Pemigatinib

治疗FGFR2异常的胆管癌等实体瘤 KNT-0916 高选择性FGFR2抑制剂     在恶性肿瘤治疗进入精准医学的时代，分子靶向药物的研发与应用彻底改变了传统放化疗"杀敌一千自损八百"的治疗格局。成纤维细胞生长因子受体2（FGFR2）作为实体瘤中高频异常的驱动基因，已成为胆管癌、乳腺癌、胃癌等多种癌症治疗的关键靶点。然而，第一代泛FGFR抑制剂在临床应用中暴露的选择性不足、耐药频发、毒性显著等问题，成为制约治疗效果的重要瓶颈。     KNT-0916作为中国原研的高选择性FGFR2抑制剂，由广州科恩泰生物医药科技有限公司与中国科学院上海有机化学研究所马大为院士、丁克教授团队联合研发，通过创新性的分子设计实现了对FGFR2的精准靶向。这款药物不仅在临床前研究中展现出优异的抗肿瘤活性，更在早期临床试验中为FGFR2异常实体瘤患者带来了新的治疗希望，标志着中国在FGFR靶向治疗领域跻身国际先进行列。 （一）FGFR2异常：实体瘤的关键驱动因素     FGFR家族属于受体酪氨酸激酶（RTK）超家族，包括FGFR1、FGFR2、FGFR3和FGFR4四个成员，在细胞增殖、分化、迁移及血管生成等生理过程中发挥核心调控作用。FGFR2作为该家族的重要成员，其基因异常可通过多种机制导致信号通路持续激活，进而驱动肿瘤发生发展。     在胆管癌中，FGFR2异常尤为常见，发生率可达10%-20%，主要表现为基因融合、点突变和扩增三种形式。其中FGFR2融合最为典型，常见融合伴侣包括BICC1、CASP7、MGEA5等，形成的融合蛋白具有自主磷酸化活性，可constitutively激活下游RAS/RAF/MEK/ERK和PI3K/AKT/mTOR信号通路，促进肿瘤细胞无限增殖。点突变则集中于S252W、P253R等位点，这些突变改变了FGFR2蛋白结构，使其对配体亲和力增强，导致通路异常激活。基因扩增则通过增加基因拷贝数导致蛋白过表达，同样引发信号通路过度激活。     除胆管癌外，FGFR2异常在多种实体瘤中均有检出：在乳腺癌中，FGFR2扩增发生率约5%-10%，与肿瘤侵袭性增强和预后不良相关；在胃癌中，FGFR2扩增占比约7%，尤其在Lauren肠型胃癌中更为常见；在非小细胞肺癌中，FGFR2融合虽发生率仅1%-2%，但因其预后极差而成为重要治疗靶点。这些数据表明，FGFR2异常是跨瘤种的关键驱动因素，为靶向治疗提供了广泛的应用基础。 （二）现有治疗方案的局限与未满足需求     传统治疗手段疗效有限：对于FGFR2异常实体瘤，传统治疗以化疗为主，但效果欠佳。以胆管癌为例，晚期患者一线采用顺铂联合吉西他滨化疗的客观缓解率（ORR）仅15%-26%，中位无进展生存期（PFS）不足6个月，中位总生存期（OS）仅11-12个月。对于化疗耐药或不耐受的患者，后续治疗选择匮乏，生存期往往不足6个月。     第一代泛FGFR抑制剂的瓶颈：为突破传统治疗困境，泛FGFR抑制剂应运而生，包括佩米替尼（Pemigatinib）、福巴替尼（Futibatinib）、英菲格拉替尼（Infigratinib）等，已获批用于FGFR2融合胆管癌的二线治疗。但这类药物存在明显缺陷：选择性不足引发毒性：泛FGFR抑制剂同时抑制FGFR1-4，导致正常组织FGFR信号通路受抑，引发高磷血症（发生率50%以上）、腹泻（30%-40%）、口腔炎、眼部毒性等不良反应。其中高磷血症需通过饮食控制或药物干预管理，严重时需剂量调整甚至停药，影响治疗连续性。耐药问题突出：临床应用中，患者通常在治疗6-9个月后出现耐药，主要机制包括FGFR2二次突变（如V561E、F276C）、旁路信号激活（如EGFR、MET扩增）等。对于耐药患者，目前缺乏有效治疗手段。适用人群受限：现有药物主要获批用于FGFR2融合/重排患者，对于点突变、扩增等其他异常类型的疗效尚未明确，大量FGFR2异常患者无法获益。     临床需求的迫切性：随着分子检测技术的普及，越来越多FGFR2异常实体瘤患者被识别，但现有治疗手段无法满足其临床需求。尤其对于化疗失败、对泛FGFR抑制剂耐药或不耐受的患者，亟需安全性更高、疗效更持久、适用范围更广的新型靶向药物。KNT-0916的研发正是针对这一临床痛点，通过极致的选择性设计实现治疗突破。 01、药物作用机制 （一）FGFR2信号通路的异常激活机制     正常生理状态下，FGFR2需与配体FGF结合才能形成二聚体，进而引发细胞内激酶结构域反式磷酸化，激活下游信号通路。而在肿瘤细胞中，FGFR2异常可通过三种核心机制打破这一调控平衡：     融合驱动激活：FGFR2与伴侣基因融合后，其激酶结构域脱离extracellular配体调控区域，形成持续激活的融合蛋白，不依赖配体即可启动信号传导。     点突变激活：S252W、P253R等位点突变导致FGFR2蛋白构象改变，增强其与FGF配体的结合能力，或使受体处于持续激活状态。     扩增驱动激活：FGFR2基因拷贝数增加导致蛋白过表达，通过配体依赖性方式增强信号传导强度，促进肿瘤进展。     这些异常激活最终通过下游RAS/MAPK通路促进细胞增殖，通过PI3K/AKT通路抑制细胞凋亡，同时激活血管内皮生长因子（VEGF）通路促进肿瘤血管生成，形成肿瘤发展的恶性循环。 （二）KNT-0916的分子作用机制     KNT-0916基于FGFR2激酶结构域的晶体结构设计，通过创新性的分子结构实现了对靶点的精准调控，其作用机制具有三大核心特征：     不可逆共价结合模式：KNT-0916分子包含丙烯酰胺基团，可与FGFR2激酶结构域中的半胱氨酸残基（Cys477）形成不可逆共价键，从而持久占据 ATP 结合口袋，抑制激酶活性。这种结合模式区别于传统泛FGFR抑制剂的可逆结合，使得药物在体内能够维持较长的靶点抑制效应，延长作用时间，为提高疗效奠定基础。质谱分析已证实KNT-0916与FGFR2的共价结合特性，而对其他FGFR家族成员无此类结合能力。     超高靶点选择性：通过对分子骨架的系统性优化，KNT-0916实现了对FGFR2的高度特异性识别。体外激酶活性检测显示，其对FGFR2的半数抑制浓度（IC50）仅为2.8nM，而对FGFR1的选择性达290倍，对FGFR4的选择性更是超过2000倍，对FGFR3及其他75种酪氨酸激酶的抑制率均低于1%。这种极致选择性的分子基础在于，KNT-0916的侧链结构能够精准适配FGFR2特有的氨基酸残基构象，而无法有效结合其他FGFR亚型的相应结构域。     广谱抗突变活性：针对临床常见的FGFR2耐药突变，KNT-0916展现出显著的抑制活性。在BaF3细胞模型中，对于携带FGFR2 V561E、F276C等耐药突变的细胞株，KNT-0916仍能有效抑制其增殖，IC50值均保持在纳摩尔级别；而传统泛FGFR抑制剂对这些突变株的抑制活性显著下降，IC50值升高数十至数百倍。这一特性使其能够克服部分原发性和获得性耐药，扩大治疗获益人群。 （三）从分子抑制到肿瘤消退的效应传导     KNT-0916通过上述机制实现对FGFR2信号通路的精准阻断，进而产生多重抗肿瘤效应：     直接抑制肿瘤细胞增殖：FGFR2信号通路被阻断后，下游RAS/MAPK通路激活受抑，导致肿瘤细胞周期停滞于G1期，无法进入增殖期；同时PI3K/AKT通路抑制使细胞凋亡信号增强，促进肿瘤细胞死亡。     抑制肿瘤血管生成：FGFR2信号是血管内皮细胞存活和增殖的关键调控因素，KNT-0916通过抑制肿瘤血管内皮细胞的FGFR2活性，减少新生血管形成，切断肿瘤营养供应，实现"饿死肿瘤"的效应。     抑制肿瘤侵袭转移：FGFR2信号通路激活可增强肿瘤细胞的上皮-间质转化（EMT）能力，促进侵袭转移。KNT-0916通过阻断该通路，降低肿瘤细胞的迁移和侵袭能力，延缓疾病进展。     在临床前动物模型中，这些效应得到充分验证：在FGFR2融合的胆管癌PDX模型中，KNT-0916口服给药4周后，肿瘤体积平均缩小70%，部分模型实现肿瘤完全消退；而同等剂量的佩米替尼肿瘤缩小率仅为40%-50%。在FGFR2扩增的胃癌模型中，KNT-0916同样展现出显著的肿瘤抑制作用，且未观察到明显的毒性反应。 02、科学严谨的临床试验研究 01 临床试验推进中     KNT-0916目前已完成临床前研究，并在中国和美国同步启动临床试验。截至2025年6月，其I期临床试验已公布初步数据，展现出优异的安全性和疗效特征。该研究为单臂、开放、剂量递增及扩展试验，共纳入50例经标准治疗失败的FGFR2异常晚期实体瘤患者，其中胆管癌占60%，乳腺癌占18%，胃癌占12%，其他实体瘤占10%。 02 （一）剂量递增阶段：确定安全有效剂量     剂量递增阶段纳入12例患者，探索了5个剂量水平（10mg qd至200mg qd）。研究结果显示：     安全性特征：在10mg-150mg剂量范围内，未观察到剂量限制性毒性（DLT）；200mg剂量组出现2例3级口腔炎，确定为DLT。     药代动力学特征：KNT-0916口服吸收良好，达峰时间（Tmax）约2小时，半衰期（T1/2）约18小时，支持每日一次给药；血药浓度随剂量成比例增加，在100mg qd剂量下，稳态血药浓度可达FGFR2抑制所需浓度的8倍以上。     初步疗效：在可评估的10例患者中，3例（30%）达到部分缓解（PR），5例（50%）达到疾病稳定（SD），疾病控制率（DCR）达80%。     基于上述结果，确定II期推荐剂量（RP2D）为100mg qd，口服给药，直至疾病进展或出现不可耐受毒性。 03 （二）剂量扩展阶段：疗效与安全性深度验证     剂量扩展阶段基于FGFR2异常类型分为4个队列（融合/重排、扩增、点突变、过表达），共纳入38例患者，其中25例可评估疗效。截至2025年6月，核心结果如下：     客观缓解率（ORR）：35例可评估患者中，14例达到PR，ORR达40.0%；其中12例患者缓解持续时间超过4个月，中位缓解持续时间（DoR）尚未达到。     疾病控制率（DCR）：29例患者达到PR或SD，DCR达82.9%。     无进展生存期（PFS）：中位PFS达8.5个月，6个月PFS率为68.6%。     不同瘤种疗效差异：胆管癌队列（21例）：ORR达45.2%，DCR达85.7%，中位PFS达9.2个月；其中1例患者治疗6个月后仍维持PR，肿瘤缩小幅度达65%。乳腺癌队列（9例）：ORR达33.3%，DCR达77.8%，中位PFS达7.8个月。胃癌队列（6 例）：ORR达33.3%，DCR达83.3%，中位PFS达8.0个月。不同 FGFR2 异常类型疗效：融合/重排队列（18例）：ORR达44.4%，DCR达88.9%，中位PFS达9.5个月。点突变队列（9例）：ORR达33.3%，DCR达77.8%，中位PFS达7.2个月，其中1例FGFR2 S252W突变胆管癌患者达到PR。扩增队列（8例）：ORR达37.5%，DCR达87.5%，中位PFS达8.3个月。      安全性数据：总体耐受性良好：所有患者均出现治疗相关不良事件（TRAE），但多为1-2级。常见TRAE：口腔炎（30.0%）、乏力（25.0%）、皮疹（18.0%）、食欲下降（16.0%），均为轻度可控。严重TRAE：仅2例（4.0%）出现3级血小板减少，无4级及以上TRAE发生。特征性毒性缺失：整个试验期间未观察到高磷血症或腹泻病例，与临床前研究结果一致。 04 典型病例：从耐药绝境到临床获益     48岁的李先生确诊FGFR2-BICC1融合晚期胆管癌2年，先后接受顺铂+吉西他滨化疗、佩米替尼靶向治疗，均因疾病进展或毒性反应停药。佩米替尼治疗期间，李先生出现3级高磷血症，需长期服用磷酸盐结合剂，生活质量严重下降；停药后1个月，肝内肿瘤进展至5cm，CA19-9（肿瘤标志物）升至1200U/ml，被医生判断为预后极差。2024年10月，李先生加入KNT-0916临床试验，接受100mg qd口服治疗：治疗1个月：CA19-9降至600U/ml，肝内肿瘤缩小至4.2cm，未出现任何不适症状。治疗3个月：CA19-9进一步降至200U/ml，肝内肿瘤缩小至2.8cm，达到PR标准；复查血磷水平始终维持正常范围。治疗6个月：肿瘤持续稳定在2.5cm左右，CA19-9降至150U/ml；李先生已恢复正常饮食，每日可散步1小时，生活质量显著提升。该病例充分体现了KNT-0916在泛FGFR抑制剂耐药、不耐受患者中的治疗价值，为这类难治性患者提供了新的生存希望。 03、显著优势：相较传统药物的突破性特征 01 极致选择性带来的安全性飞跃     安全性优势是KNT-0916最核心的突破点，其根源在于对FGFR2的超高选择性。与现有泛FGFR抑制剂相比，安全性差异极为显著。这种安全性优势带来了多重临床价值：无需监测血磷：患者无需频繁检测血磷水平，减少就医次数和医疗负担。治疗连续性保障：避免了因高磷血症、腹泻等毒性导致的剂量调整或停药，确保药物持续发挥作用。