Fedratinib Hydrochloride

JAK抑制剂行业深度报告 一、导语：一个靶点的三十年沉浮 1992年，当科学家们在研究干扰素如何激活细胞信号时，意外发现了一条全新的信号通路——JAK-STAT。这条以罗马双面神Janus命名的激酶家族，因其氨基末端激酶结构域前面带有调节性假激酶结构域的"双面"特征而得名。谁也不曾想到，这个诞生于基础科学研究的发现，将在三十年后催生出一个年销售额超百亿美元、覆盖从肿瘤到自身免疫疾病多个治疗领域的重磅药物类别。 2011年，Incyte/诺华联合开发的芦可替尼（Ruxolitinib）获FDA批准，成为全球首个JAK抑制剂，用于治疗骨髓纤维化。2012年，辉瑞的托法替尼（Tofacitinib）获批用于类风湿关节炎，标志着JAK抑制剂正式进入自身免疫疾病的主流治疗舞台。 此后十年间，JAK抑制剂经历了从第一代泛JAK抑制到第二代高选择性JAK1抑制，再到第三代TYK2变构抑制的技术迭代，也经历了从"重磅炸弹"到"黑框警告"再到"绝地反击"的市场波折。 2024年，全球JAK抑制剂市场规模约45.9亿美元，预计到2025年将增长至52亿美元，2033年有望突破156.8亿美元，年复合增长率高达50.6%。在中国市场，JAK抑制剂同样处于高速增长期，2023年销售总额达21.5亿元，其中芦可替尼以8.6亿元销售额领跑，占市场份额近40%。 然而，这个看似光鲜的市场背后，是激烈的代际竞争、严峻的安全性挑战和复杂的国产替代博弈。当普祺医药的普美昔替尼凝胶于2026年2月申报上市，有望成为全球首款JAK抑制剂外用凝胶时，中国创新药企正在以"局部递送"的差异化策略，试图在这个由跨国巨头主导的赛道中撕开一道裂缝。 技术演进史：三代JAK抑制剂的代际革命 第一代：泛JAK抑制的开拓与代价 第一代JAK抑制剂以芦可替尼、托法替尼、巴瑞替尼为代表，其核心特征是同时抑制多个JAK亚型（JAK1、JAK2、JAK3、TYK2中的两种或多种），通过广谱阻断JAK-STAT信号通路发挥抗炎作用。 芦可替尼（Ruxolitinib）：2011年获批，JAK1/JAK2抑制剂，首个适应症为骨髓纤维化，2017年进入中国，2019年纳入医保，2023年中国销售额8.6亿元，年复合增长率76.95%。其乳膏剂型于2021年获FDA批准用于特应性皮炎和白癜风，成为全球首个外用JAK抑制剂。 托法替尼（Tofacitinib）：2012年获批，JAK1/JAK3抑制剂，是FDA批准的首个用于类风湿关节炎的JAK抑制剂。2017年进入中国，但2021年因一项长达6年的安全性研究失败，FDA对其添加黑框警告，提示心血管事件和癌症风险增加。2024年全球销售额约11.68亿美元，同比下降31%。 巴瑞替尼（Baricitinib）：2017年获批，JAK1/JAK2抑制剂，2019年进入中国，2020年纳入医保后价格降幅达73.38%，销售额从2019年的0.12亿元飙升至2023年的4.22亿元，年复合增长率141.9%。2020年获FDA紧急使用授权用于新冠肺炎治疗，成为JAK抑制剂拓展感染性疾病适应症的标志性案例。 第一代JAK抑制剂的共同困境在于安全性。由于其泛抑制特性，在阻断致病性炎症信号的同时，也干扰了JAK2介导的血小板生成、JAK3介导的免疫功能等正常生理过程，导致贫血、血小板减少、感染、心血管事件等不良反应。2021年9月，FDA对所有JAK抑制剂（包括后续上市的第二代产品）发布黑框警告，涵盖心血管、肿瘤、血栓、感染及死亡风险。这一监管风暴严重打击了JAK抑制剂的市场声誉，托伐替尼销售额应声下滑，近半数风湿病医生减少开具处方。 第二代：高选择性JAK1抑制的崛起与局限 第二代JAK抑制剂的核心策略是提高对JAK1的选择性，减少对JAK2、JAK3的脱靶抑制，从而在保持疗效的同时降低安全性风险。 乌帕替尼（Upadacitinib）：艾伯维研发，2019年获FDA批准，是全球首个高选择性JAK1抑制剂，对JAK1的选择性是对JAK2的16倍。2022年进入中国并纳入医保，2023年销售额1.63亿元，全球销售额则达到约27亿美元，2024年上半年同比增长60.4%至25.23亿美元，成为艾伯维接替"药王"修美乐的核心产品。艾伯维预计2027年乌帕替尼销售额将达110亿美元。 阿布昔替尼（Abrocitinib）：辉瑞研发，2021年获批，高选择性JAK1抑制剂，2022年进入中国，2023年进入医保，价格从225元/片降至78元/片。在特应性皮炎领域，阿布昔替尼与生物制剂度普利尤单抗的头对头试验显示，其对头颈部、躯干、上下肢的皮损清除疗效更优，且起效更快，有望打破度普利尤单抗一家独大的局面。 第二代JAK抑制剂虽在安全性上有所改善，但FDA的黑框警告并未解除。2023年8月，国家知识产权局宣告乌帕替尼核心化合物专利全部无效或部分无效，国内6家企业（天地恒一、四川国为、杨凌科森、江苏华阳、山东齐都、重庆华邦）已提交仿制申请，艾伯维在中国市场将提前面对仿制药竞争。 第三代：TYK2变构抑制的范式突破 2022年9月，BMS的氘可来昔替尼（Deucravacitinib）获FDA批准，成为全球首个第三代JAK抑制剂，也是首个TYK2变构抑制剂。 氘可来昔替尼的独特之处在于其作用机制：通过靶向TYK2的假激酶结构域JH2，而非传统的催化活性位点JH1，实现变构抑制。这种机制使其对TYK2具有极高选择性（Ki=0.02 nM），对JAK1、JAK2、JAK3几乎无抑制作用，从而避免了传统JAK抑制剂的泛抑制副作用。 更重要的是，氘可来昔替尼是目前唯一未被FDA添加黑框警告的JAK抑制剂，标志着JAK抑制剂安全性的里程碑式突破。 2023年，氘可来昔替尼进入中国市场，2025年5月新适应症银屑病关节炎上市申请获受理。其全球销售额增长迅速，成为BMS在自免领域的重要增长点。 三、市场格局：百亿赛道的竞争与分化 全球市场：从"一超多强"到"群雄逐鹿" 2024年，全球JAK抑制剂市场规模超102.4亿美元，预计2025年达110亿美元。市场呈现以下特征： 托法替尼衰退：因黑框警告和专利到期（2026年），2024年销售额仅11.68亿美元，同比下降31%。 乌帕替尼崛起：2024年销售额约54.51亿美元（艾伯维自免业务整体），同比增长64%，成为JAK抑制剂新"药王"。 芦可替尼稳健：2024年销售额28亿美元，在骨髓纤维化领域保持领先。 氘可来昔替尼放量：作为唯一无黑框警告的JAK抑制剂，增长潜力巨大。 中国市场：医保放量与国产替代的双重变奏 中国JAK抑制剂市场虽规模较小（2023年21.5亿元），但增速迅猛，2019-2024年复合增长率达92.2%，预计2030年将达481亿元。 进口产品主导：目前中国市场已有芦可替尼、托法替尼、巴瑞替尼、乌帕替尼、阿布昔替尼5款原研药上市，其中托法替尼、巴瑞替尼、乌帕替尼、阿布昔替尼已纳入医保。 国产替代加速： 恒瑞医药艾玛昔替尼（SHR0302）：2025年3月获批强直性脊柱炎、类风湿关节炎、特应性皮炎三项适应症，成为国内第4款、国产第2款JAK抑制剂，对JAK1选择性是对JAK2的16倍。 