Albumin-Bound Paclitaxel

撰文 | 咸姐 胰腺导管腺癌（PDAC）是一种极具侵袭性的恶性肿瘤，因其早期诊断困难和对现有治疗的高度抵抗，患者预后极差。尤其是在免疫治疗领域，尽管免疫检查点抑制剂已在多种实体瘤中取得突破，但在PDAC中客观缓解率不足5%，显示出其独特的免疫抵抗特性。然而，近年来的研究发现，部分PDAC患者肿瘤内存在一种称为“三级淋巴结构”（TLS）的异位淋巴组织，这些结构由T细胞、B细胞和抗原呈递细胞聚集而成，与患者的较长生存期及对免疫治疗的更好响应密切相关。TLS的形成依赖于肿瘤微环境中特定基质细胞的引导，尤其是具有淋巴组织形成功能的成纤维网状细胞。在淋巴结中，这类细胞通过响应淋巴毒素β受体（LTBR）和肿瘤坏死因子受体（TNFR）信号，上调趋化因子如CCL19、CCL21和CXCL13，从而招募并组织淋巴细胞。然而，在PDAC中，肿瘤相关成纤维细胞（CAF）主要表现为由转化生长因子β（TGFβ）驱动的肌成纤维细胞（myCAF）表型，这类细胞通常与免疫抑制和基质纤维化相关，而具有免疫促进功能的网状CAF（rCAF）则极为罕见【1-3】。因此，尽管已知TLS的存在与良好预后相关，但在PDAC中为何仅部分肿瘤能够形成TLS，以及TGFβ信号如何影响成纤维细胞的分化进而抑制TLS形成，仍缺乏系统性的机制研究。 为此，近日，来自美国俄亥俄州立大学韦克斯纳医学中心的Andrew J. Gunderson团队在Cancer Cell上在线发表题为Myofibroblast programming blocks differentiation of TLS-organizing fibroblastic reticular cells in pancreatic cancer的文章，发现myCAF中的TGFβ受体信号通路会阻断与TLS形成相关的rCAF的分化，阐明了TGFβ信号通过诱导myCAF分化，阻断LTBR介导的rCAF编程，从而抑制TLS形成的机制；同时证实拮抗TGFβR1可实现依赖于LTBR的T细胞和B细胞募集，并增强肿瘤控制效果。这项工作不仅揭示了PDAC中TLS形成的障碍，为克服PDAC免疫治疗抵抗提供了新的策略，其机制也适用于其他对免疫治疗耐药的实体瘤。 本文研究人员首先对九种源自KPC（Pdx1-Cre/LSL-KRasG12D/+/LSL-p53R172H/+）转基因小鼠的PDAC细胞系进行了表征，以探究肿瘤基质免疫反应的异质性及其与肿瘤进展的关系。些细胞系被植入C57BL/6小鼠胰腺原位后，显示出差异显著的肿瘤生长动力学。为评估其体内形成TLS的能力，研究人员使用了一种具有激动活性的淋巴毒素β受体单克隆抗体（αLTBR）进行处理。结果显示，KPCL-1和KPC-6原位肿瘤在接受αLTBR治疗后生长显著减缓，肿瘤边缘出现包含高内皮微静脉和CXCL13阳性细胞的淋巴细胞聚集体，而对照组则罕见此类结构。这些早期TLS聚集体主要由B细胞构成，同时伴有CD3+CD8+ T细胞围绕。流式细胞术分析表明，LTBR在肿瘤微环境中的多种细胞表面均有表达，其中成纤维细胞和内皮细胞表达水平最高。值得注意的是，尽管肿瘤细胞也表达LTBR，但αLTBR治疗并未上调其PD-L1或MHC-I的表达，表明促炎反应并非由肿瘤细胞直接介导。这些数据表明，激动LTBR是一种可重复的诱导淋巴细胞募集和早期TLS形成的方法，为研究异质性PDAC模型中影响TLS发育和功能的机制提供了实验基础。 随后，研究人员探究了其他KPC细胞系对αLTBR治疗的响应，发现KPCL-4和KPCL-3细胞系既未产生淋巴聚集体，也未出现生长延缓，因此被定义为“TLS抵抗型”，而响应的KPC-6和KPCL-1则称为“TLS允许型”。流式细胞术分析显示，TLS允许型肿瘤富集ICAM-1+VCAM-1+的rCAF，而TLS抵抗型则以ICAM-1-VCAM-1+的myCAF为主。同时，TLS抵抗型肿瘤中αSMA表达和磷酸化SMAD2信号均更高，反映出myCAF和TGFβR信号通路的活化。这些CAF表型的差异与αLTBR处理后TLS允许型肿瘤中PD1+TCF1+干细胞样CD8+ T细胞、PD1+TCF1+耗竭CD8+ T细胞以及PD1+CXCR5+Foxp3+CD4+滤泡辅助性T细胞的显著增加相关。这些数据表明，不同小鼠PDAC模型对TLS诱导治疗（如LTBR激动）的响应差异与CAF表型异质性密切相关，且这种异质性不能简单地用肿瘤细胞的内在差异或基线水平内源性TNFR和LTBR配体的升高来解释。 基于以上发现，研究人员从小鼠皮肤分离原代成纤维细胞，深入探究TNFR/LTBR信号对其分化的调控。实验结果显示，TNFα与αLTBR联合处理可协同上调VCAM-1及趋化因子CXCL13和CCL19的表达，而TGFβ1处理则抑制VCAM-1、PDGFRα和LTBR的表达并上调PDGFRβ（TGFβ信号传导的直接靶点，并且是TGFβ诱导的myCAF分化的标志物。）。更重要的是，TGFβ1预处理完全阻断了αLTBR介导的VCAM-1上调及趋化因子的诱导，同时促使成纤维细胞上调myCAF标志物Acta2和Ctgf。而IL-1α或干扰素单独或联合αLTBR处理均未能诱导出rCAF的分化或趋化因子表达。从正常小鼠胰腺分离的成纤维细胞与皮肤成纤维细胞在基线标志物表达及对TGFβ1和TNFα/αLTBR的响应上表现出相似的模式。这些数据表明，TNFα和LTBR共同介导的成纤维细胞网状编程可被TGFβ诱导的myCAF分化所拮抗。进一步通过Transwell迁移实验证实，初始B细胞、初始CD8+ T细胞及Th1型CD4+ T细胞向TNFα/αLTBR激活的成纤维细胞迁移均显著增强，而当成纤维细胞预先经TGFβ1处理分化为myCAF后，这种迁移能力被显著抑制。值得注意的是，用TNFα/αLTBR处理TLS允许型KPC-6肿瘤细胞并未诱导CD8+ T细胞的迁移，这证明成纤维细胞而非肿瘤细胞是该模型中主要的淋巴组织形成细胞。这些结果表明，myCAF编程通过抑制趋化因子表达，阻断了淋巴细胞向rCAF的迁移。 那么，抑制TGFβR1信号能否逆转rCAF表型的抑制呢？答案是肯定的。体外实验显示，TGFβR1拮抗剂可解除TGFβ1对TNFα/αLTBR诱导的Cxcl13和Ccl19表达的抑制，并阻断myCAF分化。体内实验中，在TLS抵抗型肿瘤中联合αLTBR与TGFβR1抑制剂可将CAF从myCAF重编程为rCAF，并显著延缓肿瘤生长，而任一单药治疗均效果有限。此外，在TLS抵抗型模型中联合化疗（吉西他滨和白蛋白紫杉醇）与αLTBR及TGFβR1抑制剂可以进一步增强抗肿瘤效果。为明确CAF是否为TGFβ信号的关键靶细胞，研究人员构建了CAF特异性TGFβR1敲除小鼠，结果显示，在成纤维细胞缺失TGFβR1信号的情况下，αLTBR治疗足以诱导rCAF表型、增加T细胞和B细胞浸润，并显著缩小肿瘤体积。进一步地，研究人员通过对TLS抵抗型肿瘤进行αLTBR联合TGFβR1抑制剂治疗，成功将myCAF重编程为rCAF。流式细胞术分析显示，经联合治疗后，肿瘤内CD8+ T细胞和B细胞的浸润数量显著增加。然而，只有CD4+和CD8+ T细胞的减少削弱了αLTBR联合TGFβR1抑制剂治疗的效果，表明治疗效果取决于T细胞。有趣的是，尽管早期TLS的总数相似，但清除T细胞后聚集体尺寸减小，且CD8+ T细胞在早期TLS内的驻留消失，这表明仅靠B细胞聚集体不足以发挥功能，需要T细胞来介导抗肿瘤免疫。 最后，研究人员利用空间转录组学技术对PDAC患者肿瘤样本进行分析，发现rCAF富集的点显著富集于TLS及其邻近区域，而myCAF富集的点则主要分布在远离TLS的肿瘤实质区域。通过计算TLS聚集体周围不同距离内的CAF丰度，研究人员发现rCAF的丰度在靠近TLS处最高，并随距离增加而逐渐降低，myCAF则呈现相反分布。此外，TLS近端的rCAF亚群中TNFR和非经典NF-κB信号激活水平较高，而TGFβR信号水平较myCAF降低。由此在人类PDAC中也证明，rCAF与TLS存在密切的空间关联，而myCAF则定位于TLS远端。 综上所述，本研究表明，在PDAC中，TGFβ信号通过诱导myCAF分化，拮抗了由TNFR/LTBR信号介导的rCAF编程，从而抑制了TLS的形成。通过联合抑制TGFβR与激活LTBR信号，可将myCAF重编程为rCAF，恢复趋化因子表达，促进T细胞和B细胞向肿瘤内浸润，并增强抗肿瘤免疫反应。