老年患者适用性：对于体能状态较差的老年患者，良好的耐受性使其能够安全接受治疗，扩大了获益人群。 02 广谱抗突变活性克服耐药难题     耐药是FGFR靶向治疗面临的主要挑战，而KNT-0916的抗突变活性为解决这一问题提供了有效方案。临床前研究显示，其对多种FGFR2突变均有显著抑制活性。这种广谱活性使其能够覆盖三类患者：初治患者：作为一线治疗可延缓耐药发生，延长治疗获益时间。原发性耐药患者：对于携带FGFR2二次突变的原发性耐药患者，仍能有效发挥作用。获得性耐药患者：对于经泛FGFR抑制剂治疗后出现耐药的患者，KNT-0916可作为挽救治疗方案。 03 跨瘤种治疗潜力扩大应用范围     与现有主要获批用于胆管癌的FGFR2抑制剂不同，KNT-0916在多种FGFR2异常实体瘤中均展现出疗效，具有显著的跨瘤种治疗潜力。这一优势源于其作用机制的普适性——无论FGFR2异常表现为融合、突变还是扩增，只要通路异常激活是肿瘤驱动因素，KNT-0916即可通过抑制FGFR2活性发挥抗肿瘤作用。临床试验数据已初步证实其跨瘤种价值：在乳腺癌、胃癌队列中，ORR均超过30%，DCR超过75%，与胆管癌队列疗效相近。此外，临床前研究显示，在FGFR2过表达的子宫内膜癌模型中，KNT-0916同样能显著抑制肿瘤生长，为后续临床试验拓展奠定基础。这种跨瘤种潜力意味着KNT-0916未来可能惠及更多FGFR2异常实体瘤患者，具有更广阔的临床应用前景。 04 中国原研的自主创新优势     KNT-0916作为中国原研新药，具有显著的自主创新特征：核心技术自主可控：其分子结构设计基于马大为院士团队的原创性研究，拥有全球范围内的专利保护，避免了知识产权纠纷。符合中国患者特征：临床试验纳入大量中国患者，疗效和安全性数据更贴合中国人群，为国内临床应用提供更可靠的证据支持。产业化潜力巨大：作为口服制剂，KNT-0916生产工艺成熟，成本可控，未来上市后可及性更高，能够惠及更多普通患者。中国科学院院士评价指出："KNT-0916的研发成功，是产学研协同创新的典范，标志着中国在高选择性激酶抑制剂领域已达到国际领先水平。"     KNT-0916的研发与早期临床进展，是中国原研药物在精准医疗领域取得的重要突破。它通过创新性的分子设计，解决了第一代泛FGFR抑制剂选择性不足、毒性显著、耐药频发的核心痛点，为FGFR2异常实体瘤患者带来了全新的治疗选择。从临床前研究中70%的肿瘤缩小率，到I期试验中40%的ORR和零高磷血症发生率，每一组数据都彰显了其精准靶向的治疗优势。     在全球肿瘤药物研发竞争激烈的背景下，KNT-0916的成功不仅体现了中国科研团队在激酶抑制剂设计领域的技术突破，更展现了产学研协同创新的强大活力。它的出现，标志着中国在FGFR靶向治疗领域从"跟跑"向"领跑"转变，为全球实体瘤精准治疗贡献了中国智慧。     展望未来，随着临床试验的深入推进和治疗策略的不断优化，KNT-0916有望成为FGFR2异常实体瘤治疗的标杆药物，改变无数患者的生存命运。同时，它也将为中国原研靶向药物的研发提供可借鉴的模式，推动更多创新药物问世，最终实现"精准抗癌，让生命更有质量"的目标。正如医学发展的历史所示，每一个突破性药物的出现，都在推动癌症治疗向治愈的目标迈进一大步——KNT-0916正承载着这样的使命，在精准医疗的道路上稳步前行。

WILMINGTON, Del.--(BUSINESS WIRE)--Incyte (Nasdaq:INCY) today reported financial results for the third quarter of 2025 and provided a business update. “Our third-quarter results demonstrate strong growth across our product portfolio, with net product revenues increasing 19% year-over-year, which highlights the momentum in our business and effective commercial execution,” said Bill Meury, President & CEO. “Our third-quarter results demonstrate strong growth across our product portfolio, with net product revenues increasing 19% year-over-year, which highlights the momentum in our business and effective commercial execution,” said Bill Meury, President and Chief Executive Officer, Incyte. “We are taking a deliberate approach to pipeline prioritization. We are actively reviewing our R&D efforts and focusing on high-value programs that are scientifically differentiated, address unmet medical needs, and have the potential to significantly drive Incyte’s next phase of growth." Third Quarter 2025 Results Total revenues: Total revenues were $1.37 billion, an increase of 20% compared to the third quarter of 2024, primarily driven by an increase in total net product revenues. Total net product revenue for the third quarter of 2025 was $1.15 billion, an increase of 19%. The increase was primarily related to patient demand for Jakafi ® (ruxolitinib) across all indications and strong uptake of the initial launch of Niktimvo ™ (axatilimab-csfr). Cost of product revenues: GAAP and non-GAAP cost of product revenues were $99.0 million and $92.7 million, an increase of 15% and 16%, respectively, compared to the prior year period. Research and development (R&D) expenses: GAAP and non-GAAP R&D expenses were $506.6 million and $467.0 million, a decrease of 12% and 11%, respectively, compared to the prior year period. Selling, general and administrative (SG&A) expenses: GAAP and non-GAAP SG&A expenses were $329.1 million and $308.0 million, an increase of 6% and 11%, respectively, compared to the prior year period. Cash, cash equivalents and marketable securities position: As of September 30, 2025 and December 31, 2024, cash, cash equivalents and marketable securities totaled $2.9 billion and $2.2 billion, respectively. Full-year 2025 Financial Guidance The Company is raising its full-year 2025 net product revenue guidance to $4.23 - $4.32 billion to account for higher demand for Jakafi and other hematology and oncology marketed products. The update includes raised guidance for Jakafi to $3.050 - $3.075 billion, as well as other hematology and oncology marketed products to $550 - $575 million. The Opzelura ® (ruxolitinib) cream revenue guidance of $630 - $670 million is maintained. The Company reiterates its guidance for GAAP and non-GAAP cost of product revenues, R&D, and SG&A expenses for full year 2025, which reflects the continued investment in mid- and late-stage clinical development programs and commercial capabilities. Key Business Updates Myeloproliferative Neoplasms (MPNs) and Graft-Versus-Host Disease (GVHD) The Company is on track to submit ruxolitinib extended-release (XR) bioequivalence data to the U.S. Food and Drug Administration (FDA) in the fourth quarter. Results from the Phase 1 trial evaluating INCA033989, an investigational mutant calreticulin (mutCALR) selective monoclonal antibody, in mutCALR positive patients with myelofibrosis (MF) are expected in the second half of 2025. The Phase 1 results will include safety and efficacy data evaluating INCA033989 as a monotherapy in patients who are resistant, refractory or intolerant to JAK inhibitor treatment, as well as data evaluating INCA033989 as a combination therapy with ruxolitinib in patients who are exhibiting a suboptimal response to ruxolitinib monotherapy. Hematology/Oncology In October, results from the Phase 1 trial evaluating INCA33890 (TGFBR2xPD-1 bispecific antibody) in solid tumors were presented at the European Society for Medical Oncology (ESMO) Congress. In the trial, INCA33890 demonstrated a manageable tolerability profile and clinical efficacy across multiple tumors, including