泽璟制药杰克替尼：2022年递交骨髓纤维化上市申请，对JAK2和TYK2抑制作用最强，同时抑制ACVR1降低铁调素转录，改善贫血。 诺诚健华ICP-332：TYK2抑制剂，针对特应性皮炎的II期临床取得积极结果，进度全球靠前。 普祺医药普美昔替尼：JAK1/JAK2抑制剂，凝胶和鼻喷雾剂两种局部递送剂型，2026年2月凝胶申报上市，有望成为全球首款JAK抑制剂凝胶。 竞争焦点：从"系统性给药"到"局部递送" 传统JAK抑制剂均为口服或注射给药，系统性暴露导致全身性副作用。近年来，局部递送成为差异化竞争的重要方向： 芦可替尼乳膏（Incyte/康哲药业）：2021年FDA批准用于特应性皮炎和白癜风，是全球首个外用JAK抑制剂。 迪高替尼凝胶（日本烟草）：2020年日本批准用于特应性皮炎，全球首款JAK局部外用药物。 普美昔替尼凝胶（普祺医药）：2026年2月申报上市，III期临床显示EASI降低70.2%，EASI 75应答率53.8%，有望成为中国及全球首款JAK抑制剂凝胶。 局部递送的优势在于：病灶部位药物浓度高、全身暴露量低、安全性显著改善、无黑框警告风险。这一技术路径为JAK抑制剂开辟了轻中度患者市场，与口服制剂形成互补。 安全性博弈：黑框警告的阴影与突围 安全性始终是JAK抑制剂的核心挑战。2021年FDA的黑框警告源于托法替尼的一项长期研究：与TNF抑制剂相比，托法替尼组心血管事件风险增加33%，癌症风险增加近50%。尽管该研究纳入的是50岁以上且至少存在一个心血管风险因素的人群，但FDA将警告范围扩展至所有JAK抑制剂。 然而，随着临床数据的积累和真实世界研究的深入，JAK抑制剂的安全性认知正在重构： 皮肤病领域风险较低：2025年研究表明，以治疗皮肤疾病的剂量使用JAK抑制剂时，严重副作用并不常见，黑框警告源于风湿性疾病的高剂量使用经验。 第二代产品改善显著：乌帕替尼、阿布昔替尼在头对头试验中显示出与生物制剂相当的安全性，痤疮、恶心等不良反应多为轻中度。 第三代产品破局：氘可来昔替尼因变构抑制机制，避免了JAK1/2/3的脱靶效应，成为唯一无黑框警告的JAK抑制剂。 安全性争议的持续，为局部递送型JAK抑制剂提供了市场机遇。普祺医药的普美昔替尼凝胶通过外用给药，血药浓度显著低于口服制剂，理论上可规避系统性副作用，这一差异化优势可能成为其商业化破局的关键。 五、国产突围：普祺医药的"局部递送"赌局 在中国JAK抑制剂市场的激烈竞争中，普祺医药选择了一条独特的路径——局部递送。 技术差异化：从"口服"到"外用" 普美昔替尼是JAK1/JAK2抑制剂，与已上市的芦可替尼乳膏机制相似，但剂型创新使其具备差异化竞争力： 凝胶剂型：用于特应性皮炎，2026年2月申报上市，有望成为全球首款JAK抑制剂凝胶。III期临床数据显示，每日2次3%凝胶治疗8周后，EASI降低70.2%，显著优于安慰剂组的32.5%。 鼻喷雾剂：用于过敏性鼻炎，处于III期临床，预计2026年Q4申报上市，有望成为全球首款JAK抑制剂鼻喷雾剂。 局部递送的技术护城河在于：避开口服JAK抑制剂的红海竞争，满足轻中度患者对非激素外用治疗的需求，同时规避黑框警告对处方的限制。 商业化策略：授权合作与轻资产运营 2026年2月，普祺医药与济川药业达成最高1亿元的合作协议（4000万元首付款+6000万元里程碑款），将普美昔替尼鼻喷雾剂的大中华区商业化权益授权给后者。这一策略的优势在于： 快速变现：首付款直接补充现金流，缓解公司资金压力（截至2025年9月现金仅1.55亿元）。 借力销售：济川药业在呼吸领域拥有成熟销售网络，可弥补普祺医药商业化经验短板。 风险共担：里程碑付款与销售业绩挂钩，降低自建团队的不确定性。 挑战与风险 普祺医药的"局部递送"策略并非没有风险： 进度滞后：恒瑞医药艾玛昔替尼软膏已于2025年2月申报上市，领先普美昔替尼整整一年，时间窗口的错失可能削弱"首款"优势。 市场教育：外用JAK抑制剂作为新剂型，需要投入大量资源进行医生和患者教育。 估值争议：公司累计亏损超5亿元，零营收，北交所IPO撤回后转道港股，对赌协议2026年6月到期，时间紧迫。 未来趋势：JAK抑制剂的下一个十年 适应症拓展：从自免到肿瘤、感染 JAK抑制剂的适应症正在从传统的类风湿关节炎、银屑病、特应性皮炎向更多领域拓展： 肿瘤：芦可替尼用于骨髓纤维化、真性红细胞增多症等血液肿瘤，Fedratinib、Pacritinib等针对骨髓纤维化的新药陆续上市。 感染：巴瑞替尼、托法替尼在新冠肺炎中的成功应用，开辟了JAK抑制剂在细胞因子风暴管理中的新场景。 罕见病：利特昔替尼（Ritlecitinib）成为全球首个获批用于重度斑秃的JAK3/TEC抑制剂，开辟全新市场。 联合疗法：JAK抑制剂与生物制剂的协同 JAK抑制剂与生物制剂的联合应用正在探索中。例如，JAK抑制剂与IL-23抑制剂联用可能通过双重阻断炎症通路增强疗效，或与低剂量生物制剂联用以减少用量、降低副作用。这种"小分子+大分子"的组合策略，可能成为未来自免疾病治疗的重要方向。 技术迭代：双靶点与AI驱动 下一代JAK抑制剂的研发方向包括： 双靶点抑制剂：如JAK1/TYK2双抑制剂，通过同时阻断多个炎症通路提高疗效。 AI辅助设计：利用AlphaFold等AI工具预测最佳靶点组合，加速新药发现。 精准医疗：基于生物标志物筛选优势人群，实现个体化治疗。 七、结语：代际革命中的中国机遇 JAK抑制剂行业正经历从第一代泛抑制到第二代高选择、再到第三代变构抑制的代际革命，从系统性给药到局部递送的剂型革命，从进口垄断到国产替代的市场革命。在这个过程中，中国创新药企正从"跟随者"向"并跑者"甚至"领跑者"转变。 普祺医药的普美昔替尼凝胶申报上市，标志着中国企业在JAK抑制剂局部递送领域实现了全球同步甚至领先。 然而，真正的考验在于商业化：能否在跨国巨头的围剿中建立起医生和患者的品牌认知，能否在医保谈判中争取到合理定价，能否在持续亏损中支撑到产品放量盈利。 JAK抑制剂的下一个十年，将是技术差异化、临床价值重构和全球市场竞争的十年。 对于中国企业而言，这不仅是一场关于创新的赌局，更是一次从"中国制造"到"中国创造"的跃迁。当普美昔替尼的凝胶涂抹在特应性皮炎患者的皮损上，当鼻喷雾剂喷入过敏性鼻炎患者的鼻腔，中国创新药的"局部递送"故事，正在书写新的篇章。

