Nintedanib esylate

The pivotal TETON-1 phase 3 study of nebulized Tyvaso® (treprostinil) Inhalation Solution in idiopathic pulmonary fibrosis ( IPF ) preserved lung function as measured by absolute forced vital capacity ( FVC ) and demonstrated reduced risk of a clinical worsening event, meeting both its primary endpoint and a key secondary endpoint with statistical significance, respectively In combined analyses of TETON-1 and TETON-2 — also included in the NEJM publication and presented at ATS — nebulized Tyvaso achieved statistically significant treatment effects across the primary and most secondary efficacy endpoints Nebulized Tyvaso combines direct lung delivery with multi-modal activity across fibrotic, vascular, and inflammatory pathways that are not currently addressed by existing IPF therapies SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--United Therapeutics Corporation (Nasdaq: UTHR ), a public benefit corporation, today announced that the New England Journal of Medicine has published the full results of its TETON-1 study, as well as combined analyses of its TETON-1 and TETON-2 studies, evaluating the use of nebulized Tyvaso for the treatment of IPF. The publication is available here . A summary of the publication was also presented today during a symposium at the annual meeting of the American Thoracic Society ( ATS ) International Conference in Orlando. The use of nebulized Tyvaso for IPF has not been approved by the U.S. Food and Drug Administration ( FDA ) and remains investigational for IPF. The results of TETON-1 were also presented at ATS during the Breaking News: 2026 Clinical Trial Results in Pulmonary Medicine session on Sunday, May 17. Combined results from TETON-1 and TETON-2 were presented today during an oral session at ATS. TETON-1 met its primary efficacy endpoint, with nebulized Tyvaso demonstrating statistically significant improvement in absolute FVC relative to placebo from baseline to week 52 in an IPF population broadly treated with background therapy. The median change in FVC at week 52 was −43.3 mL (95% confidence interval [CI], −92.1 to −9.1) in the nebulized Tyvaso group and −196.2 mL (95% CI, −227.1 to −155.6) in the placebo group; between-group difference was 130.1 mL (95% CI, 82.2 to 178.1; P<0.001). Nebulized Tyvaso reduced the risk of a clinical worsening event by 33% (hazard ratio [HR], 0.67; 95% CI, 0.52 to 0.88; P=0.0034) relative to placebo, a statistically significant improvement in this key secondary endpoint. Nebulized Tyvaso showed numerical improvement in other important secondary endpoints, including improved change in percent of predicted FVC, King’s Brief Interstitial Lung Disease quality of life questionnaire ( K-BILD ), and change in percent of predicted diffusion capacity of lungs for carbon monoxide ( DLCO ). Benefits of nebulized Tyvaso in TETON-1 were observed across all subgroups, including use of background therapy (nintedanib, pirfenidone, or no background therapy), smoking status, and supplemental oxygen use. Combined analyses of TETON-1 and TETON-2 showed that