microsatellite stable colorectal cancer (MSS CRC) patients with and without active liver metastases. Based on these initial findings, the Company plans to initiate a registrational program evaluating INCA33890 in MSS CRC in 2026. Preliminary results from the Phase 1 trial evaluating INCB161734 (KRAS G12D selective inhibitor) were presented at the ESMO Congress in October. In the trial, INCB161734 demonstrated a manageable safety profile and clinical efficacy in heavily pretreated pancreatic ductal adenocarcinoma (PDAC) patients with a KRAS G12D mutation. Evaluation of INCB161734 in PDAC patients as a monotherapy, and in combination with chemotherapy, is ongoing and will support potential future development efforts. A Phase 2 trial evaluating INCB123667 (CDK2i) in patients with platinum-resistant ovarian cancer (PROC) with Cyclin E1 overexpression was initiated in the third quarter. The Phase 3 study evaluating tafasitamab (Monjuvi ® ) as first-line treatment for diffuse large B-cell lymphoma (DLBCL) is ongoing, with data anticipated around year-end 2025. Inflammation and Autoimmunity (IAI) Ruxolitinib cream In September, the FDA approved the supplemental New Drug Application (sNDA) for Opzelura for pediatric atopic dermatitis (AD). Opzelura is now indicated for the short-term and non-continuous chronic treatment of mild to moderate AD in non-immunocompromised adult and pediatric patients two years of age and older whose disease is not well controlled with topical prescription therapies, or when those therapies are not recommended. In October, Phase 3 results from the TRuE-AD4 trial evaluating Opzelura in patients with moderate AD were presented at the International Symposium on Atopic Dermatitis (ISAD). Results from the study demonstrated that by Week 8, treatment with Opzelura significantly improved the clinical signs of AD, rapidly improved itch, improved quality of life measures and was well tolerated in adults with moderate AD who had an inadequate response, intolerance or contraindication to topical corticosteroid (TCS)s and topical calcineurin inhibitor (TCI)s. The Company anticipates filing a Type-II variation application for ruxolitinib cream 1.5% for the treatment of adults with moderate AD in the European Union (EU) by year-end 2025. Povorcitinib In September, longer-term data for povorcitinib were presented at the European Association of Dermatology and Venereology (EADV) which demonstrated continued clinically meaningful and statistically significant improvements in patients with active moderate to severe hidradenitis suppurativa (HS). Regulatory submissions for povorcitinib in moderate to severe HS in the EU and the U.S. are anticipated by year end 2025 and early 2026, respectively. Data from the Phase 3 studies evaluating povorcitinib in prurigo nodularis (PN) and vitiligo, as well as data from the Phase 2 proof-of-concept trial in asthma, are anticipated in 2026. Corporate and Business Development Updates The Company strengthened its executive leadership team through the appointment of Soni Basi as Executive Vice President and Chief Human Resources Officer and Dave Gardner as Executive Vice President and Chief Strategy Officer in the third quarter. Based on ongoing pipeline prioritization efforts, the Company has paused further development of the INCA034460 (anti-CD122) and INCB57643 (BET inhibitor) programs, as well as the development of povorcitinib in chronic spontaneous urticaria (CSU). The Company announced a strategic partnership with Enable Injections, Inc., to develop and commercialize specific assets in Incyte’s portfolio, including INCA033989, with Enable’s enFuse ® on-body delivery system. Under the terms of the agreement, Incyte will obtain a worldwide, exclusive license to use the enFuse technology with INCA033989 in essential thrombocythemia (ET) and MF, with the potential to expand to additional assets and indications. 2025 Third Quarter Financial Results The financial measures presented in this press release for the three and nine months ended September 30, 2025 and 2024 have been prepared by the Company in accordance with U.S. Generally Accepted Accounting Principles (“GAAP”), unless otherwise identified as a Non-GAAP financial measure. Management believes that Non-GAAP information is useful for investors, when considered in conjunction with Incyte’s GAAP disclosures. Management uses such information internally and externally for establishing budgets, operating goals and financial planning purposes. These metrics are also used to manage the Company’s business and monitor performance. The Company adjusts, where appropriate, for expenses in order to reflect the Company’s core operations. The Company believes these adjustments are useful to investors by providing an enhanced understanding of the financial performance of the Company’s core operations. The metrics have been adopted to align the Company with disclosures provided by industry peers. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used in conjunction with and to supplement Incyte’s operating results as reported under GAAP. Non-GAAP measures may be defined and calculated differently by other companies in our industry. As changes in exchange rates are an important factor in understanding period-to-period comparisons, Management believes the presentation of certain revenue results on a constant currency basis in addition to reported results helps improve investors’ ability to understand its operating results and evaluate its performance in comparison to prior periods. Constant currency information compares results between periods as if exchange rates had remained constant period over period. The Company calculates constant currency by calculating current year results using prior year foreign currency exchange rates and generally refers to such amounts calculated on a constant currency basis as excluding the impact of foreign exchange or being on a constant currency basis. These results should be considered in addition to, not as a substitute for, results reported in accordance with GAAP. Results on a constant currency basis, as the Company presents them, may not be comparable to similarly titled measures used by other companies and are not measures of performance presented in accordance with GAAP. Financial Highlights Financial Highlights (unaudited, in thousands, except per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2025 2024 2025 2024 Total GAAP revenues $ 1,365,980 $ 1,137,871 $ 3,634,407 $ 3,062,519 Total GAAP operating income (loss) 443,518 146,085 1,179,000 (240,147 ) Total Non-GAAP operating income 498,296 255,236 1,164,516 37,618 GAAP net income (loss) 424,169 106,456 987,371 (168,597 ) Non-GAAP net income (loss) 455,972 209,651 997,358 (53,762 ) GAAP basic EPS $ 2.17 $ 0.55 $ 5.08 $ (0.80 ) Non-GAAP basic EPS $ 2.33 $ 1.09 $ 5.13 $ (0.25 ) GAAP diluted EPS1 $ 2.11 $ 0.54 $ 4.95 $ (0.80 ) Non-GAAP diluted EPS1 $ 2.26 $ 1.07 $ 5.00 $ (0.25 ) 1 All stock options and stock awards were excluded from the diluted share calculation for the nine months ended September 30, 2024 because their effect would have been anti-dilutive, as we were in a net loss position. Revenue Details Revenue Details (unaudited, in thousands) Three Months Ended September 30, % Change (as reported) % Change (constant currency)1 Nine Months Ended September 30, % Change (as reported) % Change (constant currency)1 2025 2024 2025 2024 Net product revenues: Jakafi $ 791,071 $ 741,181 7 % NA $ 2,264,271 $ 2,018,993 12 % NA Opzelura 187,968 139,272 35 % 33 % 471,172 346,691 36 % 35 % Iclusig 37,582 29,745 26 % 19 % 99,855 86,950 15 % 11 % Pemazyre 22,741 20,661 10 % 9 % 63,373 58,606 8 % 8 % Minjuvi/ Monjuvi 41,990 31,439 34 % 32 % 102,672 86,429 19 % 18 % Niktimvo 45,830 — NM NA 95,597 — NM NA Zynyz 22,674 694 3,167 % NA 34,604 1,812 1,810 % NA Total net product revenues 1,149,856 962,992 19 % 19 % 3,131,544 2,599,481 20 % 20 % Royalty revenues: Jakavi 125,645 115,741 9 % 4 % 327,504 304,653 8 % 5 % Olumiant 37,111 34,796 7 % 4 % 101,393 97,087 4 % 5 % Tabrecta 6,513 5,928 10 % NA 19,558 16,460 19 % NA Other 1,855 414 348 % NA 4,408 1,838 140 % NA Total royalty revenues 171,124 156,879 9 % 452,863 420,038 8 % Total net product and royalty revenues 1,320,980 1,119,871 18 % 3,584,407 3,019,519 19 % Milestone and contract revenues 45,000 18,000 150 % 150 % 50,000 43,000 16 % 16 % Total GAAP revenues $ 1,365,980 $ 1,137,871 20 % $ 3,634,407 $ 3,062,519 19 % NM = not meaningful NA = not applicable 1 Percentage change in constant currency is calculated using 2024 foreign exchange rates to recalculate 2025 results. Product and Royalty Revenues Total net product revenues for the quarter ended September 30, 2025 increased 19% over the prior year comparative period. Jakafi net product revenue increased 7% in the third quarter of 2025 versus the prior year comparable period to $791 million, primarily driven by a 10% increase in paid demand across all indications. Jakafi inventory levels were within normal range at the end of the third quarter of 2025. Opzelura net product revenue increased 35% in the third quarter of 2025 versus the prior year comparable period to $188 million driven by increased patient demand and refills in both atopic dermatitis (AD) and vitiligo. Opzelura inventory levels were within normal range at the end of the third quarter of 2025. Niktimvo net product revenue increased 27% versus the second quarter of 2025 to $46 million driven by strong uptake following the product launch in the first quarter of 2025. Total net product and royalty revenues for the quarter ended September 30, 2025 increased 18% over the prior year comparative period. Operating Expenses Operating Expense Summary (unaudited, in thousands) Three Months Ended September 30, % Change Nine Months Ended September 30, % Change 2025 2024 2025 2024 GAAP cost of product revenues $ 99,001 $ 85,993 15 % $ 250,955 $ 223,583 12 % Non-GAAP cost of product revenues1 92,694 79,981 16 % 232,183 205,839 13 % Contract dispute settlement — — NM (242,251 ) — NM Non-GAAP contract dispute settlement2 — — NM — — NM GAAP research and development 506,584 573,174 (12 %) 1,438,780 2,140,814 (33 %) Non-GAAP research and development3 466,950 525,343 (11 %) 1,322,605 2,002,870 (34 %) GAAP selling, general and administrative 329,081 309,209 6 % 985,794 915,447 8 % Non-GAAP selling, general and administrative4 308,040 277,311 11 % 915,103 817,217 12 % GAAP (gain) loss on change in fair value of acquisition-related contingent consideration (12,204 ) 23,410 NM 22,129 23,847 NM Non-GAAP (gain) loss on change in fair value of acquisition-related contingent consideration — — NM — — NM GAAP (profit) and loss sharing under collaboration agreements — — NM — (1,025 ) NM NM = not meaningful 1 Non-GAAP cost of product revenues excludes the amortization of licensed intellectual property for Iclusig relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc. and the cost of stock-based compensation. 2 Non-GAAP contract dispute settlement excludes the contract dispute settlement reached with Novartis. 