Consolidated net revenue of € 2,618.4 million for full year 2025, +11.8% or +8.3% on a like-for-like basis (3) at constant exchange rates (CER) EBITDA (1) of € 991.1 million, +14.5%, margin on net revenue of 37.8% Adjusted net income (2) of € 651.1 million, +14.5%, margin on net revenue of 24.9% Net income of € 443.6 million, +6.5% Free cash flow (4) of € 558.8 million, +€ 23.7 million reflecting strong EBITDA partially offset by U.S. inventory build-up, higher interests and income tax paid Net debt (5) at € 2,037.3 million, just below 2.1x EBITDA FY 2026 financial targets: Net revenue € 2,730-€2,800 million with FX headwind of ~-3.5% ; EBITDA (1) € 995-€1,030 million, margin +/- 36.5% ; Adjusted net income (2) € 655-€ 685 million, margin +/- 24.0% In January 2026, the Group received a B‑ rating with ‘Prime’ status from ISS ESG, recognizing its leading sustainability performance within the industry Milan, February 17, 2026 – The Board of Directors of Recordati S.p.A. has reviewed and approved the preliminary consolidated financial statements for 2025. The Group’s final consolidated annual financial statements for 2025 will be submitted to the Board of Directors for approval on March 19, 2026. Rob Koremans, Chief Executive Officer of Recordati, commented: “2025 was another year of solid progress across the business, reflecting the strength of our execution. We delivered once again on our financial targets despite a challenging macroenvironment, including increased FX headwinds. During the year, we further strengthened our portfolio through strategic partnerships in both Rare Diseases and Specialty and Primary Care. There is excellent momentum in Rare Diseases, which continues to be a key driver of growth and value creation for the Group. We are excited by Isturisa’s opportunity to address the broader Cushing’s syndrome market, with uptake accelerating in the U.S. With such a strong foundation in place, we expect 2026 to be another year of disciplined execution as we continue to deliver on our strategic objectives, maintain sector-leading margins and create sustainable value for all our stakeholders.” Financial highlights Consolidated net revenue for full year 2025 was € 2,618.4 million, up 11.8% versus full year 2024 or 8.3% on a like-for-like (3) basis at CER, driven by solid contribution from both Specialty & Primary Care and Rare Diseases. The adverse FX impact for full year 2025 was € 64.2 million (-2.7%). Specialty & Primary Care revenue was € 1,477.9 million for full year 2025, up 2.0% or 3.8% on a like-for-like basis (3) at CER (+1.6% excluding Türkiye). This reflects continued positive performance of all core therapeutic areas (promoted product evolution index of 105), despite a slight slowdown in relevant market growth. In particular, the Urology and Cardiovascular franchises grew 2.5% and 2.8%, respectively, while the Gastrointestinal franchise grew 9.9%, driven by the strong in-market performance of several products in the portfolio, both prescription and OTC. Rare Diseases revenue was € 1,081.4 million for full year 2025, up 29.7% as compared to full year 2024, or 16.6% on a like-for-like (3) basis at CER, driven by strong volume growth across all three franchises. The Endocrinology franchise achieved net revenue of € 394.1 million, an increase of 22.5%, reflecting an acceleration of new patient uptake of Isturisa ® in the