nebulized Tyvaso achieved statistically significant treatment effects compared to placebo from baseline to week 52 for the primary endpoint and for most key secondary endpoints. The median change in FVC at 52 weeks in the combined data set was −45.4 mL (95% CI, −73.8 to −23.1) in the nebulized Tyvaso group and −161.7 mL (95% CI, −194.5 to −134.1) in the placebo arm; between-group difference was 111.8 mL (95% CI, 79.7 to 144; P<0.0001). Nebulized Tyvaso reduced the risk of a clinical worsening event in the combined data set by 31% (HR: 0.69; 95% CI, 0.57 to 0.84; P=0.0002) and the risk of acute IPF exacerbation by 48% (HR: 0.52; 95% CI, 0.30 to 0.91; P=0.0223) relative to placebo. Nebulized Tyvaso also achieved statistically significant improvements in changes in percent predicted FVC, K-BILD score, and DLCO. Overall survival at week 52 trended in favor of Tyvaso but did not meet statistical significance. “The results of TETON-1 validate what was seen in TETON-2 . The combined analysis provides an incredibly powerful dataset with both studies complementing each other well. The meaningful effect on FVC decline observed across all subgroups, as well as achieving positive results for five out of six secondary endpoints in the combined analysis, is truly impressive for a 52-week treatment duration. These findings have the potential to fundamentally impact how we target IPF and manage patients living with this devastating disease. Speaking on behalf of the steering committee, we are incredibly grateful to all the investigators, research coordinators, and most importantly, to all the patients who participated. Their willingness to participate epitomizes taking the fight back to the disease,” said Steven D. Nathan, M.D. , Schar Chair, Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital and Chair of the TETON Steering Committee. “The profound impact of the TETON clinical program in IPF, with combined results showing significantly improved preservation of lung function and quality of life, as well as reductions in disease worsening and acute IPF exacerbations, represents a truly important advancement for people living with this progressive, life-threatening disease,” said Martine Rothblatt, Ph.D. , Chairperson and Chief Executive Officer of United Therapeutics. “We are incredibly proud that our rigorous clinical trials and their unprecedented results continue to receive prestigious recognition from a high caliber journal like The New England Journal of Medicine and from ATS leadership.” “Nebulized Tyvaso combines direct lung delivery with multimodal activity across fibrotic, vascular, and inflammatory pathways that are not currently addressed by existing IPF therapies. The unprecedented results of our TETON clinical program — in which nebulized Tyvaso achieved statistical significance in endpoints never before attained in other IPF clinical trials — support the importance of this differentiated, multi-pathway activity,” said Peter Smith, Pharm.D. , Senior Vice President, Product Development at United Therapeutics and the lead for the global TETON