这一机制在人类PDAC样本中也得到了验证，为克服免疫治疗耐药提供了新的联合治疗策略。 原文链接： https://doi.org/10.1016/j.ccell.2026.03.004 制版人： 十一 参考文献 1. J Gunderson, A., Rajamanickam, V., Bui, C., et al. (2021). Germinal center reactions in tertiary lymphoid structures associate with neoantigen burden, humoral immunity and long-term survivorship in pancreatic cancer. OncoImmunology 10, 1900635. 2. Saute`s-Fridman, C., Petitprez, F., Calderaro, J., and Fridman, W.H. (2019). Tertiary lymphoid structures in the era of cancer immunotherapy. Nat. Rev. Cancer 19, 307–325. 3. Khanal, S., Wieland, A., and Gunderson, A.J. (2023). Mechanisms of tertiary lymphoid structure formation: cooperation between inflammation and antigenicity. Front. Immunol. 14, 1267654. 学术合作组织 （*排名不分先后） 战略合作伙伴 （*排名不分先后） · 转载须知 【原创文章】BioArt原创文章，欢迎个人转发分享，未经允许禁止转载，所刊登的所有作品的著作权均为BioArt所拥有。BioArt保留所有法定权利，违者必究。 BioArt Med Plants 人才招聘 近期直播推荐 点击主页推荐活动 关注更多最新活动！

Data demonstrate a 35 percent reduction in risk of death Lifyorli, in combination with nab-paclitaxel, added to NCCN Guidelines ® as a preferred regimen Lifyorli approved by the FDA in March 2026 REDWOOD CITY, Calif.--(BUSINESS WIRE)--Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, today presented final overall survival data from its pivotal Phase 3 ROSELLA trial of Lifyorli™ (relacorilant) combined with the chemotherapeutic agent nab-paclitaxel in patients with platinum-resistant ovarian cancer in a late-breaking oral presentation at the Society of Gynecologic Oncology (SGO) 2026 Annual Meeting on Women’s Cancer. The SGO presentation slides can be found here . These data were simultaneously published in The Lancet : “ Overall survival with relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): a phase 3 randomised controlled trial .” Lifyorli plus nab-paclitaxel has now been added to the National Comprehensive Cancer Network ® Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) as a preferred regimen for patients with platinum-resistant ovarian cancer. Lifyorli, in combination with nab-paclitaxel, was approved by the U.S. Food and Drug Administration (FDA) in March 2026 for the treatment of adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens, at least one of which included bevacizumab. Lifyorli is the first FDA-approved selective glucocorticoid receptor antagonist (SGRA). The ROSELLA trial met its dual primary endpoints of overall and progression-free survival, regardless of biomarker status and without an increased safety burden. Patients treated with Lifyorli in addition to nab-paclitaxel chemotherapy experienced a 35 percent reduction in the risk of death compared to patients treated with nab-paclitaxel alone (hazard ratio: 0.65; p-value: 0.0004). Median overall survival was 4.1 months longer for patients who received Lifyorli, compared to patients receiving nab-paclitaxel alone (16.0 v. 11.9 months). Patients who received Lifyorli in addition to nab-paclitaxel also experienced a 30 percent reduction in the risk of disease progression (hazard ratio: 0.70; p-value: 0.0076), as assessed by blinded independent central review compared to patients treated with nab-paclitaxel alone. The combination of Lifyorli with nab-paclitaxel was well-tolerated. Adverse events in the combination arm were comparable to those in the nab-paclitaxel monotherapy arm. The prescribing information for Lifyorli includes warnings and precautions for neutropenia and severe infections, adrenal insufficiency, exacerbation of conditions treated with glucocorticoids and embryo-fetal toxicity. The most common adverse reactions experienced by more than 20 percent of patients (including laboratory