U.S. in the second half of 2025 with approximately 1,400 net active patients at the end of the year, as well as double-digit growth of Signifor ® . The Hema-Oncology franchise achieved net revenue of € 414.9 million, growing by 63.8%, reflecting the contribution of Enjaymo ® of € 146.3 million (+26.7% vs full year 2024 proforma (6) ), and driven by strong growth of Sylvant ® and Qarziba ® . The Metabolic franchise achieved net revenue of € 272.5 million, sustaining mid-single digit growth of 5.2%, driven by Carbaglu ® and Panhematin ® . Adjusted operating income (7) was € 774.9 million for full year 2025, up 13.2% over full year 2024, and 29.6% of net revenue versus 29.2% in the previous year. Operating income was € 670.8 million for full year 2025, up 5.0% over full year 2024, absorbing gross margin-related non-cash charges of € 66.8 million as compared to € 37.5 million for full year 2024, arising from the unwind of the fair value step up of acquired Rare Diseases inventory including € 62.5 million for Enjaymo ® . Non-recurring costs were € 37.3 million for full year 2025, versus € 8.0 million for full year 2024. These costs reflect primarily the continued optimization of the Specialty and Primary Care commercial organization, mainly in Italy and Spain. The non‑recurring costs also include a one‑off provision of €12.8 million (8) related to the settlement of a litigation case with AIFA concerning prior years payback for Urorec ® . Additionally, non‑recurring items include the impact of the ongoing voluntary liquidation of the Rare Diseases subsidiary in China, following the rejection of the National Reimbursement Drug List approval for Isturisa ® . The availability of Qarziba ® and Sylvant ® in the territory continues to be provided through a local distributor. EBITDA (1) was € 991.1 million for full year 2025, up 14.5% compared to full year 2024, with margin on net revenue of 37.8%. The improvement over the prior year was driven by a positive business mix and strong operating performance across both business units, despite the significant foreign exchange headwinds and higher investments to support the U.S. launch of the expanded Isturisa ® label, the continued development of Enjaymo ® and ongoing geographic expansion in Rare Diseases. Financial expenses were € 89.5 million for full year 2025, down by € 2.1 million as compared to full year 2024. New loans obtained in 2024, related to the acquisition of Enjaymo ® , and in 2025 led to an increase in interest expenses of € 17.4 million. Net exchange gains over the period were € 15.0 million (mainly unrealized and driven by the devaluation of the U.S. dollar), against net FX losses of € 9.3 million in FY 2024. This was partly offset by € 5.3 million of net monetary losses from hyperinflation accounting (compared to a loss of € 6.7 million in full year 2024) mainly driven by the net effect of the revaluation of Turkish balance sheet items. Adjusted Net Income was € 651.1 million, 24.9% of revenue, up by 14.5% compared to full year 