program. United Therapeutics plans to seek priority review of a supplemental New Drug Application, to be submitted to the FDA by the end of this summer, to add IPF to the labeled indications for nebulized Tyvaso based on data from the TETON-1 and TETON-2 studies. Both the FDA and the European Medicines Agency have granted orphan designation for treprostinil to treat IPF. Full results of the TETON-2 study were also recently published in the New England Journal of Medicine and are available online at NEJM.org . TETON Clinical Program A post-hoc analysis of the INCREASE study in patients with pulmonary hypertension associated with interstitial lung disease suggested that nebulized Tyvaso was associated with a significant improvement in FVC, laying the foundation for the TETON clinical program to evaluate the use of nebulized Tyvaso in IPF and progressive pulmonary fibrosis ( PPF ). TETON-1 enrolled patients with IPF in the United States and Canada, and TETON-2 enrolled patients with IPF outside the United States and Canada. TETON-PPF is evaluating the use of nebulized Tyvaso in PPF in patients globally, and enrollment is ongoing. The use of nebulized Tyvaso for IPF and PPF has not been approved by the FDA and remains investigational. TETON-1 Study Design The TETON-1 study ( NCT04708782 ) was a 598-patient, multicenter, randomized, double-blind, placebo-controlled phase 3 registration study evaluating the safety and efficacy of nebulized Tyvaso in patients with IPF over a 52-week period at sites in the United States and Canada. The study reached full enrollment in January 2025. The primary endpoint of the study was the change in absolute FVC from baseline to week 52. Secondary endpoints included: (1) time to clinical worsening; (2) time to first acute exacerbation of IPF; (3) overall survival at week 52; (4) change in percent predicted FVC from baseline to week 52; (5) change in the K-BILD questionnaire from baseline to week 52; and (6) change in DLCO from baseline to week 52. Safety assessments included the development of adverse events, serious adverse events, vital signs, clinical laboratory parameters, and electrocardiogram parameters. Eligible patients completing the TETON-1 study could enroll in the TETON-OLE study ( NCT04905693 ), an ongoing open-label extension study to evaluate the long-term safety and tolerability of nebulized Tyvaso in patients with fibrotic lung disease. About IPF Idiopathic pulmonary fibrosis, or IPF, is a scarring disease of the lungs of an unknown (idiopathic) cause and is the most common of the idiopathic interstitial pneumonias. IPF is characterized by the progressive loss of the ability of the lungs to transfer oxygen into the blood, ultimately resulting in respiratory failure and death. While the precise causes of IPF remain unknown, IPF rarely presents before age 50 and can be associated with cigarette smoking and certain genetic dispositions. In addition, some evidence suggests that gastroesophageal reflux (acid reflux, or heartburn), certain viral infections, air pollution, and workplace exposures may