abnormalities) were decreased hemoglobin, decreased neutrophils, fatigue, nausea, diarrhea, decreased platelets, rash, and decreased appetite. “The safety and efficacy findings from ROSELLA are remarkable,” said Alexander B. Olawaiye, M.D., Professor and Vice Chair of Diversity and Inclusion at Magee-Women’s Hospital of the University of Pittsburgh, Principal Investigator in the ROSELLA trial, SGO presenter and Lancet publication author. “They give hope to patients and oncologists now that we have a new preferred regimen in this devastating and difficult-to-treat cancer.” “Patients with platinum-resistant ovarian cancer need more good treatment options. Relacorilant provides one. It significantly extends overall survival, with very little added toxicity,” said Domenica Lorusso, M.D., Ph.D., Director of the Gynaecological Oncology Unit at Humanitas Hospital San Pio X in Milan, and Full Professor of Obstetrics and Gynaecology at Humanitas University, Pieve Emanuele, Lancet publication senior author and European Network of Gynaecological Oncological Trial groups (ENGOT) investigator in the ROSELLA trial. “This regimen is firmly positioned as a new standard-of-care treatment for patients in the United States. We anticipate regulatory approval in Europe soon.” “ROSELLA’s positive findings affirm our confidence that selective glucocorticoid receptor (GR) antagonists, such as relacorilant, may help treat any patient whose tumor type expresses the GR,” said Bill Guyer, PharmD, Corcept’s Chief Development Officer. “With our recent FDA approval, we are now focused on delivering this therapy to patients and continuing cortisol modulation research in solid tumors that express GR across many different treatment settings. We are grateful for the patients and investigators who make our trials possible.” ROSELLA enrolled 381 patients with platinum-resistant ovarian cancer at sites in the United States, Europe, South Korea, Brazil, Argentina, Canada and Australia. Patients were randomized 1:1 to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone. The ROSELLA trial was conducted in collaboration with The GOG Foundation, Inc. (GOG-F) (GOG-3073), the European Network of Gynaecological Oncological Trial groups (ENGOT) (ENGOT-ov72), the Asia-Pacific Gynecologic Oncology Trials Group (APGOT) (APGOT-Ov10), the Latin American Cooperative Oncology Group (LACOG) (LACOG-0223) and the Australia New Zealand Gynaecological Oncology Group (ANZGOG) (ANZGOG-221/2023). About Ovarian Cancer Ovarian cancer is the fifth most common cause of cancer death in women. Patients whose disease returns less than six months after receiving platinum-containing therapy have "platinum-resistant" disease. There are few treatment options for these women. Approximately 20,000 women with platinum-resistant disease are candidates to start a new therapy each year in the United States, with at least an equal number in Europe. About Cortisol's Role in Oncology Cortisol plays a role in tumor growth through several mechanisms. It helps solid tumors resist chemotherapy by inhibiting cellular apoptosis — the tumor-killing effect chemotherapy is meant to stimulate. In some cancers, cortisol promotes tumor growth by activating oncogenic signaling in the cells to which it binds. Cortisol also suppresses the body's immune response, which weakens its ability to fight all diseases, including cancer. Corcept is developing relacorilant in ovarian, endometrial, cervical, pancreatic and prostate cancers. Relacorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents. It has been designated an orphan