2024. This growth reflects improvements in adjusted operating income as well as lower financial expenses partially offset by higher income taxes. Net income was € 443.6 million, 16.9% of revenue, increasing by 6.5% versus full year 2024, mainly driven by the higher operating income and lower financial expenses. Free cash flow (4) was € 558.8 million for full year 2025, an increase of € 23.7 million versus full year 2024, with strong EBITDA partially offset by higher working capital absorption (mainly driven by higher U.S. inventory levels), higher interests and income tax paid. Net debt (5) as of December 31, 2025 was € 2,037.3 million, or leverage of just below 2.1x EBITDA, compared to net debt of € 2,154.3 million on December 31, 2024, following dividend payments of € 267.6 million, treasury shares purchased for € 112.5 million (net of proceeds from exercising stock options), the upfront payment for Vazkepa ® rights of USD 25 million and the upfront payment for Inrebic ® rights of USD 11 million. Shareholders’ equity was € 1,919.8 million. Pipeline Update On April 15, 2025, the U.S. Food and Drug Administration (FDA) approved the supplemental new drug application (sNDA) for Isturisa ® (osilodrostat) for the treatment of endogenous hypercortisolemia in adults with Cushing’s syndrome for whom surgery is not an option or has not been curative. This was an expansion of the previous indication for the treatment of patients with Cushing’s disease, which is a sub-type of Cushing’s syndrome. The Isturisa ® indication expansion was supported by the extensive Isturisa ® clinical development program, which included over 350 patients. In addition, during the second quarter of 2025, Isturisa ® was granted regulatory approval in both Canada and Russia. A Phase IV study to assess the efficacy and safety of osilodrostat in adults with mild hypercortisolemia and uncontrolled hypertension (HTN) due to Cushing’s syndrome is expected to start in 2026. During the second quarter of 2025, an investigator-sponsored clinical trial (IST) was initiated to investigate the safety, dose and early signs of effect for dinutuximab beta (Qarziba ® ) in combination with chemotherapy for the treatment of patients with GD2-positive Ewing sarcoma. On July 28, 2025, the European Commission issued a positive decision and granted marketing authorization, under exceptional circumstances, for Maapliv ® , a solution of amino acids intended for the treatment of maple syrup urine disease (MSUD) presenting with an acute decompensation episode in patients from birth who are not eligible for an oral and enteral branched-chain amino acids (BCAA)-free formulation. The Company completed enrollment of the pasireotide Phase 2 trial for the treatment of post-bariatric hypoglycemia in August 2025. Top-line results are expected in the second quarter of 2026. Following the meeting with the U.S. Food and Drug Administration (FDA) in early September, a potential U.S. biologics license application (BLA) pathway was established with the