3 Non-GAAP research and development expenses exclude the cost of stock-based compensation, MorphoSys transition costs, and Escient acquisition related compensation expense related to cash settled unvested Escient equity awards and severance payments. 4 Non-GAAP selling, general and administrative expenses exclude the cost of stock-based compensation, MorphoSys transition costs, and Escient acquisition related compensation expense related to cash settled unvested Escient equity awards and severance payments. Cost of product revenues GAAP and Non-GAAP cost of product revenues for the quarter ended September 30, 2025 were $99.0 million and $92.7 million, an increase of 15% and 16%, respectively, compared to the same period in 2024, primarily driven by growth in net product revenues, the Niktimvo profit share and increased manufacturing related costs, partially offset by the impact of the contract dispute settlement with Novartis. Research and development expenses GAAP and Non-GAAP research and development expenses for the quarter ended September 30, 2025 were $506.6 million and $467.0 million, a decrease of 12% and 11%, respectively, compared to the same period in 2024, primarily due to the $100 million milestone payment made to MacroGenics during the third quarter of 2024. Excluding upfront and milestone payments and Escient severance payments, research and development expenses for the quarter ended September 30, 2025 increased 7% compared to the same period in 2024 primarily driven by continued investment in our late stage development assets. Selling, general and administrative expenses GAAP and Non-GAAP selling, general and administrative expenses for the quarter ended September 30, 2025 were $329.1 million and $308.0 million, an increase of 6% and 11%, respectively, compared to the same period in 2024, primarily due to international marketing activities to support product launches. Other Financial Information Contract dispute settlement In May 2025, Incyte and Novartis entered into a settlement agreement with respect to litigation relating to the duration of royalty payments owed under the Collaboration and License Agreement between Incyte and Novartis. We recorded $242.2 million in contract dispute settlement on the condensed consolidated statement of operations for the nine months ended September 30, 2025, representing the difference between the accrued royalties and the total amount paid by us to Novartis. Change in fair value of acquisition-related contingent consideration The change in fair value of contingent consideration during the quarter ended September 30, 2025, compared to the same period in 2024, was primarily due to updated projections of future net revenues of Iclusig, including the impacts from fluctuations in foreign currency exchange rates. Operating income GAAP and Non-GAAP operating income for the quarter ended September 30, 2025 increased 204% and 95%, respectively, compared to the same period in 2024, driven primarily by growth in net product revenues and the $100 million milestone payment made to MacroGenics during the third quarter of 2024. Cash, cash equivalents and marketable securities position As of September 30, 2025 and December 31, 2024, cash, cash equivalents and marketable securities totaled $2.9 billion and $2.2 billion, respectively. 2025 Financial Guidance Incyte’s guidance for the fiscal year 2025 is summarized below. Incyte is raising its full year 2025 net product revenue guidance to $4.23 - $4.32 billion to account for higher demand for Jakafi and other hematology and oncology marketed products. The update includes raised guidance for Jakafi to $3.050 - $3.075 billion, as well as other hematology and oncology marketed products to $550 - $575 million. Incyte is reaffirming its guidance across all other categories. Current Previous Jakafi net product revenues $3,050 - $3,075 million $3,000 - $3,050 million Opzelura net product revenues Unchanged $630 - $670 million Other oncology net product revenues(1) $550 - $575 million $500 - $520 million GAAP Cost of product revenues Unchanged 8.0% - 9.0% of net product revenues Non-GAAP Cost of product revenues(2) Unchanged 7.0% - 8.0% of net product revenues GAAP Research and development expenses Unchanged $1,965 - $1,995 million Non-GAAP Research and development expenses(3) Unchanged $1,815 - $1,840 million GAAP Selling, general and administrative expenses Unchanged $1,280 - $1,310 million Non-GAAP Selling, general and administrative expenses(3) Unchanged $1,160 - $1,185 million 1Pemazyre in the U.S., EU and Japan; Niktimvo, Monjuvi and Zynyz in the U.S.; and Iclusig and Minjuvi in the EU. 2Adjusted to exclude the amortization of licensed intellectual property for Iclusig relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc. and the estimated cost of stock-based compensation. 