、零负债、临近的里程碑付款，极大降低了投资的下行风险。4.高壁垒的商业模式：在细分领域拥有专利保护的市场独占产品和基于独特生物学见解的潜在首创疗法。5.明确的管理层承诺：承诺将超额资本返还股东，体现了资本配置的股东友好导向。4.3结论与估值展望TheravanceBiopharma是一家战略清晰、财务健康、正处于关键拐点的特色生物科技公司。其投资逻辑的核心在于对Ampreloxetine成功概率的定价。短期（未来12个月）：股价将主要围绕Ampreloxetine的III期数据波动。积极的临床数据可能驱动市值向10-20亿美元区间迈进，而失败则可能导致市值回落至现金价值附近（约4-5亿美元）。中长期：若Ampreloxetine成功上市，公司将转型为拥有呼吸和神经两大稳定收入来源的盈利生物制药公司，具备独立发展或被高价收购的潜力。当前，投资者支付的价格部分反映了对Ampreloxetine的部分成功预期。对于能够承受生物科技投资固有高风险、并寻求不对称回报（下行有现金保护、上行空间巨大）的投资者而言，TheravanceBiopharma提供了一个极具吸引力的案例。建议投资者紧密跟踪CYPRESS试验的顶线数据发布，并关注YUPELRI®的季度销售趋势以判断基本盘的稳固性。