FDA for Qarziba ® requiring an additional set of clinical data from the ongoing BEACON-2 investigator-sponsored trial. Results of the interim analysis are expected in the first half of 2028 and are expected to form the basis, together with existing clinical data, for a potential regulatory filing. On January 5, 2026, the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization for Eligard ® for the treatment of hormone dependent advanced prostate cancer and for the treatment of high-risk localized and locally advanced hormone dependent prostate cancer in combination with radiotherapy. The other lifecycle management programs are progressing in line with plans. Corporate Development On June 24, 2025, Recordati announced a licensing and supply agreement with Amarin to commercialize the marketed cardiovascular medicine, Vazkepa ® (icosapent ethyl) across 59 countries, focused in Europe. Vazkepa ® is indicated to reduce the risk of cardiovascular events in statin-treated adult patients at high cardiovascular risk with elevated triglycerides and either established cardiovascular disease or diabetes with at least one other cardiovascular risk factor. Vazkepa ® is expected to achieve over € 40 million in revenues in 2027 and to be EBITDA positive from 2026. Under the terms of the agreement, Recordati paid Amarin an upfront cash payment of USD 25 million. On December 17, 2025, Recordati announced the exclusive license agreement with Impact Biomedicines, Inc., a Bristol Myers Squibb subsidiary, and the related supply agreement with Celgene Logistics Sàrl to commercialize Inrebic ® (fedratinib dihydrochloride monohydrate) in Japan. Impact Biomedicines, Inc. will retain exclusive rights to develop and commercialize Inrebic® in the rest of the world. Inrebic ® is an oral kinase inhibitor with activity against wild-type and mutationally activated JAK2 to suppress the pathological features of myelofibrosis patients. Inrebic ® received regulatory approval from the Ministry of Health, Labour and Welfare (MHLW) in Japan in June 2025 for the treatment of myelofibrosis and is expected to launch in mid 2026. Under the terms of the agreement, Recordati paid Impact Biomedicines, Inc. an upfront payment of USD 11 million. On January 29, 2026, Recordati announced a collaboration and license agreement with Moderna to develop and commercialize worldwide mRNA-3927, an investigational product for the treatment of propionic acidemia (PA). Under the terms of the agreement, Moderna will continue to lead the development of mRNA-3927, in collaboration with Recordati, and if approved, Recordati will lead global commercialization. mRNA-3927 is a post proof-of-concept, investigational product aimed to restore propionyl-CoA carboxylase (PCC) enzyme activity in patients with propionic acidemia. If approved, this could be the first disease-modifying treatment option on the market for this severe disease. mRNA-3927 is currently being evaluated in a potential registrational clinical study. The target patient enrollment