3Adjusted to exclude the estimated cost of stock-based compensation. Conference Call and Webcast Information Incyte will hold a conference call and webcast this morning at 8:00 a.m. ET. To access the conference call, please dial 877-407-3042 for domestic callers or 201-389-0864 for international callers. When prompted, provide the conference identification number, 13756261. If you are unable to participate, a replay of the conference call will be available for 90 days. The replay dial-in number for the United States is 877-660-6853 and the dial-in number for international callers is 201-612-7415. To access the replay you will need the conference identification number, 13756261. The conference call will also be webcast live and can be accessed at investor.incyte.com. About Incyte A global biopharmaceutical company on a mission to Solve On., Incyte follows the science to find solutions for patients with unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. Incyte's unique expertise in medicinal chemistry and biology has enabled us to establish a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia. For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn, X, Instagram, Facebook, YouTube. About Jakafi® (ruxolitinib) Jakafi® (ruxolitinib) is a JAK1/JAK2 inhibitor approved by the U.S. FDA for the treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea; intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults; steroid-refractory acute GVHD in adult and pediatric patients 12 years and older; and chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. Jakafi is a registered trademark of Incyte. About Opzelura® (ruxolitinib) Cream Opzelura® (ruxolitinib) cream, a novel cream formulation of Incyte’s selective JAK1/JAK2 inhibitor ruxolitinib, approved by the U.S. FDA for the topical treatment of nonsegmental vitiligo in patients 12 years of age and older, is the first and only treatment for repigmentation approved for use in the United States. Opzelura is also approved in the U.S. for the topical short-term and non-continuous chronic treatment of mild to moderate AD in non-immunocompromised patients 2 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. Use of Opzelura in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants, such as azathioprine or cyclosporine, is not recommended. In Europe, Opzelura (ruxolitinib) cream 15mg/g is approved for the treatment of non-segmental vitiligo with facial involvement in adults and adolescents from 12 years of age. Incyte has worldwide rights for the development and commercialization of ruxolitinib cream, marketed in the United States as Opzelura. Opzelura and the Opzelura logo are registered trademarks of Incyte. About Monjuvi® (tafasitamab-cxix) Monjuvi® (tafasitamab-cxix) is a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody. Tafasitamab incorporates an XmAb® engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP). Incyte licenses exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. In the U.S., Monjuvi is approved by the U.S. FDA in combination with lenalidomide and rituximab for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL). Monjuvi is not indicated and is not recommended for the treatment of patients with relapsed or refractory marginal zone lymphoma outside of controlled clinical trials. Additionally, Monjuvi received accelerated approval in the United States in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). In Europe, Minjuvi® (tafasitamab) received conditional Marketing Authorization from the European Medicines Agency in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for ASCT. XmAb® is a registered trademark of Xencor, Inc. Monjuvi, Minjuvi, the Minjuvi and Monjuvi logos and the “triangle” design are registered trademarks of Incyte. About Pemazyre® (pemigatinib) Pemazyre® (pemigatinib) is a kinase inhibitor indicated in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Pemazyre is also the first targeted treatment approved for use in the United States for treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer (BTC) with an FGFR2 fusion gene, worsening after cancer chemotherapy. In Europe, Pemazyre is approved for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or rearrangement that have progressed after at least one prior line of systemic therapy. Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations. Pemazyre is marketed by Incyte in the United States, Europe and Japan. Pemazyre is a trademark of Incyte. About Iclusig® (ponatinib) tablets Iclusig® (ponatinib), targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved tyrosine kinase inhibitors. In the EU, Iclusig is approved for the treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or the treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation. Click here to view the Iclusig EU Summary of Medicinal Product Characteristics. Incyte has an exclusive license from Takeda Pharmaceuticals International AG to commercialize ponatinib in the European Union and 29 other countries, including Switzerland, UK, Norway, Turkey, Israel and Russia. Iclusig is marketed in the U.S. by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. About Zynyz® (retifanlimab-dlwr) Zynyz® (retifanlimab-dlwr) is a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), indicated in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic SCAC and as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression or intolerance to platinum-based chemotherapy in the U.S. Zynyz is also indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) in the U.S. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Zynyz is marketed by Incyte in the United States. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab. Zynyz is a registered trademark of Incyte. About Niktimvo™ (axatilimab-csfr) Niktimvo™ (axatilimab-csfr) is a first-in-class colony stimulating factor-1 receptor (CSF-1R)-blocking antibody approved for use in the U.S. for the treatment of chronic GVHD after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs). In 2016, Syndax licensed exclusive worldwide rights to develop and commercialize axatilimab from UCB. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab in chronic GVHD and any future indications. Axatilimab is being studied in frontline combination trials in chronic GVHD – a Phase 2 combination trial with ruxolitinib (NCT06388564) and a Phase 3 combination trial with steroids (NCT06585774) are underway. Axatilimab is also being studied in an ongoing Phase 2 trial in patients with idiopathic pulmonary fibrosis (NCT06132256). Niktimvo is a trademark of Incyte. All other trademarks are the property of their respective owners. Forward-Looking Statements Except for the historical information set forth herein, the matters set forth in this release contain predictions, estimates and other forward-looking statements, including any discussion of the following: Incyte’s strategic priorities and its plans for executing on same; Incyte’s financial guidance for 2025, including its expectations regarding sales of and demand for Jakafi and Opzelura; expected revenue contribution from Niktimvo and other hematology and oncology products; Incyte’s potential for continued performance and growth; expectations regarding regulatory submissions, approvals and launches of ruxolitinib XR, ruxolitinib cream in Europe and povorcitinib; the potential and progress of programs in our pipeline, including povorcitinib, our TGFBR2xPD1 bispecific (INCA33890), our KRASG12D inhibitor (INCB161734) and INCA033989; ongoing clinical trials and clinical trials to be initiated; expectations regarding discussions with regulators, regulatory submissions and regulatory approvals; and 2025 newsflow items. These forward-looking statements are based on Incyte’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials and the ability to enroll subjects in accordance with planned schedules; determinations made by the FDA, EMA and other regulatory agencies; Incyte’s dependence on its relationships with and changes in the plans of its collaboration partners; the efficacy or safety of Incyte’s products and the products of Incyte’s collaboration partners; the acceptance of Incyte’s products and the products of Incyte’s collaboration partners in the marketplace; market competition; unexpected variations in the demand for Incyte’s products and the products of Incyte’s collaboration partners; the effects of announced or unexpected price regulation or limitations on reimbursement or coverage for Incyte’s products and the products of Incyte’s collaboration partners; sales, marketing, manufacturing and distribution requirements, including Incyte’s and its collaboration partners’ ability to successfully commercialize and build commercial infrastructure for newly approved products and any additional products that become approved; greater than expected expenses, including expenses relating to litigation or strategic activities; variations in foreign currency exchange rates; and other risks detailed in Incyte’s reports filed with the Securities and Exchange Commission, including its annual report on form 10-K for the year ended December 31, 2024. Incyte disclaims any intent or obligation to update these forward-looking statements. INCYTE CORPORATION CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited, in thousands, except per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2025 2024 2025 2024 GAAP GAAP Revenues: Product revenues, net $ 1,149,856 $ 962,992 $ 3,131,544 $ 2,599,481 Product royalty revenues 171,124 156,879 452,863 420,038 Milestone and contract revenues 45,000 18,000 50,000 43,000 Total revenues 1,365,980 1,137,871 3,634,407 3,062,519 Costs, expenses and other: Cost of product revenues (including definite-lived intangible amortization) 99,001 85,993 250,955 223,583 Contract dispute settlement — — (242,251 ) — Research and development 506,584 573,174 1,438,780 2,140,814 Selling, general and administrative 329,081 309,209 985,794 915,447 (Gain) loss on change in fair value of acquisition-related contingent consideration (12,204 ) 23,410 22,129 23,847 (Profit) and loss sharing under collaboration agreements — — — (1,025 ) Total costs, expenses and other 922,462 991,786 2,455,407 3,302,666 Income (loss) from operations 443,518 146,085 1,179,000 (240,147 ) Interest income 26,781 19,266 74,846 107,512 Interest expense (592 ) (774 ) (1,846 ) (1,861 ) Gain (loss) on equity investments 8,558 (12,982 ) 3,064 126,206 Other, net 4,043 4,929 19,446 11,196 Income before provision for income taxes 482,308 156,524 1,274,510 2,906 Provision for income taxes 58,139 50,068 287,139 171,503 Net income (loss) $ 424,169 $ 106,456 $ 987,371 $ (168,597 ) Net income (loss) per share: Basic $ 2.17 $ 0.55 $ 5.08 $ (0.80 ) Diluted $ 2.11 $ 0.54 $ 4.95 $ (0.80 ) Shares used in computing net income (loss) per share: Basic 195,670 192,629 194,459 211,763 Diluted 201,429 195,838 199,405 211,763 INCYTE CORPORATION CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited, in thousands) September 30, 2025 December 31, 2024 ASSETS Cash, cash equivalents and marketable securities $ 2,929,820 $ 2,158,092 Accounts receivable 895,890 853,154 Property and equipment, net 798,634 763,411 Finance lease right-of-use assets, net 28,155 30,803 Inventory 449,957 407,199 Prepaid expenses and other assets 402,878 181,382 Equity investments 21,870 18,814 Other intangible assets, net 119,421 113,803 Goodwill 155,593 155,593 Deferred income tax asset 528,138 762,071 Total assets $ 6,330,356 $ 5,444,322 LIABILITIES AND STOCKHOLDERS’ EQUITY Accounts payable, accrued expenses and other liabilities $ 1,459,790 $ 1,765,733 Finance lease liabilities 35,372 