be risk factors for IPF. IPF is estimated to affect between 0.33 and 4.51 people per 10,000 persons worldwide. Further, United Therapeutics estimates there are over 100,000 IPF patients in the United States. About Tyvaso® (treprostinil) Inhalation Solution INDICATION TYVASO (treprostinil) Inhalation Solution is a prostacyclin mimetic indicated for the treatment of: Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with TYVASO establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities. While there are long-term data on use of treprostinil by other routes of administration, nearly all clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with TYVASO was limited to 12 weeks in duration. Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with TYVASO establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS TYVASO is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, TYVASO may produce symptomatic hypotension. TYVASO inhibits platelet aggregation and increases the risk of bleeding. Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both C max and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness. Like other inhaled prostaglandins, TYVASO may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with TYVASO. DRUG INTERACTIONS/SPECIFIC POPULATIONS The concomitant use of TYVASO with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both C max and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8. Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production. Safety and effectiveness in pediatric patients have not been established. Across clinical studies used to establish the effectiveness of TYVASO in patients with PAH and PH ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety pro in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy. ADVERSE REACTIONS Pulmonary Arterial Hypertension (WHO Group 1) In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%). In addition, adverse reactions occurring in ≥4% of patients were dizziness and diarrhea. Pulmonary Hypertension Associated with ILD (WHO Group 3) In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions with TYVASO were similar to the experience in studies of PAH. Please see Full Prescribing Information for TYVASO, the TD-300 TYVASO® Inhalation System Instructions for Use manual, and additional information at or call 1 844 UNITHER (1-844-864-8437). About United Therapeutics Founded by CEO Martine Rothblatt to discover a cure for her daughter's life-threatening rare disease, pulmonary arterial hypertension, United Therapeutics transforms the treatment of rare diseases and pioneers alternatives to expand the supply of transplantable organs. From our innovative therapies to our groundbreaking manufactured organs, we are bold and unconventional. We move quickly from scientific theory to practical technologies that can save lives. As a public benefit corporation, even our legal structure reflects our commitments. We serve patients, act with integrity, create long-term shareholder value, and operate with sustainable practices that protect the future we are working