drug by the European Commission (EC) for the treatment of ovarian cancer. Corcept has submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for relacorilant to treat patients with platinum-resistant ovarian cancer. About Lifyorli™ Lifyorli (relacorilant), approved in combination with nab-paclitaxel, is the first U.S. Food and Drug Administration (FDA)-approved selective glucocorticoid receptor antagonist for adults with platinum-resistant ovarian cancer. Lifyorli is an oral medication taken the day before, the day of and the day after treatment with nab-paclitaxel. There is no biomarker requirement for Lifyorli. Lifyorli competitively binds to the glucocorticoid receptor (GR), where it enhances chemotherapy sensitivity by inhibiting cortisol’s suppression of apoptosis – the programmed cell death that chemotherapies such as nab-paclitaxel are meant to cause. Lifyorli does not have any effect at the body’s other steroid receptors. Corcept is committed to timely patient access for Lifyorli. For questions regarding product availability, please contact Lifyorli Support™ at 1-85-LIFYORLI (1-855-439-6754). LIFYORLI Indication & Usage LIFYORLI is indicated in combination with nab-paclitaxel for the treatment of adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens, at least one of which included bevacizumab. IMPORTANT SAFETY INFORMATION Contraindications: LIFYORLI is contraindicated in patients receiving systemic glucocorticoids for lifesaving purposes (e.g., immunosuppression after organ transplantation) because LIFYORLI antagonizes the effect of glucocorticoids. Warnings and Precautions: Neutropenia and Severe Infections LIFYORLI in combination with nab-paclitaxel can cause neutropenia, including febrile neutropenia and severe infections. There was one fatal event of septic shock with febrile neutropenia. Thirty-eight percent of patients initiated granulocyte colony-stimulating factor (G-CSF) during the first or second cycle of therapy. Monitor complete blood counts prior to each weekly treatment with LIFYORLI in combination with nab-paclitaxel and as clinically indicated. Based on the severity of neutropenia, delay dose, reduce dose or permanently discontinue LIFYORLI in combination with nab-paclitaxel. Consider short-acting G-CSF administration as applicable. Consider the possibility of concurrent adrenal insufficiency, particularly in the setting of serious infection. Adrenal Insufficiency LIFYORLI is a reversible glucocorticoid receptor antagonist and can cause adrenal insufficiency. Adrenal insufficiency can occur at any time during treatment with LIFYORLI. The risk of adrenal insufficiency is increased in situations of stress, such as acute illness, infection, or surgery. Consider whether supplemental glucocorticoids are required in the perioperative period in patients who have received LIFYORLI within 30 days of surgery. Monitor patients receiving LIFYORLI for signs and symptoms of adrenal insufficiency. Withhold LIFYORLI and administer glucocorticoid therapy if adrenal insufficiency is suspected. High doses of supplemental glucocorticoids may be needed to overcome the glucocorticoid receptor antagonism produced by LIFYORLI. After resolution of adrenal insufficiency, resume previous dose, reduce dose or permanently discontinue LIFYORLI based on severity. Exacerbation of Conditions Treated with Glucocorticoids Use of LIFYORLI in patients taking systemic glucocorticoids for other conditions (e.g., autoimmune disorders) may exacerbate these conditions. LIFYORLI is a glucocorticoid receptor antagonist that may make systemic