has been reached, with a potential data readout expected by the end of 2026. Under the terms of the agreement, Recordati will pay Moderna an upfront payment of USD 50 million and up to an additional USD 110 million in near-term development and regulatory milestones. Moderna is also eligible to receive commercial and sales milestones, as well as tiered royalties on annual net sales. Recordati does not expect any significant impact on its EBITDA prior to a potential launch. Business outlook The financial targets for full year 2026 are as follows: Net revenue between € 2,730 and € 2,800 million with FX headwind of ~-3.5% EBITDA (1) between € 995 and € 1,030 million; margin of +/- 36.5% Adjusted net income (2) between € 655 and € 685 million; margin of +/- 24.0% The full year 2027 targets (9) remain unchanged, with strong organic growth complemented by bolt-on BD and M&A. (1) Net income before income taxes, financial income and expenses, depreciation, amortization and write-downs of property, plant and equipment, intangible assets and goodwill, non-recurring items and non-cash charges arising from the allocation of the purchase price of acquisitions to the gross margin of acquired inventory as foreseen by IFRS (2) Net income excluding amortization and write-downs of intangible assets (except software) and goodwill, non-recurring items, non-cash charges arising from the allocation of the purchase price of acquisitions to the gross margin of acquired inventory as foreseen by IFRS 3, monetary net gains/losses from hyperinflation (IAS 29), net of tax effects. (3) Proforma growth calculated excluding revenue of Vazkepa® for FY 2025 (Specialty & Primary Care) and Enjaymo® for both FY 2025 and FY 2024 (Rare Diseases) (4) Total cash flow excluding financing items, milestones, dividends, purchases of treasury shares net of proceeds from exercise of stock options. (5) Cash and cash equivalents, less bank debts and loans, which include the measurement at fair value of hedging derivatives. (6) Comparing FY 2025 revenue (which considers also the margin retained by Sanofi’s on in market sales for those countries where it was still holding the MA) with proforma FY 2024 revenue also including sales totally realized by Sanofi. (7) Net income before income taxes, financial income and expenses and non-recurring items, non-cash charges arising from the allocation of the purchase price of acquisitions to the gross margin of acquired inventory as foreseen by IFRS 3. (8) The provision has been revised since September to reflect the terms of the final settlement agreement with AIFA (9) FY 2027 targets: Net Revenue €3,000 - €3,200 million, EBITDA €1,140 - €1,225 million, Adjusted Net Income €770- €820 million, excluding potential impact from tariffs and/or most favored nation pricing policies in the U.S. Conference Call Recordati will host a conference call on February 18 th , at 2:00 p.m. CET ( 1:00 p.m. GMT ) to present the results for full year 2025. Please find the pre-registration link here with all the