to build. Visit us at and follow us on LinkedIn , Facebook , and Instagram . Forward-Looking Statements Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements regarding the timing and anticipated outcome of our planned regulatory submission to the FDA to seek approval to add IPF to the labeled indications for nebulized Tyvaso, including our plan to seek priority review; our expectations concerning the potential benefits of nebulized Tyvaso for IPF patients, including the potential to fundamentally impact how physicians target IPF and manage patients living with this devastating disease; and our goals of expanding the supply of transplantable organs, developing practical technologies that can save lives, creating long-term shareholder value, and operating with sustainable practices. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language, and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of May 18, 2026, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events or any other reason. TYVASO is a registered trademark of United Therapeutics Corporation. Contacts For Further Information Contact: Investor Inquiries Media Inquiries communications@unither.com

He 核 Xin 心 Guan 观 Dian 点 国内稀缺的创新转型Pharma。公司早年从肠外营养起家，2012年起坚定走“仿制创新双线作战、国内海外并行发展”之路。目前，仿制药板块已充分消化集采冲击，筑牢现金流压舱石；创新药领域，继环泊酚大单品后，安瑞克芬、克利加巴林和考格列汀接连上市，2026年创新药营收占比有望突破50%；出海方面，环泊酚预计2026Q2在美国获批上市，DPP-1、PDE3/4、NAV1.8、TYK2等5款已出海新药将带来里程碑收入。此外，其他管线26年将迎来密集数据读出，有望带来新一轮对外授权和国内上市。 以终为始，围术期新龙头崛起。多数手术患者已实现术中安全无痛与生命体征稳定调控，但术后长期疼痛管理等问题亟待解决。公司精准布局麻醉镇痛，新药三箭齐发：环泊酚镇静麻醉安全性优势明显，克利加巴林无需滴定、快速起效、抢先布局神经病理性疼痛，安瑞克芬主打非成瘾阿片类镇痛，其术后疼痛适应症NDA已获CDE受理，完整覆盖轻/中/重度术后疼痛患者。此外，公司还布局了NAV1.8抑制剂，瞄准下一代非阿片镇痛市场。我们认为，依托差异化产品矩阵与专业化学术推广，海思科将会成长为国内围手术期麻醉镇痛龙头。 再启新程，多元管线出海接力。公司管线已拓展至代谢、自免和呼吸等赛道：1）代谢：考格列汀是全球首款双周DPP-4抑制剂，国内老年糖尿病患者一线用药。HSK31679是全球第二、国内首个纳入突破性疗法的THR-β激动剂，剑指百亿美元MASH市场；2）自免：HSK39297是国内首批申报上市的国产CFB抑制剂。HSK44459作为全球第二的PDE4B抑制剂，肺纤维化适应症已挺进III期，共推进6个适应症。而IL-23R已完成银屑病II期临床；3）呼吸：HSK31858是潜在同类最佳DPP-1抑制剂，预计26年进入海外III期，27年国内NDA。HSK39004是全球第一PDE3/4粉雾剂，临床试验快速推进，稳步兑现海外价值。 盈利预测与投资建议   我们预测公司2026-2028年每股收益分别为0.54、0.76、0.92元，考虑到公司诸多创新药管线仍处于临床阶段，因此采取DCF估值法，对应目标价为70.11元，首次给予“买入”评级。 风险提示 创新药研发失败、商业化不及预期、市场竞争加剧、国内国外医保政策变化、核心人员流失等风险 一、海思科：国内稀缺的创新转型Pharma 国内出海双开花的综合型创新药企。公司成立于2000年，早年从肠外营养等特色仿制药起家，2012年在深交所上市后正式开启创新征程，已有环泊酚注射液、安瑞克芬注射液、苯磺酸克利加巴林胶囊和考格列汀片4款创新药上市。 此外，自2015年起便通过独立出海、对外授权、联合开发等多种模式推进国际化布局，已有环泊酚、TYK2、DPP-1、PDE3/4、Nav1.8共5款创新药出海，国际化步入正轨。  1.1 存量业务筑底，创新占比近半 步入创新发展周期，业绩再上新台阶。2021-2025年，公司营收和扣非归母净利润CAGR分别为12.2%和47.6%，营收重回上行通道，利润实现高速增长。2025年，公司实现营收44亿元（同比+18%），实现扣非归母净利润1.7亿元（同比+26%），跑出成长加速度。 集采风险基本出清，存量业务已然筑底。从营收拆分看，2021-2025年，仿制药板块占比由98%下降至60%以下，同时摆脱了对肠外营养、消化肝病大单品的过度依赖，收入结构更加多元更具韧性；从具体产品看，全营达、思务已消化集采影响，思复、立必复等独家品种集采风险较小。 环泊酚快速放量，创新占比近半。聚焦创新药板块，环泊酚在2021年纳入医保目录后快速放量，2025H1贡献收入8亿元（同比+55%）。此外，苯磺酸克利加巴林胶囊、考格列汀片、安瑞克芬均已纳入医保，且医院准入速度远超慢病国谈产品平均水平，成为业绩增长有力补充，估计2025年公司创新药收入占比接近50%。 1.2 管线阵容闪耀，出海已然成行 创新成果密集兑现。首先，HSK39297（CFB）、HL231（LAMA+LABA）预计27年国内获批上市，HSK31858（DPP-1）、HSK31679（THR-β）、HSK44459（PDE4B）等III期管线有望自28年起接力上市，开启新一轮创新成长；其次，HSK39004（PDE3/4吸入粉雾剂）、HSK47388（IL-23R）和HSK55718（NAV1.8）年内均有望推进至III期临床阶段；此外，HSK42360（BRAF）等早研管线进展顺利，年内或将进入II期临床阶段。 多元成长曲线清晰。