Exatecan mesilate

Media ReleaseCOPENHAGEN, Denmark; April 13, 2026 Phase 1/2 RAINFOL™-01 data showed the combination of rinatabart sesutecan (Rina-S®) and bevacizumab was tolerable, with no new safety signals in patients with advanced ovarian cancer The ongoing Phase 3 RAINFOL-04 trial will further evaluate the combination in patients with recurrent platinum-sensitive ovarian cancer (PSOC) Genmab A/S (Nasdaq: GMAB) announced today new data demonstrating that rinatabart sesutecan (Rina-S®), an investigational folate receptor alpha (FRα)-targeted, topoisomerase I (TOPO1)-inhibitor antibody-drug conjugate (ADC), evaluated in combination with bevacizumab in patients with advanced ovarian cancer, showed a safety profile consistent with the known safety profiles of Rina-S and bevacizumab. These data are from the combination therapy cohort D2 of the multi-part Phase 1/2 RAINFOL™-01 study and were presented during an oral session at the 2026 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO) in San Juan, Puerto Rico. “Advanced ovarian cancer is a complex and difficult-to-treat disease, and the ability for investigational therapies such as Rina-S to be safely combined with bevacizumab can provide clinicians with more options to help improve disease control and manage resistance,” said Cara Mathews, M.D., study investigator and Associate Professor, Obstetrics and Gynecology at the Women and Infants Hospital, Brown University. “Rina-S has shown a manageable safety profile as a monotherapy, and these safety data suggest that it may be combined with a standard-of-care therapy such as bevacizumab without significantly increasing the risk of additional side effects.” As of data cutoff, 40 patients with recurrent ovarian cancer had received Rina-S (120 mg/m2) plus bevacizumab every three weeks until disease progression or unacceptable toxicity. The primary endpoint was safety and tolerability. The combination of Rina-S and bevacizumab was tolerable, with manageable adverse events (AEs). The safety profile of the combination was consistent with the known safety profiles of the individual agents, with no new or unexpected safety signals. The most common (≥25%) treatment-emergent AEs (TEAEs) included nausea (80%), fatigue (67.5%), anemia (55%), and neutropenia (45%). No safety signals of ocular toxicities, peripheral neuropathy or interstitial lung disease were reported, and no clinically significant bleeding was observed. Serious TEAEs occurred in six patients (15.0%), and TEAEs leading to Rina-S dose reductions occurred in 11 patients (27.5%). Rina-S and bevacizumab discontinuation occurred in two patients (5%). No fatal TEAEs were reported. “Today’s safety results from RAINFOL-01 add to the growing body of clinical evidence supporting further development of Rina-S in advanced ovarian cancer, including its potential to be used in a combination regimen,” said Tahamtan Ahmadi, M.D., Ph.D., Executive Vice President and Chief Medical Officer, Head of Experimental Medicines, Genmab. “Rina-S has the potential to meaningfully expand treatment possibilities for patients with certain gynecologic cancers, and we look forward to further investigating additional opportunities, alone and with other therapies, as Rina-S advances through late-stage clinical development.” Rina-S is advancing through late-stage development supported by a growing portfolio of clinical trials, including the ongoing Phase 1/2 RAINFOL-01 trial (NCT05579366), the Phase 3 RAINFOL-02 trial (NCT06619236) in patients with platinum-resistant ovarian cancer (PROC), the Phase 3 RAINFOL-03 trial (NCT07166094) in patients with recurrent or progressive endometrial cancer (EC) who have disease progression on or following prior treatment with a platinum-containing regimen and a PD-(L)1 therapy, and the Phase 3 RAINFOL-04 trial (NCT07225270) in patients with recurrent platinum-sensitive ovarian cancer (PSOC) as maintenance therapy. Rina-S is also being evaluated in the Phase 2 RAINFOL-05 study (NCT07288177) in patients with non-small cell lung cancer (NSCLC). About the RAINFOL-01 TrialRAINFOL-01 (NCT05579366) is an open-label, multicenter Phase 1/2 study designed to evaluate the safety and efficacy of Rina-S Q3W at various doses in solid tumors that are known to express FRα. The study consists of multiple parts including Part D combination therapy cohorts. About Ovarian CancerOvarian cancer is a major global health issue, with over 320,000 new cases diagnosed annually worldwide.i It ranks as the eighth most common cancer and the eighth leading cause of cancer-related deaths among women globally.ii The disease is often diagnosed at an advanced stage due to its subtle and non-specific symptoms, such as abdominal bloating, pelvic pain and difficulty eating.iii Standard of care for PROC typically involves single-agent chemotherapy (pegylated liposomal doxorubicin (PLD), topotecan, gemcitabine or paclitaxel) and mirvetuximab for FRα-positive (≥75% positive tumor cells) patients.iv,v