37,961 Acquisition-related contingent consideration 184,000 193,000 Stockholders’ equity 4,651,194 3,447,628 Total liabilities and stockholders’ equity $ 6,330,356 $ 5,444,322 INCYTE CORPORATION RECONCILIATION OF GAAP NET (LOSS) INCOME TO SELECTED NON-GAAP ADJUSTED INFORMATION (unaudited, in thousands, except per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2025 2024 2025 2024 GAAP Net Income (Loss) $ 424,169 $ 106,456 $ 987,371 $ (168,597 ) Adjustments1: Non-cash stock compensation from equity awards (R&D)2 39,634 45,808 114,058 117,141 Non-cash stock compensation from equity awards (SG&A)2 21,041 31,486 70,511 75,607 Non-cash stock compensation from equity awards (COGS)2 923 628 2,620 1,592 Non-cash interest3 82 81 245 333 (Gain) loss on equity investments4 (8,558 ) 12,982 (3,064 ) (126,206 ) Amortization of acquired product rights5 5,384 5,384 16,152 16,152 (Gain) loss on change in fair value of contingent consideration6 (12,204 ) 23,410 22,129 23,847 Contract dispute settlement7 — — (242,251 ) — MorphoSys transition costs8 — 132 — 7,084 Escient acquisition related compensation expense9 — 2,303 2,297 36,342 Tax effect of Non-GAAP pre-tax adjustments10 (14,499 ) (19,019 ) 27,290 (37,057 ) Non-GAAP Net Income (Loss) $ 455,972 $ 209,651 $ 997,358 $ (53,762 ) Non-GAAP net income (loss) per share: Basic $ 2.33 $ 1.09 $ 5.13 $ (0.25 ) Diluted11 $ 2.26 $ 1.07 $ 5.00 $ (0.25 ) Shares used in computing Non-GAAP net income (loss) per share: Basic 195,670 192,629 194,459 211,763 Diluted11 201,429 195,838 199,405 211,763 1 Included within the Milestone and contract revenues line item in the Condensed Consolidated Statements of Operations (in thousands) for the three and nine months ended September 30, 2025 are milestones of $45,000 and $50,000 earned from our collaborative partners, as compared to $18,000 and $43,000 of milestones earned for the three and nine months ended September 30, 2024. Included within the Research and development expenses line item in the Condensed Consolidated Statements of Operations (in thousands) for the three and nine months ended September 30, 2025 are upfront consideration and milestones of $100 and $28,150, respectively, related to our collaborative partners as compared to upfront consideration and milestones of $100,000 and $101,414, respectively, for the three and nine months ended September 30, 2024. 2 As included within the Cost of product revenues (including definite-lived intangible amortization) line item; the Research and development expenses line item; and the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations. 3 As included within the Interest expense line item in the Condensed Consolidated Statements of Operations. 4 As included within the Gain (loss) on equity investments line item in the Condensed Consolidated Statements of Operations. 5 As included within the Cost of product revenues (including definite-lived intangible amortization) line item in the Condensed Consolidated Statements of Operations. Acquired product rights of licensed intellectual property for Iclusig is amortized utilizing a straight-line method over the estimated useful life of 12.5 years. 6 As included within the (Gain) loss on change in fair value of acquisition-related contingent consideration line item in the Condensed Consolidated Statements of Operations. 7 As included within the Contract dispute settlement line item in the Condensed Consolidated Statements of Operations. 8 Included within the Research and development line item in the Condensed Consolidated Statements of Operations (in thousands) is $226 and $6,489 for the three and nine months ended September 30, 2024, respectively, and included within the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations (in thousands) is a benefit of $94 and expense of $595 for the three and nine months ended September 30, 2024, respectively. MorphoSys transition costs primarily represent employee related costs to transition research and development and selling, general and administrative activities to us under the former collaboration agreement with MorphoSys. 9 Included within the Research and development line item in the Condensed Consolidated Statements of Operations (in thousands) is $0 and $2,117 for the three and nine months ended September 30, 2025, and included within the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations is $0 and $180 for the three and nine months ended September 30, 2025. Included within the Research and development line item in the Condensed Consolidated Statements of Operations (in thousands) is $1,797 and $14,314, respectively, for the three and nine months ended September 30, 2024, and included within the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations (in thousands) is $506 and $22,028, respectively, for the three and nine months ended September 30, 2024. Escient acquisition related compensation expense represents non-recurring charges associated with (i) cash settled unvested Escient equity awards in connection with the acquisition, and (ii) severance payments to former Escient employees. 10 Income tax effects of Non-GAAP pre-tax adjustments are calculated using an estimated annual effective tax rate, taking into consideration any permanent items and valuation allowances against related deferred tax assets. 11 All stock options and stock awards were excluded from the diluted share calculation for the nine ended September 30, 2024 because their effect would have been anti-dilutive, as we were in a net loss position.