从创新药在研管线看，海思科依托环泊酚大单品成长为围手术期龙头，并全面布局呼吸、代谢、自免和肿瘤等赛道，未来将多领域、国内外协同发展，远期成长价值凸显。  国际化正在兑现。短期来看，环泊酚海外上市申请已获FDA受理，或将于26Q2在美国获批上市。TYK2银屑病关键Ⅲ期临床大获成功，有望于27年美国上市，并带来里程碑收入；长期来看，DPP-1和PDE3/4有望于2030年在美国获批上市，带来双位数销售分成。此外，PDE4B、BRAF等后续产品出海潜力较大。 授权MNC，合作再升级。仅2026年以来，公司便已推动PDE3/4和NAV1.8两大重磅产品出海：PDE3/4的交易通过NEWCO深度绑定合作伙伴，且合作方转向专业团队和顶级资本组合；而NAV1.8的合作对象升级为全球顶级MNC艾伯维，国际化再上新台阶。 我们认为，已出海资产不仅会带来稳定现金流，更能深度参与海外临床开发与商业化决策，而随着更多早研平台和管线接力出海，公司有望走出真正可持续的国际化道路。 二、以终为始，围术期新龙头崛起 从环泊酚大单品到围手术期龙头。麻醉的本质是尽量减少伤害性刺激及对人体的影响，如今多数手术患者已实现术中安全无痛与生命体征稳定调控，但术后严重并发症高发、死亡率高及远期健康生存受限等问题仍待解决。 在麻醉领域，公司已构建环泊酚注射液、苯磺酸克利加巴林胶囊和安瑞克芬注射液3款创新产品组合，依托学术推广和品牌建设，有望从环泊酚大单品主导，成长为围手术期龙头。 2.1 新药三箭齐发，商业化立竿见影 丙泊酚是静脉麻醉基石。麻醉药主要分为镇静（无意识）、镇痛（无应激）和肌松（无体动）三类，在麻醉中分别起到基础、核心和辅助作用，由于临床普遍复合用药，故药物间是互补关系。在镇静麻醉药中，起效快、苏醒快的丙泊酚从临床应用至今近五十年，仍是静脉全身麻醉基石，广泛应用于麻醉诱导和维持、手术室内外镇静。 环泊酚有望替代丙泊酚。近年来，镇静麻醉药领域涌现出瑞马唑仑、环泊酚和磷丙泊酚等创新药，向丙泊酚发起挑战。我们认为，环泊酚有望加速替代丙泊酚，主要有两点原因： 1）磷丙泊酚应用场景相对局限。磷丙泊酚通过水溶性前药设计，具有作用更持久、无脂质相关风险等优势，但由于起效和苏醒时间慢，与丙泊酚起效快、苏醒快的特点相比，存在明显差异，因此更适合用于长时间镇静（如ICU镇静），应用场景局限。 2）相较瑞马唑仑，环泊酚更适配临床。环泊酚和瑞马唑仑在丙泊酚起效快、苏醒快的基础上在安全性方面有明显改善（如注射痛、呼吸抑制等），但相比瑞马唑仑粉针剂型及通常需要搭配氟马西尼加快患者苏醒，环泊酚用药方式更简便，推广难度低。 环泊酚加速替代丙泊酚，空间广阔。根据药智网数据，2025年环泊酚已跃升为国内静脉麻醉药第一大品种，销售额20.8亿元，快速放量。我们认为，一方面，随着人口老龄化及舒适医疗服务需求升级带来的手术量增加，麻醉需求仍将刚性增长；另一方面，丙泊酚国内用量巨大，环泊酚替代仍处于早中期。因此，环泊酚未来成长空间广阔。 克利加巴林是第三代钙离子通道调节剂中的翘楚。神经病理性疼痛（NP）是常见多发慢性疼痛，目前一线治疗药物为加巴喷丁和普瑞巴林，克利加巴林作为全球首款无需滴定的第三代钙离子调节剂，相当程度上克服了前两者滴定麻烦、疗效安全性不足、国内缺乏适应症、滥用等诸多挑战。 克利加巴林较美洛加巴林优势显著。从临床数据对比看，美洛加巴林仅具备安全优势（如头晕发生率低、停药率低），但克利加巴林相关不良反应均为轻中度且可自行缓解。更重要的是，克利加巴林在快速起效、强效镇痛、综合获益和无需滴定等方面优势显著。 率先切入国内市场。值得注意的是，克利加巴林作为国内首个获批DPNP（糖尿病周围神经痛）的1类新药，其神经病理性疼痛适应症已纳入CDE优先审评，将在学术推广层面抢占先机。 安瑞克芬：非成瘾K阿片镇痛新药，白处方受限少。阿片类药物是术后镇痛和中重度疼痛治疗核心，但由于成瘾性风险，在我国被列为管制类药品，其生产、销售、处方和定价均受到严格管控。 安瑞克芬是全球首个获批术后镇痛的高选择性外周κ阿片受体激动剂，通过阿片κ受体的选择性激动作用和药物分布的外周选择性，最大限度地避免了阿片类药物的成瘾性、呼吸抑制等不良反应，因此未被列入管制药品，使用受限更少。 强效镇痛止吐止痒，拓展大适应症。在腹部手术轻中度疼痛III期研究中，安瑞克芬可显著降低术后24h内疼痛近40%，较曲马多非劣效，呕吐和恶心发生率远低于安慰剂。在中重度疼痛与泰吉利定的头对头研究中，镇痛效果相当，术后止吐优势明显。于是，公司继续探索安瑞克芬用于术后恶心呕吐（PONV），初步疗效显示完全缓解率为75.6%-81.6%，显著优于安慰剂组。 安瑞克芬治疗血液透析患者瘙痒（CKD-aP）已上市。CKD-aP患病率高、危害重，已获批仅有中枢 κ 阿片受体激动剂，同样面临成瘾性和副作用，缺乏长期控制药物。安瑞克芬能显著改善血液透析患者的瘙痒评分及生活质量，长期应用持续缓解患者瘙痒。 安瑞克芬术后疼痛NDA已获CDE受理，开创先河。安瑞克芬是国内首个完成术后疼痛3期临床的药物，该适应症覆盖了所有术后疼痛患者（轻度/中度/重度），成长天花板被大大抬升。 2.2 NAV1.8先人一步，剑指千亿市场 慢性疼痛是真正的、远未被满足的临床需求。慢性疼痛（持续超过3个月）影响全球超30%人群，患者人数超糖尿病、心血管和肿瘤病人之和。尽管有一些非阿片类镇痛药物上市，但许多慢性疼痛患者仍未能获得足够缓解，最终不得不转向阿片类药物，然而后者的成瘾性风险易导致过度使用。 预计2030年中国镇痛药市场规模达2000亿元。据 Mordor intelligence 调查，2021年全球疼痛管理市场规模794 亿美元，预计到 2027 年将增长至 1207 亿美元（CAGR为 7.39%）。另外，2023 年国内镇痛药市场规模达1300亿元（同比+6%），预计到 2030 年有望突破 2000 亿元。 NAV1.8抑制剂带来非阿片镇痛曙光，但慢性疼痛未突破&术后急性疼痛起效慢。VX-548于2025年获FDA批准上市，实现了非阿片类镇痛新药研发的原创突破，证明了NaV1.8阻断剂作为镇痛靶点的可行性，并由于无阿片受体作用机制，不作用于大脑，成瘾风险低。 然而，VX-458被批准用于急性疼痛的术后痛适应症，慢性疼痛并未迎来突破。此外，其镇痛效果虽较氨酚氢可酮非劣效，但起效速度更慢，其作用在术后8小时才首次显现。 VX-993遭遇滑铁卢之后，靶点创新空间仍巨大。VX-993是Vertex宣称的第三代NAV1.8抑制剂，其于25年8月宣布Ⅱ期临床失败：三个剂量组在主要疗效终点SPID48h上较安慰剂组差异无统计学意义，NAV1.8靶点价值受到质疑。 但是，我们认为针对NAV1.8靶点研发仍有创新和提升空间，主要有以下两点： 1）VX-993疗效结果无统计意义但具有临床意义。在镇痛类临床研究中，通常把较基线降低2分（NRS）或14-17mm（VAS）或减少30%称为有效缓解，而VX-993的中剂量组和高剂量组较安慰剂的疗效差异具备一定临床意义。 2）VX-993结果表明提高暴露量带来的临床获益有限。VX-993相比VX-548主要是暴露量得到改善，那为何二者在同样适应症中一胜一败？对比临床设计和数据，我们发现VX-993的疼痛模型强度提升明显。