Approximately 70-90% of women with advanced-stage ovarian cancer worldwide experience a recurrence after initial treatment.vi Ovarian cancer has a low five-year survival rate, which varies significantly by region, but generally hovers around 30-50%.vii,viii About Rinatabart Sesutecan (Rina-S; GEN1184) Rina-S (GEN1184) is an investigational ADC. It is composed of a novel human monoclonal antibody directed at FRα, a hydrophilic protease-cleavable linker, and exatecan, a TOPO1 inhibitor payload. The clinical trial program for Rina-S continues to expand, including ovarian, endometrial and other cancers with unmet need. The safety and efficacy of Rina-S has not been established. Please visit https://clinicaltrials.gov/ for more information. About GenmabGenmab is an international biotechnology company dedicated to improving the lives of people with cancer and other serious diseases through innovative antibody medicines. For over 25 years, its passionate, innovative and collaborative team has advanced a broad range of antibody-based therapeutic formats, including bispecific antibodies, antibody-drug conjugates (ADCs), immune-modulating antibodies, and other next-generation modalities. Genmab’s science powers eight approved antibody medicines, and the company is advancing a strong late-stage clinical pipeline, including wholly owned programs, with the goal of delivering transformative medicines to patients. Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us on LinkedIn and X. Contact: David Freundel, Senior Director, Global Communications & Corporate AffairsT: +1 609 613 0504; E: dafr@genmab.com Andrew Carlsen, Vice President, Head of Investor RelationsT: +45 3377 9558; E: acn@genmab.comThis Media Release contains forward-looking statements. The words “believe,” “expect,” “anticipate,” “intend” and “plan” and similar expressions identify forward-looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with preclinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab’s most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab’s most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward-looking statements in this Media Release nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law. Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo®; HuMax®; DuoBody®; HexaBody®; DuoHexaBody®, HexElect®, KYSO® and RAINFOL™; Rina-S® is a trademark of ProfoundBio, US, Co. and Genmab (Suzhou) Co., Ltd. i World Cancer Research Fund International. https://www.wcrf.org/cancer-trends/ovarian-cancer-statistics/. Accessed Oct 2025.ii World Ovarian Cancer Coalition. https://worldovariancancercoalition.org/about-ovarian-cancer/key-stats/. Accessed Oct 2025.iii Dilley, James et al. Ovarian cancer symptoms, routes to diagnosis and survival - Population cohort study in the 'no screen' arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Gynecologic oncology vol. 158,2 (2020): 316-322. doi:10.1016/j.ygyno.2020.05.002.iv Eskander RN, Moore KN, Monk BJ, Herzog TJ, Annunziata CM, O’Malley DM and Coleman RL (2023) Overcoming the challenges of drug development in platinum-resistant ovarian cancer. Front. Oncol. 13:1258228.v National Comprehensive Cancer Network (NCCN). NCCN Guidelines for Patients®: Ovarian Cancer. Version 3.2024. July 15, 2024. https://www.nccn.org/patients/guidelines/content/PDF/ovarian-patient.pdf vi Ovarian Cancer Research Alliance. https://ocrahope.org/patients/diagnosis-and-treatment/recurrence/vii European Institute of Women's Health. https://eurohealth.ie/policy‐brief‐women‐and‐ovarian‐cancer‐in‐the‐eu‐2018/. Accessed Oct 2025.viii American Cancer Society. Stages of Ovarian Cancer. https://www.cancer.org/cancer/types/ovarian-cancer/detection-diagnosis-staging/survival-rates.html. Accessed Oct 2025. Media Release no. 05CVR no. 2102 3884LEI Code 529900MTJPDPE4MHJ122 Genmab A/SCarl Jacobsens Vej 302500 ValbyDenmark Attachment 041326_MR05_SGO2026

2026年4月11日，礼来靶向PTK7的ADC药物LY4175408在中国申请IND获CDE受理。 蛋白酪氨酸激酶 7（PTK7）是受体酪氨酸激酶家族中一种无催化活性的成员，在卵巢癌、非小细胞肺癌（NSCLC）、食管癌及三阴性乳腺癌（TNBC）等实体瘤中高表达，且与tumor-initiating cells相关。 LY4175408源自礼来收购的MabLink Bioscience，是靶向PTK7的ADC药物，其分子设计如下： 丫抗体： Fc silence的新型全人源抗 PTK7 IgG1 抗体 💊载荷：Topo1i Ecatecan 🔒连接子：VA-PAB-聚肌氨酸（PSAR）亲水连接子，根据专利分析，其连接子-载荷结构与已经进入临床III期的FRa ADC Sofetabart mipitecan一致 🔢DAR值：8 🐓MOA： 🐭体内活性： 👴目前已经启动肺癌，三阴性乳腺癌和子宫内膜癌的临床I期研究 🏃♀️竞争格局方面： PTK7的ADC 开发比较挑战，首个PTK7 ADC Cofetuzumab pelidotin (PF-06647020/ ABBV-647)由于低疗高毒被辉瑞和艾伯维放弃；Genmab因“总体收益风险状况”停止了通过收购普方生物获得的GEN1107项目。 科伦博泰的SKB518是全球进度最快的PTK7 ADC。目前已经启动2项临床2期，适应症涵盖肺癌（NCT07019675）和妇科肿瘤（NCT07448922）。 DayOne/普众发现的MTX-13DAY301，同样采用Exatecan为有效载荷，于2026年12月在美国和加拿大启动临床1期研究（NCT06752681）。 Whitehawk于近期启动了PTK7 ADC HWK-007的临床（Whitehawk启动PTK7 ADC HWK-007临床，源自药明/多禧） Kivu Bioscience采用synaffix糖偶联技术开发了KIVU-107，已经启动临床1期（NCT07229313），即将在AACR2026公开临床前研究数据 除了前述几款进入临床的ADC，双抗ADC也值得重点关注，Zymeworks开发了双表位 ADC ZW418 百奥赛图开发了多款PTK7双靶点ADC，其中授权给IDEAY的PTK7/B7H3 ADC药物IDE034/BCG034已经启动临床I期（NCT07503808）（百奥赛图又一里程碑，IDEAYA双抗ADC IDE034完成首例患者入组）。 点关注，不迷路 参考文献: WO2025227010A1.pdf