glucocorticoids less effective. Similarly, coadministration of systemic glucocorticoids may make LIFYORLI less effective. Monitor patients for reduced effectiveness of LIFYORLI and glucocorticoids in patients receiving both. Embryo-Fetal Toxicity LIFYORLI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Verify pregnancy status of females of reproductive potential prior to initiating LIFYORLI treatment. Advise females of reproductive potential, including male patients with female partners of reproductive potential, to use effective contraception during treatment with LIFYORLI and for 1 week after the last dose. Adverse Reactions: Serious adverse reactions occurred in 35% of patients who received LIFYORLI in combination with nab-paclitaxel. Serious adverse reactions (≥2%) in patients were neutropenia (4%), pneumonia (3.2%), pleural effusion (3.2%), febrile neutropenia (2.1%), and fatigue (2.1%). Fatal adverse reactions (2.1%) in patients were septic shock (0.5%), cardiac arrest (0.5%), ischemic stroke (0.5%), and intestinal perforation (0.5%). Permanent discontinuation of LIFYORLI in combination with nab-paclitaxel due to adverse reactions occurred in 9% of patients. The adverse reaction (>2%) that resulted in permanent discontinuation of LIFYORLI in patients was intestinal obstruction (2.6%). Dosage interruptions of LIFYORLI due to an adverse reaction occurred in 72% of patients. Adverse reactions (≥5%) that required dosage interruptions of LIFYORLI in combination with nab-paclitaxel in patients included neutropenia (44%), anemia (12%), and fatigue (7%). Adverse reactions requiring dose reductions of LIFYORLI included fatigue (1.6%), decreased appetite (1.2%), abdominal pain (0.5%), neutropenia (0.5%), edema (0.5%), and sciatica (0.5%). LIFYORLI should be interrupted or discontinued when nab-paclitaxel is interrupted or discontinued. The most common adverse reactions (>20%) of patients treated with LIFYORLI plus nab-paclitaxel, including laboratory abnormalities, were decreased hemoglobin, decreased neutrophils, fatigue, nausea, diarrhea, decreased platelets, rash, and decreased appetite. Drug Interactions: Strong CYP3A Inducers : Avoid coadministration of LIFYORLI plus nab-paclitaxel with strong CYP3A inducers. Both relacorilant and paclitaxel are CYP3A substrates. Coadministration of strong CYP3A inducers can decrease concentrations of relacorilant and paclitaxel, which may reduce their effectiveness. CYP2C8 and Moderate CYP3A Inducers: Monitor for reduced effectiveness of LIFYORLI plus nab-paclitaxel with CYP2C8 inducers and moderate CYP3A inducers. Paclitaxel is a substrate of CYP2C8 and CYP3A, and relacorilant is a CYP3A substrate. Coadministration of CYP2C8 and moderate CYP3A inducers can decrease concentrations of paclitaxel and relacorilant, which may reduce their effectiveness. CYP2C8 Inhibitors: Monitor for increased adverse reactions and modify the dosage for adverse reactions as recommended. Paclitaxel is a substrate of CYP2C8. Coadministration of CYP2C8 inhibitors may increase concentrations of paclitaxel, which may increase the risk of adverse reactions. CYP3A Substrates: Avoid concomitant use unless otherwise recommended in the Prescribing Information for CYP3A substrates. Relacorilant is a strong CYP3A inhibitor. Relacorilant increases exposure of CYP3A substrates which may increase the risk for adverse reactions related to these substrates. Certain CYP2C8 Substrates: Avoid concomitant use unless otherwise recommended in the Prescribing Information for CYP2C8 substrates where minimal concentration changes may lead to