一是阳性组、试验组和对照组SPID48评分明显下降；二是VX-993未采用腘窝阻滞，未合并阻滞的患者往往术后镇痛药物效果消退后迅速加重，这可能是由于NAV1.8抑制剂起效慢，故镇痛效果无法覆盖疼痛强度。 下一代NAV1.8抑制剂格局未定，慢性疼痛才是重点。上述起效时间、药效强度问题表明NAV1.8这一赛道新药研发格局未定，同时为NAV1.8后续在慢性疼痛开发指明方向，如VX-548和VX-993的临床开发计划已转向糖尿病周围神经病理性疼痛（DPNP）这一常见慢性疼痛。 海思科布局新一代NAV1.8抑制剂，有望颠覆现状。早在VX-548阳性结果公开后，国内企业迅速布局第二代NAV1.8抑制剂。但是，海思科研发优势明显，有望赶超一众对手： 1）DPNP有“knowhow”积累，构成核心竞争优势。国内进度领先的管线布局主要是基于VX-548的二代NAV1.8抑制剂结构，进行专利突破并快速推进术后急性镇痛临床。然而，NAV1.8的研发领域已转向DPNP，而海思科有克利加巴林的成功开发经验，有望超越国内外竞争对手。 2）临床推进速度更快。镇痛赛道药物的研发特点是“短平快”，海思科今年内会进入II/III期临床，可能在临床推进上实现赶超。 三、再启新程，多元管线出海接力 麻醉镇痛作为特色细分领域，市场容量有限，天花板明显。可以发现，公司围绕“代谢+自免+呼吸+肿瘤”四大领域布局了新一轮创新药的研发。 3.1 代谢：首个品种商业化，MASH市场容量大 考格列汀：全球首个双周DPP-4抑制剂。口服降糖药中，DPP-4抑制剂因其疗效明确、安全性良好而被广泛使用，然而多数药物需每日服药，患者用药依从性欠佳。考格列汀片是全球首个超长效DPP-4抑制剂，实现双周一次给药，有望显著提升便利性和依从性。 DPP-4抑制剂商业价值仍可观。在2型糖尿病庞大的慢病市场中，临床治疗手段日趋丰富，尤其SGLT2-i、GLP-1RA等新型降糖药物可带来心血管、肾脏等多元获益，因此市场普遍认为DPP-4抑制剂将受冲击，国内商业化价值有限，但我们认为其仍具备较大商业化潜力，核心原因在于： 1）DPP-4抑制剂更适用于亚洲患者。亚洲患者BMI较低，主要驱动因素是β细胞功能障碍导致的胰岛素分泌不足。由于DPP-4抑制剂的作用机制是增强内源性GLP-1水平以刺激胰岛素分泌，故在胰岛素抵抗不严重的亚洲人群中展现出更好降糖效力； 2）DPP-4抑制剂更适合老年患者。首先，GLP-1RA亮眼的减重数字背后，伴随瘦体重流失，对老年患者可能造成灾难性影响，直接引发跌倒、骨折，甚至丧失生活自理能力；其次，SGLT2i主要通过抑制肾脏近端小管对葡萄糖与钠的重吸收实现降糖，易引发糖尿与尿钠排泄，进而增加脱水风险。 DPP-4抑制剂不增加胃肠道反应、对体重呈中性影响且无低血糖风险，因此被《中国老年糖尿病指南（2024版）》列为老年糖尿病患者的首选或一线用药。 THR-β：已获验证的百亿MASH赛道。代谢功能障碍相关性脂肪性肝炎（MASH）市场容量巨大，2023年全球患病人数超3.3亿人，2025年中国成人患病率高达6.7%，但是药物干预手段极为有限，仅THR-β和GLP-1获批，后期临床产品主要是FGF21。 Resmetirom是全球首个获FDA批准的专门用于治疗伴有中度至重度肝纤维化的成人MASH药物，2025年是首个上市完整年度，销售额近10亿美元同时渗透率仅12%，彻底点燃THR-β赛道创新药研发热情。 HSK31679：全球第二、国内第一的下一代THR-β激动剂。Resmetirom 的成功为未来 THR-β激动剂的开发提供了一个基础框架，但其疗效有限，只有30%的患者达到 MASH 缓解且纤维化没有恶化。HSK31679是临床进度全球第二、国内首个纳入突破性疗法的THR-β激动剂，已经进入III期临床，进度全球领先。 机制差异，疗效有望超越Resmetirom。IIa期数据显示，HSK31679 160mg组治疗12周可使肝脏脂肪含量降低29%，近半数患者肝脏脂肪降幅超过30%。此外，研究还显示其具备微生物群调节效应，这一差异化作用机制表现为在小鼠中改善脂肪性肝炎的效果优于Resmetirom。 3.2 自免：补体B NDA，全力攻克IBD和银屑病 IgA肾病：新药稀缺的慢病大市场。IgA肾病是全球最常见的原发性肾小球肾炎之一，中国发病率达39.7%，进展虽慢但20%-50%的患者最终发展为肾衰竭，远期预后极差。目前，全球仅6款药物获批，诺华的伊普可泮（Iptacopan）是全球首个近端补体旁路B因子（CFB）抑制剂，2023年底获批，2025年销售额即达到5.1亿美元。 伊普可泮：优异疗效验证CFB靶点。补体系统是先天免疫的核心防线，通过经典、凝集素和替代三条途径激活，最终形成膜攻击复合物清除病原体并桥接获得性免疫。 补体B途径的过度激活与 aHUS（非典型溶血性尿毒症）、PNH（阵发性血红蛋白尿症）、AMD（年龄相关性黄斑变性）、C3肾小球病、IgA肾病及狼疮性肾炎等多种疾病密切相关。伊普可泮在关键Ⅲ期IgA临床中展现优异疗效：与安慰剂相比，将第9个月的基线蛋白尿水平降低38.3%。 HSK39297：上市在即，抢占进口替代先机。除伊普可泮外，已有三款国产CFB抑制剂国内申报上市，首发适应症相同且均已被纳入优先审评。HSK39297凭借“覆盖初治+经治耐药”的双适应症布局，有望在竞争中抢占先机。 PDE4B：成熟靶点亚型再开发，肺纤维化迎来新突破。全球获批上市的PDE靶向药物共9款，主要集中在：慢阻肺、特应性皮炎和银屑病。PDE4B 是 PDE4 亚型靶点，较PDE4在安全性和疗效方面都更有优势。 目前，临床在研的 PDE4B共 5 款。其中，那米司特进展最快，随着III期临床成功其有望于2026年同时获批特发性肺纤维化（IPF）和进行性肺纤维化（PPF）两个适应症，差异化适应症为PDE4B开辟了全新赛道。 IPF/PPF：治疗格局佳，市场空间大。IPF获批上市药物仅有吡非尼酮和尼达尼布，且近10年无新药获批；PPF获批药物仅尼达尼布，二者均存在显著未满足临床需求。 此外，那米司特针对PPF侧重炎症早期干预，尼达尼布聚焦纤维化进程抑制，PDE4B与现有疗法形成互补，赛道治疗格局优异。目前，尼达尼布占据市场主导地位，2024年全球销售额高达40亿美元。 HSK44459：全球第二PDE4B，进入III期临床。除那米司特外，HSK44459是PDE4B在IPF和PPF人群中全球进展第二的产品，已进入III期临床，另外还有4个适应症同步推进。 IL-23R口服环肽：两百亿美元赛道新星，有望打破单抗垄断。IL-23是自免领域重磅靶点，全球已获批6款IL-23 单抗。其中，艾伯维利生奇珠单抗（Skyrizi）凭借长效优势，在银屑病、炎症性肠病领域建立绝对领先地位，2025年全球销售175.6亿美元（+49.9%），根据公司指引2026年有望突破200亿美元。 白介素受体（IL-23R）是IL23对应的受体靶点，可开发为小分子或多肽。其中，Icotrokinra作为全球首个IL-23R口服环肽，具备“疗效对标、便捷给药”差异化优势，有望突破生物制剂垄断。 海思科IL-23R全球第二，大幅领先。全球来看，HSK47388处于临床II期，进度大幅领先同类管线。小鼠体内药代动力学研究数据显示，该化合物口服生物利用度达0.482%，在体内外展现出优异的稳定性，为口服给药可行性提供了有力支撑。 