dial-in details and a calendar invitation to follow. Alternatively, if not pre-registered, the dial-in numbers for the conference call are: Italy + 39 02 802 09 11, toll free 800 231 525 UK + 44 1 212818004, toll free (44) 0 800 0156371 USA +1 718 7058796, toll free (1) 1 855 2656958 France +33 1 70918704 Germany +49 6917415712 Participants are invited to dial in 10 minutes before the start of the conference call. If operator assistance is required to connect, please dial *0. The slides that will be referenced during the call will be available at under Investors/Company Presentations. Recordati is an international pharmaceutical group listed on the Italian Stock Exchange (XMIL: REC), with roots dating back to a family-run pharmacy in Northern Italy in the 1920s. We are uniquely structured to provide treatments across specialty and primary care, and rare diseases. Our fully integrated operations span clinical development, chemical and finished product manufacturing, commercialization and licensing. We operate in approximately 150 countries across EMEA, the Americas and APAC with over 4,500 employees. We believe that health is a fundamental right, not a privilege. Today, our purpose of “unlocking the full potential of life” aims at empowering individuals to live life to the fullest, whether addressing common health challenges or the rarest. Investor Relations Eugenia Litz eugenia.litz@recordati.com Gianluca Saletta saletta.g@recordati.it Media Relations Laura Conti conti.l@recordati.it Rebecca Kerr rebecca.kerr@recordati.com This document contains forward-looking statements relating to future events and future operating, economic and financial results of the Recordati group. By their nature, forward-looking statements involve risk and uncertainty because they depend on the occurrence of future events and circumstances. Actual results may therefore differ materially from forecasts for a variety of reasons, most of which are beyond the Recordati group ’ s control. The information on the pharmaceutical specialties and other products of the Recordati group contained in this document is intended solely as information on the activities of the Recordati Group, and, as such, it is not intended as a medical scientific indication or recommendation, or as advertising . DECLARATION BY THE FINANCIAL REPORTING OFFICER The Financial Reporting Officer, Niccolò Giovannini, declares, pursuant to paragraph 2 of Article 154- bis of the Consolidated Law on Finance, that the accounting information contained in this press release corresponds to the Company’s documentation, books and accounting records. RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA S.p.A. Registered Office Via Matteo Civitali, 1 20148 Milano, Italy Tel. +39 02 487871 Fax +39 02 40073747 Share Capital € 26.140.644,50 fully paid-up Milano, Monza, Brianza and Lodi Comp. Reg. No. 00748210150 Tax Code/VAT No. 00748210150 Milano R.E.A. No. 401832 Company subject to the Management and Coordination Activity of Rossini Luxembourg S.àr.l