reduced effectiveness. Relacorilant is a weak CYP2C8 inducer. Relacorilant decreases exposure of CYP2C8 substrates which may decrease the effectiveness related to these substrates. Use in Specific Populations: Lactation: Advise women not to breastfeed during treatment with LIFYORLI and for 1 week after the last dose. Geriatric Use: A higher incidence of grade 3-4 adverse events and dosage modification occurred in patients aged ≥65 years compared to younger adult patients. Hepatic Impairment: Avoid LIFYORLI in combination with nab-paclitaxel in patients with moderate or severe hepatic impairment (total bilirubin >1.5 to 10x ULN and any AST). Please see the full Prescribing Information for additional Important Safety Information. About Corcept Therapeutics For over 25 years, Corcept has focused on cortisol modulation and its potential to treat patients with a wide variety of serious disorders and has discovered more than 1,000 proprietary selective cortisol modulators and glucocorticoid receptor antagonists. Corcept is conducting advanced clinical trials in patients with Cushing’s syndrome, solid tumors, ALS and liver disease. In 2012, the company introduced Korlym ® , the first medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with endogenous Cushing’s syndrome, and in 2026, the company introduced Lifyorli™, approved in combination with nab-paclitaxel, the first FDA-approved selective glucocorticoid receptor antagonist for adults with platinum-resistant ovarian cancer. Corcept is headquartered in Redwood City, California. For more information, visit Corcept.com . Forward-Looking Statements Statements in this press release, other than statements of historical fact, are forward-looking statements based on our current plans and expectations and are subject to risks and uncertainties that might cause our actual results to differ materially from any future results expressed or implied by such forward-looking statements. In this press release, forward-looking statements include statements concerning: Lifyorli’s efficacy, safety pro other clinical attributes and its potential to provide a new standard-of-care treatment option for patients with platinum-resistant ovarian cancer; the anticipated regulatory approval of relacorilant in Europe; our confidence that selective GR antagonists, such as relacorilant, may help treat any patient whose tumor type expresses the GR; our focus on delivering selective GR antagonist therapy to patients and continuing cortisol modulation research in solid tumors that express GR across many different treatment settings; our further development of relacorilant in ovarian, endometrial, cervical, pancreatic and prostate cancers; and our commitment to timely patient access for Lifyorli. A further description of risks and uncertainties can be found in our SEC filings, which are available at our website and the SEC’s website. These risks and uncertainties include, but are not limited to, those related to: our ability to operate our business; our efforts to study and develop Korlym, relacorilant, miricorilant, dazucorilant, nenocorilant and our other product candidates; those molecules’ clinical attributes; regulatory approvals, mandates, oversight and other requirements imposed on our products or our business by laws, regulations or discretion of government authorities; and the scope and protective power of our intellectual property. We disclaim any intention or duty to update forward-looking statements made in this press release. Contacts Investor inquiries: ir@corcept.com Media inquiries: communications@corcept.com