3.3 呼吸：DPP-1即将NDA，PDE3/4弯道超车 DPP-1是中性粒细胞相关炎症疾病的潜在靶点。DPP-1是一种半胱氨酸肽酶，通过切割氨基末端的二肽结构来激活促炎性中性粒细胞丝氨酸蛋白酶（Neutrophil Serine Proteases，NSPs）家族。研究发现，过度活化的NSPs与中性粒细胞相关炎症疾病导致的组织损伤相关，包括：慢性阻塞性肺疾病（COPD）和非囊性纤维化支气管扩张（NCFBE）等。 Brensocatib获批上市，解决NCFBE无药可用。NCFBE是由感染和炎症引起的支气管异常和持久性扩张，其残酷性在于患者往往陷入一个难以打破的恶性循环：慢性咳嗽、痰液分泌过多、呼吸困难和呼吸道反复感染相互交织，导致疾病持续恶化。 更令人担忧的是，全球NCFBE患者已逾百万，但临床治疗只能依赖抗生素控制感染、使用支气管扩张剂缓解症状，这些“治标不治本”的权宜之计远远无法满足患者的迫切需求。 Brensocatib ASPEN三期临床入组1680例NCFBE患者，对于主要终点Pes（肺部恶化年发生率），10mg、25mg剂量组相比于安慰机组分别下降了21.1%、19.4%。对于支气管扩张的患者来说，ASPEN是一项里程碑式的胜利。 HSK31858：全球领先且有望BIC。Brensocatib已经证明了DPP-1抑制剂的疗效，但这仅仅是序幕。HSK31858在II期研究中取得了潜在BIC（同类最佳）的积极结果，正推进III期临床，同时海外权益成功BD意大利凯西。除NCFBE外，未来还有望在COPD、哮喘等呼吸系统疾病中发挥作用。 COPD有望诞生大药。COPD是由气道或肺泡异常导致的异质性疾病，核心特征为慢性呼吸道症状（呼吸困难、咳嗽、咳痰、急性加重）和持续性、进行性气流受限。2020年，全球约4.8亿人罹患COPD（中国患者逾1亿），中重度占35%，年致死超300万人。 尽管长效β₂受体激动剂（LABA）、长效毒蕈碱拮抗剂（LAMA）及吸入性糖皮质激素（ICS）组成的联合疗法可缓解症状、减少急性加重，但是无法逆转肺功能下降或改变疾病自然进程、仅部分患者获益且依从性差，背后蕴藏着蓝海机遇。 PDE3/4兼具支气管扩张与非甾体抗炎，备受MNC青睐。磷酸二酯酶（PDEs）是一类通过调节环核苷酸水平影响多种细胞功能的酶。PDE3主要调控气道平滑肌中的环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）浓度，PDE4 则通过调控 cAMP 水平，参与炎症细胞的激活。 抑制PDE3可导致气道平滑肌松弛（支气管扩张），而抑制PDE4则具有抗炎作用。因此，PDE3/4抑制剂在抗炎和支气管扩张方面可产生协同或叠加效应。 值得注意的是，PDE3/4赛道已诞生两笔百亿美元交易，包括：默沙东收购Verona Pharma（其核心资产正是Ensifentrine）和 GSK收购HRS-9821海外权益。 HSK39004：全球进展最快的PDE3/4粉雾剂。首先，HSK39004吸入混悬液和吸入粉雾剂两种剂型分别进入临床III期和临床II期，位居全球前列，其中粉雾剂型进度全球第一；其次，作为小分子吸入制剂，患者依从性好、工艺壁垒高，未来竞争格局好。 此外，HSK39004已经成功NEWCO美国AirNexis，考虑到公司在国内强大的商业化能力，以及合作伙伴背后的顶级资本和专业团队对海外临床和商业化的赋能，其价值将稳步兑现。 四、盈利预测与投资建议 4.1 盈利预测 海思科是一家综合型创新药公司，已有产品上市销售，同时存在诸多潜力在研新药，我们基于对公司管线国内商业化销售、BD出海和临床开发进度的研判，对公司未来盈利预测作出如下假设： 1、公司2026-2028年收入分别为59.0、71.4和88.9亿元，收入高速增长的动能主要来自环泊酚、安瑞克芬、克利加巴林和考格列汀四款已上市创新药。与此同时，2027年起HSK39297、HL231等重磅新药在国内接力上市，开启新一轮成长； 2、公司2026-2028年毛利率分别为76.9%、79.5%和81.9%。毛利率的提升主要来自产品结构优化，即高毛利率的创新药收入占比持续提升； 3、公司2026-2028年销售费用率为37.6%、38.8%和40.0%，管理费用率为9.5%、9.3%和8.9%，研发费用率为19.5%、20.3%和20.3%。管理费用率下降主要系收入规模扩大带来的摊薄效应，销售费用率和研发费用率上升主要考虑到公司需加大投入支持产品销售和临床试验推进。 4.2 投资建议 公司存在诸多临床阶段潜力管线，我们对各管线开发进度的研判如下： 1、环泊酚有望于26Q2美国获批上市； 2、HSK39297（CFB）、HL231（LAMA+LABA）有望于2027年国内获批上市，HSK31858（DPP1）、HSK31679（THR-β）、HSK44459（PDE4B）等III期管线有望自28年起接力上市，开启新一轮创新成长； 3、HSK39004（吸入粉雾剂，PDE3/4）、HSK47388（IL-23R）和HSK55718（NAV1.8）年内均有望推进至III期临床； 4、此外，HSK42360（BRAF）等早研管线进展顺利，年内或将进入II期临床。 考虑到公司创新药商业化快速放量，同时诸多高潜力创新药管线仍处于临床阶段，有望接力上市驱动业绩成长，长期增长动能强劲，因此采取DCF估值法，对应目标价为70.11元，首次给予“买入”评级。 五、风险提示 创新药研发失败风险：如果在研管线临床数据读出不及预期，则会对公司估值水平及发展空间造成较大影响； 商业化不及预期风险：如果已上市产品国内销售不及预期，在研管线BD交易及交易后的海外临床和商业化进展不及预期，则会对公司估值水平及发展空间带来负面冲击； 市场竞争加剧风险：同适应症、同靶点产品存在新药不断上市和市场竞争加剧风险； 国内外政策风险：创新药上市后医保谈判对价格和销量影响大，如果国内外医保政策变化，可能对公司产品商业化价值造成影响； 核心人员流失风险：作为创新药公司，技术、管理和销售团队核心人员离开会对公司未来经营发展产生一定压力。 说明： 本内容系对我司已发布研报的解读，报告标题《国内稀缺的创新转型Pharma——海思科首次覆盖报告》，发布日期：2026年05月16日。 分析师：伍云飞 执业证书编号：S0860524020001 联系人：袁润璞 执业证书编号：S0860124100008 提醒客户阅读我司报告发布平台统一发布的完整的证券研究报告,仔细阅读其所附风险提示、各项声明及信息披露。 重要提示：本订阅号为东方证券股份有限公司（以下称“东方证券”）研究所医药研究团队运营的订阅号，并非东方证券研究报告的发布平台, 本订阅号仅转发东方证券已发布研究报告的部分内容或对报告进行的跟踪与解读。通过本订阅号发布的资料仅供东方证券研究所指定客户参考。因本订阅号无法设置访问限制，若您并非东方证券研究所指定客户，为控制投资风险，请您请取消关注，请勿订阅、接收或使用本订阅号中的任何信息。东方证券不因任何单纯订阅本公众号的行为而将订阅人视为客户。 免责声明：本订阅号不是东方证券研究报告的发布平台，本订阅号仅转发东方证券已发布研究报告的部分内容或对报告进行的跟踪与解读, 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